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Genetics : Discovery News

New test returns fewer false positives than standard testing.

Reaching a ripe old age seems to have little to do with lifestyle and a lot to do with genes, concludes a new study on 17 of the oldest people on the planet. Continue reading

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What is Low Testosterone (Hypogonadism)? – Urology A-Z

What is Testosterone

Testosterone is the sex hormone that helps boys become men. This hormone is key during puberty and the development of male physical features. Testosterone helps to maintain men’s muscle strength and mass, facial and body hair, and a deeper voice. Testosterone levels can affect men’s sex drive, erections, mood, muscle mass and bone density. Testosterone is also needed for men to produce sperm.

Some men have low levels of testosterone. This is called hypogonadism, or low-T.

A man’s testosterone level normally decreases with age. About 4 out of 10 men over the age of 45 have low testosterone. It is seen in about 2 out of 10 men over 60, 3 out of 10 men over 70, and 3 out of 10 men over 80 years old.

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Female Hereditary Hair Loss Treatment & Genetic Testing …

http://www.baumanmedical.com – Hair loss affects tens of millions of American women, but new diagnostic procedures, effective treatments and tracking methods are available.

LaserCap delivers an effective, clinical dose of laser therapy anywhere, anytime because it is the first cordless, rechargeable, portable laser that has 224 separate laser diodes (not LEDs) that fits conveniently under a standard baseball hat. Laser treatments with LaserCap are 30 minutes, every other day. 650nm wavelength, 5mW per laser diode. Laser therapy does not regrow dead hair follicles, but it makes weaker hair follicles produce thicker, stronger and longer hair fibers. All laser patients should be measured in three areas using a HairCheck(TM) Cross sectional hair bundle measurement tool.

Female Androgen Sensitivity Genetic Testing is performed to determine if a women is likely to experience severe female hereditary hair loss and predict a post-menopausal woman’s response to the off-label treatment finasteride (propecia). The female Androgen Sensitivity test is performed in minutes in the doctor’s office using a cheek swab.

For more information on LaserCap, visit http://www.lasercap.info

To learn more about Hair Restoration Physician, Dr. Alan J. Bauman, M.D. visit http://www.baumanmedical.com

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Hypopituitarism: MedlinePlus Medical Encyclopedia

The pituitary gland is a small structure that is located just below the brain. It is attached by a stalk to the hypothalamus. This isthe area of the brain that controlsthe pituitary gland’sfunction.

The hormones released by the pituitary gland (and their functions) are:

In hypopituitarism, there is a lack of one or more pituitary hormones. Lack of a hormone leads to loss of function in the gland or organ the hormone controls. For example, lack of TSH leads to loss of normal function of the thyroid gland.

Hypopituitarism may be caused by:

Occasionally, hypopituitarism is due to uncommon immune system or metabolic diseases, such as:

Hypopituitarism is also a rare complication after pregnancy, a condition called Sheehan’s syndrome.

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Hypopituitarism: MedlinePlus Medical Encyclopedia

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Hypogonadism: MedlinePlus Medical Encyclopedia

Ali O, Donohoue PA. Hypofunction of the testes. In: Kliegman RM, Stanton BF, St. Geme JW III , et al., eds.Nelson Textbook of Pediatrics.

Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: An Endocrine Society Clinical Practice guideline.J Clin Endocrinol Metab.www.ncbi.nlm.nih.gov/pubmed/?term=20525905

Kansra AR, Donohoue PA. Hypofunction of the ovaries. In: Kliegman RM, Stanton BF, St. Geme JW III, et al., eds.Nelson Textbook of Pediatrics.

Swerdloff RS, Wang C. The testis and male sexual function. In: Goldman L, Schafer AI.Goldman’s Cecil Medicine.

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Stem Cell Therapy, Stem Cells 21 | Treatment Provider …

http://www.stemcells21.comSource: http://www.scoop.itAvailable stem cell therapy programs and pricing. Contact us now for a free consultation. Visit herehttp://stemcells21.com/index.php/contact-us/

Although 2014 was the shining year for numerous foods, many would attest that turmeric held the gold medal in hottest foods of 2014. The spice

Healthy foods not only provide you with life-giving nutrients and fuel for all the organs in your body, they also help you keep an ideal

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Genetic Engineering – HowStuffWorks

Genetic Engineering, the process of extracting DNA (deoxyribonucleic acid, which makes up the genes of all living things) from one organism and combining it with the DNA of another organism, thus introducing new hereditary traits into the recipient organism. The nature and characteristics of every living creature is determined by the special combinations of genes carried by its cells. The slightest alteration in these combinations can bring about significant changes in an organism and also its progeny. The science of devising techniques of modifying or controlling genes and genetic combinations is referred to as genetic engineering. It was practiced in one form or another in the past by farmers and agriculturists trying to create economically viable species of plants and animals through various breeding techniques Genetic engineering, as a science, was developed in the mid-1970’s primarily to create new strains of microorganisms that produce certain chemicals useful in manufacturing or as drugs. Genetic engineering is now also applied to improving plants and creating transgenic animals (animals containing foreign genetic material).

Some persons oppose genetic engineering on religious, ethical, or social grounds. Among the religious questions is whether humans have the right to transfer traits from one organism to another. A social concern is the possibility of creating harmful organisms that, if accidentally released into the environment, could cause epidemics.The creation of human clones, for example, is facing serious opposition especially on moral grounds. Organizations, such as the National Institutes of Health (NIH), are seeking to control the harmful effects of genetic engineering by imposing guidelines and safety measures for genetic experimentation. Treatment of hereditary defects through gene transplantation and controlled interchange of genes between specified species was approved in 1985 and 1987 respectively by the NIH and the National Academy of Sciences. The USDA has framed regulations for the genetic alteration of plants by plant breeders.

The U.S. Supreme Court ruled in 1980 that genetically engineered microorganisms could be patented. In 1988 the U.S. Patent and Trademark Office issued its first patent for a higher form of life, a transgenic mouse that is highly susceptible to certain cancers that appear frequently in humans. This mouse is used in cancer research.

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Genomics |Genetic Testing

Genetic tests have been developed for thousands of diseases. Most tests look at single genes and are used to diagnose rare genetic disorders, such as Fragile X Syndrome and Duchenne Muscular Dystrophy. In addition, some genetic tests look at rare inherited mutations of otherwise protective genes, such as BRCA1 and BRCA2, which are responsible for some hereditary breast and ovarian cancers. However, a growing number of tests are being developed to look at multiple genes that may increase or decrease a persons risk of common diseases, such as cancer or diabetes. Such tests and other applications of genomic technologies have the potential to help prevent common disease and improve the health of individuals and populations. For example, predictive gene tests may be used to help determine the risk of developing common diseases, and pharmacogenetic tests may be used to help identify genetic variations that can influence a persons response to medicines. There is much we still need to learn about how effective these new tests are, and the best way to use them to improve health. Learn more.

Despite the many scientific advances in genetics, researchers have only identified a small fraction of the genetic component of most diseases. Therefore, genetic tests for many diseases are developed on the basis of limited scientific information and may not yet provide valid or useful results to individuals who are tested. However, many genetic tests are being marketed prematurely to the public through the Internet, TV, and other media. This may lead to the misuse of these tests and the potential for physical or psychological harms to the public. At the same time, valid and useful tests, such as those for hereditary breast and ovarian cancer or for Lynch syndrome, a form of hereditary colorectal cancer, are not widely used, in part because of limited research on how to get useful tests implemented into practice across U.S. communities. Individuals can learn more about specific genetic tests by visiting the Web sites listed below or by talking with their doctor.

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In 2008, the former Secretary’s Advisory Committee on Genetics, Health and Society of the U.S. Department of Health and Human Services released a report identifying gaps in the regulation, oversight, and usefulness of genetic testing. They expressed the need for timely, reliable information that health care providers, payers, public health practitioners, policy makers, and consumers could use to make more informed decisions about the appropriate use of these tests in clinical and public health practice.

To begin addressing this need for reliable information, CDCs Office of Public Health Genomics (OPHG) established the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative project to systematically evaluate genetic tests and other applications of genomic technology that are in transition from research to clinical and public health practice. Since 2005, the independent EGAPP Working Group has released nine recommendations on the validity and utility of specific genetic tests.

The U.S. Preventive Services Task Force (USPSTF) has also released recommendations on specific genetic tests used in selected clinical scenarios involving breast cancer, colorectal cancer, and hemochromatosis.

In addition the Genetic Test Registry was developed by NCBI. The article “The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency” in the journal Nucleic Acids Research describes in detail this database.

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Also see the genetic testing and genetic counseling sections of CDCs Office of Public Health Genomics resource guide.

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What is genetic testing? – American Cancer Society

Genetic testing is the process of using medical tests to look for changes (mutations) in a persons genes or chromosomes. Hundreds of different genetic tests are used today, and more are being developed.

Genetic testing can be used in different situations. The type of testing most often used to check for cancer risk is called predictive gene testing. Its used to look for gene mutations that might put a person at risk of getting a disease. Its usually done in families with a history that suggests theres a disease that may be inherited. An example is testing for changes in the BRCA1 and BRCA2 genes (known breast cancer genes) in a woman whose mother and sister had breast cancer.

Genetic testing is also used for other reasons:

All of these forms of genetic testing, including predictive gene testing, look for gene changes that are passed from one generation to the next and are found in every cell in the body. Except for the newborn screening tests, they are used mainly for people with certain types of disease that seem to run in their families. They are not needed by most people.

Cancer-related genetic tests are most commonly done as predictive genetic tests. They may be used:

Sometimes after a person has been diagnosed with cancer, the doctor will order tests to look for gene changes in a sample of the cancer cells. These tests can give information on a persons outlook (prognosis) and can sometimes help tell whether certain types of treatment might be useful.

These types of tests look for gene changes only in the cancer cells that are taken from the patient. These tests are not the same as the tests used to find out about inherited cancer risk.

This document does not cover gene testing done on cancer cells. For more about this kind of testing and its use in cancer treatment, see our information on specific types of cancer.

The rest of this document focuses on predictive genetic testing for inherited mutations as they relate to cancer.

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HGH Therapy | HGH Clinics | Human Growth Hormone Therapy

Since 2003, AAG Health & Wellness has pioneered the field of health, vitality and wellness for men and women who want to achieve specific health goals.

We combine ongoing expertise in clinical research related to every area of wellness, with access to a unique team of board-certified physicians, wellness coaches and nutritionists at our hormone therapy clinics.

Our expertise is in the integrative field of age management and anti-aging. Our unique approach enables our clients to achieve optimum performance, productivity and appearance in the most efficient way possible.

Please find below a list of our most popular treatment plans designed to make you look good and feel better than ever:

We also offer a great selection of diagnostic tests at our clinics that are designed to identify health and wellness markers:

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Genetic engineering news, articles and information:

TV.NaturalNews.com is a free video website featuring thousands of videos on holistic health, nutrition, fitness, recipes, natural remedies and much more.

CounterThink Cartoons are free to view and download. They cover topics like health, environment and freedom.

The Consumer Wellness Center is a non-profit organization offering nutrition education grants to programs that help children and expectant mothers around the world.

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Dr Rajiv Desai Blog Archive GENE THERAPY

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GENE THERAPY:

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Caveat:

Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. I have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publishing this article. However, in view of the possibility of human error or changes in medical sciences, I do not assure that the information contained herein is in every respect accurate or complete, and I disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. I have taken some information from articles that were published few years ago. The facts and conclusions presented may have since changed and may no longer be accurate. Questions about personal health should always be referred to a physician or other health care professional.

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Prologue:

BLASPHEMY! some cried when the concept of gene therapy first surfaced. For them tinkering with the genetic constitution of human beings was equivalent to playing God, and this they perceived as being sacrilegious! On the other side was the scientific community, abuzz with excitement at the prospect of being able to wipe certain genetic disorders in humans entirely from the human gene pool. Although the term gene therapy was first introduced during the 1980s, the controversy about the rationality of this line of treatment still rages on. In the center of the debate lie the gene therapy pros and cons that derive opinions from religious, ethical and undoubtedly, political domains. The concept of genes as carriers of phenotypic information was introduced in the early 19th century by Gregor Mendel, who later demonstrated the properties of genetic inheritance in peas. Over the next 100 years, many significant discoveries lead to the conclusions that genes encode proteins and reside on chromosomes, which are composed of DNA. These findings culminated in the central dogma of molecular biology, that proteins are translated from RNA, which is transcribed from DNA. James Watson was quoted as saying we used to think that our fate was in our stars, but now we know, in large measures, our fate is in our genes. Genes, the functional unit of heredity, are specific sequences bases that encode instructions to make proteins. Although genes get a lot of attentions, it is the proteins that perform most life functions. When genes are altered, encoded proteins are unable to carry out their normal functions, resulting in genetic disorders. Gene therapy is a novel therapeutic branch of modern medicine. Its emergence is a direct consequence of the revolution heralded by the introduction of recombinant DNA methodology in the 1970s. Gene therapy is still highly experimental, but has the potential to become an important treatment regimen. In principle, it allows the transfer of genetic information into patient tissues and organs. Consequently, diseased genes can be eliminated or their normal functions rescued. Furthermore, the procedure allows the addition of new functions to cells, such as the production of immune system mediator proteins that help to combat cancer and other diseases. Most scientists believe the potential for gene therapy is the most exciting application of DNA science, yet undertaken.

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Note:

Please read my other articles Stem cell therapy and human cloning, Cell death and Genetically modified before reading this article.

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The rapid pace of technological advances has profound implications for medical applications far beyond their traditional roles to prevent, treat, and cure disease. Cloning, genetic engineering, gene therapy, human-computer interfaces, nanotechnology, and designer drugs have the potential to modify inherited predispositions to disease, select desired characteristics in embryos, augment normal human performance, replace failing tissues, and substantially prolong life span. As gene therapy is uprising in the field of medicine, scientists believe that after 20 years, this will be the last cure of every genetic disease. Genes may ultimately be used as medicine and given as simple intravenous injection of gene transfer vehicle that will seek our target cells for stable, site-specific chromosomal integration and subsequent gene expression. And now that a draft of the human genome map is complete, research is focusing on the function of each gene and the role of the faulty gene play in disease. Gene therapy will ultimately play Copernican part and will change our lives forever.

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Gene therapy, the experimental therapy as on today:

Gene therapy is an experimental technique that uses genes to treat or prevent diseases. Genes are specific sequences of bases that encode instructions on how to make proteins. When genes are altered so that the encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is used for correcting defective genes responsible for disease development. Researchers may use one of several approaches for correcting faulty genes. Although gene therapy is a promising treatment which helps successfully treat and prevent various diseases including inherited disorders, some types of cancer, and certain viral infections, it is still at experimental stage. Gene therapy is presently only being tested for the treatment of diseases that have no other cures. Currently, the only way for you to receive gene therapy is to participate in a clinical trial. Clinical trials are research studies that help doctors determine whether a gene therapy approach is safe for people. They also help doctors understand the effects of gene therapy on the body. Your specific procedure will depend on the disease you have and the type of gene therapy being used.

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Introduction to gene therapy:

Gene therapy is a clinical strategy involving gene transfer with therapeutic purposes. It is based on the concept that an exogenous gene (transgene) is able to modify the biology and phenotype of target cells, tissues and organs. Initially designed to definitely correct monogenic disorders, such as cystic fibrosis, severe combined immunodeficiency or muscular dystrophy, gene therapy has evolved into a promising therapeutic modality for a diverse array of diseases. Targets are expanding and currently include not only genetic, but also many acquired diseases, such as cancer, tissue degeneration or infectious diseases. Depending on the duration planned for the treatment, type and location of target cells, and whether they undergo division or are quiescent, different vectors may be used, involving nonviral methods, non-integrating viral vectors or integrating viral vectors. The first gene therapy clinical trial was carried out in 1989, in patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral transduction. In the early nineties, a clinical trial with children with severe combined immunodeficiency (SCID) was also performed, by retrovirus transfer of adenosine deaminase gene to lymphocytes isolated from these patients. Since then, more than 5,000 patients have been treated in more than 1,000 clinical protocols all over the world. Despite the initial enthusiasm, however, the efficacy of gene therapy in clinical trials has not been as high as expected; a situation further complicated by ethical and safety concerns. Further studies are being developed to solve these limitations.

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Historical development of gene therapy:

Chronology of development of gene therapy technology:

1970s, 1980s and earlier:

In 1972 Friedmann and Roblin authored a paper in Science titled Gene therapy for human genetic disease? Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects. However, these authors concluded that it was premature to begin gene therapy studies in humans because of lack of basic knowledge of genetic regulation and of genetic diseases, and for ethical reasons. They did, however, propose that studies in cell cultures and in animal models aimed at development of gene therapies be undertaken. Such studiesas well as abortive gene therapy studies in humanshad already begun as of 1972. In the 1970s and 1980s, researchers applied such technologies as recombinant DNA and development of viral vectors for transfer of genes to cells and animals to the study and development of gene therapies.

1990s:

The first approved gene therapy case in the United States took place on 14 September 1990, at the National Institute of Health, under the direction of Professor William French Anderson. It was performed on a four year old girl named Ashanti DeSilva. It was a treatment for a genetic defect that left her with ADA-SCID, a severe immune system deficiency. The effects were only temporary, but successful. New gene therapy approach repairs errors in messenger RNA derived from defective genes. This technique has the potential to treat the blood disorder thalassaemia, cystic fibrosis, and some cancers. Researchers at Case Western Reserve University and Copernicus Therapeutics are able to create tiny liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane. Sickle-cell disease is successfully treated in mice. The mice which have essentially the same defect that causes sickle cell disease in humans through the use a viral vector, were made to express the production of fetal hemoglobin (HbF), which normally ceases to be produced by an individual shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF has long been shown to temporarily alleviate the symptoms of sickle cell disease. The researchers demonstrated this method of gene therapy to be a more permanent means to increase the production of the therapeutic HbF. In 1992 Doctor Claudio Bordignon working at the Vita-Salute San Raffaele University, Milan, Italy performed the first procedure of gene therapy using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases. In 2002 this work led to the publication of the first successful gene therapy treatment for adenosine deaminase-deficiency (SCID). The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or bubble boy disease) held from 2000 and 2002 was questioned when two of the ten children treated at the trials Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the United States, the United Kingdom, France, Italy, and Germany. In 1993 Andrew Gobea was born with severe combined immunodeficiency (SCID). Genetic screening before birth showed that he had SCID. Blood was removed from Andrews placenta and umbilical cord immediately after birth, containing stem cells. The allele that codes for ADA was obtained and was inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses entered and inserted the gene into the stem cells chromosomes. Stem cells containing the working ADA gene were injected into Andrews blood system via a vein. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed. The 1999 death of Jesse Gelsinger in a gene therapy clinical trial resulted in a significant setback to gene therapy research in the United States. Jesse Gelsinger had ornithine transcarbamylase deficiency. In a clinical trial at the University of Pennsylvania, he was injected with an adenoviral vector carrying a corrected gene to test the safety of use of this procedure. He suffered a massive immune response triggered by the use of the viral vector, and died four days later. As a result, the U.S. FDA suspended several clinical trials pending the re-evaluation of ethical and procedural practices in the field.

2003:

In 2003 a University of California, Los Angeles research team inserted genes into the brain using liposomes coated in a polymer called polyethylene glycol. The transfer of genes into the brain is a significant achievement because viral vectors are too big to get across the bloodbrain barrier. This method has potential for treating Parkinsons disease. RNA interference or gene silencing may be a new way to treat Huntingtons disease. Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.

2006:

In March 2006 an international group of scientists announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and which gives a defective immune system. The study, published in Nature Medicine, is believed to be the first to show that gene therapy can cure diseases of the myeloid system. In May 2006 a team of scientists led by Dr. Luigi Naldini and Dr. Brian Brown from the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) in Milan, Italy reported a breakthrough for gene therapy in which they developed a way to prevent the immune system from rejecting a newly delivered gene. Similar to organ transplantation, gene therapy has been plagued by the problem of immune rejection. So far, delivery of the normal gene has been difficult because the immune system recognizes the new gene as foreign and rejects the cells carrying it. To overcome this problem, the HSR-TIGET group utilized a newly uncovered network of genes regulated by molecules known as microRNAs. Dr. Naldinis group reasoned that they could use this natural function of microRNA to selectively turn off the identity of their therapeutic gene in cells of the immune system and prevent the gene from being found and destroyed. The researchers injected mice with the gene containing an immune-cell microRNA target sequence, and the mice did not reject the gene, as previously occurred when vectors without the microRNA target sequence were used. This work will have important implications for the treatment of hemophilia and other genetic diseases by gene therapy. In August 2006, scientists at the National Institutes of Health (Bethesda, Maryland) successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells. This study constitutes one of the first demonstrations that gene therapy can be effective in treating cancer. In November 2006 Preston Nix from the University of Pennsylvania School of Medicine reported on VRX496, a gene-based immunotherapy for the treatment of human immunodeficiency virus (HIV) that uses a lentiviral vector for delivery of an antisense gene against the HIV envelope. In the Phase I trial enrolling five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens, a single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was safe and well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. In addition, all five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in U.S. Food and Drug Administration-approved human clinical trials for any disease. Data from an ongoing Phase I/II clinical trial were presented at CROI 2009.

2007:

On 1 May 2007 Moorfields Eye Hospital and University College Londons Institute of Ophthalmology announced the worlds first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23 year-old British male, Robert Johnson, in early 2007. Lebers congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in New England Journal of Medicine in April 2008. They researched the safety of the subretinal delivery of recombinant adeno-associated virus (AAV) carrying RPE65 gene, and found it yielded positive results, with patients having modest increase in vision, and, perhaps more importantly, no apparent side-effects.

2008:

In May 2008, two more groups, one at the University of Florida and another at the University of Pennsylvania, reported positive results in independent clinical trials using gene therapy to treat Lebers congenital amaurosis. In all three clinical trials, patients recovered functional vision without apparent side-effects. These studies, which used adeno-associated virus, have spawned a number of new studies investigating gene therapy for human retinal disease.

2009:

In September 2009, the journal Nature reported that researchers at the University of Washington and University of Florida were able to give trichromatic vision to squirrel monkeys using gene therapy, a hopeful precursor to a treatment for color blindness in humans. In November 2009, the journal Science reported that researchers succeeded at halting a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.

2010:

A paper by Komromy et al. published in April 2010, deals with gene therapy for a form of achromatopsia in dogs. Achromatopsia, or complete color blindness, is presented as an ideal model to develop gene therapy directed to cone photoreceptors. Cone function and day vision have been restored for at least 33 months in two young dogs with achromatopsia. However, the therapy was less efficient for older dogs. In September 2010, it was announced that an 18 year old male patient in France with beta-thalassemia major had been successfully treated with gene therapy. Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions. A team directed by Dr. Phillipe Leboulch (of the University of Paris, Bluebird Bio and Harvard Medical School) used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007. The patients haemoglobin levels were stable at 9 to 10 g/dL, about a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions had not been needed. Further clinical trials were planned. Bone marrow transplants are the only cure for thalassemia but 75% of patients are unable to find a matching bone marrow donor.

2011:

In 2007 and 2008, a man being treated by Gero Htter was cured of HIV by repeated Hematopoietic stem cell transplantation with double-delta-32 mutation which disables the CCR5 receptor; this cure was not completely accepted by the medical community until 2011. This cure required complete ablation of existing bone marrow which is very debilitating. In August 2011, two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The study carried out by the researchers at the University of Pennsylvania used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease. In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free. Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.

2012:

The FDA approves clinical trials of the use of gene therapy on thalassemia major patients in the US. Researchers at Memorial Sloan Kettering Cancer Center in New York begin to recruit 10 participants for the study in July 2012. The study is expected to end in 2014. In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment, called Alipogene tiparvovec (Glybera), compensates for lipoprotein lipase deficiency (LPLD), which can cause severe pancreatitis. People with LPLD cannot break down fat, and must manage their disease with a restricted diet. However, dietary management is difficult, and a high proportion of patients suffer life-threatening pancreatitis. The recommendation was endorsed by the European Commission in November 2012 and commercial rollout is expected in late 2013. In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission or very close to it three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1 which exist only on cancerous myeloma cells.

2013:

In March 2013, Researchers at the Memorial Sloan-Kettering Cancer Center in New York, reported that three of five subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not. The researchers believed that the patients immune systems would make normal T-cells and B-cells after a couple of months however they were given bone marrow to make sure. One patient had relapsed and died and one had died of a blood clot unrelated to the disease. Following encouraging Phase 1 trials, in April 2013, researchers in the UK and the US announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients at several hospitals in the US and Europe to use gene therapy to combat heart disease. These trials were designed to increase the levels of SERCA2a protein in the heart muscles and improve the function of these muscles. The FDA granted this a Breakthrough Therapy Designation which would speed up the trial and approval process in the USA. In July 2013 the Italian San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) reported that six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months the results were promising. Three of the children had metachromatic leukodystrophy which causes children to lose cognitive and motor skills. The other children had Wiskott-Aldrich syndrome which leaves them to open to infection, autoimmune diseases and cancer due to a faulty immune system. In October 2013, the Great Ormond Street Hospital, London reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and their immune systems were showing signs of full recovery. Another three children treated since then were also making good progress. ADA-SCID children have no functioning immune system and are sometimes known as bubble children. In October 2013, Amit Nathswani of the Royal Free London NHS Foundation Trust in London reported that they had treated six people with haemophilia in early 2011 using genetically engineered adeno-associated virus. Over two years later all six were still producing blood plasma clotting factor.

2014:

In January 2014, researchers at the University of Oxford reported that six people suffering from choroideremia had been treated with a genetically engineered adeno-associated virus with a copy of a gene REP1. Over a six month to two year period all had improved their sight. Choroideremia is an inherited genetic eye disease for which in the past there has been no treatment and patients eventually go blind. In March 2014 researchers at the University of Pennsylvania reported that 12 patients with HIV had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation known to protect against HIV (CCR5 deficiency). Results were promising.

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The three main issues for the coming decade will be public perceptions, scale-up and manufacturing, and commercial considerations. Focusing on single-gene applications, which tend to be rarer diseases, will produce successful results sooner than the current focus on the commoner, yet more complex, cancer and heart diseases.

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What is Gene?

A gene is an important unit of hereditary information. It provides the code for living organisms traits, characteristics, function, and physical development. Each person has around 25,000 genes that are located on 46 chromosomes. Gene is a segment of DNA found on chromosome that codes for a particular protein. It acts as a blue print for making enzymes and other proteins for every biochemical reaction and structure of body.

What is allele?

Alleles are two or more alternative forms of a gene that can occupy a specific locus (location) on a chromosome.

What is DNA?

Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic information used in the development and function of all known living organisms. The main role of DNA is the long-term storage of information. DNA is often compared to a set of blueprints or a recipe or code, since it contains the instructions needed to construct other components of cells, such as proteins. The DNA segments that carry this genetic information are called genes.

What are Chromosomes?

A chromosome is a singular piece of DNA, which contains many genes. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. Chromosomes are found inside the nucleus of cells.

What are Proteins?

Proteins are large organic compounds made of amino acids. They are involved in many processes within cells. Proteins act as building blocks, or function as enzymes and are important in communication among cells.

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What are plasmids?

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Plasmid is any extrachromosomal heritable determinant. Plasmids are fragments of double-stranded DNA that can replicate independently of chromosomal DNA, and usually carry genes. Although they can be found in Bacteria, Archaea and Eukaryotes, they play the most significant biological role in bacteria where they can be passed from one bacterium to another by horizontal gene transfer, usually providing a context-dependent selective advantage, such as antibiotic resistance.

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In the center of every cell in your body is a region called the nucleus. The nucleus contains your DNA which is the genetic code you inherited from each of your parents. The DNA is ribbon-like in structure, but normally exists in a condensed form called chromosomes. You have 46 chromosomes (23 from each parent), which are in turn comprised of thousands of genes. These genes encode instructions on how to make proteins. Proteins make up the majority of a cells structure and perform most life functions. Genes tell cells how to work, control our growth and development, and determine what we look like and how our bodies work. They also play a role in the repair of damaged cells and tissues. Each person has more than 25,000 genes, which are made up of DNA. You have 2 copies of every gene, 1 inherited from your mother and 1 from your father.

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DNA or deoxyribonucleic acid is the very long molecule that encodes the genetic information. A gene is a stretch of DNA required to make a functional product such as part or all of a protein. People have about 25,000 genes. During gene therapy, DNA that codes for specific genes is delivered to individual cells in the body.

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The Human Genome:

The human genome is the entire genetic code that resides in every cell in your body (with the exception of red blood cells). The genome is divided into 23 chromosome pairs. During reproduction, two copies of the chromosomes (one from each parent) are passed onto the offspring. While most chromosomes are identical for males and females, the exceptions are the sex chromosomes (known as the X and Y chromosomes). Each chromosome contains thousands of individual genes. These genes can be further divided into sequences called exons and introns, which are in turn made up of even shorter sequences called codons. And finally, the codons are made up of base pairs, combinations of four bases: adenine, cytosine, thymine, and guanine. Or A, C, T, and G for short. The human genome is vast, containing an estimated 3.2 billion base pairs. To put that in perspective, if the genome was a book, it would be hundreds of thousands of pages long. Thats enough room for a dozen copies of the entire Encyclopaedia Britannica, and all of it fits inside a microscopic cell.

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Our genes help make us unique. Inherited from our parents, they go far in determining our physical traits like eye color and the color and texture of our hair. They also determine things like whether babies will be male or female, the amount of oxygen blood can carry, and the likelihood of getting certain diseases. Scientists believe that every human has about 25,000 genes per cell. A mutation, or change, in any one of these genes can result in a disease, physical disability, or shortened life span. These mutations can be passed from one generation to another, inherited just like a mothers curly hair or a fathers brown eyes. Mutations also can occur spontaneously in some cases, without having been passed on by a parent. With gene therapy, the treatment or elimination of inherited diseases or physical conditions due to these mutations could become a reality. Gene therapy involves the manipulation of genes to fight or prevent diseases. Put simply, it introduces a good gene into a person who has a disease caused by a bad gene. Variations on genes are known as alleles. Because of changes in the genetic code caused by mutations, there are often more than one type of gene in the gene pool. For example, there is a specific gene to determine a persons blood type. Therefore, a person with blood type A will have a different version of that gene than a person with blood type B. Some genes work in tandem with each other.

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Genes to protein:

Chromosomes contain long chains of DNA built with repeating subunits known as nucleotides. That means a single gene is a finite stretch of DNA with a specific sequence of nucleotides. Those nucleotides act as a blueprint for a specific protein, which gets assembled in a cell using a multistep process.

1. The first step, known as transcription, begins when a DNA molecule unzips and serves as a template to create a single strand of complementary messenger RNA.

2. The messenger RNA then travels out of the nucleus and into the cytoplasm, where it attaches to a structure called the ribosome.

3. There, the genetic code stored in the messenger RNA, which itself reflects the code in the DNA, determines a precise sequence of amino acids. This step is known as translation, and it results in a long chain of amino acids a protein.

Proteins are the workhorses of cells. They help build the physical infrastructure, but they also control and regulate important metabolic pathways. If a gene malfunctions if, say, its sequence of nucleotides gets scrambled then its corresponding protein wont be made or wont be made correctly. Biologists call this a mutation, and mutations can lead to all sorts of problems, such as cancer and phenylketonuria. Gene therapy tries to restore or replace a defective gene, bringing back a cells ability to make a missing protein.

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Length measurements of DNA/RNA:

The following abbreviations are commonly used to describe the length of a DNA/RNA molecule:

bp = base pair(s) one bp corresponds to approximately 3.4 (340 pm) of length along the strand, or to roughly 618 or 643 daltons for DNA and RNA respectively.

kb (= kbp) = kilo base pairs = 1,000 bp

Mb = mega base pairs = 1,000,000 bp

Gb = giga base pairs = 1,000,000,000 bp.

For case of single-stranded DNA/RNA units of nucleotides are used, abbreviated nt (or knt, Mnt, Gnt), as they are not paired.

Note:

Please do not confuse these terms with computer data units.

kb in molecular biology is kilobase pairs = 1000 base pairs

kb in computer data is kilobytes = 1000 bytes

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Dr Rajiv Desai Blog Archive GENE THERAPY

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Life Extension – Products on Sale, Coupons, Reviews, Free …

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The Female Form: Embrace Your Genetics and Find Beauty in …

The following is a guest post by Amber Larsen of Massage and Health by Amber Kim:

My body, my face, my features will never be repeated. How I look is not going to mimic the girl next to me in the gym. My body shape will not be the same as another female that I may be slightly jealous of because shes thinner than me. My ass is going to be bigger and there is nothing I can do about it.

My genetics did it.

It’s amazing – on average, most women will have about thirteen negative thoughts about their appearance per day. If you break it down, it means that every waking hour we think negatively about ourselves. I cant lie; I know I have done the same. My ass is too big, my abs stick out, my latissimus dorsi is getting a bit too big because my bras are cutting into my skin (CrossFit did it).

According to cognitive behavioral psychology, the self-hate is called withdrawal emotions. These emotions make us want to withdraw from situations or things that are linked to the emotions that are causing us to feel this way. Essentially, you can say you can be withdrawing from yourself. This can cause us to either make drastic decisions, such as not to eat, or do things that can do us harm, or do the opposite – not take care of ourselves because we ask whats the use? I hope in writing this it can shed some light as to why you body looks the way it does, and how to embrace that you are unique and to work with your genetics.

What exactly is genetics? Genetics is a wide domain, but in short it is the study of heredity, more specifically the characteristics we inherit from our parents. Our appearance, abilities, susceptibility to disease, and even life span is influenced by heredity. That is just skimming the surface of genetics, but an overall view is that your body shape and your abilities in the gym are inherited from your parents. So what does that say about my personal body? My lower half will always be bigger because it is inherited from my father side. My upper body will always be a wee bit smaller because its inherited from my mothers side. The bottom line is, ladies, I will never weigh 110 pounds. Its not in my genetics, and you know what? Im okay with that.

Many times the media portrays an ideal size for a woman, but you know what? For a healthy woman who eats correctly and exercises on a regular basis there is no ideal size. The reason is because genetically we are all different. There is nothing wrong with a woman who has a leaner, thinner body, because she may be genetically predisposed to having a leaner frame. There is also nothing wrong with a woman who tends to be stronger looking with a larger frame for the same reason. Both body images are different, but both are ideal based on each individual womans inherited genetics.

Is your view on your body slowly changing?

So take a good look at my body (yes this is more difficult for me then you think). This photo is from 2012 and this is me at 140 pounds. If you see, my body is a bit stocky, bulky, and (since I am 53) technically overweight. By the way, you can see some of my cellulite and, yes, I did throw away my scale! My abs stick out and so does my ass.

You can see my body is made up of mostly fast-twitch muscle fibers, or type II muscle fibers. My muscles are different in that they contain a higher number of glycolytic enzymes, which means my muscles do very well anaerobically. Also, my body can be viewed as a bit of a subtype of fast twitch muscles in that I am efficient in strength movements and halfway decent at aerobic movements (not the best though). My body is adaptable with endurance training, but it will not be my strongest area of fitness. Bottom line, the body you see is genetically predisposed to strength work.

Now, a slow-twitch body will not look exactly like this. A slow-twitch body will be leaner because the muscle fibers tend to be longer. These muscles contain larger amounts of mitochondria and higher concentrations of myoglobin than my own body. Again, slow twitch muscle tissue is an inherited trait.

I am not super skinny (as you can see above), but its important to realize that each body is unique and has strengths and weaknesses. Each body is beautiful in its own right, and its important for all of you to embrace what makes you an individual. There is no ideal weight or look for any woman. Women look different based off of their genetic make up, and thats truly a beautiful thing. Just think – no one will ever look exactly like you. And you have automatically inherited strengths that will help you in your fitness goals.

Embrace the person you are. I know it can be difficult to stop the negative self talk that your body does not look like the skinny Victorias Secret model, but you know what? Maybe you were never meant to look that way based off of your genetic heredity. Maybe you were meant to look strong and maybe you were built for strength, which is beautiful. Even if you are a leaner person who wishes to look stronger, well you can, even with a leaner frame, and you can also embrace that your body allows you to work efficiently aerobically based on your genetic make-up.

The image you have of your body should be positive. No one can be you, and no one can look exactly like you because you are genetically different. There is so much beauty in that. Embrace the genetic make up that make your body unique to those around you. I hope you will not be afraid to wear that bikini this summer or to workout without a shirt on. Your body is beautiful because its uniquely you.

This is my body. I have learned to embrace the body that allows me to do amazing things. I hope you will do the same.

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The Female Form: Embrace Your Genetics and Find Beauty in …

Recommendation and review posted by Bethany Smith

Bio-Identical Hormones & Women’s Services at Dr. Wright’s …

The Tahoma Clinic has a variety of programs for women who are interested in optimizing their health. The programs range from basic gynecological exams, menopausal support, gynecological conditions such as endometriosis and fibroids, to prevention against osteoporosis, Alzheimers, cardiovascular disease, and cancers. Each program is individualized to meet personal needs, as well as address your prior history and family history.

Our most popular program involves evaluation and use of Bio-identical natural hormone replacement therapy. The Tahoma Clinic offers the latest in Bio-identical natural hormone replacement therapy for women in a safe and effective manner. Dr. Jonathan Wright, MD originated the Triest blend of estrogens 25 years ago and is still leading the way today. Dr. Wright currently has two physicians on staff specializing in womens health, and has worked extensively with each of them in Bio-identical natural hormone replacement therapy.

Menopause is a natural process a womans body goes through as she ages. Many different approaches can be taken to help address this change. Diet and lifestyle are always at the core of the program. Vitamins, minerals, and other supplements as necessary are then added to support the foundation. Lastly, the Bio-identical hormones, which look exactly like the hormones you produce in your own body and originate from wild yam or soy, are formulated for you.

As we age, our hormone levels change. For example, as early as 30 years of age, our DHEA levels start declining. At the same time, our Cortisol starts to rise. This combination can result in weight gain, especially around the middle, increasing your risk of cardiovascular disease and insulin resistance. Other symptoms that occur with menopause include:

Each woman experiences these changes to varying degrees. There are many different approaches to managing your symptoms, and we will work with you to find the treatment that best supports your needs. To start, your hormone levels will be evaluated by a 24-hour urinalysis which allows for multiple metabolites to be measured accurately. Then, a physician will work with you to focus on methods to help you balance your hormones safely and effectively for your natural body composition.

Please , pleasecontact usto make an appointment with one of our doctors that specialize in womens health.

Learn more about the physicians at the Tahoma Clinic

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Bio-Identical Hormones & Women’s Services at Dr. Wright’s …

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Renal cell carcinoma – Wikipedia, the free encyclopedia

Renal cell carcinoma (RCC, also known as hypernephroma, Grawitz tumor, renal adenocarcinoma) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport waste molecules from the blood to the urine. RCC is the most common type of kidney cancer in adults, responsible for approximately 90-95% of cases.[1] Initial treatment is most commonly either partial or complete removal of the affected kidney(s) and remains the mainstay of curative treatment.[2] Where the cancer has not metastasised (spread to other organs) or burrowed deeper into the tissues of the kidney the 5-year survival rate is 65-90%,[3] but this is lowered considerably when the cancer has spread. It is relatively resistant to radiation therapy and chemotherapy, although some cases respond to targeted therapies such as sunitinib, temsirolimus, bevacizumab, interferon alfa and sorafenib which have improved the outlook for RCC.[4]

The body is remarkably good at hiding the symptoms and as a result people with RCC often have advanced disease by the time it is discovered.[5] The initial symptoms of RCC often include: blood in the urine (occurring in 40% of affected persons at the time they first seek medical attention), flank pain (40%), a mass in the abdomen or flank (25%), weight loss (33%), fever (20%), high blood pressure (20%), night sweats and generally feeling unwell.[1] RCC is also associated with a number of paraneoplastic syndromes (PNS) which are conditions caused by either the hormones produced by the tumour or by the body’s attack on the tumour and are present in about 20% of those with RCC.[1] These syndromes most commonly affect tissues which have not been invaded by the cancer.[1] The most common PNSs seen in people with RCC are: anaemia (due to an underproduction of the hormone, erythropoietin), high blood calcium levels, polycythaemia (the opposite to anaemia, due to an overproduction of erythropoietin), thrombocytosis (too many platelets in the blood, leading to an increased tendency for blood clots and bleeds) and secondary amyloidosis.[6] When RCC metastasises it most commonly spreads to the lymph nodes, lungs, liver, adrenal glands, brain or bones.[6]

Historically, medical practitioners expected a person to present with three findings. This classic triad[7] is 1: haematuria, which is when there is blood present in the urine, 2: flank pain, which is pain on the side of the body between the hip and ribs, and 3: an abdominal mass, similar to bloating but larger. It is now known that this classic triad of symptoms only occurs in 10-15% of cases, and is usually indicative that the renal cell carcinoma (RCC) in an advanced stage.[7] Today, RCC is often asymptomatic (meaning little to no symptoms) and is generally detected incidentally when a person is being examined for other ailments.[8]

Other signs and symptom may include haematuria;[7] loin pain;[7] abdominal mass;[8]malaise, which is a general feeling of feeling unwell;[8] weight loss and/or loss of appetite;[9]anaemia resulting from depression of erythropoietin;[7]erythrocytosis (increased production of red blood cells) due to increased erythropoietin secretion;[7]varicocele, which is seen in males as an enlargement of the tissue at the testicle (more often the left testicle)[8]hypertension (high blood pressure) resulting from secretion of renin by the tumour;[10]hypercalcemia, which is elevation of calcium levels in the blood;[11] sleep disturbance or night sweats;[9] recurrent fevers;[9] and chronic fatigue.[12]

The greatest risk factors for RCC are lifestyle-related; smoking, obesity and hypertension (high blood pressure) have been estimated to account for up to 50% of cases.[13] Occupational exposure to some chemicals such as asbestos, cadmium, lead, chlorinated solvents, petrochemicals and PAH (polycyclic aromatic hydrocarbon) has been examined by multiple studies with inconclusive results.[14][15][16] Another suspected risk factor is the long term use of non-steroidal anti-inflammatory drugs (NSAIDS).[17]

Finally, studies have found that women who have had a hysterectomy are at more than double the risk of developing RCC than those who have not.[18] The reason for this remains unclear.

Hereditary factors have a minor impact on individual susceptibility with immediate relatives of people with RCC having a two to fourfold increased risk of developing the condition.[19] Other genetically linked conditions also increase the risk of RCC, including hereditary papillary renal carcinoma, hereditary leiomyomatosis, Birt-Hogg-Dube syndrome, hyperparathyroidism-jaw tumor syndrome, familial papillary thyroid carcinoma, von Hippel-Lindau disease[20] and sickle cell disease.[21]

The most significant disease affecting risk however is not genetically linked patients with acquired cystic disease of the kidney requiring dialysis are 30 times greater more likely than the general population to develop RCC.[22]

The tumour arises from the cells of the proximal renal tubular epithelium.[1] It is considered an adenocarcinoma.[6] There are two subtypes: sporadic (that is, non-hereditary) and hereditary.[1] Both such subtypes are associated with mutations in the short-arm of chromosome 3, with the implicated genes being either tumour suppressor genes (VHL and TSC) or oncogenes (like c-Met).[1]

The first steps taken to diagnose this condition are consideration of the signs and symptoms, and a medical history (the detailed medical review of past health state) to evaluate any risk factors. Based on the symptoms presented, a range of biochemical tests (using blood and/or urine samples) may also be considered as part of the screening process to provide sufficient quantitative analysis of any differences in electrolytes, renal and liver function, and blood clotting times.[21] Upon physical examination, palpation of the abdomen may reveal the presence of a mass or an organ enlargement.[23]

Although this disease lacks characterization in the early stages of tumor development, considerations based on diverse clinical manifestations, as well as resistance to radiation and chemotherapy are important. The main diagnostic tools for detecting renal cell carcinoma are ultrasound, computed tomography (CT) scanning and magnetic resonance imaging (MRI) of the kidneys.[24]

Renal cell carcinoma (RCC) is not a single entity, but rather a collection of different types of tumours, each derived from the various parts of the nephron (epithelium or renal tubules) and possessing distinct genetic characteristics, histological features, and, to some extent, clinical phenotypes.[21]

Clear Cell Renal Cell Carcinoma (CCRCC)

Array-based karyotyping can be used to identify characteristic chromosomal aberrations in renal tumors with challenging morphology.[28][29] Array-based karyotyping performs well on paraffin embedded tumours[30] and is amenable to routine clinical use. See also Virtual Karyotype for CLIA certified laboratories offering array-based karyotyping of solid tumours.

The 2004 World Health Organization (WHO) classification of genitourinary tumours recognizes over 40 subtypes of renal neoplasms. Since the publication of the latest iteration of the WHO classification in 2004, several novel renal tumour subtypes have been described:[31]

Laboratory tests are generally conducted when the patient presents with signs and symptoms that may be characteristic of kidney impairment. They are not primarily used to diagnose kidney cancer, due to its asymptomatic nature and are generally found incidentally during tests for other illnesses such as gallbladder disease.[33] In other words, these cancers are not detected usually because they do not cause pain or discomfort when they are discovered. Laboratory analysis can provide an assessment on the overall health of the patient and can provide information in determining the staging and degree of metastasis to other parts of the body (if a renal lesion has been identified) before treatment is given.

The presence of blood in urine is a common presumptive sign of renal cell carcinoma. The haemoglobin of the blood causes the urine to be rusty, brown or red in colour. Alternatively, urinalysis can test for sugar, protein and bacteria which can also serve as indicators for cancer. A complete blood cell count can also provide additional information regarding the severity and spreading of the cancer.[34]

The CBC provides a quantified measure of the different cells in the whole blood sample from the patient. Such cells examined for in this test include red blood cells (erythrocytes), white blood cells (leukocytes) and platelets (thrombocytes). A common sign of renal cell carcinoma is anaemia whereby the patient exhibits deficiency in red blood cells.[35] CBC tests are vital as a screening tool for examination the health of patient prior to surgery. Inconsistencies with platelet counts are also common amongst these cancer patients and further coagulation tests, including Erythrocyte Sedimentation Rate (ESR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) should be considered.

Blood chemistry tests are conducted if renal cell carcinoma is suspected as cancer has the potential to elevate levels of particular chemicals in blood. For example, liver enzymes such as aspartate aminotransferase [AST] and alanine aminotransferase [ALT] are found to be at abnormally high levels.[36] The staging of the cancer can also be determined by abnormal elevated levels of calcium, which suggests that the cancer may have metastasised to the bones.[37] In this case, a doctor should be prompted for a CT scan. Blood chemistry tests also assess the overall function of the kidneys and can allow the doctor to decide upon further radiological tests.

The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour. It will frequently have an irregular or lobulated margin and may be seen as a lump on the lower pelvic or abdomen region. Traditionally, 85 to 90% of solid renal masses will turn out to be RCC but cystic renal masses may also be due to RCC.[38] However, the advances of diagnostic modalities are able to incidentally diagnose a great proportion of patients with renal lesions that may appear to be small in size and of benign state. Ten percent of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat.[39] Deciding on the benign or malignant nature of the renal mass on the basis of its localized size is an issue as renal cell carcinoma may also be cystic. As there are several benign cystic renal lesions (simple renal cyst, haemorrhagic renal cyst, multilocular cystic nephroma, polycystic kidney disease), it may occasionally be difficult for the radiologist to differentiate a benign cystic lesion from a malignant one.[40] The Bosniak classification system for cystic renal lesions classifies them into groups that are benign and those that need surgical resection, based on specific imaging features.[41]

The main imaging tests performed in order to identify renal cell carcinoma are pelvic and abdominal CT scans, ultrasound tests of the kidneys (ultrasonography), MRI scans, intravenous pyelogram (IVP) or renal angiography.[42] Among these main diagnostic tests, other radiologic tests such as excretory urography, positron-emission tomography (PET) scanning, ultrasonography, arteriography, venography, and bone scanning can also be used to aid in the evaluation of staging renal masses and to differentiate non-malignant tumours from malignant tumours.

Contrast-enhanced Computed tomography (CT) scanning is a routinely used imaging procedure in determining the stage of the renal cell carcinoma in the abdominal and pelvic regions of the patient. CT scans have the potential to distinguish solid masses from cystic masses and may provide information on the localization, stage or spread of the cancer to other organs of the patient. Key parts of the human body which are examined for metastatic involvement of renal cell carcinoma may include the renal vein, lymph node and the involvement of the inferior vena cava.[43] According to a study conducted by Sauk et al., multidetector CT imaging characteristics have applications in diagnosing patients with clear renal cell carcinoma by depicting the differences of these cells at the cytogenic level.[44]

Ultrasonographic examination can be useful in evaluating questionable asymptomatic kidney tumours and cystic renal lesions if Computed Tomography imaging is inconclusive. This safe and non-invasive radiologic procedure uses high frequency sound waves to generate an interior image of the body on a computer monitor. The image generated by the ultrasound can help diagnose renal cell carcinoma based on the differences of sound reflections on the surface of organs and the abnormal tissue masses. Essentially, ultrasound tests can determine whether the composition of the kidney mass is mainly solid or filled with fluid.[42]

A Percutaneous biopsy can be performed by a radiologist using ultrasound or computed tomography to guide sampling of the tumour for the purpose of diagnosis by pathology. However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient may make it unfavourable from a risk-benefit perspective.[11] However, biopsy tests for molecular analysis to distinguish benign from malignant renal tumours is of investigative interest.[11]

Magnetic Resonance Imaging (MRI) scans provide an image of the soft tissues in the body using radio waves and strong magnets. MRI can be used instead of CT if the patient exhibits an allergy to the contrast media administered for the test.[45][46] Sometimes prior to the MRI scan, an intravenous injection of a contrasting material called gadolinium is given to allow for a more detailed image. Patients on dialysis or those who have renal insufficiency should avoid this contrasting material as it may induce a rare, yet severe, side effect known as nephrogenic systemic fibrosis.[47] A bone scan or brain imaging is not routinely performed unless signs or symptoms suggest potential metastatic involvement of these areas. MRI scans should also be considered to evaluate tumour extension which has grown in major blood vessels, including the vena cava, in the abdomen. MRI can be used to observe the possible spread of cancer to the brain or spinal cord should the patient present symptoms that suggest this might be the case.

Intravenous pyelogram (IVP) is a useful procedure in detecting the presence of abnormal renal mass in the urinary tract. This procedure involves the injection of a contrasting dye into the arm of the patient. The dye travels from the blood stream and into the kidneys which in time, passes into the kidneys and bladder. This test is not necessary if a CT or MRI scan has been conducted.[48]

Renal angiography uses the same principle as IVP, as this type of X-ray also uses a contrasting dye. This radiologic test is important in diagnosing renal cell carcinoma as an aid for examining blood vessels in the kidneys. This diagnostic test relies on the contrasting agent which is injected in the renal artery to be absorbed by the cancerous cells.[49] The contrasting dye provides a clearer outline of abnormally-oriented blood vessels believed to be involved with the tumour. This is imperative for surgeons as it allows the patients blood vessels to be mapped prior to operation.[43]

The staging of renal cell carcinoma is the most important factor in predicting its prognosis.[50] Staging can follow the TNM staging system, where the size and extent of the tumour (T), involvement of lymph nodes (N) and metastases (M) are classified separately. Also, it can use overall stage grouping into stage I-IV, with the 1997 revision of AJCC described below:[50]

At diagnosis, 30% of renal cell carcinomas have spread to the ipsilateral renal vein, and 5-10% have continued into the inferior vena cava.[51]

The gross and microscopic appearance of renal cell carcinomas is highly variable. The renal cell carcinoma may present reddened areas where blood vessels have bled, and cysts containing watery fluids.[52] The body of the tumour shows large blood vessels that have walls composed of cancerous cells. Gross examination often shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, haemorrhage and scarring. In a microscopic context, there are four major histologic subtypes of renal cell cancer: clear cell (conventional RCC, 75%), papillary (15%), chromophobic (5%), and collecting duct (2%). Sarcomatoid changes (morphology and patterns of IHC that mimic sarcoma, spindle cells) can be observed within any RCC subtype and are associated with more aggressive clinical course and worse prognosis. Under light microscopy, these tumour cells can exhibit papillae, tubules or nests, and are quite large, atypical, and polygonal.

Recent studies have brought attention to the close association of the type of cancerous cells to the aggressiveness of the condition. Some studies suggest that these cancerous cells accumulate glycogen and lipids, their cytoplasm appear “clear”, the nuclei remain in the middle of the cells, and the cellular membrane is evident.[53] Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularised. The tumour compresses the surrounding parenchyma, producing a pseudocapsule.[54]

The most common cell type exhibited by renal cell carcinoma is the clear cell, which is named by the dissolving of the cells’ high lipid content in the cytoplasm. The clear cells are thought to be the least likely to spread and usually respond more favourably to treatment. However, most of the tumours contain a mixture of cells. The most aggressive stage of renal cancer is believed to be the one in which the tumour is mixed, containing both clear and granular cells.[55]

The recommended histologic grading schema for RCC is the Fuhrman system (1982), which is an assessment based on the microscopic morphology of a neoplasm with haematoxylin and eosin (H&E staining). This system categorises renal cell carcinoma with grades 1, 2, 3, 4 based on nuclear characteristics. The details of the Fuhrman grading system for RCC are shown below:[56]

Nuclear grade is believed to be one of the most imperative prognostic factors in patients with renal cell carcinoma.[21] However, a study by Delahunt et al. (2007) has shown that the Fuhrman grading is ideal for clear cell carcinoma but may not be appropriate for chromophobe renal cell carcinomas and that the staging of cancer (accomplished by CT scan) is a more favourable predictor of the prognosis of this disease.[57] In relation to renal cancer staging, the Heidelberg classification system of renal tumours was introduced in 1976 as a means of more completely correlating the histopathological features with the identified genetic defects.[58]

The type of treatment depends on multiple factors and the individual, some of which include:[7][59]

Every form of treatment has both risks and benefits; a health care professional will provide the best options that suit the individual circumstances.

Active surveillance or “watchful waiting” is becoming more common as small renal masses or tumours are being detected and also within the older generation when surgery is not always suitable.[60] Active surveillance involves completing various diagnostic procedures, tests and imaging to monitor the progression of the RCC before embarking on a more high risk treatment option like surgery.[60] In the elderly, patients with co-morbidities, and in poor surgical candidates, this is especially useful.

Different procedures may be most appropriate, depending on circumstances.

Radical nephrectomy is the removal of the entire affected kidney including Gerota’s fascia, the adrenal gland which is on the same side as the affected kidney, and the regional lymph nodes, all at the same time.[7] This method, although severe, is effective. But it is not always appropriate, as it is a major surgery that contains the risk of complication both during and after the surgery and can have a longer recovery time.[61] It is important to note that the other kidney must be fully functional, and this technique is most often used when there is a large tumour present in only one kidney.

Nephron-sparing partial nephrectomy is used when the tumor is small (less than 4cm in diameter) or when the patient has other medical concerns such as diabetes or hypertension.[7] The partial nephrectomy involves the removal of the affected tissue only, sparing the rest of the kidney, Gerota’s fascia and the regional lymph nodes. This allows for more renal preservation as compared to the radical nephrectomy, and this can have positive long term health benefits.[62] Larger and more complex tumors can also be treated with partial nephrectomy by surgeons with a lot of kidney surgery experience.[63]

Laparoscopic nephrectomy uses laparoscopic surgery, with minimally invasive surgical techniques. Commonly referred to as key hole surgery, this surgery does not have the large incisions seen in a classically performed radical or partial nephrectomy, but still successfully removes either all or part of the kidney. Laparoscopic surgery is associated with shorter stays in the hospital and quicker recovery time but there are still risks associated with the surgical procedure.

Surgery for metastatic disease: If metastatic disease is present surgical treatment may still a viable option. Radical and partial nephrectomy can still occur, and in some cases if the metastasis is small this can also be surgically removed.[7] This depends on what stage of growth and how far the disease has spread.

Targeted ablative therapies are also known as percutaneous ablative therapies. Although the use of laparoscopic surgical techniques for complete nephrectomies has reduced some of the risks associated with surgery,[64] surgery of any sort in some cases will still not be feasible. For example, the elderly, people already suffering from severe renal dysfunction, or people who have several comorbidities, surgery of any sort is not warranted.[65] Instead there are targeted therapies which do not involve the removal of any organs or serious surgery. Rather, these therapies involve the ablation of the tumor or the affected area. Ablative treatments use imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) to identify the location of the tumors, which ideally are smaller than 3.5cm and to guide the treatment. However there are some cases where ablation can be used on tumors that are larger.[65]

The two main types of ablation techniques that are used for renal cell carcinoma are radio frequency ablation and cryoablation.[65]

Radio frequency ablation uses an electrode probe which is inserted into the affected tissue, to send radio frequencies to the tissue to generate heat through the friction of water molecules. The heat destroys the tumor tissue.[7] Cell death will generally occur within minutes of being exposed to temperatures above 50C.

Cryoablation also involves the insertion of a probe into the affected area,[7] however, cold is used to kill the tumor instead of heat. The probe is cooled with chemical fluids which are very cold. The freezing temperatures cause the tumor cells to die by causing osmotic dehydration, which pulls the water out of the cell destroying the enzyme, organelles, cell membrane and freezing the cytoplasm.[65]

Immunotherapy is a method that activates the person’s immune system and uses it to their own advantage. It was developed after observing that in some cases there was spontaneous regression.[66] That is, the renal cell carcinoma improved with no other therapies. Immunotherapy capitalises on this phenomenon and aims to build up a person’s immune response to cancer cells.[66] Other medications target things such as growth factors that have been shown to promote the growth and spread of tumours.[67] They inhibit the growth factor in order to prevent tumours from forming.[68] There have been many different medications developed and most have only been approved in the last seven or so years.[69]

Some of the most recently developed treatments are listed below:[70]

Each of the treatments listed above is slightly different; some only work for a little while and others need to be used in conjunction with other therapies. There are also different side effects and risks associated with different forms of medication. As always, the advice of a health care professional should be sought if considering any of the therapies mentioned.

Chemotherapy and radiotherapy are not as successful in the case of RCC. RCC is resistant in most cases but there is about a 4-5% success rate sometimes, but this is often short lived with more tumours and growths developing later.[7]

Cancer vaccines are being developed but so far have been found to be effective for only certain forms of the RCC.[7] The vaccines are being designed to “prime” the immune system to provide tumour specific immunity.[66] They are still being developed but the present another treatment possibility.

Adjuvant therapy, which refers to therapy given after a primary surgery, has not been found to be beneficial in renal cell cancer.[72] Conversely, neoadjuvant therapy is administered before the intended primary or main treatment. In some cases neoadjuvant therapy has been shown to decrease the size and stage of the RCC to then allow it to be surgically removed.[68] This is a new form of treatment and the effectiveness of this approach is still being assessed in clinical trials.

Metastatic renal cell carcinoma (mRCC) is the spread of the primary renal cell carcinoma from the kidney to other organs. 25-30% of people have this metastatic spread by the time they are diagnosed with renal cell carcinoma.[73] This high proportion is explained by the fact that clinical signs are generally mild until the disease progresses to a more severe state.[74] The most common sites for metastasis are the lymph nodes, lung, bones, liver and brain.[8] How this spread affects the staging of the disease and hence prognosis is discussed in the Diagnosis and Prognosis section.

MRCC has a poor prognosis compared to other cancers although average survival times have increased in the last few years due to treatment advances. Average survival time in 2008 for the metastatic form of the disease was under a year[75] and by 2013 this improved to an average of 22 months.[76] Despite this improvement the 5 year survival rate for mRCC remains under 10%[77] and 20-25% of suffers remain unresponsive to all treatments and in these cases, the disease has a rapid progression.[76]

The available treatments for RCC discussed in the Treatment section are also relevant for the metastatic form of the disease. Options include interleukin-2 which is a standard therapy for advanced renal cell carcinoma.[72] In the past six years, seven new treatments have been approved specifically for mRCC (sunitinib, temsirolimus, bevacizumab, sorafenib, everolimus, pazopanib and axitinib).[4] These new treatments are based on the fact that renal cell carcinomas are very vascular tumors they contain a large number of blood vessels. The drugs aim to inhibit the growth of new blood vessels in the tumors, hence slowing growth and in some cases reducing the size of the tumors.[78] Side effects unfortunately are quite common with these treatments and include:[79]

Radiotherapy and chemotherapy are more commonly used in the metastatic form of RCC to target the secondary tumors in the bones, liver, brain and other organs. While not curative, these treatments do provide relief for suffers from symptoms associated with the spread of tumors.[76] Other potential treatments are still being developed, including tumor vaccines and small molecule inhibitors.[73]

The prognosis for renal cell carcinoma is largely influenced by a variety of factors, including tumour size, degree of invasion and metastasis, histologic type, and nuclear grade.[21] For metastatic renal cell carcinoma, factors which may present a poor prognosis include a low Karnofsky performance-status score (a standard way of measuring functional impairment in patients with cancer), a low haemoglobin level, a high level of serum lactate dehydrogenase, and a high corrected level of serum calcium.[80][81] For non-metastatic cases, the Leibovich scoring algorithm may be used to predict post-operative disease progression.[82]

Renal cell carcinoma is one of the cancers most strongly associated with paraneoplastic syndromes, most often due to ectopic hormone production by the tumour. The treatment for these complications of RCC is generally limited beyond treating the underlying cancer.

For those that have tumour recurrence after surgery, the prognosis is generally poor. Renal cell carcinoma does not generally respond to chemotherapy or radiation. Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise. Recent trials are testing newer agents, though the current complete remission rate with these approaches is still low, around 12-20% in most series. Most recently, treatment with tyrosine kinase inhibitors including nexavar, pazopanib, and rapamycin have shown promise in improving the prognosis for advanced RCC.[83]

The incidence of the disease varies according to geographic, demographic and, to a lesser extent, hereditary factors. There are some known risk factors, however the significance of other potential risk factors remains more controversial. The incidence of the cancer has been increasing in frequency worldwide at a rate of approximately 2-3% per decade[75] until the last few years where the number of new cases has stabilised.[14]

The incidence of RCC varies between sexes, ages, races and geographic location around the world. Men have a higher incidence than women (approximately 1.6:1)[72] and the vast majority are diagnosed after 65 years of age.[72] Asians reportedly have a significantly lower incidence of RCC than whites and while African countries have the lowest reported incidences, African Americans have the highest incidence of the population in the United States.[14] Developed countries have a higher incidence than developing countries, with the highest rates found in North America, Europe and Australia / New Zealand[84]

Daniel Sennert made the first reference suggesting a tumour arising in the kidney in his text Practicae Medicinae, first published in 1613.[85]

Miril published the earliest unequivocal case of renal carcinoma in 1810.[86] He described the case of Franoise Levelly, a 35 year old woman, who presented to Brest Civic Hospital on April 6, 1809, supposedly in the late stages of pregnancy.[85]

Koenig published the first classification of renal tumours based on macroscopic morphology in 1826. Koenig divided the tumors into scirrhous, steatomatous, fungoid and medullary forms.[87]

Following the classification of the tumour, researchers attempted to identify the tissue of origin for renal carcinoma.

The pathogenesis of renal epithelial tumours was debated for decades. The debate was initiated by Paul Grawitz when in 1883, he published his observations on the morphology of small, yellow renal tumours. Grawitz concluded that only alveolar tumours were of adrenal origin, whereas papillary tumours were derived from renal tissue.[85]

In 1893, Paul Sudeck challenged the theory postulated by Grawitz by publishing descriptions of renal tumours in which he identified atypical features within renal tubules and noted a gradation of these atypical features between the tubules and neighboring malignant tumour. In 1894, Otto Lubarsch, who supported the theory postulated by Grawitz coined the term hypernephroid tumor, which was amended tohypernephroma by Felix Victor Birch-Hirschfeld to describe these tumours.[88]

Vigorous criticism of Grawitz was provided by Oskar Stoerk in 1908, who considered the adrenal origin of renal tumours to be unproved. Despite the compelling arguments against the theory postulated by Grawitz, the term hypernephroma, with its associated adrenal connotation, persisted in the literature.[85]

Foot and Humphreys, and Foote et al. introduced the term Renal Celled Carcinoma to emphasize a renal tubular origin for these tumours. Their designation was slightly altered by Fetter to the now widely accepted term Renal Cell Carcinoma.[89]

Convincing evidence to settle the debate was offered by Oberling et al. in 1959 who studied the ultrastructure of clear cells from eight renal carcinomas. They found that the tumour cell cytoplasm contained numerous mitochondria and deposits of glycogen and fat. They identified cytoplasmic membranes inserted perpendicularly onto basement membrane with occasional cells containing microvilli along the free borders. They concluded that these features indicated that the tumours arose from the epithelial cells of the renal convoluted tubule, thus finally settling one of the most debated issues in tumour pathology.[85][90]

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Renal cell carcinoma – Wikipedia, the free encyclopedia

Recommendation and review posted by Bethany Smith

NIH Clinical Center: Graduate Medical Education (GME …

Graduate Medical Education (GME): Medical Genetics

Maximilian Muenke, MD

Eligibility CriteriaCandidates with the MD degree must have completed an accredited U.S. residency training program and have a valid U.S. license. Previous training is usually in, but not limited to, Pediatrics, Internal Medicine or Obstetrics and Gynecology.

OverviewThe NIH has joined forces with training programs at the Children’s National Medical Center, George Washington University School of Medicine and Washington Hospital Center. The combined training program in Medical Genetics is called the Metropolitan Washington, DC Medical Genetics Program. This is a program of three years duration for MDs seeking broad exposure to both clinical and research experience in human genetics.

The NIH sponsor of the program is National Human Genome Research Institute (NHGRI). Other participating institutes include the National Cancer Institute (NCI), the National Eye Institute (NEI), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Child Health and Human Development (NICHD), the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Institute of Mental Health (NIMH). Metropolitan area participants include Children’s National Medical Center (George Washington University), Walter Reed Army Medical Center, and the Department of Pediatrics, and the Department of Obstetrics and Gynecology at Washington Hospital Center. The individual disciplines in the program include clinical genetics, biochemical genetics, clinical cytogenetics, and clinical molecular genetics.

The primary goal of the training program is to provide highly motivated physicians with broad exposure to both clinical and research experiences in medical genetics. We train candidates to become effective, independent medical geneticists, prepared to deliver a high standard of clinical genetics services, and to perform state-of-the-art research in the area of genetic disease.

Structure of the Clinical Training Program

RotationsThis three year program involves eighteen months devoted to learning in clinical genetics followed by eighteen months of clinical or laboratory research.

Year 1Six months will be spent on rotation at the NIH. Service will include time spent on different outpatient genetics clinics, including Cancer Genetics and Endocrine Disorders and Genetic Ophthalmology; on the inpatient metabolic disease and endocrinology ward; on inpatient wards for individuals involved in gene therapy trials; and on the NIH Genetics Consultation Service.

Three months will be spent at Children’s National Medical Center and will be concentrated on pediatric genetics. Fellows will participate in outpatient clinics, satellite and outreach clinics. They will perform consults on inpatients and patients with metabolic disorders and on the neonatal service. Fellows will be expected to participate in the relevant diagnostic laboratory studies on patients for whom they have provided clinical care.

One month will be spent at Walter Reed Army Medical Center and will concentrate on adult and pediatric clinical genetics. One month will be spent at Washington Hospital Center on rotations in prenatal genetics and genetic counseling.

Year 2 Fellows will spend one month each in clinical cytogenetics, biochemical genetics, and molecular diagnostic laboratories. The remaining three months will be devoted to elective clinical rotations on any of the rotations previously mentioned. The second six months will be spent on laboratory or clinical research. The fellow will spend at least a half-day per week in clinic at any one of the three participating institutions.

Year 3This year will be devoted to research, with at least a half day per week in clinic.

NIH Genetics Clinic (Required)Fellows see patients on a variety of research protocols. The Genetics Clinic also selectively accepts referrals of patients requiring diagnostic assessment and genetic counseling. Areas of interest and expertise include: chromosomal abnormalities, congenital anomalies and malformation syndromes, biochemical defects, bone and connective tissue disorders, neurological disease, eye disorders, and familial cancers.

Inpatient Consultation Service (Required)Fellows are available twenty-four hours daily to respond to requests for genetics consultation throughout the 325-bed hospital. Written consultation procedures call for a prompt preliminary evaluation, a written response within twenty-four hours, and a subsequent presentation to a senior staff geneticist, with an addendum to the consult, as needed. The consultant service fellow presents the most interesting cases from the wards during the Post-Clinic Patient Conference on Wednesday afternoons during which Fellows present interesting clinical cases for critical review. Once a month the fellow presents relevant articles for journal club.

Metropolitan Area Genetics Clinics

Other Clinical Opportunities: Specialty Clinics at NIHThe specialty clinics of NIH treat a large number of patients with genetic diseases. We have negotiated a supervised experience for some of the fellows at various clinics; to date, fellows have participated in the Cystic Fibrosis Clinic, the Lipid Clinic, and the Endocrine Clinic.

Lectures, Courses and SeminarsThe fellowship program includes many lectures, courses and seminars. Among them are a journal club and seminars in medical genetics during which invited speakers discuss research and clinical topics of current interest. In addition, the following four courses have been specifically developed to meet the needs of the fellows:

Trainees are encouraged to pursue other opportunities for continuing education such as clinical and basic science conferences, tutorial seminars, and postgraduate courses, which are plentiful on the NIH campus.

Structure of the Research Training ProgramFellows in the Medical Genetics Program pursue state-of-the-art research related to genetic disorders. Descriptions of the diverse interests of participating faculty are provided in this catalog. The aim of this program is to provide fellows with research experiences of the highest caliber and to prepare them for careers as independent clinicians and investigators in medical genetics.

Fellows entering the program are required to select a research supervisor which may be from among those involved on the Genetics Fellowship Faculty Program. It is not required that this selection be made before coming to NIH.

In addition to being involved in research, all fellows attend and participate in weekly research seminars, journal clubs and laboratory conferences, which are required elements of each fellow’s individual research experience.

Program Faculty and Research Interests

Examples of Papers Authored by Program Faculty

Program GraduatesThe following is a partial list of graduates including their current positions:

Application Information

The NIH/Metropolitan Washington Medical Genetics Residency Program is accredited by the ACGME and the American Board of Medical Genetics. Upon successful completion of the three year program, residents are eligible for board certification in Clinical Genetics. During the third residency year, residents may elect to complete either (a) the requirements for one of the ABMG laboratory subspecialties, such as Clinical Molecular Genetics, Clinical Biochemical Genetics or Clinical Cytogenetics, or (b) a second one year residency program (e.g., Medical Biochemical Genetics).

Candidates should apply through ERAS, beginning July 1 of the year prior to their anticipated start date. Candidates with the MD or MD and PhD degree must have completed a U.S. residency in a clinically related field. Previous training is usually in, but not limited to, Pediatrics, Internal Medicine or Obstetrics and Gynecology. Four new positions are available each year. Interviews are held during August and September.

Electronic Application The quickest and easiest way to find out more about this training program or to apply for consideration is to do it electronically.

The NIH is dedicated to building a diverse community in its training and employment programs.

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NIH Clinical Center: Graduate Medical Education (GME …

Recommendation and review posted by Bethany Smith

Are People Born Gay? Genetics and Homosexuality

Introduction

There is a common belief among liberals that people are born either gay or straight. Conservatives tend to believe that sexual orientation is actually sexual preference, which is chosen by the individual. This page represents a review of the scientific literature on the basis for homosexual orientation.

Are people born gay or straight? Much of the current media sources assume the question is a solved scientific problem with all the evidence pointing toward a biological (probably genetic) basis for a homosexual orientation. Contrary to this perception, the question has been poorly studied (or studied poorly), although there is some evidence on both sides of question. In addition, many of the initial studies, which were highly touted by the media as “proof” for a biological basis for homosexuality, have been contradicted by later, more thorough studies. This evidence falls into four basic categories:

Until a few years ago, sexual orientation used to be called sexual preference. Obviously, the two terms denote significant differences in the the manner by which sexuality develops. A preference is something that is chosen, whereas orientation is merely something that defines us. The differences are potentially important regarding how the law applies to those who are gay. If homosexuality is not chosen, but actually is a biologically-determined characteristic over which we have no choice, then laws should not treat gays and straights differently, since homosexuality would be equivalent to one’s race, over which we have no control.

Since sexual attraction begins in the brain, researchers first examined the question of sexual orientation by comparing the anatomy of brains from males and females. These studies showed that male and female brains showed sexual dimorphism in the pre-optic area of the hypothalamus, where males demonstrated a greater than two-fold difference in cell number and size compared to females.1 A second study found that two of four Interstitial Nuclei of the Anterior Hypothalamus (INAH) were at least twice as large in males as females.2 Since the INAH was involved in sexual dimorphism, it was hypothesized by Simon LeVay that there might be differences in this region in heterosexual vs. homosexual men. Postmortem examination of the brains of AIDS patients vs. control male subjects (presumed to be heterosexual) showed that the presumably heterosexual men exhibited INAH3 that were twice the size of both females and presumably homosexual men who had died of AIDS.3 The study has been criticized for its uncertainty of sexual orientation of the subjects, and potential complications caused by the AIDS virus (which does infect the human brain), and also by lowered testosterone levels found in AIDS patients. A popularized Newsweek cover story, “Is This Child Gay?”4 characterized LeVay as a “champion for the genetic side,” even though the study involved no genetic data at all.

A subsequent study by Byne, et al. examined the question of INAH3 size on the basis of sex, sexual orientation, and HIV status.5 The study found large differences in INAH3 volume on the basis of sex (with the male INAH3 being larger than the female INAH3). However, the volume of IHAH3 was decreased in male heterosexual men who had contracted AIDS (0.108 mm3 compared with 0.123 mm3 in male controls). There was no statistically significant difference between IHAH3 sizes of male heterosexuals vs. male homosexuals who had contracted AIDS (0.108 mm3 and 0.096 mm3, respectively). The study also found that there were no differences in the number of neurons in the INAH3 based upon sexual orientation, although researchers found significant differences between males and females, as in other studies.5 It was obvious from this study that LeVay’s study was fatally flawed due to the AIDS complication, and that there were no differences in the INAH3 based upon sexual orientation.

The role of the hypothalamus in sexual orientation was further studied by Swaab, et al. Other researchers had hypothesized that differentiation of the hypothalamus occurred before birth. However, Swaab’s study showed that the sexually dimorphic nucleus (SDN) of more than 100 subjects decreased in volume and cell number in the females only 2-4 years postnatal. This finding complicated the findings of the brain studies, since not only chemical and hormonal factors, but also social factors, might have influenced this process.6

A study by Allen and Gorski examined the anterior commissure of the brain, finding that females and homosexual males exhibited a larger size than heterosexual males.7 However, later studies using larger sample sizes found no such differences.8

Complicating the issue of brain differences between homosexuals and heterosexuals is the problem that sexual experiences themselves can affect brain structure.9 So, the question will always be whether homosexual practice changes the brain or whether the brain results in homosexual practice.

Since sexual differentiation occurs within the womb, as a result of hormonal influences, it has been hypothesized that homosexuality may result from a differential hormone balance in the wombs of those who eventually exhibit a homosexual orientation. Since hormonal levels within the womb are not available, proxies for hormonal influences have been used to examine the question of how hormonal influences might impact sexual orientation. These proxies include differences in skeletal size and shape, including the ratio of the long bones of the arms and legs relative to arm span or stature and the hand bones of adults (the ratio of the length of the various phalanges).

Studies have shown that ratios of digit length are predictors of several hormones, including testosterone, luteinizing hormone and estrogen.10 In women, the index finger (2D, second digit) is almost the same length as the fourth digit (4D). However, in men, the index finger is usually shorter than the fourth. It has been shown that this greater 2D:4D ratio in females is established in two-year-olds. It has been hypothesized that the sex difference in the 2D:4D ratio reflects the prenatal influence of androgen on males. A study by Williams, et al. showed that the 2D:4D ratio of homosexual men was not significantly different from that of heterosexual men for either hand.11 However, homosexual women displayed significantly smaller 2D:4D ratios compared with heterosexual women (see figure to right). It has been hypothesized that women exposed to more androgens in the womb tend to express a homosexual orientation. However, since these hormone levels were never measured, one is left with the proxy of finger lengths as a substitute. Studies have found that the more older brothers a boy has, the more likely he is to develop a homosexual orientation.12 This study also found that homosexual men had a greater than expected proportion of brothers among their older siblings (229 brothers: 163 sisters) compared with the general population (106 males: 100 females). Males who had two or more older brothers were found to have lower 2D:4D ratios,11 suggesting that they had experienced increased androgens in the womb. Why increased androgens would predispose both males and females to be homosexual was not explained in the study.

Another study examined the length of long bones in the arms, legs and hands. Both homosexual males and heterosexual females had less long bone growth in the arms, legs and hands, than heterosexual males or homosexual females.13 Accordingly, the researchers hypothesized that male homosexuals had less androgen exposure during development than male heterosexuals, while female homosexuals had greater steroid exposure during development than their heterosexual counterparts. Of course, with regard to male homosexuality, this study directly contradicted the presumed results of the Williams study above, which “showed” that males with multiple older brothers (who tended to be homosexual) experienced increased androgen exposure.

A study of one homosexual vs. two heterosexual male triplets found that the homosexual triplets scored more on the female side of the Masculinity-Femininity scale of the Minnesota Multiphasic Personality Inventory,14 suggesting a possible hormonal influence (decreased androgens) involved in male homosexual orientation.

All of the studies reporting possible hormonal influence on homosexuality suffer from the lack of any real evidence that hormones actually play any role in sexual orientation. The fact that contradictory studies report increased11,15 vs. decreased13-14 androgens as a basis for homosexuality doesn’t provoke confidence that the proxies are really true. Obviously, a study that documented real hormone levels, as opposed to proxies, would probably provide more definitive data.

Studies involving a rare hormonal imbalance, congenital adrenal hyperplasia (CAH), caused by defective 21-hydroxylase enzyme, suggest that hormonal abnormalities can influence sexual orientation. CAH results in increased production of male hormones during development. In males, increased androgens has little effect. However, female fetuses that develop in this environment develop ambiguous external genitalia, which complicates subsequent development. In utero treatment with dexamethasone reduces the androgen imbalance, resulting in an individual who is genetically and phenotypically female. However, dexamethasone treatment also results in reduced homosexual orientation among treated females,16 suggesting that some homosexuality may result from hormonal influences during development. Homosexual rights groups have suggested that dexamethasone treatment not be given, because it reduces homosexual orientation in females affected by CAH.

The observation that familial factors influence the prevalence of homosexuality led to a the initiation of number of twin studies, which are a proxy for the presence of possible genetic factors. Most of these early studies suffered from methodological flaws. Kallmann sampled subjects from correctional and psychiatric institutionsnot exactly representative “normal” populations.17 Bailey et al. published a number of studies in the early 1990’s, examining familial factors involved in both male and female homosexuality. These studies suffered from the manner in which subjects were recruited, since the investigators advertised in openly gay publications, resulting in skewed populations.18 Later studies by the same group did not suffer from this selection bias, and found the heritability of homosexuality in Australia was up to 50 and 60% in females but only 30% in males.19

A study by Kendler et al. in 2000 examined 1,588 twins selected by a random survey of 50,000 households in the United States.20 The study found 3% of the population consisted of non-heterosexuals (homosexuals and bisexuals) and a genetic concordance rate of 32%, somewhat lower than than found in the Australian studies. The study lost statistical significance when twins were broken down into male and female pairs, because of the low rate (3%) of non-heterosexuals in the general U.S. population.

A Finnish twin study reported the “potential for homosexual response,” not just overt homosexual behavior, as having a genetic component.21

On a twist on homosexual twin studies, an Australian research group examined the question of whether homophobia was the result of nature or nurture.22 Surprisingly, both familial/environmental and genetic factors seemed to play a role as to whether or not a person was homophobic. Even more surprising, a separate research group in the U.S. confirmed these results (also adding that attitudes towards abortion were also partly genetic).23 Now, even homophobes can claim that they were born that way!

Twin studies suffer from the problem of trying to distinguish between environmental and genetic factors, since twins tend to live within the same family unit. A study examining the effect of birth order on homosexual preference concluded, “The lack of relationship between the strength of the effect and degree of homosexual feelings in the men and women suggests the influence of birth order on homosexual feelings was not due to a biological, but a social process in the subjects studied.”12 So, although the twin studies suggest a possible genetic component for homosexual orientation, the results are certainly not definitive.

An examination of family pedigrees revealed that gay men had more homosexual male relatives through maternal than through paternal lineages, suggesting a linkage to the X chromosome. Dean Hamer24 found such an association at region Xq28. If male sexual orientation was influenced by a gene on Xq28, then gay brothers should share more than 50% of their alleles at this region, whereas their heterosexual brothers should share less than 50% of their alleles. In the absence of such an association, then both types of brothers should display 50% allele sharing. An analysis of 40 pairs of gay brothers and found that they shared 82% of their alleles in the Xq28 region, which was much greater than the 50% allele sharing that would be expected by chance.25 However, a follow-up study by the same research group, using 32 pairs of gay brothers and found only 67% allele sharing, which was much closer to the 50% expected by chance.26 Attempts by Rice et al. to repeat the Hamer study resulted in only 46% allele sharing, insignificantly different from chance, contradicting the Hamer results.27 At the same time, an unpublished study by Alan Sanders (University of Chicago) corroborated the Rice results.28 Ultimately, no gene or gene product from the Xq28 region was ever identified that affected sexual orientation. When Jonathan Marks (an evolutionary biologist) asked Hamer what percentage of homosexuality he thought his results explained, his answer was that he thought it explained 5% of male homosexuality. Marks’ response was, “There is no science other than behavioral genetics in which you can leave 97.5% of a phenomenon unexplained and get headlines.”29

A study of 13,000 New Zealand adults (age 16+) examined sexual orientation as a function of childhood history.30 The study found a 3-fold higher prevalence of childhood abuse for those who subsequently engaged in same sex sexual activity. However, childhood abuse was not a major factor in homosexuality, since only 15% of homosexuals had experienced abuse as children (compared with 5% among heterosexuals).30 So, it would appear from this population that only a small percentage of homosexuality (~10%) might be explained by early childhood abusive experiences.

If homosexual orientation were completely genetic, one would expect that it would not change over the course of one’s life. For females, sexual preference does seem to change over time. A 5-year study of lesbians found that over a quarter of these women relinquished their lesbian/bisexual identities during this period: half reclaimed heterosexual identities and half gave up all identity labels.31 In a survey of young minority women (16-23 years of age), half of the participants changed their sexual identities more than once during the two-year survey period.32 In another study of subjects who were recruited from organizations that serve lesbian/gay/bisexual youths (ages 14 to 21 years) in New York City, the percentage that changed from a lesbian/gay/bisexual orientation to a heterosexual orientation was 5% over the period of just 12 months (the length of the survey).33 Other studies have confirmed that sexual orientation is not fixed in all individuals, but can change over time, especially in women.34 A recent example of an orientation change occurred with The Advocate’s “Person of the Year” for 2005. Kerry Pacer was the youngest gay advocate, chosen for her initiation of a “gay-straight alliance” at White County High School in Cleveland, Georgia. However, four years later, she is raising her one year old daughter, along with the baby’s father.35 Another former lesbian, British comedienne Jackie Clune, spent 12 years in lesbian relationships before marrying a man and producing 4 children.36 Michael Glatze came out at age 20 and went on to be a leader in the homosexual rights movement. At age 30, he came out in the opposite direction, saying, “In my experience, “coming out” from under the influence of the homosexual mindset was the most liberating, beautiful and astonishing thing I’ve ever experienced in my entire life.”37 A 2011 study of Christian gays who wanted to change their sexual orientation found that 23% of the subjects reported a successful “conversion” to heterosexual orientation and functioning, while an additional 30% reported stable behavioral chastity with substantive dis-identification with homosexual orientation.38 However, 20% of the subjects reported giving up on the process and fully embraced a gay identity, while another 27% fell in between the two extremes.38 Obviously, for at least some individuals, being gay or straight is something they can choose.

The question of nature vs. nurture can also be seen by examining children of homosexual vs. heterosexual parents. If homosexuality were purely biological, one would expect that parenting would not influence it. Paul Cameron published a study in 2006 that claimed that the children of homosexual parents expressed a homosexual orientation much more frequently than the general population.39 Although claims of bias were made against the study, another study by Walter Schuum in 2010 confirmed Cameron’s results by statistically examining the results of 10 other studies that addressed the question.40 In total, 262 children raised by homosexual parents were included in the analysis. The results showed that 16-57% of such children adopted a homosexual lifestyle. The results were even more striking in daughters of lesbian mothers, 33% to 57% of whom became lesbians themselves. Since homosexuals makeup only ~5% of the population, it is clear that parenting does influence sexual orientation.

It always amazes me when people say that they were born gay. Looking back on my own experience, I would never say that I was “born straight.” I really didn’t have any interest in females until about the seventh grade. Before that time, they weren’t really interesting, since they weren’t interested in sports or riding bikes or anything else I liked to do.

I am not a huge fan of Neo Darwinian evolution. Nevertheless, there is some clear evidence that natural selection (and sexual selection) does act upon populations and has acted on our own species to produce racial differences.41 Natural selection postulates that those genetic mutations that favor survival and reproduction will be selected, whereas those that compromise survival and reproduction will be eliminated. Obviously, a gene or series of genes that produce non-reproducing individuals (i.e., those who express pure homosexual behavior) will be rapidly eliminated from any population. So, it would be expected that any “gay gene” would be efficiently removed from a population. However, it is possible that a gene favoring male homosexuality could “hide” within the human genome if it were located on the X-chromosome, where it could be carried by reproducing females, and not be subject to negative selection by non-reproducing males. In order to survive, the gene(s) would be expected to be associated with higher reproductive capacity in women who carry it (compensating for the generation of non-reproducing males). I can’t imagine a genetic scenario in which female homosexuality would ever persist within a population.

Within the last decade, genetic analysis of heritable traits has taken a huge step forward with the advent of DNA microarray technology. Using this technology, it is possible to scan large lengths of the human genome (even an entire genome wide scanGWAS) for numerous individuals, at quite reasonable costs. This DNA microarray technology has led to the discovery of genes that are associated with complex diseases, such as Crohn’s Disease, which is the topic of my research. If homosexuality truly has a genetic component, DNA microarray studies would not only definitively prove the point, but would identify specific gene(s) or loci that might be associated with those who express a homosexual orientation. The first attempt to do genome wide scans on homosexual males was done by Mustanski et al. in 2005.42 The results suggested possible linkage near microsatellite D7S798 on chromosome 7q36. However, an attempt to repeat the finding (along with ~6000 well-defined SNPs spread comparatively evenly across the human genome) failed to find any significant SNPs.43 However, a third study using Chinese subjects found a weak association at the SHH rs9333613 polymorphism of 7q36.44 A more general study, examining mate choice among different populations, found no genetic link, prompting the investigators to speculate that such choices were “culturally driven.”45 The largest genome wide scan was conducted by 23andMe. 7887 unrelated men and 5570 unrelated women of European ancestry were analyzed by GWAS. Although unpublished, the data was presented at the American Society of Human Genetics annual meeting in San Francisco, showing that there were no loci associated with sexual orientation, including Xq28 on the X chromosome.46 So, the preliminary studies on possible genetic causes of homosexual orientation tends to rule out any dramatic genetic component to sexual orientation.

Why are people gay? The question of how homosexual orientation originates has been the subject of much press, with the general impression being promoted that homosexuality is largely a matter of genes, rather than environmental factors. However, if one examines the scientific literature, one finds that it’s not quite as clear as the news bytes would suggest. The early studies that reported differences in the brains of homosexuals were complicated by HIV infection and were not substantiated by larger, better controlled studies. Numerous studies reported that possible hormonal differences affected homosexual orientation. However, these studies were often directly contradictory, and never actually measured any hormone levels, but just used proxies for hormonal influences, without direct evidence that the proxies were actually indicative of true hormone levels or imbalances. Twin studies showed that there likely are genetic influences for homosexuality, although similar studies have shown some genetic influences for homophobia and even opposition to abortion. Early childhood abuse has been associated with homosexuality, but, at most, only explains about 10% of those who express a homosexual orientation. The fact that sexual orientation is not constant for many individuals, but can change over time suggests that at least part of sexual orientation is actually sexual preference. Attempts to find a “gay gene” have never identified any gene or gene product that is actually associated with homosexual orientation, with studies failing to confirm early suggestions of linkage of homosexuality to region Xq28 on the X chromosome. The question of genetic influences on sexual orientation has been recently examined using DNA microarray technology, although, the results have largely failed to pinpoint any specific genes as a factor in sexual orientation.

La Gentica y la Homosexualidad: Nace la gente, homosexual?

http://www.godandscience.org/evolution/genetics_of_homosexuality.html Last updated November 25, 2013

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Are People Born Gay? Genetics and Homosexuality

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Researchers create lab-grown brain using human skin cells …

Published August 19, 2015

This image of the lab-grown brain is labeled to show identifiable structures: the cerebral hemisphere, the optic stalk and the cephalic flexure, a bend in the mid-brain region, all characteristic of the human fetal brain.(The Ohio State University)

Researchers at The Ohio State University were able to create a nearly complete human brain that matches the brain maturity of a 5-week-old fetus by using adult human skin cells.

The brain organoid is about the size of a pencil eraser and has an identifiable structure containing 99 percent of the genes present in the human fetal brain, according to a news release. Scientists say its the most complete human brain model yet developed.

It not only looks like the developing brain, its diverse cell types express nearly all genes like a brain, Rene Anand, a professor of biological chemistry and pharmacology at Ohio State, said in a news release. Weve struggled for a long time trying to solve complex brain disease problems that cause tremendous pain and suffering. The power of this brain model bodes very well for human health because it gives us better and more relevant options to test and develop therapeutics other than rodents.

Anand, who began his quest four years ago, studies the association between nicotinic receptors and central nervous system disorders. Hes hopeful that the lab-grown brain will provide ethical and more rapid and accurate testing of experimental drugs before the clinical trial stage.

In central nervous system diseases, this will enable studies of either underlying genetic susceptibility or purely environmental influences, or a combination, Anand said in the news release. Genomic science infers there are up to 600 genes that give rise to autism, but we are stuck there. Mathematical correlations and statistical methods are insufficient to in themselves identify causation. You need an experimental system you need a human brain.

Anand and his team built the model system in 15 weeks, using techniques to convert adult skin cells into pluripotent cells, which are immature cells that can be programmed to become any tissue in the body. They worked to differentiate pluripotent stem cells into cells that are designed to become neural tissue, according to the news release.

While the model lacks a vascular system, it does contain a spinal cord, all major regions of the brain, multiple cell types, signaling circuitry and a retina, according to the news release.

Anand reported on his research at the 2015 Military Health System Research Symposium.

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Researchers create lab-grown brain using human skin cells …

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ETHICAL Stem Cells Grow Human Brain | National Review Online

This is an achievement: Scientists have used skin cells to build a rudimentary human brain. (These were induced pluripotent stem cells.) From The Guardian story:

Though not conscious the miniature brain, which resembles that of a five-week-old foetus, could potentially be useful for scientists who want to study the progression of developmental diseases. It could also be used to test drugs for conditions such as Alzheimers and Parkinsons, since the regions they affect are in place during an early stage of brain development.

The brain, which is about the size of a pencil eraser, is engineered from adult human skin cells and is the most complete human brain model yet developed, claimed Rene Anand of Ohio State University, Columbus, who presented the work today at the Military Health System Research Symposium in Fort Lauderdale, Florida.

May it be so.

Lets analyze what this breakthrough could portend:

1. No need for unethical human cloning to derive cells for use in research and drug testing.

2. No need for fetal farming for experimentation and organ transplants.

3. No need for Planned Parenthood dismemberments of fetuses killed in a less crunchy way in abortion.

Remember when embryonic stem cells were OUR ONLY HOPE?

And that those of us who said that particular meme wasnt true were anti science? Pshaw.

#applause

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ETHICAL Stem Cells Grow Human Brain | National Review Online

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Hypopituitarism Symptoms and Treatment | Hormone Health …

What is hypopituitarism?

Hypopituitarism (also called pituitary insufficiency) is a rare condition in which your pituitary gland doesnt make enough of certain hormones. Your body cant work properly when important glands, such as your thyroid gland and adrenal gland, dont get the hormones they need from your pituitary gland.

The pituitary gland is a pea-sized gland found at the base of your brain. It is called the master gland because it affects the action of many other important glands that produce their own hormones. The pituitary gland affects almost all parts of your body.

Hypopituitarism can develop very slowly, over several months or even over several years.

Hypopituitarism can be caused by

Sometimes, the cause is unknown.

Symptoms can include one or more of the following:

Your doctor will check your hormone levels with blood tests. You may have other tests, such as an MRI of your pituitary gland, to help find the cause of your hypopituitarism.

Treatment usually includes taking the hormones youre missing, sometimes for life. Your doctor also will teach you how to take extra cortisone (a hormone) when you are sick or under stress. If a tumor is causing your hypopituitarism, you might need surgery to remove it and/or possibly radiation treatment. If needed, you can take medicine for infertility.

You will need to get regular check-ups. Its wise to wear medical identification, such as a bracelet or pendant, which provides information about your condition in case of an emergency.

You can expect a normal life span, as long as you regularly take the medications recommended by your doctor.

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Hypopituitarism Symptoms and Treatment | Hormone Health …

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Stem cell and skin care. | Esthetics Association Florida

It is astonishing how the cosmetic industry uses medical discoveries and put these formulas into skin cream jars.

In 2009 the American company Voss laboratories was the first that introduced stem cell active ingredients into a cosmetic product. Due to the fact that the company didnt reveal their secret ingredients, it created a worldwide rumor that the company might be using human stem cells.

The world started to question if this would be ethical and safe.

Coming from the medical stand point: with human stem cells you can actually build and rebuild human organs but also carcinogenic cell. For that reason it created great concerns.

Now days many trendsetting companies producing stem cell creams and serums that dont use human stem cells

Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, liver, and the Skin ( basal layer and fat layer) . They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.

Adult stem cells can divide ( copy) or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerates the entire original organ.

Plant Stem Cells benefits human skin.

Stem cells from a rare red grape variety provide the basis for Israel based company On-Macabim latest skin care ingredient.

This variety is one of the few red grapes that have red flesh and juice the majority have red skin but white flesh and juice which is due to the high quantity of anthocyanins in the fruit.

The anthocyanins, also present in the flesh, leading to higher antioxidant levels overall.

The technology was developed last year and allows to extract stem cells from the plant which can then be formulated into a cosmetic ingredient to help protect the stem cells in human skin.

To harvest the stem cells the company first induces a wound in the plant which causes the surrounding cells to dedifferentiate (turn back into stem cells) and form a wound healing tissue called a callus.

Once the wound has healed these cells can differentiate again and build new tissue

According to On-macabim, these plant stem cells contain components and epigenetic factors that can protect human skin stem cells form UV radiation, inflammation, oxidative stress, neutralize free radicals and reverse the effects of photoaging.

Stem cells are found in the epidermal layer of the skin and are involved in skin growth and regeneration. If they are harmed by UV radiation,

their power to regenerate will be jeopardized.

Grape stem cells have the ability to promote healthy skin proliferation.

Grape Stem Cells Counteract Negative

Effects of UV Radiation on

Skin Stem Cells

In an in-vitro study, skin stem cells were treated with and without

the Grape Stem Cells.

Some were exposed to UVA+UVB-light; others were unexposed.

CFE was determined in each case.

Results confirmed that cells treated with the Grape Stem Cells increased

the CFE of the skin stem cells. A 58% decrease in CFE was observed

when skin stem cells were exposed to UV radiation (control).

However, the presence of the Grape Stem Cells counteracted the negative effect of UV radiation on the cells as the CFE remained at the same level when exposed to the UV radiation.

Therefore, the Grape Stem Cells protect skin stem cells against UV stress.

Benefits of the Grape Stem Cell products

Regenerative, repair and rejuvenating properties

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Stem cell and skin care. | Esthetics Association Florida

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Genetic Counseling Program – University of South Carolina …

The two year curriculum includes course work, clinical rotations, and a research-based thesis. Students are afforded a wide range of clinical opportunities in prenatal, pediatric and adult settings as well as specialty clinics through our clinical rotation network. International rotations are encouraged.

In 1991 and 1998, the Program received rare Commendation for Excellence citations from the South Carolina Commission of Higher Education. The Program was awarded American Board of Genetic Counseling accreditation in 2000 and reaccreditation in 2006. Most recently, the Accreditation Council for Genetic Counseling re-accredited the Program for the maximum eight year period, 2014-2022.

We invite you to explore the University of South Carolina Genetic Counseling Program through this site. Please also visit the National Society of Genetic Counselors, the American Board of Genetic Counseling websites to learn more about the profession. Check out the latest U.S. Department of Labor, Occupational Outlook Handbook, 2014-15 Edition projections for genetic counselors. The future is bright for genetic counselors!

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Genetic Counseling Program – University of South Carolina …

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About Life Extension: Anti-Aging, Health Supplements …

Established in 1980, the Life Extension Foundation is a nonprofit organization, whose long-range goal is to radically extend the healthy human lifespan by discovering scientific methods to control aging and eradicate disease. One of the largest organizations of its kind in the world, the Life Extension Foundation has always been at the forefront of discovering new scientific breakthroughs for use in developing novel disease prevention and treatment protocols to improve the quality and length of human life. Through its private funding of research programs aimed at identifying and developing new therapies to slow and even reverse the aging process, the Life Extension Foundation seeks to reduce, and ultimately eliminate, such age-related killers as heart disease, stroke, cancer and Alzheimers disease.

The Life Extension Foundation is a nonprofit organization whose goal is to extend the healthy human lifespan by discovering scientific methods to control aging and eradicate disease. continue >>

Since its inception in 1980, the Life Extension Foundation has continued its dedication to finding new scientific methods for eradicating old age, disease and death. continue >>

The Life Extension Foundation has been a world leader in uncovering pioneering approaches for preventing and treating diseases. continue >>

Long-time members are keenly aware of the scientific research that Life Extension Foundation funds to develop validated methods to slow and reverse the aging process. continue >>

Life Extension Foundation Federal Income Tax information is now available to download in Adobe PDF format. continue >>

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About Life Extension: Anti-Aging, Health Supplements …

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Change of the Heterogametic Sex From Male to Female in the …

M. Ogata*, H. Ohtani, T. Igarashi, Y. Hasegawa, Y. Ichikawa** and I. Miura,1 * Kanazawa Zoological Gardens, Kanagawa 236-0042, Japan Institute for Amphibian Biology, Graduate School of Science, Hiroshima University, Higashihiroshima 739-8526, Japan Preservation and Research Center, Kanagawa 241-0804, Japan RIKEN Genomic Sciences Center, Kanagawa 230-0045, Japan ** Department of Health Science, Faculty of Human Life and Environment Science, Hiroshima Prefectural Women’s University, Hiroshima 734-8558, Japan 1 Corresponding author: Institute for Amphibian Biology, Graduate School of Science, Hiroshima University, Kagamiyama 1-3-1, Higashihiroshima 739-8526, Japan. E-mail: imiura{at}hiroshima-u.ac.jp Abstract

Two different types of sex chromosomes, XX/XY and ZZ/ZW, exist in the Japanese frog Rana rugosa. They are separated in two local forms that share a common origin in hybridization between the other two forms (West Japan and Kanto) with male heterogametic sex determination and homomorphic sex chromosomes. In this study, to find out how the different types of sex chromosomes differentiated, particularly the evolutionary reason for the heterogametic sex change from male to female, we performed artificial crossings between the West Japan and Kanto forms and mitochondrial 12S rRNA gene sequence analysis. The crossing results showed male bias using mother frogs with West Japan cytoplasm and female bias using those with Kanto cytoplasm. The mitochondrial genes of ZZ/ZW and XX/XY forms, respectively, were similar in sequence to those of the West Japan and Kanto forms. These results suggest that in the primary ZZ/ZW form, the West Japan strain was maternal and thus male bias was caused by the introgression of the Kanto strain while in the primary XX/XY form and vice versa. We therefore hypothesize that sex ratio bias according to the maternal origin of the hybrid population was a trigger for the sex chromosome differentiation and the change of heterogametic sex.

THE most common mechanisms of genetic sex determination are male heterogamety as designated XX female/XY male and female heterogamety as designated ZZ male/ZW female (Bull 1983). In vertebrates, the heterogametic sex is male in mammals whereas in birds it is female. The other lower vertebrates such as reptiles, amphibians, and fishes have both types; the type may differ between species or any larger taxonomic groups. In Amphibia, female heterogamety is assumed to have evolved first, because the morphologically primitive species are most commonly heterogametic in females. Male heterogamety is thought to have appeared later at certain evolutionary branching points and quite rarely to have reversed back again to females (Hillis and Green 1990). Here, the following questions concerning sex determination arise: Why do the two types of heterogamety exist? How is the one type changed to the other? These are the basic questions to be solved to understand the genetic mechanisms of sex determination and their evolution.

Concerning the evolution of the sex-determining mechanisms, the Japanese frog Rana rugosa is quite unique (Figure 1). Two different types of sex chromosomes exist in two separate local forms (XX/XY and ZZ/ZW forms), which are assumed to share a common origin in hybridization between the other West Japan and Kanto forms, both having homomorphic sex chromosomes and male heterogametic sex determination (Miuraet al. 1998). Coexistence of the two types of sex-determining mechanisms in the same species is unusual and, apart from R. rugosa, has been reported only in the platy fish, housefly, and midge (Bellamy 1922; Gordon 1927, 1944; Thompson 1971; Macdonald 1978). Such a species would be an excellent animal model to study the evolution of one heterogametic mechanism to another. Because the ancestral-type forms of R. rugosa still remain and are separated geographically, it is possible to trace sequentially the evolution of male heterogamety to female heterogamety. In this study, to find out how the two different types of sex chromosomes differentiated in this species, we artificially performed crossings between the two ancestral-type forms of West Japan and Kanto according to the hybrid origin hypothesis, paying special attention to the sex ratio of the offspring. Also, we examined the maternal (cytoplasmic) origins of the XX/XY and ZZ/ZW forms by analyzing the mitochondrial 12S rRNA gene sequence. On the basis of the results, we infer the evolutionary reason why the two different types of sex chromosomes differentiated and discuss the evolution of male heterogamety to female heterogamety.

Frogs: The frogs used for crossing were prepared from the strains of Hiroshima (West Japan form) and Isehara (Kanto form) that had been reared through inbreeding at the Institute for Amphibian Biology (Higashihiroshima, Japan). Ovulation was accelerated by injection of pituitary gland solution prepared from R. nigromaculata (Ohtaniet al. 1997). The gynogenetic diploids ZZ and WW were produced according to the method of Ohtani et al. (1997). The localities from which the frogs used for mitochondrial gene analysis were collected are shown in Figure 1. One male and one female per population were used for the analysis.

The four geographic forms of R. rugosa in Japan. The West Japan and Kanto forms have a male heterogametic sex determination with homomorphic sex chromosomes. The other two forms with ZZ/ZW and XX/XY sex chromosomes are designated, respectively, ZZ/ZW and XX/XY forms. The sex chromosomes, together with the homologous no. 7 chromosomes of the West Japan and Kanto forms, are diagrammatically shown. The numbers on the map denote the localities from which the frogs were collected for mitochondrial gene analysis. 1, Takigawa city of Hokkaido; 2, Namioka-machi of Aomori Prefecture; 3, Niigata city of Niigata Prefecture; 4, Kanazawa city of Ishikawa Prefecture; 5, Isehara city of Kanagawa Prefecture; 6, Kamogawa city of Chiba Prefecture; 7, Fujieda city of Shizuoka Prefecture; 8, Hamakita city of Shizuoka Prefecture; 9, Hiroshima city of Hiroshima Prefecture; 10, Hakata-cho of Ehime Prefecture; 11, Kaimon-cho of Kagoshima Prefecture.

Mitochondrial 12S rRNA gene analysis: Mitochondrial DNA was isolated from blood or liver cells together with nuclear genomic DNA. The 409 bp of 12S rRNA was amplified using 20 m sense and antisense primers (Sumidaet al. 1998) in a 50-l reaction solution containing 5 l of 10 buffer, 4 l of 2.5 mm dNTP, 1 l of Taq polymerase (Takara, Berkeley, CA), and distilled water, 30 cycles at 95 for 1 min, 50 for 1 min, and 72 for 1 min. The products were purified with MicroSpin TMS-300HR columns (Pharmacia Biotech, Piscataway, NJ) and sequenced by PCR direct sequencing method with an ABI PRISM 310 genetic analyzer. To construct the gene tree, a distance matrix based on Kimura’s two-parameter method (Kimura 1980) was calculated and clustered by the neighbor-joining method (Saitou and Nei 1987) using PHYLIP version 3.572 software (Felsenstein 1996).

cDNA subtraction and RT-PCR: Total RNA was prepared from the gonads and mesonephroi of ZZ and WW tadpoles at day 20 after fertilization according to the manufacturer’s instruction [Promega (Madison, WI) SV total RNA isolation system]. cDNA was synthesized and subjected to subtraction between ZZ and WW tadpoles according to the manual of the CLONTECH (Palo Alto, CA) PCR-select cDNA subtraction kit. The cDNA sources of WW tadpoles subtracted with that of ZZ ones were ligated into PCR vector (Invitrogen, San Diego). Out of 64 clones picked up, 24 distinct clones were identified and 11 of them showed higher expression in female tadpoles than in male tadpoles at day 20. Out of the 11 clones, only 1 showed much higher expression in females and almost none in the ZZ males or in the tadpoles from the Hiroshima (West Japan) and Isehara (Kanto) forms at the same stage. It was designated W13.

Expression of W13 at day 19, 21, and 23 after fertilization was examined by reverse transcription polymerase chain reaction (RT-PCR). Total RNA was isolated and purified from the gonads plus mesonephroi of tadpoles at the days indicated above. First-strand cDNA was synthesized using 1 g of the total RNA as the template for 1 hr at 42 in a 20-l reaction solution containing 4 l of 5 buffer, 4 l of 2.5 mm dNTP, 2 l of 0.1 m dithiothreitol, 2 m of dT24 oligomer, 1 l of Superscript (BRL), and distilled water. One microliter of the cDNA solution was amplified in a 50-l reaction solution containing 5 l of 10 buffer, 0.3 l of Ex Taq (Takara), 4 l of 2.5 mm dNTP, and 1 l of 12.5 m each of W13 sense and antisense primers, 35 cycles at 94 for 40 sec, 62 for 40 sec, 72 for 50 sec, ending with 72 for 2 min. Amplification of the 304-bp EF1 fragment of R. rugosa was according to the method of Nakajima et al. (2000). ZZ male and ZW female tadpoles were sexed by polymerase chain reaction-restriction fragment length polymorphism of the sex-linked gene ADP/ATP translocase (Sakisakaet al. 2000).

PCR for genomic DNA: Amplification of a genomic DNA fragment of W13 was carried out using 0.5 g of ZZ or WW DNA under the same conditions as those for RT-PCR of total RNA.

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Change of the Heterogametic Sex From Male to Female in the …

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