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Kohane leads multiple collaborations at Harvard Medical School and its hospital affiliates in the use of genomics and computer science to study diseases (particularly cancer and autism) order imuran 50 mg with amex. He has developed several computer systems to allow multiple hospital systems to be used as "living laboratories" to study the genetic basis of disease while preserving patient privacy buy 50 mg imuran otc. Among these buy 50mg imuran free shipping, the i2b2 (Informatics for Integrating Biology and the Bedside) National Computing Center has been deployed at over 52 academic health centers internationally. Kohane has published over 180 papers in the medical literature and authored a widely used book on microarrays for Integrative Genomics. He has been elected to multiple honor societies including the American Society for Clinical Investigation, the American College of Medical Informatics, and the Institute of Medicine. He is also a practicing pediatrics endocrinologist and father of three energetic children. Manuel Llinás is an Assistant Professor of Molecular Biology and a member of the Lewis-Sigler Institute for Integrative Genomics at Princeton University. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease ͺ͹ Ph. Llinás’ laboratory studies the deadliest of the four human Plasmodium parasites, Plasmodium falciparum. His research combines tools from functional genomics, molecular biology, computational biology, biochemistry, and metabolomics to understand the fundamental molecular mechanisms underlying the development of this parasite. The focus is predominantly on the red blood cell stage of development, which is the stage in which all of the clinical manifestations of the malaria disease occur. His research has focused on two major areas: the role of transcriptional regulation in orchestrating parasite development, and an in-depth characterization of the malaria parasite’s unique metabolic network. These two approaches explore relatively virgin areas in the malaria field with the goal of identifying novel strategies for therapeutic intervention. He is also National Program Director for the Greenwall Faculty Scholars Program in Bioethics, a career development award for bioethics researchers. He is co-chair of the Standards Working Group of the California Institute of Regenerative Medicine, which recommends regulations for stem cell research funded by the state of California. He also serves on the Board of Directors of the Association for the Accreditation of Human Research Protection Programs. He has pioneered the field of genome cell biology by developing live-cell microscopy approaches to study the nuclear organization of the genome and gene expression in intact cells, and his laboratory aims to apply this knowledge to the development of novel diagnostic and therapeutic strategies for cancer and aging. Dr Misteli has received numerous awards for his work, and currently serves as Editor-in-Chief of The Journal of Cell Biology and of Current Opinion in Cell Biology. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 88 Sean J. Morrison, PhD, is the Director of the Children’s Research Institute and the Mary McDermott Cook Chair in Pediatric Genetics at the University of Texas Southwestern Medical Center as well as an Investigator of the Howard Hughes Medical Institute. The Morrison laboratory is investigating the mechanisms that regulate stem cell function in the nervous and hematopoietic systems and the ways in which these mechanisms are hijacked by cancer cells to enable neoplastic proliferation and metastasis. The Morrison laboratory is particularly interested in the mechanisms that regulate stem cell self-renewal, stem cell aging, and the role these mechanisms play in cancer. Parallel studies of these mechanisms in two tissues reveals the extent to which different types of stem cells and cancer cells depend upon similar mechanisms to regulate their function. The Morrison laboratory has discovered a number of critical mechanisms that distinguish stem cell self-renewal from the proliferation of restricted progenitors. They have shown that stem cell self-renewal is regulated by networks of proto-oncogenes and tumor suppressors and that the balance between proto-oncogenic and tumor suppressor signals changes with age. This likely explains why the mutation spectrum changes with age in cancer patients, as different mechanisms become competent to hyper-activate self-renewal pathways in patients at different ages. The Morrison laboratory has further shown that in some cancers many tumor cells are capable of driving disease growth and progression while other cancers are driven by minority subpopulations of cancer cells that adopt “stem cell” characteristics. These insights into the cellular and molecular mechanisms of self-renewal have suggested new approaches for promoting normal tissue regeneration and cancer treatment.

However buy generic imuran 50mg, no significant associations have been observed between Dietary Fiber intake and risk of prostate cancer (Andersson et al 50mg imuran with mastercard. Although interesting to note 50 mg imuran with visa, this literature is in its infancy and cannot be used to set a recommended intake level for Dietary Fiber. Dietary Fiber and Functional Fiber and Glucose Tolerance, Insulin Response, and Amelioration of Diabetes Epidemiological Studies Epidemiological evidence suggests that intake of certain fibers may delay glucose uptake and attenuate the insulin response, thus providing a protective effect against diabetes. Evidence for the protective effect of Dietary Fiber intake against type 2 diabetes comes from several prospective studies that have reported on the relationship between food intake and type 2 diabetes (Colditz et al. One study examined the relationship between specific dietary patterns and risk of type 2 diabetes in a cohort of 42,759 men, while controlling for major known risk factors (Salmerón et al. The results suggest that diets with a high glycemic load and low cereal fiber content are positively associated with risk of type 2 diabetes, indepen- dent of other currently known risk factors (Figure 7-1). In a second study, diet and risk of type 2 diabetes in a cohort of 65,173 women were evalu- ated (Salmerón et al. Of particular importance is that this combination resulted in a relative risk of 2. In theory, the hypothesis as to how Dietary Fiber may be protective against type 2 diabetes is that it attenuates the glucose response and decreases insulin concentrations. This theory is supported by results from the Zutphen Elderly Study, where a negative relationship was observed between Dietary Fiber intake and insulin concentrations (Feskens et al. Intervention Studies In some clinical intervention trials ranging from 2 to 17 weeks, con- sumption of Dietary Fiber was shown to decrease insulin requirements in type 2 diabetics (Anderson et al. In addition, resistant starch has not been shown to have an effect on glycemic index. This is in contrast to the differences in “slow release” versus “fast release” starches, which have differential effects on postprandial glycemic and insulinemic profiles (Golay et al. Viscous Dietary and Functional Fibers, such as are found in oat products, beans, isolated pectin, and isolated guar gum, have been found to produce significant reductions in glycemic response in 33 of 50 studies (66 per- cent) reviewed by Wolever and Jenkins (1993), which is in contrast to only 3 of 14 studies with nonviscous fiber (21 percent). Mechanistic data and hypotheses support this effect of viscous fibers as they delay gastric empty- ing and delay the absorption of glucose and other nutrients (Jenkins et al. However, a seeming anomaly is that the blood glucose response of foods is more closely related to their nonviscous fiber content than to their viscous fiber content (Wolever, 1995). It is not clear as to how significant the viscosity of fiber is to its contribution to the reduction in glycemic response in the overall observation of a lower inci- dence of type 2 diabetes with high fiber diets. Therefore, viscosity should not be considered the most important attribute of fiber with respect to this endpoint. Further dis- cussion is provided in the later section, “Findings by Life Stage and Gender Group. This is an important consideration since obesity is such a prevalent problem and contributes to the risk of many diseases. Support for the concept that fiber consumption helps with weight maintenance is provided by studies showing that daily Dietary Fiber intake is lower for obese men (20. Intervention Studies Several intervention studies suggest that diets high in fiber may assist in weight loss (Birketvedt et al. For example, Birketvedt and coworkers (2000) conducted a study in which 53 moder- ately overweight females consumed a reduced energy diet (1,200 kcal/d) with or without a fiber supplement, which was 6 g/d for 8 weeks and then 4 g/d thereafter. High fiber diets are charac- terized by a very low energy density compared to diets high in fat, and a greater volume must be consumed in order to reach a certain energy level (Duncan et al. The issue of whether fiber has implications in the modulation of appetite has been reviewed (Blundell and Burley, 1987; Levine and Billington, 1994). Consumption of viscous fibers delays gastric emptying (Roberfroid, 1993), which in turn can cause an extended feeling of fullness (Bergmann et al. Some investigators suggest that the delayed absorption of nutrients is associated with an extended feeling of satiety and delayed return of appetite (Grossman, 1986; Holt et al. A number of studies investigated the effect of consumption of a high fiber meal and food intake at a later eating occasion. For example, eating a breakfast supplemented with 29 g of sugar beet fiber resulted in 14 per- cent less energy consumption at the subsequent lunch (Burley et al.

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The feeding of diets con- taining up to 10% monosodium glutamate to beagle dogs for 2 years order imuran 50mg mastercard. The effects of different levels of energy intake on protein metabolism and of different levels of protein intake on energy metabolism: A statistical evaluation from the published literature cheap 50mg imuran amex. Hyper- methioninemia: A metabolic disorder associated with cirrhosis purchase imuran 50 mg visa, islet cell hyperplasia, and renal tubular degeneration. Acute effects of dietary protein on food intake, tissue amino acids, and brain serotonin. Total body protein, collagen and non- collagen protein in infantile protein malnutrition. Histidine-induced bizarre behaviour in rats: The possible involvement of central cholinergic system. Treatment of rheumatoid arthritis with L-histidine: A randomized, placebo-controlled, double-blind trial. Toxicity and tolerance to mono- sodium glutamate studied by a conditioned avoidance test. Monosodium glutamate administration to the newborn reduces reproductive ability in female and male mice. Somatic, behavioral, and reproductive dis- turbances in mice following neonatal administration of sodium L-aspartate. Developmental sequel from early nutritional deficiencies: Conclu- sive and probability judgements. Measurement of oxygen consumption and locomotor activity in monosodium glutamate-induced obesity. Effects of glutamic acid on maze learning and recovery from electroconvulsive shocks in albino rats. Behavioral changes in adult rats treated with mono- sodium glutamate in the neonatal stage. Biochemical changes of brain and liver in neonatal offspring of rats fed monosodium-L-glutamate. A tracer investigation of obligatory oxida- tive amino acids losses in healthy, young adults. Milk protein intake in the term infant I: Meta- bolic responses and effects on growth. Statistical analysis of nitrogen balance data with refer- ence to the lysine requirement in adults. Conventional (“long-term”) nitrogen balance studies for protein quality evaluation in adults: Rationale and limita- tions. Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on nitrogen loss in traumatic states? Immunologic effects of arginine supplementation in tumor-bearing and non-tumor-bearing hosts. Nitrogen balances of women maintained on various levels of methionine and cystine. Aspartame administration to the infant monkey: Hypothalamic morphology and plasma amino acid levels. Use of the ileal conduit as a model for studying human small intestinal mucus glycoprotein secretion. Tyrosine requirement of healthy men receiving a fixed phenylalanine intake determined by using indi- cator amino acid oxidation. Enteral glutamine supplementation for the very low birthweight infant: Plasma amino acid concentrations. Dietary arginine supplementation does not enhance lymphocyte proliferation or interleukin-2 production in young and aged rats. Effect of oral alanine loads on the serum triglycerides of oral contraceptive users and normal subjects. Maximal rates of excretion and synthesis of urea in normal and cirrhotic sub- jects. Phenylalanine and aspartame fail to alter feeding behavior, mood and arousal in men.

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It might not even be deemed to merit therapeutic intervention order 50 mg imuran, unless the woman desired to get pregnant cheap imuran 50mg on-line. In Hippocratic and Galenic thought buy cheap imuran 50 mg online, ab- sence of menstruation—or rather, retention of the menses, for the waste ma- terial was almost always thought to be collecting whether it issued from the body or not—was cause for grave concern, for it meant that one of the major purgative systems of the female body was inoperative. It is for this reason that the largest percentage of prescriptions for women’s diseases in most early medi- eval medical texts (which reflected the Hippocratic tradition only) were aids for provoking the menses. Between the ages of fourteen (‘‘or a little earlier or a little later, depending on how much heat abounds in her’’)84 and thirty-five to sixty Introduction  (upped to sixty-five in the standardized ensemble), a woman should be men- struating regularly if she is to remain healthy. In overall length, the four sections on menstruation (¶¶– on the general physiology and pathology of menstruation, ¶¶– on menstrual retention, ¶¶– on paucity of the menses, and ¶¶– on excess men- struation) constitute more than one-third of the text of the original Conditions of Women. Throughout these long sections on menstruation, the author is adhering closely to his sources: the Viaticum for overall theory and basic therapeutics and the Book on Womanly Matters for supplemental recipes. In ¶, the author tells us that the menses are commonly called ‘‘the flowers’’ because just as trees without their flowers will not bear fruit, so, too, women without their ‘‘flowers’’ will be deprived of off- spring. This reference to ‘‘women’s flowers’’ has no precedent in the Viaticum (the source for the rest of this general discussion on the nature of the menses) nor in any earlier Latin gynecological texts, which refer to the menses solely as menstrua (literally, ‘‘the monthlies’’). Theterm‘‘flower’’(flos) had been used systematically throughout the Trea- tise on the Diseases of Women (the ‘‘rough draft’’ of Conditions of Women, which had employed frequent colloquialisms), and at least fourteen of the twenty- two different vernacular translations of the Trotula (including Dutch, English, French, German, Hebrew, and Italian) employ the equivalent of ‘‘flowers’’ when translating the Latin menses. But just as a tree which lacks viridity is said to be unfruitful, so, too, the woman who does not have the viridity of her flowering at the proper age is called infertile. Menstrual blood is like the flower: it must emerge before the fruit—the baby—can be born. In the Hippocratic writings themselves, although there is discussion of suffocation caused by the womb, the actual term ‘‘uterine suffocation’’ (in Greek, hysterike pnix) is never used. It was only out of loose elements of Hip- pocratic disease concepts (which were always very vaguely defined and iden- tified) that the etiological entity of uterine suffocation was created, probably sometime before the second century . Such movement was thought to be caused by retention of the menses, excessive fatigue, lack of food, lack of (hetero)sexual activity, and dryness or lightness of the womb (particu- larly in older women). When these conditions obtain, the womb ‘‘hits the liver and they go together and strike against the abdomen—for the womb rushes and goes upward towards the moisture. When the womb hits the liver, it produces sudden suffocation as it occupies the breathing passage around the belly. For example, when the womb strikes the liver or abdomen, ‘‘the woman turns up the whites of her eyes and becomes chilled; some women are livid. If the womb lingers near the liver and the abdomen, the woman dies of the suffocation. Multiple means of treat- ment were employed, including the recommendation that, when the womb moves to the hypochondria (the upper abdomen or perhaps the diaphragm), young widows or virgins be urged to marry (and preferably become preg- nant). This was premised, apparently,on the belief that thewombwas capable of sensing odors. Fetid odors (such as pitch, burnt hair, or castoreum) were applied to the nos- trils to repel the womb from the higher places to which it had strayed, while sweet-smelling substances were applied to the genitalia to coax the uterus back into its proper position. Not all the symptoms were listed every time uterine movement was men- tioned by the Hippocratic writers, nor did all cases of pnix involve uterine movement. Whenanattack occurs, sufferers from the disease collapse, show aphonia, labored breathing, a seizure of the senses, clenching of the teeth, stridor, convulsive contraction of the extremities (but sometimes only weakness), upper abdominal distention, retraction of the uterus, swelling of the thorax, bulging of the network of ves- sels of the face. The whole body is cool, covered with perspiration, the pulse stops or is very small. Critical to his views, and to all contemporary criticisms of the ‘‘wandering womb’’ (in- cluding Galen’s, as we shall see in a moment) were the anatomical discover- ies made at Alexandria in the third century . The womb ‘‘does not issue forth like a wild animal from the lair’’ but is instead ‘‘drawn together because of the stricture caused by the inflammation’’ of these uterine ligaments. Soranus also adamantly rejected the Hippocratic odoriferous therapy, or at least the part of it that employed foul- smelling substances. Yet for all his modifi- cations, Soranus never questioned the disease category itself. On the contrary, his thorough engagement with it was to help render it canonical in almost all later gynecological texts up through the Renaissance.

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