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Biologic origin: the importance of genetics as a determinant of obesity is indicated by the observation that children who are adopted usually show a body weight that correlates with their biologic rather than adoptive parents womens health education buy evista 60 mg line. For example women's health center colorado buy evista 60mg on-line, mutations in the gene for the adipocyte hormone leptin or its receptor produce hyperphagia (increased appetite for and consumption of food) and massive obesity (Figure 26 menstrual period age 8 purchase on line evista. Most obese humans have elevated leptin levels but appear to be resistant to the appetite-regulating effects of this hormone pregnancy low blood pressure order evista online now. Environmental and behavioral contributions the epidemic of obesity occurring over the last decade cannot be simply explained by changes in genetic factors, which are stable on this short time scale. However, the mechanism underlying this imbalance involves a complex interaction of biochemical, neurologic, environmental, and psychologic factors. Patient at age 9 years after 48 months of therapy with subcutaneous injection of recombinant leptin. Leptin: Leptin is an adipocyte peptide hormone that is secreted in proportion to the size of fat stores. When we consume fewer calories than we need, body fat declines, and leptin production from the fat cell decreases. The body adapts by minimizing energy utilization (decreasing activity) and increasing appetite. Unfortunately, in many individuals, the leptin system may be better at preventing weight loss than preventing weight gain. Although a meal or overeating increases leptin and this should, in theory, also dampen appetite (an anorexigenic effect) and prevent overconsumption of calories, other cues that stimulate appetite can apparently overcome the leptin system in many individuals. Short-term signals Short-term signals from the gastrointestinal tract control hunger and satiety, which affect the size and number of meals over a time course of minutes to hours. Thus, there are many and complex regulatory loops that control the size and number of meals in relationship to the status of body fat stores. These metabolic abnormalities reflect molecular signals originating from the increased mass of adipocytes. Metabolic syndrome Abdominal obesity is associated with a cluster of metabolic abnormalities that is referred to as the metabolic syndrome and includes glucose intolerance (hyperglycemia below that classified as diabetes; see p. The metabolic syndrome is also associated with a state of low-grade, chronic, systemic inflammation that contributes to the pathogenesis of insulin resistance and atherosclerosis. Additionally, low levels of the adipocyte hormone adiponectin that normally dampens inflammation and sensitizes tissues, especially the liver, to insulin, may contribute to the metabolic syndrome and, therefore, the risk of T2D and heart disease. The relationship between obesity and associated morbidities is stronger among individuals younger than age 55 years. To achieve weight reduction, the obese patient must decrease energy intake or increase energy expenditure, although decreasing energy intake is thought to contribute more to inducing weight loss. Typically, a prescription for weight reduction combines dietary change; increased physical activity; and behavioral modification, which can include nutritional education and meal planning, recording and monitoring food intake through food diaries, modifying factors that lead to overeating, and relearning cues to satiety. Once weight loss is achieved, weight maintenance is a separate process that requires vigilance because the majority of patients regain weight after they stop their weight loss efforts. Although adding exercise to a hypocaloric regimen may not produce a greater weight loss initially, exercise is a key component of programs directed at maintaining weight loss. Studies show that individuals who maintain their exercise program regain less weight after their initial weight loss. Caloric restriction Dieting is the most commonly practiced approach to weight control. Because 1 pound of adipose tissue corresponds to approximately 3,500 kcal, one can estimate the effect that caloric restriction will have on the amount of adipose tissue. Nonetheless, it is important to recognize that, although few individuals will reach their ideal weight with treatment, weight losses of 10% of body weight over a 6-month period often reduce blood pressure and lipid levels and enhance control of T2D. The health benefits of even relatively small weight losses should, therefore, be emphasized to the patient. Pharmacologic treatment Several weight-loss medications are currently approved by the U. Three approved for longterm use are: 1) orlistat (decreases absorption of dietary fat), 2) lorcaserin (promotes satiety), and 3) a combination of phentermine (suppresses appetite) and extendedrelease topiramate (controls seizures).
Causes of these gastrointestinal infections include Shigella women's health university discount 60mg evista overnight delivery, Salmonella womens health half marathon training effective 60mg evista, Yersinia breast cancer month 2014 trusted evista 60mg, and Campylobacter women's health center bethlehem pa evista 60 mg without a prescription. Serologic tests for rickettsia include complement fixation tests and the Weil-Felix agglutination reaction. The basis for the latter test is the fact that the sera of infected patients can agglutinate strains of Proteus vulgaris. The vector in the Rocky Mountains is the wood tick (Dermacentor andersoni), while in the southeast it is the dog tick (Dermacentor variabilis) and in the south central United States it is the Lone Star tick. Intracellular bacilli form parallel rows in an end-to-end arrangement ("flotilla at anchor facing the wind"). Histologically, this disease is characterized by the formation of stellate microabscesses with necrotizing granulomas. Numerous bacilli in packets within histiocytes (lepra cells) are also found in the lesions of lepromatous leprosy. Polyclonal hypergammaglobulinemia often occurs in lepromatous leprosy, in which patients do not have the adequate cellular immune response of the tuberculoid form. Large amounts of antilepra antibody occur in the lepromatous form with frequent formation of antigen-antibody complexes and resultant disorders such as erythema nodosum. A "clear" zone between infiltrate and overlying epidermis is characteristic of lepromatous leprosy, unlike the encroachment on basal epidermis of the tuberculoid infiltrate. Mycobacteriaceae are General Pathology Answers 151 slow-growing aerobic rods with cell walls rich in glycolipids, true waxes, and long-chain fatty acids called mycolic acids. The initial infection of primary tuberculosis, the Ghon complex, consists of a subpleural lesion near the fissure between the upper and lower lobes and enlarged caseous lymph nodes that drain the pulmonary lesion. Although primary pulmonary tuberculosis is usually asymptomatic, systemic and localizing symptoms can occur. These symptoms include malaise, anorexia, weight loss, fever, night sweats, cough, and hemoptysis. The pulmonary lesion of secondary tuberculosis is usually located in the apex of one or both lungs. Progressive pulmonary tuberculosis may result in cavitary fibrocaseous tuberculosis, miliary tuberculosis, or tuberculous bronchopneumonia. Miliary tuberculosis consists of multiple small yellow-white lesions scattered throughout the entire lung. These lesions are the result of erosion of a granulomatous lesion into a blood vessel with subsequent lympho-hematogenous dissemination. Acid-fast stains of sputum are followed with culture, not only to identify the species of mycobacterium but to determine the pattern of antibiotic sensitivity. This organism is almost ubiquitous in water and is spread by inhalation of contaminated airborne droplets. Infection results in a patchy bronchopneumonia, and microscopically the alveolar spaces are filled with an inflammatory exudate of neutrophils and macrophages. Organisms cannot be visualized by routine stains, so instead a Dieterle silver stain is used. They are separated into different classes (Runyon classes) based on several culture characteristics, such as pigment production, colony morphology, and rate of growth. Histologic sections in these immunosuppressed patients do not reveal granulomas because the cellular immune reactions of these patients are defective. It can cause superficial disease or skin and subcutaneous disease, and can be obtained from infected aquariums or swimming pools. Coccidioidomycosis is endemic in California, Arizona, New Mexico, and parts of Nevada, Utah, and Texas, where it resides in the arid soils and is contracted by direct inhalation of airborne dust. If inhaled, it produces a primary pulmonary infection that is usually benign and self-limiting in immunologically competent persons, often with several days of fever and upper respiratory flulike symptoms. However, certain ethnic groups, such as some blacks, Asians, and Filipinos, are at risk of developing a potentially lethal disseminated form of the disease that can involve the central nervous system. If the large, double-walled spherule containing numerous endospores can be demonstrated outside the lungs. Antibodies of high titers are detectable by means of complement fixation studies in patients undergoing spontaneous recovery.
This disaccharide is not a reserve material in prokaryotes women's health center king of prussia pa buy evista, but many bacteria can use trehalose as their sole carbon and energy source 42 menstrual cycle order genuine evista on-line. Some bacteria women's health clinic liverpool generic 60mg evista with visa, including Desulfovibrio halophilus and several purple sulfur and nonsulfur bacteria women's health center of grand rapids discount evista 60 mg on-line, synthesize trehalose under high osmotic pressure as a compatible solute, but this disaccharide is not regarded as a reserve material. This disaccharide is metabolized in three different ways depending on the organism. Trehalase hydrolyzes it to two molecules of glucose, while trehalose phosphorylase cleaves it to glucose and glucose-1-phosphate. In other organisms, trehalose is phosphorylated to trehalose-6-phosphate by the action of trehalose kinase before being cleaved to glucose-6phosphate and glucose by a hydrolase. On the other hand, only a few prokaryotes have the property of accumulating triacylglycerides as a reserve material, a property that is widespread in eukaryotes. Coenzyme A transferase activates acetoacetate to acetoacetyl-CoA consuming succinyl-CoA. Under nitrogen-limited conditions, a strain of Acinetobacter calcoaceticus accumulates up to 25% of the cell dry weight. Since acetoacetyl-CoA is an intermediate in degradation as well as in the synthesis of this reserve material, reactions involving this intermediate are tightly controlled to avoid a futile cycle which would waste a high energy bond in the form of succinyl-CoA. A strain of Vibrio furnissii isolated from a sewage works accumulated lipid material extracellularly to 1. Many cyanobacteria accumulate cyanophycin as a reserve material for carbon and nitrogen. Cyanophycin has a structure composed of polyaspartate, each monomer of which is linked with a molecule of arginine (Figure 13. This peptide is synthesized under phosphate- or sulfate-limited conditions with nitrogen and light in excess. When the synthesis of protein and nucleic acids is inhibited, cyanophycin production is activated. Its synthesis is not inhibited by tetracycline, showing that cyanophycin is synthesized through a non-ribosomal mechanism. When the nitrogen supply is limited, cyanophycin is degraded producing ammonia and carbon dioxide. In heterocystous cyanobacteria, the heterocysts have a higher enzyme activity for cyanophycin synthesis than the vegetative cells. When the nitrogen supply is limited, this peptide is also degraded as a nitrogen source. Cyanobacteria have a bluish-green colour under normal conditions but become yellowish-green under nitrogen-limited conditions because the blue coloured phycocyanin is degraded. It Figure 13:5 Structure of cyanophycin, a peptide reserve material in cyanobacteria. These granules are composed of polyphosphate and are known in prokaryotes and eukaryotes. Polyphosphate has functions other than just as a phosphate and energy reserve material. These include regulation of the concentration of cytoplasmic cations because of its strong anionic properties, stabilization of the cytoplasmic membrane and regulation of gene expression and enzyme activity. In Escherichia coli, polyphosphate is synthesized during the stringent response (Section 12. As in other cell differentiation processes, sporulation is the result of a complex regulated process which includes signal transduction from environmental and physiological factors. Sporulation is regulated through a series of phosphate transfers known as a phosphorelay.
An early success was Tracy menstruation with large fleshy clots generic evista 60mg online, a transgenic ewe Theme 2: New drugs and new therapies for genetic diseases Introduction to theme 2: proteins as drugs One of the earliest commercial applications of gene-manipulation techniques was the production in bacteria of human proteins with therapeutic applications menstruation visceral fat purchase 60mg evista. Not surprisingly 8 menopause myths buy genuine evista on-line, the first such products were recombinant versions of proteins already used as therapeutics: human growth hormone and insulin menstrual like cramping in late pregnancy evista 60 mg for sale. Prior to the advent of genetic engineering, human growth hormone was produced from pituitary glands removed from cadavers. As the methods for cloning genes became more and more sophisticated, an increasing number of lymphokines and cytokines were identified and significant amounts of them produced for the first time. A number of these were shown to have therapeutic potential and found their way into clinical practice (Table 14. System Milk Species Mouse Product Sheep b-lactoglobulin Human tissue-plasminogen activator Human urokinase Human growth hormone Human fibrinogen Human nerve growth factor Spider silk Human erythropoietin Human a1-antitrypsin Human tissue-plasminogen activator Human a1-antitrypsin Recombinant antibodies Human growth hormone Human growth hormone Reference Simons et al. Four females, including Tracy, and one male were found to have incorporated intact copies of the gene and all five developed normally. The transgenic female underwent two pregnancies and one out of five offspring was transgenic. The production of foreign proteins in secreted body fluids has the obvious advantage that transgenic animals can be used as a renewable source of the desirable molecule. In addition to milk, other production systems have been investigated, including serum (Massoud et al. In each case, an important consideration is whether the protein is stable and whether it folds and assembles correctly. The assembly of complex proteins comprising up to three separate polypeptides has been demonstrated in milk. There has already been some success with the latter, using both microinjection. The use of animals as bioreactors has been extensively reviewed (Clark 1998, Rudolph 1999, Wall 1999, Houdebine 2000). Plants as bioreactors Plants are a useful alternative to animals for recombinant-protein production because they are inexpensive to grow and scale-up from laboratory testing to commercial production is easy. Therefore, there is much interest in using plants as production systems for the synthesis of recombinant proteins and other speciality chemicals. There is some concern that therapeutic molecules produced in animal expression systems could be contaminated with small quantities of endogenous viruses or prions, a risk factor that is absent from plants. Furthermore, plants carry out very similar post-translational modification reactions to animal cells, with only minor differences in glycosylation patterns (CabanesMacheteau et al. Thus plants are quite suitable for the production of recombinant human proteins for therapeutic use. A selection of therapeutic proteins that have been expressed in plants is listed in Table 14. The first such report was the expression of human growth hormone, as a fusion with the Agrobacterium nopaline synthase enzyme, in transgenic tobacco and sunflower (Barta et al. Tobacco has been the most frequently used host for recombinant-protein expression although edible crops, such as rice, are now becoming popular, since recombinant proteins produced in such crops could in principle be administered orally without purification. The expression of human antibodies in plants has particular relevance in this context, because the consumption of plant material containing recombinant antibodies could provide passive immunity. Since then, many different types of antibody have been expressed in plants, predominantly tobacco, including full-size immunoglobulins, Fab fragments and single-chain Fv fragments (scFvs). Species Tobacco, sunflower (plants) Tobacco, potato (plants) Tobacco (plants) Rice (plants) Tobacco (cell culture) Tobacco (plants) Tobacco (cell culture) Tobacco (root culture) Rice (cell culture) Tobacco (seeds) Tobacco (chloroplasts) Recombinant human product Growth hormone Serum albumin Epidermal growth factor a-Interferon Erythropoietin Haemoglobin Interleukins-2 and 4 Placental alkaline phosphatase a1-Antitrypsin Growth hormone Growth hormone Reference Barta et al. Even secretory IgA (sIgA) antibodies, which have four separate polypeptide components, have been successfully expressed in plants. This experiment involved the generation of four separate transgenic tobacco lines, each expressing a single component, and the sequential crossing of these lines to generate plants in which all four transgenes were stacked (Ma et al. Plants producing recombinant sIgA against the oral pathogen Streptococcus mutans have been generated (Ma et al. A number of other biotechnology companies are bringing antibody-expressing transgenic plants into commercial production (see Fischer & Emans 2000).
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