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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The author provides data pertinent to the modern classification of erythrocytosis, which rests on the pathogenetic principle. The difference in the pathogenesis of erythremia and secondary erythrocytoses was proved with the help of an erythroid culture and by examination of erythropoietins, which can be thus used for diagnostic purposes. Analysis of so-called "pure" erythrocytosis has shown that this term implies different patterns of erythrocytosis from the standpoint of the pathogenesis: erythremia, secondary erythrocytoses that are difficult to diagnose, and hereditary erythrocytosis associated with erythropoietin hyperproduction. There is no evidence for the existence of the "pure" erythroid leukemia and thus the author doubts this disease entity. Analysing the different patterns of secondary absolute erythrocytosis the author discusses specific problems of their pathogenesis. Attention is paid to erythrocytosis of a tobacco smoker, to the role of obesity and concomitant action of some factors on the development of hypoxic erythrocytosis. The data are presented on the new types of erythrocytosis, on the post-transplantation one, in particular, which occurs after kidney transplantation, and finally on erythrocytosis that develops occasionally in patients on hemodialysis. Attention is paid as well to relative erythrocytoses, risk factor in the development of thrombotic complications. The problems of etiologically and pathogenetically valid therapy of secondary erythrocytoses are reviewed.
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PMID:[Secondary erythrocytoses]. 404 68

The ob gene product, leptin, has been shown in several studies to be involved in weight control and recombinant leptin recently has entered clinical trials to treat obesity. The leptin receptor (OB-R/B219) is expressed in a variety of protein isoforms not only in the central nervous system, but also in reproductive, and hematopoietic tissues. We reported recently that the OB-R/B219 was associated with a variety of hematopoietic lineages as well as the small fraction of cells containing the long-term reconstituting hematopoietic stem cells. Herein we report that leptin significantly stimulates the proliferation and differentiation of yolk sac cells and fetal liver cells and stimulates directly hematopoietic precursors. Leptin alone can increase the number of macrophage and granulocyte colonies, and leptin plus erythropoietin act synergistically to increase erythroid development. These data show that leptin has a significant, direct effect on early hematopoietic development and can stimulate the differentiation of lineage-restricted precursors of the erythrocytic and myelopoietic lineages. These observations along with a recent report strongly support our previous hypothesis that leptin has an unanticipated important role in hematopoietic and immune system development.
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PMID:Leptin stimulates fetal and adult erythroid and myeloid development. 937 66

Internists are frequently asked to do preoperative consultations and to manage perioperative complications. Realistic goals are to identify patient factors that increase the risk of surgery, to quantify this risk in order to make decisions about the appropriateness of and timing of the surgery, to provide recommendations on how to minimize the risk, to identify and manage coexisting medical conditions and their associated medication requirements, to monitor the patient for perioperative problems, and to make recommendations to deal with these problems when they occur. With few exceptions, nonselective imaging and laboratory screening tests have repeatedly been shown to be of little value when the history and physical do not suggest a problem. The risk associated with the planned surgery can be estimated, with the most common serious complications being cardiac events. Updated versions of Goldman's risk indices are particularly helpful for this. Clinical variables are optimally combined with selective stress testing to discern which patients will benefit from preoperative revascularization. This has been studied best in the setting of vascular surgery. A critical guiding principle is that the value of revascularization must be judged in terms of long term gains rather than just immediate perioperative benefit. Other interventions include the selective use of beta blockers, adequate analgesia for all, control of hypertension, and appropriate volume management, especially in the settings of preexisting CHF or valvular disease. It must also be recognized that perioperative ischemia and CHF often present atypically. An approach that combines aspects of both the ACC/AHA and the ACP guidelines seems optimal. A variety of noncardiac issues must also be addressed. Postoperative pulmonary complications are common, especially with preexisting pulmonary disease, thoracic and upper abdominal surgery, and obesity. PFTs and ABGs are indicated in selected patients. Stopping smoking, incentive spirometry, and selective use of bronchodilators and antibiotics are helpful. Patients with rheumatologic diseases have specific concerns based on systemic manifestations of disease including anemia, thrombocytopenia, pulmonary fibrosis, pericarditis, and hypercoagulability; medication effects particularly from steroids and nonsteroidal anti-inflammatory drugs; and specific joint problems including contractures and atlantoaxial joint instability. Diabetes increases the risk of infection and cardiac complications. Prevention of ketoacidosis and glucose control are necessary and can be achieved through a variety of approaches, depending on whether the patient suffers from Type 1 or Type 2 diabetes. The threshold for transfusion has increased in recent years, as has the use of erythropoietin and autologous blood donation. There is no longer an absolute hemoglobin that requires transfusion, although most require transfusion for hemoglobins less than 8 mg/dL, especially in the setting of cardiac disease and bloody surgery. The elderly require surgery at an increased rate and often do not do as well as younger patients. The primary issues are, however, not their age but their increased frequency of underlying disease and diminished reserve. The latter makes them prone to postoperative delirium, sensitivity to medications, and cardiac and pulmonary problems. Despite the many diseases that patients often have and the stresses of surgery itself, modern anesthetic and surgical techniques allow almost all patients to undergo necessary procedures at acceptable risk. The internist plays a critical role in minimizing this risk even further.
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PMID:Recognition and management of preoperative risk. 1046 30

An erythrocytosis describes an increased peripheral blood packed cell volume (PCV) and is deemed to be absolute or apparent depending on whether or not the measured red cell mass (RCM) is above the reference range. This reference range must be related to the individual's height and weight to avoid erroneous interpretations using ml/kg total body weight expressions in obesity. Absolute erythrocytoses are divided into primary, where the erythropoietic compartment is intrinsically abnormal, secondary, where the erythropoietic compartment is normal but is responding to external pathological events leading to an increased erythropoietin drive, and idiopathic, where neither a primary nor a secondary erythrocytosis can be established. Both primary and secondary erythrocytoses have congenital and acquired forms. The only form of primary acquired erythrocytosis that has been defined is the clonal myeloproliferative disorder, polycythaemia vera (PV). Modified diagnostic markers for PV are proposed. Thrombocytoses can be classified into primary, where megakaryopoiesis is intrinsically abnormal, secondary, where megakaryopoiesis is normal but increased platelet production is a reaction to some other unrelated pathology, and finally idiopathic. This latter new group would be used for patients not satisfying the criteria for primary or secondary thrombocytoses, if these were more precise and rigidly used than currently is the case. While theoretically congenital and acquired forms of primary and secondary thrombocytoses might exist, only one cause of secondary congenital thrombocytosis has been established, and primary congenital thrombocytosis has not yet been precisely defined. Primary (essential) thrombocythaemia (PT) is one of the forms of primary acquired thrombocytoses. The diagnostic criteria of PT traditionally involve the exclusion of secondary thrombocytoses and other myeloproliferative disorders but marrow histology could hold a key positive diagnostic role if objective histological features of PT were agreed.
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PMID:Diagnosis and classification of erythrocytoses and thrombocytoses. 1064 Feb 13

Protein-energy malnutrition (PEM) and inflammation are common and usually concurrent in maintenance dialysis patients. Many factors that appear to lead to these 2 conditions overlap, as do assessment tools and such criteria for detecting them as hypoalbuminemia. Both these conditions are related to poor dialysis outcome. Low appetite and a hypercatabolic state are among common features. PEM in dialysis patients has been suggested to be secondary to inflammation; however, the evidence is not conclusive, and an equicausal status or even opposite causal direction is possible. Hence, malnutrition-inflammation complex syndrome (MICS) is an appropriate term. Possible causes of MICS include comorbid illnesses, oxidative and carbonyl stress, nutrient loss through dialysis, anorexia and low nutrient intake, uremic toxins, decreased clearance of inflammatory cytokines, volume overload, and dialysis-related factors. MICS is believed to be the main cause of erythropoietin hyporesponsiveness, high rate of cardiovascular atherosclerotic disease, decreased quality of life, and increased mortality and hospitalization in dialysis patients. Because MICS leads to a low body mass index, hypocholesterolemia, hypocreatininemia, and hypohomocysteinemia, a "reverse epidemiology" of cardiovascular risks can occur in dialysis patients. Therefore, obesity, hypercholesterolemia, and increased blood levels of creatinine and homocysteine appear to be protective and paradoxically associated with a better outcome. There is no consensus about how to determine the degree of severity of MICS or how to manage it. Several diagnostic tools and treatment modalities are discussed. Successful management of MICS may ameliorate the cardiovascular epidemic and poor outcome in dialysis patients. Clinical trials focusing on MICS and its possible causes and consequences are urgently required to improve poor clinical outcome in dialysis patients.
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PMID:Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. 1458 32

Adeno-associated viral (AAV) vectors are derived from a nonpathogenic, replication-deficient virus with a small (~4.7-kb) single-stranded DNA genome. AAV vectors are devoid of viral-coding sequences and may efficiently transfer genes to nondividing cells such as muscle fibers or hepatocytes following in vivo transduction. Recombinant AAV can be administered to skeletal muscle of experimental animals and, as recently documented in a Phase I clinical trial, to humans at high vector doses without local or systemic toxicity (8,9). The potential of the vector to activate cytotoxic T lymphocytes is greatly reduced compared with some other viral vectors, thereby reducing the risk of inflammation at the site of gene transfer (7,10,11). Sustained expression of therapeutic transgenes such as coagulation factor IX (F.IX), erythropoietin, leptin, insulin-like growth factor (IGF), sarcoglycans, mini-dystrophin genes, alpha1-antitrypsin, and others have been demonstrated (2,12-18). Efficient gene transfer to myofibers by intramuscular (im) injection has been shown in several species including mice, hamsters, dogs, and nonhuman primates (6-8,13,19). These studies resulted in various levels of correction of the disease phenoypes in small and large animal models of hemophilia B (F.IX deficiency), muscular dystrophy, obesity, age-related atrophy, and beta-thalassemia (8,12,13,15,17,18,20-25).
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PMID:AAV-mediated gene transfer to skeletal muscle. 1497 May 92

Insulin resistance is a characteristic feature of obesity and type 2 diabetes mellitus, but it is also present in up to 25% of healthy nonobese individuals. The molecular mechanisms causing insulin resistance are not yet fully understood. Recently, overexpression of several potential inhibitors of the insulin receptor tyrosine-kinase activity, a key step in insulin signaling, has been described in insulin-resistant subjects . PC-1 is expressed in many tissues and inhibits insulin signaling either at the level of the insulin receptor or downstream at a postreceptor site. An elevated PC-1 content in insulin target tissues may play an important role in the development of insulin resistance in obesity and type 2 diabetes mellitus. A polymorphism in PC-1 has been demonstrated to be associated with insulin resistance. This was a DNA polymorphism in exon 4 that causes an amino acid change from lysine to glutamine at codon 121 (K121Q). PC-1 121Q allele might predispose independently of other well established risk factors for early myocardial infarction. Testing for the PC-1 K121Q polymorphism might be valuable in patients with a family history of atherosclerotic vascular disease and myocardial infarction. There is growing evidence that genetic factors play an important role in the development of diabetic nephropathy (DN). Efforts to identify these factors rely primarily on the candidate gene approach; candidate genes for insulin resistance may be considered candidates for DN as well. In a stratified analysis according to duration of diabetes, the risk of early-onset end-stage renal disease (ESRD) for carriers of the Q variant was 2.3 times that for noncarriers. The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. Women with GDM have an increased PC-1 content and excessive phosphorylation of serine/threonine residues in muscle insulin receptors. The postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life. Although widely explored, the true cause of insulin resistance in uremic patients is not entirely elucidated yet. During the last decade it was found that erythropoietin (EPO) therapy, used for correction of anemia in patients with end stage renal failure, ameliorates insulin resistance. An increased lymphocyte PC-1 activity over control was found in hemodialysis patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uremic patients treated with EPO. Current investigations implicate that therapeutic modification of PC-1 expression would be of great benefit for insulin-resistant type 2 diabetics. Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics. Thiazolidinedione (TZD) insulin-sensitizing drugs are a class of compounds that improve insulin action in vivo. Treatment of patients with TZDs seems to have a beneficial effect on most, if not all, components of metabolic syndrome. TZDs have also been used in the treatment of nondiabetic human insulin-resistant states, and have demonstrated an improvement in insulin sensitivity. Although much remains to be learned about PPAR gamma receptor and TZD action, the advent of TZD insulin-sensitizing agents has an enormous impact on our understanding of insulin resistance. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms.
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PMID:Plasma cell membrane glycoprotein 1 (PC-1): a marker of insulin resistance in obesity, uremia and diabetes mellitus. 1520 35

The rising incidence of type 2 diabetes mellitus and of its complications will make it the most important health care challenge in the first quarter of the 21st Century. Diabetic nephropathy left unchecked will overwhelm the renal resources. Simple methods (proper diet and exercise, prevention of obesity) are successful in preventing type 2 diabetes in the great majority of the persons at risk. In patients with established type 2 diabetes, nephropathy can be prevented or greatly delayed by strict metabolic control, strict control of blood pressure using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers as the first line of drugs, tight control of serum lipids using statins as indicated, low protein diet, avoidance of smoking and other nephrotoxic influences, prevention of abnormalities in calcium/phosphorus metabolism, and prevention of renal anemia by the early use of erythropoietin. Current research offers the promise of definitive prevention of both type 2 diabetes and diabetic nephropathy.
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PMID:Prevention of nephropathy in patients with type 2 diabetes mellitus. 1630 58

Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been recognized as a predominant factor to induce the ischemic retinal neovascularization. We found that retinal vascular cells have a characteristic pattern in VEGF receptor expression, which causes vascular pathology more frequently in the retina than in other organs. Neuropilin 1 (NRP 1), which enhances VEGF receptor function, is abundantly expressed in the retinal endothelial cells and is upregulated by VEGF itself and by hypoxia to regulate a positive feedback mechanism in retinal neovascularization. This receptor could be a unique target for retina-specific therapy. Lifestyle-related diseases increase along with aging and have further increased due to changes in Japanese lifestyle imitating that of Western countries. We found that the renin-angiotensin system which regulates hypertension and cardiovascular diseases, and adipocytokines which are abnormally secreted in obesity, act as proangiogenic factors. Regulation of such lifestyle-related disease factors is important for the treatment of retinal vascular diseases. Finally, we found that erythropoietin is an ischemia-induced angiogenic factor that acts independently and as potently as VEGF in proliferative diabetic retinopathy (PDR). Our study utilizing human vitreous samples demonstrates that the VEGF level is particularly high and strongly associated with angiogenic activity in PDR patients. The potential of VEGF inhibitors has recently been recognized in clinical applications. The manipulation of each angiogenic factor and adipocytokine that we report here could become potential therapy in the near future.
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PMID:[Aging and retinal vascular diseases]. 1740 63

Cystic renal lymphangiectasia (CRL) is a rare malformation of lymphatics that can present in childhood and adulthood. Symptoms and radiologic features are relatively well defined, but clinical evolution and prognosis remain unclear. We treated a boy with CRL who developed chronic renal insufficiency. The first manifestation was abdominal swelling associated with an umbilical hernia noted incidentally at 1.6 years. Computed tomography with intravenous contrast administration demonstrated perirenal cysts with fluid collection, suggesting CRL. Intractable ascites resisted pharmacologic treatments such as diuretics. After approximately 7 years, the ascites resolved spontaneously, but the perirenal cysts persisted. At 11 years, proteinuria was noted. A renal biopsy specimen showed interstitial abnormalities consistent with CRL, glomeruli showed a focal segmental mesangial increase. Proteinuria persisted despite administration of an angiotensin-converting enzyme inhibitor, increasing as obesity and hypertension worsened. Renal function gradually declined in the ensuing years. Polycythemia coexisted with a normal serum erythropoietin concentration. A follow-up renal biopsy specimen disclosed glomerular enlargement together with focal segmental mesangial expansion, suggesting obesity-related glomerulopathy. Our observation suggest that under some specific circumstances like our patient CRL may exacerbate. Management of complicating obesity and hypertension are likely to be important for maintaining normal renal function, especially in the diffuse bilateral type of CRL present in our patient.
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PMID:Chronic renal insufficiency in a boy with cystic renal lymphangiectasia: morphological findings and long-term follow-up. 1818 26


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