Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sex-, age-, obesity, and protease inhibitor-matched study of pulmonary function and ventilatory control was performed on 26 sons of 19 patients with chronic obstructive pulmonary disease (COPD) and 26 control subjects. Mean values for FEV1/FVC and V25 were significantly lower and CV/VC was significantly higher in sons of patients than in the controls. VC, airway resistance, static pulmonary compliance. delta N2, arterial blood gases and pH were not different between sons and controls. When the sons of patients were divided into two groups according to the arterial blood gases of their parents, sons of hypoxemic, hypercapnic parents showed significantly lower hypoxic ventilatory responses than sons of normoxemic, normocapnic parents. Hypercapnic ventilatory responses were not different between sons and controls. Abnormal pulmonary function and low ventilatory responses were more frequently detected in sons than in controls. The association of smoking with abnormalities of pulmonary function was not clearly seen in sons. These results suggest that familial factors (either genetic or environmental) play a significant role in determining the pathogenesis and clinical types of COPD.
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PMID:Familial aggregation of abnormal ventilatory control and pulmonary function in chronic obstructive pulmonary disease. 722 84

Insulin resistance is a common clinical feature of obesity and non-insulin-dependent diabetes mellitus, and is characterized by elevated serum levels of glucose, insulin, and lipids. The mechanism by which insulin resistance is acquired is unknown. We have previously demonstrated that upon chronic treatment of fibroblasts with insulin, conditions that mimic the hyperinsulinemia associated with insulin resistance, the membrane-associated insulin receptor beta subunit is proteolytically cleaved, resulting in the generation of a cytosolic fragment of the beta subunit, beta', and that the generation of beta' is inhibited by the thiol protease inhibitor E64 (Knutson, V. P. (1991) J. Biol. Chem. 266, 15656-15662). In this report, we demonstrate that in 3T3-L1 adipocytes: 1) cytosolic beta' is generated by chronic insulin administration to the cells, and that E64 inhibits the production of beta'; 2) chronic administration of insulin to the adipocytes leads to an insulin-resistant state, as measured by lipogenesis and glycogen synthesis, and E64 totally prevents the generation of this insulin-induced cellular insulin resistance; 3) E64 has no effect on the insulin-induced down-regulation of insulin receptor substrate-1, and therefore insulin resistance is not mediated by the down-regulation of insulin receptor substrate-1; 4) under in vitro conditions, partially purified beta' stoichiometrically inhibits the insulin-induced autophosphorylation of the insulin receptor beta subunit; and 5) administration of E64 to obese Zucker fatty rats improves the insulin resistance of the rats compared to saline-treated animals. These data indicate that beta' is a mediator of insulin resistance, and the mechanism of action of beta' is the inhibition of the insulin-induced autophosphorylation of the beta subunit of the insulin receptor.
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PMID:Insulin resistance is mediated by a proteolytic fragment of the insulin receptor. 755 25

To our knowledge, an association between human immunodeficiency virus infection and pseudo-Cushing's syndrome has not previously been described. We describe four HIV-infected patients with pseudo-Cushing's syndrome, characterized by striking dorsocervical and submandibular fat accumulation and central obesity. In each case, cortisol levels were either normal or suppressed adequately with administration of dexamethasone, excluding the diagnosis of true Cushing's syndrome. Immune function and weight improved significantly preceding the development of pseudo-Cushing's syndrome. Three of the four patients were taking a common protease inhibitor at the onset of symptoms, and the fourth reported the exacerbation of his symptoms with the addition of a protease inhibitor. The observed characteristic pattern of fat deposition may be attributable to a specific effect of new antiretroviral therapies or may relate to recovery independent of medication usage. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. Further research into the mechanisms of this novel phenomenon is needed.
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PMID:Pseudo-Cushing's syndrome in human immunodeficiency virus-infected patients. 967 55

The development of lipodystrophy as evidenced by central obesity, "moon facies," and a "buffalo hump" is a classical feature of Cushing's disease. Recently an association of "lipodystrophy" with the use of protease inhibitors has been reported. We describe a patient with lipodystrophy secondary to protease inhibitor therapy for HIV infection.
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PMID:Protease inhibitor-induced lipodystrophy. 1018 89

In 1997, and mainly in 1998 and 1999, a lipodystrophic syndrome with central obesity, peripheral fat loss, hyperlipidemia, hyperglycemia and insulin-resistant-diabetes II, was described as the most frequent manifestation of toxicity of HIV1 virostatic therapy, associated with protease inhibitors (PI) in 83% of the patients who used them for 10 months. Almost similar syndromes had been published before the latter, due, for example, to graft vs host reaction, or autoimmunity against insulin receptors, or to caloric excess in the presence of androgens (the mediator being hyperinsulinemia). Carr and Cooper have presented an original pathophysiological mechanism for the PI-associated syndrome, residing in 63% homology between HIV1-protease and the 3-low-density-lipoprotein-receptor-related protein (LRP), and in 53% homology between this virus enzyme and retinoid-binding-protein type 1 (CRAB1). The treatment should be more subtle than those of common obesity and/or type II diabetes. This HIV1-protease inhibitor toxicity can be prevented by alternating several antiproteases in short sequences of the different ones.
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PMID:Human obesity and thinness, hyperlipidemia, hyperglycemia, and insulin resistance associated with HIV1 protease inhibitors. Prevention by alternating several antiproteases in short sequences. 1066 36

The nutritional condition of children with human immunodeficiency virus (HIV) infection continues to be a problem both in developed and developing countries. HIV-infected children grow below normal standards in both height and weight when compared with HIV-exposed non-infected children. These patterns persist over time. It is possible that acute infectious episodes and increased HIV viral burden contribute to decrements in all growth variables. Potential aetiologies for abnormal growth include inadequate dietary intake, gastrointestinal malabsorption, increased energy utilization and psycho-social problems. It is likely that all these factors contribute to the growth problems of these children to some extent. With the development of protease inhibitor anti-retroviral therapy and highly-active anti-retroviral treatment regimens, children with HIV infection in developed countries are living longer with a chronic illness. New nutritional problems have arisen with the development of the fat redistribution syndrome or lipodystrophy. Emerging problems are now being recognized, with the development of insulin resistance and truncal obesity which may potentially lead to premature cardiovascular disease.
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PMID:Nutrition in paediatric human immunodeficiency virus infection. 1082 85

The introduction of HAART has changed the nutritional status of HIV patients. In the pre-protease inhibitor (PI) era, more than 60% of HIV-positive persons presented with protein energy malnutrition (PEM) and vitamin and mineral deficit. This caused progressive physical-metabolic wasting (wasting syndrome/cachexia) and increased susceptibility to opportunistic infections and drug toxicity. PEM was a concurrent cause in 80% of deaths attributed to AIDS. Since 1996, the year in which PIs were introduced, the number of patients dying as a result of AIDS has decreased by two thirds, and cachexia is no longer the AIDS terminal phase in developed countries. But different patterns of nutritional status changes have appeared in association with the use of newer anti-HIV therapies and with longer survival of HIV-infected patients. A new clinical and laboratory syndrome--lipodystrophy syndrome--now affects patients receiving PI-based therapy. This syndrome consists of changes in body shape that are caused by an abnormal redistribution of fat. Fat accumulates in the abdominal area (truncal and visceral obesity), in the axillary pads (bilateral symmetric lipomatosis), and in the dorsocervical pads ("buffalo hump," "bull neck") but decreases in the legs, arms, and nasolabial and cheek pads (peripheral lipodystrophy). Hyperlipidemia and insulin resistance are also frequently present (metabolic syndrome X). Pathogenic mechanisms of lipid and fat tissue disturbances are discussed in this article, and the clinical approach to patient management and therapeutic options for lipodystrophy and lipid dysmetabolism is evaluated.
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PMID:Reversal of cachexia in patients treated with potent antiretroviral therapy. 1088 68

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long-Evans Tokushima Otsuka (LETO) rats. By Northern blot analysis, we confirmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal partial amino acid sequence of OL-64 revealed that it showed approximately 40% homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gene family. VAT of OLEFT rats had a unique gene expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.
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PMID:Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats. 1101 3

Reports of success with protease inhibitor-based HAART are appearing at the same time as reports of puzzling metabolic effects. These effects include loss of peripheral subcutaneous fat, truncal obesity, hyperlipidemia, and frank diabetes. There is no consensus on how often these problems manifest themselves. Patients taking protease inhibitors (PIs) also appear to be at higher risk of developing coronary disease, although more study is needed. Another question explored is whether PI-related complications can be reversed.
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PMID:Metabolic complications of protease inhibitors: what have we learned so far? 1136 49

HIV infection was first reported in 1981 in USA. It has been 20 years since then. Owing to understandings of pathogenesis of this disease and development of new drugs such as the HIV-specific protease inhibitor (PI), prognosis of disease has been tremendously improved. Especially after 1997 in Japan, the strategy of anti-HIV treatment shifted from two drugs combination to three drugs combination, which is called highly active antiretoviral therapy (HAART). HAART was so effective that prevalence of HIV associated opportunistic infections were decreased dramatically. Mortality among hospitalized HIV-infected patients was decreased from 6.7% in 1996 to 2.6% since then in ACC. However, 80% of patients receiving HAART suffered from side effects and 15% of them had to be changed their treatment due to side effects. Furthermore, an unexpected side effect, namely lipodystrophy syndrome (LDS), was emerged among patients who were receiving HAART more than one year. LDS was first reported as re-distribution of lipid such as central obesity with or without lipo-atrophy from extremities and/or face. Now only cosmetic change, but also it is associated with elevation of lipid and glucose level. Therefore, those patients who have LDS are in face of the risk for the ischemic heart diseases. Our survey indicated that the rate of LDS in Japanese patients were almost same as that of Caucasian patients reported elsewhere. Opportunistic infections associated with HIV infection Treatment for HIV infection consists of two major arms; one is use of anti-HIV drugs to prevent development of AIDS described above and the other is diagnosis, treatment, and prophylaxis of opportunistic infections. There are five very important opportunistic infections; Pneumocystis carinii pneumonia (PCP), cryptococcus meningitis, toxoplasma encephalitis, cytomegalovirus (CMV) infection, and Mycobacterium avium complex (MAC) bacteremia. Because if these five were able to diagnose, a patient can survive under appropriate treatment. On the other hand, if these were not diagnosed, patient must be AIDS death. After introducing HAART, number of CMV retinitis, MAC bacteremia, and AIDS dementia complex were decreasing. However, number of PCP sustained high because PCP is the first indicator disease of AIDS if the patient did not know his HIV status. The first choice of drug is sulfamethoxazole/trimethoprim (ST) for PCP treatment. If the patient were in severe respiratory failure, corticosteroid is used concomitantly. Treatment is usually continued for 3 weeks. We have successfully treated 45 out of 47 cases of PCP for 4 years. However, those patients treated with ST for 3 weeks were limited only 35% because of very high rate of side effects of ST. If the patient was intolerant to ST, treatment was switched to pentamidine. After finishing the treatment, the patient is to be treated with a 5-day course of oral desensitization to ST. More than 80% of patients who were previously intolerant to ST became successfully getting tolerance by this method.
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PMID:[Pulmonary complications in patients with AIDS]. 1185 78


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