Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human cytomegalovirus (HCMV) encodes a G protein-coupled receptor (GPCR), named US28, which shows homology to chemokine receptors and binds several chemokines with high affinity. US28 induces migration of smooth muscle cells, a feature essential for the development of atherosclerosis, and may serve as a co-receptor for human immunodeficiency virus-type 1 entry into cells. Previously, we have shown that HCMV-encoded US28 displays constitutive activity, whereas its mammalian homologs do not. In this study we have identified a small nonpeptidergic molecule (VUF2274) that inhibits US28-mediated phospholipase C activation in transiently transfected COS-7 cells and in HCMV-infected fibroblasts. Moreover, VUF2274 inhibits US28-mediated HIV entry into cells. In addition, VUF2274 fully displaces radiolabeled RANTES (regulated on activation normal T cell expressed and secreted) binding at US28, apparently with a noncompetitive behavior. Different analogues of VUF2274 have been synthesized and pharmacologically characterized, to understand which features are important for its inverse agonistic activity. Finally, by means of mutational analysis of US28, we have identified a glutamic acid in transmembrane 7 (TM 7), which is highly conserved among chemokine receptors, as a critical residue for VUF2274 binding to US28. The identification of a full inverse agonist provides an important tool to investigate the relevance of US28 constitutive activity in viral pathogenesis.
 ...
PMID:Identification of the first nonpeptidergic inverse agonist for a constitutively active viral-encoded G protein-coupled receptor. 1245 73

The use of Human Immunodeficiency Virus (HIV) protease inhibitors as part of the Highly Active Antiretroviral Therapy (HAART) is associated with atherogenic dyslipoproteinemia, insulin resistance, hypertension and endothelial dysfunction, all of which contribute to premature coronary heart disease. These abnormalities appear to be associated with an increase in cardiovascular events in HIV-infected patients. Beneficial metabolic effects of anti-diabetic agents used in HIV-infected patients have been reported. The thiazolidinediones (TZDs), a new group of antidiabetic drugs, may modulate the proliferative and inflammatory cascades involved in atherosclerosis. Thus, an increasing totality of evidence suggests that TZDs may represent a unique and powerful research tool to find a common denominator underlying the pathophysiology and treatment of the metabolic cardiovascular risk factors associated with HIV infection.
 ...
PMID:Thiazolidinediones could improve endothelial dysfunction and risk of premature coronary heart disease in HIV-infected patients. 1249 Sep 65

The occurrence of stroke in patients with human immunodeficiency virus (HIV) infection has been traditionally associated with opportunistic infections and tumors, and advanced stages of immunosuppression. However, this reality is undergoing major changes. Effective antiretroviral regimens are now able to forestall the progression of HIV infection and avoid early mortality. As HIV-infected patients are growing older, clinicians are facing new challenges, including an increasing incidence of vascular complications. The use of protease inhibitors is associated with a variety of metabolic derangements that could produce accelerated atherosclerosis. Cerebrovascular hemodynamic function is impaired in HIV-infected patients with evidence of abnormal vasoreactivity even in otherwise healthy individuals. The potential contribution from these novel mechanisms should be added to the high incidence of classic vascular risk factors in the HIV-infected population and the cardiac abnormalities frequently observed in these patients. Large-scale epidemiological studies should be carried out to define the true incidence of stroke in HIV-infected patients and the factors associated with its occurrence.
 ...
PMID:Stroke in HIV-infected patients: a clinical perspective. 1249 9

We recently identified two stably expressed cell surface markers, IL-18R and ST2L, which are selectively expressed on T1/NK1 and T2/NK2 cells, respectively. Here we use these molecules in direct ex vivo analysis of PBMCs from patients with AIDS, psoriasis (PS) atherosclerosis and to show the importance of these markers as determinants of the functional dichotomy of lymphocyte subsets, in particular NKT. In a cohort of 22 HIV patients made up of a mixture of long term non-progressors, seroconvertors, progressors and asymptomatics, we found a clear NKT1 to NKT2 shift (P=0.001) in the HIV-infected individuals. We also show a predominance of NKT2 cells over NKT1 cells in the PBMCs of patients with mild to moderate PS (N=13, P=0.005) but not in atopic dermatitis or healthy controls. However, in patients (N=6) requiring surgery for aneurysm, a predominance of Type 1 (IL-18R(+)) NKT lymphocytes over NKT2 was detected among infiltrating lymphocytes isolated from atherosclerotic plaques. Our data therefore demonstrate that ST2L and IL-18R could serve as important determinants of the immune status of human diseases.
 ...
PMID:NKT cell subsets in infection and inflammation. 1252 23

The endothelium participates in haemostasis, inflammation, blood pressure regulation and other physiological systems. Consequently, endothelial dysfunction has been related to hypertension, thrombosis and atherosclerosis. Both von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA) are synthesized by the endothelium and their plasma levels increased during endothelium activation or injury. So far, they are well-known markers of endothelial cell function. Many circumstances activate or damage the endothelium, such as viruses, bacterium and inflammation. Circulating vWF and t-PA were studied in 92 unselected human immunodeficiency virus-1 (HIV-1)-infected patients [27 patients with and 65 patients without acquired immunodeficiency syndrome (AIDS)] and correlated with plasma levels of pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-6), viral load, CD4 T-cell count and infectious status. HIV-1-infected patients had significantly higher plasma levels of vWF (152 versus 90%), tumour necrosis factor-alpha (31.3 versus 9.0 pg/ml) and interleukin-6 (3.5 versus 1.9 pg/ml) but not t-PA (5.9 versus 4.2 ng/ml) than the control group. These two endothelial markers correlated significantly with viral load and interleukin-6 levels in HIV-1-infected patients. The highest levels of vWF and t-PA were found in patients with AIDS. In conclusion, endothelial cell perturbation is present in HIV infection and may be a consequence of different mechanisms such as viral load, cytokines and advanced diseases.
 ...
PMID:Viral load and disease progression as responsible for endothelial activation and/or injury in human immunodeficiency virus-1-infected patients. 1254 23

Protease inhibitors decrease the viral load in HIV patients, however the patients develop hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. It has been assumed that protease inhibitor-dependent increases in atherosclerosis are secondary to the dyslipidemia. Incubation of THP-1 cells or human PBMCs with protease inhibitors caused upregulation of CD36 and the accumulation of cholesteryl esters. The use of CD36-blocking antibodies, a CD36 morpholino, and monocytes isolated from CD36 null mice demonstrated that protease inhibitor-induced increases in cholesteryl esters were dependent on CD36 upregulation. These data led to the hypothesis that protease inhibitors induce foam cell formation and consequently atherosclerosis by upregulating CD36 and cholesteryl ester accumulation independent of dyslipidemia. Studies with LDL receptor null mice demonstrated that low doses of protease inhibitors induce an increase in the level of CD36 and cholesteryl ester in peritoneal macrophages and the development of atherosclerosis without altering plasma lipids. Furthermore, the lack of CD36 protected the animals from protease inhibitor-induced atherosclerosis. Finally, ritonavir increased PPAR-gamma and CD36 mRNA levels in a PKC- and PPAR-gamma-dependent manner. We conclude that protease inhibitors contribute to the formation of atherosclerosis by promoting the upregulation of CD36 and the subsequent accumulation of sterol in macrophages.
 ...
PMID:HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages. 1256 55

Experiments in Space clearly show that various cellular processes, such as growth rates, signaling pathways and gene expression, are modified when cells are placed under conditions of weightlessness. As yet, there is no coherent explanation for these observations, though recent experiments, showing that microtubule self-organization is gravity-dependent suggest that investigations at the molecular level might fill the gap between observation and understanding of Space effects. Lipoxygenases are a family of dioxygenases which have been implicated in the pathogenesis of several inflammatory conditions, in atherosclerosis, in brain aging and in HIV infection. In plants, lipoxy-genases favour germination, participate in the synthesis of traumatin and jasmonic acid and in the response to abiotic stress. Here, we took advantage of a fibre optics spectrometer developed on purpose, the EMEC (Effect of Microgravity on Enzymatic Catalysis) module, to measure the dioxygenation reaction by pure soybean lipoxygenase-1 (LOX-1) during the 28th parabolic flight campaign of the European Space Agency (ESA). The aim was to ascertain whether microgravity can affect enzyme catalysis.
 ...
PMID:Lipoxygenase activity during parabolic flights. 1265 Jan 98

Changes in body fat in persons infected with the human immunodeficiency virus (HIV) have been associated with deleterious changes in blood lipids and insulin resistance, raising concern that these changes will increase the risk for accelerated atherosclerosis. Changes in body fat are often identified in advanced disease but may also occur early after HIV infection is detected. Conflicting evidence suggests that fat maldistribution may be related to use of protease inhibitors, nonnucleoside reverse transcriptase inhibitors, or a combination of these two classes of drugs, but the etiologies of the various changes in body fat remain uncertain. To date there have been no remedies for the loss of subcutaneous fat, but recent evidence has suggested that discontinuation of stavudine or zidovudine therapy may be associated with limited restoration of extremity fat. For fat accumulation, a number of strategies have been attempted, including treatment with human growth hormone, androgens, or metformin, and changes in diet and exercise. As in persons not infected with HIV, it is expected that the cornerstone of management, especially in the presence of central obesity, dyslipidemia, and insulin resistance, will include a diet low in saturated fat, with low-glycemic index carbohydrates, and high in fiber. Very limited evidence in persons infected with HIV has suggested that a supervised exercise program may be beneficial.
 ...
PMID:Body habitus changes related to lipodystrophy. 1265 76

The absence or deficiency of specific platelet glycoprotein receptors has a well-defined role in causing several rare bleeding disorders such as Bernard-Soulier syndrome or Glanzmann's thrombasthenia. Several new rare disorders caused by defects in other receptors or their signalling pathways have recently been described. Platelet receptors are also often targets for antibodies in pathological conditions. The roles of platelet receptors or their polymorphism variants in diseases such as cardiovascular disorders have started to be intensively investigated over the last 5 years. Many of these findings still remain controversial. Recent evidence points to a fundamental role for platelets and their receptors in the origins of atherosclerosis. Studies on the role of platelet receptors in diseases such as asthma, diabetes and HIV are still at an early stage.
 ...
PMID:Platelet receptors and their role in diseases. 1270 29

Chemokines are a group of small, pro-inflammatory molecules first described for their pivotal role in the mobilization of specific leukocyte subsets towards sites of inflammation and their activation once they arrive. They have now emerged as key regulators in the development, differentiation and anatomic distribution of inflammatory cells. Chemokines also orchestrate both the innate immune response and antigen specific immunity through their coordination of dendritic cells and lymphocytes. Due to their vast functional responsibilities, they are linked to the pathogenesis of many seemingly unrelated diseases that include HIV infection, cancer, atherosclerosis, autoimmune diseases, graft rejection and dermatological disorders. This review focuses on the physiology of chemokines and their significant roles in the pathogenesis and progression of major diseases.
 ...
PMID:Chemokines and diseases. 1280 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>