Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polypeptides have been prepared by solid-phase peptide synthesis and labelled with 15N at single sites to be used for static or magic angle spinning solid-state NMR spectroscopy. After reconstitution into oriented membranes, the alignment of polypeptide alpha-helices with respect to the bilayer surface is accessible by proton-decoupled 15N solid-state NMR spectroscopy. In addition, limiting values of rotational diffusion coefficients are obtained. The effects of membrane inserted peptides on the bilayer phospholipids have been investigated by 2H and 31P solid-state NMR spectroscopy. Long hydrophobic peptides such as the channel-forming domains of Vpu of HIV-1 or M2 of influenza A adopt stable alignments approximately parallel to the bilayer normal in agreement with models suggesting transmembrane helical bundle formation. The 15N chemical shift data agree with tilt angles of approximately 20 degrees and 33 degrees, respectively. In contrast, multi-charged amphipathic alpha-helices adopt stable orientations parallel to the bilayer surface. In the presence of these peptides, decreased order parameters of the fatty acyl chains, membrane thinning, and the loss of long-range order are observed. Peptides that change topology in a pH dependent manner are more potent in antibiotic assays under experimental conditions where they show in-plane alignments. This result suggests that their detergent-like properties, rather than the formation of transmembrane helical bundles, are responsible for their cell-killing activities. Topological equilibria are also observed within proteins or for polypeptides that do not match the hydrophobic thickness of the bilayer.
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PMID:Biophysical investigations of membrane perturbations by polypeptides using solid-state NMR spectroscopy (review). 1112 72

Several small studies conducted by the Centers for Disease Control and Prevention (CDC) have shown that although progesterone appears to increase the likelihood of simian immunodeficiency virus (SIV) transmission in exposed monkeys, women using hormone contraceptives do not appear to have the same increased risk for HIV. The results, published in the May issue of Science, show little, if any, increase in the rate of HIV infection in women on Depo-Provera, an injectable contraception containing progestin, compared to those who were not taking it. Another study, conducted in Thailand, found similar results. However, this contrasts sharply with the results of a monkey study that found that rhesus monkeys given progesterone experienced significant thinning of the vaginal wall. Researchers are examining the effects of progesterone on the lining of the vagina. Researchers are finding some thinning, but not to a significant degree. The CDC continues to stress that only abstinence or the use of latex condoms can prevent the spread of AIDS.
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PMID:Progesterone-HIV link questioned by new studies. 1136 49

After a recent study showing that monkeys given progesterone are more likely to acquire simian immunodeficiency virus (SIV), women's reproductive health experts are advising clinicians to stress the importance of condom use and calm worried women by pointing out that other studies are needed to understand the relationship between hormones and HIV risk. Researchers have learned that progestin causes a thinning of the vaginal wall--possibly an explanation for the increase in SIV infection in the monkey study. Because Depo-Provera and Norplant are long-acting progestin-based contraceptives, women using them to prevent pregnancy may be especially alarmed by reports of the monkey study. Women should be advised that using these contraceptives do protect them from pregnancy; women should assess the risk of contracting HIV or other sexually transmitted diseases; and women should modify their behavior to lower their risk.
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PMID:Advice for women seeking progesterone counseling. 1136 50

A recent National Institutes of Health (NIH)-funded study indicating that rhesus monkeys implanted with long-acting progesterone pellets were more likely to become infected after vaginal exposure to simian immunodeficiency virus (SIV) than their nontreated counterparts has raised concerns about the contribution of hormonal contraception to sexually transmitted disease (STD) risk. 14 of 18 monkeys treated with progesterone, compared with only 1 of 10 controls, developed SIV. Researchers speculated that progesterone-induced thinning of the vaginal epithelium provided a pathway for virus transmission. The NIH has emphasized that the possible increased SIV risk among animals does not necessarily imply a similar increased risk of HIV. Epidemiologic studies have failed to document any such link. Family Health International has stressed that the animal study findings are not sufficient to produce any change in the organization's position that oral contraceptives are a safe, effective family planning method. On the other hand, couples who require protection against both pregnancy and STDs must use two contraceptive methods, including latex condoms.
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PMID:Hormonal contraceptives and the risk of STDs. 1229 88

Summaries of seven recently published studies on the association between contraceptive method and sexually transmitted diseases (STDs) have confirmed the effectiveness of latex condom use, but produced inconclusive findings in terms of other methods. It has been suggested that physiological changes induced by the progesterone in oral contraceptives (OCs) (e.g., cervical ectropion and a higher incidence of chlamydia) and injectables (e.g., irregular menstrual bleeding and thinning of the vaginal lining) may increase susceptibility to HIV. On the other hand, a Kenyan study found no significant trend in HIV risk with duration of use of OCs, injectables, or IUDs. In a study from Rwanda, HIV prevalence was significantly elevated among injectable and OC users; however, this association disappeared when type of sexual relationship (e.g., nonmonogamous) and marital status were controlled. Couples who want simultaneous protection against pregnancy and STDs may need to use two contraceptive methods.
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PMID:Progesterone and STDs: selected studies. 1229 89

Although the ganciclovir implant is an effective and well-tolerated treatment for cytomegalovirus retinitis in patients with human immunodeficiency virus infection, complications that may occur include retinal detachment, implant extrusion, and endophthalmitis. A 22-year-old woman with human immunodeficiency virus infection presented with a painful left eye with scleritis overlying previous ganciclovir implant sclerotomy sites. The inflammation progressed 360 degrees around the pars plana with progressive thinning at the implant sites. Post-surgical necrotizing scleritis is another complication that can occur in patients with ganciclovir implants.
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PMID:Post-surgical scleritis associated with the ganciclovir implant. 1518 97

Efficacy of topical microbicidal drug delivery formulations against HIV depends in part on their coating distributions and retention on vaginal epithelium. This study focused on gravity-induced coating flows of vaginal gels, and effects of formulation composition and surface wettability on coating. We hypothesized that presence of a yield stress, and surface wettability, affect coating. Experiments imaged and analyzed coating flows of gels on inclined model hydrophilic or hydrophobic surfaces. The in vitro wettability conditions bracket those believed to exist on vaginal epithelium in vivo. Six commercial vaginal gels were studied: three polyacrylic acid-based (PAA) and three cellulose-based. Our research group uses these gels in complementary human in vivo studies and other in vitro experimental analyses; this study is a first step in linking the in vivo and in vitro measurements. Coating by PAA gels was different from cellulose-based gels: the former exhibited yield stresses, which prevented initial gel shape from deforming during sliding. Coating flows of cellulose gels depended upon surface wettability. The slipping rates of the PAA gels ranked inversely with fitted yield stress values. The coating flow rates of the cellulose gels (hydrophilic surface) did not correlate with consistency index, but ranked inversely with the shear-thinning index. This study introduces a simple methodology for comparing trial formulations and relating their flows to gel constituents and physical properties. It also suggests differences in coating by current commercial gels.
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PMID:Gravity-induced coating flows of vaginal gel formulations: in vitro experimental analysis. 1545 49

Human immunodeficiency virus type 1 (HIV-1) must bind to and enter lymphocytes to replicate and cause the acquired immunodeficiency syndrome. The association of viral particles with the lymphocyte plasma membrane may vary according to a multitude of unknown variables, including lymphocyte membrane receptor mobilization, lipid raft aggregation, clathrin, caveolin, endosomes, microendosome-mediated penetration or penetration through a hole in the membrane. The time course of this delivery appears to be short. Fusion of the virion membrane and lymphocyte plasma membrane leads to destabilization of the lymphocyte membrane. Five morphological stages of membrane alteration were observed in the infected lymphocytes: (1) swelling, (2) splitting, (3) fusion, (4) breaking, and (5) thinning of the lipid bilayer. These plasma membrane alterations were not contributed by fixation artifacts, because the dimensions and distance between the subunits of the surface glycoprotein (SU, gp120) and the transmembrane glycoprotein (gp41) of the viral particles adjacent to the infected cells and processed at the same time remained unchanged. Destabilization of lipid raft patches in the lymphocyte plasma membrane by unknown variables may facilitate HIV-1 penetration of lymphocyte, and other cell types. This a combined review of the pertinent literature with our data showing that HIV-1 may take advantage of multiple penetration approaches simultaneously in the same cell type (H9) to overwhelm the infected cells. The ultrastructural details of H9 cultured cells infected in vitro with HIV-1 contribute to our understanding of viral particle association with the plasma membrane of infected cells.
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PMID:Alterations of lymphocyte membranes during HIV-1 infection via multiple and simultaneous entry strategies. 1627 9

Effective therapies are available that can stop or slow down the progression of HIV infection. Highly active antiretroviral therapy (HAART) is a combination of antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue reverse-transcriptase inhibitors. Among the side effects due to these drugs, lipodystrophy is a pathology characterized by fat wasting in face and limbs, accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia (hypertriglyceridemia and hypercholesterolemia), insulin resistance, and lactic acidemia. The main clinical features include peripheral fat loss (presumed lipoatrophy in the face, limbs, and buttocks) and central fat accumulation (within the abdomen, breasts, and over the dorsocervical spine, so-called "buffalo hump"). Histopathological features disclose a peculiar type of involutional lipodystrophy. Skin biopsies generally show thinning of the subcutaneous fat, associated with fibrosis, lipogranuloma and sometimes vessel proliferation. There is still an open debate concerning the precise responsibility of HAART as well as the metabolic pathways and mechanisms that are involved in the onset of lipodystrophy. There is no proven therapy for any component of lipodystrophy syndrome.
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PMID:[Antiretroviral treatments-related lipodystrophy syndrome: clinico-pathological findings]. 1632 57

Nonrigid registration and atlas-based parcellation methods were used to compare the volume of the ventricular system and the cross-sectional area of the midsagittal corpus callosum on brain MRIs from 272 subjects in four groups: patients with HIV infection, with and without alcoholism comorbidity, alcoholics, and controls. Prior to testing group differences in regional brain metrics, each measure was corrected by regression analysis for significant correlations with supratentorial cranial volume and age, observed in 121 normal control men and women, whose age spanned six decades. Disregarding HIV disease severity, we observed a graded pattern of modest enlargement of the total ventricular system (0.28 SD for uncomplicated HIV, 0.65 SD for HIV comorbid with alcoholism, and 0.72 SD for the alcoholism group). The pattern of callosal thinning showed a similar but small ( approximately 0.5 SD) graded effect. A different pattern emerged, however, when HIV severity in the context of alcoholism comorbidity was factored into the analysis. Substantially greater volume abnormalities were present in individuals with a history of an AIDS-defining event or low CD4+ T cell counts (<or=200 mm(3)) irrespective of alcoholism comorbidity, and the effect of HIV severity was disproportionately exacerbated by alcoholism comorbidity, with 1 SD size deficit in the genu of corpus callosum and nearly 2 SD greater volume of the frontal and body regions of the ventricles for the AIDS + alcohol comorbid group. The differences in brain volumes between the AIDS groups with vs. without alcoholism could not be attributed to differences in HIV disease severity, defined by CD4+ count, viral load, or Karnofsky score. The substantial effect of the alcoholism-AIDS interaction on ventricular and callosal dysmorphology, in the context of the modest changes observed in non-AIDS, nonalcohol abusing HIV-infected individuals, highlight the need to consider alcohol use disorders as a major risk factor for neuropathology among HIV-infected persons.
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PMID:Contribution of alcoholism to brain dysmorphology in HIV infection: effects on the ventricles and corpus callosum. 1687 10


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