Biomedical subjects

Jack T Stapleton

Publications and source records attributed to Jack T Stapleton.

26 records · Page 2Linked to original sources

PubMed2003

Clinical isolates of GB virus type C vary in their ability to persist and replicate in peripheral blood mononuclear cell cultures.

GB virus C/hepatitis G virus (GBV-C) replication in vitro is inefficient and inconsistent. In this study, clinical isolates of GBV-C were evaluated using peripheral blood mononuclear cell (PBMC) based culture methods. Isolates varied consistently in their ability to persistently replicate, and yield increased in cells grown without PHA/IL-2 stimulation. The deduced polyprotein sequence of an isolate that replicated well was determined (GenBank AY196904) and compared to 20 full-length GBV-C sequences. Fourteen of the 16 unique amino acid polymorphisms identified were in the coding regions for nonstructural proteins associated with interferon resistance and RNA replication. These data indicate that clinical GBV-C isolates vary in their ability to persist in culture, do not require PHA/IL-2 stimulation, and that sequence variability in key regulatory regions may affect growth in PBMC cultures. Since GBV-C appears to inhibit HIV replication in a coinfection model, these studies should facilitate determination of the mechanism of this interaction.

Amino Acid Sequence↗

PubMed2003

Inaccurate glycosylated hemoglobin A1C measurements in human immunodeficiency virus-positive patients with diabetes mellitus.

Persistent differences in blood glucose and serum glycosylated hemoglobin (HbA1C) measurements were observed in 4 human immunodeficiency virus-positive patients with diabetes mellitus, all of whom were taking drugs associated with hemolysis, which interferes with the reliability of HbA1C levels. Determination of fructosamine levels was a more accurate alternative for measuring average glycemic control in these patients.

Adult↗

PubMed2003

GB virus type C/hepatitis G virus: a non-pathogenic flavivirus associated with prolonged survival in HIV-infected individuals.

GB virus C (GBV-C) is a common virus that does not appear to cause disease. GBV-C persists in up to 50% of exposed individuals, and virus replication appears to be in lymphocytes including CD4+ T cells. GBV-C infection is common among HIV-positive people, and several studies have found that HIV-positive individuals co-infected with GBV-C survive for statistically significantly longer periods of time than people without GBV-C. In vitro studies suggest that GBV-C inhibits HIV replication and alters cytokine, chemokine and chemokine receptor expression. Thus, GBV-C may be a major factor influencing the natural history of HIV disease.

Animals↗

PubMed2003

Concealment of homosexual identity, social support and CD4 cell count among HIV-seropositive gay men.

OBJECTIVE: Previous research has indicated that the concealment of homosexuality is related to poorer health among gay men with HIV. This study explored mechanisms by which concealment of homosexuality may be related to HIV disease status by examining associations between concealment of homosexuality, social support, social constraints, depressive symptoms and CD4 count among HIV-seropositive gay men. METHOD: Questionnaires assessing concealment of homosexuality, social support, depressive symptoms and social constraints were administered to 73 HIV-seropositive gay men. Medical charts were accessed to gather HIV disease information including CD4 counts. Regression analyses were conducted to examine associations between psychosocial variables and CD4 counts. RESULTS: Concealment of homosexuality was associated with lower CD4 count, greater social constraints, greater depressive symptoms and less social support. The association between concealment of homosexuality and CD4 count varied according to level of social support. Among participants with higher levels of social support, those with greater concealment had lower CD4 counts than those with lower concealment. Concealment of homosexuality was not related to CD4 count among participants reporting low social support. CONCLUSION: Concealment of homosexuality among HIV-seropositive gay men is associated with lower CD4 counts, depressive symptoms and strained social relationships. In addition, the benefits of being open about homosexuality may be most evident under conditions of greater social support.

Adult↗

PubMed2003

GB virus type C/Hepatitis G virus.

After hepatitis G virus (HGV) and GB virus type C (GBV-C) were independently discovered, it was determined that they were two isolates of the same virus. The HGV/GBV-C genome sequence and organization are closely related to hepatitis C virus. Although HGV/GBV-C infection is common and frequently persists in humans, infection has not been found to be associated with any known disease state. Because this virus is not associated with acute or chronic hepatitis, most people refer to it as GBV-C. GBV-C appears to grow in lymphocytes and not in hepatocytes, and presumably this is why the virus does not cause liver disease. Recent studies suggest that GBV-C infection in HIV-positive people is associated with prolonged survival. In vitro coinfection of human lymphocytes with GBV-C and HIV lead to decreased HIV replication. Further understanding of the mechanism(s) responsible for this interaction with HIV may provide novel approaches for treating HIV and AIDS.

Flaviviridae Infections↗

PubMed2002

Hepatitis C virus viremia in HIV-infected individuals with negative HCV antibody tests.

Hepatitis C virus (HCV) viremia may occur in persons without detectable HCV antibodies and has been reported in as many as 5.5% of HIV-positive persons. To better characterize serosilent HCV infection, the authors prospectively tested 131 HIV-positive persons and 102 HIV-negative control subjects with diabetes for the presence of HCV antibody (Ab) and HCV RNA. Thirty of 31 HCV Ab-positive (AbP) HIV-positive people tested positive for HCV RNA as did both HCV AbP, HIV-negative control subjects. Similarly, none of the 100 HIV-negative, HCV Ab-negative (AbN) control subjects was HCV RNA positive (p<.001). In contrast, 19 of 100 HIV-positive, HCV AbN persons met stringent criteria for HCV viremia, and 9 of these 19 people were HCV RNA positive when tested by a commercially available HCV RNA detection method. The mean duration of HCV viremia in HCV AbN people was 26.8 months (range, 1-99 months). None of the subjects developed HCV antibody during the study. The HIV-positive, HCV AbP, and RNA-positive group was significantly more likely to have acquired HIV parenterally (p<.001), have higher initial CD4 counts (p=.029), and have higher ALT values than the HCV AbN group (p<.002). In summary, HCV infection appears to occur more frequently among HIV-infected, HCV-seronegative persons than appreciated, especially if HIV acquisition was through sexual as opposed to parenteral risk factors and was associated with a lower initial CD4 count and lower ALT values.

Adult↗

PubMed2002

Alcohol use and HIV pharmacotherapy.

Alcohol consumption by individuals infected with HIV is an important medical management issue with significant implications for the effectiveness of antiretroviral therapy as well as an important evolving field of HIV research. Alcohol consumption is a risk factor for poor medication adherence and can modify liver drug metabolism, both of which can lead to the emergence of drug-resistant virus. Research indicates that alcohol consumption greater than 50 g/day (four or five drinks) is a risk factor for liver disease progression among patients with HIV/HCV coinfection. In addition, alcohol-induced cirrhosis can result in changes in drug metabolism in the liver through compromised liver function. More research studies are needed to elucidate the biological and molecular basis of the clinical changes induced by alcohol consumption in HIV-infected individuals and on the relationship of these changes to the effectiveness of HIV pharmacotherapy. Specifically, research areas that are of particular importance are (1) determining alcohol consumption levels and patterns and its impact on antiretroviral medication adherence, efficacy, and physician prescribing practices; (2) identifying behavioral interventions to enhance adherence to HIV medications and reduce alcohol consumption; (3) clarifying the relationships and interactions among alcohol metabolism, HIV drug metabolism, and pharmacogenetics; (4) elucidating the extent of liver toxicity due to antiretroviral therapy and drug-drug interactions in individuals who consume alcohol; and (5) delineating the contribution of alcohol consumption to end-stage organ damage, particularly in HIV/HCV coinfection.

Alcoholism↗

PubMed2002

Recombinant hepatitis C virus-like particles expressed by baculovirus: utility in cell-binding and antibody detection assays.

Hepatitis C virus (HCV) is difficult to study due to the lack of an efficient cell culture system or small animal model. As a result, HCV-cell interactions are not well-defined. In addition, several studies have identified a subset of patients in whom HCV RNA is present, but HCV antibody is not detected. We produced recombinant baculoviruses that expressed HCV structural proteins (core, E1 and E2, nt 342-2651) or control proteins. The HCV structural protein precursor was processed into immunoreactive proteins of appropriate size, and sucrose density sedimentation and electron microscopy of infected cell lysates demonstrated particle formation. To evaluate HCV antigenicity, particularly in patients who tested negative for HCV antibody in commercial HCV immunoassays but had persistent viremia, we evaluated the virus-like particles (VLPs) in solid-phase immunoassays. VLPs reacted with sera from HCV antibody positive subjects in these solid phase immunoassays, but not with control sera. Plasma samples from 19% (5/26) of HCV antibody negative subjects who were persistently HCV RNA positive also reacted with the HCV VLPs. When incubated with MOLT-4 cells at 4 degrees C, HCV VLPs demonstrated cell binding, and behaved similar to plasma-derived HCV preparations in a flow cytometry-based cell binding assay. These data suggest that recombinant HCV VLPs may allow identification of HCV antibody in patients, including some patients with persistent viremia and who are seronegative with current assays. In addition, HCV VLPs seem useful for evaluating HCV-cell interactions.

Animals↗