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V G Bain

Publications and source records attributed to V G Bain.

11 recordsLinked to original sources
PubMed1992

High-level expression of hepatitis B viral antigens in fibrosing cholestatic hepatitis.

The expression of hepatitis B viral antigens was quantified in liver tissue from four transplant recipients with fibrosing cholestatic hepatitis (FCH) and compared with five other transplant recipients who did not develop this syndrome and 30 patients with chronic hepatitis B virus (HBV) infection. As measured by radioimmunoassays, the liver tissue from patients with FCH had significantly greater amounts of both hepatitis B surface antigen (HBsAg) and nucleocapsid antigens than to transplant patients without this syndrome (P less than 0.01) or patients with chronic HBV infection (P less than 0.001). Intrahepatic expression of pre-S1/pre-S2 in FCH was also extensive with a distribution parallel to that of HBsAg. High-level expression of intrahepatic HBsAg and hepatitis B core antigen in the explanted liver was associated with subsequent development of FCH in the liver graft, suggesting that viral/host factors may also be important. This pattern of intrahepatic hepatitis viral antigen expression, by analogy with Chisari's transgenic mice model and Roingeard's HBV-transfected HepG2 cell model, may be the cause of direct hepatocytopathic injury in this condition.

Adult↗
PubMed1992

Modulation of hepatitis B viral antigen expression by immunosuppressive drugs in primary hepatocyte culture.

In one pattern of hepatitis B virus (HBV) recurrence following orthotopic liver transplantation--namely, fibrosing cholestatic hepatitis (FCH), the intrahepatic expression of HBV antigens was found to be markedly increased, suggesting that HBV may be directly cytopathic to the liver cells. Understanding how immunosuppressive drugs influence HBV may be of considerable clinical relevance in the treatment of patients with chronic HBV infection after liver transplantation. To determine how these drugs influence intrahepatic HBV antigen expression, hepatocytes isolated from patients with chronic HBV infection were incubated in the absence or presence of prednisolone (10(-6)-10(-10) M), methylprednisolone (10(-6)-10(-10) M), azathioprine (0.1-10 micrograms/ml), or cyclosporine (50-1000 ng/ml) and the amount of intracellular/secreted antigen was measured by radioimmunoassay. Intracellular HBsAg increased by 25.0-51.1% with prednisolone 10(-8)-10(-6) M (n = 14, P less than 0.05) and methylprednisolone 10(-9)-10(-6) M (n = 8, P less than 0.05). Immunocytochemistry of cytospins showed that the proportion of cells containing HBsAg increased by 20-38% with stronger staining, but the distribution of HBsAg remained diffusely cytoplasmic; the changes in intracellular pre-S1 and pre-S2 paralleled those of HBsAg. Secreted HBsAg was, however, not affected. There was also an increase in intracellular nucleocapsid antigens by 24.1-32.5% with an increase in hepatocytes containing nucleocapsid antigens by 8-18%. Methylprednisolone exerted similar effects to prednisolone. On the other hand, neither azathioprine (n = 11) nor cyclosporine (n = 12) had any effect on intracellular or secreted HBsAg or nucleocapsid antigens. These data indicate that corticosteroids, but not azathioprine or cyclosporine, enhance intracellular HBV antigen expression in this short-term culture system. This may be an important factor in the evolution of FCH and careful attention to the use of corticosteroids may be beneficial in patients with chronic HBV infection undergoing liver transplantation.

Adult↗
PubMed1991

Postshunt myelopathy.

Postshunt myelopathy is a rare, severely debilitating syndrome complicating portosystemic shunts that is characterized by spastic paraparesis. In this report we describe a 39-year-old woman with alcoholic liver disease and postshunt myelopathy resulting in an inability to walk. The syndrome did not become manifest until eight years after construction of a side-to-side portacaval shunt. This case is compared with reported literature on the subject.

Adult↗
PubMed1991

Expression of intrahepatic hepatitis D viral antigen in chronic hepatitis D virus infection.

To elucidate the biological importance of intrahepatic hepatitis D virus antigen, its expression was correlated with biochemical and histological inflammatory activity in 98 biopsy specimens from 68 patients seropositive for total antibody to the virus. Seventy five specimens were positive for intrahepatic nuclear antigen for HDV antigen accompanied by cytoplasmic HDV antigen in only one biopsy specimen. This group had significantly higher serum transaminase activities and inflammatory activity than the remaining cases that were negative for HDV antigen. Among the group positive for HDV antigen, there was no correlation between the proportion of hepatocytes containing HDV antigen and either serum transaminase activity or histological inflammatory indices. In 22 HDV antigen positive patients who had follow up biopsy specimens taken at a median of two years, the proportion with cirrhosis increased from 36% to 73%. Serum transaminase activities remained the same during this period, but the proportion of HDV antigen positive cells dropped. Follow up of 51 patients showed that 21 died or underwent liver transplantation within three years. The absence of an association between intrahepatic HDV antigen expression and progression of histological liver damage does not support the view that HDV is directly cytopathic to hepatocytes. Immune mediated mechanisms may have a role in the pathogenesis of chronic liver disease related to HDV infection.

Adult↗
PubMed1991

Export of intracellular HBsAg in chronic hepatitis B virus infection is related to viral replication.

Serum and liver HBsAg bear an inverse relation to each other during the evolution of chronic hepatitis B virus infection and the quantity of HBsAg in tissue rises gradually with time. In this study, intracellular and extracellular levels of HBsAg were measured by radioimmunoassay in primary culture of hepatocytes from 30 patients with chronic hepatitis B virus infection to determine a possible relationship with hepatitis B virus replication. Serum levels of HBsAg correlated with markers of active viral replication (serum hepatitis B virus DNA, p less than 0.005, and tissue HBcAg, p less than 0.02) but inversely with tissue HBsAg (p less than 0.05). In similar fashion, in vitro export of HBsAg was also related to the presence of active viral replication markers (serum hepatitis B virus DNA, p less than 0.02, and tissue HBcAg, p less than 0.05) and negatively with tissue HBsAg (p less than 0.001). Export of HBeAg also correlated positively with markers of active viral replication (serum hepatitis B virus DNA, p less than 0.05 and tissue HBcAg, p less than 0.05). Further experiments indicated that intrahepatic pre-S1 and pre-S2 correlated closely with intrahepatic HBsAg, indicating that a failure to export HBsAg was unlikely to be attributable to deficient intracellular expression of pre-S1 or pre-S2. These data indicate that in vitro primary hepatocyte culture of hepatitis B virus-infected cells provides an accurate reflection of in vivo export of HBsAg and that this is closely related to the presence of active viral replication.

Adult↗
PubMed1991

Effect of interferon-gamma on hepatitis B viral antigen expression in primary hepatocyte culture.

Interferon-alpha has been shown recently to selectively enhance hepatocyte expression of HBsAg/pre-S2 in chronic hepatitis B virus infection in a way that may enhance immune recognition. To determine the effect of interferon-gamma on hepatitis B virus antigen expression, hepatocytes isolated from patients with chronic hepatitis B virus infection were incubated in the absence or presence of interferon-gamma and viral antigen expression was assessed by both radioimmunoassay and immunocytochemistry using appropriate monoclonal antibodies. Interferon-gamma inhibited the expression of all hepatitis B virus antigens tested. Intracellular HBsAg measured by radioimmunoassay of sonicated hepatocytes fell by 29% with 1 U/ml (p less than 0.01) and 36% with 10 U/ml of interferon-gamma (p less than 0.001) compared with control treatment. Secreted HBsAg was reduced by 19% with 10 U/ml of interferon-gamma (p less than 0.01). Intracellular HBeAg was also decreased by 29% with 1 U/ml (p less than 0.05) and 42% with 10 U/ml of interferon-gamma (p less than 0.05), but no significant change was found in the amount of secreted HBeAg. The proportion of hepatocytes containing various hepatitis B virus antigens and the intracellular viral antigen staining densities also fell significantly with interferon-gamma incubation. Interestingly, the addition of interferon-gamma abolished the augmenting effect of interferon-alpha on intracellular HBsAg. These data indicate that interferon-gamma, in contrast to interferon-alpha, has an inhibitory effect on hepatocyte expression of all hepatitis B virus antigens including HBsAg/pre-S2, suggesting that this may be one factor that accounts for their difference in clinical activity in patients with chronic hepatitis B virus infection.

Cells, Cultured↗
PubMed1989

Foscarnet therapy in chronic hepatitis B virus E antigen carriers.

Foscarnet (trisodium phosphonoformate) is a novel antiviral agent that inhibits viral-specific DNA polymerase. In the present study, eight males with chronic HBV carriage (HBeAg and HBV-DNA seropositivity greater than 12 months) showing chronic persistent hepatitis (CPH) or chronic active hepatitis (CAH) on liver biopsy received either a continuous infusion of foscarnet at 0.15 mg/kg/min for 7 days or 180 mg/kg/day divided into three daily boluses for 2 weeks. In all eight, HBV-DNA levels fell during therapy (median, 401 pg/40 microliters serum; range, 4-3, 100) vs. pretreatment levels (median, 533 pg/40 microliters; range, 30-4, 175), but in none was HBV-DNA undetectable at any stage. Within 1 month, the HBV-DNA had risen to pretreatment levels in all but one patient (with the lowest pretreatment level), who cleared HBeAg and developed anti-HBe within 3 months. Two further patients were anti-HBe positive at 6 months, but their pretreatment serum HBV-DNA levels were already low, suggesting a high probability of spontaneous seroconversion. Toxicity was not evident with the continuous infusion, but for those receiving IV bolus therapy, serum creatinine and phosphate levels rose in three of four patients, necessitating a 25% dose reduction. There was no difference in the effect on serum HBV-DNA between the two regimes. We conclude that foscarnet has only modest antiviral activity in chronic HBV carriers.

Adult↗
PubMed1988

Biliary ascariasis.

We report biliary lithiasis secondary to infestation with Ascaris lumbricoides in a young man. We review the pathogenesis and clinical features of this condition and discuss the differential diagnosis.

Adult↗
PubMed1985

Lymphocyte populations with abnormal kappa:lambda ratios in reactive lymphoid hyperplasia.

The lymph node biopsies of 12 patients with lymphadenopathy due to reactive hyperplasia contained lymphocyte populations with increased percentages of B-cells and abnormal numbers of cells with single class surface immunoglobulins. Ten patients were followed for periods of 3-30 months: one developed a non-Hodgkin's lymphoma and one Hodgkin's disease. One other has persisting lymph node enlargement. Two patients had nonlymphoid malignancies. The other six remain well without lymphadenopathy. Twenty-five of 40 patients with reactive lymph node hyperplasia and normal kappa/lambda ratios followed for 9-36 months had a similar incidence of lymphoid malignancy and persistent lymph node enlargement. The follow-up data so far available do not support a hypothesis that reactive lymphoid hyperplasia with increased numbers of cells with single class surface immunoglobulin is associated with higher morbidity than reactive hyperplasia containing the usual polytypic lymphocyte populations.

Adolescent↗
PubMed1984

Increased numbers of lymphocytes with single class surface immunoglobulins in Hodgkin's disease.

Lymphocyte populations with abnormal kappa/lambda ratios have been described previously in B-cell non-Hodgkin's lymphomas and in lymphoid hyperplasia. The authors studied 12 patients in whom lymph nodes diagnostic of Hodgkin's disease contained evidence of monoclonal lymphocyte proliferation. One patient subsequently was found to have a B-cell lymphoma. The others have not been found to differ in any important characteristic from 25 Hodgkin's disease patients with normal ratios studied for comparison.

Adult↗