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Biomedical subjects

S Govindarajan

Publications and source records attributed to S Govindarajan.

At least 73 records · Page 4Linked to original sources
PubMed1994

Short-term prednisone therapy affects aminotransferase activity and hepatitis C virus RNA levels in chronic hepatitis C.

BACKGROUND/AIMS: The effects of corticosteroids on chronic hepatitis B have provided insight into the mechanism of liver cell injury caused by hepatitis B. In this study, this model was applied to investigate the effects of prednisone on alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels in chronic hepatitis C. METHODS: Ten patients with chronic hepatitis C who had increased levels of ALT and HCV RNA detectable in serum were given a 7-week course of a tapering dose of prednisone. Quantitation of serum HCV RNA was determined by polymerase chain reaction (PCR) and by branched-chain DNA amplification. RESULTS: ALT levels decreased in 8 of 10 patients during therapy. Mean ALT levels of all 10 patients decreased from 184 to 84 U/L (P = 0.002) and then rebounded in 7 of the 8 patients after discontinuation of prednisone. HCV RNA was detectable by the branched DNA technique in 9 of 10 patients. These values increased in all 9 patients during prednisone therapy. The mean serum HCV RNA levels increased from 40.9 before treatment to 414.3 Eq/mL x 10(5) during treatment (P = 0.043). Using PCR, HCV RNA titers increased one log-fold in 8 of 10 patients (geometric mean of 1:4420 to 1:23410). HCV RNA levels decreased to pretreatment values within a mean of 2.8 weeks (range, 1-5) after discontinuation of prednisone. CONCLUSIONS: These responses in ALT and HCV RNA suggest the participation of an immune-mediated mechanism in the liver cell injury in chronic hepatitis C.

Adult↗
PubMed1994

The effect of HIV disease on serum markers of hepatitis delta infection in intravenous drug abusers.

The prevalence of serum markers of delta hepatitis was determined prospectively in 82 intravenous drug abusers at various stages of human immunodeficiency virus (HIV) disease. Seventeen were HIV negative, 30 were HIV positive without acquired immunodeficiency syndrome (AIDS) and 35 had been diagnosed as having AIDS. Antihepatitis D virus (HDV) in serum was measured by a commercially available enzyme-linked immunosorbent assay (ELISA) and also by solid phase capture radioimmunoassays (RIAs) for immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-HDV. HDV antigen and hepatitis B virus (HBV) DNA were also measured. Hepatitis B surface antigen (HBsAg) and anti-HBs were determined by using a commercially available RIA. Anti-HDV (RIA) was only detected in serum that contained HBsAg. These anti-HDV (RIA) positive samples also tested positive with the commercial anti-HDV electroimmunoassay. In addition, the commercial anti-HDV ELISA detected anti-HDV in some serum samples that were negative for HBsAg; these anti HDV-positive HBsAg-negative samples were frequently lipemic or contained rheumatoid factor. The prevalence of HBsAg and anti-HBs did not differ significantly with the stage of HIV disease. HBsAg was detected in 3 of 13 (23%) HIV-negative, 5 of 29 (17%) HIV-positive, and 4 of 18 (22%) patients with AIDS. IgG and IgM anti-HDV (RIA) was positive in 2 of 3 HIV-negative and 4 of 5 HIV-positive pre-AIDS HBsAg-positive subjects. However, none of 4 AIDS patients had anti-HDV. The difference between AIDS and non-AIDS patients was statistically significant (Fisher's exact test, p = 0.03). HDV antigen was detected in serum from one AIDS patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Update on chronic hepatitis: changing views on nomenclature and outcome.

As old terminologies begin to fail, the author says that the world of hepatopathology is ready to reassess the classification of chronic hepatitis. This chapter reviews the current status of diagnostic features and terminologies for chronic B, C, and D hepatitis and discusses recent recommendations for future directions in nomenclature.

Chronic Disease↗
PubMed1993

Variation in course of hepatitis E in experimentally infected cynomolgus monkeys.

Five cynomolgus monkeys (Macaca fascicularis) developed hepatitis after inoculation with a prototype strain of hepatitis E virus (HEV) from Pakistan. Although all 5 monkeys displayed liver enzyme elevations, viremia, virus secretion in feces, and seroconversion, two different patterns of these parameters were observed. For 4 monkeys, increased alanine aminotransferase (ALT) activity was first observed on days 21-26, viremia occurred before and during enzyme elevation, and the animals seroconverted coincidentally with the end of viremia or shortly thereafter. One of these monkeys had a more severe hepatitis, with peak ALT values more than twice the peak levels of the other monkeys. The fifth monkey developed biphasic hepatitis with peaks of ALT activity on days 26 and 54. In this case, viremia and seroconversion were correlated only with the second peak of enzyme elevation and liver histopathology only with the first peak. Viral shedding in this fifth animal lasted two times longer than in other animals.

Alanine Transaminase↗
PubMed1993

The stability of serum hepatitis C viral RNA in various handling and storage conditions.

To investigate whether certain handling and storage conditions of serum samples could alter the sensitivity and specificity of the hepatitis C virus (HCV) RNA assay, we studied serum samples obtained from five patients known to be positive for HCV RNA and two patients with autoimmune chronic active hepatitis. Samples were subjected to one of the following conditions: (1) immediate storage at -20 degrees C, (2) five freeze-thaw cycles, (3) storage at 4 degrees C for 5 days, and (4) storage at room temperature for 5 days. Detection of HCV RNA was performed by polymerase chain reaction. Titers of HCV RNA were determined by serial end point dilutions. We found that the titer of HCV RNA was reduced by only one logfold in samples subjected to conditions 2 through 4 in two of the five patients. False-positive results were not seen with the serum samples that were subjected to similar conditions from the two negative control patients. We conclude that serum HCV RNA is resistant to degradation under routine laboratory handling and storage conditions.

Blood Preservation↗
PubMed1992

Lack of protective immunity against reinfection with hepatitis C virus.

Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV.

Acute Disease↗
PubMed1992

Improved detection of hepatitis C virus antibodies in high-risk populations.

Sera from 483 patients at high (group 1, n = 313) and lower (group 2, n = 170) risk for exposure to hepatitis C were tested for antibodies to hepatitis C using first-generation (c100-3) and second-generation enzyme-linked immunosorbent assays and four-antigen recombinant immunoblot assay. The second-generation enzyme-linked immunosorbent assay and nitrocellulose-based immunoblot assay differ from c100-3-based systems in the addition of expression products from the NS3/NS4 (c33c, c200) and putative nucleocapsid (c22-3) region of the hepatitis C genome. In group 1, the sensitivity of detection of hepatitis C antibodies was 45%, 55% and 46% by the first- and second-generation enzyme-linked immunosorbent assays and recombinant immunoblot assay, respectively. In group 2, antibodies were detected by each test system in 26%, 32% and 7% of patients, respectively. Most sera (99%) reactive with the first-generation enzyme-linked immunosorbent assay were reactive with the second-generation enzyme-linked immunosorbent assay (in group 1, 89% of these specimens demonstrated reactivity to at least one antigen with the immunoblot assay, compared with only 31% in group 2). An additional 12% (group 1) and 6% (group 2) of specimens demonstrated reactivity with the second-generation enzyme-linked immunosorbent assay only (of these, 75% [group 1] and 9% [group 2] demonstrated reactivity to at least one antigen with the immunoblot assay). Ninety-eight percent of specimens not reactive with both enzyme-linked immunosorbent assay test systems were also nonreactive by recombinant immunoblot assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗
PubMed1992

Spontaneous exacerbation of disease activity in patients with chronic delta hepatitis infection: the role of hepatitis B, C or D?

Forty-six patients with chronic hepatitis delta virus infection were followed between 6 and 116 mo (mean = 32.8 mo; median = 24 mo). Nineteen patients (41%) demonstrated clinical courses with episodes of biochemical reactivation (ALT levels greater than or equal to 10 times baseline values [group A]). Twenty-seven patients (59%) had stable clinical courses without biochemical reactivation (group B). Patients in group A were younger than those in group B (30.5 vs. 35.3 yr; p = 0.03), were less likely to be intravenous drug abusers (16% vs. 52%; p = 0.01) and were more likely to be homosexual (58% vs. 22%; p = 0.01). Serum hepatitis B virus DNA, hepatitis delta virus RNA, IgM antibody to HBc, HBeAg, antibody to HBe and IgG and IgM antibody to hepatitis delta virus were measured in all patients. In group A, these markers were studied before and during reactivation and during remission. In group B, these parameters were studied in a random fashion at 7- to 10-mo intervals. The presence of antibodies to human immunodeficiency virus and hepatitis C virus was assessed in all patients. A total of 38 biochemical reactivation episodes was noted among the 19 patients in group A. Eleven had sequential changes in hepatitis delta virus markers, suggesting that the exacerbations were due to hepatitis delta virus. In three, the sequential changes of viral markers were consistent with the exacerbations due to hepatitis B virus. In five other patients, no sequential changes in viral markers could be demonstrated to correlate with the biochemical exacerbations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Evolution of hepatitis delta virus RNA during chronic infection.

The complete RNA sequences of hepatitis delta virus (HDV) isolated at three different time points from a chronic delta hepatitis patient were determined. These time points represented three different periods of clinical flare-ups. The sequence analysis showed that these three different HDV isolates evolved at a rate ranging from 3.0 x 10(-2) to 3.0 x 10(-3) substitutions/nucleotide/year, depending on the period of infection. The evolution rates appeared to correlate with the changes of clinical pictures of hepatitis, i.e., the more drastic the change in the symptom of hepatitis was, the more nucleotide changes were detected. Except during the transition from the acute phase to chronic phase of delta hepatitis, when there was a much larger number of changes in HDV RNA sequence, the overall evolution rate of HDV RNA in the chronic phase appeared to be similar to those of other RNA viruses. Sequence relationship of these HDV RNAs suggested that acute exacerbations in chronic delta hepatitis were associated with the evolution of the persistently infected HDV, rather than resulting from new viral infections. However, some of the mutations were not cumulative, suggesting that HDV isolated at a later time was not directly evolved from the immediately previous one. Thus, HDV at any time point was a mixture of viruses with slight sequence variations, and a specific HDV RNA species was selected from this virus population under different environments. These findings indicate that HDV RNA is heterogeneous and evolves at a fast rate. The evolution rates in different parts of HDV RNA also varied. The evolution rate of HDV RNA determined here was higher than the ones determined previously from partial RNA sequences of two Japanese HDV isolates.

Adult↗
PubMed1992

Inactivated hepatitis A vaccine: active and passive immunoprophylaxis in chimpanzees.

Studies of active and passive immunoprophylaxis were carried out in chimpanzees to determine whether a candidate hepatitis A virus (HAV) vaccine could stimulate antibody to HAV (anti-HAV) that was qualitatively similar to anti-HAV stimulated by natural infection. Normal immune globulin (Ig) was prepared from plasma obtained from human volunteers before and after vaccination with the HAV vaccine, and these preparations or commercially prepared Ig were administered to chimpanzees. Protective efficacy was compared to that obtained after vaccination of chimpanzees. As expected, pre-vaccination Ig did not protect chimpanzees against challenge with virulent hepatitis A. In contrast, chimpanzees were protected against hepatitis A by Ig prepared from volunteers who had received hepatitis A vaccine. The protection was qualitatively similar to that afforded by commercial normal Ig containing convalescent anti-HAV. The minimum protective dose of passively acquired anti-HAV was approximately the minimum dose detectable by serological means. This information will be useful in calculating minimum acceptable titres of anti-HAV in normal Ig. Whereas administration of Ig protected chimpanzees against hepatitis A pathology, it did not protect them from infection with HAV. Thus, these chimpanzees were protected by classical passive-active immunoprophylaxis. In contrast, chimpanzees actively immunized with HAV vaccine were apparently protected against both hepatitis A pathology and HAV infection. The mechanism of this complete protection is unknown but may simply represent the higher titre of anti-HAV in the vaccinated chimpanzees, compared to the passively protected animals.

Animals↗
PubMed1992

Hepatitis C antibodies in patients with alcoholic liver disease commonly have an identifiable risk factor.

Hepatitis C virus (HCV) antibodies detected by radioimmunoassay (RIA) and immunoblot assay were determined in 139 patients with alcoholic liver disease (ALD). Risk factors for exposure to HCV were recorded. Anti-HCV was detected by RIA in 38 (27%), but only 18 (13%) were confirmed with an immunoblot assay. One hundred seven (77%) had risk factors. Of these 107, anti-HCV was detected in 36 by RIA and in 17 by immunoblot assay. Only 2 of 32 patients without risk factors had anti-HCV detected by RIA (1 was reactive with immunoblot, p < 0.05 vs. patients with risk factors). Parenteral drug use and multiple heterosexual contacts were significantly associated with anti-HCV. Age, sex, duration of alcoholism, race, and birthplace did not correlate with detectable HCV antibodies.

Adult↗
PubMed1992

Hepatocellular carcinoma in a case of Wilson's disease.

Hepatocellular carcinoma has rarely been reported in Wilson's disease, particularly in women. We describe the case of a female patient who was diagnosed with Wilson's disease at the age of 39 years, after presenting with severe neurological symptoms. She had significant neurological improvement following penicillamine therapy and succumbed to hepatocellular carcinoma at the age of 72 years, following 33 years of penicillamine therapy. The patient described here was the oldest and only the third female patient with hepatocellular carcinoma complicating Wilson's disease to be reported in the literature.

Adult↗
PubMed1992

cDNA clone of hepatitis A virus encoding a virulent virus: induction of viral hepatitis by direct nucleic acid transfection of marmosets.

Direct inoculation of marmoset livers with an in vitro transcription mixture containing cDNA and full-length genomic RNA transcripts of hepatitis A virus resulted in acute viral hepatitis. Elevations in serum levels of liver enzymes were correlated with appearance of antibody to hepatitis A virus. Genomes of infectious hepatitis A virus isolated from the feces of transfected marmosets contained the same mutation as the cDNA template used for transfection. Liver biopsies confirmed that the virus encoded by the cDNA clone induced histopathological changes equivalent to those caused by virulent wild-type virus.

Animals↗
PubMed1992

Incidence of hepatitis D virus infection in Japanese patients with hepatocellular carcinoma--immunohistochemical investigation of the delta antigen.

In order to clarify the incidence of the delta agent among hepatocellular carcinomas (HCCs) in Kurume, where the hepatitis B infection and its related HCC are most prevalent in Japan, liver tissues from sero hepatitis B surface antigen-positive autopsy cases, with or without HCC, were immunohistochemically investigated for detection of the delta antigen. Only one patient (1.7%) among 58 patients with HCC was found to have delta-antigen in the nuclei in the hepatocytes, which were diffusely distributed throughout the non-cancerous liver. None of 26 patients with liver cirrhosis showed delta-antigen in the liver tissue. The incidence is so low that the delta agent is unlikely to have a role in the development of HCC in our areas.

Antigens, Viral↗
PubMed1992

Molecular cloning and sequence analysis of an isolate of hepatitis C virus from Southern California, U.S.A.

We obtained a cDNA clone representing a partial RNA sequence of a human hepatitis C virus (HCV) isolate from Southern California. RNA was extracted from the liver tissue of a patient with post-transfusion hepatitis, and used for cDNA synthesis and polymerase chain reaction (PCR) amplification using oligonucleotide primers specific for the prototype HCV RNA. The cDNA clone obtained contains 585 base pairs of HCV sequences and represents the region encoding the putative nonstructural protein NS3 of HCV. Sequence analysis of this clone showed that it shares 93.8%, 78.7% and 79.6% similarity, respectively, with the previously published American, Japanese and Taiwanese isolates at the nucleotide level, indicating the heterogeneity of HCV RNA in different geographic areas. By contrast, it shares 97.3%, 92.9% and 92.9% with these respective isolates at the amino acid level, suggesting the functional conservation of viral genes.

Amino Acid Sequence↗