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Biomedical subjects

S Govindarajan

Publications and source records attributed to S Govindarajan.

At least 145 records · Page 8Linked to original sources

Pathologic and ultrastructural changes of acute and chronic delta hepatitis in an experimentally infected chimpanzee.

A hepatitis B surface antigen (HBsAg) chronic carrier chimpanzee experimentally superinfected with delta virus (DV) developed chronic DV infection. Over a period of 12 months, serologic and biochemical changes were correlated with morphologic abnormalities of the liver. Severe hepatic necrosis and inflammation accompanied the initial acute episode of hepatitis on Day 35 after inoculation, followed by complete resolution of these lesions over the next 3 months. A second episode of hepatitis occurred on Day 145, and severe necrosis and inflammation recurred along with the reappearance of delta antigen in the hepatocytes. Delta antigen persisted in the liver following the second episode of hepatitis and has remained positive throughout the observation period of 1 year. During the initial acute episode, the hepatocytes exhibited foamy cytoplasmic changes resembling microvesicular fat. However, ultrastructural studies of the same cells revealed only vacuolization of the cytoplasm without evidence of fat droplets. The inflammatory infiltrate during both episodes of hepatitis demonstrated a striking predominance of macrophages over lymphocytes. Hepatocyte abnormalities observed by electron microscopy included vacuoles, proliferated endoplasmic reticulum, and tubules similar to those seen in posttransfusion non-A, non-B hepatitis. However, the tubular and reticular abnormalities coincided with delta antigen expression in liver biopsies detected by direct immunoperoxidase staining and abnormal alanine aminotransferase levels in the serum, which suggests a possible causal relationship. Nuclear abnormalities were not seen.

Acute Disease↗

Role of delta agent in fulminant B hepatitis.

The prevalence of hepatitis Delta virus among those with fulminant hepatitis has been found to be 34 to 39% as reported from different parts of the world. The majority of these patients were parenteral drug users. The mortality rate appears to be age-related.

Hepatitis B↗

Immunoperoxidase study on adenomatoid tumor of the epididymis using anti-mesothelial cell serum.

The mesothelial origin of epididymal adenomatoid tumor is supported by the current study for the presence of mesothelial antigen in the tumor cells. By an indirect immunoperoxidase technique, anti-mesothelial cell serum showed positive cytoplasmic staining in five of the six adenomatoid tumors studied. Previous findings of the presence of strong cytoplasmic keratin and the absence of carcinoembryonic antigen and Factor VIII-related antigen in these tumor cells are also confirmed by this study.

Antigens↗

Morphologic and immunohistochemical features of fulminant delta hepatitis.

Recent studies have indicated that some cases of fulminant hepatitis that were ostensibly type B were actually acute viral hepatitis, types B and delta, or persistent hepatitis, type B with superimposed acute delta infection. Histologic characterization of the various types has not yet been undertaken. Within ten to 37 days of the onset of initial symptoms, liver tissues from a total of 16 patients who had acute delta hepatitis with fulminant clinical courses were examined. Tissues were from biopsies in nine cases and from autopsies in seven. Based on the serologic absence of IgM hepatitis B core antibody, chronic forms of hepatitis B with acute delta infection were diagnosed in five of the 16 patients. The underlying liver disease in three of these five patients was identifiable as chronic active hepatitis with fibrosis, and that in the others was apparently persistent hepatitis B. Coded liver tissues from these seven autopsies were evaluated without the knowledge of serologic diagnosis for qualitative and quantitative light microscopic features, together with autopsy liver tissues from five patients with fulminant B hepatitis without serologic evidence of delta infection and five patients with fulminant non-A, non-B hepatitis. No specific features that would allow discrimination among these three types of hepatitis were found.

Acute Disease↗

Acute delta hepatitis without circulating HBsAg.

Infection with the delta agent can only occur in the context of coexistent hepatitis B virus infection. We describe a patient in whom the clinical features of acute delta hepatitis developed when seroconversion from hepatitis B surface antigen to antibody had already occurred and diagnosis of recent acute hepatitis B was based on high titre IgM antibody to hepatitis B core antigen. We discuss the significance of such a serological profile, not previously described.

Acute Disease↗

Delta agent superinfection. Rapidly progressive liver disease in a hepatitis B virus carrier.

We report a case of rapidly progressive chronic active hepatitis (CAH) following acute delta infection in a previously asymptomatic hepatitis B virus carrier. Serologic evidence of delta superinfection coincided with an acute icteric hepatitis, and was followed by the development of clinically evident chronic liver disease. The liver biopsy specimens documented the acute hepatitis and subsequent progression of severe CAH. This case illustrates the clinical and pathologic changes that may follow acute delta infection in chronic hepatitis B carriers.

Adult↗

Serum hepatitis B virus-DNA in chronic hepatitis B and delta infection.

Hepatitis B-associated delta agent, a defective RNA virus requiring helper functions of hepatitis B virus (HBV), has been shown to interfere with HBV replication. Low titers of serum hepatitis B surface antigen, absence of hepatitis B e antigen, and low levels of stainable hepatitis B core antigen in liver cells usually seen in chronic delta infection are indirect evidences of such an interference. Measurement of serum HBV-DNA by hybridization with phosphorus 32-labeled HBV-clone DNA is the most sensitive method currently available to detect HBV replication. Using this method, we found that only two of 13 patients with chronic delta infection showed serum HBV-DNA positivity in comparison with seven of 14 patients who had chronic hepatitis B without delta infection. These two groups were matched for hepatitis B e antigen status and liver histopathology. Thus, we report direct evidence of delta agent interfering with the replication of the helper (HBV) virus.

Chronic Disease↗

Fulminant delta hepatitis in chronic hepatitis B infection.

Two male homosexual patients, one an intravenous (IV) drug abuser, had hepatitis B surface antigen-positive fulminant hepatitis. On the basis of tests for IgM antibody to hepatitis B core antigen (HBcAg) and for IgM and IgG antibodies to delta agent, acute delta hepatitis in chronic hepatitis B infection was diagnosed. The delta agent appeared to have a role in producing fulminant hepatic failure. Accurate diagnosis of fulminant hepatitis may be impossible without recourse to tests for IgM antibody to HBcAg and antibodies to delta agent. Although delta hepatitis in the United States primarily affects IV drug abusers, this infection can also occur in male homosexuals.

Acute Disease↗

Prevalence of delta antigen/antibody in B-viral-associated hepatocellular carcinoma.

Sera from 39 patients with B-viral associated hepatocellular carcinoma were studied for the presence of delta antibody using solid-phase blocking radioimmunoassay. Only one patient (2.5%) had circulating delta antibody in the serum, and stainable delta antigen in the nuclei of the nontumor liver. A similar study of the sera of 57 patients with chronic B-viral disease without hepatocellular carcinoma revealed 18 patients (31.5%) with delta antibody. This significant difference (P less than 0.001) in the prevalence of delta antibody among these two groups is probably related to the epidemiologic background, reflected as a racial difference.

Animals↗

Prevalence of delta agent among Chinese in Taiwan and Los Angeles.

The prevalence of delta agent among 120 Chinese patients with HBsAg-positive chronic active and hepatocellular carcinoma from Taiwan and Los Angeles were studied by serological assay for antibody to delta antigen and immunoperoxidase staining for delta antigen in the liver biopsies. Of 120 patients, only four with chronic active hepatitis and one with hepatocellular carcinoma from Taiwan had antibody to delta antigen in their sera, while none was detected in the patients from Los Angeles. Indirect immunoperoxidase staining for delta antigen in the liver tissue from three of the patients with circulating anti-delta was positive. Thus, the overall prevalence of delta infection was 5.8% among the 86 patients from Taiwan, and 0% in the 34 Chinese patients from Los Angeles.

Adult↗

Evaluation of enzyme immunoassay for anti-HBc IgM in the diagnosis of acute hepatitis B virus infection.

Corzyme-MTM (Abbott Laboratories, North Chicago, IL), a newly introduced kit for the measurement of serum IgM antihepatitis B core antigen by enzyme immunoassay, was evaluated for the diagnosis of acute B-viral hepatitis (AVH-B). The study included 175 acute viral hepatitis patients with transient hepatitis B surface antigen (HBsAg). Sera from 160 were tested on multiple occasions until their HBsAg cleared. IgM anti-HBc was found in 171 of 175 patients (98.4%) during the acute phase. The serum samples from 42 patients with liver biopsy-proven chronic active hepatitis, type B (CAH-B), and 18 patients with persistent hepatitis, type B (PH-B), were analyzed for the presence of IgM anti-HBc, using the same technic. None of the sera from 42 patients with CAH-B and only 2 of the 18 patients with PHB had IgM anti-HBc. Thus, the measuring IgM anti-HBc using Corzyme-M kit is helpful in the diagnosis of AVH-B and in the discrimination of acute from chronic HBV infections.

Acute Disease↗

Immunohistochemical localization of the delta antigen associated with hepatitis B virus in liver biopsy sections embedded in Araldite.

Immunohistochemical localization of the delta antigen in the nuclei of the liver tissue embedded in Araldite was successfully carried out by an indirect immunoperoxidase technique. Deplasticization, using sodium ethoxide solution, was required prior to application of immunochemical reagents. The specificity of the staining was confirmed by the abolition of positive staining after absorption of the antibody with the delta antigen.

Biopsy↗

Chronic delta infection and liver biopsy changes in chronic active hepatitis B.

The delta agent consists of particles of RNA nucleoprotein and is probably a defective virus present only in the livers of patients with B-viral acute or chronic liver disease. Its frequency is significantly greater in patients with chronic active hepatitis B than in those with persistent viral hepatitis B, suggesting that chronic delta infection may increase the severity of liver disease. We studied biopsy or autopsy tissue samples from 57 patients with chronic active hepatitis B for morphologic differences between chronic delta-positive and delta-negative cases. The delta-positive cases had significantly greater portal and parenchymal inflammatory change, parenchymal necrosis, and nuclear dysplastic and polyploid change than did the delta-negative cases. These findings suggest that chronic delta infection, with ongoing delta replication, may increase the degree of hepatic damage, and possibly hasten the progression of liver disease, in patients with chronic active hepatitis B.

Antibodies, Viral↗

The bile duct adenoma. A lesion distinct from Meyenburg complex.

We studied 16 cases of bile duct adenomas, lesions that are distinct from Meyenburg complex. The former lesion is made up of small tubular structures with little or no lumen, is usually single and subcapsular, and is unrelated to cystic disease. It must be differentiated from early carcinoma. Of the six cases encountered at surgery, follow-up information was available on two patients. There was no development of carcinoma in any of these cases.

Adenoma↗