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Biomedical subjects

S Govindarajan

Publications and source records attributed to S Govindarajan.

162 records · Page 9Linked to original sources
PubMed1984

Fulminant B viral hepatitis: role of delta agent.

The prevalence of delta-markers among 71 patients with fulminant B viral hepatitis was found to be 33.8%. The majority of the patients with delta-markers showed serologic evidence of simultaneous acute delta-infection and B viral infection. Only 5 of the 24 patients with serologic markers of acute delta-infection in this fulminant group were presumably infected chronically with hepatitis B virus as shown by the absence of immunoglobulin M antibody to hepatitis B core antigen. A study of serologic markers of acute delta-infection among 118 patients with nonfulminant acute B viral hepatitis, in contrast, revealed only 4.2% incidence. This significant difference in the prevalence of simultaneous acute B and delta viral infections between the fulminant and the nonfulminant acute hepatitis groups indicates a higher morbidity rate associated with simultaneous infection. When the fulminant group was divided into acute B viral infection without delta-markers (subgroup 1), simultaneous acute B and delta-infections (subgroup 2), and chronic asymptomatic B with acute delta-infections (subgroup 3), for comparison of survival data, the mortality rate was not significantly different in the first two groups when the patients were age matched.

Acute Disease↗
PubMed1983

A lymphocytotoxic factor(s) in plasma of patients with minimal change nephrotic syndrome: partial characterization.

The incidence, relationship to clinical disease, and physical characteristics of a plasma cytotoxic factor(s) were studied in steroid-responsive minimal change nephrotic syndrome (MCNS) and other renal diseases. Plasma activity was found in 76% of 67 children with MCNS and in 67% of 9 children with focal segmental sclerosis (FSS). Of 31 normal adults and children and 7 adults with membranous glomerulonephritis, only 1 individual had toxic plasma. In MCNS, degree of plasma activity was not related to clinical disease, prednisone dosage, or serum levels of IgG or alpha-2-macroglobulin. The active factor(s) was found more frequently in plasma than in serum, was heat stable and nondialyzable by selected filtration, and was approximately 100,000 to 300,000 molecular weight. By DEAE column chromatography, activity coincided with fractions containing IgA and IgM but not IgG. While the nature of the plasma factor(s) has not been identified, these data indicate that MCNS plasma may adversely affect lymphocyte viability by a slow process of cytotoxicity requiring 24 or more hr, and that such plasma activity occurs frequently in children with MCNS and also with the more severe FSS.

Adolescent↗
PubMed1983

Identification of T lymphocytes and subsets in liver biopsy cores of acute viral hepatitis.

The lymphocytic infiltrates were examined in 10 liver biopsy cores taken from nine cases of acute viral hepatitis (AVH), using cryostat sections. The cells were identified and characterized, using the monoclonal antibodies to T lymphocytes (OKT3), T helper cells (OKT4), and T suppressor/cytotoxic cells (OKT8) in an indirect immunofluorescence technique. Of the nine cases of AVH, three were type B, one was acute type A, with underlying chronic hepatitis type B, and the remaining five were non-A, non-B, with no serological markers. One of the patients with acute non-A, non-B hepatitis was biopsied twice with a 2-month interval due to clinical relapse. Both these biopsies were included in the study. The cellular infiltrates, both lobular and portal, were graded from 1 + to 4 + and evaluated by examining the histological sections stained with hematoxylin and eosin. The approximate percentage of each set of cells staining with different antibodies was estimated in each case. The predominant cells were found to be T lymphocytes in all nine cases of AVH; of the two subsets, T suppressor/cytotoxic cells formed the majority in all except one patient who had AVH type A superimposed on chronic B hepatitis.

Acute Disease↗
PubMed1983

Prevalence of delta-antibody among chronic hepatitis B virus infected patients in the Los Angeles area: its correlation with liver biopsy diagnosis.

The overall prevalence of delta-antibody among 80 patients with chronic infection of hepatitis B virus in the Los Angeles area was found to be 24%. Twenty-three patients had a histologic diagnosis of persistent hepatitis and 57 had chronic active hepatitis with or without cirrhosis. Only 1 patient among those with persistent viral hepatitis had delta-antibody, whereas 18 with chronic active hepatitis had delta-antibody in their sera (p less than 0.05).

Antibodies, Viral↗
PubMed1982

Immunocytochemical identity of hepatocellular hyalin in alcoholic and non-alcoholic liver diseases.

Intracellular, eosinophilic, hyaline inclusions (alcoholic hyalin, Mallory bodies) are found in livers of patients with a number of hepatic disorders, although they are most common in alcoholic liver disease. Tissues from patients with primary biliary cirrhosis, jejunoileal bypass, hepatocellular carcinoma, Wilson's disease, and Indian childhood cirrhosis were all positive for hyalin by hematoxylin and eosin staining. Immunocytochemical labeling, using guinea-pig antiserum specific for alcoholic hyalin, was utilized to determine the extent of crossreactivity between hepatocellular hyalin in these various conditions. This antiserum bound to hyalin in fixed paraffin-embedded sections of all liver tissues studied as detected by indirect immunoperoxidase labeling. Binding to normal human liver, however, was restricted to light staining at the surface of hepatocytes. Preimmune guinea-pig serum did not bind to either normal liver or to the test tissues. Our results suggest that hyalin found found in a diverse group of liver conditions represents an immunologically related structure and that its formation may involve a common mechanism.

Adolescent↗
PubMed1980

Hemoglobin Ohio (beta 142 Ala replaced by): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis.

Hemoglobin Ohio [beta 142 (H20) Ala replaced by Asp] was found in three members of a white family, all of whom showed erythrocytosis. The variant hemoglobin has a high oxygen affinity, a reduced Bohr effect, and diminished cooperativity. The functional abnormalities of Hb Ohio are explained by the proximity of the substituent beta 142 residue, both to beta 143 His, which is involved in the DPG binding site of hemoglobin, and to the critical C terminal region of the beta chain, which participates in the stabilization of the deoxy (T) conformation.

Adult↗
PubMed1979

IgD myeloma. Report of a case with unusual clinical and immunologic features.

A case of IgD myeloma in a 48-year-old Caucasian man is reported. The unusual features of this case included the absence of osteolytic lesions by x-ray, absence of anemia, absence of monoclonal spike on serum electrophoresis, association of kappa light chains, absence of Bence Jones proteinemia and Bence Jones proteinuria, and a remarkable, temporary clinical response to therapy. Immunoelectrophoresis of whole serum yielded a pattern consistent with IgD kappa monoclonal gammopathy. Immunoelectrophoresis of a pure serum IgD preparation, previously separated by gel chromatography (Sephadex G-200), revealed definitive information about an IgD kappa monoclonal gammopathy. Immunomicroscopic examination of bonemarrow smears showed the presence of delta and kappa chains only in the cytoplasm of plasma cells.

Humans↗
PubMedDate not supplied

alpha-1-Antitrypsin phenotypes in hepatocellular carcinoma.

alpha-1-Antitrypsin deficiency due to homozygous Pi ZZ state is reported to be associated with cirrhosis and hepatocellular carcinoma (HCC); however, the role of heterozygous Pi Z state is not definitely known. In order to investigate the possible association, we studied the phenotypic distribution of alpha-1-antitrypsin variants (Pi) in 124 cases of HCC. Two thousand ten normal American Red Cross blood donors were studied as controls. Twelve patients with HCC had aberrant phenotypes, an incidence of 9.67% as compared to 8.36% among normal controls. Nine of 12 patients with HCC with aberrant Pi type had cirrhosis; 5 of the 9 had cirrhosis due to hepatitis B virus; 2 of the 9 had alcoholic liver disease with cirrhosis, and 2 had cryptogenic cirrhosis. The three patients with HCC arising in noncirrhotic livers who also had aberrant Pi phenotypes, had a relatively rare variety of HCC called fibrolamellar type. Z gene was found in five patients: all five were MZ. Incidence of MZ phenotype in HCC was similar to that of the normal control population (4.0% in HCC and 2.9% in the controls). However, 3 of 5 MZ were associated with fibrolamellar HCC. Another aberrant phenotype found among the patients with HCC was MF (fast moving) which occurred with an incidence of 2.41% as compared to none in the control group. In conclusion, we found no significant increase in the incidence of Z gene among 124 patients with HCC as compared to the normal population.

Adult↗
PubMedDate not supplied

Natural course of delta superinfection in chronic hepatitis B virus-infected patients: histopathologic study with multiple liver biopsies.

We evaluated the natural course of delta superinfection in patients with chronic B viral hepatitis by examining serial liver biopsy specimens from 23 patients. The mean follow-up period was 2.5 years, and the average number of liver biopsies per patient was 2.8. The striking features were: (i) the prolonged acute hepatitis-like necroinflammatory activity (mean = 15 months) following acute delta hepatitis and (ii) rapid progression to severe forms of liver disease within a mean interval of 24 months from the onset of delta superinfection. Although there was a high frequency of stainable delta antigen (90%) in these liver biopsy specimens, there was no correlation between the degree of positivity and the histopathological changes.

Antibodies, Viral↗
PubMedDate not supplied

Immunohistochemical distribution of renal prostaglandin endoperoxide synthase and prostacyclin synthase: diminished endoperoxide synthase in the hepatorenal syndrome.

To evaluate possible causes of the diminished prostaglandin production in advanced hepatorenal syndrome, prostaglandin endoperoxide synthase and prostacyclin synthase were localized and semiquantitated by immunofluorescence in postmortem, biopsy and nephrectomy renal tissues. In normal kidneys, antiprostacyclin synthase serum caused intense staining in peritubular capillaries, in the adjacent renal interstitial cells and in glomerular mesangial regions. Antiprostaglandin endoperoxide synthase serum caused staining of collecting duct epithelial cells, cells of the thin ascending limb and possibly glomerular mesangial cells. Prostacyclin synthase-positive staining was graded 5+ (scale of 0+ to 5+) in all kidney samples. Medullary collecting tubule prostaglandin endoperoxide synthase-positive staining was graded 4+ or 5+ in kidney samples from patients with acute tubular necrosis or acute tubulointerstitial nephritis and from patients with liver failure without the hepatorenal syndrome. However, prostaglandin endoperoxide synthase-positive staining was markedly diminished or absent (average 1+) in patients with the hepatorenal syndrome. These data suggest that loss of the medullary prostaglandin endoperoxide synthase is the cause of diminished urinary prostaglandin E2 excretion in the hepatorenal syndrome.

Adult↗
PubMedDate not supplied

Spontaneous reactivation of hepatitis B in Chinese patients with HBsAg-positive chronic active hepatitis.

Eleven patients of Chinese origin experienced spontaneous reactivation of chronic active hepatitis B. Eight HBsAg-positive patients were followed for an average of 15 months prior to, while three others presented during reactivation. Fatigue, hepatomegaly and jaundice were frequent findings. Elevation of both serum ALT (average = 1,212 units per liter) and hepatitis B virus DNA levels were noted in all patients, and reactivation lasted an average of 4.4 months. During resolution, clinical symptoms abated, serum ALT levels reverted toward normal, and in nine patients, the hepatitis B virus DNA values became undetectable. All patients lacked evidence for acute hepatitis A, Epstein-Barr Virus, cytomegalovirus or hepatitis delta virus infection. Histologic findings of liver tissue from eight patients showed piecemeal necrosis and fibrosis. Within the parenchyma, varying degrees of hepatocytolysis with cuffing, perivenular necrosis and acidophilic bodies were noted. Ground-glass cells and regenerative changes also were observed. Cirrhosis was not present in any of the liver biopsies. These findings suggest that spontaneous reactivation of hepatitis B occurs in heterosexual patients with chronic active hepatitis B and contributes to chronic inflammation and to the progression of their liver disease.

Adult↗
PubMedDate not supplied

Status of hepatitis B virus DNA in alcoholic liver disease: a study of a large urban population in the United States.

Two reports have shown hepatitis B virus DNA in serum and liver tissue in alcoholic liver disease with negative serum HBsAg, suggesting a pathogenetic role for hepatitis B virus. We studied hepatitis B virus DNA in serum and liver from three groups of alcoholic patients; (Group 1) 50 patients without liver disease, (Group 2) 108 patients with alcoholic liver disease and (Group 3) five patients with alcoholic liver disease and hepatocellular carcinoma. Serum was tested for HBsAg, anti-hepatitis B core and anti-hepatitis B surface by radioimmunoassay and hepatitis B virus DNA by direct spot hybridization. Liver tissue from Groups 2 and 3 (113 patients) was examined by Southern blot analysis using 32P-labeled hepatitis B virus DNA clone from pBR322. Controls were 21 patients with chronic hepatitis B virus (14 patients with chronic active hepatitis, seven patients with cirrhosis and hepatocellular carcinoma). Serum and tissue were analyzed for hepatitis B virus DNA. Hepatitis B virus DNA was not detected in either serum or liver tissue in any of the 163 patients (Groups 1 to 3). In contrast, among the controls, hepatitis B virus DNA was present in the serum of 15 of the 21. Tissue DNA in those with chronic active hepatitis revealed 10/14 with free hepatitis B virus DNA, two with integrated sequences and two with no viral sequences. All seven patients with hepatocellular carcinoma had integrated viral DNA sequences in the tumor tissues. From these results, it appears that hepatitis B virus does not play a role in the pathogenesis of alcoholic liver disease.

Adult↗
PubMedDate not supplied

Exploration of sequence space for protein engineering.

The process of protein engineering is currently evolving towards a heuristic understanding of the sequence-function relationship. Improved DNA sequencing capacity, efficient protein function characterization and improved quality of data points in conjunction with well-established statistical tools from other industries are changing the protein engineering field. Algorithms capturing the heuristic sequence-function relationships will have a drastic impact on the field of protein engineering. In this review, several alternative approaches to quantitatively assess sequence space are discussed and the relatively few examples of wet-lab validation of statistical sequence-function characterization/correlation are described.

Algorithms↗
PubMedDate not supplied

Molecular cloning and sequencing of a human hepatitis delta (delta) virus RNA.

Human hepatitis delta (delta) virus (HDV) is a form of defective virus, which infects humans only in the presence of a co-infecting hepatitis B virus (HBV). HDV superinfection in a chronic HBV carrier often results in severe chronic hepatitis and cirrhosis, whereas acute HDV and HBV co-infection is frequently associated with fulminant hepatitis. HDV consists of a 36-nm particle, which contains an envelope with HBV surface antigen, and a nucleocapsid containing the hepatitis delta-antigen (HDAg) and an RNA genome of 1.75 kilobases (kb). Recently, the genomic RNA from an HDV serially passaged in chimpanzees has been cloned and sequenced in a study which showed that the HDV RNA is a single-stranded circular molecule with properties similar to those of viroid or virusoid. However, it is not known whether serial passages in chimpanzees had altered the properties of human HDV. Here we report the cloning and sequencing of an HDV RNA isolated directly from a patient with acute delta-hepatitis. The sequence showed considerable divergence (11%) from that of the chimpanzee-adapted HDV. Five open reading frames (ORFs) of more than 100 amino acids in both genomic and anti-genomic sense were found. The largest ORF in antigenomic sense, which can code for 214 amino acids, may correspond to the HDAg.

Amino Acid Sequence↗
PubMedDate not supplied

Evaluation of anti-HBc IgM estimation by radioimmunoassay for anti-HBc on column separated IgM.

Tests for Igm antibody to hepatitis B core antigen (anti-HBc IgM) are useful diagnostic tools in the evaluation of patients with hepatitis B virus (HBV) infection. A method is described for detecting anti-HBc IgM based on application of a commercially available radioimmunoassay for total anti-HBc to column separated serum IgM and the technique is evaluated in patients with acute and chronic HBV infection. Our test is both sensitive and specific for diagnosing acute hepatitis B, although duration of positivity is highly variable. This technique is simple, inexpensive, and might be particularly useful for laboratories performing limited numbers of examinations, or with limited resources. A 45 percent savings in reagent costs is realized in our laboratory.

Chromatography, Gel↗
PubMedDate not supplied

Nodular regenerative hyperplasia of the liver with and without portal hypertension: a comparison.

The clinical and the pathologic features of seven patients with nodular regenerative hyperplasia of the liver are analyzed and compared with those of 37 patients reported in the literature in an attempt to distinguish the features of those with portal hypertension from those without. Severe degrees of obliterative portal venopathy usually associated with the portal hypertension were found among the various pathological features. The association of nodular regenerative hyperplasia with a variety of chronic diseases suggests a heterogeneous group of pathogenic mechanisms. Our study reveals that only some of these mechanisms lead to the hepatic changes that cause portal hypertension.

Adult↗