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Biomedical subjects

S K Panda

Publications and source records attributed to S K Panda.

At least 73 records · Page 4Linked to original sources

Enteric non-A, non-B hepatitis: epidemics, animal transmission, and hepatitis E virus detection by the polymerase chain reaction.

We studied epidemics of viral hepatitis occurring at three different places in India. One was a combined epidemic due to hepatitis E virus (HEV) and hepatitis A virus (HAV) infections. In this epidemic, HAV affected children below 10 years of age, whereas HEV infected the young adult population. HEV was transmitted to rhesus monkeys (Macaca mulata) and confirmed by the polymerase chain reaction (PCR) on bile from the animals. Fecal material from acutely infected patients in one of the epidemics was also found positive for HEV RNA by PCR. This may help in confirming the nature of future epidemics. The bile and liver from experimental animals can be used as a source of material for further virological and molecular biological studies of HEV.

Adolescent↗

Macromolecular self-association of a synthetic peptide derived from the hepatitis B surface antigen: construction of a quaternary epitope.

A major impediment to the development of peptide vaccines has been the inability accurately to mimic conformationally constrained epitopes on the envelope proteins of pathogens. This limitation is further compounded by the fact that several viral envelope proteins exist either as covalently or non-covalently associated homo-oligomers in the native state. Evidence is now accumulating to indicate that, at least in some instances, these homo-oligomers display antigenic determinants that are not present in the dissociated monomer units. Clearly this problem will have to be addressed if peptide-based vaccines are ever to become feasible alternatives. In this report we demonstrate that an oligomerized synthetic peptide that was derived from the hepatitis B surface antigen aggregates in solution to form macromolecular structures. These aggregates appear to represent a 'native' form of the group-specific determinant presented by the hepatitis B surface antigen.

Amino Acid Sequence↗

Immune response to hepatitis B virus surface antigen peptides during HBV infection.

Antibody responses of patients with acute (n = 73), fulminant (n = 30) and chronic (n = 51) hepatitis B virus (HBV) infection as well as recovered individuals (n = 7) were studied against three synthetic peptides, Pre-S1 amino acids (aa. 12-32), Pre-S2 amino acids (aa. 120-145), and S amino acids (aa. 124-147) of the envelope region (HBsAg). T cell blastogenic response was investigated in a proportion of the patients (27 acute, nine fulminant, 13 chronic hepatitis and seven recovered individuals) along with seven HBV vaccinated and three normal individuals. The presence of T cell response against S peptide was observed in all the cases (9/9, 100%) during early acute hepatitis. This was suppressed during late stages (8/18, 44%) followed by partial reversal during recovery (5/7, 71%). T cell response and antibodies to Pre-S1 and Pre-S2 peptides were present only in one-third of the patients throughout these periods. The T cell blastogenic response as well as antibody reactivity against these peptides were absent and minimal in chronic hepatitis. Immune response against envelope protein appears to play a major role in acute hepatic injury due to HBV infection and help in virus clearance.

Acute Disease↗

Comparative evaluation of the immunogenicity of yeast-derived (recombinant) and plasma-derived hepatitis B vaccine in infants.

The immunogenicity of plasma-derived (HB Vax,MSD) and recombinant hepatitis B virus (Engerix B, SK&F) vaccines was evaluated in infants born to hepatitis B virus carrier mothers. The vaccination was carried out at 1 day, 1 month, and 6 months of age using 10 micrograms of the vaccine given intramuscularly. A total of 83/88 (94.3%) and 74/79 (93.6%) of the infants receiving the plasma-derived vaccine and yeast-derived vaccine showed antibody to hepatitis B surface antigen (anti-HBs). None of the maternal factors studied apart from the HBeAg positivity corellated with vaccine failure. The yeast-derived vaccine gives marginally lower antibody titre than the plasma-derived vaccine. The group-specific anti-"a" antibody was less than 10% of the total anti-HBsAg titre. It was observed that the vaccine alone without prior administration of hepatitis B immunoglobulin is effective in perinatal infection.

Biomarkers↗

Significance of natural polymerized albumin and its receptor in hepatitis B infection of hepatocytes.

Lack of information regarding the presence of native albumin polymer in serum and its structural similarity to the one produced by glutaraldehyde treatment casts doubt on the postulate that hepatitis B virus attachment to hepatocytes is mediated through polymerized albumin. We used a sandwich enzyme-linked immunosorbent assay with murine monoclonal antibodies raised against glutaraldehyde-polymerized albumin to detect native albumin polymer in human serum and its cross-reactivity with other albumin polymers. Presence of polymerized albumin receptor on the HepG2 cell was studied by radioreceptor assay. Purified hepatitis B virus and synthetic peptide analogous to part of pre-S2 sequence (120-145) were used to study polymerized albumin-dependent attachment of the virus to HepG2 cells. Antibodies raised against pre-S2 peptide were used to inhibit the pre-S2 and hepatitis B virus attachment to HepG2 cells. Glutaraldehyde-treated polymerized albumin was found to be immunologically cross-reactive with native albumin polymer. Its levels were found to be significantly raised in sera of patients with liver diseases. Polymerized albumin has specific saturable receptor on HepG2 cells with two classes of binding sites of different equilibrium dissociation constant (Kd1 = (16 +/- 9.6)pmol/L and Kd2 = (1,019 +/- 172)pmol/L. Albumin monomer was unable to compete for the polymerized albumin receptor sites on HepG2 cells. Anti-pre-S2 antibodies inhibit hepatitis B virus and pre-S2 binding to hepatocyte by 40% and 70%, respectively. Added extraneous polymerized albumin and the antibody against it did not interfere with virus attachment to HepG2 cells.

Cross Reactions↗

Enterically transmitted non-A, non-B hepatitis: recovery of virus-like particles from an epidemic in south Delhi and transmission studies in rhesus monkeys.

An epidemic of viral hepatitis, serologically characterized as due to non-A, non-B hepatitis, occurred in a village of South Delhi, India, in December, 1986, through January, 1987. Water contaminated with fecal matter was the apparent source of infection. Disease-associated virus-like particles were detected by immune electron microscopy in the feces of three patients within 5 days of illness. The virus-like particles were agglutinated by autologous acute-phase serum but not by convalescent serum. Rhesus monkeys inoculated with particle-containing fecal suspensions developed biochemical and morphologic features of acute, self-limited hepatitis. The findings in the present study and in earlier investigations of sporadic non-A, non-B hepatitis suggest that (i) the epidemic form and a proportion of sporadic cases of this infection in India may be related, both being enterically transmitted and associated with infection by a 27- to 32-nm virus-like particle, (ii) antibody responses to this virus occur early in disease and are transient and (iii) the rhesus monkey may prove to be a suitable model for studies of epidemic non-A, non-B hepatitis.

Adolescent↗

Significance of maternal and infant serum antibodies to hepatitis B core antigen in hepatitis B virus infection of infancy.

The significance of IgM and IgG class antibodies to hepatitis B virus (HBV) core component (anti-HBc) was investigated in a study of maternal-fetal HBV transmission. An IgM anti-HBc response was lacking in the majority (49/53) of HBV-infected infants. This antibody thus cannot be used as an indicator of transplacental infection. However, most infants who became HBsAg positive during the first 6 months of life acquire infection in the perinatal period rather than transplacentally. Passively transferred maternal IgG anti-HBc in the infant and additional IgM anti-HBc positively in the carrier mother have no modulating influence on HBV infection of infants born to HBV carrier women.

Age Factors↗

Trichomonal vaginitis: evaluation of serological tests and identification of immunoreactive surface peptides.

An indirect haemagglutination assay (IHA) with polysaccharide and protein antigens of Trichomonas vaginalis and an enzyme linked immunosorbent assay (ELISA) were used to test for antibodies against T vaginalis in 58 women with trichonomal vaginitis and 48 with non-specific vaginitis. Eleven antibody positive sera were used in a radioimmunoprecipitation assay (RIPA) to identify surface peptides that elicited antibody responses in infected women. The serological tests were less sensitive than biological tests (smear examination and culture); antibodies were detected in 22 of the 58 women with trichomonal vaginitis by IHA using polysaccharide as antigen, in 27 by IHA using protein antigen, and in 36 by ELISA. The ELISA was also found to be of low specificity. Only two of the 11 sera tested by RIPA showed positive reactions with surface antigens, which were confirmed by autoradiography.

Adolescent↗

Dynamics and impact of perinatal transmission of hepatitis B virus in North India.

The magnitude and significance of perinatal transmission of hepatitis B virus (HBV) were assessed in infants of 8,575 women, of whom 3.7% were seropositive for HBV surface antigen (HBsAg). The e antigen of HBV (HBeAg) was found in 7.8% of these carriers, the antibody to HBeAg (anti-HBe) was found in 30.1% of them, and HBsAg alone was found in 62.1% of them. The estimated incidence of HBsAg positivity by 6 months of age in infants of carrier women was significantly (P less than .001) higher than in controls (18.6% vs 3.0%). Transmission was most frequent (87.5%) if the carrier mother was HBeAg positive and was much less so if she was positive for anti-HBe (17.5%) or for HBsAg alone (9.6%). Toward the end of infancy incidence of HBsAg positivity among offspring of carriers and among controls was not different. Most infants positive for HBsAg and HBeAg continued with the infection beyond 6 months of age. It is estimated that about one-third of the adult asymptomatic HBV carriers in India evolve directly from perinatal infection, while the majority become infected during childhood or early adulthood.

Adolescent↗

Urinary catechol estrogens in cycles stimulated by human menopausal gonadotropin.

Catechol estrogens, estrogen metabolites of potential physiologic significance, were measured in infertile women undergoing ovulation induction with human menopausal gonadotropins. Urinary 2-hydroxyestrone (2-OH-E1) specimens were obtained from 12 women in one or more stimulated cycles. The actual time for the administration of human chorionic gonadotropin to induce ovulation was based on serial plasma estradiol (E2) specimens. A significant correlation between plasma E2 and urinary 2-OH-E1 was demonstrated, similar but more pronounced than that seen in normal cycling women. This confirms previous work that showed that 2-OH-E1 is the major urinary estrogen metabolite in the nonpregnant state and further suggests that urinary catechol estrogens are a useful index of ovarian function.

Estradiol↗

Radioimmunoassay of 2-hydroxyestrone in plasma during the estrous cycle of the rat: interrelationships with estradiol, progesterone, and the gonadotropins.

A RIA for 2-hydroxyestrone (2-OHE1) in rat plasma has been developed. The assay employs an antiserum that is specific for catechol estrogens. Specificity is further ensured by purification of plasma extracts on Sephadex LH-20 columns before RIA. Blood was collected at 0 C in the presence of ascorbic acid to prevent oxidation. Under these conditions, the conversion of 2-OHE1 to methylated derivatives was found to be negligible. Plasma 2-OHE1, LH, FSH, PRL, estradiol, and progesterone were measured at 3-h intervals throughout the 4-day estrous cycle of the rat. The 2-OHE1 concentration varied from undetectable to 11 pg/ml plasma. No clearly defined relationship with the other hormones analyzed was observed. Thus, it is unlikely that changes in circulating 2-OHE1 levels are involved in the regulation of the gonadotropin surge and ovulation.

Animals↗

Hepatic granulomas due to visceral larva migrans in adults: appearance on US and MRI.

Visceral larva migrans is a syndrome characteristically involving children with a history of pica, and usually presents with fever, abdominal pain, tender hepatomegaly, and hypereosinophilia. Hepatic granulomas of visceral larva migrans are rare in adults. We describe three adult patients with hepatic lesions which on histopathology demonstrated characteristic granulomas of visceral larva migrans. All patients had abdominal sonograms and two had additional MR scans of the liver. Both ultrasound and magnetic resonance imaging demonstrated characteristic appearances which have not been described previously (viz., ill-defined central necrotic areas surrounded by concentric thick walls and perifocal edema in the liver parenchyma).

Adult↗

Aetiology and outcome of acute viral hepatitis in pregnancy.

The aetiologic types of sporadic acute viral hepatitis in 169 pregnant women were compared with those of 70 non-pregnant women and 287 adult men. The majority of pregnant women (87.6%) came with acute hepatitis in the last trimester of pregnancy. Non-A, non-B (NANB) hepatitis accounted for 81.6% of hepatitis during pregnancy in comparison with 48.6% in non-pregnant women and 57.1% in adult men. Hepatitis A was extremely uncommon during pregnancy. Hepatitis B infection accounted for 17% of all cases in pregnant women compared with 45% in controls. Acute viral hepatitis in pregnancy had a poor outcome as assessed by maternal and/or fetal mortality (28.5%). The outcome was equally bad in hepatitis NANB and hepatitis B. Pregnant women generally had significantly lower immunoglobulin levels in comparison with non-pregnant women. In acute NANB hepatitis during pregnancy, serum IgG and IgM levels were lower and higher, respectively, compared with those in non-pregnant women and pregnant women with acute hepatitis B. It is suggested that an immune suppression during pregnancy might be responsible for increased susceptibility to acute NANB viral hepatitis, which, by itself, seems to induce only a transient acute phase IgM response.

Female↗

Polymerized albumin binding to serum in various liver diseases: its significance and relation to hepatitis B virus infection.

Sensitive and specific enzyme-linked immunosorbent assays (ELISA) were developed to detect separately the binding of polymerized human serum albumin (PHSA) to its antibody (A-PHSA) and to the hepatitis B surface antigen (HBsAg). A-PHSA was not detected in normal serum, whereas more than one-third to about half of sera from patients with acute liver cell injury showed this antibody. Frequency of A-PHSA positivity was low in chronic liver diseases, being relatively higher in those with continuing liver injury. A-PHSA detection was not related to seropositivity for HBsAg. PHSA binding of HBsAg positive sera showed a higher frequency of positivity in chronic carriers than acute hepatitis B. Of 172 asymptomatic HBsAg carriers, PHSA binding was demonstrated in 25 (15%), the frequency being significantly high if HBeAg was also present (84%). Binding was infrequent in sera having anti-HBe (2.9%) and in those negative for both HBeAg and anti-HBe (2.7%). Binding of HBsAg to PHSA was significantly higher than to human serum albumin (HSA). Immunoblotting of separated HBsAg components showed PHSA binding specifically to the high molecular weight peptide. PHSA binding in HBsAg positive serum may indicate the latter's infectivity as detected in a study of maternal-fetal transmission, where it demonstrates 100% infectivity in HBsAg and HBeAg positive mothers. PHSA possibly mediates the attachment of the HBV to the hepatocyte and a competitive binding between A-PHSA with HBsAg for PHSA may modulate the course of HBV infection.

Antibodies↗

Diagnostic utility of ultrasonography in hepatic venous outflow tract obstruction in a tropical country.

The present study was undertaken to define the role of ultrasonography (US) in screening and diagnosis of hepatic venous outflow tract obstruction. Forty-five consecutive patients clinically suspected to have hepatic venous outflow tract obstruction were included in the study for screening by US and for assessment of patency or block in the hepatic vein (HV) and/or inferior vena cava (IVC). Four patients were excluded from the study. Eleven patients had a diagnosis other than hepatic venous outflow tract obstruction and all these patients were found to have patent HV and IVC. Thirty patients were finally diagnosed to have hepatic venous outflow tract obstruction. Using US, as a screening test 27 (90%) out of 30 such cases were correctly identified as cases of hepatic venous outflow tract obstruction and in these cases the site of block in hepatic venous outflow tract (major HV and/or IVC) was correctly diagnosed in 90% of the cases. Our results indicate that US is a sensitive and accurate test and should be the initial investigation for screening and identifying the site of obstruction in patients with hepatic venous outflow tract obstruction.

Adolescent↗

Prevalence of hepatitis C virus antibodies in chronic liver disease and hepatocellular carcinoma patients in India.

The prevalence of antibodies to hepatitis C virus (HCV) was investigated in 129 patients with chronic liver disease (85 with chronic active hepatitis and 44 with cirrhosis) and 53 patients with hepatocellular carcinoma. The commercially available second generation anti-HCV enzyme immunoassay kit was used. Antibodies to hepatitis C virus were detected in 16.2% of the patients with chronic liver disease and in 15.1% with hepatocellular carcinoma. Of the HCV positive patients in all groups 51.7% were positive for hepatitis B virus (HBV) markers indicating present or past infection. Prevalence of HBV markers in all the three groups (CAH, cirrhosis and HCC) was higher as compared with anti-HCV prevalence. These results suggest that HCV infection may not be a major cause of chronic liver disease and hepatocellular carcinoma in India and indicate the presence of other aetiological agents.

Adolescent↗