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Biomedical subjects

R J Gerety

Publications and source records attributed to R J Gerety.

At least 37 records · Page 2Linked to original sources
PubMed1985

Protection against hepatitis B virus infection by immunization with hepatitis B core antigen.

Although antibody to the hepatitis B surface antigen usually provides protection against hepatitis B virus (HBV) infection, recent reports indicate that this is not always the case. To study the possible role of immune responses to hepatitis B core antigen in immunity to HBV infection, chimpanzees were immunized with chimpanzee liver-derived or genetically cloned hepatitis B core antigen and later challenged with known infectious HBV. Two chimpanzees, which received liver-derived or cloned hepatitis B core antigen in Freund's adjuvant and developed hepatitis B core antibody and low-titer hepatitis B e antibody, were completely protected against HBV infection following challenge. In contrast, another chimpanzee, which received liver-derived hepatitis B core antigen without adjuvant, developed hepatitis B core antibody only in serum and had a subclinical HBV infection when challenged. These findings demonstrate that protection against HBV infection can be induced by immunization with hepatitis B core antigen in adjuvant and that protection, in this case, is not solely dependent on hepatitis B surface antibody. This fact has important implications in our understanding of the biology of HBV infection and in the design of future hepatitis B vaccines.

Animals↗
PubMed1985

A glycoprotein associated with the non-A, non-B hepatitis agent(s): isolation and immunoreactivity.

A glycoprotein was isolated and purified to homogeneity from the serum of a patient with chronic non-A, non-B hepatitis. NaDodSO4/PAGE of the glycoprotein revealed a single major band at Mr approximately 77,000. Antibodies to this glycoprotein were shown to possess the following immunoreactivity: (i) they reacted by radioimmunoassay with sera obtained at the time of diagnosis from 17 of 42 patients with non-A, non-B hepatitis and with only 2 of 58 sera from either matched controls or patients with hepatitis A or hepatitis B, (ii) they reacted with sucrose gradient fractions from a proven infectious non-A, non-B hepatitis serum at a peak density of 1.14 g/ml and in the soluble protein fractions on top of the gradient, and (iii) they reacted in ELISA with disrupted human T-cell lymphocytotropic virus type III (HTLV-III), and (iv) they reacted in immunoblots with a protein of Mr 74,000 derived from HTLV-III.

Antigens, Viral↗
PubMed1985

Serologic markers of hepatitis A and B in the population of Bali, Indonesia.

A total of 343 sera from Balinese subjects in different age groups and geographic locations were tested by radioimmunoassay (RIA) for serum antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc); most sera were also tested for hepatitis B surface antigen (HBsAg), and for antibody to hepatitis A virus (anti-HAV). One hundred percent of the adult population was found to have anti-HAV, with antibody acquisition beginning in early childhood and reaching a level of 95% by the age of 10 years. Antibodies to hepatitis B virus were also frequent in young children, rapidly peaking to near 80% in older children and adolescents, then declining to a plateau that fluctuated between 40% and 60% throughout adult life. Overall, anti-HBc (49%) was detected slightly more often than anti-HBs (45%), but the relative frequencies of the 2 antibodies varied considerably from group to group. Despite these high antibody prevalences, HBsAg was detected in only 1.5% of the general population, and in no woman of child-bearing age. In utero infection is thus far less likely to account for the early acquisition of antibody to hepatitis B virus than inapparent percutaneous transmission occurring under conditions of close personal contact.

Adolescent↗
PubMed1985

Ultrastructural and cytochemical study of hepatocytes and lymphocytes during experimental non-A, non-B infections in chimpanzees.

A human agent of non-A, non-B hepatitis (Inoculum I) was transmitted to chimpanzees and alterations in liver and lymphocytes were studied by electron microscopy and by cytochemical techniques during the acute phase of the disease. Three types of cytoplasmic alterations, consisting of a membraneous and an amorphous part were observed in the hepatocytes. The density of the amorphous constituent decreased after treatment with pronase, but not after treatment with ribonuclease (RNase) or deoxyribonuclease (DNase). The wall of C-III, but not C-II had fibrils with a periodicity the contrast of which markedly increased after pronase treatment. Cytochemical data suggest that the inclusions (C-I-III) represent a cellular reaction to the infectious agent rather than the virus itself. Intranuclear vermicular inclusions (INI) were observed in hepatocytes and lymphocytes as well, mainly in degenerating cells. Tubuloreticular inclusions (TRS) did not appear in circulating lymphocytes during acute infection; however, they could be induced by human alpha interferon treatment in vitro. Increased numbers of lymphocytes with parallel tubular arrays (PTA) were noted at the peak of serum aminotransferase elevations. The latter two alterations (TRS and PTA) most likely represent immunologic reactions of the host to the infectious agent.

Animals↗
PubMed1984

Detection of reverse transcriptase activity in association with the non-A, non-B hepatitis agent(s).

Particle-associated reverse transcriptase activity was detected in four human serum specimens and in two plasma-derived products, all of which had been shown to transmit non-A, non-B hepatitis (NANBH) to other human beings and/or chimpanzees. Reverse transcriptase activity was also detected in all twelve sera from patients with acute or chronic NANBH. In contrast, reverse transcriptase activity was found in only 2 of 49 serum specimens from healthy plasma donors and laboratory workers. Sucrose density gradient fractions of two of the infectious human sera (peak reverse transcriptase activity at 1.14 g/ml) transmitted NANBH to chimpanzees. Biochemical and enzymatic data indicate that the NANBH agent(s) is a retrovirus or is retrovirus-like.

Animals↗
PubMed1984

Community-acquired non-A, non-B hepatitis: clinical characteristics and chronicity.

The characteristics of 86 patients with acute non-A, non-B hepatitis were compared to 23 patients with acute hepatitis A and 76 with acute hepatitis B by medical record reviews of patients seen at 5 hospitals in Baltimore, Maryland, as part of case-control study of viral hepatitis. Results of serum aminotransferase levels, bilirubin, albumin, and prothrombin times alone could not distinguish the type of viral hepatitis because of extensive overlap. The alanine aminotransferase range for non-A, non-B hepatitis was 56 to 1819 IU/liters, for hepatitis A 250 to 1995 IU/liters, and for hepatitis B 203 to 2120 IU/liters. The ranges of aspartate aminotransferase and bilirubin for the types of hepatitis also overlapped. Fewer patients with non-A, non-B hepatitis or hepatitis A had a prolonged prothrombin time compared to patients with hepatitis B. Hepatic encephalopathy was seen only in two patients with hepatitis B. Forty-two percent of non-A, non-B hepatitis patients followed for 6 months or longer continued to have elevated alanine aminotransferase levels. Chronic alanine aminotransferase elevation was independent of the source of infection: transfusion, parenteral drug use, or all other sources. Prolonged follow-up is necessary to evaluate chronicity in patients with non-A, non-B hepatitis.

Alanine Transaminase↗
PubMed1984

Ultrastructural alterations in serial liver biopsy specimens from chimpanzees experimentally infected with a human non-A, non-B hepatitis agent.

Four chimpanzees experimentally infected with an agent of human non-A, non-B hepatitis were studied to determine the sequence of ultrastructural alterations in hepatocytes during infection. Three of the four types of cytoplasmic alterations previously described in association with non-A, non-B hepatitis were observed in the hepatocytes. Sponge-like cytoplasmic inclusions (designated C-I) were detected at or near the time of peak serum aminotransferase elevations in two of the four chimpanzees. Undulating membranes (designated C-II) were observed in all four chimpanzees, at the time of the first elevation of serum aminotransferase levels. Cytoplasmic tubules (designated C-III) were first observed four, eight, and twelve weeks, respectively, after inoculation in three of the chimpanzees. Four weeks after the peak of serum aminotransferase elevations, cytoplasmic alterations could no longer be detected in hepatocytes of the four chimpanzees. Intranuclear inclusions consisting of 20-27 nm granules and vermicular particles were observed in hepatocytes from preinoculation liver biopsy specimens, as well as biopsies obtained during non-A, non-B hepatitis. The number of these particles was greatest near the time of peak elevation of serum aminotransferase levels, however. Tubulo-crystalline inclusions were noted as well in the endothelial cells from both preinoculated and infected chimpanzees. Cytoplasmic alterations in hepatocytes of chimpanzees experimentally infected with an agent of non-A, non-B hepatitis appear characteristic of infection with this agent. In contrast, intranuclear particles were not specifically related to the non-A, non-B hepatitis infection.

Animals↗
PubMed1983

Inactivation of hepatitis B virus by three methods: treatment with pepsin, urea, or formalin.

Dilutions of human sera containing between 10(3) and 10(5) chimpanzee infectious doses of hepatitis B virus per ml, subtype adr or ayw, were treated with either 1 microgram/ml pepsin at pH 2.0 for 18 hours, 8 M urea for four hours, or 1:4,000 formalin for 72 hours. One ml of the serum containing hepatitis B virus subjected to each of the procedures was inoculated intravenously into one or two susceptible chimpanzees (total of eight chimpanzees). No evidence of hepatitis B infection was detected in weekly serum samples from the chimpanzees during six months of observation. These three procedures are currently applied during manufacture to inactivate HBV which might be present in the hepatitis B vaccine licensed in the United States. The data from this study combined with data documenting that the physical purification of the vaccine is capable of removing hepatitis B virus provide assurance that there is no residual live hepatitis B virus in the vaccine.

Animals↗
PubMed1983

Use of and interpretation of results using inocula of hepatitis B virus with known infectivity titers.

The infectivity of three inocula (subtypes ayw, adr, and adw) of hepatitis B virus was evaluated by intravenous inoculation of 54 chimpanzees. End-point infectivity titers were 10(-7.5) (ayw), 10(-8.0) (adr), and 10(-7.0) (adw). In contrast, the end-point titers for detection of hepatitis B surface antigen by radioimmunoassay were 10(-4) (ayw), 10(-4) (adr), and 10(-5) (adw). The mean incubation period for infections transmitted by each dilution of each of the inocula was inversely proportional to the amount of infectious virus in the dilution, but substantial overlap was observed among proximate dilutions. The severity of hepatitis in the chimpanzees differed among the inocula, but it was unrelated to the amount of virus inoculated. Thus, conclusions about the infectivity of hepatitis B virus after inactivation based on titers of hepatitis B surface antigen or on the inverse relationship between the incubation period and the end-point infectivity titer must be made with caution.

Animals↗
PubMed1983

Concomitant hepatitis B surface antigen and antibody in thirteen patients.

Both hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) were found in 13 patients. Nine patients had HBsAg subtype ad, and 7 had anti-HBs monotypic subtype anti-y. Nine patients had HBsAg before detectable levels of anti-HBs were present. Of the 6 patients whose serum contained subtypes of both HBsAg and anti-HBs, 4 had HBsAg before development of the monotypic antibody. All patients have remained positive for HBsAg and anti-HBs (mean duration, 55.5 weeks). Nine patients were positive for HBeAg, and 7 had renal disease. Six of these seven patients are on hemodialysis. Because of the differing subtype specificities of the circulating HBsAg and anti-HBs, we conclude that HBsAg and anti-HBs occur concomitantly. The presence of HBeAg, which indicates infectivity, is common in our study group, suggesting that these patients are a reservoir for transmission of hepatitis-B-virus infection. Therefore, the presence of anti-HBs alone does not indicate a noninfectious serum. Concomitant HBsAg and anti-HBs seems to be particularly common in patients with renal disease who are on hemodialysis.

Adult↗
PubMed1983

Primate animal models and titered inocula for the study of human hepatitis A, hepatitis B, and non-A, non-B hepatitis.

Although many primate species have been inoculated with the agents of human hepatitis A, B, and non-A, non-B, only a small number of species have been shown to be susceptible, and only the chimpanzee (Pan troglodytes) has been shown to be reproducibly susceptible to all three types of human hepatitis. Infectious inocula containing each agent have been identified in different laboratories and the end-point titers of infectivity determined, in most cases by inoculation of chimpanzees. These inocula and the nonhuman primate models have permitted investigators to study the inactivation of these agents and to evaluate passive and active immunization against the agents.

Animals↗