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Biomedical subjects

E Tabor

Publications and source records attributed to E Tabor.

At least 109 records · Page 6Linked to original sources
PubMed1983

Repair of potentially lethal and sublethal damage induced by neocarzinostatin in normal and ataxia-telangiectasia skin fibroblasts.

Neocarzinostatin is a radiomimetic antibiotic with a potent cytotoxic effect which elicits a hypersensitive response in human cells homozygous or heterozygous for the gene for ataxia-telangiectasia. The extent and the time course of potentially lethal damage repair and sublethal damage repair following neocarzinostatin treatment were investigated in human skin fibroblast strains and were found to be remarkably similar to those obtained following X-irradiation. Ataxia-telangiectasia homozygous cells essentially lacked potentially lethal damage repair, but were able to perform some degree of sublethal damage repair following neocarzinostatin treatment. Ataxia-telangiectasia heterozygous cells which show an intermediate degree of neocarzinostatin sensitivity could perform both processes but with somewhat reduced efficiency as compared to normal cells. These observations provide further evidence for a DNA repair defect in ataxia-telangiectasia cells.

Antibiotics, Antineoplastic↗
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

A low thymidine kinase-producing mutant of herpes simplex virus type 1 causes latent trigeminal ganglia infections in mice.

The wild type NIH strain of herpes simplex virus type 1 (HSV-1) has a mixed plaque morphology of both large and small plaques. From this virus we selected a large plaque isolate that was a high producer of thymidine kinase (TK) activity (designated TK+) and a small plaque isolate that produced 25 per cent of the TK activity of the large plaque mutant (designated TK 1/4). A TK- mutant of the large plaque virus was obtained after passage of the virus in the presence of BUdR. The pathogenicity of the TK 1/4 virus strain in relation to the TK+ and TK- strains was investigated in mice after inoculation of the virus into the eyes by corneal scarification. The TK+ strain was highly pathogenic, caused encephalitis and killed most of the mice, whereas the TK- strain did not cause latent infections in the trigeminal ganglia or kill the mice. The TK 1/4 virus strain replicated in the eyes within 24 hours after inoculation and entered the trigeminal ganglia, establishing a latent infection in almost all of the mice. By increasing the infectious dose tenfold, the TK 1/4 virus caused an active infection in the trigeminal ganglia (ganglionitis), migrated to the brain, and killed the mice. The results indicate that not only is a low level of TK required to establish latent infections in mice, but also the degree of virulence is determined by the amount of TK produced by the infecting virus.

Animals↗
PubMed1983

Similar repair of O6-methylguanine in normal and ataxia-telangiectasia fibroblast strains. Deficient repair capacity of lymphoblastoid cell lines does not reflect a genetic polymorphism.

The ability of human fibroblast strains to repair the mutagenic DNA adduct O6-methylguanine (O6-MeG) induced by brief exposure to N-methyl-N'-nitroso-N-nitrosoguanidine (MNNG) was investigated. The repair reaction proceeded rapidly during the first hour after alkylation, followed by a slow, continuous phase of repair, and both processes were saturated by low doses of carcinogen. This was similar to what had previously been found in human lymphoblastoid lines. Three fibroblast strains from healthy donors and six strains from patients with ataxia telangiectasia were all proficient in their capacity to repair O6-MeG and had the same sensitivity to the cytotoxicity of MNNG and methyl methanesulphonate as normal cells. Three of these cell strains were derived from individuals whose lymphoblastoid lines were deficient in their ability to repair O6-MeG. These lymphoblastoid lines were also extremely hypersensitive to killing by methylating carcinogens. Because non-transformed cells from the same donors behaved normally with regard to both parameters, we concluded that the repair deficiency accompanied by carcinogen hypersensitivity of the lymphoblastoid lines does not indicate a genetic deficiency in the donor. These findings imply that lymphoblastoid lines may not always be the appropriate cell type for investigating genetic susceptibility to chemical mutagens.

Ataxia Telangiectasia↗
PubMed1983

Abnormal response of ataxia-telangiectasia cells to agents that break the deoxyribose moiety of DNA via a targeted free radical mechanism.

A defect in DNA repair coupled to anomalous DNA synthesis after induction of certain radiogenic DNA damage is suspected to underlie the radiosensitivity of cells from patients with ataxia-telangiectasia (A-T). The response of cultured skin fibroblasts from A-T patients and A-T heterozygotes to six agents inducing various levels of DNA strand breakage by different mechanisms was studied to obtain further information on the nature of the 'A-T critical DNA lesion'. The A-T cells showed varying degrees of hypersensitivity to the cytotoxic action of the quinone-containing anti-tumor antibiotics streptonigrin and adriamycin and to hydrogen peroxide. This hypersensitivity was accompanied by reduced inhibition of DNA synthesis compared to normal cells after treatment with these agents. A limited degree of cellular hypersensitivity that was not sufficient to allow for definition of a separate sensitivity range was shown by A-T heterozygous cells. On the other hand, the A-T cells showed a normal response to paraquat, saframycin A and ellipticine. Taken together with previous results showing hypersensitivity of A-T cells to ionizing radiation, bleomycin and neocarzinostatin, these data indicate that the critical DNA lesion in A-T cells is a strand break caused by deoxyribose destruction following the action of free radicals targeted into the DNA.

Ataxia Telangiectasia↗
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↗
PubMed1983

Standardization of the antibody to hepatitis A virus (anti-HAV) content of immunoglobulin.

A batch of standard immunoglobulin was selected as a United States Reference Hepatitis A Immunoglobulin. Subsequent to its testing in research laboratories, public health laboratories, hospitals and universities throughout North America and Europe, this immunoglobulin was provided to the World Health Organization and accepted as an International Hepatitis A Immunoglobulin Reference Preparation. This reference preparation is provided lyophilized in flame-sealed ampules which have been back-filled with argon. When the contents of one ampule are reconstituted to a volume of 1.0 ml, the reciprocal end-point dilution titer of anti-HAV in this reference preparation is approximately 1:500 by competitive-inhibition radioimmunoassay (RIA). Based on data in the literature and that obtained from testing more than 200 batches of immunoglobulin manufactured in the United States between 1967 and 1977, it appears that the level of anti-HAV in the reference preparation could be achieved in each batch of immunoglobulin. Standardization will assure the continued and consistent efficacy of immunoglobulin batches for prophylaxis against hepatitis A.

Antibodies, Viral↗
PubMed1982

Immunogenicity in chimpanzees of experimental hepatitis B vaccines prepared from intact hepatitis B virus, purified polypeptides, or polypeptide micelles.

The immunogenicity of three experimental hepatitis B vaccines was evaluated in chimpanzees. Although no antibody to hepatitis B surface antigen (anti-HBs) was detected in two chimpanzees that received an aqueous polypeptide vaccine subcutaneously, a strong anti-HBs response was observed two and ten weeks, respectively, following challenge with hepatitis B virus. Inoculation of two additional chimpanzees with a micellar preparation of these polypeptides by the intravenous route resulted in anti-HBs production in one of the chimpanzees. Two chimpanzees inoculated subcutaneously with an aqueous vaccine of formalin-inactivated intact hepatitis B virus developed anti-HBs in low titers, but the development of antibody to the hepatitis B core antigen following challenge inoculations suggested that subclinical HBV infections may have occurred despite prior vaccination.

Animals↗
PubMed1982

Sporadic non-A, non-B hepatitis: frequency and epidemiology in an urban U.S. population.

Patients with acute viral hepatitis were identified at five hospitals in Baltimore, Maryland between February 1979-August 1980. Of the 295 patients with serologically diagnosed hepatitis, 42% had non-A, non-B hepatitis; 48% had hepatitis B; and 10% had hepatitis A. Compared with matched control patients with no liver disease, patients with non-A, non-B hepatitis more often had received a blood transfusion (11% vs. O, P less than 0.001), used parenteral drugs (42% vs. 4%, P less than 0.001), were employed as health workers in direct patient care or hospital laboratory work (6% vs. 3%, P less than 0.05), had personal contact with others who had hepatitis (16% vs. 1%, P less than 0.001), or had ingested raw shellfish (34% vs. 20%, P less than 0.01). A history of previous clinical hepatitis and serologic markers indicating previous hepatitis B infection were found in patients with non-A, non-B hepatitis more often than in the control patients. Chronic non-A, non-B hepatitis was found in 34 (42.5%) of 80 patients with non-A, non-B hepatitis.

Adolescent↗