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Biomedical subjects

G R Dreesman

Publications and source records attributed to G R Dreesman.

At least 73 records · Page 4Linked to original sources

Common idiotypic determinant associated with human antibodies to hepatitis B surface antigen.

Anti-Id antisera generated to purified anti-HBs isolated from two different individuals recognized a common idiotype. This idiotype was detected in purified anti-Hbs preparations from three individuals and also in anti-HBs-positive sera obtained from six hemophilic patients. The ability of both HBsAg and a virus-derived HBsAg native polypeptide to inhibit the idiotype-anti-idiotype reaction suggested that the anti-HBs idiotype was associated with the antibody-combining site.

Antibodies, Viral↗

Characteristics of a shared idiotype by two IgM anti-herpes simplex virus monoclonal antibodies that recognize different determinants.

Two IgM monoclonal antibodies (McAb) that recognized distinct antigenic determinants of herpes simplex virus type 2 (HSV2) were shown to share idiotypes. Seven other IgM McAb generated to either HSV2 or the major envelope glycoprotein of HSV2, VP119, did not express this shared idiotype. The idiotypic determinants were associated with the antibody-combining site, because HSV2 inhibited the idiotype-anti-idiotype reactions. Anti-HSV2 sera raised in BALB/c mice also expressed the idiotype shared by the two anti-HSV2 McAb.

Animals↗

Epitopes associated with a synthetic hepatitis B surface antigen peptide.

A synthetic peptide (SP1), corresponding to the amino acid residues 122 through 137 of the major polypeptide derived from hepatitis B surface antigen (HBsAg), subtype ayw, was analyzed for the presence of the major epitopes of HBsAg. Both a cyclic form, produced by introduction of an intrachain disulfide bond, and a linear form of the peptide were characterized. A panel of monoclonal antibodies with defined specificity for the cross-reactive group a antigenic determinant(s) and for the y and w subtype specificities was used for this analysis. The cyclic, but not the linear, form of SP1 reacted with five of 14 anti-a monoclonal antibodies, demonstrating that the cyclic peptide contains a conformation-dependent a epitope. Only one anti-a antibody was found to react with both cyclic and linear forms of SP1. Because SP1 failed to react with the remaining 8 anti-a monoclonal antibodies, it was concluded that the a antigenic reactivity associated with HBsAg contains an additional epitope(s) unrelated to that expressed on SP1. Both cyclic and linear SP1 reacted with three of three anti-y monoclonal antibodies, indicating that a sequential y epitope is also present on SP1; no w reactivity was detected. Analysis of the idiotypes associated with the monoclonal antibodies showed those that combined with cyclic SP1 also inhibited the binding of a common human anti-HBs (CHBs) idiotype with its rabbit anti-idiotype serum, whereas a monoclonal antibody that did not react with the cyclic SP1 epitope failed to inhibit the CHBs idiotype-anti-idiotype reaction. Thus, the conformational a epitope present on cyclic SP1 appears to contain the predominant epitope recognized by humans in response to a natural HBV infection.

Animals↗

Kinetics of human antibody responses to primary genital herpes simplex virus infection.

5 patients with primary genital herpes simplex virus (HSV) infection were studied prospectively for the production of serum antibody reactivity as measured by the virus micro-neutralization test (NT), micro-solid phase radioimmunometric assay (micro-SPRIA), and antibody-dependent cellular-cytotoxic (ADCC) test. ADCC antibody was detected before reactivity measured by either NT or micro-SPRIA in 2 of the patients. A 3rd patient failed to produce neutralizing antibody, whereas specific activity was detected by the other two methods. In 2 other patients a good correlation was observed for development of antibody by all three methods. There were several discordant results in the kinetics of production of antibody detected by these assays, suggesting that not all individuals produce similar types of antiviral antibody.

Adult↗

Immunogenicity of conjugates and micelles of synthetic hepatitis B surface antigen peptides.

A cyclic peptide containing the amino acid sequence 122 through 137 of the major hepatitis B surface antigen (HBsAg) polypeptide was synthesized. The immunogenicity of this synthetic peptide, aggregated in micelles or covalently coupled to tetanus toxoid, was assessed in mice. Antibodies against HBsAg (anti-HBs) were obtained with both preparations, administered either in saline suspension or adsorbed on aluminum gel. The peptide-tetanus toxoid conjugate was more immunogenic than the peptide micelles, producing high levels of specific anti-HBs.

Animals↗

The role of herpes simplex virus in cervical and vulvar cancer.

This report extends the association of herpes simplex virus type 2 (HSV2) with cervical cancer to vulvar carcinoma. In addition to seroepidemiologic observations linking prior HSV2 infection to genital cancer, the new evidence involves the neoplasms themselves. Biopsies of cervical and vulvar cancers were found to contain HSV2-specified antigens. The virus-induced antigens are nonstructural DNA-binding proteins normally present in the nuclei of infected cells; however, in the cancer cells they were found in the cytoplasm. Whole virus structural antigens were not detected in the biopsies. In recent years there has been a parallel rise in prevalence of HSV2 infections and vulvar carcinomas, particularly in women under 40 years of age, reaffirming the association of the virus infection and the neoplasms.

Animals↗

Herpesvirus-induced antigens in squamous-cell carcinoma in situ of the vulva.

Antigens induced by herpes simplex virus Type 2 (HSV2) were found to be associated with squamous-cell carcinoma in situ of the vulva in nine of 10 patients. The HSV2-induced antigens are DNA-binding proteins that are normally present in the nuclei of infected cells, but in the cells of the carcinomas in situ they were found in the cytoplasm. Whole-virion structural antigens were not present, although there was serologic evidence of previous HSV2 infection in patients tested for the presence of antibodies. The observations reported here and the recent parallel rise in the prevalence of both HSV2 infections and vulvar carcinoma in situ, particularly in women under 40 years of age, suggest an association of HSV2 infection with this type of neoplasia, the nature of which remains to be determined.

Adult↗

Enzyme potentiated radioimmunoassay (EPRIA): a sensitive third-generation test for the detection of hepatitis B surface antigen.

A sensitive, specific immunoassay for detection of hepatitis B surface antigen (HBsAg) is described. The assay combined enzyme-linked immunosorbent assay and solid-phase radioimmunoassay and is termed enzyme potentiated radioimmunoassay (EPRIA). HBsAg was quantitated by enzymatic conversion of L[14C]glutamic acid to 14CO2 and gamma-aminobutyric acid by glutamate decarboxylase (GDC) conjugated wih goat anti-HGs IgG. Conjugation of IgG and GDC was by a thiol-disulfide bond exchange reaction after reacting N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) with each reagent. A positive/negative ratio of 2.2 was established as significant by examination of 40 normal sera negative for HBsAg. This value was the mean cpm plus 3 standard deviations. By an identical statistical analysis of sensitivity, EPRIA was found to be approximately 100-fold more sensitive than Ausria II (Abbott Laboratories, North Chicago, IL).

Animals↗

Induction of hepatitis B surface antigen in human hepatoma-derived cell lines.

Cultures of two human hepatoma cell lines were examined for expression of hepatitis B virus surface antigen (HBsAg). The PLC/PRF/5 cells secreted HBsAg continuously into the culture medium, whereas Mahlavu cells did not secrete the antigen. However, cytoplasmic antigen was detected in a low percentage (less than 5%) of the Mahlavu cells. The expression of HBsAg also was assayed in cultures treated wtih dexamethasone (DXM), 5-iodo-2'-deoxyuridine (IdUrd), or both. The results demonstrated that: (i) DXM stimulated secretion of HBsAg by PLC/PRF/5 cells but not by Mahlavu cells; (ii) the percentage of Mahlavu cells expressing cytoplasmic HBsAg was not increased in any cultures if the medium was replaced at 24 t0 48 h intervals but was increased approx. fivefold within 4 days in cultures treated with DXM or IdUrd/DXM if the medium was not changed. However, no increase was noted in the intensity of the immunoperoxidase stain of PLC/PRF/5 cells that expressed cytoplasmic antigen in any DXM cultures; (iii) HBsAg expression was stimulated to a lesser extent in IdUrd/DXM cultures than in DXM cultures and was not enhanced in IdUrd cultures. Thus, DXM enhanced secretion of HBsAg by PLC/PRF/5 cells within 24 h and, after a delay, enhanced expression of cytoplasmic antigen by Mahlavu cells. However, antigen secretion by Mahlavu cells evidently was blocked.

Carcinoma, Hepatocellular↗

Immunological and biophysical alteration of hepatitis B virus antigens by sodium hypochlorite disinfection.

Sodium hypochlorite (NaOCl) was examined as an effective disinfectant in hepatitis laboratories. Concentrations of NaOCl containing 5,600 ppm (5,600 microgram/ml) of available chlorine were found to be effective in destroying the antigenicity of hepatitis B surface antigen (HBsAg) in virion-rich plasma after an exposure time of 1 min or more. In the treatment of protein-deficient solutions containing HBsAg, smaller concentrations of available chlorine (less than 500 pm) are equally effective. Neither 17-to 25-nm HBsAg particles nor 45-nm virion particles could be detected by electron microscopy after treatment. chemical interaction of protein and NaOCl was confirmed by isoelectrofocusing of 125I-labeled HBsAg. More than 90% of the labeled material was found at pH 3.0 or lower, indicating complete antigen oxidation. Labeled HBsAg was reduced in density from 1.21 g/cm3 in CsCl to approximately 1.07 g/cm3 after treatment with NaOCl. Both hepatitis B core antigen and deoxyribonucleic acid polymerase activity were significantly reduced after interaction with hypochlorite solutions. These results show that NaOCl destroys hepatitis B antigenicity and virus structures and therefore may be utilized as a disinfectant for the virus.

Centrifugation, Density Gradient↗

Immunization of chimpanzees with hepatitis B virus-derived polypeptides.

Previous studies established that the purified polypeptides derived from the 22-nm particles associated with hepatitis B surface antigen (HBsAg) produce both humoral and cellular immunity against HBsAg in guinea pigs. Therefore, the two major polypeptides with molecular weights of 22,000 and 25,000 (P22 and P25, respectively) were isolated, adsorbed to an alum adjuvant, and used to immunize four nonimmune chimpanzees. A vigorous anti-HBs response was observed in all four animals after one inoculation of an alum-adsorbed polypeptide vaccine containing 40 micrograms of protein. After one to two booster inoculations, anti-HBs switched from being predominantly immunoglobulin M to the immunoglobin G class, indicating the establishment of immunological memory. Challenge of the vaccinated chimpanzees with 30,000 chimpanzee infectious doses of hepatitis B virus provided evidence for the efficacy of this vaccine. None of the four animals developed serological markers associated with an active hepatitis B infection, and no biochemical or histopathological changes of hepatitis were observed. A nonvaccinated control chimpanzee that was inoculated with the same hepatitis B virus material developed hepatitis B infection, confirming infectivity of the challenge inoculum.

Alanine Transaminase↗