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Biomedical subjects

R H Stevens

Publications and source records attributed to R H Stevens.

At least 73 records · Page 4Linked to original sources
PubMed1982

Production of anti-basement membrane-zone antibody by peripheral blood leukocytes of pemphigoid patients.

Peripheral blood leukocytes (PBL) from patients with bullous pemphigoid stimulated by pokeweed mitogen (PWM) produce an anti-basement membrane-zone(BMZ) antibody. the antibody produced in vitro was biosynthetically radiolabeled, and its binding to the BMZ was histologically demonstrated by autoradiography. The IgG nature of the antibody was evidence by the fact that it was absorbed by rabbit anti-human IgG antiserum immunoabsorbents. The peak antibody production in vitro occurred after 6 days of culture. Antibody produced in vitro did not bind to the BMZ of human skin, but it did bind to the BMZ of the monkey esophagus. Normal human volunteers and control patients did not produce such an antibody. In other experiments the effects of adding serum containing anti-BMZ antibody to the synthesis of Ig by cells of patients and normal subjects were studied. Although serum from patients with bullous pemphigoid stimulated Ig production with either normal or BP-patient PBL, the difference was not statistically significant. The availability of the assay system allows for studying the immunoregulatory mechanism of autoantibody production in bullous pemphigoid.

Aged↗
PubMed1982

Adenosine 3',5'-cyclic monophosphate dependent and independent protein kinase activities in 1,2-dimethylhydrazine induced rat colon cancer.

The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent and cAMP-independent kinase activities were measured in the 1,2-dimethylhydrazine (DMH) induced rat colon cancer and in untreated colon. Previous studies had shown that intestinal tumors induced by chronic exposure to DMH contained 2-fold less intracellular cAMP. The present findings indicate that reduction in cAMP-dependent protein kinase activities also occur in colon cancer cells. Similar hydrogen ion dependence (pH 6-7) and approximate association constants (Ka approximately 0.1 microM) were observed for the enzymes existing in both normal and tumor tissues, while the cAMP-dependent tumor protein kinase was found to phosphorylate phosvitin and casein to a greater degree. These recent findings are consistent with the concept that the concentrations of cAMP and activities of its associated enzyme system are inversely related to the cell proliferation state.

1,2-Dimethylhydrazine↗
PubMed1982

Detection of carcinogenic exposures by urinalysis: induction of cell-mediated immunity.

Studies were undertaken to determine whether urine collected from rats during the 24 h following exposure to the colon carcinogen 1,2-dimethylhydrazine (DMH) contained substances which would induce specific antitumor immunity. The evaluation for such components was carried out by administering the test and control urine to young male adult Fisher F344 inbred rats and then establishing the animals' antitumor cell-mediated immunity (CMI) at a 14-day post-exposure interval. The CMI was measured by determining the injury and destruction inflicted upon cultured X-ray-induced rat small bowel adenocarcinoma target cells by peripheral blood lymphoid cells obtained from the animals exposed to the urine. A significantly increased CMI was found to be induced by the urine collected from the chemically exposed rats, thus suggesting the presence of mutagenic/carcinogenic components. In addition, exposure through the levels of CMI that were induced, with an approximate threshold detection limit of 100 microgram (1.7 mumol)/kg body weight (100 ppb) to the chemical. These preliminary findings suggest that such immune measurements might serve as a basis for the development of a rapid and inexpensive bioassay for monitoring population exposures to carcinogenic substances.

1,2-Dimethylhydrazine↗
PubMed1982

Characterization of an inducible bacteriophage from a leukotoxic strain of Actinobacillus actinomycetemcomitans.

A bacteriophage, designated phi Aa17, was isolated by mitomycin C induction from leukotoxic Actinobacillus actinomycetemcomitans strains 651. Electron microscopy of the virus revealed particles with regular, nonelongated, polyhedral heads, and tails consisting of a contractile sheath and core. Spikes emanated from the base of the tail. The head had a diameter of 70 nm. The fully extended tail sheath had a length of 127 nm and a diameter of 22 nm. In its contracted form, the tail sheath measured 47 nm in length and 25 nm in diameter. The phage had a buoyant density of 1.370 in CsCl, and its genome was found to be double-stranded DNA. A single-cycle growth curve revealed that the phage had a latent period of 30 min and a burst size of 435 PFU per cell. The host range of the phage was examined, and A. actinomycetemcomitans strains ATCC 29523 and ATCC 29524 were found to be phage sensitive, whereas strains Y4, ATCC 29522, 2043, 652, 651, 627, 2097, N27, 2112, and 511 were resistant. The host range of this virus does not suggest any association between the phage and leukotoxin production.

Actinobacillus↗
PubMed1982

The selective role of membrane IgG in the antigen-induced inhibition of human in vitro antibody synthesis.

IgG-anti-tetanus toxoid-producing B cell precursors from recently immunized individuals can be stimulated by pokeweed mitogen and T cells to produce IgG-Tet antibodies in vitro. Treatment of these cells with tetanus toxoid selectively inhibits the synthesis of IgG-Tet. Because the IgG-Tet precursors display heterogeneity in their surface isotypes (mu, delta, gamma), the aim of this study was to determine the surface isotype responsible for transmitting this antigen-induced inhibitory signal to the B cell. B cells were fractionated by rosetting techniques on the basis of surface IgM or IgD. The 4 resulting B cell subsets (SIgM+, sIgM-, sIgD+, sIgD-) were found to be equally susceptible to antigen-induced inhibition. Experiments were then performed with anti-isotype antibodies to investigate further the roles of sIgM, sIgD, and sIgG in antigen inhibition. Treatment of peripheral blood lymphocytes with 10 micrograms/ml of anti-gamma antibody inhibited IgG-Tet antibody production, whereas the addition of up to 100 micrograms of anti-mu or anti-delta antibodies did not. Tetanus toxoid and anti-gamma antibody inhibition of IgG-Tet synthesis in vitro followed similar temporal kinetics, with the IgG-Tet precursors being sensitive to inhibition by either tetanus toxoid or anti-gamma antibodies during the first 3 days of culture and not becoming totally resistant to these agents until day 5 of culture. Capping off of sIgG receptors, with the subsequent addition of tetanus toxoid, abolished the antigen-induced inhibition of IgG-Tet seen previously, whereas capping off of sIgD or sIgM did not affect antigen inhibition of IgG-Tet antibodies. These results implicate sIgG molecules as those responsible for rendering IgG-Tet precursors susceptible to antigen-induced inhibition.

Animals↗
PubMed1982

Chemical-and X-ray-induced antitumor cell-mediated immunity to rat fetal cells.

Gastrointestinal cancer was induced in Fischer F344 inbred rats in their: (i) small bowel by localized exposure to X-rays, (ii) colon by administration of the carcinogen 1,2-dimethylhydrazine (DMH), and (iii) pancreas by implantation of the polyaromatic hydrocarbon 7,12-dimethylbenz[a]anthracene into the 'head' of the organ. A common tumor-associated fetal antigen (TAFA) and cell-mediated immunity (CMI) was noted in these three animal cancer models. The present investigation was a preliminary attempt to delineate the relationship between the TAFA and CMI. Findings indicate that those cells having the TAFA are suitable targets for cytotoxicity expressed by the educated peripheral blood lymphoid cells (PBLC) obtained from the tumor-bearing rats, and that components containing the TAFA (tumor cell membrane extracts, serum) are capable of competing with such targets in the CMI responses. In addition, cells derived from 16-18-day-old rat fetuses were found to be significantly injured and killed by these PBLC. Probably the most important results in this initial study was the findings that cancers induced by these three completely different cellular mechanisms in different tissues resulted in common TAFA and CMI responses and that there is a relationship between these two phenomena which is at this time unclear.

Animals↗
PubMed1981

Expression of surface membrane IgG on pokeweed mitogen-reactive anti-tetanus toxoid antibody-producing cells.

Anti-tetanus toxoid antibody-producing cells, differentially expressing surface membrane IgM, were analyzed for the additional expression of surface membrane IgG. micron+ and micron- cells were rosetted with anti-gamma-ox red blood cells and separated by density centrifugation into fractions enriched or depleted of gamma + cells. These B-cell subsets were assayed for the production of IgM and IgG anti-tetanus toxoid antibody and total IgM and IgG. The results indicated that the majority of anti-tetanus toxoid antibody synthesis in the micron- fraction was by gamma + cells. In the microm+ fraction, however, both IgM and IgG anti-tetanus toxoid antibody production was detected in the micron+ gamma- and micron+ gamma+ fraction. The inclusion of isotype-specific antisera during the first 2 days of culture further established that gamma was expressed on the surface of the majority of the precursors for IgG anti-tetanus antibody production in vitro. Studies performed to determine the culture requirements of micron- and micron+ cells revealed that production of IgG anti-tetanus toxoid antibody by both cell subsets was dependent on T cells and pokeweed mitogen. However, some micron- cells could produce IgG in the presence of T cells alone.

Animals↗
PubMed1981

Identification of a common oncofoetal protein in x-ray and chemically induced rat gastrointestinal tumours.

An apparently unique circulating common oncofoetal protein has been identified in rat small-bowel, colonic and pancreatic adenocarcinomas. The tumours were induced by ionizing radiation (small bowel), an alkyl hydrocarbon, 1,2-dimethylhydrazine (colon) and a polyaromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (pancreas). The oncofoetal protein was identified by the use of specific xenogenic antitumour rabbit sera generated to the X-ray-induced neoplasm. In addition, the foetal protein was also found always to occur in the liver and lungs of those animals bearing the chemically induced tumours as well as in their serum. These results suggest the existence of a close relationship at the molecular level in the tumorigenic processes, even though induction is by apparently different mechanisms, for cancers arising in tissue or common embryonic origin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Evidence that pokeweed-mitogen-reactive B cells are pre-committed in vivo to the high-rate secretion of a single immunoglobulin isotype in vitro.

Normal human peripheral blood B cells that respond to pokeweek mitogen (PWM)-activated irradiated T cells with high-rate immunoglobulin secretion in vitro were analysed with respect to the frequency of the cells stimulated to high-rate immunoglobulin secretion in vitro and whether the progeny of each cell had the potential to secrete one or multiple immunoglobulin isotypes. In vitro cultures containing limiting numbers of human B cells were initiated in the presence of PWM and excess irradiated T cells, and the quantity of IgM, IgG and IgA secreted was determined after 9 days. The level of immunoglobulin secretion per cell in limiting-dilution microcultures was shown to be equivalent to that seen in the routinely used macrocultures, indicating that major loss of B-cell function was not occurring in the microcultures. At limiting B-cell numbers, individual microcultures were of ten shown to produce immunoglobulin of a single isotype, either IgM, IgG or IgA. Cultures that did produce multiple immunoglobulin isotypes occurred with a frequency predicted by the random distribution of B cells committed to production of a single isotype. A similar independent distribution of IgM anti-tetanus toxoid and IgG anti-tetanus toxoid antibody-producing precursors was observed when B cells selected on the basis of surface IgM were used in the microcultures. These results suggest that PWM-reactive B cells are at a stage of maturation in vivo such that they have the potential to secrete a single immunoglobulin isotype when activated in vitro.

Adult↗