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Biomedical subjects

B Morrison

Publications and source records attributed to B Morrison.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effect of anti-DNP IgG1- and IgG2a-secreting hybridomas in vivo on the development of an anti-DNP IgE antibody response in mice.

We reported previously that CBA mice pretreated with dinitrophenyl-Bordetella pertussis (DNP-BP) conjugates exhibited sharply decreased anti-DNP IgE, and increased IgG2a antibodies following immunization with DNP-ovalbumin (DNP-OA) in alum. The objective of the present experiments was to determine whether the decrease in anti-DNP IgE was attributed to a regulatory effect exerted by IgG2a antibodies. Anti-DNP monoclonal antibodies (Mab) of the IgG1 or IgG2a isotype were passively transferred to mice, 24 h before a primary immunization with DNP-OA in alum. Anti-DNP IgE production was drastically suppressed in recipients of IgG1 but not of IgG2a Mab. Similar results were obtained when the Mab were endogenously produced by intraperitoneal implantation of anti-DNP-secreting hybridomas into (BALB/cxCBA)F1 (BCF1) mice. However, neither IgG1 nor IgG2a isotypes suppressed IgE antibody production if the hybridoma implantation took place 10 days after hapten priming. These results are, to our knowledge, the first to show a clear dissociation between the effect of either passively transferred or endogenously secreted IgG1 and IgG2a antibodies in their ability to inhibit a primary anti-hapten IgE antibody response.

Animals↗
PubMed1991

The spontaneous apoptotic cell death of normal human lymphocytes in vitro: the release of, and immunoproliferative response to, nucleosomes in vitro.

Nucleosomes released spontaneously in short-term culture from murine spleen cells have a significant immunoproliferative effect in vitro, including the stimulation of anti-DNA antibody responses. The present studies show that during short-term cultures, tonsil lymphoid cells also undergo spontaneous apoptosis revealed morphologically (electron microscopy) by the appearance of changes in nuclear chromatin, typical of apoptosis and similar to morphologic changes of apoptosis in cultured normal splenic lymphocytes. This process is followed by the release, in the greater than 30-kDa cell free supernatant fraction, of core histones (H2A, H2B, H3, H4) and low molecular weight DNA (approx 160 bp) constituents of nucleosomes. The greater than 30-kDa tonsil lymphocyte cell-free supernatant material containing the constituents of core nucleosomes, as well as the greater than 30-kDa supernatant fractions of tonsil cell lysates harvested at the same time, had a significant immunoproliferative effect on human or murine lymphocytes, increasing both DNA and immunoglobulin synthesis (protein A plaque-forming cells). Thus the release of immunoproliferative nucleosomes form dying human lymphoid cells provides an autocrine lymphocyte stimulatory network which may be important in immunoproliferative disorders and in normal cell turnover. Apoptosis in vivo may also provide a potential source for the circulating nucleosomal DNA identified in plasma in some systemic lupus erythematosus patients as well as contributing to increased polyclonal B lymphocyte stimulation and autoantibody responses in this disorder.

Cell Survival↗
PubMed1990

Immunogenic DNA-related factors. Nucleosomes spontaneously released from normal murine lymphoid cells stimulate proliferation and immunoglobulin synthesis of normal mouse lymphocytes.

The cell-free supernatants of normal spleen and thymus lymphocytes in short-term culture release low molecular weight (LMW) DNA protein molecules that have an immunoproliferative effect (polyclonal B cell activation) in vitro. We have determined that the protein-LMW DNA complexes responsible for these effects are nucleosomal constituents of chromatin, since the mitogenically active fractions of these cell-free supernatants contain the constituents of core histones (H3, H2A, H2B, H4) together with LMW DNA (140-180 bp), and since the immunoproliferative effects of these cell-free supernatants could be mimicked by various other nucleoprotein preparations (including calf thymus and chicken erythrocyte nucleosomes). The spontaneous cellular release of cleaved chromatin constituents in vitro can be attributed to a form of programmed cell death termed apoptosis, since the cultured spleen cells exhibited (a) morphologic evidence consistent with this process by electron microscopy, and (b) evidence of intracellular cleavage of chromatin which, like apoptosis, could be blocked with ZnSO4. This resulted in inhibition of the extracellular release of nucleosomal constituents as well as the immunoproliferative effects of the cell-free supernatants. The immunoproliferative effect of nucleosomes released from cells during apoptosis could be responsible for previously observed spontaneous in vitro anti-DNA and anti-histone antibody responses of murine spleen cells, and in vivo in normal lymphoid tissues, resulting in renewed cellular proliferation after cell death. In pathological states, this could result in abnormal polyclonal B cell proliferation and autoantibody formation.

Animals↗
PubMed1989

Potential exposure of cooks to airborne mutagens and carcinogens.

Recent case-control and proportionate mortality studies in Canada, the United States, Britain, and Denmark have shown that cooks and other food-service workers may have elevated risks of cancers of the nasopharynx, buccal cavity, esophagus, lung, and bladder. The purpose of this pilot study was to determine if there might be airborne products of cooking which may be risk factors for these cancers in cooks. Eight air samples were taken in four restaurants and subsequently analyzed for mutagenicity using the Ames assay, and for carcinogens using gas chromatography/mass spectrometry. All four samples taken in the restaurant cooking areas were mutagenic to TA98 without metabolic activation, and two were mutagenic to TA100 also without metabolic activation. Of the four dining area samples, one was mutagenic to TA100 and one to TA98, both without metabolic activation. Compounds tentatively identified by mass spectrometry did not include known carcinogens. The ventilation systems in all four restaurants allow the exposure of cooks to both the air from dining room smoking areas and the volatile products of cooking.

Air Pollutants, Occupational↗
PubMed1983

Simian virus 40 tumor antigen: isolation of the origin-specific DNA-binding domain.

To localize the origin-specific DNA-binding domain on the simian virus 40 tumor (T) antigen molecule, we used limited proteolysis with trypsin to generate fractional peptides for analysis. A 17,000-Mr peptide was found to be capable of binding not only to calf thymus DNA, but also specifically to the simian virus 40 origin of DNA replication. This approximately 130-amino-acid peptide was derived from the extreme N-terminus of the T antigen and represented less than one-fifth of the entire molecule. The coding sequence for this tryptic peptide was located approximately between 0.51 and 0.67 map units (excluding the intron, which maps between 0.54 and 0.59). Since the first 82 amino acids are shared between large T and small t antigens, and since the latter does not bind DNA, it can be concluded that the sequence between isoleucine 83 and approximately arginine 130 is necessary for origin-specific binding by the T antigen. We also observed that in vivo phosphorylation of the T antigen within this region completely abolished the ability of the 17,000-Mr peptide to bind DNA. This observation is consistent with the idea that DNA binding by the T antigen is regulated by posttranslational modifications.

Animals↗
PubMed1981

Airway responsiveness to histamine as a test for overall severity of asthma in children.

Seventy-eight children who had a history of asthma were studied while they were symptom-free. There was a highly significant correlation between the dose of aerosolized histamine that produced a decrease in FEV1 of 20% and each of the features in the history that indicated severity of asthma. The correlation was strengthened by the combination of these features into a weighted asthma history score. None of the subjects with mildly increased bronchial reactivity had a history score of severe asthma, and none with markedly increased bronchial reactivity had mild asthma. There was also a highly significant correlation between histamine dose and the results of spirometric tests for airway obstruction. However, the correlation between asthma history score and provocative histamine dose was highly significant even in the 21 subjects who were apparently free of airway obstruction at the time of testing. Furthermore, the correlation between asthma history score and histamine dose was stronger than that between asthma score and any spirometric test, indicating that the histamine test more accurately assessed the overall severity of the asthma. Measurement of bronchial responsiveness to histamine is a useful adjunct to history in determining the severity of asthma in an individual and should be considered as an objective way of grading subjects according to severity of asthma in a clinical study.

Adolescent↗
PubMed1981

Metabolism of 4-benzamido-1-[4-(indol-3-yl)-4-oxobutyl]piperidine in rats and monkeys.

1. Studies on the absorption, biotransformation and excretion of the potential anti-hypertensive agent 4-benzamido-1-[4-(indol-3-yl)-4-oxobutyl]piperidine (Wy 23699) have been carried out in monkeys and rats. 2. Absorption of the drug in both species was good, as shown by the relative proportions of radioactivity found in the urine after i.v. and oral dosage. 3. Biotransformation was extensive in both species, but the major routes of metabolism were different. In monkey N-dealkylation gave rise to 4-benzamidopiperidine as the principal metabolite; two other minor metabolites were identified as 2-oxo-4-benzamidopiperidine and 4-benzamido-1-[4-(5-hydroxyindol-3-yl)-4-oxo-butyl]piperidine. In the rat, this latter compound (as its conjugate) was the major metabolite; small amounts of benzamidopiperidine but not 2-oxobenzamidopiperidine were found. 4. There was a marked species difference in the route of excretion. Monkeys excreted greater than 60% dose of the drug in the urine, while rats excreted only 19% by this route. This may reflect the species difference in routes of metabolism, metabolic scission of the drug molecule seen in the monkey favouring renal rather than biliary excretion. The toxicological consequences of this are discussed.

Animals↗
PubMed1980

Tobacco use, occupation, coffee, various nutrients, and bladder cancer.

In a Canadian population-based case-control study of 480 males and 152 female case-control pairs, the relative risk for development of bladder cancer for ever used versus never used cigarettes was 3.9 for males and 2.4 for females, with a dose-response relationship in both sexes. A reduced risk was associated with the use of filter cigarettes compared to nonfilter cigarettes. After control for cigarette usage, a significant risk was noted for male pipe smokers. For male ex-smokers the risk after 15 years of no smoking was less than one-half that of current male smokers. Bladder cancer risk was found for workers in the chemical, rubber, photographic, petroleum, medical, and food processing industries among males and for workers occupationally exposed to dust or fumes among both sexes. Bladder cancer risk was elevated for males consuming all types of coffee, regular coffee, and instant coffee and for females consuming instant coffee, but no dose-response relationship was found. Risk was found for males consuming water from nonpublic supples but not for females. No risk was observed in males or females consuming nitrate-containing foods, beverages other than coffee, or fiddlehead greens. Hair dye usage in females and phenacetin usage in males and females carried no risk. Divergent findings by area for aspirin suggested that an overall association was not causal. Reevaluation of the data on artificial sweeteners confirmed a significant bladder cancer risk in males and a dose-response relationship. The cumulated population attributable risk for bladder cancer was 90% for males from cigarette smoking, industrial exposure, and exposure to nonpublic water supplies and 29% for females from cigarette smoking, industrial exposure, and instant coffee consumption.

Age Factors↗