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Biomedical subjects

J Gamble

Publications and source records attributed to J Gamble.

At least 91 records · Page 5Linked to original sources
PubMed1983

An epidemiological study of salt miners in diesel and nondiesel mines.

A cross-sectional study of 5 NaCl mines and 259 miners addressed the following questions: 1) Is there an association of increased respiratory symptoms, radiographic findings, and reduced pulmonary function with exposure to nitrogen dioxide (NO2) and/or respirable particulate (RP) among these miners? 2) Is there increased morbidity of these miners compared to other working populations? Personal samples of NO2 and respirable particulate for jobs in each mine were used to estimate cumulative exposure. NO2 is used as a surrogate measure of diesel exposure. Cough was associated with age and smoking, dyspnea with age; neither symptom was associated with exposure (years worked, estimated cumulative NO2 or RP exposure). Phlegm was associated with age, smoking, and exposure. Reduced pulmonary function (FVC, FEV1, peak, flow, FEF50, FEF75) showed no association with exposure. There was one case of small rounded and one case of small irregular opacities; pneumoconiosis was not analyzed further. Compared to underground coal miners, above ground coal miners, potash miners, and nonmining workers, the study population after adjustment for age and smoking generally showed no increased prevalence of cough, phlegm, dyspnea, or obstruction (FEV1/FVC less than 0.7). Obstruction in younger salt miners and phlegm in older salt miners was elevated compared to nonmining workers. Mean predicted pulmonary function was reduced 2-4% for FEV1 and FVC, 7-13% for FEF50, and 18-22% for FEF75 below all comparison populations.

Adult↗
PubMed1983

Fusion of DNA region to murine immunoglobulin heavy chain locus corresponds to plasmacytoma-associated chromosome translocation.

Murine plasmacytomas frequently exhibit a translocation of the distal region of chromosome 15 to the end of chromosome 12, where the immunoglobulin heavy chain locus resides. A candidate for the DNA across the chromosome fusion point is a cloned region of non-immunoglobulin DNA which in most plasmacytomas has recombined near the alpha heavy chain constant region gene. That the incoming DNA, provisionally designated LyR (lymphoid rearranging) DNA, does derive from chromosome 15 is shown here by blot analysis of DNA from two panels of somatic cell hybrids: hybridomas between an AKR T-lymphoma (Tikaut) and CBA mouse cells with a cytogenetically distinctive chromosome 15, and between mouse and Chinese hamster cells. LyR DNA segregated with chromosome 15 in all lines and the results assign LyR to the distal two thirds of that chromosome. This assignment, together with the previously reported high frequency of recombination between LyR and C(alpha) in plasmacytomas and associated alteration of LyR transcription suggests that translocation activates a LyR gene involved in plasmacytoma oncogenesis. Moreover, LyR rearrangement in certain T-lymphomas, such as the Tikaut line examined here, also implicate that gene in oncogenesis of some T-lymphomas.

Animals↗
PubMed1983

New inhibitors of human renin tested in vitro and in vivo in the anaesthetized baboon.

A new inhibitor of human renin (H. 189) is described. It is a decapeptide analogue of human renin substrate with the amino acid, statine, substituted for leucine in the scissile bond. Its inhibitory potency as shown by IC50 is 1.0 X 10(-8) M with human plasma renin and 1.5 X 10(-8) M with baboon plasma renin. It is less effective with dog and rat renin, but its inhibitory potency with human renin is similar to that of another inhibitor of ours (H. 142) having a reduced isostere in the scissile bond. H. 189 has some inhibitory effect on cathepsin D (IC50 6.5 X 10(-5) M) but H. 142 has no discernible effect. Pepstatin, on the other hand, was highly effective against cathepsin D (IC50 1.2 X 10(-8) M). H. 142 and H. 189 were infused intravenously at 10 mg/kg/h in four anaesthetized salt-deplete baboons (Papio hamadryas). The activity of renin in plasma decreased markedly as did the circulating concentration of its products, angiotensin I and angiotensin II.

Anesthesia, General↗
PubMed1983

Influence of pH on capillary filtration coefficient of rat mesenteries perfused with solutions containing albumin.

A preparation of rat mesentery was vascularly isolated from the intestine and perfused with a physiological salt solution containing either Ficoll 70 or bovine serum albumin, to act as colloidal agents. The capillary filtration coefficient (Kf; units, ml. min-1 100 g-1 mmHg-1) was measured by following the weight change after graded increases in venous pressure. At pH values greater than 7.05, Kf, during perfusion with 3 and 4% bovine serum albumin solutions, was 0.219 +/- 0.023 (mean +/- S.E. of mean), ninety-eight observations in thirteen experiments, which was significantly less than the value of 0.507 +/- 0.038 which was obtained during perfusion with albumin solutions at pH less than 7.05, seventy-six observations in eleven experiments, (P less than 0.05). The value of Kf obtained during perfusion with 4% Ficoll solutions was 0.267 +/- 0.018, 119 observations in sixteen experiments, and remained uninfluenced by pH over the same range that had been used with the albumin solutions; however, perfusion of the tissues with Ficoll solutions at pH greater than 7.05, after perfusion with albumin solution pH less than 7.05, did cause the Ficoll-derived value of Kf to rise to 0.502 +/- 0.055, seventy-two observations in eleven experiments. It was concluded that the changes in Kf were not due to pH alone, but were mediated by albumin at acidic pH.

Animals↗
PubMed1981

The role of chromosome 15 in murine leukemogenesis. I. Contrasting behavior of the tumor vs. normal parent-derived chromosomes No. 15 in somatic hybrids of varying tumorigenicity.

G-banding analysis was carried out on a series of hybrids derived from the fusion of a chromosome 15-trisomic murine T-cell leukemia of AKR origin and normal diploid fibroblasts or lymphocytes of the CBT6T6 strain. Due to the 14;15 translocation involved in the generation of the T6 marker, the chromosomes No. 15 and 14 derived from the normal and the tumor parent can be distinguished cytogenetically. Highly tumorigenic, in vitro maintained hybrids, and high-tumorigenic segregants of originally low-tumorigenic in vitro hybrids, selected by in vivo passage, showed a similar cytogenetic pattern. It was characterized by the amplification of the tumor-derived chromosomes No. 15 from the expected 3 to 5.5 +/- 0.2 copies and a concomitant decrease of the normal derived T(14;15)6 from 2 copies to 0.9 +/- 0.2. All other autosomes except No. 14 showed only minor random variations, around the expected number of 4 copies. The tumor-derived chromosome 14 was amplified from the expected 2 to 3 copies. The low-tumorigenic hybrids showed the opposite pattern with a decrease in the number of the tumor-derived 15 chromosome from 3 to 2.6 +/- 0.1 and the maintenance of the two normal parent derived T(14;15)6 chromosomes. These findings suggest the existence of a qualitative difference between the 15 chromosomes derived from the tumor vs. the normal parent, due to mutation or proviral DNA insertion in the tumor-derived homologue. Amplification of the change locus and a decrease in the dosage of its normal counterpart appear to favor tumorigenicity.

Animals↗
PubMed1979

Influence of thymus genotype on acquisition of responsiveness in delayed-type hypersensitivity.

Antigen-pulsed macrophages (Mph) could sensitize syngeneic mice for delayed-type hypersensitivity (DTH) and also elicit sensitivity from mice sensitized to antigen in adjuvant provided these were syngeneic or semi-allogeneic to the strain providing the Mph. Sensitivity could not be elicited with antigen-pulsed allogeneic Mph. Antigen-pulsed Mph from low-responder (LR) strains could not sensitize LR mice nor F1 hybrids between responder (R) and LR strains. Normal F1 mice could be sensitized to respond to antigen presented on Mph or either parental type (i.e. P1 or P2): if, however, they were sensitized to antigen on P1 Mph, DTH transfer was restricted to naive P1 mice, not to P2 (restriction imposed by priming). F1 T cells derived from stem cells differentiating in a P1 thymus graft could be sensitized but could transfer sensitivity only to naive P1 mice, not to P2 (restriction imposed in thymus). When an antigen under Ir gene control was used, LR derived T cells differentiating in an (R X LR)F1 thymus could be sensitized but only if antigen was presented on (R X LR)F1 Mph not on LR Mph. Totally allogeneic chimaeras could be sensitized but only if given antigen in association with the appropriate Mph. These findings suggest that restriction of T cell activities can be imposed as a result of priming in some cases and as a result of differentiation within the thymus in others. LR strains appear to have a lesion at the level of antigen presentation by Mph; whether they also have a defect at the level of generation of T cell repertoire cannot be determined from the present investigations.

Animals↗
PubMed1979

Occupational safety and health implications of increased coal utilization.

An area of major concern in considering increased coal production and utilization is the health and safety of increased numbers of workers who mine, process, or utilize coal. Hazards related to mining activities in the past have been especially serious, resulting in many mine related accidental deaths, disabling injuries, and disability and death from chronic lung disease. Underground coal mines are clearly less safe than surface mines. Over one-third of currently employed underground miners experience chronic lung disease. Other stresses include noise and extremes of heat and cold. Newly emphasized technologies of the use of diesel powered mining equipment and the use of longwall mining techniques may be associated with serious health effects. Workers at coal-fired power plants are also potentially at risk of occupational diseases. Occupational safety and health aspects of coal mining are understood well enough today to justify implementing necessary and technically feasible and available control measures to minimize potential problems associated with increased coal production and use in the future. Increased emphasis on safety and health training for inexperienced coal miners expected to enter the work force is clearly needed. The recently enacted Federal Mine Safety and Health Act of 1977 will provide impetus for increased control over hazards in coal mining.

Anthracosilicosis↗
PubMed1978

T cell-dependent suppression of antibody production. I. Characteristics of suppressor T cells following tolerance induction.

Specific immunological tolerance was induced in adult CBA mice by a single injection of deaggregated human IgG (dHGG). Spleen cells taken 7 to 42 days later, produced consistent suppression of a DNP-HGG collaborative antibody response on adoptive transfer into heavily irradiated recipients. Noncentrifuged F(ab')2 fragments of HGG were as effective as dHGG in the production of suppressor cells. Suppression was antigen-specific since HGG-tolerant cells failed to abrogate either a DNP-keyhole limpet hemocyanin collaborative response or antibody production to the noncross-reactive antigen, horse erythrocytes. Pretreatment of the tolerant cell population with anti-Thy-1 serum and complement reversed the suppressive effect. However, purified tolerant T cells obtained by passage through nylon wool or anti-Ig columns were less effective than the original spleen cells in mediating suppression. Analysis of the cell types appearing in the column effluents indicated that the reduction in suppressive activity is best explained by retention of T cells rather than macrophages. Different T cell populations, however, were retained on the two types of columns. In the case of anti-Ig columns, these consisted of Ly-2,3+, Ia+ effector cells, whereas nylon wool columns caused depletion of Ly-1,2,3+ cells which are known to act as amplifiers of suppression. Suppression could not be explained in terms of delay in differentiation of antibody-forming cell precursors since the effect persisted for up to 15 days after transfer of tolerant cells. The demonstration of a reduction in serum anti-DNP and anti-HGG antibodies excluded the possibility of antibody production in sites other than the spleen. A role for anti-carrier antibody-antigen complexes in mediating the effector phase of suppression was rendered unlikely by the finding that the suppressive effect of tolerant cells persisted in the absence of detectable anti-HGG antibody production. Effector T cells mediating suppression in this system were shown to bear the phenotype Ia+, Ly-2,3+ as judged by the effect of pretreatment with appropriate antisera and complement. They were spleen-seeking, but were not detected in the thymus or recirculating lymphocyte pool. Adult thymectomy failed to cause a significant reduction in suppressive activity by tolerant spleen cells indicating that at least a major component of the immediate precursors is not of recent thymic origin.

Animals↗
PubMed1978

Major histocompatibility complex gene products on macrophages influence T cell activation.

Antigen-pulsed macrophages were used to sensitize or elicit sensitivity from mice of different strains to a variety of antigens. The results indicate that sensitization is directed, not to antigen as such, but to a complex structure on the macrophage surface determined partly by the antigen, and partly by a product coded by the major histocompatibility complex. Delayed type hypersensitivity could be provoked by antigen in responder (R) mice and in the F1 between responder and low responder (LR) strains, but not in LR mice unless pretreated by cyclophosphamide. Sensitivity could be transferred to naive LR-strain mice by lymph node cells taken 5 days after sensitization of cyclophosphamide-pretreated LR mice but not of F1 hybrids between LR and R strains. Sensitivity from these could be transferred only to naive F1 or R-strain mice. The results suggest that low responsiveness cannot be accounted for solely in terms of the operation of a cyclophosphamide-sensitive suppressor mechanism. It is postulated that antigen is less immunogenic when presented by LR-strain cells than by R-strain cells.

Animals↗
PubMed1977

Histocompatibility linked immune responsiveness and restrictions imposed on sensitized lymphocytes.

Delayed-type hypersensitivity (DTH) transfer to GAT was restricted by the I-A region of the major histocompatibility complex (MHC). Sensitized cells from F1 hybrid mice between responder and nonresponder strains transferred DTH to syngeneic F1 mice and to naive parental strain recipients of the responder but not of the nonresponder haplotypes. These results are interpreted to favor the postulate that the MHC-linked Ir genes exert their effects by coding for components which allow interactions between particular I region gene products and the region to form stable structures immunogenic for DTH T cells.

Alanine↗