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Biomedical subjects

J B Cologne

Publications and source records attributed to J B Cologne.

28 records · Page 2Linked to original sources

Radiosensitivity of atomic bomb survivors as determined with a micronucleus assay.

If A-bomb survivors include a disproportionately large number of either radioresistant or radiosensitive persons, the surviving population would provide a biased estimate of the true risk of radiogenic cancer. To test this hypothesis, the in vitro X-ray sensitivities of peripheral blood lymphocytes obtained from 937 A-bomb survivors were measured with a cytokinesis-blocking micronucleus assay. Background frequencies (no irradiation in vitro) of micronuclei show a wide distribution. Frequencies in both males and females tend to increase with increasing donor age. Frequencies in females are significantly higher than those in males. Donor age decreases the sensitivity of lymphocytes to in vitro X-ray exposure at a rate of about 0.001 micronuclei per cell per year per gray. There is no effect of donors' sex on in vitro radiation sensitivity. Atomic bomb radiation and cigarette smoking had no significant effect on background and X-ray-induced micronuclei frequencies. Thus there is no difference in radiosensitivity of peripheral blood lymphocytes between proximally and distally exposed survivors.

Age Factors↗

Development of a flow-cytometric HLA-A locus mutation assay for human peripheral blood lymphocytes.

A flow-cytometric technique was developed to measure the frequency of variant lymphocytes lacking expression of HLA-A2 or A24 allele products among donors heterozygous for HLA-A2 or A24. It was found that the variant frequency of lymphocytes in peripheral blood was of the order of 10(-4) and increased with donor age. Molecular analyses of mutant clones revealed that about one-third were derived from somatic recombinations and that the remaining two-thirds did not show any alterations after Southern blotting analysis. In contrast, mutants obtained after in vitro X-ray mutagenesis study were found to be mostly derived from large chromosomal deletions. A small-scale study on atomic bomb survivors did not show a significant dose effect.

Adult↗

X-ray induction of micronuclei in human lymphocyte subpopulations differentiated by immunoperoxidase staining.

In this study we sought to confirm the radiosensitivity of human peripheral blood lymphocyte subpopulations using a micronucleus assay. Mononucleated cells isolated from peripheral blood were irradiated with X rays. After being cultured for 3 days, cells were fixed and stained using the immunoperoxidase staining technique. Lymphocyte subpopulations were characterized by means of the monoclonal antibodies Leu4 (CD3), Leu2a (CD8) and Leu19 (CD56). Dose-response curves were obtained by scoring the number of micronuclei in binucleated cells that reacted with a specific antibody and were then stained. The dose response of CD8+ (suppressor/cytotoxic) cells was quite similar to that of CD3+ (pan T) cells. In comparison, CD56+ (natural killer) cells were significantly less sensitive, although scorable binucleated CD56+ cells made up less than 4% of the total number of binucleated cells.

Adult↗

Flow cytometric measurements of somatic cell mutations in Thorotrast patients.

Exposure to ionizing radiation has long been well-recognized as a risk factor for cancer development. Since ionizing radiation can induce mutations, an accurate way of measuring somatic mutation frequencies could be a useful tool for evaluating cancer risks. In the present study, we have examined in vivo somatic mutation frequencies at the erythrocyte glycophorin A (GPA) and T-cell receptor (TCR) loci in 18 Thorotrast patients who have been continuously irradiated with alpha-particles emitted from the internal deposition of thorium dioxide and who thus have increased risks of certain malignant tumors. When compared with controls, the results showed a significantly higher frequency of mutants at the lymphocyte TCR loci but not at the erythrocyte GPA loci in the Thorotrast patients. The discrepancy between the results of the two assays is discussed.

Aged↗

Gamma-ray- and fission neutron-induced micronuclei in PHA stimulated and unstimulated human lymphocytes.

Two groups of normal human blood cells, one stimulated with phytohaemagglutinin (PHA) for 24 hr (G1-S phase of the cell cycle) and one unstimulated (G0 phase), were irradiated with 60Co gamma rays or 252Cf radiation. A comparison of radiation-induced micronucleus frequencies showed that the high-dose-rate gamma rays were more effective in inducing micronuclei than low-dose-rate gamma rays. In the cells exposed to low-dose-rate irradiation, there was little difference between the frequency of micronuclei in the G0 phase and the G1-S phase. However, cells in the G1-S phase were more sensitive than G0-phase cells to high-dose-rate gamma rays. The relative biological effectiveness of 252Cf neutron irradiation measured in micronucleus assays was consistent with the value obtained for the lethal effect of 252Cf on cultured cells.

Adult↗

Statistical comparison of ligand-binding kinetics.

We describe the application of generalized linear model methodology to the problem of testing differences among ligand-receptor interactions, and show that the method is analogous to weighted least squares regression methodology and F tests familiar to many investigators. The method accommodates incomplete block designs so that one can obtain kinetic parameter estimates directly comparable among samples analysed on incompletely overlapping sets of experimental runs. We demonstrate the method with data that compare saturation kinetics for a single penicillin-binding protein in isogenic ampicillin susceptible and resistant bacteria.

Ampicillin Resistance↗

Comparison of isotonic and hypertonic fluids in resuscitation from hypovolemic shock.

Hypertonic electrolyte solutions provide effective fluids for resuscitation of burn patients and concurrent replacement of hemorrhage. Infusion of mannitol has also been advocated as a means of increasing cardiac output in acutely ill patients. Pigs which were bled to one-third of their blood volume were used in this random study of resuscitation with Ringer's lactate solution (RL), hypertonic saline solution (HSL) and RL with mannitol added (HMR) to give the same osmolality as HSL. Smaller volumes of the hyposmolar solution than of RL restored blood pressure and cardiac output. RL and HSL restored and maintained cardiac output more effectively than HMR. At 24 hours, HSL maintained blood pressure most effectively.

Animals↗

Quantitation of skeletal-muscle necrosis in a model compartment syndrome.

UNLABELLED: Skeletal-muscle necrosis was evaluated in previously pressurized canine compartments using technetium-99m stannous pyrophosphate and classic histological criteria. Intracompartmental necrosis was quantitated in the anterolateral muscle compartment of each dog by uptake of 99mTc stannous pyrophosphate using the contralateral anterolateral compartment as an internal control. Representative specimens of muscle were sampled in experimental and control legs of each dog and were analyzed by qualitative histological techniques. Muscle necrosis was assessed in compartments forty-eight hours after pressurization to levels of ten to 120 millimeters of mercury for eight hours in thirty-seven dogs. In another dog, neither anterolateral compartment was pressurized so that both compartments acted as control muscle. The results in these experiments identify a threshold pressure level (thirty millimeters of mercury) and duration (eight hours) at which significant muscle necrosis occurs at normal blood pressure. Our findings imply that a quantitative relationship exists between incorporation of 99mTc stannous pyrophosphate and the level of intracompartmental pressure. This uptake technique, however, is not suitable for diagnosing compartment syndrome in patients with a threatened compartment syndrome. We suggest that intracompartmental pressure measurements by the wick-catheter technique, in conjunction with clinical findings, offer the best means for diagnosing compartment syndrome. CLINICAL RELEVANCE: Significant muscle necrosis associated with an impending compartment syndrome occurs at a threshold intracompartmental pressure of thirty millimeters of mercury after eight hours. Since time variables are often unknown in suspected compartment syndromes, fasciotomy is recommended when intracompartmental pressure exceeds thirty millimeters of mercury in a patient with normal blood pressure. The use of this threshold pressure level as an indication for fasciotomy requires a device for measuring intracompartmental pressure such as the wick catheter.

Animals↗

Risk factors for primary breast cancer in Japan: 8-year follow-up of atomic bomb survivors.

BACKGROUND: Findings from the Life Span Study (LSS) of the health effects of exposure to atomic bomb radiation have documented a strong dose-response relation between radiation exposure and breast cancer incidence. PURPOSE: We analyzed data from the LSS cohort to identify nonradiation risk factors for breast cancer and to determine whether these factors were independent of the effects of radiation on breast cancer occurrence. METHODS: Breast cancer incidence was ascertained among a cohort of 22,200 residents of Hiroshima and Nagasaki, Japan, who had completed a mail survey between 1979 and 1981 to study nonradiation risk factors for disease. During the subsequent follow-up period (average 8.31 years), 161 cases of primary breast cancer were identified through population-based tumor registries in the two cities. RESULTS: The risk of breast cancer was inversely related to age at menarche and weakly positive in relation to age at menopause and years of menstruation. A significant negative association of full-term pregnancy against breast cancer was observed, although the number of pregnancies beyond the first was not related to the rate of breast cancer in the cohort. Women having their first full-term pregnancy before age 30 were at decreased risk of breast cancer relative to older women, but there was no trend. A nonsignificant, positive trend in risk was associated with increasing weight and body mass (kg/m2). The risk of breast cancer among women with a history of estrogen use was 1.64 (95% confidence interval 1.02-2.64) and with diabetes 2.06 (95% confidence interval 1.27-3.34). It was not possible to distinguish among additive and multiplicative models of the joint association of radiation dose and various non-radiation-related exposures (age at menarche, full-term pregnancy, female hormone preparations) identified in this analysis. CONCLUSIONS: Nonradiation risk factors for breast cancer among Japanese atomic bomb survivors were consistent with those identified among other populations of women, although the prevalence of common risk factors was low. Reproductive factors and hormone use appear to act independently of radiation exposure on the risk of breast cancer among this population.

Aged↗