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Biomedical subjects

B Armstrong

Publications and source records attributed to B Armstrong.

At least 127 records · Page 7Linked to original sources

Neonatal 6-hydroxydopamine lesion of forebrain norepinephrine does not eliminate critical period for behavioral effects of gonadal hormone manipulation.

Newborn rats were injected s.c. with 6-hydroxydopamine to deplete forebrain norepinephrine (NE) or with the vehicle. The males were then castrated at 4 days and the females injected with testosterone at 5 days of age. Both sexes were tested for female-like sexual responsiveness to a stud male at 6 months of age. The loss of forebrain NE did not prevent the feminization of the males due to castration or the masculinization of the females due to testosterone. This result contraindicates a general permissive-requisite role for forebrain NE for the mammalian brain's plasticity during its critical periods.

Animals↗

Cohort study of mortality of vermiculite miners exposed to tremolite.

A cohort of 406 men employed before 1963 for at least one year in a vermiculite mine in Montana was followed up until July 1983. The vermiculite ore as fed to the mill contained 4-6% of amphibole fibre in the tremolite series. Vital status was established in all but one of the 406 and death certificates were obtained and coded for 163 of the 165 men who died. Compared with white men in the United States, the cohort experienced excess mortality from all causes (SMR 1.17), respiratory cancer (SMR 2.45), non-malignant respiratory disease (SMR 2.55), and accidents (SMR 2.14). Four deaths were from malignant mesothelioma (proportional mortality 2.4%). Compared with Montana death rates, the SMR for respiratory cancer was somewhat higher (3.03). Man-year analyses of respiratory cancer and estimated cumulative exposure gave a relation that did not depart significantly from linearity. The results of this and case-referent analyses indicate an increased risk of mortality from respiratory cancer in this cohort of about 1% for each fibre year of exposure. In relation to estimated exposure the mortality experienced by the cohort from both lung cancer and mesothelial tumours was higher than in chrysotile mining.

Aluminum Silicates↗

Radiological survey of past and present vermiculite miners exposed to tremolite.

Chest radiographs taken by a standard technique were obtained from 173 current employees (164 men, 9 women) of a vermiculite mine in Montana, from 80 of 110 past employees resident within 200 miles, and from 47 men from the same area without known exposure to dust. In 43 of the 80 and 24 of the 47 an earlier chest x ray film was retrieved from the hospital archives. All 367 films were assessed blind and independently by three experienced readers using the ILO 1980 classification. Median radiographic assessment scores were analysed in relation to estimated cumulative exposure to the amphibole fibres that contaminate the vermiculite. Logistic regression analyses showed independent effects of age, smoking, and exposure on the prevalence of small opacities and of age and probably of exposure on pleural thickening. Overall, the data suggest that by retirement age the increase in prevalence of small opacities (greater than or equal to 1/0) lies between 5% and 10% per 100 f/ml years. This gradient may be somewhat steeper than for chrysotile miners and millers, but not much so.

Adult↗

The natural history of asbestosis in former crocidolite workers of Wittenoom Gorge.

The course of pulmonary asbestosis and its determinants have been examined in 280 applicants for compensation among former workers of the crocidolite mine and mill at Wittenoom Gorge, Western Australia. Serial chest radiographs accrued over more than 3 decades were graded for parenchymal disease separately by two observers according to the 1980 ILO Classification of Radiographs for Pneumoconioses and without knowledge of exposure histories or compensation details. In 136 subjects whose median duration of exposure was 37 months, radiographic asbestosis appeared between 1 and 34 yr after initial exposure and then progressed continuously. Total exposure to asbestos and time from first exposure to the appearance of definite radiographic asbestosis were significant determinants of the rate of progression of profusion of radiographic abnormality. Asbestosis should be considered to be an active disease even 3 decades after exposure has ended.

Adult↗

Distribution of developmental markers in rat mammary tumors induced by N-nitrosomethylurea.

We have examined the distribution of immunological markers in 55 intraductal carcinomas induced in rats by N-nitrosomethylurea using several different regimens of carcinogen treatment. The goal was to determine the possible relationship of the marker distribution to those existing at various stages of development of the mammary gland. We have also examined two passage lines in syngeneic rats derived from two of the tumors. The distribution of markers was not affected by the regimen of administration. The primary tumors were found to maintain the general topography of mammary ducts but with infoldings of the basal layer without accompanying stroma. We attribute this to an abnormal expression of the tendency of basal cells to migrate towards the lumen to generate luminal cells. The distribution of markers in the tumors was evaluated by identifying 13 special features of distribution that are common in tumors, using all-or-none criteria. The distribution of these features bears out the high heterogeneity of tumors in which the various features vary in a seemingly independent way. There is also heterogeneity within tumors, adjacent nodes often having different marker distributions. The distribution of the markers is related to that found in the early stages of mammary development. Because of this characteristic and of the fact that the tumors contain both basal and luminal cells, they must originate from multipotent cells, probably the stem cells present in end buds and ducts as already proposed by other work. As they develop, the tumors can both differentiate towards the adult type and dedifferentiate towards a fetal type. Of the two transplanted lines one retained the same general features of primary tumors in several passages, whereas the other evolved into a fusiform cell type with a marker distribution not seen at any stage of mammary development. Foci of similar cells were already present in the primary tumor, suggesting that the tendency to progress was already determined at an early stage. The fusiform cells are similar and probably equivalent to the fusiform cells that arise in vitro in cultures of rat mammary cancers.

Animals↗

Spontaneous abortion and occupation.

Occupational factors in spontaneous abortion were studied in the current and previous pregnancies of 56,012 women interviewed in 11 Montreal maternity departments, 1982 to 1984. Ratios of observed to expected abortions (RR), after allowance for nonoccupational confounders, were significantly increased (P less than .05) among nursing assistants and attendants (RR 1.24 in current and 1.13 in previous pregnancies), food and beverage servers (RR 1.31 in current and 1.11 in previous pregnancies) and sales persons (RR 1.18 in current and 1.12 in previous pregnancies). Women whose work entailed heavy lifting, other physical effort, long hours, exposure to noise, and exposure to cold had also significantly increased risk ratios. However, when occupational groups were ranked according to work demands, thus avoiding potential bias from prior knowledge of outcome, increased risks were associated consistently only with heavy lifting and other physical effort.

Abortion, Spontaneous↗

Two monoclonal antibodies selective for human mammary carcinoma.

Mouse myeloma cells were fused with spleen cells from BALB/c mice immunized with the MCF-7 human mammary carcinoma cell line. Among hybridomas, two (3B18 and 15A8) were selected and cloned. Hybridoma 3B18 produces kappa-IgG1 antibodies that react with a cytoplasmic component of MCF-7 cells. In immunoperoxidase assays, 3B18 reacts with 27 of 31 specimens of human mammary carcinoma. It reacts most consistently with poorly differentiated and infiltrating ductal breast cancers, but it also reacts with isolated cells in 3 of 5 benign mammary pathological lesions with a variable distribution. The antibody does not react with normal mammary epithelium. It does not react with any normal human tissues, and it reacts with only one of 19 other cancers tested. Hybridoma 15A8 produces kappa-IgG1 antibodies that react with the surface membranes of the cells of two human breast cancer cell lines but not with a human fibroblast cell line. In immunoperoxidase assays, the antibody reacted with 28 out of 31 human mammary carcinomas. The antibody also reacts more weakly with normal human epithelial cells of breast, renal proximal tubule, skin, esophagus, and salivary gland, but no other normal tissue. The antibody was unreactive with 14 of 18 other malignant tissues tested. Since 3B18 and 15A8 detect antigens found predominantly in human mammary carcinomas and, possibly, distinguish overlapping categories of human mammary carcinomas, they may prove useful in determining the cellular lineage from which human mammary carcinomas arise, or they may have other clinical applications in breast cancer.

Antibodies, Monoclonal↗

Developmental regulation of cytokeratins in cells of the rat mammary gland studied with monoclonal antibodies.

We have isolated two monoclonal antibodies to cytokeratins and determined their cell specificities. They display interesting localization within the rat mammary gland. One (1A10) shows specificity for myoepithelial cells; the other (24B42) is specific for lumenal cells at various stages of development. These two monoclonal antibodies and three others to cytokeratin previously isolated were used in conjunction with antibodies to myosin and collagen IV to confirm and extend our previous findings on epithelial cell types and development within the mammary gland.

Aging↗

A comparison of populations self-selected and randomly selected for coronary risk factor screening.

Levels of coronary risk factors in 3,090 adults who sought screening over a 2-year period in Perth, Western Australia, were compared with those in 722 subjects who were selected at random to attend the screening center. Self-referred (SR) subjects were less likely than random-sample (RS) subjects to have suffered from, or be on treatment for, heart disease, hypertension, gout, or diabetes but were more likely to have a family history of premature heart disease. They were less likely to be current smokers and overweight (women only) but more likely to be sedentary at work and have higher mean serum cholesterol levels. SR also had more knowledge about coronary heart disease (CHD) and its causes and were more likely to believe that this knowledge had influenced their behavior, but were less likely than RS to be satisfied with their knowledge level. Smokers among SR were more likely to express a wish to give up smoking than smokers in the RS. These findings are consistent with previous observations. The differences, although statistically significant, were generally small and did not clearly favor one group with respect to total risk of CHD. Therefore the effectiveness of risk factor modification following screening should not be greatly affected by self-selection for screening. Effectiveness may be greater in self-selected subjects because of their apparently greater motivation toward risk factor change.

Adult↗

Epithelial cell types and their evolution in the rat mammary gland determined by immunological markers.

We have used immunological reagents for characterizing epithelial cell types in the adult rat mammary gland. Some were sera against purified proteins; others were monoclonal antibodies to mammary cells. On the basis of marker distribution we have identified 10 different cell types. We have established the developmental connection between these types by adopting the principle that cells displaying the same markers are directly related to each other. The results concur with those previously obtained by studying the growth response of mammary cells to the hormonal changes of the estrus cycle.

Animals↗

Cell types and morphogenesis in the mammary gland.

Cell types present in the mammary gland and their evolution were studied by labeling female rats with radioactive thymidine at various phases of the estrus cycle. The results suggest that the stem cells for mammary development are present in the terminal end buds and that they generate a lineage for lumenal cells and possibly a distinct one for myoepithelial cells. Growth and differentiation are controlled by both hormones and local factors.

Animals↗

Endocrine factors in human carcinogenesis.

Endogenous hormones probably do not initiate cancer directly but may influence carcinogenesis by facilitation or inhibition of endogenous production of carcinogens; effects on the metabolic activation or inactivation of carcinogens; alteration of the susceptibility of tissues to the initiation of cancer; promotion of the development of clinical cancer from initiated cells; and (theoretically) alteration of the body's capacity to eliminate initiated cells. Evidence exists for a role of endogenous hormones in cancers of the salivary gland, colon and rectum, liver, gall-bladder, pancreas, breast, cervix uteri, corpus uteri, ovary, prostate, testis, kidney, thyroid and pituitary glands and malignant melanoma. Oestrogens are the most commonly implicated hormone, and there is sufficient evidence for their causal association with cancers of the breast and endometrium. The most commonly postulated mechanisms of action are alteration of the susceptibility of tissues to initiation, and promotion of the once-initiated cancer. In human beings and, to some extent, in animals it is difficult to distinguish between these two mechanisms, both of which are based on hormone-induced cell proliferation, because the time of initiation cannot be pinpointed. Environmental factors may influence carcinogenesis by effects on the production, transport, peripheral action, inactivation and excretion of endogenous hormones. Examples that illustrate some of these possibilities may be derived from the effects of diet on risk of breast, endometrial and thyroid cancers.

Biotransformation↗