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Biomedical subjects

B G Miller

Publications and source records attributed to B G Miller.

At least 91 records · Page 5Linked to original sources

Hypertrophy of arteriolar smooth muscle cells in the rat small intestine during maturation.

The purpose of this study was to define structural characteristics for vascular smooth muscle (VSM) cells from the submucosal arteriolar system of the rat small intestine during maturation. Arterioles from 6- to 8-week-old and 10- to 12-week-old male WKY animals were selected from tissue prepared for scanning electron microscopy and mounted on end so that the entire circumference of each vessel could be observed by serial photography using scanning electron microscopy. From each vessel segment, the following measurements were made: outer vessel diameter, number of VSM cells occupying a length of vessel, the number of resolutions each VSM cell makes around the vessel, length of individual VSM cells, and width of lateral processes along their length. At a given age, the length and width of the VSM cell was statistically similar for all types of arterioles. However, the VSM cell increased substantially in length and width from the 6-8- to 10-12-week time periods. The outer diameter for a particular arteriolar type also increased with age. These data suggest that the intestinal vasculature as a common population of smooth muscle cells at a given age in terms of their length, size, and process morphology for the various types of arterioles. Furthermore, maturation of the microvessels is associated with a uniform hypertrophy of the VSM cells from the majority of arterioles such that cells of young adult rats and those of juvenile animals represent distinctly different populations.

Aging↗

Inhalation studies on the effects of tremolite and brucite dust in rats.

Samples of commercially used asbestos, especially chrysotile, are frequently contaminated by small amounts of other fibrous minerals. Among these are tremolite and brucite although pure tremolite is also produced commercially in relatively small quantities. In order to determine how harmful commercially exploited tremolite might be in comparison with other asbestos types and to explore the possibility that small amounts of tremolite and brucite as contaminants could significantly affect the pathogenicity of industrially used chrysotile, long-term animal inhalation and injection studies using rats were undertaken with what were considered to be mineralogically pure samples of these minerals. Rats treated with tremolite developed very high levels of pulmonary fibrosis as well as 16 carcinomas and two mesotheliomas in a group of 39 animals. Tremolite thus proved to be the most dangerous mineral that we have studied. Animals treated with 'brucite' developed moderate levels of pulmonary fibrosis and two carcinomas. Both tremolite and brucite produced mesotheliomas in greater than 90% of animals following i.p. injection. However, it was found that the supposedly pure brucite in fact contained 10% chrysotile, a level of contamination that could well have been responsible for the pathological changes found in both inhalation and intraperitoneal injection studies. The greatest care should be exercised by industry in handling tremolite or materials contaminated with it.

Air Pollutants, Occupational↗

Dust exposure, pneumoconiosis, and mortality of coalminers.

General mortality in approximately 25 000 British coalminers over 22 year periods ending in 1980 was 13% lower on average than in English and Welsh men in the same regions of Britain. There were significant within region variations between collieries, and standardised mortality ratios increased during the later years of the follow up, approaching or slightly exceeding 100 in most of the 20 coalmines studied. Age specific comparisons of 22 year survival rates were made in subgroups. Relative risks of death from all non-violent causes for men with the earliest stage of progressive massive fibrosis (PMF category A), compared with risks in miners with no pneumoconiosis (category O), ranged from 1.2 in those aged 55-64 initially to 3.5 for those aged 25-34. Mortality in miners with higher categories of PMF (B or C) was even more severe. Survival rates in men with category 1 simple pneumoconiosis were about 2% to 3% lower than in miners with radiographs classified as category O, but there was no consistent evidence of an increase in mortality with increasing category of simple pneumoconiosis. Mortality from all non-violent causes increased systematically with increases in estimates of exposure to dust before the start of the follow up. That gradient was attributable primarily to deaths certified as due to pneumoconiosis and those recorded as due to bronchitis and emphysema (p less than 0.001). There was some evidence of a dust related increase in deaths from cancers of the digestive system (p approximately equal to 0.05), but none of an association between exposure to coalmine dust and lung cancer. Lung cancer mortality, assessed over 17 year periods, was about 5.5 times higher in smokers than in life long non-smokers. Smokers with no pneumoconiosis had slightly higher lung cancer death rates than smokers with pneumoconiosis. We conclude that miners exposed to excessive amounts of respirable coalmine dust are at increased risk of premature death, either from progressive massive fibrosis or from chronic bronchitis or emphysema.

Adult↗

Cellular and vessel wall morphology of cerebral cortical arterioles after short-term diabetes in adult rats.

Microvascular pathology is one of the major problems associated with prolonged diabetes mellitus. The purpose of the present study was to determine if anatomical cellular pathology of the cerebral cortical microvessels could be detected very early after the onset of a streptozotocin-induced model of diabetes. Male rats at age 14-16 weeks were hyperglycemic (greater than 250 mg/dl) for 4 weeks prior to scanning and transmission electron microscopic analysis of the external and internal cell and vessel wall morphology of the arterioles. Scanning electron microscopic studies indicated that many processes of vascular smooth muscle cells changed their normal spindle shape to a branched or stellate configuration. The internal cellular changes included swollen mitochondria and cisternae of the endoplasmic reticulum and reduced cytoplasmic staining. Necrosis of arteriolar endothelial cells was evident in virtually every vessel section studied. These data indicate that vascular smooth muscle and endothelial cellular degeneration of cerebral cortical arterioles begins in the very early stages of the streptozotocin model of diabetes.

Animals↗

Effect of forage: concentrate on kinetics of forage fiber digestion in vivo.

With five rumen-fistulated Holstein steers in a Latin square design, we determined the effect of dietary concentrate (0, 20, 40, 60, or 80% cracked corn) on kinetic characteristics influencing forage fiber digestion in vivo. Rate and potential extent of neutral detergent fiber degradation were determined for fescue hay in situ by nylon bag technique. Rate of fiber passage from the rumen was measured by fecal excretion of chromium-mordanted fescue cell walls. Apparent extent of forage fiber digestion was predicted by a model in which fiber disappearance from the rumen is conceptualized as the sum of two competing first-order processes, digestion and passage, modified further by a discrete lag time during which fiber passes from the rumen before digestion commences. Stepwise multiple regression analysis revealed that potential extent of fiber degradation in situ was the primary determinant of depression of fiber digestibility as dietary concentrate increased. Rate of digestion, rate of passage, and lag effects collectively accounted for a small portion of the depression of fiber digestibility.

Animals↗

Influence of diet on postweaning malabsorption and diarrhoea in the pig.

Five-day-old pigs challenged with 10(3) pathogenic Escherichia coli (nalidixic acid resistant) showed no clinical signs of disease until subsequently weaned at three weeks. Dietary manipulation was shown to influence xylose malabsorption, diarrhoea and bacterial proliferation after weaning. Brief, but not continuous, contact with the diet before weaning markedly increased the severity of subsequent disease after weaning. Immunogenicity of the weaning diet was critical for the development of the disease. Two diets, identical except that in one the protein source (casein) had previously been enzymatically hydrolysed, were compared. Pigs fed the predigested diet showed no clinical signs of post weaning diarrhoea whereas those fed the untreated casein all developed diarrhoea.

Animal Feed↗

The importance of dietary antigen in the cause of postweaning diarrhea in pigs.

Food was given to pigs before weaning to determine whether a hypersensitive response to dietary antigen might be a predisposing factor to postweaning diarrhea. Small amounts of food increased the severity and accelerated the onset of postweaning diarrhea. Postweaning diarrhea was dependent on the presence within the diet of antigenic material (bovine casein). A weaning diet, containing little antigenic material (hydrolyzed casein), had less effect on sucrase concentration in intestinal brush borders than did diets rich in antigens (native casein). Seemingly, immune-mediated intestinal damage may predispose the pig to postweaning diarrhea.

Animal Feed↗

Endometrial protein secretion during early pregnancy in entire and ovariectomized ewes.

The secretion and synthesis of protein in vitro by explants of endometrium were examined in entire ewes during the first 10 days of the oestrous cycle and during an equivalent interval in ovariectomized ewes which received injections of oestradiol and progesterone. The schedule of steroid injections given was designed to simulate endogenous ovarian secretion of progesterone during the luteal phase before oestrus, of oestradiol around oestrus and of progesterone during the luteal phase after oestrus. The rate of protein synthesis and tissue RNA:DNA and protein:DNA ratios in intercaruncular and caruncular endometrium were generally higher in entire than in ovariectomized ewes. In ovariectomized ewes oestradiol increased these activities at 2-4 days after oestrus, whereas progesterone preceding oestradiol caused increases at oestrus, but not thereafter. In entire ewes and in ovariectomized ewes receiving the full steroid treatment regimen, protein secretion was high at oestrus and declined markedly during the next 4-6 days. In ovariectomized ewes not receiving progesterone before oestradiol, secretion increased between 4 and 6 days after oestrus, or during the equivalent stage of treatment in ewes which did not show oestrus. The omission of this progesterone did not modify secretion by caruncular endometrium. Oestradiol increased protein secretion by both tissues. The data suggest that progesterone given before oestradiol (or its equivalent in entire ewes) inhibits the secretion, at about 4-7 days after oestrus, of uterine proteins which may impair embryo development in ovariectomized ewes which do not receive this progesterone.

Animals↗

Growth of the endometrium and cotyledons during pregnancy in the ewe: rates of protein secretion and synthesis and nuclear and cytosol steroid hormone receptor levels.

The time-course of cell hypertrophy and changes in in-vitro rates of secretion and synthesis of protein in intercaruncular and caruncular endometrium and maternal and fetal cotyledonary placenta have been examined during days 0-112 of pregnancy in the ewe. The concentrations of high-affinity receptors for oestradiol and progesterone in nuclear and cytosol fractions from these tissues were also determined. Protein secretion by intercaruncular endometrium increased 25-fold between days 0 and 84. On day 84 10(-5) M-colchicine blocked 75% of total secretion. Protein secretion did not increase in the other tissues. Protein synthesis and RNA:DNA ratio in intercaruncular endometrium increased steadily between days 0 and 112, whereas they did not change in caruncular endometrium between days 0 and 28 and declined in cotyledon between days 56 and 112. The levels of cytosol receptor for oestradiol and progesterone and of nuclear receptor for oestradiol in all tissues during days 56-112 were very low in relation to the corresponding levels in caruncular endometrium on day 0. The level of nuclear progesterone receptor in caruncular endometrium increased threefold between oestrus and day 28. The level of this receptor in cotyledon remained low on days 56-112, but in intercaruncular endometrium it increased to high values on days 84-112. The results demonstrated a major surge in secretory activity by the intercaruncular endometrium at around mid-gestation, which was associated with a marked increase in nuclear progesterone receptor levels but only a low level of nuclear oestradiol receptor. The observations do not suggest any important role for oestradiol or progesterone in the growth of fetal and maternal cotyledon.

Animals↗

A new morphological procedure for viewing microvessels: a scanning electron microscopic study of the vasculature of small intestine.

The present study details a new method for the exposure and viewing of individual microvessels located within the small intestine of rats. This procedure will selectively and consistently remove the outer muscle layers and underlying submucosa of the intestinal wall and thereby expose a variety of arterioles in their normal location within the tissue, with their normal relationship to each other undisturbed. The small intestine of the rat was initially fixed by vascular perfusion with 2.5% glutaraldehyde in 0.1 M cacodylate/HCL buffer, reinfused with heparinized whole blood, removed from the animal, and secured to a dissecting petri dish for further fixation. Subsequently, the external muscularis was dissected from the sample which exposed the submucosa. In order to remove the connective tissue elements from this layer and uncover the submucosal vasculature, the samples were first transferred to a solution of 30% potassium hydroxide for 2-5 minutes and then to a final digesting solution containing collagenase. Thereafter, the samples were routinely processed for light microscopy and for scanning (SEM) or transmission (TEM) electron microscopy. Examination of the samples revealed excellent preservation of the three-dimensional organization of the arteriolar wall with minimal membrane damage. This new technique now makes it possible to visualize the shape and position of individual smooth muscle cells along arterioles of differing size and branching order.

Animals↗

Longitudinal study of lung function in coal-miners.

Longitudinal loss of lung function in 1677 coal-miners from five British collieries has been calculated from the results of serial cross-sectional epidemiological surveys and compared with measured concurrent individual respirable dust exposures and partially estimated previous cumulative exposures. Loss of forced expired volume in one second (FEV1) over approximately 11 years was found to increase with previous cumulative dust exposure after allowing for the effects of age, height, smoking, and overall colliery differences. This relationship was found to hold with concurrent dust exposure only when colliery differences were ignored. These results confirm by direct measurement inferences drawn indirectly from previous cross-sectional studies of the relationship between FEV1 and dust exposure.

Adult↗

Timing of anti-uterotrophic effects of a single injection of progesterone in the oestrogen-stimulated uterus: comparison of the sheep and mouse.

Progesterone (P) is anti-uterotrophic in the oestradiol (E2)-stimulated uterus of the mouse but not the sheep. To further understand this species difference, the time course of some early effects of a single injection of P on the E2-stimulated uterus has been examined. In the mouse, P caused a prompt (2-4 h) decline in uterine wet weight and in vitro rate of RNA synthesis, and a more gradual decrease (4-12 h) in RNA: DNA and protein: DNA ratios and in vitro rate of protein synthesis in whole uterus. In the sheep, P had no effect at any time on either whole uterus or caruncular endometrium. The results support the concepts that (1) anti-uterotrophic effects of P in E2-stimulated mice are mediated by a direct P effect on nuclear E2 receptor level, and (2) in the sheep P is not anti-uterotrophic because it does not regulate nuclear E2 receptor level.

Animals↗

Effects of progesterone on nuclear and cytosol steroid receptor levels in the oestrogen-stimulated uterus: comparison of the sheep and mouse.

Methods for the measurement of nuclear receptors for oestradiol (E2) and progesterone (P) in mouse uterus and sheep endometrium have been established. Scatchard analysis of nuclear receptors gave the following dissociation constants (nM) and binding site concentrations (pmol steroid/mg DNA): E2 receptor, mouse 3.76 and 2.68, sheep 2.03 and 5.37; P receptor, mouse 5.77 and 2.52, sheep 5.34 and 3.58. The effects of a single injection of P on nuclear and cytosol levels of E2 and P receptors have been contrasted in these tissues from E2-treated mice and sheep. In both species, P treatment resulted, in 30-120 min, in depletion of its own cytosol receptor and accumulation of its nuclear receptor. A significant reduction of cytosol E2 receptor was seen only in the mouse at 24 h. P decreased the nuclear E2-receptor level in the mouse at 2-8 h, but had no such effect in the sheep. The results indicate that the anti-uterotrophic action of P in mouse uterus is caused by an early direct effect of P on nuclear E2-receptor retention, and appear also to explain why P is not anti-uterotrophic in sheep uterus.

Animals↗