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Biomedical subjects

B Stevens

Publications and source records attributed to B Stevens.

At least 19 recordsLinked to original sources

Effects of cigarette smoke on the clearance of short asbestos fibres from the lung and a comparison with the clearance of long asbestos fibres.

Long asbestos fibres are generally considered to have greater disease-producing potential than short asbestos fibres. However, recent reports have suggested that short fibre asbestos appears to be as effective an inducer of macrophage growth factors and toxic oxygen species as long fibre asbestos, but that short fibres are readily removed from lung and do not gain access to tissues. Because smoke is believed to impair the clearance of asbestos fibres from lung, we examined the clearance of a short (geometric mean length 1.3 microns) amosite preparation administered by intratracheal instillation to guinea-pigs. Half the animals in each group were exposed to the smoke of 10 cigarettes daily. Animals were sacrificed 1 day, 1 week, or 1 month later, the macrophages recovered by lavage, and fibre concentrations and sizes determined by analytical electron microscopy in macrophages and lung tissue. A 30-fold increase was seen in total numbers of fibres retained in macrophages in smokers compared to non-smokers by 1 month, and there was an eightfold increase in retention of short fibres in the lung tissue by 1 month. By contrast, a long fibre amosite preparation (geometric mean length 8.9 microns) showed approximately the same increase in fibre retention in macrophages, but only a twofold increase in tissue retention. We conclude that (1) cigarette smoke markedly impairs the clearance of short amosite fibres from the lung with enhanced retention of fibres in both macrophages and tissue; (2) the effects of smoke on short fibre tissue retention appear to be greater than those on long fibre retention; (3) with the long fibre preparation, smoke causes increased tissue retention of relatively shorter fibres; (4) for both fibre size experiments, the increase in total fibres in macrophages in smoke-exposed animals reflects an increase in the total number of fibre-containing macrophages, rather than an increase in the number of fibres phagocytized per macrophage; (5) enhanced short fibre retention markedly increases total fibre surface area, a parameter which has been suggested as a measure of fibre toxicity, to the point where short fibres might under some circumstances have roughly the same potential toxicity as long fibres. These observations suggest that short asbestos fibres could play an important role in the pathogenesis of some types of asbestos-related disease in cigarette smokers.

Animals

Respiratory effects from the inhalation of hydrogen chloride in young adult asthmatics.

Almost no human data exist from controlled studies using low levels of hydrogen chloride (HCl), and, with no existing HCl ambient standards in the United States, the need for human health effects research is evident. In this study, five female and five male 18 to 25-year-old asthmatic subjects were exposed to filtered air, 0.8 ppm and 1.8 ppm HCl while wearing half-face masks, during three separate 45-minute experimental sessions involving 15 minutes exercise (treadmill walking), 15 minutes rest, followed again by exercise. Baseline and postexposure pulmonary function measurements were taken including forced expiratory volume in 1 second (FEV1), forced expiratory volume (FVC), maximal flow at 50% of expired vital capacity (Vmax50), maximal flow at 75% of expired vital capacity (Vmax75), and total respiratory resistance as well as peak flow. Nasal work of breathing and oral ammonia levels also were measured preexposure and postexposure. No significant pulmonary effects were found at these HCl concentrations and exposure duration. Nasal power showed no significant differences between test atmospheres; however, in isolation a significant decrease (P less than .01) was found in measurements of inspiration with exposure to 0.80 ppm. Ammonia levels showed a significant rise postexposure after both concentrations of HCl (paired t test, (P less than .01)), not seen after air exposure. In summary, the asthmatic subjects in this study showed no adverse respiratory health effects of inhalation of low concentrations of HCl.

Administration, Inhalation

Long-term metabolic function of pancreas transplants and influence of rejection episodes.

Pancreas grafts, when not rejected, can sustain an insulin-independent state in type I diabetic recipients for indefinite periods. To what extent the metabolic control achieved approaches that of normal individuals, the relationships between graft endocrine and exocrine function, the effect of reversible rejection episodes on subsequent graft function, and the correlation between the results of serial tests of graft function were determined by studies at 1 month, 1 year, and 2 years in a cohort of 39 recipients (29 females, 10 males; mean age (+/- SD), 33 +/- 5 years; mean duration of diabetes, 22 +/- 6 years) of bladder-drained pancreas transplants performed between November 1984 and December 1988. Fifteen patients received a pancreas transplant alone, 8 a pancreas after a kidney, and 16 a simultaneous pancreas/kidney transplant. Graft endocrine function was tested by a 24-hr metabolic profile of blood glucose levels before meals, at 1 and 2 hr after meals, and during the night (14 values in all), by intravenous and oral blood glucose tolerance tests, and by glycosylated hemoglobin levels (HA1 and HA1c). Graft exocrine function was assessed by urine amylase activity (U/hr). The results of the tests in the recipients were subjected to paired comparisons between timepoints and at each timepoint to the results of the same tests in 55 normal nondiabetic control individuals. The means of the mean 24-hr profile glucose (mg/dl) values were significantly lower (P less than 0.05) at 1 and 2 years posttransplant (116 +/- 27 and 115 +/- 15, respectively) than at 1 month (128 +/- 31) in the recipients, but the mean of the mean values in the normal controls (100 +/- 7) was even lower (P less than 0.05). Mean values of individual timepoints during the profile were significantly lower for 6 of the 14 values in the controls than in the recipients. The mean IVGTT K value of the normal controls (-1.9 +/- 0.4%) was significantly lower than the 1-month and 2-year values of the recipients (-1.5 +/- 0.5% and -1.3 +/- 0.6%, respectively), but the comparison with the 1-year value (-1.6 +/- 0.6%) was not significant. The mean glucose levels at zero minutes and between 120 and 300 min of the OGTTs were significantly lower at both 1 and 2 years than at 1 month in the recipients, and the values in the control group were also significantly lower than in the recipients at 1 month but not at 1 and 2 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose

Localization and characterization of prostaglandin E1 receptors in rat small intestine.

While prostaglandins of the E series are known to affect several small intestinal functions, their cellular mechanisms are poorly understood. The purposes of our study were to determine whether receptors for PGE are present in rat small intestine and to locate and characterize the receptor binding in the subcellular fractions. Small intestinal binding of prostaglandin E1 was significantly higher than that of prostaglandin E2. Highest receptor binding for prostaglandin E1 was found in the plasma membrane fraction of isolated small intestinal enterocytes. Curvilinearity of prostaglandin E1 binding in plasma membranes upon Scatchard analysis indicated two receptor binding sites in rat small intestine. Competitive binding studies demonstrated that receptor binding was highest for prostaglandins of the E series. These studies are the first to demonstrate specific prostaglandin E1 receptors in different subcellular fractions of rat small intestine. We suggest that receptor binding of prostaglandin E may be an important initial step in the mechanism of prostaglandin-E-induced responses in the small intestine.

Animals

Association of lung cancer and airway particle concentration.

Using 15 autopsy lungs containing nonresected lung cancers, we evaluated the exogenous mineral particle content of the upper and lower lobe parenchyma and of the upper and lower lobe bronchial mucosa. The bronchial mucosa from the lobe with the cancer was found to contain about three times the median mineral particle load of the bronchial mucosa from the lobe without the cancer, a statistically significant difference. No such difference was seen for mineral content of the parenchyma. This observation suggests that mineral particle deposition or accumulation in the bronchial mucosa may be related to respiratory carcinogenesis.

Adult

Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation.

A full length cDNA for human 3-hydroxy-3-methylglutaryl coenzyme A reductase, the membrane-bound glycoprotein that regulates cholesterol synthesis, was isolated from a human fetal adrenal cDNA library. The nucleotide sequence of this cDNA shows that the human reductase is 888 amino acids long and shares a high degree of homology with the hamster enzyme. The amino-terminal membrane-bound domain is the most conserved region between the two species (7 substitutions out of 339 amino acids). This region, which is predicted to span the endoplasmic reticulum membrane seven times, mediates accelerated degradation of reductase in the presence of sterols. The carboxyl-terminal catalytic domain is also highly conserved (22 substitutions out of 439 amino acids). However, the linker region between these two domains has diverged (32 substitutions out of 110 amino acids). Conservation of the structure of the membrane-bound domain in HMG-CoA reductase supports the hypothesis that sterol-regulated degradation is an important mechanism for suppression of reductase activity and for regulation of cholesterol metabolism in humans as well as in hamsters.

Amino Acid Sequence

Binding of Al by protein in plasma of patients on maintenance hemodialysis.

Gel filtration of plasma from hemodialysis patients, with use of reagents and apparatus with carefully minimized background Al concentrations, reproducibly showed a single peak for Al, corresponding exactly to the elution position of transferrin. The Al/transferrin molar ratio in adjacent fractions was constant (mean 0.126, SE 0.006) in replicate experiments. In contrast, the association of Al with albumin varied. Using both equilibrium dialysis and gel-filtration techniques, in the presence and absence of calcium or phosphate, we could demonstrate no significant binding of Al by human albumin at Al concentrations of 1 to 12 mumol/L. We saw no Al peak in pooled, concentrated, low-molecular-mass fractions of plasma gel-filtered on Sephadex G-50. Evidently, transferrin is the sole Al-binding protein in plasma of hemodialysis patients.

Aluminum