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Biomedical subjects

D S Miller

Publications and source records attributed to D S Miller.

At least 145 records · Page 8Linked to original sources
PubMed1989

Role of arachidonic acid metabolites in hypoxic contractions of isolated porcine pulmonary artery and vein.

Recently it has been proposed that hypoxic pulmonary vasoconstriction (HPV) is mediated by local release of sulfidopeptide leukotriene products of the lipoxygenase pathway of arachidonic acid metabolism. In the present study the response to reduced oxygen supply of isolated porcine lobar pulmonary artery and pulmonary vein spiral strips has been studied. Contractions of the pulmonary artery (mean maximum tension 66.9 +/- 13.0 mg, n = 10) required an increase in baseline tone of the preparation followed by exposure to anoxia (mean bath PO2 O +/- 3 mm Hg), whereas contractions of the pulmonary vein (mean maximum tension 75.2 +/- 13.3 mg, n = 10) could be elicited in response to hypoxia alone (mean bath PO2 40 +/- 4 mm Hg). Indomethacin (5.6 microM), a cyclooxygenase inhibitor, attenuated the arterial contraction, but the mechanism may have been independent of the cyclooxygenase pathway since phenidone, an inhibitor of both cyclooxygenase and lipoxygenase pathways, had no effect. Inhibition by FPL 55712, a leukotriene end-organ antagonist, was achieved only at a high concentration (20 microM). In the case of the pulmonary vein, both indomethacin and phenidone inhibited the contractile response, whereas FPL 55712 had no effect. Contractile responses to reduced oxygen supply can be induced in isolated porcine pulmonary artery and vein strips, but probably are not mediated by leukotrienes.

Animals↗
PubMed1989

Dendritic cells and IFN-alpha-producing cells are two functionally distinct non-B, non-monocytic HLA-DR+ cell subsets in human peripheral blood.

At least two distinct HLA-DR+ cell subsets lacking surface markers specific for B cells, monocytes or other known lineages are present in human peripheral blood. One subset is non-adherent to plastic, produces interferon-alpha (IFN-alpha) when incubated with cytomegalovirus-infected target cells and provides an accessory function required for natural killer (NK) cell-mediated lysis of such cells. These non-adherent HLA-DR+ cells express the surface antigen recognized by antibody anti-D44 and do not stimulate mixed leucocyte reaction (MLR). The other HLA-DR+ cell subset is loosely adherent to plastic, produces only minimal levels of IFN-alpha when incubated with cytomegalovirus-infected target cells and does not provide the accessory function required for NK cell-mediated lysis of such cells. These HLA-DR+ cells stimulate a strong MLR, do not express D44 antigen and meet the criteria of dendritic cells (DC) morphologically and functionally.

Antigen-Presenting Cells↗
PubMed1988

Stimulation of RNA and protein synthesis by intracellular insulin.

Like insulin-sensitive somatic cells, stage IV oocytes from Xenopus laevis increase their synthesis of RNA, protein, and glycogen in response to extracellular insulin. Synthesis of RNA and protein are also increased when oocytes are maintained under paraffin oil and insulin is microinjected into the cytoplasm. The effects of external and intracellular insulin are additive, suggesting separate mechanisms of action. Experiments with nuclei isolated under oil show that RNA synthesis can be stimulated by applying insulin to the nucleus directly. Thus, the nucleus appears to be one intracellular site of hormone action.

Animals↗
PubMed1988

A low-budget and easy-to-operate room respirometer for measuring daily energy expenditure in man.

Accurate assessment of energy requirements of humans under various physiological, pathological, and environmental conditions is hampered by the high cost of techniques for measuring daily energy expenditure. A room respirometer novel in its novel in its low cost of construction and simplicity of operation is described, together with an appreciation of errors and assumptions. It is suitable for measurements of daily energy expenditure in humans with an accuracy of +/- 1.5% and can be reproduced without difficulty in both developed and developing countries.

Adult↗
PubMed1988

Membrane potential drives organic cation transport into teleost renal proximal tubules.

The relationship between organic cation uptake and basolateral membrane potential was studied in renal tubules from two marine teleost fish, Southern flounder (Paralicthys lethostigma) and killifish (Fundulus heteroclitis). Carrier-mediated uptake of the model organic cation, tetraethylammonium (TEA), increased when K+ was changed from 2.5 to 0.2 mM and decreased when medium K+ was increased to 20 mM. Uptake was also reduced by the K+ channel blocker barium (1 mM). Furthermore, basolateral membrane potential hyperpolarized 15-25 mV in low-K+ medium and depolarized 30-40 mV in high-K+ medium. Barium also depolarized. Finally, basolateral membrane potential was depolarized in a concentration-dependent manner by addition of 100-500 microM TEA or Darstine. Thus treatments that hyperpolarize the basolateral membrane potential increase carrier-mediated TEA uptake, whereas those that depolarize basolateral membrane potential reduce uptake. Furthermore, organic cation transport into tubular cells involves the net influx of positive charge. Together, these findings support the argument that carrier-mediated organic cation uptake at the basolateral membrane is a potential-driven, electrogenic process.

Animals↗
PubMed1988

Effect of hypoxia on responses of respiratory smooth muscle to histamine and LTD4.

The aim of the present study was to compare the effect of reduced oxygenation on the contractions of pulmonary vascular and airway smooth muscle induced by leukotriene D4 (LTD4) with those induced by histamine (an agonist with similar mechanisms of smooth muscle contraction) and KCl (a voltage-dependent stimulus). During hypoxia (PO2: 40 +/- 4 Torr) the responses of isolated porcine pulmonary artery and vein spiral strips to LTD4 increased approximately three- and two-fold, respectively, and the vein also exhibited an augmented response to histamine. The augmentation was blunted (LTD4) or reversed (histamine) during anoxia (PO2: 0 +/- 2 Torr). Responses to KCl were not systematically altered by reduced oxygenation. In contrast, the contractions of the guinea pig parenchymal lung strip by all three agonists were generally suppressed by reduced oxygenation. After reoxygenation, the contractile responses of each of the three smooth muscle preparations were generally increased compared with previous and concurrent base-line observations, particularly the LTD4-induced pulmonary vein contraction that increased approximately sevenfold after reoxygenation after anoxia. The contribution (if any) of leukotrienes to hypoxic pulmonary vasoconstriction may reflect increased vascular responsiveness to leukotrienes during hypoxia as well as (or instead of) increased leukotriene release.

Animals↗
PubMed1988

Natural killing of fibroblasts infected with low-passage clinical isolates of human cytomegalovirus.

Fibroblasts infected with most low-passage clinical isolates of human cytomegalovirus (CMV) were as susceptible to lysis by human natural killer (NK) cells as high passage AD-169-infected fibroblasts. NK lysis occurred despite the absence of detectable CMV-specific late membrane antigen(s) on the majority of the target cells infected with most of the low passage strains. The magnitude of NK lysis of different CMV-infected target cells did not correlate with their ability to induce IFN-alpha. NK cell-mediated lysis of cells infected with low-passage clinical isolates of CMV required both NK cells and HLA-DR+ accessory cells, as previously shown for AD-169-infected target cells.

Antigen-Presenting Cells↗
PubMed1988

Classification and staging of gestational trophoblastic tumors.

Standard terminology for the gestational trophoblastic diseases has been defined by the World Health Organization. An anatomic staging system has also been adopted by FIGO, but it has not yet been widely utilized by American and European centers which prefer to determine therapy and report results based on risk grouping or prognostic scoring. Appropriate work-up of gestational trophoblastic tumors should be based on an understanding of the biology and natural history of the disease, that allows for efficient and cost-effective determination of the extent of spread and optimal therapeutic decisions.

Female↗
PubMed1988

Lower metabolic rates of post-obese versus lean women: thermogenesis, basal metabolic rate and genetics.

Components of daily metabolic rate (thermogenesis, BMR and net exercise) were compared between 16 women predisposed to obesity (post-obese) and 16 naturally lean controls of matching age, weight and height, at three levels of activity, in a whole-body respirometer. At all levels of activity, the mean metabolic rate of the post-obese was 15 per cent lower than that of the lean controls. Expenditure on net exercise showed the same relationship, but BMR was only 10 per cent lower, while thermogenesis was 50 per cent lower. The latter was partly due to the smaller food intake of the post-obese and also to a lower thermogenic response. In absolute terms BMR accounted for less than half of the difference in total energy expenditure between the post-obese and the lean (45 per cent). Thermogenesis accounted for approximately 40 per cent of the difference, and 15 per cent after adjusting for the different energy intakes. Significantly more post-obese subjects had a family history of obesity (88 per cent) than lean subjects (38 per cent). Within the post-obese and lean groups there was a consistent trend at each level of activity for those with a family history to have lower metabolic rates, indicating that family history of obesity has an influence on energy expenditure over and above personal history of obesity.

Adult↗
PubMed1988

Children in sheltered homeless families: reported health status and use of health services.

Studies of the health status of homeless people have primarily focused on alcoholic men and have reported numerous excess health risks. To determine the health status of children in homeless families, we performed a population-based, cross-sectional survey of a probability sample of 82 homeless families having a total of 158 children 17 days to 17 years of age living in emergency shelters in King County, Washington. Heights and weights were also measured. Seventy-five percent of the children belonged to racial minorities, and 54% were less than 6 years old. Nearly half the children (49%) had a wide variety of reported acute and chronic health problems. Less than 10% of the children measured were short for their age or underweight, whereas 35% were greater than the 95th percentile for weight-for-height. When compared with the US general pediatric population, the proportion of homeless children reported to be in "fair" or "poor" health was four times higher (13% v 3.2%). Thirty-five percent of the children had no health insurance, and 59% of the children had no regular health care provider. The homeless children used emergency rooms at a rate that was two to three times higher than the US general pediatric population (480/1,000 homeless children for 6-month period v 254/1,000 US children for 12-month period), twice as likely to lack measles immunization (21% v 9.0%), and twice as likely to never have had a tuberculosis skin test (48% v 27%). The data suggest that children in homeless families have poorer reported health status and are not obtaining preventive medical care.

Adolescent↗
PubMed1988

Metabolic rate during and after aerobic exercise in post-obese and lean women.

The effect of aerobic exercise (cycling on bicycle ergometer for four 10-min periods/60-80 per cent max VO2) on energy expenditure following the activity was investigated in 16 post-obese and 16 lean control women over 24 h and shorter periods. In addition, net energy expenditure during aerobic exercise was compared to that during prolonged mild activity (stepping for four 30-min periods at 12 steps/min). The measurements were made in a room respirometer. Aerobic exercise did not significantly stimulate the 24-h resting metabolic rate of either the post-obese (3 per cent, 50 kcal) or lean controls (2 per cent, 30 kcal), nor was there any significant stimulation over shorter periods: during waking hours RMR was non-significantly increased by 5 per cent in both the post-obese and lean controls. Sleeping expenditure remained the same in the post-obese and was decreased by 2 per cent in the lean controls. All subjects found the aerobic exercise to be quite uncomfortable, yet in both groups the net cost was smaller than that of prolonged mild exercise which was found to be acceptable (post-obese: aerobic 180 kcal, mild 250 kcal; lean controls: 220 kcal, 290 kcal). It is suggested that prolonged mild activity (eg, as in walking frequently) is more appropriate in increasing energy expenditure as a means of preventing or controlling obesity. Total expenditure at each level of activity is also expressed as multiples of BMR calculated from FAO/WHO/UNU (1985) prediction equations and from measured sleep values. The results show that the equations overestimated BMR in the post-obese.

Adult↗
PubMed1987

Cooperation between CD16(Leu-11b)+ NK cells and HLA-DR+ cells in natural killing of herpesvirus-infected fibroblasts.

We reported previously that natural killer (NK) cell-mediated lysis of cytomegalovirus-infected targets requires the presence of HLA-DR+ nonadherent peripheral blood mononuclear cells (NPBMC). In the present study we determined whether NK cell-mediated lysis of other herpesvirus-infected targets also requires HLA-DR+ cells. Depletion of either cluster designation (CD)16+ NK cells or HLA-DR+ cells from NPBMC significantly reduced their ability to lyse herpes simplex virus (HSV)- and varicella-zoster virus (VZV)-infected fibroblasts. When CD16- and HLA-DR- populations were mixed, lysis of both HSV- and VZV-infected targets was virtually completely restored, indicating that NK cells and HLA-DR+ cells were required for lysis to occur. Cell-free supernatants, obtained by incubating NPBMC or CD16- cells with HSV-o-VZV-infected targets, contained antiviral activity and stimulated HLA-DR-cells to mediate lysis of corresponding virus-infected targets. The addition of anti-interferon-alpha to supernatants abolished their ability to stimulate lysis. Thus, secretion of interferon-alpha by HLA-DR+ cells contributes to NK cell-mediated lysis of herpesvirus-infected targets.

Antigens, Differentiation↗
PubMed1987

Aspirin as a promoter of ephedrine-induced thermogenesis: potential use in the treatment of obesity.

Chronic administration of aspirin to obese mice had no effect on energy balance and body composition. In contrast, ephedrine increased energy expenditure by 9% and reduced body weight and body fat by 18% and 50%, respectively: obesity, however, was reduced but not reversed. In the presence of both ephedrine and aspirin, increase in energy expenditure found during treatment with ephedrine alone was doubled, and the obese group lost greater than 75% of body fat: obesity was reversed. These studies indicate that although aspirin administered alone has no influence on energy balance it can markedly potentiate thermogenic properties of ephedrine, effects which led to a normalization of body composition of the obese to that of the lean. Such ephedrine-aspirin mixtures, often found in over-the-counter preparations for asthma and bronchial disorders, could be put to new use as aids for treatment of human obesity.

Adipose Tissue↗
PubMed1987

The daily metabolic rate of the post-obese and the lean.

Daily metabolic rates of 16 post-obese women and 16 matched, lean controls were measured at three different levels of activity in a room respirometer. Both groups had similar height, weight, age, and other anthropometric indices. Results show that the post-obese have metabolic rates approximately 15% lower than their controls at any level of activity. They also eat less. Slimmed-down, obese women have a normal body composition. For both groups, aerobic exercise did not have a prolonged stimulatory effect on metabolic rate after the exercise had finished. Mild exercise was more effective than aerobic exercise in increasing daily metabolic rate because it could be comfortably sustained for a longer time. Implications of these findings are discussed in relation to the etiology and treatment of obesity.

Activities of Daily Living↗
PubMed1987

Milk and casein-based diets for the study of brain catecholamines in copper-deficient rats.

Copper deficiency in rats results in disruption of catecholamine metabolism, the norepinephrine and dopamine concentrations in total brain being decreased in some, but not all, experiments. This study was designed to explain the discrepancies. Offspring of dams fed low copper diets (0.5 mg/kg) based on nonfat milk plus sucrose, or casein plus sucrose with and without 30% lactose, were fed the same diets until 8 wk of age. The respective control diets were supplemented with 10 mg copper/kg diet. The low copper offspring were severely deficient as indicated by liver copper levels of approximately 2 mg/kg dry weight, gross signs of enlarged and fragile hearts and neuropathological signs. On average, the dopamine concentrations in the corpus striatum of deficient rats fed milk-based diets were 70% of control values; comparable values for deficient rats fed casein-based diets were 60% of controls. Lactose had no effect on the brain pathology of copper deficiency. Approximately one-half of the deficient animals in all groups displayed low dopamine concentrations (20-50% of control values), whereas the remainder were similar to controls. Norepinephrine concentrations were consistently lower in the total brain, but actually higher in the hypothalamus of copper-deficient rats than in that of controls. Extreme variation in the norepinephrine concentrations was not observed. The high variability in the incidence of low dopamine levels suggests that another condition besides copper deficiency must be imposed to produce severe central nervous system pathology. This could be a genetic or environmental factor.

Animals↗
PubMed1987

Reversal of obesity in the genetically obese fa/fa Zucker rat with an ephedrine/methylxanthines thermogenic mixture.

Administration of a thermogenic mixture of ephedrine, caffeine and theophylline to grossly obese (11-12 mo old) fa/fa Zucker rats led to a rapid decline in their body weight, which reached lean levels within 9-10 wk, and this postobese weight was maintained for another 5-6 wk. Compared to the no-drug obese controls (O-ND), food intake was reduced by 70% during the dynamic phase of weight loss and by 50% during the postobese period in the food-restricted animals (O-FR) and by about 40% during both phases in the ephedrine/methylxanthines (O-E/Mx) animals. Energy expenditure in the O-FR group was lower than in the O-E/Mx group by 25-33%. Analysis of body composition showed that body fat in both O-FR and O-E/Mx groups was much lower than in the O-ND group, by 2.5- and 4-fold, respectively, and body protein was lower by 50 and 28%, respectively. Thus, compared to the O-ND group, the fat:protein ratio was only 25% lower in the O-FR animals but was three times less in the O-E/Mx group. These findings demonstrate that in the fa/fa rat a mixture of ephedrine and methylxanthines reduces food intake but also minimizes the fall in metabolic rate that usually accompanies such an energy deficit, effects that led to a reversal of their gross obesity. The ability of ephedrine alone or in combination with methylxanthines to reverse obesity in animal models with dietary and hypothalamic etiologies is thus extended to the obesity resulting from the inheritance of a single-gene recessive defect.

Animals↗