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Biomedical subjects

D S Miller

Publications and source records attributed to D S Miller.

At least 163 records · Page 9Linked to original sources
PubMed1987

Organic cation secretion by Cancer borealis urinary bladder.

In the crab, Cancer borealis, initial clearance studies showed a potent renal excretory system for the model organic cation, tetraethylammonium (TEA). TEA clearance averaged 145 +/- 32 ml/day, which was 18 times the paired polyethylene glycol clearance. TEA uptake by slices of urinary bladder was concentrative, saturable, inhibitable by N1-methylnicotinamide chloride, and dependent on glycolytic, but not oxidative, metabolism. When mounted in flux chambers, bladders exhibited a large net secretory flux. For 0.1 mM TEA, the ratio of secretory to reabsorptive fluxes was 65. Urinary bladders from another crab, Cancer irroratus, and a lobster, Homarus americanus, also exhibited net TEA secretion. In C. borealis bladder, secretory transport was concentrative, saturable, and nearly abolished by addition of 1 mM quinine to the serosal bath. Reabsorptive transport was not concentrative and was not reduced by luminal quinine. The data are consistent with a secretory pathway that is transcellular and mediated by carriers at both the serosal and luminal membranes.

Animals↗
PubMed1987

Prevention of genetic fa/fa obesity with an ephedrine-methylxanthines thermogenic mixture.

A thermogenic mixture containing ephedrine and methylxanthines was administered to 8-wk-old genetically obese fa/fa rats (O-E/Mx group) for a period of 15 wk. Their energy balance and the final body composition were compared with an untreated ad libitum-fed (O-AL) group, as well as to other fa/fa obese animals that were either pair fed to lean controls (O-PF group), or that were food restricted to such an extent they maintained a similar body weight to that of lean animals (O-WF group). Energy intake was elevated above lean or O-PF levels by approximately 27 and 10% in the O-AL and O-E/Mx groups, respectively, but lower by 18% in the O-WF group. Energy expenditure, compared with the lean values, was 10% higher in both the O-AL and O-E/Mx groups, but reduced by 13 and 30% in the O-PF and O-WF groups, respectively. The gain in body energy and the efficiency of energy deposition remained elevated above the lean values by 2.3- to 3.5-fold in the O-AL, O-PF, and O-WF groups but were reduced to lean levels in the O-E/Mx groups. These studies indicate that, unlike food restriction, the ephedrine-methylxanthine mixture prevents or arrests the development of the obesity in the fa/fa mutant by normalizing their energetic efficiency to that of the lean.

Animals↗
PubMed1987

Organic cation secretion in flounder renal tissue.

In the winter flounder, Pseudopleuronectes americanus, renal clearance experiments showed that the model organic cations, tetraethylammonium (TEA) and N'-methylnicotinamide (NMN), were strongly secreted; organic cation-to-polyethylene glycol (glomerular filtration rate marker) clearance ratios averaged 130 and 30, respectively. TEA uptake by isolated renal tubular masses was concentrative and saturable. Transport was inhibited by competitor organic cations and reduced by exposure to NaCN,2,4-dinitrophenol, ouabain, and HgCl2. Organic anions did not reduce TEA uptake. NMN was the poorest inhibitor of TEA uptake of all the organic cations tested. In addition, the rate of NMN uptake was slower than that of TEA, and the steady-state tissue-to-medium ratio was lower (5 for NMN vs. 10 for TEA; both at 25 microM). The data show the presence of an organic cation secretory system in flounder tissue that resembles the mammalian systems in several respects.

2,4-Dinitrophenol↗
PubMed1987

Screening of drugs for thermogenic anti-obesity properties: antidepressants.

Twelve antidepressant drugs, currently in clinical use, were screened for thermogenic properties on the basis of their ability to stimulate the activity of the sympathetic nervous system via an inhibitory effect on noradrenaline reuptake into the sympathetic neurons. Drug screening was carried out on mice made obese by hypothalamic lesioning using monosodium glutamate. Preliminary experiments, based on changes in body weight and food intake in response to increased doses of the drugs, indicate that most of the twelve antidepressants possess thermogenic potential. In particular, butriptyline, protriptyline and nortriptyline were most effective in causing marked losses in body weight without altering the food intake of the mice. The potent anti-obesity thermogenic properties of these three antidepressants were confirmed during a 10-week energy balance study involving measurements of energy expenditure over the entire period by the comparative carcass method, as well as by measurement of 24 h oxygen consumption. These studies indicate that the methodology employed in the preliminary screening is valid for identifying drugs with thermogenic potential, and demonstrate that many antidepressants currently in clinical use have marked thermogenic properties, and could therefore influence the nutritional status of patients under drug therapy.

Animals↗
PubMed1987

Aquatic models for the study of renal transport function and pollutant toxicity.

Studies of renal cell transport mechanisms and their impairment by xenobiotics are often limited by technical difficulties related to renal tubule complexity. Problems include the juxtaposition of multiple tubule segments with different transport functions and severely limited access to the tubular lumen. Some limitations can be overcome by the careful selection of an appropriate aquatic experimental system. Two aquatic models for the vertebrate proximal segment are discussed here. The first is the kidney from certain marine flounder, which offers the following advantages: long-term viability, little tissue of nonproximal origin, and easy tubule isolation. Data are presented to demonstrate how studies with flounder kidney can be used to elucidate cellular mechanisms whereby different classes of toxic pollutants may interact. Results from these experiments indicate that the excretion of certain anionic xenobiotics can be delayed by other anionic xenobiotics that compete for secretory transport sites and by compounds that disrupt cellular ion gradients and energy metabolism needed to drive transport. The second system is the crustacean urinary bladder, a simple, flatsheet epithelium. Bladder morphology and transport physiology closely resemble those of vertebrate proximal segment. Electron micrographs show a brush border membrane at the luminal surface, numerous mitochondria, and an infolded serosal membrane, while in vivo and in vitro transport studies show reabsorption of NaCl, nutrients and water and secretion of organic cations; organic anions are secreted in bladders from some species and reabsorbed in others. Moreover, since bladders can be mounted as flat sheets in flux chambers, studies with this tissue avoid the problems of complex renal tubule geometry and tissue heterogeneity that limit transport studies in proximal tubule.

Animals↗
PubMed1987

Effects of interferons and interleukin 2 on natural killing of cytomegalovirus-infected fibroblasts.

The ability of nonadherent peripheral blood mononuclear cells of normal individuals to lyse noninfected and cytomegalovirus (CMV)-infected human fibroblasts was enhanced by preincubation with recombinant human alpha interferon (alpha-rIFN) or beta (beta-rIFN). In contrast, recombinant human gamma IFN (gamma-rIFN) augmented natural killing (NK) against both targets relatively poorly. Recombinant or natural human interleukin 2(IL-2) also augmented NK against noninfected and CMV-infected targets. Augmentation of NK by IFN or IL-2 could be blocked by the addition of corresponding antisera. IL-2-enhanced NK against CMV-infected targets was usually independent of alpha-IFN production.

Cytomegalovirus Infections↗
PubMed1986

Intracellular compartmentalization of adenosine triphosphate.

The intracellular distribution and diffusivity of adenosine triphosphate (ATP) was studied by cryomicrodissection of individual Rana pipiens oocytes. We measured ATP concentrations in the nucleus, in animal and vegetal hemisphere cytoplasm, and in an intracellular reference phase (iRP, a microinjected gelatin "organelle") which samples diffusive ATP. Regional concentrations were not equal: nucleus much greater than animal ooplasm greater than vegetal ooplasm. ATP binding and water availability (as solvent) were determined by plotting nuclear and cytoplasmic ATP concentrations as a function of reference phase ATP concentrations (isothermal analysis). The nucleus/iRP isotherm for ATP was an equimolar line, showing that nucleoplasm resembles iRP gelatin (and consequently a simple aqueous solution) in its solvent properties. Cytoplasm/iRP isotherms were more complex, having slopes much less than unity and ordinal intercepts above the graph's origin. They demonstrate the presence in cytoplasm of mechanisms that are capable of excluding and binding ATP. These mechanisms are responsible for the inhomogeneity in ATPs intracellular distribution. In addition, exclusion and binding have different and opposing effects on ATP concentrations in the cell's "soluble space," and hence on ATP availability to enter into cellular reactions. It follows that these phenomena must be considered in attempts to model ATPs role in metabolism.

Adenosine Triphosphate↗
PubMed1986

Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus-infected fibroblasts.

The role of HLA-DR+ cells in NK activity against CMV-infected FS4 foreskin fibroblasts and K562 erythroleukemia cells was examined. When nonadherent PBMC were depleted of either HLA-DR+ or Leu-11b+ cells by treatment with mAbs plus C, NK activity against CMV-FS4 target cells was markedly reduced. In contrast, depletion of HLA-DR+ cells had no effect on NK activity against K562 target cells. When HLA-DR-depleted cells were added to Leu-11b-depleted cells, NK activity against CMV-FS4 was restored. Negative selection experiments indicated that the HLA-DR+ cells contributing to NK activity against CMV-FS4 are not B or T cells, while negative and positive selection experiments excluded a role for monocytes. Experiments in which HLA-DR- and Leu-11b- cells were mixed in varying proportions indicated that NK(CMV-FS4) is mediated by Leu-11b+ cells, while HLA-DR+ cells provide an accessory function. Irradiation (50 GY) abolished the NK effector function of Leu-11b+ cells, but not the accessory function of HLA-DR+ cells. The NK activity against CMV-FS4 of HLA-DR- cells was restored by the addition of rIFN-alpha or of cell-free supernatants generated by coculturing PBMC or Leu-11b- cells with CMV-FS4. The ability of these supernatants to restore NK activity of HLA-DR- cells was completely abrogated by the addition of neutralizing amounts of antibody to IFN-alpha. In related experiments, neutralization of IFN-alpha in NK assays had little or no effect on NK activity against CMV-FS4, suggesting that the accessory function of HLA-DR+ cells might be mediated by alternative mechanisms in addition to the secretion of extracellular IFN-alpha.

Antigen-Presenting Cells↗
PubMed1986

A critical reassessment of second-look laparotomy in epithelial ovarian carcinoma.

Eighty-eight women with epithelial ovarian carcinoma, treated by first-line chemotherapy, achieved a complete clinical response and underwent second-look laparotomy to assess the true pathologic status of their disease. Persistent tumor was found in 50 patients (57%). Thirty-two of these (36%) had obvious gross tumor, whereas, 16 (18%) had microscopic disease. Thirty-eight patients (43%) had no pathologic evidence of persistent ovarian carcinoma. With a follow-up of 6 to 60 months, 30 of these patients (79%) remain without evidence of recurrence. Multivariate logistic regression analysis revealed three covariates that were independently significant in predicting continued disease-free status. These included: the greatest diameter of the largest residual tumor left at the primary operation; histologic features of the tumor; and the diameter of the largest tumor aggregate found at initial operation. A mathematical model based on the most significant covariates was designed to assess the relative risk of any patient having persistent tumor at second-look laparotomy. A comparison of the predicted to actual outcome revealed a sensitivity of the model of 88%, a specificity of 71%, and an accuracy of 77%. Second-look laparotomy represents the basis on which potentially curative second-line salvage therapy can be initiated. With an increasing period of follow-up and with greater numbers of patients, it can potentially document a complete pathologic response to first-line therapy administered with curative intent, and identify patients for additional, adjunctive therapy, who are at risk of recurrence.

Carcinoma↗
PubMed1986

Epithelial ovarian carcinoma in patients with intersex disorders: the role of pituitary gonadotropins in ovarian tumorigenesis.

The common epithelial tumors of the human ovary have rarely been found in the gonads of intersex patients with gonadal dysgenesis or true hermaphroditism. This report describes a patient with ovarian serous cystadenocarcinoma and mixed gonadal dysgenesis (45,X/46,XY) and reviews other reported cases. Intersex patients require early evaluation with treatment based on the karyotypic risk of malignant gonadal transformation. Epithelial ovarian tumors arising in dysgenetic gonads, which lack ova and are incapable of ovulating, provide a unique model for understanding the role of pituitary gonadotropins in ovarian epithelial tumorigenesis.

Chorionic Gonadotropin↗
PubMed1986

The thermogenic properties of ephedrine/methylxanthine mixtures: animal studies.

An over-the-counter preparation containing ephedrine, caffeine, and theophylline was examined for thermogenic anti-obesity properties. Administration of the methylxanthines to MSG-induced obese mice for 6 wk had no effect on energy balance or body composition. In contrast, treatment with ephedrine alone caused losses of 14% in body weight and 42% in body fat, effects brought about mainly by a 10% increase in energy expenditure. These changes were accentuated when ephedrine was administered together with one or both methylxanthines: energy expenditure was increased by a further 10%, and led to a reduction of about 25% in body weight and 75% in body fat, while the total food intake and body protein were unaltered. These results indicate that dietary methylxanthines like caffeine and theophylline, although alone have little effect on energy balance, can nevertheless markedly potentiate the thermogenic anti-obesity effect of ephedrine and normalize the body composition of the obese to the lean levels.

Administration, Oral↗
PubMed1986

The effect of parasympathetic drugs on energy expenditure: relevance to the autonomic hypothesis.

The influence of the parasympathetic nervous system in the control of energy expenditure was investigated in obese and lean rodents during chronic administration of drugs that alter parasympathetic transmission. In the genetically obese ob/ob mice and fa/fa rats and in monosodium glutamate induced hypothalamic obese mice, administration of the parasympathetic inhibitors hyoscine, benztropine, and mecamylamine either had no effect on energy balance or caused losses in body weight that could entirely be accounted for by a reduction in food intake; 24-h oxygen consumption in drug-treated animals was no different from that of the nontreated controls. In the lean animals, both the parasympathetic inhibitors (hyoscine, benztropine, and mecamylamine) and stimulators (bethanecol and neostigmine) had no influence on energy balance nor on body composition. These studies refute the concept that an overactive parasympathetic tone underlies the elevated energetic efficiency of obese models and suggests that the parasympathetic nervous system is unlikely to play an important role in the long-term control of energy expenditure.

Animals↗
PubMed1986

Genetic and dietary influences on the levels of diet-induced thermogenesis and energy balance in adult mice.

Genetic and dietary influences on energy balance and diet-induced thermogenesis were investigated in 5 strains of adult mice fed either a stock diet or a varied and palatable cafeteria diet for 4 weeks. Compared to their stock-fed controls, the total metabolisable energy intake of mice fed a cafeteria diet increased by 60, 45, 28, 50 and 35% in the ob/+ or +/+, C57BL/6, DBA/2, BALB/C and CFLP strains, respectively, while energy expenditure, over the entire period, was increased by 53, 21, 24, 53 and 34%, respectively. The results show the presence of diet-induced thermogenesis in most strains studied, and also indicate that variations in food intake were more strongly determined by diet, whereas variations in energy efficiencies were more strongly influenced by genetics.

Animals↗
PubMed1986

Absenteeism. Nursing service's albatross.

Absenteeism negatively impacts sick leave benefits, staff hours, overtime pay, salary losses, productivity, employee moral, continuity, and quality of patient care. This paper describes findings from a large study that was conducted for the purpose of identifying variables contributing to absenteeism. Variables identified by the study included child care problems, conflict between the parent and employee roles, staffing and scheduling difficulties, and attitudes toward sick leave. While valuable information was identified by the study, the findings raised some serious questions about productivity, staff attitudes, and work ethics.

Absenteeism↗
PubMed1986

The thermogenic properties of ephedrine/methylxanthine mixtures: human studies.

The thermogenic effect of an over-the-counter preparation containing 22 mg ephedrine, 30 mg caffeine and 50 mg theophylline was investigated in human volunteers with a predisposition to obesity and also in the lean. The ephedrine/methylxanthines mixture was twice as effective as ephedrine alone in increasing the fasting metabolic rate of both subject groups, and it normalized the reduced thermogenic response to a 1.25-MJ meal observed in those predisposed to obesity. Measurements of 24-h energy expenditure in a respirometer indicate that the mixture had no effect on the daily metabolic rate of the lean, but was effective in causing a significant 8 percent increase in the 24-h energy expenditure of those subjects predisposed to obesity. These studies indicate that relatively mild doses of dietary methylxanthines in combination with ephedrine can raise daily energy expenditure of those predisposed to obesity, mainly by correcting their defective thermogenic response to food. Such ephedrine/methylxanthine preparations could be useful as aids in the treatment of obesity.

Adult↗