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Biomedical subjects

D S Miller

Publications and source records attributed to D S Miller.

At least 199 records · Page 11Linked to original sources

Development of nutrient transport systems in chick jejunum.

Glutamate, beta-alanine, choline, and myoinositol transport was characterized in jejunal slices and brush-border membrane vesicles from 2- and 21-day chicks. Carrier-mediated, i.e., competitor-inhibitable, transport in slices (wet weight basis) and vesicles (protein basis) declined with age for the two amino acids but increased with age for myo-inositol; transport of choline did not change. These findings, along with previous data for the hexose system, cannot be explained solely by nonspecific changes in brush-border membrane architecture or permeability or by changes in the electrochemical sodium gradient that drives cotransport. They indicate that each specific brush-border membrane transport mechanism follows separate developmental time tables.

Animals↗

PAH excretion in two species of cancroid crab Cancer irroratus and C. borealis.

To determine the characteristics of p-aminohippuric acid (PAH) excretion in Cancer irroratus and C. borealis, crabs were given a single injection of radiolabeled PAH and polyethylene glycol (PEG), and serum, urine, tissue, and seawater concentrations of each were measured over the next 6 days. In both species, PEG clearances averaged 5-10 ml serum/day; serum PAH concentrations fell exponentially after a 1-day equilibration period. In C. irroratus, urine PAH rose over the first 2 days and then fell; during days 2-6, mean urine PAH averaged two to four times mean serum PAH. In C. borealis, urine-to-serum ratios for PAH were 20-40 during days 2-6. PAH-to-PEG clearance ratios exceeded unity in both species, with ratios in C. borealis about three to six times those in C. irroratus. Tissue distribution data showed that C. irroratus midgut gland accumulated up to 50% of injected PAH, with gland-to-serum concentration ratios of 15-45; in this species, stomach fluid-to-serum PAH concentration ratios averaged 87, and nonurinary routes accounted for more than half of excreted PAH. In C. borealis, midgut gland-to-serum ratios never exceeded 2, and the urinary routes accounted for all excreted PAH. Thus, in C. irroratus, injected PAH accumulated in the midgut gland, with slow excretion through renal and nonrenal routes; in C. borealis, PAH remained in hemolymph, and only the renal route of excretion was utilized.

Aminohippuric Acids↗

The effect of freeze-drying on the quaternary structure of L-asparaginase from Erwinia carotovora.

L-Asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) from Erwinia carotovora undergoes extensive dissociation from active tetramer to inactive monomers when freeze-dried. The monomeric state is stabilized by reconstitution of the freeze-dried enzyme with buffers of high pH and high ionic strength. Some compounds, particularly sugars and sugar derivatives, prevent dissociation on freeze-drying, whereas others, such as urea and chaotropic ions, increase dissociation. The effects of additives are not related to water retention. The dissociation is completely reversible on reconstitution at neutral pH, but the alkali-stabilized monomer only partially reassociates when the pH is brought back to neutrality.

Asparaginase↗

Pulsatile administration of low-dose gonadotropin-releasing hormone. Ovulation and pregnancy in women with hypothalamic amenorrhea.

We administered pulsatile low doses of gonadotropin-releasing hormone (GnRH) (1 to 5 micrograms) to patients whose anovulation was caused by relative and absolute deficiency of endogenous GnRH. Eight such patients, including one with previous pituitary stalk transection, were treated during a total of 23 cycles; pulses of GnRH were administered via a portable pump every 96 or 120 minutes. Activation of pituitary-ovarian function with orderly development of a single dominant follicle, a luteinizing hormone surge, and ovulation occurred in 20 of the 23 cycles. The other three cycles were anovulatory. All patients responded, and five (62%) of the eight conceived, for a total of seven pregnancies and four full-term deliveries of normal infants. This study demonstrates that small pulsatile doses of GnRH can activate cyclic pituitary-ovarian function in hypogonadotropin-acyclic women and induce ovulation resulting in pregnancy and live birth.

Amenorrhea↗

Thermogenic drugs for the treatment of obesity: screening using obese rats and mice.

The thermogenic activity of ephedrine, ethinyloestradiol and triiodothyronine were compared by incorporating the drugs into the diets fed to groups of adult rats and mice. The animals used were normal lean mice, hypothalamic obese mice, dietary-induced obese mice and rats, and genetically obese mice and rats. Food intake and body weight were monitored throughout and oxygen consumption measurements were made. Finally, the animals were killed and their carcasses analysed. Generally, ethinyloestradiol reduced body weight by causing anorexia. Triiodothyronine increased oxygen consumption but also increased food intake such that in most cases body weight did not change; it killed the genetically obese animals, but reduced fat in the hypothalamic and dietary induced obese animals. The animals treated with ephedrine lost body weight and body fat without increasing food intake, and had elevated oxygen consumptions. This experiment not only demonstrated marked differences between the various laboratory animal models of obesity, but also that ephedrine is a potential slimming agent. It is relatively safe and has been used by us to obtain successful breeding using the genetically obese male animals which are normally sterile.

Animals↗

Attitudes toward clinical trials among patients and the public.

Attitudes toward clinical research, the focus of recent and damaging media attention, were assessed through questionnaires completed anonymously by 104 patients with cancer, 84 cardiology patients, and 107 members of the general public. Responses differed neither by subgroup nor by demographic variables. Data are therefore reported on the total population of 295 subjects. Most respondents (71%) believed that patients should serve as research subjects. In support of this belief, the majority cited potential benefit ot others and the opportunity to increase scientific knowledge, but a different bias emerged when they were asked about their own potential participation. This study shows that diverse respondents view clinical trials as important, ethical, and as a means of attaining superior clinical care. Major importance is attributed to making contributions to medical knowledge and to helping future patients. Contrasts are noted in patients' views of their own treatments v treatments of "'hypothetical others."

Adult↗

PAH transport in rock crab urinary bladder. II. Luminal and serosal steps.

To characterize the organic anion transport properties of the luminal (1) and serosal (s) membranes of crab urinary bladder, initial (10 min) fluxes (J) and tissue accumulations (Ac) of 10 microM PAH were measured in the absence and presence of 1 mM BCG (nontransported, high-affinity competitor). Control bladders exhibited net reabsorptive transport with a mean Jl leads to s/Js leads to 1 of about 7; concentrative transport of p-aminohippuric acid (PAH) occurred only across the luminal cell (c) membrane. With luminal PAH, luminal bromocresol green (BCG) reduced Jl leads to c, Jc leads to s, and Ac by about 85%; serosal BCG reduced Jc leads to s, increased Ac but had no effect on Jl leads to c. With serosal PAH, serosal BCG reduced Js leads to c, Jc leads to l, and Ac; luminal BCG had no effects on either fluxes or tissue accumulation. When bladder sheets were loaded with radiolabeled PAH, mounted in a chamber, and exposed to flowing crab Ringer solution on both sides, Jc leads to s was nearly twice as large as Jc leads to l; BCG significantly reduced Jc leads to s but not Jc leads to l. With unlabeled PAH in the efflux media, Jc leads to s was increased. The data are consistent with a model featuring an inwardly directed pump at the luminal membrane, a facilitated carrier at the serosal membrane, and nonmediated pathways at both membranes.

Aminohippuric Acids↗

PAH secretion in the urinary bladder of a crab Cancer borealis.

Uptake of 10 microM p-aminohippuric acid (PAH) by sections of Cancer borealis urinary bladder was concentrative, saturable (Km 67 microM, Vmax 1.7 nmol.mg tissue-1.h-1), inhibitable by other organic anions, and dependent on medium Na and glycolytic metabolism. Bladders mounted in flux chambers exhibited net secretory transport of PAH, with serosa-to-lumen fluxes (Js leads to l) being about 4 times lumen-to-serosa fluxes (Jl leads to s). In 60-min flux chamber studies, tissue-to-medium ratios exceeded unity with serosal, but not luminal, PAH. Initial (10 min) fluxes and tissue accumulations (Ac) were measured in the absence and presence of 1-5 mM BCG (bromocresol green; competitor organic anion). With serosal PAH, serosal BCG (1 mM) reduced serosa-to cell flux (Js leads to c), Ac, and Jc leads to l by 60-75%. With luminal PAH, luminal BCG (1 mM) had no effect on Jl leads to c, Ac, or Jc leads to s; increasing the luminal BCG concentration to 5 mM reduced Jl leads to c, Ac, and Jc leads to s by 40-50%. The data are consistent with a model featuring an inwardly directed pump on the serosal membrane, cellular accumulation, and a facilitated carrier on the luminal membrane.

Aminohippuric Acids↗

Effect of Na+ and ATP on peritubular Ca transport by the marine teleost renal tubule.

Ca uptake rates and efflux rate coefficients were determined in isolated renal tubules of the winter flounder, Pseudopleuronectes americanus. Na-free medium and 10(-4) M ouabain depressed while 0.2 mM dinitrophenol stimulated Ca efflux. The effects on Ca movement appeared to be associated with the adenosine triphosphate (ATP) concentration of the tubular fluid space (TFS), rather than the bath-to-tissue Na gradient. Elevation of the ATP concentration of TFS by incubation of tissue in external ATP more than doubled Ca uptake rate. Inhibition of Ca uptake by lanthanum and stimulation by Ca ionophore A23187 suggested that ATP altered plasma membrane Ca transport. Incubation in external phosphate had no effect. Plasma membrane vesicles (PMV) prepared from flounder tubules showed saturable Ca uptake inhibited by Mg, unaffected by Na gradients, and stimulated by intravesicular but not extravesicular ATP. ATP appeared to stimulate PMV Ca uptake by increasing membrane Ca binding. We concluded that Ca uptake across the peritubular membranes was not directly linked to the serosal Na gradient but was greatly influenced by the intracellular ATP concentration.

Adenosine Triphosphate↗