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Biomedical subjects

A Collins

Publications and source records attributed to A Collins.

At least 199 records · Page 11Linked to original sources

Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers.

Single-dose oral administration of 100 mg caffeine increased the resting metabolic rate of both lean and postobese human volunteers by 3-4% (p less than 0.02) over 150 min and improved the defective diet-induced thermogenesis observed in the postobese subjects. Measurements of energy expenditure (EE) in a room respirometer indicate that repeated caffeine administration (100 mg) at 2-h intervals over a 12-h day period increased the EE of both subject groups by 8-11% (p less than 0.01) during that period but had no influence on the subsequent 12-h night EE. The net effect was a significant increase (p less than 0.02) in daily EE of 150 kcal in the lean volunteers and 79 kcal in the postobese subjects. Caffeine at commonly consumed doses can have a significant influence on energy balance and may promote thermogenesis in the treatment of obesity.

Adult↗

Family resemblance for glucose tolerance in a Melanesian population, the Tolai.

Path analysis of family resemblance for plasma glucose concentration, 2 h after an oral glucose challenge, failed to detect significant genetic heritability. There were no intergenerational differences and marital resemblance was moderate. Over one-third of sibling environmental similarity was due to non-inherited factors. Cultural inheritance was very strong, tending to mimic genetic inheritance, and cultural heritability was considerable. Measures of obesity were included in the environmental index, an estimate of familial environment, in this analysis, for comparability with previous studies. Since obesity appears, in part, to be a heritable trait, in future studies a bivariate approach to family resemblance for both glucose tolerance and obesity could yield important additional insight.

Adolescent↗

Hydroxyurea: effects on deoxyribonucleotide pool sizes correlated with effects on DNA repair in mammalian cells.

We have measured deoxyribonucleotide pool sizes in different cell types: normal human, transformed human (HeLa), and the permanent hamster line CHO-K1. The range of sizes of the four DNA precursor pools in CHO cells is far greater than in human cells. It is a general rule that hydroxyurea causes rapid depletion of pools (except for dTTP) until the pool present in smallest amount is exhausted; this suggests a tight coupling of the pools to DNA replication (the presumed main cause of the depletion). The effect of hydroxyurea on DNA repair after ultraviolet irradiation (namely, a relatively small accumulation of incomplete repair sites blocked at the resynthesis stage) is probably accounted for by the reduced availability of DNA precursors. However, depletion of the dCTP pool is not an adequate explanation for the observed enhancement by hydroxyurea of the inhibitory effect of cytosine arabinoside; we suggest other possible modes of action. Ultraviolet irradiation has only small effects on the levels of deoxyribonucleotides.

Animals↗

Estimates of the rate of ligation during excision repair of ultraviolet-damaged DNA in mammalian cells.

When ultraviolet-irradiated mammalian cells are incubated with inhibitors of repair DNA synthesis, incomplete repair sites--seen as DNA breaks--accumulate. If the inhibition is reversed, the breaks are joined. Thus the ligation step of excision repair can be investigated. With aphidicolin as inhibitor, ligation occurs at up to 15-times the rate of incision. 3-Aminobenzamide (which inhibits poly(ADPribose) synthesis) does not delay the rejoining of DNA breaks.

Adenosine Diphosphate Ribose↗

Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis).

Skin biopsy specimens from four patients who had recurrent bouts of lesions conforming to the clinical description of acne necrotica were studied. The pathologic findings were dominated by lymphocytic inflammation around centrally placed follicles evolving to follicular necrosis that extended to the perifollicular epidermis and dermis. Early lesions showed the development of multiple individual necrotic keratinocytes within the follicular sheath and adjacent epidermis with lymphocytic exocytosis. Later lesions showed more intense necrosis and scale crust obscuring the central target but were still dominated by a peripheral lymphocytic infiltrate. The early pathologic findings of acne necrotica (varioliformis) are represented by a necrotizing lymphocytic folliculitis and differ from the pattern seen in association with nonspecific excoriations, acute bacterial folliculitis, classic comedogenic acne, or acnitis.

Acne Vulgaris↗

Exploring environments by hand or foot: time-based heuristics for encoding distance in movement space.

In Experiment 1, blindfolded observers judged (a) the distance of pathways felt by hand and (b) the straight-line distance between pathway endpoints inferred from such exploration. In Experiment 2, blindfolded observers made corresponding estimates after traversing similar pathways on foot. Pathways were explored under three different speeds. Under both manipulatory and ambulatory exploration, there was substantial length distortion of inferred distance: The straight-line distance was increasingly overestimated with increases in the length of the explored pathway. With manipulatory exploration, slower movements increased length distortion, but duration effects proved secondary to effects of spatial extent. For ambulatory exploration, no duration effects were obtained. Observers used time-independent heuristics, that is, a footstep metric for estimating the pathway actually travelled and a spatial imaging strategy for estimating the inferred line between pathway endpoints. The studies establish length distortion as a general phenomenon in movement space and identify its major causes as spatial rather than temporal.

Adult↗

Cellular responses to ionizing radiation: effects of interrupting DNA repair with chemical agents.

This review is concerned with the influence of different classes of chemical agents on cellular repair of DNA damage induced by ionizing radiation. Single-strand break rejoining is little affected by inhibitors of DNA synthesis; however, such inhibitors do lead to a persistence of double-strand breaks in the DNA, and this correlates with an enhancement of chromosome aberrations and cell killing. Experiments with antagonists of topoisomerase II suggest an intriguing role for this DNA unwinding enzyme in double-strand break repair. Interference with poly(ADP-ribose) synthesis, by means of the inhibitor 3-aminobenzamide, does not have a clear-cut effect on recovery from ionizing radiation damage. Various substances (for example, caffeine and trypsin) affect DNA repair via a modulation of the cell cycle, altering the time available to the cell for repairing potentially lethal DNA damage before such damage is 'fixed' by the process of DNA replication. Finally, disturbing cellular energy metabolism, and depressing the level of ATP, can inhibit the repair of radiation damage.

Cell Cycle↗

Platelet serotonin uptake and effects of vitamin B6-treatment in premenstrual tension.

The platelet serotonin uptake kinetics was studied in 19 women with premenstrual tension syndrome (PMS) and 19 age-matched symptom-free controls during the pre- and postmenstrual phases. Both groups exhibited stable Vmax and Km values at the two phases of the menstrual cycle. There were no differences between the two groups regarding the level of Vmax and Km, respectively. The effect of season (p less than 0.001), with lowered values of Vmax during spring compared to corresponding values during the later half of the year, was identical in both groups. A tendency to lowered Vmax values in the follicular phase in women with PMS during spring may indicate that women with PMS are more vulnerable to developing depressive episodes during this period than symptom-free women. The blood platelet count in whole blood was decreased in the luteal phase in the control group but remained stable in the PMS group. The effect of vitamin B6 on clinical symptoms and the platelet serotonin uptake during the luteal phase was investigated in a double-blind crossover design. Vitamin B6 treatment did not significantly improve the PMS symptoms. There was no effect of treatment on Km. Vmax increased significantly in response to treatment (F = 9.6; p less than 0.001) in both groups, but there was no significant difference between placebo and vitamin B6.

Adult↗

DNA repair mutants in higher eukaryotes.

Over the past ten years or so, we have seen a proliferation of reports of new cell lines of various vertebrate species, showing hypersensitivity to killing by DNA damaging agents. Regrettably, but predictably, there is no standard terminology to describe the mutants, and as a result the literature is liberally scattered with fragments of individualistic nomenclature. There is no way of imposing order at this stage, but it may be helpful to bring together in this chapter as much information as possible on the mutants now available. As well as being an aid for reference, this should serve as a pointer towards further investigation--either in characterizing the mutants we have, or in developing new ones to fill gaps in our knowledge.

Animals↗

Coughing horses.

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Animals↗

The time course of repair of ultraviolet-induced DNA damage; implications for the structural organisation of repair.

Alternative molecular mechanisms can be envisaged for the cellular repair of UV-damaged DNA. In the "random collision" model, DNA damage distributed throughout the genome is recognised and repaired by a process of random collision between DNA damage and repair enzymes. The other model assumes a "processive" mechanism, whereby DNA is scanned for damage by a repair complex moving steadily along its length. These two models give different predictions concerning the time course of repair. Random collision should result in a declining rate of repair with time as the concentration of lesions in the DNA falls; but the processive model predicts a constant rate of repair until scanning is complete. We have examined the time course of DNA repair in human fibroblasts given low (generally sublethal) doses of UV light. Using 3 distinct assays, we find no sign of a constant repair rate after 4 J/m2 or less, even when the first few hours after irradiation are examined. Thus DNA repair is likely to depend on random collision. The implications of this finding for the structural organisation of repair are discussed.

DNA Ligases↗

Rapid high-efficiency hemodialysis.

Reductions in treatment time are attractive for patients and dialysis centers. However, there are concerns related to treatment adequacy and increased intradialytic symptoms. Treatment times were progressively reduced in 12 stable patients on standard 4-h acetate hemodialysis, solute clearances being increased proportionately, until the tolerance limit manifested by increased complications or 2.5 h of treatment was reached. Once shortened schedules (mean reduction approximately 31%) were achieved, a 2-month surveillance period was initiated, followed by 2 additional months of bicarbonate therapy, treatment time being unchanged. Rapid bicarbonate hemodialysis was associated with a significantly lower incidence of hypotension, nausea, and vomiting than rapid acetate or standard acetate therapies. Fluid removal was comparable with that of standard treatment, and serum chemistry levels remained stable. Based on the success of these studies treatment times have been reduced in greater than 200 patients with high-efficiency bicarbonate therapy for long-term evaluations.

Acetates↗

Technical requirements for rapid high-efficiency therapies.

Significant reductions in treatment time are possible with rapid high-efficiency hemodialysis and hemodiafiltration, provided the therapies are implemented so as to maintain adequacy of solute and fluid removal without compromising patient comfort. The key technical elements necessary for such implementation include high blood flow rates, higher efficiency dialyzers/diafilters, ultrafiltration control systems, and bicarbonate as the buffer source. In addition, hemodiafiltration requires schemes to ensure sterility and nonpyrogenicity of the infusion fluid and appropriate balancing of the rates of ultrafiltration and reinfusion. In general, rapid high-efficiency therapies are technically more complex than standard therapy, and rapid hemodiafiltration appears to be more complex than rapid hemodialysis. The technology required for rapid hemodialysis currently exists, but it needs to be fine-tuned and integrated for routine application.

Acetates↗