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Biomedical subjects

D E Moore

Publications and source records attributed to D E Moore.

At least 109 records · Page 6Linked to original sources

Number and size of human X chromosome fragments transferred to mouse cells by chromosome-mediated gene transfer.

Labeled probes of unique-sequence human X chromosomal deoxyribonucleic acid, prepared by two different procedures, were used to measure the amount of human X chromosomal deoxyribonucleic acid in 12 mouse cell lines expressing human hypoxanthine phosphoribosyltransferase after chromosome-mediated gene transfer. The amount of X chromosomal deoxyribonucleic acid detected by this procedure ranged from undetectable levels in the three stable transformants and some unstable transformants examined to about 20% of the human X chromosome in two unstable transformants. Reassociation kinetics of the X chromosomal probe with deoxyribonucleic acid from the two unstable transformants containing 15 to 20% of the human X chromosome indicate that a single copy of these sequences is present. In one of these lines, the X chromosomal sequences exist as multiple fragments which were not concordantly segregated when the cells were selected for loss of hprt.

Animals↗

Sperm penetration assay: useful test in evaluation of male fertility.

The recently developed sperm penetration assay (SPA) tests the functional capacity of sperm. It is based upon the ability of in vitro capacitated human spermatozoa to penetrate zona-free hamster eggs in vitro. The SPA was superior to seminal fluid analysis in predicting both fertility and infertility; in the prediction of infertility, the difference was highly significant. Data further indicated that fertility in the male may not remain constant with the passage of time. The SPA would appear to have wide application both clinically and experimentally.

Animals↗

Photosensitization by drugs: photolysis of some chlorine-containing drugs.

Irradiation with ultraviolet light of chlorpromazine, prochlorperazine, frusemide or hydrochlorothiazide in either aqueous or methanol solution yielded free chloride ion. Potentiometric methods were used to detect one mol of chloride ion produced per mol of drug irradiated in deoxygenated solution, with a concomitant equimolar appearance of hydrogen ion. Saturation of the solutions with oxygen strongly inhibited the photolysis reaction in methanol but only partially inhibited the production of Cl- and H+ in aqueous solution. The oxidation of 2,5-dimethylfuran is photosensitized by these drugs more effectively in methanol compared with aqueous solution. The photochemical behaviour is consistent with a photodissociative process occurring predominantly in methanol while photoionization predominates in aqueous media. No chloride ion was detected after extended irradiation of chlortetracycline, demeclocycline, chlordiazepoxide and hexachlorophane. The photolability of the chlorine in the compounds tested correlated with their ability to photosensitize oxidation by the Type I (free radical) mechanism.

Chemistry, Pharmaceutical↗

An in vivo system in man for quantitation of estrogenicity. I. Physiologic changes in binding capacity of serum corticosteroid-binding globulin.

A modified method of measuring the binding capacity of corticosteroid-binding globulin (CBG-BC) in serum using 3H-cortisol saturation-charcoal adsorption is described. Forty serum samples per day can be assayed in duplicate, each sample with a heated nonspecific binding blank (60 degrees C.). The interassay coefficient of variation is less than 6 per cent. All age groups of men and women had similar levels of CBG-BC, except postmenopausal women, whose levels were higher (15.9 +/- 0.2 vs. 18.7 +/- 0.8 microgram per 100 ml., mean +/- standard error of the mean, respectively; z = -3.51, p less than 0.001). The variance of serum levels of CBG-BC throughout the menstrual cycle in five women was small (coefficient of variation = 13 per cent) and showed no relationship to the marked and cyclic changes in estradiol levels (coefficient of variation = 73 per cent). In pregnancy the levels of CBG-BC increased linearly after estradiol levels exceeded 1,300 pg. per milliliter and after estrone levels exceeded 500 pg. per milliliter (r = 0.88, p less than 0.001; and r = 0.85, p less than 0.001, logarithmic regression analysis). The findings of this study indicate that serum levels of CBG-BC are relatively constant in men and menstruating women. In pregnancy after a high threshold of endogenous estrogen is reached, CBG-BC increases in a direct dose-response manner as levels of estradiol increase further.

Adult↗

Recovery of midcycle human follicular oocytes: correlation of their morphology with endomethrial and follicular histology.

The ovarian follicles of 23 of 33 women undergoing elective pelvic laparotomy during menstrual cycle days 11 to 17 were aspirated by a low-vacuum device. The study compared the ovulatory status of women in midcycle with the health of the oocytes obtained, and determined the frequency of recovery of mature oocytes without the preadministration of exogenous hormones. Maturing or mature oocytes were obtained from 22% and nonmature oocytes from 48% of the 23 women. Sixty per cent of the women in each of the maturing or mature and nonmature groups were postovulatory as judged by evaluation of the endometrial and ovarian tissue recovered. Furthermore, 20% of the maturing or mature oocytes and 65% of the nonmature oocytes showed a moderately heavy amount of cytoplasmic degeneration, which was independent of ovulatory status. Therefore, it is concluded that, because of the relatively low rate of return of oocytes, the frequent postovulatory status of patients in midcycle, and uncertainty about the viability of the oocytes so obtained, women not stimulated by exogenous hormones are ill-suited for recovery of maturing or mature follicular oocytes for in vitro fertilization studies.

Adult↗

The percutaneous absorption of phenolic compounds: the mechanism of diffusion across the stratum corneum.

The effect of temperature on the permeation of phenolic compounds from aqueous solution through excised human skin has been examined. From a thermodynamic analysis of the data, a mechanism is postulated by which these solutes penetrate through human skin. For the more polar solutes it is suggested that the main resistance to penetration is the lipid barriers in the stratum corneum. Diffusion of these substances through the stratum corneum appears to depend on the breaking of hydrogen bonds in the desolvation of the solute during this penetration process and by the overall 'viscosity' of the stratum corneum. With non-polar solutes, the aqueous boundary layers appear to provide an additional barrier to the penetration of phenolic compounds.

Chemical Phenomena↗

Allosteric interactions between the membrane-bound acetylcholine receptor and chemical mediators: equilibrium measurements.

An approach to equilibrium dialysis measurements has been developed which enables one to study the interaction of chemical mediators with the membrane-bound acetylcholine receptor and to gain information of a type previously obtainable only with soluble proteins. Equilibrium dialysis experiments conducted at pH 7.0,4 degrees C, and mu = 0.18 M, with electroplax membrane preparations from Electrophorus electricus revealed apparently homogeneous binding isotherms for decamethonium with dissociation constants in the range of 0.2-0.4 muM. The following new information has been obtained. (1) The activators of neural transmission, decamethonium and carbamylcholine, occupy overlapping binding sites. (2) These activators and the inhibitors, alpha-bungarotoxin and d-tubocurarine, compete for only one-half of the sites available to them even through the stoichiometry of these is 1:1 as measured with decamethonium (a reversibly binding activator) and alpha-bungarotoxin (an irreversible specific inhibitor). Different receptor molecules, preexisting nonequivalent binding sites, or an allosteric mechanism involving ligand-induced conformational changes are often considered to account for such observations.

Acetylcholine↗

Oxidation photosensitized by tetracyclines.

Irradiation with 365-nm UV light of aerated aqueous solutions of tetracycline gives rise to oxygen uptake when the pH of the solution is above 7.5. The kinetics of the reaction were followed using a polarographic oxygen electrode at a range of pH values for seven currently prescribed tetracyclines. Variation of tetracycline concentration, UV light intensity, and temperature showed the characteristics normally associated with a sensitized photo-oxygenation mechanism rather than a free-radical process. Copper(II) ions inhibited the photo-oxidation of tetracycline, apparently by complex formation. The tetracyclines were tested for photosensitizing capability with oxidizable acceptors. In aqueous solution, no photosensitizing effect could be seen, but methanol solutions of 2,5-dimethylfuran and dl-limonene were oxidized at considerably increased rates when small amounts of tetracyclines were present. This observations has implications for the mechanism of in vivo photosensitivity reactions that occur when tetracyclines are taken internally.

Copper↗

Photosensitization by drugs.

UV irradiation (365 nm) of air-saturated methanol solutions of 20 drugs absorbing in the 300--400 nm region gave rise to oxygen uptake, as determined with a polarographic oxygen electrode. The drugs were tested for photosensitizing capability by either a Type I (free radical) or a Type II (single molecular oxygen) mechanism. This testing was done by the inclusion of either acrylamide or 2,5-dimethylfuran in the irradiated drug solution, with observation of the subsequent polymerization or oxidation, respectively. Phenothiazine and thiazide derivatives appear capable of photosensitization by both mechanisms; promethazine, trifluoperazine, and furosemide show relatively high reactivity. Diazepam (weak), hexachlorophene, aminacrine, pyrilamine, tetracycline, demeclocycline, quinine, and anthracene (strong) react only by a Type II mechanism, with a photosensitizing efficiency increasing in the order given. A correlation appears to exist with reports of in vivo photosensitivity.

Acrylamides↗

A fever index evaluation of chloramphenicol or clindamycin in patients with serious pelvic infections.

The fever index measured the responses of 102 women with serious pelvic infections who had received either chloramphenicol or clindamycin, in combination with other antibiotics. There was no statistical difference in the number of degree hours in the two populations. Patients with salpingo-oophoritis had significantly more fever than those with a septic abortion. Bacteremia did not delineate a group of women with a markedly elevated febrile response. Within the populaton with salpingo-oophoritis, neither black women nor women with an intrauterine device in place had significantly more fever, but patients requiring operation had more fever while those with an endocervical culture positive for the gonococcus at the time of admission had the most favorable clinical response. The significance of these findings is discussed.

Abortion, Septic↗