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Biomedical subjects

M W Williams

Publications and source records attributed to M W Williams.

At least 37 records · Page 2Linked to original sources

Intestinal absorption and lymphatic transport of peroxidized lipids in rats: effect of exogenous GSH.

We previously found that mucosal glutathione (GSH) plays an important role in the intestinal metabolism of luminal peroxidized lipids [T. Y. Aw, M. W. Williams, and L. Gray. Am. J. Physiol. 262 (Gastrointest. Liver Physiol. 25): G99-G106, 1992]. To determine the effects of exogenous GSH on lipid hydroperoxide elimination under conditions in which mucosal GSH was initially depleted with buthionine sulfoximine (BSO), we infused peroxidized lipid solutions without or with GSH into the proximal intestine of rats and monitored the steady-state output of hydroperoxides in lymph and recovery of luminal hydroperoxides. GSH supplementation in BSO-treated rats resulted in a concentration-dependent attenuation of lymphatic output of peroxidized lipids that was correlated with increases in mucosal GSH. Compared with BSO control, the luminal lipid hydroperoxide contents were significantly lower in GSH-supplemented rats, consistent with enhanced elimination of peroxidized lipids by exogenous GSH. The effect of GSH was ameliorated by the inhibitors of GSH uptake, suggesting that the uptake of GSH is required for promotion of intestinal removal of luminal hydroperoxides. Other thiols, either at comparable or higher concentrations than GSH, were without significant effects on lymphatic transport or luminal recovery of lipid hydroperoxides, indicating that these thiols are poor substitutes for GSH. Overall, the data are consistent with exogenous GSH being a source for cellular reduction of peroxidized lipids. Results from these studies could directly impact on future consideration of therapeutic means to increase cellular antioxidant systems to promote intestinal hydroperoxide detoxication.

Animals↗

Phallic reinnervation via the pudendal nerve.

Total phallic reconstruction presents the genitourinary reconstructive surgeon with one of the most difficult surgical challenges. The development of microsurgical techniques and free tissue transfers have advanced phallic reconstruction by reducing the number of surgical procedures and by allowing more selectivity in choosing the best innervated donor tissue. During the last 5 years 16 patients underwent total phallic reconstruction using free tissue transfers from distant donor sites. The pudendal nerve was coapted routinely to the major sensory nerves of the donor free flap. The most accurate objective baseline parameters of penile sensibility are pressure and vibratory thresholds, and electrically evoked potentials. We examined 30 normal subjects and 7 patients at least 1 year postoperatively for penile (phallic) sensibility. A pressure aesthesiometer, a biothesiometer and electrodiagnostic studies were used for testing. The 7 postoperative patients (in all of whom the pudendal nerve was incorporated into the reconstruction) had an encouraging return of tactile and erogenous sensibility compared to normal subjects. This is a promising advance in phallic reconstruction.

Adolescent↗

Cadmium resistance in Drosophila: a small cadmium binding substance.

A small cadmium-binding substance (CdBS) has been observed in adult Drosophila melanogaster that were raised for their entire growth cycle on a diet that contained 0.15 mM CdCl2. Induction of CdBS was observed in strains that differed widely in their sensitivity to CdCl2. This report describes the induction of CdBS and some of its characteristics.

Animals↗

Genetic and physiological parameters associated with cadmium toxicity in Drosophila melanogaster.

Two strains of Drosophila melanogaster represent the extremes in resistance and sensitivity to the lethal effects of CdCl2. The strain containing the mutations vermilion and brown (v; bw) and the strain Austin had LC50's of 3.3 and 1.3 mM CdCl2, respectively. The three major chromosomes from these two strains were assorted genetically into the six possible combinations. The measured LC50's for CdCl2 for these six genotypes fell into two groups according to the X chromosome; those containing the X chromosome from v; bw had LC50's 0.5-1.0 mM greater than those in which the X chromosome was from Austin. Since the parent strains differed by 2 mM, we suggest that the X chromosome is a major, but not the sole, site of genes to produce resistance to CdCl2. When 109Cd was in the diet the uptake by v; bw and Austin over 2 days was the same. After 4 days of uptake, the Austin strain excreted the 109Cd five times faster than v; bw but the six genotypes did not differ appreciably in excretion rate from one another and resembled the sensitive parent Austin more than the resistant one. Thus a second process is indicated that distinguishes resistance to CdCl2 that apparently is not associated with the X chromosome.

Animals↗

The toxicity of sixteen metallic compounds in Chinese hamster ovary cells.

The toxicity of 16 metal salts to Chinese hamster ovary (CHO) cells was determined by measuring the cloning efficiency (CE) of CHO cells after exposure to the metals. CHO cells differed by a factor of 10(5) to 10(6) in their toxic response to these metal salts. While Cd(II) was the most toxic ion, Mg(II) exhibited the least toxicity based on either CE50 (concentration required to reduce the CE to 50%) or D0 (concentration increment which reduced the CE by 63%). On the basis of CE50, the toxicity ranking was Ag greater than Tl for monovalent metals, Cd greater than Zn greater than Hg greater than Co greater Cu greater than Mn greater than Ni greater than Be greater than Pd greater than Sr greater than Mg for divalent metals, and In greater than Rh greater than Y for trivalent metals. A similar ranking was found for D0. For the 11 divalent metals, correlations of CE50 and D0 in the CHO cell assay and the Pearson-Mawby softness parameter for metals (sigma p) were reasonably strong. A good correlation exists between the results of this study on the toxic response in CHO cells and published data on toxicity in mice and Drosophila. It appears that the CHO cell cloning assay may be useful in preliminary screening of metallic compounds as an indicator of their predicted toxicity in higher organisms.

Animals↗

The organic aerosols of Titan.

A dark reddish organic solid, called tholin, is synthesized from simulated Titanian atmospheres by irradiation with high energy electrons in a plasma discharge. The visible reflection spectrum of this tholin is found to be similar to that of high altitude aerosols responsible for the albedo and reddish color of Titan. The real (n) and imaginary (k) parts of the complex refractive index of thin films of Titan tholin prepared by continuous D.C. discharge through a 0.9 N2/0.1 CH4 gas mixture at 0.2 mb is determined from x-ray to microwave frequencies. Values of n (approximately equal to 1.65) and k (approximately equal to 0.004 to 0.08) in the visible are consistent with deductions made by ground-based and spaceborne observations of Titan. Many infrared absorption features are present in k (lambda), including the 4.6 micrometers nitrile band. Molecular analysis of the volatile component of this tholin was performed by sequential and non-sequential pyrolytic gas chromatography/mass spectrometry. More than one hundred organic compounds are released; tentative identifications include saturated and unsaturated aliphatic hydrocarbons, substituted polycyclic aromatics, nitriles, amines, pyrroles, pyrazines, pyridines, pyrimidines, and the purine, adenine. In addition, acid hydrolysis produces a racemic mixture of biological and non-biological amino acids. Many of these molecules are implicated in the origin of life on Earth, suggesting Titan as a contemporary laboratory environment for prebiological organic chemistry on a planetary scale.

Aerosols↗

Investigation of correlations between chemical parameters of metal ions and acute toxicity in mice and Drosophila.

We are studying correlations between physicochemical properties associated with metal ions and observed toxicity. In order to test correlations, we obtained, under uniform conditions, LD50 values for acute toxicity in mice for 24 metal ions. The new data show a better correlation between LD50 and Pearson and Mawby's softness parameter sigma p, defined using chemical concepts of hard and soft acids and bases, than had been obtained by others. From a wide range of physicochemical parameters, the electrode potential can give almost as good a correlation as sigma p. Better correlations might exist for parameters more relevant to biological systems.

Animals↗

Toxic effects of a new boron containing heterocycle: 4,4,8,8-tetraethyl-3,3a,4,8-tetrahydro 3a,4a,4-diazabora-S-indacene.

LD50 values in mice for 4,4,8,8-tetraethyl-3,3a,4,8-tetrahydro-3a,4a,4-diazabora-S-indacene (Myborin) were determined by the ip, po, and sc routes. The LD50 value for ip was 69.5 mg/kg found by the method of Litchfield and Wilcoxon, with upper and lower confidence limits of 77.8 and 62.1 mg/kg. Oral and sc LD50's were approximated after the method of Deichmann and LeBlanc and were found to be 180 mg/kg (po) and 420 mg/kg (sc). Each of these values has a confidence range of +/- 30%. Myborin induced convulsions, hyperreflexia, and death accompanied by tetany when given by either the ip or oral routes. Moreover, Myborin induced porphyria in animals surviving for 24 hr after these routes of administration and in virtually all animals dosed sc. Death by the sc route is probably a result of acute porphyria. Hepatomegaly and skin photosensitivity were demonstrated to be profound. Boron levels in the livers of mice were determined colorimetrically 24 hr after ip injections of Myborin and in untreated control mice. The quantity of boron found in the experimental group was 15.46 mug/g wet liver as compared to 8.11 mug/g wet liver for controls (P less than 0.01). The difference corresponds to 23% of the injected quantity of boron.

Animals↗

N-Malonyl-d-tryptophan in Apple Fruits Treated with Succinic Acid 2,2-Dimethylhydrazide.

Fruit from Red Delicious apple trees treated with the growth retardant succinic acid 2,2-dimethylhydrazide contained more N-malonyl-d-tryptophan than control fruit. When succinic acid 2,2-dimethylhydrazide and tryptophan were injected into immature fruits, more N-methyl-d-tryptophan was produced than when dl-tryptophan was injected alone. Our results suggest that succinic acid 2,2-dimethylhydrazide may control fruit and vegetative growth by interfering with auxin production.

Journal Article↗