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Biomedical subjects

R A Anderson

Publications and source records attributed to R A Anderson.

At least 325 records · Page 18Linked to original sources
PubMed1981

Genetic heterogeneity of factor XIII deficiency: first description of unstable A subunits.

In previously reported cases, congenital deficiency of coagulation factor XIII has been found to result from the absence of the enzymatically active A subunits. In the family reported here two members were found to be heterozygous for an unstable A subunit which, in the homozygous state, or in the heterozygous state with the previously described null allele, would be expected to result in factor XIII deficiency. The implications that this new variant has on heterozygote screening are discussed.

Alleles↗
PubMed1981

Tetratological evaluation of mouse fetuses after paternal alcohol ingestion.

Numerous studies have appeared in the literature which suggest that paternal alcohol consumption may have adverse effects on subsequent offspring. However, to date, no teratologic examination has been performed on fetuses conceived subsequent to paternal alcohol consumption. The present study has examined fetuses conceived by alcohol-treated male Swiss webster mice for gross anatomical congenital defects in an attempt to evaluate a possible mechanism for decreased viability of offspring sired by alcoholic males. Sexually mature males were maintained for 28 days on a total liquid nutriment diet in which alcohol (6.3%, v/v, U.S.P. ethanol) comprised 32% of the caloric content. Subsequently, the animals were mated with nulliparous females. On day 18 of gestation, the gravid females were sacrificed and the fetuses were examined for congenital defects. Only 14% of the matings which occurred 3--5 days after alcohol treatment resulted in pregnancy, as compared to a pregnancy rate of 100% for matings from pair-fed controls during the same period. Fetuses sired by alcohol-treated males during this time had reduced birth weights (0.85 +/- 0.04 g vs 0.92 +/- 0.11 g;p = 0.059) and crown-rump lengths (1.83 +/- 0.06 cm vs 1.99 +/- 0.11 cm;p less than 0.001) as compared to control fetuses. The frequency of congenital defects did not differ significantly between the experimental and control groups. No significant differences were noted between experimental and control progeny conceived more than 5 days after alcohol treatment. These results suggest that although some changes may be seen in progeny sired by alcohol treated males, the specific anomalies associated with the Fetal Alcohol Syndrome are most probably not due to paternal alcoholism.

Abnormalities, Drug-Induced↗
PubMed1980

Determination of cyanide and thiocyanate in biological fluids by gas chromatography-mass spectrometry.

A sensitive, specific and accurate method is described for the determination of cyanide and thiocyanate in biological fluids. Potassium cyanide containing 95% 15N is added to the sample as internal standard and both endogenous cyanide and standard are separated by gas-phase diffusion into sodium hydroxide solution. Cyanogen chloride is prepared by reaction with sodium p-toluenesulphonchloramide and extracted into n-heptane. Quantitative analysis is carried out by gas chromatography-mass spectrometry (GC-MS) with selective ion monitoring of the molecular ions at m/e 61and m/e 62. Thiocyanate levels are determined by a similar procedure in which 15N-labelled sodium thiocyanate is used as internal standard. The method is applicable to a wide range of biological samples and is free from interference by other sample components.

Cyanides↗
PubMed1980

Stoichiometry of wheat germ agglutinin as a morphology controlling agent and as a morphology controlling agent and as a morphology protective agent for the human erythrocyte.

The lectin wheat germ agglutinin (WGA) is an unusually effective agent in controlling both the forward and reverse reactions of the reversible morphology conversion discocyte in equilibrium with echinocyte for the human erythrocyte. Under conditions severe enough to drive the reactions to completion in either direction without the lectin, WGA is able to stabilize both these morphologies and to fully prevent conversion of either morphology. The lectin can quantitatively block both reactions. The ability of WGA to carry out these functions has no obvious rate limitation. Its effectiveness depends mainly on its binding stoichiometry, particularly toward the transmembrane glycoprotein, glycophorin. The critical binding stoichiometries for both the lectin and the echinocytic agent were determined in relation to the binding isotherms using 125I-labeled WGA and 35S-labeled dodecyl sulfate. There appear to be two principal stoichiometries for WGA binding that are important in its control of erythrocyte morphology. The first stoichiometry marks the threshold of obvious protection of the discocyte against strong echinocytic agents such as detergents and, likely, is simply a 1:1 stoichiometry of WGA: glycophorin, assuming currently recognized values of 3--5 x 10(5) copies of glycophorin per cell. The second important stoichiometry, whereby the cell's morphology is protected against extremely severe stress, involves binding of approximately 4--5 WGA molecules per glycophorin. The controls that WGA exerts can be instantly abolished by added N-acetylglucosamine. However, N-acetylglucosamine ligands on the erythrocyte are of less importance than membrane neuraminic acid residues in enabling WGA to control the cell's morphology, as is shown by comparing intact cells with completely desialated cells. WGA can also be used to produce elliptocytes in vitro, but it does this at levels approaching monolayer coverage of the cell with WGA.

Acetylglucosamine↗
PubMed1980

Effect of lectins on migration of the corneal epithelium.

Rat corneas with 3 mm central corneal abrasions were organ-cultured in the presence of four plant lectins, concanavalin A (ConA), wheat germ agglutinin (WGA), lotus lectin, and soybean agglutinin (SBA), ConA at 20 and 50 micrograms/ml of culture medium slowed epithelial migration. WGA at 20 and 50 micrograms/ml of medium completely inhibited migration. The effects of the ConA at both 20 and 50 micrograms concentrations and of WGA at 20 micrograms were reversible. Lotus lectin and SBA did not effect motility at concentrations up to and including 50 micrograms/ml of medium. The specific sugar to which SBA binds, N-acetyl-galactosamine, did however, slow epithelial migrations. This study demonstrates that blocking glucose, mannose, and glucosamine sugar moities of glycoproteins on the cell surface and/or basement membrane inhibits epithelial cell migration during healing of corneal abrasions.

Acetylgalactosamine↗
PubMed1979

Enzymic determination of fructose in seminal plasma by initial rate analysis.

We describe a spectrophotometric assay for fructose in seminal plasma. The method is based on reduction of fructose by a commercially available preparation of sorbitol dehydrogenase (EC 1.1.1.14), with the concomitant oxidation of NADH. The initial rate of NADH oxidation, which is proportional to the fructose content of seminal plasma, can be measured either with a recording spectrophotometer or by conventional two-point kinetic assay. The method was as accurate, precise, and sensitive as, and more specific and rapid than, currently used colorimetric (resorcinol) methods for fructose determination. Values (mmol/L) for fructose in seminal plasma from several species are: man, 9 +/- 2 (SD); cynamolgus monkey (Macaca fasicicularis)., 108 +/- 19; bull, 30 +/- 1; and rabbit, 13 +/- 4. These values agree with previously published results. We believe the method is appropriate for both research and clinical use.

Animals↗
PubMed1979

Metal-free housing units for trace element studies in rats.

Metal-free housing units fabricated from clear plastic and polystyrene egg crate panels were used to house rats for studies involving trace elements. The cages did not require bedding, were well ventilated and fitted into commercially available cage racks. Modifications of the basic design were made to provide both maternity and metabolism cages.

Animals↗
PubMed1979

Actin filaments in cells of human trabecular meshwork and Schlemm's canal.

With subfragment-one of myosin used as the histochemical marker, actin filament distribution was mapped in cells of the aqueous outflow pathway. In uveal, corneal-scleral and juxtacanalicular meshwork cells, bundles of actin filaments were present along the basal cytoplasm. Some of these bundles terminated at adhesion plaques. Juxtacanalicular meshwork cells contained, in addition to bundles, randomly oriented actin filaments at the end of cell extensions. Giant vacuoles in the inner wall of Schlemm's canal did not have actin filaments associated with their membranes; there were, however, intermediate filaments present along the membrane. Bundles of actin filaments were also found within the cells of both inner and external walls of Schlemm's canal. Cells of both the meshwork and inner wall of Schlemm's canal had actin filaments extending out into the cytoplasm from cell junctions. In all areas of the meshwork and especially in the area external to Schlemm's canal, cells were observed which had a cytoplasm, very rich in actin filaments. These cells had characteristics common to smooth muscle cells. The actin filaments of cells of the aqueous outflow pathway could have any or all of several functions. Bundles of filaments in the meshwork could contract to lift and separate trabecular sheets and/or, through their association with adhesion plaques, they could stabilize cells on their collagen substrate, thus acting as cytoskeletal struts. Randomly oriented actin filaments, noted particularly in cells of the juxtacanalicular meshwork, may play a role in phagocytosis. Actin filaments found in association with junctions may be important structures for maintaining cell-to-cell contacts. Lack of actin filaments around giant vacuoles in Schlemm's canal indicates that they do not play a role in shuttling aqueous across the endothelium of the canal. The significance of "actin-rich" cells in the meshwork and those external to Schlemm's canal is unknown.

Actins↗
PubMed1978

Cyanide exposure in fires.

The toxic hazard from cyanide produced in fires was assessed in casualties and in firemen exposed to the fire atmosphere. The levels of cyanide and its principal metabolite, thiocyanate, were measured in blood samples from fireman, non-fetal and fatal casualties, and from controls. Although firemen did not differ significantly from controls, casualities showed significant elevation of blood-cyanide, and in a small proportion of fatalities blood-cyanide reached toxic levels.

Cyanides↗
PubMed1978

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↗
PubMed1978

Pulmonary hypertension in sepsis: measurement by the pulmonary arterial diastolic-pulmonary wedge pressure gradient and the influence of passive and active factors.

To examine the relative roles of passive factors (flow; filling pressures of left side of heart) and active factors (acidosis; arterial unsaturation) in the genesis of pulmonary hypertension when associated with sepsis, 37 patients with sepsis and 24 patients without sepsis were examined. Pulmonary hypertension was measured by the pulmonary arterial diastolic-pulmonary wedge pressure gradient (PAd-PWP gradient) and correlated reasonably with a standard formula for calculated resistance ([PA--PWP]/CI, where PA is mean pulmonary artery pressure and CI is cardiac index). In 22 of 37 patients, sepsis was associated with a significant degree of resistance to flow in the pulmonary circulation, as measured by the PAd-PWP gradient: and the higher the PAd--PWP gradient, the greater the likelihood of early death. None of the examined passive or active factors appeared to be adequate to explain pulmonary hypertension when present. By the use of previously derived formulae to estimate the compliance of the elastic pulmonary arteries, factors affecting this part of the pulmonary microcirculation could not be held accountable for apparent pulmonary hypertension. Therefore, the presence of pulmonary hypertension in sepis appears to be an active, rather than a passive, phenomenon and unrelated to arterial oxygen saturation or acid-base imbalance. Although the exact cause is unknown, pulmonary hypertension in sepis is associated with a high mortality and may be clinically followed by measurement of the PAd-PWP gradient.

Bacterial Infections↗
PubMed1977

Effect of magnesium on the properties of zinc alkaline phosphatase.

Alkaline phosphatase of Escherichia coli, isolated by procedures which do not alter its intrinsic metal content, contains 4.0 +/- 0.3 g-atoms of tightly bound zinc per mole (Kd less than 1 muM) and 1.3 +/- 0.2 g-atoms of magnesium per mole (Bosron, W.F., Kennedy, F.S., and Vallee, B.L. (1975), Biochemistry 14, 2275-2282). Importantly, the binding of magnesium is dependent both upon pH and zinc content. Hence, the failure to assign the maximal magnesium stoichiometry to enzyme isolated by conventional procedures may be considered a consequence of the conditions chosen for optimal bacterial growth and purification of the enzyme which are not the conditions for optimal binding of magnesium to alkaline phosphatase. Under the conditions employed for the present experimental studies, a maximum of six metal sites are available to bind zinc and magnesium, i.e., four for zinc and two for magnesium. Magnesium alone does not activate the apoenzyme, but it regulates the nature of the zinc-dependent restoration of catalytic activity to apophosphatase, increasing the activity of enzyme containing 2-g-atoms of zinc five-fold and that of enzyme containing 4-g-atoms of zinc 1.4-fold. Moreover, hydrogen-tritium exchange reveals the stabilizing effects of magnesium on the structural properties of phosphatase. However, neither the KM for substrate nor the phosphate binding stoichiometry and Ki are significantly altered by magnesium. Hence, magnesium, which is specificially bound to the enzyme, both stabilizes the dynamic protein structure and regulates the expression of catalytic activity by zinc in alkaline phosphatase.

Alkaline Phosphatase↗