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Biomedical subjects

D S Clark

Publications and source records attributed to D S Clark.

At least 91 records · Page 5Linked to original sources
PubMed1984

Deactivation of alpha-chymotrypsin and alpha-chymotrypsin-CNBr-Sepharose 4B conjugates in aliphatic alcohols.

Several characterization methods have been used to study the deactivation in aliphatic alcohols of alpha-chymotrypsin and alpha-chymotrypsin-CNBr-Sepharose 4B conjugates. Active-site titration measurements, which were used to determine the amount of catalytically active enzyme, revealed appreciable differences between the deactivation kinetics of free and immobilized chymotrypsin. In all cases for the immobilized enzyme, the kinetics of active-enzyme disappearance differed significantly from first-order. Interestingly, the estimated intrinsic activity of immobilized chymotrypsin remaining active after different exposure times to 50% n-propanol solution increased somewhat as a result of exposure to alcohol. These findings were complemented by direct information, provided by EPR spectroscopy, on the effects of alcohols on the active-site configuration of spin-labeled chymotrypsin. EPR spectra of the free enzyme illustrated the appearance in different alcohol solutions of different enzyme forms with different active-site structures. EPR experiments also showed that denaturation of immobilized chymotrypsin was accompanied by unfolding of the active site that followed similar multi-step kinetics as the loss of active enzyme.

Alcohols↗
PubMed1984

Effect of azone and propylene glycol on penetration of trifluorothymidine through skin and efficacy of different topical formulations against cutaneous herpes simplex virus infections in guinea pigs.

Tropical formulations of 5-trifluoromethyl-2'-deoxyuridine (TFT) containing different concentrations of TFT, Azone (Nelson Research and Development, Irvine, Calif.), and propylene glycol were evaluated for their potential efficacy in the treatment of cutaneous herpes simplex virus infections by in vitro studies of TFT penetration through skin and in vivo studies of therapeutic activity against herpes simplex virus type 1 infections in the dorsal cutaneous guinea pig model. Azone dramatically increased TFT penetration through human and guinea pig skin. Unexpectedly, high concentrations of propylene glycol were also associated with increased penetration. Studies in the guinea pig model revealed increased efficacy with Azone-propylene glycol-containing formulations, consistent with the in vitro drug diffusion results. A formulation containing 1% TFT, 5% Azone, and 80% propylene glycol decreased lesion area, in comparison to the drug vehicle control, more effectively than 5% acyclovir in polyethylene glycol (reduction of 70 versus 46%, P = 0.03). These studies demonstrate the value of penetration-enhancing agents and the need for careful preclinical evaluations in the development of topical antiviral agents.

Administration, Topical↗
PubMed1977

Effect of collagen crosslinking on the rate of resorption of implanted collagen tubing in rabbits.

Collagen tubes were tanned with glutaraldehyde for different periods of time. Some were oxidized with periodate and sterilized with either 60Co (1.5 Mrad) or propylene oxide. The tubes were coated with polyfilamentous polyester fabric, filled with x-ray contrast material, and implanted subcutaneously in rats and rabbits. Rate of resorption was ascertained by x-ray procedure of progressive leakage of contrast material. A close relation between tanning time of the collagen fabric-combined prostheses and rate of their resorption in subcutis was found in both rats and rabbits. In rabbits, however, the implants were resorbed at a significantly faster rate than in rats. No effect of oxidation of collagen on the resorption was observed. Collagen tubes tanned for shorter time periods and sterilized with propylene oxide were more resistant to degradation than those sterilized with irradiation. This difference was absent, however, with material tanned for longer times. The mechanism of resorption of implanted collagen tubes was studied by morphological methods. The role of inflammatory cells in resorption is documented. The paper indicates the advantages as well as limits of the x-ray method of studying the resorption rate of biodegradable materials.

Animals↗
PubMed1977

Non-penetrating trauma to the carotid artery with secondary thrombosis and embolism: treatment by thrombolysin.

A case of partially occluding post-traumatic thrombosis of the internal carotid artery and secondary embolism of the middle cerebral artery is reported. The patient was treated with Thrombolysin with coincident resolution of clinical symptoms and signs and clearing of the lesions on arteriography. This may have been fortuitous. The subject of traumatic carotid artery thrombosis is reviewed in detail, and its pathophysiology is discussed, especially in relation to facts known about occlusive vascular disease secondary to atherosclerosis and related embolic phenomena. Suggestions are made concerning the treatment of this condition, especially with regard to developing rational criteria for opening vascular beds through evaluation of collateral cerebral blood flow. The uses of microvascular surgical techniques and thrombolytic therapy are considered.

Adult↗
PubMed1977

Left sided segmental portal hypertension following mesocaval interposition shunt.

Following a mesocaval interposition shunt in three patients with cirrhosis of the liver, bleeding esophageal varices recurred in two and left sided portal hypertension partially persisted in one patient. Angiographic and pressure studies of the portal system demonstrated effective decompression of the greater splanchnic venous system but continued lesser splanchnic venous hypertension. Recurrent variceal hemorrhage ceased following splenectomy done as an emergency. In contrast to a standard portacaval shunt, it is suggested that after an interposition mesocaval shunt, altered jet streaming of mesenteric blood flow may divert gastrosplenic venous drainage away from the interposition shunt with persistence of lesser splanchnic venous hypertension. Recognition of this entity and of the need for splenectomy is advocated.

Adult↗
PubMed1976

Conformational properties of the complexes formed by proteins and sodium dodecyl sulfate.

Circular dichroism spectra have been obtained for albumin, alpha-chymotrypsinogen, collagen, concanavalin A, elastase, hemoglobin, histone f2b, alpha-lactalbumin, lactate dehydrogenase, beta-lactoglobulin, lysozyme, myoglobin, papain, ribonuclease A, and thermolysin in the presence of sodium dodecyl sulfate and dithiothreitol. While all spectra have the shape anticipated for a mixture of random coil and alpha helix, the intensities differ markedly ([theta]222 ranges from --1400 to --15 000 deg cm2/dmol). The variation in the circular dichroism can be quantitatively explained by a model which assumes that the arginyl, histidyl, and lysyl residues have an enhanced probability of propagating a helical segment in the presence of the detergent. The model also permits the computation of dimensional properties (unperturbed end-to-end distance and radius of gyration) for polypeptides of known amino acid sequence. Such computations have been performed for 67 proteins. The computed dimensions are compatible with experimental values and with the molecular weight dependence of the transport properties of the complexes. Furthermore, the model can account for the abnormal transport properties of the sodium dodecyl sulfate complexes formed by ribonuclease A, collagen fragments, and histones f2a1, f2a2, f2b, and f3. Even though some of the protein--sodium dodecyl sulfate complexes have helical contents as high as 50%, their overall conformation more closely approximates that of a random coil than a rod.

Amino Acids↗
PubMed1976

Relationship of splanchnic blood flow and portal venous resistance to elevated portal pressure in the dog.

To determine the relationship of splanchnic blood flow and portal venous resistance to elevated portal pressure, in situ perfusion of the splanchnic circuit was carried out in 12 freshly killed dogs at varying perfusion rates and degrees of acute and chronic portal vein constriction. In six normal dogs before being killed, portal pressure averaged 8-8 +/- 1-2 mmHg and portal flow 658 +/- 81 ml/min. In the absence of portal vein constriction, increasing splanchnic perfusion to 1800 ml/min, minimally raised portal pressure (12-8 +/- 1-5 mmHg). With progressive acute constriction of the portal vein, however, comparable perfusion rates lead to progressively higher portal pressure levels and with greater than 90% constriction, portal pressure was greater than 30 mmHg with minimal elevation in splanchnic flow rate. In six other dogs before being killed but live to nine weeks after placement of an ameroid constrictor on the portal vein, portal pressure averaged 13-6 +/- 1-4 mmHg or slightly higher than in normal dogs (P greater than 0-02). Mesenteric venography and necropsy findings uniformly demonstrated 90% occlusion of the portal vein with extensive portasystemic collateralization. With increased perfusion of the splanchnic bed, portal pressure rose rapidly to approximately 35 mmHg with a flow rate of 1 800 ml/min.. These data suggest that, in disorders where resistance to transhepatic portal flow is marked, a small increment in splanchnic blood flow, which normally exerts little or no influence on portal pressure, promotes profound portal hypertension and may account for spontaneous 'rupture' of oesophageal varices. On the other hand, where resistance to transhepatic portal flow is mild but splanchnic blood flow is markedly hyperdynamic, reducing inflow may be sufficient to ameliorate extreme portal hypertension and its sequelae.

Animals↗
PubMed1976

Factors affecting rate of methane formation from acetic acid by enriched methanogenic cultures.

A stable enrichment culture converting acetic acid to methane was successfully obtained from a pear waste digester, using a synthetic substrate solution with acetic acid as the main carbon source. This enrichment culture converted up to 10 mmol of acetic acid per litre per day at 35 degrees C and did not use hydrogen or formic acid in appreciable amounts as substrate for methane production instead of, or in addition to, acetic acid. The rate of conversion of acetic acid to methane was maximum at temperature of 40-45 degrees C, at a pH of 6.5 to 7.1, and was adversely affected by exposure to air, reducing agents, and high salt concentrations. The rate of conversion was independent of acetic acid concentration between 0.2 and 100 mM, but dropped markedly at concentrations below 0.2 mM.

Acetates↗
PubMed1976

Characterization of a strain of Methanospirillum hungatti.

The results of morphological, base ratio, nutritional, temperature, and pH studies on a strain of Methanospirillum hungatii, isolated from an anaerobic pear waste digester, are described. The isolate, designated as strain GP 1, was compared with some of the characteristics of type-strain M. hungatii JF 1. Strain GP 1 is Gram-negative, weakly motile, and a strict anaerobe with a guanine plus cytosine (G +C) content of 46.5 mol%. The preferred substrates for methane production are hydrogen, carbon dioxide, and formate. Acetate is used under certain conditions but its specific contribution to cell carbon and (or) methane formation was not established. The optimum temperature for both growth and methane production is 35 degrees C, but growth and methane production occur over the range 25-45 degrees C. Methane production is optimal at pH 7.0.

Acetates↗
PubMed1975

Effect of lactobacilli and carbon dioxide on the growth of Microbacterium thermosphactum on fresh beef.

Studies with articifially inoculated fresh beef showed that lactobacilli markedlyrestrict the growth of Microbacterium thermosphactum when the beef is vacuum-packaged. High concentrations of carbon dioxide (up to 75%) had little effect on the growthof M. thermosphactum under either aerobic or anaerobic conditions. Tests were madewith samples of lean beef inoculated with pure cultures of lactobacilli and (or) M. thermosphactum and stored unpackaged in air, in air enriched with carbon dioxide, in nitrogen-carbon dioxide mixtures, or vacuum-packaged as in commercial practice. On vacuum-packaged meat, growth of M. thermosphactum was extensive in the absence of lactorbacilli, but was restricted in the presence of lactobacilli. On unpackaged meat (i.e.stored in air) this inhibition did not occur, showing that anaerobic conditions are necessary for it to take place. These results show the import ance of lactobacilli on the storage life of vacuum-packaged fresh beef.

Actinomycetales↗
PubMed1971

Four-directional-development thin-layer chromatography of lipids using trimethyl borate.

Solvent mixtures containing trimethyl borate virtually eliminated the pronounced interconversion of 1,2- and 1,3-dipalmitins during their resolution by thin-layer chromatography on Silica Gel G. With trimethyl borate, an average of 1-2% of 1,2-dipalmitin was converted to 1,3-dipalmitin. A four-directional-development TLC procedure incorporating trimethyl borate resolves cholesteryl glucoside, ceramides, monogalactosyl diglyceride, 1- and 2-monopalmitin, palmitic acid, cholesterol, 1,2- and 1,3-dipalmitin, tripalmitin, methyl palmitate, cholesteryl palmitate, beta-carotene and some of its degradation products, squalene, and tetracosane. Digalactosyl diglyceride, phosphatidic acid, phosphatidylglucose, cerebrosides, and other phospholipids remain near the origin. A mixture containing triolein, 1,2- and 1,3-diolein, 1- and 2- monoolein, oleic acid, and cholesterol was resolved in one dimension. A similar series of palmitic-containing neutral lipids was also resolvable in one dimension. These procedures were applied to the TLC of human sera lipids.

Acetates↗