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Biomedical subjects

D Mendel

Publications and source records attributed to D Mendel.

At least 19 recordsLinked to original sources
PubMed1992

Probing protein stability with unnatural amino acids.

Unnatural amino acid mutagenesis, in combination with molecular modeling and simulation techniques, was used to probe the effect of side chain structure on protein stability. Specific replacements at position 133 in T4 lysozyme included (i) leucine (wt), norvaline, ethylglycine, and alanine to measure the cost of stepwise removal of methyl groups from the hydrophobic core, (ii) norvaline and O-methyl serine to evaluate the effects of side chain solvation, and (iii) leucine, S,S-2-amino-4-methylhexanoic acid, and S-2-amino-3-cyclopentylpropanoic acid to measure the influence of packing density and side chain conformational entropy on protein stability. All of these factors (hydrophobicity, packing, conformational entropy, and cavity formation) significantly influence protein stability and must be considered when analyzing any structural change to proteins.

Amino Acids↗
PubMed1992

Site-specific incorporation of novel backbone structures into proteins.

A number of unnatural amino acids and amino acid analogs with modified backbone structures were substituted for alanine-82 in T4 lysozyme. Replacements included alpha,alpha-disubstituted amino acids, N-alkyl amino acids, and lactic acid, an isoelectronic analog of alanine. The effects of these electronic and structural perturbations on the stability of T4 lysozyme were determined. The relatively broad substrate specificity of the Escherichia coli protein biosynthetic machinery suggests that a wide range of backbone and side-chain substitutions can be introduced, allowing a more precise definition of the factors affecting protein stability.

Alanine↗
PubMed1987

Hoogsteen base pairs proximal and distal to echinomycin binding sites on DNA.

Forms of the DNA double helix containing non-Watson-Crick base-pairing have been discovered recently based on x-ray diffraction analysis of quinoxaline antibiotic-oligonucleotide complexes. In an effort to find evidence for Hoogsteen base-pairing at quinoxaline-binding sites in solution, chemical "footprinting" (differential cleavage reactivity) of echinomycin bound to DNA restriction fragments was examined. We report that purines (A greater than G) in the first and/or fourth base-pair positions of occupied echinomycin-binding sites are hyperreactive to diethyl pyrocarbonate. The correspondence of the solid-state data and the sites of diethyl pyrocarbonate hyperreactivity suggests that diethyl pyrocarbonate may be a sensitive reagent for the detection of Hoogsteen base-pairing in solution. Moreover, a 12-base-pair segment of alternating A-T DNA, which is 6 base pairs away from the nearest strong echinomycin-binding site, is also hyperreactive to diethyl pyrocarbonate in the presence of echinomycin. This hyperreactive segment may be an altered form of right-handed DNA that is entirely Hoogsteen base-paired.

Base Composition↗
PubMed1970

Tricuspid valve replacement in rheumatic heart disease.

The diagnosis of tricuspid valve disease is often difficult; the best treatment is not yet established. Twenty patients had tricuspid valve replacements at St. Thomas's Hospital as part of multiple valve replacement procedures. The hospital mortality was 25%, most deaths being due to a low cardiac output causing hepatorenal failure. Preoperative cardiac cachexia had a fatal outcome in all cases. Except in two instances, surviving patients returned to a satisfactory level of activity.

Adolescent↗
PubMed1969

Triple Starr valve replacement.

Of nine patients who have had triple valve replacements for organic rheumatic triple valve disease two died in the postoperative period from inadequate myocardial reserve, and a third died four months later from cerebral embolism originating from clot on the left atrial wall. The remainder are well and, except for one, leading normal lives. Though cardiac transplantation has been recommended and used successfully for triple valve disease by Cooley, it is suggested that the long-term outlook today of triple valve replacement is likely to be better than that of transplantation.

Adult↗
PubMed1967

Some observations on 'autoregulatory escape' in cat intestine.

1. ;Autoregulatory escape' (Folkow, Lewis, Lundgren, Mellander & Wallentin, 1964a) in which intestinal blood flow escapes from the constrictor influence of splanchnic nerve stimulation, was investigated in the cat. Measurements were made of intestinal blood flow, movements and portal venous pH and oxygen content.2. ;Autoregulatory escape' was observed with sympathetic nerve stimulation and noradrenaline infusion. It did not occur during haemorrhage.3. The recovery of flow during noradrenaline infusion could not be explained by changes in intestinal motility or loss of effect of noradrenaline due to changes in portal venous hydrogen ion concentration.4. During a noradrenaline infusion there was a reduction in oxygen consumption associated with a fall in blood flow. During the period of ;autoregulatory escape', however, oxygen consumption increased. The significance of these observations is discussed.

Animals↗
PubMed1967

The effects of alteration of CO2 and pH on intestinal blood flow in the cat.

1. The effect of alteration of arterial blood pH on intestinal blood flow in the cat has been determined under conditions of constant perfusion pressure.2. Arterial blood pH was altered over the range 7.12-7.70 by infusion of acid and alkali. When end-tidal CO(2) was held constant, there was no change in intestinal blood flow.3. When arterial blood pH was altered over the range 7.19-7.55 by the administration of CO(2) at constant respiratory volume and rate, flow increased with increasing CO(2).4. The intestinal vascular bed was less responsive to noradrenaline at pH 7.2 than at pH 7.6. The change in sensitivity was evident when end-tidal CO(2) was controlled and depended therefore on a change in hydrogenion concentration.5. The dilator effect of CO(2) did not depend upon alteration of sensitivity to noradrenaline since it was seen after adrenergic blockade.

Animals↗