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Biomedical subjects

G Hale

Publications and source records attributed to G Hale.

At least 181 records · Page 10Linked to original sources
PubMed1983

Removal of T cells from bone marrow for transplantation. Comparison of rat monoclonal anti-lymphocyte antibodies of different isotypes.

We describe a family of six rat monoclonal antibodies which appear to recognize identical or closely related determinants present on virtually all mature human lymphocytes and monocytes, but absent from other blood cells including myeloid and erythroid colony-forming cells. Four IgM antibodies and one IgG2a fix human complement; one IgG2c antibody does so only poorly. All of the antibodies react with lymphocytes from baboons, rhesus and cynomolgus monkeys. However, in all baboons and rhesus monkeys tested, and some cynomolgus monkeys, they also recognize red cells. Nevertheless, in other cynomolgus monkeys reactivity is with lymphocytes only, so these animals will be suitable models for testing the effects of the antibodies in vivo. The antibodies described here could be useful for in vitro removal of lymphocytes from allogeneic marrow grafts (to prevent graft-versus-host disease) or malignant lymphoid cells from autologous grafts (for treatment of leukaemia) and may also find application as general immunosuppressants and for immunotherapy of leukaemia.

Animals↗
PubMed1983

Effects of monoclonal anti-lymphocyte antibodies in vivo in monkeys and humans.

The safety and efficacy in vivo of three rat monoclonal anti-lymphocyte antibodies has been tested in cynomolgus monkeys. One IgM antibody, CAMPATH 1, was found to cause rapid but transient lymphopenia associated with consumption of complement. Two other antibodies with the same specificity, YTH 34.5 (IgG2a) and YTH 86.1 (IgG2c), had little effect. No acute or chronic toxic effects were associated with administration of any of the antibodies. CAMPATH 1 was used in a Phase I clinical trial for immunotherapy of two patients with terminal malignant lymphoid disease. It had no detectable toxic effects although it caused disappearance of circulating lymphocytes and consumption of complement. An inadequate rate of synthesis of complement components was a limitation to therapy in these patients with very large tumour burden, but might not be a major problem if antibody therapy were used at an earlier stage of the disease. CAMPATH 1 may also be useful as an immunosuppressive agent.

Animals↗
PubMed1982

Mexiletine vs. lignocaine in the management of ventricular arrhythmias after open-heart surgery.

We made an open comparison of lignocaine and mexiletine in the treatment of ventricular arrhythmias occurring after open-heart surgery. Thirty patients whose arrhythmia did not respond to correction of metabolic disturbances were randomly allocated to receive treatment either with lignocaine or with mexiletine in fixed dosage schedules (15 in each group). Failure to control the rhythm or recurrent abnormality led to administration of a further dose and, if this was unsuccessful, to crossover to the alternative agent. The two drugs were comparable in efficacy, but mexiletine was slightly more effective when administered after lignocaine than the converse.

Arrhythmias, Cardiac↗
PubMed1981

The role of lipoic acid residues in the pyruvate dehydrogenase multienzyme complex of Escherichia coli.

Two lipoic acid residues on each dihydrolipoamide acetyltransferase (E2) chain of the pyruvate dehydrogenase multienzyme complex of Escherichia coli were found to undergo oxidoreduction reactions with NAD+ catalysed by the lipoamide dehydrogenase component. It was observed that: (a) 2 mol of reagent/mol of E2 chain was incorporated when the complex was incubated with N-ethylmaleimide in the presence of acetyl-SCoA and NADH; (b) 4 mol of reagent/mol of E2 chain was incorporated when the complex was incubated with N-ethylmaleimide in the presence of NADH; (c) between 1 and 2 mol of acetyl groups/mol of E2 chain was incorporated when the complex was incubated with acetyl-SCoA plus NADH; (d) 2 mol of acetyl groups/mol of E2 chain was incorporated when the complex was incubated with pyruvate either before or after many catalytic turnovers through the overall reaction. There was no evidence to support the view that only half of the dihydrolipoic acid residues can be reoxidized by NAD+. However, chemical modification of lipoic acid residues with N-ethylmaleimide was shown to proceed faster than the accompanying loss of enzymic activity under all conditions tested, which indicates that not all the lipoyl groups are essential for activity. The most likely explanation for this result is an enzymic mechanism in which one lipoic acid residue can take over the function of another.

Acetyl Coenzyme A↗
PubMed1981

Lipoic acid residues in a take-over mechanism for the pyruvate dehydrogenase multienzyme complex of Escherichia coli.

The pyruvate dehydrogenase complex of Escherichia coli contains two lipoic acid residues per dihydrolipoamide acetyltransferase chain, and these are known to engage in the part-reactions of the enzyme. The enzyme complex was treated with trypsin at pH 7.0, and a partly proteolysed complex was obtained that had lost almost 60% of its lipoic acid residues although it retained 80% of its pyruvate dehydrogenase-complex activity. When this complex was treated with N-ethylmaleimide in the presence of pyruvate and the absence of CoASH, the rate of modification of the remaining S-acetyldihydrolipoic acid residues was approximately equal to the accompanying rate of loss of enzymic activity. This is in contrast with the native pyruvate dehydrogenase complex, where under the same conditions modification proceeds appreciably faster than the loss of enzymic activity. The native pyruvate dehydrogenase complex was also treated with lipoamidase prepared from Streptococcus faecalis. The release of lipoic acid from the complex followed zero-order kinetics for most of the reaction, whereas the accompanying loss of pyruvate dehydrogenase-complex activity lagged substantially behind. These results eliminate a model for the enzyme mechanism in which specifically one of the two lipoic acid residues on each dihydrolipoamide acetyltransferase chain is essential for the reaction. They are consistent with a model in which the dihydrolipoamide acetyltransferase component contains more lipoic acid residues than are required to serve the pyruvate decarboxylase subunits under conditions of saturating substrates, enabling the function of an excised or inactivated lipoic acid residue to be taken over by another one. Unusual structural properties of the enzyme complex might permit this novel feature of the enzyme mechanism.

Amidohydrolases↗
PubMed1981

Self-instruction in a perceptual motor skill.

A self-instructional strategy using an audio-visual medium for learning the rehabilitation skill of a three-point crutch gait was developed and demonstrated to be effective with normal women of various activity levels naive to task demands. Briefly discussed are theoretical considerations based upon Fitt's three stages of acquiring a perceptual-motor skill and Fleishman and Hempel's experimental demonstrations that abilities required in learning change as learning progresses. In a modified posttest-only control group experiment with 20 women, ages 36 to 60, the hypothesis that subjects could learn the cognitive aspects of a motor skill in one viewing of a 6 1/2-minute film was supported. That some transfer of learning occurred to the performance of the skill was substantiated in a second experimental-control study with 20 women, ages 35 to 54. Six criteria were used to judge filmed motor performance of the subjects. Differences in performance between the two groups appeared to be in the quality of movement and the speed with which a subject moved from one stage of learning to the next. The limitations of the two studies and applications of the findings also were discussed.

Achievement↗
PubMed1981

Evaluation of group versus individual nutrition education in overweight patients with myocardial infarction.

Thirty-nine obese patients (weighing in excess of 110% of ideal weight) were studied for 52 weeks following admission to the Coronary Care Unit with a diagnosis of acute myocardial infarction. The aim of the study was to compare, chiefly by anthropometric measurements, the response to a structured nutrition education program provided by a dietitian using three different levels of time involvement with the patients, firstly individual patient education, secondly group education and thirdly the issuing of written material only. Although there was no significant difference in the mean weight loss between the three education groups (8.1, 7.5 and 8.9 kg respectively) there was a trend towards more uniform weight reduction in those who received individual education. All but two of the 28 who attended at 52 weeks achieved weight loss. Thirteen patients attained 110% or less of their ideal weight, a 46% success rate. Reduction in body weight and most of the other anthropometric measurements occurred in the first twelve weeks of study, with no further significant weight change to 52 weeks. While these observations suggest that the overweight patient with acute myocardial infarction need not be subject to intensive nutrition education at the time of presentation, a more aggressive follow-up programme in subsequent months is recommended.

Body Weight↗
PubMed1980

Kinetic analysis of the role of lipoic acid residues in the pyruvate dehydrogenase multienzyme complex of Escherichia coli.

The catalytic roles of the two reductively acetylatable lipoic acid residues on each lipoate acetyltransferase chain of the pyruvate dehydrogenase complex of Escherichia coli were investigated. Both lipoyl groups are reductively acetylated from pyruvate at the same apparent rate and both can transfer their acetyl groups to CoASH, part-reactions of the overall complex reaction. The complex was treated with N-ethylmaleimide in the presence of pyruvate and the absence of CoASH, conditions that lead to the modification and inactivation of the S-acetyldihydrolipoic acid residues. Modification was found to proceed appreciably faster than the accompanying loss of enzymic activity. The kinetics of the modification were fitted best by supposing that the two lipoyl groups react with the maleimide at different rates, one being modified at approximately 3.5 times the rate of the other. The loss of complex activity took place at a rate approximately equal to that calculated for the modification of the more slowly reacting lipoic acid residue. The simplest interpretation of this result is that only this residue is essential in the overall catalytic mechanism, but an alternative explanation in which one lipoic acid residue can take over the function of another was not ruled out. The kinetics of inactivation could not be reconciled with an obligatory serial interaction between the two lipoic acid residues. Similar experiments with the fluorescent N-[p-(benzimidazol-2-yl)phenyl]maleimide supported these conclusions, although the modification was found to be less specific than with N-ethylmaleimide. The more rapidly modified lipoic acid residue may be involved in the system of intramolecular transacetylation reactions that couple active sites in the lipoate acetyltransferase component.

Escherichia coli↗
PubMed1979

Polypeptide-chain stoicheiometry and lipoic acid content of the pyruvate dehydrogenase complex of Escherichia coli.

The pyruvate dehydrogenase multienzyme complex was isolated from Escherichia coli grown in the presence of [35S]sulphate. The three component enzymes were separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and the molar ratios of the three polypeptide chains were determined by measurement of the radioactivity in each band. The chain ratio of lipoamide dehydrogenase to lipoate acetyltransferase approached unity, but there was a molar excess of chains of the pyruvate decarboxylase component. The 35S-labelled complex was also used in a new determination of the total lipoic acid content. It was found that each polypeptide chain of the lipoate acetyltransferase component appears to bear at least three lipoyl groups.

Chemical Phenomena↗