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Biomedical subjects

J Roberts

Publications and source records attributed to J Roberts.

At least 577 records · Page 32Linked to original sources

Child abuse and attempted suicide.

Of a sample of families containing abused and at risk children, in 29 per cent one or both parents had attempted suicide. The rate at which the suicide attempts were repeated within a year was higher than that expected for other attempters of the same age group. A previous history of psychiatric disturbance and marital breakdown was strongly associated with the combination of child abuse and suicidal behaviour. The relationship between child abuse and attempted suicide did not appear in most cases to have been a direct one; often both forms of behaviour seemed to reflect marital difficulties.

Adolescent↗

Circulation versus photocopy: Quid pro Quo?

Information thought necessary for assessing the potential impact of a limited journal circulation policy at the University of California, San Francisco, included the effects on seating, on in-house photocopying, and on circulation. An initial survey during a "typical circulation" week showed journal circulation to be 71% of the total, with journals issued during the past five years comprising 45% of the total. A survey of user photocopying practice suggested that circulation limited to journals more than five years old might result in a 90% increase in photocopying, and results of the circulation survey were used to predict a 45% decrease in circulation. Results of implementing a limited circulation policy were a 41% decrease in circulation and a 136% increase in photocopy. Differences between prediction and results may be accounted for by the effect of duplicate copy subscriptions and by provision of convenient photocopy facilities.

Copying Processes↗

Phase I evaluation of succinylated Acinetobacter glutaminase-asparaginase in adults.

Succinylated Acinetobacter glutaminase-asparaginase (SAGA) has broader antitumor activity than Escherichia coli L-asparaginase in experimental systems; moreover, drug resistance does not develop in tumor cell lines initially sensitive to this enzyme. We have investigated the pharmacology and toxicology of SAGA after both single-dose and serial daily dose injections in 20 adult patients. Glutaminase activity in plasma after i.v. injection of single doses did not follow simple first-order kinetics (half-life during the initial 24 hr was 21 +/- 9 hr. A linear relation was observed between increasing doses of SAGA and resultant levels of plasma enzyme activity and blood glutamate. Assay of whole blood which had been deproteinized immediately following phlebotomy showed that single doses of SAGA lowered glutamine only transiently to nondetectable levels; serial daily doses were required to achieve and maintain continuous glutamine depletion. Reversible depression of the central nervous system, ranging from encephalopathy to coma, occurred in a dose-related manner and was dose limiting. Other prominent reactions included respiratory alkalosis, hyperglycemia, nausea, and vomiting. Transient antitumor effects were noted in two patients with solid tumors and in two patients with leukemia. SAGA causes considerable neurotoxicity in adults which requires close patient monitoring. Phase II studies in leukemic patients are in progress.

Acinetobacter↗

Stereochemistry and mechanism of reactions catalyzed by indolyl-3-alkane alpha-hydroxylase.

The reaction of tryptamine with indolyl-3-alkane alpha-hydroxylase is shown to remove stereospecifically the pro-S hydrogen at C-2 of the side chain and to give hydroxytryptamine of "R" configuration. The reaction therefore proceeds stereospecifically with net inversion of configuration at C-2 of the tryptamine side chain. In the reaction of L-tryptophan methyl ester, the enzyme also catalyzes stereospecific removal of the pro-S hydrogen at C-3, but the product 3-hydroxytryptophan methyl ester is racemic at C-3. The unreacted tryptophan methyl ester is shown to incorporate solvent hydrogen into the pro-S position at C-3 in an at least partially stereospecific manner, suggesting that the reaction of L-tryptophan methyl ester is reversible. The hydrogens at C-1 of the tryptamine side chain and the alpha-hydrogen of L-tryptophan methyl ester are shown to be retained in the reactions. The results support the notion that the enzyme catalyzes stereospecific 1,4-dehydrogenation of 3-substituted indoles to the coresponding alkylidene indolenines as the primary reaction, followed by stereospecific or nonstereospecific hydration of these intermediates as a secondary process. Substrate specificity studies with a number of tryptophan analogs are in excellent agreement with such a mechanism.

Carbon Radioisotopes↗

Comparison of the arrhythmogenic effect of myocardial infarction in the cat and dog.

Myocardial infarction was produced in dogs and cats by occlusion of the left anterior descending coronary artery. Arrhythmia was present in dogs but not in cats 6 to 48 h after occlusion. The absence of arrhythmia in cats was not due to persistent myocardial depressant effects of anaesthesia administered during surgery. Studies in cats with surgically-induced heart block revealed multiple ventricular pacemakers but no change in average ventricular rate following coronary occlusion. These results suggest that sinus overdrive, although not elevated compared with the dog, is sufficient to suppress arrhythmia in the cat. Further, since small dogs developed significantly less arrhythmia than large dogs, heart size may be an additional factor in explaining the absence of arrhythmia in the cat.

Animals↗

Induction of hypothermia in mice by semi-artificial cells containing indolyl-3-alkane alpha-hydroxylase.

The administration of red cell ghost encapsulated indolyl-3-alkane alpha-hydroxylase (an enzyme which destroys tryptophan by oxidation of the side chains) in CD-1 female mice causes effective tryptophan depletion in plasma and brain and induces hypothermia by probably decreasing the serotonin concentration in brain by decreasing the concentration of its precursor, L-tryptophan.

Alkanes↗

Molecular engineering of the L-tryptophan-depleting enzyme indolyl-3-alkane alpha-hydroxylase.

Polymaleic acid and polyacrylic acid polymers have been covalently linked to indolyl-3-alkane alpha-hydroxylase with a shift of the pH optimum from 3.5 to between 5.0 and 5.5. In addition, the specific activity of the modified enzyme was increased approximately threefold at pH 7.0. The Km values of the polymer-bound enzyme preparations are essentially the same as that of the native enzyme. The plasma half-life was shortened from 6-7 hours with the native enzyme to 2-4 hours with the modified enzymes. The degree of L-tryptophan depletion in the circulation of mice, however, was the same during a 24-hour period after injection of native or modified enzymes.

Animals↗