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Biomedical subjects

M Perl

Publications and source records attributed to M Perl.

At least 37 records · Page 2Linked to original sources

Findings in psychiatric consultations with patients with acquired immune deficiency syndrome.

Thirteen of 40 patients with acquired immune deficiency syndrome (AIDS) admitted to the wards of a large city hospital were seen by the staff of a psychiatric consultation service. Eleven were gay men and two were bisexual men. "Depression" was the stated reason for referral of 10 patients; of these, two met DSM-III criteria for major depression, one had dysthymic disorder, and seven had adjustment disorder with depressed mood. Recurrent psychological themes of the 13 patients were: dealing with a life-threatening illness, uncertainty about the implications of an AIDS diagnosis, social isolation, and guilt over their previous life style. The role of the primary physician and of the mental health professional in the psychological care of AIDS patients is discussed.

Acquired Immunodeficiency Syndrome↗

Missed physical diagnosis: conceptual and moral comments on the psychiatrist-patient relationship.

Diagnosis is an important element in the therapeutic alliance. It informs treatment and management decisions in the interests of the patient. The relative and discretionary factors in diagnosis are prominent in psychiatry. The problematic nature of psychiatric diagnoses and the difficulty in demarcating physical from psychic disorders suggests an approach to patients with psychiatric symptoms that is alert to possible somatic causes. The well-being of the patient is primary in the therapeutic exchange. Thus, the moral principle to "do no harm" prevails. The potential costs to patients from missed physical diagnosis counsels an open attitude by psychiatrists in the diagnostic process. There are moral, scientific, and professional reasons to support this approach. Ultimately, the good of the patient and the good of the profession require it.

Diagnosis↗

Flavokinase and FAD synthetase from Bacillus subtilis specific for reduced flavins.

A flavokinase preparation from Bacillus subtilis is described which catalyzes the phosphorylation of reduced, but not oxidized, riboflavin. The enzyme is distinguished from other known flavokinases also in having an unusually low Km for the flavin substrate, 50 to 100 nM. ATP is the obligatory phosphate donor; one ATP is utilized for each FMNH2 formed. Mg2+ or Zn2+ is required for the reaction; Co2+ and Mn2+ will substitute, but less effectively. The same enzyme preparation catalyzes the synthesis of FADH2 from FMNH2 and ATP, but not the synthesis of FAD from FMN and ATP. FADH2 is also formed from reduced riboflavin, presumably by sequential flavokinase and FAD synthetase action. Zn2+ cannot replace Mg2+ in FADH2 formation. The reverse reaction, formation of FMN from FAD, occurs only with reduced FAD, giving rise to FMNH2, and is dependent on the presence of inorganic pyrophosphate. The enzyme thus appears to be an FADH2 pyrophosphorylase. The two enzymatic activities, flavokinase and FADH2 pyrophosphorylase, although not separated during the purification procedure, are distinguished by differences in metal ion specificity, in concentration dependence for ATP (apparent Km for ATP = 300 microM for FADH2 synthesis and 6.5 microM for flavokinase), and in the inhibitory effects of riboflavin analogues.

Adenosine Triphosphate↗

Transport and binding of riboflavin by Bacillus subtilis.

Riboflavine uptake and membrane-associated riboflavin-binding activity has been investigated in Bacillus subtilis. Riboflavin uptake proceeds via a system whose general properties are indicative of a carrier-mediated process: it is inhibited by substrate analogues, exhibits saturation kinetics, and is temperature-dependent. The organism concentrates riboflavin primarily as the phosphorylated cofactors FMN and FAD. Energy is required for uptake but whether the energy demand is required for both uptake and phosphorylation or only for the phosphorylation step is not known. Membrane-associated binding activity for riboflavin has also been demonstrated in membrane vesicles prepared from B. subtilis, and the binding component can be "solubilized" with Triton X-100. Evidence supporting the function of the binding component in riboflavin uptake by the intact cells includes the following. (i) Riboflavin analogues inhibit binding and uptake to nearly the same extent and with similar specificity of action. (ii) The KD for riboflavin-binding and the Km for uptake are in the same range. Similarly the Ki determined for the inhibitory analogue 5-deazariboflavin in the uptake assay and the KD for its interaction with the riboflavin-binding component of membrane vesicles are in the same range. (iii) Uptake in cells and binding in vesicles vary in the same direction with differences in growth conditions.

Bacillus subtilis↗

Lithium therapy and toxicity.

Lithium is a potent agent for the control of psychiatric disease. It is safe and effective when properly administered; however, its use requires a maximally informed physician and careful clinical monitoring of patients. The drug's side effects are usually dose related, and certain patients are at greater risk of experiencing toxicity than others. Management of acute intoxication involves gastric lavage, sodium replacement and the administration of other agents or dialysis to facilitate clearance.

Bipolar Disorder↗

Transport of riboflavin into yeast cells.

Riboflavin-requiring mutants of Saccharomyces cerevisiae are able to transport 14C-labeled riboflavin into the cell, although no significant transport is seen in commercial yeast or in the parent strain from which the mutants were derived. Transport activity is greatest in the early to mid-log phase of anaerobic growth and declines sharply in the late log phase. In aerobically grown cells activity is substantially lower at all stages of growth. In the assay devised for its measurement, transport activity shows a sharp pH optimum at pH 7.5, a strong temperature dependence (EA = 23,100 cal/mol), and saturation kinetics with respect to riboflavin (Km = 15 muM), characteristics consistent with a carrier-mediated mechanism. Monovalent inorganic cations, particularly K+ and Rb+, stimulate riboflavin uptake, while certain organic cations are inhibitory. Besides riboflavin only 7-methylriboflavin, 8-methylriboflavin, and 5-deazaflavin have been found to serve as substrates, while lumiflavin, tetraacetylriboflavin, and N10-[4'-carboxybutyl]-7,8-dimethylisoalloxazine do not, although a number of flavin analogs in which the ribityl side chain is modified are good competitive inhibitors of riboflavin uptake. Compounds resembling the ribityl side chain, such as sugars and sugar alcohols, do not inhibit. An apparent inhibition of uptake by D-glucose, D-mannose, and D-fructose, which develops in the course of assay, proved to result from stimulation of an opposing process, the release of riboflavin from the cells.

Anaerobiosis↗

A possible ribosomal-directed regulatory system in Euglena gracilis. Chlorophyll synthesis.

Cycloheximide at concentrations of 0.1-100mum stimulated chlorophyll synthesis when dark-grown cells of Euglena were illuminated. Chloramphenicol (1-4mm) inhibited chlorophyll synthesis. The effect of cycloheximide on the incorporation of [(14)C]leucine into material insoluble in trichloroacetic acid, and its failure to affect the incorporation of [(32)P]orthophosphate into such material in short incubations, are interpreted as evidence that cycloheximide specifically inhibits protein synthesis by 80S ribosomes. Since the inhibitory effect of chloramphenicol on chlorophyll synthesis is counteracted by the presence of cycloheximide, it is suggested that chlorophyll synthesis is subject to control by a cytoplasmic repressor synthesized on 80S ribosomes, and to a de-repressor synthesized on 70S ribosomes.

Carbon Isotopes↗

A possible ribosomal-directed regulatory system in Euglena gracilis. Carbon dioxide fixation.

It was shown that cycloheximide inhibits CO(2) fixation in Euglena cells in the dark, but no effect of chloramphenicol was found. The light-dependent CO(2) fixation was inhibited by chloramphenicol and by large amounts of cycloheximide, but was stimulated by small amounts of cycloheximide. The presence of the stimulatory concentration of cycloheximide abolished the inhibition effect of high concentrations of chloramphenicol. The results indicate that the light-dependent CO(2) fixation is controlled by a repression-derepression regulatory system, which seems to be independent of chlorophyll synthesis.

Carbon Dioxide↗

Appearance of a methylated ribonucleic acid on illumination of Euglena gracillis cells grown in the dark.

Investigation of the methylation of nucleic acids by [Me-(3)H]methionine after illumination of Euglena cells grown in the dark has shown that a high-molecular-weight nucleic acid fraction undergoes methylation after exposure to light for 60-120min. This methylated nucleic acid fraction was isolated both by sucrose-density-gradient centrifugation and exclusion chromatography on Sephadex G-200. The fraction was shown to consist of a preformed RNA that is present in cells grown in the dark and which on illumination is transmethylated by methionine.

Centrifugation, Density Gradient↗