Seizures during clozapine therapy.
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Biomedical subjects
Publications and source records attributed to R R Conley.
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The sudden improvement in long-term schizophrenic patients after treatment with clozapine is frequently disconcerting to their families. In many cases the patients appear to have increased hostility toward their families because of the alleviation of negative symptoms such as apathy and blunted affect. The authors believe that psychoeducational intervention can help families adjust to the change in their family members and describe such intervention with three families. They emphasize the importance of recognizing that a patient's improvement can be a stressor in the family relationship and the need for devising appropriate interventions.
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The phosphorylation state of thioredoxin was compared in intact cells and in crude extracts. In crude extracts, the extent of phosphorylation was 0.70 to 0.80 mol of phosphate per mol of thioredoxin, with approximately equal amounts of thioredoxin phosphorylated either on cysteinyl32 (formula: see text) or on cysteinyl35 (formula: see text). By comparison, the extent of thioredoxin phosphorylation in intact cells was nearly 1.0 with phosphate present almost exclusively on cysteine32. Nonphosphorylated thioredoxin was present as the reduced thiol form (formula: see text). These findings imply that (formula: see text) is the relevant in vivo species and that a mechanism is operative in crude extracts for transfer of phosphate from cysteine32 to cysteine35.
Thioredoxin was isolated as a phosphoprotein from actively growing cultures of Escherichia coli. Labeling was performed in vivo by growing cells in the presence of 32P-labeled inorganic phosphate, and phosphothioredoxin was purified in one step by immunoabsorption to a thioredoxin antibody column. The stoichiometry of phosphate bound was 0.7 to 0.8 mol of phosphate/mol of thioredoxin. The phospho-amino acid linkage was identified as a thiol phosphate by several criteria: (a) the maximum lability of the phosphate bond was between pH 2.5 and 3.5 (t1/2 (37 degrees) = 200 h (pH 7 to 8); 0.4 h (pH 3.0); 200 h (pH 1.0)); (b) the phosphate linkage was very labile in the presence of iodine at neutral pH (t1/2 less than 1 min); and the phosphopeptide was identified as Cys32-Gly-Pro-Cys35-Lys, the same sequence previously implicated as the active site for disulfide-linked oxidation-reduction reactions. Phosphate was distributed on either cysteine, with 60% of the phosphate bound to cysteine32. Results are discussed in terms of the possible role of phosphothioredoxin as an intermediate in phosphotransferase reactions.
A scheme is described for the large scale purification of thioredoxin, thioredoxin reductase, and glutathione reductase. The scheme is based on an initial separation of thioredoxin from the two reductases by affinity chromatography on agarose-bound N6-(6-aminohexyl)-adenosine 2',5'-bisphosphate (agarose-2',5'-ADP). The two reductases were then separated by hydrophobic chromatography and purified separately to homogeneity. Thioredoxin was purified to homogeneity by immunoadsorption to agarose containing immobilized goat anti-thioredoxin. Overall yields for thioredoxin, thioredoxin reductase, and glutathione reductase exceeded 80% in each case. Both reductases exhibit an absorption band at approximately 320 nm which appears due to a residual amount of tightly bound NADP. Presence of this absorption band has no apparent effect on the specific activity of either enzyme.
OBJECTIVE: Reliability of assessment is important in any kind of neuropsychiatric study, but is particularly pivotal in schizophrenia research where symptom instability is common. MATERIALS AND METHODS: Two fluorodeoxyglucose PET scans, 1 week apart, were carried out in schizophrenic patients while they were performing a simple visual discrimination task. Subject and scan conditions were held constant. Regional metabolic rates of glucose utilization were calculated as absolute and scaled; they were compared using correlational statistics. RESULTS: Average differences between scans were 5-9% for the parietal and occipital cortices, but 1-3% for other cortical areas, differences comparable with reported variances in normal controls. CONCLUSION: These results suggest that test-retest variance in metabolic imaging in schizophrenia is relatively low and that task performance increases metabolic stability in brain areas unrelated to task performance.