Purification of the primary dihydroorotate dehydrogenase (oxidase) from rat liver mitochondria.
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Biomedical subjects
Publications and source records attributed to J Kennedy.
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The effects of long-term hyperbaric exposure on endocrine organ weight and histology and on epiphyseal-plate width were studied in growing male rats. Six groups of rats were exposed to 21 ATA He-O2 (200 mmHg O2), and six groups were maintained at 1 ATA as room-air controls. Each group contained eight rats. At intervals of of 2, 3, 5, 8, 10, and 12 weeks, one group was decompressed and studied along with a paired control group. Results indicated no changes in pituitary and adrenal gland weights. Testis weights were variable but histology and sperm content were normal. Only the accessory sex organs decreased significantly in weight; however, prostate and seminal vesicle histology were normal. Tibial epiphyseal-plate width was reduced in 21-ATA groups. These results suggest that long-term hyperbaric exposure has little effect on endocrine organs of the rat and observed weight changes are probably related to the reduced body weights.
Dysuria, uric acid crystalluria and hyperuricosuria developed in a child with cystic fibrosis and normal serum uric acid. Hyperuricosuria in this patient and two other children was directly related to ingestion of large amounts of pancreatic extract. In these three children, reducing pancreatic extract dosage by 85 percent lowered their purine intake by 307, 225, and 148 mg, respectively; urinary uric acid excretion decreased by 245, 239, and 158 mg. Overmedication resulted from parents' decisions to increase enzyme dosages. In our cystic fibrosis clinic, 15 of 32 patients screened at random were taking higher than the prescribed dose of pancreatic enzymes, and 14 of these 15 children were hyperuricosuric. On the basis of this information, we suggest that the minimal effective dose of pancreatic extract should be determined and adhered to for each child with cystic fibrosis to avoid potential renal injury from hyperuricosuria.
During the period 1960 through 1969, 990 primary neoplasms of the central nervous system were diagnosed in hospitals in the Washington, DC, Standard Metropolitan Statistical Area (SMSA). All cases were identified according to age, race, sex, histologic type, and date of diagnosis. A West African composite of 253 cases was used for comparison. In the Washington SMSA, the age-adjusted incidence rates were: for Caucasians 5.5 in males and 3.6 in females and for Negroes 4.8 in males and 3.4 in females per 100,000 annual population. Caucasians in the Washington SMSA had a higher relative proportion of gliomas than Negroes in the same area and in Africa (p less than 0.005). The relative proportion of pituitary adenomas was higher in American Negroes (p less than 0.005) and in Africans than in Caucasians. The comparable pattern of CNS tumors in American and African Negroes, relative to Caucasians, suggests that in the development of neoplasms of the central nervous system racial factors may be of importance.
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The Rye histologic classification of Hodgkin's disease has been applied to 143 previously untreated cases of Hodgkin's disease in Negro patients seen in four hospitals in Washington, D.C.,during a 16-year period (1959-1974). The frequencies and age distributions of histologic subtypes were compared with those in American and two African series. Those histologic subtypes associated with poor prognoses (mixed-cellularity and lymphocytic depletion) predominated in American Negroes and in Negroes from Ibadan, Nigeria, and Kampala, Uganda. In an American series from Connecticut (approximately 98% Caucasian) the histologic subtypes lymphocytic predominance and nodular sclerosis were preponderant. There were statistically significantly less of the nodular sclerosis subtype (P less than 0.005), and more of the mixed-cellularity subtype in American Negroes compared with the Connecticut series (P less than 0.001). In contrast to findings in predominantly Caucasian populations, there was a predilection of the nodular sclerosis subtype for males in American and in African Negroes. This study showed that Hodgkin's disease in American Negroes epidemiologically corresponds to the so-called "intermediate pattern" of the disease.
A day school for aggressive adolescents, organized cooperatively by a school system, a youth guidance center, and a state hospital, is providing an effective alternative to institutionalization. Education and therapy are combined in a supportive setting.
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Production of superoxide radical during oxidation of dihydroorotate in rat liver mitochondria was not affected by antimycin A, thenoyltrifluoroacetone, or added ubiquinone but was inhibited by orotate, a product inhibitor of dihydroorotate dehydrogenase. It appears likely that superoxide is generated at the primary dehydrogenase. Dihydroorotate dehydrogenase differs from succinate dehydrogenase both in its utilization of ubiquinone and in the mechanism of cytochrome b reduction. Thenoyltrifluoroacetone completely inhibits fumarate synthesis and reduction of cytochrome b by succinate. Formation of orotate is only partially inhibited by thenolytrifluoroacetone and the inhibitor does not prevent reduction of cytochrome b by dihydroorotate. It is proposed that several pathways exist for linkage of the primary dihydrorotate dehydrogenase with the electron transport chain. One route involves electron transfer from ubiquinone to cytochrome c and is inhibited by thenoyltrifluoroacetone. A second route bypasses ubiquinone and is inhibited by antimycin A. A third pathway utilizes both ubiquinone and cytochrome b and is partiayly inhibited by either thenoyltrifluoroacetone or antimycin A.
An unusual neuropsychiatric disorder inherited in autosomal dominant fashion occurred in three successive generations of a family. Symptoms commenced late in the fifth decade in six affected patients and led to death in four to six years. The earliest and most prominent symptom was mental depression not responsive to antidepressant drugs or electroconvulsive therapy. This was accompanied by exhaustion, sleep disturbances, and marked weight loss. Later in the disease, symptoms of parkinsonism appeared, and respiratory failure occured terminally. The most recently affected family member was investigated biochemically late in his illness. Concentrations of taurine were greatly diminished in plasma and cerebrospinal fluid, and at autopsy, all regions of brain examined had a markedly reduced taurine content. Since taurine is a putative inhibitory synaptic transmitter, deficiency of brain taurine may possibly have caused the psychiatric and neurological manifestations of this disorder.
Free amino compounds were measured in 16 rapidly frozen epileptogenic foci excised from temporal or frontal cortex of nine patients with focal epilepsy, and in single cortical biopsy specimens obtained from 16 nonepileptic patients. Unlike the findings of a previous study, glutamic and aspartic acids were not diminished in the foci, nor was there a decrease in gamma-aminobutyric acid (GABA) or taurine levels. Glycine content was markedly elevated in two of 16 epileptogenic foci. These results do not suggest that deficiencies of GABA or of taurine, amino acids that may act physiologically as inhibitory neurotransmitters or modulators of inhibition, are causes of focal epilepsy, nor do they provide a logical basis for clinical trials of taurine in treatment of human epilepsy.
The design, construction and performance of a gamma ray densitometer are described. The instrument, which is used in the investigation of regional pulmonary function, has both digital and analogue outputs.
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