The relation between the developmental timing of birth and developmental increases in urea cycle enzymes.
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Biomedical subjects
Publications and source records attributed to R Charles.
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A 10-year-old boy with discrete subaortic stenosis had coexisting abnormal systolic anterior motion of the mitral valve, demonstrated by echocardiography, a sign normally taken as indicating the presence of idiopathic hypertrophic subaortic stenosis. Surgical removal of a fibromuscular diaphragm abolished the echocardiographic signs of discrete subaortic stenosis but abnormal systolic anterior motion of the mitral valve persisted. A severe low cardiac output state complicated immediate recovery after removal of the left ventricle outflow obstruction, and was overcome only with considerable difficulty. The presence of hypertrophied septal muscle, and the associated small left ventricular cavity size, was thought to be the immediate cause of these problems, so that recognition of marked septal hypertrophy, together with abnormal anterior systolic movement of the mitral valve, should serve as a warning that similar difficulties are likely to bae encountered by other patients, after removal of the obstruction in subaortic stenosis. In our experience other forms of left ventricle outflow tract obstruction have not been found to show such a marked degree of asymmetric septal hypertrophy, but this does not mean it may not occur.
A right ventricular endomyocardial biopsy specimen from a 30-year-old male with chromic progressive external ophthalmoplegia, retinal pigmentation and complete atrioventricular block (Kearns-Sayre syndrome) was examined in the electron microscope. There was a proliferation of mitochondria between the myofibrils and beneath the sarcolemma. Many of the mitochondria showed morphologic abnormalities not previously described in this condition. There were associated accumulations of glycogen. A similarly affected female with left anterior hemiblock developed complete atrioventricular block at age 26 years, Despite the ultrastructural changes, clinically detectable myocardial disease is not a feature of Kearns-Sayre syndrome. However, intraventricular conduction defects show an unusually rapid progression to potentially fatal complete atrioventricular block and are an indication for prophylactic cardiac pacing.
1. Rabbit antiserum was raised against purified carbamoyl-phosphate synthase (ammonia) from rat liver. 2. The antiserum proved to be specific in double-diffusion test and reacted in an in situ immunohistochemical test on rat liver proteins fractionated on a sodium dodecyl sulphate polyacrylamide gel only in the region where carbamoyl-phosphate synthase (ammonia) migrated. 3. This antiserum was used for setting up a radioimmunochemical determination of carbamoyl-phosphate synthase (ammonia) in cetyltrimethylammonium bromide extracts of rat liver. To obtain reproducible results in this assay it was necessary to treat the unlabelled ligand with sodium dodecyl sulphate and dithiothreitol. This treatment led to a large increase in the percentage of labelled ligand displaceable by added unlabelled ligand. 4. Radioimmunochemical determination showed that adult rat liver (3-month old) contains 5.5 mg carbamoyl-phosphate synthase (ammonia) protein per gram wet weight.
The echophonocardiographic features in three patients with a mitral Björk-Shiley prosthesis and paravalvular regurgitation are presented. The characteristic features are an early diastolic humping of the Björk-Shiley disc echo, associated with normal rather than paradoxical septal motion, and a reduced A2-MVO interval. The diagnosis was confirmed at operation in one patient, at cardiac catheterisation and operation in the second, and at necropsy in the third. These features were abolished by surgical correction of the leak in both operated cases.
Lysine-rich histones have been isolated from the terminally differentiated erythrocytes of Xenopus laevis. Three major proteins have been separated by ion-exchange chromatography. These proteins have been characterized by electrophoresis, amino acid analysis and immunochemical techniques. It is concluded that two 'typical' lysine-rich subfractions are present in Xenopus erythrocytes and, in addition, a serine-rich histone, that shares no common antigenic determinants with the other lysine-rich histones.
Myocardial infarction in the virtual absence of risk factors occurred in a 25-year old man shortly after smoking a cigarette containing marijuana. Subsequent coronary arteriography was normal.
1. In axolotl liver, the activity of carbamoyl-phosphate synthase (ammonia), expressed per mg liver protein, decreases to a minimum at 5 months of age, then increases to a maximum at 8 months of age which is followed by a decrease again. The initial decrease between 3 and 5 months of age appears to be largely due to an increase in non-carbamoyl-phosphate synthase protein and the following increase between 5 and 8 months of age to a relative increase of carbamoyl-phosphate synthase protein. 2. Treatment of the animals with triiodothyronine causes an increase in carbamoyl-phosphate synthase activity, the extent of which is dependent upon hormone concentration and age of the animal. After 8 months of age no increase of enzyme occurs upon thyroid hormone treatment, although metamorphosis occurs. 3. Glucocorticosteroid hormones stimulate carbamoyl-phosphate synthase activity 2-to 3-fold in animals older than 6 months. However, in animals younger than 6 months, low concentrations of thyroid hormone, insufficient to induce metamorphosis, are necessary as permissive agents. 4. The stimulatory effects of high concentrations of thyroid hormones (T3) on carbamoyl-phosphate synthase appear to be mediated via a stimulatory effect on glucocorticosteroid biosynthesis. 5. The natural rise in enzyme activity between 5 and 8 months of age seems to be due to a rise in the concentration of circulating glucocorticosteroid hormones.
A case of intraperitoneal migration of a pacemaker generator is described. Chronic diarrhoea and abdominal discomfort were relieved by its removal.
An automated, computerized system, the AutoMicrobic System, has been developed for the detection, enumeration, and identification of bacteria and yeasts in clinical specimens. The biological basis for the system resides in lyophilized, highly selective and specific media enclosed in wells of a disposable plastic cuvette; introduction of a suitable specimen rehydrates and inoculates the media in the wells. An automated optical system monitors, and the computer interprets, changes in the media, with enumeration and identification results automatically obtained in 13 h. Sixteen different selective media were developed and tested with a variety of seeded (simulated) and clinical specimens. The AutoMicrobic System has been extensively tested with urine specimens, using a urine test kit (Identi-Pak) that contains selective media for Escherichia coli, Proteus species, Pseudomonas aeruginosa, Klebsiella-Enterobacter species, Serratia species, Citrobacter freundii, group D enterococci, Staphylococcus aureus, and yeasts (Candida species and Torulopsis glabrata). The system has been tested with 3,370 seeded urine specimens and 1,486 clinical urines. Agreement with simultaneous conventional (manual) cultures, at levels of 70,000 colony-forming units per ml (or more), was 92% or better for seeded specimens; clinical specimens yielded results of 93% or better for all organisms except P. aeruginosa, where agreement was 86%. System expansion in progress includes antibiotic susceptibility testing and compatibility with most types of clinical specimens.
The status of nose bleeding as a symptom of high blood pressure has been studied in patients admitted because of epistaxis. Twenty-six patients with a factor predisposing to nasal bleeding had age- and sex-adjusted systolic and diastolic scores similar to those of the general population. One hundred and sixty-eight patients with no such factor formed a different population with significantly higher age- and sex-adjusted systolic and diastolic scores. It is concluded that epistaxis is a true symptom of hypertension.
A non-invasive haemodynamic study was carried out in 13 normal subjects to compare the pharmacodynamics of glyceryl trinitrate when formulated as a moulded tablet ('Nitrostat') rather than as a generic compressed tablet. The glyceryl trinitrate moulded tablet, with a much more rapid and predictable dissolution time, produced an earlier onset of systolic blood pressure fall (p less than 0.01) and a greater maximum percentage change in peripheral blood flow (p less than 0.02). No other significant differences in effect on pulse rate, blood pressure or peripheral blood flow were noted.
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Chromatography of fourteen protein amino acids has been studied on 2-4- m long packed columns containing chiral diamide phases. Twelve of the thirteen optically active compounds examined could be resolved, with R greater than or equal to 1 in many instances. Two of the phases, N-docosanoyl-L-valine tert.-butylamide and N-lauroyl-L-valine 2-methyl-2-hepatadecylamide, can be employed at temperatures as high as 190 degrees and 180 degrees, respectively, without losing their efficiency, even after prolonged use. The problem of peak overlap in the analysis of mixtures of different amino acids was examined and partially solved.
1. We have investigated the origin of proteolytic activity which causes degradation of histones in chromatin isolated from Xenopus liver and the rat liver at neutral pH. Polyacrylamide disc gel electrophoresis was used for detection of proteolytic products of histones. 2. No proteolytic degradation of histones occurs in chromatin isolated from Xenopus erythrocytes and rat liver according to our procedure even after prolonged incubation at pH 8.0 and pH 5.0. However with chromatin isolated from Xenopus liver a high level of histone degradation is observed under similar conditions. 3. Mixing isolated nuclei from Xenopus erythrocytes with a crude cytoplasmic fraction from Xenopus liver causes histone proteolysis in isolated chromatin at pH 8.0. In similar experiments with corresponding fractions from rat liver histone proteolysis can be introduced only after repeated freezing and thawing of the cytoplasmic fraction. 4. A purified lysosomal preparation from rat liver causes a similar type of histone degradation upon incubation with chromatin from Xenopus erythrocytes and rat liver. 5. The neutral proteolytic activity that can be introduced in isolated chromatin by a crude cytoplasmic fraction and by a purified lysosomal erythrocytes and rat liver. 5. The neutral proteolytic activity that can be introduced in isolated chromatin by a crude cytoplasmic fraction and by a purified lysosomal fraction from rat liver is inhibited by sodium bisulphite. 6. We conclude that the neutral proteolytic activity which causes degradation of histones in isolated chromatin is due to a contamination with neutral protease(s) originating from cytoplasmic organelles.
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