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Biomedical subjects

M Bates

Publications and source records attributed to M Bates.

At least 55 records · Page 3Linked to original sources

Ornithine transcarbamylase from Neurospora crassa: purification and properties.

Ornithine transcarbamylase catalyzes the synthesis of citrulline from carbamyl phosphate and ornithine. This enzyme is involved in the biosynthesis of arginine in many organisms and participates in the urea cycle of mammals. The biosynthetic ornithine transcarbamylase has been purified from the filamentous fungus, Neurospora crassa. It was found to be a homotrimer with an apparent subunit molecular weight of 37,000 and a native molecular weight of about 110,000. Its catalytic activity has a pH optimum of 9.5 and Km's of about 5 and 2.5 mM for the substrates, ornithine and carbamyl phosphate, respectively, at pH 9.5. The Km's and pH optimum are much higher than those of previously characterized enzymes from bacteria, other fungi, and mammals. These unusual kinetic properties may be of significance with regard to the regulation of ornithine transcarbamylase in this organism, especially in the avoidance of a futile ornithine cycle. Polyclonal antibodies were raised against the purified enzyme. These antibodies and antibody raised against purified rat liver ornithine transcarbamylase were used to examine the structural similarities of the enzyme from a number of organisms. Cross-reactivity was observed only for mitochondrial ornithine transcarbamylases of related organisms.

Amino Acids↗

Molecular mechanism of gonadotropin releasing hormone action.

This work summarizes some of our studies related to the mechanism of action of gonadotropin releasing hormone including those leading to identification of the three steps of the gonadotropin releasing process: receptor binding, mobilization of extracellular calcium, and granule exocytosis. Evidence is also presented to suggest how these steps are integrated one to another and how they are integrated to other actions of the releasing hormone such as regulation of target cell sensitivity, and receptor regulation.

Animals↗

Carcinoid tumours of the bronchus: a 33 year experience.

The term adenoma of the bronchus is discussed, and 79 cases of bronchial carcinoid seen from 1951 to 1983 are reviewed. The symptoms, radiological findings, and bronchoscopic appearances are described. There was no case of the carcinoid syndrome. In no case did haemorrhage cause any serious problem after biopsy at rigid bronchoscopy. In three patients the tumour was reported to be an oat cell carcinoma-in two on the basis of material obtained at fibreoptic bronchoscopy. Resection was by pneumonectomy in 10 cases, lobectomy in 52, segmentectomy in six, a bronchoplastic procedure without resection of lung in seven cases, enucleation in two, and a wedge resection in one case. There was one case of atypical carcinoid which was found at operation to be unresectable. A 5-30 year follow up in 57 cases revealed a recurrence of tumour in two cases, nine and 16 years after lung resection. No recurrence occurred in the nine cases treated by conservative bronchial resection with conservation of lung tissue. An actuarially assessed life table analysis shows survival rates of 94% after 10 years, 80% after 15 years, and 64% after 25 years without recurrence. The similarity of carcinoid to oat cell carcinoma is noted and the serious clinical implications of this are analysed, especially in view of the increasing use of fibreoptic bronchoscopy. The malignant potential of carcinoid and the extent of pulmonary resection is discussed. It is concluded that a carcinoid tumour of the lung has only slight malignant potential and that it may be treated by bronchotomy or sleeve resection of the bronchus in suitable cases. If serious infective changes have occurred in the lung distal to the tumour or if the tumour has extended into the lung parenchyma (88% of cases in this series) lung resection will be necessary. The follow up period should be for at least 25 years, in view of the incidence of late recurrence.

Adolescent↗

Iopamidol: new, nonionic contrast agent for excretory urography.

Iopamidol, a new, nonionic contrast agent, was evaluated in 18 patients undergoing excretory urography. None of the 18 patients experienced any side effects or adverse reactions. No abnormalities were noted in serum chemistries, complete blood cell counts, urinalyses, or electrocardiograms. The half-life of iopamidol in 17 patients with normal renal function was 2.5 hr. The urograms were judged to be of good or excellent quality in 15 of 16 patients using doses of 200 and 250 mg l/kg of iopamidol. Two patients who were studied using a dose of only 120 mg l/kg had urograms rated poor. Fifteen iopamidol urograms (mean iodine dose, 17.4 g) were compared in a blind fashion with 15 meglumine diatrizoate studies (iodine dose, 29 g). No qualitative difference could be detected between the two groups of urograms. Iopamidol may provide equal-quality diagnostic studies with a lower iodine dose and perhaps greater safety than the currently used ionic agents.

Adult↗

Menopausal estrogen use, high density lipoprotein cholesterol subfractions and liver function.

Forty-eight menopausal women taking exogenous estrogen were compared with 246 postmenopausal women not on estrogen. The estrogen users had significantly higher total high density lipoprotein (HDL) (76.0 vs 61.4 mg/dl) and HDL2 (36.7 vs 23.0 mg/dl) cholesterol than the controls. There was a similar concentration of HDL3 cholesterol for the two groups (39.2 for the estrogen users and 38.4 for the controls). A dose-response was evident between the amount of daily estrogen and HDL-total and HDL2 cholesterol. The significant differences between the two groups remained after adjusting for body composition, alcohol intake, cigarette smoking and physical activity. There was a significant difference between the two groups in liver function as measured by the liver enzymes, SGOT, SGPT, with liver enzyme concentrations lower in the estrogen users. The results indicate that the increase in the total HDL cholesterol as a result of menopausal estrogen is primarily the result of increased HDL2. The increase could not be explained by alterations in hepatic microsomal activity as measured by liver enzymes since estrogen users had lower concentrations of liver enzymes than non-estrogen users.

Alcohol Drinking↗

Plasma insulin and lipoprotein concentrations: an atherogenic association?

Plasma insulin concentrations have been shown to be predictive of future cardiovascular disease in men. Though many clinical studies have documented correlations between plasma insulin and triglyceride concentrations, few epidemiologic studies have reported insulin-lipid correlations. In this report, the authors present correlations obtained from 323 non-diabetic first degree relatives of insulin dependent diabetic patients who underwent 4 hour oral glucose tolerance tests at Children's Hospital, Pittsburgh, Pennsylvania, in February 1980-December 1981 as part of an epidemiologic study of insulin dependent diabetes mellitus. Significant positive correlations were seen between insulin (measured as fasting insulin and the 3 hour area under the insulin curve during the oral glucose tolerance test) and the atherogenic lipids, total and low density lipoprotein cholesterol and triglycerides ranging from r = +0.14 (p less than 0.01) to r = + 0.35 (p less than 0.001). An inverse correlation with high density lipoprotein cholesterol was also noted r = -0.27 (p less than 0.001). A computed score of insulin activity, which the authors call the insulin-glucose sensitivity index, shows equally strong correlations but of reverse sign. In multivariate analyses, these insulin measures and age largely account for the associations of sex and obesity (measured as body mass index) with the atherogenic lipids, though this was only partly true for high density lipoprotein cholesterol. The biologic plausibility of these findings and their relevance to the development of atherosclerosis are discussed.

Adolescent↗

Pulmonary angiography with iopamidol and Renografin 76 in normal and pulmonary hypertensive dogs.

The cardiovascular response produced during pulmonary angiography performed with the standard ionic agent diatrizoate (Renografin 76) and a new non-ionic agent iopamidol was compared. Nine dogs were evaluated while ventilated on room air and on 10% O2 which significantly elevated pulmonary arterial pressure. Iopamidol produced similar changes in mean aortic and pulmonary arterial pressures compared with normal saline (less than 20% change). Renografin 76, however, produced a significantly greater elevation in mean pulmonary arterial pressure (a 41% increase) and depression in mean aortic pressure (a 40% reduction) than either saline or iopamidol (p less than 0.01). These results were similar for dogs being ventilated with room air and oxygen. The results indicate that iopamidol should be better tolerated and therefore a safer contrast agent for pulmonary angiography than diatrizoate.

Animals↗

A double-blind clinical trial of iopamidol versus metrizamide for lumbosacral myelography.

A double-blind study was performed to compare metrizamide with the new iodinated water-soluble nonionic contrast medium, iopamidol, for conventional and computerized tomography lumbosacral myelography. Both contrast agents were used in 30 patients, and were equivalent in terms of image quality and clinical accuracy. Headaches and nausea were less severe using iopamidol. The most striking difference was found in adverse neurobehavioral reactions and associated electroencephalographic abnormalities, which were noted in 17% of the metrizamide group but were not seen with the use of iopamidol. Iopamidol appears to be superior to metrizamide for intrathecal applications. An explanation of the differential neurotoxicity is provided.

Clinical Trials as Topic↗

B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes.

The characterization of a new B cell-specific antigen (B4) is described in this report. With the use of a monoclonal antibody to B4, it was shown that B4 is present on B cells isolated from peripheral blood and lymphoid organs, on cell lines derived from normal and malignant B cells, and on tumor cells isolated from patients with B cell-derived neoplasms. B4, in contrast, was not detected on normal, activated, or malignant cells of T or myeloid origin. The B4 antigen is distinct from known B cell antigens, including sIg, Ia, B1, B2, Fc, and C3. Examination of mitogen-stimulated B lymphocytes suggests that the B4 antigen initially increases with B cell activation and then is lost at the terminal stage of B cell differentiation. Moreover, the observation that B4 is expressed on almost all early B cell tumors suggests that it may precede B1, CALLA, cytoplasmic mu, and B2 in early B cell ontogeny.

Animals↗

Iopamidol vs metrizamide: a double blind study for cervical myelography.

A double-blind study was performed on 20 patients comparing the safety and efficacy of Iopamidol and Metrizamide in cervical myelography. The radiographic qualities of the Iopamidol and Metrizamide examinations were equivalent when using the same volume (12 to 13 ml), concentration (200 mg I/ml), and a C1-2 route of administration. The performance of a CT scan on selected patients in specified areas of interest provided additional diagnostic information in some patients (e.g syringomyelia, degenerative spondylosis). The adverse reactions were mild in the Iopamidol group with 4 of the 10 patients experiencing no adverse reactions. The more severe reactions, including disorientation, agitation, dysarthria, asterixis, hyperreflexia and EEG abnormalities were limited to the Metrizamide group with one or more occurring in 2 of the 10 patients studied. Only one Metrizamide patient experienced no adverse reactions. In this study containing a limited number of patients, Iopamidol was shown to be a diagnostically effective and safer contrast medium for performing cervical myelography.

Chemical Phenomena↗

Alveolar soft-part sarcoma.

Alveolar soft-part sarcoma is a slow-growing but nevertheless malignant soft tissue tumour arising in muscle. It occurs most frequently in young women and often presents as a painless swelling in an upper or lower limb. The swelling, which may have been present for a considerable time, is firm and appears to be well circumscribed but it may recur locally after excision. Blood-borne metastases to the lung are common and this is frequently the mode of presentation. Lymphatic metastases are unusual. The tumour is composed of nests of large cells and the histological appearances may resemble those of a renal adenocarcinoma (hypernephroma). Six new cases of this very rare tumour are presented and the published reports are reviewed.

Adult↗

Study of safety and tolerance of iopamidol in peripheral arteriography.

Iopamidol, a non-ionic contrast agent, was evaluated during peripheral arteriography in 10 patients. All reported a sensation of warmth during injection. One described the procedure as moderately painful. All objectively tolerated the injections well, and there were no significant changes in clinical or laboratory findings. Vessel opacification was good to excellent in all cases. The authors suggest that non-ionic contrast agents replace ionic agents for peripheral arteriography.

Aged↗

The pharmacokinetics of levonorgestrel and ethynylestradiol in women - studies with Ovran and Ovranette.

A radioimmunoassay for levonorgestrel (Ng), which is applicable to plasma samples obtained from women who have taken a combination type oral contraceptive, has been developed and fully validated. Plasma concentrations of Ng rise to a peak of 3.6 ng/ml after an oral dose of 150 microgram and to 5.0 ng/ml after a 250 microgram dose. Following the intravenous administration of Ng, plasma concentrations of the steroid decline bi-exponentially with mean half-lives of 0.76 and 11.55 hours. Comparison of the results of the intravenous and oral administration of the steroid show a mean systemic bioavailability of 89% after the 150 microgram dose and 99% after a 250 microgram dose. This difference was not statistically significant. The values for volume of distribution were approximately half and the values for plasma clearance three times less than that previously reported for norethindrone. The plasma ethynylestradiol levels were also measured following administration of 30 microgram both intravenously and orally. The bioavailability and kinetics were similar to that previously reported for a 50 microgram dose. The peak values after oral dosing were 103 pg/ml and were reached by 1.0 hour in all subjects.

Adult↗

The in vitro metabolism of ethinyloestradiol, mestranol and levonorgestrel by human jejunal mucosa.

1 Ethinyloestradiol was extensively metabolised in vitro by human jejunal mucosa to form ethinyloestradiol sulphate. 2 The amount of conjugation was directly related to the weight of biopsy tissue. 3 The degree of conjugation of mestranol and levonorgestrel was much lower than for ethinyloestradiol suggesting that the 17-position of the steroid nucleus is relatively inaccessible for conjugation. 4 No Phase I metabolism of ethinyloestradiol or levonorgestrel was apparent in the conditions used in these experiments.

Adult↗

Surgical treatment of bronchial carcinoma.

The surgical treatment of 2430 patients suffering from bronchial carcinoma between 1950 and 1978 is analysed and emphasis placed on conservative surgery. The histological pattern is described, with marked prevalence of the squamous-cell carcinomas. The increased age in the general population means that many patients aged 70 years or over present for surgical treatment and respond well to lobectomy or segmental resection. The place of preoperative radiotherapy in the treatment of oat-cell carcinoma is considered and it is concluded that improved results are obtained by this combined treatment. The serious consequences of a postoperative bronchial fistula are noted and the lower incidence that may be obtained by bronchial stapling is mentioned. The significance of a positive mediastinal node is stressed in relation to a long-term result from surgery, and methods whereby these results could be improved in the future are discussed.

Adenocarcinoma↗

The relationship between alcohol consumption, liver enzymes and high-density lipoprotein cholesterol.

High-density lipoprotein (HDL) cholesterol concentrations are inversely related to risk of heart attack. Alcohol consumption is a primary factor related to increased HDL concentrations. We investigated HDL cholesterol before and after cessation of high alcohol consumption in alcoholics. Men admitted to an alcohol detoxification hospital had a mean HDL cholesterol level of 85 mg/dl, which is almost twice that found in the general population. After 4 days of treatment, HDL cholesterol levels decreased an average of 12.5 mg/dl. The decrease was directly correlated with the initial HDL cholesterol levels and inversely correlated with the change in triglyceride levels. Alcoholics who abstained for at least 1 month had HDL cholesterol concentrations similar to those of the general population. The increased HDL cholesterol levels in the alcoholics were highly correlated with liver enzyme concentrations, especially SGOT. The results suggest that alcohol increases HDL cholesterol concentrations through hepatic microsomal enzyme induction.

Adult↗