Search PubMed⌕ Search

Biomedical subjects

M Lewis

Publications and source records attributed to M Lewis.

At least 487 records · Page 27Linked to original sources
PubMed1981

Zinc environment and cis peptide bonds in carboxypeptidase A at 1.75-A resolution.

The structure of the metalloenzyme carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) has been refined at 1.75 A by a restrained least-squares procedure to a conventional crystallographic R factor of 0.162. Significant results of the refined structure relative to the catalytic mechanism are described. In the native enzyme, the zinc coordination number is five (two imidazole N delta 1 nitrogens, the two carboxylate oxygens of glutamate-72, and a water molecule). In the complex (at 2.0-A resolution) of carboxypeptidase A with the dipeptide glycyl-L-tyrosine, however, the water ligand is replaced by both the carbonyl oxygen and the amino nitrogen of the dipeptide. The amino nitrogen also statistically occupies a second position near glutamate-270. Consequently, the coordination number of zinc may vary from five to six in carboxypeptidase A-substrate complexes. Implications of these results for the catalytic mechanism of carboxypeptidase A are discussed. In addition, three cis peptide bonds, none of which involves proline as the amino nitrogen donor, have been located fairly near the active site.

Animals↗
PubMed1981

Altered dopaminergic regulation of thyrotrophin release in patients with prolactinomas: comparison with other tests of hypothalamic-pituitary function.

This study was carried out to test the hypothesis that sustained hyperprolactinaemia in patients with prolactinomas stimulates hypothalamic dopaminergic activity via a short loop positive feedback effect of prolactin (PRL). The intensity of dopamine (DA) effects on the pituitary around the adenoma was evaluated by measuring thyroid stimulating hormone (TSH) responses to intravenous injection of domperidone (10 mg) a new DA receptor blocking drug that does not penetrate the blood-brain barrier. TSH responses have been compared with those of PRL to the same agent. Eight females with prolactinomas showed greater TSH release after domperidone than nine normal females (sum of TSH increments over 20 min 17.5 +/- 1.7 v. 8.9 +/- 1.5 mu/l, P less than 0.001) whilst PRL release was reduced (sum of PRL increments over 120 min 5.9 +/- 2.4 v. 21.8 +/- 3.8 mu/l x 10(-3), P less than 0.01). Amongst nineteen hyperprolactinaemic females with apparently normal pituitary fossae (plain skull X-ray), ten showed an exaggerated TSH response (delta TSH, 4.2 +/- 0.6 mu/l, range 2.5-9.0 mu/1) and reduced PRL response to domperidone, comparable with established tumor cases. In the remaining nine normal fossa hyperprolactinaemic females, the TSH and PRL responses to dopaminergic were similar to normal females. These results support the initial hypothesis and indicate the coexistence of a defect in the dopaminergic inhibition of PRL release and increased dopaminergic inhibition of TSH release in patients with prolactinomas. The presence of an exaggerated TSH response to DA antagonism in a euthyroid, radiologically normal (plain skull X-ray), hyperprolactinaemic patient is compatible with the presence of an autonomously-functioning, PRL secreting, pituitary microadenoma and the TSH changes seen in these patients after DA antagonist administration can be readily detected by sensitive TSH radioimmunoassay.

Adenoma↗
PubMed1981

Allosuppressor T lymphocytes abolish migration inhibition factor production in autoimmune thyroid disease: evidence from radiosensitivity experiments.

The ability of normal T lymphocytes to abolish the production of migration inhibition factor by antigen-sensitized T lymphocytes of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in response to thyroid antigen has been studied by a modified migration inhibition factor test using isolated T lymphocytes alone. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with GD or HT T lymphocytes in various ratios (1:9, 2:8, 5:5) as reported previously (Okita et al. 1980b). However, prior in-vitro irradiation (1000 rad) of the normal T lymphocytes resulted in loss of their ability to abolish migration inhibition factor production by the antigen-sensitized T lymphocytes of GD and HT. The effect is consistent with the radiosensitivity of suppressor T lymphocytes and indicates that the effect of normal T lymphocytes on GD and HT T lymphocytes is one of allosuppression. The results support the view that there is a defect in suppressor T cell function in GD and HT.

Antigens↗
PubMed1981

Beta-adrenoreceptor blocking drugs and thyroid hormones in hyperthyroid subjects.

Serum thyroid hormone concentrations were measured before and during 10 days' treatment with atenolol (200 mg/day), acebutolol (400 mg/day), oxprenolol (160 mg/day) and propranolol (160 mg/day) in 24 hyperthyroid patients. During propranolol treatment serum triiodothyronine (T3) concentrations fell significantly (P less than 0.05) but there was no change in thyroid hormone concentrations in the other groups although all patients reported a symptomatic improvement.

Adrenergic beta-Antagonists↗
PubMed1981

Hepatic metabolism of glucagon in the dog: contribution of the liver to overall metabolic disposal of glucagon.

The hepatic extraction (HE) of glucagon (G) and insulin (I) was measured in 27 dogs, using peripheral infusion of the hormones following elimination of endogenous secretion by pancreatectomy (Px) or somatostatin (S) infusion. HE(G) was 22.5 +/- 1.7%, and HE(I) was 45.1 +/- 3%. HE(G) in seven Px dogs was 27.9 +/- 4.2%, not significantly different from the value of 20.6 +/- 1.6% in 20 S-infused dogs, with corresponding values for HE(I) being 44.9 +/- 6 and 46.0 +/- 3.6%, respectively, suggesting that S does not affect HE of either hormone. HE of endogenous G (22.1 +/- 2.8%) was similar to that of exogenously infused G (19.1 +/- 1.9). HE(G) was nonsaturable in the physiologic and pathophysiologic range of plasma G levels, but there was evidence of saturability in the pharmacologic range. Comparison of simultaneously measured parameters of I and G metabolism indicated independence of the metabolic processes of these two islet hormones, despite distinct similarities in their overall patterns of metabolic disposal. Metabolic clearance rates (MCR) for G and I were 12.6 +/- 0.8 and 19.5 +/- 1.0 ml . kg-1 . min-1, while simultaneously measured hepatic HE rates were 4.2 +/- 0.3 and 8.1 +/- 0.6 ml . kg-1 . min-1, respectively. MCR(G) was independent of arterial G levels. Half-life of infused G and I was 5.5 +/- 0.5 and 4.1 +/- 0.3 min, respectively. The liver accounted for 34.7 +/- 2.4% of the MCR(G) and 42.0 +/- 2.9% of MCR(I). The liver is thus an important site for G removal. However, HE(G) varies widely in different animals, and it is therefore not possible to predict portal vein G concentrations or G secretion rates from G levels in peripheral vessels.

Animals↗
PubMed1981

Depression in childhood: a biopsychosocial perspective.

Diagnostic criteria and instruments for assessment of depression in children are listed; genetic, biochemical, and psychological factors in the etiology of the disorders are briefly reviewed; and the status of psychopharmacological treatment is stated. The discussion presents a biopsychosocial model for an understanding of the cause and treatment of the condition.

Adult↗
PubMed1981

T-lymphocyte sensitization in Graves' and Hashimoto's diseases confirmed by an indirect migration inhibition factor test.

T-Lymphocyte sensitization in Graves' disease (GD) and Hashimoto's thyroiditis (HT) was studied by an indirect migration inhibition factor test using normal T-lymphocytes as second stage indicator cells. In the first stage, mononuclear cells or T-lymphocytes, fractionated by the standard Ficoll-Hypaque procedure from the blood of patients with untreated GD and HT, were cultured in Eagle's medium containing thyroid antigen, and their cell-free supernatants were saved. Normal T-lymphocytes as second stage indicator cells were packed in capillary tubes and placed in planchettes with the above supernatants to complete the indirect migration inhibition factor test. Inhibition of the migration of indicator T-lymphocytes was demonstrated when either GD or HT culture supernatants were employed. Moreover, there was a good correlation between the indirect using the culture supernatants and the direct migration inhibition factor test using mononuclear cells or T-lymphocytes. On the other hand, in both direct and indirect migration inhibition factor tests using mononuclear cells and mononuclear cell culture supernatants, respectively, in the presence of human liver antigen as a nonspecific antigen, there was no significant difference between controls and patients. From these results, we can conclude that GD and HT T-lymphocytes are sensitized to thyroid antigen and produce the lymphokine, migration inhibition factor, into the supernatant when exposed to this antigen.

Adult↗
PubMed1981

Suppressor T lymphocyte dysfunction in Graves' disease: role of the H-2 histamine receptor-bearing suppressor T lymphocytes.

The allo-suppressor effect of normal T lymphocytes on the production of migration inhibition factor by sensitized T lymphocytes of Graves' disease in response to human thyroid antigen has been studied further by a modified migration inhibition factor test employing purified T lymphocyte preparations. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with the Graves' disease lymphocytes in various ratios (1:9, 2:8, and 5:5). However, pretreatment of the normal T lymphocytes with cimetidine (an H-2 histamine receptor antagonist) led to a demonstrable loss in their allo-suppressor properties, whereas pretreatment with chlorpheniramine (an H-1 histamine receptor antagonist) had no such effect. These studies indicate that a subset of normal T lymphocytes bearing H-2 histamine receptors suppresses the production or release of migration inhibition factor by sensitized T lymphocytes, and further suggest the possibility that there may be an abnormality in the H-2 receptors on Graves' disease suppressor T lymphocytes. It is conceivable that this defect is fundamental in the pathogenesis of Graves' disease.

Adult↗
PubMed1981

Factors relating to the beta blocker withdrawal syndrome.

Clinical studies were performed with groups of patients with ischaemic heart disease, patients with hyperthyroidism, and normal subjects, to investigate the possibility of a beta blocker withdrawal syndrome, by measurments of heart rate under conditions of increased sympathetic drive provided by standing with vasodilatation or by Valsalva's manoeuvre. A rebound increase in heart rate to levels significantly higher than the control heart rate off treatment was observed 2-5 days after stopping one or more weeks' treatment with dl-propranolol (160 mg/day), atenolol (200 mg/day), acebutolol (400 mg/day) or oxprenolol (160 mg/day).

Acebutolol↗
PubMed1981

A "new" low incidence "Hutterite" blood group antigen Waldner (Wda).

A "new" red cell antigen has been found so far only in members of Hutterite kindreds with the surname Waldner. The antigen, Wd(a), is inherited as an autosomal dominant and is not part of the ABO, Chido, Colton, Dombrock, Duffy, Kidd, MN, P, or Rh blood group systems.

Antigens↗
PubMed1980

A histological study of the carrageenan-induced granuloma in the rat lung.

Intralobular injection of 0.17 ml of 2% carrageenan, through a ventral slit in the trachea of rats, induced localised areas of inflammation with a high survival rate. This inflammation was characterised by immediate polymorphonuclear leucocyte (PMN) infiltration into the interstitial and alveolar spaces followed in 4 days by replacement of the PMNs by carrageenan-containing macrophages. Between days 10 to 70, the macrophages rapidly increased in size and accumulated numerous large vacuoles which stained for the presence of carrageenan. Several macrophages were so large that they each filled an entire alveolar space. From days 70 to 205, the macrophage appearance was unchanged except that the staining of their carrageenan-containing vacuoles was less metachromatic with toluidine blue. Fibrosis was first noted at day 205 and consisted of several small granulomas located near large airways and blood vessels. These granulomas had a central area filled with macrophages and a peripheral zone consisting of fibroblasts, new collagen, scattered macrophages and blood vessels. The morphology of the macrophages remained essentially unchanged from days 205 to 500 but by day 500, the macrophages were found only in numerous pockets within the inflamed lobe. They still stained positive for the presence of carrageenan at day 500. The extreme longevity of these macrophages and the lack of significant fibrosis may be due to the "un-naturalness", indigestibility, and low toxicity of the irritant, carrageenan. In addition, their size and numerous vacuoles may have inhibited their movement and subsequent removal from the lung. The paucity of significant fibrosis may be due to the lack or inhibition of a "fibroblast stimulating factor" released by the macrophages or possibly the collagen was degraded as soon as it was synthesised. This carrageenan-induced inflammation is a very suitable for the study of alveolar macrophages but appears to be inappropriate for the study of pulmonary fibrosis.

Animals↗
PubMed1980

Ventilatory support for children with whooping cough. Experience with children admitted to a paediatric intensive care unit.

Twenty-four patients with pertussis admitted to a paediatric Intensive Care Unit over a period of 42 months are reviewed. It is concluded that pertussis affects the young baby most severely, the majority of the children admitted were under the age of 3 months. Many required long term intubation and pulmonary supportive therapy and the percentage of those admitted to the Intensive Care Unit who have needed mechanical ventilation has steadily increased over the period reviewed from 25 to 71%. The youngest infant died from overwhelming respiratory infection. The other 23 patients recovered but three children developed neurological complications and their recovery is still being assessed. The importance of maintenance of the immunisation programme is stressed in view of the evidence of the severity of the disease in the very young infant.

Anti-Bacterial Agents↗