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Biomedical subjects

M Hughes

Publications and source records attributed to M Hughes.

At least 199 records · Page 11Linked to original sources
PubMed1984

Peptide inhibitors of renin.

Analogues of renin substrate that incorporated a non-cleavable isostere at the scissile bond are powerful inhibitors of renin both in vitro, and in animals and man.

Animals↗
PubMed1983

An assessment of cerebral dominance in language--disordered children via a time-sharing paradigm.

A time-sharing paradigm was used to assess language lateralization in language-disordered and normal children aged 4-7 years. Several expressive language tasks as well as a vocal, but nonlinguistic, task were administered concurrently with unimanual finger tapping. Dependent variables were percent disruption scores and number of syllables produced per concurrent trial. All language concurrent tasks produced tapping reductions for both hands for both groups. This result contrasts to similar time-sharing studies claiming asymmetrical interference and hence language lateralization in children (N. White & M. Kinsbourne, 1980, Brain and Language 10, 215-223; J. Obrzut, G. Hynd, A. Obrzut, & J. Leitgeb, 1980, Brain and Language 11, 181-194). A multiple regression analysis revealed a significant interaction effect differentiating language-disordered from normal children. Normals exhibited a parallel response pattern for speech and tapping (both increased or decreased in rate) under all lateralization conditions. Language-disordered children exhibited an inverse response pattern (e.g., if speech output increased, tapping rate decreased) only under left-hemisphere time-sharing.

Child↗
PubMed1983

Radiation-induced lethality and mutation in a repair-deficient CHO cell line.

A U.V.-sensitive, DNA repair-deficient mutant of Chinese hamster ovary cells was tested for its response to the lethal effects of X-irradiation and simulated solar light, and to the mutagenic actions of X-rays. A slight sensitivity to killing by X-rays and a greater sensitivity to solar light was observed relative to the wild-type CHO cells. More mutations were induced at a given dose of X-rays in the sensitive cell line than in the wild-type. These results are interpreted in terms of overlap in the repair processes which take place after U.V. damage in mammalian cells with those that take place after other types of radiation damage.

Animals↗
PubMed1983

New inhibitors of human renin tested in vitro and in vivo in the anaesthetized baboon.

A new inhibitor of human renin (H. 189) is described. It is a decapeptide analogue of human renin substrate with the amino acid, statine, substituted for leucine in the scissile bond. Its inhibitory potency as shown by IC50 is 1.0 X 10(-8) M with human plasma renin and 1.5 X 10(-8) M with baboon plasma renin. It is less effective with dog and rat renin, but its inhibitory potency with human renin is similar to that of another inhibitor of ours (H. 142) having a reduced isostere in the scissile bond. H. 189 has some inhibitory effect on cathepsin D (IC50 6.5 X 10(-5) M) but H. 142 has no discernible effect. Pepstatin, on the other hand, was highly effective against cathepsin D (IC50 1.2 X 10(-8) M). H. 142 and H. 189 were infused intravenously at 10 mg/kg/h in four anaesthetized salt-deplete baboons (Papio hamadryas). The activity of renin in plasma decreased markedly as did the circulating concentration of its products, angiotensin I and angiotensin II.

Anesthesia, General↗
PubMed1983

Language and social class: is verbal deprivation a myth?

A study was made of complex usages of language in the spontaneous conversation of 30 4-year-old girls, their mothers and their teachers, at home and at school. There were significant social class differences in frequency, but almost all the usages appeared in the talk of almost all the mothers and children at least once. The working class girls' language style changed more between home and school than did that of the middle class girls. The teachers' talk contained a higher proportion of these usages than the mothers', but the overall input to the children was less at school. The findings are discussed in relation to Labov's argument that verbal deprivation is a myth.

Adult↗
PubMed1983

Children's questions and adults' answers.

Radio-recordings were made of the conversation of 30 girls, aged just under four, at school with their teachers and at home with their mothers. Half the girls were middle class and half working class. The frequency and type of question asked by the children and the frequency and type of answer given by the adults were analysed. Particular attention was paid to passages of persistent questioning by the child. There were home-school and social class differences in all these measures. The significance of the findings for education is discussed.

Child, Preschool↗
PubMed1983

Peptide inhibitors of renin.

Three experiments are described using new substrate analogue inhibitors of renin. The first experiment shows that introduction of a reduced isostere in the scissile peptide bond of an analogue greatly increases its ability to inhibit renin of a particular species. However, different species of renin substrate have different amino acids in their scissile bond and variation here also greatly influences the affinity of renin and substrate and hence of renin and substrate analogues. Finally, substitution of amino acids in the C-terminal adjacent to the scissile bond influences the affinity and efficacy of substrate analogues as inhibitors. In our second experiment a peptide inhibitor of dog renin, H.77, was used in an affinity column to produce a one-stage, 2000-fold, and complete purification of human renin. In our third experiment infusion of H.77 was used to lower circulating concentrations of angiotensin I and angiotensin II in conscious sodium-deplete dogs. Captopril was then given in addition to H.77 but blood pressure did not fall further, suggesting that captopril lowers blood pressure wholly or partly by reducing angiotensin II within the circulation and in extravascular sites.

Amino Acid Sequence↗
PubMed1982

Dyserythropoiesis in homozygous haemoglobin C disease.

Electron microscope studies of the bone marrow of three patients with homozygous haemoglobin C (HbC) disease have shown marked ultrastructural abnormalities in several of the polychromatic erythroblasts and marrow reticulocytes and the presence of phagocytosed erythroblasts within the macrophages. Such abnormalities were not found in the bone marrow of three patients with sickle cell anaemia indicating that the abnormalities represented a feature of HbC disease rather than a disturbance secondary to peripheral haemolysis. The characteristic ultrastructural finding in the polychromatic erythroblasts in HbC disease was the presence of grossly-disorganized nuclei showing multiple intranuclear clefts, the loss of parts of the nuclear membrane, oozing of nuclear material into the cytoplasm and an alteration of the structure and stainability of the nuclear chromatin. It is proposed that both the dyserythropoiesis and ineffective erythropoiesis in HbC disease may have resulted from the formation in vivo of very small aggregates of HbC within erythropoietic cells.

Adolescent↗
PubMed1982

Adults' cognitive demands at home and at nursery school.

A study was made of the "cognitive demands" made of children during spontaneous conversations with their teachers at nursery school and their mothers at home. Social class differences were small compared with home/school differences. Teachers' talk contained a higher proportion of cognitive demands and "testing" demands than did mothers' talk; however, the hourly rate of these demands was higher in the mothers' talk. Teachers used more demands for attributes, simple descriptions and interpretations, whilst mothers used more demands for recall and explanation of motives and purposes. More demands were left unanswered at school than at home. The implications for nursery education are discussed.

Child Development↗
PubMed1982

A new case of congenital dyserythropoietic anaemia, type III: studies of the cell cycle distribution and ultrastructure of erythroblasts and of nucleic acid synthesis in marrow cells.

The clinical and laboratory findings in an asymptomatic 19-year-old Welshman with congenital dyserythropoietic anaemia (CDA) type III are described. The blood film showed macrocytosis and red cell fragmentation and there was biochemical evidence of intravascular haemolysis. The bone marrow showed erythroid hyperplasia, megaloblastic erythropoiesis and several giant multinucleate erythroblasts. Some mononucleate erythroblasts were large and had relative DNA contents of 4-8c and the bi- and multinucleate erythroblasts had total DNA contents of 2-16c. Some of the multinucleate erythroblasts displayed a variety of ultrastructural abnormalities, including marked differences in the appearances of the individual nuclei within the same cell. The marrow cells gave a normal deoxyuridine-suppressed value indicating that the megaloblastic changes were not caused by an impairment of the methylation of deoxyuridylate. The rates of incorporation of 14C-glycine and 14C-adenine into both the DNA and RNA of bone marrow cells were within the normal range. Furthermore, the average rate of elongation of newly-synthesised, 3H-thymidine-labelled daughter DNA strands, assessed by hydroxyapatite chromatography of alkali-denatured DNA was found to be normal. The results suggest that there is no impairment of DNA replication in the majority of the erythroblasts and that the abnormality of erythropoiesis resulted from disturbances during mitosis and the G2 phase.

Adenine↗
PubMed1981

Ineffective erythropoiesis in haemoglobin E beta -thalassaemia: an electron microscope study.

Electron microscope studies have been performed on the bone marrow cells of two non-splenectomized patients and the circulating erythroblasts and reticulocytes of three splenectomized patients with HbE/beta-thalassaemia. Some intracellular precipitates (probably consisting of alpha-chains) and mild dyserythropoietic changes were found in the early polychromatic erythroblasts within the bone marrow. Larger quantities of precipitate and more marked dyserythropoietic changes were found in the late polychromatic erythroblasts and reticulocytes both within the marrow and within the circulation. The bone marrow macrophages contained phagocytosed erythroblasts within their cytoplasm. These data indicate that the anaemia in HbE/beta-thalassaemia results largely from dyserythropoiesis and ineffective erythropoiesis. The ultrastructural abnormalities encountered in the cases of HbE/beta-thalassaemia were qualitatively and quantitatively similar to those seen in homozygous beta-thalassaemia.

Adult↗