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A Butler

Publications and source records attributed to A Butler.

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Differential scanning calorimetry of Cu,Zn-superoxide dismutase, the apoprotein, and its zinc-substituted derivatives.

We have employed differential scanning calorimetry (DSC) to investigate the thermally induced unfolding of native Cu,Zn-superoxide dismutase (SOD), the apoprotein derived from native SOD, and the zinc-substituted derivatives of the apoprotein. We observe two overlapping melting transitions for native bovine SOD with heat capacity maxima at temperatures (Tm) of 89 and 96 degrees C when a scanning rate of 0.82 deg/min is employed. By contrast, the dithionite-reduced native SOD (which contains Cu+ rather than Cu2+) exhibits only a single transition at 96 degrees C. Significantly, we find that the concentration of O2 present in native SOD samples influences the relative magnitudes of the 89 and 96 degrees C peaks. Specifically, the lower temperature transition becomes less pronounced as the concentration of O2 in the sample decreases. On the basis of these observations, we propose that the lower temperature peak corresponds to the melting of the oxidized native protein, while the higher temperature peak reflects the melting of the reduced native protein, which forms spontaneously during the heating process. Our interpretation profoundly differs from that of Lepock et al. [Lepock, J.R., Arnold, L.D., Torrie, B.H., Andrews, B., & Kruuv, J. (1985) Arch. Biochem. Biophys. 241, 243-251], who have proposed that the low-temperature transition corresponds to the reduced form of the protein. We present evidence that suggests that their experiments were complicated by the presence of potassium ferrocyanide, which, in addition to reducing the cupric center, also perturbs the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Treated blood pressure, rather than pretreatment, predicts survival in hypertensive patients. A report from the DHSS Hypertension Care Computing Project (DHCCP).

A group of hypertensive patients (n = 2855) with an untreated diastolic blood pressure greater than or equal to 90 mmHg were followed in the Department of Health and Social Security (DHSS) Hypertension Care Computing Project (DHCCP) for periods of up to 10 years. During this period 191 of these patients died. Survival was assessed in relation to pretreatment blood pressure levels and blood pressure achieved during treatment. The blood pressure during treatment was a useful predictor of mortality, but the pretreatment pressure was not. After adjusting for age, mortality was particularly related to the height of the systolic and diastolic blood pressure during the second and third years of treatment. In men, age-standardized 5-year mortality was greater than 10% in those with a first year treated systolic pressure greater than 150 mmHg or a diastolic pressure greater than 95 mmHg. In women, age standardized 5-year mortality was greater than 5% with the same levels of treated blood pressure. The longest survival occurred with the lowest bands of treated pressure, i.e. systolic pressure less than 140 and diastolic pressure less than 90 mmHg; the 5-year mortality being less than 7% in men and less than 3% in women. Treated systolic and diastolic pressures were useful in predicting death from ischaemic heart disease (IHD).

Blood Pressure

Pharmacological properties of GR38032F, a novel antagonist at 5-HT3 receptors.

1. This paper describes the pharmacology of the novel 5-hydroxytryptamine3 (5-HT3) receptor antagonist GR38032F. 2. On the isolated vagus nerve and superior cervical ganglion of the rat, R,S-GR38032F behaved as a reversible competitive antagonist of 5-HT-induced depolarization with pKB values of 8.61 +/- 0.08 (n = 19) and 8.13 +/- 0.07 (n = 16), respectively. The resolved R- and S-isomers of GR38032F were approximately equipotent as 5-HT antagonists on the rat vagus nerve: the pKB values were 8.95 +/- 0.05 (n = 16) and 8.63 +/- 0.08 (n = 17), respectively. R,S-GR38032F was also an effective antagonist of 5-HT on the rabbit isolated vagus nerve: in this case the pKB value was 9.40 +/- 0.14 (n = 4). 3. On the rabbit isolated heart, low concentrations of R,S-GR38032F (3 X 10(-11)-1 X 10(-9) M) antagonized the positive chronotropic effect of 5-HT and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT). However, the effects of the compound did not appear consistent with simple reversible competition. 4. On the longitudinal smooth muscle of the guinea-pig ileum, R,S-GR38032F caused concentration-dependent parallel rightward displacement of the 2-methyl-5-HT concentration-contraction response curve; in contrast, a portion of the response to 5-HT appeared resistant to R,S-GR38032F. pKB values estimated from the effects of the compound against 2-methyl-5-HT or the inhibitable portion of the response to 5-HT were 7.31 +/- 0.06 (n = 8) and 7.33 +/- 0.13 (n = 8), respectively. Against 2-methyl-5-HT, R-GR38032F seemed more potent (pKB 7.20 +/- 0.10; n = 6) than S-GR38032F (pKB 6.30 +/- 0.05; n = 6). 5. R,S-GR38032F is highly selective for 5-HT3 receptors, and at concentrations of 3 X 10(-6)-3 X 10(-5) M, had negligible agonist or antagonist activity on other 5-HT or non-5-HT receptor-containing tissues on which it was tested. 6. The potency and duration of action of R,S-GR38032F in blocking 5-HT3 receptors in vivo were assessed by measuring its ability to antagonize the bradycardic response to 5-HT or 2-methyl-5-HT administered intravenously (i.v.) to anaesthetized animals. For i.v. administration to the rat, the ED50 for R,S-GR38032F against 2-methyl-5-HT (100pgkg-1) was 0.4 (95% confidence limits 0.18- 0.87) ygkg-1 (n = 10); the corresponding value for oral administration to this species was 7.0 (3.0- 22.0)pgkg-' (n = 8-10 per dose level). R,S-GR38032F was similarly effective in the anaesthetized cat. 7. The present results are discussed with reference to the postulated existence of subtypes of the 5-HT3 receptor.

Animals

Beta adrenoceptor blockade is associated with increased survival in male but not female hypertensive patients: a report from the DHSS Hypertension Care Computing Project (DHCCP).

The DHCCP is a multicentre observational study of patients being treated for hypertension in the United Kingdom. The influence of the type of anti-hypertensive therapy on survival was examined in 2,697 patients followed from 1971 with 206 deaths up to November 1981. Patients were classified by three types of treatment after one year in the project: betablockers (1,387), methyldopa (452) and others (667), (70% on diuretics only). The data were analysed both for all patients and for a subset excluding patients with previous ischaemic heart disease by all cause and IHD age-adjusted rates and life table analysis. Men on beta blockers had lower rates for total mortality, when compared with men on methyldopa (64% of the methyldopa rate, P less than 0.05) and when compared with men on other treatments (76% of the other treatment rate, P less than 0.1). The results for IHD mortality were similar. This improved survival of men in the beta blocker group was also found in the subset with no prior history of IHD. The benefit of beta blockers was not apparent in women: the lowest rates were observed for women on methyldopa, but the confidence limits for the ratios of relative rates were wide. Adjustment for blood pressure and cigarette smoking using the Cox proportional hazards model did not substantially modify the ratios of the mortality rates for the treatment groups. A sub-group analysis showed the reduction in all cause and IHD mortality associated with beta blockers was mainly due to the effect in non-smoking men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists

Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.

The deduced amino acid sequence of a Drosophila gene isolated with a vertebrate sodium channel complementary DNA probe revealed an organization virtually identical to the vertebrate sodium channel protein; four homologous domains containing all putative membrane-spanning regions are repeated in tandem with connecting linkers of various sizes. All areas of the protein presumed to be critical for channel function show high evolutionary conservation. These include those proposed to function in voltage-sensitive gating, inactivation, and ion selectivity. All 24 putative gating charges of the vertebrate protein are in identical positions in the Drosophila gene. Ten introns interrupt the coding regions of the four homology units; introns with positions conserved among homology units bracket a region hypothesized to be the selectivity filter for the channel. The Drosophila gene maps to the right arm of the second chromosome in region 60D-E. This position does not coincide with any known mutations that confer behavioral phenotypes, but is close to the seizure locus (60A-B), which has been hypothesized to code for a voltage-sensitive sodium channel.

Amino Acid Sequence

Growth inhibitory effect of sodium azide in chemosensitivity assays.

In vitro chemosensitivity assays based on colony counting are plagued by persistent incidence of false-negative results. To avoid serious predictive errors, some investigators have utilized positive controls (known toxic compounds) as a quality control measure. Sodium azide (NaN3) at 6 mg/ml failed to inhibit colony formation in 17/35 (49%) assays; while in the thymidine incorporation assay, sodium azide was effective in inhibiting 124/131 (95%) specimens. Positive control substances for use in chemosensitivity assays must be carefully selected to insure accurate results.

Azides

Toxic response of hamster embryo cells on exposure to mixtures of Ni2+ and benzo(a)pyrene.

Exposure of hamster embryo cells (HEC) to mixtures of benzo(a) pyrene and soluble Ni2+ neutral salts elicits additive responses in the enhanced nucleoside excretion assay. Ni2+ shows no significant excretion response until concentrations near 10 microM are reached. Addition of 0.4 micromolar benzo(a)pyrene and 30 microM, or 325 microM Ni2+ to HEC cultures results in total excretion equal to the sum of excretions induced by the individual chemicals. These observations suggest that excretion of pyrimidines may be a useful measure of biological dosimetry.

Animals

Inflammatory bowel disease in the West Indies.

Inflammatory bowel disease is generally assumed to be rare among negroes and Indians. Over 10 years 34 cases of ulcerative colitis and 14 cases of Crohn's disease were seen in one medical and one surgical unit in Port-of-Spain, Trinidad. Twenty-six patients were Negroes, 18 were Indians, three were of mixed race, and one was Caucasian. In many of these patients the disease was extensive and several of those with Crohn's disease suffered severe complications. The assumption that inflammatory bowel disease is rare among West Indians of African and Indian origin therefore seems to be wrong.

Adolescent

Features of children taken to juvenile court for failure to attend school.

The social reports on 84 children taken to court for failure to attend school were studied. Independent raters were able to assess reliably the presence and absence of a variety of variables concerned with the individual's behaviour, school, family, and involvement with social work agencies. In 68 instances teacher's questionnaires measuring psychiatric disturbance had been completed. There was no evidence that truancy in these circumstances is a homogenous condition. At least 3 independent sets of features appear to be involved in most cases. One involves antisocial and educational problems ('clinical truancy'), a second is concerned with adverse social factors and parental complicity ('school withdrawal'), and a third set includes a tendency to social isolation ('school refusal'). There was no evidence that individuals tend to exhibit one of these features to the exclusion of the others.

Absenteeism

The outcome of adolescent school phobia.

A hundred-and-twenty-five school phobic youngsters had been treated in a psychiatric in-patient unit for young adolescents of secondary school age over a seven-year period; a hundred of them were reviewed on average three years after discharge. About a third of cases were found to have improved little; they had persistent severe symptoms of emotional disturbance and continuing social impairment. Another third had improved appreciably and were affected by neurotic symptoms rather than social impairment. The remaining third had improved substantially or completely. School attendance difficulties had remained in about half of all cases. Subsequent difficulties in going to work were less pronounced. The best predictor of outcome was clinical state on discharge. High intelligence also emerged as a significant predictor of poor outcome. Five girls and a boy had already developed severe and persistent agoraphobic difficulties when reviewed. It was found that severe school phobia in early adolescence resembled adult affective disorders in some clinical features and in outcome.

Absenteeism

Breast cancer.

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Adaptation, Psychological

Child's play is therapy.

Play can be a simple, effective way of helping the preschool child to deal with the strange and sometimes painful hospital world and to master situations that might otherwise be overwhelming. This type of play can be incorporated easily into the nursing care plan and can become an essential aspect of the care of the hospitalized preschool child. The results are rewarding in terms of happier, less anxious children, parents, and nursing staff.

Adaptation, Psychological