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A Brewer

Publications and source records attributed to A Brewer.

28 records · Page 2Linked to original sources
PubMed1989

Activation mechanisms of the Xenopus beta globin gene.

Comparative protein binding studies have been performed on the Xenopus beta globin gene promoter. Erythroblast nuclear extracts 'footprint' over the erythroid-specific consensus sequence, AGGATAAG, which is located immediately upstream of the CCAAT footprint. Nonerythroid cell extracts do not give rise to an AGGATAAG footprint but rather to an extended CCAAT footprint reminiscent of the CCAAT displacement protein (CDP). Erythroblast extracts also protect a sequence similar to the chicken stage selector element (SSE) immediately downstream of the CCAAT box footprint. In contrast to these discrete footprints observed using erythroblast extracts, Xenopus erythrocyte nuclear extracts give rise to more extensive promoter protection. We have previously reported that this promoter is active in transfected HeLa cells when linked to the SV40 enhancer and that transcriptional activation is accompanied by the formation in the chromatin of a nuclease hypersensitive site (HS) in this region. As a first step towards defining the roles of the various promoter-binding proteins in transcriptional activation and HS formation, we transfected deletion mutants of the promoter into HeLa cells. Deletion of the sequences upstream of -116 had no effect on transcription or HS formation. Indeed the upstream boundary of the HS remained unchanged (at around-170) even though plasmid sequences had replaced Xenopus sequences. If the HS boundary reflects resumption of nucleosomal structure, then sequences downstream of -116 must be able to position a nucleosome from at least 50 bp away. beta globin gene activation in a number of transfected cell lines is absolutely dependent on DNA replication. The replication requirement is not a consequence of template copy number or methylation, nor is it dependent on the direction in which the replication fork passes through the gene. We conclude that replication facilitates active transcription complex formation by disrupting a stable association of the template with negative factors, which could include histones. About 200 bp upstream of the Xenopus beta globin gene promoter is a tract of alternating A and T residues which adopts cruciform geometry at low levels of supercoiling. Because of this sensitivity to torsional stress, we have probed the structure of the (AT)n sequence in microinjected Xenopus oocytes, where the Xenopus beta globin gene is transcribed very efficiently. We find that S1 nuclease cleaves specifically in the middle of the (AT)n tract, suggesting that the gene is under torsional stress.

Animals↗
PubMed1988

Development, validation and application of computer-linked knowledge questionnaires in diabetes education.

Multiple choice questionnaires (MCQs) capable of being marked manually or by a newly developed optical mark reader, or by use of an inexpensive inter-active microcomputer system have been developed for the separate assessment of insulin-dependent and non-insulin-dependent patient knowledge. Forty-six insulin-related and non-insulin-related multiple choice questions covering six main areas of knowledge were constructed for inclusion into draft questionnaires. From the responses of a total of 180 completed questionnaires, piloted in 18 randomly selected clinics in 14 Regional Health Authorities in England, psychometric analysis was performed to determine reliability, discrimination coefficients, and facility indices. Seventy-three per cent of insulin-dependent diabetic patients (IDDM) and 92% of non-insulin-dependent diabetic patients (NIDDM) MCQ correct options had facility indices within the acceptable range of 30 to 90%. 82% IDDM and 93% NIDDM correct options had discrimination coefficients exceeding 0.2. Questionnaire reliability (internal consistency) using the Kudor-Richardson (KR20) formula was IDDM 0.87 and NIDDM 0.82. Evidence in support of the IDDM questionnaire's criterion validity was based on significant differences (p less than 0.05) identified between a number of knowledge area scores stratified according to HbA1 levels. Prescriptive correction for screen display and automatic hard copy feedback was designed for both incorrect and omitted question options, providing both educational (patient) and analytical (clinic) documentation. Both technical and psychometric properties of these knowledge assessment instruments should be acceptable for diabetic knowledge evaluation and instruction.

Diabetes Mellitus, Type 1↗
PubMed1986

Nitrogen transactions in the digestive tract of lambs exposed to the intestinal parasite, Trichostrongylus colubriformis.

1. Ten 5-month-old lambs (29 (SE 1.2) kg), reared parasite-free and prepared with rumen duodenal and ileal cannulas, were paired and given rations of Ruminant Diet AA6 (90 g/kg live weight0.75) by means of continuous feeders. From 6 months of age one of each pair was dosed daily with 2500 Trichostrongylus colubriformis larvae for 14 weeks. Untreated animals received the amount of ration consumed by their infected pair-mates the previous day. 2. During three periods, [1) the week before and the first 2 weeks of dosing with infected larvae, (2) during weeks 5-7 and (3) during weeks 11-13 of dosing) all lambs underwent a series of experiments to determine their nitrogen balance, the amounts of N leaving the small intestine, the amount of 51CrCl3-labelled plasma protein leaking into the small intestines, and the disappearance of 35S-labelled bacteria from the small intestine. 3. The infection caused varying degrees of feed refusal in all infected animals. As a result the values for N balance and for the flow of N at the ileum during the latter two periods were regressed against dry-matter intakes for each group in each period. 4. The infection caused a reduction (P less than 0.05) in N retention and increased (P less than 0.05) flow of N at the ileum. The increase in N flow at the ileum of infected lambs was greater (P less than 0.01) at weeks 11-13 of dosing (infected-control 3.6 g N/d (standard error of difference (SED) 0.57), P less than 0.01) than at weeks 5-7 of dosing (infected-control 1.5 g N/d (SED 0.57), P less than 0.05). 5. There were no between-treatment or between-period differences in the disappearance of 35S-labelled bacteria from the small intestines of infected or control lambs, but the infection did cause an increase in plasma N leakage during both periods. During weeks 5-7 and 11-13, plasma N leakage in infected lambs was 1.1 g N/d (P less than 0.01) and 1.7 g N/d (P = 0.056) respectively higher than that in the control lambs. 6. A proportion of the endogenous secretions which enter the small intestine is likely to be resorbed before the ileum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

The effects of a combined implant of trenbolone acetate and oestradiol-17 beta on protein and energy metabolism in growing beef steers.

1. The effects on growth performance, energy and nitrogen retention, and leucine metabolism of a subcutaneous combined implant of 140 mg trenbolone acetate (TBA)+ 20 mg oestradiol-17 beta (OE) have been examined in Hereford x Friesian beef steers (280-520 kg). Comparisons were made both with the same animals before implantation and with untreated control animals maintained under similar physiological and nutritional conditions. 2. Over a 10 week period the implanted steers showed an improvement in rate of live-weight gain (LWG) of 0.5-0.6 with an even greater proportional increase in N retention compared with control animals. Total energy retention was unaffected and thus the ratio, protein energy: total energy gain was 0.43 for implanted steers compared with 0.26 for untreated animals. 3. Estimates of protein synthesis and protein oxidation were obtained from the specific radioactivities of blood free-leucine and exhaled carbon dioxide during continuous infusions of [1-14C]leucine. Whole-body protein synthesis, based on metabolic size, and amino acid fractional oxidation remained similar for control steers throughout the experiment. Steroid-treated steers showed a slight decline in synthesis which was significant (P less than 0.05) at week +5 post-implant while amino acid oxidation was significantly lower at weeks +2 (P less than 0.01) and +5 (P less than 0.05) compared with control animals. The ratio, protein deposition: protein synthesis was 0.05 for control animals but 0.08-0.10 for steroid-treated animals after implantation. 4. There was a slight decrease in urinary N tau-methylhistidine elimination after implantation which suggested that muscle protein degradation may be reduced although the estimated decrease was insufficient to account for the total improvement in growth rate and N retention. 5. The results suggest that for both control and treated steers, less than 0.5 of total urine N elimination was derived directly from tissue catabolism of protein and amino acids. 6. The combined action of the exogenous steroids in the promotion of protein gain, primarily through a decrease in total protein degradation with little alteration of total energy retention, is compared with present understanding of the role of the endogenous sex hormones.

Animals↗
PubMed1983

The importance of being first: an analysis of tachistoscopic presentations of words.

The importance of the first letter of a word as a cue for the rest of the word was explored in a tachistoscopic presentation of four letter English words to the two hemispheres. The positioning of words presented bilaterally and the frequency of the words were manipulated so that the role of the first letter could be examined. The results indicate that the first letter does not play the critical role in word recognition that has been ascribed to it. In the standard bilateral presentation, subjects' recall patterns indicated that first letters were recalled equally well whether the word was presented in the right or left visual field. However, subjects did not recall as many words correctly when they went to the left visual field. The results were interpreted as supporting an information processing view of hemispheric specialization. Such a view proposes several levels of functioning in which the two hemispheres overlap, cooperate, or specialize, depending on the task to be accomplished.

Adult↗
PubMedDate not supplied

Selective vasodilator effects of atrial natriuretic peptide in the human placental vasculature.

OBJECTIVE: To determine whether atrial natriuretic peptide (ANP) attenuates the vasoconstrictor effects of angiotensin II (AII), a thromboxane mimetic (U46619), and endothelin-1 in the human fetal-placental vasculature and to determine whether nitric oxide (NO) has a role in the vasodilator activity of ANP. METHODS: Isolated placental cotyledons were dually perfused, with fetal perfusion pressure used as an index of vascular response. The effects of AII (10(-10)-10(-6) mol/L bolus injection), endothelin-1 (10(-7) mol/L bolus), and U46619 (10(-9)-10(-6) mol/L bolus or 10(-8) mol/L infusion) were established in the absence or presence of ANP (10(-8) mol/L). The role of NO as a mediator of ANP action was investigated by perfusion with n-nitro-L-arginine (NNLA, 10(-3) mol/L), an inhibitor of NO synthase. Statistical significance was determined by analysis of variance. RESULTS: Atrial natriuretic peptide caused significant attenuation of vasoconstrictor responses to AII, but weak attenuation of endothelin-1 and no attenuation of U46619. Use of NNLA did not affect the attenuation of AII-induced vasoconstriction by ANP. CONCLUSIONS: Atrial natriuretic peptide is a vasodilator of the fetal-placental vasculature constricted with AII and endothelin-1, but not with U46619. Nitric oxide does not mediate the action of ANP.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗