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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 577 records · Page 32Linked to original sources

Views of general practitioners in the Oxford region on microcomputing and collaboration with health authorities and family practitioner committees.

A postal questionnaire was sent to the senior partners of all 353 general practices in the Oxford region to investigate their interest in microcomputing and in pooling data with other general practitioners, health authorities and family practitioner committees. The response rate was 58%. Twenty per cent of responders already used a microcomputer and a further 59% intended to purchase a microcomputer for the practice. Nearly all the practices with an interest in microcomputing wanted to use it to produce age-sex registers, to establish recall groups and for repeat prescribing. Approximately 90% of interested practices reported that they would be prepared to link their data with family practitioner committees or health authorities, while 76% were interested in collaborating with other general practitioners for research. The results show that general practitioners will require support in utilizing the data that they produce.

Attitude of Health Personnel↗

Antioxidants, enzyme induction, and chronic pancreatitis: a reappraisal following studies in patients on anticonvulsants.

Our published dietary and pharmakokinetic studies in 15 patients with idiopathic chronic pancreatitis and 15 age- and sex-matched controls suggested that a combination of subnormal antioxidant intakes and chronic induction of the cytochromes P450 facilitates the pancreatic problem. We have now attempted to determine the relative importance of these two factors by studying a group of 15 institutionalized patients with epilepsy (EP), but without abdominal pain, who were on long-term treatment with anticonvulsant inducers of cytochromes P450 so that their clearance of theophylline (which reflects cytochromes P450 activities, and thereby provides an index of antioxidant demand) was as high as in the patients with chronic pancreatitis (CP) (mean +/- s.d., 123 +/- 59 ml/kg/h versus 120 +/- 62 respectively), and significantly higher than in controls (74 +/- 16 ml/kg/h, P less than 0.02). Canonical variate analysis of the drug kinetic and dietary data provided two functions with which to separate the three groups. The first function, heavily weighted on selenium, separated the controls from the other two groups whose values were lower; the second function, equally weighted on methionine and vitamin C, separated the EP group from the CP group whose values were generally lower. The results suggest that enzyme induction per se is not the critical factor in the development of CP. Instead, suboptimal availability of antioxidants in the face of increased demand--in particular of those substances that protect cells against non-biological free radicals--may be the key consideration, a deduction reinforced by observations in patients with epilepsy who went on to develop chronic pancreatitis.

Adult↗

Mutations in the gene for EF-G reduce the requirement for 4.5S RNA in the growth of E. coli.

A general strategy is described for the isolation of suppressors of essential genes whose functions are unknown. This strategy was used to analyze the role of 4.5S RNA, an essential RNA of E. coli. In this strategy, the structural gene for 4.5S RNA is fused to the Ptac promoter in such a way that the strain becomes dependent upon inducers of lac for growth. Mutants mapping to fus, the structural gene for protein synthesis elongation factor G, appear as spontaneous, inducer-independent revertants. These mutants alter the intracellular distribution of 4.5S RNA such that it sediments at 70S or greater. Furthermore, the increased sedimentation velocity is sensitive to the antibiotic puromycin. These results show that 4.5S RNA physically associates with the ribosome in performing its essential function, and that this association is mediated by elongation factor G.

Chromosome Mapping↗

The cytoplasmic expression of CD3 antigens in normal and malignant cells of the T lymphoid lineage.

Anti-CD3 (T3) Ab reacting with different proportions of thymocytes (anti-CD3a: UCHT1, anti-CD3b: T10B9, and anti-CD3c: OKT3) were tested for cytoplasmic (cCD3) and membrane (mCD3) expression in the bone marrow, thymus, and blood in man and selected primates. The expression of cCD3a and cCD3c in the perinuclear and Golgi area of large, BrdU-incorporating, strongly TdT+ thymic blasts probably represents one of the earliest signs of T cell commitment, because these blast cells are CD1-, CD4-, CD8-, and mCD3-. The cCD3+, TdT+ cells are normally restricted to the thymus and are absent among the TdT+ cells of bone marrow. The anti-CD3b Ab used, T10B9, co-caps and co-modulates with the other anti-CD3 Ab and is a T cell-specific reagent at a membrane level but does not bind to perinuclear cCD3. Instead, this reagent cross-reacts with a filamentous cytoplasmic network in non-T cells in man and in primates S. oedipus and M. rhesus despite their T cell negativity for mCD3. The characteristics of all T-ALL cases studied: cCD3+, CD7+ along with nuclear TdT+ suggest lineage fidelity to early thymic blasts. As a marked contrast, cCD3 is absent in common ALL and in AML, including cases that concomitantly express CD7 and myeloid antigens. Thus, the cCD3, TdT combination provides a very sensitive assay for residual T-ALL blasts outside the normal thymus.

Adult↗

Flow cytometric analysis and sorting of plant chromosomes from Petunia hybrida protoplasts.

A method to obtain a high metaphase index and thereafter a plant chromosome suspension is described for Petunia hybrida (2n = 14). Mesophyll protoplast cultures have been used, giving easily disrupted cell walls and a high percentage of dividing cells after 42 h. On 2.5 mM colchicine-treated cells, metaphase indexes reaching 10% were routinely obtained. The lysis medium in which the protoplast-derived cells were disrupted was a simplified culture medium. After chromosome release, samples were stained with Hoechst 33342 dye and analysed by flow cytofluorometry. The histogram of fluorescence intensities included three peaks of metaphase chromosomes and a duplication of this flow karyotype provoked by "monochromatid chromosome." This interpretation was established after flow sorting; micronuclei could also be observed and sorted. Of the 7 chromosomes, only the largest formed a distinct peak while the others were incompletely resolved, due to the similar DNA content of various chromosomes. Model distributions of Petunia hybrida chromosomes have been computed according to the relative chromosome length. The theoretical histograms indicated that low variability is indispensable for resolving distinctive chromosome peaks. The experimental flow karyotype was consistent with one of the models having CV of 2.5%.

Benzimidazoles↗

Infertility surgery for pelvic inflammatory disease: success rates after salpingolysis and salpingostomy.

Eighty-seven patients with infertility due to pelvic inflammatory disease were retrospectively studied to determine pregnancy rates after infertility surgery. Patients were divided into two groups on the basis of the type of surgical procedure: group 1, lysis of adhesions only (22 patients); group 2, terminal salpingostomy with lysis of adhesions (65 patients). A significantly greater number of patients in group 1 (nine of 22, 41%) than in group 2 (12 of 65, 18%) (p less than 0.05) achieved intrauterine pregnancy. The incidence of ectopic pregnancy was 23% in group 1 (five of 22) and 9% in group 2 (six of 65) (p = 0.12). Almost all pregnancies that were conceived more than 16 months after operation were ectopic gestations. Patients were classified according to severity of disease on the basis of several factors. Although few patients with severe pelvic inflammatory disease conceived after operation, the effect of disease severity on the likelihood of successful operation was not statistically significant.

Adult↗

Habituation to fear stimuli in a case of obsessive compulsive disorder: examining the generalization process.

The purpose of this investigation was to determine if habituation of anxiety to a visual form of the number 13 would generalize to other forms (auditory, behavioral and cognitive) of the number 13 in a 20-year-old male with obsessive compulsive disorder. Treatment included exposure and response prevention. A multiple baseline design across fear stimulus forms was used. Habituation to the visual form began generalizing to other forms of the number 13 before prolonged exposures to these three stimulus forms were instituted. Results suggest that exposure to a single stimulus form may result in sufficient generalization of treatment effects in cases involving seemingly independent fear responses to several forms of a stimulus.

Adult↗

Comparison of the molecular structure of GABA/benzodiazepine receptors purified from rat and human cerebellum.

The use of improved affinity chromatographic techniques has allowed for the substantial copurification of both the benzodiazepine and the GABA receptor from brain. These preparations have been used to begin characterization of the benzodiazepine receptor at a molecular level. We have recently purified benzodiazepine receptor from human and rat cerebellum, and SDS-PAGE has revealed that both preparations consist of a major protein of 50 kDa and a minor protein of 55 kDa. These proteins are recognized by a series of monoclonal antibodies prepared against the rat benzodiazepine receptor suggesting the rat and human receptors share several common antigenic domains. Several other approaches have been employed to further investigate possible homology between the rat and human receptors. Proteolytic degradation studies have shown that the major limiting photolabeled peptide fragment generated in rat and human is similar as determined by HPLC analysis. Isoelectric focusing and SDS (two-dimensional) electrophoresis have revealed that the immunoreactive, photolabeled 50 kDa protein, and the purified receptor have identical PI values. The receptor from both human and rat are glycoproteins as determined by lectin binding studies. However, exposure of these proteins to neuraminidase fails to alter the pharmacology of the receptors indicating possible similarities in their posttranslational glycosylation. Thus, it appears that some degree of structural homology exists between the rat and human benzodiazepine receptors.

Animals↗

New mutations in the pRM promoter of bacteriophage lambda.

A pRM-cI-lacZ fusion inserted into the b2 region of bacteriophage lambda imm21 was used to isolate mutations in the lambda pRM promoter. Among the mutations causing defects in synthesis of both repressor (cI gene product) and beta-galactosidase, new promoter mutations were identified at positions -11 and -32 relative to the cI transcription start point. Both mutations are changes in conserved (consensus) nucleotides in pRM, but the mutation at -11, which alters a more highly conserved nucleotide, has a somewhat greater effect on promoter function in vitro than does the mutation at -32. We also isolated a mutation at -69 in the repressor-binding site OR1, which presumably prevents activation of pRM by repressor.

Bacteriophage lambda↗

Morbidity and mortality in small bowel atresia. Jejuno-ileal atresia.

One hundred and one babies were admitted to the Hospital for Sick Children, Great Ormond Street, London, between 1967 and 1981, suffering from small bowel atresia. The overall mortality in this period was 23%, although in the years 1974-81 this fell to 12%. Mortality was considerably higher in jejunal atresia than in ileal atresia. The improved survival in the second half of the series was related to more frequent use of parenteral nutrition. Morbidity and mortality following the Bishop-Koop procedure was high and this operation is inappropriate for the treatment of small bowel atresia.

Humans↗

Translational polarity of a mutation in the initiator AUG codon of the lambda cI gene.

A PRM-cI-lacZ fusion inserted into the b2 region of bacteriophage lambda was used to isolate mutations affecting expression of both the lambda cI gene and the lacZ gene. One such mutation, a change in the cI initiator codon from AUG to AUA, reduces immunity of a lambda prophage to superinfection, and causes a 60-70% reduction in beta-galactosidase synthesis, even when repressor is supplied in trans. The effect of the mutation on lacZ gene expression is eliminated in a rho- bacterial strain, and the mutation has no effect on transcription initiated at PRM in vitro. Therefore, the effects of the mutation are due to premature p-dependent termination of transcription in the absence of translation of the cI gene, as if the mutation were a nonsense polar mutation.

Bacteriophage lambda↗

Epoxide hydrolase expression in human and rodent established cell lines.

Four human, four hamster and three mouse established cell lines have been analysed for epoxide hydrolase activity, and these have been compared with activities of human and mouse tissue preparations. Activities expressed by the cell lines, using styrene oxide as substrate, varied between less than 0.005 and 0.44 nmol/min per mg total cellular protein. Human liver and human kidney expressed 12.2 nmol and 2.7 nmol/min per mg total protein respectively. Antibodies prepared against purified human- and mouse-liver epoxide hydrolase enzymes were used to characterize the enzyme in the cell lines. Antihuman antibody was able to inactivate and precipitate enzyme in human cell lines and partially inactivate and precipitate hamster enzymes. It was much less effective against mouse cell lines. Antimouse antibody was able to precipitate mouse enzymes and partially precipitate hamster enzymes but did not precipitate human enzymes. These data may reflect evolutionary divergence of the three species.

Animals↗