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Biomedical subjects

G W Brown

Publications and source records attributed to G W Brown.

At least 19 recordsLinked to original sources

Conservation of structure and function of DNA replication protein A in the trypanosomatid Crithidia fasciculata.

Human replication protein A (RP-A) is a three-subunit protein that is required for simian virus 40 (SV40) replication in vitro. The trypanosome homologue of RP-A has been purified from Crithidia fasciculata. It is a 1:1:1 complex of three polypeptides of 51, 28, and 14 kDa, binds single-stranded DNA via the large subunit, and is localized within the nucleus. C. fasciculata RP-A substitutes for human RP-A in the large tumor antigen-dependent unwinding of the SV40 origin of replication and stimulates both DNA synthesis and DNA priming by human DNA polymerase alpha/primase, but it does not support efficient SV40 DNA replication in vitro. This extraordinary conservation of structure and function between human and trypanosome RP-A suggests that the mechanism of DNA replication, at both the initiation and the elongation level, is conserved in organisms that diverged from the main eukaryotic lineage very early in evolution.

Animals

Purification and characterization of DNA ligase I from the trypanosomatid Crithidia fasciculata.

A DNA ligase has been purified approximately 5000-fold, to near homogeneity, from the trypanosomatid Crithidia fasciculata. The purified enzyme contains polypeptides with molecular masses of 84 and 80 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both polypeptides formed enzyme-adenylate complexes in the absence of DNA, contained an epitope that is highly conserved between human and bovine DNA ligase I and yeast and vaccinia virus DNA ligases, and were identified in fresh lysates of C. fasciculata by antibodies raised against the purified protein. Hydrodynamic measurements indicate that the enzyme is an asymmetric protein of approximately 80 kDa. The purified DNA ligase can join oligo(dT) annealed to poly(dA), but not oligo(dT) annealed to poly(rA), and can ligate blunt-ended DNA fragments. The enzyme has a low Km for ATP of 0.3 microM. The DNA ligase absolutely requires ATP and Mg2+, and is inhibited by N-ethylmaleimide and by KCI. Substrate specificity, Km for ATP, and the conserved epitope all suggest that the purified enzyme is the trypanosome homologue of DNA ligase I.

Animals

Recent developments in life-event research and their relevance for the study of addictions.

The idea that stressful life events can on occasions contribute to the development of addictive disorders is fairly well-accepted within both clinical and research communities. However, little support is available: research is sparse and investigators have generally neglected methodological refinements and innovations in the broader field of life-event research. Some of these developments are discussed, especially as they relate to the measurement of the meaning of life events. Findings from research based on such techniques are summarized, and their relevance for the study of addictions discussed under three headings: specification of life events, vulnerability, and diagnostic specificity.

Adaptation, Psychological

The effectiveness of a single intravenous dose of ondansetron.

This paper reviews data from 3 randomised, double-blind, parallel-group studies carried out in patients receiving high-dose cisplatin chemotherapy (50-120 mg/m2). These comparative trials show that a single intravenous dose of ondansetron (8-32 mg) is as effective as the continuous infusion and intermittent dose regimens used in previous clinical trials (8 mg i.v. followed by a 1 mg/h infusion for 24 h and 0.15 mg/kg i.v. x 3). One of the studies, carried out in Europe, demonstrated that a single 8 mg i.v. dose was as effective as 32 mg given either as an 8 mg loading dose followed by an infusion or as a single intravenous dose of 32 mg before chemotherapy. A similar study conducted in the United States showed that a 32 mg i.v. single dose was significantly more effective than both the 8 mg i.v. dose and the intermittent dose schedule. This study used a prospective stratification based on the dose of cisplatin (50-70 mg/m2 and greater than or equal to 100 mg/m2). In both strata the 32 mg dose was superior. These results emphasise the importance of selecting the dose of ondansetron (8-32 mg) based on factors that predispose patients to emesis, e.g., female gender, patients with a history of chemotherapy or motion sickness and the dose of cisplatin. The ondansetron dosing regimen for patients receiving a highly-emetogenic chemotherapy (8-32 mg i.v. followed by 8 mg orally twice daily) is both simple and flexible.

Adult

Social factors and recovery from anxiety and depressive disorders. A test of specificity.

Analysis of 33 instances of recovery or improvement among 92 women with anxiety, and 49 instances of recovery and improvement among 67 episodes of depression, showed that recovery and improvement, when compared with conditions not changing, were associated with a prior positive event. Such events were characterised by one or more of three dimensions: the 'anchoring' dimension involved increased security; 'fresh-start', increased hope arising from a lessening of a difficulty or deprivation; and 'relief', the amelioration of a difficulty not involving any sense of a fresh start. Events characterised by anchoring were more often associated with recovery or improvement in anxiety, and those characterised as fresh-start were associated with recovery or improvement in depression. Recovery or improvement in both disorders was more likely to be associated with both anchoring and fresh-start events. The study involved the reworking of some social and clinical material, and although done blind should be seen as exploratory.

Adult

Conceptual and methodological issues for behavioral pediatrics research.

Three prescriptions are made to improve behavioral pediatrics research: (1) Focus behavioral pediatrics on preventive research from environmental and social perspectives. (2) Ground research questions more extensively within a conceptual framework. (3) Enhance research quality with reliable, valid measurement. Conceptual and methodological improvements in research will facilitate integration of the multidisciplinary, multimethodological, and multitheoretical scope of behavioral pediatrics and further its contributions to science.

Behavioral Medicine

Monoclonal antibodies to the major nonstructural nuclear protein of minute virus of mice.

Monoclonal antibodies were raised against a bacterial fusion protein containing amino acids 364 to 623 of the major nonstructural protein, NS-1, of minute virus of mice (MVMp), an autonomous parvovirus. By immunoblot analyses, these antibodies all recognized an 83-kDa protein in MVM-infected mouse fibroblast cells. Indirect immunofluorescence studies showed that five of the six react against a nuclear protein in MVM-infected mouse cells resulting in discrete foci of fluorescence. These foci do not correspond with the nucleoli, the site of MVM DNA replication. The epitopes of the antibodies were mapped using carboxy-terminal deleted bacterial fusion proteins derived from the plasmid encoding the original antigen and showed that four distinct epitopes were recognized by the different antibodies. A 25-amino-acid peptide was used in competition ELISAs to confirm the location of the epitope recognized by two antibodies CE10 and AC6. Preliminary characterization of an NS-1/NS-2 fusion protein synthesized in insect cells using a baculovirus expression vector showed that this fusion protein is also localized within the nucleus; however, in contrast, the full-length NS-1 polypeptide is located within the cytoplasm.

Amino Acid Sequence

Science policy, science funding, and the science community.

The ongoing federal budget crisis has led to extensive debate over how much money the federal government should spend on scientific research. In the struggle for limited funds, many advocacy groups will covet the large sums proposed for science research, and the scientific community may be called upon to justify its large share of the discretionary funding, especially the large increases for some science agencies and "big science" projects. Many would instinctively support the assertion that scientific progress is a cornerstone of national well-being, but the connection between strong federal support of research and vigorous economic growth or societal vitality is not straightforward. Two variables--science and technology, not science alone, are basic to the larger issues of the economy and social welfare. Federal policy must facilitate development in coordination with support for basic science. Scientists, in turn, must help foster a perspective that encompasses research and development as a whole and that seeks to identify explicitly the connections between the nature of the R&D effort and economic vitality and quality of life. Furthermore, society needs a free flow of information between all members of the science and technology community and an end to the artificial and harmful barriers between them. The science community must focus on setting priorities, refining science and technology policy to maximize available resources, and convincing voters that science can make crucial contributions to the long-term welfare of the nation.

Budgets

Comparison of propofol and thiopentone for laryngeal mask insertion.

Conditions for insertion of the laryngeal mask were assessed following induction of anaesthesia with either propofol 2.5 mg/kg or thiopentone 4.0 mg/kg in 80 patients premedicated with diazepam 10 mg. Insertion following induction with thiopentone resulted in a greater incidence of gagging (p less than 0.01). The use of additional induction agent, where necessary, resulted in no ultimate significant difference between the groups for the provision of satisfactory conditions.

Adult

Early sexual abuse and clinical depression in adult life.

Sexual abuse in childhood and adolescence was studied in 286 working-class mothers living in Islington, who were contacted on three occasions over a two-year period. The sample was collected primarily to study current vulnerability factors in the onset of depression, but childhood measures were also included to look at longer-term risk factors. Twenty-five women - 9% of the sample - reported sexual abuse involving physical contact before age 17 and, of these, 64% had case depression in a three-year period (which included the year before first interview). While such abuse was related to other earlier stressful experiences such as parental indifference, violence to the child and institutional stay, it was associated with an increased risk of depression over and above these factors. Sexual abuse before age 17 also related to having been divorced/separated or never having married/cohabited.

Adolescent

Elastofibroma dorsi: report of two cases and literature review.

Two cases of elastofibroma dorsi are added to the 125 non-Asian cases reported in the last 31 years. Rapid growth followed by spontaneous total regression is reported for the first time. Confirmation of these observations by others and tissue confirmation are encouraged. Physician awareness of elastofibromas may reveal a higher incidence of occurrence and help avoid unnecessarily radical surgery. A comprehensive review of the literature discloses several current misconceptions.

Aged

P values.

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Binomial Distribution

Self-esteem and depression. 1. Measurement issues and prediction of onset.

Research on the efficacy of measures of self-esteem to predict onset of depression has produced highly variable results. Longitudinal population studies in London and Edinburgh have produced positive findings, but there are a number of studies with negative results. This paper examines in more detail than hitherto the results of the London, Islington, longitudinal study and discusses issues of measurement which might explain the variable success of such predictions.

Attitude to Health