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Biomedical subjects

B Cooper

Publications and source records attributed to B Cooper.

At least 19 recordsLinked to original sources

Capsid protein gene and the type of host plant differentially modulate cell-to-cell movement of cowpea chlorotic mottle virus.

A study was undertaken to measure the rate of coat protein (CP) independent cell-to-cell movement of cowpea chlorotic mottle bromovirus (CCMV) in three different host plants. A CCMV RNA3 variant in which the CP gene was substituted with enhanced green fluorescent protein (C3/DeltaCP-EGFP) was coinoculated to three different host plants with transcripts of wild type RNAs 1 and 2. Comparative analysis of cell-to-cell movement monitored by the EGFP expression at various days post inoculation revealed that the rate of spread varied with the type of host species inoculated: fastest movement was observed in Nicotiana benthamiana while the rate spread was significantly slower in the natural host cowpea. When CP was expressed as EGFP fusion (C3/CP:EGFP) the rate of spread in N. benthamiana and C. quinoa was slower than that was observed in the absence of CP and remained subliminal in cowpea. Analysis of infection foci by confocal laser scanning microscope revealed that localization of CP:EGFP fusion was distinct in N. benthamiana and C.quinoa and accumulated as fluorescent inclusions at the cell periphery. Additional experiments involving coinoculation of either C3/DeltaCP-EGFP or C3/CP:EGFP with heterologous brome mosaic bromovirus (BMV) genomic RNAs 1 and 2 revealed that, in addition to movement protein and CP, viral replicase also influences cell-to-cell spread. The significance of these results in relation to the mechanism of bromovirus movement is discussed.

Bromovirus↗

Public-health psychiatry in today's Europe: scope and limitations.

BACKGROUND: Public-health psychiatry is concerned, on the one hand, to ensure access to mental health services for all persons in need and, on the other hand, to advance knowledge of the social and environmental risk factors of mental disorders, and to establish a basis for preventive action. It is unclear how far current European Community (EC) policies will serve to achieve these objectives. This study aimed to review the mental health reform policies adopted in European countries since 1970, and to identify the main factors impeding progress in practice and research. METHOD: The relevant publications and statistical documentation for EC countries over the period in question were analysed. RESULTS: Despite a broad consensus on principles and aims, the implementation of mental health reforms in EC countries has been slow. Progress is subject to constraints imposed by service infrastructures, reductions in state responsibility, changing public attitudes, and growth of relative poverty. Much inferential evidence has accumulated on the importance of social risk factors such as unemployment and socio-economic deprivation, but most studies have had to rely on analysis of ecological correlations, based on administrative data, and there is an urgent need for more direct research making use of case- control and cohort study designs. CONCLUSIONS: EC harmonization will lead to improved mental health care only if the basic principles of public-health psychiatry are adopted and put into practice.

Community Psychiatry↗

The gene encoding the immunoregulatory signaling molecule CMRF-35A localized to human chromosome 17 in close proximity to other members of the CMRF-35 family.

The immunoregulatory signaling (IRS) family includes several molecules, which play major roles in the regulation of the immune response. The CMRF-35A and CMRF-35H molecules are two new members of the IRS family of molecules, that are found on a wide variety of haemopoietic lineages. The extracellular functional interactions of these molecules is presently unknown, although CMRF-35H can initiate an inhibitory signal and is internalized when cross-linked. In this paper, we described the gene structure for the CMRF-35A gene and its localization to human chromosome 17. The gene consists of four exons spanning approximately 4.5 kb. Exon 1 encodes the 5' untranslated region and leader sequence, exon 2 encodes the immunoglobulin (Ig)-like domain, exon 3 encodes the membrane proximal region and exon 4 encodes the transmembrane region, the cytoplasmic tail and the 3' untranslated region. A region in the 5' flanking sequence of the CMRF-35A gene, that promoted expression of a reporter gene was identified. The genes for the CMRF-35A and CMRF-35H molecules are closely linked on chromosome 17. Similarity between the Ig-like exons and the preceding intron of the two genes suggests exon duplication was involved in their evolution. We also identified a further member of the CMRF-35 family, the CMRF-35J pseudogene. This gene appears to have arisen by gene duplication of the CMRF-35A gene. These three loci - the CMRF-35A, CMRF-35J and CMRF-35H genes-form a new complex of IRS genes on chromosome 17.

3' Untranslated Regions↗

Collateral gene expression changes induced by distinct plant viruses during the hypersensitive resistance reaction in Chenopodium amaranticolor.

Hypersensitive reactions to plant diseases are typically mediated by R genes. Many R genes that have been cloned only confer resistance to a particular pathogen. However, Chenopodium spp. have multivirus hypersensitive resistance, thus making the understanding of this broad-spectrum resistance mechanism attractive. Using tobacco mosaic virus (TMV) tagged with green fluorescent protein to follow infection over time, cDNA-AFLP to find genes up-regulated during virus infection in C. amaranticolor and quantitative RT-PCR to accurately measure gene expression at different time points, the first dissection of this significant defense response pathway is presented. The detected disease-expressed sequences in C. amaranticolor (DESCA) are similar to those that encode p450 monooxegenases, hypersensitivity-related genes, cellulases, ABC transporters, receptor-like kinases, serine/threonine kinases, phosphoribosylanthranilate transferases and hypothetical R genes, many of which are associated with pathogen defense in other plants. The expressions of these DESCA genes are also induced by infection with the taxonomically distinct tobacco rattle virus (TRV) in C. amaranticolor. In particular, DESCA1, one of the gene fragments from C. amaranticolor that lacks similarity to any other sequence in the GenBank database, is induced at least 200 fold 4 d after infection (dai) by both TMV and TRV. The potential role of DESCA genes in a C. amaranticolor multivirus defense response with regard to their levels and time of gene expression is discussed.

Chenopodiaceae↗

Constitutive salicylic acid-dependent signaling in cpr1 and cpr6 mutants requires PAD4.

Salicylic acid (SA)-dependent signaling controls activation of a set of plant defense mechanisms that are important for resistance to a variety of microbial pathogens. Many Arabidopsis mutants that display altered SA-dependent signaling have been isolated. We used double mutant analysis to determine the relative positions of the pad4, cpr1, cpr5, cpr6, dnd1 and dnd2 mutations in the signal transduction network leading to SA-dependent activation of defense gene expression and disease resistance. The pad4 mutation causes failure of SA accumulation in response to infection by certain pathogens, while the other mutations cause constitutively high levels of SA, defense gene expression and resistance. The cpr1 pad4, cpr5 pad4, cpr6 pad4, dnd1 pad4 and dnd2 pad4 double mutants were constructed and assayed for stature, presence of spontaneous lesions, resistance to Pseudomonas syringae and Peronospora parasitica, SA levels, expression of PAD4, PR-1 and PDF1.2, and accumulation of camalexin. We found that the effects of the cpr1 and cpr6 mutations on SA-dependent gene expression are completely dependent on PAD4 function. In contrast, SA accumulation in the lesion-mimic mutant cpr5 is partially PAD4-independent, while in dnd1 and dnd2 mutants it is completely PAD4-independent. A model describing a possible arrangement of activities in the signal transduction network is presented.

Anti-Bacterial Agents↗

A survey of nocturnal hypoxaemia and health related quality of life in patients with cryptogenic fibrosing alveolitis.

BACKGROUND: A survey of overnight oximetry was conducted to estimate the prevalence of nocturnal hypoxaemia in patients with cryptogenic fibrosing alveolitis and to establish whether nocturnal hypoxaemia is related to quality of life. METHODS: All patients with cryptogenic fibrosing alveolitis attending Nottingham City Hospital were invited to enter the study. Spirometric measurements and capillary blood gas tensions were obtained and overnight oxygen saturation was recorded at home. Quality of life was assessed using the Short Form-36, Chronic Respiratory Questionnaire, Hospital Anxiety Depression Scale, and Epworth Sleepiness Score questionnaires. RESULTS: Sixty seven eligible patients were identified and 50 agreed to enter the study, although two were subsequently excluded because they already used oxygen overnight. In the remaining 48 the mean (SD) overnight oxygen saturation (SaO(2)) was 92.5 (4.3)% and the median number of dips greater than 4% per hour was 2.3 (interquartile range 1.5-5.3). Daytime oxygen level predicted mean overnight SaO(2) (1.94%/kPa, 95% CI 1.22 to 2.66, p<0.001) but percentage predicted forced vital capacity (FVC) did not (0.018%/% predicted FVC, 95% CI -0.04 to 0.08, p=0.5). Nocturnal hypoxaemia was associated with decreased energy levels and impaired daytime social and physical functioning, and these effects were independent of FVC. CONCLUSIONS: Nocturnal hypoxaemia is common in patients with cryptogenic fibrosing alveolitis and may have an impact on health related quality of life.

Aged↗

Introduction.

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Journal Article↗

Nature, nurture and mental disorder: old concepts in the new millennium.

BACKGROUND: Evidence from twin and adoption studies has highlighted the importance of gene-environment interaction in the aetiology of mental disorders, and advances in molecular genetics have raised hopes of more rapid progress in this field of investigation. AIMS: To review epidemiological knowledge concerning genetic and environmental risk factors for a cross-section of psychiatric conditions, and evidence of interaction between the two types. METHOD: Searches of the literature in genetic and psychiatric epidemiology, including contributions to this supplement. RESULTS: Overall, firm knowledge on both genetic and environmental causal factors is still fragmentary, although progress has varied among diagnostic categories. Environmental aspects have been dealt with only perfunctorily in most genetic epidemiological research. CONCLUSIONS: Better definition and classification of environmental hazards, and closer inter-disciplinary cooperation, will be necessary in future. Specific gene-environment interaction effects seem likely to prove most important in neuropsychiatric syndromes, and a less specific genetic influence on susceptibility to environmental stress among the common mental disorders.

Adolescent↗

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Adult↗

Regulation of the tinman homologues in Xenopus embryos.

Vertebrate homologues of the Drosophila tinman transcription factor have been implicated in the processes of specification and differentiation of cardiac mesoderm. In Xenopus three members of this family have been isolated to date. Here we show that the XNkx2-3, Xnkx2-5, and XNkx2-10 genes are expressed in increasingly distinctive patterns in endodermal and mesodermal germ layers through early development, suggesting that their protein products (either individually or in different combinations) perform distinct functions. Using amphibian transgenesis, we find that the expression pattern of one of these genes, XNkx2-5, can be reproduced using transgenes containing only 4.3 kb of promoter sequence. Sequence analysis reveals remarkable conservation between the distalmost 300 bp of the Xenopus promoter and a portion of the AR2 element upstream of the mouse and human Nkx2-5 genes. Interestingly, only the 3' half of this evolutionarily conserved sequence element is required for correct transgene expression in frog embryos. Mutation of conserved GATA sites or a motif resembling the dpp-response element in the Drosophila tinman tinD enhancer dramatically reduces the levels of transgene expression. Finally we show that, despite its activity in Xenopus embryos, in transgenic mice the Xenopus Nkx2-5 promoter is able to drive reporter gene expression only in a limited subset of cells expressing the endogenous gene. This intriguing result suggests that despite evolutionary conservation of some cis-regulatory sequences, the regulatory controls on Nkx2-5 expression have diverged between mammals and amphibians.

Animals↗

Primary pancreatic lymphoma: a case report, literature review, and proposal for nomenclature.

Primary neoplasms of the pancreas are most often adenocarcinoma. Non-Hodgkin's lymphoma (NHL) involving the pancreas is less common but well documented; the pancreas as the primary site of NHL is rare. The majority of patients with pancreatic cancer, whether it is adenocarcinoma or lymphoma, present with a mass in the head of the gland. Pancreatic lymphoma is often described as a large homogeneous mass with extra-pancreatic extension, with or without associated lymphadenopathy. Less common presentations are masses in the body or tail, or more rarely diffuse involvement of the pancreas. We present a case of diffuse pancreatic lymphoma with extra-pancreatic dissemination to the spleen and lymph nodes, and review the literature on pancreatic lymphoma. Because the definition of pancreatic lymphoma and primary pancreatic lymphoma varies, we also propose a nomenclature system to make future studies of pancreatic lymphoma more comparable.

Diagnosis, Differential↗

Quantitative autoradiography of Na+-dependent [3H]L-aspartate binding to L-glutamate transporters in rat brain: structure-activity studies using L-trans-pyrrolidine-2,4-dicarboxylate (L-t-PDC) and 2-(carboxycyclopropyl)-glycine (CCG).

Sodium-dependent binding of [3H]L-aspartate was studied in thaw-mounted horizontal sections of fresh-frozen (i.e. not fixed) rat brain. After the incubation with [3H]L-aspartate, the sections were exposed against a 3H-sensitive film and the resulting autoradiograms were evaluated by quantitative densitometry. Effects of several inhibitors were examined and their potency expressed as IC50 and nH. Together with previously published data, the present study supports the view that [3H]L-aspartate binding to fresh-frozen sections of rat brain represents interaction of the radioligand with the substrate-binding sites on glutamate transporters. The most potent inhibitors were (2S,3S,4R)-2-(carboxycyclopropyl)-glycine (L-CCG III) and (2S,4R)-4-methylglutamate. In contrast, L-anti,endo-3,4-methanopyrrolidine dicarboxylate (L-a,e-MPDC) was about an order of magnitude less potent. Only subtle regional variations in the characteristics of inhibitors of [3H]L-aspartate binding were detected. It is not certain whether these differences reflect regional variations in the distribution of individual glutamate transporters or regional peculiarities in their pharmacological characteristics. In particular, (2S,4R)-4-methylglutamate, shown previously to differentiate between GLT-1 (principal glutamate transporter in the forebrain) and GLAST (expressed mainly in the cerebellum), did not strongly differentiate between the binding of [3H]L-aspartate in forebrain and cerebellum. Computer-assisted molecular modelling using selected glutamate analogues with restricted conformation (L-trans-pyrrolidine-2,4-dicarboxylate and four isomers of 2-(carboxycyclopropyl)-glycine: L- and D-CCG I, L-CCG III and L-CCG IV) identified at least one area of unfavourable steric interaction. We conclude that the quantitative autoradiographic studies using [3H]L-aspartate or other transporter-specific ligands, will be a useful tool to study the pharmacology of substrate binding sites on glutamate transporters in the mammalian brain in situ.

ATP-Binding Cassette Transporters↗

Gender-specific differences in temporomandibular retrodiscal tissues of the goat.

Healthy, adult, male and female goat temporomandibular retrodiscal tissues were characterized to determine if biochemical differences existed between the genders. RNA concentrations were not different between male and female retrodiscal tissues; however, the DNA concentration in female retrodiscal tissues was 82% greater than in male retrodiscal tissues. Collagen concentrations were significantly greater in male retrodiscal tissues, and this was reflected in significant gender differences of type I and III collagen concentrations. More specifically, male temporomandibular retrodiscal tissues contained 70% more type I collagen and 119% more type III collagen when compared to female retrodiscal tissues. These differences in collagens and DNA reflect a gender difference in temporomandibular retrodiscal tissue composition that underlies divergent biomechanical and neurophysiological properties.

Animals↗

Prophylactic indomethacin: factors determining permanent ductus arteriosus closure.

BACKGROUND: Permanent closure of the ductus arteriosus (DA) requires both effective muscular constriction to block luminal blood flow and anatomic remodeling to prevent later reopening. OBJECTIVE: We examined the role of prophylactic indomethacin in producing permanent DA closure and the mechanism by which this occurs. METHODS: We studied 2 separate approaches to managing a patent DA in 257 preterm infants (gestation 24 to 27 weeks): (1) prophylactic indomethacin (all infants treated during the first 15 hours after birth) or (2) symptomatic treatment (infants in this group received indomethacin only if clinical symptoms appeared; infants whose ductus closed spontaneously and never received indomethacin were included in this group). Echocardiography was performed 24 to 36 hours after the last dose of indomethacin was administered or by age 5 days if spontaneous closure occurred. Infants were monitored for the development of ductus reopening. RESULTS: The prophylactic treatment group had a greater degree of initial ductus constriction, a higher rate of permanent anatomic closure, and a decreased need for surgical ligation than did the symptomatic treatment group. The degree of initial ductus constriction was the most important factor determining the rate of ductus reopening. Post-treatment echocardiography proved to be the best test for predicting eventual reopening. CONCLUSION: Prophylactic indomethacin improved the rate of permanent ductus closure by increasing the degree of initial constriction. Prophylactic indomethacin did not affect the remodeling process, nor did it alter the inverse relationship between infant maturity and subsequent reopening. Even when managed with prophylactic indomethacin, the rate of ductus reopening remained unacceptably high in the most immature infants.

Cardiovascular Agents↗