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Biomedical subjects

C Sargent

Publications and source records attributed to C Sargent.

At least 19 recordsLinked to original sources
PubMed2006

Swine and circovirus.

In the 1990s Post-weaning, multi-systemic wasting syndrome (PMWS) emerged in N. America and Europe as a major disease problem with significant welfare and economic consequences for pig producers. The disease, characterised by wasting, respiratory, enteric and lymphoid system problems in pigs of 4-16 weeks of age, has since spread so that today it has a global distribution. PCV-2 is consistently associated with PMWS, is more abundant in association with PMWS and is considered by many to be the causative agent of the syndrome. However, several lines of evidence indicate that PCV-2 is necessary but not sufficient to cause the full range of clinical signs associated with PMWS, suggesting the involvement of an as yet unidentified factor or factors. The process of identifying unknown agents and their respective roles in the pathogenesis of complex syndromes now has an ever broadening spectrum of analytical techniques available. Immune phenotyping, cytokine responses, micro-array profiling, and proteomics are just some of the techniques available. This paper describes the philosophy and the application of these and classical techniques in an integrated, holistic manner to the problem of PMWS and circoviruses, by examination of samples collected from a prospective, clinical case-control study, and discusses some of the preliminary findings in relation to the efforts to understand the aetiopathogenesis of PMWS.

Animals↗
PubMed2000

Selective ET(A) antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives.

The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ET(A) receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ET(A) antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC(50) 59 nM, rat aortic ET(A)). Optimization of 13a led to the identification of 27b, which exhibited an IC(50) of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 micromol/kg) and was duly proposed and accepted as a development candidate.

Administration, Oral↗
PubMed1999

Dietary exposure estimates of 30 elements from the UK Total Diet Study.

Dietary exposures of consumers to 30 elements (aluminium, antimony, arsenic, barium, bismuth, boron, cadmium, calcium, chromium, cobalt, copper, germanium, gold, iridium, iron, lead, lithium, manganese, mercury, molybdenum, nickel, palladium, platinum, rhodium, ruthenium, selenium, strontium, thallium, tin and zinc) estimated from the UK 1994 Total Diet Study are reported, and compared with those from previous UK Total Diet Studies and those from other countries. Dietary exposure estimates were generally low and, where comparisons are possible, similar to those from other countries and below the relevant Provisional Tolerable Weekly Intakes and Provisional Maximum Tolerable Daily Intakes. For most of those elements included in previous UK Total Diet Studies, dietary exposures have declined.

Diet↗
PubMed1998

Selective endothelin A receptor antagonists. 3. Discovery and structure-activity relationships of a series of 4-phenoxybutanoic acid derivatives.

The third in this series of papers describes our further progress into the discovery of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of diseases in which a pathophysiological role for endothelin has been implicated. These include hypertension, ischemic diseases, and atherosclerosis. In earlier publications we have outlined the discovery and structure-activity relations of two moderately potent series of nonpeptide ETA receptor antagonists. In this paper, we describe how a pharmacophore model for ETA receptor binding was developed which enabled these two series of compounds to be merged into a single class of 4-phenoxybutanoic acid derivatives. The subsequent optimization of in vitro activity against the ETA receptor led to the discovery of (R)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]-4-(2-methylphenyl)b utanoi c acid (12m). This compound exhibits low-nanomolar binding to the ETA receptor and a greater than 1000-fold selectivity over the ETB receptor. Data are presented to demonstrate that 12m is orally bioavailable in the rat and is a functional antagonist in vitro and in vivo of ET-1-induced vasoconstriction.

Administration, Oral↗
PubMed1998

Intercessory Prayer for ill Health: A Systematic Review.

OBJECTIVES: To review the effectiveness of prayer as an additional intervention for those with health problems already receiving standard medical care. SEARCH STRATEGY: Electronic Searches of Biological Abstracts, CINAHL, The Cochrane Controlled Trials Register, EM-BASE, MEDLINE, PsycLIT, and Sociofile were undertaken. All references of articles selected were searched for further relevant trials. SELECTION CRITERIA: Randomised and quasi-randomised trials of personal, focused, committed and organised intercessory prayer on behalf of anyone with a health problem were considered. Outcomes such as achievement of desired goals, death, illness, quality of life and well-being for the recipients of prayer, those praying and the caregivers were sought. DATA COLLECTION AND ANALYSIS: Studies were reliably selected and assessed for methodological quality. Data were extracted by 4 reviewers working independently. Dichotomous data were analysed on an intention-to-treat basis, and continuous data with over 50% completion rate are presented. MAIN RESULTS: There was no evidence that prayer affected the numbers of people dying from leukaemia or heart disease (OR 0.64, CI 0.32-1.27), or that it decreased coronary care complications (OR 1.05, CI 0.49-2.26) or the time participants stayed in hospital. There were significantly fewer 'intermediat//poor outcomes' for those with heart disease in the prayed-for group (OR 0.49, CI 0.30-0.80), and this finding was robust to some changes in definition. CONCLUSIONS: This review provides no guidance for those wishing to uphold or refute the effect of intercessory prayer on the outcomes studied in the available trials. Therefore, in the light of the best available data, there are no grounds to change current practices. There are very few completed trials of the value of intercessory prayer. The evidence presented so far is interesting enough to justify further study. If prayer is seen as a human endeavour it may or may not be beneficial, and further trials could uncover this. It could be the case that any effects are due to elements beyond present scientific understanding that will, in time, be understood. If any benefit derives from God's response to prayer it may be beyond any such trials to prove or disprove.

Journal Article↗
PubMed1996

Kainic acid increases the expression of the prohormone convertases furin and PC1 in the mouse hippocampus.

Prohormone convertases (PCs) belong to the mammalian family of subtilisin/kexin-like enzymes which have been implicated in the posttranslational processing of precursor proteins. Several PCs are produced in the central and peripheral nervous system, and only a few specific precursor-substrates have been identified in vivo. In the nervous system, PCs may be involved in intracellular processing of precursors for neuropeptides, hormones and neurotrophic factors, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). To study the interrelationships between the convertases furin, PC1 and PC2, and the neurotrophins NGF, BDNF and NT-3, we compared their mRNA distribution in different tissues. We also examined their expression in the hippocampus of mice undergoing kainic acid-induced seizures. In this experiment, in situ hybridization (ISH) demonstrated that the levels of mRNA for furin, PC1 and BDNF increased maximally at 3 h after kainic acid administration, followed by a decline to normal levels by 96 h. NGF showed small changes, while NT-3 was downregulated with minimal expression levels between 3 to 12 h. Double ISH with radioactively-labeled riboprobes and digoxigenin-labeled riboprobes demonstrated colocalization of furin with NGF and BDNF in the mouse submaxillary gland, and of furin and PC1 with BDNF in the trigeminal ganglion. Based on colocalization studies and evidence of coordinate expression with NGF and BDNF, we suggest the involvement of furin in processing of proNGF, and of both furin and PC1 in processing of proBDNF.

Animals↗
PubMed1996

Ways of knowing about birth in three cultures.

This article examines the concept of authoritative knowledge elaborated by Brigitte Jordan, using examples of birthing systems in Mexico, Texas, and Jamaica. We explore the linkages between the distribution of knowledge about birth and the use of technology; the valuation of biomedical and alternative "ways of knowing" about birth; the production of authoritative knowledge through interaction; and the relationship between authoritative knowledge and social status. In the Maya low-technology, collaborative birthing system in Mexico, the midwife and other adult women share knowledge about birth. In contrast, Spanish-speaking women undergoing cesarean delivery in a high-technology public hospital in Texas are, due to their limited English, only minimally able to interact with hospital staff. While they acknowledge the authoritative position of biomedical personnel and value technology, they protest their inability to communicate during their hospitalization. Jamaican women deliver in a formerly high-technology hospital system that is now experiencing economic austerity measures that render it increasingly dysfunctional. While use of technology is infrequent in the Jamaican case, authoritative knowledge remains vested in biomedicine. By means of three examples we respond to Jordan's call for a rethinking of authoritative knowledge in high- and low-technology settings.

Authoritarianism↗
PubMed1995

A bioassay for topical and systemic effect of three inhaled corticosteroids.

BACKGROUND: Comparisons of relative potency for the three inhaled corticosteroids in the United States are limited to assessment of skin blanching. OBJECTIVE: Development of a method for comparing relative potencies of inhaled corticosteroids for topical effect on human airway and systemic effect. METHODS: With use of partial suppression of immediate response to inhaled allergen and 24-hour urinary free cortisol output, three-point dose-response curves were constructed for beclomethasone dipropionate (50 micrograms/puff), triamcinolone acetonide (100 micrograms/puff), and flunisolide (250 micrograms/puff). A randomized, parallel, single-blind study design was used. Dosing began with one puff four times a day for flunisolide and two puffs four times a day for the others. Doses were doubled after 1 week and again after a second week. RESULTS: Twenty-five patients completed the study. Dose-response relationships were shown for each inhaled corticosteroid for both topical and systemic effect. Dose-response curves for the three preparations were similar when response was plotted against delivered dose in micrograms. CONCLUSION: Within the limits of the assays, relative potencies of the three preparations appeared to be approximately equivalent for both topical and systemic effect when dose was expressed in micrograms. Relative potency per puff is therefore approximately proportional to the dose delivered. This method has potential for evaluation of relative potency of newer inhaled corticosteroids and the relative advantage of alternative delivery systems.

Administration, Inhalation↗
PubMed1993

ATP-sensitive potassium channels and skeletal muscle function in vitro.

Compounds that act at ATP-modulated potassium channels (KATP) were tested in an in vitro model of skeletal muscle ischemia. The extensor digitorum longus muscles were removed from anesthetized rats and placed in tissue baths, and contractions were elicited by electrical field stimulation at 0.2 Hz. During normoxia, the force of contraction gradually decayed to about 55% of the peak over 85 min. None of the KATP openers tested, cromakalim (300 microM), P-1075 (10 microM) and pinacidil (100 microM), affected twitch force during normoxia. However, when the muscles were made anoxic, all three compounds greatly accelerated the loss of function in a concentration-related manner. For example, the cromakalim/vehicle ratios of the area under the force-time curve during anoxia were 0.98 +/- 0.03, 0.77* +/- 0.03 and 0.72* +/- 0.04 for cromakalim at 30, 100 and 300 microM, respectively (*P < .05). Upon reoxygenation, muscles treated with the KATP openers recovered twitch force to a greater extent than those treated with vehicle. Glyburide (1 or 10 microM) had no effect on its own, but it was able to prevent fully the effects of KATP openers during both anoxia and reoxygenation, indicating that the effects of the KATP openers were mediated by KATP. These results suggest that KATP openers would not be beneficial in the treatment of skeletal muscle ischemia in vivo but that they may be useful in preserving skeletal muscle function in cases of ischemia followed by reperfusion.

Animals↗
PubMed1992

Transformations in maternity services in Jamaica.

Analysis of the current organization and delivery of maternity care in Jamaica profits not only from an assessment of recent health issues but from consideration of the development of maternity services over the past century. Historical analysis indicates that a critical element in public health policy has been the effort to encourage use of biomedical obstetrical care and to eliminate the lay midwife. However, while women increasingly patronize hospitals, the delivery of services has deteriorated, resulting in widespread client dissatisfaction. Economic contingencies have contributed to the decline in maternity services, but health personnel manifest the ideology prevalent throughout the colonial era equating social irresponsibility with health complications. The cultural construction of illegitimacy and maternity is shown to be a dimension of class relations having an impact on health policy throughout Jamaica's history.

Health Policy↗
PubMed1991

Comparison of ZFY and ZFX gene structure and analysis of alternative 3' untranslated regions of ZFY.

We have cloned and sequenced transcripts from the X- and Y-linked zinc-finger genes ZFX and ZFY respectively and discuss a possible mechanism of post-transcriptional control by which these genes can be widely expressed but translated in only specific tissues. We report the identification of a novel 3'UTR (untranslated region) present in ZFY which is highly conserved among primates and contains a series of motifs implicated as mRNA instability determinants. These sequences can be substantially removed by polyadenylation directed from consensus (AATAAA) and non-consensus (AATATAAA) sequences in adult testis. The DNA-binding domains of the ZFY and ZFX proteins are compared using present models for zinc-finger/DNA interactions. Additionally, the genomic organisation of the ZFY coding sequence is presented as compared to that of ZFX.

Amino Acid Sequence↗