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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 361 records · Page 20Linked to original sources

m-Chlorophenylpiperazine decreases food intake in a test meal.

We studied the effect of the 5-HT receptor agonist, m-chlorophenylpiperazine (mCPP) (0.4 mg/kg), on food intake in 12 healthy female volunteers, in a double-blind placebo controlled design. Compared to placebo, mCPP significantly lowered food intake in a test meal. Treatment with mCPP also caused significant increases in ratings of nausea and light-headedness, though these effects had remitted by the time of the test meal. The results suggest that activation of brain 5-HT2C receptors may lower food intake in humans; it is also possible, however, that the hypophagic effect of mCPP in the present study could be a consequence of its adverse subjective side effects.

Adult↗

Immediate-early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischaemic injury to the young rat brain.

A unilateral hypoxia-ischaemia (HI) 21-day-old rat preparation was used to assess the effects of HI on the expression of the immediate-early gene proteins (IEGPs) c-Fos/FRAs, Fos B, c-Jun, Jun B, Jun D, Krox 20, Krox 24, and on the mRNA for the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Moderate HI (15 min hypoxia) produced delayed, selective neuronal death and was associated with a rapid induction of c-Fos, Fos B, Jun B, Jun D, and c-Jun proteins, but not Krox 20 protein or BDNF mRNA, in neurons on the side of HI and also a delayed expression of c-Jun (and to a lesser extent c-Fos/FRA's and Fos B) 24-48 h after HI in neurons that underwent delayed neuronal death. Krox 24 showed an initial induction followed by a long-lasting suppression of its expression in regions undergoing cell loss. Severe HI (60 min hypoxia) resulted in seizures and rapid neuronal loss and infarction (necrotic cell death) on the side of HI, and was associated with early induction of c-Fos, Fos B, c-Jun, Jun B, Jun D, Krox 20 and Krox 24 protein and BDNF mRNA in neurons on the non-ligated side of the brain. Fos, c-Jun, Jun B, Jun D and Krox 24, but not Krox 20, Fos B, or BDNF mRNA, were also induced in non-nerve cells on the damaged side of the brain after both moderate and severe HI, and many of these cells appeared to be dividing. Thus, moderate HI induces IEGP's in neurons and non-nerve cells in damaged regions, whereas severe HI induces IEGP's and BDNF in non-damaged regions. c-Jun (and to a lesser extent c-Fos/FRA's) showed a prolonged expression in neurons undergoing delayed, but not necrotic, cell death suggesting that they may be involved in the biochemical cascade that causes selective delayed neuronal death. BDNF was not induced by HI, and therefore, does not appear to play an endogenous neuroprotective role in the CNS.

Animals↗

A strategy for trauma debriefing after railway suicides.

Following an increase in the incidence of railway suicide from an average of four events a year up to 1989 to 12 in 1990 an initiative was developed between the District Department of Clinical and Community Psychology, Exeter Health Authority and British Rail, Western Region. Traincrew leaders and management had become increasingly aware of the severity of the short- and long-term effects on drivers of experiencing a suicide. Although a management strategy had been developed over time to deal with what had been a rare phenomenon it was clear that such a dramatic increase in suicides warranted a more professional approach to debriefing and trauma counselling. This paper describes the strategies adopted by psychologists in developing an understanding of the stresses of experiencing suicides and other major incidents. The outcome of small group sessions with affected drivers is outlined. An account of the strategy developed through workshops with traincrew leaders is detailed and a three-stage debriefing (shock, search, adjustment) and follow-up protocol is discussed. This process is proposed for adoption as normal procedure following suicides or similar traumas for drivers and line managers.

Adaptation, Psychological↗

Competitive enzyme-linked immunosorbent assay for the determination of zinc bacitracin in animal feedingstuffs.

Traditionally, bioassay has been the chosen technique for the determination of bacitracin compounds in animal feedingstuffs. However, detection and determination of this antibiotic have given problems when it is present at low levels. A competitive enzyme-linked immunosorbent assay (ELISA) by which it is possible to detect both bacitracin and zinc bacitracin at levels as low as 1 mg kg-1 in animal feeds is described. The ELISA technique has been used in this laboratory to monitor samples from a drug stability storage trial for the presence of zinc bacitracin. In addition, individual polypeptide components of zinc bacitracin have been separated by high-performance liquid chromatography. Fractions were collected and tested by the ELISA technique to assess the response between individual components and the primary antibody. The response was compared with known microbiological activity.

Animal Feed↗

Investigation of the stability of medicinal additives in animal feedingstuffs to prepare reference feeds.

The stability of several medicinal additives in cattle, pig and poultry feeds has been monitored. The feeds were stored at various temperatures under different conditions; processes such as freeze-drying, gamma-irradiation and pelletization were also applied. The medicinal additives appeared to be more stable in the feeds stored at reduced temperatures and under conditions that totally exclude light. Processing of feeds and storage at elevated temperature appeared to reduce the content of the medicinal additives examined.

Animal Feed↗

Somataglycan-S: a neuronal surface proteoglycan defines the spinocerebellar system.

The formation and maintenance of functionally specific neuronal networks may depend on specific proteoglycans localized to the surface membranes of a subset of neurons. Monoclonal antibody (MAb) 6A2 labeled a distinct subset of CNS neurons: the somas and proximal dendrites of cells making up the spinocerebellar and reticular systems. These pathways contribute to proprioceptive and exteroceptive functions. Ultrastructurally, MAb 6A2 immunoreactivity was distributed focally along the cell surface membranes and the adjacent extracellular space. On western blots of immunoaffinity-purified preparations from cerebellar homogenates, a major, broad band of approximately 400 kDa is labeled by MAb 6A2. Increased electrophoretic mobility of the purified antigen after digestion with chondroitinase ABC and keratanase suggests that the antigen is a proteoglycan bearing chondroitin sulfate and keratan sulfate glycosaminoglycans. Unsulfated N-acetyl-galactosamine residues linked to unsaturated uronic acid constituted the initial disaccharide in the chondroitin sulfate glycosaminoglycan chains. N- and O-linked oligosaccharides on the core protein were detected by the biotinylated lectins wheat germ agglutinin and Jacalin, respectively, and by MAb anti-HNK-1. Lyase and glycosidase digests result in a 280-kDa band. This proteoglycan, somataglycan-S, may provide a key to the role of glycoconjugates in determining neuronal diversity and system specificity.

Animals↗

Evaluating customer satisfaction with colonoscopy.

Twenty patients were interviewed shortly after colonoscopy, and the adjectives and phrases they used to describe the experience were formed into a 31-item questionnaire, on which each item was rated using a seven-point scale. This questionnaire was completed by 110 similar patients. Principal components analysis of these responses yielded three components: satisfaction, physical discomfort, and emotional distress. This demonstrates that patients' experience of colonoscopy is multi-dimensional; whether or not a patient feels satisfied is unrelated to how distressing or uncomfortable it is. Component-based scale scores were calculated so as to quantify every patient's experience on each dimension. Procedures performed by the most experienced endoscopist were no less uncomfortable than others, but they were less distressing. Female patients experienced more discomfort than males, but were no more distressed or less satisfied. This questionnaire could be useful in any future audit of colonoscopy from the patients' point of view.

Analysis of Variance↗

Accumulated oxygen deficit and short-distance running performance.

Recent studies have suggested that determining the accumulated oxygen deficit (AOD), in units of oxygen equivalents per kilogram body mass (ml O2 Eq.kg-1), during a short exhaustive run, may represent a non-invasive measure of anaerobic metabolism. However, there is little information either on the reproducibility of the laboratory determination or its relationship with human performance. The purpose of the present investigation was to determine the reproducibility of AOD during inclined treadmill running (study 1), and to examine its relationship with short-distance running performance (study 2). Twelve volunteers (11 males, 1 female) took part in study 1 and AOD was determined (relative exercise intensity approximately 120% VO2 max) on two separate occasions at a treadmill inclination of 10.5%; the laboratory-measured AOD values were 65.2 +/- 10.9 vs 66.3 +/- 12.5 ml O2 Eq.kg-1, respectively (r = 0.94, P < 0.01). A second subject group (10 males, 4 females) undertook study 2, which investigated AOD values and track times over 100, 400 and 800 m. The mean calculated AOD value was 66.1 +/- 12.0 ml O2 Eq.kg-1, and the average track times were 13.6 +/- 1.3, 60.9 +/- 6.8 and 138.8 +/- 18.5 s for the 100, 400 and 800 m, respectively. The r-values for the relationship between AOD and track time were -0.88, -0.82 (P < 0.01) and -0.61 (P < 0.05) for the 100, 400 and 800 m, respectively. The results of the present study suggest that the AOD (ml O2 Eq.kg-1) is a unique and reproducible physiological characteristic which is strongly correlated with sprint capacity.

Adult↗

Identification of quantitative trait loci influencing wood specific gravity in an outbred pedigree of loblolly pine.

We report the identification of quantitative trait loci (QTL) influencing wood specific gravity (WSG) in an outbred pedigree of loblolly pine (Pinus taeda L.). QTL mapping in an outcrossing species is complicated by the presence of multiple alleles (> 2) at QTL and marker loci. Multiple alleles at QTL allow the examination of interaction among alleles at QTL (deviation from additive gene action). Restriction fragment length polymorphism (RFLP) marker genotypes and wood specific gravity phenotypes were determined for 177 progeny. Two RFLP linkage maps were constructed, representing maternal and paternal parent gamete segregations as inferred from diploid progeny RFLP genotypes. RFLP loci segregating for multiple alleles were vital for aligning the two maps. Each RFLP locus was assayed for cosegregation with WSG QTL using analysis of variance (ANOVA). Five regions of the genome contained one or more RFLP loci showing differences in mean WSG at or below the P = 0.05 level for progeny as grouped by RFLP genotype. One region contained a marker locus (S6a) whose QTL-associated effects were highly significant (P > 0.0002). Marker S6a segregated for multiple alleles, a prerequisite for determining the number of alleles segregating at the linked QTL and analyzing the interactions among QTL alleles. The QTL associated with marker S6a appeared to be segregating for multiple alleles which interacted with each other and with environments. No evidence for digenic epistasis was found among the five QTL.

Alleles↗

Digital imaging colposcopy, image analysis and quantification of the colposcopic image.

OBJECTIVE: To investigate the use of a digital imaging system for colposcopy, its use for image analysis and quantification of the colposcopic features that may predict histological outcome as defined by large loop excision of transformation zone. DESIGN: Prospective programme study of all patients undergoing colposcopy for cytological abnormalities. SETTING: Dudley Road Hospital, Birmingham. SUBJECTS: Fifty consecutive patients having cytological and colposcopic abnormality treated with large loop excision of transformation zone formed the study group. MAIN OUTCOME MEASURES: Pretreatment and colposcopic features correlated with histological diagnosis of excised transformation zone. RESULTS: Index cytology and current smoking status are the most important variables for prediction of histological diagnosis. Other important variables are focality of lesion, surface pattern, intercapillary distance and degree of acetowhiteness. CONCLUSION: Digital imaging colposcopy allows image capture, processing and objective analysis. This methodology holds advantages for basic and clinical research, teaching, diagnostics and clinical audit. The system can act as a quality control tool for colposcopy units. This system should prove invaluable for further quantitative studies, for natural history studies and for those patients with deferred treatment of their cytological and colposcopic abnormalities. The statistical models described may be incorporated into the system and can aid the colposcopist in management of the woman with abnormal cervical cytology and colposcopic abnormality.

Adolescent↗

Urease-mediated destruction of bacteria is specific for Helicobacter urease and results in total cellular disruption.

The survival of Helicobacter mustelae, Proteus mirobilis, Escherichia coli and Campylobacter jejuni in the presence of urea and citrate at pH 6.0 was examined. H. mustelae, which has urease activity similar to H. pylori, had a markedly reduced survival, median 2.5% (0-78%) (P < 0.001) when incubated under these conditions. Only 7% of the ammonia produced by H. mustelae urease activity was recovered from the buffer, a similar percentage to that previously reported with H. pylori. None of the other organisms, all of which had lower urease activity, had impaired survival under these conditions. Electron microscopical studies demonstrated extensive structural damage to H. pylori following exposure to urea and citrate at pH 6.0. This structural damage to the organisms makes it unlikely that the low recovery of ammonia was due to retention of ammonia within the bacteria and suggests that the ammonia may have been incorporated into glutamate or other amino acids. Incorporation of ammonia into these compounds would deplete the cell of the key metabolic intermediate alpha-ketoglutarate and could thus explain the mechanism of the urease-dependent destruction of the organism.

Ammonia↗

Comparison between carbohydrate feedings before and during exercise on running performance during a 30-km treadmill time trial.

The purpose of this study was to compare the effects of a carbohydrate-electrolyte solution, ingested during exercise, with the effects of a preexercise carbohydrate meal on endurance running performance. Ten endurance-trained males completed two 30-km treadmill runs. In one trial subjects consumed a placebo solution 4 hr before exercise and a carbohydrate-electrolyte solution immediately before exercise and every 5 km (C). In the other trial, subjects consumed a 4-hr preexercise high-carbohydrate meal and water immediately before exercise and every 5 km (M). Performance times were identical for M and C, and there was no difference in the self-selected speeds. Oxygen uptake, heart rates, perceived rate of exertion, and respiratory exchange ratios were also similar. However, blood glucose concentration was higher in C during the first 20 km of the 30-km run. In M, blood glucose concentration was maintained above 4.5 mmol.L-1 throughout exercise. Thus, the two conditions produced the same 30-km treadmill running performance time.

Adult↗

Neutralization of primary human immunodeficiency virus type 1 isolates by the broadly reactive anti-V3 monoclonal antibody, 447-52D.

Human monoclonal antibody 447-52D binds to the V3 determinant of the human immunodeficiency virus type 1 (HIV-1) gp120 external glycoprotein. Its binding requires the expression of the GPxR sequence at the center of the V3 domain. HIV-1 variants that are adapted to replication in T-lymphoid cell lines and express this sequence motif are efficiently neutralized by the antibody (M. K. Gorny, A. J. Conley, S. Karwowska, A. Buchbinder, J.-Y. Xu, E. A. Emini, S. Koenig, and S. Zolla-Pazner, J. Virol. 66:7538-7542, 1992). In the present study, the antiviral activity of 447-52D was further defined with regard to its ability to mediate neutralization of primary HIV-1 clinical isolates. Again, the antibody was found to potently neutralize those isolates that expressed the binding sequence. We confirmed that this determinant is commonly expressed by virus isolates belonging to the subtype (clade) B sequence classification. As such, 447-52D may be useful for prophylactic and immunotherapeutic intervention. In addition, the study demonstrated that neutralization of primary HIV-1 isolates is possible if mediated by an appropriate antibody.

AIDS Vaccines↗

Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of human immunodeficiency virus type 1.

A human immunoglobulin G1 lambda monoclonal antibody (MAb), 697-D, was developed that recognizes the V2 region of human immunodeficiency virus type 1 (HIV-1) gp120. Substitutions at amino acid positions 176/177, 179/180, 183/184, and 192 to 194 in the V2 loop of gp120 each completely abolished the binding capacity of 697-D in an enzyme-linked immunosorbent assay format. Competition analysis with three different neutralizing murine anti-V2 MAbs confirmed the specificity of 697-D. The 697-D epitope is primarily conformation dependent, although there was weak reactivity of the MAb with a V2 peptide spanning residues 161 to 180. Treatment of recombinant gp120 HIVIIIB with sodium metaperiodate, which oxidizes carbohydrates, abolished the binding of the MAb, showing the dependence of the epitope on intact carbohydrates. The broad reactivity of 697-D was displayed by its binding to the gp120 molecules from four of four laboratory isolates and five of five primary isolates. The MAb 697-D neutralized three out of four primary isolates but failed to neutralize any of four laboratory strains of HIV-1. 697-D and a human anti-V3 MAb, 447-52-D, displayed similar potency in neutralizing primary isolates, indicating that the V2 region of gp120, like the V3 region and the CD4-binding domain, can induce potent neutralizing antibodies against HIV-1 in humans.

Amino Acid Sequence↗

The influence of pre-exercise glucose ingestion on endurance running capacity.

Drinking a concentrated glucose solution less than 1 h before the start of prolonged submaximal exercise has been reported to reduce endurance capacity during cycling. The purpose of this study was to re-examine the influence of pre-exercise ingestion of a concentrated glucose solution on endurance running capacity. Nine recreational runners (five men and four women) ran to exhaustion on a level treadmill, at speeds equivalent to 70% VO2max, on two occasions separated by at least 1 week. The runners ingested either a solution containing 75 g of glucose in 300 ml of water (G trial), or 300 ml of sweetened water (P trial) 30 min before each trial. As a consequence, the blood glucose concentrations were 55% higher at the beginning of the G trial compared with those recorded for the P trial (G trial, mean(s.e.) blood glucose = 6.3(0.7) mmol l-1 versus P trial, mean(s.e.) blood glucose = 4.1(0.3) mmol l-1; P < 0.01). Nevertheless, there were no differences in the running times to exhaustion between the two trials (G trial, mean(s.e.) 133.79(11.0) min versus P trial, mean(s.e.) 121.16(8.1) min). The results of this study show that ingesting a 25% glucose solution 30 min before exercise does not reduce the endurance capacity of recreational runners when the exercise intensity is equivalent to 70% VO2max.

Adult↗

Low prevalence of Helicobacter pylori in inflammatory bowel disease: association with sulphasalazine.

The prevalence of IgG antibodies to Helicobacter pylori was examined in 110 patients with inflammatory bowel disease (IBD) (63 ulcerative colitis, 47 Crohn's disease) and compared with 100 age and sex matched control patients. The overall prevalence of H pylori seropositivity in the IBD patients was 22%, which was significantly less than that of 52% in the controls (p < 0.002). There was no difference in prevalence between ulcerative colitis and Crohn's patients. The low seropositivity in the IBD patients resulted from a very low prevalence of 10% in those currently receiving sulphasalazine (n = 40) and similarly low prevalence of 7% in those previously receiving sulphasalazine (n = 30). In those receiving olsalazine or mesalazine and who had never had sulphasalazine, the prevalence of seropositivity was 45%. Further studies using 14C urea breath test and microscopy of antral biopsy specimens confirmed that the negative serology in patients receiving sulphasalazine resulted from absence of the infection rather than absence of humoral immune response to it. In six control patients with H pylori infection, a two week course of sulphasalazine (500 mg four times daily) only caused slight suppression of the 14C urea breath test. In vitro studies failed to show any direct antibacterial effect of sulphasalazine on H pylori. These findings indicate that longterm treatment with sulphasalazine leads to eradication of H pylori infection and that this does not result from a direct antibacterial effect. It may be caused by the drug treating the gastritis and thereby depriving the bacterium of essential nutrients exuded by the inflamed mucosa.

Adult↗

Narratives of aging and social problems in medical encounters with older persons.

This study asks: How do older patients and their doctors deal with social problems in the discourse of routine medical encounters? Our research has been influenced by a growing recognition of narratives as an important analytic focus in the study of patient-doctor communication. We attempted to advance theoretical knowledge by emphasizing elements of sociocultural context, ideology, social control, underlying structure, and features of discourse that appear marginal to medicine's technical tasks. Based on a critical review of both quantitative and qualitative techniques in research on patient-doctor communication, we tried to move methodologically beyond prior work by developing a new interpretive method with systematic criteria to guide the sampling of encounters, transcription of recordings, interpretation of transcripts, and presentation of findings. We applied the interpretive method to 50 encounters selected randomly from a stratified random sample of 336 audiotaped encounters involving patients and primary care internists. As shown by illustrative encounters, a characteristic narrative structure and sequencing emerge, which tend to marginalize contextual problems, to leave them incompletely expressed, and to reinforce ideologies of stoicism and individualism.

Aged↗