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Biomedical subjects

J West

Publications and source records attributed to J West.

At least 127 records · Page 7Linked to original sources

Exercise and diving, two conflicting stimuli influencing cardiac vagal tone in man.

1. In order to increase our understanding of the central regulation of human cardiac vagal motoneurones we studied the interaction between two opposing influences on cardiac vagal tone, one related to diving and the other to exercise. 2. The heart rate response to cooling the face (0 degrees C, trigeminal cutaneous receptor stimulation, TGS) and to a brief isometric muscle contraction was studied in fourteen healthy young adults (8 males, 6 females) during controlled ventilation at supine rest. 3. Fluctuations in R-R interval were quantified by spectral analysis. In addition the absolute values of R-R intervals occurring in any one of ten arbitrary phases of a respiratory cycle were measured over thirty to sixty cycles to give a graph of the changes in R-R interval throughout a respiratory cycle. 4. TGS produced a significant decrease in heart rate (-21 +/- 2 beats min-1 in females, -19 +/- 2 beats min-1 in males; means +/- S.E.M.). In addition the autospectral plots of R-R interval variability showed that during TGS there was a significant increase both in the high frequency peak and in the low frequency peak in all subjects. These data suggested that in these experiments the bradycardia of TGS was due to an increase in cardiac vagal tone. 5. Voluntary isometric contractions at 40 and 60% of maximum (40% MVC, 60% MVC) were timed to occur early in expiration or early in inspiration. Analysis of the changes in R-R interval produced by these contractions was confined to the respiratory cycle in which they were initiated. The early onset of these changes was interpreted as showing a decrease in cardiac vagal tone. 6. The 40% MVC and 60% MVC increased heart rate significantly within one respiratory cycle with maximum effects having a mean of 9.5 +/- 3 and 11 +/- 3 beats min-1, respectively. When isometric muscle contraction was initiated during TGS the 60% MVC but not the 40% MVC was able to significantly decrease R-R interval and hence increase heart rate. 7. It is concluded that the TGS excitatory inputs and the muscle inhibitory inputs to cardiac vagal neurones do not interact by one input gating the other early in the pathway but more probably by a process of algebraic summation closer to the cardiac vagal neurone.

Adult↗

Physical map and organization of Arabidopsis thaliana chromosome 4.

A physical map of Arabidopsis thaliana chromosome 4 was constructed in yeast artificial chromosome clones and used to analyze the organization of the chromosome. Mapping of the nucleolar organizing region and the centromere integrated the physical and cytogenetic maps. Detailed comparison of physical with genetic distances showed that the frequency of recombination varied substantially, with relative hot and cold spots occurring along the whole chromosome. Eight repeated DNA sequence families were found in a complex arrangement across the centromeric region and nowhere else on the chromosome.

Arabidopsis↗

B lymphocytes can be competent antigen-presenting cells for priming CD4+ T cells to protein antigens in vivo.

The potential role of different subsets of APCs to stimulate naive CD4+ T cells to peptide and protein Ags in vivo was examined. Mice lacking B cells (microMT knockout mice) were impaired in their priming to protein but not peptide Ags, suggesting a requirement for B cells in priming to protein Ags in vivo. Experiments designed to determine the ability of splenic dendritic cells (DCs) and B lymphocytes to take up peptide or protein Ags in vivo demonstrated that peptide Ags were taken up preferentially by DCs, whereas proteins were taken up by Ag-specific B cells in vivo. A further examination of the Ag-specific B cells pulsed in vivo with protein Ags revealed a marked up-regulation in surface expression of B7-2 costimulatory molecules, detectable as early as 4 h after Ag administration. Based on their potency in the uptake and processing of protein Ags as well as their ability to up-regulate costimulatory molecules through Ag internalization, we suggest that Ag-specific B cells will be an important APC in priming naive CD4+ T cells to protein Ags in vivo.

Animals↗

Anger attacks in eating disorders.

As central nervous system serotonergic dysregulation has been postulated to exist in both eating and aggression disorders, we hypothesized that anger attacks would be more common among patients with eating disorders than among control subjects. In addition, we wanted to examine possible relationships between the presence of anger attacks and the type or severity of the eating disorder. Subjects were 39 normal female volunteers and 132 female outpatients with anorexia nervosa, bulimia nervosa, or both. Forty-one (31%) of the patients met criteria for anger attacks compared with four (10%) of the control subjects. Bulimic patients reported the highest prevalence of anger attacks to be associated with greater severity of illness. In addition, patients with eating disorders who have anger attacks had significantly more depressive symptoms than patients without these attacks. Central serotonergic function is involved in such diverse processes as feeding behavior, mood regulation, and anger and aggression. The higher prevalence of anger attacks among patients than among control subjects may reflect central hyposerotonergic function, found in previous studies to be present in both eating disorders and pathologic aggression. Supporting this interpretation is the finding that the prevalence of anger attacks increased, although nonsignificantly, with the severity of bulimia, which has previously been shown to be inversely correlated with central serotonergic activity.

Adolescent↗

Recent studies on the zoopharmacognosy, pharmacology and neurotoxicology of sesquiterpene lactones.

Aspects of recent research on the biological activities of sesquiterpene lactones (SQLs) are presented. Several SQLs have been identified as important constituents of plants consumed by animals for presumed medicinal value and is a focus of research in zoopharmacognosy. Recent in vivo antitumor studies with parthenin and eupatoriopicrin are discussed as well as the reports of the antiulcer activity of dehydroleucodin. Helenalin has recently been reported to have cardiotonic activity. Research on the neurotoxicity of repin, a compound reported to cause a Parkinson's-like disease in horses, is also highlighted.

Animals↗

Role of ECMO in the treatment of respiratory syncytial virus bronchiolitis: a collaborative report.

AIM: To report the collaborative experience of extracorporeal membrane oxygenation (ECMO) in the treatment of respiratory syncytial virus (RSV) bronchiolitis between April 1989 and January 1995. METHODS: The medical records of patients with confirmed RSV bronchiolitis referred to three centres (Leicester, Glasgow, and Great Ormond Street) were reviewed. RESULTS: Twenty four infants were identified. Seventeen had been born prematurely (gestational range 23-40 weeks, median 30 weeks). Thirteen infants had been mechanically ventilated after birth and seven of these had evidence of bronchopulmonary dysplasia (BPD). The age of onset of RSV infection varied from three to 64 weeks (mean 17.4 weeks, median 12 weeks). Ventilation before ECMO ranged from one to 16 days and oxygenation indices at the time of referral ranged from 21-73 (mean 39). Ribavirin was used in eight of the 24 patients. Sixteen patients received venoarterial and eight veno-venous ECMO. ECMO hours ranged from 32-647 (median 196 hours). One infant died (survival rate 96%). Cranial ultrasound abnormalities were detected in three patients. However, at follow up only one of the 23 survivors had evidence of developmental delay. CONCLUSION: A group of paediatric patients in whom ECMO can be of benefit has been identified. The use of ECMO should be considered when other means of support prove unsuccessful.

Age of Onset↗

Fecal contamination in child day care centers: cloth vs paper diapers.

OBJECTIVES: Cloth diapers with front closure and all-in-one design were compared with paper diapers containing absorbent gel material for their influence on fecal contamination of the environment in licensed child day care centers. METHODS: One infant room and two toddler rooms in each of four day care centers were monitored for the presence of fecal bacteria. Microbial samples were taken from the play/sleep area, the diaper-changing area, and the hands of the caregivers and the children. Sampling was done twice weekly for two 4-week periods. Each center used either cloth or paper diapers during the first period, changing to the other diaper type during the second period. RESULTS: A total of 1722 samples were cultured, 881 during the first 4 weeks and 841 during the second 4 weeks. The frequency of isolation of fecal organisms ranged from a low of 12% of the total bacteria isolates at a center using cloth diapers, to highs of 46% and 45%, respectively, at a center using first paper and then cloth diapers. Sink faucets and the hands of the caregivers and the children were often contaminated. CONCLUSIONS: Analysis of the results of comparisons between cloth and paper diapers showed no significant difference in the frequency (F = .380, P < .535) or the intensity of fecal contamination in child day care centers.

Bacteria↗

Does routine child health surveillance reach children most at risk of accidental injury?

BACKGROUND: There is currently an increasing emphasis on accident prevention as part of routine child health surveillance, which unlike opportunistic accident prevention has the potential to reach the whole population. However, non-attenders at routine child health surveillance may also be children at higher risk of accidental injury, as there is some evidence that non-attenders may be more likely to live in socio-economic disadvantage, which is a risk factor for accidental injury. METHODS: A case control study was carried out in one general practice in Nottingham with 253 cases and 243 controls, aged four years and under, obtained from the practice age-sex register. Cases were defined as children who had attended the accident and emergency department, the general practitioner or the practice nurse after an accidental injury at any time during their life. Controls were children who had not had a medically attended accidental injury. Attendance at routine child health surveillance, before the date of the case's accidental injury, was assessed by attendance at the eight-month hearing test, immunization status, child health clinic visits and home visits by the health visitor. RESULTS: There was no significant difference between cases and controls in attendance for the hearing test, or immunization status. Cases received significantly more home visits after adjusting for confounding variables (odds ratio 2.44, 95 per cent confidence intervals 1.28-4.66). CONCLUSIONS: These findings suggest that non-attenders at routine child health surveillance activities are not at an increased risk of medically attended accidental injury. They also suggest that health visitors can identify those children most at risk of accidental injury using criteria for classifying priorities in caseloads.

Accident Prevention↗

Are primed CD4+ T lymphocytes different from unprimed cells?

Primed and unprimed lymphocytes are usually classified as separate subsets of cells, based on phenotypic and functional distinctions. In the case of CD4+ T lymphocytes, primed cells are thought to proliferate more vigorously, quickly and easily, and to release a different profile of cytokines, than their naive equivalent. However, most of these data were obtained from studies in which populations of lymphocytes were compared before and after antigenic stimulation, and therefore did not distinguish between the effects resulting from the clonal expansion of specific precursor cells within such populations and those due to cell differentiation per se. We have investigated the contribution of precursor cell frequency to some of the functional changes observed in populations of CD4+ T cells following antigenic stimulation, using approaches in which antigen-specific precursor frequencies are high in both primary and secondary stimulations: mixed leukocyte reaction responses and cells from alpha beta T cell receptor transgenic mice. Our data suggest that when equivalent numbers of antigen-specific naive and previously primed CD4+ responder T cells are compared, there is no difference in their potency to proliferate but only the previously activated subset can generate cytokines such as interferon-gamma.

Animals↗

Analysis of clones carrying repeated DNA sequences in two YAC libraries of Arabidopsis thaliana DNA.

YAC clones carrying repeated DNA sequences from the Arabidopsis thaliana genome have been characterized in two widely used Arabidopsis YAC libraries, the EG library and the EW library. Ribosomal, chloroplast and the paracentromeric repeat sequences are differentially represented in the two libraries. The coordinates of YAC clones hybridizing to these sequences are given. A high proportion of EG YAC clones were classified as containing chimaeric inserts because individual clones carried unique sequences and repetitive sequences originating from different locations in the genome. None of the EW YAC clones analysed were chimaeric in this way. YAC clones carrying tandemly repeated sequences, such as the paracentromeric or rDNA sequences, exhibited a high degree of instability. These observations need to be taken into account when using these libraries in the development of a physical map of the Arabidopsis genome and in chromosome walking experiments.

Arabidopsis↗

Child molestation, rape, and ethnicity.

Of 206 convicted sex offenders in a men's prison a disproportionate number of child molesters were white and a disproportionate number of rapists were black. Of the 758 inmates in general, a disproportionate number of both child molesters and rapists were white (n = 171 vs 35 black men).

Adult↗

Potential role for phosphatidic acid in mediating the inflammatory responses to TNF alpha and IL-1 beta.

Tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and endotoxin (LPS) are potent pro-inflammatory mediators which induce multiple and diverse biological responses in a wide variety of cell types. However, these pro-inflammatory mediators also have significant overlap and redundancy in their biological effects. This suggests that there is significant diversity in second messenger signal transduction systems induced by these stimuli to explain the diversity in biological responses, as well as significant redundancy. Here we show that one such second messenger common to several proinflammatory stimuli may be phosphatidic acid (PA). Intracellular PA species, which may have intracellular signaling functions, are rapidly induced in P388 monocytic leukemia cells by TNF alpha, IL-1 beta, or LPS. These PA species vary according to the bond type (i.e., sn-1 ester vs. ether vs. vinyl ether), acyl chain length, and the degree of saturation in the sn-1 and sn-2 positions. Although PA itself may have direct second messenger activities, many of the PA species induced are converted to diacylglycerol species (DG), which are structurally distinct from the DGs generated by phosphatidylcholine-specific phospholipase C (PC-PLC). Lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine; LSF] selectively inhibits generation of selected species of PA in P388 cells induced by TNF alpha, IL-1 beta or LPS. TNF alpha-induced sphingomyelin hydrolysis, PLC-mediated PC hydrolysis, and DG kinase-mediated PA formation or TNF alpha-induced NF-kappa B activation and apoptosis are not inhibited by LSF. LSF has a marked protective effect in a variety of acute inflammatory animal models that may be due to inhibition of this shared second messenger pathway involving PA.

Animals↗

Cloning from the thyroid of a protein related to actin binding protein that is recognized by Graves disease immunoglobulins.

Human actin binding protein (ABP) links specific membrane glycoproteins to cytoskeletal actin microfilaments. In human platelets and leukocytes, ABP directly links, respectively, the membrane glycoproteins GPIb and the high-affinity Fc receptor for IgG (Fc gamma IR) to cytoskeletal actin microfilaments. Similar interaction between the thyrotropin (TSH) receptor and ABP in endocrine cells might explain the rapid and profound disruption of actin microfilaments induced by TSH in cultured thyroid follicular cells. By screening a thyroid lambda gt11 cDNA expression library with serum from a Graves disease patient, we identified a clone encoding a protein, designated truncated ABP (TABP), that shares extensive homology (approximately 70%) with ABP. TABP is a truncated ABP-like protein with an open reading frame of 195 aa that encodes a protein of approximately 21 kDa. TABP lacks an actin binding domain but contains two predicted beta-sheet repeats within which is a putative dimerization domain and between which lies a putative glycoprotein binding site containing a consensus site for phosphorylation by Ca(2+)-calmodulin kinase II. TABP contains a unique C-terminal insertion within which lies a hydrophobic predicted membrane-associated region, absent from ABP. Although TABP mRNA is expressed widely, immunoblot analysis demonstrated the presence of TABP antibodies specifically in the sera of a minority of subjects with autoimmune thyroid disease. A 24-residue sequence of similarity was identified between the TSH receptor and platelet glycoprotein GPIb alpha that may represent a transmembrane ABP binding site. We suggest, therefore, that signal transduction by TSH in the thyroid involves direct linkage of the TSH receptor to actin microfilaments by ABP and that TABP may interact with ABP to mediate TSH-induced actin microfilament disruption.

Amino Acid Sequence↗

Large loop excision of the transformation zone (LLETZ) as an alternative to both local ablative and cone biopsy treatment: a series of 1000 patients.

One thousand patients, referred to the Oxford Colposcopy Clinic, were treated with either large loop excision of the transformation zone (LLETZ, 891 cases) or LLETZ cone (109 cases). Forty-five LLETZ cones were performed empirically, 64 under microcolposcopic guidance. Over 98% of patients were managed as outpatients under local anaesthesia, and 87% of new patients treated with LLETZ had treatment at their first visit. Ninety percent of patients had at least cervical intraepithelial neoplasia grade one (CIN I) and 73% had CIN II or worse. Seventeen cases of invasive or possibly invasive disease were detected, 6 of them unsuspected. The overall rate of complete excision of CIN or worse was 72%. Follow-up was cytologic with or without colposcopy depending on lesion severity. Ninety-one percent of 967 treated patients were free of dyskaryosis at a mean follow-up of 23 months, with complete excision of CIN or worse at LLETZ a significant predictive factor. No cases of invasive carcinoma have developed following treatment. Major morbidity was uncommon, with 3.8% severe hemorrhage. Stenosis was noted in 3.8% cases, mostly after LLETZ cone. One patient (0.1%) has reduced fertility possibly attributable to LLETZ. Questionnaire assessment revealed a very high degree of acceptability of the treatment to patients. LLETZ and LLETZ cone have proved highly acceptable and effective outpatient diagnostic and treatment alternatives to both local ablation and cone biopsy in the Oxford Colposcopy Clinic.

Adolescent↗

Local action transcutaneous flurbiprofen in the treatment of soft tissue rheumatism.

The objective of the present study was to establish the efficacy and tolerability of local action transcutaneous flurbiprofen (flurbiprofen LAT) in the treatment of soft tissue lesions. A randomized, double-blind, parallel-group placebo-controlled study was carried out in two hospital outpatient rheumatology clinics. One hundred and four patients aged 18-75 yr were randomized to receive a non-woven polyester-backed patch supporting a formulation containing 40 mg flurbiprofen 12-hourly over 14 days; or a non-medicated (but otherwise identical) control. Statistically significant differences in favour of the active preparation were seen at both days 7 (P = 0.02) and 14 (P = 0.009) for the investigator's overall opinion of severity of the condition, and at day 7 for the investigator's assessment of pain severity (P = 0.04 intention-to-treat; P = 0.052 N.S. eligible data). The need for further treatment in the form of steroid injections after the trial was greater in the controls (29/44, 66%) than in the flurbiprofen LAT group (17/46, 37%) (chi 2 = 7.54 on 1 d.o.f., P = 0.006). Plasma flurbiprofen levels in 11 patients ranged from 13.4 to 338.7 ng/ml (mean 116; median 57.9). Eight out of 53 (15%) patients receiving flurbiprofen LAT reported a total of 10 adverse events, compared with three out of 51 (6%) reporting seven events among controls. Patients found the patch convenient and soothing. We conclude that flurbiprofen LAT is an effective and acceptable treatment for soft tissue lesions, and should be considered as an alternative therapy to local steroid injection.

Administration, Cutaneous↗