tbuckley/cabot-search huggingface dataset:
Pericytes influence endothelial cell growth characteristics: Role of plasminogen activator inhibitor type 1 (PAI-1)
Authors: M MCILROY, M OROURKE, S MCKEOWN, D HIRST, T ROBSON
Journal: Cardiovascular Research (2005)

Pericytes, located in close proximity to the underlying endothelium, form an integral component of the microvasculature. These cells are intimately involved in angiogenesis, which is of fundamental importance in many physiological and pathological processes. We evaluated the influence of pericyte-conditioned medium (PCM) on endothelial cell growth characteristics and modulation of endothelial gene expression.Migration and tubule formation assays were performed in vitro to determine the effect of PCM on endothelial growth characteristics. cDNA microarray analysis was used to identify alterations in gene expression following exposure of human microvascular endothelial cells (HMEC-1) to PCM. Overexpression of PAI-1 using recombinant protein or transient transfection, and inhibition using an inhibitory antibody against PAI-1, were used to determine whether up- or down-regulation of this gene was responsible for the changes in endothelial cell characteristics observed in response to PCM exposure.We have shown that PCM exerts a dramatic inhibitory influence on endothelial cell migration in vitro. In addition, endothelial cells cultured on Matrigel and exposed to PCM were found to generate significantly fewer angiogenic branches. Microarray analysis of endothelial cells exposed to PCM identified PAI-1 as the gene showing the greatest level of differential expression (3.4-fold induction). Studies using an inhibitory antibody to PAI-1 suggest that induction of this protein by PCM is pivotal to the observed inhibitory influence on the migratory and angiogenic potential of HMEC-1. We further investigated this by overexpressing PAI-1, which was shown to have a potent inhibitory influence on EC migration and angiogenic branching, although the concentration of PAI-1 was clearly important.Collectively, these findings suggest that PCM contains a bioactive element(s) that controls both endothelial cell migration and tubule formation in vitro and that these responses may be partially controlled by increased endothelial cell expression of PAI-1.
TRICHOPHYTON SOUDANENSE IN AND OUTSIDE AFRICA
Authors: R. VANBREUSEGHEM
Journal: British Journal of Dermatology (1968)

SUMMARY. The morphology, cultural characteristics and diagnostic features of Trichophyton soudanense are fully described. The impression conveyed by most publications that the fungus is predominantly a cause of tinea capitis is proved to be erroneous by the report of 14 cases in which the glabrous skin, including the foot, and the nails were involved. The clinical features of scalp and skin infections are described. Both occur in adults and children. T. soudanense infections which have occurred outside Africa including 6 new Belgian cases are tabulated and discussed. With very few exceptions, which are not beyond criticism, all reported infections have originated in Africa.
An Epidemic, Toxin Gene–Variant Strain of<i>Clostridium difficile</i>
Authors: L. Clifford McDonald, George E. Killgore, Angela Thompson, Robert C. Owens, Sophia V. Kazakova, Susan P. Sambol, Stuart Johnson, Dale N. Gerding
Journal: New England Journal of Medicine (2005)

Recent reports suggest that the rate and severity of Clostridium difficile-associated disease in the United States are increasing and that the increase may be associated with the emergence of a new strain of C. difficile with increased virulence, resistance, or both.A total of 187 C. difficile isolates were collected from eight health care facilities in six states (Georgia, Illinois, Maine, New Jersey, Oregon, and Pennsylvania) in which outbreaks of C. difficile-associated disease had occurred between 2000 and 2003. The isolates were characterized by restriction-endonuclease analysis (REA), pulsed-field gel electrophoresis (PFGE), and toxinotyping, and the results were compared with those from a database of more than 6000 isolates obtained before 2001. The polymerase chain reaction was used to detect the recently described binary toxin CDT and a deletion in the pathogenicity locus gene, tcdC, that might result in increased production of toxins A and B.Isolates that belonged to one REA group (BI) and had the same PFGE type (NAP1) were identified in specimens collected from patients at all eight facilities and accounted for at least half of the isolates from five facilities. REA group BI, which was first identified in 1984, was uncommon among isolates from the historic database (14 cases). Both historic and current (obtained since 2001) BI/NAP1 isolates were of toxinotype III, were positive for the binary toxin CDT, and contained an 18-bp tcdC deletion. Resistance to gatifloxacin and moxifloxacin was more common in current BI/NAP1 isolates than in non-BI/NAP1 isolates (100 percent vs. 42 percent, P<0.001), whereas the rate of resistance to clindamycin was the same in the two groups (79 percent). All of the current but none of the historic BI/NAP1 isolates were resistant to gatifloxacin and moxifloxacin (P<0.001).A previously uncommon strain of C. difficile with variations in toxin genes has become more resistant to fluoroquinolones and has emerged as a cause of geographically dispersed outbreaks of C. difficile-associated disease.
Evaluation of nutrition knowledge and dietary intake of male academy rugby union players undertaking a nutrition education program
Authors: E Tester, L Sutton, L Duckworth
Journal: British Journal of Sports Medicine (2011)

The aim was to determine if the implementation of a nutrition education program can improve the nutritional knowledge and dietary practice of male academy rugby union players. On obtaining institutional ethics approval, 16 players were recruited and split by age category. Both an under 16 (U16) group N=9 (17 ± 1 y) and under 19 (U19) group N=7 (19 ± 0 y) participated in an eight session program. The sessions informed participants on the principles of sports nutrition and met individual nutrition needs. Both groups completed a nutrition knowledge questionnaire and a 7 day diet diary pre and post program delivery. Dietary analysis was conducted and adequacy of intake was assessed by comparison with calculated recommended values. Delta values were used to assess the difference between required and actual intake values for different dietary components. Results show increases in nutrition knowledge scores for all participants, 31.5–37.2 (p=0.000). There was a strong positive correlation between age and nutrition knowledge scores both pre (r=0.518, n=18, p&lt;0.027) and post (r=0.472, n=18, p&lt;0.48). There was improvement in energy and carbohydrate intake within the U19 group, t (6) = −3.837, p&lt;0.009, t (6) = −4.653, p&lt;0.003 respectively. Although not significant, improvements in fluid intake were seen as average intakes increased by 1.72 l (U19) and 0.68 l (U18). The main finding was improvements in nutrition knowledge following a nutrition education program. A link between age and knowledge was highlighted. There were improvements in dietary intake whereby participants more closely met recommended intakes. For the U19, improvements were statistically significant, but for the U18 who are not solely responsible for their dietary intake improvements were less evident. Further research into the barriers facing younger athletes in achieving adequate dietary intake is warranted.
Effect of vagal stimulation on the overflow of norepinephrine into the coronary sinus during cardiac sympathetic nerve stimulation in the dog.
Authors: M N Levy, B Blattberg
Journal: Circulation Research (1976)

In anesthetized dogs with the chest open, supramaximal stimulation of the left cardiac sympathetic nerves at 2 and 4 Hz produced an increase of 40-50% in ventricular contractile force (CF) and of 40-65% in coronary sinus blood flow. At these frequencies of stimulation, norepinephrine (NE) overflow into the coronary sinus was 29.8 +/- 5.1 (SE) and 54.9 +/- 13.2 ng/min, respectively. Concurrent, supramaximal vagal stimulation, at a frequency of 15 Hz, had no significant effect on coronary sinus blood flow, but caused a 25% reduction in CF and a 30% decrease in NE overflow. The changes in CF and NE overflow evoked by vagal stimulation were prevented by atropine. These results are consistent with the hypothesis that there are muscarinic receptors on the postganglionic sympathetic terminals in the walls of the ventricles. Acetylcholine released during vagal stimulation combines with these receptors, causes a reduction in the liberation of NE, and thereby attenuates the positive inotropic response.
Stress, lies and red tape: the views, success rates and stress levels of the MTAS cohort
Authors: Paul Whelan, Maja Meerten, Rahul Rao, Peter Jarrett, Anandamurugan Muthukumaraswamy, Dinesh Bhugra
Journal: Journal of the Royal Society of Medicine (2008)

Summary Objective To track the success rates in obtaining a specialist training (ST) post of a cohort of medical training application system (MTAS) applicants, as well as canvassing their views of the process and measuring symptoms of psychological distress during application and after job allocation. Design A follow-up cross-sectional survey. Setting Two large south London psychiatry training schemes. Participants 101 MTAS applicants. Main outcome measures Success in obtaining an ST post, respondents' views about MTAS and General Health Questionnaire-12 (GHQ-12) scores. Results 48 of the original sample responded to the follow-up survey. Data were available about post-MTAS job status for a further 41 trainees. 64% of candidates obtained an ST post. Of those, however, 12% were only offered a fixed-term post. Most unsuccessful candidates were doing locum (34%) or non-training grade (21%) jobs. UK/European Economic Area (EEA) doctors were more successful than non-EEA applicants in obtaining an ST post (odds ratio 5.5, 95% confidence interval 2.1–14.3), as were women candidates compared to men (3.7, 0.5–9.3). The respondents' views about MTAS were globally negative (even if they were successful in obtaining an ST post). The median GHQ-12 score for respondents was 7 out of a potential total score of 12. 79% of the sample scored above the threshold (GHQ-12 ≥4) for psychological distress and 21% experienced significant distress (GHQ-12 ≥8). Conclusions MTAS was a flawed system. A considerable proportion (36%) of candidates who had been on a Senior House Officer training scheme were left without a training post after MTAS. The system seems to favour UK/EEA applicants. Applicants suffered significant psychological distress during and after the MTAS process.
Randomised clinical trial of synbiotic therapy in elective surgical patients
Authors: A D G Anderson
Journal: Gut (2004)

<b>Background:</b> It is possible to manipulate the composition of the gastrointestinal microflora by administration of pre- and probiotics. This may help to preserve gut barrier function and reduce the incidence of septic morbidity. <b>Aims:</b> To assess the effects of a combination of pre- and probiotics (synbiotic) on bacterial translocation, gastric colonisation, systemic inflammation, and septic morbidity in elective surgical patients. <b>Patients:</b> Patients were enrolled two weeks prior to elective abdominal surgery. Seventy two patients were randomised to the synbiotic group and 65 to the placebo group. Patients were well matched regarding age and sex distribution, diagnoses, and POSSUM scores. <b>Methods:</b> Patients in the synbiotic group received a two week preoperative course of <i>Lactobacillus acidophilus La5</i>, <i>Bifidobacterium lactis Bb-12</i>, <i>Streptococcus thermophilus</i>, and <i>Lactobacillus bulgaricus</i>, together with the prebiotic oligofructose. Patients in the placebo group received placebo capsules and sucrose powder. At surgery, a nasogastric aspirate, mesenteric lymph node, and scrapings of the terminal ileum were harvested for microbiological analysis. Serum was collected preoperatively and on postoperative days 1 and 7 for measurement of C reactive protein, interleukin 6, and antiendotoxin antibodies. Septic morbidity and mortality were recorded. <b>Results:</b> There were no significant differences between the synbiotic and control groups in bacterial translocation (12.1% <i>v</i> 10.7%; p = 0.808, χ<sup>2</sup>), gastric colonisation (41% <i>v</i> 44%; p = 0.719), systemic inflammation, or septic complications (32% <i>v</i> 31%; p = 0.882). <b>Conclusions:</b> In this study, synbiotics had no measurable effect on gut barrier function in elective surgical patients. Further studies investigating the place of pre- and probiotics in clinical practice are required.
Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis
Authors: Siddharth Singh, Sushil Kumar Garg, Preet Paul Singh, Prasad G Iyer, Hashem B El-Serag
Journal: Gut (2013)

<h3>Background and aims</h3> Acid-suppressive medications, particularly proton pump inhibitors (PPIs), may decrease the risk of oesophageal adenocarcinoma (OAC) in patients with Barrett9s oesophagus (BO). We performed a systematic review with meta-analysis of studies evaluating the association between acid-suppressive medications (PPIs and histamine receptor antagonists (H2RAs)) and risk of OAC or high-grade dysplasia (BO-HGD) in patients with BO. <h3>Methods</h3> We performed a systematic search of multiple electronic databases and conference proceedings up to June 2013 to identify studies reporting the association between use of acid-suppressive medications and risk of OAC and/or BO-HGD in patients with BO. Summary ORs with 95% CIs were estimated. <h3>Results</h3> We identified seven observational studies (2813 patients with BO, 317 cases of OAC or BO-HGD, 84.4% PPI users). On meta-analysis, PPI use was associated with a 71% reduction in risk of OAC and/or BO-HGD in patients with BO (adjusted OR 0.29; 95% CI 0.12 to 0.79). There was a trend towards a dose–response relationship with PPI use for &gt;2–3 years protective against OAC or BO-HGD (three studies; PPI use &gt;2–3 years vs &lt;2–3 years: OR 0.45 (95% CI 0.19 to 1.06) vs 1.09 (0.47 to 2.56)). Considerable heterogeneity was observed. Two studies reported the association between H2RA use and risk of OAC and/or BO-HGD (1352 patients with BO, 156 cases of OAC, 25.4% on H2RAs), and both studies did not show a significant effect. <h3>Conclusions</h3> Based on meta-analysis of observational studies, the use of PPIs is associated with a decreased risk of OAC and/or BO-HGD in patients with BO. None of the studies showed an increased risk of OAC. PPI use should be considered in BO, and chemopreventive trials of PPIs in patients with BO are warranted.
Caveolae: From Cell Biology to Animal Physiology
Authors: Babak Razani, Scott E. Woodman, Michael P. Lisanti
Journal: Pharmacological Reviews (2002)

Among the membrane compartments of a cell, vesicles known as "caveolae" have long defied functional characterization. However, since the identification of a family of proteins termed "caveolins", that form and reside in caveolae, a better understanding has emerged. It is now clear that caveolae do not merely play a singular role in the cell, but are pleiotropic in nature—serving to modulate many cellular functions. The purpose of this review is to explicate what is known about caveolins/caveolae and highlight growing areas of caveolar research.
Mechanical inefficiency of the thoracic cage in scoliosis.
Authors: R S Jones, J D Kennedy, F Hasham, R Owen, J F Taylor
Journal: Thorax (1981)

The mechanism of impairment of ventilatory function in idiopathic scoliosis has been studied in 23 children, all girls, and compared with 27 normal children and 24 normal young adult females. The vital capacity, FEV 1, gas transfer factor, and the maximum static expiratory airway pressure were all significantly reduced. total lung capacity and the maximum inspiratory pressure were lower than in the normal subjects, but the difference was not significant. Restriction of thoracic cage movement by a belt showed that the thorax in the children with scoliosis was as mobile as in the normal subjects. The results are explained in terms of the characteristic deformity in scoliosis which causes one hemi-thorax to become relatively smaller than the other. It is concluded that this causes an inherent mechanical inefficiency of ventilation which is likely to contribute to respiratory failure in these subjects.
Right Frontal Hypergyria Differentiation in Affected and Unaffected Siblings From Families Multiply Affected With Schizophrenia: A Morphometric MRI Study
Authors: Kai Vogeley, Ralf Tepest, Ute Pfeiffer, Thomas Schneider-Axmann, Wolfgang Maier, William G. Honer, Peter Falkai
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors used magnetic resonance imaging to corroborate the postmortem finding of right frontal hypergyria associated with schizophrenia. METHOD: Twelve affected-unaffected sibling pairs from families multiply affected with schizophrenia were studied. Bilateral measurement of the gyrification index, the ratio of the inner and outer surface contours, was performed on three different slices of the prefrontal region. RESULTS: The mean gyrification index on the right side was significantly higher in siblings with schizophrenia or schizoaffective disorder than in the unaffected siblings. CONCLUSIONS: In this family cohort study, the postmortem finding of right-sided hypergyria in subjects with schizophrenia was replicated in vivo with magnetic resonance imaging. This observation provides further support for a neurodevelopmental mechanism in the pathogenesis of schizophrenia.
Blood flow in psoriatic plaques before and after selective treatment of the superficial capillaries
Authors: S. Hern, A.W.B. Stanton, R.H. Mellor, C.C. Harland, J.R. Levick, P.S. Mortimer
Journal: British Journal of Dermatology (2005)

Background Blood flow is substantially raised in psoriatic plaques. In addition, mechanisms of vasoconstriction and vasodilatation (locally and neurally mediated), although intact, are altered in magnitude. The elevated blood flow is considered to be a result of abnormalities (increase in vessel number, width and length) in the superficial capillary loops rather than changes in the deeper feeding vessels (arterioles). Objectives To determine if selective thermolysis of psoriatic capillaries with a pulsed dye laser (PDL) leads to normalization of blood flow and also if the vasoconstrictor and vasodilator responses are returned to normal magnitude. Methods Laser Doppler red cell flux was recorded from plaques on the forearm or elbow (untreated plaque site) and from clinically uninvolved skin at an equivalent site on the opposite limb. Plaques were treated on three occasions, at 2-weekly intervals, with a PDL. Laser Doppler red cell flux measurements were then repeated, 2 weeks after the final laser treatment was performed (treated plaque site). Results There was significant clinical improvement in plaques after treatment (P = 0·02), but complete clearance of lesions did not occur. Blood flow in plaques under basal conditions remained significantly elevated above blood flow in clinically uninvolved skin, despite laser treatment (P < 0·001). The physiological tests of resistance vessel function showed that the laser did not impair the ability of psoriatic resistance vessels to constrict and dilate. However, there was only partial resolution of the percentage responses to the provocation tests towards the values recorded in clinically uninvolved skin. Conclusions The results indicate that it is unlikely that the reduced resistance of the expanded superficial capillary bed is solely responsible for the massively elevated blood flow in plaque skin. It is more likely that the vascular abnormalities in psoriasis also extend to involve the deeper, larger resistance vessels (arterioles).
Gene Duplication Events Producing Muscle (M) and Brain (B) Isoforms of Cytoplasmic Creatine Kinase: cDNA and Deduced Amino Acid Sequences from Two Lower Chordates
Authors: Nicole A. Graber, W. Ross Ellington
Journal: Molecular Biology and Evolution (2001)

Creatine kinase (CK) is coded for by at least four loci in higher vertebrates—two cytoplasmic isoforms, muscle (M) and brain (B), and two mitochondrial isoforms, sarcomeric and ubiquitous. M is expressed primarily in skeletal muscle, while B is expressed in a variety of cells, including cardiac and smooth muscle fibers, neurons, transport epithelia, and photoreceptors. M and B subunits form very stable homodimers (MM [M-CK], BB [B-CK]) and heterodimers (MB). M-CK is capable of binding to the M line of the myofibril, thereby creating an energy transfer microcompartment; BB and MB CKs are not. M- and B-like CKs are present in all vertebrates yet examined, including fish. Cytoplasmic, dimeric CKs are widely distributed in the invertebrates. The only available amino acid sequence for an invertebrate dimeric CK, that of the protostome polychaete Chaetopterus variopedatus, is just as similar to the vertebrate M isoform as to the B isoform. Echinoderms lack dimeric, cytoplasmic CKs, which appear to be replaced by a dimeric arginine kinase which evolved secondarily from CK. Thus, it is likely that the gene duplication event producing the M and B isoforms occurred after the divergence of the chordates from echinoderms. To narrow down the timing of this duplication event, we obtained the cDNA and deduced amino acid sequences of dimeric CKs from the tunicate Ciona intestinalis (subphylum Urochordata) and the lancelet Branchiostoma floridae (subphylum Cephalochordata). Our results show that these CKs are strikingly similar to both invertebrate and vertebrate CKs. However, phylogenetic analyses by neighbor-joining and parsimony show that these two enzymes appeared to have diverged before the point of divergence of the M and B isoforms. Thus, the gene duplication event for formation of the muscle and brain isoforms of CK most likely occurred during the radiation of the fish, a time noted for gene duplication events at a variety of other loci.
A Critical Role for the Protein Apoptosis Repressor With Caspase Recruitment Domain in Hypoxia-Induced Pulmonary Hypertension
Authors: Ari L. Zaiman, Rachel Damico, Alan Thoms-Chesley, D. Clark Files, Priya Kesari, Laura Johnston, Mara Swaim, Shehzin Mozammel, Alan C. Myers, Marc Halushka, Hazim El-Haddad, Larissa A. Shimoda, Chang-Fu Peng, Paul M. Hassoun, Hunter C. Champion, Richard N. Kitsis, Michael T. Crow
Journal: Circulation (2011)

Pulmonary hypertension (PH) is a lethal syndrome associated with the pathogenic remodeling of the pulmonary vasculature and the emergence of apoptosis-resistant cells. Apoptosis repressor with caspase recruitment domain (ARC) is an inhibitor of multiple forms of cell death known to be abundantly expressed in striated muscle. We show for the first time that ARC is expressed in arterial smooth muscle cells of the pulmonary vasculature and is markedly upregulated in several experimental models of PH. In this study, we test the hypothesis that ARC expression is essential for the development of chronic hypoxia-induced PH.Experiments in which cells or mice were rendered ARC-deficient revealed that ARC not only protected pulmonary arterial smooth muscle cells from hypoxia-induced death, but also facilitated growth factor-induced proliferation and hypertrophy and hypoxia-induced downregulation of selective voltage-gated potassium channels, the latter a hallmark of the syndrome in humans. Moreover, ARC-deficient mice exhibited diminished vascular remodeling, increased apoptosis, and decreased proliferation in response to chronic hypoxia, resulting in marked protection from PH in vivo. Patients with PH have significantly increased ARC expression not only in remodeled vessels but also in the lumen-occluding lesions associated with severe disease.These data show that ARC, previously unlinked to pulmonary hypertension, is a critical determinant of vascular remodeling in this syndrome.