tbuckley/cabot-search huggingface dataset:
The Duty to Attend Upon the Sick
Authors: James Pascal Imperato
Journal: JAMA (1992)

<h3>To the Editor.</h3> —In their article on patterns of house staff recruitment to municipal and voluntary New York City hospitals, Ness et al<sup>1</sup>conclude that the decline in matches is due to multiple economic and social factors, including AIDS. Clarke and Conley,<sup>2</sup>in their accompanying editorial, cogently point out the possibility that match applicants have not distinguished between high-and low-AIDS residency programs in New York, thus accounting for the decline in matches to all programs. Gerbert et al,<sup>3</sup>in their study published in the same issue of<i>JAMA</i>, report that 50% of primary care physicians surveyed would not, if given a chance, treat people with HIV infection. Our medical school is situated in a high-AIDS incidence area where half the medical beds are occupied by HIV-positive patients. A survey of 174 second-year medical students in 1988 found that 48.3% believed that physicians should have the prerogative of
Association of the Neurotrophic Tyrosine Kinase Receptor 3 (<i>NTRK3</i>) Gene and Childhood-Onset Mood Disorders
Authors: Yu Feng, Ágnes Vetró, Eniko Kiss, Krisztina Kapornai, Gabriella Daróczi, László Mayer, Zsuzsanna Tamás, Ildikó Baji, Júlia Gádoros, Nicole King, James L. Kennedy, Karen Wigg, Maria Kovacs, Cathy L. Barr
Journal: American Journal of Psychiatry (2008)

Genome scans have revealed significant evidence for linkage of depression to chromosome 15q25.3-q26.2. The gene for neurotrophic tyrosine kinase receptor 3 (NTRK3), the receptor for neurotrophin-3 (trkC) and a key gene in neurotrophin signaling, is located within this region and, given evidence for synaptic plasticity as a mechanism in mood disorders, was considered a prime candidate. The authors investigated NTRK3 as a susceptibility gene for childhood-onset mood disorders.The study sample consisted of 603 families with 723 affected children and adolescents diagnosed with a mood disorder with onset of the first episode by age 15. The authors genotyped 18 polymorphic markers across the NTRK3 gene in this sample and tested for association.Results identified significant evidence for association for five of the markers using the transmission disequilibrium test. Four of the five markers were located in a region of strong linkage disequilibrium and were highly correlated. Haplotype results provided significant evidence for association to haplotypes composed of markers located in two haplotype blocks.The results for NTRK3 as well as the authors' previous finding for association to brain-derived neurotrophic factor in this sample support synaptic plasticity as a mechanism contributing to mood disorders that begin during childhood and adolescence and specifically implicate the NTRK3 gene as a contributing factor in the 15q-linked region.
Why is creativity attractive in a potential mate?
Authors: Daniel Nettle
Journal: Behavioral and Brain Sciences (2008)

Abstract A number of studies suggest that women find artistically creative men attractive, especially in the short-term mating context. Artistic creativity (but not mathematical or technical creativity) is linked to psychosis-proneness. I hypothesise that in preferring artistically creative men, women may be choosing paternal genotypes that make babies that are not excessively somatically demanding on them.
Associations between objectively measured physical activity and academic attainment in adolescents from a UK cohort
Authors: J N Booth, S D Leary, C Joinson, A R Ness, P D Tomporowski, J M Boyle, J J Reilly
Journal: British Journal of Sports Medicine (2013)

Background To test for cross-sectional (at age 11) and longitudinal associations between objectively measured free-living physical activity (PA) and academic attainment in adolescents.Method Data from 4755 participants (45% male) with valid measurement of PA (total volume and intensity) by accelerometry at age 11 from the Avon Longitudinal Study of Parents and Children (ALSPAC) was examined. Data linkage was performed with nationally administered school assessments in English, Maths and Science at ages 11, 13 and 16. Results In unadjusted models, total volume of PA predicted decreased academic attainment. After controlling for total volume of PA, percentage of time spent in moderate-vigorous intensity PA (MVPA) predicted increased performance in English assessments in both sexes, taking into account confounding variables. In Maths at 16 years, percentage of time in MVPA predicted increased performance for males (standardised β=0.11, 95% CI 0.00 to 0.22) and females (β=0.08, 95% CI 0.00 to 0.16). For females the percentage of time spent in MVPA at 11 years predicted increased Science scores at 11 and 16 years (β=0.14 (95% CI 0.03 to 0.25) and 0.14 (0.07 to 0.21), respectively). The correction for regression dilution approximately doubled the standardised β coefficients. Conclusions Findings suggest a long-term positive impact of MVPA on academic attainment in adolescence.
Epidermolytic variant of hereditary palmoplantar keratoderma
Authors: CHARLES CAMISA, HOMER WILLIAMS
Journal: British Journal of Dermatology (1985)

The seventh family with autosomal dominant epidermolytic palmoplantar keratoderma is reported. The lesions are clinically indistinguishable from Unna-Thost disease but resemble epidermolytic hyperkeratosis (bullous ichthyroderma) histopathologically. A skin biopsy is essential for making the correct diagnosis. One of our patients was treated with isotretinoin for 13 weeks without significant improvement.
An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome
Authors: J. Kellow, O. Y. Lee, F. Y. Chang, S. Thongsawat, M. Z. Mazlam, H. Yuen, K. A. Gwee, Young-Tae Bak, J. Jones, A. Wagner
Journal: Gut (2003)

<b>Background:</b> Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western populations. However, little information is available regarding the use of tegaserod in the Asia-Pacific population. <b>Aims:</b> To evaluate the efficacy, safety, and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region. <b>Patients:</b> A total of 520 patients from the Asia-Pacific region with IBS, excluding those with diarrhoea predominant IBS. <b>Methods:</b> Patients were randomised to receive either tegaserod 6 mg twice daily (n=259) or placebo (n=261) for a 12 week treatment period. The primary efficacy variable (over weeks 1–4) was the response to the question: "Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?" Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS. <b>Results:</b> The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1–4 (56% <i>v</i> 35%, respectively; p&lt;0.0001) and weeks 1–12 (62% <i>v</i> 44%, respectively; p&lt;0.0001). A clinically relevant effect was observed as early as week 1 and was maintained throughout the treatment period. Reductions in the number of days with at least moderate abdominal pain/discomfort, bloating, no bowel movements, and hard/lumpy stools were greater in the tegaserod group compared with the placebo group. Headache was the most commonly reported adverse event (12.0% tegaserod <i>v</i> 11.1% placebo). Diarrhoea led to discontinuation in 2.3% of tegaserod patients. Serious adverse events were infrequent (1.5% tegaserod <i>v</i> 3.4% placebo). <b>Conclusions:</b> Tegaserod 6 mg twice daily is an effective, safe, and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea.
The role of αv integrins during angiogenesis: insights into potential mechanisms of action and clinical development
Authors: Brian P. Eliceiri, David A. Cheresh
Journal: Journal of Clinical Investigation (1999)

Angiogenesis depends on specific molecular interactions between vascular cells and components of the extracellular matrix (ECM). This Perspective focuses on the functional role of integrins in angiogenesis and neovascularization. Specifically, we discuss the mechanism by which antagonists of αv integrins disrupt angiogenesis in vivo and how they may impact patients with cancer and inflammatory disease. Role of ECM and integrins during angiogenesis and vasculogenesis. Angiogenesis depends not only on growth factors and their receptors but is also influenced by receptors for ECM proteins. In general, cell adhesion to the ECM is mediated by integrins, heterodimeric transmembrane proteins that comprise a diverse family of over 15 α and 8 β subunits. Integrin subunits can heterodimerize in over 20 combinations. Different integrin combinations may recognize a single ECM ligand, while others bind several different ECM proteins. Integrin-mediated adhesion leads to intracellular signaling events that regulate cell survival, proliferation, and migration (1). These signals include elevation in intracellular pH and calcium, inositol lipid synthesis, and the tyrosine phosphorylation of a wide range of nonreceptor tyrosine kinases such as focal adhesion kinase and Src kinases, as well as adaptor proteins such as Shc, p130 CAS, and Crk II. These signaling events trigger a number of downstream signals, including activation of the Ras/mitogen-activated protein (MAP) kinase pathway (1).
Heterogeneous expression of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase genes in the rat liver lobulus.
Authors: J Twisk, M F Hoekman, W H Mager, A F Moorman, P A de Boer, L Scheja, H M Princen, R Gebhardt
Journal: Journal of Clinical Investigation (1995)

We investigated the lobular localization and molecular level of expression of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase, two key enzymes in bile acid synthesis, in isolated periportal and pericentral hepatocytes and by in situ hybridization of rat liver. Enzyme activity, mRNA, and gene transcription of cholesterol 7 alpha-hydroxylase were predominant in pericentral hepatocytes of control rats, being 7.9-, 9.9-, and 4.4-fold higher than in periportal hepatocytes, respectively. Similar localization was found for sterol 27-hydroxylase: 2.9-, 2.5-, and 1.7-fold higher enzyme activity, mRNA, and gene transcription, respectively, was found in pericentral hepatocytes. Interruption of the enterohepatic circulation with colestid resulted in upregulation of these parameters for both enzymes, as a consequence of stimulated gene expression mainly in the periportal zone. In contrast, mRNA levels and gene transcription of 3-hydroxy-3-methylglutaryl CoA reductase showed opposite lobular distribution. Selective periportal expression for the latter was enhanced, but remained local, after colestid treatment. In situ hybridization showed unambiguously that cholesterol 7 alpha-hydroxylase mRNA is localized exclusively in the pericentral zone and that sterol 27-hydroxylase mRNA is expressed preferentially in the pericentral region, though less pronounced. Administration of colestid led to expression of both genes within a larger area of the liver lobulus. In conclusion, we suggest that cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase are coordinately regulated by the bile acid gradient over the lobulus, resulting in predominant expression in the pericentral zone. Opposite lobular localization of cholesterol and bile acid synthesis provides an alternative view to interregulation of these metabolic pathways.
Localization and Regulation of the Epithelial Ca2+ Channel TRPV6 in the Kidney
Authors: Tom Nijenhuis, Joost G. J. Hoenderop, Annemiete W. C. M. van der Kemp, René J. M. Bindels
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The family of epithelial Ca 2+ channels consists of two highly homologues members, TRPV5 and TRPV6, which constitute the apical Ca 2+ entry mechanism in active Ca 2+ (re)absorption in kidney and small intestine. In kidney, TRPV5 expression has been extensively studied, whereas TRPV6 localization and regulation has been largely confined to the small intestine. The present study investigated the renal distribution of TRPV6 and regulation by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). In mouse kidney, TRPV6 was detected by immunohistochemistry at the apical domain of the distal convoluted tubules (DCT2), connecting tubules (CNT), and cortical and medullary collecting ducts (CD). Furthermore, several putative vitamin D-responsive elements were detected upstream of the mouse TRPV6 start codon, and 1,25(OH) 2 D 3 treatment significantly increased renal TRPV6 mRNA and protein expression. In DCT2 and CNT, TRPV6 co-localizes with the other known Ca 2+ transport proteins, including TRPV5 and calbindin-D 28K . Together, these data suggest a role for TRPV6 in 1,25(OH) 2 D 3 -stimulated Ca 2+ reabsorption in these segments. Interestingly, distribution of TRPV6 extended to the CD, where it localized to the apical domain of principal and intercalated cells, which are not generally implicated in active Ca 2+ reabsorption. In addition, TRPV6 mRNA levels were quantified in a large set of tissues, and in the order of decreasing expression level were detected: prostate &gt; stomach, brain &gt; lung &gt; duodenum, kidney, bone, cecum, heart &gt; colon &gt; skeletal muscle &gt; pancreas. Therefore, additional physiologic functions for TRPV6 are feasible. In conclusion, TRPV6 is expressed along the apical domain of DCT2, CNT, and CD, where TRPV6 expression is positively regulated by 1,25(OH) 2 D 3 . E-mail: r.bindels@ncmls.kun.nl
NOTCH Decoys That Selectively Block DLL/NOTCH or JAG/NOTCH Disrupt Angiogenesis by Unique Mechanisms to Inhibit Tumor Growth
Authors: Thaned Kangsamaksin, Aino Murtomaki, Natalie M. Kofler, Henar Cuervo, Reyhaan A. Chaudhri, Ian W. Tattersall, Paul E. Rosenstiel, Carrie J. Shawber, Jan Kitajewski
Journal: Cancer Discovery (2014)

A proangiogenic role for Jagged (JAG)-dependent activation of NOTCH signaling in the endothelium has yet to be described. Using proteins that encoded different NOTCH1 EGF-like repeats, we identified unique regions of Delta-like ligand (DLL)-class and JAG-class ligand-receptor interactions, and developed NOTCH decoys that function as ligand-specific NOTCH inhibitors. N110-24 decoy blocked JAG1/JAG2-mediated NOTCH1 signaling, angiogenic sprouting in vitro, and retinal angiogenesis, demonstrating that JAG-dependent NOTCH signal activation promotes angiogenesis. In tumors, N110-24 decoy reduced angiogenic sprouting, vessel perfusion, pericyte coverage, and tumor growth. JAG-NOTCH signaling uniquely inhibited expression of antiangiogenic soluble (s) VEGFR1/sFLT1. N11-13 decoy interfered with DLL1-DLL4-mediated NOTCH1 signaling and caused endothelial hypersprouting in vitro, in retinal angiogenesis, and in tumors. Thus, blockade of JAG- or DLL-mediated NOTCH signaling inhibits angiogenesis by distinct mechanisms. JAG-NOTCH signaling positively regulates angiogenesis by suppressing sVEGFR1-sFLT1 and promoting mural-endothelial cell interactions. Blockade of JAG-class ligands represents a novel, viable therapeutic approach to block tumor angiogenesis and growth.This is the first report identifying unique regions of the NOTCH1 extracellular domain that interact with JAG-class and DLL-class ligands. Using this knowledge, we developed therapeutic agents that block JAG-dependent NOTCH signaling and demonstrate for the first time that JAG blockade inhibits experimental tumor growth by targeting tumor angiogenesis.
Neutrophillic spongiosis. A new entity?
Authors: G. Batista, A.N.C. Santos, S.A.P. Sampaio
Journal: British Journal of Dermatology (1986)

Journal Article Neutrophillic spongiosis. A new entity? Get access G. Batista, G. Batista Departments of Dermatology, Felicio Rocho Hospital, Av. Contorno, 9.681, 3 andar, Belo Horizonte, 30000, Brasil Search for other works by this author on: Oxford Academic Google Scholar A.N.C. Santos, A.N.C. Santos Internal Medicine, Felicio Rocho Hospital, Av. Contorno, 9.681, 3 andar, Belo Horizonte, 30000, Brasil Search for other works by this author on: Oxford Academic Google Scholar S.A.P. Sampáio S.A.P. Sampáio Department of Dermatology, Hospital das Clinicas, University of São Paulo, São Paulo, 01000, Brasil Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 114, Issue 1, 1 January 1986, Pages 131–134, https://doi.org/10.1111/j.1365-2133.1986.tb02788.x Published: 01 January 1986
EVIDENCE FOR LINKAGE BETWEEN HL-A HISTOCOMPATIBILITY GENES AND THOSE INVOLVED IN THE SYNTHESIS OF THE SECOND COMPONENT OF COMPLEMENT
Authors: S. M. Fu, H. G. Kunkel, H. P. Brusman, F. H. Allen, M. Fotino
Journal: The Journal of Experimental Medicine (1974)

HL-A analysis of a family with C2 deficiency revealed evidence for close linkage between the C2 defect and the histocompatibility HL-A loci. The propositus was homozygous both for C2 deficiency and the HL-A haplotype 10,W18. Among seven children of three double backcross matings, no recombinants were found. The possible significance of such linkage is discussed.
Acute effects of transdermal nicotine on sleep architecture, snoring, and sleep-disordered breathing in nonsmokers.
Authors: D G Davila, R D Hurt, K P Offord, C D Harris, J W Shepard
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Previous research has suggested that nicotine may be therapeutically useful in the treatment of sleep-disordered breathing. The development of transdermal nicotine delivery systems has allowed us to test the overnight effectiveness of nicotine. Twenty nonsmoking subjects (10 men, 10 women) were recruited on the basis of a history of habitual snoring that was confirmed by overnight laboratory monitoring. Subjects were then randomized (double-blind crossover design) to receive either placebo or an active patch that delivers 11 mg of nicotine over a 24-h period. Patches were applied at 6 P.M. and removed at 6 A.M. the following morning, at which time venous blood was obtained for determination of serum nicotine concentrations. Polysomnography was performed using standard techniques to assess sleep architecture and sleep-disordered breathing. Snoring was monitored with a sound-level meter and quantitatively analyzed to determine the snoring index (SI) (number of snores per hour of sleep) and mean and maximum snoring intensities. The age of the subjects was 46.9 +/- 11.4 yr (mean +/- SD) and their mean body mass index (BMI) 33.3 +/- 4.6 kg/m2. A mean nicotine level was nondetectable with placebo and 7.8 +/- 2.3 ng/ml with wearing of an active patch. Nicotine decreased total sleep time (TST) by 33 min (p < or 0.01), sleep efficiency from 89.7 to 83.5% (p < or = 0.01), and percent rapid eye movement (REM) sleep from 18.8 to 15.1% (p < or = 0.01), and prolonged initial sleep latency (ISL) from 6.7 to 18.2 min (p < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
NHS may miss target on reducing MRSA by 2008, minister says
Authors: Adrian O'Dowd
Journal: BMJ (2006)

The government's target to halve infections of methicillin resistant Staphylococcus aureus (MRSA) in the blood by 2008 is looking uncertain, a UK government minister hinted last week.

The health minister Andy Burnham, giving evidence to MPs in the parliamentary health committee, said that the results he had received showed progress towards the target but that this was not good enough.

The former health secretary John Reid announced in 2004 a new target to halve rates of MRSA infection in the blood by 2008.

Mr Burnham was pessimistic about how well NHS organisations …
Diagnosing patients with longstanding shoulder joint pain
Authors: J Norregaard
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objective:</b> To examine the interobserver agreement of commonly used clinical tests and diagnoses in patients with shoulder pain, and the accuracy of these tests and ultrasonographic findings in comparison with arthroscopic findings. <b>Methods:</b> Eighty six patients with longstanding shoulder joint pain were "blindly" examined by two trained doctors using several clinical tests. In all patients an ultrasonographic examination was performed, and in 42 (49%) an arthroscopy. <b>Results:</b> Tests for impingement showed poor to moderate agreement. Tenderness of muscles, muscle weakness, and tests for labral lesion also showed poor agreement. Pain during muscle contraction showed moderate agreement. The agreement of clinical diagnoses was poor and the accuracy was low in comparison with arthroscopy. Ultrasonography was accurate in full thickness supraspinatus tendon tears, but inaccurate for partial tears and labral lesions. <b>Conclusions:</b> Most clinical tests showed poor agreement. Clinical and ultrasonographic diagnoses had low accuracy in comparison with arthroscopy.
PTU-086 KLF6 splice variant 1 in patients with colorectal liver metastasis correlates with a higher clinical risk score
Authors: K Y D Hui, S Robinson, G L Patman, D Manas, H L Reeves, S White
Journal: Gut (2012)

<h3>Introduction</h3> In its wild type form KLF6 (KLF6-WT) acts as a tumour suppressor gene whose expression is lost in a variety of human cancers. Conversely, KLF-6 splice variant 1 (KLF6-SV1) is able to function as an oncogene playing an important role in tumour proliferation and invasion. The aim of this study was to determine how the expression of these two KLF6 variants in patients with colorectal liver metastases (CRLM) correlates with an established prognostic scoring system. <h3>Methods</h3> Patients undergoing resection of CRLM over a 2-year period were identified for inclusion within this study. Immunohistochemistry was performed using antibodies directed against KLF6-WT and KLF6-SV1 on formalin fixed paraffin embedded tumour samples and the proportion of positively stained nuclei for each was determined using an automated computerised image analysis system. Clinical data were collected and Fong9s Clinical Risk Score (CRS) was calculated as a marker of patients outcome. Spearmans correlation coefficient was used to determine the relationship between nuclear staining of KLF-6 and the CRS. Continuous variables were compared with Mann–Whitney U test. A p value &lt;0.05 was considered significant. <h3>Results</h3> 25 patients (male 64 %) were included in this study with a mean age of 69.2 years (range 52–81). The distribution of CRS were as follows; CRS score 0 n=2, CRS score 1 n=6, CRS score 2 n= 3, CRS score 3 n=10, CRS score 4 n=3, CRS score 5 n=1. Nine patients developed recurrence within 1 year of liver resection. All patients remained alive at the end of the study period. There was a positive correlation between KLF6-SV1 and the calculated CRS (Spearman9s correlation efficient = 0.481, p=0.015) whereas no such correlation existed with KLF6-WT. In those with a CRS &lt;3 the mean proportion of positive nuclear staining for KLF6-SV1 was 5% as compared to 15% in those with a CRS≥3 (p&lt;0.05) <h3>Conclusion</h3> In this preliminary study, high expression of KLF6-SV1 in patients with CRLM correlates with a higher CRS. Further long-term follow-up data are required to determine what affect this has on prognosis and overall patient survival. <h3>Competing interests</h3> K Y D Hui: Grant/Research Support from: Cancer Research UK, the Dowager Countess Eleanor Peel Trust, S Robinson: None declared, G Patman: None declared, D Manas: None declared, H Reeves: None declared, S White: None declared.
Was early man caught knapping during the cognitive (r)evolution?
Authors: Rich Masters, Jon Maxwell
Journal: Behavioral and Brain Sciences (2002)

Wynn describes a revolution in cognitive abilities some 500,000 years ago, which added new sophistication to the curiosity of early man – the ability to form hypotheses. This derivative of archaic curiosity is a fundamental feature of learning, and it is our contention that the naive hypothesis testing behavior of early man will have left a distinctive trail in the archaeological record.