tbuckley/cabot-search huggingface dataset:
Function of Natural Internal Mammary–to–Coronary Artery Bypasses and Its Effect on Myocardial Ischemia
Authors: Michael Stoller, Stefano F. de Marchi, Christian Seiler
Journal: Circulation (2014)

The function of naturally existing internal mammary (IMA)-to-coronary artery bypasses and their quantitative effect on myocardial ischemia are unknown.The primary end point of this study was collateral flow index (CFI) obtained during two 1-minute coronary artery balloon occlusions, the first with and the second without simultaneous distal IMA occlusion. The secondary study end point was the quantitatively determined intracoronary ECG ST-segment elevation. CFI is the ratio of simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. A total of 180 pairs of CFI measurements were performed among 120 patients. With and without IMA occlusion, CFI was 0.110±0.074 and 0.096±0.072, respectively (P<0.0001). The difference of CFI obtained in the presence minus CFI obtained in the absence of IMA occlusion was highest and most consistently positive during left IMA with left anterior descending artery occlusion and during right IMA with right coronary artery occlusion (ipsilateral occlusions): 0.033±0.044 and 0.025±0.027, respectively. This CFI difference was absent during right IMA with left anterior descending artery occlusion and during left IMA with right coronary artery occlusion (contralateral occlusions): -0.007±0.034 and 0.001±0.023, respectively (P=0.0002 versus ipsilateral occlusions). The respective CFI differences during either IMA with left circumflex artery occlusion were inconsistently positive. Intracoronary ECG ST-segment elevations were significantly reduced during ipsilateral IMA occlusions but not during contralateral or left circumflex artery occlusions.There is a functional, ischemia-reducing extracardiac coronary artery supply via ipsilateral but not via contralateral natural IMA bypasses.http://www.clinicaltrials.gov. Unique identifier: NCTO1676207.
Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary disease: long term survival and predictors of in-hospital outcome
Authors: P K Plant
Journal: Thorax (2001)

Background-Non-invasive ventilation (NIV) reduces the need for intubation and the mortality associated with an exacerbation of chronic obstructive pulmonary disease (COPD).This study aimed to identify factors that could be used to stratify patients according to their risk of requiring invasive mechanical ventilation.The second aim was to determine the long term survival of patients treated with and without NIV.Methods-In this prospective multicentre randomised controlled trial 118 patients were allocated to standard treatment and 118 to NIV between November 1996 and September 1998.Arterial blood gas tensions and respiratory rate were recorded at enrolment and after 1 and 4 hours.Prognostic factors were identified using logistic regression analysis.All patients were followed until death or 1 January 1999.Results-At enrolment the H + concentration (OR 1.22 per nmol/l, 95% CI 1.09 to 1.37, p<0.01) and PaCO 2 (OR 1.14 per kPa, 95% CI 1.14 to 1.81, p<0.01) were associated with treatment failure.Allocation to NIV was protective (OR 0.39, 95% CI 0.19 to 0.80).After 4 hours of treatment improvement in acidosis (OR 0.89 per nmol/l, 95% CI 0.82 to 0.97, p<0.01) and fall in respiratory rate (OR 0.92 per breaths/min, 95% CI 0.84 to 0.99, p=0.04) were associated with success.Median length of survival was 16.8 months in those treated with NIV and 13.4 months in those receiving standard treatment (p=0.12).The trend in improved survival was attributable to prevention of death during the index admission.Conclusion-Initial pH and hypercapnia can be used to stratify groups of patients according to their risk of needing intubation.NIV reduces this risk and progress should be monitored using change in respiratory rate and pH.The long term survival after NIV is suYciently good to render treatment appropriate.
Demonstration, of Insulin Resistance in Coronary Artery Disease Documented With Angiography
Authors: Kazuya Shinozaki, Masaaki Suzuki, Motoyoshi Ikebuchi, Yasushi Hara, Yutaka Harano
Journal: Diabetes Care (1996)

OBJECTIVE To evaluate the relation between insulin resistance and coronary atherosclerosis, insulin sensitivity in lean nondiabetic, normotensive subjects with and without obstructive coronary artery disease (CAD). The correlation between insulin resistance and degree of coronary stenosis was also investigated. RESEARCH DESIGN AND METHODS Four groups were studied: 1) nine subjects with normal glucose tolerance(NGT) without CAD, 2) 10 subjects with NGT with CAD, 3) nine subjects withimpaired glucose tolerance (IGT) without CAD, and 4) 10 subjects with IGT with CAD. Insulin sensitivity was determined by the steady-state plasma glucose (SSPG) method using Sandostatin. Coronary angiography was performed in all study subjects, and the severity of coronary artery atherosclerosis wasquantified in a modified Gensini score. RESULTS The SSPG (millimoles per liter) levels were significantly higher in the patients with CAD compared with control subjects (control vs. patient group: 4.8 ±0.5 vs. 7.9 ± 0.9 with NGT, P &amp;lt; 0.05; 5.6 ± 0.5 vs. 11.1 ± 0.8 with IGT, P &amp;lt; 0.001), indicating the presence of insulin resistance in patients with CAD. The coronary atherosclerosis score (CAS) was significantly and positively correlated with SSPG (r = 0.74, P &amp;lt; 0.05) and 2-h insulin area (r = 0.78, P &amp;lt; 0.01) in NGT subjects with CAD. On the other hand, the percentage fall of plasma free fatty acid (0–30 min) during an insulin sensitivity test was significantly decreased in the subjects with CAD and was inversely correlated with the CAS (r = −0.43, P &amp;lt; 0.05), especially in NGT subjects with CAD. CONCLUSIONS These data suggest that in patients with CAD, insulin-mediated glucose metabolism is significantly impaired, and a significant correlation was noted between insulin resistance and severity of CAD. Therefore, the hyperinsulinemia often observed in patients with CAD is attributable to the compensatory mechanism of the β-cell to the inadequate action of insulin for glucose metabolism. Hyperinsulinemia in the presence of insulin resistance aggravates dyslipidemia and may stimulate the atheromatous process by an as-yet-unknown mechanism.
Desert Hedgehog Promotes Ischemia-Induced Angiogenesis by Ensuring Peripheral Nerve Survival
Authors: Marie-Ange Renault, Candice Chapouly, Qinyu Yao, Frédéric Larrieu-Lahargue, Soizic Vandierdonck, Annabel Reynaud, Myriam Petit, Béatrice Jaspard-Vinassa, Isabelle Belloc, Elisabeth Traiffort, Martial Ruat, Cécile Duplàa, Thierry Couffinhal, Claude Desgranges, Alain-Pierre Gadeau
Journal: Circulation Research (2013)

Blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves.The purpose of this study was to investigate the contribution of Dhh to angiogenesis in the setting of ischemia.We induced hindlimb ischemia in wild-type and Dhh(-/-) mice. First, we found that limb perfusion is significantly impaired in the absence of Dhh. This effect is associated with a significant decrease in capillary and artery density in Dhh(-/-). By using mice in which the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial cells, we demonstrated that Dhh does not promote angiogenesis by a direct activation of endothelial cells. On the contrary, we found that Dhh promotes peripheral nerve survival in the ischemic muscle and, by doing so, maintains the pool of nerve-derived proangiogenic factors. Consistently, we found that denervation of the leg, immediately after the onset of ischemia, severely impairs ischemia-induced angiogenesis and decreases expression of vascular endothelial growth factor A, angiopoietin 1, and neurotrophin 3 in the ischemic muscle.This study demonstrates the crucial roles of nerves and factors regulating nerve physiology in the setting of ischemia-induced angiogenesis.
Catching breath: monitoring airway inflammation using exhaled breath condensate
Authors: O. Holz
Journal: European Respiratory Journal (2005)

Airway inflammation plays a key role in asthma, chronic obstructive pulmonary disease (COPD) and other airway diseases. Noninvasive methods as tools to study these inflammatory processes and to monitor airway diseases are in high demand. This has lead to the rediscovery of sputum analysis and sputum induction as noninvasive tools to obtain samples from the airways 1. Around this time increased concentrations of nitric oxide (NO) were detected in the exhaled air of asthmatics 2, stimulating interest in breath analysis as an even easier way to assess airway inflammation. The analysis of exhaled breath condensate (EBC) was already known at this time, but only 15 publications related to EBC (between 1990 and 1997) show that only a few researchers used this method as a tool to collect material from the respiratory system. Interest grew steadily, resulting in ∼50 publications in the following 4 yrs and the creation of a joint European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force at the 2001 ERS meeting in Berlin. This was an early effort to standardise the methodology of collecting and analysing EBC. In this issue of the European Respiratory Journal 3, the leading experts in the field present their final report providing methodological recommendations and a summary of unresolved questions to serve as a guideline for future research.

The appeal of EBC lies in its ability to noninvasively collect a wide range of nonvolatile molecules from the respiratory tract. However, this large number of potentially interesting molecules, which all need to be investigated and validated, seem to be the reason for the rather slow overall progress and the considerable number of open questions listed …
Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis
Authors: Afam Okoye, Haesun Park, Mukta Rohankhedkar, Lia Coyne-Johnson, Richard Lum, Joshua M. Walker, Shannon L. Planer, Alfred W. Legasse, Andrew W. Sylwester, Michael Piatak, Jeffrey D. Lifson, Donald L. Sodora, Francois Villinger, Michael K. Axthelm, Joern E. Schmitz, Louis J. Picker
Journal: The Journal of Experimental Medicine (2009)

Depletion of CD8+ lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8+ lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8+ lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4+ effector memory T (TEM) cells and, to a lesser extent, transitional memory T (TTrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4+/CCR5+ SIV “target” cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8+ lymphocytes in SIV− RMs led to a sustained increase in the number of potential CD4+ SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4+ TEM cell proliferation of CD8+ lymphocyte–depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4+ TEM and TTrM cell proliferation, it did not recapitulate the viral dynamics of CD8+ lymphocyte depletion. These data suggest that CD8+ lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production.
Purification and characterization of Haemophilus influenzae pili, and their structural and serological relatedness to Escherichia coli P and mannose-sensitive pili.
Authors: N G Guerina, S Langermann, G K Schoolnik, T W Kessler, D A Goldmann
Journal: The Journal of Experimental Medicine (1985)

Haemophilus influenzae pili were purified, and their physical and serological properties were examined. The solution properties of the pili were determined, and then a purification scheme involving repeated cycles of precipitation and solubilization was developed. The purified pili from one type b isolate (A02) were found to consist of multiple copies of a 25,000 mol wt subunit. Amino-terminal sequence analysis of A02 pili was carried out to 40 amino acid residues, and a remarkable degree of sequence homology was found with E. coli P and mannose-sensitive (MS) pili (27.5 and 25% homology, respectively). Purified A02 pili were found to be highly immunogenic, and serological analysis by enzyme-linked immunosorbent assay and whole piliated cell agglutination revealed significant cross-reactivity between A02 pilus antiserum and the pili of seven other H. influenzae strains tested (heterologous titers = 2-100% of the homologous titer). Cross-reactivity was also observed between the H. influenzae pili (five of eight strains tested) and the P pili from E. coli strains HU849 and 3669; no cross-reactivity was detected with MS pili from E. coli strain H10407 and C94. The structural similarities between H. influenzae and E. coli P and MS pili suggest a common gene ancestry.
I Ks response to protein kinase A-dependent KCNQ1 phosphorylation requires direct interaction with microtubules
Authors: Céline S. Nicolas, Kyu-Ho Park, Aziza El Harchi, Jacques Camonis, Robert S. Kass, Denis Escande, Jean Mérot, Gildas Loussouarn, Françoise Le Bouffant, Isabelle Baró
Journal: Cardiovascular Research (2008)

AimsKCNQ1 (alias KvLQT1 or Kv7.1) and KCNE1 (alias IsK or minK) co-assemble to form the voltage-activated K+ channel responsible for IKs—a major repolarizing current in the human heart—and their dysfunction promotes cardiac arrhythmias. The channel is a component of larger macromolecular complexes containing known and undefined regulatory proteins. Thus, identification of proteins that modulate its biosynthesis, localization, activity, and/or degradation is of great interest from both a physiological and pathological point of view.
The Relationship Between Serum Ghrelin and the Risk of Gastric and Esophagogastric Junctional Adenocarcinomas
Authors: G. Murphy, F. Kamangar, S. M. Dawsey, F. Z. Stanczyk, S. J. Weinstein, P. R. Taylor, J. Virtamo, C. C. Abnet, D. Albanes, N. D. Freedman
Journal: JNCI Journal of the National Cancer Institute (2011)

Cancers of the upper gastrointestinal tract remain a substantial cause of morbidity and mortality worldwide. Ghrelin is a hormone produced in the oxyntic glands of the stomach, and under conditions of chronic inflammation and atrophy, serum ghrelin concentrations decrease. However, the relationship between ghrelin and the risk of gastric and esophagogastric junctional cancers has not been investigated.We conducted a nested case-control study within the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to examine the relationship between serum ghrelin concentration and the risk of gastric noncardia adenocarcinoma (GNCA) and esophagogastric junctional adenocarcinoma (EGJA). Data from 261 GNCA patients, 98 EGJA patients, and 441 control subjects were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression with adjustment for potential confounders. Lag analysis was also performed to investigate the temporal nature of the associations between baseline serum pepsinogen I and ghrelin in GNCA and EGJA patients. All statistical tests were two-sided.Lower concentrations of serum ghrelin were statistically significantly associated with an increased risk of both GNCA (adjusted OR = 1.75, 95% CI = 1.49 to 2.04; P < .001) and EGJA (adjusted OR = 1.56, 95% CI = 1.28 to 1.89, P < .001). A multivariable model found that the risk of both GNCA and EGJA were statistically significantly increased for those individuals in the lowest quartile of serum ghrelin levels compared with those in the highest quartile (OR of GNCA = 5.63, 95% CI = 3.16 to 10.03; OR of EGJA = 4.90, 95% CI = 2.11 to 11.35). The statistical significance of these associations remained even after restricting the analysis to those patients who developed cancer more than 10 years after baseline serum ghrelin measurements.Low baseline concentrations of serum ghrelin were associated with a statistically significant increase in the risk of GNCA and EGJA, suggesting a potential role for gastric hormones in carcinogenesis.
Genomic homogeneity in fibrolamellar carcinomas
Authors: Y Sirivatanauksorn
Journal: Gut (2001)

<h3>BACKGROUND</h3> Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC) with distinctive clinical and histological features. To date there have been few studies on the genotypic aspects of FLC and no previous attempts have been made to use the arbitrarily primed-polymerase chain reaction (AP-PCR) technique to detect genetic alterations in this disease. <h3>AIM</h3> The aim of this study was to assess the degree of genomic heterogeneity of FLC using the AP-PCR technique. <h3>METHODS</h3> A total of 50 tissue samples of primary and metastatic FLCs from seven patients were microdissected. AP-PCR amplification of each genomic DNA sample was carried out using two arbitrary primers. <h3>RESULTS</h3> DNA fingerprints of the primary FLCs and all their metastatic lesions (both synchronous and metachronous disease) were identical in an individual patient. The fingerprints were different between tumours of different patients. No evidence of intratumour heterogeneity was observed. <h3>CONCLUSIONS</h3> Such genomic homogeneity in FLCs may explain their indolent growth. The absence of clonal evolution, which is present in other tumours (particularly HCCs), may explain the distinct behaviour in this tumour. The tumorigenic pathway and degree of somatic genomic changes in this disease may be less complex than in HCC.
What’s new in bacterial meningitis
Authors: Matthijs C. Brouwer, Eelco F. M. Wijdicks, Diederik van de Beek
Journal: Intensive Care Medicine (2015)

Hypothermia is associated with increased mortality Ajdukiewicz et al. [16] Adults, Malawi Glycerol vs. placebo 265 Glycerol is associated with increased mortality
Policy on the rebound: trends and causes of delayed discharges in the NHS
Authors: S Godden, D McCoy, AM Pollock
Journal: Journal of the Royal Society of Medicine (2009)

Summary Objectives The Community Care (Delayed Discharges, etc.) Act, 2003 was aimed at reducing the number of patients whose discharge from hospital was delayed, incorporating financial incentives based on a model from Sweden. The Act permitted NHS hospital trusts to charge local authority Social Service Departments for delays they were deemed responsible for and was accompanied by grants aimed at supporting improvements in the transfer of care. This study aims to assess how far the subsequent reduction in delays has been due to the operation of the Act, and to evaluate the extent that the legislation increased efficiency across health and social care. Design Analysis and interpretation of a range of official routine health statistics plus unpublished performance data. Setting Data on patients delayed in hospital in England from 2001–2002 to 2006–2007 and trends in hospital activity. Main outcome measures Trend analysis of health statistics and performance data relating to delayed discharges and other relevant indicators. Results Althought there has been an overall reduction in delayed discharges, this trend predates the implementation of the Act. Overall, bed- days lost to delayed discharges accounted for only a small proportion of all bed-days – 1.6% in 2006–2007, and over the period studied the causes of the majority of delays were attributed to the NHS (68%). Conclusions These findings indicate lttle evidence to support the policy of charging social services to improve public sector efficiency. The focus on reducing delays should be set in the context of the wider health economy. There are a number of pressures to reduce the time patients spend in hospital including fewer beds and increasing numbers of admissions, plus a rise in emergency readmission rates is noted. There are few good data available to monitor the impact of earlier discharge, such as on the quality and availability of post-discharge care.
Identification of a Novel Antibody Associated with Autoimmune Pancreatitis
Authors: Luca Frulloni, Claudio Lunardi, Rita Simone, Marzia Dolcino, Chiara Scattolini, Massimo Falconi, Luigi Benini, Italo Vantini, Roberto Corrocher, Antonio Puccetti
Journal: New England Journal of Medicine (2009)

Autoimmune pancreatitis is characterized by an inflammatory process that leads to organ dysfunction. The cause of the disease is unknown. Its autoimmune origin has been suggested but never proved, and little is known about the pathogenesis of this condition.
Protein Kinase C-β Contributes to Impaired Endothelial Insulin Signaling in Humans With Diabetes Mellitus
Authors: Corey E. Tabit, Sherene M. Shenouda, Monica Holbrook, Jessica L. Fetterman, Soroosh Kiani, Alissa A. Frame, Matthew A. Kluge, Aaron Held, Mustali M. Dohadwala, Noyan Gokce, Melissa G. Farb, James Rosenzweig, Neil Ruderman, Joseph A. Vita, Naomi M. Hamburg
Journal: Circulation (2012)

Abnormal endothelial function promotes atherosclerotic vascular disease in diabetes. Experimental studies indicate that disruption of endothelial insulin signaling, through the activity of protein kinase C-β (PKCβ) and nuclear factor κB, reduces nitric oxide availability. We sought to establish whether similar mechanisms operate in the endothelium in human diabetes mellitus.We measured protein expression and insulin response in freshly isolated endothelial cells from patients with type 2 diabetes mellitus (n=40) and nondiabetic controls (n=36). Unexpectedly, we observed 1.7-fold higher basal endothelial nitric oxide synthase (eNOS) phosphorylation at serine 1177 in patients with diabetes mellitus (P=0.007) without a difference in total eNOS expression. Insulin stimulation increased eNOS phosphorylation in nondiabetic subjects but not in diabetic patients (P=0.003), consistent with endothelial insulin resistance. Nitrotyrosine levels were higher in diabetic patients, indicating endothelial oxidative stress. PKCβ expression was higher in diabetic patients and was associated with lower flow-mediated dilation (r=-0.541, P=0.02). Inhibition of PKCβ with LY379196 reduced basal eNOS phosphorylation and improved insulin-mediated eNOS activation in patients with diabetes mellitus. Endothelial nuclear factor κB activation was higher in diabetes mellitus and was reduced with PKCβ inhibition.We provide evidence for the presence of altered eNOS activation, reduced insulin action, and inflammatory activation in the endothelium of patients with diabetes mellitus. Our findings implicate PKCβ activity in endothelial insulin resistance.
Differentiation of Effector CD4 T Cell Populations
Authors: Jinfang Zhu, Hidehiro Yamane, William E. Paul
Journal: Annual Review of Immunology (2010)

CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.