tbuckley/cabot-search huggingface dataset:
Matrix metalloproteinases in tuberculosis
Authors: P.T. Elkington, C.A. Ugarte-Gil, J.S. Friedland
Journal: European Respiratory Journal (2011)

Tuberculosis (TB) remains a global health pandemic. Infection is spread by the aerosol route and Mycobacterium tuberculosis must drive lung destruction to be transmitted to new hosts. Such inflammatory tissue damage is responsible for morbidity and mortality in patients. The underlying mechanisms of matrix destruction in TB remain poorly understood but consideration of the lung extracellular matrix predicts that matrix metalloproteinases (MMPs) will play a central role, owing to their unique ability to degrade fibrillar collagens and other matrix components. Since we proposed the concept of a matrix degrading phenotype in TB a decade ago, diverse data implicating MMPs as key mediators in TB pathology have accumulated. We review the lines of investigation that have indicated a critical role for MMPs in TB pathogenesis, consider regulatory pathways driving MMPs and propose that inhibition of MMP activity is a realistic goal as adjunctive therapy to limit immunopathology in TB.
The effect of capsaicin on gallbladder fluid absorption
Authors: Stephen Fitzgerald, Yashwant G. Deshpande, Han Q. Nguyen, Donald L. Kaminski
Journal: Hepatology (1991)

The role of the enteric nervous system of the gallbladder on mucosal water absorption was evaluated by intraluminal administration of capsaicin, a selective stimulant of afferent nerve endings. It has been postulated that the neural responses of the gallbladder are peptidergic and mediated by prostanoids. Anesthetized cats underwent gallbladder perfusion with a physiological buffer solution containing 14C polyethylene glycol as a nonabsorbable tracer to quantitate mucosal water absorption. Capsaicin was added to the perfusate and administered intraluminally at a rate of 5 mg/kg−1/hr− for 2 hr. One experiment on five cats was performed when capsaicin was administered and five control experiments were performed when only vehicle was added to the perfusate. Five experiments were performed when indomethacin was administered intravenously (5 mg/kg−1/hr−1) and buffer solution alone was used to perfuse the gallbladder, and five experiments were performed when capsaicin was added to the perfusate and indomethacin was administered intravenously. Additional experiments were performed when lidocaine was added to the perfusate and when lidocaine and capsaicin were administered simultaneously. Gallbladder absorption and perfusate and tissue prostaglandin E and 6 keto prostaglandin F1α concentrations were evaluated. To determine whether capsaicin induced gallbladder inflammation, tissue myeloperoxidase concentrations were measured. Control feline gallbladders absorbed approximately 0.6 ml/hr. Indomethacin alone significantly decreased gallbladder absorption. Capsaicin administration increased gallbladder absorption to approximately 1.6 ml/hr, and this increase was significantly inhibited by indomethacin. Lidocaine significantly decreased control, and capsaicin stimulated gallbladder absorption. Capsaicin significantly increased perfusate prostaglandin E and 6 keto prostaglandin F1α concentrations with significant depletion of tissue prostanoids. Indomethacin significantly decreased perfusate prostanoid concentrations while decreasing the water absorption during capsaicin administration, suggesting that the two processes are related. Lidocaine eliminated the increased perfusate prostaglandin E concentrations produced by capsaicin but did not alter the increased concentrations of 6 keto prostaglandin F1α in the perfusate. Gallbladder tissue myeloperoxidase concentrations were not significantly changed by capsaicin. The results suggest that gallbladder water absorption is affected by afferent nerve stimulation by a prostanoid-mediated mechanism. (HEPATOLOGY 1991;14:660–664.)
THE HISTOLOGICAL CHANGES IN THE THYROID GLAND OF THE RABBIT FOLLOWING LOBECTOMY
Authors: J. Hamilton Crawford, J. N. J. Hartley
Journal: The Journal of Experimental Medicine (1925)

1. In a series of rabbits the changes which took place in the histology of the left lobe of the thyroid gland after excision of the right lobe have been studied at varied intervals of time. 2 days after the removal of one lobe the other lobe showed a slightly increased colloid content, an increased vacuolation of the colloid, and a slight increase in the size of the epithelial cells. At the end of a week the vesicles were greatly increased in size, distended with colloid, and the epithelial cells were flattened, while after 3 to 4 months signs of compensatory hypertrophy were present. 2. The changes observed were uninfluenced by division of the vagus or cervical sympathetic.
The FGF-2-triggered protection of cardiac subsarcolemmal mitochondria from calcium overload is mitochondrial connexin 43-dependent
Authors: Wattamon Srisakuldee, Zhanna Makazan, Barbara E. Nickel, Feixiong Zhang, James A. Thliveris, Kishore B.S. Pasumarthi, Elissavet Kardami
Journal: Cardiovascular Research (2014)

AimsFibroblast growth factor 2 (FGF-2) protects the heart from ischaemia- and reperfusion-induced cell death by a mechanism linked to protein kinase C (PKC)ε-mediated connexin 43 (Cx43) phosphorylation. Cx43 localizes predominantly to gap junctions, but has also been detected at subsarcolemmal (SSM), but not interfibrillar (IFM), mitochondria, where it is considered important for cardioprotection. We have now examined the effect of FGF-2 administration to the heart on resistance to calcium-induced permeability transition (mPTP) of isolated SSM vs. IFM suspensions, in relation to mitochondrial PKCε/Cx43 levels, phosphorylation, and the presence of peptide Gap27, a Cx43 channel blocker.
Significant Associations of Mismatch Repair Gene Polymorphisms With Clinical Outcome of Pancreatic Cancer
Authors: Xiaoqun Dong, Li Jiao, Yanan Li, Douglas B. Evans, Huamin Wang, Kenneth R. Hess, James L. Abbruzzese, Donghui Li
Journal: Journal of Clinical Oncology (2009)

DNA mismatch repair (MMR) is critical in maintaining genomic stability and may modulate the cellular response to gemcitabine. We hypothesized that genetic variations in MMR may affect the clinical outcome of patients with pancreatic cancer.We evaluated 15 single-nucleotide polymorphisms (SNPs) of eight MMR genes in 154 patients with potentially resectable pancreatic adenocarcinoma who were enrolled onto phase II clinical trials for preoperative gemcitabine-based chemoradiotherapy from 1999 to 2006. Associations of genotypes with tumor response to therapy (change of tumor size by radiologic evaluation at restaging), margin-negative tumor resection, and overall survival were evaluated using logistic regression and Cox proportional regression models.Five, six, and 10 genotypes were significantly associated with tumor response to preoperative chemoradiotherapy, tumor resectability, and overall survival, respectively, in univariable analysis. TREX1 EX14-460C>T and TP73 Ex2+4G>A genotypes remained as significant predictors for tumor response, MLH1 IVS12-169C>T and TP73 remained as significant predictors for tumor resectability, and EXO1 R354H, TREX1, and TP73 remained as significant predictors for overall survival in multivariable models that included all clinical factors and genotypes examined. A strong combined genotype effect on each clinical end point was observed. For example, 20 of the 25 patients with zero to one adverse genotypes were alive, those with two, three, four, five, and six to seven adverse genotypes had median survival times of 36.2, 23.9, 16.3, 13.0, and 8.3 months, respectively (P < .001).SNPs of MMR genes have a potential value as predictors for clinical response to chemoradiotherapy and as prognostic markers for tumor resectability and overall survival of patients with resectable pancreatic cancer.
Identical Outcome After Autologous or Allogeneic Genoidentical Hematopoietic Stem-Cell Transplantation in First Remission of Acute Myelocytic Leukemia Carrying Inversion 16 or t(8;21): A Retrospective Study From the European Cooperative Group for Blood and Marrow Transplantation
Authors: Norbert-Claude Gorin, Myriam Labopin, Francesco Frassoni, Noel Milpied, Michel Attal, Didier Blaise, Giovanna Meloni, Anna P. Iori, Mauricette Michallet, Roel Willemze, Eric Deconninck, Jean-Luc Harousseau, Emmanuelle Polge, Vanderson Rocha
Journal: Journal of Clinical Oncology (2008)

Patients with acute myelocytic leukemia carrying inversion 16 (inv16) or t(8;21) have a better initial response to high-dose cytarabine than patients without these chromosomal abnormalities. They presently do not undergo transplantation in first remission (CR1), but there is concern about late relapses.From 1990 to 2004, 325 adult patients received transplantations in CR1 (159 patients with inv16 and 166 patients with t(8;21), including 35 and 60 patients, respectively, with additional chromosomal abnormalities). Genoidentical allografts were performed in 64 patients with inv16 and 81 patients with t(8;21), and autografts were performed in 95 patients with inv16 and 85 patients with t(8;21).In patients with inv16, after allogeneic and autologous transplantation, the 5-year leukemia-free survival (LFS) rates were 59% and 66% (P = .5), the relapse incidence (RI) rates were 27% and 32% (P = .45), and the transplantation-related mortality (TRM) rates were 14% and 2% (P = .003), respectively. Female patients had a lower RI and a higher LFS. Additional chromosomal abnormalities, compared with no additional abnormalities, were associated with lower RI rate (12% v 34%, respectively; P = .01) and higher 5-year LFS rate (78% v 59%, respectively; P = .04). In patients with t(8;21), after allogeneic and autologous transplantation, the 5-year LFS rates were 60% and 66% (P = .69), the RI rates were 15% and 28% (P = .03), and the TRM rates were 24% and 6% (P = .003), respectively. Younger age and a lower WBC count at diagnosis were associated with a lower TRM and a better LFS. The TRM was lower and the RI was higher in patients with autologous transplantations versus allogeneic transplantations.Both autologous and allogeneic transplantation resulted in similar outcomes.
Reflex Changes in Human Skeletal Muscle Blood Flow Associated with Intrathoracic Pressure Changes
Authors: I. C. RODDIE, J. T. SHEPHERD, R. F. WHELAN
Journal: Circulation Research (1958)

Rapid alternating intrathoracic pressure changes caused by rapid breathing with partial obstruction to airflow caused a three to four fold increase in forearm blood flow whereas following the Valsalva maneuver the blood flow was decreased. Evidence is presented that these changes are brought about reflexly through alterations in vasoconstrictor tone. It is demontrated that the reflex changes are confined to skeletal muscle vessels, providing further evidence that the vasomotor centers controlling skin and muscle vessels can function independently.
An Official American Thoracic Society/European Respiratory Society Policy Statement: Disparities in Respiratory Health
Authors: Dean E. Schraufnagel, Francesco Blasi, Monica Kraft, Mina Gaga, Patricia W. Finn, Klaus F. Rabe
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Section:ChooseTop of pageAbstract <<ContentsExecutive SummaryBackgroundMethodsWhat the ATS and the ERS ...THE ATS and ERS Plans to ...ReferencesCITING ARTICLES
First Documented Rhythm and Clinical Outcome From In-Hospital Cardiac Arrest Among Children and Adults
Authors: Vinay M. Nadkarni, Gregory Luke Larkin, Mary Ann Peberdy, Scott M. Carey, William Kaye, Mary E. Mancini, Graham Nichol, Tanya Lane-Truitt, Jerry Potts, Joseph P. Ornato, Robert A. Berg
Journal: JAMA (2006)

ContextCardiac arrests in adults are often due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), which are associated with better outcomes than asystole or pulseless electrical activity (PEA). Cardiac arrests in children are typically asystole or PEA.ObjectiveTo test the hypothesis that children have relatively fewer in-hospital cardiac arrests associated with VF or pulseless VT compared with adults and, therefore, worse survival outcomes.Design, Setting, and PatientsA prospective observational study from a multicenter registry (National Registry of Cardiopulmonary Resuscitation) of cardiac arrests in 253 US and Canadian hospitals between January 1, 2000, and March 30, 2004. A total of 36 902 adults (≥18 years) and 880 children (&lt;18 years) with pulseless cardiac arrests requiring chest compressions, defibrillation, or both were assessed. Cardiac arrests occurring in the delivery department, neonatal intensive care unit, and in the out-of-hospital setting were excluded.Main Outcome MeasureSurvival to hospital discharge.ResultsThe rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than adults (27% [236/880] vs 18% [6485/36 902]; adjusted odds ratio [OR], 2.29; 95% confidence interval [CI], 1.95-2.68). Of these survivors, 65% (154/236) of children and 73% (4737/6485) of adults had good neurological outcome. The prevalence of VF or pulseless VT as the first documented pulseless rhythm was 14% (120/880) in children and 23% (8361/36 902) in adults (OR, 0.54; 95% CI, 0.44-0.65; P&lt;.001). The prevalence of asystole was 40% (350) in children and 35% (13 024) in adults (OR, 1.20; 95% CI, 1.10-1.40; P = .006), whereas the prevalence of PEA was 24% (213) in children and 32% (11 963) in adults (OR, 0.67; 95% CI, 0.57-0.78; P&lt;.001). After adjustment for differences in preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, intensive care unit location of arrest, and duration of cardiopulmonary resuscitation, only first documented pulseless arrest rhythm remained significantly associated with differential survival to discharge (24% [135/563] in children vs 11% [2719/24 987] in adults with asystole and PEA; adjusted OR, 2.73; 95% CI, 2.23-3.32).ConclusionsIn this multicenter registry of in-hospital cardiac arrest, the first documented pulseless arrest rhythm was typically asystole or PEA in both children and adults. Because of better survival after asystole and PEA, children had better outcomes than adults despite fewer cardiac arrests due to VF or pulseless VT.
Renal accumulation of salicylate and phenacetin: possible mechanisms in the nephropathy of analgesic abuse
Authors: Lewis W. Bluemle, Martin Goldberg
Journal: Journal of Clinical Investigation (1968)

Since either aspirin or phenacetin might be causative in the nephropathy of analgesic abuse, studies were designed to examine the renal accumulation and distribution of the major metabolic products of these compounds, salicylate and N-acetyl-p-aminophenol (APAP) respectively, in dogs. Nineteen hydropenic animals were studied, of which seven were given phenacetin, nine received acetyl salicylic acid, two were given both aspirin and phenacetin, and one received APAP directly. Two of three hydrated animals were given phenacetin and one was given aspirin. During peak blood levels of salicylate and (or) APAP, the kidneys were rapidly removed, frozen, sliced from cortex to papillary tip, and analyzed for water, urea, APAP, and salicylate.
Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms
Authors: M.I. Gunnbjörnsdóttir, E. Omenaas, T. Gíslason, E. Norrman, A‐C. Olin, R. Jõgi, E.J. Jensen, E. Lindberg, E. Björnsson, K. Franklin, C. Janson
Journal: European Respiratory Journal (2004)

Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5–10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI &gt;30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults.
DNA methylation is associated with downregulation of the organic cation transporter OCT1 (SLC22A1) in human hepatocellular carcinoma
Authors: Elke Schaeffeler, Claus Hellerbrand, Anne T Nies, Stefan Winter, Stephan Kruck, Ute Hofmann, Heiko van der Kuip, Ulrich M Zanger, Hermann Koepsell, Matthias Schwab
Journal: Genome Medicine (2011)

Organic cation transporters (OCTs) determine not only physiological processes but are also involved in the cellular uptake of anticancer agents. Based on microarray analyses in hepatocellular carcinoma (HCC), SLC22A1/OCT1 mRNA seems to be downregulated, but systematic protein expression data are currently missing. Moreover, the underlying molecular mechanisms responsible for altered SLC22A1 expression in HCC are not fully understood. Therefore, we investigated the role of DNA methylation in the transcriptional regulation of the family members SLC22A1/OCT1, SLC22A2/OCT2 and SLC22A3/OCT3 in HCC. Semiquantitative immunohistochemistry of SLC22A1 protein expression was performed in paired HCC and histological normal adjacent liver tissues (n = 71) using tissue microarray analyses, and the results were correlated with clinicopathological features. DNA methylation, quantified by MALDI-TOF mass spectrometry and gene expression of SLC22A1, SLC22A2 and SLC22A3 were investigated using fresh-frozen HCC (n = 22) and non-tumor adjacent liver tissues as well as histologically normal liver samples (n = 120) from a large-scale liverbank. Based on tissue microarray analyses, we observed a significant downregulation of SLC22A1 protein expression in HCC compared to normal adjacent tissue (P < 0.0001). SLC22A1 expression was significantly inverse correlated with expression of the proliferation marker MIB1/Ki-67 (rs = -0.464, P < 0.0001). DNA methylation of SLC22A1 was significantly higher in HCC compared with non-tumor adjacent liver tissue and was lowest in histologically normal liver tissue. Methylation levels for SLC22A1 in combination with RASSF1A resulted in a specificity of > 90% and a sensitivity of 82% for discriminating HCC and tumor-free liver tissue. DNA methylation of SLC22A1 is associated with downregulation of SLC22A1 in HCC and might be a new biomarker for HCC diagnosis and prognosis. Moreover, targeting SLC22A1 methylation by demethylating agents may offer a novel strategy for anticancer therapy of HCC.
The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking
Authors: Shupeng Li, ZhaoXia Li, Lin Pei, Anh D. Le, Fang Liu
Journal: The Journal of Experimental Medicine (2012)

Smoking is the leading preventable cause of disease, disability, and premature death. Nicotine, the main psychoactive drug in tobacco, is one of the most heavily used addictive substances, and its continued use is driven through activation of nicotinic acetylcholine receptors (nAChRs). Despite harmful consequences, it is difficult to quit smoking because of its positive effects on mood and cognition that are strong reinforcers contributing to addiction. Furthermore, a formidable challenge for the treatment of nicotine addiction is the high vulnerability to relapse after abstinence. There is no currently available smoking cessation product able to achieve a &amp;gt;20% smoking cessation rate after 52 wk, and there are no medications that directly target the relapse process. We report here that the α7nAChR forms a protein complex with the NMDA glutamate receptor (NMDAR) through a direct protein–protein interaction. Chronic nicotine exposure promotes α7nAChR–NMDAR complex formation. Interestingly, administration of an interfering peptide that disrupts the α7nAChR–NMDAR complex decreased extracellular signal-regulated kinase (ERK) activity and blocked cue-induced reinstatement of nicotine seeking in rat models of relapse, without affecting nicotine self-administration or locomotor activity. Our results may provide a novel therapeutic target for the development of medications for preventing nicotine relapse.
Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity
Authors: Rekha Chaudhuri, Charles McSharry, Jeffrey Brady, Iona Donnelly, Christal Grierson, Stephen McGuinness, Lisa Jolly, Christopher J. Weir, C. Martina Messow, Mark Spears, Gino Miele, Karl Nocka, Dan Crowther, Joyce Thompson, Maureen Brannigan, Jane Lafferty, Michael Sproule, William MacNee, Martin Connell, John T. Murchison, Malcolm C. Shepherd, Giora Feuerstein, Douglas K. Miller, Neil C. Thomson
Journal: Journal of Allergy and Clinical Immunology (2012)
US (Officially) Honors Physicians With First 'National Doctors' Day'
Authors: Andrew Skolnick
Journal: JAMA (1991)

MEDICAL SOCIETY auxiliaries throughout the country are busy with a multitude of plans for observing the first National Doctors'  on March 30.  This national  is authorized by Congress and the President. In signing the proclamation, President George Bush noted that the March 30 special day honors physicians for what he and Congress call their invaluable  to the welfare of the nation.  Actually, Doctors' Day began 58 years ago when Eudora B. Almond of the Barrow County (Ga) Medical Society Auxiliary suggested that her auxiliary set aside March 30 to recognize the contributions of local physicians. March 30 was selected because it was on that day in 1842 that Crawford W. Long, MD, a Georgian, became the first physician to use ether anesthesia in surgery.  Well Received  The Barrow County auxiliary immediately approved the suggestion. Members agreed that this could be an observance demanding some act of kindness,
Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association
Authors: Pawaree Saisawat, Stefan Kohl, Alina C. Hilger, Daw-Yang Hwang, Heon Yung Gee, Gabriel C. Dworschak, Velibor Tasic, Tracie Pennimpede, Sivakumar Natarajan, Ethan Sperry, Danilo S. Matassa, Nataša Stajić, Radovan Bogdanovic, Ivo de Blaauw, Carlo L.M. Marcelis, Charlotte H.W. Wijers, Enrika Bartels, Eberhard Schmiedeke, Dominik Schmidt, Stefanie Märzheuser, Sabine Grasshoff-Derr, Stefan Holland-Cunz, Michael Ludwig, Markus M. Nöthen, Markus Draaken, Erwin Brosens, Hugo Heij, Dick Tibboel, Bernhard G. Herrmann, Benjamin D. Solomon, Annelies de Klein, Iris A.L.M. van Rooij, Franca Esposito, Heiko M. Reutter, Friedhelm Hildebrandt
Journal: Kidney International (2013)