tbuckley/cabot-search huggingface dataset:
Activation of gadolinium-sensitive ion channels in cardiomyocytes in early adaptive stages of volume overload-induced heart failure
Authors: C MCNICHOLASBEVENSEE, K DEANDRADE, W BRADLEY, L DELLITALIA, P LUCCHESI, M BEVENSEE
Journal: Cardiovascular Research (2006)

The objective of this study was to investigate whether gadolinium (Gd(3+))-sensitive stretch-activated ion channels (SAC) are basally active in left ventricular (LV) myocytes in early stages of heart failure (HF) induced by volume overload.The aortocaval fistula (ACF) model was employed to induce HF due to volume overload in rat. At specific time-points, LV myocytes were acutely isolated using a modified Langendorff apparatus. Whole-cell currents were measured using the patch-clamp technique and intracellular Ca(2+)(Ca(2+)(i)) was examined using fluorescence imaging and the Ca(2+)-sensitive dye Fura-2.Current-voltage data were obtained from sham and ACF myocytes at 5-d and 2-, 6-, 8- and 10-wk post surgery. Compared to data from matching sham rats, a 10 microM Gd(3+)-sensitive current at -100 mV comprised a larger fraction of total current in myocytes from 5-d, 2-wk, and 6-wk ACF rats. In general, the Gd(3+)-sensitive current contributed to inward currents at mV< or =-80 and outward currents at >+20 mV. The enhanced Gd(3+)-sensitive current was absent in myocytes from 8- and 10-wk ACF rats. 10 or 100 microM Gd(3+) had no appreciable effect on resting Ca(2+)(i) of myocytes from 5-d ACF or corresponding sham rats. The Gd(3+)-sensitive current in 5-d ACF myocytes was i) sensitive to the cation-selective SAC inhibitor, GsMTx-4, ii) non-selective for Na(+)/K(+), and iii) impermeable to Ca(2+).A basally-active, Gd(3+)- and GsMTx-4-sensitive SAC current that is non-selective for Na(+) and K(+), but impermeable to Ca(2+) under resting conditions is transiently elevated in LV myocytes from rats in early stages of volume overload-induced HF.
Nephrin Deficiency Activates NF-κB and Promotes Glomerular Injury
Authors: Sagair Hussain, Leile Romio, Moin Saleem, Peter Mathieson, Manuel Serrano, Jorge Moscat, Maria Diaz-Meco, Peter Scambler, Ania Koziell
Journal: Journal of the American Society of Nephrology (2009)

Increasing evidence implicates activation of NF-kappaB in a variety of glomerular diseases, but the mechanisms involved are unknown. Here, upregulation of NF-kappaB in the podocytes of transgenic mice resulted in glomerulosclerosis and proteinuria. Absence of the podocyte protein nephrin resulted in NF-kappaB activation, suggesting that nephrin negatively regulates the NF-kappaB pathway. Signal transduction assays supported a functional relationship between nephrin and NF-kappaB and suggested the involvement of atypical protein kinase C (aPKCzeta/lambda/iota) as an intermediary. We propose that disruption of the slit diaphragm leads to activation of NF-kappaB; subsequent upregulation of NF-kappaB-driven genes results in glomerular damage mediated by NF-kappaB-dependent pathways. In summary, nephrin may normally limit NF-kappaB activity in the podocyte, suggesting a mechanism by which it might discourage the evolution of glomerular disease.
Intra-islet insulin permits glucose to directly suppress pancreatic A cell function.
Authors: C J Greenbaum, P J Havel, G J Taborsky, L J Klaff
Journal: Journal of Clinical Investigation (1991)

Inhibition of pancreatic glucagon secretion during hyperglycemia could be mediated by (a) glucose, (b) insulin, (c) somatostatin, or (d) glucose in conjunction with insulin. To determine the role of these factors in the mediation of glucagon suppression, we injected alloxan while clamping the arterial supply of the pancreatic splenic lobe of dogs, thus inducing insulin deficiency localized to the ventral lobe and avoiding hyperglycemia. Ventral lobe insulin, glucagon, and somatostatin outputs were then measured in response to a stepped IV glucose infusion. In control dogs glucagon suppression occurred at a glucose level of 150 mg/dl and somatostatin output increased at glucose greater than 250 mg/dl. In alloxan-treated dogs glucagon output was not suppressed nor did somatostatin output increase. We concluded that insulin was required in the mediation of glucagon suppression and somatostatin stimulation. Subsequently, we infused insulin at high rates directly into the artery that supplied the beta cell-deficient lobe in six alloxan-treated dogs. Insulin infusion alone did not cause suppression of glucagon or stimulation of somatostatin; however, insulin repletion during glucose infusions did restore the ability of hyperglycemia to suppress glucagon and stimulate somatostatin. We conclude that intra-islet insulin permits glucose to suppress glucagon secretion and stimulate somatostatin during hyperglycemia.
Sex Differences in Language Dysfunction in Schizophrenia
Authors: Deborah J Walder, Larry J Seidman, Nicole Cullen, Jessica Su, Ming T Tsuang, Jill M Goldstein
Journal: American Journal of Psychiatry (2006)

Normal sex differences in language functions are disrupted in schizophrenia. However, identification of specific language components most vulnerable in schizophrenia and how they may differ by sex remain unexamined. The current study investigated this issue in the domains of phonology, semantics, and grammar, which have been closely linked with neuroanatomic regions for which sex differences have been identified.Thirty-one outpatients with DSM-III-R schizophrenia and 27 healthy subjects comparable within sex on age, handedness, parental socioeconomic status, and ethnicity were systematically ascertained from a Boston catchment area. The subjects were administered an extensive language battery in the context of a comprehensive neuropsychological battery that included measures of phonology, semantics, and grammar.Male patients performed significantly worse than their healthy counterparts on all three domains, with phonology least affected. In contrast, language function was relatively preserved in the female patients, compared to their healthy counterparts, with phonology most affected. Across domains, the effect sizes in comparisons of male patients and healthy male subjects had a twofold difference, whereas the difference in effect sizes in comparisons of female patients and healthy female subjects was less in all areas.Findings were consistent with prior evidence of overall language dysfunction in schizophrenia and may have implications for understanding sex differences in neuroanatomic abnormalities in regions associated with phonological processing.
Highly heterogeneous nature of δ-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria
Authors: Motoyoshi Maruno, Kazumichi Furuyama, Reiko Akagi, Yutaka Horie, Kuniaki Meguro, Luba Garbaczewski, Nicholas Chiorazzi, Manfred O. Doss, Alexandre Hassoun, Rudolf Mercelis, Luc Verstraeten, Pauline Harper, Ylva Floderus, Stig Thunell, Shigeru Sassa
Journal: Blood (2001)
Adverse Effects of Multiple Physical Symptoms on the Course of Depressive and Anxiety Symptoms in Primary Care
Authors: K.M.L. Huijbregts, H.W.J. van Marwijk, F.J. de Jong, B. Schreuders, A.T.F. Beekman, C.M. van der Feltz-Cornelis
Journal: Psychotherapy and Psychosomatics (2010)
Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study
Authors: Tea Restuccia, Rolando Ortega, Monica Guevara, Pere Ginès, Carlo Alessandria, Osman Ozdogan, Miquel Navasa, Antoni Rimola, Juan Carlos Garcia-Valdecasas, Vicente Arroyo, Juan Rodés
Journal: Journal of Hepatology (2003)
Duodenal adenoma and cancer in FAP
Authors: A R Latchford
Journal: Gut (2004)

We congratulate the authors ( Gut 2004; 53 :381–6) on gathering this large cohort of patients in this important area in familial adenomatous polyposis (FAP) but would like to express some reservations with regards to the study. Our first concern relates to the means of endoscopic assessment. Standard forward viewing endoscopy was used, whereas in clinical practice side viewing endoscopy is recommended as duodenal polyposis in FAP is more severe in the periampullary region1 and this is likely to be missed with standard endoscopy. This will therefore underestimate both adenoma staging and frequency. This matter is raised in their discussion where they …
A Randomized Trial of On-Pump Beating Heart and Conventional Cardioplegic Arrest in Coronary Artery Bypass Surgery Patients With Impaired Left Ventricular Function Using Cardiac Magnetic Resonance Imaging and Biochemical Markers
Authors: Tammy J. Pegg, Joseph B. Selvanayagam, Jane M. Francis, Theodoros D. Karamitsos, Zoe Maunsell, Ly-Mee Yu, Stefan Neubauer, David P. Taggart
Journal: Circulation (2008)

Beating heart coronary artery bypass grafting (CABG) improves early postoperative cardiac function in patients with normal ventricular function, but its effect in patients with impaired function is uncertain. We compared a novel hybrid technique of on-pump beating heart CABG (ONBEAT) with conventional on-pump CABG (ONSTOP) in patients with impaired ventricular function.In a single-center randomized trial, 50 patients with impaired ventricular function were randomly assigned to ONBEAT or ONSTOP. Patients underwent cardiac magnetic resonance imaging for function and delayed hyperenhancement early and later after surgery. Serial assessment of biochemical markers was also undertaken. Preoperative characteristics were well matched; cardiac index was 2.85+/-0.53 (ONBEAT) and 2.62+/-0.59 L x min(-1) x m(-2) (ONSTOP). Early after surgery, there was a trend toward a greater reduction in end-systolic volume index in ONSTOP patients versus ONBEAT (-9+/-8 versus -4+/-11 mL x m(-2); P=0.06). The changes were sustained and significant at 6 months (-14+/-18 versus -2+/-19 mL x m(-2); P=0.04). Furthermore, the incidence of new hyperenhancement at 6 days was higher in ONBEAT patients (P=0.05), with 6 of 17 (35%) sustaining 8.2+/-5.2 g of new hyperenhancement each versus 2 of 23 (9%) in the ONSTOP group, each with 9.8+/-9.0 g (P=0.86). Finally, median area under the curve for troponin was higher in ONBEAT at 461 (interquartile range, 226 to 1141) microg/L versus 160 (interquartile range, 98 to 357) microg/L for ONSTOP (P=0.002).The incidence of new irreversible myocardial injury was significantly higher in ONBEAT than in ONSTOP patients. Furthermore, at 6 months, only ONSTOP patients demonstrated an improvement in ventricular geometry. The most likely mechanism is inadequate coronary perfusion to distal myocardial territories in patients with severe proximal coronary disease.
Evidence that in Xeroderma Pigmentosum Variant Cells, which Lack DNA Polymerase η, DNA Polymerase ι Causes the Very High Frequency and Unique Spectrum of UV-Induced Mutations
Authors: Yun Wang, Roger Woodgate, Terrence P. McManus, Samantha Mead, J. Justin McCormick, Veronica M. Maher
Journal: Cancer Research (2007)

Abstract Xeroderma pigmentosum variant (XPV) patients have normal DNA excision repair, yet are predisposed to develop sunlight-induced cancer. They exhibit a 25-fold higher than normal frequency of UV-induced mutations and very unusual kinds (spectrum), mainly transversions. The primary defect in XPV cells is the lack of functional DNA polymerase (Pol) η, the translesion synthesis DNA polymerase that readily inserts adenine nucleotides opposite photoproducts involving thymine. The high frequency and striking difference in kinds of UV-induced mutations in XPV cells strongly suggest that, in the absence of Pol η, an abnormally error-prone polymerase substitutes. In vitro replication studies of Pol ι show that it replicates past 5′T-T3′ and 5′T-U3′ cyclobutane pyrimidine dimers, incorporating G or T nucleotides opposite the 3′ nucleotide. To test the hypothesis that Pol ι causes the high frequency and abnormal spectrum of UV-induced mutations in XPV cells, we identified an unlimited lifespan XPV cell line expressing two forms of Pol ι, whose frequency of UV-induced mutations is twice that of XPV cells expressing one form. We eliminated expression of one form and compared the parental cells and derivatives for the frequency and kinds of UV-induced mutations. All exhibited similar sensitivity to the cytotoxicity of UV(254 nm), and the kinds of mutations induced were identical, but the frequency of mutations induced in the derivatives was reduced to ≤50% that of the parent. These data strongly support the hypothesis that in cells lacking Pol η, Pol ι is responsible for the high frequency and abnormal spectrum of UV-induced mutations, and ultimately their malignant transformation. [Cancer Res 2007;67(7):3018–26]
Adenotonsillectomy Outcomes in Treatment of Obstructive Sleep Apnea in Children
Authors: Rakesh Bhattacharjee, Leila Kheirandish-Gozal, Karen Spruyt, Ron B Mitchell, Jungrak Promchiarak, Narong Simakajornboon, Athanasios G Kaditis, Deborah Splaingard, Mark Splaingard, Lee J Brooks, Carole L Marcus, Sanghun Sin, Raanan Arens, Stijn L Verhulst, David Gozal
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The overall efficacy of adenotonsillectomy (AT) in treatment of obstructive sleep apnea syndrome (OSAS) in children is unknown. Although success rates are likely lower than previously estimated, factors that promote incomplete resolution of OSAS after AT remain undefined.To quantify the effect of demographic and clinical confounders known to impact the success of AT in treating OSAS.A multicenter collaborative retrospective review of all nocturnal polysomnograms performed both preoperatively and postoperatively on otherwise healthy children undergoing AT for the diagnosis of OSAS was conducted at six pediatric sleep centers in the United States and two in Europe. Multivariate generalized linear modeling was used to assess contributions of specific demographic factors on the post-AT obstructive apnea-hypopnea index (AHI).Data from 578 children (mean age, 6.9 +/- 3.8 yr) were analyzed, of which approximately 50% of included children were obese. AT resulted in a significant AHI reduction from 18.2 +/- 21.4 to 4.1 +/- 6.4/hour total sleep time (P < 0.001). Of the 578 children, only 157 (27.2%) had complete resolution of OSAS (i.e., post-AT AHI <1/h total sleep time). Age and body mass index z-score emerged as the two principal factors contributing to post-AT AHI (P < 0.001), with modest contributions by the presence of asthma and magnitude of pre-AT AHI (P < 0.05) among nonobese children.AT leads to significant improvements in indices of sleep-disordered breathing in children. However, residual disease is present in a large proportion of children after AT, particularly among older (>7 yr) or obese children. In addition, the presence of severe OSAS in nonobese children or of chronic asthma warrants post-AT nocturnal polysomnography, in view of the higher risk for residual OSAS.
Ultrasonographic Screening before Hospital Discharge for Deep Venous Thrombosis after Arthroplasty: The Post-Arthroplasty Screening Study: A Randomized, Controlled Trial
Authors: K. Sue Robinson
Journal: Annals of Internal Medicine (1997)

The clinical significance of asymptomatic deep venous thrombosis that develops after joint arthroplasty and the value of screening tests to detect thrombi are uncertain.To determine 1) the rate of symptomatic deep venous thrombosis or pulmonary embolism occurring after hospitalization for joint arthroplasty and 2) the value of screening compression ultrasonography.Double-blind, randomized, controlled trial.Tertiary care hospital.1024 patients undergoing elective total hip or knee arthroplasty who received warfarin prophylaxis.Patients were randomly assigned to undergo either bilateral compression ultrasonography or a sham procedure before hospital discharge. Patients with a diagnosis of asymptomatic deep venous thrombosis were treated after discharge with standard anticoagulant therapy; other patients had warfarin therapy discontinued at discharge. All patients were followed for 90 days.In the screening group, asymptomatic proximal deep venous thrombosis was detected in 13 of 518 patients (2.5%). Another 4 patients subsequently developed symptomatic proximal deep venous thrombosis, and 1 patient treated for asymptomatic deep venous thrombosis developed major bleeding, for a total outcome event rate of 1.0% (5 of 518 patients). In the placebo group, 3 patients developed symptomatic proximal deep venous thrombosis and 2 had nonfatal pulmonary embolism, for a total event rate of 1.0% (5 of 506 patients) (difference, 0 percentage points [95% CI, -1.2 to 1.2 percentage points]).In patients undergoing total hip or knee arthroplasty, the use of warfarin prophylaxis during hospitalization results in a very low rate of symptomatic deep venous thrombosis or pulmonary embolism after hospital discharge. The use of screening compression ultrasonography at hospital discharge does not seem to be justified in this setting.
Progress in Intravenous Thrombolytic Therapy for Acute Stroke
Authors: Randolph S. Marshall
Journal: JAMA Neurology (2015)

Intravenous recombinant tissue plasminogen activator (alteplase) was approved by the US Food and Drug Administration in 1996 for the treatment of acute ischemic stroke. Nearly 20 years later, it remains the only approved treatment, despite limitations in both efficacy and safety. With a growing capacity for stroke treatment worldwide, physicians need to understand where we have come from and what the future of stroke treatment might be.To present a historical prospective as well as current trends in thrombolytic therapy, focusing on characteristics of drugs that have worked and clinical trials that are moving the field forward.Sources are published pivotal clinical trials; seminal articles on physiology, pharmacology, and neuroimanging; and listings from clinical trial registries.The slow progress in thrombolysis for acute stroke has been multifactorial. A focus on extending the time window for alteplase beyond 4.5 hours has encumbered substantial resources in the field for many years, yet these efforts have been largely unsuccessful. New drug development has also been slow. Several drugs have failed in clinical trials and currently only tenecteplase remains to be tested as a potential alternative to alteplase. The parallel pursuit for catheter-based interventional revascularization in acute stroke, which appears to be successful, has shifted emphasis away from pharmacologically based studies.Although the field of acute thrombolysis has been making progress slowly for many years, advances in neuroimaging and new clinical trials that combine thrombolytics with other pharmacological and interventional techniques are beginning to gain momentum once again. The emergence of new approaches based largely on combination therapy strategies has reset a course to advance thrombolytic treatment for acute stroke and promises to improve outcomes in acute stroke in the near future.
The size-weight illusion, emulation, and the cerebellum
Authors: Edward M. Hubbard, Vilayanur S. Ramachandran
Journal: Behavioral and Brain Sciences (2004)

In this commentary we discuss a predictive sensorimotor illusion, the size-weight illusion, in which the smaller of two objects of equal weight is perceived as heavier. We suggest that Grush's emulation theory can explain this illusion as a mismatch between predicted and actual sensorimotor feedback, and present preliminary data suggesting that the cerebellum may be critical for implementing the emulator.
Nitric oxide synthase inhibition augments acute allergic reactions in the pig airways in vivo
Authors: RJ Middelveld, WC Zetterquist, D Bergman, K Alving
Journal: European Respiratory Journal (2000)

The aim of this study was to examine the effects of nitric oxide synthase inhibition on antigen- and histamine-induced acute airway reactions, in order to clarify the possible modulating role of NO. Twelve specific-pathogen-free pigs (sensitized with Ascaris suum antigen) were challenged with an antigen aerosol during mechanical ventilation and anaesthesia. Six pigs were pretreated with N(G)-nitro-L-arginine (L-NA, 10 mg x kg(-1)), a NO synthase inhibitor, 30 min before challenge. In separate experiments, seven sensitized pigs received histamine (5 mg) aerosols before and after L-NA treatment. It was found that pretreatment with L-NA resulted in an enhanced airways resistance response to antigen (areas under the curve 0-90 min were (mean+/-SEM) 1,119+/-160 versus 555+/-56 (cmH2O x L(-1) x s(-1) x min for controls, p&lt;0.05 (Mann-Whitney U-test), whereas this response to histamine was not affected by L-NA. Moreover, L-NA pretreatment significantly enhanced total protein (1.85+/-0.43 versus 0.31+/-0.06 g x L(-1), p&lt;0.01) and histamine levels (42.8+/-16.0 versus 2.6+/-0.8 nM, p&lt;0.05) in bronchoalveolar lavage fluid 45 min after antigen challenge. In conclusion, this study showed that N(G)-nitro-L-arginine enhanced reactions occurring during the acute allergic reaction in pigs in vivo. This indicates a protective role of nitric oxide, which might occur through downregulation of histamine release from mast cells rather than a direct bronchodilating effect of nitric oxide.
Association of Azithromycin With Mortality and Cardiovascular Events Among Older Patients Hospitalized With Pneumonia
Authors: Eric M. Mortensen, Ethan A. Halm, Mary Jo Pugh, Laurel A. Copeland, Mark Metersky, Michael J. Fine, Christopher S. Johnson, Carlos A. Alvarez, Christopher R. Frei, Chester Good, Marcos I. Restrepo, John R. Downs, Antonio Anzueto
Journal: JAMA (2014)

Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events.To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia.Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy.This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital.Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines.Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression.Of 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 patients exposed to azithromycin and 31,863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95% CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR, 1.17; 95% CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95-1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04).Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use.
Outpatient Glycemic Control with a Bionic Pancreas in Type 1 Diabetes
Authors: Steven J. Russell, Firas H. El-Khatib, Manasi Sinha, Kendra L. Magyar, Katherine McKeon, Laura G. Goergen, Courtney Balliro, Mallory A. Hillard, David M. Nathan, Edward R. Damiano
Journal: New England Journal of Medicine (2014)

The safety and effectiveness of automated glycemic management have not been tested in multiday studies under unrestricted outpatient conditions.