tbuckley/cabot-search huggingface dataset:
L- and T-type Ca2+ channels in canine cardiac Purkinje cells. Single-channel demonstration of L-type Ca2+ window current.
Authors: S R Shorofsky, C T January
Journal: Circulation Research (1992)

Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-type Ca2+ "window" current. We used the on-cell, patch-clamp technique to study Ca2+ channels from isolated cardiac Purkinje cells. Patches contained one or more Ca2+ channels 75% of the time. L-type channels were seen in 69% and T-type channels in 73% of these patches. With 110 mM Ba2+ as the charge carrier, the conductances of the L- and T-type Ca2+ channels were 24.2 +/- 0.8 pS (n = 9) and 9.0 +/- 0.5 pS (n = 8), respectively (mean +/- SEM). With 110 mM Ca2+ as the charge carrier, the conductance of the L-type Ca2+ channel decreased to 9.7 +/- 1.2 pS (n = 4), whereas the T-type Ca2+ channel conductance was unchanged. Voltage-dependent inactivation was shown for both L- and T-type Ca2+ channels, although for L-type Ca2+ channel with Ba2+ as the charge carrier, inactivation took at least 30 seconds at a potential of +40 mV. After channel inactivation was complete, L-type Ca2+ channel reopenings were observed following repolarizing steps into the window voltage range. Thus, our data identify both L- and T-type Ca2+ channels in cardiac Purkinje cells and demonstrate, at the single-channel level, L-type channel transitions expected for a window current. Window current may play an important role in shaping the action potential and in arrhythmogenesis.
Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation
Authors: Lijian Shao, Yan Sun, Zhonghui Zhang, Wei Feng, Yongxing Gao, Zailong Cai, Zack Z. Wang, A. Thomas Look, Wen-Shu Wu
Journal: Blood (2010)
Sorafenib in Advanced Hepatocellular Carcinoma
Authors: Josep M. Llovet, Sergio Ricci, Vincenzo Mazzaferro, Philip Hilgard, Edward Gane, Jean Frédéric Blanc, Andre Cosme De Oliveira, Armando Santoro, Jean Luc Raoul, Alejandro Forner, Myron Schwartz, Camillo Porta, Stefan Zeuzem, Luigi Bolondi, Tim F. Greten, Peter R. Galle, Jean François Seitz, Ivan Borbath, Dieter Häussinger, Tom Giannaris, Minghua Shan, Marius Moscovici, Dimitris Voliotis, Jordi Bruix
Journal: New England Journal of Medicine (2008)

No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma.
Glycogen-Synthase Kinase3β/β-Catenin Axis Promotes Angiogenesis Through Activation of Vascular Endothelial Growth Factor Signaling in Endothelial Cells
Authors: Carsten Skurk, Henrike Maatz, Edward Rocnik, Ann Bialik, Thomas Force, Kenneth Walsh
Journal: Circulation Research (2005)

Glycogen-Synthase Kinase 3beta (GSK3beta) has been shown to function as a nodal point of converging signaling pathways in endothelial cells to regulate vessel growth, but the signaling mechanisms downstream from GSK3beta have not been identified. Here, we show that beta-catenin is an important downstream target for GSK3beta action in angiogenesis and dissect the signal transduction pathways involved in the angiogenic phenotype. Transduction of human umbilical vein endothelial cells (HUVECs) with a kinase-mutant form of the enzyme (KM-GSK3beta) increased cytosolic beta-catenin levels, whereas constitutively active GSK3beta (S9A-GSK3beta) reduced beta-catenin levels. Lymphoid enhancer factor/T-cell factor promoter activity was upregulated by KM-GSK3beta and diminished by S9A-GSK3beta, whereas manipulation of Akt signaling had no effect on this parameter. beta-Catenin transduction induced capillary formation in a Matrigel-plug assay in vivo and promoted endothelial cell differentiation into network structures on Matrigel-coated plates in vitro. beta-Catenin activated the expression of vascular endothelial growth factor (VEGF)-A and VEGF-C in endothelial cells, and these effects were mediated at the levels of protein, mRNA, and promoter activity. Consistent with these data, beta-catenin increased the phosphorylation of the VEGF receptor 2 (VEGF-R2) and promoted its association with PI3-kinase, leading to a dose-dependent activation of the serine-threonine kinase Akt. Inhibition of PI3-kinase or Akt signaling led to a significant reduction in the pro-angiogenic activity of beta-catenin. Collectively, these data show that the growth factor-PI3-kinase-Akt axis functions downstream of GSK3beta/beta-catenin signaling in endothelial cells to promote angiogenesis.
Atrial Tachycardia Remodeling of Pulmonary Vein Cardiomyocytes
Authors: Tae-Joon Cha, Joachim R. Ehrlich, Liming Zhang, Denis Chartier, Tack Ki Leung, Stanley Nattel
Journal: Circulation (2005)

The pulmonary veins (PVs) are important in the pathophysiology of atrial fibrillation (AF), as is atrial tachycardia (AT) remodeling. The relative importance of AT remodeling in PVs versus other atrial sites is unknown. The present study assessed AT-induced cellular changes in PVs versus left atrium (LA) and their relationship to arrhythmogenesis.We studied ionic currents (single-cell patch clamp) and action potentials (APs; coronary-perfused multicellular preparations) in the PVs and LA free wall of dogs after 7-day AT pacing (400 bpm), as well as in nonpaced control dogs. In controls, rapid (I(Kr)) and slow (I(Ks)) delayed-rectifier currents were larger in PVs; transient-outward (I(to)), inward-rectifier (I(K1)), and L-type Ca2+ (I(Ca)) currents and AP duration were smaller. AT remodeling reduced I(Ca) and I(to), left I(Kr) and I(Ks) unchanged, and increased I(K1) in both LA and PV. AT reduced action potential duration in both LA and PV. LA-PV AP differences became smaller in AT than in control dogs. Premature extrastimuli induced atrial tachyarrhythmias at 4.5+/-2.8% (mean+/-SEM) sites in 6 control multicellular preparations compared with 64.2+/-7.3% sites in 9 AT-remodeled preparations (P<0.001). Resection of all PVs failed to alter atrial tachyarrhythmia inducibility in AT-remodeled preparations (67.5+/-13.1%). PV resection did not significantly change tachyarrhythmia duration (mean 3.9 seconds per heart, range 0.7 to 15.7 seconds before resection; mean 7.0 seconds per heart, range 0.9 to 36.0 seconds after resection) or cycle length (120+/-6 ms before resection, 115+/-8 ms after resection).AT produces qualitatively similar ionic remodeling in LA and PVs but reduces PV-LA AP differences. PVs are not essential for AT-induced atrial tachyarrhythmia promotion in this model, which may relate to the failure of PV isolation to prevent AF in some patient populations.
An Esophageal Electrode For Recording Arrhythmias
Authors: Stafford I. Cohen
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Identification of atrial activity is essential to the accurate electrocardiographic diagnosis of basic rhythm disturbances. When atrial activity is obscured by a rapid ventricular rate, right-sided precordial leads or esophageal leads should always be obtained.<sup>1</sup>Often the latter method is the most rewarding because of the proximity of the esophagus to the left atrium. Simple esophageal recording electrodes have been modified to increase the definition of atrial activity. Innovations have included bipolar and tripolar electrodes with a salt bridge<sup>2</sup>and the inclusion of many recording points along the electrode. These improved electrodes were made to individual specifications and not employed by the general medical community. Transvenous pacemakers have been utilized since 1959 for the management of Adams-Stokes attacks and heart-block. These pacemakers are manufactured in unipolar, bipolar, or tripolar models, any one of which can be employed as an esophageal electrode in the usual manner.
Endoscopic removal of a large rectal foreign body using a large balloon dilator: report of a case and description of the technique
Authors: P. Billi, M. Bassi, F. Ferrara, A. Biscardi, S. Villani, F. Baldoni, N. D’Imperio
Journal: Endoscopy (2010)

Retained rectal foreign bodies are commonly encountered, and various shapes and sizes have been described. Although many foreign bodies can be extracted safely, some patients require hospitalization and surgery [1] [2] [3].
Common mistakes about numerical representations
Authors: Mauro Pesenti, Michael Andres
Journal: Behavioral and Brain Sciences (2009)

Abstract Cohen Kadosh &amp; Walsh (CK&amp;W) argue that recent findings challenge the hypothesis of abstract numerical representations. Here we show that because, like many other authors in the field, they rely on inaccurate definitions of abstract and non-abstract representations, CK&amp;W fail to provide compelling evidence against the abstract view.
Immunotherapy of verrucae vulgares with dinitrochlorobenzene
Authors: DOROTHY BUCKNER, NORMAN M. PRICE
Journal: British Journal of Dermatology (2006)

A study using daily topical applications of dinitrochlorobenzene on recalcitrant verrucae vulgares demonstrated this to be of practical value. Complete resolution of lesions occurred in 66% of 35 patients, with a complication rate of 24%. The results of other studies are reviewed and recommendations for use of this medication are given. DNCB therapy should, however, be reserved for use on recalcitrant lesions because of the complications associated with its usage.
Kazanjian &amp;amp; Converse's Surgical Treatment of Facial Injuries
Authors: Lester M. Cramer
Journal: JAMA (1975)

There is no such thing as the perfect book on any subject, but this one comes close to approaching that goal. The wealth of clinical material, the depth of basic scientific background, and the literary fluency combine to make this a masterpiece. The complete coverage of the field of facial trauma, drawing on the experiences of two master surgeons, is neatly done from the early supportive care to late reconstruction. It has been accomplished in a scholarly but still clinically practical manner. Both the neophyte and the expert surgeon can benefit from the concepts presented and the technical planning and accomplishments described. The only major criticism that can be made is that the portion dealing with flaps (chapter 17) has been less critically edited than the remainder of the two volumes. The line drawings in this section are not as accurate; the author's preference for which flap to select from
Reduced glutathione depletion causes necrosis and sensitization to tumor necrosis factor-α-induced apoptosis in cultured mouse hepatocytes
Authors: Hidenari Nagai, Katsuhiko Matsumaru, Guoping Feng, Neil Kaplowitz
Journal: Hepatology (2002)

The effect of reduced glutathione (GSH) depletion by acetaminophen (APAP), diethylmaleate (DEM), or phorone on the mode of cell death and susceptibility to tumor necrosis factor (TNF)-induced cell death was studied in cultured mouse hepatocytes. Dose-dependent necrosis was the exclusive mode of cell death with APAP alone, but the addition of TNF-α induced a switch to about half apoptosis without changing total loss of viability. This effect was seen at 1 and 5 mmol/L but was inhibited at 10 and 20 mmol/L APAP. The switch to apoptosis was associated with increased caspase activities, release of cytochrome c, and DNA laddering and was inhibited by caspase inhibitors. DEM and phorone also induced dose-dependent necrosis. Treatment with TNF-α under these conditions lead to incremental cell death in the form of apoptosis at 0.25 and 0.5 mmol/L DEM and 0.1 and 0.2 mmol/L phorone. At 1.0 and 2.0 mmol/L DEM and 0.5 mmol/L phorone, 90% to 100% necrosis was observed with resistance to TNF-α effects. The apoptosis with TNF-α plus DEM was confirmed by DNA laddering and inhibition by caspase inhibitors. However, in the presence of caspase inhibitors, the increment in cell death induced by TNF-α persisted as an increase in necrosis. A combination of antioxidants, vitamin E, and butylated hydroxytoluene (BHT) markedly inhibited necrosis induced by APAP or DEM alone, but the sensitization to TNF-α-induced apoptosis was unaffected. GSH monoethylester (GSH-EE) protected against necrosis and apoptosis. In conclusion, depletion of GSH by APAP, DEM, or phorone causes oxidative stress-induced necrosis and sensitizes to an oxidative stress independent TNF-α-induced apoptosis.
Transcriptional profiling after bile duct ligation identifies PAI-1 as a contributor to cholestatic injury in mice
Authors: Hongtao Wang, Bhupinder P.S. Vohra, Yan Zhang, Robert O. Heuckeroth
Journal: Hepatology (2005)

Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery. The most upregulated gene identified encodes plasminogen activator inhibitor 1 (PAI-1, Serpine 1), a protease inhibitor that blocks urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity. Because PAI-1, uPA, and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling, we evaluated the role of PAI-1 in cholestatic liver injury by comparing the injury and repair processes in wild-type (WT) and PAI-1-deficient (PAI-1-/-) mice after BDL. PAI-1-/- mice had fewer and smaller bile infarcts, less neutrophil infiltration, and higher levels of cholangiocyte and hepatocyte proliferation than WT animals after BDL. Furthermore, PAI-1-/- mice had higher levels of tPA activation and mature hepatocyte growth factor (HGF) after BDL than WT mice, suggesting that PAI-1 effects on HGF activation critically influence cholestatic liver injury. This was further supported by elevated levels of c-Met and Akt phosphorylation in PAI-1-/- mice after BDL. In conclusion, PAI-1 deficiency reduces liver injury after BDL in mice. These data suggest that inhibiting PAI-1 might attenuate liver injury in cholestatic liver diseases.
The Influence of Advanced Congestive Heart Failure on Pulsus Alternans
Authors: JOSEPH M. RYAN, JAMES F. SCHIEVE, HUGH B. HULL, BERYL M. OSER
Journal: Circulation (1955)

Evidence is presented which indicates that in certain instances pulsus alternans may be abolished or diminished in the presence of advanced congestive heart failure. The observations suggest that in severe congestive failure the ventricular filling pressure may increase to the point where it causes the diastolic stretch of the left ventricle to be more equal from one beat to the next. This in turn would bring about more uniform systolic ejections and hence ventricular alternation would disappear or be lessened in degree.
Biomedical Research and Biosecurity
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2005)

Even as they have advanced our understanding and treatment of disease, the achievements of modern biomedical research have also increased people's ability to misuse discoveries in ways that could threaten the public health or national security. The phrase “dual-use research” attempts to capture this occasionally uneasy relation between scientific advances and the potential development of new pathogens or biologic weapons. “In the language of arms control and disarmament, dual use refers to technologies intended for civilian application that can also be used for military purposes,” according to a 2003 report from a committee of the National Research Council on biotechnology . . .
Health workers fear cholera outbreak in Pakistan
Authors: N. Siva
Journal: BMJ (2010)

As the monsoon rains and flooding continue in Pakistan, health workers are now extremely concerned that the lack of clean drinking water and inaccessibility of large pockets of the country will lead to an outbreak of cholera.

The National Disaster Management Authority in Pakistan has reported that 12 million people have been affected by the floods. Around 1400 people have died, 273 000 houses have been damaged, and 1.5 million people are now homeless. 

In Khyber Pakhtunkhwa province, in the north west of the country, 80% of the water systems are now polluted with silt and …
Kidney Function after Methoxyflurane Analgesia during Labour
Authors: M. Rosen, P. Latto, A. W. Asscher
Journal: BMJ (1972)

In a study of the effects of methoxyflurane on renal function, the urinary and blood urea concentrations, the urinary and plasma osmolalities, and the packed cell volume were studied in each of 50 mothers before and after delivery. Methoxyflurane 0·35% was used as an analgesic in 25 patients and the other 25 had 50% nitrous oxide and 50% oxygen (Entonox). There was no evidence of renal dysfunction in either group, nor were there any significant differences between the groups. In a further 200 mothers, of whom 100 had methoxyflurane and 100 had nitrous oxide analgesia, the urinary and blood urea concentrations were measured on the morning of discharge from hospital. There were no significant differences between the groups. These results suggest that methoxyflurane is not nephrotoxic when used as a self-administered analgesic.
Federal Recognition of Chiropractic
Authors: JOHN D. SLADE
Journal: Annals of Internal Medicine (1975)

Comments and Corrections1 September 1975Federal Recognition of ChiropracticJOHN D. SLADE, M.D.JOHN D. SLADE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-3-427 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The editorial "Federal Recognition of Chiropractic: A Double Standard" by H. Thomas Ballantine, Jr. (Ann Intern Med 82:712-713, 1975) is a useful narrative about recent policy decisions involving chiropractic and contains important suggestions for the medical profession and the federal government. I must take issue, however, with the final recommendation.Dr. Ballantine would like to empower the Commissioner of the U. S. Department of Education with the ability "to pass on 'the legitimacy . . . of the field of training of the agency seeking listing' " as an accrediting body. He would give an appointed bureaucrat... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JOHN D. SLADE, M.D.Affiliations: Department of Medicine Presbyterian-St. Luke's Medical Center Chicago, Illinois 60618 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCatalysis and Related Reactions with Compounds Containing Heteronuclear Metal Metal Bonds 1 September 1975Volume 83, Issue 3Page: 427-427KeywordsChiropractic ePublished: 1 December 2008 Issue Published: 1 September 1975 PDF downloadLoading ...
TG4010 immunotherapy combined with first-line therapy in advanced non-small cell lung cancer (NSCLC): phase IIb results of the TIME study
Authors: Elisabeth Quoix, Lecia Sequist, John Nemunaitis, Thaddeus Beck, Piotr Jaskiewicz, Jean-Philippe Oster, Arnaud Scherpereel, Erzsébet Juhász, Zsuzsanna Mark, Rosa Alvarez, Saiama Waqar, Joseph Potz, Nandagopal Vrindavanam, Anton Melnyk, Helen Ross, Jean-Marc Limacher
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts TG4010 immunotherapy product is a poxvirus (MVA) coding for MUC1 tumor-associated antigen and interleukin-2. A previous study showed that a normal baseline level of Triple Positive Activated Lymphocytes (TrPAL, CD16+CD56+CD69+) might be a predictive biomarker for TG4010 efficacy
ACUTE PAN-SINUSITIS: A SEVERE CASE
Authors: S. Thomson
Journal: BMJ (1923)

ACUTE PAN-SINUSlTlS.[MBDRC JOu 94 , MZDIC&L JOUSIgAl~~~~~~~~~ the United States and have been so wisely utilized there, it caii hardly be doubted that a considerable economic saving would accrue to the community, while to the inidividual patient there would be given that truest source of happiness-the increased power of exercising an activity.For much of the information in this paper I am indebted to the
Approaches for protection standards for ionizing radiation and combustion pollutants.
Authors: G C Butler
Journal: Environmental Health Perspectives (1978)

The question "can the approach used for radiation protection standards, i.e., to extrapolate dose--response relationships to low doses, be applied to combustion pollutants?" provided a basis for discussion. The linear, nonthreshold model postulated by ICRP and UNSCEAR for late effects of ionizing radiation is described and discussed. The utility and problems of applying this model to the effects of air pollutants constitute the focus of this paper. The conclusion is that, in the absence of evidence to the contrary, one should assume the same type of dose--effect relation for chemical air pollutants as for ionizing radiation.
Undetected Ventricular Fibrillation in Transvenous Implantable Cardioverter-Defibrillators
Authors: Andrea Natale, Jasbir Sra, Kathi Axtell, Masood Akhtar, Keith Newby, Virginia Kent, Mary J. Geiger, M. Joan Brandon, Margaret M. Kearney, Antonio Pacifico
Journal: Circulation (1996)

Background The purpose of this study was to prospectively analyze redetection problems after unsuccessful shock with different lead systems and devices. Methods and Results We prospectively analyzed detection and redetection characteristics among transvenous implantable cardioverter-defibrillators (ICDs) using standard bipolar and integrated bipolar sensing. Monophasic and biphasic ICDs were included. Subthreshold shocks were intentionally delivered, and redetection of ventricular fibrillation (VF) was assessed before discharge and at 1, 3, 6, and 12 months later. Sensing of VF resulting from antitachycardia pacing and low-energy cardioversion (≤2 J) also was analyzed. Before inclusion in the study, each patient underwent subthreshold shock testing at three different time intervals. Among the 160 ICDs with standard bipolar sensing, 530 VF inductions were analyzed. After the failed shocks, undersensing was more frequent (3% versus 20%, P &lt;.01) but did not remarkably prolong redetection (3.1±0.8 versus 3.3±1.1 seconds). Among the 201 ICDs with integrated bipolar sensing, 80 were connected to a CPI device (60 Ventak 1600–Endotak 60 series and 20 PRx II 1715–Endotak 70 series) and 121 to the Ventritex defibrillator (91 Endotak 60 series, 14 TVL systems, and 16 Endotak 70 series). After 252 failed shocks, redetection was prolonged with the CPI system (3.1±1.4 versus 4.6±3.6 seconds, P &lt;.05) but did not change after 396 failed shocks with the Ventritex ICD (5.4±1.9 versus 4.9±2.2 seconds). This may reflect different nominal settings for detection and redetection. In 9 of 121 patients with Ventritex and 1 of 80 with the CPI ICDs, the devices failed to redetect VF. However, redetection malfunction was never observed in patients with integrated bipolar systems with &gt;6-mm electrode separation. After antitachycardia pacing in 1 patient and a 2-J shock in 1 patient, ventricular tachycardia turned into VF, which was undetected. Both patients used the Endotak 60 series–Cadence combination. None of the patients showing VF undersensing had sudden death at follow-up. Only 3 of the 12 patients with sensing malfunction were on antiarrhythmia drugs at the time of testing. Analysis of endocardial electrograms showed that failure to redetect VF is not associated with a uniform reduction but with a rapid and repetitive change of electrogram amplitude. Conclusions Standard bipolar sensing redetects VF more effectively than integrated bipolar sensing. Endocardial electrogram analysis provides insights into the understanding of the mechanism of undersensing, and certain lead-device combinations result in a higher occurrence of VF undersensing. The clinical relevance of this phenomenon remains unknown.