tbuckley/cabot-search huggingface dataset:
Cardiac Gap Junction Channels Show Quantitative Differences in Selectivity
Authors: Virginijus Valiunas, Eric C. Beyer, Peter R. Brink
Journal: Circulation Research (2002)

Several proteins including connexin40 (Cx40) and connexin43 (Cx43) form gap junctions between cells of the heart; they may be found separately or may be coexpressed. These connexins form channels with differing conductance and permeability properties. Cx40 and Cx43 are each required for normal electrical conduction between cells in different regions of the heart. We hypothesized that the major difference between these connexins might be in their selective intercellular passage of small molecules such as second messengers, which can be assessed using biologically inert fluorescent probes. Therefore, we designed experimental paradigms to quantitate the permeability properties of these cardiac connexins using simultaneous measurement of junctional conductance (g(j)) by the double whole-cell patch-clamp technique and intercellular transfer of Lucifer Yellow (LY) by fluorescence microscopy. These studies were performed in HeLa cells stably transfected with Cx40 or Cx43 or cotransfected with both connexins. We found that homotypic Cx43 channels were about 5 times more permeable to LY than homotypic Cx40 channels (flux of approximately 1560 versus approximately 300 molecules/channel per second). Channels between heterotypic (Cx40-Cx43) cell pairs and between pairs of coexpressing cells exhibited intermediate LY permeability. The permeability ratio for LY relative to monovalent cation (K+) ranged from 0.0025 for Cx40 to 0.028 for Cx43. These permeability ratios suggest that the connexins are highly selective for solutes in the size and charge range of many second messengers. Moreover, the data indicate that coexpression of connexins does not generate unique permeability characteristics, but rather results in an intermediate permeability for solutes involved in metabolic/biochemical coupling.
An investigation of the inflammatory cytokine and chemokine network in systemic sclerosis
Authors: Veronica Codullo, Helen M Baldwin, Mark D Singh, Alasdair R Fraser, Catherine Wilson, Ashley Gilmour, Axel J Hueber, Claudia Bonino, Iain B McInnes, Carlomaurizio Montecucco, Gerard J Graham
Journal: Annals of the Rheumatic Diseases (2011)

Objectives Systemic sclerosis (SSc) is characterised by vasculopathy, an aberrantly activated immune system and excessive extracellular matrix deposition. Inflammatory chemokines control migration of cells to sites of tissue damage; their removal from inflamed sites is essential for resolution of the inflammatory response. The atypical chemokine receptor D6 has a critical role in this physiological balance. To explore potential deregulation of this system in SSc, inflammatory chemokine and D6 expression were compared with that in healthy controls (HC). Methods Serum levels of inflammatory mediators were assessed by luminex analysis. Peripheral blood mononuclear cells (PBMCs) were used in molecular and immunocytochemical analysis. Platelet-rich plasma was collected and assessed by western blotting for D6 expression levels. Sex-matched HC were used for comparison. Results 72 patients with SSc and 30 HC were enrolled in the study. The chemokines MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4 and IL-8/CXCL8 were significantly increased in patients with SSc, regardless of disease subtype and phase. Quantitative PCR analysis revealed a significant 10-fold upregulation of D6 transcripts in patients with SSc compared with controls, and this was paralleled by increased D6 protein expression in the PBMCs of patients with SSc. Platelet lysates also showed strong D6 expression in patients with SSc but not in controls. Importantly, high levels of D6 expression correlated with reduced levels of its ligands in serum. Conclusions Inflammatory chemokines and the regulatory receptor D6 are significantly upregulated in SSc and high D6 levels are associated with lower systemic chemokine levels, indicating that some patients control systemic chemokine levels using D6. These results suggest that chemokines may represent a therapeutic target in SSc.
Hemoglobin H (Hb H) disease in Canada: Molecular diagnosis and review of 116 cases
Authors: John S. Waye, Barry Eng, Margaret Patterson, Lynda Walker, Manuel D. Carcao, Nancy F. Olivieri, David H.K. Chui
Journal: American Journal of Hematology (2001)

Abstract Over the past decade, we have characterized at the DNA level a total of 116 hemoglobin H (Hb H) disease patients living in Canada. The majority of patients were of southeast Asian descent (Chinese, Filipino, Laotian, Vietnamese), with a small number being of Mediterranean, Middle Eastern or East Indian background. A total of 15 distinct genotypes were detected, all but one being compound heterozygotes for a two‐gene cis deletion and a single‐gene deletion (‐α/−) or a non‐deletion mutation of the α2‐globin gene (α T α/−). Seven different two‐gene cis deletions were encountered, along with nine single‐gene deletions and point mutations. The wide range of mutations associated with Hb H disease in Canada is a reflection of the population heterogeneity. The diagnosis of Hb H disease at the molecular level is important with respect to genetic counseling and the identification of families at risk for having pregnancies affected with Hb Bart's hydrops fetalis syndrome and/or Hb H disease. Six of the Hb H disease patients in our cohort had spouses who carried single‐gene deletions, making these couples at risk for having children with Hb H disease. More important, seven patients had partners who carried two‐gene cis deletions. These couples are at reproductive risk for both Hb Bart's hydrops fetalis syndrome and Hb H disease. Am. J. Hematol. 68:11–15, 2001. © 2001 Wiley‐Liss, Inc.
P70 Can Endobronchial Ultrasound (EBUS) Guided Transbronchial Needle Aspiration (TBNA) be Used as a First Line Investigation in the Diagnosis of Central Lung Parenchymal Lesions?
Authors: S Leyakathali Khan, M Haris, S Diver, B Miller, M Munavvar
Journal: Thorax (2012)

<h3>Background</h3> Accurate diagnosis and staging remains a cornerstone in the management of patients with lung cancer. EBUS-TBNA has been demonstrated to be a safe and minimally invasive tool to evaluate mediastinal and hilar lymph nodes in patients with suspected lung cancer. It has also shown to be effective in sampling central lung parenchymal lesions with no obvious bronchoscopic findings. The aim of the study was to evaluate the role of EBUS TBNA as an early investigative tool in the diagnosis of lung cancer with central lung parenchymal lesions. <h3>Methods</h3> Retrospective study of 119 consecutive patients who had EBUS-TBNA from paratracheal and peribronchial masses between January 2009 and February 2012. All patients had a non-diagnostic flexible bronchoscopy just before having EBUS. 15 of these also had mediastinal or hilar lymph node sampling at the time of procedure. <h3>Results</h3> N=119, mean age 68 years (SD 10); male: female, 56(%): 63(%). 37 paratracheal and 82 peribronchial lesions were identified using convex-probe EBUS. 5 with no further data were excluded. Of the 114 samples, 110 were diagnostic confirming lung malignancy 107(97%), lymphoma 1 (1%) and bronchial cysts 2(2%); 1 sample was insufficient and 3 showed no malignant cells (1 had surgical biopsy confirming squamous cell carcinoma, 1 was benign on follow imaging, 1 had CT guided biopsy positive for adenocarcinoma, 1 was not suitable for further invasive tests but CT showed progressive changes suggestive of lung malignancy). Of the 107 lung malignancy, 31 were adenocarcinoma, 34 squamous cell carcinoma, 25 small cell carcinoma, 12 non-small cell carcinoma – not otherwise specified (NOS), 3 malignant cells - NOS and 2 extrapulmonary metastases. The sensitivity of EBUS-TBNA for the diagnosis of lung cancer was 97% (95% confidence interval 92–99%) with a negative predictive value 56% (95% CI 26–83%). <h3>Conclusion</h3> Our results show that EBUS TBNA has a very high sensitivity in the diagnosis of central lung masses related to lung cancer. It could be used as a “one stop” as an early minimally invasive tool in the lung cancer diagnostic pathway to enable accurate diagnosis and a negative result may warrant other invasive tests.
Modulating Influence of Chemotactic Factor-Induced Cell Adhesiveness on Granulocyte Function
Authors: Jorg Fehr, Clemens Dahinden
Journal: Journal of Clinical Investigation (1979)

The importance of adhesion in regulating locomotion and accumulation of polymorphonuclear leukocytes (PMN) has remained vague. We found that the chemotaxis of human PMN resuspended in heat-inactivated plasma was maximal toward 1-10 nM N-formyl-met-leu-phe (f-Met-Leu-Phe), but fell below random motility toward >/= 100 nM. This impressive decrease of motility was paralleled by increased cell adherence on Petri dishes being minimal at 1 nM and maximal at >10 nM f-Met-Leu-Phe (6+/-1 and 37+/-2% [SE] adherent cells, respectively). Checked by phase-contrast microscopy, cells under stimulated adhesion lost the typical bipolar shape of moving PMN and became immobilized and highly flattened. PMN, preexposed to 250 nM f-Met-Leu-Phe and tested after washing, retained increased adhesiveness and showed extremely low random and chemotactic motility. In contrast, preexposure to 1 nM f-Met-Leu-Phe had no effect on chemotaxis. Supporting the concept that immobilizing hyperadhesiveness does not correspond to a general functional hyporesponsiveness of PMN, no depression of the initial ingestion rate was observed in the presence of 250 nM f-Met-Leu-Phe. Moreover, a close correlation was found between the induction of PMN adhesiveness and the stimulation of the hexose monophosphate pathway activity as well as of lysomal enzyme release (r >/= 0.98). Thus, "chemotactic deactivation" and "high-dose inhibition of chemotaxis" by N-formyl peptides is the consequence of increased cell adhesiveness. This phenomenon provides a mechanism for cell trapping at the inflammatory site. Conversely, if operative in circulating blood, e.g., in septicemia, it may impair PMN emigration to such sites.
Phase II study of combination chemotherapy of 5-fluorouracil, low-dose leucovorin, and oxaliplatin (FLOX regimen) in pretreated advanced gastric cancer
Authors: J. Jeong, H.-C. Jeung, S.Y. Rha, C.K. Im, S.J. Shin, J.B. Ahn, S.H. Noh, J.K. Roh, H.C. Chung
Journal: Annals of Oncology (2008)
Secret government: the Scott report
Authors: M. McKee
Journal: BMJ (1996)

The Scott report on the export of British arms to Iraq is much more than simply an examination of British policy on weapons sales in the run up to the Gulf War.1 It provides the most detailed account ever of the innermost workings of Whitehall and paints a picture of an organisation permeated by secrecy and deceit. Ministers and civil servants see their first duty to advance the interests of major industrial concerns, even when they mislead parliament and the public in doing so. The secretive links between government and industry, in this case the arms industry, are at times almost seamless, without anyone seeming to appreciate the scope for conflict of interest. But what has this to do with health? Potentially quite a lot. Despite years of rhetoric about reducing the role of government, by publishing Health of the Nation2 the government has accepted that it has a legitimate role in promoting the health of the public. But after the Scott report, can anyone be sure that the government is acting in the interests of the public rather than those of the corporate backers of …
Viscosity of Contrast Media Perturbs Renal Hemodynamics
Authors: Erdmann Seeliger, Bert Flemming, Thomas Wronski, Mechthild Ladwig, Karen Arakelyan, Michael Godes, Martin Möckel, Pontus B. Persson
Journal: Journal of the American Society of Nephrology (2007)

Contrast-induced nephropathy is a common cause of acute renal failure, and the mechanisms underlying this injury are not completely understood. We sought to determine how physicochemical properties of contrast media may contribute to kidney damage in rats. We administered contrast media of equivalent iodine concentrations but differing physiocochemical properties: the high-osmolality iopromide was compared to the high-viscosity iodixanol. In addition, the non-iodinated substances mannitol (equivalent osmolality to iopromide) and dextran (equivalent viscosity to iodixanol) were also studied. Both types of contrast media transiently increased renal and hindquarter blood flow. The high-osmolality agents iopromide and mannitol markedly increased urine production whereas iodixanol, which caused less diuresis, significantly enhanced urine viscosity. Only the high-viscosity agents iodixanol and dextran decreased renal medullary blood flux, erythrocyte concentration, and pO2. Moreover, iodixanol prolonged the tubuloglomerular feedback response and increased plasma creatinine levels to a greater extent than iopromide or dextran. Therefore, the viscosity of contrast media may play a significant role in contrast-induced nephropathy.
Impairment of the Auditory Brainstem Function in Diabetic Neuropathy
Authors: Tamás T. Várkonyi, Ferenc Tóth, László Rovó, Csaba Lengyel, József Géza Kiss, Póter Kempler, Jónos Lonovics
Journal: Diabetes Care (2002)

Diabetes may alter both the peripheral and the central nerve function, but the peripheral manifestations of diabetic neuropathy are more frequently discussed in the literature than the impairment of the central nervous system. Delay of the evoked potentials in the central pathways has been reported in diabetic patients (1), but the exact pathophysiology of these alterations is still unclear (2). The aims of our study were to characterize the afferent brainstem function by detection of the auditory-evoked potentials in patients with long-standing type 1 diabetes and to analyze possible connections between the central neural dysfunction and the autonomic and peripheral sensory neuropathies.

We enrolled 12 patients with long-standing type 1 diabetes who had normal hearing (age [mean ±SD] 42.1 ±14.8 years, duration of diabetes 23 ±8.9 years, BMI 26.8 ±4.6 kgm2). The quantitative characteristics of the brainstem function were evaluated …
Community-acquired pneumonia guidelines: much guidance, but not much evidence
Authors: M. Woodhead
Journal: European Respiratory Journal (2002)

Community-acquired pneumonia (CAP) is changing. The emergence and spread of antibiotic resistance in common causative bacteria, the development of new microbiological diagnostic techniques, new understandings in the area of severity assessment and the development of new antibiotics are just some of the issues. Methods of guideline writing have also evolved 1. The categorisation of evidence and the strength attributed to recommendations are perhaps the most important additions to this methodology 2. Some aspects of the older guidelines for CAP management may therefore be out of date 35.

The publication of the British Thoracic Society (BTS) 6 and American Thoracic Society (ATS) Guidelines for the management of CAP 7 in 2001 and the Canadian 8, 9 and The Infectious Disease Society of North America (IDSA) Guidelines 10 in 2000 were most welcome. They all updated or revised earlier publications (after intervals of 8, 8, 7 and 2 yrs, respectively) and attempted to take account of the issues mentioned above. The scope of each document is similar and they include issues such as clinical presentation and diagnosis, microbial and nonmicrobial investigation and general and antibiotic management. A separate publication confined to antibiotic recommendations was presented by the Centers for Disease Control and Prevention 11. It is not the purpose of this paper to compare these documents item by item, but more to assess in general terms, their potential value and limitations and how and where they may or may not be used.

Guidelines are, whether we …
High Rates of Viral Suppression After Long-term Entecavir Treatment of Asian Patients With Hepatitis B e Antigen–Positive Chronic Hepatitis B
Authors: Calvin Q. Pan, Myron Tong, Kris V. Kowdley, Ke–Qin Hu, Ting–Tsung Chang, Ching–Lung Lai, Seung Kew Yoon, Samuel S. Lee, David Cohen, Hong Tang, Naoky Tsai
Journal: Clinical Gastroenterology and Hepatology (2012)
An Update on Pharmacological, Pharmacokinetic Properties and Drug–Drug Interactions of Rotigotine Transdermal System in Parkinson’s Disease and Restless Legs Syndrome
Authors: Jan-Peer Elshoff, Willi Cawello, Jens-Otto Andreas, Francois-Xavier Mathy, Marina Braun
Journal: Drugs (2015)

This narrative review reports on the pharmacological and pharmacokinetic properties of rotigotine, a non-ergolinic D₃/D₂/D₁ dopamine receptor agonist approved for the treatment of early- and advanced-stage Parkinson's disease (PD) and moderate to severe restless legs syndrome (RLS). Rotigotine is formulated as a transdermal patch providing continuous drug delivery over 24 h, with a plasma concentration profile similar to that of administration via continuous intravenous infusion. Absolute bioavailability after 24 h transdermal delivery is 37 % of the applied rotigotine dose. Following a single administration of rotigotine transdermal system (24-h patch-on period), most of the absorbed drug is eliminated in urine and feces as sulphated and glucuronidated conjugates within 24 h of patch removal. The drug shows a high apparent volume of distribution (>2500 L) and a total body clearance of 300-600 L/h. Rotigotine transdermal system provides dose-proportional pharmacokinetics up to supratherapeutic dose rates of 24 mg/24 h, with steady-state plasma drug concentrations attained within 1-2 days of daily dosing. The pharmacokinetics of rotigotine transdermal patch are similar in healthy subjects, patients with early- or advanced-stage PD, and patients with RLS when comparing dose-normalized area under the plasma concentration-time curve (AUC) and maximum plasma drug concentration (Cmax), as well as half-life and other pharmacokinetic parameters. Also, it is not influenced in a relevant manner by age, sex, ethnicity, advanced renal insufficiency, or moderate hepatic impairment. No clinically relevant drug-drug interactions were observed following co-administration of rotigotine with levodopa/carbidopa, domperidone, or the CYP450 inhibitors cimetidine or omeprazole. Also, pharmacodynamics and pharmacokinetics of an oral hormonal contraceptive were not influenced by rotigotine co-administration. Rotigotine was generally well tolerated, with an adverse event profile consistent with dopaminergic stimulation and use of a transdermal patch. These observations, combined with the long-term efficacy demonstrated in clinical studies, support the use of rotigotine as a continuous non-ergot D₃/D₂/D₁ dopamine receptor agonist in the treatment of PD and RLS.
Low injury rate strongly correlates with team success in Qatari professional football
Authors: Cristiano Eirale, J L Tol, Abdulaziz Farooq, Faten Smiley, Hakim Chalabi
Journal: British Journal of Sports Medicine (2012)

Although the incidence of football injuries should relate to team success there is little empirical evidence.We investigated the relationship between injury incidence and team success in Qatar first-division football clubs.Using a prospective cohort study design, we captured exposure and injuries in Qatar male elite football for a season. Club performance was measured by total league points, ranking, goal scored, goals conceded and number of matches won, drawn or lost.Lower injury incidence was strongly correlated with team ranking position (r=0.929, p=0.003), more games won (r=0.883, p=0.008), more goals scored (r=0.893, p=0.007), greater goal difference (r=0.821, p=0.003) and total points (r=0.929, p=0.003).Lower incidence rate was strongly correlated with team success. Prevention of injuries may contribute to team success.
Twenty four hour intragastric acidity and plasma gastrin concentration in healthy volunteers taking nizatidine 150 mg, nizatidine 300 mg, ranitidine 300 mg, or placebo at 21:00 h.
Authors: S Lanzon-Miller, R E Pounder, N A Chronos, F Raymond, M R Hamilton, D Dalgleish
Journal: Gut (1988)

Nine healthy volunteers were studied on the seventh day of dosing at 21:00 h with nizatidine 150 mg (N 150), nizatidine 300 mg (N 300), ranitidine 300 mg (R 300), or placebo, given in a predetermined random order. The double-blind 24 hour studies, using the Royal Free Hospital standard protocol, simultaneously measured intragastric acidity and plasma gastrin concentration. Compared with placebo, subjects responded to dosing with each H2-antagonist by a significant decrease of 24 hour intragastric acidity (N 150-45%; N 300-49% R 300-56%; p less than 0.01) and a significant rise of plasma gastrin concentration (N 150 + 20%; N 300 + 27%; R 300 + 58%; p less than 0.01). All three drug regimens caused similar significant decreases of nocturnal acidity (N 150-72%; N 300-79%; R 300-85%; p less than 0.01) and increases of nocturnal plasma gastrin concentration (N 150 + 41%; N300 + 52%; R 300 + 80%; p less than 0.01). Dosing with ranitidine 300 mg at 21:00 h also caused a simultaneous significant decrease of morning acidity (-32%; p less than 0.05) with a significant increase of plasma gastrin concentration (+36%; p less than 0.05), but the antisecretory effects of nizatidine 150 or 300 mg at 21:00 h were only observed during the night, with no effect during the morning. No drug regimen had any effect on acidity or plasma gastrin in the afternoon or early evening.
Left coronary pressure–flow relations of the beating and arrested rabbit heart at different ventricular volumes
Authors: P Sipkema
Journal: Cardiovascular Research (1998)

Objective: To study the effect of cardiac contraction on left coronary artery pressure–flow relations at different vascular volumes and to compare these relations in the beating heart with those in the heart arrested in systole and diastole. Methods: Maximally vasodilated, Tyrode perfused, rabbit hearts (n=6) with an intra-ventricular balloon were used. The left coronary artery was separately perfused via a cannula in the left main coronary artery. The slopes and the intercepts of left coronary pressure-flow relations were determined in the beating and arrested heart at different chamber volumes. A 3-factor design with repeated measures was used to compare the effect of three factors: phase of contraction (systole and diastole), chamber volume (V0 and V1, left ventricular end-diastolic pressure 1.4 and 20 mm Hg, respectively) and the type of contraction (beating and arrested; a measure of capacitive effects). Results: The phase of contraction has a significant effect on the intercepts (>40 mmHg, p=0.00032) but not on the slopes of the pressure–flow relations. Chamber volume had a small effect on the intercepts (<5 mm Hg, p=0.037), but not on the slopes of the pressure–flow relations. The type of contraction has a significant effect on the slopes (∼10%, p=0.00021) but not on the intercepts of the pressure–flow relations. Conclusions: In the isolated Tyrode perfused rabbit heart left coronary pressure–flow relations are mainly determined by contraction, while left ventricular chamber volume and capacitive effects contribute little.