tbuckley/cabot-search huggingface dataset:
Heparin kinetics in venous thrombosis and pulmonary embolism.
Authors: J Hirsh, W G van Aken, A S Gallus, C T Dollery, J F Cade, W L Yung
Journal: Circulation (1976)

The response to a standard dose of heparin was studied in 20 patients with venous thromboembolism. The heparin regimen consisted of intravenous injection of 70 units per kg, followed after 90 minutes by a maintenance dose of 400 units per kg per 24 hours given by continuous infusion. Plasma heparin activity and the activated partial thromboplastin time (APTT) were measured at intervals to determine clearance of the initial injection and the response to maintenance dose. Large inter-individual variations were found in the anticoagulant effect and these were due in part to differences in heparin clearance and in part to differences in the APTT response to given amounts of heparin (heparin effect index). The heparin half-life was 63 +/- 15 minutes when plasma heparin activities were used for this calculation and 84 +/- 71.5 minutes when the APTT was used. These results are similar to values previously reported in normal volunteers. Four of the 20 patients had pulmonary embolism and in these heparin half-life was significantly shortened (P less than 0.005).
There is more to healing ulcers than suppressing acid.
Authors: D G Colin-Jones
Journal: Gut (1986)

<h3>Abstract</h3> Some of the most dangerous bacterial pathogens (Gram-negative and mycobacterial) deploy a formidable secondary membrane barrier to reduce the influx of exogenous molecules. For Gram-negative bacteria, this second exterior membrane is known as the outer membrane, while for the Gram-indeterminate <i>Mycobacteria,</i> it is known as the ‘myco’ membrane. Although different in composition, both the outer membrane and mycomembrane are key structures that restrict the passive permeation of small molecules into bacterial cells. While it is well-appreciated that such structures are principal determinants of small molecule permeation, it has proven to be challenging to assess this feature in a robust and quantitative way or in complex, infection-relevant settings. Herein, we describe the development of the Bacterial Chloro-Alkane Penetration Assay (BaCAPA), which employs the use of a genetically encoded protein called HaloTag, to measure the uptake and accumulation of molecules into model Gram-negative and mycobacterial species, <i>Escherichia coli</i> and <i>Mycobacterium smegmatis,</i> respectively, and into the human pathogen <i>M. tuberculosis.</i> Directing the localization of the HaloTag protein to either the cytoplasm or periplasm of bacteria enabled a compartmental analysis of permeation across individual cell membranes. Significantly, we also showed that BaCAPA can be used to analyze the permeation of molecules into host cell-internalized <i>E. coli</i> and <i>M. tuberculosis,</i> a critical capability for analyzing intracellular pathogens. Together, our results show that BaCAPA affords facile, compartment-specific measurement of permeability across four barriers: the host plasma and phagosomal membranes and the diderm bacterial cell envelope.
The Safety of Valproic Acid Use for Patients With Hepatitis C Infection
Authors: Bradford L Felker, Kevin L Sloan, Jason A Dominitz, Robert F Barnes
Journal: American Journal of Psychiatry (2002)

Valproic acid is frequently not recommended for patients with hepatic dysfunction. The authors evaluated the association between hepatitis C and alanine aminotransferase (ALT) values during valproic acid treatment.ALT changes in 564 individuals beginning valproic acid treatment were examined. Changes among those with positive hepatitis C status were compared with changes among patients with positive hepatitis C status who were taking other psychotropic agents.ALT elevations with valproic acid were significantly greater among patients with positive hepatitis C status than those with negative or unknown status. Among patients with positive hepatitis C status, ALT increases did not differ significantly between valproic acid and other medications.Use of valproic acid may be possible for some patients with hepatitis C. ALT increases in seropositive patients may be partially related to chronic hepatitis infection. However, ALT levels should be closely monitored in all hepatitis C patients taking valproic acid.
HOXB13 Homeodomain Protein Suppresses the Growth of Prostate Cancer Cells by the Negative Regulation of T-Cell Factor 4
Authors: Chaeyong Jung, Ran-Sook Kim, Sang-Jin Lee, Chihuei Wang, Meei-Huey Jeng
Journal: Cancer Research (2004)

Abstract In prostate gland, HOXB13 is highly expressed from the embryonic stages to adulthood. However, the function of HOXB13 in normal cell growth and tumorigenesis is not yet known. We investigated the role of HOXB13 and mechanism by which it functions in HOXB13-negative cells. Expression of HOXB13 was forced in HOXB13-negative PC3 prostate cancer cells using a liposome-mediated gene transfer approach. Compared with the control clones, HOXB13-expressing PC3 cells exhibited significant inhibition of in vitro and in vivo cell growth with G1 cell cycle arrest mediated by the suppression of cyclin D1 expression. Because cyclin D1 is mainly regulated by β-catenin/T-cell factor (TCF), TCF-4 response element was used in a reporter gene transcription assay, demonstrating that HOXB13 significantly inhibits TCF-4-mediated transcriptional activity in both prostate and nonprostate cells. This inhibition occurred in a dose-responsive manner and was specific to TCF-4 response element. Western blot analysis demonstrated that HOXB13 down-regulates the expression of TCF-4 and its responsive genes, c-myc and cyclin D1. HOXB13 also suppressed the activity of natural c-myc promoter. This study suggests that HOXB13, a transcription factor, functions as a cell growth suppressor by negatively regulating the expression of TCF-4, which eventually provides negative signals for cell proliferation. This observation will provide valuable insight into the molecular basis of prostate tumorigenesis.
Exhaled carbon monoxide is not elevated in patients with asthma or cystic fibrosis
Authors: W. Zetterquist, H. Marteus, M. Johannesson, S.L. Nordvall, E. Ihre, J.O.N. Lundberg, K. Alving
Journal: European Respiratory Journal (2002)

Increased levels of exhaled carbon monoxide (fractional concentration of CO in expired gas ( F E,CO )), measured with an electrochemical sensor, have been reported in patients with inflammatory airway disorders, such as asthma, rhinitis and cystic fibrosis. This study aimed to evaluate these findings by using a fast-response nondisperse infrared (NDIR) analyser, and to compare these measurements with the fractional concentration of nitric oxide in exhaled air ( F E,NO ). Thirty-two steroid-naïve asthmatics, 24 steroid-treated asthmatics (16 patients with allergic rhinitis, nine patients with cystic fibrosis), and 30 nonsmoking healthy controls were included. CO measurements with the NDIR analyser were performed simultaneously with nitric oxide (NO) analysis (chemiluminescence technique). After 15 s of breath-hold, single-breath exhalations over 10 s were performed at two flow rates and end-tidal plateau concentrations were registered. An electrochemical CO sensor was used independently with an exhalation to residual volume, after a 15 s breath-hold. None of the two CO analysers gave a significant increase in F E,CO in the groups of patients with inflammatory airway disorders compared to controls. F E,NO was significantly elevated in steroid-naïve asthmatics and subjects with allergic rhinitis, but not in steroid-treated asthmatics and subjects with cystic fibrosis. Reducing exhalation flow rate by 50% gave a two-fold increase in F E,NO , while F E,CO was unaffected. A significant increase was seen in F E,CO , but not in F E,NO , when comparing with and without a 10 s breath-hold. In conclusion, the fractional concentration of carbon monoxide in expired gas was not increased in any of the patient groups, while the fractional concentration of nitric oxide in expired gas was significantly elevated in patients with steroid-naïve asthma and allergic rhinitis. Moreover, carbon monoxide was unaffected by flow rate but increased with breath-hold, suggesting an origin in the alveoli rather than the conducting airways.
Relative Merits of Left Ventricular Dyssynchrony, Left Ventricular Lead Position, and Myocardial Scar to Predict Long-Term Survival of Ischemic Heart Failure Patients Undergoing Cardiac Resynchronization Therapy
Authors: Victoria Delgado, Rutger J. van Bommel, Matteo Bertini, C. Jan Willem Borleffs, Nina Ajmone Marsan, Arnold C.T. Ng, Gaetano Nucifora, Nico R.L. van de Veire, Claudia Ypenburg, Eric Boersma, Eduard R. Holman, Martin J. Schalij, Jeroen J. Bax
Journal: Circulation (2010)

The relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome after cardiac resynchronization therapy remain unknown and were evaluated in the present study.In 397 ischemic heart failure patients, 2-dimensional speckle tracking imaging was performed, with comprehensive assessment of LV radial dyssynchrony, identification of the segment with latest mechanical activation, and detection of myocardial scar in the segment where the LV lead was positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used. Segments with <16.5% radial strain in the region of the LV pacing lead were considered to have extensive myocardial scar (>50% transmurality, validated in a subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position was derived from chest x-ray. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was 133±98 milliseconds. In 271 patients (68%), the LV lead was placed at the latest activated segment (concordant LV lead position), and the mean value of peak radial strain at the targeted segment was 18.9±12.6%. Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995; P=0.001), whereas a discordant LV lead position (hazard ratio, 2.086; P=0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; P<0.001) were independent predictors of worse outcome. Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters.Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in ischemic heart failure patients treated with cardiac resynchronization therapy. Larger baseline LV dyssynchrony predicted superior long-term survival, whereas discordant LV lead position and myocardial scar predicted worse outcome.
Identification of<i>CCND3</i>and<i>BYSL</i>as Candidate Targets for the 6p21 Amplification in Diffuse Large B-Cell Lymphoma
Authors: Yumiko Kasugai, Hiroyuki Tagawa, Yoshihiro Kameoka, Yasuo Morishima, Shigeo Nakamura, Masao Seto
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Increases in gene dosage through DNA amplification represents a common feature of many tumors and can result in the up-regulation of tumor-promoting genes. Our recent genome-wide, array-based comparative genomic hybridization analysis of 66 cases of diffuse large B-cell lymphoma found that genomic gain of 6p21 was observed in as many as 17 cases, including 14 cases with low-level copy number gain and three cases with high-level copy number gains (amplifications). Experimental Design and Results: To identify the target gene(s) for 6p21 amplification, we constructed a detailed amplicon map at the region of genomic amplification with the aid of high-resolution contig array-based comparative genomic hybridization glass slides, consisting of contiguously ordered bacterial artificial chromosome/P1-derived artificial chromosome clones covering 3 Mb throughout the 6p21 amplification region. Alignment of the amplifications identified a minimally overlapping 800 kb segment containing 15 genes. Quantitative expression analysis of the genes from both patient samples and the SUDHL9 cell line revealed that CCND3 and BYSL (1.9 kb telomeric to the CCND3 gene locus) are the targets of 6p21 genomic gain/amplification. Conclusions: Although it is known that t(6;14)(p21;q32) induces aberrant overexpression of CCND3 in B-cell malignancies, we were able to show that CCND3, which encodes the cyclin D family member protein that controls the G1-S phase of cell cycle regulation, can also be a target of genomic gain/amplification. Overexpression of CCND3 through genomic amplification is likely to lead to aberrant cell cycle control, although the precise biological role of BYSL with respect to tumorigenesis remains to be determined.
NHS regulator delays inspections as it struggles to fill posts in tougher regime
Authors: A. O'Dowd
Journal: BMJ (2014)

The main regulator of the NHS has admitted that it faces a challenge in finding enough “high calibre” inspectors to become part of its new, more thorough inspection regime, despite receiving extra investment from central government.

The Care Quality Commission (CQC) plans to increase its workforce of inspectors from around 850 currently to 1450 by the end of next year, but it has had to delay some planned inspections while it tries to recruit enough new staff.

MPs on the parliamentary health committee quizzed witnesses at their annual accountability hearing with the CQC on 16 December. They asked David Prior, CQC chairman, whether the regulator was fit for purpose. Prior replied, “We’ve come a long way, but we haven’t got to where we want to be. We are a very different organisation to the one that we were over a year …
Hypophosphorylation of the Stiff N2B Titin Isoform Raises Cardiomyocyte Resting Tension in Failing Human Myocardium
Authors: Attila Borbély, Ines Falcao-Pires, Loek van Heerebeek, Nazha Hamdani, István Édes, Cristina Gavina, Adelino F. Leite-Moreira, Jean G.F. Bronzwaer, Zoltán Papp, Jolanda van der Velden, Ger J.M. Stienen, Walter J. Paulus
Journal: Circulation Research (2009)

High diastolic stiffness of failing myocardium results from interstitial fibrosis and elevated resting tension (F(passive)) of cardiomyocytes. A shift in titin isoform expression from N2BA to N2B isoform, lower overall phosphorylation of titin, and a shift in titin phosphorylation from N2B to N2BA isoform can raise F(passive) of cardiomyocytes. In left ventricular biopsies of heart failure (HF) patients, aortic stenosis (AS) patients, and controls (CON), we therefore related F(passive) of isolated cardiomyocytes to expression of titin isoforms and to phosphorylation of titin and titin isoforms. Biopsies were procured by transvascular technique (44 HF, 3 CON), perioperatively (25 AS, 4 CON), or from explanted hearts (4 HF, 8 CON). None had coronary artery disease. Isolated, permeabilized cardiomyocytes were stretched to 2.2-microm sarcomere length to measure F(passive). Expression and phosphorylation of titin isoforms were analyzed using gel electrophoresis with ProQ Diamond and SYPRO Ruby stains and reported as ratio of titin (N2BA/N2B) or of phosphorylated titin (P-N2BA/P-N2B) isoforms. F(passive) was higher in HF (6.1+/-0.4 kN/m(2)) than in CON (2.3+/-0.3 kN/m(2); P<0.01) or in AS (2.2+/-0.2 kN/m(2); P<0.001). Titin isoform expression differed between HF (N2BA/N2B=0.73+/-0.06) and CON (N2BA/N2B=0.39+/-0.05; P<0.001) and was comparable in HF and AS (N2BA/N2B=0.59+/-0.06). Overall titin phosphorylation was also comparable in HF and AS, but relative phosphorylation of the stiff N2B titin isoform was significantly lower in HF (P-N2BA/P-N2B=0.77+/-0.05) than in AS (P-N2BA/P-N2B=0.54+/-0.05; P<0.01). Relative hypophosphorylation of the stiff N2B titin isoform is a novel mechanism responsible for raised F(passive) of human HF cardiomyocytes.
N-acetylcysteine inhibits loss of diaphragm function in streptozotocin-treated rats.
Authors: W Hida, C Shindoh, J Satoh, M Sagara, Y Kikuchi, T Toyota, K Shirato
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We examined whether streptozotocin (STZ)-induced diabetic rats have an impairment in diaphragm contractility, and if so, whether N-acetylcysteine (NAC), a nonspecific antioxidant, prevents this impairment. First, diaphragm contractility, assessed by tension-frequency relationships and twitch kinetics in in vitro diaphragm strip preparations of Wistar rats, was obtained on Days 3 and 7 after administration of STZ of 30 or 60 mg/kg body weight, and compared with that of the control group. Second, NAC at 500 mg/kg body weight or vehicle solution was administered orally every day in rats treated with STZ at 60 mg/kg body weight, and diaphragm function on Day 7 after starting NAC treatment was compared between vehicle control and STZ-treated groups. We found that diaphragm function in STZ-treated rats, which had hyperglycemia, decreased in a dose- and time-dependent manner. NAC inhibited the decrease in diaphragm contractility in STZ-treated rats without reducing blood glucose. These findings suggest that the loss of diaphragm function in STZ-induced diabetic rats is not directly related to hyperglycemia. The data are consistent with secondary alterations of normal cytokine signaling or changes in the redox state of the cell, both of which could be affected by NAC treatment.
Response: Re: Pregnancies, Breastfeeding, and Breast Cancer Risk in the International BRCA1/2 Carrier Cohort Study (IBCCS)
Authors: N. Andrieu, D. E. Goldgar, D. F. Easton, M. Rookus, R. Brohet, A. C. Antoniou, J. Chang-Claude
Journal: JNCI Journal of the National Cancer Institute (2007)
Docetaxel-Induced Apoptosis of Human Melanoma Is Mediated by Activation of c-Jun NH2-Terminal Kinase and Inhibited by the Mitogen-Activated Protein Kinase Extracellular Signal-Regulated Kinase 1/2 Pathway
Authors: Nizar M. Mhaidat, Xu Dong Zhang, Chen Chen Jiang, Peter Hersey
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Our studies have shown variable sensitivity of cultured melanoma cells to docetaxel. To better understand this response, we studied the role of signal transduction pathways in modulating docetaxel-induced melanoma killing. Experimental Design: Involvement of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and Akt signaling was studied by evaluating their extent of activation in melanoma cells after treatment with docetaxel. The effect of their activation on docetaxel-induced apoptosis was assessed using biochemical inhibitors of the pathways and Western blot analysis of proteins involved. Results: Docetaxel induced activation of both JNK and ERK1/2 but not p38 mitogen-activated protein kinase or Akt kinases. Apoptosis was dependent on activation of JNK and mediated through activation of caspase-2 and caspase-dependent changes in Bax and Bak. The levels of activated JNK in individual lines showed a close correlation with the levels of apoptosis. In contrast, activation of ERK1/2 by docetaxel inhibited apoptosis and the levels of activation in individual lines were inversely correlated to the degree of apoptosis. Studies on the Bcl-2 family proteins seemed to reflect changes induced by activation of JNK and ERK1/2 pathways. Docetaxel-induced JNK activation was required for Bcl-2 phosphorylation as well as caspase-2–dependent activation of Bax and Bak and subsequent mitochondrial release of apoptosis-inducing factor and cytochrome c. In contrast, activation of ERK1/2 resulted in degradation of BH3-only protein Bim and phosphorylation of Bad. Conclusions: These studies provide further insights into sensitivity of melanoma cells to taxanes and provide a basis for the current rationale of combining taxanes with inhibitors of the Raf-ERK1/2 pathway.
Basal Ganglia Shape Alterations in Bipolar Disorder
Authors: Jaeuk Hwang, In Kyoon Lyoo, Stephen R Dager, Seth D Friedman, Jung Su Oh, Jun Young Lee, Seog Ju Kim, David L Dunner, Perry F Renshaw
Journal: American Journal of Psychiatry (2006)

Shape differences in the caudate heads and putamen were compared between drug-naive and drug-treated patients with bipolar disorder and healthy comparison subjects by using spherical harmonic (SPHARM) techniques. On the basis of previous studies, the authors hypothesized that the drug-naive patients would exhibit shape differences of the caudate heads and putamen, especially on the right side, relative to the healthy comparison subjects, and that shape differences, relative to healthy comparison subjects, would differ between drug-naive and drug-treated patients.Brain magnetic resonance images were acquired from 49 bipolar disorder patients (21 drug-naive and 28 drug-treated patients) and 37 healthy comparison subjects. Volumetric measurements were obtained, and SPHARM descriptions were used to measure between-group radius differences in the surfaces of the caudate heads and putamen.Although no significant between-group volume differences were found in the striatal structures, significant shape differences in the anterior and ventral surfaces of the striatum were observed. Specifically, shape differences, more prominent for the right side, were found for drug-naive bipolar disorder patients, relative to the healthy comparison subjects, but not for drug-treated bipolar disorder subjects.The findings suggest that drug-naive bipolar disorder patients have shape differences of the striatum, relative to healthy comparison subjects, and that these differences may be modulated by treatment. The findings more generally demonstrate the sensitivity of the SPHARM analytic technique for detecting subtle anatomical shape differences in small brain regions in the absence of volume differences.
Treatment of so-called idiopathic follicular mucinosis with hydroxychloroquine
Authors: S.W. Schneider, D. Metze, G. Bonsmann
Journal: British Journal of Dermatology (2010)

Journal Article Treatment of so‐called idiopathic follicular mucinosis with hydroxychloroquine Get access S.W. Schneider, S.W. Schneider Department of Dermatology, Venereology and Allergology, Experimental Dermatology, Medical Faculty Mannheim, Heidelberg Ruprecht‐Karls‐University, Mannheim, Germany Search for other works by this author on: Oxford Academic Google Scholar D. Metze, D. Metze Department of Dermatology, University Hospital of Münster, Von‐Esmarch‐Str. 58, D‐48149 Münster, Germany Search for other works by this author on: Oxford Academic Google Scholar G. Bonsmann G. Bonsmann Department of Dermatology, University Hospital of Münster, Von‐Esmarch‐Str. 58, D‐48149 Münster, Germany Gisela Bonsmann E‐mail: bonsmag@uni‐muenster.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 2, 1 August 2010, Pages 420–423, https://doi.org/10.1111/j.1365-2133.2010.09759.x Published: 01 August 2010