tbuckley/cabot-search huggingface dataset:
Characterization of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: Evidence for it being a hepatitic form of PBC in genetically susceptible individuals
Authors: Ansgar W. Lohse, Karl-Hermann Meyer zum Büschenfelde, Beate Franz, Stephan Kanzler, Guido Gerken, Hans-Peter Dienes
Journal: Hepatology (1999)

Some patients with autoimmune liver disease present with a clinical and/or histological picture showing characteristic findings of both autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). Various names, mostly overlap syndrome, have been used to describe these cases, which have thus far not been more closely characterized. The aim of this study was the comparison of 20 patients with overlapping features to representative patients considered suffering from typical AIH or typical PBC (20 patients in each group). We found these patients to indeed show a very mixed picture of both conditions biochemically, serologically, and histologically. However, closer analysis suggested that all of these patients were primarily suffering from PBC as all of them had at least either bile duct destruction on histology or anti–M2 positive antimitochondrial antibodies (AMA). We suggest that these PBC patients because of their genetic susceptibility, evidenced by the AIH–characteristic histocompatibility leukocyte antigen (HLA) type B8, DR3, or DR4, developed a more hepatitic picture. Response to immunosuppressive therapy was excellent. We propose that the name “overlap syndrome” be abandoned for “PBC, hepatitic form.” These observations not only have pathophysiological implications, but also suggest that therapy of PBC should be guided by the degree of biochemical and histological hepatic involvement
Interleukin-6 Regulation of Matrix Metalloproteinase (MMP-2 and MMP-9) and Tissue Inhibitor of Metalloproteinase (TIMP-1) Expression in Malignant Non-Hodgkin’s Lymphomas
Authors: Anna E. Kossakowska, Dylan R. Edwards, Christopher Prusinkiewicz, Melissa C. Zhang, Dianlin Guo, Stefan J. Urbanski, Thomas Grogan, Leah A. Marquez, Anna Janowska-Wieczorek
Journal: Blood (1999)
An exuberant inflammatory response to E coli: implications for the pathogenesis of ulcerative colitis and pyoderma gangrenosum
Authors: D J B Marks, F Z Rahman, M Novelli, R C Yu, S McCartney, S Bloom, A W Segal
Journal: Gut (2006)

A recent study investigated acute inflammatory responses in patients with inflammatory bowel disease.1 Subjects received 1 mg of heat killed Escherichia coli subcutaneously into each forearm. The magnitude of the ensuing local inflammatory responses, measured as increases in local blood flow, peaked in healthy individuals by 24 hours and resolved within 48 hours. In contrast, the response in two patients with ulcerative colitis was abnormally protracted (supplementary fig 1; supplementary fig 1 can be viewed on the Gut website at http://www.gutjnl.com/supplemental).



 Figure 1  
 Macroscopic and microscopic appearances of the skin lesions. (A) A prolonged erythematous reaction developed at each injection site in this patient. These subsequently (B) blistered and (C) ulcerated. (D) Ulcers completely re-epithelialised after sequential treatment with infliximab, clobetasol, and topical tacrolimus. (E) Biopsies taken from the margin of the lesion showed granulation tissue, active inflammation in the subcutis, fibrin exudation into the superficial dermis, and pseudoepithelialomatous hyperplasia. High power images (inset) revealed a predominantly neutrophilic leucocyte infiltrate. …
Fractional versus ablative erbium:yttrium-aluminum-garnet laser resurfacing for facial rejuvenation: An objective evaluation
Authors: Moetaz El-Domyati, Talal Abd-El-Raheem, Hossam Abdel-Wahab, Walid Medhat, Wael Hosam, Hasan El-Fakahany, Mustafa Al Anwer
Journal: Journal of the American Academy of Dermatology (2012)
Mammography Facility Characteristics Associated With Interpretive Accuracy of Screening Mammography
Authors: S. Taplin, L. Abraham, W. E. Barlow, J. J. Fenton, E. A. Berns, P. A. Carney, G. R. Cutter, E. A. Sickles, D. Carl, J. G. Elmore
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundAlthough interpretive performance varies substantially among radiologists, such variation has not been examined among mammography facilities. Understanding sources of facility variation could become a foundation for improving interpretive performance.
Non-ulcer dyspepsia and short term De-Nol therapy: a placebo controlled trial with particular reference to the role of Campylobacter pylori.
Authors: T Rokkas, C Pursey, E Uzoechina, L Dorrington, N A Simmons, M I Filipe, G E Sladen
Journal: Gut (1988)

This double blind randomised study tested the effectiveness of colloidal bismuth subcitrate (De-Nol) in non-ulcer dyspepsia (NUD) and if any benefit is associated with clearance of Campylobacter pylori (C pylori) from the gastric mucosa. Sixty six patients with dyspepsic symptoms, normal abdominal ultrasound, and upper GI endoscopy, were randomly allocated to placebo or De-Nol for eight weeks. Antral biopsies were taken for bacteriological and histological examination, and endoscopies and clinical questionnaires were administered before and after treatment. Fifty two patients (25 on De-Nol and 27 on placebo) completed the trial. De-Nol cleared C pylori from 10 of the 12 C pylori positive patients (83.3%), whereas placebo did not clear C pylori from any of the eight C pylori positive patients (p less than 0.01). In patients receiving De-Nol gastritis improved (p less than 0.01) and symptomatic response was better (p less than 0.001) compared with placebo. In the placebo group seven of the 19 C pylori negative patients became positive: this was associated with significant deterioration of symptoms, a phenomenon not seen in the De-Nol treated group.
Efficacy of occupational therapy for patients with Parkinson's disease: a randomised controlled trial
Authors: Ingrid H W M Sturkenboom, Maud J L Graff, Jan C M Hendriks, Yvonne Veenhuizen, Marten Munneke, Bastiaan R Bloem, Maria W Nijhuis-van der Sanden
Journal: The Lancet Neurology (2014)
Clinical management of Staphylococcus aureus bacteraemia
Authors: Guy E Thwaites, Jonathan D Edgeworth, Effrossyni Gkrania-Klotsas, Andrew Kirby, Robert Tilley, M Estée Török, Sarah Walker, Heiman FL Wertheim, Peter Wilson, Martin J Llewelyn
Journal: The Lancet Infectious Diseases (2011)
Diagnostic Accuracy of Intracellular <i>Mycobacterium tuberculosis</i> Detection for Tuberculous Meningitis
Authors: Guo-dong Feng, Ming Shi, Lei Ma, Ping Chen, Bing-ju Wang, Min Zhang, Xiao-lin Chang, Xiu-chu Su, Yi-ning Yang, Xin-hong Fan, Wen Dai, Ting-ting Liu, Ying He, Ting Bian, Li-xin Duan, Jin-ge Li, Xiao-ke Hao, Jia-yun Liu, Xin Xue, Yun-zhang Song, Hai-qin Wu, Guo-qiang Niu, Li Zhang, Cui-juan Han, Hong Lin, Zhi-hui Lin, Jian-jun Liu, Qian Jian, Jin-she Zhang, Ye Tian, Bai-yu Zhou, Jing Wang, Chang-hu Xue, Xiao-fang Han, Jian-feng Wang, Shou-lian Wang, Guy E. Thwaites, Gang Zhao
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity.Objectives: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis.Methods: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6–expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis.Measurements and Main Results: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6–6.7%), compared with 82.9% (95% confidence interval, 77.4–87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8–80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4–93.8%) and 90.0% (95% confidence interval, 75.4–96.7%), respectively.Conclusions: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.
Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding
Authors: Xinle Cui, Feras Hawari, Sura Alsaaty, Marion Lawrence, Christian A. Combs, Weidong Geng, Farshid N. Rouhani, Dianne Miskinis, Stewart J. Levine
Journal: Journal of Clinical Investigation (2002)

Proteolytic cleavage of TNF receptor 1 (TNFR1) generates soluble receptors that regulate TNF bioactivity. We hypothesized that the mechanism of TNFR1 shedding might involve interactions with regulatory ectoproteins. Using a yeast two-hybrid approach, we identified ARTS-1 (aminopeptidase regulator of TNFR1 shedding) as a type II integral membrane protein that binds to the TNFR1 extracellular domain. In vivo binding of membrane-associated ARTS-1 to TNFR1 was confirmed by coimmunoprecipitation experiments using human pulmonary epithelial and umbilical vein endothelial cells. A direct relationship exists between membrane-associated ARTS-1 protein levels and concordant changes in TNFR1 shedding. Cells overexpressing ARTS-1 demonstrated increased TNFR1 shedding and decreased membrane-associated TNFR1, while cells expressing antisense ARTS-1 mRNA demonstrated decreased membrane-associated ARTS-1, decreased TNFR1 shedding, and increased membrane-associated TNFR1. ARTS-1 neither bound to TNFR2 nor altered its shedding, suggesting specificity for TNFR1. Although a recombinant ARTS-1 protein demonstrated selective aminopeptidase activity toward nonpolar amino acids, multiple lines of negative evidence suggest that ARTS-1 does not possess TNFR1 sheddase activity. These data indicate that ARTS-1 is a multifunctional ectoprotein capable of binding to and promoting TNFR1 shedding. We propose that formation of a TNFR1-ARTS-1 molecular complex represents a novel mechanism by which TNFR1 shedding is regulated.
Improvement of Lipoprotein Lipid Composition in Type II Diabetic Patients With Concomitant Hyperlipoproteinemia by Acipimox Treatment: Results of a multicenter trial
Authors: D Koev, S Zlateva, M Susic, D Babic, V Profozic, Z Skrabalo, H Langrová, A L Cvrkalová, E Rajecová, I Klimes
Journal: Diabetes Care (1993)

To study the tolerability and efficacy of acipimox on hyperlipidemia and diabetes compensation in patients with NIDDM under conditions of a routine clinical practice.We recruited 121 patients (60 men and 61 women) from 10 participating clinical centers. They were randomly divided into two groups and treated for 3 mo either with acipimox (250 mg three times a day) or placebo, using an open study design.Acipimox treatment led to a significant drop in fasting serum total triglyceride levels (by 28%) after 1 mo of drug administration. This decrease prevailed up to the end of the 3-mo study. Serum total cholesterol levels declined by 14%, and high-density lipoprotein tended to rise in acipimox-treated patients. These changes in lipid metabolism were not accompanied by any adverse effects of acipimox on glucose metabolism as judged by HbA1c measurements and the oral glucose tolerance test. Eight patients (out of 82 treated with acipimox) reported moderate adverse events of transient character, such as skin reactions and gastric disturbances.Acipimox seems to be a useful agent for treatment of diabetic dyslipidemia and does not deteriorate glycemic control.
Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma
Authors: Weijie Poh, Winnie Wong, Huimin Ong, Myat Oo Aung, Seng Gee Lim, Boon Tin Chua, Han Kiat Ho
Journal: Molecular Cancer (2012)

Abstract Background We had previously demonstrated overexpression of fibroblast growth factor receptor-4 (FGFR4) in hepatocellular carcinoma (HCC). However, additional molecular mechanisms resulting in amplified FGFR4 signaling in HCC remain under-studied. Here, we studied the mechanistic role of its co-receptor klotho-beta (KLB) in driving elevated FGFR4 activity in HCC progression. Results Quantitative real-time PCR analysis identified frequent elevation of KLB gene expression in HCC tumors relative to matched non-tumor tissue, with a more than two-fold increase correlating with development of multiple tumors in patients. KLB-silencing in Huh7 cells decreased cell proliferation and suppressed FGFR4 downstream signaling. While transient repression of KLB-FGFR4 signaling decreased protein expression of alpha-fetoprotein (AFP), a HCC diagnostic marker, prolonged inhibition enriched for resistant HCC cells exhibiting increased liver stemness. Conclusions Elevated KLB expression in HCC tissues provides further credence to the oncogenic role of increased FGFR4 signaling in HCC progression and represents a novel biomarker to identify additional patients amenable to anti-FGFR4 therapy. The restricted tissue expression profile of KLB, together with the anti-proliferative effect observed with KLB-silencing, also qualifies it as a specific and potent therapeutic target for HCC patients. The enrichment of a liver stem cell-like population in response to extended KLB-FGFR4 repression necessitates further investigation to target the development of drug resistance.
A Case–Control Study of Smoking and Bladder Cancer Risk: Emergent Patterns Over Time
Authors: Dalsu Baris, Margaret R. Karagas, Castine Verrill, Alison Johnson, Angeline S. Andrew, Carmen J. Marsit, Molly Schwenn, Joanne S. Colt, Sai Cherala, Claudine Samanic, Richard Waddell, Kenneth P. Cantor, Alan Schned, Nathaniel Rothman, Jay Lubin, Joseph F. Fraumeni, Robert N. Hoover, Karl T. Kelsey, Debra T. Silverman
Journal: JNCI Journal of the National Cancer Institute (2009)

Cigarette smoking accounts for about 65% of bladder cancer risk in men and 20% -30% in women ( 1 ).Studies have consistently shown a two-to threefold risk of bladder cancer among regular cigarette smokers, defined as those who smoked at least one cigarette per day for at least 6 months, compared with those who never smoked ( 1 ).Experimental evidence has suggested that 2-naphthylamine and 4-aminobiphenyl may be the bladder carcinogens in cigarette smoke ( 1 -8 ).Numerous studies have demonstrated that bladder cancer risk increases with increasing duration and intensity (cigarettes per day) of smoking, although risk levels off at higher intensity but not at higher duration ( 1 , 9 ).Bladder cancer risk decreases as time since quitting increases ( 10 -12 ), but it is unclear whether risk eventually returns to that of never-smokers ( 1 ).Moreover, previous bladder cancer studies ( 8 , 13 -17 ) have yielded equivocal results on the risk associated with exposure to environmental tobacco smoke (ETS).
Live and let die: is neutrophil apoptosis defective in severe asthma?
Authors: H. Parfrey, N. Farahi, L. Porter, E. R. Chilvers
Journal: Thorax (2010)

those unregistered with GPs and those in anomalous positionsdsuch as asylum seekersdwill remain and will require alternative initiatives.Are sticks necessary as well as carrotsdas in The Netherlands which links residency permits with TB screening?The autonomy of the individual in decisions about their own healthcare is fundamental in the UK and many other countries.The rights of those who actually have infectious TB which is a risk to others are, though, already constrained in the UK both by Act of Parliament (Public Health Act 1984) and potentially by decisions of the Courts.An extension of these limitations to those who merely might have active TB or who might get it in future would be a very hot political issue.TB, though, is already a hot political issue, 4 and a rational, informed and wide-ranging debate is overdue.The present system is not adequate, and the 'status quo' is no longer a sensible or scientific position, but merely x-raying all potential immigrants would be worse.Answers as to the utility, yield and cost of various screening strategies should be readily obtainable at little additional cost because of the heterogeneity of what actually is being done across England and Wales, in both primary and secondary care, and sometimes across the interface between the two.
Standardized Approach for Microsatellite Instability Detection in Colorectal Carcinomas
Authors: I. Gonzalez-Garcia
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Ubiquitous mutations in microsatellite DNA sequences define a specific type of genetic instability, termed microsatellite instability (MSI). Various approaches have been used to identify the presence and degree of MSI. To define standard diagnostic criteria for MSI, we developed and tested a mathematical model. Methods: We designed an algorithm for the efficient characterization of MSI and used it to analyze data on six microsatellite markers in colorectal carcinoma and normal tissues from 415 patients. Theoretical models considering one, two, or three populations were tested against the data collected. Results: The observed frequencies of MSI in our series of samples best fit a two-population model, stable and unstable, defined by instability in two or more of four to six markers analyzed. MSI was observed in 7.5% of the tumors. The misclassification rate was less than 5% when any four loci were analyzed and less than 1% when the six markers were used. A stepwise strategy, consisting first of a bulk screening of two loci and then a second screening of two to four additional markers, provided excellent sensitivity (≥97%) and specificity (100%). Tumors with MSI had distinctive genetic and clinicopathologic features, including better patient survival. Conclusion: To assess the presence of MSI in colorectal cancer, we have developed a simple, sensitive, and specific approach based on the apparent good fit of the data to a two-population model. Its application to a prospective series of patients with colorectal carcinomas demonstrates that the presence of MSI characterizes a subset of less aggressive tumors.
Increased Levels and Activity of Matrix Metalloproteinase-9 in Obstructive Sleep Apnea Syndrome
Authors: Toshiyuki Tazaki, Kenji Minoguchi, Takuya Yokoe, Karen Thursday R. Samson, Hideko Minoguchi, Akihiko Tanaka, Yoshio Watanabe, Mitsuru Adachi
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Matrix metalloproteinases (MMPs) are involved in the pathogenesis of cardiovascular diseases. We examined serum levels of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), activity of MMP-9, and the effect of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). After polysomnography, venous blood was collected at 5:00 A.M. from 44 patients with OSAS and 18 control subjects who were obese, and serum levels of MMP-9, TIMP-1, and enzymatic activity of MMP-9 were measured. In addition, the effects of 1 month of treatment with nCPAP were studied in patients with moderate to severe OSAS. Although serum levels of MMP-9 (p < 0.03) and MMP-9 activity (p < 0.01) were higher in patients with OSAS than in control subjects who were obese, TIMP-1 levels did not differ significantly. In patients with OSAS, the severity of OSAS was the primary factor influencing levels (p < 0.01) and activity (p < 0.01) of MMP-9. nCPAP significantly decreased serum levels (p < 0.01) and activity (p < 0.001) of MMP-9 but did not affect TIMP-1 levels. Therefore, OSAS may increase risks of cardiovascular morbidity, and nCPAP might be useful for decreasing these risks.
Sequentially induced sputum in patients with asthma or chronic obstructive pulmonary disease
Authors: K. Richter, O. Holz, R.a. Jörres, M. Mücke, H. Magnussen
Journal: European Respiratory Journal (1999)

It has been demonstrated that consecutive samples of induced sputum may differ with respect to cellular composition. The aim of this study was to compare two sequential sputum samples in patients with chronic obstructive pulmonary disease (COPD) and asthma with different severity. Two sputum inductions were performed 30 min apart and processed separately in healthy subjects (n=11), patients with moderate to severe COPD (n=10), asthmatics treated with beta2-agonists alone (group 1, n=11), inhaled steroids (group 2, n=12) or systemic steroids (group 3, n=7). In healthy subjects and asthma group 2, percentages of neutrophils decreased significantly between the two sputum inductions but did not change in COPD and asthma group 3. Percentages of eosinophils did not change significantly in any group of patients. Concentrations of interleukin (IL)-8 decreased significantly in the control group and asthma groups 1 and 2 but not in asthma group 3 and the COPD group. These data demonstrate differences in sputum composition between two consecutive samples which were most pronounced in healthy subjects. Therefore, pooling of sputum samples may affect the results, particularly in healthy subjects, in contrast to subjects with more severe asthma or chronic obstructive pulmonary disease. These findings may be suggestive of differences in the distribution of inflammation along the airways between distinct airway diseases.
Sphingosine kinase isoforms and cardiac protection
Authors: Y NISHINO, I WEBB, M MARBER
Journal: Cardiovascular Research (2007)

See article by Jin et al.  [3]  (pages 41–50) in this issue. 

Sphingolipids are complex, ubiquitous lipids commonly believed to protect the cell surface against harmful environmental factors by forming a mechanically stable and chemically resistant outer leaflet of the plasma membrane lipid bilayer. Over the last decade relatively simple sphingolipid catabolites, such as ceramide and sphingosine-1-phosphate (S1P), have been identified as signal-transducing molecules involved in the regulation of cell growth, viability, mitosis, cytoskeletal rearrangement, immunity and angiogenesis in a variety of cells and tissues [1]. Ceramide and S1P are products of the membrane phospholipid sphingomyelin, and they appear to exert opposing biological actions; the sphingosine precursor ceramide is associated with cardiomyocyte apoptosis, whilst S1P, derived from phosphorylation of sphingosine by sphingosine kinases (SphK), may exert an anti-apoptotic effect. Activation of SphK is the final and rate-limiting step in the cellular synthesis of S1P, and accordingly is an important modulator of both ceramide and S1P levels. SphK exists as two isoforms which may have opposing roles; thus, activation of SphK1 appears to be protective, whereas SphK2 is considered to be pro-apoptotic [2]. Hence, the actions of S1P may in part be determined by the SphK directing … 

*Corresponding author. Department of Cardiology, Kings College London, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK mike.marber{at}kcl.ac.uk