tbuckley/cabot-search huggingface dataset:
Primary lymphomas of the small intestine: East‐west contrast
Authors: Hamid Al‐Mondhiry
Journal: American Journal of Hematology (1986)

Primary small intestinal lymphoma (PSIL) represents a heterogenous group of disorders with variable clinical and pathologic features and a characteristic age, socioeconomic, and geographic distribution. In developed countries, PSIL usually occurs as a localized ileal tumor, shows a bimodal age distribution, and most frequently presents with abdominal pain and obstructive symptoms. Histologically, most of these tumors are diffuse histiocytic, lymphocytic, or undifferentiated lymphomas. Other variants of PSIL, collectively referred to as immunoproliferative small intestinal disease, occur most often among young patients of poor socioeconomic status in Third World countries, mostly in the Middle East and Mediterranean area. They are characterized by involvement of long loops of the upper small intestine and commonly present with abdominal pain, diarrhea, malabsorption, and clubbing of the fingers. A subgroup of these patients shows a serological abnormality with the appearance of part of the alpha heavy chain of IgA in the serum. Histologically, the lesion appears as a dense diffuse lymphoplasmacytic infiltrate of the mucosa of the upper jejenum or duodenum. A form of malignant lymphoma of true histiocytic origin complicates long-standing celiac disease. The contrasting clinical, epidemiological, histopathological, and immunological features of these variants of PSIL raise interesting questions about the pathogenesis of small bowel lymphoma.
Small interfering RNA targeting CDC25B inhibits liver tumor growth in vitro and in vivo
Authors: Xinrui Yan, Mei-Sze Chua, Jing He, Samuel K So
Journal: Molecular Cancer (2008)

Using gene expression profiling, we previously identified CDC25B to be significantly highly expressed in hepatocellular carcinoma (HCC) compared to non-tumor liver. CDC25B is a cell cycle-activating phosphatase that positively regulates the activity of cyclin-dependent kinases, and is over-expressed in a variety of human malignancies. In this study, we validated the over-expression of CDC25B in HCC, and further investigated its potential as a therapeutic target for the management of HCC.Quantitative real-time polymerase chain reaction and immunohistochemical staining of patient samples confirmed the significant over-expression of CDC25B in HCC compared to non-tumor liver samples (P < 0.001). Thus, intefering with the expression and activity of CDC25B may be a potential way to intervene with HCC progression. We used RNA interference to study the biological effects of silencing CDC25B expression in HCC cell lines (Hep3B and Hep40), in order to validate its potential as a therapeutic target. Using small oligo siRNAs targeting the coding region of CDC25B, we effectively suppressed CDC25B expression by up to 90%. This was associatetd with significant reductions in cell growth rate, cell migration and invasion through the matrigel membrane, and caused significant cell cycle delay at the G2 phase. Finally, suppression of CDC25B significantly slowed the growth of Hep40 xenografts in nude mice.Our data provide evidence that the inhibition of CDC25B expression and activity lead to suppression of tumor cell growth and motility, and may therefore be a feasible approach in the clinical management of HCC.
Contemporary cardiogenesis: new insights into heart development
Authors: D. Franco, R. G. Kelly
Journal: Cardiovascular Research (2011)

Cardiac development is a dynamic process during which progressive specification and differentiation of cardiovascular progenitor cells are intrinsically linked to complex morphogenetic events conferring function to the forming heart.1,2 Cardiogenesis initiates in the mesoderm of the anterior lateral region of the early embryo in response to inductive signals from surrounding tissues. Differentiation of the first cardiomyocytes surrounding an endocardial tube is rapidly followed by formation of a linear heart tube that subsequently elongates, loops to the right and undergoes ballooning morphogenesis to generate distinct atrial and ventricular chambers. Cardiac valve development, septation, and establishment of the coronary vasculature and conduction system follow as the heart acquires its definitive form. Defects in these processes result in a wide range of congenital heart anomalies, including major life-threatening defects such as cardiac arrhythmias and failure to separate systemic and pulmonary circulatory systems. Furthermore, the onset of certain cardiac pathologies in the adult is associated with activation of embryonic transcriptional programmes. Thus, understanding cardiac development, in particular through the study of model organisms, is crucial for both basic and translational research. This is an exciting period in the field of heart development as new molecular, genetic, and cellular approaches accelerate our understanding of the origins and diversification of different cardiac cell lineages as well as the molecular mechanisms and cellular interactions underlying normal and pathological heart development. The collection of reviews in this spotlight issue of Cardiovascular Research aims to provide a broad introduction to aspects of heart development of clinical relevance in addition to highlighting the most recent achievements, as well as the current potential and challenges, in the field of cardiac development.

The first step in …
Transient arthritis with positive tests for rheumatoid factor as presenting sign of shunt nephritis.
Authors: E J ter Borg, M H Van Rijswijk, C G Kallenberg
Journal: Annals of the Rheumatic Diseases (1991)

Shunt nephritis is a rare complication of a chronically infected ventriculoatrial shunt. A 17 year old boy is described, with arthritis in both ankles and positive rheumatoid factor tests, who presented with symptoms of shunt nephritis. Blood cultures were positive for Staphylococcus epidermidis. The patient recovered completely after removal of the shunt and antibiotic treatment. Shunt nephritis should be considered in patients with a ventriculoatrial shunt presenting with arthritis, and the arthritis may be an early indicator of an infected ventriculoatrial shunt.
Case of Amputation Performed under the Influence of Chloroform
Authors: T. B. Torr
Journal: BMJ (1848)

61 mischievous in practice.The return of the hernia does not occur in the way described, nor is it the primary object of the taxis to " get the contents of the intestine out.')Strangulated hernia is an accident involving con.siderations, not mechanical only, but anatomical, phy- siological, and pathological.First, a portion of intes- tine is forced through the ring, together with a portion of omentum or mesenterv, or both; the substance of the latter fills up the ring.Compression upon the veins is the next occurrence.The arteries, from their tone and elasticity, continue to pour blood into the
IL-13-induced cytokine release and hyperresponsiveness in precision cut lung slices of different species - Characterization of a model potentially suitable for translational research of asthma cellular events
Authors: Sharon Jimenesz, Olga Danov, Armin Braun, Olaf Pfennig, Christine Förster, Andreas Hohlbaum, Laurent Audoly, Jens Hohlfeld, Katherina Sewald
Journal: European Respiratory Journal (2013)

Rationale:  Precision cut lung slices (PCLS) display an ex vivo tissue model that maintain microanatomy and functionality of the respiratory tract. It allows the investigation of the efficacy of biopharmaceuticals in lung tissue of different species. In the present study, the effect of interleukin-13 (IL-13) on cytokine release and methacholine-induced bronchoconstriction was evaluated in rodent and human PCLS.   Methods:  PCLS were prepared from lungs of mouse, rats, and humans. The tissue was incubated with 1-100 nM IL-13. Bronchoconstriction was induced by methacholine and visualized by videomicroscopy. Cytokines were measured by ELISA.   Results:  Methacholine-induced bronchoconstriction in mouse and rat PCLS exhibited an EC50 of 80 nM and 220 nM, respectively. Pre-incubation with IL-13 decreased EC50 to 60 nM (mouse) and 160 nM (rat). Pre-incubation of rodent PCLS with IL-13 resulted in 20% stronger bronchoconstriction at maximum methacholine concentration. IL-13-induced hyperresponsiveness could so far not be demonstrated in human PCLS. Nevertheless, it was shown, that IL-13 stimulated the secretion of eotaxin-2/-3 and TARC in human PCLS - cytokines that are associated with asthma pathophysiology. The IL-13-induced cytokine release could be reduced significantly by 100 % by addition of specific inhibitors acting either on the IL-13 itself or the IL-13/IL-4 receptor complex.   Conclusions:  IL-13 induces cytokines and hyperresponsiveness in PCLS. It shows that PCLS can be used as model to study certain features of respiratory diseases.
Ribavirin: Current role in the optimal clinical management of chronic hepatitis C
Authors: K. Rajender Reddy, David R. Nelson, Stefan Zeuzem
Journal: Journal of Hepatology (2008)

Ribavirin in combination with peginterferon alfa shows strong clinical efficacy against chronic hepatitis C, and is now established as the standard of care. However, the precise role of ribavirin is still being defined, suggesting that optimal ribavirin dose should be maintained over the whole treatment period. Ribavirin dosage varies by bodyweight for genotype 1 disease (1000mg/day in patients <or =75kg and 1200mg/day in patients >75kg), whereas 800mg/day is sufficient to ensure optimal response in all genotype 2/3 patients. Similarly, genotype 1 patients benefit from 48 weeks of therapy, while 24 weeks is sufficient for genotype 2/3 disease. Recent data suggest treatment success is dependent on cumulative ribavirin exposure, as patients who receive <60% of the planned dose have lower response rates, regardless of whether reductions are from temporary interruptions or premature cessation of therapy. All patients should be monitored for hemolytic anemia, as early diagnosis allows management through small dose reductions and stepwise return to the target dose, maximizing cumulative exposure. Despite these recent advances in our knowledge, many questions remain, such as whether the role of ribavirin will change or even be eliminated as new therapies are developed.
Oxidative stress and male infertility—a clinical perspective
Authors: Kelton Tremellen
Journal: Human Reproduction Update (2008)

Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.
Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT
Authors: K. Sanpei, H. Takano, S. Igarashi, T. Sato, M. Oyake, H. Sasaki, A. Wakisaka, K. Tashiro, Y. Ishida, T. Ikeuchi, R. Koide, M. Saito, A. Sato, T. Tanaka, S. Hanyu, Y. Takiyama, M. Nishizawa, N. Shimizu, Y. Nomura, M. Segawa, K. Iwabuchi, I. Eguchi, H. Tanaka, H. Takahashi, S. Tsuji
Journal: Nature Genetics (1996)
Multiple Markers for Lung Cancer Diagnosis: Validation of Models for Localized Lung Cancer
Authors: M. H. Gail, L. Muenz, K. R. McIntire, B. Radovich, G. Braunstein, P. R. Brown, L. Deftos, A. Dnistrian, M. Dunsmore, R. Elashoff, N. Geller, V. L. W. Go, K. Hirji, M. R. Klauber, D. Pee, G. Petroni, M. Schwartz, A. R. Wolfsen
Journal: JNCI Journal of the National Cancer Institute (1988)

Sera from 171 patients with advanced lung cancer, from 110 normals, and from 123 subjects with benign respiratory diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen. Individual markers were studied, and optimal combinations of markers were sought for discriminating lung cancer patients from normals and from patients with benign lung disease. Numerous methods for combining the markers were examined, but the methods of logistic regression and recursive partitioning were finally adopted. The best discrimination rules we could find used only carcinoembryonic antigen (CEA) and total sialic acid (TSA). The performance of these rules was validated on an independent serum panel containing sera from 68 patients with advanced lung cancer, from 40 normals, and from 52 patients with benign respiratory disease. The combination rules based on TSA and CEA performed better than a rule based on CEA alone. Logistic discrimination rules with TSA and CEA that were designed to have 95% specificity achieved 54% sensitivity for discriminating advanced lung cancer from normal controls and 52% sensitivity for discriminating advanced lung cancer from controls with benign disease. Some aspects of clinical applicability are discussed, including planned studies for localized lung cancer and the requirement for further testing in specific clinical settings.
Regulation of functional cytodifferentiation and histogenesis in mammary epithelial cells: role of the extracellular matrix.
Authors: M J Bissell, T G Ram
Journal: Environmental Health Perspectives (1989)

Primary mammary epithelial cells provide a versatile system for the study of hormone and extracellular matrix (ECM) influences on tissue-specific gene expression. We have characterized the formation of alveolarlike morphogenesis and mammary-specific functional differentiation that occur when these cells are cultured on a reconstituted basement membrane (EHS). Cells cultured on EHS exhibit many ultrastructural and biochemical features indicative of polarized and functionally differentiated mammary epithelium in vivo. The increased expression and specific vectorial secretion of milk proteins into lumina formed in culture are accompanied by large increases in milk protein mRNA expression. However, when individual ECM components are tested, smaller increases in milk protein mRNA are measured on heparan sulfate proteoglycan (HSPG) and laminin, and these responses are not associated with full functional cytodifferentiation or histotypic configuration. This indicates that multiple levels of regulation are involved in mammary-specific gene expression, and that in addition to individual ligand requirements cooperative interactions between various ECM molecules and cells are necessary for functional differentiation in culture. We have also shown that endogenous production of ECM molecules and changes in cell geometry are correlated with changes in functional and histogenic gene expression. We have previously proposed a model of cell-ECM interactions that is consistent with these data.
PTU-179 Acetowhitening as a novel diagnostic tool for the diagnosis and characterisation of neoplasia within Barrett's oesophagus
Authors: G Longcroft-Wheaton, P Bhandari
Journal: Gut (2012)

<h3>Introduction</h3> The identification of Barrett9s neoplasia using acetic acid has relied upon the examination of surface patterns, which involves subjective judgement. When sprayed onto Barrett9s tissue acetic acid causes an acetowhitening reaction. We have observed that neoplastic tissue loses this whitening more quickly than non-neoplastic Barrett9s. This study aims to quantify the acetowhitening time and develop an objective tool for the diagnosis of Barrett9s neoplasia. <h3>Methods</h3> Patients referred for suspected Barrett9s neoplasia and for routine Barrett9s surveillance were assessed. A 50 ml mucolytic drink of 10% N-acetyl cysteine and 5 ml of simethicone was taken prior to the procedure. Fujinon gastroscopes with EPX 4400 processor were used. 20 ml of 2.5% acetic acid was applied to the Barrett9s mucosa via a spray catheter. Timing was recorded with a stopwatch and started after the oesophagus had been coated with acetic acid and the excess dye sucked away. Disappearance of the acetowhitening was defined as the appearance of erythema within the Barrett9s epithelium. After a maximum of 5 min the Barrett9s epithelium was washed using 20 ml of water and targeted biopsies of any neoplasia and quadrantic 2 cm biopsies of the residual Barrett9s was taken. The histology was correlated to the acetowhitening disappearance time. ROC curves were produced to identify threshold timings for optimum sensitivity and specificity for high risk neoplasia and invasive cancer within Barrett9s. <h3>Results</h3> Data from 146 areas of Barrett9s was collected from 121 patients. 84% were male. Mean age 69. 72/86 metaplasia, 6/14 LGD, 26/27 HGD, 15/15 IMC and 12/12 areas of invasive cancer were recognised correctly by the endoscopist. A ROC curve was produced for the identification of high risk neoplasia (HGD, IMC and invasive cancer) using the acetowhitening timings. The area under the curve was 0.93 (95% CI 0.89 to 0.97), with an asymptomatic significance of p=0.000. Using a threshold of 142 s a sensitivity for neoplasia of 98% (95% CI 89% to 100%) and specificity of 84% (95% CI 74% to 91%) was achieved. A further ROC curve was produced for HGD + IMC vs invasive cancer. The area under the curve was 0.786 (61 to 96). Using a cut off of 20 s, a sensitivity for invasive cancer of 67% (95% CI 35% to 90%) and specificity of 85% (95% CI 69% to 95%) could be achieved. <h3>Conclusion</h3> The acetowhitening reaction can be exploited for the diagnosis of neoplasia within Barrett9s. This provides the endoscopist with an objective and simple numerical tool for predicting whether an area is neoplastic, and to predict the presence of sub-mucosally invasive disease. This has important implications for the treatment of neoplasia within Barrett9s, and could prevent inappropriate attempts at endoscopic resection of invasive cancer. <h3>Competing interests</h3> None declared.
Visceral leishmaniasis complicating systemic lupus erythematosus
Authors: P. J. W. Wallis, C. J. M. Clark
Journal: Annals of the Rheumatic Diseases (1983)

Active systemic lupus erythematosus in a 32-year-old Chinese woman was successfully controlled by plasmapheresis and steroids. However, occult visceral leishmaniasis was uncovered during therapy and responded to appropriate treatment.
Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration
Authors: Matthias W. Lorenz, Jackie F. Price, Christine Robertson, Michiel L. Bots, Joseph F. Polak, Holger Poppert, Maryam Kavousi, Marcus Dörr, Eva Stensland, Pierre Ducimetiere, Kimmo Ronkainen, Stefan Kiechl, Matthias Sitzer, Tatjana Rundek, Lars Lind, Jing Liu, Göran Bergström, Liliana Grigore, Lena Bokemark, Alfonsa Friera, David Yanez, Horst Bickel, M. Arfan Ikram, Henry Völzke, Stein Harald Johnsen, Jean Philippe Empana, Tomi-Pekka Tuomainen, Peter Willeit, Helmuth Steinmetz, Moise Desvarieux, Wuxiang Xie, Caroline Schmidt, Giuseppe D. Norata, Carmen Suarez, Dirk Sander, Albert Hofman, Ulf Schminke, Ellisiv Mathiesen, Matthieu Plichart, Jussi Kauhanen, Johann Willeit, Ralph L. Sacco, Stela McLachlan, Dong Zhao, Björn Fagerberg, Alberico L. Catapano, Rafael Gabriel, Oscar H. Franco, Alpaslan Bülbül, Frank Scheckenbach, Anja Pflug, Lu Gao, Simon G. Thompson
Journal: Diabetes Care (2015)

OBJECTIVE Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND METHODS In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33–92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. RESULTS Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12–1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between −0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91–1.08). CONCLUSIONS Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.
Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13)
Authors: Wyman T. McGuirt, Sai D. Prasad, Andrew J. Griffith, Henricus P.M. Kunst, Glenn E. Green, Karl B. Shpargel, Christina Runge, Christy Huybrechts, Robert F. Mueller, Eric Lynch, Mary-Claire King, Han G. Brunner, Cor W.R.J. Cremers, Masamine Takanosu, Shi-Wu Li, Machiko Arita, Richard Mayne, Darwin J. Prockop, Guy Van Camp, Richard J.H. Smith
Journal: Nature Genetics (1999)
Differential Effects of Cream, Glucose, and Orange Juice on Inflammation, Endotoxin, and the Expression of Toll-Like Receptor-4 and Suppressor of Cytokine Signaling-3
Authors: Rupali Deopurkar, Husam Ghanim, Jay Friedman, Sanaa Abuaysheh, Chang Ling Sia, Priya Mohanty, Prabhakar Viswanathan, Ajay Chaudhuri, Paresh Dandona
Journal: Diabetes Care (2010)

OBJECTIVE We have recently shown that a high-fat high-carbohydrate (HFHC) meal induces an increase in plasma concentrations of endotoxin (lipopolysaccharide [LPS]) and the expression of Toll-like receptor-4 (TLR-4) and suppresser of cytokine signaling-3 (SOCS3) in mononuclear cells (MNCs) in addition to oxidative stress and cellular inflammation. Saturated fat and carbohydrates, components of the HFHC meal, known to induce oxidative stress and inflammation, also induce an increase in LPS, TLR-4, and SOCS3. RESEARCH DESIGN AND METHODS Fasting normal subjects were given 300-calorie drinks of either glucose, saturated fat as cream, orange juice, or only water to ingest. Blood samples were obtained at 0, 1, 3, and 5 h for analysis. RESULTS Indexes of inflammation including nuclear factor-κB (NF-κB) binding, and the expression of SOCS3, tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β in MNCs, increased significantly after glucose and cream intake, but TLR-4 expression and plasma LPS concentrations increased only after cream intake. The intake of orange juice or water did not induce any change in any of the indexes measured. CONCLUSIONS Although both glucose and cream induce NF-κB binding and an increase in the expression of SOCS3, TNF-α, and IL-1β in MNCs, only cream caused an increase in LPS concentration and TLR-4 expression. Equicaloric amounts of orange juice or water did not induce a change in any of these indexes. These changes are relevant to the pathogenesis of atherosclerosis and insulin resistance.