tbuckley/cabot-search huggingface dataset:
Regression of gastric T cell lymphoma with eradication of Helicobacter pylori
Authors: C Bariol
Journal: Gut (2001)

<i>Helicobacter pylori </i>is thought to be important in the pathogenesis of chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric B cell lymphoma of mucosa associated lymphoid tissue. The mechanism of evolution from chronic gastritis to monoclonal B cell proliferation is not known but is thought to be dependent on antigen specific T cells to<i>H pylori </i>and its products. Here, we report a case of gastric T cell lymphoma associated with chronic<i>H pylori </i>gastritis which regressed with eradication of the organism. This is the first report of a gastric T cell lymphoma regressing with <i>H pylori</i>eradication, and suggests a causal link between primary gastric T cell lymphoma and this organism.
HIF-1 reduces ischaemia–reperfusion injury in the heart by targeting the mitochondrial permeability transition pore
Authors: Sang-Ging Ong, Won Hee Lee, Louise Theodorou, Kazuki Kodo, Shiang Y. Lim, Deepa H. Shukla, Thomas Briston, Serafim Kiriakidis, Margaret Ashcroft, Sean M. Davidson, Patrick H. Maxwell, Derek M. Yellon, Derek J. Hausenloy
Journal: Cardiovascular Research (2014)

Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tolerance against acute myocardial ischaemia–reperfusion injury (IRI). However, the mechanism through which HIF-1 stabilization actually confers this cardioprotection is not clear. We investigated whether HIF-1α stabilization protects the heart against acute IRI by preventing the opening of the mitochondrial permeability transition pore (MPTP) and the potential mechanisms involved. Stabilization of myocardial HIF-1 was achieved by pharmacological inhibition of prolyl hydroxylase (PHD) domain-containing enzyme using GSK360A or using cardiac-specific ablation of von Hippel–Lindau protein (VHLfl/fl) in mice. Treatment of HL-1 cardiac cells with GSK360A stabilized HIF-1, increased the expression of HIF-1 target genes pyruvate dehydrogenase kinase-1 (PDK1) and hexokinase II (HKII), and reprogrammed cell metabolism to aerobic glycolysis, thereby resulting in the production of less mitochondrial oxidative stress during IRI, and less MPTP opening, effects which were shown to be dependent on HKII. These findings were further confirmed when HIF-1 stabilization in the rat and murine heart resulted in smaller myocardial infarct sizes (both invivo and ex vivo), decreased mitochondrial oxidative stress, and inhibited MPTP opening following IRI, effects which were also found to be dependent on HKII. We have demonstrated that acute HIF-1α stabilization using either a pharmacological or genetic approach protected the heart against acute IRI by promoting aerobic glycolysis, decreasing mitochondrial oxidative stress, activating HKII, and inhibiting MPTP opening.
MG53 participates in ischaemic postconditioning through the RISK signalling pathway
Authors: Yan Zhang, Fengxiang Lv, Li Jin, Wei Peng, Ruisheng Song, Jianjie Ma, Chun-Mei Cao, Rui-Ping Xiao
Journal: Cardiovascular Research (2011)

AimsRecent studies show that ischaemic postconditioning (PostC), similar to the well-established ischaemic preconditioning (IPC), confers cardioprotection against ischaemia/reperfusion (IR) injury, and both IPC and PostC can activate the reperfusion injury salvage kinase (RISK) pathway and the survivor activating factor enhancement (SAFE) pathway. PostC is clinically more attractive because of its therapeutic application at the predictable onset of reperfusion. Our previous studies have demonstrated that MG53 is a primary component of the IPC machinery. Here, we investigated the potential role of MG53 in PostC-mediated myocardial protection and explored the underlying mechanism.
Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies
Authors: Jacoba P Greving, Marieke J H Wermer, Robert D Brown, Akio Morita, Seppo Juvela, Masahiro Yonekura, Toshihiro Ishibashi, James C Torner, Takeo Nakayama, Gabriël J E Rinkel, Ale Algra
Journal: The Lancet Neurology (2013)
Bimodality surveillance of high-risk patients for lung cancer
Authors: G. H Downie
Journal: Thorax (2007)

Are new diagnostic strategies providing answers?

Thoracic oncology providers confronted with the task of diagnosing and following patients at risk for cancer of the lung face a number of major dilemmas, some of which directly affect the ability to diagnose. First, the majority of patients with lung cancer are diagnosed at a late stage and <15% survive 5 years, so a degree of nihilism is present in patients, providers and policy makers. Second, risk paradigms are changing, from smoking only to occupational, environmental or home carcinogens to the risk associated with premalignant airway changes. Third, advances in early diagnostic options have the potential to discover lung carcinoma while still in a pre-invasive, minimally invasive stage or as small peripheral nodules. These points, taken in conjunction with the initial clinical results of the ELCAP study suggesting that cure is possible,1 raise the need to examine early diagnostic strategies critically.

In this issue of Thorax ( see page 335 ) Loewen et al report their initial clinical findings in bimodality surveillance of high risk for lung cancer populations using low dose spiral CT scanning (SCT) and autofluorescence bronchoscopy (AFB).2 They examined two null hypotheses: (1) AFB was equivalent to conventional sputum cytology (CSC) for the detection of pre-malignant lesions and (2) AFB and SCT would be equivalent to SCT alone for the detection of lung cancer in high-risk patients. The authors conclude that AFB is significantly superior to CSC for the detection of airway pre-malignancy in this cohort of high-risk patients and, in fact, argue that, as a surveillance tool, AFB exceeds the cancer detection rate of colonoscopy in patients with positive fecal occult blood. However, the authors were not able to demonstrate a significant superiority of bimodality surveillance with both AFB and SCT over SCT alone, but question whether a larger …
Molecular Pathways: Targeting MALT1 Paracaspase Activity in Lymphoma
Authors: Lorena Fontán, Ari Melnick
Journal: Clinical Cancer Research (2013)

Abstract MALT1 mediates the activation of NF-κB in response to antigen receptor signaling. MALT1, in association with BCL10 and CARD11, functions as a scaffolding protein to activate the inhibitor of IκB kinase (IKK) complex. In addition, MALT1 is a paracaspase that targets key proteins in a feedback loop mediating termination of the NF-κB response, thus promoting activation of NF-κB signaling. Activated B-cell subtype of diffuse large B-cell lymphomas (ABC-DLBCL), which tend to be more resistant to chemotherapy, are often biologically dependent on MALT1 activity. Newly developed MALT1 small-molecule inhibitors suppress the growth of ABC-DLBCLs in vitro and in vivo. This review highlights the recent advances in the normal and disease-related functions of MALT1. Furthermore, recent progress targeting MALT1 proteolytic activity raises the possibility of deploying MALT1 inhibitors for the treatment of B-cell lymphomas and perhaps autoimmune diseases that involve increased B- or T-cell receptor signaling. Clin Cancer Res; 19(24); 6662–8. ©2013 AACR.
Mental health research priorities for Europe
Authors: Til Wykes, Josep Maria Haro, Stefano R Belli, Carla Obradors-Tarragó, Celso Arango, José Luis Ayuso-Mateos, István Bitter, Matthias Brunn, Karine Chevreul, Jacques Demotes-Mainard, Iman Elfeddali, Sara Evans-Lacko, Andrea Fiorillo, Anna K Forsman, Jean-Baptiste Hazo, Rebecca Kuepper, Susanne Knappe, Marion Leboyer, Shôn W Lewis, Donald Linszen, Mario Luciano, Mario Maj, David McDaid, Marta Miret, Szilvia Papp, A-La Park, Gunter Schumann, Graham Thornicroft, Christina van der Feltz-Cornelis, Jim van Os, Kristian Wahlbeck, Tom Walker-Tilley, Hans-Ulrich Wittchen
Journal: The Lancet Psychiatry (2015)
Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor
Authors: Yasuyuki Kihara, Satoshi Ishii, Yoshihiro Kita, Akiko Toda, Atsuyoshi Shimada, Takao Shimizu
Journal: The Journal of Experimental Medicine (2005)

Experimental allergic encephalomyelitis (EAE) serves as a model for multiple sclerosis and is considered to be a CD4+ Th1 cell–mediated autoimmune disease. To investigate the role of platelet-activating factor (PAF) in this disease, PAF receptor (PAFR) KO (PAFR-KO) and wild-type (WT) mice, on a C57BL/6 genetic background, were immunized with myelin oligodendrocyte glycoprotein 35–55. The levels of PAF production and PAFR mRNA expression in the spinal cord (SC) correlated with the EAE symptoms. PAFR-KO mice showed lower incidence and less severe symptoms in the chronic phase of EAE than WT mice. However, no difference was observed in T cell proliferation, Th1-cytokine production, or titer of IgG2a between both genotypes. Before onset, as revealed by microarray analysis, mRNAs of inflammatory mediators and their receptors—including IL-6 and CC chemokine receptor 2—were down-regulated in the SC of PAFR-KO mice compared with WT mice. Moreover, in the chronic phase, the severity of inflammation and demyelination in the SC was substantially reduced in PAFR-KO mice. PAFR-KO macrophages reduced phagocytic activity and subsequent production of TNF-α. These results suggest that PAF plays a dual role in EAE pathology in the induction and chronic phases through the T cell–independent pathways.
N-Acetylcysteine for the Prevention of Radiocontrast Induced Nephropathy
Authors: Abhijit V. Kshirsagar, Charles Poole, Amy Mottl, David Shoham, Nora Franceschini, Gail Tudor, Malay Agrawal, Cindy Denu-Ciocca, E. Magnus Ohman, William F. Finn
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. N-acetylcysteine has been recommended for patients with renal insufficiency who are to receive radiocontrast media. However, trials of oral N-acetylcysteine for the prevention of radiocontrast-induced nephropathy have yielded inconsistent results. A systematic review of patient and study characteristics was undertaken to discover possible explanations of the inconsistencies. The databases MEDLINE, EMBASE, and CENTRAL (1966 to March 2003) were searched in all languages, and conference proceedings from several professional societies from the years 1999 to 2003 were also searched. Only prospective controlled trials of oral N-acetylcysteine were included. Risk difference estimates and 95% confidence intervals were calculated. The estimates were examined for evidence of publication bias and heterogeneity. Stratified and meta-regression analyses were used to compare estimates by study and patient characteristics. Identified were 16 studies, 15 published and 1 unpublished. There was no evidence of publication bias, but there was substantial evidence of heterogeneity, thus precluding reliance on a meaningful summary effect estimate. Meta-regression identified several patient and study characteristics, with some evidence of association with study-specific estimates. None of these characteristics, however, formed subsets of studies with results that were homogeneous enough to aggregate. Research on N-acetylcysteine and the incidence of radiocontrast nephropathy is too inconsistent at present to warrant a conclusion on efficacy or a recommendation for its routine use. Identified patient and study characteristics may be responsible for some, but not all, of this inconsistency. A large, randomized, placebo-controlled trial, a pooled analysis of patient-level data, or both may resolve this issue.
Xanthine derivatives inhibit the increase in intracellular Ca2+ concentration induced by acetylcholine in nasal gland acinar cells of the guinea-pig
Authors: K Ishitani, K Ikeda, H Sunose, D Wu, H Honda, T Takasaka
Journal: European Respiratory Journal (1995)

Intracellular calcium is considered to play a major role in secretory responses of various exocrine cell types. We examined whether xanthine derivatives can inhibit Ca2+ mobilization and entry in secretory cells in the airways. Therefore, the inhibitory effect of xanthines in the intracellular Ca2+ concentration ([Ca2+]i) in the isolated submucosal acinar cells of the guinea-pig nasal septum was investigated by means of fluorescence ratio microscopy. The inhibitory effects on Ca2+ release from stores was examined in Ca(2+)-free conditions. Effects on Ca2+ entry were estimated by two different protocols; 1) the sustained phase in a long-term application of acetylcholine (ACh) and 2) the [Ca2+]i overshoot following removal of ACh in Ca(2+)-free conditions. Xanthine derivatives, 3-isobutyl-1-methyl-xanthine (IBMX), caffeine, and theophylline, significantly inhibited the increase in [Ca2+]i evoked by ACh; both mobilization from internal Ca2+ stores and Ca2+ entry from the external space. The rank order of potency of these xanthine derivatives was IBMX &gt; theophylline &gt; caffeine. The addition of dibutyryl-cyclic adenosine monophosphate (cAMP) and forskolin to nasal gland acinar cells failed to inhibit the ACh-evoked increase in [Ca2+]i. Furthermore, a protein kinase A inhibitor, H-89, did not affect the inhibitory effect of the xanthine derivatives. The action of xanthines on the present acinar cells did not involve Ca(2+)-induced Ca2+ release (CICR) or an interaction with purinergic receptors. Thus, xanthines have a direct inhibitory effect both on Ca2+ release and entry in nasal gland acinar cells, and might thereby have antisecretory activity within the airways.
Circulating Levels of TNF Receptor II Are Prognostic for Patients with Peripheral T-cell Non–Hodgkin Lymphoma
Authors: Christina Heemann, Markus Kreuz, Irene Stoller, Nils Schoof, Frederike von Bonin, Marita Ziepert, Markus Löffler, Wolfram Jung, Michael Pfreundschuh, Lorenz Trümper, Dieter Kube
Journal: Clinical Cancer Research (2012)

Peripheral T-cell non-Hodgkin lymphomas (T-NHL) represent a small but heterogeneous and clinically aggressive subset of NHLs with a poor outcome. Cytokines or their receptors might be associated with the clinical outcome of these lymphomas. Therefore, we tested whether gene variations and serum levels of soluble TNF receptor (TNFR)I (sTNFRI), sTNFRII, interleukin (IL)-10, or sIL-4R are predictive for treatment response in T-NHLs.Peripheral blood DNA from 117 patients with T-NHL treated in prospective clinical trials was subjected to genotyping analysis. Whenever possible, pretreatment sera were obtained, and circulating levels of sTNFRI, sTNFRII, IL-10, and sIL-4R were determined with a specific capture enzyme-linked immunoassay.Patients characterized by TNFRI-609GG (rs4149570) showed a trend toward better event free survival [EFS; univariate: P = 0.041; multivariate: HR, 1.76; confidence interval (CI), 0.99-3.14 with P = 0.056]. A protective role of IL-10-1087A, -824T, and -597A reported in another study was not confirmed in our cohort. Patients with circulating levels of soluble TNFRII ≥2.16 ng/mL had a 2.07-fold increased relative risk for shorter overall survival (OS; univariate: P = 0.0034; multivariate: HR, 2.07; CI, 0.92-4.70 with P = 0.081) and a 2.49-fold higher risk for shorter EFS (univariate: P = 0.00068; multivariate: HR, 2.49; CI, 1.22-5.08 with P = 0.012). Elevations of circulating levels of sTNFRI, IL-10, and sIL-4R are frequent, but the clinical response in these patients is not significantly different.Our findings suggest a critical role for TNF-TNFR signaling for the clinical outcome of patients with peripheral T-NHLs.
Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment
Authors: L C Coates, J Fransen, P S Helliwell
Journal: Annals of the Rheumatic Diseases (2009)

To create minimal disease activity (MDA) criteria for psoriatic arthritis (PsA). With recent therapeutic advances, this is now a goal for treatment and may represent a measure to compare therapies. It defines a satisfactory state of disease activity rather than a change, and encompasses all aspects of the disease.40 patient profiles were sampled from an observational PsA database. Sixty experts in PsA classified these as in MDA or not. A consensus of > or =70% was accepted, identifying 13 profiles in MDA. Summary statistics created possible cut-off points for the definition. Considering the number of measures that must be met, 35 candidate definitions were created and tested using receiver operating characteristic curves (ROC) for sensitivity and specificity.Four candidate definitions showed high area under the curve values on ROC testing. Definitions with high outlying values were excluded as they were not considered to represent MDA. Aiming for high specificity to reduce false positives resulted in a preference for the following definition: "A patient is classified as achieving MDA when meeting 5 of the 7 following criteria: tender joint count < or =1; swollen joint count < or =1; Psoriasis Activity and Severity Index < or =1 or body surface area < or =3; patient pain visual analogue score (VAS) < or =15; patient global disease activity VAS < or =20; health assessment questionnaire < or =0.5; tender entheseal points < or =1".This study provides the first definition of a "state" of MDA in PsA and defines a target for treatment. It must now be validated in other populations and tested in clinical trials.
Predicting Costs of Stem-Cell Transplantation
Authors: Stephanie J. Lee, Neil Klar, Jane C. Weeks, Joseph H. Antin
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Few studies have formally evaluated the relationship between costs, baseline patient characteristics, and major complications of stem-cell transplantation. We sought (1) to determine whether obtaining baseline information enabled identification of patients whose treatments would be the most costly and (2) to estimate inpatient costs for managing specific transplantation complications. PATIENTS AND METHODS: We collected inpatient costs and clinical information for 236 consecutive patients undergoing transplantation at a single institution between July 1, 1994, and February 20, 1997. Multivariable linear regression was used to evaluate the associations between baseline patient characteristics and costs of hospitalization for initial transplantation and between clinical events and such costs. RESULTS: The median initial inpatient cost in 1997 dollars was $55,500 for autologous transplantation (range, $28,200 to $148,200) and $105,300 for allogeneic transplantation (range, $32,500 to $338,000). When only baseline variables were considered, use of a mismatched allogeneic donor and year of transplantation were significant predictors of costs. No characteristics predicted which patients would incur the highest 10% of costs. When clinical events were considered, infection and in-hospital death were associated with higher costs in autologous transplant recipients ($18,400 and $20,500, respectively), whereas infection, veno-occlusive disease, acute graft-versus-host disease, and death were predicted to add between $15,300 and $28,100 each to allogeneic transplantation costs. CONCLUSION: We were not able to identify before transplantation the patients whose treatments would be the most costly. However, the association between clinical complications and higher costs suggests that prevention may have significant economic benefits. Interventions that decrease these complications may have favorable cost-benefit ratios even if they do not affect overall survival.
Gain of GRHL2 is associated with early recurrence of hepatocellular carcinoma
Authors: Yasuo Tanaka, Fumihiko Kanai, Motohisa Tada, Ryosuke Tateishi, Masashi Sanada, Yasuhito Nannya, Miki Ohta, Yoshinari Asaoka, Motoko Seto, Shuichiro Shiina, Haruhiko Yoshida, Takao Kawabe, Osamu Yokosuka, Seishi Ogawa, Masao Omata
Journal: Journal of Hepatology (2008)
283 TRACING THE DYNAMICS OF T-CELL SUBSETS IN DIFFERENT PHASES OF HBEAG NEGATIVE CHRONIC HBV INFECTION
Authors: S. Ghosh, K. Das, M. Nandi, D. Mukhopadhyay, P. Banerjee, R.K. Mondai, P. Pandit, A. Santra, S. Banerjee, M. Chatterjee, A. Chowdhury, S. Datta
Journal: Journal of Hepatology (2011)
Ancient Structure in Africa Unlikely to Explain Neanderthal and Non-African Genetic Similarity
Authors: M. A. Yang, A.-S. Malaspinas, E. Y. Durand, M. Slatkin
Journal: Molecular Biology and Evolution (2012)

Neanderthals have been shown to share more genetic variants with present-day non-Africans than Africans. Recent admixture between Neanderthals and modern humans outside of Africa was proposed as the most parsimonious explanation for this observation. However, the hypothesis of ancient population structure within Africa could not be ruled out as an alternative explanation. We use simulations to test whether the site frequency spectrum, conditioned on a derived Neanderthal and an ancestral Yoruba (African) nucleotide (the doubly conditioned site frequency spectrum [dcfs]), can distinguish between models that assume recent admixture or ancient population structure. We compare the simulations to the dcfs calculated from data taken from populations of European, Chinese, and Japanese descent in the Complete Genomics Diversity Panel. Simulations under a variety of plausible demographic parameters were used to examine the shape of the dcfs for both models. The observed shape of the dcfs cannot be explained by any set of parameter values used in the simulations of the ancient structure model. The dcfs simulations for the recent admixture model provide a good fit to the observed dcfs for non-Africans, thereby supporting the hypothesis that recent admixture with Neanderthals accounts for the greater similarity of Neanderthals to non-Africans than Africans.
Growth Hormone Therapy for Adults: Not Ready for Prime Time?
Authors: William L. Isley
Journal: Annals of Internal Medicine (2002)

Human growth hormone is now readily available and approved for treatment of the growth hormone deficiency syndrome in adults. However, physicians have been slow to adopt this therapeutic modality. Reasons for skepticism about the use of growth hormone for the growth hormone deficiency syndrome include doubts about whether growth hormone deficiency causes increased morbidity and mortality in patients with hypopituitarism; availability of highly efficacious, easier to use, and less expensive agents for certain aspects of the growth hormone deficiency syndrome, especially cardiovascular disease; and concerns about possible toxicity in adults. Long-term studies in patients receiving appropriate comprehensive management for other hormonal deficiencies and for concomitant abnormalities will be required to convince physicians of the utility and safety of growth hormone replacement therapy.