tbuckley/cabot-search huggingface dataset:
Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients
Authors: Christiane Drechsler, Andreas Meinitzer, Stefan Pilz, Vera Krane, Andreas Tomaschitz, Eberhard Ritz, Winfried März, Christoph Wanner
Journal: European Journal of Heart Failure (2011)

Sudden cardiac death (SCD) is a major contributor to the excess mortality of patients on maintenance dialysis. Homoarginine deficiency may lead to decreased nitric oxide availability and endothelial dysfunction. Based on this rationale we assessed whether homoarginine deficiency is a risk factor for SCD in dialysis patients.This study examined the association of homoarginine with cardiovascular outcomes in 1255 diabetic haemodialysis patients from the German diabetes and dialysis study. During a median of 4 years of follow-up, hazard ratios (HR) (95% CI) for reaching the following pre-specified, adjudicated endpoints were determined: SCD, myocardial infarction, stroke, death due to heart failure, and combined cardiovascular events. There was a strong association of low homoarginine concentrations with the presence of congestive heart failure and left ventricular hypertrophy as well as increased levels of brain natriuretic peptide. Per unit decrease in homoarginine, the risk of SCD increased three-fold (HR 3.1, 95% CI 2.0-4.9), attenuating slightly in multivariate models (HR 2.4; 95% CI 1.5-3.9). Patients in the lowest homoarginine quintile experienced a more than two-fold increased risk of SCD, and more than three-fold increased risk of heart failure death than patients in the highest quintile, which accounted for the high incidence of combined cardiovascular events. Low homoarginine showed a trend towards increased risk of stroke, however, myocardial infarction was not meaningfully affected.Low homoarginine is a strong risk factor for SCD and death due to heart failure in haemodialysis patients. Further studies are needed to elucidate the underlying mechanisms, offering the potential to develop new interventional strategies.
De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome
Authors: Matthew N Bainbridge, Hao Hu, Donna M Muzny, Luciana Musante, James R Lupski, Brett H Graham, Wei Chen, Karen W Gripp, Kim Jenny, Thomas F Wienker, Yaping Yang, V Reid Sutton, Richard A Gibbs, H Hilger Ropers
Journal: Genome Medicine (2013)

Molecular diagnostics can resolve locus heterogeneity underlying clinical phenotypes that may otherwise be co-assigned as a specific syndrome based on shared clinical features, and can associate phenotypically diverse diseases to a single locus through allelic affinity. Here we describe an apparently novel syndrome, likely caused by de novo truncating mutations in ASXL3, which shares characteristics with Bohring-Opitz syndrome, a disease associated with de novo truncating mutations in ASXL1.We used whole-genome and whole-exome sequencing to interrogate the genomes of four subjects with an undiagnosed syndrome.Using genome-wide sequencing, we identified heterozygous, de novo truncating mutations in ASXL3, a transcriptional repressor related to ASXL1, in four unrelated probands. We found that these probands shared similar phenotypes, including severe feeding difficulties, failure to thrive, and neurologic abnormalities with significant developmental delay. Further, they showed less phenotypic overlap with patients who had de novo truncating mutations in ASXL1.We have identified truncating mutations in ASXL3 as the likely cause of a novel syndrome with phenotypic overlap with Bohring-Opitz syndrome.
Transbronchial decompression of emphysematous bullae: a new therapeutic approach
Authors: P. Bhattacharyya, D. Sarkar, S. Nag, S. Ghosh, S. Roychoudhury
Journal: European Respiratory Journal (2007)

Bullae are common accompaniments of chronic obstructive pulmonary disease especially emphysema. They contribute to increased lung volume and worsen the mechanical disadvantage of the inspiratory muscles by increasing the residual volume (RV) and RV/total lung capacity ratio. Thus effective decompression of a large bulla or bullae is thus important to improve the lung function of affected patients and also to provide symptomatic relief. Surgery and thoracoscopy are two commonly performed procedures used to treat bullae. Although bronchoscopic lung volume reduction has been successfully accomplished for emphysema, isolated decompression of bullae bronchoscopically has not been tried to date. A large emphysematous bulla in the left lower lobe of a surgically unfit patient was bronchoscopically punctured with a transbronchial aspiration needle; the position of the needle inside the bulla was confirmed and the air from the bulla was aspirated slowly to allow collapse. Finally, some autologous blood was instilled into the bulla before the needle was withdrawn. The patient had immediate and sustained symptomatic relief with significant improvement in lung function. Bronchoscopic transbronchial decompression of emphysematous bullae can be an effective therapeutic option and warrants further investigation.
Melanoma-Associated Antigens in Esophageal Adenocarcinoma
Authors: Jules Lin, Lin Lin, Dafydd G. Thomas, Joel K. Greenson, Thomas J. Giordano, Gregory S. Robinson, Ruteja A. Barve, Frank A. Weishaar, Jeremy M. G. Taylor, Mark B. Orringer, David G. Beer
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The melanoma-associated antigens (MAGEs) are tumor-specific antigens recognized by cytotoxic T lymphocytes. In this study, expression of MAGE family A members was evaluated during the development of esophageal adenocarcinoma (EA) as potential targets for immunotherapy. Experimental Design: MAGE-A mRNA expression was evaluated in 46 samples including Barrett’s metaplasia (BM), dysplasia, and EA using oligonucleotide microarrays. Expression of MAGE-A proteins was confirmed by immunohistochemistry on tissue microarrays containing 59 EA, 11 dysplasia, and 9 BM samples and by Western blot. To further evaluate MAGE-A10 expression, reverse transcription-polymerase chain reaction (RT-PCR) products were sequenced, and protein expression was determined using a specific antibody. Results: Overexpression of MAGE-A1, MAGE-A2b, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A9, MAGE-A10, and MAGE-A12 was found in EAs relative to BM on oligonucleotide microarrays. MAGE-A3 overexpression was confirmed by real-time RT-PCR in 21.4% (6 of 28) of esophageal tumors. Immunohistochemistry on tissue microarray revealed MAGE-A proteins in 20.3% (12 of 59) of EAs and MAGE-A10 staining in 16.9% (10 of 59) of EAs. MAGE-A expression was confirmed by Western blot in several esophageal tumors and in two EA cell lines, Flo-1 and Seg-1, whereas Flo-1 also expressed MAGE-A10. Tumors produced from these cell lines in nude mice retained MAGE-A expression. Interestingly, RT-PCR in primary tumors expressing MAGE-A10 protein revealed additional PCR products that were identified as novel MAGE-A10 alternative splice variants using DNA sequencing. Conclusions: This is the first report of these MAGE-A10 alternative splice sequences, and characterization of MAGE-A expression may provide potential targets for immunotherapy in patients with EA.
Canonical Wnt Signaling Negatively Modulates Regulatory T Cell Function
Authors: Jorg van Loosdregt, Veerle Fleskens, Machteld M. Tiemessen, Michal Mokry, Ruben van Boxtel, Jenny Meerding, Cornelieke E.G.M. Pals, Dorota Kurek, Miranda R.M. Baert, Eveline M. Delemarre, Andrea Gröne, Marianne J.A. Groot Koerkamp, Alice J.A.M. Sijts, Edward E.S. Nieuwenhuis, Madelon M. Maurice, Johan H. van Es, Derk ten Berge, Frank C. Holstege, Frank J.T. Staal, Dietmar M.W. Zaiss, Berent J. Prakken, Paul J. Coffer
Journal: Immunity (2013)
T-cellular immune reactions (in macrophage inhibition factor assay) against Mycobacterium paratuberculosis, Mycobacterium kansasii, Mycobacterium tuberculosis, Mycobacterium avium in patients with chronic inflammatory bowel disease.
Authors: C A Seldenrijk, H A Drexhage, S G Meuwissen, C J Meijer
Journal: Gut (1990)

A mycobacterial aetiology has been suggested for Crohn9s disease. A slow growing mycobacterium, biochemically and genetically identical to M paratuberculosis, the causative agent of enteritis in ruminants (Johne9s disease), has been isolated from gut specimens of patients affected by Crohn9s disease. If M paratuberculosis or other mycobacteria play a role in the pathogenesis of Crohn9s disease, then patients may have been sensitised to these mycobacteria or show an anergy immune reaction. We therefore investigated the T-cell mediated immune response to sonicates of M paratuberculosis, M kansasii, M avium, and M tuberculosis in 35 patients with Crohn9s disease, 28 with ulcerative colitis, and 25 controls using a macrophage inhibition factor assay on peripheral blood lymphocytes. Two types of reaction patterns were identified--that is, 9responders9 (subjects with a macrophage inhibition factor assay in which a dose response relation was present and a percentage of inhibition exceeding 20%), and 9non-responders9. There was no significant difference in the prevalence of responders (59%-80%) and non-responders (20%-41%) to these mycobacteria between the group of Crohn9s disease, ulcerative colitis, and control group. We found also that a large proportion of controls showed T-cell immunisation to the mycobacteria which supports the contention that the antigens are practically commensal. Our results do not support the proposed involvement of mycobacteria in the pathogenesis of Crohn9s disease.
Model-Based Noninvasive Estimation of Intracranial Pressure from Cerebral Blood Flow Velocity and Arterial Pressure
Authors: Faisal M. Kashif, George C. Verghese, Vera Novak, Marek Czosnyka, Thomas Heldt
Journal: Science Translational Medicine (2012)

A model-based, patient-specific, and calibration-free approach is used for continuous, noninvasive estimation of intracranial pressure.
Polymorphisms in Genes Related to Oxidative Stress (<i>CAT, MnSOD, MPO</i>, and<i>eNOS</i>) and Acute Toxicities from Radiation Therapy following Lumpectomy for Breast Cancer
Authors: Jiyoung Ahn, Christine B. Ambrosone, Peter A. Kanetsky, Chunqiao Tian, Teresa A. Lehman, Silke Kropp, Irmgard Helmbold, Dietrich von Fournier, Wulf Haase, Marie Luise Sautter-Bihl, Frederik Wenz, Jenny Chang-Claude
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Because radiotherapy exerts cytotoxic effects via generation of massive oxidative stress, we hypothesized that catalase, manganese superoxide dismutase, myeloperoxidase (MPO), and endothelial nitric oxide synthase (eNOS) genotypes might result in greater risk of radiotoxicity. Experimental Design: Cases (n = 446) were Caucasian women with breast cancer who received radiotherapy following lumpectomy. Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight. The development of acute reactions (moist desquamation) associated with genotypes was modeled using the Cox proportional hazards model, accounting for cumulative biologically effective radiation dose. Results: Genotypes associated with higher levels of reactive oxygen species (ROS) were not associated with risk of radiotoxicity. However, relationships between overweight/obesity [body mass index (BMI), &amp;gt;25] and radiotoxicity risk seemed to be modified by eNOS and MPO genotypes associated with higher generation of nitric oxide and ROS, respectively. Women with high BMI (&amp;gt;25) and eNOS GG genotypes were at more than a 6-fold increase in risk (hazard ratio, 6.39; 95% confidence interval, 2.53-16.15) compared with those with BMI &amp;lt;25, and for MPO, those with high BMI (&amp;gt;25) and GG genotypes also had greater risk of radiotoxicity (hazard ratio, 3.61; 95% confidence interval, 1.78-7.35) compared with those with BMI &amp;lt;25. Overweight/obesity was not a strong risk factor among women with other eNOS and MPO genotypes. Exploratory analysis using classification and regression trees indicated that total number of risk alleles contributed, in part, to acute toxicity outcomes among a subgroup of women. Conclusions: Associations between BMI and radiotoxicity risk may be most apparent among women with genotypes related to higher levels of oxidative stress. Regression trees may be useful in future studies to examine the contributions of multiple factors to individual susceptibility to adverse effects of cancer treatment.
Stromelysin-1 (Matrix Metalloproteinase-3) and Tissue Inhibitor of Metalloproteinase-3 Are Overexpressed in the Wall of Abdominal Aortic Aneurysms
Authors: Tom W.G. Carrell, Kevin G. Burnand, Graham M.A. Wells, John M. Clements, Alberto Smith
Journal: Circulation (2002)

Background — Atherosclerosis is implicated in the pathogenesis of abdominal aortic aneurysm (AAA) but more often causes aortic occlusive disease (AOD). The matrix metalloproteinases (MMPs) degrade extracellular matrix and may play a central role in the pathogenesis of AAA. The aim of this study was to examine differences in the patterns of MMP and MMP inhibitor expression between AAA and AOD. Methods and Results — The expression of mRNA for 14 MMPs and 4 tissue inhibitors of metalloproteinases (TIMPs) was estimated in samples of aortic wall from 8 patients with AAA and 8 with AOD using the reverse-transcriptase polymerase chain reaction with a synthetic multicompetitor standard. AAA wall expressed significantly more stromelysin-1 (MMP-3) (mean log 10 ratio [copy enzyme cDNA/copy GAPDH cDNA], −1.9; range, −3.3 to −0.7) than the AOD wall (mean, 4; range, −5.7 to −2.4), P &lt;0.005. TIMP-3 expression was significantly higher in AAA (mean, −1.7; range, −2.9 to −1.0) than AOD (mean, −3.6; range, −5.7 to −1.8), P &lt;0.01. Expression of 8 other MMPs (1, 2, 7, 9, 11, 12, 14, and 17) was detected and was similar in AAA and AOD. Expression of the remaining 5 MMPs (−8, −10, −13, −15, and −16) was not detected in any of the samples. Conclusions — Both AAA and AOD walls express similar levels of a wide range of MMPs, including cell membrane–bound MT-MMPs. Stromelysin-1 (MMP-3) and TIMP-3 were, however, over expressed in the AAA samples and may be involved aneurysm pathogenesis. Stromelysin-1 could provide a target for pharmacological inhibition.
Interleukin (IL)-4 inhibits IL-10 to promote IL-12 production by dendritic cells
Authors: Yongxue Yao, Wei Li, Mark H. Kaplan, Cheong-Hee Chang
Journal: The Journal of Experimental Medicine (2005)

Interleukin (IL)-4 is known to be the most potent cytokine that can initiate Th2 cell differentiation. Paradoxically, IL-4 instructs dendritic cells (DCs) to promote Th1 cell differentiation. We investigated the mechanisms by which IL-4 directs CD4 T cells toward the Th1 cell lineage. Our study demonstrates that the IL-4–mediated induction of Th1 cell differentiation requires IL-10 production by DCs. IL-4 treatment of DCs in the presence of lipopolysaccharide or CpG resulted in decreased production of IL-10, which was accompanied by enhanced IL-12 production. In IL-10–deficient DCs, the level of IL-12 was greatly elevated and, more importantly, the ability of IL-4 to up-regulate IL-12 was abrogated. Interestingly, IL-4 inhibited IL-10 production by DCs but not by B cells. The down-regulation of IL-10 gene expression by IL-4 depended on Stat6 and was at least partly caused by decreased histone acetylation of the IL-10 promoter. These data indicate that IL-4 plays a key role in inducing Th1 cell differentiation by instructing DCs to produce less IL-10.
Development of Chronic Inflammatory Arthropathy Resembling Rheumatoid Arthritis in Interleukin 1 Receptor Antagonist–Deficient Mice
Authors: Reiko Horai, Shinobu Saijo, Hidetoshi Tanioka, Susumu Nakae, Katsuko Sudo, Akihiko Okahara, Toshimi Ikuse, Masahide Asano, Yoichiro Iwakura
Journal: The Journal of Experimental Medicine (2000)

Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation, host defense, and the neuro-immuno-endocrine network. IL-1 receptor antagonist (ra) is an endogenous inhibitor of IL-1 and is supposed to regulate IL-1 activity. However, its pathophysiological roles in a body remain largely unknown. To elucidate the roles of IL-1ra, IL-1ra–deficient mice were produced by gene targeting, and pathology was analyzed on different genetic backgrounds. We found that all of the mice on a BALB/cA background, but not those on a C57BL/6J background, spontaneously developed chronic inflammatory polyarthropathy. Histopathology showed marked synovial and periarticular inflammation, with articular erosion caused by invasion of granulation tissues closely resembling that of rheumatoid arthritis in humans. Moreover, elevated levels of antibodies against immunoglobulins, type II collagen, and double-stranded DNA were detected in these mice, suggesting development of autoimmunity. Proinflammatory cytokines such as IL-1β, IL-6, and tumor necrosis factor α were overexpressed in the joints, indicating regulatory roles of IL-1ra in the cytokine network. We thus show that IL-1ra gene deficiency causes autoimmunity and joint-specific inflammation and suggest that IL-1ra is important in maintaining homeostasis of the immune system. Possible involvement of IL-1ra gene deficiency in RA will be discussed.
Urinary Angiotensinogen as a Marker of Intrarenal Angiotensin II Activity Associated with Deterioration of Renal Function in Patients with Chronic Kidney Disease
Authors: Tatsuo Yamamoto, Tsutomu Nakagawa, Hiroyuki Suzuki, Naro Ohashi, Hirotaka Fukasawa, Yoshihide Fujigaki, Akihiko Kato, Yukio Nakamura, Fumiaki Suzuki, Akira Hishida
Journal: Journal of the American Society of Nephrology (2007)

In chronic kidney disease (CKD), enhanced intrarenal angiotensin II (AngII) is involved in deterioration of renal function, but it is difficult to measure it. For assessment of the potential of urinary angiotensinogen as a marker of intrarenal AngII activity, the correlation of plasma and urinary renin-angiotensin system components, including angiotensinogen, with deterioration of renal function was investigated in 80 patients who had CKD and were not treated with AngII blocking agents. Changes that were induced by 14 d of losartan treatment (25 mg/d) were also measured in 28 patients. Angiotensinogen was measured by RIA of AngI after incubation with renin. Urinary angiotensinogen levels were greater in patients with low estimated GFR and elevated urinary protein and type IV collagen and correlated with renal AngII and type I collagen immunostaining intensities. The risk for deterioration of renal function (i.e., estimated GFR decline of >2.5 ml/min per yr) during a mean follow-up period of 23 mo (maximum 43 mo) was associated with urinary angiotensinogen of >3.0 nmol AngI equivalent per 1 g of urinary creatinine (AngI Eq/g Cre) at enrollment (hazard ratio 3.52). The event-free survival for deterioration of renal function was better in patients with urinary angiotensinogen <3.0 nmol AngI Eq/g Cre than those >3.0 nmol AngI Eq/g Cre. Losartan reduced urinary and plasma angiotensinogen, urinary protein and type IV collagen, and systolic BP, despite concomitant increases in plasma renin and AngII. These data suggest that urinary angiotensinogen is a potentially suitable marker of intrarenal AngII activity associated with increased risk for deterioration of renal function in patients with CKD.
Onset and Recurrence of Depression as Predictors of Cardiovascular Prognosis in Depressed Acute Coronary Syndrome Patients: A Systematic Review
Authors: Marij Zuidersma, Brett D. Thombs, Peter de Jonge
Journal: Psychotherapy and Psychosomatics (2011)

&lt;i&gt;Background:&lt;/i&gt; Depression after acute coronary syndrome (ACS) is associated with worse cardiac outcomes. This systematic review evaluated whether depressed ACS patients are at differential risk depending on the recurrence and timing of onset of depressive episodes. &lt;i&gt;Methods:&lt;/i&gt; MEDLINE, EMBASE and PsycINFO were searched from inception to 11 April 2009. Additionally, reference lists and recent tables of contents of 34 selected journals were manually searched. Eligible studies evaluated cardiovascular outcomes for subgroups of ACS patients with depression or depressive symptoms according to recurrence or onset. &lt;i&gt;Results:&lt;/i&gt; Six studies were included that reported outcomes for subgroups of ACS patients with first-ever versus recurrent depression. Four of these reported also outcomes for post-ACS onset versus pre-ACS onset depression, and incident versus nonincident depression. Worse outcomes (odds ratio &gt;1.4) were reported for ACS patients with first-ever depression in 3 of 6 studies (1 study p &lt; 0.05), for patients with post-ACS onset depression in 3 of 4 studies (1 study p &lt; 0.05, but better outcomes in one study) and for patients with incident depression in 2 of 4 studies (no studies p &lt; 0.05). &lt;i&gt;Conclusions:&lt;/i&gt; Although it is still suggested that ACS patients with first and new-onset depression are at particularly increased risk of worse prognosis, the inconsistent results from the studies included in this systematic review show that there is no consistent evidence to support such statements.
Significance of a fall in serum CEA concentration in patients treated with cytotoxic chemotherapy for disseminated colorectal cancer.
Authors: T G Allen-Mersh, N Kemeny, D Niedzwiecki, B Shurgot, J M Daly
Journal: Gut (1987)

'Tumour response', defined as clinical or radiological evidence of tumour shrinkage is frequently regarded as an objective of chemotherapy, rather than as a predictor of prolonged survival. This study has assessed whether a fall in the serum CEA concentration after chemotherapy for disseminated colorectal cancer is a predictor of prolonged survival and compared it with tumour response as a predictor of survival. There was a 37% improvement in median survival among patients whose serum CEA concentration fell after chemotherapy (70% of patients treated) compared with patients whose serum CEA did not fall. The use of greater than 25% clinical or radiological tumour shrinkage as a predictor of prolonged survival identified a smaller proportion (36%) of patients in whom there was a 52% prolongation in median survival compared with patients whose tumours shrank less than 25%, or did not shrink. Proportional hazards regression analysis suggested that tumour shrinkage was a stronger predictor of survival. A fall in serum CEA concentration, however, identified a group of patients whose tumours did not shrink, but who had a 27% improvement in median survival compared with those whose tumours did not shrink and whose serum CEA concentration did not fall. Monitoring of the serum CEA during the first two months of treatment appears to provide a sensitive and economical means of identifying those patients whose survival is likely to be prolonged by chemotherapy for colorectal cancer.
Prospective Evaluation of 11C-Choline Positron Emission Tomography/Computed Tomography and Diffusion-Weighted Magnetic Resonance Imaging for the Nodal Staging of Prostate Cancer with a High Risk of Lymph Node Metastases
Authors: Tom Budiharto, Steven Joniau, Evelyne Lerut, Laura Van den Bergh, Felix Mottaghy, Christophe M. Deroose, Raymond Oyen, Filip Ameye, Kris Bogaerts, Karin Haustermans, Hendrik Van Poppel
Journal: European Urology (2011)