tbuckley/cabot-search huggingface dataset:
Smoking history, alcohol consumption, and systemic lupus erythematosus: a case-control study
Authors: C. J Hardy, B. P Palmer, K. R Muir, A. J Sutton, R. J Powell
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To investigate the effect of smoking on the development of systemic lupus erythematosus (SLE), and the association between alcohol consumption and the disease. <h3>METHODS</h3> 450 subjects (150 SLE patients and 300 controls) from Nottingham, UK were interviewed in a case-control study. Controls were matched to cases for age and sex. All patients met at least four of the American Rheumatology Association criteria for SLE. Controls were randomly selected from the Nottingham Family Health Services Authority register. Information was collected by interview administered questionnaire concerning demographic variables, smoking histories, and drinking habits. <h3>RESULTS</h3> Analysis of the data by conditional logistic regression revealed current smokers to have a significantly increased risk of development of SLE compared with never smokers (odds ratio (OR) 1.95, 95% confidence intervals (CI) 1.14, 3.31), although ex-smokers were not at increased risk. There was also suggestion of a marked, highly significant negative association between SLE and alcohol consumption, the magnitude of which increased with units consumed. <h3>CONCLUSIONS</h3> This study suggests that current smokers are at increased risk of developing SLE compared with non-smokers and ex-smokers. In contrast, alcohol consumption seems to be negatively associated with the disease.
Somatic Hypermethylation of <i>MSH2</i> Is a Frequent Event in Lynch Syndrome Colorectal Cancers
Authors: Takeshi Nagasaka, Jennifer Rhees, Matthias Kloor, Johannes Gebert, Yoshio Naomoto, C. Richard Boland, Ajay Goel
Journal: Cancer Research (2010)

Abstract Heritable germline epimutations in MSH2 have been reported in a few Lynch syndrome families that lacked germline mutations in the MSH2 gene. It is not known whether somatic MSH2 methylation occurs in MSH2 mutation–positive Lynch syndrome subjects or sporadic colorectal cancers (CRC). Therefore, we determined the methylation status of the MSH2 gene in 268 CRC tissues, including 222 sporadic CRCs and 46 Lynch syndrome tumors that did not express MSH2. We also looked for microsatellite instability (MSI), germline mutations in the MSH2 and EpCAM genes, somatic mutations in BRAF and KRAS, and the CpG island methylator phenotype (CIMP). We observed that somatic MSH2 hypermethylation was present in 24% (11 of 46) of MSH2-deficient (presumed Lynch syndrome) tumors, whereas no evidence for MSH2 methylation existed in sporadic CRCs (MSI and microsatellite stable) or normal colonic tissues. Seven of 11 (63%) patients with MSH2 methylation harbored simultaneous pathogenic germline mutations in the MSH2 gene. Germline EpCAM deletions were present in three of four patients with MSH2 methylation but without pathogenic MSH2 germline mutations. The mean methylation scores at CIMP-related markers were significantly higher in Lynch syndrome tumors with MSH2 methylation than MSH2-unmethylated CRCs. In conclusion, our data provide evidence for frequent MSH2 hypermethylation in Lynch syndrome tumors with MSH2 deficiency. MSH2 methylation in this subset of individuals is somatic and may serve as the “second hit” at the wild-type allele. High levels of aberrant methylation at CIMP-related markers in MSH2-methylated tumors raise the possibility that MSH2 is a target susceptible to aberrant methylation in Lynch syndrome. Cancer Res; 70(8); 3098–108. ©2010 AACR.
Style Matters: Manuscript requirements: the advance from Vancouver
Authors: E. Huth
Journal: BMJ (1981)

The agreement on uniform requirements for manuscripts developed in January 1978 in Vancouver, British Columbia, by a small group of clinical editors is now adhered to by more than 130 journals. This development was reported at a meeting of the International Committee of Medical Journal Editors held at Leeds Castle, Kent, England, in October 1980. Suggestions for revision of the requirements document were reviewed, and closer consideration of possible changes was scheduled for October 1981.
Incremental value of myocardial viability for prediction of Long-Term prognosis in surgically revascularized patients with left ventricular dysfunction
Authors: Stephen Sawada, Ashutosh Bapat, Dev Vaz, Juan Weksler, Naomi Fineberg, Adam Greene, Irmina Gradus-Pizlo, Harvey Feigenbaum
Journal: Journal of the American College of Cardiology (2003)
PME-1 Modulates Protein Phosphatase 2A Activity to Promote the Malignant Phenotype of Endometrial Cancer Cells
Authors: Ewa Wandzioch, Michelle Pusey, Amy Werda, Sophie Bail, Aishwarya Bhaskar, Mariya Nestor, Jing-Jing Yang, Lyndi M. Rice
Journal: Cancer Research (2014)

Protein phosphatase 2A (PP2A) negatively regulates tumorigenic signaling pathways, in part, by supporting the function of tumor suppressors like p53. The PP2A methylesterase PME-1 limits the activity of PP2A by demethylating its catalytic subunit. Here, we report the finding that PME-1 overexpression correlates with increased cell proliferation and invasive phenotypes in endometrial adenocarcinoma cells, where it helps maintain activated ERK and Akt by inhibiting PP2A. We obtained evidence that PME-1 could bind and regulate protein phosphatase 4 (PP4), a tumor-promoting protein, but not the related protein phosphatase 6 (PP6). When the PP2A, PP4, or PP6 catalytic subunits were overexpressed, inhibiting PME-1 was sufficient to limit cell proliferation. In clinical specimens of endometrial adenocarcinoma, PME-1 levels were increased and we found that PME-1 overexpression was sufficient to drive tumor growth in a xenograft model of the disease. Our findings identify PME-1 as a modifier of malignant development and suggest its candidacy as a diagnostic marker and as a therapeutic target in endometrial cancer.
Type 1 Diabetes Among Sardinian Children Is Increasing
Authors: Anna Casu, Cristiana Pascutto, Luisa Bernardinelli, Marco Songini
Journal: Diabetes Care (2004)

The Sardinian type 1 diabetes register represented the basis to determine the most recent trends and the age distribution of type 1 diabetes incidence among Sardinians <15 years of age during 1989-1999. Part of the data (1989-1998) has been already published by the EURODIAB Group with a lower completeness of ascertainment (87%). The geographical distribution of type 1 diabetes risk was also investigated.The new cases of type 1 diabetes in children aged 0-14 years in Sardinia were prospectively registered from 1989 to 1999 according to the EURODIAB ACE criteria. The completeness of ascertainment calculated applying the capture-recapture method was 91%. Standardized incidence rates and 95% CI were calculated assuming the Poisson distribution. Trend of type 1 diabetes incidence was analyzed using the Poisson regression model. Maps of the geographical distribution of type 1 diabetes risk for the whole time period and separately for 1989-1994 and 1995-1999 were produced applying a Bayesian method.A total of 1214 type 1 diabetic patients were registered yielding to an overall age- and sex-standardized incidence rate of 38.8/100000 (95% CI 36.7-41.1). There was a male excess with an overall male-to-female ratio of 1.4 (1.3-1.8). The increase of incidence during the 11 years analyzed was statistically significant (P = 0.002) with a yearly increasing rate of 2.8% (1.0-4.7). No evidence of an effect of age and sex on this trend has been found. The geographical distribution of type 1 diabetes relative risk (RR) showed that the highest risk areas are located in the southern and central-eastern part of the island and the lowest risk in the northeastern part, even if most of these differences were not statistically significant. This geographical distribution seemed to remain mainly the same between 1989-1994 and 1995-1999.The homogeneity of diabetes risk and the increase of incidence over the age-groups in the Sardinian population stress the role of an environmental factor uniformly distributed among the genetically high-risk Sardinians.
Rapid detection of multidrug-resistant tuberculosis
Authors: M Goyal, RJ Shaw, DK Banerjee, RJ Coker, BD Robertson, DB Young
Journal: European Respiratory Journal (1997)

Transmission of multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB) presents a serious problem for infection control in hospitals, particularly in the context of co-infection with the human immunodeficiency virus (HIV). We report on the use of molecular genetic tools to allow rapid assessment of samples from patients potentially infected with MDR-TB. Sputum and bronchoalveolar lavage samples were obtained from two HIV-positive patients with suspected tuberculosis, who had previous contact with a known MDR-TB index case. Polymerase chain reaction (PCR) was used directly on clinical samples to amplify genetic loci associated with rifampicin resistance (rpoB), and strain-specific polymorphisms (the direct repeat (DR) region). Drug resistance was determined using a commercially available kit for detection of point mutations in the rpoB gene (Inno-Lipa RifTB; Innogenetics, Belgium), and confirmed by nucleotide sequencing. Strain variation was determined using the spoligotyping method, based on the presence or absence of variable linker sequences within the DR region. In one patient, infection with a MDR strain identical to that of a known index case was demonstrated. A second patient, although positive for M. tuberculosis, was found to be infected with a rifampicin-sensitive strain. Results were obtained within 48 h, allowing appropriate treatment to be initiated and infection control measures to be implemented. PCR-based tests for strain-typing and for identification of rifampicin resistance provide important tools for identifying patients with MDR-TB and for rapid monitoring of potential nosocomial spread of MDR-TB. Prompt confirmation or exclusion of possible transmission allows early clinical intervention to prevent future outbreaks of multidrug-resistant M. tuberculosis.
Reply to: Clinical and immunological findings in 104 cases of paraneoplastic pemphigus
Authors: K.T. Amber
Journal: British Journal of Dermatology (2015)

Journal Article Reply to: Clinical and immunological findings in 104 cases of paraneoplastic pemphigus Get access K.T. Amber K.T. Amber Department of Dermatology University of California Irvine Medical Center Irvine CA U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 2, 1 February 2016, Page 461, https://doi.org/10.1111/bjd.14234 Published: 01 February 2016
High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy.
Authors: S Rich, B H Brundage
Journal: Circulation (1987)

In an attempt to produce substantial reductions in pulmonary arterial pressure and pulmonary vascular resistance in patients with primary pulmonary hypertension, a new treatment strategy using high doses of calcium channel-blocking drugs was developed. Thirteen patients were given an initial test dose of 60 mg diltiazem or 20 mg nifedipine followed by consecutive hourly doses until a 50% fall in pulmonary vascular resistance and 33% fall in pulmonary arterial pressure was achieved or untoward side effects developed. The initial drug challenges failed to produce significant reductions in mean pulmonary arterial pressure or pulmonary vascular resistance. In eight of 13 patients, continued hourly doses produced a reduction in mean pulmonary arterial pressure of 48% (61 to 35 mm Hg, p less than .01) and a reduction in pulmonary vascular resistance of 60% (15 to 6 units, p less than .01). These patients were discharged on high-dose (up to 720 mg/day diltiazem or 240 mg/day nifedipine) calcium channel-blocking drugs as long-term therapy. Five patients have returned for restudy after 1 year. In four of five the reductions in pulmonary arterial pressure and pulmonary vascular resistance were sustained and were associated with regression of right ventricular hypertrophy as assessed by electrocardiography and echocardiography. One patient who reduced her dose to a conventional level had a return of her pulmonary arterial pressure and pulmonary vascular resistance toward previous levels. We conclude that substantial reductions in pulmonary arterial pressure and pulmonary vascular resistance that are associated with regression of right ventricular hypertrophy are possible in some patients with primary pulmonary hypertension by use of calcium channel-blocking drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of extracellular matrix by mechanical stress in rat glomerular mesangial cells.
Authors: T Yasuda, S Kondo, T Homma, R C Harris
Journal: Journal of Clinical Investigation (1996)

Increases in intraglomerular pressure are known to predispose to the development of glomerular sclerosis, which is characterized by accumulation of extracellular matrix within the glomerulus. Glomerular mesangial cells are exposed to pulsatile capillary pressures and are a potential target for mechanical stress. In the present studies, we subjected cultured rat mesangial cells to continuous cycles of stretching and relaxation (stretch/relaxation) and examined alterations in extracellular matrix gene expression. After 48 h of stretch/relaxation, immunofluorescent localization of matrix accumulation indicated increases in types I, III, and IV collagens, fibronectin, and laminin, with the greatest increases seen at the periphery of the culture dish, at the point of the greatest deformation. Northern blot analysis of total RNA revealed time-dependent induction of alpha1(I) collagen, alpha1(III) collagen, alpha1(IV) collagen, fibronectin, and laminin by stretch/relaxation, with maximal increases occurring between 12 and 24 h. Transient transfection of reporter gene constructs of the 5' flanking region of alpha1(I) collagen gene indicated that stimulation of gene transcription was involved in the increased expression of matrix mRNA. Gelatinolytic activity in conditioned media was decreased at 24 and 48 h of stretch/relaxation, in association with a significant decrease in levels of mRNA for matrix metalloproteinase-2 (68-72 kD type IV collagenase) occurring within 6 h of stretch/relaxation. In contrast, expression of tissue inhibitor of metalloproteinase-2 was increased within 12 h of stretch/relaxation. Stretch/relaxation increased immunoreactive TGF-beta at 48 but not 12 h. TGF-beta1 mRNA levels remained unchanged during the initial 12 h of stretch/relaxation, but were significantly elevated at 48 h, and no differences in TGF-beta bioactivity could be detected in conditioned media for up to 12 h of stretch/relaxation. These findings demonstrate that in glomerular mesangial cells, repeated cycles of stretching and relaxation lead to matrix accumulation by stimulating production of extracellular matrix and decreasing activity of degradative enzymes. The observed induction of TGF-beta1 suggests a role in matrix accumulation occurring in response to continued mechanical deformation.
An evaluation of extubation failure predictors in mechanically ventilated infants and children
Authors: J. Farias, I. Alía, A. Retta, F. Olazarri, A. Fernández, A. Esteban, K. Palacios, L. Di Nunzio, G. Fernández, A. Bordón, C. Berrondo, G. Sheehan
Journal: Intensive Care Medicine (2002)
Organic cation transporter 3 modulates murine basophil functions by controlling intracellular histamine levels
Authors: Elke Schneider, François Machavoine, Jean-Marie Pléau, Anne-France Bertron, Robin L. Thurmond, Hiroshi Ohtsu, Takehiko Watanabe, Alfred H. Schinkel, Michel Dy
Journal: The Journal of Experimental Medicine (2005)

In this study, we identify the bidirectional organic cation transporter 3 (OCT3/Slc22a3) as the molecule responsible for histamine uptake by murine basophils. We demonstrate that OCT3 participates in the control of basophil functions because exogenous histamine can inhibit its own synthesis—and that of interleukin (IL)-4, IL-6, and IL-13—through this means of transport. Furthermore, ligands of H3/H4 histamine receptors or OCT3 inhibit histamine uptake, and outward transport of newly synthesized histamine. By doing so, they increase the histamine content of basophils, which explains why they mimic the effect of exogenous histamine. These drugs were no longer effective in histamine-free histidine decarboxylase (HDC)-deficient mice, in contrast with histamine itself. Histamine was not taken up and lost its inhibitory effect in mice deficient for OCT3, which proved its specific involvement. Intracellular histamine levels were increased strongly in IL-3–induced OCT3−/− bone marrow basophils, and explained why they generated fewer cytokines than their wild-type counterpart. Their production was enhanced when histamine synthesis was blocked by the specific HDC inhibitor α-fluoro-methyl histidine, and underscored the determinant role of histamine in the inhibitory effect. We postulate that pharmacologic modulation of histamine transport might become instrumental in the control of basophil functions during allergic diseases.
Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial)
Authors: Antoni Dávalos, José Alvarez-Sabín, José Castillo, Exuperio Díez-Tejedor, Jose Ferro, Eduardo Martínez-Vila, Joaquín Serena, Tomás Segura, Vitor T Cruz, Jaime Masjuan, Erik Cobo, Julio J Secades
Journal: The Lancet (2012)
Clonal History of Papillomavirus-Induced Dysplasia in the Female Lower Genital Tract
Authors: Svetlana Vinokurova, Nicolas Wentzensen, Jens Einenkel, Ruediger Klaes, Corina Ziegert, Peter Melsheimer, Heike Sartor, Lars-Christian Horn, Michael Höckel, Magnus von Knebel Doeberitz
Journal: JNCI Journal of the National Cancer Institute (2005)

Dysplastic lesions of the vagina or the vulva often occur in women who have a previous history of cervical dysplasia. Most lesions in the female lower genital tract are induced by infections with high-risk oncogenic human papillomaviruses (HR-HPVs), including HPV16 and HPV18. HR-HPV genomes frequently integrate into host cell chromosomes at random sites. We analyzed viral integration sites in multiple metachronous lesions of the lower genital tract from women previously treated for HR-HPV-positive cervical dysplasia or cancer to determine whether the metachronous lesions emerged from a single common preexisting dysplastic cell clone or as consequence of independent HR-HPV infection events in the female lower genital tract.From among 1500 patients with anogenital lesions, seven patients with high-grade vaginal or vulvar lesions and with a previous history of cervical disease (five with prior high-grade cervical dysplasia and two with a history of cervical cancer) were included in this study. Integration sites of HPV16 or HPV18 in vaginal or vulvar lesions were mapped by an adaptor ligation polymerase chain reaction (PCR) method. The sequence information was used to design an integrate-specific PCR assay that was applied to DNA extracted from archival paraffin-embedded material derived from biopsy samples of cervical lesions.Identical HPV DNA integration loci were found in vaginal or vulvar and cervical samples of all lesions available for four of the five patients with a prior history of high-grade cervical dysplasia and for both patients with a history of cervical cancer.These data indicate that high-grade dysplastic lesions in the female lower genital tract may emerge primarily as monoclonal lesions from a transformed cell population derived from the uterine cervix.
Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)
Authors: Martin Tristani-Firouzi, Judy L. Jensen, Matthew R. Donaldson, Valeria Sansone, Giovanni Meola, Angelika Hahn, Said Bendahhou, Hubert Kwiecinski, Anna Fidzianska, Nikki Plaster, Ying-Hui Fu, Louis J. Ptacek, Rabi Tawil
Journal: Journal of Clinical Investigation (2002)

Andersen syndrome (AS) is a rare, inherited disorder characterized by periodic paralysis, long QT (LQT) with ventricular arrhythmias, and skeletal developmental abnormalities. We recently established that AS is caused by mutations in KCNJ2, which encodes the inward rectifier K+ channel Kir2.1. In this report, we characterized the functional consequences of three novel and seven previously described KCNJ2 mutations using a two-microelectrode voltage-clamp technique and correlated the findings with the clinical phenotype. All mutations resulted in loss of function and dominant-negative suppression of Kir2.1 channel function. In mutation carriers, the frequency of periodic paralysis was 64% and dysmorphic features 78%. LQT was the primary cardiac manifestation, present in 71% of KCNJ2 mutation carriers, with ventricular arrhythmias present in 64%. While arrhythmias were common, none of our subjects suffered sudden cardiac death. To gain insight into the mechanism of arrhythmia susceptibility, we simulated the effect of reduced Kir2.1 using a ventricular myocyte model. A reduction in Kir2.1 prolonged the terminal phase of the cardiac action potential, and in the setting of reduced extracellular K+, induced Na+/Ca2+ exchanger–dependent delayed afterdepolarizations and spontaneous arrhythmias. These findings suggest that the substrate for arrhythmia susceptibility in AS is distinct from the other forms of inherited LQT syndrome.
Response to: ‘Paying attention to enthesitis in early untreated arthritis: MRI for the evaluation of enthesitis’, by Zhou<i>et al</i>
Authors: Jacqueline E Paramarta, Dominique Baeten
Journal: Annals of the Rheumatic Diseases (2014)

We thank Zhou et al for their interest in our publication on the share of enthesitis and synovitis in peripheral arthritis in early onset spondyloarthritis (SpA).1

The aim of our study was to assess the validity of the hypothesis by McGonagle et al 2 proposing that in peripheral arthritis, synovitis is the primary feature in rheumatoid arthritis (RA), whereas, enthesitis is the primary lesion in SpA. The …
Angiotropic large cell lymphoma presenting as interstitial lung disease.
Authors: T B Tan, P J Spaander, M Blaisse, F M Gerritzen
Journal: Thorax (1988)

A case of angiotropic large cell lymphoma is reported in which the patient presented with only pulmonary symptoms. It suggests that this rare and highly malignant lymphoma should be considered in the differential diagnosis of interstitial lung disease, and shows the value of open lung biopsy in unexplained interstitial lung disease. This patient responded well to treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone.