tbuckley/cabot-search huggingface dataset:
Self-reported time spent watching television is associated with arterial stiffness in young adults: the Amsterdam Growth and Health Longitudinal Study
Authors: Roel J van de Laar, Coen D Stehouwer, Martin H Prins, Willem van Mechelen, Jos W Twisk, Isabel Ferreira
Journal: British Journal of Sports Medicine (2013)

To investigate whether time spent watching television (a marker of sedentary behaviour) is associated with arterial stiffness, a major determinant of cardiovascular disease, and whether any such association could be explained by related deleterious levels of habitual physical activity (HPA) and/or other lifestyle and biological risk factors.Prospective measures (ages 32 and 36 years) of television time and risk factors were retrieved from 373 participants (196 women) in whom stiffness of the carotid, brachial and femoral arteries was assessed by means of ultrasonography at age 36 years. Data were analysed with generalised estimating equations.Participants with stiffer carotid arteries spent more time (in min/day) watching television during the four preceding years than did those with less stiff arteries, as defined on the basis of the highest compared with the lowest gender-specific tertiles of the distensibility or compliance coefficients (reversed) or the Young's elastic modulus: +22.4 (95%CI 8.7 to 36.1), +18.4 (4.2 to 32.5) and +19.7 (6.0 to 33.4), respectively. These differences were independent of potential confounders, such as vigorous intensity HPA and other lifestyle risk factors, and could only in part (up to 31%) be explained by the adverse associations of television time with traditional biological risk factors. Qualitatively similar results were found for femoral, but not brachial, stiffness estimates.Given the independent associations of time spent watching television and vigorous intensity HPA with arterial stiffness, our study suggests that not only promotion of physical activity, but also discouragement of sedentary behaviours should be targeted in younger adults to prevent arterial stiffening.
Genetic Investigation of Autosomal Recessive Distal Renal Tubular Acidosis
Authors: Rosa Vargas-Poussou, Pascal Houillier, Nelly Le Pottier, Laurence Strompf, Chantal Loirat, Véronique Baudouin, Marie-Alice Macher, Michèle Déchaux, Tim Ulinski, Franc[COMBINING CEDILLA]ois Nobili, Philippe Eckart, Robert Novo, Mathilde Cailliez, Rémi Salomon, Hubert Nivet, Pierre Cochat, Ivan Tack, Anne Fargeot, Franc[COMBINING CEDILLA]ois Bouissou, Gwenaelle Roussey Kesler, Stéphanie Lorotte, Nathalie Godefroid, Valérie Layet, Gilles Morin, Xavier Jeunemai[Combining Circumflex Accent]tre, Anne Blanchard
Journal: Journal of the American Society of Nephrology (2006)

Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of apical H(+) ATPase, cause recessive forms of distal renal tubular acidosis (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing loss (SNHL), whereas ATP6V0A4 mutations are classically associated with either late-onset SNHL or normal hearing. The phenotype and genotype of 39 new kindreds with recessive dRTA, 18 of whom were consanguineous, were assessed. Novel and known loss-of-function mutations were identified in 31 kindreds. Fourteen new and five recurrent mutations of the ATP6V0A4 gene were identified in 21 families. For the ATP6V1B1 gene, two new and two previously described mutations were identified in 10 families. Surprisingly, seven probands with ATP6V0A4 gene mutations developed severe early SNHL between the ages of 2 mo and 10 yr. No mutation was detected in eight families. These data extend the spectrum of disease-causing mutations and provide evidence for genetic heterogeneity in SNHL. The data also demonstrate that mutations in either of these genes may cause early deafness, and they highlight the importance of genetic screening for recessive forms of dRTA independent of hearing status.
Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases
Authors: G Zollner
Journal: Hepatology (2001)

Reduced hepatobiliary transporter expression could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resulting in cholestasis and jaundice. Because little is known about alterations of hepatobiliary transport systems in human cholestatic liver diseases, it was the aim of this study to investigate such potential changes. Hepatic mRNA levels in hepatobiliary transport systems for bile salts (NTCP, BSEP), organic anions (OATP2, MRP2, MRP3), organic cations (MDR1), phospholipids (MDR3), and aminophospholipids (FIC1) were determined in 37 human liver biopsies and control livers by competitive reverse-transcription polymerase chain reaction (RT-PCR). Transporter tissue distribution was investigated by immunofluorescence microscopy. In patients with inflammation-induced icteric cholestasis (mainly cholestatic alcoholic hepatitis), mRNA levels of NTCP, OATP2, and BSEP were reduced by 41% (P < .001), 49% (P < .005), and 34% (P < .05) compared with controls, respectively. In addition, NTCP and BSEP immunostaining was reduced. MRP2 mRNA levels remained unchanged, but canalicular immunolabeling for MRP2 was also decreased. mRNA expression of MRP3, MDR1, MDR3, and FIC1 remained unchanged. In contrast to the alterations of transporter expression in inflammation-induced icteric cholestasis, transporter expression did not change in anicteric cholestasis caused by primary biliary cirrhosis (PBC) stages I and II. In conclusion, reduced expression of hepatobiliary transport systems for bile salts and other organic anions may contribute to inflammation-induced cholestasis in humans. Reduction of transporter gene expression can occur at the mRNA level as observed for NTCP, OATP2, and BSEP. However, reduced MRP2 immunostaining in the presence of conserved MRP2 mRNA levels suggests an additional role for posttranscriptional/posttranslational mechanisms.
Relations between steroid hormones and cytokines in rheumatoid arthritis and systemic lupus erythematosus
Authors: M. CUTOLO, A. SULLI, B. VILLAGGIO, B. SERIOLO, S. ACCARDO
Journal: Annals of the Rheumatic Diseases (1998)

Relations between steroid hormones and cytokines in rheumatoid arthritis and systemic lupus erythematosus Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are multifactorial autoimmune diseases that originate from the patient's excessive immune and inflammatory response to a pathogenic agent (that is, an infective antigen). 1][15] Th1 lymphocytes produce mainly interleukin 2 (IL2) and interferon (IFN ) and are primarly responsible for cell mediated immunity, while Th2 lymphocytes produce mainly IL4, IL5, IL13, and IL10, and are responsible for Annals of the Rheumatic Diseases
Identification of T cell epitopes occurring in a meningococcal class 1 outer membrane protein using overlapping peptides assembled with simultaneous multiple peptide synthesis.
Authors: E J Wiertz, J A van Gaans-van den Brink, H Gausepohl, A Prochnicka-Chalufour, P Hoogerhout, J T Poolman
Journal: The Journal of Experimental Medicine (1992)

The meningococcal class 1 outer membrane protein (OMP) plays an important role in the development of protective immunity against meningococcal infection, and is therefore considered to be a promising candidate antigen (Ag) for a meningococcal vaccine. The induction of an effective antibody response entirely depends upon T helper cells. To identify T cell epitopes of the OMP, we prepared 45 overlapping synthetic peptides representing the entire sequence of the class 1 protein of reference strain H44/76. Fully automated simultaneous multiple peptide synthesis (SMPS) was used to assemble the 45 twenty mer which overlapped by 12 amino acid residues on a 12 mumol scale. The peptides were tested for recognition by peripheral blood mononuclear cells (PBMC) obtained from 34 volunteers. Surprisingly, all synthetic peptides induced proliferative responses of PBMC isolated from one or more human histocompatibility leukocyte antigen (HLA)-typed immune adults. With PBMC from seven nonimmune donors, no proliferative response was observed. Immunodominant regions were found, recognized by PBMC from many volunteers, irrespective of their HLA type. Most of the immunodominant T cell epitopes are located outside the variable regions and, thus, will be conserved among different meningococcal (and gonococcal) strains. Furthermore, the overlapping peptides could be used to identify the epitopes recognized by OMP-specific T cell clones with known HLA restriction. It is interesting that the epitopes defined with the clones occur in highly conserved areas, shared by all neisserial porin proteins. In summary, this analysis of the T cell response to the meningococcal class 1 OMP constitutes a complete study of reactivity to a foreign protein, and illustrates some important features of Ag recognition by T cells. Our data demonstrate unexpected diversity in the T cell recognition of the OMP, and imply that the T cell repertoire against foreign Ag may be greater than previously assumed. This observation is supported by recent data on the interaction of peptide and major histocompatibility complex (MHC) class II, the latter being much less selective than MHC class I. Finally, a comparative analysis pointed out the limitations of algorithms predicting T cell determinants, and the importance of the empirical methodology provided by SMPS.
EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer
Authors: N van Zandwijk, A Mathy, L Boerrigter, H Ruijter, I Tielen, D de Jong, P Baas, S Burgers, P Nederlof
Journal: Annals of Oncology (2006)
Selection, management, and early outcome of 113 patients with symptomatic gall stones treated by percutaneous cholecystolithotomy.
Authors: S Cheslyn-Curtis, A R Gillams, R C Russell, J J Donald, S P Lake, C A Ainley, A R Hatfield, W R Lees
Journal: Gut (1992)

Between January 1988 and December 1990, 283 patients with symptomatic gall stones were referred for non-operative treatment. After ultrasound scanning including a functional assessment, 220 (78%) patients were found to be suitable for percutaneous cholecystolithotomy. Of these, 113 underwent the procedure including 10 in whom extracorporeal shock-wave lithotripsy or methyl tert-butyl ether therapy had failed. Forty four patients underwent extracorporeal shockwave lithotripsy, methyl tert-butyl ether therapy or rotary lithotripsy, 46 chose laparoscopic cholecystectomy or minicholecystectomy and 27 declined treatment. Percutaneous cholecystolithotomy was successfully performed in 100 patients. Thirty four patients were a high operative risk and 14 presented with an acute complication of gall stone disease. Complications developed in 15 patients, all of whom were managed conservatively and most occurred during development of the technique. Outcome has been assessed clinically and by ultrasound scanning in 92 patients with a median follow up period of 14 months (six to 37 months). Seventy nine per cent were completely cured of their symptoms. Ninety three per cent of gall bladders were shown to be functioning and nine (9.8%) contained stones, although five of these are believed to have developed from residual fragments. Percutaneous cholecystolithotomy is a safe, non-operative treatment for symptomatic gall stones and enabled the patient to fully recover within two to three weeks; it has a definite role in the management of the elderly and high risk patient but its use for the treatment of other groups is likely to remain controversial.
Germline epimutations of APC are not associated with inherited colorectal polyposis
Authors: M Hitchins
Journal: Gut (2006)

<h3>Background:</h3> Comprehensive systems for surveilling prescription opioid–related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid–related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid–related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. <h3>Methods:</h3> We identified all prescription opioid–related deaths from Ontario coroners’ data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid–related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid–related deaths. <h3>Results:</h3> Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. <h3>Interpretation:</h3> In the absence of specific systems for monitoring prescription opioid–related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid–related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies.
Does Ovarian Cancer Treatment and Survival Differ by the Specialty Providing Chemotherapy?
Authors: Jeffrey H. Silber, Paul R. Rosenbaum, Daniel Polsky, Richard N. Ross, Orit Even-Shoshan, J. Sanford Schwartz, Katrina A. Armstrong, Thomas C. Randall
Journal: Journal of Clinical Oncology (2007)

Purpose Chemotherapy for ovarian cancer is usually administered by medical oncologists (MOs) or gynecologic oncologists (GOs). GOs perform a broad spectrum of surgical and medical activities while managing a limited number of diseases; MOs specialize in the administration of chemotherapy but manage a broad array of diseases. We asked whether survival, treatment, and toxicity differed according to the type of specialist providing the chemotherapy after surgery. Patients and Methods Using Surveillance, Epidemiology, and End Results (SEER) -Medicare data for patients ≥ 65 years old from 1991 through 2001 from eight SEER sites, we identified 344 patients with ovarian cancer who were treated with chemotherapy by a GO after surgery. Using optimal matching and propensity scores based on 36 characteristics, we matched these patients to 344 similar patients who were operated on and staged by the same type of surgeon but who received chemotherapy from an MO. Results MOs administered chemotherapy over more weeks than did the GOs (16.5 v 12.1 weeks, respectively; P &lt; .0023), and MO patients had substantially more weeks that included chemotherapy-associated adverse events than GO patients (16.2 v 8.9 weeks, respectively; P &lt; .0001). However, there was no difference in 5-year survival rate between the GO and MO groups (35% v 34%, respectively; P = .45). Conclusion GO- and MO-treated patients who were closely matched on prognostic characteristics experienced very different rates of chemotherapy-associated adverse events and very different chemotherapy treatment styles by specialty type; however, their survival was virtually identical.
Transforming Growth Factor- β Expression in Mucosal Biopsies in Asthma and Chronic Bronchitis
Authors: ANTONIO M. VIGNOLA, PASCAL CHANEZ, GIUSEPPINA CHIAPPARA, ANNA MERENDINO, ELISABETTA PACE, AROLDO RIZZO, ANTONIO M. la ROCCA, VINCENZO BELLIA, GIOVANNI BONSIGNORE, JEAN BOUSQUET
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We assessed whether transforming growth factor- β (TGF- β ), a fibrogenic growth factor, may be involved in remodeling of asthma and chronic bronchitis; its expression was compared with that of epidermal growth factor (EGF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in bronchial mucosal biopsies from 13 normal subjects, 24 asthmatics, and 19 patients with chronic bronchitis. TGF- β immunoreactivity was highly increased in epithelium and submucosa of those with bronchitis and to a lesser extent in asthmatics. By comparison, with normal subjects, EGF immunoreactivity was significantly increased in the epithelium of bronchitic subjects and submucosa of asthmatics, and, GM-CSF immunoreactivity was increased in both epithelial and submucosal cells of asthmatics and to a lesser extent in submucosa of bronchitics. A significant correlation was found between the number of epithelial or submucosal cells expressing TGF- β in both asthma and chronic bronchitis and basement membrane thickness and fibroblast number. No such correlation was found for EGF or GM-CSF. In situ hybridization for TGF- β 1 mRNA confirmed the results obtained by immunohistochemistry. By combining in situ hybridization and immunohistochemistry, it was found that eosinophils and fibroblasts were synthetizing TGF- β in asthma and bronchitis. These data suggest that TGF- β , but not EGF or GM-CSF, is involved in airways remodeling in asthma and chronic bronchitis.
Screening of Untreated Schoolchildren with Allergic Symptoms - How many are left untreated?
Authors: K. Mukaida, T. Kusunoki, T. Morimoto, T. Yasumi, R. Nishikomori, T. Heike, T. Fujii, T. Nakahata
Journal: Journal of Allergy and Clinical Immunology (2010)

RATIONALE: Allergic diseases continue to increase among children. However, it is unclear as to how many of these children are under appropriate medical care. To establish the number of schoolchildren being treated for their allergic symptoms and determine if their symptoms and treatment status are associated with their total and allergen-specific IgE levels. METHODS: A total of 618 out of the 627 (94.5%) 11-year-old schoolchildren living in Shiga, Japan answered a questionnaire designed to determine the presence of allergic symptoms and treatment status. Levels of total IgE, mite-specific IgE and three pollen-specific IgEs were measured at the same time the questionnaire was filled out and used to analyze relationships between the questionnaire data and IgE levels. RESULTS: The rates of diagnosis and treatment were 100% and 81% among those with bronchial asthma (BA) symptom. However, the rates for other allergic symptoms (atopic dermatitis, allergic rhinitis and allergic conjunctivitis) were significantly lower (ranging from 44 to 88% for diagnosis and 28 to 52% for treatment). When subjects were screened for a total IgE of 300 or more and/or a mite-specific IgE class 3 or more, 70% of those with untreated moderate or severe allergic symptoms were detected. CONCLUSIONS: Subjects with allergic symptoms other than BA exhibited significantly poorer treatment rates. Total and allergen-specific IgE screening at schools might be useful in determining untreated symptomatic children and helping advise them on appropriate medical care.
Improved Outcome of Allogeneic Transplantation in High-Risk Multiple Myeloma Patients After Nonmyeloablative Conditioning
Authors: A. Badros
Journal: Journal of Clinical Oncology (2002)

PURPOSE: We present our experience with relapsed and recently diagnosed patients with high-risk multiple myeloma (MM) receiving immunosuppressive, nonmyeloablative melphalan (MEL)-based conditioning regimens (mini-allograft). PATIENTS AND METHODS: Thirty-one MM patients received allografts from HLA-matched siblings (n = 25) or unrelated donors (n = 6) using a mini-allograft. Seventeen had progressive disease (PD) and 14 had responsive disease (RD) (six with primary RD and eight with responsive relapse). Thirty patients had received one (n = 13) or two or more (n = 17) prior autologous transplantations (ATs). Median age was 56 years (range, 38 to 69 years). Twenty-one patients had chromosome 13 abnormality. Two patients were hemodialysis dependent. Blood and bone marrow grafts were administered to 28 and three patients, respectively. Donor lymphocyte infusions were given to 18 patients either to attain full donor chimerism (n = 6) or to eradicate residual disease (n = 12). RESULTS: By day 100, 25 (89%) of 28 patients were full donor chimeras, one was a mixed chimera, and two had autologous reconstitution. Acute graft-versus-host disease (GVHD) developed in 18 patients (58%), and 10 progressed to chronic GVHD (limited in six and extensive in four). At a median follow-up of 6 months, 19 (61%) of 31 patients achieved complete/near complete remission. Twelve patients (39%) have died: three of PD, three of early treatment-related mortality (TRM) (before day 100), and six of late TRM. Median overall survival (OS) was 15 months. At 1 year, there was a significantly longer event-free survival (86% v 31%, P = .01) and OS (86% v 48%, P = .04) when a mini-allograft was performed after one versus two or more prior ATs, respectively. When compared with historical MM controls (n = 93) receiving conventional allografts, early TRM was significantly lower (10% v 29%, P = .03), and OS at 1 year was better (71% v 45%; P = .08) in the mini-allograft MM patients. CONCLUSION: Mini-allograft induced excellent disease control in MM patients with high-risk disease, but is still associated with a significant GVHD.
Addition of Azathioprine to Corticosteroids Does Not Benefit Patients with IgA Nephropathy
Authors: Claudio Pozzi, Simeone Andrulli, Antonello Pani, Patrizia Scaini, Lucia Del Vecchio, Giambattista Fogazzi, Bruno Vogt, Vincenzo De Cristofaro, Landino Allegri, Lino Cirami, Aldo Deni Procaccini, Francesco Locatelli
Journal: Journal of the American Society of Nephrology (2010)

The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events.