tbuckley/cabot-search huggingface dataset:
Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: Correlation with IQ
Authors: D. J. Mabbott
Journal: Neuro-Oncology (2006)

Treatment of children with cranial-spinal radiation (CSR) for brain tumors is associated with adverse intellectual outcome and white matter damage. However, the correlation between IQ and measures of white matter integrity has received little attention. We examined apparent diffusion coefficient (ADC), fractional anisotropy (FA), and intelligence in pediatric patients treated with CSR for medulloblastoma relative to control subjects. ADC and FA measures were obtained for eight patients and eight control children and evaluated in multiple regions of interest in the cerebral hemispheres. Mean ADC and mean FA for each region were calculated, group differences were evaluated, and the relationship between these measures and intelligence were examined. In our study group, decreased IQ was associated with increased ADC and decreased FA (P < 0.01). Mean IQ for the CSR group was lower than that for the control group, but the difference was not significant when controlling for overall mean FA or ADC (P > 0.10). Overall mean FA was lower and ADC was higher in the CSR group relative to controls (P < 0.01). Specifically, FA was lower in the genu of the corpus callosum, the anterior and posterior limbs of the internal capsule, inferior frontal white matter, and high frontal white matter, and ADC was higher in all regions in patients relative to controls (P < 0.01). Compromised white matter integrity was observed for multiple regions within the cerebral hemispheres following CSR. A novel finding was that microscopic damage in normal-appearing white matter, as indexed by higher ADC and lower FA, was related to poor intellectual outcome relative to age-matched controls.
Jnk1 but not jnk2 promotes the development of steatohepatitis in mice
Authors: Jörn M. Schattenberg, Rajat Singh, Yongjun Wang, Jay H. Lefkowitch, Raina M. Rigoli, Philipp E. Scherer, Mark J. Czaja
Journal: Hepatology (2005)

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and varying degrees of necroinflammation. Although chronic oxidative stress, inflammatory cytokines, and insulin resistance have been implicated in the pathogenesis of NAFLD, the mechanisms that underlie the initiation and progression of this disease remain unknown. c-Jun N-terminal kinase (JNK) is activated by oxidants and cytokines and regulates hepatocellular injury and insulin resistance, suggesting that this kinase may mediate the development of steatohepatitis. The presence and function of JNK activation were therefore examined in the murine methionine- and choline-deficient (MCD) diet model of steatohepatitis. Activation of hepatic JNK, c-Jun, and AP-1 signaling occurred in parallel with the development of steatohepatitis in MCD diet-fed mice. Investigations in jnk1 and jnk2 knockout mice demonstrated that jnk1, but not jnk2, was critical for MCD diet-induced JNK activation. JNK promoted the development of steatohepatitis as MCD diet-fed jnk1 null mice had significantly reduced levels of hepatic triglyceride accumulation, inflammation, lipid peroxidation, liver injury, and apoptosis compared with wild-type and jnk2 -/- mice. Ablation of jnk1 led to an increase in serum adiponectin but had no effect on serum levels of tumor necrosis factor-alpha. In conclusion, JNK1 is responsible for JNK activation that promotes the development of steatohepatitis in the MCD diet model. These findings also provide additional support for the critical mechanistic involvement of JNK1 overactivation in conditions associated with insulin resistance and the metabolic syndrome.
Spirometric Reference Values from a Sample of the General U.S. Population
Authors: JOHN L. HANKINSON, JOHN R. ODENCRANTZ, KATHLEEN B. FEDAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Spirometric reference values for Caucasians, African-Americans, and Mexican-Americans 8 to 80 yr of age were developed from 7,429 asymptomatic, lifelong nonsmoking participants in the third National Health and Nutrition Examination Survey (NHANES III). Spirometry examinations followed the 1987 American Thoracic Society recommendations, and the quality of the data was continuously monitored and maintained. Caucasian subjects had higher mean FVC and FEV1 values than did Mexican-American and African-American subjects across the entire age range. However, Caucasian and Mexican-American subjects had similar FVC and FEV1 values with respect to height, and African-American subjects had lower values. These differences may be partially due to differences in body build: observed Mexican-Americans were shorter than Caucasian subjects of the same age, and African-Americans on average have a smaller trunk:leg ratio than do Caucasians. Reference values and lower limits of normal were derived using a piecewise polynomial model with age and height as predictors. These reference values encompass a wide age range for three race/ethnic groups and should prove useful for diagnostic and research purposes.
Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation
Authors: Chia-Ti Tsai, Ling-Ping Lai, Jiunn-Lee Lin, Fu-Tien Chiang, Juey-Jen Hwang, Marylyn D. Ritchie, Jason H. Moore, Kuan-Lih Hsu, Chuen-Den Tseng, Chiau-Suong Liau, Yung-Zu Tseng
Journal: Circulation (2004)

The activated local atrial renin-angiotensin system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that RAS genes might be among the susceptibility genes of nonfamilial structural AF and conducted a genetic case-control study to demonstrate this.A total of 250 patients with documented nonfamilial structural AF and 250 controls were selected. The controls were matched to cases on a 1-to-1 basis with regard to age, gender, presence of left ventricular dysfunction, and presence of significant valvular heart disease. The ACE gene insertion/deletion polymorphism, the T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen gene, and the A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In multilocus haplotype analysis, the angiotensinogen gene haplotype profile was significantly different between cases and controls (chi2=62.5, P=0.0002). In single-locus analysis, M235T, G-6A, and G-217A were significantly associated with AF. Frequencies of the M235, G-6, and G-217 alleles were significantly higher in cases than in controls (P=0.000, 0.005, and 0.002, respectively). The odds ratios for AF were 2.5 (95% CI 1.7 to 3.3) with M235/M235 plus M235/T235 genotype, 3.3 (95% CI 1.3 to 10.0) with G-6/G-6 genotype, and 2.0 (95% CI 1.3 to 2.5) with G-217/G-217 genotype. Furthermore, significant gene-gene interactions were detected by the multifactor-dimensionality reduction method and multilocus linkage disequilibrium tests.This study demonstrates the association of RAS gene polymorphisms with nonfamilial structural AF and may provide the rationale for clinical trials to investigate the use of ACE inhibitor or angiotensin II antagonist in the treatment of structural AF.
Activity of Cabazitaxel in Castration-resistant Prostate Cancer Progressing After Docetaxel and Next-generation Endocrine Agents
Authors: Carmel J. Pezaro, Aurelius G. Omlin, Amelia Altavilla, David Lorente, Roberta Ferraldeschi, Diletta Bianchini, David Dearnaley, Christopher Parker, Johann S. de Bono, Gerhardt Attard
Journal: European Urology (2013)
Expression Profiles and Clinical Correlations of Degradome Components in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma
Authors: Angela Stokes, Juho Joutsa, Risto Ala-aho, Mark Pitchers, Caroline J. Pennington, Craig Martin, Don J. Premachandra, Yasunori Okada, Juha Peltonen, Reidar Grénman, Helen A. James, Dylan R. Edwards, Veli-Matti Kähäri
Journal: Clinical Cancer Research (2010)

Head and neck squamous cell carcinomas (HNSCC) are characterized by high morbidity and mortality, largely due to the high invasive and metastatic potential of these tumors, high recurrence rates, and low treatment responses. Proteinases have been implicated in several aspects of tumor growth and metastasis in a broad range of tumors including HNSCC.Comprehensive expression profiling of proteinases [matrix metalloproteinases (MMPs), A disintegrin and metalloproteinase (ADAMs), and ADAMs with thrombospondin motif (ADAMTSs)] and their inhibitors [tissue inhibitor of metalloproteinases (TIMPs)] was done using quantitative real-time reverse transcription-PCR analysis of a large cohort of tissue samples representing the tumor (n = 83), the invasive margin (n = 41), and the adjacent tissue (n = 41) from 83 HNSCC patients, along with normal tissue controls (n = 13), as well as cell lines established from tumors of 34 HNSCC patients.The results show specifically elevated gene expression of several proteinases, including MMP1, MMP3, MMP10, and MMP13 within tumor tissue and peritumoral adjacent tissue. In addition, the results identify several novel HNSCC-associated proteinases, including ADAM8, ADAM9, ADAM17, ADAM28, ADAMTS1, ADAMTS8, and ADAMTS15. There were also significant differences in proteinase expression based on clinical parameters, i.e., tumor location, grade, and local invasion. MMP13 expression was significantly higher in large (>4 cm) locally invasive tumors (P < 0.05). MMP9 expression was significantly decreased in tumors with regional metastasis, whereas increased expression of ADAM8 was noted in the metastatic tumors (P < 0.001 for both).These findings suggest the HNSCC degradome as a valuable source of diagnostic, predictive, and prognostic molecular markers for these malignant tumors.
An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
Authors: Sandra Grumelli, David B Corry, Li-Zhen Song, Ling Song, Linda Green, Joseph Huh, Joan Hacken, Rafael Espada, Remzi Bag, Dorothy E Lewis, Farrah Kheradmand
Journal: PLoS Medicine (2004)

Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear.We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4+ and CD8+ T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells), but not CCR3 or CCR4 (markers of T helper 2 cells). Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma--often associated with T helper 1 cells--and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12), a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema.These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon.
Whether QOF has reduced premature death rates is still unclear
Authors: M. Roland
Journal: BMJ (2015)

Premature death rates have been declining for years, and a key question is whether this has anything to do with medical care. Kontopantelis and colleagues try to answer this question in relation to the Quality and Outcomes Framework (QOF; the UK’s pay for performance scheme for primary care).1 They asked whether GP practice performance on QOF is associated with …
Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy
Authors: S. Priem, G. R Burmester, T. Kamradt, K. Wolbart, M. G Rittig, A. Krause
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVES</h3> To identify possible sites of bacterial persistence in patients with treatment resistant Lyme arthritis. It was determined whether <i>Borrelia burgdorferi</i> DNA may be detectable by polymerase chain reaction (PCR) in synovial membrane (SM) when PCR results from synovial fluid (SF) had become negative after antibiotic therapy. <h3>METHODS</h3> Paired SF and SM specimens and urine samples from four patients with ongoing or recurring Lyme arthritis despite previous antibiotic therapy were investigated. A PCR for the detection of <i>B burgdorferi</i> DNA was carried out using primer sets specific for the <i>ospA </i>gene and a<i>p66</i> gene of <i>B burgdorferi.</i> <h3>RESULTS</h3> In all four cases, PCR with either primer set was negative in SF and urine, but was positive with at least one primer pair in the SM specimens. In all patients arthritis completely resolved after additional antibiotic treatment. <h3>CONCLUSIONS</h3> These data suggest that in patients with treatment resistant Lyme arthritis negative PCR results in SF after antibiotic therapy do not rule out the intraarticular persistence of <i>B burgdorferi </i>DNA. Therefore, in these patients both SF and SM should be analysed for borrelial DNA by PCR as positive results in SM are strongly suggestive of ongoing infection.
Proteomic analysis of the secretome of Leishmania donovani
Authors: J Maxwell Silverman, Simon K Chan, Dale P Robinson, Dennis M Dwyer, Devki Nandan, Leonard J Foster, Neil E Reiner
Journal: Genome biology (2008)

Abstract Background Leishmania and other intracellular pathogens have evolved strategies that support invasion and persistence within host target cells. In some cases the underlying mechanisms involve the export of virulence factors into the host cell cytosol. Previous work from our laboratory identified one such candidate leishmania effector, namely elongation factor-1α, to be present in conditioned medium of infectious leishmania as well as within macrophage cytosol after infection. To investigate secretion of potential effectors more broadly, we used quantitative mass spectrometry to analyze the protein content of conditioned medium collected from cultures of stationary-phase promastigotes of Leishmania donovani , an agent of visceral leishmaniasis. Results Analysis of leishmania conditioned medium resulted in the identification of 151 proteins apparently secreted by L. donovani . Ratios reflecting the relative amounts of each leishmania protein secreted, as compared to that remaining cell associated, revealed a hierarchy of protein secretion, with some proteins secreted to a greater extent than others. Comparison with an in silico approach defining proteins potentially exported along the classic eukaryotic secretion pathway suggested that few leishmania proteins are targeted for export using a classic eukaryotic amino-terminal secretion signal peptide. Unexpectedly, a large majority of known eukaryotic exosomal proteins was detected in leishmania conditioned medium, suggesting a vesicle-based secretion system. Conclusion This analysis shows that protein secretion by L. donovani is a heterogeneous process that is unlikely to be determined by a classical amino-terminal secretion signal. As an alternative, L. donovani appears to use multiple nonclassical secretion pathways, including the release of exosome-like microvesicles.
The mechanisms of antiinflammatory effect of mucolytic therapy
Authors: Usman Farkhutdinov, Valeriy Petryakov, Rafagat Farkhutdinov
Journal: European Respiratory Journal (2014)

Active oxygen forms (AOF) are of great importance in pathogenesis of lung inflammation. The efficacy of Ambroxol (A) in patients with lung diseases may be attributed to its potential influence on the production AOF by inflammatory cells.  The aim was to study the efficacy of A in complex therapy of patients with COPD.  Methods: The study included 52 patients with exacerbations of COPD. The production of AOF in the blood of patients was studied by registration of luminol dependent chemiluminescence (ChL). Bronchoalveolar lavage fluid (BALF) obtained during bronchofiberoscopy was examined for the determination of cell composition. The patients were divided into 2 groups. 25 patients with COPD received standard therapy (antibiotics, bronchodilators, glucocorticosteroids) and A inhalations. The other 27 patients received standard therapy and inhalations with placebo (sodium chloride solution).  Results: ChL intensity of blood in patients with COPD exacerbations was found to be increased by 1.5 times. It indicated increased production of AOF by blood cells. In comparison to normal findings in BALF of patients the content of alveolar macrofages was reduced and the content of neutrofiles was high. The use of A in patients decreased generation of AOF in blood and the intensity of clinical symptoms, improved cellular composition of BALF. In the case of standard therapy high ChL intensity of blood and disorders in the cell composition of BALF were maintained, the duration of exacerbation period was longer.  Conclusion: A administration in COPD exacerbations reduced AOF generation, improved the cell differential of BALF, increased the treatment efficiency.
Donor Pretreatment With Hypertonic Saline Attenuates Primary Allograft Dysfunction
Authors: Mitesh V. Badiwala, Danny Ramzy, Laura C. Tumiati, Elissa D. Tepperman, Rohit Sheshgiri, Jessica L. Prodger, Christopher M. Feindel, Vivek Rao
Journal: Circulation (2009)

Hypertonic saline (HTS) has been previously demonstrated to have immune modulatory and vascular protective effects. We assessed the effect of donor pretreatment with HTS on allograft preservation in a porcine model of orthotopic heart transplantation.Orthotopic transplants were performed after 6 hours of cold static allograft storage. Donor pigs were randomly assigned to pretreatment with (n=7) or without (n=6) HTS (4.5 mL/kg of 7.5% NaCl) administered 1 hour before donor heart arrest. Administration of HTS increased serum sodium level from 138+/-2 mmol/L to 154+/-4 mmol/L, which normalized to 144+/-3 mmol/L 1 hour after infusion. Successful weaning from cardiopulmonary bypass was significantly greater in HTS-treated hearts (6/7 vs 1/6; P=0.029). Preload recruitable stroke work after transplantation was improved compared to control (88+/-21% vs 35+/-8% of baseline; P=0.0001). Similarly, end-systolic elastance was improved compared to control (85+/-17% vs 42+/-12% of baseline; P=0.0002). Posttransplantation systolic blood pressure was significantly higher in the donor HTS group (60+/-9 mm Hg vs 35+/-6 mm Hg; P=0.04). Donor HTS treatment improved coronary artery endothelial-dependent vasorelaxation compared with control (Emax: HTS, 59+/-4%; control, 47+/-3%; P=0.04). HTS also resulted in improved endothelial-independent vasorelaxation compared with control (Emax: HTS, 71+/-3%; control, 59+/-4%; P=0.03; ED-50: HTS, 0.56x10 to 6+/-0.23 mol/L; control, 2.5x10 to 6+/-1.0 mol/L; P=0.04). Sensitivity to endothelin-1-induced vasospasm was reduced with HTS pretreatment (% maximum contraction [Cmax]: HTS, 338+/-15%; control, 419+/-40%; P=0.01).Donor HTS pretreatment attenuates posttransplantation cardiac allograft myocardial dysfunction, improves posttransplantation systemic hemodynamic function, and preserves posttransplantation cardiac allograft vascular function. HTS may be a novel organ donor intervention to prevent primary graft dysfunction.
Metabolic and Inflammatory Links to Depression in Youth With Diabetes
Authors: Korey K. Hood, Jean M. Lawrence, Andrea Anderson, Ronny Bell, Dana Dabelea, Stephen Daniels, Beatriz Rodriguez, Lawrence M. Dolan
Journal: Diabetes Care (2012)

OBJECTIVE Youth with diabetes are at increased risk for depression. The objectives of this study were to provide preliminary evidence that this at-risk status for depression is associated with metabolic and inflammatory markers and to inform future, more stringent examinations of the directionality of these associations. RESEARCH DESIGN AND METHODS Data from SEARCH for Diabetes in Youth (SEARCH), an observational study of U.S. children diagnosed with diabetes at &amp;lt;20 years of age, were used for these analyses. SEARCH participants were drawn from four geographically defined populations in Ohio, Washington, South Carolina, and Colorado; health plan enrollees in Hawaii and California; and Indian Health Service beneficiaries from four Native American populations. Participants were 2,359 youth with diabetes from the 2001 prevalent and 2002–2004 incident SEARCH cohorts. Depression was measured with the Center for Epidemiologic Studies Depression scale. Eight metabolic and inflammatory markers were measured: adiponectin, leptin, C-reactive protein, serum amyloid A, apolipoprotein B (apoB), lipoprotein A, interleukin-6, and LDL. RESULTS Six of eight markers were significantly (P &amp;lt; 0.006) associated with depression in youth with diabetes in bivariate analyses. In general, higher levels of depression were associated with indicators of worse metabolic or inflammatory functioning. In regression models stratified by diabetes type and accounting for demographic and clinical characteristics, only higher levels of apoB remained associated with higher levels of depression in youth with type 1 diabetes. CONCLUSIONS These data suggest that depression reported by youth with diabetes is partially associated with metabolic abnormalities and systemic inflammation.
Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts
Authors: R. A. Douma, G. le Gal, M. Sohne, M. Righini, P. W. Kamphuisen, A. Perrier, M. J. H. A. Kruip, H. Bounameaux, H. R. Buller, P. M. Roy
Journal: BMJ (2010)

<b>Objectives</b> In older patients, the the D-dimer test for pulmonary embolism has reduced specificity and is therefore less useful. In this study a new, age dependent cut-off value for the test was devised and its usefulness with older patients assessed. <b>Design</b> Retrospective multicentre cohort study. <b>Setting</b> General and teaching hospitals in Belgium, France, the Netherlands, and Switzerland. <b>Patients</b> 5132 consecutive patients with clinically suspected pulmonary embolism. <b>Intervention</b> Development of a new D-dimer cut-off point in patients aged &gt;50 years in a derivation set (data from two multicentre cohort studies), based on receiver operating characteristics (ROC) curves. This cut-off value was then validated with two independent validation datasets. <b>Main outcome measures</b> The proportion of patients in the validation cohorts with a negative D-dimer test, the proportion in whom pulmonary embolism could be excluded, and the false negative rates. <b>Results</b> The new D-dimer cut-off value was defined as (patient’s age×10) μg/l in patients aged &gt;50. In 1331 patients in the derivation set with an “unlikely” score from clinical probability assessment, pulmonary embolism could be excluded in 42% with the new cut-off value versus 36% with the old cut-off value (&lt;500 μg/l). In the two validation sets, the increase in the proportion of patients with a D-dimer below the new cut-off value compared with the old value was 5% and 6%. This absolute increase was largest among patients aged &gt;70 years, ranging from 13% to 16% in the three datasets. The failure rates (all ages) were 0.2% (95% CI 0% to 1.0%) in the derivation set and 0.6% (0.3% to 1.3%) and 0.3% (0.1% to 1.1%) in the two validation sets. <b>Conclusions</b> The age adjusted D-dimer cut-off point, combined with clinical probability, greatly increased the proportion of older patients in whom pulmonary embolism could be safely excluded.