tbuckley/cabot-search huggingface dataset:
Role of interleukin-2 in the development and persistence of lymphocytic alveolitis in farmer's lung
Authors: A Dakhama, E Israel-Assayag, Y Cormier
Journal: European Respiratory Journal (1998)

Farmer's lung (FL) is characterized by an intense lymphocytic alveolitis which persists after an acute episode with continuous exposure to the offending antigens. This study aimed to examine the role of interleukin-2 (IL-2) in the development and persistence of this lymphocytic alveolitis. Three groups of dairy farmers were studied: acute FL, ex-FL (past history of FL but no clinical evidence of active disease) and asymptomatic farmers (no lung disease). IL-2 was measured by enzyme immunosorbent assay and T-cell proliferation was evaluated by 3H-thymidine incorporation. Acute and ex-FL patients had more lymphocytes (p&lt;0.01) and higher levels of IL-2 (p&lt;0.05) in their bronchoalveolar lavage (BAL) than asymptomatic farmers. BAL T-lymphocytes from acute and ex-FL patients released considerable amounts of IL-2 after stimulation with concanavalin A and showed dose-dependent proliferative responses to IL-2. IL-2 production was decreased after treatment with prednisone. Acute FL patients, but not ex-FL, had higher levels of soluble CD25 in their serum than asymptomatics (p=0.009). These results suggest that interleukin-2 may play a role in farmer's lung by providing a stimulus not only for the accumulation of lymphocytes but also for their persistence at the site of hypersensitivity reaction, and that the lung is a likely source of this cytokine in vivo.
Phase II Study of Dasatinib in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Faye M. Johnson, B. Nebiyou Bekele, Lei Feng, Ignacio Wistuba, Xi Ming Tang, Hai T. Tran, Jeremy J. Erasmus, Li-Ling Hwang, Naoko Takebe, George R. Blumenschein, Scott M. Lippman, David J. Stewart
Journal: Journal of Clinical Oncology (2010)

Src family kinases (SFKs) promote cancer progression and are commonly expressed in non-small-cell lung cancer (NSCLC), but the clinical effects of SFK inhibition in NSCLC are unknown. We conducted a phase II trial of the SFK inhibitor dasatinib for advanced NSCLC. We tested the hypotheses that the activation of epidermal growth factor receptor (EGFR) or SFK or modulation of serum cytokines may predict a response to dasatinib.Patients received dasatinib as first-line therapy. Response was measured by tumor size on computed tomography scans and by metabolic activity on positron emission tomography scans. Tissue samples taken before patients received dasatinib were tested for EGFR and Kras mutation and phosphorylated SFK expression.Thirty-four patients were enrolled. The overall disease control rate (partial responses plus stable disease) for dasatinib was 43%. One patient had a partial response to therapy. Eleven patients (32%) had a metabolic response to dasatinib. SFK activation and EGFR and Kras mutations in tumor tissue did not predict response to dasatinib. Significant toxicities included fatigue and dyspnea. The presence of a pleural effusion before dasatanib therapy predicted the development of a clinically significant effusion during therapy.Dasatinib as a single agent had modest clinical activity that was lower than that generally observed in patients with NSCLC who receive chemotherapy. Pleural effusion was an expected and problematic toxicity that was successfully treated with steroids, diuretics, and dose interruptions. Marked activity in one patient and prolonged stable disease in four others suggested a potential subpopulation of patients with dasatinib-sensitive NSCLC.
Intron Length Evolution in Drosophila
Authors: Daven C Presgraves
Journal: Molecular Biology and Evolution (2006)

I present data on the evolution of intron lengths among 3 closely related Drosophila species, D. melanogaster, Drosophila simulans, and Drosophila yakuba. Using D. yakuba as an outgroup, I mapped insertion and deletion mutations in 148 introns (spanning approximately 30 kb) to the D. melanogaster and D. simulans lineages. Intron length evolution in the 2 sister species has been different: in D. melanogaster, X-linked introns have increased slightly in size, whereas autosomal ones have decreased slightly in size; in D. simulans, both X-linked and autosomal introns have decreased in size. To understand the possible evolutionary causes of these lineage- and chromosome-specific patterns of intron evolution, I studied insertion-deletion (indel) polymorphism and divergence in D. melanogaster. Small insertion mutations segregate at elevated frequencies and enjoy elevated probabilities of fixation, particularly on the X chromosome. In contrast, there is no detectable X chromosome effect on fixations in D. simulans. These findings suggest X chromosome-specific selection or biased gene conversion-gap repair favoring insertions in D. melanogaster but not in D. simulans. These chromosome- and lineage-specific patterns of indel substitution are not easily explained by existing general population genetic models of intron length evolution. Genomic data from D. melanogaster further suggest that the forces described here affect introns and intergenic regions similarly.
Health status measurement in chronic obstructive pulmonary disease
Authors: P W Jones
Journal: Thorax (2001)

Health status measurement is a common feature of studies in chronic obstructive pulmonary disease (COPD). This review assesses recent evidence for the validity of these measurements and their role as measures of the overall impact of the disease on the patient9s daily life and wellbeing. It reviews the mostly widely used COPD specific questionnaires and examines the contribution that they make to an assessment of the overall effect of treatment. Finally, it addresses the question of how symptomatic benefit may be assessed in individual patients in routine practice.
585 A FRENCH MULTICENTRIC LONGITUDINAL DESCRIPTIVE STUDY OF HEPATOCELLULAR CARCINOMA MANAGEMENT (THE CHANGH COHORT): PRELIMINARY RESULTS
Authors: I. Rosa, J. Denis, P. Renard, B. Lesgourgues, A.S. Dobrin, C. Becker, R. Faroux, X. Causse, E. Diaz, G. Le Dréau, B. Marks, J. Henrion, F. Zerouala, T. Decaens, R. Baderr, O. Danne, A.J. Rémy, B. Nalet, T. Morin, C. Renou, H. Ha gège
Journal: Journal of Hepatology (2010)
Benzodiazepine use and risk of dementia: prospective population based study
Authors: S. Billioti de Gage, B. Begaud, F. Bazin, H. Verdoux, J.-F. Dartigues, K. Peres, T. Kurth, A. Pariente
Journal: BMJ (2012)

<b>Objective</b> To evaluate the association between use of benzodiazepines and incident dementia. <b>Design</b> Prospective, population based study. <b>Setting</b> PAQUID study, France. <b>Participants</b> 1063 men and women (mean age 78.2 years) who were free of dementia and did not start taking benzodiazepines until at least the third year of follow-up. <b>Main outcome measures</b> Incident dementia, confirmed by a neurologist. <b>Results</b> During a 15 year follow-up, 253 incident cases of dementia were confirmed. New use of benzodiazepines was associated with an increased risk of dementia (multivariable adjusted hazard ratio 1.60, 95% confidence interval 1.08 to 2.38). Sensitivity analysis considering the existence of depressive symptoms showed a similar association (hazard ratio 1.62, 1.08 to 2.43). A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia. The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46 (1.10 to 1.94). Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia (adjusted odds ratio 1.55, 1.24 to 1.95) compared with never users. The results were similar in past users (odds ratio 1.56, 1.23 to 1.98) and recent users (1.48, 0.83 to 2.63) but reached significance only for past users. <b>Conclusions</b> In this prospective population based study, new use of benzodiazepines was associated with increased risk of dementia. The result was robust in pooled analyses across cohorts of new users of benzodiazepines throughout the study and in a complementary case-control study. Considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects of this drug class in the general population, indiscriminate widespread use should be cautioned against.
Independent and inverse association of healthcare utilisation with physical activity in older adults with multiple chronic conditions
Authors: T Y L Liu-Ambrose, M C Ashe, C Marra
Journal: British Journal of Sports Medicine (2008)

In this study, whether physical activity is independently associated with direct healthcare costs in community-dwelling older adults with multiple chronic conditions was examined.Cross-sectional analysis.Research laboratory.299 community-dwelling men and women volunteers aged 65 years and older with chronic conditions.None.Primary dependent variable was direct healthcare costs incurred in the previous 3 months. Participants completed the Health Resource Utilisation (HRU) questionnaire. To estimate HRU, direct costs in the previous 3 months were calculated using the three-party payer perspective of the British Columbia Ministry of Health, deemed representative of the Canadian healthcare system costs. For medications, the Retail Pharmacy Dispensed prescription cost tables were used. Primary independent variables were (1) self-report current level of physical activity as assessed by the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) and (2) general balance and mobility as assessed by the National Institute on Aging Balance Scale.The mean number of chronic conditions per participant was six. Current level of physical activity was independently and inversely associated with HRU. Age, sex, number of chronic conditions, global cognitive function, body mass index, and general balance and mobility together accounted for 24.3% of the total variance. Adding the PASIPD score resulted in an R2 change of 3.3% and significantly improved the model. The total variance accounted by the final model was 27.6%.Physical activity promotion may reduce healthcare costs in older adults with chronic conditions.
Clinical and neuroanatomical predictors of cerebellar mutism syndrome
Authors: N. Law, M. Greenberg, E. Bouffet, M. D. Taylor, S. Laughlin, D. Strother, C. Fryer, D. McConnell, J. Hukin, C. Kaise, F. Wang, D. J. Mabbott
Journal: Neuro-Oncology (2012)

Cerebellar mutism syndrome (CMS) is an important medical challenge in the management of pediatric posterior fossa brain tumors, because it occurs in a subset of children following tumor resection. A definitive clinical profile and neuroanatomical substrate associated with CMS remains unclear. We investigated the relationship between presurgical and clinical variables and the incidence of CMS, along with diffusion tensor imaging, to characterize the integrity of cerebello-thalamo-cerebral white matter pathways. Seventeen children with posterior fossa tumors and CMS, 34 children with posterior fossa tumors without CMS, and 28 healthy children were enrolled in this study. Bilateral cerebello-thalamo-cerebral pathways were delineated and segmented into anatomical regions. Mean integrity measures for each region were compared among children with CMS, children without CMS, and healthy children. Left-handedness, medulloblastoma histology, and larger tumor size distinguished between patients with CMS and patients without CMS (P < .04). Right cerebellar white matter within the cerebello-thalamo-cerebral pathway was compromised in children with CMS relative to children without CMS and healthy children (P < .02). We provide a potential schema for CMS risk among children treated for posterior fossa tumors. Left-handed children treated for medulloblastoma may be the most at risk for CMS, and unilateral, localized damage within the cerebello-thalamo-cerebral pathway at the level of the right cerebellum is implicated in the presentation of CMS. This disruption in communication between the right cerebellum and left frontal cortex may contribute to speech-language problems observed in children with CMS. Our findings may be relevant for surgical planning and speech-language therapy to mitigate symptoms of CMS.
Hypogonadism and Infertility in Testicular Cancer Survivors
Authors: Linda A. Jacobs, David J. Vaughn
Journal: Journal of the National Comprehensive Cancer Network (2012)

Testicular cancer is the most common cancer in men in their 20s and 30s, and has been considered a model of a curable neoplasm. The longer life expectancy of testicular cancer survivors makes minimizing the long-term health issues related to hypogonadism particularly important, and because testicular cancer affects men mostly in their reproductive years, infertility can also be a major concern. Hypogonadism, infertility, and testicular cancer have been associated with one another. These associations suggest the existence of common etiologic factors, including improper testicular development during fetal life. The effect of cancer treatment on testosterone, luteinizing hormone, and follicle-stimulating hormone levels, and on fertility and overall paternity rates among testicular cancer survivors, are potentially significant issues. As the biologic mechanisms underlying hypogonadism, infertility, and testicular cancer become clearer, more research is needed to provide clinicians with evidence-based guidelines for the management of testicular cancer survivors.
Criteria for intraventricular conduction disturbances and pre-excitation
Authors: Jos L. Willems, Etienne O. Robles de Medina, Roland Bernard, Philippe Coumel, Charles Fisch, Dennis Krikler, Nicolai A. Mazur, Frits L. Meijler, Lars Mogensen, Pierre Moret, Zbynek Pisa, Pentti M. Rautaharju, Borys Surawicz, Yoshio Watanabe, Hein J.J. Wellens
Journal: Journal of the American College of Cardiology (1985)
IL1 may be elevated but is it all bad in ARDS
Authors: David R. Thickett, Gavin D. Perkins
Journal: Thorax (2008)

Frank et al have elegantly demonstrated in animal models of ventilator associated lung injury (VALI) that interleukin 1β (IL1β) may play a role in the development of alveolar barrier dysfunction. However, the ventilation strategy used for these experiments (with a very high tidal volume of 30 ml/kg) induced an increase in IL1β of only 36 pg/ml in lavage as opposed to 7 pg/ml in their control animals, a level that in their in vitro models of epithelial resistance and permeability did not significantly affect …
Ectopic Expression of the Proto-oncogene Mer in Pediatric T-Cell Acute Lymphoblastic Leukemia
Authors: Douglas K. Graham, Dana B. Salzberg, Joanne Kurtzberg, Susan Sather, Glenn K. Matsushima, Amy K. Keating, Xiayuan Liang, Mark A. Lovell, Sara A. Williams, Thomas L. Dawson, Michael J. Schell, Adil A. Anwar, H. Ralph Snodgrass, H. Shelton Earp
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The Mer receptor tyrosine kinase, cloned from a B-lymphoblastoid library, is the mammalian orthologue of the chicken retroviral oncogene v-eyk and sends antiapoptotic and transforming signals when activated. To determine if Mer expression is ectopic in T-cell acute lymphoblastic leukemia (ALL) and potentially important in leukemogenesis, we analyzed Mer expression in normal human thymocytes and lymphocytes and in pediatric ALL patient samples. Experimental Design: Reverse transcription-PCR, flow cytometry, and immunohistochemistry were used to determine expression of Mer in sorted human thymocyte populations, lymphocytes, and lymphocytes activated by phytohemagglutinin or phorbol 12-myristate 13-acetate/ionophore. Mer expression in 34 T-cell ALL (T-ALL) patient samples was evaluated by reverse transcription-PCR, and Mer protein expression in a separate cohort of 16 patient samples was assayed by flow cytometry and Western blot. Results: Mer expression was absent in normal thymocytes or lymphocytes, and in T cells activated with phytohemagglutinin or phorbol 12-myristate 13-acetate/ionophore. In contrast, Jurkat cells and T-ALL patient samples expressed unique 180 to 185 kDa Mer protein glycoforms. Substantial Mer RNA levels were principally observed in a subset of T-ALL patient samples that expressed B220 (P = 0.004) but lacked surface expression of CD3 (P = 0.02) and CD4 (P = 0.006), a phenotypic profile consistent with immature lymphoblasts. In addition, 8 of 16 T-ALL patient samples had Mer protein detected by flow cytometry and Western blot. Conclusions: Transforming Mer signals may contribute to T-cell leukemogenesis, and abnormal Mer expression may be a novel therapeutic target in pediatric ALL therapy.
Different localization and regulation of two types of vasopressin receptor messenger RNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction.
Authors: Y Terada, K Tomita, H Nonoguchi, T Yang, F Marumo
Journal: Journal of Clinical Investigation (1993)

Recent studies have revealed that arginine vasopressin (AVP) has at least two types of receptors in the kidney: V1a receptor and V2 receptor. In this study, microlocalization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in the glomerulus, initial cortical collecting duct, cortical collecting duct, outer medullary collecting duct, inner medullary collecting duct, and arcuate artery. Small but detectable signals were found in proximal convoluted and straight tubules, inner medullary thin limbs, and medullary thick ascending limbs. Large signals for V2 receptor mRNA were detected in the cortical collecting duct, outer medullary collecting duct, and inner medullary collecting duct. Small signals for V2 receptor were found in the inner medullary thick limbs, medullary thick ascending limbs, and initial cortical collecting duct. Next, we investigated V1a and V2 receptor mRNA regulation in the dehydrated state. During a 72-h water restriction state, the plasma AVP level increased and V2 receptor mRNA decreased in collecting ducts. In contrast, V1a receptor mRNA did not change significantly. Thus, the two AVP receptor subtypes are distributed differently along the nephron, and these mRNAs are regulated differently in the dehydrated state.
Regional lung function in unilateral diaphragmatic paralysis.
Authors: J B Ridyard, R M Stewart
Journal: Thorax (1976)

Radioactive xenon-133 was used to study the regional lung function of five patients with unilateral diaphragmatic paralysis unassociated with intrathoracic disease. All patients showed a reduction in total lung capacity to which the affected side contributed an average of 37%. There was a decrease in the amount of inhaled xenon and a lesser decrease in the amount of injected xenon reaching the lung base on the paralysed side.The distribution in the opposite lung did not differ significantly from that found in normal subjects although the proportion of inhaled xenon reaching the lung base was rather less than in the normal group. The washout of injected xenon was normal except for slight impairment at the lung base on the paralysed side in one patient and at both bases in another.
Regulation of Renal Sodium Transporters during Severe Inflammation
Authors: Christoph Schmidt, Klaus Ho[Combining Diaeresis]cherl, Frank Schweda, Armin Kurtz, Michael Bucher
Journal: Journal of the American Society of Nephrology (2007)

Sepsis-associated acute renal failure is characterized by decreased GFR and tubular dysfunction. The pathogenesis of endotoxemic tubular dysfunction with failure in urine concentration and increased fractional sodium excretion is poorly understood. This study investigated the regulation of renal sodium transporters during severe inflammation in vivo and in vitro. Injection of high-dosage LPS reduced BP and GFR, increased fractional sodium excretion, and strongly decreased the expression of Na(+)/H(+)-exchanger, renal outer medullary potassium channel, Na(+)-K(+)-2Cl(-) co-transporter, epithelial sodium channel, and Na(+)/K(+)-ATPase in mice. Also, injection of TNF-alpha, IL-1beta, or IFN-gamma decreased renal function and expression of renal sodium transporters. LPS-induced downregulation of sodium transporters was not affected in cytokine-knockout mice. However, supplementary glucocorticoid treatment, which inhibited LPS-induced increase of tissue cytokine concentrations, attenuated LPS-induced renal dysfunction and downregulation of tubular sodium transporters. Injection of low-dosage LPS increased renal tissue cytokines and downregulated renal sodium transporters without arterial hypotension. In vitro, in cortical collecting duct cells, cytokines also decreased expression of renal outer medullary potassium channel, epithelial sodium channel, and Na(+)/K(+)-ATPase. Renal hypoperfusion by renal artery clipping did not influence renal sodium transporter expression, in contrast to renal ischemia-reperfusion injury, which depressed transporter expression. These findings demonstrate downregulation of renal sodium transporters that likely accounts for tubular dysfunction during inflammation. These data suggest that alteration of renal sodium transporters during LPS-induced acute renal failure is mediated by cytokines rather than renal ischemia. However, in a complex in vivo model of severe inflammation, the possible presence and influence of renal hypoperfusion and reperfusion on the expression of renal sodium transporters cannot be completely excluded.
R<scp>OUGH AND</scp> R<scp>OCKY</scp> R<scp>OAD TO THE</scp> R<scp>ETINOID</scp> R<scp>EVOLUTION</scp>
Authors: Frank Chytil
Journal: Annual Review of Nutrition (2003)

▪ Abstract Some of us who were born in the middle of Europe between World Wars I and II had to face quite a few unusual challenges that we all met in different ways. I was born and raised in Prague, Czechoslovakia, a country at the time of my birth that was governed by a Western style of democracy, which was later destroyed by the occupation by Nazi Germany and subsequently by the takeover by the equally cruel Communists. Life required special means of adaptation to the changing living conditions and a great deal of luck to survive. After graduating from the School of Technology, I started working in the Department of Medicine at Charles University in Prague as a clinical chemist in endocrinology. This work was followed with training in basic biochemistry and the study of metabolic changes in stress. This rather diversified research, due to my changing of workplaces, led to the findings that diet can change enzymatic activity of liver tryptophan oxygenase. For a short time I worked on the metabolism of cyclic AMP in Escherichia coli, and at the age of 41, I made a risky move and succeeded in escaping with my family from the “paradise of communism.” The reasons for this decision will become clear. After settling in the United States, I worked on the mechanism of activation of liver tryptophan oxygenase by cyclic AMP and eventually moved to the Vanderbilt University School of Medicine. There I initially worked on the mechanism of action of steroid hormones and finally on the molecular mechanism of action of retinoids, retinol, and retinoic acid. Also in cooperation with neonatologists, I initiated studies on prematurely born human neonates which led to successful supplementation of these patients with vitamin A. The work from my laboratory and my coworkers eventually became recognized. “Who does not remember the past, is condemned to repeat it.” George Santayana (1863–1952)