tbuckley/cabot-search huggingface dataset:
Gefitinib monotherapy in advanced nonsmall cell lung cancer: a large Western community implementation study
Authors: R. van Puijenbroek, L. Bosquée, A-P. Meert, D. Schallier, J-C. Goeminne, G. Tits, P. Collard, K. Nackaerts, J-L. Canon, F. Duplaquet, D. Galdermans, P. Germonpré, M-A. Azerad, G. Vandenhoven, J. De Greve, J. Vansteenkiste
Journal: European Respiratory Journal (2006)

Epidermal growth factor receptor tyrosine kinase inhibitors represent a new treatment option for patients with advanced nonsmall cell lung cancer (NSCLC). This retrospective study examined to what extent previous clinical trial experience matches large-scale Western community implementation of this treatment. In the Belgian expanded access programme, the data from 513 patients with advanced or metastatic NSCLC, not suitable for further chemotherapy and receiving oral gefitinib 250 mg.day(-1) until disease progression, death or unacceptable toxicity, were analysed. The median (range) duration of gefitinib treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or third-line treatment. The overall response and disease control rates were 8.9 and 41.2%, respectively. In univariate analysis, response was more common in females and never-smokers. In multivariate analysis, female sex was the only significant predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129-0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%) progressed. Gefitinib was well tolerated; only 7.8% of the patients reported grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr survival rate of 21%. Survival was strongly influenced by a better performance status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI) 0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in the present large Western community implementation study. Response, present in a small subgroup, led to a rewarding survival and could be predicted by sex only. Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma features histology were significant factors for survival.
Impairment in Pure and Comorbid Generalized Anxiety Disorder and Major Depression at 12 Months in Two National Surveys
Authors: Ronald C. Kessler, Robert L. DuPont, Patricia Berglund, Hans-Ulrich Wittchen
Journal: American Journal of Psychiatry (1999)

Generalized anxiety disorder might be better conceptualized as a prodrome, residual, or severity marker of major depression or other comorbid disorders than as an independent diagnosis. The authors questioned whether generalized anxiety disorder itself is associated with role impairment or whether the impairment of patients with generalized anxiety disorder is due to depression or other comorbid disorders.The authors assessed data from the National Comorbidity Survey and the Midlife Development in the United States Survey for generalized anxiety disorder and major depression at 12 months by using the DSM-III-R criteria with modified versions of the Composite International Diagnostic Interview.The prevalences of generalized anxiety disorder at 12 months were 3.1% and 3.3%, respectively, in the National Comorbidity Survey and the Midlife Development in the United States Survey; the prevalences of major depression at 12 months were 10.3% and 14.1%. The majority of respondents with generalized anxiety disorder at 12 months in the National Comorbidity Survey (58.1%) and the Midlife Development in the United States Survey (69.7%) also met the criteria for major depression at 12 months. Comparisons of respondents with one versus neither disorder showed that both disorders had statistically significant independent associations with impairment that were roughly equal in magnitude. These associations could not be explained by the other comorbid DSM-III-R disorders or by sociodemographic variables.These results show that a substantial amount of generalized anxiety disorder occurs independently of major depression and that the role impairment of generalized anxiety disorder is comparable to that of major depression.
Exercise testing in pulmonary arterial hypertension and in chronic heart failure
Authors: G. Deboeck, G. Niset, M. Lamotte, J‐L. Vachiéry, R. Naeije
Journal: European Respiratory Journal (2004)

Exercise capacity is reduced in pulmonary arterial hypertension and in chronic left heart failure, but it is not known whether the cardiopulmonary exercise testing profile is different in the two conditions at the same severity of functional limitation. Nineteen patients with pulmonary arterial hypertension and 19 with chronic heart failure underwent a 6‐min walk test and symptom-limited maximal incremental cycle ergometry. The patients with pulmonary arterial hypertension and chronic heart failure did not differ in New York Heart Association Functional Class (mean±sem 2.8±0.1 versus 2.8±0.2), 6‐min walking distance (395±30 versus 419±20 m), peak work-rate, oxygen consumption, ventilation and cardiac frequency. However, patients with pulmonary arterial hypertension exhibited higher dyspnoea scores (5.8±0.6 versus 3.8±0.5) higher ventilatory equivalents for carbon dioxide (58±3 versus 44±3 at the anaerobic threshold) and lower peak oxygen pulse (5.9±0.4 versus 8.7±0.5 mL·beat −1 , or 53±4 versus 64±4% of the predicted value). It is concluded that the cardiopulmonary exercise testing profile in pulmonary arterial hypertension differs from that in chronic heart failure by showing more dyspnoea at comparable work-rates, related to greater reductions in ventilatory efficiency and stroke volume.
Increased interleukin (IL)-7Rα expression in salivary glands of patients with primary Sjögren's syndrome is restricted to T cells and correlates with IL-7 expression, lymphocyte numbers and activity
Authors: A Bikker, A A Kruize, M Wenting, M A Versnel, J W J Bijlsma, F P J G Lafeber, J A G van Roon
Journal: Annals of the Rheumatic Diseases (2012)

To identify interleukin (IL)-7Rα expression in the labial salivary gland (LSG) of patients with primary Sjögren's syndrome (pSS) and non-Sjögren's syndrome sicca (nSS-sicca) and to study its correlation with glandular inflammation and IL-7 expression.The presence of infiltrating immune cells and IL-7Rα cells in inflamed LSG of patients with pSS (n=12) and nSS-sicca controls (n=7) was studied by immunohistochemistry and fluorescence activated cell sorting analysis upon tissue digestion (n=15 and n=13, respectively). Additionally, the correlations of IL-7Rα cells with hallmark disease parameters of pSS, major infiltrating inflammatory cells and IL-7 were assessed.In the LSG of patients with pSS increased numbers of IL-7Rα cells were found as compared with nSS-sicca patients. IL7Rα cells strongly correlated with the lymphocytic focus score, IL-7 expression, the decrease in percentage of IgA plasma cells and numbers of CD3 T cells, CD20 B cells, and CD1a and CD208 myeloid dendritic cells. Analysis of isolated cells from the LSG demonstrated strongly increased percentages of IL-7Rα CD3 T cells in pSS as compared with nSS, showing abundant IL-7Rα expression on both CD4 and CD8 T cells. Other CD45 leucocytes and CD45- tissue cells scarcely expressed IL-7Rα. Percentages of IL-7Rα T cells also significantly correlated with glandular inflammation.This study shows the presence of increased IL-7Rα T cells in the LSG of patients with pSS and their association with the severity of sialadenitis, disease parameters and IL-7 expression. Considering the immunostimulatory ability of IL-7Rα T cells and IL-7, this suggests that IL-7(R)-dependent T cell-driven immune activation plays an important role in inflammation in pSS.
Hormonal Control of Collateral Circulation
Authors: William Meffert, Averill A. Liebow
Journal: Circulation Research (1966)

The possible regulatory effects of growth hormone and of cortisone on the development of pulmonary collateral vessels after ligation of one pulmonary artery were investigated in the rat. The weights of the animals were regulated so that they did not differ significantly in the control and experimental groups at the end of the experiment. The extent of the collateral circulation was judged by visual inspection and by weighing the casts. Animals injected with cortisone acetate intramuscularly in doses of 5 mg daily for two weeks and then maintained on an average dose of 15 mg weekly, had less development of collateral circulation at four and eight weeks than did controls. Animals injected with growth hormone in doses of 0.1 mg daily, had significantly larger collaterals than did controls at eight but not at four weeks, as determined by the visual ranking method. These results indicate 1) that there can be chemical control of collateral circulation, and 2) that cortisone and growth hormone can influence the development of collateral vessels in part by mechanisms other than an effect on body weight.
Fibronectin receptor of human macrophages recognizes the sequence Arg-Gly-Asp-Ser.
Authors: S D Wright, B C Meyer
Journal: The Journal of Experimental Medicine (1985)

When cultured human monocytes (MO) were spread on fibronectin (Fn)-coated surfaces, C3 receptors on the MO exhibited markedly enhanced capacity to promote phagocytosis. The activation of C3 receptors by Fn was mediated by a receptor that recognizes a sequence, Arg-Gly-Asp-Ser (RGDS), present in the cell-binding domain of Fn. Soluble, RGDS-containing peptides inhibited the activation of C3 receptors caused by surface-bound Fn, and surface-bound, RGDS-containing peptides themselves caused activation of the C3 receptors of attached MO. Although soluble, RGDS-containing peptides bound to Fn receptors, such monovalent ligation was insufficient to activate C3 receptors.
Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow
Authors: K. J. Selvaggi, J. W. Wilson, L. E. Mills, G. G. Cornwell, D. Hurd, W. Dodge, R. Gingrich, S. E. Martin, R. McMillan, W. Miller, E. D. Ball
Journal: Blood (1994)
Enteric Fever Commencing with and Complicated by an Attack of Influenza
Authors: J. C. Potter
Journal: BMJ (1901)

commissure for about half-an-inch antero-posteriorly, Ixl inch in both the vertical and transvere diameters.It was a round-celled sarcoma.The lateral ventricles were muclh distended with clear fluid owing to the pressure on the-aqueduct.
Screening for Diabetes
Authors: Beverley Balkau
Journal: Diabetes Care (2008)

teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.Screening for diabetes.
Five-Year Risk of Cardiac Mortality in Relation to Initial Severity and One-Year Changes in Depression Symptoms After Myocardial Infarction
Authors: François Lespérance, Nancy Frasure-Smith, Mario Talajic, Martial G. Bourassa
Journal: Circulation (2002)

Background — Although previous research demonstrated an independent link between depression symptoms and cardiac mortality after myocardial infarction (MI), depression was assessed only once, and a dose-response relationship was not evaluated. Methods and Results — We administered the Beck Depression Inventory to 896 post-MI patients during admission and at 1 year. Five-year survival was ascertained using Medicare data. We observed a significant long-term dose-response relationship between depression symptoms during hospitalization and cardiac mortality. Results remained significant after control for multiple measures of cardiac disease severity. Although 1-year scores were also linked to cardiac mortality, most of that impact was explained by baseline scores. Improvement in depression symptoms was associated with less cardiac mortality only for patients with mild depression. Patients with higher initial scores had worse long-term prognosis regardless of symptom changes. Conclusions — The level of depression symptoms during admission for MI is more closely linked to long-term survival than the level at 1 year, particularly in patients with moderate to severe levels of depression, suggesting that the presumed cardiovascular mechanisms linking depression to cardiac mortality may be more or less permanent for them.
Experimental myocardial infarction in the cat. I. Reversible decline in contractility of noninfarcted muscle.
Authors: P Mathes, D Romig, D Sack, W Erhardt
Journal: Circulation Research (1976)

The contractile state of the noninfarcted myocardium was examined in adult cats after myocardial infarction produced by ligation of several branches of the left coronary artery. At 2 days, 7 days, and 6 weeks after infarction, and after determination of intracardiac pressures, papillary muscles were exicised from the noninfarcted segment of the right ventricle and attached to a myograph for analysis of contractile function. One week after infarction there was a decline in actively developed force at Lmax, caused by a decrease in the rate of force development. In addition, the response to procedures that augment myocardial contractility, such as paired stimulation and increasing the frequency of electrical stimulation, was significantly depressed. Two days after infarction, changes were less significant, although similar in direction. Six weeks after infarction, developed force at Lmax had returned to normal values. The response to procedures augmenting contractility also had returned to normal. There appears to be a distinct, reversible loss of contractility in the remaining viable myocardium in the early phase after experimental infarction.
Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects.
Authors: S Domschke, W Domschke, S R Bloom, P Mitznegg, S J Mitchell, G Lux, U Strunz
Journal: Gut (1978)

Graded doses of 0.6, 1.3, and 3.3 pmol/kg/min of vasoactive intestinal peptide (VIP) were intravenously infused over 30 minute periods in four healthy volunteers and plasma VIP levels were measured by radioimmunoassay. Even with the smallest dose of VIP, plasma concentrations rose markedly above normal values. Infusion of higher VIP doses resulted in mean plateau levels of circulating VIP which were in the range of VIP values found in the Verner-Morrison syndrome. After cessation of the VIP infusions, plasma VIP levels fell strikingly by first order kinetics with an average disappearance half-time of one minute. The apparent metabolic clearance rate was about 9 ml/kg/min and the apparent volume of distribution for VIP was approximately 14 ml/kg. During infusion of the highest VIP dose, previously shown to induce one-fifth maximum pancreatic juice secretion, plasma concentrations of glucose, free fatty acids, and calcium were slightly but significantly raised, the pulse rate and the amplitude of blood pressure were increased, and cutaneous flushing occurred. The spectrum of effects accords well with some abnormalities seen in the Verner-Morrison syndrome. The present data, however, do not support a role for VIP as a circulating hormone, at least under physiological conditions.
A Phase I and Pharmacokinetic Trial of Erlotinib in Combination with Weekly Docetaxel in Patients with Taxane-Naive Malignancies
Authors: E. Gabriela Chiorean, Jennifer M. Porter, Anne E. Foster, Amal S.H. Al Omari, Christy A. Yoder, Karen L. Fife, R. Matthew Strother, Daryl J. Murry, Menggang Yu, David R. Jones, Christopher J. Sweeney
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study aimed to define the maximum tolerated dose of weekly docetaxel combined with daily erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor. Experimental Design: Patients with any solid tumor received 150 mg erlotinib with escalating doses of docetaxel (20, 25, 30, and 35 mg/m2) on days 1, 8, and 15 every 28 days. The pharmacokinetics of docetaxel and erlotinib was determined on cycle 2, day 1. Erlotinib was given for a maximum of 12 cycles and docetaxel was given for up to 6 cycles. Results: Twenty-five patients (17 males and 8 females) were enrolled with a median age of 56 years (range, 34-76); Eastern Cooperative Oncology Group performance status of 0/1 was 20/5. One patient had a dose-limiting toxicity in cycle 1 at the 25 mg/m2 level (grade 3 enterocolitis). At 35 mg/m2 docetaxel dose level, 6 of 10 patients required dose reductions to 30 mg/m2 beyond cycle 1 due to neutropenia (3 patients) and mucositis, increased bilirubin, and diarrhea (1 patient each). The clearance of docetaxel and erlotinib of 61.7 and 8.16 L/h, respectively, did not seem to differ from historical controls. Responses were seen in non–small cell lung cancer, prostate cancer, and hepatobiliary cancers, including a complete response lasting 36+ months in a patient with hepatocellular carcinoma. Conclusion: Although no maximum tolerated dose was reached in cycle 1 with 35 mg/m2 docetaxel, repetitive dosing proved intolerable in a substantial number of patients; thus, the recommended phase II dose of weekly docetaxel is 30 mg/m2 when combined with 150 mg of daily erlotinib.
Early and late allergic reaction in the nose assessed by whole body plethysmography
Authors: MS de Bruin-Weller, FR Weller, A Scholte, LH Rijssenbeek, S van der Baan, JM Bogaard, JG de Monchy
Journal: European Respiratory Journal (1996)

Physiological changes during late phase nasal responses after allergen challenge are difficult to establish and different criteria are used for the definition of a positive late phase nasal reaction. The objective of this study was to assess the value of whole body plethysmography in detecting changes in nasal airway resistance after allergen challenge and to suggest criteria for the definition of early and late phase nasal reactions. Nasal challenge with allergen was performed in 15 allergic patients. Nasal resistance was followed until 10 h after allergen challenge and on a control day using whole body plethysmography. The mean percentage changes in the inspiratory nasal resistance during the early phase period (0.25-2 h) and the late phase period (4-10 h) were significantly higher on the allergen challenge day than on the control day (p=0.001 and p=0.01, respectively). The mean percentage change in the inspiratory nasal resistance during the early and late phase period on the control day plus 2 times the standard deviation served as cut-off point for a positive reaction. Using this definition, all patients had early reactions and 7 of the 15 patients (47%) also had late reactions. We conclude that whole body plethysmography is a useful, noninvasive method for the measurement of the physiological changes in the nose following allergen challenge.
Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse
Authors: Joseph C. Cheng, Aiping Bai, Thomas H. Beckham, S. Tucker Marrison, Caroline L. Yount, Katherine Young, Ping Lu, Anne M. Bartlett, Bill X. Wu, Barry J. Keane, Kent E. Armeson, David T. Marshall, Thomas E. Keane, Michael T. Smith, E. Ellen Jones, Richard R. Drake, Alicja Bielawska, James S. Norris, Xiang Liu
Journal: Journal of Clinical Investigation (2013)

Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy.
Infrequent Detection of Germline Allele-Specific Expression of TGFBR1 in Lymphoblasts and Tissues of Colon Cancer Patients
Authors: Kishore Guda, Leanna Natale, James Lutterbaugh, Georgia L. Wiesner, Susan Lewis, Stephan M. Tanner, Jerneja Tomsic, Laura Valle, Albert de la Chapelle, Robert C. Elston, Joseph Willis, Sanford D. Markowitz
Journal: Cancer Research (2009)

Recently, germline allele-specific expression (ASE) of the gene encoding for transforming growth factor-beta type I receptor (TGFBR1) has been proposed to be a major risk factor for cancer predisposition in the colon. Germline ASE results in a lowered expression of one of the TGFBR1 alleles (>1.5-fold), and was shown to occur in approximately 20% of informative familial and sporadic colorectal cancer (CRC) cases. In the present study, using the highly quantitative pyrosequencing technique, we estimated the frequency of ASE in TGFBR1 in a cohort of affected individuals from familial clusters of advanced colon neoplasias (cancers and adenomas with high-grade dysplasia), and also from a cohort of individuals with sporadic CRCs. Cases were considered positive for the presence of ASE if demonstrating an allelic expression ratio <0.67 or >1.5. Using RNA derived from lymphoblastoid cell lines, we find that of 46 informative Caucasian advanced colon neoplasia cases with a family history, only 2 individuals display a modest ASE, with allelic ratios of 1.65 and 1.73, respectively. Given that ASE of TGFBR1, if present, would likely be more pronounced in the colon compared with other tissues, we additionally determined the allele ratios of TGFBR1 in the RNA derived from normal-appearing colonic mucosa of sporadic CRC cases. We, however, found no evidence of ASE in any of 44 informative sporadic cases analyzed. Taken together, we find that germline ASE of TGFBR1, as assayed in lymphoblastoid and colon epithelial cells of colon cancer patients, is a relatively rare event.