tbuckley/cabot-search huggingface dataset:
Progressive static pulmonary hyperinflation in survivors of severe bronchopulmonary dysplasia by mid-adulthood
Authors: Daniel Trachsel, Martin H Brutsche, Henriette Hug-Batschelet, Jürg Hammer
Journal: Thorax (2011)

Severe bronchopulmonary dysplasia (BPD) might be associated with an accelerated age-related decline of lung function.14 individuals were studied longitudinally at 15±4, 18±3 and 38±3.2 years. Information on personal history was completed, and lung function testing and skin prick testing were performed. Longitudinal data were compared intra-individually and with matched controls from the NHANES III dataset.The ratio of residual volume/total lung capacity (RV/TLC) increased markedly from 25.9±7.0% to 39.3±6.8%. A significant time-effect was found compared to controls for the forced vital capacity (FVC) which decreased more rapidly than expected. Flow values were at the lower limit of normal range but remained relatively stable over time. Some individuals had completely normal lung function results.Increasing static pulmonary hyperinflation with age is indicative of bronchiolar dysfunction or early emphysematous changes in survivors of severe BPD. Susceptibility for long-term sequelae shows significant variability.
A measure of limited joint motion and deformity correlates with HLA-DRB1 and DQB1 alleles in patients with rheumatoid arthritis
Authors: A. Cranney, R. Goldstein, B. Pham, M. M Newkirk, J. Karsh
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To assess factors associated with a poor outcome in rheumatoid arthritis (RA), a measure was developed of limited joint motion and deformity, a deformity index (DI), and correlated biochemical and genetic variables with the magnitude of the DI. <h3>METHODS</h3> Forty patients were evaluated in a cross sectional study. Clinical measures included the DI and Health Assessment Questionnaire, and disease variables included the erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and HLA-DRB1 and DQB1 alleles. <h3>RESULTS</h3> Significant correlations were noted between increasing DI and duration of RA and concentration of C reactive protein. Patients with a DQB1*301 allele or DR4 allele had a higher DI than those without, and a positive trend was noted between increasing DI and dose of DRB1 RA susceptibility alleles. The trend was lost when a non-linear regression technique was used to remove the effect attributable to C reactive protein, suggesting an interrelation between persistent inflammation and genetics in determining total joint damage. <h3>CONCLUSIONS</h3> The DI may be useful to study interactions between genetic and inflammatory processes in rheumatoid disease progression.
Capsaicin cough sensitivity in bronchiectasis
Authors: A Torrego
Journal: Thorax (2006)

Bronchiectasis is a suppurative airway disease characterised by persistent cough and sputum production associated with bronchial dilatation. A study was undertaken to determine whether cough sensitivity is increased in bronchiectatic patients.Twenty two patients with bronchiectasis and 20 healthy non-smoking controls matched for age and sex were recruited into the study. Quality of life (Leicester Cough Questionnaire score), total cough symptom score, and extent of bronchiectasis on HRCT scans were recorded. Cough sensitivity was assessed using incremental inhalation of capsaicin concentrations; the concentration at which 5 or more coughs occurred (C5) was recorded.Patients with bronchiectasis had increased sensitivity to capsaicin compared with controls (mean (SE) log10 C5 1.22 (0.20) v 1.89 (0.21); p<0.03). Capsaicin sensitivity correlated positively with the Leicester Cough Questionnaire score (r = 0.64; p = 0.005) and inversely with the total cough symptom score (r = -0.58; p = 0.004), but not with the extent of the disease. It also correlated with forced expiratory volume in 1 second (FEV1) in litres (r = 0.58; p = 0.005) but not with FEV1 % predicted. Capsaicin sensitivity was not related to the presence of infected sputum or to corticosteroid or bronchodilator use.: Patients with bronchiectasis have a sensitive cough reflex which reflects the severity of cough symptoms. A measure of cough severity could be part of health assessment for patients with bronchiectasis.
Effects of cardiac resynchronization therapy on coronary blood flow: Evaluation by transthoracic Doppler echocardiography☆
Authors: Cinzia Valzania, Fredrik Gadler, Reidar Winter, Frieder Braunschweig, Lars‐Åke Brodin, Petri Gudmundsson, Giuseppe Boriani, Maria J. Eriksson
Journal: European Journal of Heart Failure (2008)
Erectile dysfunction in diabetic subjects in Italy. Gruppo Italiano Studio Deficit Erettile nei Diabetici.
Authors: D Fedele, C Coscelli, F Santeusanio, A Bortolotti, L Chatenoud, E Colli, M Landoni, F Parazzini
Journal: Diabetes Care (1998)

OBJECTIVE: Our objective was to analyze the prevalence and risk factors for erectile dysfunction (ED) in men with diabetes in Italy in a cross-sectional study. RESEARCH DESIGN AND METHODS: Eligible for the study were men aged 20-69 years with a diagnosis of IDDM or NIDDM who were observed on randomly selected days in 178 diabetes centers in Italy. ED was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: Of the 9,868 diabetic men interviewed, 3,534 (35.8%) reported ED. The prevalence increased with age, from 4.6% in men aged 20-29 to 45.5% in those aged &amp;gt; or =60 years (test for trend, P = 0.0001). After taking into account the confounding role of age, men with NIDDM reported ED less frequently than did men with IDDM (odds ratio [OR], 0.7; 95% CI 0.6-0.8). In comparison with men reporting diabetes lasting &amp;lt; or =5 years, the ORs for ED were 1.3 and 2.0 for subjects with diabetes lasting 6-10 and 11-30 years, respectively. In comparison with men with good metabolic control, the ORs for ED were 1.7 and 2.3 in men with fair and poor control, respectively. A history of diabetes-related arterial, retinal, or renal diseases and neuropathy was associated with an increased risk of ED. Finally, in comparison with never-smokers, the ORs for ED were 1.5 (95% CI 1.3-1.6) for current smokers and 1.4 (95% CI 1.3-1.6) for ex-smokers. The OR increased with number of cigarettes smoked per day: in comparison with men smoking &amp;lt;12 cigarettes per day, the OR was 1.5 (95% CI 1.3-1.7) for those smoking &amp;gt; or =30 cigarettes day. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and of its main risk factors in Italian men with diabetes.
Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells
Authors: Svenja Steinfelder, Stefan Floess, Dirk Engelbert, Barbara Haeringer, Udo Baron, Laura Rivino, Bodo Steckel, Andreas Gruetzkau, Sven Olek, Jens Geginat, Jochen Huehn, Alf Hamann
Journal: Blood (2011)
Total smoking ban best way to narrow health gap between rich and poor, MPs told
Authors: Adrian O'Dowd
Journal: BMJ (2005)

Doctors have warned MPs that anything less than a full ban on smoking in public places is unacceptable if the country is to fight the deadly effects of secondhand smoke.

Representatives of the Royal College of Physicians, giving evidence last week to the health select committee, underlined the futility of the government's plan for partially banning smoking.

Speaking at the first evidence session of the committee inquiry into smoking in public places, doctors said nothing but a full ban would be good enough to help prevent strokes, heart disease, lung cancer, and chronic bronchitis. …
p27 Kip1 and Cyclin E Expression and Breast Cancer Survival After Treatment With Adjuvant Chemotherapy
Authors: Peggy L. Porter, William E. Barlow, I-Tien Yeh, Ming Gang Lin, Xiaopu P. Yuan, Elizabeth Donato, George W. Sledge, Charles L. Shapiro, James N. Ingle, Charles M. Haskell, Kathy S. Albain, James M. Roberts, Robert B. Livingston, Daniel F. Hayes
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Abnormal expression of the cell cycle regulatory proteins p27 Kip1 (p27) and cyclin E may be associated with breast cancer survival and relapse. We studied these markers in a clinical trial setting with patients with breast cancer treated by a uniform drug regimen so that treatment was not associated with variability in outcome. Methods: We used tissue microarrays to evaluate the expression of p27 and cyclin E proteins by immunohistochemistry in tumor tissue from 2123 (68%) of 3122 patients with moderate-risk primary breast cancer who were enrolled in Southwest Oncology Group–Intergroup Trial S9313, in which patients were assigned to receive doxorubicin and cyclophosphamide administered concurrently (n = 1595) or sequentially (n = 1527). Disease-free and overall survival were equivalent in the two arms. Expression of the proteins was rated on a scale of 1–7, and the median value was used as the cut point. Log-rank tests and Cox regression analyses were used to assess associations with survival. Overall survival was defined as time to death from all causes; disease-free survival was defined as time to recurrence or death. All P values were from two-sided statistical tests. Results: Lower p27 expression was associated with worse overall survival (unadjusted hazard ratio [HR] = 1.50, 95% confidence interval [CI] = 1.21 to 1.86) and disease-free survival (unadjusted HR = 1.31, 95% CI = 1.10 to 1.57) than higher p27 expression. Among hormone receptor–positive patients, lower p27 expression was associated with worse overall survival (HR = 1.42, 95% CI = 1.05 to 1.94) and worse disease-free survival (HR = 1.27, 95% CI = 0.99 to 1.63) than higher p27 expression after adjustment for treatment, menopausal status, tumor size, and number of positive lymph nodes. Among these patients, 5-year overall survival associated with higher p27 expression (0.91, 95% CI = 0.89 to 0.93) was similar to that associated with lower p27 expression (0.85, 95% CI = 0.82 to 0.87). No association between p27 expression and survival was found in hormone receptor–negative patients. Cyclin E expression was not statistically significantly associated with overall survival (HR = 1.12, 95% CI = 0.91 to 1.38) or disease-free survival (HR = 1.09, 95% CI = 0.92 to 1.29). Conclusions: Low p27 expression appears to be associated with poor prognosis, especially among patients with steroid receptor–positive tumors.
Feasibility of sentinel lymph node biopsy in multiple unilateral synchronous breast cancer: results of a French prospective multi-institutional study (IGASSU 0502)
Authors: S. Giard, M.-P. Chauvet, N. Penel, H. Mignotte, P. Martel, C. Tunon de Lara, P. Gimbergues, P. Dessogne, J.-M. Classe, E. Fondrinier, T. Marmousez
Journal: Annals of Oncology (2010)
EXPERIMENTAL STUDIES ON ENCEPHALITIS
Authors: Leslie T. Webster, Anna D. Clow, Johannes H. Bauer
Journal: The Journal of Experimental Medicine (1935)

Anopheles quadrimaculatus mosquitoes, fed on mice in which encephalitis virus (St. Louis type) is present in the blood stream, take up and retain the virus for the duration of their lives. The titre of the virus in mosquitoes 4 hours after engorging on mice with a maximum blood stream infection represents about 10,000 lethal mouse intracerebral doses per mosquito. This titre drops during the following 2 weeks to about 100 lethal doses per mosquito, but from the 3rd week to the death of the mosquito, usually increases to approximately the original level and remains there. The titre of virus in mosquitoes which have engorged on mouse blood containing smaller quantities of virus exhibits the same drop and subsequent rise to the original level. The virus-containing mosquitoes did not infect mice or monkeys by biting.
SWINE INFLUENZA
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1934)

A strain of swine influenza has been observed to change from a condition of full contagiousness, in which both H. influenzae suis and the swine influenza virus were transferred by pen contact, to one of only partial contagiousness, in which the virus alone was transferred, resulting in the mild filtrate disease instead of swine influenza in animals infected by contact. Swine that had been experimentally converted into carriers of H. influenzae suis developed swine influenza following contact with animals infected with the altered strain of the disease. Experiments in which the etiological components of a freshly obtained and fully contagious strain of swine influenza were substituted for the corresponding components of the altered strain of the disease revealed the fact that the change in the contagious character of the latter was due to an alteration in the bacterial component of the etiological complex and that the virus component was in no way responsible.
Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1)
Authors: A WILSON, K QUINN, F GRAVES, M BITNERGLINDZICZ, A TINKER
Journal: Cardiovascular Research (2005)

In the hereditary long QT syndromes the commonest defect is in the K+ channel pore forming subunit, KCNQ1. In this study we investigated the role that abnormal KCNQ1 trafficking has in the pathogenesis of the hereditary long QT syndrome (LQT1).We introduced nine missense and nonsense mutations occurring in LQT1 into the cDNA encoding KCNQ1 fused in frame to the green fluorescent protein. These mutations occur in syndromes that are inherited in both autosomal dominant and recessive fashions. We used biochemistry, electrophysiology and cell imaging to examine the behaviour of wildtype and mutant channel subunits expressed together with the auxiliary subunit KCNE1 expressed in CHO-K1 and C2C12 cells.We found that a number of mutations in KCNQ1 are retained in the endoplasmic reticulum and unable to translocate to the plasma membrane. Furthermore, some mutations act in a dominant negative fashion and have the ability to suppress the trafficking of wildtype channel. We use fluorescence resonance energy transfer microscopy to show that this occurs because of direct interaction between the mutant subunit and wildtype channel in the endoplasmic reticulum. Finally, a number of specific and nonspecific pharmacological tools are unable to promote the delivery of these mutants to the plasma membrane.Our data revealed that channel trafficking may contribute to the pathogenesis of LQT1.
Cutaneous B‐cell lymphomas: 2013 update on diagnosis, risk‐stratification, and management
Authors: Ryan A. Wilcox
Journal: American Journal of Hematology (2012)

Abstract Disease overview : Approximately one‐fourth of cutaneous lymphomas are B‐cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle‐center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCLBCL, LT). Diagnosis : Diagnosis and disease classification is based on histologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B‐cell lymphomas from systemic B‐cell lymphomas with secondary skin involvement. Risk‐stratification : Disease histology remains the most important prognostic determinant. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with an excellent long‐term prognosis. In contrast, PCLBCL, LT is an aggressive lymphoma with an inferior prognosis. Risk‐adapted therapy : PCFCL and PCMZL patients with solitary or relatively few skin lesions may be affectively managed with local radiation therapy. Although single‐agent rituximab may be employed for patients with more widespread skin involvement, multiagent chemotherapy is rarely appropriate. In contrast, management of patients with PCLBCL, LT is comparable to the management of patients with systemic DLBCL. © Am. J. Hematol. 2013. © 2012 Wiley Periodicals, Inc.
Pancreatic Insulinomas in Multiple Endocrine Neoplasia, Type I Knockout Mice Can Develop in the Absence of Chromosome Instability or Microsatellite Instability
Authors: Peter C. Scacheri, Alyssa L. Kennedy, Koei Chin, Meghan T. Miller, J. Graeme Hodgson, Joe W. Gray, Stephen J. Marx, Allen M. Spiegel, Francis S. Collins
Journal: Cancer Research (2004)

Abstract Multiple endocrine neoplasia, type I (MEN1) is an inherited cancer syndrome characterized by tumors arising primarily in endocrine tissues. The responsible gene acts as a tumor suppressor, and tumors in affected heterozygous individuals occur after inactivation of the wild-type allele. Previous studies have shown that Men1 knockout mice develop multiple pancreatic insulinomas, but this occurs many months after loss of both copies of the Men1 gene. These studies imply that loss of Men1 is not alone sufficient for tumor formation and that additional somatic genetic changes are most likely essential for tumorigenesis. The usual expectation is that such mutations would arise either by a chromosomal instability or microsatellite instability mechanism. In a study of more then a dozen such tumors, using the techniques of array-based comparative genomic hybridization, fluorescent in situ hybridization, loss of heterozygosity analysis using multiple microsatellite markers across the genome, and real time PCR to assess DNA copy number, it appears that many of these full-blown clonal adenomas remain remarkably euploid. Furthermore, the loss of the wild-type Men1 allele in heterozygous Men1 mice occurs by loss and reduplication of the entire mutant-bearing chromosome. Thus, the somatic genetic changes that are postulated to lead to tumorigenesis in a mouse model of MEN1 must be unusually subtle, occurring at either the nucleotide level or through epigenetic mechanisms.
Telomerase-Dependent Oncolytic Adenovirus Sensitizes Human Cancer Cells to Ionizing Radiation via Inhibition of DNA Repair Machinery
Authors: Shinji Kuroda, Toshiya Fujiwara, Yasuhiro Shirakawa, Yasumoto Yamasaki, Shuya Yano, Futoshi Uno, Hiroshi Tazawa, Yuuri Hashimoto, Yuichi Watanabe, Kazuhiro Noma, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
Journal: Cancer Research (2010)

The inability to repair DNA double-strand breaks (DSB) leads to radiosensitization, such that ionizing radiation combined with molecular inhibition of cellular DSB processing may greatly affect treatment of human cancer. As a variety of viral products interact with the DNA repair machinery, oncolytic virotherapy may improve the therapeutic window of conventional radiotherapy. Here, we describe the mechanistic basis for synergy of irradiation and OBP-301 (Telomelysin), an attenuated type-5 adenovirus with oncolytic potency that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 infection led to E1B55kDa viral protein expression that degraded the complex formed by Mre11, Rad50, and NBS1, which senses DSBs. Subsequently, the phosphorylation of cellular ataxia-telangiectasia mutated protein was inhibited, disrupting the signaling pathway controlling DNA repair. Thus, tumor cells infected with OBP-301 could be rendered sensitive to ionizing radiation. Moreover, by using noninvasive whole-body imaging, we showed that intratumoral injection of OBP-301 followed by regional irradiation induces a substantial antitumor effect, resulting from tumor cell-specific radiosensitization, in an orthotopic human esophageal cancer xenograft model. These results illustrate the potential of combining oncolytic virotherapy and ionizing radiation as a promising strategy in the management of human cancer.
Dietary Flaxseed Enhances the Inhibitory Effect of Tamoxifen on the Growth of Estrogen-Dependent Human Breast Cancer (MCF-7) in Nude Mice
Authors: Jianmin Chen, Evon Hui, Terence Ip, Lilian U. Thompson
Journal: Clinical Cancer Research (2004)

Abstract Purpose: This study determined the effect of 10% dietary flaxseed (FS) and tamoxifen (TAM), alone and in combination, on the growth of estrogen-dependent human breast cancer (MCF-7) in athymic mice with or without 17β-estradiol (E2) supplementation. Experimental Design: Ovariectomized mice received injection with MCF-7 cells, were implanted with an E2 pellet (1.7 mg), and fed the basal diet (BD). When tumor reached ∼40 mm2, the E2 implant was removed, and mice were randomized to the following groups and maintained at either low (E2 pellet removed) or high E2 level (new E2 pellet implanted) for 6 weeks: (a) positive control with new E2 pellet, fed BD, (b) negative control with no E2 implant, fed BD, (c) TAM group with TAM pellet (5 mg) implant, fed BD, (d) FS group fed 10% FS, (e) FS+TAM group with TAM implant, fed 10% FS. Tumor growth was monitored weekly. Results: At low E2 level, FS regressed the pretreatment tumor size by 74%. TAM regressed tumor initially but later induced an increase so that the tumor size was finally similar to the pretreatment size. A tumor regression &amp;gt;53% was induced by FS+TAM than by TAM alone. At high E2 level, FS, TAM, and FS+TAM inhibited the tumor growth by 22, 41, and 50%, respectively, compared with the positive control. Decreased tumor size was attributable to reduced tumor cell proliferation and increased apoptosis. Conclusions: FS inhibited the growth of human estrogen-dependent breast cancer and strengthened the tumor-inhibitory effect of TAM at both low and high E2 levels.
PGC1α Promotes Tumor Growth by Inducing Gene Expression Programs Supporting Lipogenesis
Authors: Kavita Bhalla, Bor Jang Hwang, Ruby E. Dewi, Lihui Ou, William Twaddel, Hong-bin Fang, Scott B. Vafai, Francesca Vazquez, Pere Puigserver, Laszlo Boros, Geoffrey D. Girnun
Journal: Cancer Research (2011)

Despite the role of aerobic glycolysis in cancer, recent studies highlight the importance of the mitochondria and biosynthetic pathways as well. PPARγ coactivator 1α (PGC1α) is a key transcriptional regulator of several metabolic pathways including oxidative metabolism and lipogenesis. Initial studies suggested that PGC1α expression is reduced in tumors compared with adjacent normal tissue. Paradoxically, other studies show that PGC1α is associated with cancer cell proliferation. Therefore, the role of PGC1α in cancer and especially carcinogenesis is unclear. Using Pgc1α(-/-) and Pgc1α(+/+) mice, we show that loss of PGC1α protects mice from azoxymethane-induced colon carcinogenesis. Similarly, diethylnitrosamine-induced liver carcinogenesis is reduced in Pgc1α(-/-) mice as compared with Pgc1α(+/+) mice. Xenograft studies using gain and loss of PGC1α expression showed that PGC1α also promotes tumor growth. Interestingly, while PGC1α induced oxidative phosphorylation and tricarboxylic acid cycle gene expression, we also observed an increase in the expression of two genes required for de novo fatty acid synthesis, ACC and FASN. In addition, SLC25A1 and ACLY, which are required for the conversion of glucose into acetyl-CoA for fatty acid synthesis, were also increased by PGC1α, thus linking the oxidative and lipogenic functions of PGC1α. Indeed, using stable (13)C isotope tracer analysis, we show that PGC1α increased de novo lipogenesis. Importantly, inhibition of fatty acid synthesis blunted these progrowth effects of PGC1α. In conclusion, these studies show for the first time that loss of PGC1α protects against carcinogenesis and that PGC1α coordinately regulates mitochondrial and fatty acid metabolism to promote tumor growth.
Hemocompatibility of drug-eluting coronary stents coated with sulfonated poly (styrene-block-isobutylene-block-styrene)
Authors: Jin-Zhou Zhu, Xiao-Wei Xiong, Run Du, Ya-Jun Jing, Yuan Ying, Xiao-Ming Fan, Tian-Qi Zhu, Rui-Yan Zhang
Journal: Biomaterials (2012)