tbuckley/cabot-search huggingface dataset:
Lung Function and Risk of Type 2 Diabetes and Fatal and Nonfatal Major Coronary Heart Disease Events: Possible Associations With Inflammation
Authors: S. Goya Wannamethee, A. Gerald Shaper, Ann Rumley, Naveed Sattar, Peter H. Whincup, Mary C. Thomas, Gordon D. Lowe
Journal: Diabetes Care (2010)

OBJECTIVE We prospectively examined the relationship between lung function and risk of type-2 diabetes and fatal and nonfatal coronary heart disease (CHD) events and investigated the hypothesis that inflammation may underlie these associations. RESEARCH DESIGN AND METHODS A prospective study of 4,434 men aged 40–59 years with no history of cardiovascular disease (CHD or stroke) or diabetes drawn from general practices in 24 British towns and followed up for 20 years. RESULTS There were 680 major CHD events (276 fatal, 404 nonfatal) and 256 incident type 2 diabetes during the 20 years follow-up. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) but not FEV1-to-FVC ratio were significantly and inversely associated with incident type 2 diabetes and fatal CHD events (not nonfatal events) after adjustment for age, potential confounders, and metabolic risk factors. The adjusted relative risk (RR) for type 2 diabetes (Quartile 1 vs. Quartile 4) were 1.59 (1.07–2.56) and 1.74 (1.16–2.61) for FVC and FEV1, respectively (P = 0.03 and P = 0.04 for trend). The corresponding RR for fatal CHD were 1.48 (1.00–2.21) and 1.81 (1.19–2.76) (P = 0.002 and P = 0.0003 for trend). Lung function was significantly and inversely associated with C-reactive protein and interleukin-6; the inverse associations with type 2 diabetes for FVC and FEV1 were attenuated after further adjustment for these factors (P = 0.14 and P = 0.11 for trend) but remained significant for fatal CHD (P = 0.03 and P = 0.01, respectively). CONCLUSIONS Restrictive rather than obstructive impairment of lung function is associated with incident type 2 diabetes (and fatal CHD) with both associations partially explained by traditional and metabolic risk factors and inflammation.
Phase II Study of Pemetrexed With and Without Folic Acid and Vitamin B<sub>12</sub> as Front-Line Therapy in Malignant Pleural Mesothelioma
Authors: Giorgio V. Scagliotti, Dong-M. Shin, Hedy L. Kindler, Michael J. Vasconcelles, Uwe Keppler, Christian Manegold, Howard Burris, Ulrich Gatzemeier, Johannes Blatter, James T. Symanowski, James J. Rusthoven
Journal: Journal of Clinical Oncology (2003)

Purpose: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM). Patients and Methods: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m 2 ) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B 12 supplementation to improve safety. Results: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients. Conclusion: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B 12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.
Implantable Cardioverter-Defibrillators and Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy
Authors: Barry J. Maron, Paolo Spirito, Win-Kuang Shen, Tammy S. Haas, Francesco Formisano, Mark S. Link, Andrew E. Epstein, Adrian K. Almquist, James P. Daubert, Thorsten Lawrenz, Giuseppe Boriani, N. A. Mark Estes, Stefano Favale, Marco Piccininno, Stephen L. Winters, Massimo Santini, Sandro Betocchi, Fernando Arribas, Mark V. Sherrid, Gianfranco Buja, Christopher Semsarian, Paolo Bruzzi
Journal: JAMA (2007)

Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved.To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM.Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope.Appropriate ICD intervention terminating ventricular tachycardia or fibrillation.The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%).In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.
Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models
Authors: Michelle Day, Zhongfeng Wang, Jun Ding, Xinhai An, Cali A Ingham, Andrew F Shering, David Wokosin, Ema Ilijic, Zhuoxin Sun, Allan R Sampson, Enrico Mugnaini, Ariel Y Deutch, Susan R Sesack, Gordon W Arbuthnott, D James Surmeier
Journal: Nature Neuroscience (2006)
Neoadjuvant Chemotherapy With Methotrexate, Cisplatin, and Doxorubicin With or Without Ifosfamide in Nonmetastatic Osteosarcoma of the Extremity: An Italian Sarcoma Group Trial ISG/OS-1
Authors: Stefano Ferrari, Pietro Ruggieri, Graziella Cefalo, Angela Tamburini, Rodolfo Capanna, Franca Fagioli, Alessandro Comandone, Rossella Bertulli, Gianni Bisogno, Emanuela Palmerini, Marco Alberghini, Antonina Parafioriti, Alessandra Linari, Piero Picci, Gaetano Bacci
Journal: Journal of Clinical Oncology (2012)

We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity.Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS).From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B.IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.
Laser augmented by brachytherapy versus laser alone in the palliation of adenocarcinoma of the oesophagus and cardia: a randomised study
Authors: G M Spencer
Journal: Gut (2002)

Many patients with advanced malignant dysphagia are not suitable for definitive treatment. The best option for palliation of dysphagia varies between patients. This paper looks at a simple technique for enhancing laser recanalisation.To assess the value of adjunctive brachytherapy in prolonging palliation of malignant dysphagia by endoscopic laser therapy.Twenty two patients with advanced malignant dysphagia due to adenocarcinoma of the oesophagus or gastric cardia, unsuitable for surgery or radical chemoradiotherapy.Patients able to eat a soft diet after laser recanalisation were randomised to no further therapy or a single treatment with brachytherapy (10 Gy). Results were judged on the quality and duration of dysphagia palliation, need for subsequent intervention, complications, and survival.The median dysphagia score for all patients two weeks after initial treatment was 1 (some solids). The median dysphagia palliated interval from the end of initial treatment to recurrent dysphagia or death increased from five weeks (control group) to 19 weeks (brachytherapy group). Three patients had some odynophagia for up to six weeks after brachytherapy. There was no other treatment related morbidity or mortality. Further intervention was required in 10 of 11 control patients (median five further procedures) compared with 7/11 brachytherapy patients (median two further procedures). There was no difference in survival (median 20 weeks (control), 26 weeks (brachytherapy)).Laser therapy followed by brachytherapy is a safe, straightforward, and effective option for palliating advanced malignant dysphagia, which is complementary to stent insertion.
Longevity and Determinants of Protective Humoral Immunity after Pandemic Influenza Infection
Authors: Saranya Sridhar, Shaima Begom, Katja Hoschler, Alison Bermingham, Walt Adamson, William Carman, Steven Riley, Ajit Lalvani
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Antibodies to influenza hemagglutinin are the primary correlate of protection against infection. The strength and persistence of this immune response influences viral evolution and consequently the nature of influenza epidemics. However, the durability and immune determinants of induction of humoral immunity after primary influenza infection remain unclear.The spread of a novel H1N1 (A[H1N1]pdm09) virus in 2009 through an unexposed population offered a natural experiment to assess the nature and longevity of humoral immunity after a single primary influenza infection.We followed A(H1N1)pdm09-seronegative adults through two influenza seasons (2009-2011) as they developed A(H1N1)pdm09 influenza infection or were vaccinated. Antibodies to A(H1N1)pdm09 virus were measured by hemagglutination-inhibition assay in individuals with paired serum samples collected preinfection and postinfection or vaccination to assess durability of humoral immunity. Preexisting A(H1N1)pdm09-specific multicytokine-secreting CD4 and CD8 T cells were quantified by multiparameter flow cytometry to test the hypothesis that higher frequencies of CD4(+) T-cell responses predict stronger antibody induction after infection or vaccination.Antibodies induced by natural infection persisted at constant high titer for a minimum of approximately 15 months. Contrary to our initial hypothesis, the fold increase in A(H1N1)pdm09-specific antibody titer after infection was inversely correlated to the frequency of preexisting circulating A(H1N1)pdm09-specific CD4(+)IL-2(+)IFN-γ(-)TNF-α(-) T cells (r = -0.4122; P = 0.03).The longevity of protective humoral immunity after influenza infection has important implications for influenza transmission dynamics and vaccination policy, and identification of its predictive cellular immune correlate could guide vaccine development and evaluation.
Generation of a lymphocyte growth factor by treatment of human cells with neuraminidase and galactose oxidase.
Authors: A Novogrodsky, M Suthanthiran, B Saltz, D Newman, A L Rubin, K H Stenzel
Journal: The Journal of Experimental Medicine (1980)

Supernates of neuraminidase and galactose oxidase (NAGO)-treated lymphocytes induce blastogenesis in nonproliferating cells harvested 7--14 d after treatment with mitogen or alloantigen and in cells incubated with mitogen for 7--14 d but not in freshly isolated peripheral blood lymphocytes9 Virtually all the growth factor is produced by NAGO-treated cells during the first 24 h of incubation, and no increase in factor activity is detected upon further cell culture. Serum is not required for growth factor production. NAGO-primed medium induces generation of specific cytotoxic T cells from mixed lymphocyte culture (MLC) memory cells to approximately the same extent as that induced by allogeneic cells (stimulating cells in the primary MLC). NAGO-primed medium provides a useful reagent for isolation and characterization of lymphocyte growth factors and other lymphokines.
A FRACTION OF TUBERCLE BACILLI POSSESSING PRIMARY TOXICITY
Authors: John K. Spitznagel, René J. Dubos
Journal: The Journal of Experimental Medicine (1955)

Tubercle bacilli separated from young cultures were thoroughly extracted with monochlorobenzene at temperatures never exceeding 50 degrees C. From the soluble material, a fraction corresponding to approximately 1 per cent of the total bacillary weight was separated by fractional precipitation with petrolic ether at temperatures of 0 degrees or 4 degrees C.-depending upon the strain of bacilli. The monochlorobenzene-soluble-ether-insoluble material (fraction 7) prepared from BCG-P was found to contain 0.14 per cent nitrogen and 0.4 per cent phosphorus. Some of its other chemical characteristics are described. Fraction 7 proved unable to elicit tuberculin allergy in guinea pigs, but injection of 5 microg. of it into the skin produced severe local reactions. In albino mice, a single intraperitoneal injection of 20 microg. caused loss of muscular tone and of weight followed by death within 9 days. The only tissue reaction observed was a slight degree of peritonitis. In mice of the C57 BL strain, a single injection of 40 microg. also caused death in the same time, but with pulmonary hemorrhages-usually massive. Material similar to fraction 7 was obtained from one virulent, two attenuated, and one avirulent strain of mammalian tubercle bacilli (bovine and human). The fractions obtained from the various strains differed somewhat in solubility and toxicity. The more virulent the culture, the more toxic was the fraction obtained from it; but it is possible that this relation was the result of differences in the effectiveness of the extraction procedures, rather than of characteristics inherent to the cultures. Evidence is presented that the toxicity of fraction 7 accounts for much of the primary toxicity of tubercle bacilli.
Long term outcome of asthma in adults; study design and participation
Authors: Britt-Marie Eklund, Linnea Hedman, Helena Backman, Ann-Christin Jonsson, Anne Lindberg, Bo Lundbäck, Eva Rönmark
Journal: European Respiratory Journal (2014)

Background : Asthma is regarded as a chronic disease but recovery in children is common. The natural history of asthma in adults in a long term perspective is rarley studied.   Aim : To investigate the participation in a long term follow-up of asthma in adults.   Methods : The participants were recruited from The Obstructive Lung Disease in Northern Sweden (OLIN) Studies. Subjects with asthma or suspected asthma were identified by clinical examinations of 5 representative cohorts from the general population, recruited from 1985 to 2001. Base-line data included a lung function test and structured interview covering respiratory symptoms and medications, smoking habits, socio-economic status, profession, early life events. Skin prick test and bronchial reactivity test were performed in 3 cohorts. Follow-ups started in 2012 and included structured interview, lung function test, skin prick test, specific IgE, and inflammatory markers in blood.   Results : In total 2,056 subjects fulfilled the inclusion criteria, aged 20-69 years at inclusion. The follow-up time ranges from 11 to 30 years. At the follow-up, 1,425 subjects were alive and still lived in the area, and 70% participated, Of non-participaants, 85 subjects could not participate due to illness, 15 had moved, 14 had died after 2012, 242 reported lack of time or interest, and 70 could not be traced. Non-participation due to illness was more common among the elderly while more young people did not participate due to lack of time or interest.   Conclusion : The large, representative sample and high participation rate constitute an excellent base for long term study of asthma. To increase the participation rate, the scheduled visit time must meet the individual9s needs.
Adrenomedullin Receptor Antagonism by Calcitonin Gene-Related Peptide(8-37) Inhibits Carotid Artery Neointimal Hyperplasia After Balloon Injury
Authors: Koichi Shimizu, Hiroyuki Tanaka, Makoto Sunamori, Fumiaki Marumo, Masayoshi Shichiri
Journal: Circulation Research (1999)

Abstract —Intimal injury by angioplasty results in a series of changes, including smooth muscle cell hyperplasia, that lead to vascular restenosis. Adrenomedullin, a potent vasodilator peptide, has natriuretic effects, and its plasma concentration is elevated in cardiovascular diseases. Adrenomedullin is secreted by endothelial and vascular smooth muscle cells, but its role in neointimal hyperplasia after balloon injury has not been previously described. We investigated the role of endogenous adrenomedullin in neointimal hyperplasia using an in vivo rat model of postinjury vascular restenosis. In the injured rats, bromodeoxyuridine-labeled nuclei in the media of untreated common carotid arteries were increased 2 days after injury, which were suppressed by in vivo treatment with the adrenomedullin receptor antagonist calcitonin gene-related peptide (CGRP)(8-37). Inhibition of neointimal hyperplasia by CGRP(8-37) was distinct at 7 and 14 days, whereas CGRP(1-37) had no effect. The expression of adrenomedullin in the media of both untreated and treated common carotid arteries was elevated at 2 days and further enhanced in hyperplastic intima of untreated common carotid arteries at 7 days. Our findings suggest a novel role for endogenous adrenomedullin in balloon injury–induced restenosis and indicate that CGRP(8-37) may be useful for the prevention of vascular restenosis.
Site-Specific Alteration of Actin Assembly Visualized in Living Renal Epithelial Cells during ATP Depletion
Authors: Eric A. Shelden, Joel M. Weinberg, Dorothy R. Sorenson, Chris A. Edwards, Fiona M. Pollock
Journal: Journal of the American Society of Nephrology (2002)

Disruption of normal actin organization in renal tubular epithelial cells is an important element of renal injury induced by ischemia. Studies of fixed cells indicate that the cytoskeleton is disrupted by both ischemia and ATP depletion in a site-specific manner. However, few studies have examined these effects in living cells, and the relationship between the time course of ATP reduction and alteration of the cytoskeleton remains unclear. Here, time-lapse video images of cultured renal epithelial cells expressing an enhanced green fluorescent protein (EGFP)-actin fusion protein were obtained, and the kinetics of fluorescence actin distribution before and during ATP depletion is quantified and compared with measured ATP levels. This study found that assembly of lamellar actin is inhibited rapidly as cellular ATP levels are reduced, whereas disruption of actin in stress fibers is more gradual and persistent. Actin associated with focal adhesions is largely resistant to ATP depletion in these experiments, and, consistent with previous studies, particulate aggregates of actin were formed within the cytoplasm of ATP-depleted cells. Most surprisingly, time-lapse imaging of EGFP-actin distribution, quantitative fluorescence imaging of phalloidin-stained cells, and ultrastructural studies indicate that assembly of actin filaments occurs at sites of epithelial cell-cell attachment in ATP-depleted cells. This assembly is initiated early during ATP depletion and continues after ATP levels are maximally reduced. Assembly of actin at sites of cell-cell attachment may be an element of the pathology of injury induced by ischemia, or alternatively, could reflect the function of a protective mechanism. These studies directly demonstrate site-specific alteration of actin assembly in living epithelial cells during ATP depletion. The results also reveal that actin reorganization continues after ATP levels are maximally decreased and that epithelial cell-cell attachments are sites of actin assembly in ATP-depleted cells.