tbuckley/cabot-search huggingface dataset:
Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease
Authors: M. Confalonieri, E. Mainardi, R. Della Porta, S. Bernorio, L. Gandola, B. Beghe, A. Spanevello
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Airways inflammation is a feature of chronic obstructive pulmonary disease (COPD), but the role of corticosteroids in the management of clinically stable patients has yet to be established. A randomised controlled study was carried out to investigate the effect of high dose inhaled beclomethasone dipropionate (BDP) administered for two months to patients with stable, smoking related COPD. Sputum induction was used to evaluate bronchial inflammation response. <h3>METHODS</h3> 34 patients (20 men and 14 women) were examined on three separate occasions. At the initial clinical assessment (visit 0), spirometry and blood gas analysis were performed. On visit 1 (within one week of visit 0) sputum induction was performed and each patient was randomised to receive either BDP 500 μg three times daily (treated group) or nothing (control group). After two months (visit 2), all patients underwent repeat clinical assessment, spirometry, and sputum induction. <h3>RESULTS</h3> There were no differences in sputum cell counts between the groups at baseline. After two months of treatment, induced sputum samples from patients in the treated group showed a reduction in both neutrophils (−27%) and total cells (−42%) with respect to baseline, while the control group did not (neutrophils +9%, total cells +7%). Macrophages increased in the treated group but not in the control group. The mean final value of sputum neutrophils was 52% in the treated group and 73.3% in the control group (95% confidence interval (CI) −27.2 to −15.4). The mean final value of sputum macrophages was 35.8% in treated group and 19.3% in control group (95% CI 10.3 to 22.8). The differences between the treated and control groups for neutrophils (−21.3%), macrophages (+16.5%), and total cells (−65%) were significant. Spirometry and blood gas data did not change from baseline in either patient group. <h3>CONCLUSIONS</h3> A two month course of treatment with high dose inhaled BDP reduces significantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness of inhaled steroids in COPD are needed to confirm the clinical importance of this observation.
Cytotoxic T Lymphocyte–based Control of Simian Immunodeficiency Virus Replication in a Preclinical AIDS Vaccine Trial
Authors: Tetsuro Matano, Masahiro Kobayashi, Hiroko Igarashi, Akiko Takeda, Hiromi Nakamura, Munehide Kano, Chie Sugimoto, Kazuyasu Mori, Akihiro Iida, Takahiro Hirata, Mamoru Hasegawa, Takae Yuasa, Masaaki Miyazawa, Yumiko Takahashi, Michio Yasunami, Akinori Kimura, David H. O'Connor, David I. Watkins, Yoshiyuki Nagai
Journal: The Journal of Experimental Medicine (2004)

Recently, encouraging AIDS vaccine trials in macaques have implicated cytotoxic T lymphocytes (CTLs) in the control of the simian human immunodeficiency virus SHIV89.6P that induces acute CD4+ T cell depletion. However, none of these vaccine regimens have been successful in the containment of replication of the pathogenic simian immunodeficiency viruses (SIVs) that induce chronic disease progression. Indeed, it has remained unclear if vaccine-induced CTL can control SIV replication. Here, we show evidence suggesting that vaccine-induced CTLs control SIVmac239 replication in rhesus macaques. Eight macaques vaccinated with DNA-prime/Gag-expressing Sendai virus vector boost were challenged intravenously with SIVmac239. Five of the vaccinees controlled viral replication and had undetectable plasma viremia after 5 wk of infection. CTLs from all of these five macaques rapidly selected for escape mutations in Gag, indicating that vaccine-induced CTLs successfully contained replication of the challenge virus. Interestingly, analysis of the escape variant selected in three vaccinees that share a major histocompatibility complex class I haplotype revealed that the escape variant virus was at a replicative disadvantage compared with SIVmac239. These findings suggested that the vaccine-induced CTLs had “crippled” the challenge virus. Our results indicate that vaccine induction of highly effective CTLs can result in the containment of replication of a highly pathogenic immunodeficiency virus.
Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial
Authors: D. Rayson, T.M. Suter, C. Jackisch, S. van der Vegt, B. Bermejo, J. van den Bosch, G.L. Vivanco, A.M. van Gent, H. Wildiers, A. Torres, L. Provencher, M. Temizkan, J. Chirgwin, J.L. Canon, G. Ferrandina, S. Srinivasan, L. Zhang, D.J. Richel
Journal: Annals of Oncology (2011)
Low expression allele alpha LELY of red cell spectrin is associated with mutations in exon 40 (alpha V/41 polymorphism) and intron 45 and with partial skipping of exon 46.
Authors: R Wilmotte, J Maréchal, L Morlé, F Baklouti, N Philippe, R Kastally, L Kotula, J Delaunay, N Alloisio
Journal: Journal of Clinical Investigation (1993)

The alpha V/41 polymorphism of erythroid alpha-spectrin has been characterized initially by an increased susceptibility to proteolysis of the alpha IV-alpha V domain junction (Alloisio N., L. Morlé, J. Maréchal, A.-F. Roux, M.-T. Ducluzeau, D. Guetarni, B. Pothier, F. Baklouti, A. Ghanem, R. Kastally, et al. 1991. J. Clin. Invest. 87:2169-2177). Until now, it has been found associated invariably with a low expression level of the corresponding alpha chain. Among 61 chromosomes investigated in French and North African individuals or kindreds, we observed 19 chromosomes with the alpha V/41 polymorphism. With no single exception, the latter displayed a point mutation in exon 40 (Leu-->Val; CTA-->GTA) at position alpha 1857. According to the triple helical model of spectrin structure, this change accounts for the peptide maps' abnormalities. Sequencing the entire alpha V domain cDNA disclosed, in addition, a partial skipping of exon 46. At the gene level, a substitution (C-->T) was evidenced at nucleotide -12 of intron 45. This mutation appeared linked to the exon 40 mutation in 17 chromosomes, again with no single exception, among 53 examined chromosomes. We hypothesized that the lack of exon 46 would hamper the nucleation process and eventually account for the low expression feature. The present doubly mutated allele was renamed allele alpha LELY (low expression, Lyon).
Longitudinal change of prebronchodilator spirometric obstruction and health outcomes: results from the SAPALDIA cohort
Authors: N. M. Probst-Hensch, I. Curjuric, B. Pierre-Olivier, U. Ackermann-Liebrich, R. W. Bettschart, O. Brandli, M. Brutsche, L. Burdet, M. W. Gerbase, B. Knopfli, N. Kunzli, M. G. Pons, C. Schindler, J.-M. Tschopp, T. Rochat, E. W. Russi
Journal: Thorax (2009)

<h3>Background</h3> Understanding the prognostic meaning of early stages of chronic obstructive pulmonary disease (COPD) in the general population is relevant for discussions about underdiagnosis. To date, COPD prevalence and incidence have often been estimated using prebrochodilation spirometry instead of postbronchodilation spirometry. In the SAPALDIA (Swiss Study on Air Pollution and Lung Disease in Adults) cohort, time course, clinical relevance and determinants of severity stages of obstruction were investigated using prebronchodilator spirometry. <h3>Methods</h3> Incident obstruction was defined as an FEV<sub>1</sub>/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio ≥0.70 at baseline and &lt;0.70 at follow-up, and non-persistence was defined inversely. Determinants were assessed in 5490 adults with spirometry and respiratory symptom data in 1991 and 2002 using Poisson regression controlling for self-declared asthma and wheezing. Change in obstruction severity (defined analogously to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) classification) over 11 years was related to shortness of breath and health service utilisation for respiratory problems by logistic models. <h3>Results</h3> The incidence rate of obstruction was 14.2 cases/1000 person years. 20.9% of obstructive cases (n = 113/540) were non-persistent. Age, smoking, chronic bronchitis and non-current asthma were determinants of incidence. After adjustment for asthma, only progressive stage I or persistent stage II obstruction was associated with shortness of breath (OR 1.71, 95% CI 0.83 to 3.54; OR 3.11, 95% CI 1.50 to 6.42, respectively) and health service utilisation for respiratory problems (OR 2.49, 95% CI 1.02 to 6.10; OR 4.17 95% CI 1.91 to 9.13, respectively) at follow-up. <h3>Conclusions</h3> The observed non-persistence of obstruction suggests that prebronchodilation spirometry, as used in epidemiological studies, might misclassify COPD. Future epidemiological studies should consider both prebronchodilation and postbronchodilation measurements and take specific clinical factors related to asthma and COPD into consideration for estimation of disease burden and prediction of health outcomes.
Molecular relationship between private and public H-2 antigens as determined by antigen redistribution method.
Authors: V Hauptfeld, J Klein
Journal: The Journal of Experimental Medicine (1975)

Molecular relationship of public H-2 antigens 1, 5, 6, 8, 11, 13, 25, and 28 to private antigens controlled by K and D regions was studied using the technique of antibody-induced resistance to complement-mediated cytotoxicity. The results indicate physical association in the cell membrane between H-2 antigens 1 and 23 of H-2-a, 8 and 31 of H-2-d, 11 and 17 of H-2-q, 13 and 30 of H-2-q, 25 and 23 of H-2-k, and 28 and 31 of H-2-g. These results are in agreement with genetic mapping placing the determinants of antigens H-2.8, 11 and 25 in the K region , the determinant of antigen H-2.13 in the D region, and the determinants of antigens H-2.1 and 28 in either the K or the D region. In contrast to genetic mapping placing the determinant for antigen H-2.6 in the D region, we found that in the H-2-b haplotype the antigen is associated with K region antigen H-2.33 and H-2.32, and interpreted this result as evidence for two homologous H-2.5 sites controlled by opposite ends of the H-2 complex. Although the data do not prove that public antigens are carried by the same molecules as private ones, they demonstrate a close physical association in the membrane between the two groups of loci, K and D, coding for the first 33 classical H-2 antigens (with the exception of antigen H-2.7), and thus support the two-locus model. The data also support the duplication model of H-2 by demonstrating two homologous H-2.5 sites associated with K and D molecules.
Oxygen Radicals and Human Disease
Authors: Carroll E. Cross, Barry Halliwell, Edward T. Borish, William A. Pryor, Bruce N. Ames, Robert L. Saul, Joe M. McCORD, Denham Harman
Journal: Annals of Internal Medicine (1987)

Toxic oxygen free radicals have been implicated as important pathologic mediators in many clinical disorders. We discuss the chemistry of oxygen radical production and the roles of iron and of various antioxidants as well as the diseases that have received active attention in oxyradical research. Particular attention is focused on cigarette smoke oxidants, ischemia-reperfusion-induced radical production, carcinogenesis, and aging. Such research may well provide a firm foundation for therapeutic breakthroughs.
Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community
Authors: C. Armour, S. Bosnic-Anticevich, M. Brillant, D. Burton, L. Emmerton, I. Krass, B. Saini, L. Smith, K. Stewart
Journal: Thorax (2007)

Despite national disease management plans, optimal asthma management remains a challenge in Australia. Community pharmacists are ideally placed to implement new strategies that aim to ensure asthma care meets current standards of best practice. The impact of the Pharmacy Asthma Care Program (PACP) on asthma control was assessed using a multi-site randomised intervention versus control repeated measures study design.Fifty Australian pharmacies were randomised into two groups: intervention pharmacies implemented the PACP (an ongoing cycle of assessment, goal setting, monitoring and review) to 191 patients over 6 months, while control pharmacies gave their usual care to 205 control patients. Both groups administered questionnaires and conducted spirometric testing at baseline and 6 months later. The main outcome measure was asthma severity/control status.186 of 205 control patients (91%) and 165 of 191 intervention patients (86%) completed the study. The intervention resulted in improved asthma control: patients receiving the intervention were 2.7 times more likely to improve from "severe" to "not severe" than control patients (OR 2.68, 95% CI 1.64 to 4.37; p<0.001). The intervention also resulted in improved adherence to preventer medication (OR 1.89, 95% CI 1.08 to 3.30; p = 0.03), decreased mean daily dose of reliever medication (difference -149.11 microg, 95% CI -283.87 to -14.36; p=0.03), a shift in medication profile from reliever only to a combination of preventer, reliever with or without long-acting beta agonist (OR 3.80, 95% CI 1.40 to 10.32; p=0.01) and improved scores on risk of non-adherence (difference -0.44, 95% CI -0.69 to -0.18; p=0.04), quality of life (difference -0.23, 95% CI -0.46 to 0.00; p=0.05), asthma knowledge (difference 1.18, 95% CI 0.73 to 1.63; p<0.01) and perceived control of asthma questionnaires (difference -1.39, 95% CI -2.44 to -0.35; p<0.01). No significant change in spirometric measures occurred in either group.A pharmacist-delivered asthma care programme based on national guidelines improves asthma control. The sustainability and implementation of the programme within the healthcare system remains to be investigated.
Psychosomatic Medicine
Authors: Th. von Uexküll
Journal: Psychotherapy and Psychosomatics (1973)

The resistance of medicine to accept psychosomatic approach as a special discipline has considerably diminished in the last 20 years. The difficulties to integrate it into the institutional branches of somatic medicine remain unchanged. The reasons for this contradictory attitude and its consequences for psychosomatic medicine are analyzed in respect to personal experiences of the author.
Efflorescence of new warts: a sign of onset of involution in flat warts
Authors: ALEXANDER BERMAN, JAMES E. BERMAN
Journal: British Journal of Dermatology (1978)

Journal Article Efflorescence of new warts: a sign of onset of involution in flat warts Get access ALEXANDER BERMAN, ALEXANDER BERMAN Medical College of Wisconsin, 7400 W. Brown Deer Rd., Milwaukee, Wisconsin 53223 Search for other works by this author on: Oxford Academic Google Scholar JAMES E. BERMAN JAMES E. BERMAN University of Wisconsin, Madison, Wisconsin, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue 2, 1 August 1978, Pages 179–182, https://doi.org/10.1111/j.1365-2133.1978.tb01979.x Published: 01 August 1978
APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study
Authors: Alessandro Biffi, Christopher D Anderson, Jeremiasz M Jagiella, Helena Schmidt, Brett Kissela, Björn M Hansen, Jordi Jimenez-Conde, Caroline R Pires, Alison M Ayres, Kristin Schwab, Lynelle Cortellini, Joanna Pera, Andrzej Urbanik, Javier M Romero, Natalia S Rost, Joshua N Goldstein, Anand Viswanathan, Alexander Pichler, Christian Enzinger, Raquel Rabionet, Bo Norrving, David L Tirschwell, Magdy Selim, Devin L Brown, Scott L Silliman, Bradford B Worrall, James F Meschia, Chelsea S Kidwell, Joseph P Broderick, Steven M Greenberg, Jaume Roquer, Arne Lindgren, Agnieszka Slowik, Reinhold Schmidt, Daniel Woo, Jonathan Rosand
Journal: The Lancet Neurology (2011)
Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: a study by the Cancer and Leukemia Group B.
Authors: T A Ahles, P M Silberfarb, J Herndon, L H Maurer, A B Kornblith, J Aisner, M C Perry, W L Eaton, L L Zacharski, M R Green, J C Holland
Journal: Journal of Clinical Oncology (1998)

The current study assessed the psychologic and neuropsychologic functioning of patients with small-cell lung cancer who were randomized in a large clinical trial to receive intensive doxorubicin, cyclophosphamide, etoposide (ACE)/cisplatin, cyclophosphamide, etoposide (PCE) chemotherapy and radiation therapy (RT) to the primary tumor and prophylactic whole-brain irradiation with (regimen I) or without (regimen II) warfarin.Patients' emotional states and cognitive functioning were assessed using the Profile of Mood States (POMS) and Trail Making B Test (Trails B), respectively. Two hundred ninety-five patients completed the POMS and Trails B at pretreatment, 224 patients after the completion of the ACE course of chemotherapy (week 9), and 177 patients after the completion of the PCE chemotherapy and RT (week 17).No differences on the POMS or Trails B measures were found between the two treatment arms as predicted, given that the only difference between the two treatment arms was the presence or absence of warfarin. Analysis of the POMS revealed that, overall, mean scores remained stable over the course of treatment; however, women showed a trend toward higher mean scores, which indicated a higher level of distress, compared with men at the pretreatment assessment. Examination of cognitive functioning, measured by the Trails B, revealed improved performance from baseline to post-ACE chemotherapy, which is consistent with a practice effect, but a significant worsening of Trails B scores post-RT compared with the pre-RT assessments, which is consistent with impaired cognitive functioning because of treatment (P < .0001).Emotional state, measured by the POMS, did not differ between the groups or change significantly over time in this study of small-cell lung cancer patients treated with a combination of chemotherapy and RT plus or minus warfarin. However, the pattern of relatively stable POMS scores and poorer Trails B performance post-RT suggested that this combination of chemotherapy and RT had a negative impact on cognitive functioning.
Naturally Occurring Mutations in the <i>MPS1</i> Gene Predispose Cells to Kinase Inhibitor Drug Resistance
Authors: Mark D. Gurden, Isaac M. Westwood, Amir Faisal, Sébastien Naud, Kwai-Ming J. Cheung, Craig McAndrew, Amy Wood, Jessica Schmitt, Kathy Boxall, Grace Mak, Paul Workman, Rosemary Burke, Swen Hoelder, Julian Blagg, Rob L.M. Van Montfort, Spiros Linardopoulos
Journal: Cancer Research (2015)

Abstract Acquired resistance to therapy is perhaps the greatest challenge to effective clinical management of cancer. With several inhibitors of the mitotic checkpoint kinase MPS1 in preclinical development, we sought to investigate how resistance against these inhibitors may arise so that mitigation or bypass strategies could be addressed as early as possible. Toward this end, we modeled acquired resistance to the MPS1 inhibitors AZ3146, NMS-P715, and CCT251455, identifying five point mutations in the kinase domain of MPS1 that confer resistance against multiple inhibitors. Structural studies showed how the MPS1 mutants conferred resistance by causing steric hindrance to inhibitor binding. Notably, we show that these mutations occur in nontreated cancer cell lines and primary tumor specimens, and that they also preexist in normal lymphoblast and breast tissues. In a parallel piece of work, we also show that the EGFR p.T790M mutation, the most common mutation conferring resistance to the EGFR inhibitor gefitinib, also preexists in cancer cells and normal tissue. Our results therefore suggest that mutations conferring resistance to targeted therapy occur naturally in normal and malignant cells and these mutations do not arise as a result of the increased mutagenic plasticity of cancer cells. Cancer Res; 75(16); 3340–54. ©2015 AACR.
Endoscopic needle aspiration cytology: a new method for the diagnosis of upper gastrointestinal cancer.
Authors: C J Ingoldby, M K Mason, R I Hall
Journal: Gut (1987)

A technique for obtaining needle aspiration cytology specimens from upper gastrointestinal lesions at endoscopy is described. The validity of the technique was initially confirmed by applying it to resected gastric carcinomas. Thirty seven endoscopically visualised lesions were then sampled by forceps biopsy, brush and needle cytology. Ten lesions were subsequently found to be carcinomas. Needle aspiration produced identifiable malignant cells from seven of these lesions. In two it was the only sampling method which provided the correct diagnosis. This technique may be a useful addition to conventional endoscopic sampling methods, particularly where tumours lie deep to normal mucosa, or necrotic slough.
STUDIES ON ACUTE DISSEMINATED ENCEPHALOMYELITIS PRODUCED EXPERIMENTALLY IN RHESUS MONKEYS
Authors: Charles E. Lumsden, Elvin A. Kabat, Abner Wolf, Ada E. Bezer
Journal: The Journal of Experimental Medicine (1950)

1. Animals injected with emulsions of monkey brain with adjuvants show a complex pattern of antibody response as determined by complement fixation tests. 2. Organ-specific complement-fixing antibodies to constituents of brain tissue may be formed which fix complement with brain tissues of various animal species but fail to react with other organs or with rabbit placenta. 3. Antibodies may be formed to some constituent of brain other than nervous tissue. It would seem that these can be detected by the strong complement fixation given with rabbit placenta. 4. Sera from individual animals may contain antibodies to the brain or placenta constituents, to both, or to neither. Occasional individual sera show unique patterns of antibody response as determined with various additional antigens such as fetal brain, posterior pituitary, or peripheral nerves. 5. No evidence of any etiological relationship between the development of encephalomyelitis and the complement-fixing antibodies to brain demonstrable in the sera could be found. The complement-fixing antibody to the placental constituent was unrelated to the encephalomyelitis.
An Indolent Case of Severe Acute Respiratory Syndrome
Authors: Man-Fai Lam, Gaik C. Ooi, Bing Lam, James C. Ho, Wing H. Seto, Pak L. Ho, Poon C. Wong, Raymond Liang, Wah K. Lam, Kenneth W. Tsang
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.