tbuckley/cabot-search huggingface dataset:
Exacerbations in non-COPD patients: truth or myth
Authors: Deepak Aggarwal, Alkesh Kumar Khurana
Journal: Thorax (2014)

Exacerbations in non-COPD patients: truth or mythWe read with great interest the article by Tan et al, 1 whereby they have discussed the occurrence of exacerbation-like events in patients without COPD.The basic concept of the study needs debate and clarification.The authors have used the terms 'non-COPD patients' and 'exacerbation like event' to mention the group of patients who didn't fulfil the spirometric criteria for COPD.Without mentioning its causes, this non-COPD group with chronic respiratory symptoms seems to be a new disease process.Here, it should be clarified that this non-COPD group is not a distinct aetiological entity.Rather, these chronic symptoms are the result of any of the undetected upper and lower respiratory tract diseases, like bronchitis, bronchiectasis, postnasal drip, chronic pharyngitis, chronic cough due to Gastro-oesophageal Reflux Disease (GERD), early COPD, mild asthma, heart failure, and so on, which were not properly investigated and, hence, might have become chronic. 2Also, inclusion of acute conditions, like pneumonia, pneumothorax and using the term, exacerbation, for these patients in the non-COPD group needs explanation.Without getting a broncho-provocative challenge test, it is likely that a good number of subjects in non-COPD group might actually have asthma.The significant economic and healthcare burden of this non-COPD group is hence obvious and not surprising. 3In view of diverse aetiologies in a non-COPD group, it is difficult to justify the use of the term 'exacerbation like events' for this varied patient group, and compare their symptom spurts with those of acute exacerbations of COPD.These terminologies 'non-COPD patients' and 'exacerbation like event' should be used with caution, as it may, inadvertently, lead to the creation of a separate disease group, creating confusion about the correct terminology.Moreover, being easy to label, these terms are prone to be misused for all non-COPD patients, without subjecting them to detailed investigations.It would be useful if authors exclude known causes of chronic symptoms in non-COPD patients before evaluating and comparing them with COPD.Proper diagnosis and categorisation of these non-COPD patients could help in proper management, as well as may change the course of their disease.
DNA Polymorphism in Active Gene and Pseudogene of the Cytosolic Phosphoglucose Isomerase (PgiC) Loci in Arabidopsis halleri ssp. gemmifera
Authors: Akira Kawabe, Naohiko T Miyashita
Journal: Molecular Biology and Evolution (2003)

DNA variations in two PgiC loci were investigated in 15 strains of Arabidopsis halleri ssp. gemmifera. In a 5.5-kb region of the PgiC1 locus, 127 nucleotide substitutions and 33 length variations were observed. In a 6.0-kb region of the PgiC2 locus, 138 nucleotide substitutions and 33 length variations were observed. Frame shift, novel stop codons, and large length variations were observed in the PgiC2 coding region. These findings suggested that PgiC2 may be a pseudogene. The nucleotide diversities (pi) for the entire regions of both PgiC loci were approximately 0.0033. Tajima's test of both PgiC loci yielded significantly negative results. In the coding regions, the high proportions of replacement substitutions caused significant deviations from neutrality in McDonald and Kreitman's test. An excess of singletons and a high proportion of replacement polymorphic sites have been observed in the Adh and ChiA regions of A. halleri ssp. gemmifera. Thus, the A. halleri ssp. gemmifera population may not have reached equilibrium, and thus nonneutral patterns of DNA polymorphism were observed.
NF-κB translocation prevents host cell death after low-dose challenge by<i>Legionella pneumophila</i>
Authors: Vicki P. Losick, Ralph R. Isberg
Journal: The Journal of Experimental Medicine (2006)

Legionella pneumophila, the causative agent of Legionnaires' disease, grows within macrophages and manipulates target cell signaling. Formation of a Legionella-containing replication vacuole requires the function of the bacterial type IV secretion system (Dot/Icm), which transfers protein substrates into the host cell cytoplasm. A global microarray analysis was used to examine the response of human macrophage-like U937 cells to low-dose infections with L. pneumophila. The most striking change in expression was the Dot/Icm-dependent up-regulation of antiapoptotic genes positively controlled by the transcriptional regulator nuclear factor κB (NF-κB). Consistent with this finding, L. pneumophila triggered nuclear localization of NF-κB in human and mouse macrophages in a Dot/Icm-dependent manner. The mechanism of activation at low-dose infections involved a signaling pathway that occurred independently of the Toll-like receptor adaptor MyD88 and the cytoplasmic sensor Nod1. In contrast, high multiplicity of infection conditions caused a host cell response that masked the unique Dot/Icm-dependent activation of NF-κB. Inhibition of NF-κB translocation into the nucleus resulted in premature host cell death and termination of bacterial replication. In the absence of one antiapoptotic protein, plasminogen activator inhibitor–2, host cell death increased in response to L. pneumophila infection, indicating that induction of antiapoptotic genes is critical for host cell survival.
Control of Airway Inflammation in Asthma Patients Receiving Fluticasone Propionate (FP)/Salmeterol, FP Alone or FP Plus Montelukast
Authors: N. Jarjour, P. Dorinsky, J. Stauffer, D. Reilly, S. Yancey, L. Edwards, L. Sutton
Journal: Journal of Allergy and Clinical Immunology (2006)
What makes for an effective stop-smoking service?
Authors: L. S. Brose, R. West, M. S. McDermott, J. A. Fidler, E. Croghan, A. McEwen
Journal: Thorax (2011)

<h3>Background</h3> The English network of stop-smoking services (SSSs) is among the best-value life-preserving clinical intervention in the UK NHS and is internationally renowned. However, success varies considerably across services, making it important to examine the factors that influence their effectiveness. <h3>Methods</h3> Data from 126 890 treatment episodes in 24 SSSs in 2009–10 were used to assess the association between intervention characteristics and success rates, adjusting for key smoker characteristics. Treatment characteristics examined were setting (eg, primary care, specialist clinics, pharmacy), type of support (eg, group, one-to-one) and medication (eg, varenicline, single nicotine replacement therapy (NRT), combination of two or more forms of NRT). The main outcome measure was abstinence from smoking 4 weeks after the target quit date, verified by carbon monoxide concentration in expired air. <h3>Results</h3> There was substantial variation in success rates across intervention characteristics after adjusting for smoker characteristics. Single NRT was associated with higher success rates than no medication (OR 1.75, 95% CI 1.39 to 2.22); combination NRT and varenicline were more successful than single NRT (OR 1.42, 95% CI 1.06 to 1.91 and OR 1.78, 95% CI 1.57 to 2.02, respectively); group support was linked to higher success rates than one-to-one support (OR 1.43, 95% CI 1.16 to 1.76); primary care settings were less successful than specialist clinics (OR 0.80, 95% CI 0.66 to 0.99). <h3>Conclusions</h3> Routine clinic data support findings from randomised controlled trials that smokers receiving stop-smoking support from specialist clinics, treatment in groups and varenicline or combination NRT are more likely to succeed than those receiving treatment in primary care, one-to-one and single NRT. All smokers should have access to, and be encouraged to use, the most effective intervention options.
Phenotypic changes of bone marrow-derived mast cells after intraperitoneal transfer into W/Wv mice that are genetically deficient in mast cells.
Authors: K Otsu, T Nakano, Y Kanakura, H Asai, H R Katz, K F Austen, R L Stevens, S J Galli, Y Kitamura
Journal: The Journal of Experimental Medicine (1987)

The ability of mouse IL-3-dependent, bone marrow culture-derived mast cells (BMMC) to generate serosal mast cells (SMC) in vivo after adoptive transfer to mast cell-deficient mice has been defined by chemical and immunochemical criteria. BMMC differentiated and grown from WBB6F1-+/+ mouse progenitor cells in medium containing PWM/splenocyte-conditioned medium synthesized a approximately 350,000 Mr protease-resistant proteoglycan bearing approximately 55,000 Mr glycosaminoglycans, as defined by gel filtration of each. Approximately 85% of the glycosaminoglycans bound to the cell-associated BMMC proteoglycans were chondroitin sulfates based upon their susceptibility to chondroitinase ABC digestion; HPLC of the chondroitinase ABC-generated unsaturated disaccharides revealed these glycosaminoglycans to be chondroitin sulfate E. As determined by heparinase and nitrous acid degradations, approximately 10% of the glycosaminoglycans bound to BMMC proteoglycans were heparin. In contrast, mast cells recovered from the peritoneal cavity of congenitally mast cell-deficient WBB6F1-W/Wv mice 15 wk after intraperitoneal injection of BMMC synthesized approximately 650,000 Mr protease-resistant proteoglycans that contained approximately 80% heparin glycosaminoglycans of approximately 105,000 Mr. Thus, after adoptive transfer, the SMC of the previously mast cell-deficient mice were like those recovered from the normal WBB6F1-+/+ mice that were shown to synthesize approximately 600,000 Mr proteoglycans that contained approximately 80% heparin glycosaminoglycans of approximately 115,000 Mr. As assessed by indirect immunofluorescence staining and flow cytometry using the B1.1 rat mAb (an antibody that recognizes an epitope located on the neutral glycosphingolipid globopentaosylceramide), approximately 5% of BMMC bound the antibody detectably, whereas approximately 72% of the SMC that were harvested from mast cell-deficient mice 15 wk after adoptive transfer of BMMC were B1.1-positive; approximately 82% of SMC from WBB6F1-+/+ mice bound the antibody. These biochemical and immunochemical data are consistent with the results of previous adoptive transfer studies that characterized mast cells primarily on the basis of morphologic and histochemical criteria. Thus, IL-3-dependent BMMC developed in vitro, cells that resemble mucosal mast cells, can give rise in vivo to SMC that express phenotypic characteristics of connective tissue mast cells.
Involvement of simultaneous multiple transcription factor expression, including cAMP responsive element binding protein and OCT-1, for synovial cell outgrowth in patients with rheumatoid arthritis
Authors: S. Wakisaka, N. Suzuki, M. Takeno, Y. Takeba, H. Nagafuchi, N. Saito, H. Hashimoto, T. Tomita, T. Ochi, T. Sakane
Journal: Annals of the Rheumatic Diseases (1998)

To elucidate possible roles of several transcription factors in the pathogenesis of rheumatoid arthritis (RA), the transcription factor expression in RA synovial tissue and their contribution to RA synovial cell functions were studied.Single cell suspension of dissociated synovial tissue was cultured to induce in vitro tissue outgrowth of RA synovial cells. Transcription factors were immunohistochemically identified in RA synovial tissue obtained by joint surgery and in the in vitro tissue outgrowth, and confirmed by western blotting and gel shift assays.Immunohistochemical examination of RA synovial tissue revealed simultaneous expression of various transcription factors (NF-kappa B, c-Jun (a component of AP-1), cAMP responsive element binding protein (CREB), and OCT-1). The same set of transcription factors was expressed in the in vitro tissue outgrowth of RA patients. The early passage RA synovial cells were treated with interleukin 1 beta (IL1 beta) and confirmed translocation of transcription factors into the nucleus by western blotting, and their DNA binding activity by gel shift assays.This study emphasises the importance of the simultaneous expression of several transcription factors for the hyperactivity of RA synovial cells that leads to tissue outgrowth.
Regulation of CD20 in Rituximab-Resistant Cell Lines and B-cell Non-Hodgkin Lymphoma
Authors: Ping-Chiao Tsai, Francisco J. Hernandez-Ilizaliturri, Naveen Bangia, Scott H. Olejniczak, Myron S. Czuczman
Journal: Clinical Cancer Research (2012)

The aim of this research was to further investigate the contribution of CD20 antigen expression to rituximab activity and define the mechanisms responsible for CD20 downregulation in rituximab-resistant cell lines (RRCL).Rituximab-sensitive cell lines, RRCL, and primary neoplastic B cells were evaluated by chromium-51 release assays, ImageStream image analysis, immunohistochemical staining, flow cytometric analysis, CD20 knockdown, promoter activity, chromatin immunoprecipitation (ChIP) analysis of CD20 promoter, and CD20 plasmid transfection experiments to identify mechanisms associated with CD20 regulation in RRCL.RRCL exhibited a gradual loss of CD20 surface expression with repeated exposure to rituximab. We identified a CD20 antigen surface threshold level required for effective rituximab-associated complement-mediated cytotoxicity (CMC). However, a direct correlation between CD20 surface expression and rituximab-CMC was observed only in rituximab-sensitive cell lines. CD20 promoter activity was decreased in RRCL. Detailed analysis of various CD20 promoter fragments suggested a lack of positive regulatory factors in RRCL. ChIP analysis showed reduced binding of several key positive regulatory proteins on CD20 promoter in RRCL. Interleukin-4 (IL-4) induced higher CD20 promoter activity and CD20 expression but modestly improved rituximab activity in RRCL and in primary B-cell lymphoma cells. Forced CD20 expression restored cytoplasmic but not surface CD20, suggesting the existence of a defect in CD20 protein transport in RRCL.We identified several mechanisms that alter CD20 expression in RRCL and showed that, whereas CD20 expression is important for rituximab activity, additional factors likely contribute to rituximab sensitivity in B-cell lymphoma.
Chelation of cadmium without increased renal cadmium deposition.
Authors: M G Cherian
Journal: Environmental Health Perspectives (1984)

Cadmium (Cd) is mainly accumulated in liver and kidney bound to metallothionein (MT) and excreted very slowly from the body. In chronic exposure, Cd is gradually transported from liver to kidney; the renal toxic effects appear when renal Cd concentration exceeds the critical concentration. In order to prevent the Cd-induced renal disease, it is important to control the movement of Cd to the kidney and its renal deposition. However, the chelation of Cd from liver is difficult because of the high affinity of intracellular MT for Cd. A number of chelating agents containing both carboxyl and thiol groups were able to mobilize and excrete Cd more easily in a short time (1/2 hr) after Cd exposure than longer times (24 hr), after MT synthesis. The renal deposition of Cd increased on BAL (2,3-dimercaptopropanol) treatment a short time (1/2 hr) after Cd exposure. However, it was observed that if BAL was administered 24 hr after Cd exposure, it could mobilize Cd from hepatic MT and increase the biliary excretion of Cd without any increase in renal Cd concentration. Studies using a number of structurally related thiols (mono-, di- and trithiols) showed that the major structural requirement for in vivo chelation of Cd from intracellular MT were the vicinal thiol groups on an aliphatic chain, and lipophilicity. BAL was the most effective of all the compounds studied and it did not mobilize Cd to the kidney, when most of the intracellular Cd was bound to MT. Furthermore, a delayed treatment with BAL or DTPA (diethylenetriamine pentaacetic acid) after synthesis of MT resulted in an increase in fecal or urinary excretion of Cd in rat model experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
Long-term effects of anastrozole on bone mineral density: Seven-year results from the ATAC trial
Authors: R. E. Coleman
Journal: Journal of Clinical Oncology (2008)

587 Background: At a median follow-up of 100 months, the ATAC trial has established the long-term efficacy of anastrozole compared with tamoxifen. The study also demonstrates that, whilst adjuvant anastrozole is associated with higher fracture rates than tamoxifen during active treatment, after cessation of therapy there is a rapid decline in fracture rates in the anastrozole group to levels similar to those in the tamoxifen group. Examining the changes in bone mineral density (BMD) during the follow-up period provides additional important information on the skeletal health effects of anastrozole treatment following cessation of therapy. Methods: This randomized, prospective sub-study of the ATAC trial assessed BMD changes in postmenopausal women with invasive primary breast cancer receiving anastrozole (1 mg/day) or tamoxifen (20 mg/day) as adjuvant therapy for five years. Lumbar spine (L1-L4) and total hip BMD were assessed at baseline and after 1, 2, 5, 6, and 7 years using dual energy x-ray absorptiometry. Results: Two years after cessation of treatment, BMD measurements were available for 24 patients in the anastrozole group and 29 in the tamoxifen group. The table below shows the percentage change in BMD in each group (anastrozole vs. tamoxifen, **p<0.01, ***p<0.001). Conclusions: The increased bone loss seen with anastrozole compared with tamoxifen during the five-year adjuvant treatment period did not continue into the off-treatment follow-up period. A recovery of BMD at the lumbar spine and a slowing down in loss at the hip was observed in the anastrozole group. Treatment Anastrozole 0 to 5 years Tamoxifen 0 to 5 years Anastrozole 5 to 7 years Tamoxifen 5 to 7 years N 57 51 24 29 Lumbar spine, % (95% CI) -6.1*** (-10,7, -3.0) +2.8 (-1.4, 5.7) +4.0** (2.2, 5.9) -0.2 (-1.8, 1.5) Total hip, % (95% CI) -7.2*** (-12.4, -3.7) 0.7 (-2.5, 2.8) -0.9 (-2.3, 0.6) -2.4 (-3.7, 1.1) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Cholinergic mechanisms in the cerebral circulation of the newborn piglet: effect of inhibitors of arachidonic acid metabolism.
Authors: L C Wagerle, D W Busija
Journal: Circulation Research (1989)

The cerebrovascular response to cholinergic stimulation and the effect of inhibition of the lipoxygenase and cyclooxygenase pathways on the response to acetylcholine (ACh) was investigated in newborn piglets. Responsiveness of pial arterioles to ACh, methacholine, and nicotine was studied using a closed cranial window. Pial arteriolar diameter was measured using intravital microscopy. Pial arteriolar responses to ACh, 10(-8)-10(-4)M, applied to the cortical surface, were variable and dose-dependent. At low concentration, 10(-7)M, 45% of the arterioles increased diameter by 9 +/- 1%, 19% responded by decreasing diameter by 9 +/- 1%, and 35% did not respond. The response to high concentration, 10(-4)M, was a profound decrease in diameter, 28 +/- 3%, in 78% of the arterioles studied. These effects were abolished by atropine (0.5 mg/kg i.v.). Muscarinic agonist, methacholine, 10(-5)-10(-3)M, also resulted in a decrease in cerebral vascular diameter, while nicotine, 10(-6)-10(-4)M, had no effect. In six animals, administration of cyclooxygenase inhibitor, indomethacin (5 mg/kg i.v.), blocked the response to 10(-4)M ACh but did not affect the response to 10(-7)M ACh. In five animals, administration of lipoxygenase inhibitor, nordihydroguaiaretic acid (2 mg/kg i.v.) augmented the vasoconstrictor response at both ACh concentrations. The data suggest that, in the newborn piglet, vasoactive prostanoids released following cholinergic activation of a muscarinic-type receptor mediate vasoconstriction in cerebral arterioles.
Case-Control Comparison of At-Home to Total Hospital Care for Autologous Stem-Cell Transplantation for Hematologic Malignancies
Authors: Francesc Fernández-Avilés, Enric Carreras, Alvaro Urbano-Ispizua, Montserrat Rovira, Carmen Martínez, Anna Gaya, Miquel Granell, Laia Ramiro, Cristina Gallego, Adela Hernando, Susana Segura, Lourdes García, Manel González, Montserrat Valverde, Emili Montserrat
Journal: Journal of Clinical Oncology (2006)

Purpose One of the most significant limitations of at-home autologous stem-cell transplantation (ASCT) is the necessity for hospital readmission. We developed an at-home ASCT program in which prophylactic ceftriaxone and treatment of febrile neutropenia with piperacillin and tazobactam was introduced to minimize the readmission rate. Patients and Methods Between November 2000 and February 2005, 178 consecutive patients underwent ASCT for a hematologic malignancy. Of these, 50 patients fulfilled the requirements for at-home ASCT. Results were compared with those observed in a control group of 50 patients individually matched to the group of patients treated at home for age, sex, diagnosis, stage of disease, conditioning, and source of stem cells. Results Febrile neutropenia occurred in fewer patients in the at-home group as compared with the hospitalized group (76% v 96%: P = .008), and duration of fever was also shorter in the at-home group (median, 2 and 6 days, respectively; range, 1 to 11 and 1 to 20 days, respectively; P = .00003). Hospital readmission in the at-home group was required in only four cases (8%). This resulted in a reduction of 18.6 days of hospitalization per patient. Likewise, total median charges were approximately half in the at-home group as compared with the in-hospital group (3,345 € v 6,250 €, respectively; P &lt; .00001). Conclusion Results of at-home ASCT with prophylactic administration of ceftriaxone and domiciliary treatment of febrile neutropenia with piperacillin and tazobactam are highly satisfactory and significantly cheaper compared with those obtained with conventional in-hospital ASCT.
CHEMICAL CHANGES IN THE BLOOD OF THE DOG AFTER OBSTRUCTION OF THE ESOPHAGUS AND OF THE CARDIAC END OF THE STOMACH
Authors: Russell L. Haden, Thomas G. Orr
Journal: The Journal of Experimental Medicine (1923)

Ligation of the cardiac end of the stomach or of the esophagus in ten dogs produced a severe toxemia, and rapid death. In seven of the animals there occurred a marked rise in the total non-protein nitrogen and urea nitrogen of the blood. The dogs living longest with cardiac obstruction showed a fall in blood chlorides and a rise in the CO(2)-combining power of the plasma. All the dogs with an obstruction of the esophagus showed a fall in blood chlorides. Control animals subjected to other types of abdominal operations showed no significant changes in the blood.