tbuckley/cabot-search huggingface dataset:
Recombinant human granulocyte colony-stimulating factor hastens granulocyte recovery after high-dose chemotherapy and autologous bone marrow transplantation in Hodgkin's disease.
Authors: K M Taylor, S Jagannath, G Spitzer, J A Spinolo, S L Tucker, B Fogel, F F Cabanillas, F B Hagemeister, L M Souza
Journal: Journal of Clinical Oncology (1989)

To determine whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) can accelerate granulocyte recovery after high-dose combination chemotherapy with autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease, we performed a nonrandomized phase II study using historical controls as a comparison. Eighteen relapsed/refractory Hodgkin's disease patients who received cyclophosphamide at 1.5 g/m2/day (days -6 to -3), carmustine (BCNU) at 300 mg/m2 (day -6), and etoposide (VP-16) at 125 mg/m2 every 12 hours (days -6 to -4), followed by ABMT (day 0) were treated with rhG-CSF at 60 micrograms/kg/day for a maximum of 28 days beginning on day 1. rhG-CSF dosage was gradually diminished and stopped once an adequate granulocyte count was maintained. rhG-CSF significantly accelerated absolute granulocyte count (AGC) compared with historical controls recovery to the 100/microL level (median, 9 days v 13 days; P = .103 x 10(-4), 500/microL level (median, 13 days v 22 days; P = 0.189 x 10(-2), and 1000/microL level (median, 16 days v 30 days levels; P = .125 x 10(-5). Platelet recovery to 50,000/microL was not significantly altered (P = .370). rhG-CSF was well tolerated, bone pain and myalgia being the only side effects noted. rhG-CSF hastens granulocyte recovery after high-dose chemotherapy with ABMT in patients with relapsed/refractory Hodgkin's disease without significant toxicity.
Effectiveness of an additional tobacco-dehabituation-coaching (TDC) through nursing staff during inpatient pulmonary rehabilitation (PR)
Authors: Birgit Schwaighofer, Angela Burgschwaiger, Renata Stochelska, Zuzana Jurdikova, Konrad Schultz
Journal: European Respiratory Journal (2012)

Background: Tobacco dehabituation (TD) is an essential component of PR. The nursing staff could be able to make an important contribution to TD. We studied the effectiveness of additional coaching from the nursing staff to an already existing comprehensive TD programme (TDP). Methods: From February until July 2011 717 patients were admitted (3-week inpatient PR) of which 26% were smokers. The classification of “smoker” was made in data consolidation served by patients, the physician's estimation and biomonitoring (COHb). Intervention group (TD+coaching through nursing staff=TDC): All smokers within the observed ward were invited to short supportive conversations by the nursing staff (in the first week twice a day, in the following weeks twice a week). In the observed time span 336 patients (95 of which smokers) were assigned to the ward with the associated pilot study. 63 smokers participated in the offered TDC voluntarily (78% male, 55±8 y). 61 patients regularly used NRT. The control group  consisted of 381 consecutive patients from a different ward, observed within the same time span, of which 90 were smokers (59% male, 52±9 years). These patients took part in the same TDP, but without TDC. Results: 

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Discussion: Those smokers who took part in the TDC refrained from smoking significantly more often than those who did not obtain this support.
High Blood Pressure and Its Association With Incident Diabetes Over 10 Years in the Korean Genome and Epidemiology Study (KoGES)
Authors: Nam H. Cho, Kyoung Min Kim, Sung Hee Choi, Kyong Soo Park, Hak Chul Jang, Sung Soo Kim, Naveed Sattar, Soo Lim
Journal: Diabetes Care (2015)

OBJECTIVE No prospective, community-based cohort studies have investigated the association between blood pressure and diabetes in Asian ethnicity. We investigated this issue in a 10-year prospective, community-based study of Koreans. RESEARCH DESIGN AND METHODS We studied whether high blood pressure was associated with the development of diabetes in a population-based cohort, where we sampled ∼5,000 random subjects each from rural and urban areas (age range 40–69 years) during 2001–2010. Among 10,038 subjects, 8,359 without diabetes at baseline were categorized into normal (n = 4,809), prehypertension (n = 2,141), stage 1 hypertension (n = 804), and stage 2 hypertension (n = 605) groups, according to their blood pressure readings of &amp;lt;120/80 mmHg, 120–139/80–89 mmHg, 140–159/90‒99 mmHg, and ≥160/100 mmHg, respectively. The development of diabetes was defined as a fasting glucose concentration of ≥126 mg/dL or a postload glucose concentration of ≥200 mg/dL, based on a 75-g oral glucose tolerance test, or the use of antidiabetic medication. RESULTS During the 10-year follow-up period, diabetes developed in 1,195 subjects (14.3%). The incidence of diabetes increased from 11.1% in the normal group to 17.0% in the prehypertension group, 17.7% in the stage 1 hypertension group, and 25.8% in the stage 2 hypertension group (P &amp;lt; 0.001). After adjusting for anthropometric factors; family history of diabetes; biochemical parameters including C-reactive protein, A1C, and fasting glucose and postload 2-h glucose levels; and the use of lipid-lowering medications, the hazard risks of diabetes development were 1.23 (95% CI 1.06–1.42), 1.26 (1.04–1.54), and 1.60 (1.30–1.96), respectively, in the prehypertension, stage 1 hypertension, and stage 2 hypertension groups. CONCLUSIONS Our findings indicate a grade association of baseline blood pressure with the development of diabetes in Korean individuals.
Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies
Authors: Allison A. King, Naynesh Kamani, Nancy Bunin, Indira Sahdev, Joel Brochstein, Robert J. Hayashi, Michael Grimley, Allistair Abraham, Jacqueline Dioguardi, Ka Wah Chan, Dorothea Douglas, Roberta Adams, Martin Andreansky, Eric Anderson, Andrew Gilman, Sonali Chaudhury, Lolie Yu, Jignesh Dalal, Gregory Hale, Geoff Cuvelier, Akshat Jain, Jennifer Krajewski, Alfred Gillio, Kimberly A. Kasow, David Delgado, Eric Hanson, Lisa Murray, Shalini Shenoy
Journal: American Journal of Hematology (2015)

Fifty-two children with symptomatic sickle cell disease sickle cell disease (SCD) (N = 43) or transfusion-dependent thalassemia (N = 9) received matched sibling donor marrow (46), marrow and cord product (5), or cord blood (1) allografts following reduced intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan between March 2003 and May 2014*. The Kaplan-Meier probabilities of overall and event-free survival at a median of 3.42 (range, 0.75-11.83) years were 94.2% and 92.3% for the group, 93% and 90.7% for SCD, and 100% and 100% for thalassemia, respectively. Treatment-related mortality (all related to graft versus host disease, GVHD) was noted in three (5.7%) recipients, all 17-18 years of age. Acute and chronic GVHD was noted in 23% and 13%, respectively, with 81% of recipients off immunosuppression by 1 year. Graft rejection was limited to the single umbilical cord blood recipient who had prompt autologous hematopoietic recovery. Fourteen (27%) had mixed chimerism at 1 year and beyond; all had discontinued immunosuppression between 4 and 12 months from transplant with no subsequent consequence on GVHD or rejection. Infectious complications included predominantly bacteremia (48% were staphylococcus) and CMV reactivation (43%) necessitating preemptive therapy. Lymphocyte recovery beyond 6 months was associated with subsidence of infectious complications. All patients who engrafted were transfusion independent; no strokes or pulmonary complications of SCD were noted, and pain symptoms subsided within 6 months posttransplant. These findings support using RIC for patients with hemoglobinopathy undergoing matched sibling marrow transplantation (*www.Clinical Trials.gov: NCT00920972, NCT01050855, NCT02435901).
Novel experimental model of maintained acute lung injury
Authors: Ferranda Puig, Raquel Herrero, Raquel Guillamat, Laura Chimenti, Jéssica Tijero, Maria Neus Gómez, Maria Elisa Quílez, Josefina López-Aguilar, Lluis Blanch, Anna Serrano-Mollar, Antonio Artigas
Journal: European Respiratory Journal (2013)

Rationale: Several animal models have been developed to study acute lung injury (ALI); however the majority of these studies are focused on different mechanisms within the acute phase. These models do not allow studying the mechanisms in the later phases or testing any possible long-term treatment. The aim of this study was to develop an experimental ALI model simulating bronchial aspiration of gastric contents with bacterial superinfection with alveolar epithelial damage persisting over time. Methods: Sprague-Dawley rats (200-250g) were anesthetized with isofluorane. ALI was induced by intratracheal instillation of HCl (1 µl/g, 0.1 mol/L pH=1.4) followed by instillation of LPS from Escherichia coli O55:B5 (0, 10, 20, 30 or 40µg/g b.w.) two hours later. Control rats were treated with intratracheal instillations of saline. After 72h, the animals were sacrificed and bronchoalveolar lavage fluid (BALF) was sampled for further analysis of total protein concentration by bicinchoninic acid method. Results: At 72 h, rats suffered a significant loss of weight proportional to the administered dose of LPS (5.6% with 10µg/g b.w, 12.6% with 20µg/g b.w, 14.2% with 30µg/g b.w and 17.7% with 40µg/g b.w). Control rats gained in weight at 72h. LPS at 10, 20, 30 and 40µg/g b.w induced a 1.7, 2.5, 2.9 and 3.4 fold increase in total protein concentration in BAL fluid, respectively, reflecting a substantial increase proportional to the LPS dose. Conclusion: The degree of weight loss and the increase of total protein concentration in BAL fluid in the current model may reflect disease severity and progression. This model would be useful in future for new therapeutical options. Grant acknowledgements: FIS-PI12/02548 and Fundacio Parc Tauli.
Dual training in general internal medicine and rheumatology: the Irish context
Authors: Barry J Sheane
Journal: Annals of the Rheumatic Diseases (2015)

I read with interest the study conducted by Sivera et al ,1 pertaining to differences and similarities in rheumatology training programmes in European League Against Rheumatism (EULAR)-affiliated countries. In particular, as an Irish doctor who has recently completed our national programme and had the fortune to work under some excellent rheumatologists, I was dismayed but not surprised to see that general internal medicine (GIM) plays such a dominant role in official rheumatology training in Ireland. We lead all 41 countries surveyed, where trainees …
Expression of hyperoxidized peroxiredoxins is enhanced in peripheral blood mononuclear cells of bronchial asthma patients
Authors: Yun-Jeong Bae, Tae-Bum Kim, Jae Hyung Roh, Hee-Bom Moon, You Sook Cho, Keun Ai Moon
Journal: European Respiratory Journal (2011)

Background and objectives: Increased oxidative stress is related to the pathogenesis of asthma. Peroxireoxin (Prx), ubiquitous antioxidant enzymes, also termed thioredoxin peroxidases. However, its role in the allergic inflammation remains unidentified. The present study investigates the expression and possible role of Prx and hyperoxidized Prx (Prx-SO3) in asthmatic patients.

Methods: At first, the expression of Prx and Prx-SO3 in peripheral blood mononuclear cells (PBMCs) of asthma patients were semi-quantitatively measured by using Western blot methods from asthma patients and control subjects. And then, to evaluate if higher sensitivity to oxidative stress exposure exists in PBMCs from asthmatics, intracellular ROS levels with hydrogen peroxide treatment were also determined by flowcytometry.

Results: The levels of Prx-SO3/Prx in PBMCs of asthma patients were significantly higher compared to those in normal subjects and were also related with asthma severity. Furthermore, the intracellular ROS after hydrogen peroxide treatment were remarkably enhanced and prolonged in PBMCs from asthmatics, while transiently increased intracellular ROS levels were observed in control subjects.

Conclusions: The hyperoxidation of Prx may be related with increases susceptibility to oxidative stress and possibly play a role in the pathogenesis of severe asthma.
The effects of INTS12 knockdown on processing of snRNAs
Authors: Abdul Kader Kheirallah, Emily Hodge, Carl Nelson, Ian Sayers, Ian Hall
Journal: European Respiratory Journal (2014)

Introduction : Polymorphisms spanning 4q24 are associated with lung function and risk of COPD. The integrator complex subunit 12 gene ( INTS12 ) is a candidate gene in the region for these phenotypes. INTS12 is part of a complex responsible for processing spliceosomal small nuclear RNAs (snRNAs) (1). Human INTS12 shows homology to other proteins involved in gene regulation (2).   Aims : The aim of this study was to optimize INTS12 knockdown in primary human bronchial epithelial cells (HBECs) in order to investigate the function of INTS12 including snRNA processing.   Methods : siRNA delivery to HBECs (passage 3) was optimized by transfecting Cy3-siRNA with INTERFERin followed by epifluorescent imaging. Three siRNA sequences (10nM) targeting human INTS12 were assessed for knockdown of INTS12 expression using qPCR. HPRT1 silencing acted as a positive control. The ratio of immature to total U2 transcripts was assayed by qPCR, to indicate U2 processing.   Results : HPRT1 mRNA expression was attenuated by 90% in HPRT1 siRNA-transfected HBECs (relative to scrambled siRNA transfected cells, n=2). INTS12 mRNA expression in HBECs transfected with INTS12-targeting siRNAs was decreased by 80 ± 6% and 69 ± 3% (pl0.05, n=3) for two siRNAs while not significant for the third siRNA. Preliminary data indicate that maximal INTS12 knockdown has a functional effect on U2 processing and results in ∼60-fold accumulation of immature U2 as assessed by the ratio of primary/total U2 (n=2).   Conclusions : INTS12 is likely to play an important role in HBEC function via snRNA processing: this may affect transcription globally.   Funding : Medical Research Council  1. Baillat  et al.  (2005) Cell 123 (2): 265–76.  2. Obeidat  et al.  (2013) PLoSOne 18;8(9): e74630.
Are there serum levels of MMP-2 and MMP-9 may be markers of COPD phenotypes?
Authors: Bogdana Basina, Tetyana Pertseva, Lyudmyla Konopkina, Vitalii Berezovskyi, Juliya Gordienko
Journal: European Respiratory Journal (2012)

Aim : to optimize an anti-inflammatory therapy in COPD patients (pts).

Materials and methods . 24 pts in stable phase (age – 63.5 ± 3,9 yrs), divided into the subgroups according to the stage of COPD. Measurements included clinical status, spirometry, serum levels of MMP-2 and MMP-9 by immune-fluorescent method (in conventional units).

Results. Level of MMP-2 in all COPD pts was lower than in control (Table 1), besides it correlated with FEV1 (r=-0.47, p=0.02). Level of MMP-9 in COPD pts in the whole was significantly higher than in control; but regardless of FEV1 there were selected two phenotypes of COPD: 1st– with normal level of MMP-9, 2nd – with high one (Table 2).

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table 2





Conclusion : 1) low level of MMP-2 in all COPD pts reflects delay of tissues regeneration and intensification of inflammation because of degradation of monocyte chemotactive protein-3 even starting with II st.; 2) high level of MMP-9 in some COPD pts reflects degradation of collagen, remodulation of tissues and intensification of inflammation; 3) MMP-9 may be used as a marker of COPD phenotypes and thus – to optimize an anti-inflammatory therapy.
Preparation of Concanavalin A-Ricin A-Chain Conjugate and Its Biologic Activity Against Various Cultured Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Teruhito Yamaguchi, Reiko Kato, Masatoshi Beppu, Tadao Terao, Yoshio Inoue, Yoji Ikawa, Toshiaki Osawa
Journal: JNCI Journal of the National Cancer Institute (1979)

For the development of therapeutic agents that possess tissue-specific carriers, a method was devised to synthesize an artificial protein hybrid conjugate containing a moiety which binds to a cell membrane receptor and an active fragment of a toxic protein. By the introduction of an activated sulfhydryl group into concanavalin A (Con A), a conjugate of Con A and the ricin A-chain cross-linked with a dlsulfide linkage was synthesized. The purified conjugate was studied with regard to its inhibitory activity against protein synthesis in cell-free and cultured cell systems. The Con A-ricin A-chain conjugate retained about one-third the inhibitory activity of ricin in a cell-free protein synthesis system. It also was highly toxic to cultured normal cells. These results indicate that the conjugate is a structural and functional analog of ricin and that the original membrane-binding chain (B-chain of ricin) could be replaced by Con A. Transformed cells were insensitive to this conjugate and required a longer preincubation time. The sensitivity of the normal cells was reduced in the presence of local anesthetics.
Direct Infection of Primary Salivary Gland Epithelial Cells by Human T Lymphotropic Virus Type I in Patients With Sjögren's Syndrome
Authors: Hideki Nakamura, Yoshiko Takahashi, Tomomi Yamamoto‐Fukuda, Yoshiro Horai, Yoshikazu Nakashima, Kazuhiko Arima, Tatsufumi Nakamura, Takehiko Koji, Atsushi Kawakami
Journal: Arthritis & Rheumatology (2014)

To investigate whether human T lymphotropic virus type I (HTLV-I) directly infects salivary gland epithelial cells (SGECs) and induces the niche of the salivary glands in patients with Sjögren's syndrome (SS).SGECs were cultured with the HTLV-I-producing CD4+ T cell line HCT-5 or with Jurkat cells. Antibody arrays, immunofluorescence analysis, and enzyme-linked immunosorbent assay (ELISA) were used to determine the profiles of inflammation-related molecules, and the profiles of apoptosis-related molecules were determined by antibody array and immunofluorescence analysis. The presence of HTLV-I-related molecules was assessed by immunofluorescence analysis and in situ polymerase chain reaction. Apoptosis of SGECs was evaluated by TUNEL staining.Among the SGECs, 7.8 ± 1.3% (mean ± SD) were positive for HTLV-I-related proteins after 96-hour coculture with HCT-5 cells. Nuclear NF-κB p65 was also detected in 10% of the SGECs. The presence of HTLV-I proviral DNA in SGECs after coculture with HCT-5 cells was detected by in situ polymerase chain reaction. After coculture of SGECs with HCT-5, the expression of cytokines and chemokines, including soluble intercellular adhesion molecule 1, RANTES, and interferon γ-induced protein 10 kd (IP-10/CXCL10) was increased in a time-dependent manner. The expression of proapoptotic molecules (e.g., cytochrome c and Fas) and antiapoptotic molecules (e.g., Bcl-2, Heme oxygenase 2, and Hsp27) was increased in the SGECs cocultured with HCT-5, showing that apoptosis of SGECs was not detected after coculture with HCT-5 or Jurkat cells.HTLV-I is thought to infect SGECs and alter their cellular functions. These changes may induce the niche of SS and contribute to the development of SS in anti-HTLV-I antibody-positive individuals.
A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases.
Authors: J H Turner, P G Claringbold, E L Hetherington, P Sorby, A A Martindale
Journal: Journal of Clinical Oncology (1989)

Thirty-five patients with disseminated skeletal metastases from a variety of tumor types underwent clinical trial of samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) on a day-patient basis. Individual beta radiation dosimetry was based on pharmacokinetic studies of a 20 mCi tracer dose of 153Sm-EDTMP. The retained skeletal activity varied unpredictably from 40% to 95% of the administered dose, but in all patients greater than 98% of the nonosseous activity was cleared in the urine within 6 hours. Prospective calculation of radiation dosimetry in each patient permitted an accurate dosage schedule based upon total red marrow exposure, starting at 100 cGy and escalating to 280 cGy to define the dose-limiting myelotoxicity. Pain was relieved in 22 of 34 evaluable patients (65%) for periods ranging from 4 to 35 weeks, following a single administration of 153Sm-EDTMP. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of nine patients. The dose-limiting toxicity was myelosuppression manifested particularly by delayed thrombocytopenia. Platelet counts less than 100 x 10(9)/L occurred in 42% of courses when bone marrow radiation absorbed dose exceeded 200 cGy. Myelosuppression was transient and platelet counts had recovered to pretreatment levels within 10 weeks of treatment. 153Sm-EDTMP is effective for the amelioration of pain due to disseminated skeletal metastases particularly with carcinoma of breast or prostate where 83% of patients experienced pain relief. In 15 of the 34 evaluable patients there was evidence of stabilization or regression of skeletal metastases on radiographs and follow-up technetium-99m methylene diphosphonate (99mTc-MDP) bone scans.
GM-CSF stimulates granulopoiesis in a congenital neutropenia patient with loss-of-function biallelic heterozygous CSF3R mutations
Authors: Maksim Klimiankou, Olga Klimenkova, Murat Uenalan, Alexander Zeidler, Sabine Mellor-Heineke, Siarhei Kandabarau, Julia Skokowa, Cornelia Zeidler, Karl Welte
Journal: Blood (2015)
Inhaled corticosteroids (ICS) attenuates epithelial mesenchymal transition (EMT) in COPD: A key to understanding long term benefits?
Authors: Sukhwinder Singh Sohal, Amir Soltani, David Reid, Chris Ward, Steven Weston, Hans Konrad Muller, Richard Wood-Baker, Eugene Haydn Walters
Journal: European Respiratory Journal (2012)

Introduction:  We recently published that EMT is an active process in COPD airways. Our knowledge about the effects of ICS on this process in COPD is very limited.   Objective:  To assess the effects of ICS on EMT in endobronchial biopsies (ebb) from COPD patients.   Methods:  A double-blinded, randomized, placebo-controlled study assessed the effects of inhaled fluticasone propionate (FP; 500µg twice daily) on EMT in 34 COPD patients. Ebb were assessed for EMT related reticular basement membrane (Rbm) fragmentation and immunostained for the EMT signatures S100A4 (a fibroblast epitope), matrix-metalloproteinase-9 (MMP-9) and epithelial activation marker, epidermal growth factor receptor (EGFR).   Results:    Conclusions:  This is the first study to report that ICS have potent anti-EMT effects in COPD. This may be a mechanistic link between ICS treatment and long term reduction in smoking-related lung cancer seen in COPD.
The effect of adenosine on VEGF release from airway smooth muscle from subjects with asthma
Authors: Varsha Kanabar, Rachel Brown, Domenico Spina, Clive Page
Journal: European Respiratory Journal (2013)

Introduction Airway smooth muscle cells (ASM) from subjects with mild asthma secrete increased levels of VEGF and increased expression of adenosine A1 receptor in bronchial biopsies compared to healthy subjects. We hypothesised that VEGF release from ASM in asthma is mediated via adenosine A1 receptors.   Objectives To examine the effect of adenosine on VEGF release in ASM derived from asthmatic subjects.   Methods ASM from healthy (n=4) and mild asthmatic (n=3) subjects were treated with and without adenosine receptor agonists (0.01-100µM) targeting A1 (CPA), A2 (CV1808), A2a (CGS21680), A3 (IB-MECA) or non-selective (adenosine, NECA). ASM were also treated with 10µM NECA following pre-treatment with adenosine receptor antagonists (1-100nM). After 24hr, VEGF levels in cell-conditioned media were determined by ELISA.   Results Constitutive levels of VEGF in ASM derived from asthmatics (275±34pg/ml/10 6  cells) were 1.7 fold greater than ASM derived from healthy subjects (159±34pg/ml/10 6  cells, p   Conclusions VEGF release induced by adenosine receptor activation in ASM derived from mild asthmatic subjects was mediated through A2a and A2b receptors.