tbuckley/cabot-search huggingface dataset:
Expression of immunoproteasome subunits LMP2 and LMP7 by alveolar macrophages is reduced in patients with idiopathic pulmonary fibrosis
Authors: Xuan He, Francesco Bonella, Miao-tian Cai, Toshio Mori, Josune Guzman, Ulrich Costabel
Journal: European Respiratory Journal (2013)

Rationale:  Proteasomes are involved in the degradation of ubiquitinated proteins and the MHC I-restricted antigen presentation. Low molecule weight protein (LMP) 2 and LMP7 are interferon γ-inducible and catalytic subunits of 20S proteasome, and turn it to immunoproteasome. This study was aimed to compare the expression of LMP2 and LMP7 in alveolar macrophages (AMs) from patients with idiopathic pulmonary fibrosis (IPF) and cryptogenic organized pneumonia (COP).   Methods:  BAL cells were collected from 31 patients: 12 IPF, 11 COP and 8 control subjects. Immunocytochemistry was used to stain the cells with monoclonal antibodies against LMP2 and LMP7. Proportions of LMP2 and LMP7 positive AMs were calculated and the strength of LMP2 and LMP7 expression was estimated semi-quantitatively by a staining-intensity score system.   Results:  The expression of LMP2 and LMP7 by AMs from IPF patients was significantly decreased in comparison to controls (Table 1): for COP only a tendency was seen. The expression of LMP7 but not LMP2 in IPF patients treated with steroids was significantly higher compared with those without steroids (positive rates,  p =0.026; scores,  p =0.003).   Conclusions:  The expression of the immunoproteasome subunits seems to be reduced in IPF. The influence of steroid therapy on the expression of LMP7 cannot be excluded.
Changes in the treatment of Enterococcus faecalis infective endocarditis in Spain in the last 15 years: from ampicillin plus gentamicin to ampicillin plus ceftriaxone
Authors: J.M. Pericas, C. Cervera, A. del Rio, A. Moreno, C. Garcia de la Maria, M. Almela, C. Falces, S. Ninot, X. Castañeda, Y. Armero, D. Soy, J.M. Gatell, F. Marco, C.A. Mestres, J.M. Miro, None The Hospital Clinic Endocarditis Study Group
Journal: Clinical Microbiology and Infection (2014)
Bee venom enhances the differentiation of human regulatory T cells
Authors: I. Caramalho, A. Melo, E. Pedro, M. M. P. Barbosa, R. M. M. Victorino, M. C. Pereira Santos, A. E. Sousa
Journal: Allergy (2015)

Venom-specific immunotherapy (VIT) is well recognized by its efficacy, and compelling evidence implicates regulatory T cells (Tregs) in the underlying tolerogenic mechanisms. Additionally, hymenoptera venom has for a long time been claimed to modulate immunity. Here, we investigated the putative role of bee venom (Bv) in human FOXP3-expressing Treg homeostasis and differentiation, irrespective of the donors' allergic status. We found that Bv significantly enhanced the differentiation of FOXP3-expressing cells both from conventional naïve CD4 T cells and mature CD4 thymocytes, a property that may contribute to the VIT's capacity to expand circulating Tregs in allergic individuals. We expect that our data enlightening the Treg-mediated immunomodulatory properties of Bv regardless of TCR specificity, to have application in other allergies, as well as in other clinical settings, such as autoimmunity and transplantation.
The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies
Authors: Matthew J. Niederst, Haichuan Hu, Hillary E. Mulvey, Elizabeth L. Lockerman, Angel R. Garcia, Zofia Piotrowska, Lecia V. Sequist, Jeffrey A. Engelman
Journal: Clinical Cancer Research (2015)

A secondary EGFR mutation, T790M, is the most common resistance mechanism in EGFR-mutant adenocarcinomas that have progressed on erlotinib. Third-generation EGFR inhibitors capable of inhibiting mutant EGFR with T790M produce responses in nearly two thirds of patients. However, acquired resistance mechanisms in patients treated with these drugs are yet to be described.To study acquired resistance to third-generation EGFR inhibitors, T790M-positive cells derived from an erlotinib-resistant cancer were made resistant to a third-generation TKI and then characterized using cell and molecular analyses.Cells resistant to a third-generation TKI acquired an additional EGFR mutation, C797S, which prevented suppression of EGFR. Our results demonstrate that the allelic context in which C797S was acquired may predict responsiveness to alternative treatments. If the C797S and T790M mutations are in trans, cells will be resistant to third-generation EGFR TKIs, but will be sensitive to a combination of first- and third-generation TKIs. If the mutations are in cis, no EGFR TKIs alone or in combination can suppress activity. If C797S develops in cells wild-type for T790 (when third-generation TKIs are administered in the first-line setting), the cells are resistant to third-generation TKIs, but retain sensitivity to first-generation TKIs.Mutation of C797S in EGFR is a novel mechanism of acquired resistance to third-generation TKIs. The context in which the C797S develops with respect to the other EGFR alleles affects the efficacy of subsequent treatments.
Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B cells
Authors: S. Oeder, F. Alessandrini, O. F. Wirz, A. Braun, M. Wimmer, U. Frank, M. Hauser, J. Durner, F. Ferreira, D. Ernst, M. Mempel, S. Gilles, J. T. M. Buters, H. Behrendt, C. Traidl-Hoffmann, C. Schmidt-Weber, M. Akdis, J. Gutermuth
Journal: Allergy (2015)

Background B cells play a central role in IgE-mediated allergies. In damaged airway epithelium, they are exposed directly to aeroallergens. We aimed to assess whether direct exposure of B cells to pollen constituents affects allergic sensitization. Methods B cells from murine splenocytes and from blood samples of healthy donors were incubated for 8 days under Th2-like conditions with aqueous ragweed pollen extracts (Amb-APE) or its constituents. Secreted total IgM, IgG, and IgE was quantified by ELISA. Additionally, birch, grass, or pine-pollen extracts were tested. The number of viable cells was evaluated by ATP measurements. B-cell proliferation was measured by CFSE staining. IgE class switch was analyzed by quantitation of class switch transcripts. In an OVA/Alum i.p.-sensitization mouse model, Amb-APE was intranasally instilled for 11 consecutive days. Results Upon Th2 priming of murine B cells, ragweed pollen extract caused a dose-dependent increase in IgE production, while IgG and IgM were not affected. The low-molecular-weight fraction and phytoprostane E1 (PPE1) increased IgE production, while Amb a 1 did not. PPE1 enhanced IgE also in human memory B cells. Under Th1 conditions, Amb-APE did not influence immunoglobulin secretion. The IgE elevation was not ragweed specific. It correlated with proliferation of viable B cells, but not with IgE class switch. In vivo, Amb-APE increased total IgE and showed adjuvant activity in allergic airway inflammation. Conclusions Aqueous pollen extracts, the protein-free fraction of Amb-APE, and the pollen-contained substance PPE1 specifically enhance IgE production in Th2-primed B cells. Thus, pollen-derived nonallergenic substances might be responsible for B-cell-dependent aggravation of IgE-mediated allergies.
Effectiveness of pulmonary rehabilitation including occupational therapy (OT) on the prognosis of patients with COPD
Authors: Ryoji Maekura, Touru Hiraga, Keisuke Miki, Seigo Kitada, Kenji Yosimura, Yositaka Tateishi, Mari Miki, Masahide Mori
Journal: European Respiratory Journal (2012)

Aim: We reported that the appropriate pulmonary rehabilitation including OT according to the pathophysiology of patient with COPD improved his or her prognosis in the historical control study. In this prospective observational study, we investigated the effectiveness of our pulmonary rehabilitation program on the survival prognosis of COPD patients with long-term oxygen therapy (LTOT).  Method: The subjects were 72 patients with COPD (male: female, 65:7, 69.6±6.8 years old, FEV1 0.76±0.29 L, % predicted 31.6±11.0%, FEV1/FVC 0.38±0.10) who underwent LTOT between 1995 and 2005. All patients were on medication and underwent CPET before pulmonary rehabilitation program. We decided the safe range using the data of CPET, and it was represented by each patient9s Spo2 and pulse rate when a using pulse oximeter during exercise training and in daily life. All patients have been monthly followed up in our specialized clinic for the patients with LTOT.  Result: Forty-six patients died during the follow-up period. Causes of death were the respiratory failure in 20 cases (43.5%), malignant diseases in 10 cases (21.7%) and other diseases in 16 cases (34.8%). The overall 50 % survival time was 9.0 years after LTOT. The 50 % survival times in patients with less than 30% of FEV1 % predicted, 11ml/kg/min of peak oxygen uptake were 8.7 years and 8.1 years after CPET, respectively.  Conclusion: The appropriate pulmonary rehabilitation including OT according to the pathophysiology of each individual patient with COPD decreased the number of death caused by respiratory failure and greatly improved the prognosis of patients with very severe COPD as compared to the previous studies.
What factors explain racial differences in lung volumes?
Authors: PM Donnelly, TS Yang, JK Peat, AJ Woolcock
Journal: European Respiratory Journal (1991)

In order to examine the physical characteristics that may determine racial differences in lung volumes, we studied healthy, nonsmoking Caucasian, Chinese and Indian males of similar ages (range 18-51 yrs). We measured spirometric function, flow volume curves, lung volumes, inspiratory and expiratory muscle pressures, alveolar distensibility and diffusing capacity, together with height, weight and fat free mass. Chest shape was measured using radiographs. The mean total lung capacity and vital capacity in the Caucasian group, expressed as percentage predicted, were 5 and 10% higher than in the Chinese group and 17 and 20% higher than in the Indian group. Chinese values for these measurements were 12 and 10% greater than Indian. We found that Caucasians had higher fat free masses, higher inspiratory and expiratory muscle pressures and wider chests than the other races. The Caucasians and Chinese had longer chests than the Indians. There was no difference in alveolar distensibility or in the diffusion coefficient between the groups. These findings suggest that Caucasians have larger lung volumes than Chinese and Indians because they have increased numbers of alveoli and physically larger chest cavities, and not because of greater alveolar distensibility. Chest dimensions, together with height and race explained 90% of the variation in forced vital capacity and 86% of the variation in total lung capacity. Height multiplied by fat free mass, a "physique factor", previously suggested as the best predictive factor for forced vital capacity in Caucasians, did not account for much of the variation in forced vital capacity between Caucasians and Indians, presumably because it takes no account of differences in chest dimensions.
Effect of PS-K, a Protein Polysaccharide, on Pulmonary Metastases of a C3H Mouse Squamous Cell Carcinoma 2
Authors: S. Usui, M. Urano, S. Koike, Y. Kobayashi
Journal: JNCI Journal of the National Cancer Institute (1976)

We studied the effects of PS-K, a protein polysaccaride isolated from a basidiomycete, on the formation of blood-borne metastases. Experimental tumors were fifth-generation isotransplants of a spontaneous C3Hf mouse squamous cell carcinoma that was weakly antigenic. A single-cell suspension from fourth generation tumors was transplanted, and the tumor-bearing legs of the mice were amputated when transplants reached a certain diameter. Daily administrations of PS-K followed immediately, and both lungs were excised on the 21st postamputation day. The number of lung colonies formed on the surfaces of both lungs was counted and total volumes of metastatic colonies were estimated. PS-K, if administered alone, did not inhibit the lung colony formation. Marked reduction in this formation was observed when five daily doses of PS-K were administered simultaneously with cyclophosphamide. These observations indicate that PS-K may be a potent agent in the therapy of cancer if used as an adjuvant to a chemotherapeutic agent.
Some Electron-Dense Particles Associated With Certain Murine Tumors&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Harold E. Pearson, Richard F. Raker
Journal: JNCI Journal of the National Cancer Institute (1962)

Types A and B (Bernhard) electrondense particles were found in spontaneous adenocarcinomas lof a C3H/Crgl and a randombred Swiss mouse. Type C particles were in Sarcoma 180 of DBA/2 mice, Adenocarcinoma 755 of C57BL/6 × DBA2 mice, and a testicular interstitial-cell tumor (Huseby #20752) of BALB/c mice. Type A occurred in an ependymoma of strain A mice. No bodies were seen in the RC carcinoma of Swiss mice or the P815 mast-cell tumor of (AKR × DBA/2)F1 mice. Attempts to transmit some of these bodies by inoculation of cell-free material to tissue cultures of mouse tumors, and of mouse and hamster embryonic tissue, failed.
Influenza but not rhinovirus viral strain causes exacerbation of a house dust mite driven severe asthma mouse model
Authors: Jorge De Alba, Elena Calama, Raquel Otal, Félix Gil, Montserrat Miralpeix
Journal: European Respiratory Journal (2014)

RATIONALE: Viruses are known to exacerbate asthma and other respiratory diseases. Our objective was to compare the ability of influenza and rhinovirus viral strains to exacerbate a model of allergic inflammation driven by house dust mite (HDM) in Freund9s Complete Adjuvant (FCA). This model mimics certain aspects of severe asthma (1).  METHODS: BALB/c mice were sensitized on day 0 with HDM as previously described (1). On day 14, mice were exposed intranasally (i.n.)to saline or HDM. RV or Influenza strains were administered i.n. 0hrs or 72hrs respectively before HDM challenge. 24hrs post-challenge, non-invasive whole-body plethysmography was used to assess AHR to aerosolised methacholine (MCh). 48hrs after HDM challenge, the bronchoalveolar lavage fluid (BALF) was collected to measure inflammatory cells.  RESULTS: Influenza, but not rhinovirus, strain exacerbated BALF neutrophils and macrophages in the HDM challenged animals (table 1). Influenza also significantly exacerbated the AHR associated with MCh challenge.  CONCLUSIONS: Influenza, but not rhinovirus, exacerbates the inflammation and AHR in our model of allergic inflammation. This model could be used to investigate new mechanisms of action underlying viral exacerbation in severe asthma and for evaluation of novel therapies for such condition.  (1) Nasra J. et al. Am J Respir Crit Care Med 181;2010:A2842.
Estimation of relatedness by DNA fingerprinting.
Authors: M Lynch
Journal: Molecular Biology and Evolution (1988)

The recent discovery of hypervariable VNTR (variable number of tandem repeat) loci has led to much excitement among population biologists regarding the feasibility of deriving individual estimates of relatedness in field populations by DNA fingerprinting. It is shown that unbiased estimates of relatedness cannot be obtained at the individual level without knowledge of the allelic distributions in both the individuals of interest and the base population unless the proportion of shared marker alleles between unrelated individuals is essentially zero. Since the latter is usually on the order of 0.1-0.5 and since there are enormous practical difficulties in obtaining the former, only an approximate estimator for the relatedness can be given. The bias of this estimator is individual specific and inversely related to the number of marker loci and frequencies of marker alleles. Substantial sampling variance in estimates of relatedness arises from variation in identity by descent within and between loci and, with finite numbers of alleles, from variation in identity in state between genes that are not identical by descent. In the extreme case of 25 assayed loci, each with an effectively infinite number of alleles, the standard error of a relatedness estimate is no less than 14%, 20%, 35%, and 53% of the expectation for full sibs and second-, third-, and fourth-order relationships, respectively. Attempts to ascertain relatedness by means of DNA fingerprinting should proceed with caution.
Haemoptysis in adults: a 5-year study using the French nationwide hospital administrative database
Authors: Caroline Abdulmalak, Jonathan Cottenet, Guillaume Beltramo, Marjolaine Georges, Philippe Camus, Philippe Bonniaud, Catherine Quantin
Journal: European Respiratory Journal (2015)

Haemoptysis is a serious symptom with various aetiologies. Our aim was to define the aetiologies, outcomes and associations with lung cancer in the entire population of a high-income country.This retrospective multicentre study was based on the French nationwide hospital medical information database collected over 5 years (2008-2012). We analysed haemoptysis incidence, aetiologies, geographical and seasonal distribution and mortality. We studied recurrence, association with lung cancer and mortality in a 3-year follow-up analysis.Each year, ~15 000 adult patients (mean age 62 years, male/female ratio 2/1) were admitted for haemoptysis or had haemoptysis as a complication of their hospital stay, representing 0.2% of all hospitalised patients. Haemoptysis was cryptogenic in 50% of cases. The main aetiologies were respiratory infections (22%), lung cancer (17.4%), bronchiectasis (6.8%), pulmonary oedema (4.2%), anticoagulants (3.5%), tuberculosis (2.7%), pulmonary embolism (2.6%) and aspergillosis (1.1%). Among incident cases, the 3-year recurrence rate was 16.3%. Of the initial cryptogenic haemoptysis patients, 4% were diagnosed with lung cancer within 3 years. Mortality rates during the first stay and at 1 and 3 years were 9.2%, 21.6% and 27%, respectively.This is the first epidemiological study analysing haemoptysis and its outcomes in an entire population. Haemoptysis is a life-threatening symptom unveiling potentially life-threatening underlying conditions.
Intensive intravenous methotrexate and mercaptopurine treatment of higher-risk non-T, non-B acute lymphocytic leukemia: A Pediatric Oncology Group study.
Authors: B Camitta, D Mahoney, B Leventhal, S J Lauer, J J Shuster, S Adair, C Civin, L Munoz, P Steuber, D Strother
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the potential efficacy and toxicity of intravenous (i.v.) methotrexate (MTX) and mercaptopurine (MP) as postremission intensification treatment for children with B-lineage acute lymphoblastic leukemia (ALL) at higher risk to relapse. PATIENTS AND METHODS Eighty-three patients (age 1 to 20 years) with higher-risk B-lineage ALL were entered onto this protocol. Following standard four-drug remission induction, 80 patients received 12 intensive 2-week cycles of MTX/MP: MTX 200 mg/m2 i.v. push, then 800 mg/m2 i.v. 24-hour infusion on day 1; MP 200 mg/m2 i.v. in 20 minutes, then 800 mg/m2 i.v. 8-hour infusion day 2; MTX 20 mg/m2 intramuscularly day 8; and MP 50 mg/m2 by mouth days 8 to 14. Age-based triple intrathecal therapy (MTX, hydrocortisone, and cytarabine) was administered for CNS prophylaxis. Continuation therapy was weekly MTX/MP (as on days 8 to 14) for 2 years. RESULTS Eighty-one patients (98%) entered remission. There were 28 relapses (marrow, n = 11; marrow and CNS, n = 2; isolated CNS, n = 9; testes, n = 5; ovaries, n = 1). No overt relapse occurred during the intensive phase of therapy. The event-free survival (EFS) rate at 4 years is 57.4% +/- 9.1% (SE). Hematologic, mucosal, and infectious toxicities were seen in 12%, 9%, and 5% of intensive MTX/MP courses, but were generally mild. CONCLUSION Combined data from this and our previous trial suggest that intensive MTX/MP may produce long-term disease-free survival in 70 to 75% of children with B-lineage ALL. In comparison to other intensive regimens, intensive MTX/MP is easy to administer, effective, and relatively nontoxic. If patients at risk for failure of MTX/MP can be identified prospectively, more aggressive regimens could be restricted to this smaller (25% to 30%) cohort.
Multifunctional Theranostic Nanoplatform for Cancer Combined Therapy Based on Gold Nanorods
Authors: Wei‐Hai Chen, Cai‐Xia Yang, Wen‐Xiu Qiu, Guo‐Feng Luo, Hui‐Zhen Jia, Qi Lei, Xiao‐Yong Wang, Gang Liu, Ren‐Xi Zhuo, Xian‐Zheng Zhang
Journal: Advanced Healthcare Materials (2015)

Nanomaterials that integrate diagnostic and therapeutic functions within a single nanoplatform promise great advances in revolutionizing cancer therapy. A smart multifunctional theranostic drug‐delivery system (DDS) based on gold nanorods (abbreviated as GNR/TSDOX) is designed for cancer‐targeted imaging and imaging‐guided therapy. In this intelligent theranostic DDS, the active targeting ligand biotin is introduced to track cancer sites in vivo. With the aid of photothermal/photoacoustic imaging, GNR/TSDOX can ablate cancer specifically and effectively. When stimulated with a single near‐infrared (NIR) light source, this NIR light energy is effectively absorbed and converted into heat by GNR/TSDOX for localized photothermal therapy and the increase in temperature also further triggers the cascaded release of the anticancer drug for combined thermo‐chemotherapy. More importantly, the in vivo cure effect can be well guided by regulating the irradiation time and intensity of the NIR light.
Ultraviolet irradiation induces cyclooxygenase-2 expression in keratinocytes
Authors: None Isoherranen, None Punnonen, None Jansen, None Uotila
Journal: British Journal of Dermatology (1999)

We examined the effect of ultraviolet (UV) irradiation on the expression of cyclooxygenases in cultured HaCaT keratinocytes and in human skin in vivo. UVB irradiation (10 and 50 mJ/cm2) and hydrogen peroxide (200 μmol/L) increased cyclooxygenase‐2 mRNA expression in HaCaT keratinocytes. No clear expression of cyclooxygenase‐1 mRNA was detected in either control or stimulated HaCaT cells. Genistein, a tyrosine kinase inhibitor, suppressed both the basal and stimulated expression of cyclooxygenase‐2 in HaCaT cells. UVB‐induced cyclooxygenase‐2 mRNA expression was partly inhibited by the antioxidant N‐acetylcysteine and by H‐7, a non‐specific inhibitor of protein kinase C. Solar‐simulated irradiation (40 mJ/cm2) was found to induce in vivo both cyclooxygenase‐2 mRNA and protein expression in human skin, whereas the expression of cyclooxygenase‐1 mRNA remained at the basal level. Our results show that cyclooxygenase‐2 expression is induced by UV irradiation and suggest that tyrosine kinases and reactive oxygen intermediates are involved in this induction of cyclooxygenase‐2.
Phenotypic and Genotypic Characteristics of a Cell Line From a Squamous Cell Carcinoma of Human Skin&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: Petra Boukamp, Wolfgang Tilgen, Rule T. Dzarlieva, Dirk Breitkreutz, Dietrich Haag, Rüdiger K. Riehl, Axel Bohnert, Norbert E. Fusenig
Journal: JNCI Journal of the National Cancer Institute (1982)

A human cell line (SCL-1) from a poorly differentiating cutaneous squamous cell carcinoma (SCC) ws studied through 20 passages during 2 years. Cells maintained their original morphology with low degree of keratinization, as indicated by light and electron microscopy. The keratin peptide pattern resembled the type in SCC tumors, and the corresponding filaments were detected by immunofluorescence at all passage levels. Cells did not grow in soft agar but formed tumor-like nodules in an "organotypic" culture assay (on lifted collagen gels) and grew invasively after transplantation to immunosuppressed inbred C3H mice. After injection into BALB/c nu/nu mice, tumors of SCC morphology were formed. The hypodiploid tumor stem-line was maintained for about 10 passages, when a shift to hyperploidy started, as determined by chromosome and DNA flow microfluorometric analyses. Two stable marker chromosomes (in 100 and 70% of the metaphases, respectively), involving chromosomes 7 and 9, strongly indicated a monoclonal origin of this cell line.