tbuckley/cabot-search huggingface dataset:
Proteasome function in lung fibrosis
Authors: Nora Pfister, Oliver Eickelberg, Silke Meiners
Journal: European Respiratory Journal (2013)

The proteasome is a multicatalytic protease complex responsible for the degradation of proteins in numerous cellular processes. Inhibition of the proteasome has been shown to provide antifibrotic effects in different organs. The mechanisms of these antifibrotic actions are not well understood but suggest a role of proteasome function in the pathogenesis of fibrosis.  We hypothesize, that proteasome activity is abnormally regulated and involved in mediating profibrotic effects in lung fibrosis.  To analyze a profibrotic role of the proteasome, CCL206 fibroblasts were treated with TGF-β1 and proteasome activities were examined using specific luminescent substrates and native gel. Proteasome activities were significantly increased in TGF-β1 treated cells without changes in expression of proteasome subunits on mRNA or protein levels. This increase in activity could be blocked by specific proteasome inhibitors and was associated with reduced fibroblast proliferation and collagen deposition. These findings were confirmed in primary lung fibroblasts. Only the regulatory subunit Rpn6, proposed to serve as a key regulator in the assembly of highly active 26S proteasomes, was elevated on protein level. Proteasome activities and Rpn6 levels were also significantly increased in fibrotic lungs of bleomycin-treated mice. We are currently performing siRNA knockdown of Rpn6 to analyze its causal role for mediating TGF-β1 induced proteasome activation.  Increased proteasome activities in TGF-β1 treated fibroblasts and in fibrotic mouse lungs propose a major role of the proteasome in profibrotic processes. This might be caused by Rpn6, mediating the formation of more active proteasome complexes and therefore contributing to the pathogenesis of lung fibrosis.
Point: Hyperthermia with Radiation for Chest Wall Recurrences
Authors: Ellen L. Jones, Lawrence B. Marks, Leonard R. Prosnitz
Journal: Journal of the National Comprehensive Cancer Network (2007)

Treatment of a locoregional recurrence of breast cancer after mastectomy remains a clinically challenging problem. Often these patients have undergone prior radiotherapy and chemotherapy. Therapeutic options usually include resection or additional radiation; however, the long-term control rates are often suboptimal with these approaches. Data from several randomized trials suggest that the addition of hyperthermia to radiation can increase the response rate for such local recurrences. Therefore, in settings where the available therapies are unlikely to yield local control (e.g., local/regional recurrence after prior radiation), a reasonable option to consider is radiation with hyperthermia as a radiation sensitizer. This article reviews the rationale and supporting literature for this recommendation.
Airway Hyperresponsiveness in Asthma
Authors: GRAHAM P. BURNS, G. JOHN GIBSON
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Airway hyperresponsiveness in asthma has been attributed to impaired ability of deep inspiration (DI) to stretch airway smooth muscle. We have retested this hypothesis by comparing the responses to methacholine of 10 asthmatic and 10 control subjects. After each dose subjects breathed tidally without deep inspiration for 4 min, followed by a forced partial expiration from which flow was measured at a constant volume, 35% baseline VC (Vp 35). This index is independent of both DI and increases in end-inspiratory lung volume (EILV). EILV increased significantly more in the asthmatic group than in the control group (15.0 versus 2.5% of baseline VC, p = 0. 019), a factor that if not taken into account would tend to mask the difference in the two responses. Comparisons were made after a cumulative dose of 50 microg methacholine, which was the highest dose common to all subjects. The asthmatic response was significantly greater than that seen in the control group, with reductions to 25.9 and 72.1% of baseline Vp 35, respectively (p = 0. 0007). We conclude that the sensitivity of asthmatic airways to methacholine is greater than that of normal airways even when DI is prohibited. Therefore, the hyperresponsiveness of asthmatic airways is not attributable simply to an inability of DI to stretch airway smooth muscle.
Implication of Epstein‐Barr Virus Infection in Disease‐Specific Autoreactive B Cell Activation in Ectopic Lymphoid Structures of Sjögren's Syndrome
Authors: Cristina Croia, Elisa Astorri, William Murray‐Brown, Amanda Willis, Karl A. Brokstad, Nurhan Sutcliffe, Kim Piper, Roland Jonsson, Anwar R. Tappuni, Costantino Pitzalis, Michele Bombardieri
Journal: Arthritis & Rheumatology (2014)

To examine whether the B cell tropic γ-herpesvirus Epstein-Barr virus (EBV) is aberrantly expressed in its latent and lytic forms within ectopic lymphoid structures (ELS) in the salivary glands of patients with Sjögren's syndrome (SS), and to investigate the relationship between EBV dysregulation, B cell activation, in situ differentiation of autoreactive plasma cells, disease-specific autoantibody production, and cytotoxicity.Latent and lytic EBV infection in the salivary glands of 28 patients with SS and 38 patients with nonspecific chronic sialadenitis (NSCS), characterized for the presence or absence of ELS, was investigated by reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemical/immunofluorescence staining. Glandular versus synovial production of anti-Ro 52, anti-citrullinated protein antibodies (ACPAs), and anti-EBV peptide antibodies was analyzed in situ or in vivo in human SS/SCID and human rheumatoid arthritis/SCID mouse chimeras.EBV dysregulation within inflammatory infiltrates was observed exclusively in ELS+ SS salivary gland tissue, as revealed by latent EBV infection and lytic EBV infection in B cells and plasma cells, respectively. Conversely, epithelial latent membrane protein 2A expression was observed in both patients with SS and patients with NSCS. Importantly, perifollicular plasma cells displaying Ro 52 immunoreactivity were frequently infected by EBV. Furthermore, ELS-containing SS salivary gland tissue that was transplanted into SCID mice supported the production of anti-Ro 52/anti-La 48 and anti-EBV antibodies but not ACPAs. Analysis of CD4+ and CD8+ T cell localization and granzyme B expression demonstrated that the persistence of EBV in ELS-containing SS salivary glands was associated with follicular exclusion of CD8+ T cells and impaired CD8-mediated cytotoxicity.Active EBV infection is selectively associated with ELS in the salivary glands of patients with SS and appears to contribute to local growth and differentiation of disease-specific autoreactive B cells.
Bronchial Responsiveness among Inbred Mouse Strains
Authors: ALEXANDRE DUGUET, KELTOUM BIYAH, ELEANOR MINSHALL, RUTE GOMES, CHONG-GANG WANG, MAJDA TAOUDI-BENCHEKROUN, JASON H. T. BATES, DAVID H. EIDELMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To investigate the relationship between bronchial responsiveness and airway smooth-muscle (ASM) contractile properties, we studied inbred mice with known interstrain differences in airway responsiveness. Using oscillatory mechanics, we confirmed that A/J mice were hyperresponsive to methacholine (MCh) as compared with mice of the C3H/HeJ and C57BL/6J strains. Analysis of respiratory system resistance and elastance at different flow oscillation frequencies indicated that interstrain differences in responsiveness are present in both central and peripheral airways of these mice. We used video microscopy to measure the rate of contraction of explanted airways, and found that the airways of A/J mice contracted more rapidly than those of C3H/HeJ or C57BL/6J mice. In studies of a fourth strain (Balb/C) of mice, we found both bronchial hyperresponsiveness and increased ASM shortening velocity. The rank order of responsiveness among strains was the same as that for shortening velocity (A/J > Balb/C > C3H/HeJ > C57BL/6J). Furthermore, in each strain of mice, shortening velocity correlated with the achieved degree of airway narrowing and with a greater likelihood of airway closure in individual airways. In contrast, generation of isometric tension in trachealis, morphometric measurements of tracheal ASM, tracheal myosin content, and dose–response curves for MCh of explanted intraparenchymal bronchi failed to correspond to the in vivo phenotype of airway reactivity. These results indicate that bronchial responsiveness is related to ASM shortening velocity, and underscore the importance of smooth-muscle dynamics in understanding the mechanisms of bronchial responsiveness. Duguet A, Biyah K, Minshall E, Gomes R, Wang C-G, Taoudi-Benchekroun M, Bates JHT, Eidelman DH. Bronchial responsiveness among inbred mouse strains: role of airway smooth-muscle shortening velocity.
Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia
Authors: Atsushi Yamada, Takahiro Horimatsu, Yoshinaga Okugawa, Naoshi Nishida, Hajime Honjo, Hiroshi Ida, Tadayuki Kou, Toshihiro Kusaka, Yu Sasaki, Makato Yagi, Takuma Higurashi, Norio Yukawa, Yusuke Amanuma, Osamu Kikuchi, Manabu Muto, Yoshiyuki Ueno, Atsushi Nakajima, Tsutomu Chiba, C. Richard Boland, Ajay Goel
Journal: Clinical Cancer Research (2015)

Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms.A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR.Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (≤5 mm) than in healthy subjects.Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia.
Physiological changes in respiratory function associated with ageing
Authors: J.P. Janssens, J.C. Pache, L.p Nicod
Journal: European Respiratory Journal (1999)

Physiological ageing of the lung is associated with dilatation of alveoli, enlargement of airspaces, decrease in exchange surface area and loss of supporting tissue for peripheral airways ("senile emphysema"), changes resulting in decreased static elastic recoil of the lung and increased residual volume and functional residual capacity. Compliance of the chest wall diminishes, thereby increasing work of breathing when compared with younger subjects. Respiratory muscle strength also decreases with ageing, and is strongly correlated with nutritional status and cardiac index. Expiratory flow rates decrease with a characteristic alteration in the flow-volume curve suggesting small airway disease. The ventilation-perfusion ratio (V'A/Q') heterogeneity increases, with low V'A/Q' zones appearing as a result of premature closing of dependent airways. Carbon monoxide transfer decreases with age, reflecting mainly a loss of surface area. In spite of these changes, the respiratory system remains capable of maintaining adequate gas exchange at rest and during exertion during the entire lifespan, with only a slight decrease in arterial oxygen tension, and no significant change in arterial carbon dioxide tension. Ageing tends to diminish the reserve of the respiratory system in cases of acute disease. Decreased sensitivity of respiratory centres to hypoxia or hypercapnia results in a diminished ventilatory response in cases of heart failure, infection or aggravated airway obstruction. Furthermore, decreased perception bronchoconstriction and diminished physical activity may result in lesser awareness of the disease and delayed diagnosis.
Long-Term Immune Reconstitution and Outcome After HLA-Nonidentical T-Cell–Depleted Bone Marrow Transplantation for Severe Combined Immunodeficiency: A European Retrospective Study of 116 Patients
Authors: Elie Haddad, Paul Landais, Wilhelm Friedrich, Bert Gerritsen, M. Cavazzana-Calvo, Gareth Morgan, Yves Bertrand, Anders Fasth, Fulvio Porta, Andrew Cant, Theresa Espanol, Susannah Müller, Paul Veys, Jaak Vossen, Alain Fischer
Journal: Blood (1998)
Cancer Mortality In Iowa Farmers, 1971–78&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L F Burmeister
Journal: JNCI Journal of the National Cancer Institute (1981)

Age-adjusted cancer mortality rates from 1971 to 1978 for male farmers and nonfarmers were computed from Iowa death certificate information. Only data for white males were included in the study because of the limited number of nonwhite farmers in Iowa and because of incomplete occupational information available on females. Mortalities from major types of cancer for farmers and nonfarmers were compared by means of proportionate mortality ratios (PMR). The combined mortality rate for all types of cancer was significantly lower for farmers (PMR = 0.97), due primarily to the significantly lower rates for smoking-related cancers: lung, PMR = 0.78; esophagus, PMR = 0.74; mouth other than lip, PMR = 0.82; and other respiratory cancers, PMR = 0.65. However, the mortality rates for the following cancers were significantly higher for farmers: lip, PMR = 1.62; stomach, PMR = 1.14; leukemia, PMR = 1.10; lymphatic, PMR = 1.14; multiple myeloma, PMR = 1.27; and prostate, PMR = 1.10. Each of the six types of cancer with a significantly elevated mortality in Iowa farmers has also been reported as having an elevated mortality in farmers in other states.
Identification of mast cells in bronchoalveolar lavage fluid
Authors: A. Xaubet, J. A. Moisés, C. Agustí, J. A. Martos, C. Picado
Journal: Allergy (1991)

The present study was carried out to compare the effectiveness of different fixation and staining methods in the identification of mast cells obtained by bronchoalveolar lavage from patients with interstitial lung diseases. Cell preparations were fixed with formaldehyde or methanol. Mast cells were identified by metachromatic staining with May Grunwald Giemsa, Toluidine blue or Gallamine blue Giemsa. After formaldehyde fixation only a few mast cells were identified, regardless of the stain method used. In contrast, a significantly higher number of mast cells were observed after methanol fixation. Using this fixative, Toluidine blue stain showed a higher number of mast cells than May Grunwald Giemsa. However, there was no difference between Toluidine and Gallamine blue Giemsa in the number of cells observed. The easy identification of mast cells after staining with toluidine, combined with its easy application, suggest that Toluidine blue stain after methanol fixation is the most useful method for determining the presence of mast cells in lavage fluid.
Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.
Authors: F Boccardo, A Rubagotti, P Bruzzi, M Cappellini, G Isola, I Nenci, A Piffanelli, A Scanni, P Sismondi, L Santi
Journal: Journal of Clinical Oncology (1990)

Between November 1, 1983 and June 30, 1987, 510 node-positive, estrogen receptor (ER)-positive breast cancer patients have been randomly allocated to receive either chemotherapy (six intravenous [IV] cyclophosphamide, methotrexate, and fluorouracil [CMF] courses followed by four IV epirubicin courses) or 5 years of tamoxifen treatment or a combination of both therapies. After a median follow-up of 40 months, patients receiving the combined treatment achieved the best results, and those treated with chemotherapy alone achieved the worst, the difference being particularly evident in postmenopausal women. However, while the concurrent use of chemotherapy and tamoxifen did improve the results achieved by chemotherapy alone, particularly in postmenopausal women and in those with four or more involved nodes, it did not significantly improve the results achieved by tamoxifen alone, particularly in patients with higher ER tumor concentrations. Side effects were more numerous and more severe in patients receiving chemotherapy (with or without tamoxifen). Our findings, although still preliminary, confirm that tamoxifen should be the treatment of choice for postmenopausal breast cancer patients with node-positive, ER-positive tumors. In addition, the findings suggest that tamoxifen may represent a safe alternative to chemotherapy (at least to the cytotoxic regimen we used) for younger women, provided they have ER-positive tumors. In patients with ER-positive tumors, the addition of chemotherapy to tamoxifen does not seem to improve significantly the effectiveness of tamoxifen alone.
Relationship Between Fibrinolysis of Cultured Cells and Malignancy2
Authors: Walter E. Laug, Peter A. Jones, William F. Benedict
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Relationship Between Fibrinolysis of Cultured Cells and Malignancy Get access Walter E. Laug, Walter E. Laug Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter A. Jones, Peter A. Jones Search for other works by this author on: Oxford Academic PubMed Google Scholar William F. Benedict William F. Benedict Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 1, January 1975, Pages 173–179, https://doi.org/10.1093/jnci/54.1.173 Published: 01 January 1975 Article history Received: 11 July 1974 Accepted: 27 September 1974 Published: 01 January 1975
Mapping the “Depression Switch” During Intraoperative Testing of Subcallosal Cingulate Deep Brain Stimulation
Authors: Ki Sueng Choi, Patricio Riva-Posse, Robert E. Gross, Helen S. Mayberg
Journal: JAMA Neurology (2015)

The clinical utility of monitoring behavioral changes during intraoperative testing of subcallosal cingulate deep brain stimulation is unknown.
Gastroesophageal Reflux and Pulmonary Fibrosis in Scleroderma
Authors: Edoardo Savarino, Marco Bazzica, Patrizia Zentilin, Daniel Pohl, Andrea Parodi, Giuseppe Cittadini, Simone Negrini, Francesco Indiveri, Radu Tutuian, Vincenzo Savarino, Massimo Ghio
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) is associated with increased morbidity and mortality. Gastroesophageal reflux (GER) is considered a contributing factor in the pathogenesis of ILD.To characterize GER (acid and nonacid) in patients with SSc with and without ILD.Patients with SSc underwent pulmonary high-resolution computer tomography (HRCT) scan and 24-hour impedance-pH monitoring off-proton pump inhibitor therapy. The presence of pulmonary fibrosis was assessed using validated HRCT-scores. Reflux monitoring parameters included number of acid and nonacid reflux episodes, proximal migration of the refluxate, and distal esophageal acid exposure. Unless otherwise specified, data are presented as median (25th-75th percentile).Forty consecutive patients with SSc (35 female; mean age, 53 yr; range, 24-71; 15 patients with diffuse and 25 with limited SSc) were investigated; 18 (45%) patients with SSc had pulmonary fibrosis (HRCT score >or= 7). Patients with SSc with ILD had higher (P < 0.01) esophageal acid exposure (10.3 [7.5-15] vs. 5.2 [1.5-11]), higher (P < 0.01) number of acid (41 [31-58] vs. 19 [10-23]) and nonacid (25 [20-35] vs. 17 [11-19]) reflux episodes, and higher (P < 0.01) number of reflux episodes reaching the proximal esophagus (42.5 [31-54] vs. 15 [8-22]) compared with patients with SSc with normal HRCT scores. Pulmonary fibrosis scores (HRCT score) correlated well with the number of reflux episodes in the distal (r(2) = 0.637) and proximal (r(2) = 0.644) esophagus.Patients with SSc with ILD have more severe reflux (i.e., more reflux episodes and more reflux reaching the proximal esophagus). Whether or not the development of ILD in patients with SSc can be prevented by reflux-reducing treatments needs to be investigated.