tbuckley/cabot-search huggingface dataset:
Regulation of 26S Proteasome Activity in Pulmonary Fibrosis
Authors: Nora Semren, Vanessa Welk, Martina Korfei, Ilona E. Keller, Isis E. Fernandez, Heiko Adler, Andreas Günther, Oliver Eickelberg, Silke Meiners
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: The ubiquitin–proteasome system is critical for maintenance of protein homeostasis by degrading polyubiquitinated proteins in a spatially and temporally controlled manner. Cell and protein homeostasis are altered upon pathological tissue remodeling. Dysregulation of the proteasome has been reported for several chronic diseases of the heart, brain, and lung. We hypothesized that proteasome function is altered upon fibrotic lung remodeling, thereby contributing to the pathogenesis of idiopathic pulmonary fibrosis (IPF).Objectives: To investigate proteasome function during myofibroblast differentiation.Methods: We treated lung fibroblasts with transforming growth factor (TGF)-β and examined proteasome composition and activity. For in vivo analysis, we used mouse models of lung fibrosis and fibrotic human lung tissue.Measurements and Main Results: We demonstrate that induction of myofibroblast differentiation by TGF-β involves activation of the 26S proteasome, which is critically dependent on the regulatory subunit Rpn6. Silencing of Rpn6 in primary human lung fibroblasts counteracted TGF-β-induced myofibroblast differentiation. Activation of the 26S proteasome and increased expression of Rpn6 were detected during bleomycin-induced lung remodeling and fibrosis. Importantly, Rpn6 is overexpressed in myofibroblasts and basal cells of the bronchiolar epithelium in lungs of patients with IPF, which is accompanied by enhanced protein polyubiquitination.Conclusions: We identified Rpn6-dependent 26S proteasome activation as an essential feature of myofibroblast differentiation in vitro and in vivo, and our results suggest it has an important role in IPF pathogenesis.
A critical role for p130Cas in the progression of pulmonary hypertension in humans and rodents
Authors: Ly Tu, Frances de Man, Barbara Girerd, Marie-camille Chaumais, Florence Lecerf, Charlene Francois, Frederic Perros, Peter Dorfmuller, Elie Fadel, David Montani, Marc Humbert, Eddahibi Saadia, Christophe Guignabert
Journal: European Respiratory Journal (2012)

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by pulmonary arterial muscularization due to excessive pulmonary vascular cell proliferation and migration, a phenotype dependent upon growth factors and activation of receptor tyrosine kinases (RTKs). p130 Cas  is an adaptor protein involved in several cellular signaling pathways that control cell migration, proliferation and survival.We hypothesized that in experimental and idiopathic PAH p130 Cas  signaling is over-activated, thereby facilitating the intracellular transmission of signal induced by fibroblast growth factor (FGF)2, epidermal growth factor (EGF), and platelet derived growth factor (PDGF). In iPAH patients, levels of p130 Cas  protein are higher in the serum, in walls of distal pulmonary arteries, in cultured smooth muscle (PA-SMCs) and pulmonary endothelial cells (P-ECs) than controls. These abnormalities in the p130 Cas  signaling were also found to be in the chronically hypoxic mice and monocrotaline-injected rats. We next obtained evidence for convergence and amplification of the growth-stimulating effect of EGF, FGF2 and PDGF signaling pathways via p130 Cas  signaling pathway. Finally, we found that daily treatment with each of the EGF-R inhibitor gefitinib, the FGF-R inhibitor dovitinib and the PDGF-R inhibitor imatinib started 2 weeks after a subcutaneous monocrotaline injection substantially attenuate the abnormal increase in p130 cas  and ERK1/2 activation and regress established PH. Our findings demonstrate that p130 Cas  signaling plays a critical role in iPAH by modulating pulmonary vascular cell migration, proliferation and by acting as an amplifier of RTKs downstream signals.
Abstract 2096: LVAD Therapy Up-Regulates ACE-2 but May Decrease Apoptosis & Mediate Reverse Remodeling via a "Non Ang 1 7 - Non mas Receptor" Pathway In Patients With End Stage Heart Failure.
Authors: Y. Chandrashekhar, Ruth Anway, Aparna Godavarthy, Laurie Shekels
Journal: Circulation (2007)
LEUKOCYTE MIGRATION IN AGAROSE, A STUDY ON MULTIPLE SCLEROSIS
Authors: HÅKAN BBRGSTRAND, BENGT KÄLLÉN, OLLE NILSSON
Journal: Allergy (1975)

The effect of low concentrations of bovine encephalitogenic protein on the migration of human peripheral leukocytes in agarose was studied. A concentration of 0.3 mug/ml of the protein stimulated the migration of cells from many donors, including some healthy subjects. An indirect technique suggested that the migration enhancement is due to the production of soluble factor, possibly corresponding to the leukocyte migration enhancement factor described by others. The frequency of subjects whose cells could be stimulated and the recorded degree of stimulation tended to be higher in a group of patients with multiple sclerosis than in a group of healthy subjects. When the effect of some of the main peptide fragments of the protein was studied on cells that were stimulated by the intact protein, one or more of these peptides sometimes induced the opposite effect: a migration inhibition. There is, apparently, a complex balance between enhancing and inhibiting factors acting on leukocyte migration in vitro; and the character of the antigen seems to be one important factor.
Pivotal Phase III Trial of Two Dose Levels of Denileukin Diftitox for the Treatment of Cutaneous T-Cell Lymphoma
Authors: Elise Olsen, Madeleine Duvic, Arthur Frankel, Youn Kim, Ann Martin, Eric Vonderheid, Brian Jegasothy, Gary Wood, Michael Gordon, Peter Heald, Allan Oseroff, Lauren Pinter-Brown, Glen Bowen, Timothy Kuzel, David Fivenson, Francine Foss, Michael Glode, Arturo Molina, Elizabeth Knobler, Stanford Stewart, Kevin Cooper, Seth Stevens, Fiona Craig, James Reuben, Patricia Bacha, Jean Nichols
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB 389 IL-2, Ontak [Ligand Phar-maceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on ≥ 20% of lymphocytes were assigned to one of two dose levels (9 or 18 μg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti–interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 μg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.
Gender, degree of obesity, and discrepancy between urea and creatinine clearance in peritoneal dialysis.
Authors: A H Tzamaloukas, D Malhotra, G H Murata
Journal: Journal of the American Society of Nephrology (1998)

The effect of gender and degree of obesity on the size indicators V, used to normalize urea clearance (Kt/Vur), and body surface area (BSA), used to normalize creatinine clearance (Ccr), in peritoneal dialysis was studied by: (1) mathematical comparison of the formulae used to estimate V (Watson and Hume) with the Dubois formula used to estimate BSA in peritoneal dialysis; and (2) comparison of percent deviation of BSA (delta BSA%) and V (delta V%) from ideal weight estimates in 933 clearance studies performed in actual patients (555 in men and 378 in women on continuous ambulatory peritoneal dialysis). V was estimated by the Watson formulae and BSA by the Dubois formula in these studies. delta BSA% and delta V% were stratified in 10% increments in deviation of body weight from ideal (delta W%) in these studies. Mathematically, the relationship between V and BSA is not linear. In the same subject, as obesity develops (delta W% increases) and BSA increases in a linear manner, V increases exponentially. In addition, there are substantial differences in the relationship between V and BSA caused by gender. For the same height and BSA, men have a larger V than women. In the clearance studies performed in actual continuous ambulatory peritoneal dialysis patients, the difference between delta V% and delta BSA% increased significantly (P < 0.0001) from the wasted to the obese subjects by one-way ANOVA in both men and women. Normalization of urea and creatinine clearances by different size indicators creates two types of mathematical distortion in the relationship between the two clearances. One distortion is caused by the degree of obesity. The second distortion is caused by gender. Use of the same size indicator to normalize both urea and creatinine clearances would eliminate these distortions.
Serial study on lung function in adolescents before and after the repair of chest wall deformities
Authors: Petr Bitnar, Jan Sulc, Milan Smejkal, Jirí snajdauf, Krystof Slabý, Pavel Kolár
Journal: European Respiratory Journal (2013)

Background: Only 2 old studies had performed simple pulmonary function tests (PFT) pre- and postoperatively in patients undergoing pectus excavatum (PE) and carinatum (PC) repair.

Aim and objectives: What are the PFT parametres in chest deformities? Are there differences between groups of PE and PC?What changes occur in PFT after corrective surgery?

Methods: 26 patients PE (16.2±2.0 yrs]) and 21 PC (15.9±1.4) (M/F=42/5). We assessed respiratory performance before and after corrective surgery for chest wall deformities using a wide spectrum of PFT. We used: whole-body plethysmography; standard spirometry; respiratory muscle strength testing (RMS).

Results: 

before repair: TLC was normal in both groups (97±12% in PE ;107±14% in PC). RV%TLC increased (129±34% in PE, p<0.01 ; 125±39% in, p<0.03).Central airway obstruction was found (SGtot 61±26% PE, p<0.001; 54±13% PC, p<0.001).No periph. airway obstruction was detected. Values of maximum insp./exp. pressure (PI max/PE max) were decreased in both groups:66±25% PEmax/53±21% PImax (p<0.001/p<0.001) in PE ; 59±23% PEmax/49±23% PImax(p<0.001/p<0.001) in PC.

After the repair: No change of TLC in both groups was found. RV%TLC increased in PE by 12±41%, p<0.05 while mild regression of this parametr in PC was proved. FEF75 increased by 14±31%, p<0.04 in PE while it decreased by 20±32%, p<0.03 in PC.There were found no changes in central airway patency as well as RMS indice.

Conclusion: No restrictive disorder in either group was found.Normal peripheral airway patency and mild central airway obstruction was proved. Static lung hyperinflation was proved before repair in both groups. Finding of weak respiratory muscles persisted even after the repair.
In vitro steroid sensitivity testing: A possible means to predict response to therapy in primary hypoproliferative anemia
Authors: Nicholas Dainiak, Ronald Hoffman, A. Kim Ritchey, Victoria Floyd, Maureen Callahan
Journal: American Journal of Hematology (1980)

Abstract We investigated the effects of various steroids on erythroid colony formation by normal human bone marrow and peripheral blood, and by marrow and peripheral blood from 18 patients with primary hypoproliferative anemia. These agents were variously found to enhance both CFU‐E and BFU‐E derived colony growth by normal human cells. Fluoxymesterone and dexamethasone were the most active inducers of CFU‐E proliferation, and etiocholanolone and dexamethasone were the most potent burst augmenters. Androsterone did not significantly influence BFU‐E proliferation in 66% of the marrow cultures from hematologically normal donors. Colony formation by erythroid progenitor cells of the patients with hypoproliferative anemia was reduce (20 ± 10 CFU‐E derived colonies/6 × 10 4 marrow cells; 12 ± 5 BFU‐E derived colonies/1 × 10 5 blood cells) when compared to growth by normal cells (65 ± 14 CFU‐E derived colonies/6 × 10 4 marrow cells; 21 ± 9 BFU‐E derived colonies/1 × 10 5 blood cells). Colony formation by marrow or peripheral blood cells of eight patients with steroid‐responsive anemia was only moderately reduced (26 ± 11 CFU‐E derived colonies/6 ± 10 4 marrow cells; 17 ± 3 BFU‐E derived colonies/1 × 10 5 blood cells) when compared to growth by marrow cells of three steroid‐unresponsive patients (3 ± 1.5 CFU‐E derived colonies/6 × 10 4 cells). Whereas the addition of steroids of the same class to marrow and peripheral blood cultures of the steroid‐responsive patients enhanced colony growth by 60–300%, their addition to marrow cultures of the steroid‐unresponsive patients increased colony growth by less than 60%. It appears that further investigations using in vitro culture techniques as predictors of response to steroid therapy in patients with hypoproliferative anemia may be warranted.
“Mom, You Have to Trust Me”
Authors: Mary K. Brennan-Taylor
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Formation of Pure Suspensions of Mast Cells in Tissue Culture by Differentiation of Lymphoid Cells From the Mouse Thymus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Haim Ginsburg, Leo Sachs
Journal: JNCI Journal of the National Cancer Institute (1963)

During studies on the possible effect of a mammalian leukemia virus (isolated by Moloney) on tissue cultures of thymus cells, a synchronized mass differentiation of lymphoid cells to mast cells was observed. Cell suspensions, prepared from thymuses of normal Swiss mice, 15 to 30 days of age, were seeded and maintained in Eagle's medium with 20 percent horse serum on unirradiated feeder layers of mouse embryo cells. During the first few days there was considerable degeneration of the lymphocytes, followed by a proliferation of primitive lymphoid cells similar to large lymphocytes, which were termed mastoblasts. These primitive cells were found in colonies, scattered singly on the feeder layer, or floating freely in the medium. They exhibited a strong tendency to migration. From the chromo-phobic region located in the vicinity of the nucleus of these cells, a new cytoplasmic region morphologically distinct and rich in vacuoles started to appear, which caused the cytoplasm to increase markedly. In this new region the metachromatic granules were formed. Cells with metachromatic granules appeared in large quantities not before the 12th day in vitro. In the stage characterized by cells termed young mast cells, the metachromatic cells underwent mitosis. The course of differentiation was terminated by a stage in which the cells were rich in metachromasia, lacked nucleoli, and had no mitotic activity. As a result of the mass differentiation, pure suspensions of mature mast cells were obtained during the 2d month in vitro, while other cells from the thymus degenerated, differentiated to mast cells, or joined the feeder layer. These suspensions of mast cells were kept on feeder layers of mouse embryo cells for 80 days from initiation of the cultures. The mass differentiation to mast cells was not found in the absence of the feeder layer. A quantitative difference between virus-inoculated and control cultures was observed in all the experiments. This difference was reflected by the greater number of mast cells in the inoculated cultures. Suspensions of mast cells in vitro were not obtained in cultures from mouse spleens.
Susceptibilities to clarithromycin, amoxycillin and metronidazole of Helicobacter pylori isolates from the antrum and corpus in Tokyo, Japan, 1995–2001
Authors: E. Rimbara, N. Noguchi, M. Tanabe, T. Kawai, Y. Matsumoto, M. Sasatsu
Journal: Clinical Microbiology and Infection (2005)
A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial.
Authors: R Somers, P Carde, M Henry-Amar, M Tarayre, J Thomas, A Hagenbeek, M Monconduit, B E de Pauw, W P Breed, L Verdonck
Journal: Journal of Clinical Oncology (1994)

PURPOSE We report a prospective randomized study comparing the relative efficacy of alternating chemotherapy mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) with the standard MOPP chemotherapy in patients with stage IIIB and IV Hodgkin's disease (HD). The purpose is to study the influence of time of remission on clinical outcome. PATIENTS AND METHODS After two courses of MOPP, patients were randomized to receive six further courses of MOPP, or two courses of ABVD followed by two courses of MOPP and two courses of ABVD. Radiotherapy was given to areas presenting with masses &gt; or = 5 cm and to residual masses after course no. 4. Evaluation of response (complete remission [CR]) took place after two courses (CR2), after four courses (CR4), at the end of chemotherapy (CR8), and after additional radiotherapy (CR(CT + RT)). Logistic regression analysis was used to study prognostic factors for response at the end of chemotherapy. Cox analysis was used to study prognostic factors for survival. Two hundred seven patients were registered, 192 (93%) of whom were randomized. RESULTS The CR rate at the end of chemotherapy (CR8) was similar in both arms (57% v 59%). However, there were more progressions in the MOPP arm compared with the MOPP/ABVD arm (23% v 8%, P = .014). A significantly higher failure-free survival (FFS) rate was found in the MOPP/ABVD arm (60% v 43% at 6 years, P = .025). There was no difference in the relapse-free survival (RFS) or survival rate. Of patients not in CR4, only 28% still reached a CR8. RFS at 6 years of patients with CR4 (69%) was not different from that of patients with CR8 (68%); patients with a CR(CT + RT)) had a lower RFS rate (48%). CR4 (P &lt; .001) predicted strongly for final remission at the end of chemotherapy. Cox analysis showed that age more than 50 years, six or more involved lymph node areas, no CR by the fourth cycle, chemotherapy with MOPP alone, and no radiotherapy were unfavorable factors for survival. CONCLUSION MOPP/ABVD chemotherapy significantly improved response and FFS rates, but had no influence on RFS and survival rates. Early CR (CR4) is an important factor for final remission and might be used to select a group of patients with a good prognosis.
Effect of acenitobacter baumanii positive pneumonia on morbidity and mortality of patients
Authors: Safia Shaikh, Alvina Imran, Syed Ali Arsalan, Aneel Bhagwani
Journal: European Respiratory Journal (2013)

INTRODUCTION:  Acinetobacter Baumanii has been observed to increase morbidity and mortality especially in critically ill patients.  We conducted a study to evaluate its effect on patients admitted in Chest Medicine department that included ICU, HDU and General wing.  METHODS:  A retrospective study was conducted from June 2012 to Dec 2012.Sputum and tracheal secretions positive for Acinetobacter were included. The outcome of the patients were recorded. Our secondary outcome was to analyze the incidence in mechanically ventilated patients.  RESULTS:  28 patients in ICU were positive for Acinetobacter in respiratory samples 26 were MDR and 2 were MDS. 18 patients were mechanically ventilated.  4 patients in HDU had positive samples 3 were MDR and 1 was MDS none were mechanically ventilated.  6 patients in ward were positive for Acinetobacter 4 were MDR 1 was MDS and 1 was pan sensitive.  65 % of the patients expired within the first 10 days of having positive samples it was also noted that most of them were mechanically ventilated.  45% of the patients who survived were never mechanically ventilated had MDS or pan sensitive strain. Although they survived the first ten days their hospital stay was prolonged and 25% of them expired later on.  CONCLUSION:  It was concluded that Acinetobacter increases the morbidity and mortality of critically ill patients especially those who are mechanically ventilated.
Correlatin between PET scan and cytokine in non-small cell lung cancer (NSCLC)
Authors: Beatrice Culla, Pierluigi Filosso, Marta Morando, Caterina Bucca, Giovanni Rolla, Riccardo Cristofori, Marta Malandra, Arianna Vaudano, Monica Boita, Luisa Brussino
Journal: European Respiratory Journal (2012)

Background : Systemic and local inflammatory microenvironment may be an important contributor to morbidity and mortality associated with NSCLC. Exhaled breath condensate(EBC) is a non-invasive method to collect airway lining fluid for assessing lung inflammation. Interleukin-6 (IL-6) is associated with poor prognosis and correlates with neoplastic cachexia and with stage of disease. PET scan has been included in standard staging workup and the standardized uptake value(SUV) of PET-scan has been shown to correlate with poor prognosis in lung cancer.   Aim and Objective : to assess the correlations between serum and EBC IL-6 levels and SUV in patients with NSCLC.   Methods : Fifteen consecutive patients (12 males, mean age 64 years, range 39-82) receiving a curative resection for NSCLC were enrolled. All the patients underwent PET scan and IL-6 values measurement both in serum and EBC.   Results : PET scan was positive in all the patients with a mean SUV value 10.64 ± 4.28(range: 6-18.8). Mean IL-6 value was 1.05 pg/ml ± 1.27 in serum and 0.29 pg/ml ± 0.09 in EBC. Significant correlation between SUV and IL-6 levels both in serum and in EBC was found (r= p   Conclusions : the observed relationship suggest that lung and systemic inflammation is proportional to tumor metabolic activity.