tbuckley/cabot-search huggingface dataset:
Interstitial lung diseases in Europe
Authors: Roberto Carbone, Rosangela Filiberti, Edoardo Savarino, Riccardo Ghio, Alberto Ballestrero
Journal: European Respiratory Journal (2011)

Background: Interstitial lung diseases (ILD) comprise a disomogeneous group of more than 200 pulmonary disorders and are progressive life-threatening diseases. Etiology is unknown in a variety of ILD. ILD are considered rare diseases, nevertheless they constitute 15-20% of all respiratory pathologies as compared to 6-25% of COPD and to 0.8-0.9% of respiratory tumours. Knowledge of epidemiology of ILD would be important to the planning of services for these patients, but so far ILD have not been well characterized.

Aim: To quantify the burden of the ILD in Europe.

Methods: English articles on ILD epidemiology in Europe were reviewed using PubMed as the search engine.

Results and conclusions: In Europe, ILD incidence rates ranged from 3.62 (South of Spain) to 7.6 cases ×100,000 inhabitants (Spain) according to different studies. In the majority of cases a male predominance was found. Among ILD, the most frequent entities were idiopathic pulmonary fibrosis (IPF: 19-39% of all ILD), sarcoidosis (12-35%) and hypersensitivity pneumonia (3-12%). Incidence rates of IPF and sarcoidosis ranged from 0.93 (Greece) to 6.78 cases ×100,000 (UK) and from 1.07 (Greece) to 5.59 ×100,000 (UK), respectively. Median age at diagnosis was about 61 years for IPF and 42 years for sarcoidosis. Fibrotic NSIP was considered as a new subgroup, making up 20-35% of patients previously diagnosed as IPF. Few data exist on the frequency of ILD and discrepancies among different areas have been observed. Differences in part real, but are due to the use of disomogeneous sources (disease registries, selected clinical series, different study designs), to the inclusion of incident or prevalent cases, to variable criteria for diagnosis, or to selection bias.
Effect of large-scale social marketing of insecticide-treated nets on child survival in rural Tanzania
Authors: Joanna RM Armstrong Schellenberg, Salim Abdulla, Rose Nathan, Oscar Mukasa, Tanya J Marchant, Nassor Kikumbih, Adiel K Mushi, Haji Mponda, Happiness Minja, Hassan Mshinda, Marcel Tanner, Christian Lengeler
Journal: The Lancet (2001)
Differences in susceptibility of mature and immature mouse B lymphocytes to anti-immunoglobulin-induced immunoglobulin suppression in vitro. Possible implications for B-cell tolerance to self.
Authors: M C Raff, J J Owen, M D Cooper, A R Lawton, M Megson, W E Gathings
Journal: The Journal of Experimental Medicine (1975)

Purified goat antibodies against mouse mu-chains and rabbit antibodies against mouse Ig determinants, and their Fab fragments, inhibited the development of IgM-bearing B cells in explant cultures of 14-day mouse fetal liver, and caused the disappearance of cell surface IgM in explant and dissociated cell cultures of more developed lymphoid tissues. While treatment of cultures of fetal or newborn liver, or adult bone marrow, with low concentrations (less than or equal to 10 mug/ml) of anti-Ig for less than or equal to 24 h caused the complete, but reversible, disappearance (modulation) of cell surface IgM, treatment for greater than or less than 48 h produced irreversible IgM suppression. In contrast, anti-Ig-induced suppression of cell surface IgM in cultures of adult spleen or lymph nodes required much higher concentrations of antibody (greater than or equal to 100 mug/ml) and was always reversible. These differences between immature and mature IgM-bearing cells could not be related to differences in the amount of surface IgM on the cells. The remarkable sensitivity of newly formed B cells to IgM modulation and irreversible IgM suppression when ligands bind to their Ig receptors, may have important implications for B-cell tolerance to self antigens.
Regulation of interleukin 3 gene induction in normal human T cells.
Authors: S C Guba, G Stella, L A Turka, C H June, C B Thompson, S G Emerson
Journal: Journal of Clinical Investigation (1989)

The regulation of IL-3 gene induction in human peripheral blood T cells was studied. IL-3 gene expression was inducible by crosslinking of the T cell receptor/CD3 complex using anti-CD3 MAb G19-4. Anti-CD3-induced IL-3 gene expression was found to be limited to the CD28+ T cell subset and could be augmented by costimulating T lymphocytes with antibodies directed against CD28. IL-3 expression could also be induced by costimulation of T cells with both phorbol ester and ionomycin, which are thought to mimic the intracellular effects of T cell receptor-antigen interaction. However, unlike other lymphokines such as IL-2 or granulocyte-macrophage colony-stimulating factor, IL-3 gene expression is not induced by stimulation of cells with phorbol myristate acetate and anti-CD28. We conclude that IL-3 gene regulation is under stringent control since IL-3 gene expression occurs only in the CD28+ subset of T cells, and since IL-3 induction obligately requires increased intracellular calcium.
1421 ALISPORIVIR (ALV) PLUS PEGINTERFERON/RIBAVIRIN (PR) ACHIEVES HIGH SVR12 RATES AMONG NULL RESPONDERS, IL28BCT/TT AND CIRRHOTIC HCVG1 PATIENTS (FUNDAMENTAL STUDY INTERIM ANALYSIS)
Authors: M. Buti, R. Flisiak, J. Rasenack, G. Davis, A. Alberti, T. Goeser, C. Stanciu, W.-L. Chuang, F. Tabak, J.-H. Kao, A. Streinu-Cercel, G. Hofstetter, J. Wang, C. Avila, R. Orsenigo
Journal: Journal of Hepatology (2013)
A Comparison of Outcomes with Angiotensin-Converting–Enzyme Inhibitors and Diuretics for Hypertension in the Elderly
Authors: Lindon M.H. Wing, Christopher M. Reid, Philip Ryan, Lawrence J. Beilin, Mark A. Brown, Garry L.R. Jennings, Colin I. Johnston, John J. McNeil, Graham J. Macdonald, John E. Marley, Trefor O. Morgan, Malcolm J. West
Journal: New England Journal of Medicine (2003)

Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin–angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting–enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents.
Enigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice
Authors: Cho-Rok Jung, Jung Hwa Lim, Yoonjung Choi, Dae-Ghon Kim, Koo Jeong Kang, Seung-Moo Noh, Dong-Soo Im
Journal: Journal of Clinical Investigation (2010)

The human E3 ubiquitin ligase murine double minute 2 (MDM2) targets the tumor suppressor p53 for ubiquitination and degradation but also promotes its own ubiquitination and subsequent degradation. As the balance between MDM2 and p53 levels plays a crucial role in regulating cell proliferation and apoptosis, we sought to identify factors selectively inhibiting MDM2 self-ubiquitination. Here we have shown that the LIM domain protein Enigma directly interacts with MDM2 to form a ternary complex with p53 in vitro and in human hepatoma and colon carcinoma cell lines and mouse embryonic fibroblasts. We found that Enigma elicited p53 degradation by inhibiting MDM2 self-ubiquitination and increasing its ubiquitin ligase activity toward p53 in cells. Moreover, mitogenic stimuli such as serum, FGF, and HGF increased Enigma transcription via induction of serum response factor (SRF), leading to MDM2 stabilization and subsequent p53 degradation. We observed similar results in the livers of mice treated with HGF. In humans, we found SRF and Enigma coexpressed with MDM2 but not p53 in several liver and stomach tumors. Finally, we showed that Enigma promoted cell survival and chemoresistance by suppressing p53-mediated apoptosis in both cell lines and a mouse xenograft model. Our findings suggest a role for Enigma in tumorigenesis and uncover a mechanism whereby mitogens attenuate p53 antiproliferative activity through an SRF/Enigma/MDM2 pathway.
Control of Cigarette Smoking from a Medical Perspective
Authors: L Kuller, E Meilahn, M Townsend, G Weinberg
Journal: Annual Review of Public Health (1982)

Cigarette smoking cessation is apparently associated with decreased risk of heart attack and cancer and improvement in pulmonary function. We suspect, however, that those who quit smoking are not the "highest risk group." The preliminary results of clinical trials at least for heart disease and smoking cessation are not as impressive as the results of observational studies. Isolated smoking cessation programs with reference to a definable population contribute little to our knowledge of the health effects of smoking cessation, probably attract relatively "low risk smokers," and have a smaller public health impact than anticipated.
Use of GHb (HbA1c) in screening for undiagnosed diabetes in the U.S. population.
Authors: C L Rohlfing, R R Little, H M Wiedmeyer, J D England, R Madsen, M I Harris, K M Flegal, M S Eberhardt, D E Goldstein
Journal: Diabetes Care (2000)

OBJECTIVE: To evaluate the use of GHb as a screening test for undiagnosed diabetes (fasting plasma glucose &amp;gt; or =7.0 mmol/l) in a representative sample of the U.S. population. RESEARCH DESIGN AND METHODS: The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged &amp;gt; or =20 years. Of these subjects, 7,832 participated in a morning examination session, of which 1,273 were excluded because of a previous diagnosis of diabetes, missing data, or fasting time of &amp;lt;8 h before examination. Venous blood was obtained to measure fasting plasma glucose and GHb in the remaining 6,559 subjects. Receiver operating characteristic curve analysis was used to examine the sensitivity and specificity of GHb for detecting diabetes at increasing GHb cutoff levels. RESULTS: GHb demonstrated high sensitivity (83.4%) and specificity (84.4%) for detecting undiagnosed diabetes at a GHb cutoff of 1 SD above the normal mean. Moderate sensitivity (63.2%) and very high specificity (97.4%) were evident at a GHb cutoff of 2 SD above the normal mean. Sensitivity at this level ranged from 58.6% in the non-Hispanic white population to 83.6% in the Mexican-American population; specificity ranged from 93.0% in the nonHispanic black population to 98.3% in the non-Hispanic white population. CONCLUSIONS: GHb is a highly specific and convenient alternative to fasting plasma glucose for diabetes screening. A GHb value of 2 SD above the normal mean could identify a high proportion of individuals with undiagnosed diabetes who are at risk for developing diabetes complications.
Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City Children
Authors: William W. Busse, Wayne J. Morgan, Peter J. Gergen, Herman E. Mitchell, James E. Gern, Andrew H. Liu, Rebecca S. Gruchalla, Meyer Kattan, Stephen J. Teach, Jacqueline A. Pongracic, James F. Chmiel, Suzanne F. Steinbach, Agustin Calatroni, Alkis Togias, Katherine M. Thompson, Stanley J. Szefler, Christine A. Sorkness
Journal: New England Journal of Medicine (2011)

Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control.
Increased Expression of Wiskott-Aldrich Syndrome Protein Family Verprolin-Homologous Protein 2 Correlated with Poor Prognosis of Hepatocellular Carcinoma
Authors: Lian-Yue Yang, Yi-Ming Tao, Di-Peng Ou, Wei Wang, Zhi-Gang Chang, Fan Wu
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Because of its role in cell migration, the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) 2 has been implicated in cancer metastasis. Evidence to support such a role of WAVE2 in human cancer, however, is lacking. We thus examined the expression of WAVE2 in hepatocellular carcinoma (HCC) tissues to test whether the levels of WAVE2 expression correlated to the progression of HCC. Experimental Design: Samples of 112 HCC patients were determined immunohistochemically for WAVE2 expression and the correlation of WAVE2 levels with prognosis was analyzed. Among the 112 cases, 31 paired HCC and paracarcinomatous liver tissue specimens were analyzed for WAVE2 levels by reverse transcription-PCR and Western blotting, respectively. Results: Among 112 cases of HCCs, the immunohistochemistry data indicated significant increase of WAVE2 expression levels in 71 cases. Importantly, the increased WAVE2 expression correlated with the multiple tumor nodules (P = 0.008), the absence of capsular formation (P = 0.035), Edmondson-Steiner grade (P = 0.009), vein invasion (P = 0.023), and a shortened median survival time (326 versus 512 days; P = 0.003). Multivariable Cox regression analysis revealed the WAVE2 expression level was an independent factor for prognosis. The immunohistochemistry data were further confirmed by results of reverse transcription-PCR and Western analysis of 31 HCC cases, in which the WAVE2 mRNA and protein in HCC tissues were significantly elevated when compared with paracarcinomatous liver tissue (P &amp;lt; 0.001). Conclusions: WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC.
Spontaneous Myocardial Infarction in Mice Lacking All Nitric Oxide Synthase Isoforms
Authors: Sei Nakata, Masato Tsutsui, Hiroaki Shimokawa, Osamu Suda, Tsuyoshi Morishita, Kiyoko Shibata, Yasuko Yatera, Ken Sabanai, Akihide Tanimoto, Machiko Nagasaki, Hiromi Tasaki, Yasuyuki Sasaguri, Yasuhide Nakashima, Yutaka Otsuji, Nobuyuki Yanagihara
Journal: Circulation (2008)

The roles of nitric oxide (NO) in the cardiovascular system have been investigated extensively in pharmacological studies with NO synthase (NOS) inhibitors and in studies with NOS isoform-deficient mice. However, because of the nonspecificity of the NOS inhibitors and the compensatory interactions among NOS isoforms (nNOS, iNOS, and eNOS), the ultimate roles of endogenous NO derived from the entire NOS system are still poorly understood. In this study, we examined this point in mice deficient in all 3 NOS isoforms (triply n/i/eNOS(-/-) mice) that we have recently developed.The triply n/i/eNOS(-/-) mice, but not singly eNOS(-/-) mice, exhibited markedly reduced survival, possibly due to spontaneous myocardial infarction accompanied by severe coronary arteriosclerotic lesions. Furthermore, the triply n/i/eNOS(-/-) mice manifested phenotypes that resembled metabolic syndrome in humans, including visceral obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance. Importantly, activation of the renin-angiotensin system was noted in the triply n/i/eNOS(-/-) mice, and long-term oral treatment with an angiotensin II type 1 receptor blocker significantly suppressed coronary arteriosclerotic lesion formation and the occurrence of spontaneous myocardial infarction and improved the prognosis of those mice, along with ameliorating the metabolic abnormalities.These results provide the first direct evidence that genetic disruption of the whole NOS system causes spontaneous myocardial infarction associated with multiple cardiovascular risk factors of metabolic origin in mice in vivo through the angiotensin II type 1 receptor pathway, demonstrating the critical role of the endogenous NOS system in maintaining cardiovascular and metabolic homeostasis.
The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus
Authors: Tobias Alexander, Ramona Sarfert, Jens Klotsche, Anja A Kühl, Andrea Rubbert-Roth, Hannes-Martin Lorenz, Jürgen Rech, Bimba F Hoyer, Qingyu Cheng, Aderajew Waka, Adriano Taddeo, Michael Wiesener, Georg Schett, Gerd-Rüdiger Burmester, Andreas Radbruch, Falk Hiepe, Reinhard E Voll
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To investigate whether bortezomib, a proteasome inhibitor approved for treatment of multiple myeloma, induces clinically relevant plasma cell (PC) depletion in patients with active, refractory systemic lupus erythematosus (SLE). Methods Twelve patients received a median of two (range 1–4) 21-day cycles of intravenous bortezomib (1.3 mg/m 2 ) with the coadministration of dexamethasone (20 mg) for active SLE. Disease activity was assessed using the SLEDAI-2K score. Serum concentrations of anti–double-stranded DNA (anti-dsDNA) and vaccine-induced protective antibodies were monitored. Flow cytometry was performed to analyse peripheral blood B-cells, PCs and Siglec-1 expression on monocytes as surrogate marker for type-I interferon (IFN) activity. Results Upon proteasome inhibition, disease activity significantly declined and remained stable for 6 months on maintenance therapies. Nineteen treatment-emergent adverse events occurred and, although mostly mild to moderate, resulted in treatment discontinuation in seven patients. Serum antibody levels significantly declined, with greater reductions in anti-dsDNA (∼60%) than vaccine-induced protective antibody titres (∼30%). Bortezomib significantly reduced the numbers of peripheral blood and bone marrow PCs (∼50%), but their numbers increased between cycles. Siglec-1 expression on monocytes significantly declined. Conclusions These findings identify proteasome inhibitors as a putative therapeutic option for patients with refractory SLE by targeting PCs and type-I IFN activity, but our results must be confirmed in controlled trials.
Successful combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas
Authors: M de Perrot, M Licker, J Robert, L Nicod, A Spiliopoulos
Journal: European Respiratory Journal (1998)

Pulmonary lymphangioleiomyomatosis (LAM) and renal angiolipomas are rare but distinct clinical entities that share similar morphological features. Lung transplantation is considered as a valuable therapeutic modality in patients with end-stage pulmonary LAM. However, in some patients, renal complications due to bleeding angiomyolipomas and cyclosporin-induced nephropathy have become newly identified problems. This study reports the first case of combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas. Two years after transplantation, renal and pulmonary function have remained stable and the patient has resumed a normal daily life, including a full-time professional activity.
LMP1-deficient Epstein-Barr virus mutant requires T cells for lymphomagenesis
Authors: Shi-Dong Ma, Xuequn Xu, Julie Plowshay, Erik A. Ranheim, William J. Burlingham, Jeffrey L. Jensen, Fotis Asimakopoulos, Weihua Tang, Margaret L. Gulley, Ethel Cesarman, Jenny E. Gumperz, Shannon C. Kenney
Journal: Journal of Clinical Investigation (2014)

Epstein-Barr virus (EBV) infection transforms B cells in vitro and is associated with human B cell lymphomas. The major EBV oncoprotein, latent membrane protein 1 (LMP1), mimics constitutively active CD40 and is essential for outgrowth of EBV-transformed B cells in vitro; however, EBV-positive diffuse large B cell lymphomas and Burkitt lymphomas often express little or no LMP1. Thus, EBV may contribute to the development and maintenance of human lymphomas even in the absence of LMP1. Here, we found that i.p. injection of human cord blood mononuclear cells infected with a LMP1-deficient EBV into immunodeficient mice induces B cell lymphomas. In this model, lymphoma development required the presence of CD4+ T cells in cord blood and was inhibited by CD40-blocking Abs. In contrast, LMP1-deficient EBV established persistent latency but did not induce lymphomas when directly injected into mice engrafted with human fetal CD34+ cells and human thymus. WT EBV induced lymphomas in both mouse models and did not require coinjected T cells in the cord blood model. Together, these results demonstrate that LMP1 is not essential for EBV-induced lymphomas in vivo and suggest that T cells supply signals that substitute for LMP1 in EBV-positive B cell lymphomagenesis.
Interleukin-6, Interleukin-10, and Vascular Endothelial Growth Factor in Metastatic Renal Cell Carcinoma: Prognostic Value of Interleukin-6—From the Groupe Français d'Immunothérapie
Authors: Sylvie Negrier, David Perol, Christine Menetrier-Caux, Bernard Escudier, Michel Pallardy, Alain Ravaud, Jean-Yves Douillard, Christine Chevreau, Christine Lasset, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2004)

Purpose Few clinical prognostic factors have been identified for patients with metastatic renal cell carcinoma (MRCC), and no biomarker is known in this disease. Several endogenous cytokines have demonstrated interesting and significant correlations with survival in these patients. Our objective was to analyze the prognostic value of circulating vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and interleukin-6 (IL-6). Patients and Methods Serum levels of IL-6, IL-10, and VEGF were measured in patients with MRCC. Their prognostic value for response to treatment and progression-free and overall survival was evaluated. Pretreatment samples were obtained from 138 patients of a large randomized multicentric trial. Endogenous cytokine levels were determined using immunoassays. Univariate and multivariate analyses were performed to evaluate the prognostic value of each factor further controlled by an internal validation test. Threshold values for serum IL-6 and VEGF were determined using the quartile method. Results Serum IL-6 was detectable in 70% of the patients. IL-10 and VEGF were elevated in 8% and 71% of the patients, respectively. None of these circulating factors was correlated with response to treatment. IL-10 was not significantly correlated with progression-free or overall survival. Despite significant correlation with survival, VEGF was not an independent prognostic factor in the multivariate analysis. Finally, IL-6 was significantly correlated with progression-free survival and overall survival, and has prognostic value for overall survival. Conclusion Circulating IL-6 level appears to be an important independent prognostic factor in patients with MRCC; if confirmed in further studies, it could be considered for treatment decisions in these patients.