tbuckley/cabot-search huggingface dataset:
A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein–dependent signaling
Authors: Peisong Ma, Aleksandra Cierniewska, Rachel Signarvic, Marcin Cieslak, Hong Kong, Andrew J. Sinnamon, Richard R. Neubig, Debra K. Newman, Timothy J. Stalker, Lawrence F. Brass
Journal: Blood (2011)
Impact of Kras Mutation on the Response and Prognosis of Patients with Stage III Non-Squamous Non-Small Cell Lung Cancer
Authors: S. Yagishita, H. Horinouchi, K.S. Sunami, S. Kanda, Y. Fujiwara, H. Nokihara, N. Yamamoto, M. Sumi, K. Shiraishi, T. Kohno, K. Furuta, K. Tsuta, T. Tamura
Journal: Annals of Oncology (2014)
Chemotherapy versus hormonal treatment in platinum- and paclitaxel-refractory ovarian cancer: a randomised trial of the German Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group Ovarian Cancer
Authors: A. du Bois, W. Meier, H.J. Lück, G. Emons, V. Moebus, W. Schroeder, S. Costa, T. Bauknecht, S. Olbricht, C. Jackisch, B. Richter, U. Wagner
Journal: Annals of Oncology (2002)
Hepatitis B antigen (HBSAg) and/or antibodies (anti-HBS and anti-HBC) in fulminant hepatitis: pathogenic and prognostic significance.
Authors: C G Trepo, D Robert, J Motin, D Trepo, M Sepetjian, A M Prince
Journal: Gut (1976)

Hepatitis B surface antigen (HBSAg) and antibodies to both the surface and core antigens of the hepatitis B virus (anti-HBS and anti-HBC) have been studied in 64 consecutive cases of fulminant hepatitis. HBSAg was detected by counterelectrophoresis in 23 (35-9%) but by radioimmunoassay in 38 (59-3%). Anti-HBS was detected by passive haemagglutination in 26 (40-6%), coexisting HBSAg and anti-HBS were found in 16 cases (25%). Using an indirect immunofluorescence technique, anti-HBC was found in all of the cases in whom either HBSAg or anti-HBS was present. The highest survival rate was observed in patients with no evidence of HBV infection (31-3%) and was lowest in those who had both HBSAg and anti-HBS detected simultaneously (6-2%). The prognosis of those who exhibited anti-HBS only was no better than those with HBSAg alone. In a further case, transient interruption of the asymptomatic chronic HBSAg carrier state with seroconversion to anti-HBS was associated with the development of a fulminant hepatitis syndrome. The results suggest that an unusually strong and rapid immune clearance of HBSAg may be involved in the pathogenesis of fulminant hepatitis.
Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor–induced lethal hepatitis
Authors: Montserrat Marí, Anna Colell, Albert Morales, Covadonga Pañeda, Isabel Varela-Nieto, Carmen García-Ruiz, José C. Fernández-Checa
Journal: Journal of Clinical Investigation (2004)

S-adenosyl-L-methionine (SAM) is synthesized by methionine adenosyltransferases (MATs). Ablation of the liver-specific MAT1A gene results in liver neoplasia and sensitivity to oxidant injury. Here we show that acidic sphingomyelinase (ASMase) mediates the downregulation of MAT1A by TNF-α. The levels of MAT1A mRNA as well as MAT I/III protein decreased in cultured rat hepatocytes by in situ generation of ceramide from exogenous human placenta ASMase. Hepatocytes lacking the ASMase gene (ASMase–/–) were insensitive to TNF-α but were responsive to exogenous ASMase-induced downregulation of MAT1A. In an in vivo model of lethal hepatitis by TNF-α, depletion of SAM preceded activation of caspases 8 and 3, massive liver damage, and death of the mice. In contrast, minimal hepatic SAM depletion, caspase activation, and liver damage were seen in ASMase–/– mice. Moreover, therapeutic treatment with SAM abrogated caspase activation and liver injury, thus rescuing ASMase+/+ mice from TNF-α–induced lethality. Thus, we have demonstrated a new role for ASMase in TNF-α–induced liver failure through downregulation of MAT1A, and maintenance of SAM may be useful in the treatment of acute and chronic liver diseases.
Evaluation of bronchoalveolar cells in pulmonary paracoccidioidomycosis
Authors: M.C. Fornazim, A. Balthazar, R. Quagliato, R.L. Mamoni, C. Garcia, M.H.S.L. Blotta
Journal: European Respiratory Journal (2003)

To investigate the local immune response, the cellular infiltrate and cytokine levels were analysed in bronchoalveolar lavage (BAL) from patients with pulmonary paracoccidioidomycosis. The group consisted of 19 patients aged 34-65 yrs. The diagnosis was confirmed by demonstration of the fungus in the sputum or BAL fluid and by serological tests. Cytospin preparations showed an increased number of lymphocytes and neutrophils in BAL. A higher number of CD8+ lymphocytes were observed in BAL compared with peripheral blood. Alveolar macrophages (AM) expressed approximately three-fold more major histocompatibility class II, intercellular adhesion molecule-1 and B7-2 molecules on their surfaces than their circulating counterparts, indicating that they had differentiated into activated macrophages inside the lungs. Cultured AM produced higher levels of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-1alpha than peripheral blood monocytes. BAL fluid contained low but detectable amounts of IL-6, TNF-alpha and MIP-1alpha, and specific antibodies to Paracoccidioides brasiliensis, mainly of the immunoglobulin G2 isotype. As macrophage inflammatory protein-1alpha was shown to selectively attract CD8+ T-cells and this population was elevated in bronchoalveolar lavage, the data suggest that, besides macrophages, CD8+ T-cells may have an important role in the pathogenesis of pulmonary paracoccidioidomycosis.
NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus–Accelerated Atherosclerosis
Authors: Stephen P. Gray, Elyse Di Marco, Jun Okabe, Cedric Szyndralewiez, Freddy Heitz, Augusto C. Montezano, Judy B. de Haan, Christine Koulis, Assam El-Osta, Karen L. Andrews, Jaye P. F. Chin-Dusting, Rhian M. Touyz, Kirstin Wingler, Mark E. Cooper, Harald H. H. W. Schmidt, Karin A Jandeleit-Dahm
Journal: Circulation (2013)

In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms are unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears to play a role. Here we identify the Nox1 isoform as playing a key and pharmacologically targetable role in the accelerated development of diabetic atherosclerosis.Human aortic endothelial cells exposed to hyperglycemic conditions showed increased expression of Nox1, oxidative stress, and proinflammatory markers in a Nox1-siRNA reversible manner. Similarly, the specific Nox inhibitor, GKT137831, prevented oxidative stress in response to hyperglycemia in human aortic endothelial cells. To examine these observations in vivo, we investigated the role of Nox1 on plaque development in apolipoprotein E-deficient mice 10 weeks after induction of diabetes mellitus. Deletion of Nox1, but not Nox4, had a profound antiatherosclerotic effect correlating with reduced reactive oxygen species formation, attenuation of chemokine expression, vascular adhesion of leukocytes, macrophage infiltration, and reduced expression of proinflammatory and profibrotic markers. Similarly, treatment of diabetic apolipoprotein E-deficient mice with GKT137831 attenuated atherosclerosis development.These studies identify a major pathological role for Nox1 and suggest that Nox1-dependent oxidative stress is a promising target for diabetic vasculopathies, including atherosclerosis.
Efficacy, safety and medication cost implications of adalimumab 40 mg weekly dosing in patients with psoriasis with suboptimal response to 40 mg every other week dosing: results from an open-label study
Authors: C. Leonardi, J.M. Sobell, J.J. Crowley, U. Mrowietz, Y. Bao, P.M. Mulani, Y. Gu, M.M. Okun
Journal: British Journal of Dermatology (2012)

Journal Article Efficacy, safety and medication cost implications of adalimumab 40 mg weekly dosing in patients with psoriasis with suboptimal response to 40 mg every other week dosing: results from an open‐label study Get access C. Leonardi, C. Leonardi Central Dermatology, 1034 South Brentwood, Suite 600, St Louis, MO 63117, U.S.A Craig Leonardi E‐mail: leonardi@centralderm.com Search for other works by this author on: Oxford Academic Google Scholar J.M. Sobell, J.M. Sobell SkinCare Physicians®, Chestnut Hill, MA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar J.J. Crowley, J.J. Crowley Bakersfield Dermatology, Bakersfield, CA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar U. Mrowietz, U. Mrowietz Psoriasis Center at the Department of Dermatology, University Medical Center Schleswig‐Holstein, Campus Kiel, Germany Search for other works by this author on: Oxford Academic Google Scholar Y. Bao, Y. Bao Abbott Laboratories, Abbott Park, IL, U.S.A Search for other works by this author on: Oxford Academic Google Scholar P.M. Mulani, P.M. Mulani Abbott Laboratories, Abbott Park, IL, U.S.A Search for other works by this author on: Oxford Academic Google Scholar Y. Gu, Y. Gu Abbott Laboratories, Abbott Park, IL, U.S.A Search for other works by this author on: Oxford Academic Google Scholar M.M. Okun M.M. Okun Abbott Laboratories, Abbott Park, IL, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 3, 1 September 2012, Pages 658–667, https://doi.org/10.1111/j.1365-2133.2012.11041.x Published: 01 September 2012 Article history Accepted: 30 April 2012 Published: 01 September 2012
Adjuvant Procarbazine, Lomustine, and Vincristine Improves Progression-Free Survival but Not Overall Survival in Newly Diagnosed Anaplastic Oligodendrogliomas and Oligoastrocytomas: A Randomized European Organisation for Research and Treatment of Cancer Phase III Trial
Authors: Martin J. van den Bent, Antoine F. Carpentier, Alba A. Brandes, Marc Sanson, Martin J.B. Taphoorn, Hans J.J.A. Bernsen, Marc Frenay, Cees C. Tijssen, Wolfgang Grisold, Laslo Sipos, Hanny Haaxma-Reiche, Johannes M. Kros, Mathilde C.M. van Kouwenhoven, Charles J. Vecht, Anouk Allgeier, Denis Lacombe, Thierry Gorlia
Journal: Journal of Clinical Oncology (2006)

Anaplastic oligodendrogliomas are more responsive to chemotherapy than high-grade astrocytomas. We investigated, in a multicenter randomized controlled trial, whether adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy improves overall survival (OS) in newly diagnosed patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas.The primary end point of the study was OS; secondary end points were progression-free survival (PFS) and toxicity. Patients were randomly assigned to either 59.4 Gy of radiotherapy (RT) in 33 fractions only or to the same RT followed by six cycles of standard PCV chemotherapy (RT/PCV). 1p and 19q deletions were assessed with fluorescent in situ hybridization.A total of 368 patients were included. The median follow-up time was 60 months, and 59% of patients have died. In the RT arm, 82% of patients with tumor progression received chemotherapy. In 38% of patients in the RT/PCV arm, adjuvant PCV was discontinued for toxicity. OS time after RT/PCV was 40.3 months compared with 30.6 months after RT only (P = .23). RT/PCV increased PFS time compared with RT only (23 v 13.2 months, respectively; P = .0018). Twenty-five percent of patients were diagnosed with combined 1p/19q loss; 74% of this subgroup was still alive after 60 months. RT/PCV did not improve survival in the subgroup of patients with 1p/19q loss.Adjuvant PCV chemotherapy does not prolong OS but does increase PFS in anaplastic oligodendroglioma. Combined loss of 1p/19q identifies a favorable subgroup of oligodendroglial tumors. No genetic subgroup could be identified that benefited with respect to OS from adjuvant PCV.
Oral vs Intratympanic Corticosteroid Therapy for Idiopathic Sudden Sensorineural Hearing Loss
Authors: Steven D Rauch, Christopher F Halpin, Patrick J Antonelli, Seilesh Babu, John P Carey, Bruce J Gantz, Joel A Goebel, Paul E Hammerschlag, Jeffrey P Harris, Brandon Isaacson, Daniel Lee, Christopher J Linstrom, Lorne S Parnes, Helen Shi, William H Slattery, Steven A Telian, Jeffrey T Vrabec, Domenic J Reda
Journal: JAMA (2011)

Idiopathic sudden sensorineural hearing loss has been treated with oral corticosteroids for more than 30 years. Recently, many patients' symptoms have been managed with intratympanic steroid therapy. No satisfactory comparative effectiveness study to support this practice exists.To compare the effectiveness of oral vs intratympanic steroid to treat sudden sensorineural hearing loss.Prospective, randomized, noninferiority trial involving 250 patients with unilateral sensorineural hearing loss presenting within 14 days of onset of 50 dB or higher of pure tone average (PTA) hearing threshold. The study was conducted from December 2004 through October 2009 at 16 academic community-based otology practices. Participants were followed up for 6 months.One hundred twenty-one patients received either 60 mg/d of oral prednisone for 14 days with a 5-day taper and 129 patients received 4 doses over 14 days of 40 mg/mL of methylprednisolone injected into the middle ear.Primary end point was change in hearing at 2 months after treatment. Noninferiority was defined as less than a 10-dB difference in hearing outcome between treatments.In the oral prednisone group, PTA improved by 30.7 dB compared with a 28.7-dB improvement in the intratympanic treatment group. Mean pure tone average at 2 months was 56.0 for the oral steroid treatment group and 57.6 dB for the intratympanic treatment group. Recovery of hearing on oral treatment at 2 months by intention-to-treat analysis was 2.0 dB greater than intratympanic treatment (95.21% upper confidence interval, 6.6 dB). Per-protocol analysis confirmed the intention-to-treat result. Thus, the hypothesis of inferiority of intratympanic methylprednisolone to oral prednisone for primary treatment of sudden sensorineural hearing loss was rejected.Among patients with idiopathic sudden sensorineural hearing loss, hearing level 2 months after treatment showed that intratympanic treatment was not inferior to oral prednisone treatment.clinicaltrials.gov Identifier: NCT00097448.
US stem cell research progresses despite limitations
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Scientists in the United States, supported by private funds, are circumventing the so called “presidential” stem lines approved by President Bush in August 2001 for publicly funded research and are managing to conduct further stem cell research.

Currently, federal funding for stem cell research in the US is possible only on the 22 lines in existence before 9 August 2001. The US House of Representatives recently passed a bill to increase government funding for research on human embryos, and a Gallup poll in early May showed that 60% of Americans said medical research involving stem cells was morally acceptable. However, President Bush has said he would veto the bill ( BMJ 2005;330:1285), because of his Christian belief that embryos were “emerging human life.”

The 22 stem cell lines are all thought to be unsuitable for human treatment, because they were grown on mouse …
Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities study11The authors have no proprietary interest in the equipment and techniques described in this article.
Authors: Larry D Hubbard, Rosemary J Brothers, William N King, Limin X Clegg, Ronald Klein, Lawton S Cooper, A.Richey Sharrett, Matthew D Davis, Jianwen Cai
Journal: Ophthalmology (1999)
Relative contributions of germline gene variation and somatic mutation to immunoglobulin diversity in the mouse.
Authors: T Gojobori, M Nei
Journal: Molecular Biology and Evolution (1986)

The relative contributions of germline gene variation and somatic mutation to immunoglobulin diversity were studied by comparing germline gene sequences with their rearranged counterparts for the mouse VH, V kappa, and V lambda genes. The mutation rate at the amino acid level was estimated to be 7.0% in the first and second complementarity-determining regions (CDRs) and 2.0% in the framework regions (FRs). The difference in the mutation rate at the nucleotide level between the CDRs and FRs was of the same order of magnitude as that for the amino acid level. Analysis of amino acid diversity or nucleotide diversity indicated that the contribution of somatic mutation to immunoglobulin diversity is approximately 5%. However, the contribution of somatic mutation to the number of different amino acid sequences of immunoglobulins is much larger than that estimated by the analysis of amino acid diversity, and more than 90% of the different immunoglobulins seem to be generated by somatic mutation. Examination of the pattern of nucleotide substitution has suggested that clonal selection after somatic mutation may not be as strong as generally believed.
Serum transfer of collagen-induced arthritis in mice.
Authors: J M Stuart, F J Dixon
Journal: The Journal of Experimental Medicine (1983)

Immunization of DBA/1 mice with native chick type II collagen resulted in development of polyarthritis 4-5 wk later. Sera of these mice contained high levels of anticollagen antibodies, and immunoglobulin concentrates of their sera transferred arthritis to unimmunized recipients. Histopathologically, this passively transferred arthritis resembled the early disease of immunized donors. Immunofluorescence studies demonstrated the deposition of IgG and C3 on the articular surface but not in synovial tissue of arthritic joints. Transferred, isotopically labeled anticollagen antibodies rapidly localized to the limbs and to other cartilage-containing tissues. When transfer concentrate was administered to arthritis-resistant strains, they also developed arthritis. Indeed, immunoglobulin concentrates from rats with collagen-induced arthritis transferred arthritis to naive mice. The amount of concentrate required for transfer to B10.D2 resistant mice was reduced by immunizing them with collagen 4 wk before transfer. Although susceptibility to arthritis from immunization is H-2 linked, these studies clearly demonstrate that passive transfer of arthritis depends upon injection of specific antibody and not on other host factors.
Trends in Lower-Extremity Amputations in People With and Without Diabetes in Spain, 2001–2008
Authors: Ana López-de-Andrés, María A. Martínez-Huedo, Pilar Carrasco-Garrido, Valentin Hernández-Barrera, Ángel Gil-de-Miguel, Rodrigo Jiménez-García
Journal: Diabetes Care (2011)

To examine trends in nontraumatic lower-extremity amputations (LEAs) over an 8-year period in patients with and without diabetes in Spain.We identified all patients who underwent an LEA using national hospital discharge data. Discharges were grouped by diabetes status: type 1 diabetes, type 2 diabetes, and no diabetes. The incidence of discharges attributed to amputations were calculated overall and stratified by diabetes status and year. We calculated length of stay and in-hospital fatality stratified by diabetes status and type of LEA.From 2001 to 2008, 46,536 minor LEAs and 43,528 major LEAs were performed. In patients with type 1 diabetes, the incidence of minor and major amputations decreased significantly from 2001 to 2008 (0.88-0.43 per 100,000 inhabitants and 0.59-0.22 per 100,000 inhabitants, respectively). In patients with type 2 diabetes, the incidence of minor and major LEAs increased significantly (9.23-10.9 per 100,000 inhabitants and 7.12-7.47 per 100,000 inhabitants). Hospital stay was similar among type 1 diabetic and type 2 diabetic subjects, according to the type of LEA. Only in-hospital mortality for minor LEAs among type 1 diabetic subjects decreased significantly (4.0% in 2001 vs. 1.6% in 2008).Our national data show a decrease in the incidence of major and minor LEAs in patients with type 1 diabetes and an increase among patients with type 2 diabetes. Further improvement is necessary in the preventive care and early treatment of patients with diabetes. The management of foot lesions, especially among type 2 diabetic patients, is particularly urgent.
Generation of Antitumor Invariant Natural Killer T Cell Lines in Multiple Myeloma and Promotion of Their Functions via Lenalidomide: A Strategy for Immunotherapy
Authors: Weihua Song, Hans J.J. van der Vliet, Yu-Tzu Tai, Rao Prabhala, Ruojie Wang, Klaus Podar, Laurence Catley, Masood A. Shammas, Kenneth C. Anderson, Steven P. Balk, Mark A. Exley, Nikhil C. Munshi
Journal: Clinical Cancer Research (2008)

Abstract Purpose: CD1d-restricted invariant natural killer T (iNKT) cells are important immunoregulatory cells in antitumor immune responses. However, the quantitative and qualitative defects of iNKT cells in advanced multiple myeloma hamper their antitumor effects. Therefore, the development of functional iNKT cells may provide a novel strategy for the immunotherapy in multiple myeloma. Experimental Design: We activated and expanded iNKT cells from multiple myeloma patients with α-galactosylceramide (α-GalCer)-pulsed dendritic cells, characterized their antitumor effects by the cytokine production profile and cytotoxicity against multiple myeloma cells, and explored the effects of immunomodulatory drug lenalidomide on these iNKT cells. We also investigated the expression of CD1d by primary multiple myeloma cells and its function to activate iNKT cells. Results: We established highly purified functional iNKT cell lines from newly diagnosed and advanced multiple myeloma patients. These CD1d-restricted iNKT cell lines produced high level of antitumor Th1 cytokine in response to α-GalCer-pulsed primary multiple myeloma cells, CD1d-transfected MM1S cell line, and dendritic cells. Moreover, iNKT cell lines displayed strong cytotoxicity against α-GalCer-pulsed primary multiple myeloma cells. Importantly, lenalidomide further augmented the Th1 polarization by iNKT cell lines via increased Th1 cytokine production and reduced Th2 cytokine production. We also showed that CD1d was expressed in primary multiple myeloma cells at mRNA and protein levels from the majority of multiple myeloma patients, but not in normal plasma cells and multiple myeloma cell lines, and CD1d+ primary multiple myeloma cells presented antigens to activate iNKT cell lines. Conclusions: Taken together, our results provide the preclinical evidence for the iNKT cell-mediated immunotherapy and a rationale for their use in combination with lenalidomide in multiple myeloma treatment.
Evaluation of Therapeutic Abortion as an Element of Preventive Psychiatry
Authors: H. G. WHITTINGTON
Journal: American Journal of Psychiatry (1970)

The majority of 31 women who were surveyed after having therapeutic abortions reported that they felt content and mentally healthy. But since no studies predict which women with unwanted pregnancies might become mentally ill if abortion is denied, the author feels that psychiatry should not be legally responsible for deciding whether or not abortions should be granted. Therapeutic abortion should be covered by medical practice acts and the decision left to the woman and her physician, he believes.
Resiliency and Vulnerability in the HER2-HER3 Tumorigenic Driver
Authors: Dhara N. Amin, Natalia Sergina, Deepika Ahuja, Martin McMahon, Jimmy A. Blair, Donghui Wang, Byron Hann, Kevin M. Koch, Kevan M. Shokat, Mark M. Moasser
Journal: Science Translational Medicine (2010)

The ability of certain breast cancers to resist a tyrosine kinase inhibitor drug may be overcome with high intermittent doses.