tbuckley/cabot-search huggingface dataset:
Intensity of Myocardial Expression of Inducible Nitric Oxide Synthase Influences the Clinical Course of Human Immunodeficiency Virus-Associated Cardiomyopathy
Authors: Giuseppe Barbaro, Gabriella Di Lorenzo, Maurizio Soldini, Giuseppe Giancaspro, Benvenuto Grisorio, Adriano Pellicelli, Giorgio Barbarini
Journal: Circulation (1999)

Background —Increased levels of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) have been reported in patients with dilated cardiomyopathy. We investigated the myocardial expression of TNF-α and iNOS in patients with HIV-associated cardiomyopathy (HIV-DCM) compared with patients with idiopathic dilated cardiomyopathy (IDCM). Methods and Results —Endomyocardial biopsy specimens from 82 HIV-DCM and 80 IDCM patients were processed for determination of the immunostaining intensity of TNF-α and iNOS and for virological examination. Negative controls were derived from autopsy myocardium specimens from 32 HIV-negative patients without known heart disease. The mortality rate for congestive heart failure between groups according to the intensity of iNOS staining was also evaluated. The mean intensity of both TNF-α and iNOS staining was greater in patients with HIV-DCM (0.81 and 1.007, respectively) than in patients with IDCM (0.44 and 0.49, respectively) and controls (0.025 and 0.027, respectively). The staining intensity of both TNF-α and iNOS was inversely correlated with CD4 count. The staining intensity of iNOS was greater in HIV-DCM patients with HIV/coxsackievirus B3 (CVB3) or with HIV/cytomegalovirus coinfection than in IDCM patients showing infection with CVB3 and adenovirus alone. The staining intensity of iNOS correlated to mortality rate, because it was higher in HIV-DCM patients and, in particular, in those with an optical density unit &gt;1. Conclusions —Cytokine activation seems to play a significant pathogenetic role in both HIV-DCM and IDCM. In HIV-DCM patients, the state of immunodeficiency may favor the selection of viral variants of increased pathogenicity, influencing the clinical course of cardiomyopathy by enhancement of the inflammatory process.
Mutant FLT3: A Direct Target of Sorafenib in Acute Myelogenous Leukemia
Authors: Weiguo Zhang, Marina Konopleva, Yue-xi Shi, Teresa McQueen, David Harris, Xiaoyang Ling, Zeev Estrov, Alfonso Quintás-Cardama, Donald Small, Jorge Cortes, Michael Andreeff
Journal: JNCI Journal of the National Cancer Institute (2008)

Internal tandem duplication (ITD) mutations in the juxtamembrane domain-coding sequence of the Fms-like tyrosine kinase 3 (FLT3) gene have been identified in 30% of acute myeloid leukemia (AML) patients and are associated with a poor prognosis. The kinase inhibitor sorafenib induces growth arrest and apoptosis at much lower concentrations in AML cell lines that harbor FLT3-ITD mutations than in AML cell lines with wild-type FLT3.The antileukemic activity of sorafenib was investigated in isogenic murine Ba/F3 AML cell lines that expressed mutant (ITD, D835G, and D835Y) or wild-type human FLT3, in primary human AML cells, and in a mouse leukemia xenograft model. Effects of sorafenib on apoptosis and signaling in AML cell lines were investigated by flow cytometry and immunoblot analysis, respectively, and the in vivo effects were determined by monitoring the survival of leukemia xenograft-bearing mice treated with sorafenib (groups of 15 mice). In a phase 1 clinical trial, 16 patients with refractory or relapsed AML were treated with sorafenib on different dose schedules. We determined their FLT3 mutation status by a polymerase chain reaction assay and analyzed clinical responses by standard criteria. All statistical tests were two-sided.Sorafenib was 1000- to 3000-fold more effective in inducing growth arrest and apoptosis in Ba/F3 cells with FLT3-ITD or D835G mutations than in Ba/F3 cells with FLT3-D835Y mutant or wild-type FLT3 and inhibited the phosphorylation of tyrosine residues in ITD mutant but not wild-type FLT3 protein. In a mouse model, sorafenib decreased the leukemia burden and prolonged survival (median survival in the sorafenib-treated group vs the vehicle-treated group = 36.5 vs 16 days, difference = 20.5 days, 95% confidence interval = 20.3 to 21.3 days; P = .0018). Sorafenib reduced the percentage of leukemia blasts in the peripheral blood and the bone marrow of AML patients with FLT3-ITD (median percentages before and after sorafenib: 81% vs 7.5% [P = .016] and 75.5% vs 34% [P = .05], respectively) but not in patients without this mutation.Sorafenib may have therapeutic efficacy in AML patients whose cells harbor FLT3-ITD mutations.
Liposomal Delivery of Purified Inhibitory-κBα Inhibits Tumor Necrosis Factor-α–Induced Human Vascular Smooth Muscle Proliferation
Authors: Craig H. Selzman, Brian D. Shames, Leonid L. Reznikov, Stephanie A. Miller, Xianzhong Meng, Hazel A. Barton, Ariel Werman, Alden H. Harken, Charles A. Dinarello, Anirban Banerjee
Journal: Circulation Research (1999)

Abstract —Vessel injury results in the elaboration of various cytokines, including tumor necrosis factor-α (TNF-α), which may influence vascular smooth muscle cell (VSMC) function and contribute to atherogenesis. We tested the hypothesis that TNF-α–induced VSMC proliferation requires activation of the transcription factor nuclear factor-κB (NF-κB), which could be prevented by delivery of the NF-κB inhibitory peptide, IκBα. TNF-α induced concentration-dependent human VSMC proliferation, and neutralizing antibody to interleukin-6 reduced TNF-α–induced VSMC proliferation by 65%. In TNF-α–stimulated VSMCs, there was a 3-fold increase in NF-κB–dependent luciferase reporter activity that was associated with degradation of ΙκBα. To determine an essential role for NF-κB in TNF-α–induced VSMC proliferation, recombinant ΙκBα was introduced into VSMCs via liposomal delivery. Under these conditions, TNF-α–induced NF-κB nuclear translocation and DNA binding were inhibited, NF-κB–dependent luciferase activity was reduced by 50%, there was no degradation of native ΙκBα detected, interleukin-6 production was reduced by 54%, and VSMC proliferation was decreased by 60%. In conclusion, the mitogenic effect of TNF-α on human arterial VSMCs is dependent on NF-κB activation and may be prevented by exogenously delivered ΙκBα. Furthermore, liposomal delivery of endogenous inhibitory proteins may represent a novel, therapeutically accessible method for selective transcriptional suppression in the response to vascular injury.
Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials
Authors: Matthieu Roustit, Sophie Blaise, Yannick Allanore, Patrick H Carpentier, Evren Caglayan, Jean-Luc Cracowski
Journal: Annals of the Rheumatic Diseases (2013)

A patient with a progressive lower motor neuron syndrome and neurophysiological evidence of motor axon loss, multifocal proximal motor nerve conduction block, and high titres of anti-ganglioside GM1 antibodies. Neuropathological findings included a predominantly proximal motor radiculoneuropathy with multifocal IgG and IgM deposits on nerve fibres associated with a loss of spinal motor neurons. These findings support an autoimmune origin of this lower motor neuron syndrome with retrograde degeneration of spinal motor neurons and severe neurogenic muscular atrophy.
Relevant Issues in the Pathology and Pathobiology of Pulmonary Hypertension
Authors: Rubin M. Tuder, Stephen L. Archer, Peter Dorfmüller, Serpil C. Erzurum, Christophe Guignabert, Evangelos Michelakis, Marlene Rabinovitch, Ralph Schermuly, Kurt R. Stenmark, Nicholas W. Morrell
Journal: Journal of the American College of Cardiology (2013)
Combining Agents that Target the Tumor Microenvironment Improves the Efficacy of Anticancer Therapy
Authors: Joseph A. Blansfield, Diana Caragacianu, H. Richard Alexander, Michael A. Tangrea, Shane Y. Morita, Dominique Lorang, Peter Schafer, George Muller, David Stirling, Richard E. Royal, Steven K. Libutti
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Over the past 60 years, cytotoxic chemotherapy has targeted the cancer cell. Despite this, there have been few cancer cures. A new approach to cancer therapy is to target the multicellular biological entity of the tumor microenvironment. Experimental Design: Lenalidomide, an immunomodulatory drug, sunitinib, a tyrosine kinase inhibitor, and low-dose metronomic cyclophosphamide, were tested alone and in combination for their abilities to inhibit endothelial cell tube formation, rat aortic ring outgrowth, tumor growth, and metastatic development in mice. In addition, ectopic tumor lysates were evaluated for the presence of proangiogenic proteins. Results: The three agents alone were shown to significantly inhibit endothelial cells' ability to form tubes and significantly inhibit the multicellular microenvironment in the rat aortic ring assay (P &amp;lt; 0.01 and P &amp;lt; 0.001). This effect was also significantly augmented when the agents were combined. Furthermore, the three-drug combination was able halt the progression of tumor growth almost completely in xenograft models of ocular melanoma, colon cancer, pancreatic cancer, and cutaneous melanoma. These agents significantly decrease the number of proliferating cells in tumors, significantly increase the number of cells undergoing active cell death in tumors, and significantly decrease the number of blood vessels in treated tumors (P &amp;lt; 0.05). Combination therapy shows a decrease in the compensatory up-regulation of proangiogenic proteins after treatment when compared with single-agent therapy. Conclusions: This combination of agents causes an inhospitable microenvironment for tumor cells and shows great promise for use in the clinic.
Low HDL Cholesterol and the Risk of Diabetic Nephropathy and Retinopathy
Authors: Jamie Morton, Sophia Zoungas, Qiang Li, Anushka A. Patel, John Chalmers, Mark Woodward, David S. Celermajer, Joline W.J. Beulens, Ronald P. Stolk, Paul Glasziou, Martin K.C. Ng
Journal: Diabetes Care (2012)

Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes.A total of 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazards models were used to assess the association between baseline HDL-C and the development of new or worsening microvascular disease, defined prospectively as a composite of renal and retinal events.The mean baseline HDL-C level was 1.3 mmol/L (SD 0.45 mmol/L [range 0.1-4.0]). During follow-up, 32% of patients developed new or worsening microvascular disease, with 28% experiencing a renal event and 6% a retinal event. Compared with patients in the highest third, those in the lowest third had a 17% higher risk of microvascular disease (adjusted hazard ratio 1.17 [95% CI 1.06-1.28], P = 0.001) after adjustment for potential confounders and regression dilution. This was driven by a 19% higher risk of renal events (1.19 [1.08-1.32], P = 0.0005). There was no association between thirds of HDL-C and retinal events (1.01 [0.82-1.25], P = 0.9).In patients with type 2 diabetes, HDL-C level is an independent risk factor for the development of microvascular disease affecting the kidney but not the retina.
Potent mitogenic effects of parathyroid hormone (PTH) on embryonic chick and rabbit chondrocytes. Differential effects of age on growth, proteoglycan, and cyclic AMP responses of chondrocytes to PTH.
Authors: T Koike, M Iwamoto, A Shimazu, K Nakashima, F Suzuki, Y Kato
Journal: Journal of Clinical Investigation (1990)

The effect of PTH on chondrocyte proliferation as a function of cartilage age was examined. PTH[1-34] induced a 12- to 15-fold increase in the efficiency of colony formation in soft agar by chondrocytes from embryonic 13- to 19-d-old chickens and fetal 25-d-old rabbits with a 10-fold increase in their DNA content. It also caused a 2.5-fold increase in [3H]thymidine incorporation into DNA in fetal 25-d-old rabbit chondrocytes. No mitogenic responses to PTH were observed, however, in postnatal 7- to 21-d-old chick chondrocytes or postnatal 21-d-old rabbit chondrocytes. This age dependency was observed only with PTH: fibroblast growth factor, epidermal growth factor, and insulin stimulated chondrocyte proliferation irrespective of cartilage age. The absence of a mitogenic effect in postnatal chondrocytes was not due to a decrease in number or a reduction in affinity of receptors for PTH. PTH also increased [35S]sulfate incorporation into proteoglycans and the cyclic AMP level in fetal and postnatal chondrocytes, but at 100-fold higher concentrations (10(-8)-10(-7) M) than those (10(-10)-10(-9) M) required for the stimulation of cell division. These results suggest that PTH is a potent mitogen for embryonic chondrocytes, and that its mitogenic effect disappears selectively after birth.
Hippocampal Volume, PTSD, and Alcoholism in Combat Veterans
Authors: S. H. Woodward, D. G. Kaloupek, C. C. Streeter, M. O. Kimble, A. L. Reiss, S. Eliez, L. L. Wald, P. F. Renshaw, B. B. Frederick, B. Lane, J. I. Sheikh, W. K. Stegman, C. J. Kutter, L. P. Stewart, R. S. Prestel, N. J. Arsenault
Journal: American Journal of Psychiatry (2006)

Studies imposing rigorous control over lifetime alcohol intake have usually not found smaller hippocampal volumes in persons with posttraumatic stress disorder. Because the majority of negative studies have used adolescent samples, it has been suggested that chronicity is a necessary condition for such findings. To test the hypothesis that a smaller hippocampus in PTSD is unrelated to comorbid alcoholism or to chronicity, this study estimated hippocampal volume in a relatively large group (N=99) of combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. In subjects with histories of alcoholism, unadjusted hippocampal volume was 9% smaller in persons with PTSD than in those without PTSD. In nonalcoholic subjects, the PTSD-related difference in hippocampal volume was 3%. The failure to observe a strong association between PTSD and hippocampal volume in nonalcoholic subjects was not ascribable to younger age, reduced PTSD chronicity, or lower PTSD symptom severity. The possibility that smaller hippocampal volume is limited to groups in which PTSD is compounded by comorbid alcoholism is not necessarily incompatible with results suggesting a smaller hippocampus is predispositional to PTSD. Further examination of the role of alcoholism and other comorbid conditions in studies of brain structure and function in PTSD appears warranted.
SECTION OF DERMATOLOGY
Authors: J. E. M. WIGLEY
Journal: British Journal of Dermatology (1949)

Journal Article SECTION OF DERMATOLOGY Get access J. E. M. WIGLEY J. E. M. WIGLEY President‐Dr. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 61, Issue 10, 1 October 1949, Pages 327–339, https://doi.org/10.1111/j.1365-2133.1949.tb11039.x Published: 01 October 1949
Developing in vitro expanded CD45RA<sup>+</sup>regulatory T cells as an adoptive cell therapy for Crohn's disease
Authors: James B Canavan, Cristiano Scottà, Anna Vossenkämper, Rimma Goldberg, Matthew J Elder, Irit Shoval, Ellen Marks, Emilie Stolarczyk, Jonathan W Lo, Nick Powell, Henrieta Fazekasova, Peter M Irving, Jeremy D Sanderson, Jane K Howard, Simcha Yagel, Behdad Afzali, Thomas T MacDonald, Maria P Hernandez-Fuentes, Nahum Y Shpigel, Giovanna Lombardi, Graham M Lord
Journal: Gut (2015)

<h3>Background and aim</h3> Thymus-derived regulatory T cells (T<sub>regs</sub>) mediate dominant peripheral tolerance and treat experimental colitis. T<sub>regs</sub> can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. T<sub>reg</sub> cell therapy is also conceptually attractive for Crohn9s disease (CD). However, barriers exist to this approach. The stability of T<sub>regs</sub> expanded from Crohn9s blood is unknown. The potential for adoptively transferred T<sub>regs</sub> to express interleukin-17 and exacerbate Crohn9s lesions is of concern. Mucosal T cells are resistant to T<sub>reg</sub>-mediated suppression in active CD. The capacity for expanded T<sub>regs</sub> to home to gut and lymphoid tissue is unknown. <h3>Methods</h3> To define the optimum population for T<sub>reg</sub> cell therapy in CD, CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>lo</sup>CD45RA<sup>+</sup> and CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>lo</sup>CD45RA<sup>−</sup> T<sub>reg</sub> subsets were isolated from patients' blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background. <h3>Results</h3> T<sub>regs</sub> can be expanded from the blood of patients with CD to potential target dose within 22–24 days. Expanded CD45RA<sup>+</sup> T<sub>regs</sub> have an epigenetically stable <i>FOXP3</i> locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA<sup>−</sup> T<sub>regs</sub>. CD45RA<sup>+</sup> T<sub>regs</sub> highly express α<sub>4</sub>β<sub>7</sub> integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA<sup>+</sup> T<sub>regs</sub> also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA<sup>+</sup> T<sub>regs</sub>. These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn9s mucosa. <h3>Conclusions</h3> CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>lo</sup>CD45RA<sup>+</sup> T<sub>regs</sub> may be the most appropriate population from which to expand T<sub>regs</sub> for autologous T<sub>reg</sub> therapy for CD, paving the way for future clinical trials.
Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study
Authors: Noah D. Kauff, Susan M. Domchek, Tara M. Friebel, Mark E. Robson, Johanna Lee, Judy E. Garber, Claudine Isaacs, D. Gareth Evans, Henry Lynch, Rosalind A. Eeles, Susan L. Neuhausen, Mary B. Daly, Ellen Matloff, Joanne L. Blum, Paul Sabbatini, Richard R. Barakat, Clifford Hudis, Larry Norton, Kenneth Offit, Timothy R. Rebbeck
Journal: Journal of Clinical Oncology (2008)

Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers.A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model.During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance.The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.
Minimal liver injury in chronic hepatitis C virus infection is associated with low levels of soluble sTNFr-II and sFAS receptors and acquisition at childhood
Authors: J. Macias, A. Sanchez-Quijano, J.A. Pineda, M.A. Abad, A. Rubio, R. Rosa, M. Leal, E. Lissen
Journal: Journal of Hepatology (2001)
Photosensitivity in Sweet's syndrome: two cases that were photoinduced and photoaggravated
Authors: H. Belhadjali, M.C. Marguery, L. Lamant, F. Giordano-Labadie, J. Bazex
Journal: British Journal of Dermatology (2003)

Journal Article Photosensitivity in Sweet's syndrome: two cases that were photoinduced and photoaggravated Get access H. Belhadjali, H. Belhadjali Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar M.C. Marguery, M.C. Marguery Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar L. Lamant, L. Lamant Department of Anatomopathology, Purpan Hospital, Place du Dr Baylac, 31059 Toulouse Cedex, France E‐mail : marguery.mc@chu‐toulouse.fr Search for other works by this author on: Oxford Academic Google Scholar F. Giordano‐Labadie, F. Giordano‐Labadie Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar J. Bazex J. Bazex Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 3, 1 September 2003, Pages 675–677, https://doi.org/10.1046/j.1365-2133.2003.05487.x Published: 01 September 2003
GeneCount: genome-wide calculation of absolute tumor DNA copy numbers from array comparative genomic hybridization data
Authors: Heidi Lyng, Malin Lando, Runar S Brøvig, Debbie H Svendsrud, Morten Johansen, Eivind Galteland, Odd T Brustugun, Leonardo A Meza-Zepeda, Ola Myklebost, Gunnar B Kristensen, Eivind Hovig, Trond Stokke
Journal: Genome biology (2008)

Absolute tumor DNA copy numbers can currently be achieved only on a single gene basis by using fluorescence in situ hybridization (FISH). We present GeneCount, a method for genome-wide calculation of absolute copy numbers from clinical array comparative genomic hybridization data. The tumor cell fraction is reliably estimated in the model. Data consistent with FISH results are achieved. We demonstrate significant improvements over existing methods for exploring gene dosages and intratumor copy number heterogeneity in cancers.
Educating the design stance: Issues of coherence and transgression
Authors: Norman H Freeman, Melissa L Allen
Journal: Behavioral and Brain Sciences (2013)

Abstract Bullot &amp; Reber (B&amp;R) put forth a design stance to fuse psychological and art historical accounts of visual thinking into a single theory. We argue that this aspect of their proposal needs further fine-tuning. Issues of transgression and coherence are necessary to provide stability to the design stance. We advocate looking to Art Education for such fundamentals of picture understanding.