tbuckley/cabot-search huggingface dataset:
Outcome of renal replacement therapy in antineutrophil cytoplasmic antibody-associated systemic vasculitis.
Authors: A Allen, C Pusey, G Gaskin
Journal: Journal of the American Society of Nephrology (1998)

Antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) frequently leads to end-stage renal disease (ESRD). Potentially fatal disease activity can continue after the onset of ESRD in both dialysis and transplant patients, despite the immunosuppressive effects of uremia and rejection prophylaxis, leading to concerns that such patients have greater morbidity and mortality. To assess the outcome of AASV patients receiving renal replacement therapy, a retrospective analysis of 59 patients from our unit who received chronic dialysis, renal transplantation, or both, was performed. The survival of AASV patients with ESRD was comparable to national registry controls, as were both graft and patient survival after renal transplantation. Ther is no evidence that standard immunosuppressive protocols should be altered for AASV patients receiving renal transplants. The rate of relapse of vasculitis for patients on chronic dialysis and after transplantation was 0.09 and 0.02 per patient per year, respectively. These rates are lower than those of other series and support the contention that continued immunosuppression after ESRD, as practiced in our unit, is warranted. Relapses usually responded to cyclophosphamide and high-dose prednisolone treatment. Significantly, vasculitic flare-ups in dialysis patients were sometimes initially misdiagnosed as dialysis complications, leading to fatal delays in effective treatment. Follow-up by physicians experienced in the diagnosis and treatment of vasculitis activity should continue in these patients.
Endoscopy and computed tomography in the diagnosis and follow up of oesophageal leiomyoma.
Authors: M A Cox, B T Cooper, G Sagar
Journal: Gut (1995)

Leiomyoma of the oesophagus, although the commonest benign oesophageal tumour, is still rare compared with malignant tumours of the oesophagus. Leiomyomas of the oesophagus are usually diagnosed on barium swallow or histological examination after section. Five cases of leiomyoma of the oesophagus are reported where diagnosis was made by the combination of barium swallow, upper gastrointestinal endoscopy, and computed tomography and all but one patient were followed up for one to four years. The endoscopic biopsy specimens were non-specific in all five patients but none showed any evidence of malignancy. None of the five patients had a history of dysphagia. This paper describes a conservative approach to medical treatment in asymptomatic oesophageal leiomyoma rather than surgical excision as commonly published. It also emphasises the importance of negative endoscopic pinch biopsy specimens and the role of computed tomography in the diagnosis of oesophageal leiomyoma.
Nothing but skin and bone
Authors: F. P. Ross
Journal: Journal of Clinical Investigation (2006)

Skin and bone — what comes to mind at hearing this phrase? While certainly a metaphor for disease, it also defines two very different tissues, one a flexible and contiguous outer covering, the other a morphologically diverse hard tissue distributed at over 200 sites in the body. As the accompanying series of Reviews highlights, these tissues are indeed diverse, but there are also surprising similarities. Skin is the interface between the internal organs and the environment, and as such plays a crucial role in the body’s defense mechanism. The skin and its many appendages are responsible for functions as diverse as epidermal barrier and defense, immune surveillance, UV protection, thermoregulation, sweating, lubrication, pigmentation, the sensations of pain and touch, and, importantly, the protection of various stem cell niches in the skin. Bone serves a number of purposes: it provides protection for vital organs, a lever for locomotion, a reservoir for calcium, and the site of adult hematopoiesis. The tissue is composed of osteoblasts, osteoclasts, and their individual precursors plus a complex mixture of mesenchymal, myeloid, and lymphoid cells in the marrow space. Finally, the endothelial microenvironment provides nutrition and is a conduit for the influx and emigration of cells that impact bone biology in several important ways. This Review series guides the reader through these various facets of 2 diverse, yet interdependent, tissues.
Time course of action of two inhaled corticosteroids, fluticasone propionate and budesonide
Authors: K Phillips
Journal: Thorax (2003)

It is important to be able to compare the efficacy and systemic effects of inhaled corticosteroids but their slow onset of action makes it difficult to measure the maximum response to a given dose. Submaximal responses could be compared if the time course of action of the inhaled corticosteroids being compared was similar. We have compared the time course of action of fluticasone and budesonide, measuring response as change in the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP).Eighteen subjects with mild asthma, aged 18-65, took part in a three way randomised crossover study. Subjects took fluticasone (1500 microg/day), budesonide (1600 microg/day), and placebo each for 4 weeks with a washout period of at least 2 weeks between treatments; PD20AMP and forced expiratory volume in 1 second (FEV1) were measured during and after treatment. The time taken to achieve 50% of the maximum response (T50%) was compared as a measure of onset of action.There was a progressive increase in PD20AMP during the 4 weeks of treatment with both fluticasone and budesonide but not placebo; the increase after 1 and 4 weeks was 2.28 and 4.50 doubling doses (DD) for fluticasone and 2.49 and 3.65 DD for budesonide. T50% was 9.3 days for fluticasone and 7.5 days for budesonide with a median difference between fluticasone and budesonide of 0.1 days (95% CI -1.4 to 2.65). There was a wide range of response to both inhaled corticosteroids but good correlation between the response to fluticasone and budesonide within subjects. FEV1 and morning peak expiratory flow rate (PEFR) increased during the first week of both active treatments and were stable thereafter. There was a small progressive improvement in nocturnal symptoms with both active treatments.PD20AMP was a more sensitive marker of response to inhaled corticosteroid therapy than FEV1 and PEFR. The time course of action of fluticasone and budesonide on PD20AMP is similar, suggesting that comparative studies of their efficacy using 1 or 2 week treatment periods are valid. When a new inhaled corticosteroid becomes available, a pilot study comparing its time course of action with that of an established corticosteroid should allow comparative studies to be performed more efficiently.
Immature myeloid cells induced by a high-fat diet contribute to liver inflammation
Authors: Zhong-bin Deng, Yuelong Liu, Cunren Liu, Xiaoyu Xiang, Jianhua Wang, Ziqiang Cheng, Spandan V. Shah, Shuangyin Zhang, Liming Zhang, Xiaoying Zhuang, Sue Michalek, William E. Grizzle, Huang-Ge Zhang
Journal: Hepatology (2009)

Abstract Chronic inflammation plays a critical role in promoting obesity-related disorders, such as fatty liver disease. The inflammatory cells that mediate these effects remain unknown. This study investigated the accumulation of immature myeloid cells in the liver and their role in liver inflammation. We found that the accumulation of immature myeloid cells, i.e., CD11b + Ly6C hi Ly6G − cells, in the liver of B6 mice fed a high-fat diet contribute to liver inflammation. Adoptive transfer of CD11b + Ly6C hi Ly6G − cells isolated from the liver of obese B6 mice, but not from lean B6 mice, resulted in liver damage that was evident by an increase in the activity of liver transferases in serum. CD11b + Ly6C hi Ly6G − cells isolated from the liver of obese mice are more easily activated by way of Toll-like receptor (TLR) stimulation resulting in interleukin 12 and other inflammatory cytokine expression in an MyD88-dependent fashion. TLR7-activated CD11b + Ly6C hi Ly6G − cells also enhance liver natural killer T cell (NKT) death in an Fas-dependent manner. Experiments using mice depleted of Gr-1 + immature myeloid cells demonstrated the important role of CD11b + Ly6C hi Ly6G − in liver inflammation. Repeated injection of exosome-like particles causes CD11b + cell activation and subsequent homing to and accumulation of the cells in the liver. Conclusion: Consumption of a high-fat diet by B6 mice triggers an accumulation of immature myeloid cells in the liver. The immature myeloid cells release proinflammatory cytokines and induce NKT cell apoptosis. Activation-induced NKT apoptosis further promotes excessive production of Th-1 cytokines. This diet-induced accumulation of immature myeloid cells may contribute to obesity-related liver disease. (Hepatology 2009.)
Juvenile pemphigus foliaceus associated with severe nonscarring alopecia
Authors: A. Mlynek, M. Bär, A. Bauer, M. Meurer
Journal: British Journal of Dermatology (2009)

Journal Article Juvenile pemphigus foliaceus associated with severe nonscarring alopecia Get access A. Mlynek, A. Mlynek Department of Dermatology, Carl Gustav Carus Medical School, University of Technology Dresden, Fetscherstrasse 74, 01307 Dresden, Germany E‐mail: Alexander.Mlynek@uniklinikum‐dresden.de Search for other works by this author on: Oxford Academic Google Scholar M. Bär, M. Bär Department of Dermatology, Carl Gustav Carus Medical School, University of Technology Dresden, Fetscherstrasse 74, 01307 Dresden, Germany E‐mail: Alexander.Mlynek@uniklinikum‐dresden.de Search for other works by this author on: Oxford Academic Google Scholar A. Bauer, A. Bauer Department of Dermatology, Carl Gustav Carus Medical School, University of Technology Dresden, Fetscherstrasse 74, 01307 Dresden, Germany E‐mail: Alexander.Mlynek@uniklinikum‐dresden.de Search for other works by this author on: Oxford Academic Google Scholar M. Meurer M. Meurer Department of Dermatology, Carl Gustav Carus Medical School, University of Technology Dresden, Fetscherstrasse 74, 01307 Dresden, Germany E‐mail: Alexander.Mlynek@uniklinikum‐dresden.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 2, 1 August 2009, Pages 472–474, https://doi.org/10.1111/j.1365-2133.2009.09224.x Published: 01 August 2009
The Action of Cortisone and Desoxycorticosterone Acetate on Glomerular Filtration Rate and Sodium and Water Exchange in the Adrenalectomized Dog
Authors: Oliver Garrod, S. A. Davies, George Cahill
Journal: Journal of Clinical Investigation (1955)

Measurements of renal functionUsual procedure.After free access to water overnight, 15-minute urine collections were started between 8 and 9 A.M. Half an hour later, a priming infusion of cre- atinine and PAH4 was slowly injected, followed by a sustaining infusion4 which was continued throughout the experiment.A 45-minute period was allowed for equili- bration.After three or more clearance periods, 40 ml. of warm water per Kgm.were given by stomach tube.Clearances were then measured for a further three to six hours.The following renal functions were determined: GFR, ERPF, urinary pH, and urinary outputs of sodium, po- tassium, chloride, and phosphate.Blood was taken initially and at the midpoint of every third or fourth clearance period, and the red cells rein- fused at the end of each experiment.Plasma creatinine, PAH, specific gravity, and electrolyte concentrations were measured in each sample.The above-mentioned procedure was carried out under the following conditions: (i) before adrenalectomy, (ii) after adrenalectomy, while on optimal DCA therapy, and, in dog A, also when on inadequate and excessive DCA therapy and after intravenous saline infusion, and in both dogs during acute administration of cortisone and DCA.To observe its effects, both with and without a water load, cortisone was given, in separate experiments, three hours before the water dose, or at the time of the water dose, or three hours after it.The cortisone was given in one of three different ways: (i) intravenously, as a microcrystalline suspension of 50 mg.cortisone acetate in 1 ml.distilled water, dose 10 to 50 mg.5;(ii) intra- venously, as cortisone tricarballylate,6 dose 30 to 90 mg.freshly dissolved in a few ml. of isotonic saline, or (iii) orally, as cortisone acetate (Cortone@, Merck), dose 50 mg.
Palaeoneurology of language: Grounds for scepticism
Authors: Elizabeth Whitcombe
Journal: Behavioral and Brain Sciences (1995)

Abstract Wilkins &amp; Wakefield's identification of anatomical features in the Koobi Fora endocast, which may be thought to carry some functional significance in relation to organization for language, raises fundamental problems of method: attention is drawn to some limitations of the evidence, of endocasts and of the neuroanatomical map used to interpret them.
GITR Activation Induces an Opposite Effect on Alloreactive CD4+ and CD8+ T Cells in Graft-Versus-Host Disease
Authors: Stephanie J. Muriglan, Teresa Ramirez-Montagut, Onder Alpdogan, Thomas W. van Huystee, Jeffrey M. Eng, Vanessa M. Hubbard, Adam A. Kochman, Kartono H. Tjoe, Carlo Riccardi, Pier Paolo Pandolfi, Shimon Sakaguchi, Alan N. Houghton, Marcel R.M. van den Brink
Journal: The Journal of Experimental Medicine (2004)

Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) is a member of the tumor necrosis factor receptor (TNFR) family that is expressed at low levels on unstimulated T cells, B cells, and macrophages. Upon activation, CD4+ and CD8+ T cells up-regulate GITR expression, whereas immunoregulatory T cells constitutively express high levels of GITR. Here, we show that GITR may regulate alloreactive responses during graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Using a BMT model with major histocompatibility complex class I and class II disparity, we demonstrate that GITR stimulation in vitro and in vivo enhances alloreactive CD8+CD25− T cell proliferation, whereas it decreases alloreactive CD4+CD25− proliferation. Allo-stimulated CD4+CD25− cells show increased apoptosis upon GITR stimulation that is dependent on the Fas–FasL pathway. Recipients of an allograft containing CD8+CD25− donor T cells had increased GVHD morbidity and mortality in the presence of GITR-activating antibody (Ab). Conversely, recipients of an allograft with CD4+CD25− T cells showed a significant decrease in GVHD when treated with a GITR-activating Ab. Our findings indicate that GITR has opposite effects on the regulation of alloreactive CD4+ and CD8+ T cells.
Cyclophosphamide Inhibition of Anti-CD40 Monoclonal Antibody–Based Therapy of B Cell Lymphoma Is Dependent on CD11b+ Cells
Authors: Jamie Honeychurch, Martin J. Glennie, Timothy M. Illidge
Journal: Cancer Research (2005)

Monoclonal antibody (mAb)-based immunotherapy is now established as an important option for treating some cancers. The antitumor effects may be further enhanced by combining mAb with conventional chemotherapy. Certain novel immunomodulatory mAbs such as anti-CD40 have shown significant activity in preclinical models. We therefore assessed the efficacy of combining anti-CD40 mAb, known to elicit CTL responses against murine lymphoma models with the commonly used cytotoxic drug, cyclophosphamide. Using the syngeneic tumor model, BCL1, we have shown that timing of cyclophosphamide relative to mAb is critical to therapeutic outcome. Pretreatment with cyclophosphamide 7 to 10 days prior to mAb results in markedly reduced survival levels, similar to that achieved with cyclophosphamide alone. Conversely, when anti-CD40 is given before cyclophosphamide, the level of tumor protection was moderately increased. In vivo tracking experiments reveal that pretreatment with cyclophosphamide leads to diminished CTL expansion, as well as an increased number of CD11b+ cells that display an activated phenotype. These latter cells are able to inhibit T-cell proliferation, at least in part via production of nitric oxide, but do not induce T-cell apoptosis. Furthermore, adoptive transfer of the induced CD11b+ cells is sufficient to inhibit anti-CD40 therapy in tumor-bearing recipients. We have shown that the timing of cyclophosphamide relative to mAb administration is critical to the therapeutic outcome, and although the combination can improve survival, cyclophosphamide given prior to immunotherapy may generate a population of myeloid cells that can interfere with CTL responses and compromise the therapeutic outcome.
Combination therapy with ciclosporin and etanercept in patients with psoriatic arthritis
Authors: S. D'Angelo, M. S. Cutro, E. Lubrano, P. Leccese, G. A. Mennillo, N. Ferrara, I. Olivieri
Journal: Annals of the Rheumatic Diseases (2009)

Psoriatic arthritis (PsA) is a heterogeneous disease involving the musculoskeletal structures, the skin and nails (1, 2). Traditional DMARDs and TNFα antagonists are effective on both cutaneous and articular manifestations of psoriatic disease (3, 4).
The PPAR regulatory system in cardiac physiology and disease
Authors: B FINCK
Journal: Cardiovascular Research (2006)

Myocardial energy metabolism is an important determinant of cardiac structure and function. Modulating metabolism is therefore an attractive therapeutic avenue for the treatment of cardiac disease. The peroxisome proliferator-activated receptor family (PPARα, β/δ, γ) of nuclear receptor transcription factors is an important regulator of cardiac metabolism and has been targeted for pharmacologic therapies designed to modulate metabolism. The PPARs control myocardial metabolism by transcriptionally regulating genes encoding enzymes involved in fatty acid and glucose utilization. The expression and activity of the PPARs and their coactivator protein PGC-1α is dynamically regulated in several cardiomyopathic and metabolic diseases. This review will summarize these findings and other recent studies regarding the effects of experimental PPAR activation and deactivation and its potential impact on cardiomyopathic remodeling.
25-Hydroxyvitamin D Levels, Race, and the Progression of Kidney Disease
Authors: Michal L. Melamed, Brad Astor, Erin D. Michos, Thomas H. Hostetter, Neil R. Powe, Paul Muntner
Journal: Journal of the American Society of Nephrology (2009)

Black individuals have lower 25-hydroxyvitamin D [25(OH)D] levels and experience a disproportionate burden of ESRD compared with white individuals. Animal studies suggest that vitamin D has renoprotective effects. We evaluated the contribution of low 25(OH)D levels on incidence of ESRD using data from the Third National Health and Nutrition Examination Survey-linked Medicare claims files (n = 13,328). We included baseline (1988 through 1994) measurements of 25(OH)D and assessed the incidence of ESRD through July 31, 2001. Overall, 34% of non-Hispanic black individuals had 25(OH)D levels <15 ng/ml compared with 5% of non-Hispanic white individuals (P < 0.001). During a median of 9.1 yr, 65 participants developed ESRD. After adjustment for demographic, socioeconomic, and clinical and laboratory factors (including diabetes, hypertension, estimated GFR, and albuminuria), participants with 25(OH)D levels <15 ng/ml had a 2.6-fold greater incidence of ESRD than those with levels > or =15 ng/ml (incidence rate ratio 2.64; 95% confidence interval [CI] 1.00 to 7.05; P = 0.05). After adjustment for clinical covariates but not 25(OH)D levels, non-Hispanic black individuals had a 2.83-fold (95% CI 1.03 to 7.77) higher risk for developing ESRD compared with non-Hispanic white individuals. Additional adjustment for 25(OH)D levels reduced the risk by 58% (incidence rate ratio 1.77; 95% CI 0.38 to 8.21). In summary, low 25(OH)D levels associate with development of ESRD even after adjustment for multiple risk factors. Low 25(OH)D levels may account for a substantial proportion of the increased risk for ESRD experienced by black individuals.
Sentinel Node Mapping for Gastric Cancer: A Prospective Multicenter Trial in Japan
Authors: Yuko Kitagawa, Hiroya Takeuchi, Yu Takagi, Shoji Natsugoe, Masanori Terashima, Nozomu Murakami, Takashi Fujimura, Hironori Tsujimoto, Hideki Hayashi, Nobunari Yoshimizu, Akinori Takagane, Yasuhiko Mohri, Kazuhito Nabeshima, Yoshikazu Uenosono, Shinichi Kinami, Junichi Sakamoto, Satoshi Morita, Takashi Aikou, Koichi Miwa, Masaki Kitajima
Journal: Journal of Clinical Oncology (2013)

Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique.Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines.Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure.The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.
HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection
Authors: Benjamin Israelow, Christopher M. Narbus, Marion Sourisseau, Matthew J. Evans
Journal: Hepatology (2014)

Hepatitis C virus (HCV) exposure leads to persistent life-long infections characterized by chronic inflammation often developing into cirrhosis and hepatocellular carcinoma. The mechanism by which HCV remains in the liver while inducing an inflammatory and antiviral response remains unclear. Though the innate immune response to HCV in patients seems to be quite active, HCV has been shown in cell culture to employ a diverse array of innate immune antagonists, which suggests that current model systems to study interactions between HCV and the innate immune system are not representative of what happens in vivo . We recently showed that hepatoma-derived HepG2 cells support the entire HCV life cycle if the liver-specific microRNA, miR-122, is expressed along with the entry factor, CD81 (termed HepG2-HFL cells). We found that there was a striking difference in these cells' ability to sustain HCV infection and spread when compared with Huh-7 and Huh-7.5 cells. Additionally, HepG2-HFL cells exhibited a more robust antiviral response when challenged with other RNA viruses and viral mimetics than Huh-7 and Huh-7.5 cells. HCV infection elicited a potent interferon-lambda (IFN-λ), IFN-stimulated gene, and cytokine response in HepG2-HFL cells, but not in Huh-7 cells, suggesting that HepG2-HFL cells more faithfully recapitulate the innate immune response to HCV infection in vivo . Using this model, we found that blocking the retinoic acid-inducible gene I (RIG-I)-like receptor pathway or the IFN-λ-signaling pathway promoted HCV infection and spread in HepG2-HFL cells. Conclusion : HepG2-HFL cells represent a new system to study the interaction between HCV and the innate immune system, solidifying the importance of IFN-λ in hepatic response to HCV infection and revealing non-redundant roles of RIG-I and melanoma differentiation-associated protein 5 in HCV recognition and repression of infection. (Hepatology 2014;60:1170–1179)