tbuckley/cabot-search huggingface dataset:
Embryonic Pig Pancreatic Tissue Transplantation for the Treatment of Diabetes
Authors: Smadar Eventov-Friedman, Dalit Tchorsh, Helena Katchman, Elias Shezen, Anna Aronovich, Gil Hecht, Benjamin Dekel, Gideon Rechavi, Bruce R Blazar, Ilan Feine, Orna Tal, Enrique Freud, Yair Reisner
Journal: PLoS Medicine (2006)

Background Transplantation of embryonic pig pancreatic tissue as a source of insulin has been suggested for the cure of diabetes. However, previous limited clinical trials failed in their attempts to treat diabetic patients by transplantation of advanced gestational age porcine embryonic pancreas. In the present study we examined growth potential, functionality, and immunogenicity of pig embryonic pancreatic tissue harvested at different gestational ages. Methods and Findings Implantation of embryonic pig pancreatic tissues of different gestational ages in SCID mice reveals that embryonic day 42 (E42) pig pancreas can enable a massive growth of pig islets for prolonged periods and restore normoglycemia in diabetic mice. Furthermore, both direct and indirect T cell rejection responses to the xenogeneic tissue demonstrated that E42 tissue, in comparison to E56 or later embryonic tissues, exhibits markedly reduced immunogenicity. Finally, fully immunocompetent diabetic mice grafted with the E42 pig pancreatic tissue and treated with an immunosuppression protocol comprising CTLA4-Ig and anti–CD40 ligand (anti-CD40L) attained normal blood glucose levels, eliminating the need for insulin. Conclusions These results emphasize the importance of selecting embryonic tissue of the correct gestational age for optimal growth and function and for reduced immunogenicity, and provide a proof of principle for the therapeutic potential of E42 embryonic pig pancreatic tissue transplantation in diabetes.
Early steatosis in transplant recipients with recurrent HCV infection is associated with early short term use of steroids and delayed progression of hepatic fibrosis
Authors: M. Angelico, G. Palmieri, S. Battista, F. Casarelli, D. Di Paolo, A. Petrolati, C. Ciceroni, R. Lionetti, G. Tisone
Journal: Journal of Hepatology (2003)
Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis
Authors: Farshid Noorbakhsh, Shigeki Tsutsui, Nathalie Vergnolle, Leonie A. Boven, Neda Shariat, Mohammed Vodjgani, Kenneth G. Warren, Patricia Andrade-Gordon, Morley D. Hollenberg, Christopher Power
Journal: The Journal of Experimental Medicine (2006)

The proteinase-activated receptors (PARs) are widely recognized for their modulatory properties of inflammation and neurodegeneration. We investigated the role of PAR2 in the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in mice. PAR2 expression was increased on astrocytes and infiltrating macrophages in human MS and murine EAE central nervous system (CNS) white matter (P &amp;lt; 0.05). Macrophages and astrocytes from PAR2 wild-type (WT) and knockout (KO) mice exhibited differential immune gene expression with PAR2 KO macrophages showing significantly higher interleukin 10 production after lipopolysaccharide stimulation (P &amp;lt; 0.001). PAR2 activation in macrophages resulted in the release of soluble oligodendrocyte cytotoxins (P &amp;lt; 0.01). Myelin oligodendrocyte glycoprotein–induced EAE caused more severe inflammatory gene expression in the CNS of PAR2 WT animals (P &amp;lt; 0.05), together with enhanced T cell proliferation and interferon γ production (P &amp;lt; 0.05), compared with KO littermates. Indeed, PAR2 WT animals showed markedly greater microglial activation and T lymphocyte infiltration accompanied by worsened demyelination and axonal injury in the CNS compared with their PAR2 KO littermates. Enhanced neuropathological changes were associated with a more severe progressive relapsing disease phenotype (P &amp;lt; 0.001) in WT animals. These findings reveal previously unreported pathogenic interactions between CNS PAR2 expression and neuroinflammation with ensuing demyelination and axonal injury.
A High Tumor-Associated Macrophage Content Predicts Favorable Outcome in Follicular Lymphoma Patients Treated with Rituximab and Cyclophosphamide-Doxorubicin-Vincristine-Prednisone
Authors: Minna Taskinen, Marja-Liisa Karjalainen-Lindsberg, Heidi Nyman, Leena-Maija Eerola, Sirpa Leppä
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Tumor-associated macrophage (TAM) content predicts survival in follicular lymphoma (FL) patients treated with chemotherapy. The aim of this study was to determine how combination of rituximab with chemotherapy influences TAM-associated clinical outcome. Experimental Design: Expression of a macrophage marker, CD68, was determined immunohistochemically from FL samples of 96 patients treated with rituximab and cyclophosphamide-Adriamycin-vincristine-prednisone regimen. Of them, 71 received therapy at diagnosis and 25 at relapse. Neutrophil and CD3+ lymphocyte counts were also measured. The median follow-up time for the cohort was 54 months. Fourty-five patients previously treated with chemotherapy served as a control group. Results: Consistent with previous studies, high TAM amount was associated with adverse outcome in chemotherapy-treated patients (P = 0.026). In contrast, after rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone regimen, high TAM content correlated with longer survival rates. According to Kaplan Meier estimates, the median progression free survival (PFS) was not reached for patients with high TAM content compared with 45 months for patients with low TAM scores (P = 0.006). A trend toward a better overall survival (OS) at 5 years was also observed for patients with high TAM content (OS, 97% versus 90%, P = 0.116). The positive prognostic value of TAMs was seen both for the patients treated at diagnosis and at relapse. In multivariate analyses, TAM content remained an independent prognostic factor for OS and PFS. Neutrophil and CD3+ lymphocyte counts did not correlate with outcome. Conclusions: The data suggest that high TAM score is associated with a favorable prognosis in FL patients treated with immunochemotherapy.
Surgical treatment of aneurysms of the ascending aorta associated with severe aortic regurgitation.
Authors: M J Antunes, A L Baptista, P R Colsen, R H Kinsley
Journal: Thorax (1984)

From January 1979 to June 1982 31 patients have had simultaneous ascending aortic aneurysm repair and aortic valve replacement. Fifteen patients (group 1) received a composite graft; seven patients (group 2) had separate aortic valve and supracoronary ascending aorta prostheses; and nine patients (group 3) had aortic valve replacement and "tailoring" of the ascending aorta. The mean age was 50 (SD 14) years. Nine patients had acute dissection, five with the coronary ostia affected. Emergency surgery was performed in 10 cases. There were six early deaths (19.4%), none of them due to technical complications during surgery. The mortality rate was 56% for patients with acute dissection operated on as an emergency and 4.5% for patients having elective operations. Appreciable haemorrhage occurred in four patients (12.9%). No neurological complications occurred. There was one late death. The survivors were followed up for one to four years. There was one case of recurrence of aneurysm. No ischaemic complications resulted from coronary reimplantation. There were no significant differences in the results of the three groups. Simultaneous ascending aortic aneurysm repair and aortic valve replacement can be accomplished with an acceptable mortality rate and little morbidity.
Role for Hydrogen Peroxide in Flow-Induced Dilation of Human Coronary Arterioles
Authors: Hiroto Miura, John J. Bosnjak, Gang Ning, Takashi Saito, Mamoru Miura, David D. Gutterman
Journal: Circulation Research (2003)

Flow-induced dilation (FID) is dependent largely on hyperpolarization of vascular smooth muscle cells (VSMCs) in human coronary arterioles (HCA) from patients with coronary disease. Animal studies show that shear stress induces endothelial generation of hydrogen peroxide (H 2 O 2 ), which is proposed as an endothelium-derived hyperpolarizing factor (EDHF). We tested the hypothesis that H 2 O 2 contributes to FID in HCA. Arterioles (135±7 μm, n=71) were dissected from human right atrial appendages at the time of cardiac surgery and cannulated with glass micropipettes. Changes in internal diameter and membrane potential of VSMCs to shear stress, H 2 O 2 , or to papaverine were recorded with videomicroscopy. In some vessels, endothelial H 2 O 2 generation to shear stress was monitored directly using confocal microscopy with 2′,7′-dichlorofluorescin diacetate (DCFH) or using electron microscopy with cerium chloride. Catalase inhibited FID (%max dilation; 66±8 versus 25±7%; P &lt;0.05, n=6), whereas dilation to papaverine was unchanged. Shear stress immediately increased DCFH fluorescence in the endothelial cell layer, whereas treatment with catalase abolished the increase in fluorescence. Electron microscopy with cerium chloride revealed shear stress–induced increase in cerium deposition in intimal area surrounding endothelial cells. Exogenous H 2 O 2 dilated (%max dilation; 97±1%, ED 50 ; 3.0±0.7×10 −5 mol/L) and hyperpolarized HCA. Dilation to H 2 O 2 was reduced by catalase, 40 mmol/L KCl, or charybdotoxin plus apamin, whereas endothelial denudation, deferoxamine, 1H- 1,2,4 -oxadiazole-[4,3-a]quinoxalin-1-one, or glibenclamide had no effect. These data provide evidence that shear stress induces endothelial release of H 2 O 2 and are consistent with the idea that H 2 O 2 is an EDHF that contributes to FID in HCA from patients with heart disease. The full text of this article is available at http://www.circresaha.org.
A plasmid DNA vaccine encoding prostatic acid phosphatase (PAP) elicits antigen-specific T cells in patients with stage D0 prostate cancer
Authors: D. G. McNeel, E. J. Dunphy, L. E. Johnson, T. P. Frye, M. J. Staab, D. L. Horvath, J. Straus, D. Alberti, G. Liu, G. Wilding
Journal: Journal of Clinical Oncology (2006)

14570 Background: Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer. Clinical trials conducted in patients with metastatic prostate cancer targeting PAP by means of antigen presenting-cell vaccines have suggested clinical benefit in terms of disease progression and overall survival. Ultimately, tumor vaccines may be most effective in the setting of minimal residual disease. We have been investigating plasmid DNA vaccines encoding PAP in rodent models. We found these to be safe and effective in eliciting PAP-specific CD8 T cells and saw evidence of anti-tumor efficacy. We report here the initial immunological results from a dose-escalation portion of a phase I trial testing a DNA vaccine encoding PAP in patients with minimal residual stage D0 prostate cancer. Methods: Patients with clinical stage D0 prostate cancer with rising PSA were vaccinated over a 12-week period, 6 times at 14-day intervals, with a plasmid DNA vaccine encoding PAP (pTVG-HP). Vaccinations were administered intradermally with 100 mcg, 500 mcg, or 1500 mcg doses, and with 200 mcg of GM-CSF co-administered as a vaccine adjuvant. Immunological responses were evaluated by antigen-specific T cell proliferation and IFNγ secretion, and by ELISA for PAP-specific IgG. Results: At present 9 patients have been enrolled in a dose-escalation portion of the trial, and 6 have completed all immunizations. No serious adverse events have been observed, and no patients have discontinued treatment. To date, immunological analysis has been performed for the first, lowest dose cohort. PAP-specific CD4 and CD8 T cell responses, measured by antigen-specific T cell proliferation, were elicited following immunization in 2 of 3 patients. PAP-specific IgG antibodies were not detectable in these patients following vaccination. Conclusions: Intradermal immunization of patients with stage D0 prostate cancer with pTVG-HP has been without evidence of adverse events in doses up to 500 mcg. CD4 and CD8 T cell responses have been observed, consistent with a predominantly cellular immune response, at even the lowest dose of vaccine. Immunological analysis will be performed for patients completing the other dose levels, and all patients will be followed for changes in serum PSA levels. No significant financial relationships to disclose.
Response to: ‘Are autoantibodies to RNA-polymerase III to be incorporated in routine diagnostic laboratory algorithms for systemic autoimmune rheumatic diseases?’ by Jan Damoiseaux
Authors: J Fransen, J Pope, M Baron, S Johnson, D Khanna, M Matucci-Cerinic, A Tyndall, F van den Hoogen
Journal: Annals of the Rheumatic Diseases (2014)

In his letter, Jan Damoiseaux advocates testing of anti-RNA polymerase III antibodies (ARA), and also other (novel) systemic sclerosis (SSc)-associated antibodies, only for those patients who are really suspected for SSc.1 Damoiseaux argues that there is a necessity to provide clinical information together with the request for testing for rheumatic systemic autoimmune diseases.

We very much agree that testing for SSc-associated antibodies should only be requested for those people who really are suspected to have SSc. We feel that a correct request of testing for these autoantibodies is, first and foremost, a responsibility of the requestor, that is, the rheumatologist. However, immunologists and rheumatologists almost certainly can learn from each other in optimising requests for antibody …
Effect of N alpha-methyl-histamine on acid secretion in isolated cultured rabbit parietal cells: implications for Helicobacter pylori associated gastritis and gastric physiology.
Authors: I L Beales, J Calam
Journal: Gut (1997)

BACKGROUND: Helicobacter pylori has been shown to produce the unusual metabolite N alpha-methyl-histamine. This compound is known to be a potent agonist at inhibitory histamine H3 receptors. There is increasing evidence implicating this receptor in the control of gastric acid secretion but the mechanism for this remains to be clarified. AIMS: To investigate the effect of N alpha-methyl-histamine on the acid secretory activity of parietal cells and to determine the mechanism for such effects, thus helping to determine the role of this compound in the pathophysiology of H pylori infection. METHODS: Rabbit parietal cells were isolated and enriched by collagenase-EDTA digestion and centrifugal elutriation. Following culture on Matrigel coated plates, acid secretion was assessed by 14C aminopyrine accumulation. RESULTS: N alpha-methyl-histamine (100 microM) was as potent as histamine (100 microM) in stimulating acid secretion. This effect was reversed by ranitidine indicating it was mediated via the H2 receptor. N alpha-methyl-histamine potentiated the effects of both carbachol (increased by 280%) and gastrin (by 350%) (p &lt; 0.01). N alpha-methyl-histamine had no inhibitory actions on forskolin or carbachol stimulated acid secretion suggesting that there is not an inhibitory H3 receptor located directly on the parietal cell. CONCLUSIONS: Bacterially produced N alpha-methyl-histamine directly stimulates acid secretion by parietal cells and this may contribute to the increased acid secretion that contributes to duodenal ulceration.
Gene Expression of Brain Natriuretic Peptide in Isolated Atrial and Ventricular Human Myocardium
Authors: Stephan Wiese, Tobias Breyer, Adrian Dragu, Reza Wakili, Thilo Burkard, Stephan Schmidt-Schweda, Ernst-Martin Füchtbauer, Ulrike Dohrmann, Friedhelm Beyersdorf, Dirk Radicke, Christian J.F. Holubarsch
Journal: Circulation (2000)

Background —We studied the effects of angiotensin II (Ang II) and diastolic overstretch on the induction of cardiac growth in isometrically contracting muscle preparations from human right atria and left ventricles. We used the gene expression of brain natriuretic peptide (BNP) as a molecular marker of cardiac hypertrophy. Methods and Results —Northern blot analysis was performed in human atrial muscle preparations, which were either incubated in 10 −6 mol/L Ang II for 45 minutes or diastolically stretched to 120% of optimum muscle length. Similar experiments were performed with human left ventricular muscle preparations. Results were as follows: (1) BNP gene expression increased in human atrial myocardium 4-fold when stimulated by Ang II (n=7, P &lt;0.001). (2) Diastolic overstretch increased BNP expression in a time-dependent manner. The linear regression equations for the BNP/GAPDH ratio as a function of time (hours) were y=1.21+0.62x ( P &lt;0.001) for overstretched preparations and y=1.07−0.01x ( P =NS) for atrial preparations kept at physiological muscle length. (3) In left ventricular human muscle preparations, diastolic overstretch and Ang II increased BNP gene expression as well. (4) In addition, the Ang II subtype 1 receptor blocker losartan was able to block the effects of Ang II and diastolic overstretch. Conclusions —Cardiac hypertrophy can be induced in isolated human atrial and left ventricular intact myocardium by Ang II and diastolic overstretch but not by isometric afterload. The fact that the induction of cardiac growth is inhibited by the blockade of Ang II subtype 1 receptors is of scientific and clinical importance.
Alcohol consumption and renal cell cancer risk in two Italian case–control studies
Authors: C. Pelucchi, C. Galeone, M. Montella, J. Polesel, A. Crispo, R. Talamini, E. Negri, V. Ramazzotti, M. Grimaldi, S. Franceschi, C. La Vecchia
Journal: Annals of Oncology (2008)
Glucocorticoid-induced changes in the quantity and secretory capacity of individual rat somatotropes.
Authors: K Niimi, R J Krieg, J D Hanna, F Santos, J C Chan
Journal: Journal of the American Society of Nephrology (1993)

Chronic glucocorticoid treatment is complicated by growth failure. The study presented here was designed to investigate the effect of cortisone on growth hormone (GH) secretion by individual pituitary cells in young male rats. Beginning at 37 days of age, animals were injected sc with cortisone acetate (CORT; 5.0 mg/rat per day) or the same volume of saline (SAL) for 8 days. At 45 days of age, the body weights of the CORT animals (134.5 +/- 5.5 g) were significantly less (P < 0.0005) than those of SAL controls (179.3 +/- 4.2 g). The secretory capacity of dispersed pituitary cells was assessed by the reverse hemolytic plaque assay. Cells were exposed to six concentrations of GH-releasing hormone (GHRH) ranging from 0.01 to 3.0 nM. CORT treatment significantly decreased the absolute number of somatotropes per pituitary gland (CORT, 1.23 +/- 0.03 x 10(6); SAL, 1.57 +/- 0.09 x 10(6); P = 0.025). Conversely, the mean plaque areas were significantly greater for CORT animals at all concentrations of GHRH tested, indicating that the amount of GH secreted by individual somatotropes was significantly increased by CORT. It was concluded that the paradoxical increase in the in vitro GHRH responsiveness, which is commonly observed after glucocorticoid treatment, was due to an increase in the capacity of fewer individual somatotropes to secrete GH.
Brazilian manual of home-based pulmonary rehabilitation: Is it a good tool to facilitate the patients to train the domiciliary exercise?
Authors: Yves Raphael, Kenia Maynard da Silva, Thiago Bartholo, Arnaldo Noronha, Rogério Rufino, Cláudia Costa
Journal: European Respiratory Journal (2014)

Introduction: A Brazilian Manual of Home-based Pulmonary Rehabilitation was developed and it could help patients to do exercises at home. Objective: To evaluate if the use of the manual can maintain the effect of the Pulmonary Rehabilitation (PR) performed in the hospital. Methods: COPD patients, ≥ 40 y-o, and without history of exacerbation within the previous 3 months were screened from pulmonary out-clinic of State University of Rio de Janeiro and started a PR for 12 weeks. After this period of time, they were randomly allocated into one of two groups: the manual group (MG) and received the Brazilian Manual to use at home; and the control group (CG), who received only verbal orientation about the exercises they should continue to perform at home. All patients performed 6 minute-walk test (6MWT) and 6 minute-step test (6MST) when the PR finished and after 12 weeks performing exercises at home (with or without the manual). Results: 23 patients were screened, but 10 participants were excluded (3 smoking, 2 musculoskeletal diseases, 5 dropouts). It was analyzed the data from 13, who performed all tests. The mean distance walked by patients (6MWT) were 451,43±58,42 m and they climbed a mean of 371,46±63,41 steps (6MST). After 12 weeks at home, the MG achieved a better result in both tests: 6MWT 489,72±42,8 vs. 355,41±59,2 m (p=0,0008); 6MST: 410,50±45 vs. 310,29±50,64 steps (p=0,0018) Conclusion: The data suggest that COPD patients who used the manual at home could kept the results achieved during the outpatient PR performed at the hospital. The Brazilian Manual could be an important tool to facilitate the continuity of the outpatient PR program.
Neutrophils Transport Antigen from the Dermis to the Bone Marrow, Initiating a Source of Memory CD8+ T Cells
Authors: Darragh Duffy, Hélène Perrin, Valérie Abadie, Nora Benhabiles, Alexandre Boissonnas, Christelle Liard, Benjamin Descours, Damien Reboulleau, Olivia Bonduelle, Bernard Verrier, Nico Van Rooijen, Christophe Combadière, Béhazine Combadière
Journal: Immunity (2012)
"Foreign Body" Sarcoidosis
Authors: R. D. Sweet.
Journal: British Journal of Dermatology (1964)

Journal Article “Foreign Body” Sarcoidosis Get access R. D. Sweet. R. D. Sweet. Plymouth Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 5, 1 May 1964, Pages 236–237, https://doi.org/10.1111/j.1365-2133.1964.tb14521.x Published: 01 May 1964
B.M.A. Deputizing Service in Sheffield, 1970
Authors: B. T. Williams, R. A. Dixon, J. Knowelden
Journal: BMJ (1973)

Seventy-four per cent. of Sheffield general practitioners and 78% of those in Nottingham used a deputizing service in 1970. In each city the deputizing service was used by about 80% of single-handed general practitioners, 90% of doctors in two-doctor practices, and 60% of those in partnerships of three or more.The Sheffield deputizing service handled 15,988 new calls in the year, an average of 106 per subscribing doctor, and in addition made 339 revisits. The median number of calls handled for single-handed doctors was 98, for those in two-doctor practices 95, and for those in partnerships of three or more 75. The growth of group practice has not eliminated the demand for deputizing services.Sixty-six per cent. of consultations were with deputies who were primarily hospital doctors, 20% with a full-time deputy, 11% with deputies who were primarily general practitioners, and 3% with the switchboard staff, who were also trained nurses. The deputies had been qualified, on average, for eight years. Seventy-two per cent. of patients attended were seen within one hour of receipt of the call.Calls handled by the deputizing service represented approximately 1% of all the subscribers' consultations, 5% of their home visits, and half their calls between midnight and 07.00 hours. At this level of activity the concept of "personal doctoring" was not threatened.
Improved outcomes from acute severe asthma in Australian intensive care units (1996 2003)
Authors: P. J Stow, D. Pilcher, J. Wilson, C. George, M. Bailey, T. Higlett, R. Bellomo, G. K Hart
Journal: Thorax (2007)

There is limited information on changes in the epidemiology and outcome of patients with asthma admitted to intensive care units (ICUs) in the last decade. A database sampling intensive care activity in hospitals throughout Australia offers the opportunity to examine these changes.