tbuckley/cabot-search huggingface dataset:
Human CD4+CD25+ Regulatory, Contact-dependent T Cells Induce Interleukin 10–producing, Contact-independent Type 1-like Regulatory T Cells
Authors: Detlef Dieckmann, Cord Henrik Bruett, Heidi Ploettner, Manfred Bernhard Lutz, Gerold Schuler
Journal: The Journal of Experimental Medicine (2002)

It has been recently demonstrated that regulatory CD4+CD25+ CD45RO+ T cells are present in the peripheral blood of healthy adults and exert regulatory function similar to their rodent counterparts. It remains difficult to understand how the small fraction of these T cells that regulate via direct cell-to-cell contact and not via secretion of immunosuppressive cytokines could mediate strong immune suppression. Here we show that human CD4+CD25+ T cells induce long-lasting anergy and production of interleukin (IL)-10 in CD4+CD25− T cells. These anergized CD4+CD25− T cells then suppress proliferation of syngenic CD4+ T cells via IL-10 but independent of direct cell contact, similar to the so-called type 1 regulatory T (Tr1) cells. This ‘catalytic’ function of CD4+CD25+ T cells to induce Tr1-like cells helps to explain their central role for the maintenance of immune homeostasis.
Mechanisms of Inhibition of Tumor Angiogenesis and Vascular Tumor Growth by Epigallocatechin-3-Gallate
Authors: Gianfranco Fassina, Roberta Venè, Monica Morini, Simona Minghelli, Roberto Benelli, Douglas M. Noonan, Adriana Albini
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Green tea consumption has been linked to a reduced occurrence of some tumor types. Current data indicate that the principal mediator of this chemopreventive effect is epigallocatechin-3-gallate (EGCG), the most abundant polyphenol found in dried tea leaves. Here, we examined the effects of this compound on the two key cell populations typically involved in tumor growth: tumor cells and endothelial cells. Experimental Design: The effects of green tea and EGCG were tested in a highly vascular Kaposi’s sarcoma (KS) tumor model and on endothelial cells in a panel of in vivo and in vitro assays. Results: EGCG inhibited KS-IMM cell growth and endothelial cell growth, chemotaxis, and invasion over a range of doses; high concentrations also induced tumor cell apoptosis. EGCG inhibited the metalloprotease-mediated gelatinolytic activity produced by endothelial cell supernatants and the formation of new capillary-like structures in vitro. Green tea or purified EGCG when administered to mice in the drinking water inhibited angiogenesis in vivo in the Matrigel sponge model and restrained KS tumor growth. Histological analysis of the tumors were consistent with an anti-angiogenic activity of EGCG and green tea. Conclusions: These data suggest that the green tea gallate or its derivatives may find use in the prevention and treatment of vascular tumors in a chemoprevention or adjuvant setting.
Light and Electron Microscopic Studies of Perineural Invasion by Esophageal Carcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K Takubo, A Takai, K Yamashita, N Yoshimatsu, M Kitano, K Sasajima, K Fujita
Journal: JNCI Journal of the National Cancer Institute (1985)

Light and electron microscopic findings on perineural invasion by human esophageal squamous cell carcinoma are reported. Perineural invasion was observed histologically in 30 of a total of 129 cases (23%) of esophageal squamous cell carcinoma and in 11 of the 24 cases (46%) in which tumors infiltrated other organs by passing through the esophageal adventitial layer. Electron microscopic observation showed that the perineurium of peripheral nerves was completely surrounded by carcinoma cells and that marked degeneration and loss of perineural cells occurred. Irregularly thickened basal laminae were detected in the perineurium. For nerves incompletely surrounded by carcinoma tissue, the free portion of the perineurium revealed degenerative findings similar to those for completely surrounded nerves. Cytoplasmic projections of the leading margin of the invading cancer tissue were located in the degenerated perineurium, contained many lysosomes, and were not always surrounded by basal laminae. These observations suggest that invading carcinoma tissue actively contributes to the degeneration of the perineural sheath and that the special pattern of carcinoma tissue surrounding the peripheral nerves results from infiltration along the degenerated sheath of the perineurium.
Amyloid Fibrils Composed of Hexameric Peptides Attenuate Neuroinflammation
Authors: Michael P. Kurnellas, Chris M. Adams, Raymond A. Sobel, Lawrence Steinman, Jonathan B. Rothbard
Journal: Science Translational Medicine (2013)

Amyloid fibrils may provide anti-inflammatory benefit in MS and other neuroinflammatory disorders.
Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option?
Authors: C. Vogelmeier
Journal: European Respiratory Journal (2005)

This 12-month dose-titration study assessed the effectiveness of budesonide/formoterol for maintenance plus relief with a control group using salmeterol/fluticasone for maintenance plus salbutamol for relief. Adolescents and adults (n = 2,143; mean forced expiratory volume in one second (FEV<sub>1</sub>) 73% predicted; mean inhaled corticosteroid (ICS) 884 µg·day<sup>−1</sup>) were randomised to budesonide/formoterol 160/4.5 µg two inhalations <i>b.i.d.</i> plus additional inhalations as needed, or salmeterol/fluticasone 50/250 µg <i>b.i.d.</i> plus salbutamol as needed. Treatment was prescribed open label; after 4 weeks, physicians could titrate maintenance doses in accordance with normal clinical practice. Maintenance plus as-needed budesonide/formoterol prolonged the time to first severe exacerbation <i>versus</i> salmeterol/fluticasone (25% risk reduction). The total number of severe exacerbations was significantly reduced in the budesonide/formoterol group (255 <i>versus</i> 329). Both regimens provided sustained improvements in symptoms, as-needed use, quality of life and FEV<sub>1</sub>, with differences in favour of the budesonide/formoterol group for as-needed use (0.58 <i>versus</i> 0.93 inhalations·day<sup>−1</sup>) and FEV<sub>1</sub> (post-β<sub>2</sub>-agonist values). Mean ICS dose during treatment was similar in both groups (653 µg budesonide·day<sup>−1</sup> (maintenance plus as-needed) <i>versus</i> 583 µg fluticasone·day<sup>−1</sup>). The simplified strategy using budesonide/formoterol for maintenance and reliever therapy is feasible, safe and at least as effective as salmeterol/fluticasone plus salbutamol.
Carcinoembryonic antigen-related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo
Authors: A. K. Horst
Journal: Journal of Clinical Investigation (2006)

Carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1), a cellular adhesion molecule of the Ig superfamily, is associated with early stages of angiogenesis. In vitro, CEACAM1 regulates proliferation, migration, and differentiation of murine endothelial cells. To prove that CEACAM1 is functionally involved in the regulation of vascular remodeling in vivo, we analyzed 2 different genetic models: in Ceacam1–/– mice, the Ceacam1 gene was deleted systemically, and in CEACAM1endo+ mice, CEACAM1 was overexpressed under the control of the endothelial cell–specific promoter of the Tie2 receptor tyrosine kinase. In Matrigel plug assays, Ceacam1–/– mice failed to establish new capillaries whereas in CEACAM1endo+ mice the implants were vascularized extensively. After induction of hind limb ischemia by femoral artery ligation, Ceacam1–/– mice showed significantly reduced growth of arterioles and collateral blood flow compared with their WT littermates. In agreement with a causal role of CEACAM1 in vascular remodeling, CEACAM1endo+ mice exhibited an increase in revascularization and collateral blood flow after arterial occlusion. Our findings indicate that CEACAM1 expression is important for the establishment of newly formed vessels in vivo. Hence CEACAM1 could be a future target for therapeutic manipulation of angiogenesis in disease.
Patient Selection for Lung Transplantation
Authors: Janet R. Maurer
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin.
Authors: Ching-Hung Lin, Kuan-Ting Kuo, Shih-Sung Chuang, Sung-Hsin Kuo, Julia Hueimei Chang, Kung-Chao Chang, Hui-Chen Hsu, Hwei-Fang Tien, Ann-Lii Cheng
Journal: Clinical Cancer Research (2006)

Whether diffuse large B-cell lymphoma (DLBCL) of primary central nervous system origin (PCNSL) is biologically different from DLBCL of peripheral nodal origin (NL) remains unclear. The purpose of this study was to compare the expression frequencies and prognostic significance of a panel of cell differentiation markers between these two disease entities.This study included HIV-unrelated patients with PCNSL (n = 51) and NL (n = 72) treated at four hospitals in Taiwan for whom archival tumor tissue was available. Immunohistochemistry for CD10, BCL-6, MUM-1, vs38c, CD138, and BCL-2 was done. CD10, BCL-6, and MUM-1 expression results were used to classify all cases into the germinal center B-cell (GCB) or the non-GCB subgroup. The prognostic significances of clinical and immunophenotypic markers were evaluated.Nuclear MUM-1 expression was significantly higher in PCNSL than in NL (P < 0.001; 84% versus 53%). PCNSL tumors were more frequently classified into the non-GCB subgroup than NL tumors (P = 0.020; 78% versus 62%). For patients with PCNSL, univariate analysis showed that patients with BCL-6 expression had a trend towards longer survival (P = 0.073; median survival, 25.3 versus 7.3 months), and multivariate analysis showed BCL-6 was an independent prognostic factor (P = 0.026). For patients with NL, both of univariate (P = 0.003) and multivariate analyses (P = 0.002) showed that GCB was significantly associated with favorable survival.The higher frequency of non-GCB subclassification, which was mainly contributed by nuclear MUM-1 expression in PCNSL implies that it has a more differentiated cellular origin than NL. BCL-6 expression in patients with PCNSL and GCB subgroup in patients with NL were favorable prognostic factors.
Effects of gluten enriched diet on the small intestinal mucosa of normal mice and mice with graft versus host reaction.
Authors: R Troncone, N Caputo, A Zibella, G Molitierno, L Maiuri, S Auricchio
Journal: Gut (1994)

This study looked at the effect of extra dietary gluten on the intestinal architecture of both normal mice and those with an ongoing mucosal delayed hypersensitivity reaction. BDF1 normal mice and mice in which a graft v host reaction (GvHR) had been induced, both weaned on gluten free diet, were allocated for three weeks to three different dietary regimens: gluten free, 9normal9 (3.6% gluten), and gluten enriched (15.8% gluten). In normal mice receiving the gluten containing diet, shorter villi, deeper crypts, and higher crypt cell production rate were noted when compared with those receiving gluten free diet: these changes were more pronounced in those receiving the gluten enriched diet. GvHR mice showed shorter villi and an increase in both crypt length and crypt cell production rate when compared with normal mice, but the presence of gluten in their diet did not produce additional damage. Both in normal and in GvHR mice receiving gluten containing diet there were no signs of systemic (cell mediated or humoral) or mucosal immune reactions (raised intraepithelial lymphocyte counts or enhanced epithelial Ia expression) to gliadin. In conclusion, increasing the dietary gluten content produces significant changes in the mucosal architecture of normal mice; mice with GvHR enteropathy do not show additional damage resulting from dietary gluten.
Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial
Authors: Antoinette K Tshefu, Oumar Gaye, Kassoum Kayentao, Ricardo Thompson, Kirana M Bhatt, Sanie SS Sesay, Dorina G Bustos, Emiliana Tjitra, George Bedu-Addo, Isabelle Borghini-Fuhrer, Stephan Duparc, Chang Sik Shin, Lawrence Fleckenstein
Journal: The Lancet (2010)
Cyclin D1-Dependent Induction of Luminal Inflammatory Breast Tumors by Activated Notch3
Authors: Hua Ling, Jean-René Sylvestre, Paul Jolicoeur
Journal: Cancer Research (2013)

Accumulating evidence suggests that Notch3 (N3) is involved in breast cancer development, but its precise contributions are not well understood. Here, we report that pregnant mice expressing an activated intracellular form of N3 (N3(IC)) exhibit a cyclin D1-dependent expansion of premalignant CD24(+) CD29(low) luminal progenitors with enhanced differentiation potential in vitro and in vivo. Parous mice developed luminal mammary tumors in a cyclin D1-dependent manner. Notably, mice expressing higher levels of N3(IC) exhibited tumors resembling inflammatory breast cancer that frequently metastasized. N3(IC)-induced tumors contained a large percentage of tumor-initiating cells, but these were reduced significantly in tumors derived from N3(IC) transgenic mice that were heterozygous for cyclin D1. After transplantation in the presence of normal mammary cells, N3(IC)-expressing tumor cells became less malignant, differentiating into CK6(+) CK18(+) CK5(-) alveolar-like structures akin to expanded luminal progenitors from which they were likely derived. Taken together, our results argue that activated N3 signaling primarily affects luminal progenitors among mammary cell subsets, with more pronounced levels of activation influencing tumor type, and provide a novel model of inflammatory breast cancer.
The Influence of Erythrocyte Concentration upon the Pressure-Flow Relationships in the Dog's Hind Limb
Authors: MATTHEW N. LEVY, LEONARD SHARE
Journal: Circulation Research (1953)

Since alterations in cell-plasma ratios are of paramount importance in the assessment of peripheral resistance, a study of pressure-flow relations was made in which blood having wide hematocrit values was perfused through a dog's hind limb in which collateral circulation has been excluded. When vessels were moderately dilated by denervation, the relative apparent viscosity was not affected by the perfusion pressure. When, however, the vessels were maximally dilated after a preceding period of anoxia, the relative apparent viscosity was found to become greater as perfusion pressure was progressively reduced. The in vivo relative apparent viscosity did not significantly exceed that of plasma until the erythrocyte concentration reached 30 per cent.
A decreased metabolic clearance rate of aldosterone in benign essential hypertension
Authors: W. Nowaczynski, O. Kuchel, J. Genest
Journal: Journal of Clinical Investigation (1971)

Aldosterone secretion rate, metabolic clearance rate, and/or plasma concentration were determined in 16 patients with benign, uncomplicated essential hypertension and compared with those of control subjects. The mean metabolic clearance rate of aldosterone in 10 patients was significantly (P < 0.001) lower (mean 867 liters of plasma/day per m2 ±270 SD) than in a group of 7 healthy subjects (mean 1480 liters/day per m2 ±265 SD). Secretion rates in 13 patients (including the 10 already mentioned) tended to be low (83 ±43 vs. 109 ±54 μg/day) and plasma concentrations tended to be high (13.6 ±4.6 vs. 7.5 ±4.8 ng/100 ml), but neither of these differences was statistically significant.
Emerging Pharmacology: Inhibitors of Human Immunodeficiency Virus Integration
Authors: Daria Hazuda, Marian Iwamoto, Larissa Wenning
Journal: The Annual Review of Pharmacology and Toxicology (2008)

The first integrase inhibitor licensed to treat HIV-1 infection was approved in late 2007, more than a decade after the introduction of the first inhibitors of the HIV-1 reverse transcriptase and protease. The unique biochemical and molecular mechanism of action of this novel class of antiretroviral drugs is the fundamental basis for their activity in treating multidrug-resistant HIV-1 infection and is important for understanding both the cellular and in vivo pharmacology and metabolism of these agents. In addition, available pharmacokinetic and drug interaction data for raltegravir and elvitegravir, the two integrase inhibitors that are the most advanced in clinical development to date, are reviewed.
Auditory Startle Response in Firefighters Before and After Trauma Exposure
Authors: Rachel M. Guthrie, Richard A. Bryant
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Although previous psychophysiological studies have revealed heightened muscular and autonomic responses in individuals with posttraumatic stress disorder (PTSD), these studies have not permitted inferences about whether the abnormal responses are a vulnerability factor or are acquired following trauma. The present study reports the first prospective psychophysiological investigation, to the authors' knowledge, of posttraumatic stress responses by prospectively evaluating the auditory startle response in firefighters before and after trauma exposure. METHOD: Orbicularis oculi (eye blink) electromyograms and skin conductance responses to 15 100-dB acoustic startle stimuli were assessed in 84 trainee firefighters before trauma exposure. After commencement of active duty, 35 firefighters were reassessed within 4 weeks of exposure to a traumatic event, and 36 firefighters were reassessed as a comparison group that was not exposed to trauma. RESULTS: In the trauma-exposed group, pretrauma physiological activity was predictive of posttrauma acoustic startle responses. Pretrauma skin conductance response to startle was also predictive of posttraumatic stress severity. CONCLUSIONS: These results provide initial support for elevated startle response being a vulnerability factor for posttraumatic stress responses.
Weight gain is greater with some antidepressants than others, US study finds
Authors: I. Torjesen
Journal: BMJ (2014)

Doctors might want to consider the propensity of different antidepressants for increasing a patient’s weight when prescribing to people in whom weight gain could have adverse health consequences, a group of US researchers has said.

The recommendation came after a study that they conducted that found that some antidepressants were associated with greater weight gain than others over a 12 month period. The Boston based researchers reviewed the electronic health records of a large New …
Interim Analysis Results of Above Phase II Study with Bevacizumab in Patients with Initially not Resectable/Borderline Resectable Colorectal Liver-Limited Metastases
Authors: Salvatore Artale, Guglielmo Nasti, Monica Ronzoni, Roberto Bordonaro, Maria Zampino, Silvia Brugnatelli, Andrea Sartore Bianchi, Azzurra Onofri, Angelo Vanzulli, Valentina Angelini, Salvatore Siena
Journal: Annals of Oncology (2013)
Protein kinase C epsilon mediates angiotensin II-induced activation of β-integrins in cardiac fibroblasts
Authors: P STAWOWY, C MARGETA, F BLASCHKE, C LINDSCHAU, C SPENCERHANSCH, M LEITGES, G BIAGINI, E FLECK, K GRAF
Journal: Cardiovascular Research (2005)

Objective: Angiotensin II (AII) promotes cardiac fibrosis by increased extracellular matrix production and enhanced interaction of matrix proteins with their cellular receptors, including integrins. AII and other growth factors augment β1-integrin-dependent adhesion and spreading by "inside-out signaling" without affecting the total number of integrin receptors. "Inside-out signaling" involves specific signaling pathways, including protein kinase C (PKC), leading to activation of β1-integrins. In the present study we investigated the mechanisms involved in AII-increased adhesion of adult rat cardiac fibroblasts (CFBs), obtained from Sprague–Dawley rats, to collagen I mediated by β1-integrin. Methods and results: Treatment of CFBs with AII induced a concentration-dependent increase in adhesion to collagen I (2.2-fold, p<0.01) within 3–6 h of treatment. This effect was mediated by β1-integrin via the angiotensin AT1 receptor and was significantly reduced by protein kinase C inhibition. AII significantly induced phosphorylation of PKC epsilon (PKCε), which is involved in β1-integrin-dependent adhesion and motility, and phosphorylation of the cytoplasmatic tail of β1-integrin at threonine 788/789, required for adhesion. Phosphorylation of β1-integrin and an increase in adhesion was also induced by l-α-phosphatidylinositol-3,4,5-triphosphate (l-α-PIP3), an activator of endogeneous PKCε. AII failed to increase adhesion in myofibroblasts obtained from PKCε (−/−) mice, but not in cells obtained from control mice. Co-immunoprecipitation and double immunofluorescence demonstrated that AII induced a close association of PKCε with β1-integrin in CFBs. Conclusion: The present study demonstrates that AII increased β1-integrin-dependent adhesion to collagen I in cardiac fibroblasts by inside-out signaling via PKCε and phosphorylation of the cytoplasmatic tail of the β1-integrin.
Selection Bias Explains Apparent Differential Mortality between Dialysis Modalities
Authors: Robert R. Quinn, Janet E. Hux, Matthew J. Oliver, Peter C. Austin, Marcello Tonelli, Andreas Laupacis
Journal: Journal of the American Society of Nephrology (2011)

The relative risk of death for patients treated with peritoneal dialysis compared with those treated with hemodialysis appears to change with duration of dialysis therapy. Patients who start dialysis urgently are at high risk for mortality and are treated almost exclusively with hemodialysis, introducing bias to such mortality comparisons. To better isolate the association between dialysis treatment modality and patient mortality, we examined the relative risk for mortality for peritoneal dialysis compared with hemodialysis among individuals who received ≥4 months of predialysis care and who started dialysis electively as outpatients. From a total of 32,285 individuals who received dialysis in Ontario, Canada during a nearly 8-year period, 6,573 patients met criteria for elective, outpatient initiation. We detected no difference in survival between peritoneal dialysis and hemodialysis after adjusting for relevant baseline characteristics. The relative risk of death did not change with duration of dialysis therapy in our primary analysis, but it did change with time when we defined our patient population using the more inclusive criteria typical of previous studies. These results suggest that peritoneal dialysis and hemodialysis associate with similar survival among incident dialysis patients who initiate dialysis electively, as outpatients, after at least 4 months of predialysis care. Selection bias, rather than an effect of the treatment itself, likely explains the previously described change in the relative risk of death over time between hemodialysis and peritoneal dialysis.