tbuckley/cabot-search huggingface dataset:
Mechanism responsible for the induction of I-J restriction on TS3 suppressor cells.
Authors: M Minami, N Honji, M E Dorf
Journal: The Journal of Experimental Medicine (1982)

The mechanisms responsible for the induction of I-J restrictions on third-order suppressor T cells (TS3) were analyzed. The I-J phenotype of the antigen-coupled cells used for priming restricted the specificity of the TS3 population. Thus, TS3 cells were only generated after priming with antigen-coupled I-J homologous cells. Identity at the I-JM (and I-E) subregions was sufficient for TS3 induction. Furthermore, priming of H-2 heterozygous mice with antigen-coupled parental cells generated TS3 that were restricted to the parental haplotype used for priming. The splenic cell population responsible for antigen presentation and induction of TS3 cells was fractionated. The cells involved in antigen presentation were found in the splenic adherent population and were absent in the fraction containing splenic nonadherent T and B cells. The subsequent activation and interaction of TS3 cells is also restricted by genes in the H-2 complex. The results are discussed in terms of a general mechanism responsible for the induction of restrictions in T helper and TS3 cells.
Conjugated bile acids activate the sphingosine-1-phosphate receptor 2 in primary rodent hepatocytes
Authors: Elaine Studer, Xiqiao Zhou, Renping Zhao, Yun Wang, Kazuaki Takabe, Masayuki Nagahashi, William M. Pandak, Paul Dent, Sarah Spiegel, Ruihua Shi, Weiren Xu, Xuyuan Liu, Pat Bohdan, Luyong Zhang, Huiping Zhou, Phillip B. Hylemon
Journal: Hepatology (2011)

Bile acids have been shown to be important regulatory molecules for cells in the liver and gastrointestinal tract. They can activate various cell signaling pathways including extracellular regulated kinase (ERK)1/2 and protein kinase B (AKT) as well as the G-protein-coupled receptor (GPCR) membrane-type bile acid receptor (TGR5/M-BAR). Activation of the ERK1/2 and AKT signaling pathways by conjugated bile acids has been reported to be sensitive to pertussis toxin (PTX) and dominant-negative Gα(i) in primary rodent hepatocytes. However, the GPCRs responsible for activation of these pathways have not been identified. Screening GPCRs in the lipid-activated phylogenetic family (expressed in HEK293 cells) identified sphingosine-1-phosphate receptor 2 (S1P(2) ) as being activated by taurocholate (TCA). TCA, taurodeoxycholic acid (TDCA), tauroursodeoxycholic acid (TUDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), and S1P-induced activation of ERK1/2 and AKT were significantly inhibited by JTE-013, a S1P(2) antagonist, in primary rat hepatocytes. JTE-013 significantly inhibited hepatic ERK1/2 and AKT activation as well as short heterodimeric partner (SHP) mRNA induction by TCA in the chronic bile fistula rat. Knockdown of the expression of S1P(2) by a recombinant lentivirus encoding S1P(2) shRNA markedly inhibited the activation of ERK1/2 and AKT by TCA and S1P in rat primary hepatocytes. Primary hepatocytes prepared from S1P(2) knock out (S1P(2) (-/-) ) mice were significantly blunted in the activation of the ERK1/2 and AKT pathways by TCA. Structural modeling of the S1P receptors indicated that only S1P(2) can accommodate TCA binding. In summary, all these data support the hypothesis that conjugated bile acids activate the ERK1/2 and AKT signaling pathways primarily through S1P(2) in primary rodent hepatocytes.
Severe alterations in expression and localisation of 6 4 integrin in salivary gland acini from patients with Sjogren syndrome
Authors: J Velozo, S Aguilera, C Alliende, P Ewert, C Molina, P Perez, L Leyton, A Quest, M Brito, S Gonzalez, C Leyton, M Hermoso, R Romo, M-J Gonzalez
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> In salivary glands from patients with Sjögren syndrome, overexpression of laminins 1 and 5 and disorganisation of the acinar basal lamina have been reported. Laminin 5 mediates association of the basal lamina with epithelial cells by forming adhesion complexes upon interaction with α6β4 integrin. In the present work, mRNA and protein levels of α6β4 integrin were determined and its localisation in salivary glands evaluated in patients with Sjögren syndrome. <h3>Methods:</h3> Salivary glands of 12 patients with Sjögren syndrome and 8 controls were studied. The mRNA and protein levels of α6β4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of α6β4 and laminin were evaluated by confocal microscopy. <h3>Results:</h3> In patients, no significant differences in α6 and β4 mRNA levels were detected. However, β4 integrin protein levels were significantly lower, whereas, changes in α6, were highly variable. In controls, α6β4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in α6β4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. α6β4 was also detected in the cytoplasm and lateral plasma membrane in serous and mucous acini. <h3>Conclusion:</h3> Mild alterations in the basal lamina correlated with lateral redistribution of α6β4 integrin and the formation of new cell–cell adhesions that help maintain acinar organisation and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral α6β4 redistribution was no longer sufficient to maintain acinar cell survival. Thus, maintenance of equilibrium between cell–cell and cell–basal lamina attachment is required to sustain gland cell survival.
Acrylic acid grafting and collagen immobilization on poly(ethylene terephthalate) surfaces for adherence and growth of human bladder smooth muscle cells
Authors: Isabelle Bisson, Marek Kosinski, Sylvie Ruault, Bhuvanesh Gupta, Jöns Hilborn, Florian Wurm, Peter Frey
Journal: Biomaterials (2002)
Functional Alteration of the Lymphoma Stromal Cell Niche by the Cytokine Context: Role of Indoleamine-2,3 Dioxygenase
Authors: Hélène Maby-El Hajjami, Patricia Amé-Thomas, Céline Pangault, Olivier Tribut, John DeVos, Rachel Jean, Nadège Bescher, Céline Monvoisin, Joëlle Dulong, Thierry Lamy, Thierry Fest, Karin Tarte
Journal: Cancer Research (2009)

Human mesenchymal stem cells (MSC) strongly repress activated T-cell proliferation through the production of a complex set of soluble factors, including the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which is induced by IFN-gamma. Conversely, MSCs support survival of follicular lymphoma (FL) B cells, in particular after exposure to tumor necrosis factor-alpha (TNF) and lymphotoxin-alpha1beta2 (LT). The role of MSCs on normal and malignant B-cell growth in steady-state and inflammatory conditions remains to be fully explored. We show here that resting MSCs sustain activated normal B-cell proliferation and survival, whereas IFN-gamma-conditioned MSCs mediate IDO-dependent B-cell growth arrest and apoptosis. IFN-gamma, TNF, and LT are significantly overexpressed by the microenvironment of invaded FL-lymph nodes, but their relative expression patterns are highly heterogeneous between samples. In vitro, IFN-gamma abrogates the B-cell supportive phenotype induced by TNF and LT on MSCs. Moreover, IFN-gamma overrules the growth promoting effect of MSCs on primary purified FL B cells. Altogether, these results underline the crucial role of the cytokine context in the local crosstalk between malignant cells and their microenvironment and provide new insights into our knowledge of the FL cell niche that emerges as a new promising target for innovative therapeutic strategies.
Gastric cell c-AMP stimulating autoantibodies in duodenal ulcer disease.
Authors: F De Lazzari, R Mirakian, L Hammond, C Venturi, R Naccarato, G F Bottazzo
Journal: Gut (1988)

Gastric cell c-AMP stimulating antibodies (GCS-Ab) were studied in 30 patients with duodenal ulcer (DU) disease. Semipurified immunoglobulin (Ig) preparations from 13/30 patients stimulated c-AMP production in parietal cell enriched gastric cell suspensions obtained from male guinea pig stomachs. Maximum stimulation (varying between 260 and 547%) was reached after four hours incubation with 2 and 4 mg/ml Ig concentrations. The 13 patients with gastric cell stimulating antibodies (GCS-Ab), all male patients, developed the disease at a younger age (nine of 13 under the age of 30), had a longer duration of symptoms (mean 18.4 years), and had a higher incidence of DU in their families (61%). Eight of 13 (61%) in the GCS-Ab+ group did not respond to anti-H2-R drugs, whereas in the negative patients only three of 17 (18%) were classified as 9non-responders9. Remarkably few conventional autoantibodies were detected in our series. Gastric cell stimulating antibodies are a new addition to the growing list of receptor antibodies in human diseases and the described in vitro test should provide an easier tool for screening large populations.
Scale-up of Voluntary HIV Counseling and Testing in Kenya
Authors: Elizabeth Marum, Miriam Taegtmeyer, Kenneth Chebet
Journal: JAMA (2006)

Extract: Overburdened health care systems in resource-poor countries are unable to cope with the impact of human immunodeficiency virus (HIV) and the increased responses to treatment that have been proposed internationally. There is an urgent need for robust, replicable approaches that meet the need for rapid expansion of HIV testing services. Provision and utilization of voluntary HIV counseling and testing (VCT) services in Kenya expanded rapidly between 2000 and 2005. Lessons learned from increasing access to VCT are applicable to global efforts to increase access to HIV prevention, care, and antiretroviral therapy (ART).
Turning fat into muscle
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Boosting innate immunity in cancerMature DCs and the NKT cell ligand ␣ -galactosyl ceramide ( ␣ -GalCer) are a promising combination for boosting immunity in humans, according to a study on page 1503.Chang and colleagues used ␣ -GalCer-pulsed DCs to immunize cancer patients and showed that the treatment resulted in long-term expansion of both NKT cells and virus-specific CD8 ϩ T cells.␣ -GalCer, a glycolipid derived from marine sponges, was identified based on its antitumor properties.This foreign glycolipid was later found to be presented to NKT cells by DCs.NKT cells activated by this glycolipid can promote tumor regression in mice.Attempts to extend this work to humans, however, have met with limited success.␣ -GalCer treatment alone decreased NKT cell numbers in patients with solid tumors, and vaccination with ␣ -GalCer-pulsed immature DCs induced only modest and transient NKT cell expansion.Maturation of the DCs-treatment with cytokines that enhance the expression of MHC and costimulatory molecules-was the key to the approach used by Chang and colleagues.They immunized five advanced cancer patients, none of whom had detectable NKT cells in their blood before treatment.But with ␣ -GalCer-pulsed mature DCs, all patients had a rapid and sustained increase in NKT cell numbers.Surprisingly, CD8 ϩ T cells specific for cytomegalovirus were also expanded by ␣-GalCer-pulsed DCs activate NKT cells and antiviral T cells in advanced cancer patients.
Clinical and experimental evidence of prostaglandin E1-induced angiogenesis in the myocardium of patients with ischemic heart disease
Authors: M MEHRABI, N SERBECIC, F TAMADDON, C KAUN, K HUBER, R PACHER, T WILD, G MALL, J WOJTA, H GLOGAR
Journal: Cardiovascular Research (2002)

Prostaglandin E1 (PGE-1) is a potent vasodilative agent which has been used to bridge patients with chronic heart failure listed for heart transplantation (HTX). In various experimental settings PGE-1 appears to stimulate angiogenesis by inducing vascular endothelial growth factor expression. This observational clinical study sought to investigate the angiogenic effects of PGE-1 in the failing human heart.Neovascularization was investigated in 14 explanted hearts from patients with ischemic cardiomyopathy (ICMP) who had been bridged to HTX with PGE-1 (8+/-1 mg/kg/min, 97+/-75.6 days) and compared with 14 hearts who did not receive PGE-1 prior to HTX. In three sectional areas obtained from the left ventricular wall CD34, von Willebrand factor (vWf), nuclear Ki67 (MIB-1), and VEGF were quantified by immunohistochemistry to estimate capillary density and endothelial cell proliferation. Additionally, to investigate a possible angiogenic effect of PGE-1 in vitro, cultured human coronary artery smooth muscle cells (HCASMCs) were treated with PGE-1.PGE-1-treated patients had significantly more CD34- and vWf-positive cells in the subepicardium (both P<0.01), myocardium (both P<0.0001) and subendocardium (P<0.01 and P<0.001) as compared to the nonPGE-1 group. Proliferative endothelial activity expressed by the presence of MIB-1- and VEGF-positive cells (both P<0.0001 in all layers) was increased more than twofold. Addition of PGE-1 to HCASMCs in cell culture resulted in a significant increase in VEGF production (164.0+/-19.7 pg/10(5) cells/24 h, P<0.005) as compared to the control cell line (66.6+/-8.7 pg/10(5) cells/24 h, P<0.005).Our data demonstrate that PGE-1 is a potent stimulator of angiogenesis via upregulation of VEGF expression. The induction of therapeutic angiogenesis in patients with severe ICMP might explain the favorable clinical outcome in PGE-1 treated patients until HTX.
Trimetazidine: a novel protective role via maintenance of Na+/K+-ATPase activity?
Authors: Heather R. Cross
Journal: Cardiovascular Research (2000)

See article by El Banani et al. [31] (pages 688–696) in this issue. 

Trimetazidine (1-[2,3,4-trimethoxybenzyl]-piperazine; TMZ) is a piperazine compound that has been demonstrated to protect against ischaemic injury in a variety of tissues [1–4]. As a cardiovascular therapeutic agent, TMZ is protective during coronary artery bypass graft surgery [5] and catheter angioplasty [6], has been effective in the treatment of angina [7,8] and reduces infarct size when given before thrombolysis in patients with anterior myocardial infarction [9]. There have been insights into some of the molecular mechanisms of action of TMZ, however, new mechanisms continue to be discovered [10–12]. The best known action of TMZ is inhibition of the β-oxidation pathway of fatty acid metabolism [13]. Inhibition of the β-oxidation pathway during ischaemia and reperfusion concomitantly increases glucose oxidation [13]. Protection from ischaemic injury by TMZ is hypothesized to be due to the increase in glucose oxidation leading to lower rates of glycolysis and less H+ production [14–17]. Increased fatty acid oxidation and glycolysis do result in greater H+ production [18,19] and ischaemic intracellular pH changes have been observed in TMZ-treated hearts [14]. The detrimental effect of glycolytic H+ production in the ischaemic myocardium is thought to be due to increased Na+/H+ exchange activity [20–22]. H+ activate the Na+/H+ exchanger … 

* Tel.: +1-919-541-5411; fax: +1-919-541-3385 laszlo.deszi{at}richter.hu
Renal Function as a Predictor of Outcome in a Broad Spectrum of Patients With Heart Failure
Authors: Hans L. Hillege, Dorothea Nitsch, Marc A. Pfeffer, Karl Swedberg, John J.V. McMurray, Salim Yusuf, Christopher B. Granger, Eric L. Michelson, Jan Östergren, Jan Hein Cornel, Dick de Zeeuw, Stuart Pocock, Dirk J. van Veldhuisen
Journal: Circulation (2006)

Background— Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. Methods and Results— The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (≤40%) or preserved LVEF (&gt;40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 μmol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR &lt;60 mL/min per 1.73 m 2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m 2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m 2 and 1.86 for &lt;45 mL/min per 1.73 m 2 for the primary outcome, both P &lt;0.001, and hazard ratio of 1.50, P =0.006, and 1.91, P =0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. Conclusions— Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.
Alzheimer’s disease: the new promise
Authors: Warren J. Strittmatter
Journal: Journal of Clinical Investigation (2012)

Clinical vignette: A 59-year-old aeronautical engineer is referred to you for evaluation because of increasing difficulty with job performance over the last several years. Difficulty managing home finances, getting lost driving, and forgetting appointments have become common. Previously outgoing, he is now depressed and irritable. After appropriate neurologic assessment, including brain imaging and metabolic studies, you make the diagnosis of Alzheimer's dementia and are asked by the patient's family what treatment is available.
Synovial fluid concentration of five different cytokines in rheumatic diseases.
Authors: C.I Westacott, J.T Whicher, I.C Barnes, D Thompson, A.J Swan, P.A Dieppe
Journal: Annals of the Rheumatic Diseases (1990)

Interleukin-1 beta, interleukin-2, tumour necrosis factor alpha, and the interferons, alfa and gamma, were measured concurrently in synovial fluid samples from 68 patients with rheumatic diseases. Mean interleukin-1 beta concentrations (130.3 (SD 22) pg/ml) were higher in synovial fluids from patients with rheumatoid arthritis (RA) than in those from patients with osteoarthritis (27.8(4.5)pg/ml), while measurements in synovial fluids from patients with seronegative spondarthritis were intermediate (72.7 (32) pg/ml). Interleukin-2 and tumour necrosis factor alpha concentrations were lower in the inflammatory arthropathies (RA: 4.5 (0.6) U/ml, 0.39 (0.04) ng/ml; seronegative spondarthritis: 3.1 (0.3) U/ml, 0.33 (0.03) ng/ml respectively) than those in patients with osteoarthritis (5.2 (0.6) U/ml; 0.05 (0.04) ng/ml). Interleukin-2 and tumour necrosis factor alpha concentrations correlated in all groups (r = 0.7), as did the interferons alfa and gamma (r = 0.7). There was no relation between interleukin-1 beta and either interleukin-2 or tumour necrosis factor alpha, or between the interferons and any other cytokine. Several distinct cytokine patterns were noted. Synovial fluids from two non-arthritic subjects were also examined: interleukin-1 beta concentrations were low, but concentrations of the other cytokines were higher than those seen in most arthritic fluids.
Electroresponsive Polymer–Carbon Nanotube Hydrogel Hybrids for Pulsatile Drug Delivery In Vivo
Authors: Ania Servant, Laura Methven, Rhodri P. Williams, Kostas Kostarelos
Journal: Advanced Healthcare Materials (2012)

Drug release triggered by an external non-invasive stimulus is of great interest for the development of new drug delivery systems. The preparation of an electroresponsive multiwalled carbon nanotube/poly(methylacrylic acid) (MWNT/PMAA)-based hybrid material is reported. The hydrogel hybrids achieve a controlled drug release upon the ON/OFF application of an electric field, giving rise to in vitro and in vivo pulsatile release profiles. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Mortality Risk Stratification in Chronic Kidney Disease
Authors: Ann M. O’Hare, Daniel Bertenthal, Kenneth E. Covinsky, C. Seth Landefeld, Saunak Sen, Kala Mehta, Michael A. Steinman, Ann Borzecki, Louise C. Walter
Journal: Journal of the American Society of Nephrology (2006)

Current National Kidney Foundation Kidney Disease Outcomes Quality Initiative staging criteria for chronic kidney disease (CKD) are intended to apply to all age groups. However, it is unclear whether different levels of estimated GFR (eGFR) have the same prognostic significance in older and younger patients. The study cohort was composed of Department of Veterans Affairs (VA) patients who were aged 18 to 100 yr and had at least one outpatient serum creatinine measurement between October 1, 2001, and September 30, 2002 (n = 2583,911). Patients with ESRD were excluded. GFR was estimated using the Modification of Diet in Renal Disease equation using each patient's first outpatient creatinine measurement during the study period. The association of eGFR with survival was measured by age group. Twenty percent of cohort patients had an eGFR <60 ml/min per 1.73 m2, ranging from 3% among 18- to 44-yr-olds to as high as 49% among 85- to 100-yr-olds. Fifty-two percent (n = 266,421) of cohort patients with an eGFR <60 ml/min per 1.73 m2 had "very" moderate reductions in eGFR into the 50- to 59-ml/min per 1.73 m2 range. The association of eGFR with mortality was weaker in the elderly than in younger age groups: Whereas severe reductions in eGFR were associated with an increased risk for death in all age groups, "very" moderate reductions in eGFR (50 to 59 ml/min per 1.73 m2) were associated with an increased adjusted risk for death only among patients who were younger than 65 yr. Age-related attenuation of the association of eGFR with mortality was also present among women and black patients. In the clinical setting, mortality risk stratification in elderly patients should not be based on the same eGFR cut points as for younger age groups and would benefit from finer categorization of the 30- to 59-ml/min per 1.73 m2 eGFR group.
Benign Calcified Epithelioma
Authors: J. Ll. Temple
Journal: BMJ (1951)

Since Malherbe (1880) first gave an account of a circum- scribed calcified lesion Qf the skin and named it "6pith,lioma calcifie " a number of papers have been published on this interesting condition.The more use- ful in the English language are Ch'in's (1933) compre- hensive review of the world literature, and papers by COtd (1936), Highman and Ogden (1944), and King (1947),