tbuckley/cabot-search huggingface dataset:
T-lymphocyte cytokine profiles in Compositae airborne dermatitis
Authors: None Stingeni, None Agea, None Lisi, None Spinozzi
Journal: British Journal of Dermatology (1999)

Compositae airborne dermatitis is a well‐recognized disorder characterized by erythematosquamous lesions and papules on light‐exposed areas. The presence of positive patch test reactions and the absence of specific serum IgE suggest delayed‐type hypersensitivity, the murine model of which is characterized by a Th1 cytokine production profile [high amounts of interferon (IFN)‐γ and interleukin (IL)‐2; little or no IL‐4 and IL‐5]. The aim of this study was to evaluate the cytokine profile of T‐cell lines and T‐cell clones from peripheral blood in a 38‐year‐old non‐atopic male woodcutter affected by seasonal airborne contact dermatitis. The patient showed positive patch test reactions to several Compositae extracts (Achillea millefolium, Chamomilla recutita, Tanacetum parthenium, T. vulgare) and sesquiterpene lactone mix. On prick testing with Compositae and other plants, serum‐specific IgE levels and phototesting were negative or normal. Allergen‐specific T‐cell lines produced with Compositae extracts showed a good in vitro cell proliferation only to C. recutita extract. Serial cloning performed using the C. recutita‐specific T‐cell lines revealed an αβ+CD4+ phenotype with high amounts of IFN‐γ and IL‐4 in T‐cell clones. Thus, these cells expressed a preferential Th0 phenotype. These data suggest that in addition to IFN‐γ, other T‐cell derived cytokines, such as IL‐4, may play a part in the immunopathogenesis of contact dermatitis.
Autologous Myoblast Transplantation for Chronic Ischemic Mitral Regurgitation
Authors: Emmanuel Messas, Alain Bel, Miguel Cortes Morichetti, Claire Carrion, Marc D. Handschumacher, Séverine Peyrard, Jean Thomas Vilquin, Michel Desnos, Patrice Bruneval, Alain Carpentier, Philippe Menasché, Robert A. Levine, Albert A. Hagège
Journal: Journal of the American College of Cardiology (2006)
Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall.
Authors: A J Naftilan, W M Zuo, J Inglefinger, T J Ryan, R E Pratt, V J Dzau
Journal: Journal of Clinical Investigation (1991)

Recent data demonstrate the existence of a vascular renin angiotensin system. In this study we examine the localization of angiotensinogen mRNA in the blood vessel wall of two rat strains, the Wistar and Wistar Kyoto (WKY), as well as the regulation of vascular angiotensinogen mRNA expression by dietary sodium. Northern blot analysis and in situ hybridization histochemistry demonstrate that in both strains angiotensinogen mRNA is detected in the aortic medial smooth muscle layer as well as the periaortic fat. In WKY rats fed a 1.6% sodium diet, angiotensinogen mRNA concentration is 2.6-fold higher in the periaortic fat than in the smooth muscle, as analyzed by quantitative slot blot hybridization. Angiotensinogen mRNA expression in the medial smooth muscle layer is sodium regulated. After 5 d of a low (0.02%) sodium diet, smooth muscle angiotensinogen mRNA levels increase 3.2-fold (P less than 0.005) as compared with the 1.6% sodium diet. In contrast, angiotensinogen mRNA level in the periaortic fat is not influenced by sodium diet. In summary, our data demonstrate regional (smooth muscle vs. periaortic fat) differential regulation of angiotensinogen mRNA levels in the blood vessel wall by sodium. This regional differential regulation by sodium may have important physiological implications.
Studies on synovial fluid lymphocytes in rheumatoid arthritis.
Authors: P.J Sheldon, M Papamichail, E.J Holborow
Journal: Annals of the Rheumatic Diseases (1974)

Rheumatoid arthritis (RA) is a systemic disease in which the major lesion is a chronic inflammation of the synovial membrane, with a characteristic though not pathognomonic histology.Rheumatoid activity in the synovial membrane may lead to the production of an increased amount of synovial fluid which in active cases is often richly cellular with polymorphs, monocyte-like cells, or lymphocytes predominating.The aetiology of the condition is unknown but the presence in many cases of serum rheumatoid factor, and often of increased circulating immunoglobulin and other auto-antibodies, has for long suggested involvement of the immune system.Lymphocytes are known to be closely involved in immune responses leading to graft or tumour rejection, antibody production, and delayed hypersensitivity, and it seemed prudent therefore to study their characteris- tics in the peripheral blood of controls and RA cases and in synovial effusions occurring in patients with RA, seropositive or negative.Lymphocytes may be identified as thymic-derived (T) or bone marrow-derived (B) cells.Both are involved as effectors of immune responses, though the former are especially concerned with the expression of cell mediated immunity, i.e. delayed hypersensitivity, and the latter as the precursors of plasma cells producing circulating antibodies.T cells are also important as helper cells in the response to antigensthough co-operation with other cells in all these immune processes is likely.Human T cells do not differ morphologically from B cells by ordinary light microscopy.Electron microscopy reveals differences in surface confor- mation (Polliack,
A role for neurotransmission and neurodevelopment in attention-deficit/hyperactivity disorder
Authors: Tatiana Roman, Luis A Rohde, Mara H Hutz
Journal: Genome Medicine (2009)

Attention-deficit/hyperactivity disorder (ADHD) has a moderate to high genetic component, probably due to many genes with small effects. Several susceptibility genes have been suggested on the basis of hypotheses that catecholaminergic pathways in the brain are responsible for ADHD. However, many negative association findings have been reported, indicating a limited success for investigations using this approach. The results from genome-wide association studies have suggested that genes related to general brain functions rather than specific aspects of the disorder may contribute to its development. Plausible biological hypotheses linked to neurotransmission and neurodevelopment in general and common to different psychiatric conditions need to be considered when defining candidate genes for ADHD association studies.
Transdominant ΔTAp73 Isoforms Are Frequently Up-regulated in Ovarian Cancer. Evidence for Their Role as Epigenetic p53 Inhibitors <b> <i>in Vivo</i> </b>
Authors: Nicole Concin, Kirsten Becker, Neda Slade, Susan Erster, Elizabeth Mueller-Holzner, Hanno Ulmer, Guenter Daxenbichler, Alain Zeimet, Robert Zeillinger, Christian Marth, Ute M. Moll
Journal: Cancer Research (2004)

Abstract Despite strong homology, the roles of TP53 and TP73 in tumorigenesis seem to be fundamentally different. In contrast to TP53, tumor-associated overexpression of TP73 in many different cancers, combined with virtual absence of inactivating mutations and lack of a cancer phenotype in the TP73 null mouse are inconsistent with a suppressor function but instead support an oncogenic function. The discovery of NH2-terminally truncated p73 isoforms, collectively called ΔTAp73, is now the focus of intense interest because they act as potent transdominant inihibitors of wild-type p53 and transactivation-competent TAp73. Therefore, establishing deregulated ΔTAp73 expression in tumors could be the crucial link to decipher which of the two opposing roles of this bipolar gene is the biologically relevant one. This study is the largest to date and encompasses 100 ovarian carcinomas with complete expression profile of all NH2-terminal isoforms, discriminating between TAp73 and ΔTAp73 (ΔNp73, ΔN′p73, Ex2p73, and Ex2/3p73) by isoform-specific real-time reverse transcription-PCR. We find that the set of NH2-terminal p73 isoforms distinguishes ovarian cancer patients from healthy controls and thus is a molecular marker for this diagnosis. Ovarian cancers strongly and almost universally overexpress ΔN′p73 compared with normal tissues (95% of cancers). About one-third of tumors also exhibit concomitant up-regulation of the antagonistic TAp73, whereas only a small subgroup of tumors overexpress ΔNp73. Thus, deregulation of the E2F1-responsive P1 promoter, rather than the alternate P2 promoter, is mainly responsible for the production of transdominant p53/TAp73 antagonists in ovarian cancer. Tumor stage, grade, presence of metastases, p53 status, and residual disease after resection are significant prognostic markers for overall and recurrence-free survival. A trend is found for better overall survival in patients with low expression of ΔN′p73/ΔNp73, compared with patients with high expression. A strong correlation between deregulated ΔTAp73 and p53 status exists. p53 wild-type cancers exhibit significantly higher deregulation of ΔN′p73, ΔNp73, and Ex2/3p73 than p53 mutant cancers. This data strongly supports the hypothesis that overexpression of transdominant p73 isoforms can function as epigenetic inhibitors of p53 in vivo, thereby alleviating selection pressure for p53 mutations in tumors.
No Excess Prior Cancer in Patients with Uveal Melanoma
Authors: Elizabeth A. Holly, Diana A. Aston, David K. Ahn, Jennifer J. Kristiansen, Devron H. Char
Journal: Ophthalmology (1991)

To determine whether there were more prior cancers in uveal melanoma patients than in a geographically matched control group, the authors compared the history of prior cancer in 407 uveal melanoma patients who lived in the western United States with that of 870 control subjects. Control subjects were selected by random digit dial and frequency-matched for age at diagnosis of patient, race, and sex. Fifty-one (12.5%) patients and 86 (9.9%) control subjects reported skin cancers whereas 25 (6.1 %) patients and 47 (5.4%) control subjects reported other cancers. No statistically significant elevated estimates of relative risk (RR) were found for uveal melanoma with history of skin cancer in either men (RR = 1.4, 95% confidence interval (CI) = 0.87-2.3) or women (RR = 1.1, 95% CI = 0.58-2.0), or with history of other prior cancer in either sex (men, RR = 1.0, 95% CI = 0.42-2.2; women, RR = 1.1, 95% CI = 0.552.1). Data from this study do not support an association between prior cancer and increased risk of uveal melanoma.
Airway epithelial inflammatory responses and clinical parameters in COPD
Authors: I.S. Patel, N.J. Roberts, S.J. Lloyd-Owen, R.J. Sapsford, J.A. Wedzicha
Journal: European Respiratory Journal (2003)

This study examined inflammatory responses from primary cultured human bronchial epithelial cells in chronic obstructive pulmonary disease (COPD) and the clinical factors modulating them. Epithelial cells from bronchoscopic biopsies from 14 patients with COPD ((mean±sd) age 74.6±5.7 yrs, forced expiratory volume in one second (FEV 1 ) 1.21±0.36 L, FEV 1 % predicted 51.1±15.8%, 51.5±24.0 pack-yrs of smoking, inhaled steroid dosage 1237.5±671.0 µg·day −1 , Medical Research Council (MRC) dyspnoea score 3.18±1.33) and eight current/exsmokers with normal pulmonary function (age 60.4±13.5 yrs, FEV 1 2.66±1.27 L, FEV 1 % pred 89.6±17.7%, 49±44 pack-yrs of smoking, MRC dyspnoea score 1±0) were grown in primary culture and exposed to 50 ng·mL −1 tumour necrosis factor‐α. Stimulated COPD cells produced significantly more interleukin (IL)‐6 at 24 and 48 h, and IL‐8 at 6 and 24 h than unstimulated COPD cells. This response was not seen in cells from current/exsmokers. IL‐6 and IL‐8 production was lower in COPD patients taking inhaled steroids. Following an inflammatory stimulus, bronchial epithelial cells in chronic obstructive pulmonary disease show a significant cytokine response not seen in smokers with normal pulmonary function and this may be modified by inhaled steroid therapy.
The Lupus-Related Lmb3 Locus Contains a Disease-Suppressing Coronin-1A Gene Mutation
Authors: M. Katarina Haraldsson, Christine A. Louis-Dit-Sully, Brian R. Lawson, Gabriel Sternik, Marie-Laure Santiago-Raber, Nicholas R.J. Gascoigne, Argyrios N. Theofilopoulos, Dwight H. Kono
Journal: Immunity (2008)
The Antidepressant Sertraline Inhibits Translation Initiation by Curtailing Mammalian Target of Rapamycin Signaling
Authors: Chen-Ju Lin, Francis Robert, Rami Sukarieh, Stephen Michnick, Jerry Pelletier
Journal: Cancer Research (2010)

Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner.
The Immunopathogenesis of Rheumatoid Arthritis
Authors: John B. Imboden
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Rheumatoid arthritis is a chronic inflammatory polyarthritis whose etiology remains uncertain. Recently we have learned that autoimmunity to citrullinated protein antigens has specificity for rheumatoid arthritis and defines a clinically and genetically distinct form of the disease. Multiple genes contribute to disease susceptibility, with the HLA locus accounting for 30% to 50% of overall genetic risk. Five risk loci have been identified and validated: HLA-DRB1, PTPN22, STAT4, a region in 6q23, and the TRAF1/C5 locus. Also, there is renewed interest in the contribution of T cells to ongoing inflammation in rheumatoid arthritis. Autoantibodies to citrullinated protein epitopes are specific for rheumatoid arthritis, are associated with a more aggressive disease course, and are pathogenic in an animal model of autoimmune arthritis. There is a strong association between shared-epitope-expressing HLA-DRB1 alleles and the development of rheumatoid arthritis associated with autoimmunity to citrullinated protein antigens.
Importance of 5α-Reductase Gene Polymorphisms on Circulating and Intraprostatic Androgens in Prostate Cancer
Authors: Éric Lévesque, Isabelle Laverdière, Louis Lacombe, Patrick Caron, Mélanie Rouleau, Véronique Turcotte, Bernard Têtu, Yves Fradet, Chantal Guillemette
Journal: Clinical Cancer Research (2013)

Polymorphisms in the genes SRD5A1 and SRD5A2 encoding androgen biosynthetic 5α-reductase enzymes have been associated with an altered risk of biochemical recurrence after radical prostatectomy in localized prostate cancer.To gain potential insights into SRD5A biologic effects, we examined the relationship between SRD5A prognostic markers and endogenous sex-steroid levels measured by mass spectrometry in plasma samples and corresponding prostatic tissues of patients with prostate cancer.We report that five of the seven SRD5A markers differentially affect sex-steroid profiles of dihydrotestosterone and its metabolites in both the circulation and prostatic tissues of patients with prostate cancer. Remarkably, a 32% increase in intraprostatic testosterone levels was observed in the presence of the high-risk SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated predominantly with circulating levels of inactive glucuronides. Indeed, the rs12470143 SRD5A2 protective allele was associated with high circulating androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) levels as opposed to lower levels of both 3α-diol-17G and androsterone-glucuronide observed with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349 (V89L) risk variants, in strong linkage disequilibrium, were associated with higher circulating levels of 3α-diol-3G. The SRD5A2 rs676033 variant further correlated with enhanced intraprostatic exposure to 5α-reduced steroids (dihydrotestosterone and its metabolite 3β-diol). Similarly, the SRD5A1 rs166050C risk variant was associated with greater prostatic exposure to androsterone, whereas no association was noted with circulating steroids.Our data support the association of 5α-reductase germline polymorphisms with the hormonal milieu in patients with prostate cancer. Further studies are needed to evaluate if these variants influence 5α-reductase inhibitor efficacy.
Relationship between Frequency Dependence of Lung Compliance and Distribution of Ventilation
Authors: Adam Wanner, Stephen Zarzecki, Neal Atkins, Angel Zapata, Marvin A. Sackner
Journal: Journal of Clinical Investigation (1974)

The previously demonstrated empirical association between frequency dependence of lung compliance and distribution of ventilation, the latter determined by the N(2) washout technique, was confirmed by establishing a mathematical link between the two tests. By assuming a two-compartment system with known compliances and making corrections for Pendelluft and common dead space mixing effects, the ratio of dynamic to static compliance (C(dyn)/C(st)) for any respiratory frequency can be calculated from the compartmental analysis of the N(2) washout at a single respiratory frequency. By using these equations, a good correlation was found between calculated and measured C(dyn)/C(st) in dogs with artificially induced bronchial obstruction and in young smokers or young nonsmokers after carbachol inhalation. A two-compartment N(2) washout was demonstrated in 10 young healthy smokers at one or two respiratory frequencies whereas all 10 normal controls showed a single exponential curve. These findings indicate that the non-invasive N(2) washout test is capable of predicting C(dyn)/C(st) and at the same time gives a direct measure of gas distribution. Further, it appears to be a highly sensitive method for the detection of "small airway disease."
Dectin-1 Is A Major β-Glucan Receptor On Macrophages
Authors: Gordon D. Brown, Philip R. Taylor, Delyth M. Reid, Janet A. Willment, David L. Williams, Luisa Martinez-Pomares, Simon Y.C. Wong, Siamon Gordon
Journal: The Journal of Experimental Medicine (2002)

Zymosan is a β-glucan– and mannan-rich particle that is widely used as a cellular activator for examining the numerous responses effected by phagocytes. The macrophage mannose receptor (MR) and complement receptor 3 (CR3) have historically been considered the major macrophage lectins involved in the nonopsonic recognition of these yeast-derived particles. Using specific carbohydrate inhibitors, we show that a β-glucan receptor, but not the MR, is a predominant receptor involved in this process. Furthermore, nonopsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody (mAb) against CR3, demonstrating that CR3 was not the β-glucan receptor mediating this activity. To address the role of the recently described β-glucan receptor, Dectin-1, we generated a novel anti–Dectin-1 mAb, 2A11. Using this mAb, we show here that Dectin-1 was almost exclusively responsible for the β-glucan–dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte β-glucan receptor, first described over 50 years ago, and resolves the long-standing controversy regarding the identity of this important molecule. Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of β-glucans for therapeutic drug design.
Increased β-Adrenergic Inotropy in Ventricular Myocardium From <i>Trpm4</i> <sup>−/−</sup> Mice
Authors: Ilka Mathar, Miklos Kecskes, Gerry Van der Mieren, Griet Jacobs, Juan E. Camacho Londoño, Sebastian Uhl, Veit Flockerzi, Thomas Voets, Marc Freichel, Bernd Nilius, Paul Herijgers, Rudi Vennekens
Journal: Circulation Research (2013)

The Trpm4 gene has recently been associated with several disorders, including cardiac conduction diseases and Brugada syndrome. Transient receptor potential member 4 (TRPM4) proteins constitute Ca2+ -activated, but Ca2+ -impermeable, nonselective cation channels and are expressed both in atrial and in ventricular cardiomyocytes. The physiological function of TRPM4 in the heart remains, however, incompletely understood.To establish the role of TRPM4 in cardiac muscle function.We used TRPM4 knockout mice and performed patch-clamp experiments, membrane potential measurements, microfluorometry, contractility measurements, and in vivo pressure-volume loop analysis. We demonstrate that TRPM4 proteins are functionally present in mouse ventricular myocytes and are activated on Ca2+ -induced Ca2+ release. In Trpm4(-/-) mice, cardiac muscle displays an increased β-adrenergic inotropic response both in vitro and in vivo. Measurements of action potential duration show a significantly decreased time for 50% and 90% repolarization in Trpm4(-/-) ventricular myocytes. We provide evidence that this change in action potential shape leads to an increased driving force for the L-type Ca2+ current during the action potential, which explains the altered contractility of the heart muscle.Our results show that functional TRPM4 proteins are novel determinants of the inotropic effect of β-adrenergic stimulation on the ventricular heart muscle.
Interleukin 21–Induced Granzyme B–Expressing B Cells Infiltrate Tumors and Regulate T Cells
Authors: Stefanie Lindner, Karen Dahlke, Kai Sontheimer, Magdalena Hagn, Christof Kaltenmeier, Thomas F.E. Barth, Thamara Beyer, Frank Reister, Dorit Fabricius, Ramin Lotfi, Oleg Lunov, G. Ulrich Nienhaus, Thomas Simmet, Rolf Kreienberg, Peter Möller, Hubert Schrezenmeier, Bernd Jahrsdörfer
Journal: Cancer Research (2013)

Abstract The pathogenic impact of tumor-infiltrating B cells is unresolved at present, however, some studies suggest that they may have immune regulatory potential. Here, we report that the microenvironment of various solid tumors includes B cells that express granzyme B (GrB, GZMB), where these B cells can be found adjacent to interleukin (IL)-21–secreting regulatory T cells (Treg) that contribute to immune tolerance of tumor antigens. Because Tregs and plasmacytoid dendritic cells are known to modulate T-effector cells by a GrB-dependent mechanism, we hypothesized that a similar process may operate to modulate regulatory B cells (Breg). IL-21 induced outgrowth of B cells expressing high levels of GrB, which thereby limited T-cell proliferation by a GrB-dependent degradation of the T-cell receptor ζ-chain. Mechanistic investigations into how IL-21 induced GrB expression in B cells to confer Breg function revealed a CD19+CD38+CD1d+IgM+CD147+ expression signature, along with expression of additional key regulatory molecules including IL-10, CD25, and indoleamine-2,3-dioxygenase. Notably, induction of GrB by IL-21 integrated signals mediated by surface immunoglobulin M (B-cell receptor) and Toll-like receptors, each of which were enhanced with expression of the B-cell marker CD5. Our findings show for the first time that IL-21 induces GrB+ human Bregs. They also establish the existence of human B cells with a regulatory phenotype in solid tumor infiltrates, where they may contribute to the suppression of antitumor immune responses. Together, these findings may stimulate novel diagnostic and cell therapeutic approaches to better manage human cancer as well as autoimmune and graft-versus-host pathologies. Cancer Res; 73(8); 2468–79. ©2013 AACR.