tbuckley/cabot-search huggingface dataset:
Angiotensin II, Focal Adhesion Kinase, and PRX1 Enhance Smooth Muscle Expression of Lipoma Preferred Partner and its Newly Identified Binding Partner Palladin to Promote Cell Migration
Authors: Li Jin, Michael J. Kern, Carol A. Otey, Brian R. Wamhoff, Avril V. Somlyo
Journal: Circulation Research (2007)

Lipoma preferred partner (LPP) is a proline rich LIM domain family protein highly expressed at plasma membrane dense bodies and focal adhesions in smooth muscle cells.(1) Using the C-terminus of LPP as bait in a yeast two hybrid system, palladin, an actin-associated protein was identified. The palladin interacting region of LPP was mapped to the first and second LIM domains. The N-terminus of palladin interacted with LPP both in vitro and in vivo, but not solely through its FPLPPP and FPPPP motifs. Like LPP, palladin, is highly expressed in differentiated smooth muscle, colocalized at focal adhesions, at isolated lamellipodia and at dense bodies in smooth muscle tissue. Both LPP and palladin enhanced cell migration and spreading. LPP and palladin expression was markedly decreased, in contrast to vinculin or paxillin, in migration defective focal adhesion kinase null cells, but was restored by expression of the paired-related homeobox gene-1 protein. We have previously shown in focal adhesion kinase null cells, that tetracycline induced expression of focal adhesion kinase upregulated expression of LPP(2) and now show upregulation of palladin, and paired-related homeobox gene-1 protein. The expression of both LPP and palladin, like smooth muscle alpha-actin, was increased by angiotensin II, regulated by actin dynamics, upregulated by myocardin and expressed in the neointima of injured aorta. Overall, the data suggest that the function of LPP and palladin is context dependent, that they play a critical role in cytoskeletal remodeling, respond to signals induced by vascular injury as well as signals that induce smooth muscle cell hypertrophy, such as angiotension II.
Expression of B and T lymphocyte attenuator (BTLA) in macrophages contributes to the fulminant hepatitis caused by murine hepatitis virus strain-3
Authors: Chengying Yang, Yongwen Chen, Guoning Guo, Hong Li, Dayan Cao, Huan Xu, Sheng Guo, Lei Fei, Weiming Yan, Qing Ning, Lixin Zheng, Yuzhang Wu
Journal: Gut (2012)

<h3>Objectives</h3> Fulminant viral hepatitis (FH) remains a serious clinical problem for which the underlying pathogenesis remains unclear. The B and T lymphocyte attenuator (BTLA) is an immunoglobulin-domain-containing protein that has the capacity to maintain peripheral tolerance and limit immunopathological damage during immune responses. However, its precise role in FH has yet to be investigated. <h3>Design</h3> BTLA-deficient (BTLA<sup>−/−</sup>) mice and their wild-type littermates were infected with murine hepatitis virus strain-3 (MHV-3), and the levels of tissue damage, cell apoptosis, serum liver enzymes, fibrinogen-like protein 2 (FGL2) and cytokine production were measured and compared. Survival rate was studied after MHV-3 infection with or without adoptive transferring macrophages. <h3>Results</h3> FGL2 production, liver and spleen damage, and mortality were significantly reduced in BTLA<sup>−/−</sup> mice infected with MHV-3. This effect is due to rapid, TRAIL (TNF-related apoptosis-inducing ligand)-dependent apoptosis of MHV-3-infected macrophages in BTLA<sup>−/−</sup> mice. The early loss of macrophages resulted in reduced pathogenic tumour necrosis factor α (TNFα) and FGL2 levels and lower viral titres. The importance of TNFα in MHV-3-induced pathology was demonstrated by increased mortality in TNFα-treated MHV-3-infected BTLA<sup>−/−</sup> mice, whereas TNFα<sup>−/−</sup> mice were resistant to the infection. Moreover, adoptively transferring macrophages to BTLA<sup>−/−</sup> mice caused sensitisation, whereas blocking BTLA protected wild-type mice from virus-induced FH mortality. <h3>Conclusions</h3> BTLA promotes the pathogenesis of virus-induced FH by enhancing macrophage viability and function. Targeting BTLA may be a novel strategy for the treatment of FH.
Maintenance of Long-Term Clinical Benefit With Sirolimus-Eluting Coronary Stents
Authors: Jean Fajadet, Marie-Claude Morice, Christoph Bode, Paul Barragan, Patrick W. Serruys, William Wijns, Constantino R. Constantini, Jean-Léon Guermonprez, Hélène Eltchaninoff, Didier Blanchard, Antonio Bartorelli, Gert-Jan Laarman, MarcoAntonio Perin, J. Eduardo Sousa, Gerhard Schuler, Ferenc Molnar, Giulio Guagliumi, Antonio Colombo, Ernesto Ban Hayashi, Egon Wülfert
Journal: Circulation (2005)

The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term.This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months.Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation.
Activation of CD4+ T cells in the presence of a nondepleting monoclonal antibody to CD4 induces a Th2-type response in vitro.
Authors: P Stumbles, D Mason
Journal: The Journal of Experimental Medicine (1995)

In vitro experiments using purified rat CD4+ T cells in primary and secondary mixed leukocyte cultures (MLC) have been carried out to explore the mechanism of inhibition of cell-mediated autoimmune disease in the rat by a nondepleting monoclonal antibody (mAb) to CD4. Previous work has shown that W3/25, a mouse anti-rat CD4 mAb of immunoglobulin G1 isotype, completely prevents the development of the paralysis associated with experimental allergic encephalomyelitis (EAE) in Lewis rats, but does so without eliminating the encephalitogenic T cells. The in vitro experiments described in this study have shown that when CD4+ T cells were activated in the presence of the anti-CD4 mAb in a primary MLC, the synthesis of interferon (IFN) gamma, but not interleukin (IL) 2, was completely inhibited. After secondary stimulation, now in the absence of the mAb, the synthesis of IL-4 and IL-13 mRNA was greatly enhanced compared with that observed from CD4+ T cells derived from primary cultures in which the mAb was omitted. As IL-4 and IL-13 are known to antagonize cell-mediated immune reactions, and as EAE is cell-mediated disease, the data suggest that the W3/25 mAb controls EAE by modifying the cytokine repertoire of T cells that respond to the encephalitogen. The capacity for the mAb to suppress IFN-gamma synthesis provides, in part, an explanation for this change in cytokine production. These findings are discussed in terms of what is known of the factors that determine which cytokine genes are expressed on T cell activation. Possible implications for the evolution of T cell responses in human immunodeficiency virus infection are also discussed.
Fibronectin tetrapeptide is target for syphilis spirochete cytadherence.
Authors: D D Thomas, J B Baseman, J F Alderete
Journal: The Journal of Experimental Medicine (1985)

The syphilis bacterium, Treponema pallidum, parasitizes host cells through recognition of fibronectin (Fn) on cell surfaces. The active site of the Fn molecule has been identified as a four-amino acid sequence, arg-gly-asp-ser (RGDS), located on each monomer of the cell-binding domain. The synthetic heptapeptide gly-arg-gly-asp-ser-pro-cys (GRGDSPC), with the active site sequence RGDS, specifically competed with 125I-labeled cell-binding domain acquisition by T. pallidum. Additionally, the same heptapeptide with the RGDS sequence diminished treponemal attachment to HEp-2 and HT1080 cell monolayers. Related heptapeptides altered in one key amino acid within the RGDS sequence failed to inhibit Fn cell-binding domain acquisition or parasitism of host cells by T. pallidum. The data support the view that T. pallidum cytadherence of host cells is through recognition of the RGDS sequence also important for eukaryotic cell-Fn binding.
Rituximab as First-Line and Maintenance Therapy for Patients With Indolent Non-Hodgkin’s Lymphoma
Authors: John D. Hainsworth, Sharlene Litchy, Howard A. Burris, Daniel C. Scullin, Steven W. Corso, Denise A. Yardley, Lisa Morrissey, F. Anthony Greco
Journal: Journal of Clinical Oncology (2002)

To evaluate response to single-agent rituximab in patients with indolent non-Hodgkin's lymphoma (NHL) and no previous systemic therapy, and the feasibility, toxicity, and efficacy of maintenance rituximab, administered at 6-month intervals, in patients with objective response or stable disease after first-line rituximab therapy.Patients with indolent NHL (follicular or small lymphocytic subtypes) previously untreated with systemic therapy received rituximab 375 mg/m(2) intravenously weekly for 4 weeks. Patients were restaged at week 6 for response; those with objective response or stable disease received maintenance rituximab courses (identical dose and schedule) at 6-month intervals. Maintenance was continued for a maximum of four rituximab courses or until progression. Between March 1998 and May 1999, 62 patients were entered onto this trial; minimum follow-up was 24 months.Sixty patients (97%) completed the first 4-week course of rituximab and were assessable for response. All have now completed rituximab therapy; 36 (58%) received four courses at 6-month intervals. The objective response rate at 6 weeks was 47%; 45% of patients had stable disease. With continued maintenance, final response rate increased to 73%, with 37% complete responses. Response was similar in patients with follicular versus small lymphocytic subtypes (76% v 70%, respectively). Median actuarial progression-free survival was 34 months. Two patients experienced grade 3/4 toxicity with the first dose; one patient was removed from treatment. No cumulative or additional toxicities were seen with maintenance courses.Rituximab is highly active and extremely well tolerated as first-line single-agent therapy for indolent NHL. First-line treatment with scheduled maintenance at 6-month intervals produces high overall and complete response rates and a longer progression-free survival (34 months) than has been reported with a standard 4-week treatment.
An Official American Thoracic Society/European Respiratory Society Statement: The Role of the Pulmonologist in the Diagnosis and Management of Lung Cancer
Authors: Mina Gaga, Charles A. Powell, Dean E. Schraufnagel, Nicolas Schönfeld, Klaus Rabe, Nicholas S. Hill, Jean-Paul Sculier
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Section:ChooseTop of pageAbstract <<ContentsExecutive SummaryIntroductionMethodsEpidemiology, Risk Factor...Early and Specific Diagno...Evaluation, Staging, and ...Importance of High-Volume...Importance of ResearchConclusionsReferencesCITING ARTICLES
Increased transendothelial migration of scleroderma lymphocytes
Authors: G H Stummvoll
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> CD4+ T lymphocytes play an important part in the pathogenesis of scleroderma (systemic sclerosis, SSc) and predominate in perivascular SSc skin lesions. Both soluble and membrane bound adhesion molecules are overexpressed in SSc, possibly influencing lymphocyte/endothelial cell (EC) contact. <b>Objective:</b> To assess the transendothelial migration capacity of peripheral lymphocytes in vitro. <b>Patients and methods:</b> Collagen was covered with human umbilical vein endothelial cells (HUVEC), and peripheral blood mononuclear cells (PBMC) of patients and matched healthy controls (HC) were added in parallel experiments. Before and after fractionated harvest of non-adherent, bound, and migrated lymphocytes, the CD4/CD8 ratio and the lymphocytic expression of activation markers and adhesion molecules were analysed by fluorocytometry. <b>Results:</b> 13 (SD 12)% of the SSc PBMC migrated compared with only 5 (5)% HC PBMC (p&lt;0.0002); this increase was primarily due to the migration of CD3+ T lymphocytes and mainly to a larger proportion of CD4+ cells within this CD3+ fraction (71 (SD 14)% for SSc <i>v</i> 56 (14)% for HC, p&lt;0.03), leading to an increased CD4/CD8 ratio among migrated SSc lymphocytes in comparison with controls (3.3 (1.5) <i>v</i> 1.62 (0.93), p&lt;0.006). Among migrated SSc CD4+ T lymphocytes, the frequency of HLA-DR+ cells was increased; migrated lymphocytes highly expressed the adhesion molecules CD11a, CD49d, CD29, and CD44. <b>Conclusion:</b> Transendothelial migration of CD4+ T lymphocytes is enhanced in SSc, and migrating cells exhibit an activated phenotype. The data suggest that activated CD3+CD4+ lymphocytes as found in SSc peripheral blood are prone to transvascular migration, thus contributing to the formation of typical perivascular lymphocytic infiltrates.
Distribution of HbA1c Levels For Children and Young Adults in the U.S.
Authors: Jinan B. Saaddine, Anne Fagot-Campagna, Deborah Rolka, K.M. Venkat Narayan, Linda Geiss, Mark Eberhardt, Katherine M. Flegal
Journal: Diabetes Care (2002)

OBJECTIVE—To describe the distribution of HbA1c levels among children and young adults in the U.S. and to evaluate the effects of age, sex, race/ethnicity, socioeconomic status, parental history of diabetes, overweight, and serum glucose on HbA1c levels. RESEARCH DESIGN AND METHODS—We analyzed HbA1c data from the Third National Health and Nutrition Examination Survey, 1988–1994, for 7,968 participants aged 5–24 years who had not been treated for diabetes. After adjusting for the complex sample design, we compared the distributions of HbA1c in subgroups and developed multiple linear regression models to examine factors associated with HbA1c. RESULTS—Mean HbA1c level was 4.99% (SD 0.50%) and varied from 4.93% (95% CI ±0.04) in non-Hispanic whites to 5.05% (±0.02) in Mexican-Americans to 5.17% (±0.02) in non-Hispanic blacks. There were very small differences among subgroups. Within each age- group, among men and women, among overweight and nonoverweight subjects, and at any level of education, mean HbA1c levels were higher in non-Hispanic blacks than in non-Hispanic whites. After adjusting for confounders, HbA1c levels for non-Hispanic blacks (5.15%, 95% CI ±0.04) and Mexican-Americans (5.01%, ±0.04) were higher than those for non-Hispanic whites (4.93%, ±0.04). CONCLUSIONS—These data provide national reference levels for HbA1c distributions among Americans aged 5–24 years and show statistically significant racial/ethnic differences in HbA1c levels that are not completely explained by demographic and health-related variables.
Changed phagocytic activity and pattern of Fcγ and complement receptors on blood monocytes in sarcoidosis
Authors: Anna Dubaniewicz, Monika Wybieralska, Szymon Nowakowski, Katarzyna Rogoza, Adam Sternau, Jan Marek Slominski, Piotr Trzonkowski
Journal: European Respiratory Journal (2011)

We have recently revealed that mycobacterial heat shock proteins (Mtb-hsp), involved in forming of immune complexes (CIs), can induce immune response in sarcoidosis (SA). The complexemia may result from inappropriate phagocytosis and clearance of CIs by monocytes, which results in persistent antigenemia and granuloma formation. It is also possible that aberrant expression of receptors for Fc fragment of immunoglobulin G (FcγR) and complement receptors (CR) on monocytes can be involved in this process.

To test this hypothesis, we have evaluated the expression of FcγRI (CD64), FcγRII (CD32), FcγRIII (CD16) and CR1 (CD35), CR3 (CD11b), CR4 (CD11c) receptors on blood CD14+ monocytes and phagocytic activity of mononuclear phagocytes in 24 patients with SA and 20 healthy volunteers using flow cytometry.

As compared to healthy controls, we found significantly increased expression of all examined FcγR (CD32, CD16, CD64) and decreased expression of CD35 and CD11c on CD14+ monocytes in SA patients. Analysis of the combined phenotypes of monocytes revealed significantly increased percentage of CD14+CD16+CD35-, CD14+CD64+CD35+, CD14+CD64+CD11b+, CD14+CD64+CD11c+ monocytes and decreased presence of CD14+CD32-CD35+, CD14+CD32-CD11b+ and CD14+CD32-CD11c+ monocytes in SA vs controls. The total number and percentage of phagocyting blood monocytes was significantly increased in SA as compared with healthy individuals.

In summary, altered expression of Fcγ and complement receptors on CD14+ monocytes and increased phagocytic activity of monocytes may be responsible for high antigen load, persistent antigenemia and complexemia in SA patients.
Chronic cough in children: bronchoalveolar lavage findings
Authors: P.S. Fitch, V. Brown, B.c Schock, R Taylor, M Ennis, M.d Shields
Journal: European Respiratory Journal (2000)

Isolated chronic cough in childhood is a common complaint. Although the symptom cough is included in the definition of clildhood asthma, there is debate as to whether the majoritv of these children have asthma. The authors studied children with isolated chronic cough looking for evidence of airway inflammation typical of asthma, with increased numbers of airway eosinophils as assessed from bronchoalveolar lavage (BAL). The investigations were carried out on 23 children (median age: 6.7 yrs; range: 1.7-12.75 yrs), attending the Royal Belfast Hospital for Sick Children for elective surgery, who also had a chronic unexplained cough. Written informed consent was obtained from the parent(s) and a nonbronchoscopic BAL was performed. BAL samples were analysed for total and differential white cell counts and also for the inflammatory mediators, eosinophil cationic protein (ECP) and histamine. Results were compared with a group of normal nonatopic children and also a group of atopic asthmatic children, who had been recruited for other studies on airway inflammation. There was a small but statistically significant increase in BAL percentage eosinophils in the children with chronic cough compared with nonasthmatic controls (0.28% versus 0.10%, p=0.03). However, the children with cough had lower percentage eosinophils than the atopic asthmatic controls (0.28% versus 0.66%, p=0.01). Three out of 23 children with chronic cough had BAL eosinophils greater than the normal upper 95% reference interval in BAL. There was a small but statistically significant increase in percentage neutrophils in the children with cough compared with the nonasthmatic controls (5.85% versus 3.21%, p=0.03). Four out of the 23 children had BAL neutrophils greater than the normal upper 95% reference interval in BAL. The authors conclude that only a minority of children with chronic unexplained cough have asthmatic-type airway inflammation. It is speculated that the increased percentage neutrophils in bronchoalveolar lavage from children with cough could relate to underlying persistent airways infection.
Inhibition of Restenosis With a Paclitaxel-Eluting, Polymer-Free Coronary Stent
Authors: Anthony Gershlick, Ivan De Scheerder, Bernard Chevalier, Amanda Stephens-Lloyd, Edoardo Camenzind, Christian Vrints, Nicolaus Reifart, Luc Missault, Jean-Jacques Goy, Jeffrey A. Brinker, Albert E. Raizner, Philip Urban, Alan W. Heldman
Journal: Circulation (2004)

The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis.On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.2, 0.7, 1.4, and 2.7 microg/mm2 stent surface area) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone. The primary efficacy end point was angiographic percent diameter stenosis at 6 months. At angiographic follow-up, percent diameter stenosis was 33.9+/-26.7% in controls (n=34) and 14.2+/-16.6% in the 2.7-microg/mm2 group (n=31; P=0.006). Late loss decreased from 0.73+/-0.73 to 0.11+/-0.50 mm (P=0.002). Binary restenosis (> or =50% at follow-up) decreased from 20.6% to 3.2% (P=0.056), with no significant benefit from intermediate paclitaxel doses. Freedom from major adverse cardiac events in the highest (effective) dose group was 92%, 89%, and 86% at 1, 6, and 12 months, respectively (P=NS versus control). No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only.Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent, at a dose density of 2.7 microg/mm2, reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects.
A Paclitaxel-Eluting Stent for the Prevention of Coronary Restenosis
Authors: Seung-Jung Park, Won Heum Shim, David S. Ho, Albert E. Raizner, Seong-Wook Park, Myeong-Ki Hong, Cheol Whan Lee, Donghoon Choi, Yangsoo Jang, Ricky Lam, Neil J. Weissman, Gary S. Mintz
Journal: New England Journal of Medicine (2003)

Intimal hyperplasia and resulting restenosis limit the efficacy of coronary stenting. We studied a coronary stent coated with the antiproliferative agent paclitaxel as a means of preventing restenosis.We conducted a multicenter, randomized, controlled, triple-blind study to evaluate the ability of a paclitaxel-eluting stent to inhibit restenosis. At three centers, 177 patients with discrete coronary lesions (<15 mm in length, 2.25 to 3.5 mm in diameter) underwent implantation of paclitaxel-eluting stents (low dose, 1.3 microg per square millimeter, or high dose, 3.1 microg per square millimeter) or control stents. Antiplatelet therapies included aspirin with ticlopidine (120 patients), clopidogrel (18 patients), or cilostazol (37 patients). Clinical follow-up was performed at one month and four to six months, and angiographic follow-up at four to six months.Technical success was achieved in 99 percent of the patients (176 of 177). At follow-up, the high-dose group, as compared with the control group, had significantly better results for the degree of stenosis (mean [+/-SD], 14+/-21 percent vs. 39+/-27 percent; P<0.001), late loss of luminal diameter (0.29+/-0.72 mm vs. 1.04+/-0.83 mm, P<0.001), and restenosis of more than 50 percent (4 percent vs. 27 percent, P<0.001). Intravascular ultrasound analysis demonstrated a dose-dependent reduction in the volume of intimal hyperplasia (31, 18, and 13 mm3, in the high-dose, low-dose, and control groups, respectively). There was a higher rate of major cardiac events in patients receiving cilostazol than in those receiving ticlopidine or clopidogrel. Among patients receiving ticlopidine or clopidogrel, event-free survival was 98 percent and 100 percent in the high-dose and control groups, respectively, at one month, and 96 percent in both at four to six months.Paclitaxel-eluting stents used with conventional antiplatelet therapy effectively inhibit restenosis and neointimal hyperplasia, with a safety profile similar to that of standard stents.