tbuckley/cabot-search huggingface dataset:
Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin
Authors: Shahrokh Falati, Qingde Liu, Peter Gross, Glenn Merrill-Skoloff, Janet Chou, Erik Vandendries, Alessandro Celi, Kevin Croce, Barbara C. Furie, Bruce Furie
Journal: The Journal of Experimental Medicine (2003)

Using a laser-induced endothelial injury model, we examined thrombus formation in the microcirculation of wild-type and genetically altered mice by real-time in vivo microscopy to analyze this complex physiologic process in a system that includes the vessel wall, the presence of flowing blood, and the absence of anticoagulants. We observe P-selectin expression, tissue factor accumulation, and fibrin generation after platelet localization in the developing thrombus in arterioles of wild-type mice. However, mice lacking P-selectin glycoprotein ligand 1 (PSGL-1) or P-selectin, or wild-type mice infused with blocking P-selectin antibodies, developed platelet thrombi containing minimal tissue factor and fibrin. To explore the delivery of tissue factor into a developing thrombus, we identified monocyte-derived microparticles in human platelet–poor plasma that express tissue factor, PSGL-1, and CD14. Fluorescently labeled mouse microparticles infused into a recipient mouse localized within the developing thrombus, indicating that one pathway for the initiation of blood coagulation in vivo involves the accumulation of tissue factor– and PSGL-1–containing microparticles in the platelet thrombus expressing P-selectin. These monocyte-derived microparticles bind to activated platelets in an interaction mediated by platelet P-selectin and microparticle PSGL-1. We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking.
MinK-dependent internalization of the IKs potassium channel
Authors: Xianghua Xu, Vikram A. Kanda, Eun Choi, Gianina Panaghie, Torsten K. Roepke, Stephen A. Gaeta, David J. Christini, Daniel J. Lerner, Geoffrey W. Abbott
Journal: Cardiovascular Research (2009)

KCNQ1–MinK potassium channel complexes (4α:2β stoichiometry) generate IKs, the slowly activating human cardiac ventricular repolarization current. The MinK ancillary subunit slows KCNQ1 activation, eliminates its inactivation, and increases its unitary conductance. However, KCNQ1 transcripts outnumber MinK transcripts five to one in human ventricles, suggesting KCNQ1 also forms other heteromeric or even homomeric channels there. Mechanisms governing which channel types prevail have not previously been reported, despite their significance: normal cardiac rhythm requires tight control of IKs density and kinetics, and inherited mutations in KCNQ1 and MinK can cause ventricular fibrillation and sudden death. Here, we describe a novel mechanism for this control. Whole-cell patch-clamping, confocal immunofluorescence microscopy, antibody feeding, biotin feeding, fluorescent transferrin feeding, and protein biochemistry techniques were applied to COS-7 cells heterologously expressing KCNQ1 with wild-type or mutant MinK and dynamin 2 and to native IKs channels in guinea-pig myocytes. KCNQ1–MinK complexes, but not homomeric KCNQ1 channels, were found to undergo clathrin- and dynamin 2-dependent internalization (DDI). Three sites on the MinK intracellular C-terminus were, in concert, necessary and sufficient for DDI. Gating kinetics and sensitivity to XE991 indicated that DDI decreased cell-surface KCNQ1–MinK channels relative to homomeric KCNQ1, decreasing whole-cell current but increasing net activation rate; inhibiting DDI did the reverse. The data redefine MinK as an endocytic chaperone for KCNQ1 and present a dynamic mechanism for controlling net surface Kv channel subunit composition—and thus current density and gating kinetics—that may also apply to other α–β type Kv channel complexes.
Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D?: Table 1
Authors: H Amital, Z Szekanecz, G Szücs, K Dankó, E Nagy, T Csépány, E Kiss, J Rovensky, A Tuchynova, D Kozakova, A Doria, N Corocher, N Agmon-Levin, V Barak, H Orbach, G Zandman-Goddard, Y Shoenfeld
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Low serum vitamin D concentrations have been reported in several autoimmune disorders. <h3>Objective</h3> To assess whether low serum vitamin D concentrations are related to disease activity of patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> 378 patients from several European and Israeli cohorts were pooled and their disease activity was measured by two different methods: 278 patients had SLE disease activity-2000 (SLEDAI-2K) scores and 100 patients had European Consensus Lupus Activity Measurement (ECLAM) scores. In order to combine the two systems the scores were converted into standardised values (z-scores), enabling univariate summary statistics for the two variables (SLEDAI-2K and ECLAM). The commercial kit, LIAISON 25-OH vitamin D assay (310900-Diasorin) was used to measure serum concentration of 25-OH vitamin D in 378 patients with SLE. <h3>Results</h3> A significant negative correlation was demonstrated between the serum concentration of vitamin D and the standardised values (z-scores) of disease activity scores as measured by the SLEDAI-2K and ECLAM scales (Pearson9s correlation coefficient r=−0.12, p=0.018). <h3>Conclusions</h3> In a cohort of patients with SLE originating from Israel and Europe vitamin D serum concentrations were found to be inversely related to disease activity.
European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG)
Authors: H.J. Schmoll, R. Souchon, S. Krege, P. Albers, J. Beyer, C. Kollmannsberger, S.D. Fossa, N.E. Skakkebaek, R. de Wit, K. Fizazi, J.P. Droz, G. Pizzocaro, G. Daugaard, P.H.M. de Mulder, A. Horwich, T. Oliver, R. Huddart, G. Rosti, L. Paz Ares, O. Pont, J.T. Hartmann, N. Aass, F. Algaba, M. Bamberg, I. Bodrogi, C. Bokemeyer, J. Classen, S. Clemm, S. Culine, M. de Wit, H.G. Derigs, K.P. Dieckmann, M. Flasshove, X. Garcia del Muro, A. Gerl, J.R. Germa-Lluch, M. Hartmann, A. Heidenreich, W. Hoeltl, J. Joffe, W. Jones, G. Kaiser, O. Klepp, S. Kliesch, L. Kisbenedek, K.U. Koehrmann, M. Kuczyk, M.P. Laguna, O. Leiva, V. Loy, M.D. Mason, G.M. Mead, R.P. Mueller, N. Nicolai, G.O.N. Oosterhof, T. Pottek, O. Rick, H. Schmidberger, F. Sedlmayer, W. Siegert, U. Studer, S. Tjulandin, H. von der Maase, P. Walz, S. Weinknecht, L. Weissbach, E. Winter, C. Wittekind
Journal: Annals of Oncology (2004)
Cerebral Phosphate Metabolism in First-Degree Relatives of Patients With Schizophrenia
Authors: Silke Klemm, Reinhard Rzanny, Stephan Riehemann, Hans-Peter Volz, Beate Schmidt, Uwe-Jens Gerhard, Christina Filz, Anke Schönberg, Hans-Joachim Mentzel, Werner A. Kaiser, Bernhard Blanz
Journal: American Journal of Psychiatry (2001)

Most phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) studies have described measures of lower membrane anabolism or greater catabolism in the frontal lobes of patients with schizophrenia. The purpose of the present study was to evaluate whether these findings can also be detected in young subjects at genetic risk for schizophrenia.Fourteen children and siblings of patients with schizophrenia (mean age=16.7 years) and 14 comparison subjects (mean age=16.9 years) were included in a (31)P-MRS study of the frontal lobe.The high-risk subjects had significantly lower mean ratios of phosphomonoesters to phosphodiesters (0.25 versus 0.31) and higher mean phosphodiester values (37.59% versus 34.87%) than comparison subjects.These findings suggest greater phospholipid breakdown even in young first-degree relatives of patients with schizophrenia. This suggestion is discussed with respect to the membrane phospholipid hypothesis of schizophrenia.
Cancer: Principles and Practice of Oncology, 5th Edition Vincent T. DeVita, Jr., Samuel Hellman, Steven A. Rosenberg, eds. Philadelphia:Lippincott-Raven Publishers, 1997.3125 pp., illus. $199. ISBN 0-397-51573-4
Authors: Eric J. Seifter
Journal: JNCI Journal of the National Cancer Institute (1997)
Cardiac-Specific YAP Activation Improves Cardiac Function and Survival in an Experimental Murine MI Model
Authors: Zhiqiang Lin, Alexander von Gise, Pingzhu Zhou, Fei Gu, Qing Ma, Jianming Jiang, Allan L. Yau, Jessica N. Buck, Katryna A. Gouin, Pim R.R. van Gorp, Bin Zhou, Jinghai Chen, Jonathan G. Seidman, Da-Zhi Wang, William T. Pu
Journal: Circulation Research (2014)

Rationale : Yes-associated protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte proliferation. Objective : We hypothesized that YAP activation after myocardial infarction (MI) would preserve cardiac function and improve survival. Methods and Results : We used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after MI preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP (hYAP) in the adult murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated expression of cell cycle genes and promoted a less mature cardiac gene expression signature. Conclusions : Cardiac-specific YAP activation after MI mitigated myocardial injury, improved cardiac function, and enhanced survival. These findings suggest that therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI.
Uncoupling of disease activity and structural damage. Does it matter clinically?
Authors: Edith Villeneuve, Boulos Haraoui
Journal: Annals of the Rheumatic Diseases (2012)

Rheumatoid arthritis (RA) is an autoimmune disease characterised by synovial inflammation that can lead to joint damage through bone and cartilage destruction, loss of function and decreased quality of life. Fortunately, over the past few years, we have witnessed major advances in the management of RA with new agents and treatment strategies that have improved outcomes and made remission become a realistic goal. True remission has been defined as a state where there is no evidence of disease activity with complete resolution of signs and symptoms as well as arrest of joint damage and disability progression. Hence, inhibition of radiographic progression has become a major therapeutic goal given its direct relationship to patient function and quality of life.1 Clinical remission can be achieved with disease-modifying antirheumatic drugs (DMARD) alone or may need a combination of DMARDs and biologic agents. Radiographic remission is more complex as we have learned from the probability plots that the mean/median change of radiographic progression is accounted for by a minority of patients who progress radiographically. Indeed, regardless of the therapy used, approximately 50% of patients will not show radiographic progression over 2–3 years; This percentage increases up to 75–85% of patients receiving combination therapy, and those who do progress, progress less than patients on methotrexate alone.2

It has long been thought that prevention of radiographic progression was achieved through the eradication of synovial inflammation, and that antitumour necrosis factor (TNF) agents were more effective at reducing structural progression through a better control of inflammation. However, recent posthoc …
The <i>GNAS1</i> T393C Polymorphism Is Associated with Disease Progression and Survival in Chronic Lymphocytic Leukemia
Authors: Ulrich H. Frey, Holger Nückel, Ludger Sellmann, Dörte Siemer, Ralf Küppers, Jan Dürig, Ulrich Dührsen, Winfried Siffert
Journal: Clinical Cancer Research (2006)

Abstract Purpose: B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of monoclonal mature B cells. The G protein Gαs subunit has been linked to proapoptotic processes in cancer cell lines. The TT genotype of the GNAS1 T393C polymorphism is associated with increased Gαs transcript levels and a more favorable clinical course in different solid cancers. Experimental Design: We retrospectively genotyped 144 patients with B-CLL to examine a potential association between T393C genotypes with progression-free survival (time from diagnosis to initiation of chemotherapy) and overall survival. Results: The C-allele frequency in the patient group was 0.57 and not significantly different from that of healthy blood donors. Median progression-free survival was significantly different between genotypes (TT 130 months; TC 100 months; CC 31 months; P = 0.0066). Multivariable analysis showed that besides of ZAP-70 (P = 0.005) and Binet stage (P &amp;lt; 0.001), the T393C polymorphism was an independent prognostic factor for progression-free survival [hazard ratio (HR) CC versus TT 2.7; P = 0.010]. In Binet A stages, ZAP-70–positive patients with CC genotypes had a HR of 4.4 to receive first therapy compared with ZAP-70–negative patients with T-alleles (P = 0.0001). Regarding overall survival, CC genotypes (median overall survival, 197 months) were at highest risk for death compared with T-alleles (median overall survival, 310 months) in both univariate (HR, 4.8; P &amp;lt; 0.0001) and multivariable analysis (HR, 5.6; P = 0.002). Conclusions: Here, we show that the GNAS1 T393C status is a novel independent prognostic marker in patients with B-CLL. These results could help to define patients who could benefit from an early individualized therapy.
A Rational Next Step in the Treatment of Some Rectal Adenocarcinomas
Authors: Glenn Steele, J. Michael Hamilton, James P. Karr
Journal: Journal of Clinical Oncology (1989)

A sentence in the last paragraph on page 989 of the editorial "A Rational Next Step in the Treatment of Some Rectal Adenocarcinomas" by Steele et al (J Clin Oncol 7:988–990, 1989) contained several errors. It should have read: "However, given the improbability of any randomized trial being performed, one alternative is the formation of a multiinstitutional treatment plan in which patients with T 1 or T 2 N 0 M 0 distal rectal adenocarcinomas accrue to a single treatment arm in which adequate local resection is followed in the patients with T 2 primaries (who have a 10% to 30% chance of insidious microscopic perirectal nodal disease) with the best presently available adjuvant treatment."
Removal of Heparan Sulfate from the Glomerular Basement Membrane Blocks Protein Passage
Authors: Tessa J.M. Wijnhoven, Joost F.M. Lensen, Ronnie G.P. Wismans, Dirk J. Lefeber, Angelique L.W.M.M. Rops, Johan van der Vlag, Jo H.M. Berden, Lambert P.W.J. van den Heuvel, Toin H. van Kuppevelt
Journal: Journal of the American Society of Nephrology (2007)

Heparan sulfate (HS) within the glomerular basement membrane (GBM) is thought to play a major role in the charge-selective properties of the glomerular capillary wall. Recent data, however, raise questions regarding the direct role of HS in glomerular filtration. For example, in situ studies suggest that HS may prevent plasma macromolecules from clogging the GBM, keeping it in an "open" state. We evaluated this potential role of HS in vivo by studying the passage of protein through the glomerular capillary wall in the presence and absence of HS. Intravenous administration of neuraminidase removed neuraminic acid--but not HS--from the GBM, and this led to albuminuria. Concomitant removal of HS with heparinase III, confirmed by ultrastructural imaging, prevented the development of albuminuria in response to neuraminidase treatment. Taken together, these results suggest that HS keeps the GBM in an open state, facilitating passage of proteins through the glomerular capillary wall.
Characteristics and Outcome of Diffuse Large B-Cell Lymphoma in Hepatitis C Virus–Positive Patients in LNH 93 and LNH 98 Groupe d'Etude des Lymphomes de l'Adulte Programs
Authors: Caroline Besson, Danielle Canioni, Eric Lepage, Stanislas Pol, Pierre Morel, Pierre Lederlin, Achiel Van Hoof, Hervé Tilly, Philippe Gaulard, Bertrand Coiffier, Christian Gisselbrecht, Nicole Brousse, Félix Reyes, Olivier Hermine
Journal: Journal of Clinical Oncology (2006)

Epidemiologic studies show an association between hepatitis C virus (HCV) and B-cell non-Hodgkin's lymphoma (NHL). Treatment and outcome of patients with diffuse large-cell lymphoma (DLCL) and HCV infection are still a matter of debate.We studied the HCV-positive patients with B-cell DLCL included in the Groupe d'Etude des Lymphomes de l'Adulte (GELA) programs LNH 93 and LNH 98. They were compared with the other patients with DLCL included in these programs. HCV infection prevalence was 0.5% (26 of 5,586 patients).Histologic types of HCV-positive DLCL were more frequently transformed from low-grade lymphoma than DLCL in HCV-negative patients (32% v 6%, P = .02). This is also supported by more frequent spleen involvement in HCV-positive patients (46% v 17%, P < .001). HCV-positive patients had more frequently elevated lactate dehydrogenase levels than other patients (77% v 55%, P = .02). Outcome of HCV-positive patients was poorer for overall survival (P = .02) but not for event-free survival (P = .13). After matching on age and prognosis factors, at 2 years of follow-up, the overall survival was 56% (95% CI, 33% to 76%) among HCV-positive patients, versus 80% (70% to 89%), and the event-free survival was 53% (33% to 72%) versus 74% (64% to 84%). The short-term hepatic toxicity of chemotherapy was strongly increased among HCV-positive patients. After exclusion of the two subjects with chronic hepatitis B virus infection, the overall proportion of subjects undergoing hepatic toxicity was 65% (15 of 23 patients).HCV-positive patients with DLCL differ from other patients both at presentation and during chemotherapy. Specific protocols evaluating antiviral therapy should be designed for these patients.
Independent validation of the Sleep Apnoea Quality of Life Index
Authors: Y Lacasse
Journal: Thorax (2002)

<b>Background:</b> Obstructive sleep apnoea (OSA) affects important domains of quality of life which remain unexplored by conventional sleep recordings. The objective of this study was to examine the measurement properties (both discriminative and evaluative) of the Sleep Apnoea Quality of Life Index (SAQLI), a new OSA specific quality of life questionnaire. <b>Methods:</b> Consecutive patients recently diagnosed with OSA completed a French version of the SAQLI twice over a 3 month period. Its construct validity and responsiveness were tested by comparing baseline and change scores obtained in each domain (symptoms, activities, emotions, social interactions) with those of questionnaires measuring related constructs (SF-36, Epworth Scale, Beck Depression Inventory, and Symptom Checklist 90). The symptoms scores were also correlated with physiological measures obtained at baseline polysomnographic recording. <b>Results:</b> Forty seven patients (40 men) of mean (SD) age 53 (10) years and mean (SD) apnoea/hypopnoea index 38 (21) participated in the study. During the study period 33 of the 47 patients were treated for OSA (31 with nasal CPAP, one with uvulopalatopharyngoplasty, and one with an oral appliance). Moderate to high correlations were found between the scores in each domain of the SAQLI and the corresponding instruments. There were significant differences in change scores between patients who were treated and those who were not, moderate correlations between SAQLI change scores and changes in the corresponding instruments, and no correlation between the symptoms scores and the baseline nocturnal features. Most of these correlations met the a priori predictions made regarding their magnitude. <b>Conclusion:</b> The SAQLI has strong construct validity and is responsive to change in quality of life but has the disadvantage of having to be administered by an interviewer.
Formation of cornified cell envelope in human hair follicle development
Authors: M. Akiyama, I. Matsuo, H. Shimizu
Journal: British Journal of Dermatology (2002)

Summary Background Cornified cell envelope (CCE) formation is an important step in the final stage of keratinization, in which CCE precursor proteins including involucrin and loricrin are cross‐linked by keratinocyte transglutaminases (TGases) to the inner surface of the plasma membrane of cornified cells, while the outer surface is coated with material derived from secreted lamellar granules. Objectives Skin samples from human fetuses of a series of estimated gestational age (EGA) (49–163 days) were studied for the prescence of precursor proteins. Methods TGase activity was studied by in situ TGase activity assay, and ultrastructural features of CCE formation were observed at each stage of hair follicle development. We used immunofluorescent labelling to investigate the time and site of expression of CCE precursor proteins involucrin and loricrin, TGases 1, 2 and 3, and a 25‐kDa lamellar granule‐associated protein (LGP) in developing human hair follicles. Results In the hair germ (65–84 days EGA) (corresponding to the stages 1–2 of murine hair follicle morphogenesis), only TGase 2 was observed in the entire hair germ, where in situ TGase activity was weakly positive, although thickening of cell membrane was not seen ultrastructurally. In the hair peg (85–104 days EGA) (corresponding to the stage 3 of murine hair follicle morphogenesis), loricrin and TGase 2 were seen in cells of the upper part of the hair peg while TGase 1, 3 and LGP were observed in the inner cells of the hair peg. In situ TGase activity was weakly positive in the upper part and inner cells of the hair peg. In the bulbous hair peg (105–135 days EGA) (corresponding to the stages 4–6 of murine hair follicle morphogenesis) and differentiated lanugo hair follicle (> 135 days EGA) (corresponding to the stages 7–8 of murine hair follicle morphogenesis), immunoreactivities of involucrin, loricrin, TGase 1, 2, 3, in situ TGase activity and LGP were detected in the inner root sheath cells, hair canals and inner cells of the outer root sheath in the region of the isthmus. Ultrastructurally, thickening of cell membrane was already seen in the inner root sheath cells of the bulbous hair peg and electron‐dense, thick CCE was observed in the hair cuticle and hair canal of differentiated lanugo hair follicle. Conclusions These data indicate that, in terms of CCE formation, certain portions of the developing human hair follicle have already been determined in differentiation of the hair canal and cuticle at the hair peg stage.