tbuckley/cabot-search huggingface dataset:
Influence of Child and Adolescent Psychiatric Disorders on Young Adult Personality Disorder
Authors: S Kasen, P Cohen, A E Skodol, J G Johnson, J S Brook
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: This study examines associations between childhood psychopathology and young adult personality disorder in a random sample of 551 youths, who were 9 to 16 years old at first assessment. METHOD: Subjects were evaluated for DSM-III-R psychiatric disorders. Information was obtained prospectively from youths and their mothers at three points over 10 years. The predictive effects of prior axis I disorders and adolescent axis II personality disorder clusters A, B, and C on young adult personality disorder were examined in logistic regression analyses. RESULTS: The odds of young adult personality disorder increased given an adolescent personality disorder in the same cluster. Prior disruptive disorders, anxiety disorders, and major depression all significantly increased the odds of young adult personality disorder independent of an adolescent personality disorder. In addition, comorbidity of axis I and axis II disorders heightened the odds of young adult personality disorder relative to the odds of a disorder on a single axis. CONCLUSIONS: Assessment of personality pathology before late adolescence may be warranted. Childhood or adolescent axis I disorders may set in motion a chain of maladaptive behaviors and environmental responses that foster more persistent psychopathology over time. Identification and treatment of childhood disorder may help to reduce that risk.
Matrix metalloproteinase 11 (MMP‐11; stromelysin‐3) and synthetic inhibitors
Authors: Magdalini Matziari, Vincent Dive, Athanasios Yiotakis
Journal: Medicinal Research Reviews (2006)

Abstract Matrix metalloproteinase (MMP)‐11, or Stromelysin 3, is a particular member of MMP family, a group of zinc‐dependent endopeptidases involved in matrix degradation and tissue remodeling. Despite intense efforts since its first characterization 15 years ago, its role and target substrates in different diseases remain largely unknown. While mice with MMP‐11 deficiency display no particular phenotype, analysis of different tumorigenesis models with these mice lead to the conclusion that MMP‐11 promotes tumor development. In contrast with other MMPs, MMP‐11 is unable to degrade any major extracellular matrix component and unlike most of other MMPs that are secreted as inactive proenzymes and activated extracellularly, MMP‐11 is secreted under active form. MMP‐11 may thus play a unique role in tissue remodeling processes, including those associated with tumor progression. Although MMP‐11 and other MMPs have been considered as promising targets to combat cancer, a first series of clinical trials using broad‐spectrum MMP inhibitors have not led to significant therapeutic benefits. These disappointing results highlight the need for better understanding of the exact role played by each MMP during the different stages of tumor progression. Among the different strategies to fill this gap, highly specific MMP inhibitors would be of great value. This review provides an update on the selectivity profile of phosphinic MMP‐11 synthetic inhibitors developed and discusses the opportunities and limitations to identify inhibitors able to fully discriminate MMP‐11 from the other MMPs. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 4, 528–552, 2007
High Expression of Macrophage Colony-Stimulating Factor in Peritumoral Liver Tissue Is Associated With Poor Survival After Curative Resection of Hepatocellular Carcinoma
Authors: Xiao-Dong Zhu, Ju-Bo Zhang, Peng-Yuan Zhuang, Hong-Guang Zhu, Wei Zhang, Yu-Quan Xiong, Wei-Zhong Wu, Lu Wang, Zhao-You Tang, Hui-Chuan Sun
Journal: Journal of Clinical Oncology (2008)

Purpose To investigate prognostic values of the intratumoral and peritumoral expression of macrophage colony-stimulating factors (M-CSF) in hepatocellular carcinoma (HCC) patients after curative resection. Patients and Methods Expression of M-CSF and density of macrophages (MΦ) were assessed by immunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissue from 105 patients who had undergone hepatectomy for histologically proven HCC. Prognostic value of these and other clinicopathologic factors was evaluated. Results Neither intratumoral M-CSF nor MΦ density was associated with overall survival (OS) or disease-free survival (DFS). High peritumoral M-CSF and MΦ density, which correlated with large tumor size, presence of intrahepatic metastasis, and high TNM stage, were independent prognostic factors for both OS (P = .001 and P &lt; .001, respectively) and DFS (P = .001 and P = .003, respectively) and affected incidence of early recurrence. In a small HCC subset, peritumoral M-CSF was also correlated with both OS and DFS (P = .038 and P = .001, respectively). The combination of peritumoral M-CSF and MΦ had a better power to predict the patients' death and disease recurrence (P &lt; .001 for both). Conclusion High peritumoral M-CSF and MΦ were associated with HCC progression, disease recurrence, and poor survival after hepatectomy, highlighting the importance of peritumoral tissue in the recurrence and metastasis of HCC. M-CSF and MΦ may be targets of postoperative adjuvant therapy.
Proteome-wide Analysis and CXCL4 as a Biomarker in Systemic Sclerosis
Authors: Lenny van Bon, Alsya J. Affandi, Jasper Broen, Romy B. Christmann, Renoud J. Marijnissen, Lukasz Stawski, Giuseppina A. Farina, Giuseppina Stifano, Allison L. Mathes, Marta Cossu, Michael York, Cindy Collins, Mark Wenink, Richard Huijbens, Roger Hesselstrand, Tore Saxne, Mike DiMarzio, Dirk Wuttge, Sandeep K. Agarwal, John D. Reveille, Shervin Assassi, Maureen Mayes, Yanhui Deng, Joost P.H. Drenth, Jacqueline de Graaf, Martin den Heijer, Cees G.M. Kallenberg, Marc Bijl, Arnoud Loof, Wim B. van den Berg, Leo A.B. Joosten, Vanessa Smith, Filip de Keyser, Rafaella Scorza, Claudio Lunardi, Piet L.C.M. van Riel, Madelon Vonk, Waander van Heerde, Stephan Meller, Bernhard Homey, Lorenzo Beretta, Mark Roest, Maria Trojanowska, Robert Lafyatis, Timothy R.D.J. Radstake
Journal: New England Journal of Medicine (2013)

Plasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon.We isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis who had distinct clinical phenotypes. We then performed proteome-wide analysis and validated these observations in five large cohorts of patients with systemic sclerosis. Next, we compared the results with those in patients with systemic lupus erythematosus, ankylosing spondylitis, and hepatic fibrosis. We correlated plasma levels of CXCL4 protein with features of systemic sclerosis and studied the direct effects of CXCL4 in vitro and in vivo.Proteome-wide analysis and validation showed that CXCL4 is the predominant protein secreted by plasmacytoid dendritic cells in systemic sclerosis, both in circulation and in skin. The mean (±SD) level of CXCL4 in patients with systemic sclerosis was 25,624±2652 pg per milliliter, which was significantly higher than the level in controls (92.5±77.9 pg per milliliter) and than the level in patients with systemic lupus erythematosus (1346±1011 pg per milliliter), ankylosing spondylitis (1368±1162 pg per milliliter), or liver fibrosis (1668±1263 pg per milliliter). CXCL4 levels correlated with skin and lung fibrosis and with pulmonary arterial hypertension. Among chemokines, only CXCL4 predicted the risk and progression of systemic sclerosis. In vitro, CXCL4 down-regulated expression of transcription factor FLI1, induced markers of endothelial-cell activation, and potentiated responses of toll-like receptors. In vivo, CXCL4 induced the influx of inflammatory cells and skin transcriptome changes, as in systemic sclerosis.Levels of CXCL4 were elevated in patients with systemic sclerosis and correlated with the presence and progression of complications, such as lung fibrosis and pulmonary arterial hypertension. (Funded by the Dutch Arthritis Association and others.).
Exercise and heat stress: performance, fatigue and exhaustion—a hot topic
Authors: Z J Schlader, S R Stannard, T Mündel
Journal: British Journal of Sports Medicine (2009)

Fatigue is suggested to be a general concept that is characterised by an acute impairment in performance and leads to the eventual inability to produce the necessary force, that is, volitional exhaustion.1 Homeostasis is maintained by the physiological regulatory processes occurring throughout the body,2 and during exercise, the development of fatigue and exhaustion is proposed to prevent homeostatic failure.3 Principle to the regulatory systems maintaining homeostasis is that of thermoregulation, and as such the combined stressors of exercise and heat stress are used as a model to investigate the regulatory processes that influence physical performance, the development of fatigue and the onset of exhaustion.4 5 Accordingly, theories have been developed, healthy (lively) debate has arisen and various journals have seen fit to devote special issues—for example, Sports Medicine (vol 37, issues 4–5), Journal of Applied Physiology (vol 104, issue 5) and timely reviews.4,–,7

Within the exercise and heat stress model, two exercise protocols have been used that both describe performance as a dependent variable of time: (1) fixed-intensity (ie, constant workload) exercise—exercise is undergone until volitional exhaustion, and (2) self-paced exercise—which evaluates the time to complete a given task (eg, a set amount of work) where the workload can be adjusted by the exerciser. Both exercise time-to-exhaustion and self-paced exercise performance have been found to be attenuated under heat stress.8,–,16 However, confounding these conclusions is that these exercise protocols evaluate a different combination of physiological processes. Fixed-intensity exercise provides a measure of exhaustion, whereas self-paced exercise provides an indication of the development of fatigue; and arising from this limitation, seemingly opposing theories have developed.

Thermoregulation is attained by both passive (ie, non-regulated) and active (ie, regulated) systems.17 During exercise in the heat, passive heat loss …
Changes in HRCT findings in patients with respiratory bronchiolitis-associated interstitial lung disease after smoking cessation
Authors: M. Nakanishi, Y. Demura, S. Mizuno, S. Ameshima, Y. Chiba, I. Miyamori, H. Itoh, M. Kitaichi, T. Ishizaki
Journal: European Respiratory Journal (2006)

High-resolution computed tomography (HRCT) findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are varied and nonspecific. There is no known report of changes in HRCT findings and respiratory function test results for RB-ILD patients following the cessation of smoking. Five patients with RB-ILD, confirmed by surgical lung biopsy, were retrospectively studied. Each stopped cigarette smoking and did not receive corticosteroid therapy after diagnosis. The clinical symptoms, respiratory function test results and HRCT findings obtained at the final observation were compared with those from the time of diagnosis. Ground-glass opacity and centrilobular nodules corresponding to pathological respiratory bronchiolitis, as well as intralobular fine linear-reticular opacity corresponding to fibrosis involving the subpleural alveolar septa, showed computed tomography-pathological correlations. Both clinical symptoms and the diffusing capacity of the lungs for carbon monoxide improved significantly following smoking cessation, as did ground-glass opacity and centrilobular nodules seen during the initial HRCT examination. Centrilobular nodules and ground-glass opacity, which are the main features of high-resolution computed tomography of respiratory bronchiolitis-associated interstitial lung disease patients and represent pathological respiratory bronchiolitis, can be improved by smoking cessation. The diffusing capacity of the lung for carbon monoxide in respiratory function tests can be also improved.
The Public Health Practice of Tobacco Control: Lessons Learned and Directions for the States in the 1990s
Authors: T E Novotny, R A Romano, R M Davis, S L Mills
Journal: Annual Review of Public Health (1992)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Modulation of an inactivating human cardiac K+ channel by protein kinase C.
Authors: K T Murray, S A Fahrig, K K Deal, S S Po, N N Hu, D J Snyders, M M Tamkun, P B Bennett
Journal: Circulation Research (1994)

The transient outward current (ITO) is an important repolarizing component of the cardiac action potential. In native cardiac myocytes, ITO is modulated after activation of protein kinase C, although the molecular nature of this effect is not well understood. A channel recently cloned from human ventricular myocardium (Kv1.4, HK1) produces a rapidly inactivating K+ current, which has phenotypic similarities to the 4-aminopyridine-sensitive component of ITO. Therefore, we examined whether this recombinant channel was also modulated by protein kinase C activation by investigating the effects of the diacylglycerol analogue phorbol 12-myristate 13-acetate (PMA) on Kv1.4 K+ current expressed in Xenopus oocytes. At a concentration of 10 nmol/L, PMA caused a biphasic response with an initial increase (14 +/- 4%, mean +/- SEM) in current, which peaked in 14 minutes. This was followed by a significant reduction (40 +/- 11%) in the current within 30 minutes. There was no significant change in cell membrane electrical capacitance with 10 nmol/L PMA (1 +/- 1% decline in 30 minutes), demonstrating that loss of cell membrane surface area did not explain the reduction in K+ current, although cell capacitance did decrease when using a higher concentration of PMA (81 nmol/L). The inactive stereoisomer, 4 alpha-PMA, had no effect on Kv1.4 current, whereas preincubation with the protein kinase inhibitor staurosporine or protein kinase C-selective chelerythrine prevented the effects of PMA. When purified from a stably transfected mammalian cell line by using immunoprecipitation, the channel protein was readily phosphorylated in vitro by purified protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)
Palifermin Reduces Patient-Reported Mouth and Throat Soreness and Improves Patient Functioning in the Hematopoietic Stem-Cell Transplantation Setting
Authors: Patrick J. Stiff, Christos Emmanouilides, William I. Bensinger, Teresa Gentile, Bruce Blazar, Thomas C. Shea, John Lu, John Isitt, Alessandra Cesano, Ricardo Spielberger
Journal: Journal of Clinical Oncology (2006)

Purpose To describe patient-reported outcomes of mouth and throat soreness (MTS) and related sequelae on daily activities from a phase III study of palifermin in the autologous hematopoietic stem-cell transplantation (HSCT) setting and to compare patient self-evaluations with clinicians' assessments of oral mucositis using objective scales. Patients and Methods Patients (n = 212) received palifermin (60 μg/kg/d) or placebo for 3 days before total-body irradiation (12 Gy), etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg, and 3 days after HSCT. Patients completed a daily questionnaire (Oral Mucositis Daily Questionnaire [OMDQ]) evaluating MTS severity and its effects on daily functional activities. Patients' self-assessment data were compared with clinicians' assessments of oral mucositis using the objective scales. Results Palifermin reduced the incidence and duration of severe oral mucositis, as assessed by both clinicians and patients. Comparisons between patient and clinician assessments demonstrated that the average daily scores between mucositis grade and subjective (MTS) instruments were similar, although patients reported MTS onset, peak, and resolution earlier (1 to 3 days) than clinicians' assessments. Patients receiving palifermin reported statistically significant improvements (P &lt; .001) in daily functioning activities (swallowing, drinking, eating, talking, sleeping) and required significantly less narcotic opioids (P &lt; .001); improvement in the patient's overall physical and functional well-being was also reported. This was confirmed by the results of the Functional Assessment of Cancer Treatment questionnaire. Conclusion These results support the clinical benefit of palifermin in the HSCT setting, providing evidence that a patient's self-assessment instrument (OMDQ) may serve as an alternative tool to assess oral mucositis severity in clinical trials.
Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication
Authors: Radek Szklarczyk, Martijn A Huynen
Journal: Genome biology (2009)

Mitochondria are highly complex, membrane-enclosed organelles that are essential to the eukaryotic cell. The experimental elucidation of organellar proteomes combined with the sequencing of complete genomes allows us to trace the evolution of the mitochondrial proteome. We present a systematic analysis of the evolution of mitochondria via gene duplication in the human lineage. The most common duplications are intra-mitochondrial, in which the ancestral gene and the daughter genes encode mitochondrial proteins. These duplications significantly expanded carbohydrate metabolism, the protein import machinery and the calcium regulation of mitochondrial activity. The second most prevalent duplication, inter-compartmental, extended the catalytic as well as the RNA processing repertoire by the novel mitochondrial localization of the protein encoded by one of the daughter genes. Evaluation of the phylogenetic distribution of N-terminal targeting signals suggests a prompt gain of the novel localization after inter-compartmental duplication. Relocalized duplicates are more often expressed in a tissue-specific manner relative to intra-mitochondrial duplicates and mitochondrial proteins in general. In a number of cases, inter-compartmental duplications can be observed in parallel in yeast and human lineages leading to the convergent evolution of subcellular compartments. One-to-one human-yeast orthologs are typically restricted to their ancestral subcellular localization. Gene duplication relaxes this constraint on the cellular location, allowing nascent proteins to be relocalized to other compartments. We estimate that the mitochondrial proteome expanded at least 50% since the common ancestor of human and yeast.
Postpartum Metabolic Function in Women Delivering a Macrosomic Infant in the Absence of Gestational Diabetes Mellitus
Authors: Simone Kew, Chang Ye, Mathew Sermer, Philip W. Connelly, Anthony J.G. Hanley, Bernard Zinman, Ravi Retnakaran
Journal: Diabetes Care (2011)

OBJECTIVE Gestational diabetes mellitus (GDM) is associated with fetal macrosomia and maternal postpartum dysglycemia, insulin resistance, and β-cell dysfunction. Indeed, in practice, a prior pregnancy that resulted in a large-for-gestational-age (LGA) delivery is often considered presumptive evidence of GDM, whether or not it was diagnosed at the time. If this clinical assumption is correct, however, we would expect these women to exhibit postpartum metabolic dysfunction. Thus, to test this hypothesis, we assessed metabolic function during and after pregnancy in a cohort of women stratified according to the presence/absence of GDM and LGA delivery, respectively. RESEARCH DESIGN AND METHODS A total of 562 women underwent metabolic characterization, including oral glucose tolerance test (OGTT), in late pregnancy and at 3 months’ postpartum. The women were stratified into three groups: those with neither GDM nor LGA delivery (nonGDM, n = 364), those without GDM but with LGA delivery (nonGDM–LGA, n = 46), and those with GDM (n = 152). RESULTS On logistic regression, GDM predicted postpartum glucose intolerance (OR 4.1 [95% CI 2.5–6.8]; P &amp;lt; 0.0001), whereas nonGDM–LGA did not (P = 0.65). At 3 months’ postpartum, the mean adjusted levels of fasting glucose and area under the glucose curve on the OGTT were significantly higher in the GDM women compared with either nonGDM or nonGDM–LGA (all P &amp;lt; 0.05), with no differences between the latter two groups. In a similar manner, mean adjusted insulin sensitivity (Matsuda index) and β-cell function (Insulin Secretion-Sensitivity Index-2) were lower in GDM women compared with either nonGDM or nonGDM–LGA (all P &amp;lt; 0.05), again with no differences between the latter two groups. CONCLUSIONS Women with nonGDM–LGA do not exhibit postpartum metabolic dysfunction, arguing against the assumption of undiagnosed GDM in these patients.
Characterization of novel breast carcinoma–associated BA46-derived peptides in HLA-A2.1/Db-β2mtransgenic mice
Authors: Lior Carmon, Irene Bobilev-Priel, Baruch Brenner, Dimitry Bobilev, Adrian Paz, Erez Bar-Haim, Boaz Tirosh, Tirza Klein, Mati Fridkin, Francois Lemonnier, Esther Tzehoval, Lea Eisenbach
Journal: Journal of Clinical Investigation (2002)

The human milk fat globule membrane protein BA46 (lactadherin) is highly overexpressed in human breast tumors, making it a potential target for tumor immunotherapy. We have identified BA46-derived peptides that contain the motif recognized by the MHC class I molecule HLA-A2.1 and that are processed and presented by human breast carcinoma cells. In mice lacking normal class I molecules but expressing an HLA-A2.1/Db-β2 microglobulin single chain (HHD mice), three peptides elicited specific CTL activity. Two of these peptides also stimulated cytotoxic activity in peripheral blood lymphocytes from HLA-A2.1–positive breast carcinoma patients. Adoptive transfer of HHD-derived bulk CTLs to nude mice bearing human breast carcinoma transplants reduced tumor growth. These peptides therefore represent naturally processed BA46-derived CTL epitopes that can be used in peptide-based antitumor vaccines.
Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction
Authors: Yoshinori Miyahara, Noritoshi Nagaya, Masaharu Kataoka, Bobby Yanagawa, Koichi Tanaka, Hiroyuki Hao, Kozo Ishino, Hideyuki Ishida, Tatsuya Shimizu, Kenji Kangawa, Shunji Sano, Teruo Okano, Soichiro Kitamura, Hidezo Mori
Journal: Nature Medicine (2006)
Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells
Authors: Bennett C. Weintraub, Jesse Eunsuk Jun, Anthony C. Bishop, Kevan M. Shokat, Matthew L. Thomas, Christopher C. Goodnow
Journal: The Journal of Experimental Medicine (2000)

Signal transduction through the B cell antigen receptor (BCR) is altered in B cells that express a receptor that recognizes self-antigen. To understand the molecular basis for the change in signaling in autoreactive B cells, a transgenic model was used to isolate a homogeneous population of tolerant B lymphocytes. These cells were compared with a similar population of naive B lymphocytes. We show that the BCR from naive B cells enters a detergent-insoluble domain of the cell within 6 s after antigen binding, before a detectable increase in BCR phosphorylation. This fraction appears to be important for signaling because it is enriched for lyn kinase but lacks CD45 tyrosine phosphatase and because the BCR that moves into this domain becomes more highly phosphorylated. Partitioning of the BCR into this fraction is unaffected by src family kinase inhibition. Tolerant B cells do not efficiently partition the BCR into the detergent-insoluble domain, providing an explanation for their reduced tyrosine kinase activation and calcium flux in response to antigen. These results identify an early, regulated step in antigen receptor signaling and self-tolerance.