tbuckley/cabot-search huggingface dataset:
Should the DSM-IV Diagnostic Criteria for Conduct Disorder Consider Social Context?
Authors: Jerome C Wakefield, Kathleen J Pottick, Stuart A Kirk
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The text of the DSM-IV states that a diagnosis of conduct disorder should be made only if symptoms are caused by an internal psychological dysfunction and not if symptoms are a reaction to a negative environment. However, the DSM-IV diagnostic criteria are purely behavioral and ignore this exclusion. This study empirically evaluated which approach—the text's negative-environment exclusion or the purely behavioral criteria—is more consistent with clinicians' intuitive judgments about whether a disorder is present, whether professional help is needed, and whether the problem is likely to continue. METHOD: Clinically experienced psychology and social work graduate students were presented with three variations of vignettes describing youths whose behavior satisfied the DSM-IV criteria for conduct disorder. The three variations presented symptoms only, symptoms caused by internal dysfunction, and symptoms caused by reactions to a negative environment. The clinicians rated their level of agreement that the youth described in the vignette had a disorder, needed professional mental health help, and had a problem that was likely to continue into adulthood. RESULTS: Youths with symptoms caused by internal dysfunction were judged to have a disorder, and those with a reaction to a negative environment not to have a disorder. The difference was not explained by the clinicians' judgments of the youths' need for professional help or the expected duration of symptoms. CONCLUSIONS: The clinicians' judgments supported the validity of the DSM-IV's textual claim that a diagnosis of conduct disorder is valid only when symptoms are due to an internal dysfunction.
Bronchial Hyperreactivity after Lung Transplantation Predicts Early Bronchiolitis Obliterans
Authors: MATTHEW B. STANBROOK, STEVEN KESTEN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Nonspecific bronchial hyperreactivity (NSBHR) has been observed in patients who have undergone lung transplantation, but studies have provided conflicting reports as to the incidence and significance of this finding. To delineate more clearly the natural history of NSBHR after lung transplantation, data from 111 consecutive patients undergoing double lung transplantation between February 1988 and May 1994 were reviewed. Methacholine challenge testing was requested in conjunction with regular postoperative follow-up. Among 60 patients tested at 3 mo, 18 (30%) had a positive methacholine challenge; at 6 mo, the incidence was 14 of 59 (24%). Of 21 patients for whom complete testing was performed for 12 mo or longer, 13 (62%) had exclusively negative challenges. Patients with a positive challenge at 3 mo were significantly more likely to develop bronchiolitis obliterans syndrome (BOS) (p < 0.006). Mean time to development of BOS was 16.9 mo in the group with positive challenges versus 43.9 mo for those with negative challenges. We conclude that increased NSBHR is a common, but by no means universal, finding after lung transplantation. Furthermore, early positive methacholine challenges are associated with development of BOS. We hypothesize that NSBHR may represent an early marker of chronic rejection in these patients.
Modulation of CD4 antigen on macrophages and microglia in rat brain.
Authors: V H Perry, S Gordon
Journal: The Journal of Experimental Medicine (1987)

Mononuclear phagocytes which express the HIV entry receptor CD4 have been implicated as possible sites of virus replication in brain, but there is still considerable uncertainty as to which cells in the CNS express CD4 Ag. Although it is not susceptible to HIV infection the rat provides a model to define expression of the CD4 Ag on MO in brain. We report that the CD4 epitopes W3/25 and OX35 are found only on monocytes, MO, microglia, and occasional lymphocytes and not on neurons, other glia, or endothelium. CD4 Ag levels are modulated during microglial differentiation, after reactivation after local inflammation, and within the intact blood brain barrier. MO and microglia also express other potential plasma membrane binding and entry sites for HIV viz Fc and complement receptors that are regulated independently of CD4.
P148 Correlating changes in lung function with patient reported outcomes in COPD
Authors: P. W. Jones, J. Donohue, J. Nedelman, G. Pinault, S. Pascoe
Journal: Thorax (2010)

<h3>Introduction</h3> Relationships between improvements in lung function and other outcomes in COPD patients are not documented extensively. We examined the association between changes in FEV<sub>1</sub> and patient-centred outcomes using pooled data from three indacaterol studies. <h3>Methods</h3> We calculated correlations between changes in Transition Dyspnea Index (TDI) and St. George9s Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks) and exacerbation frequency (rate/year) across five categories of ΔFEV<sub>1</sub> with boundary points (in mls) between categories: –500 (lowest value), –50, +50, +150, +250, +500 (highest value), centred at –275, 0, 100, 200 and 375 ml. We also performed generalised linear modelling adjusting for covariates including baseline severity, treatment and ICS use. <h3>Results</h3> 3313 patients with non-missing values of relevant variables were analysed, excluding extreme values of ΔFEV<sub>1</sub> (outside ±500 ml). TDI and ΔSGRQ at 12 weeks improved and exacerbation rate declined with increasing positive ΔFEV<sub>1</sub> (all p&lt;0.001) (see Abstract P148 Table 1). Individual-level correlations were weak (0.06–0.18), reflecting the large variability in the outcomes, but cohort-level correlations were strong (0.76–0.93). Results for the proportion of patients demonstrating an improvement of at least the minimal clinically important difference (MCID) for TDI and SGRQ followed a similar pattern to the meaned data. In general, adjustments for baseline covariates, including level of airway obstruction, had little impact on the relationship between ΔFEV<sub>1</sub> and outcomes. <h3>Conclusions</h3> These results suggest that larger improvements in FEV<sub>1</sub> with long-acting bronchodilator therapy are likely to be associated with larger patient-centred benefits across a range of outcomes.
Thomas Holley Chivers, M.D. (1809–1858) and the Origin of Edgar Allan Poe's “The Raven”
Authors: S. Gerald Sandler
Journal: New England Journal of Medicine (1973)

EDGAR Allan Poe regarded his poem "The Raven" as "... the greatest poem that ever was written."1 Considering the immediate popularity of "The Raven" throughout America, England and France, it appears that many of Poe's contemporaries concurred. Not so admiring, however, was Thomas Holley Chivers (Fig. 1), a Georgia physician and lyric poet. Chivers brooded with a secret knowledge of Poe's "The Raven" for more than eight years after its publication, until, in 1853, he published the sensational claim that "The Raven" had been plagiarized from a collection of poems he had written several years earlier.Writing under a nom . . .
Virulent <i>Shigella flexneri</i> subverts the host innate immune response through manipulation of antimicrobial peptide gene expression
Authors: Brice Sperandio, Béatrice Regnault, Jianhua Guo, Zhi Zhang, Samuel L. Stanley, Philippe J. Sansonetti, Thierry Pédron
Journal: The Journal of Experimental Medicine (2008)

Antimicrobial factors are efficient defense components of the innate immunity, playing a crucial role in the intestinal homeostasis and protection against pathogens. In this study, we report that upon infection of polarized human intestinal cells in vitro, virulent Shigella flexneri suppress transcription of several genes encoding antimicrobial cationic peptides, particularly the human β-defensin hBD-3, which we show to be especially active against S. flexneri. This is an example of targeted survival strategy. We also identify the MxiE bacterial regulator, which controls a regulon encompassing a set of virulence plasmid-encoded effectors injected into host cells and regulating innate signaling, as being responsible for this dedicated regulatory process. In vivo, in a model of human intestinal xenotransplant, we confirm at the transcriptional and translational level, the presence of a dedicated MxiE-dependent system allowing S. flexneri to suppress expression of antimicrobial cationic peptides and promoting its deeper progression toward intestinal crypts. We demonstrate that this system is also able to down-regulate additional innate immunity genes, such as the chemokine CCL20 gene, leading to compromised recruitment of dendritic cells to the lamina propria of infected tissues. Thus, S. flexneri has developed a dedicated strategy to weaken the innate immunity to manage its survival and colonization ability in the intestine.
The surgical assessment unit--effective strategy for improvement of the emergency surgical pathway?
Authors: M S Mohamed
Journal: Journal of the Royal Society of Medicine (2005)

A special unit was set up in an associate teaching hospital to provide a fast-track route for the assessment of acute adult surgical and urological referrals.During an audit period of eight weeks, this surgical assessment unit had 550 referrals, of which 196 (36%) came via the accident and emergency (A&E) department; the other 354 came directly from general practitioners or other hospital departments.Mondays, Tuesdays and Fridays were the busiest days of the week; 57% of all patients arrived between 8 am and 5 pm.68% were seen by a doctor within 1 hour of their arrival.68% were either discharged or admitted to the main surgical wards within 4 hours.The study showed that, over the course of a year, the surgical assessment unit might divert some 2301 patients away from the A&E department.To achieve this total it would need to be open and appropriately staffed 24 hours a day.Such a unit offers a strategy for limiting the A&E workload and streamlining the assessment of patients with surgical and urological emergencies.
Factor Xa Binding to Annexin 2 Mediates Signal Transduction via Protease-Activated Receptor 1
Authors: Gourab Bhattacharjee, Jasimuddin Ahamed, Rafal Pawlinski, Cheng Liu, Nigel Mackman, Wolfram Ruf, Thomas S. Edgington
Journal: Circulation Research (2008)

The serine protease zymogen factor X is converted to its catalytically active form factor Xa by the binary complex of factor VIIa bound to its cell surface receptor tissue factor (TF) or by the intrinsic Xase complex, which consists of active factors VIII (VIIIa), IX (IXa), factor X, and Ca2+. Factor Xa has procoagulant activity by conversion of prothrombin to thrombin and also induces signal transduction, either alone or in the ternary TF:VIIa:factor Xa coagulation initiation complex. Factor Xa cleaves and activates protease activated receptor (PAR)1 or -2, but factor Xa signaling efficiency varies among cell types. We show here that annexin 2 acts as a receptor for factor Xa on the surface of human umbilical vein endothelial cells and that annexin 2 facilitates factor Xa activation of PAR-1 but does not enhance coagulant function of factor Xa. Overexpression of TF abolishes annexin 2 dependence on factor Xa signaling and diminishes binding to cell surface annexin 2, whereas selectively abolishing TF promotes the annexin 2/factor Xa interaction. We propose that annexin 2 serves to regulate factor Xa signaling specifically in the absence of cell surface TF and may thus play physiological or pathological roles when factor Xa is generated in a TF-depleted environment.
Altered Expression of <i>MLH1</i>, <i>MSH2</i>, and <i>MSH6</i> in Predisposition to Hereditary Nonpolyposis Colorectal Cancer
Authors: Elise Renkonen, Yange Zhang, Hannes Lohi, Reijo Salovaara, Wael M. Abdel-Rahman, Mef Nilbert, Kristiina Aittomäki, Heikki J. Järvinen, Jukka-Pekka Mecklin, Annika Lindblom, Päivi Peltomäki
Journal: Journal of Clinical Oncology (2003)

Purpose: A considerable fraction (30% to 70%) of families with verified or putative hereditary nonpolyposis colorectal cancer fails to show mutations in DNA mismatch repair (MMR) genes. Our purpose was to address the genetic etiology of such families. Materials and Methods: We scrutinized a population-based cohort of 26 families from Finland that had screened mutation-negative by previous techniques. Blood was tested for allelic messenger RNA (mRNA) expression of MLH1, MSH2, and MSH6 by single nucleotide primer extension (SNuPE), and tumor tissue for MMR protein expression by immunohistochemistry (IHC) as well as for microsatellite instability (MSI). Full-length cDNAs of genes implicated by SNuPE or IHC were cloned and sequenced. Results: Unbalanced mRNA expression of MLH1 alleles was evident in two families. An inherited nonsense mutation was subsequently identified in one family, and complete silencing of the mutated allele was identified in the other family. Extinct protein expression by IHC implicated MLH1 in these two and in four other families, MSH2 in four families, and MSH6 in one family. Although no unequivocal genomic mutations were detected in the latter families, haplotype and other findings provided support for heritable defects. With one exception, all tumors with IHC alterations showed MSI, in contrast to the remaining families, which showed neither IHC changes nor MSI. Conclusion: Our expression-based strategy stratified the present “mutation-negative” cohort into two discrete categories: families linked to the major MMR genes MLH1, MSH2, and MSH6 (11 [42%] of 26) and those likely to be associated with other, as yet unknown susceptibility genes (15 [58%] of 26).
Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-I.
Authors: M Howard, L Matis, T R Malek, E Shevach, W Kell, D Cohen, K Nakanishi, W E Paul
Journal: The Journal of Experimental Medicine (1983)

Antigen-activated T lymphocytes produce within 24 h of stimulation a factor that is indistinguishable biochemically and functionally from the B cell co-stimulating growth factor, BCGF-I, originally identified in induced EL4 supernatants: Supernatants from antigen-stimulated T cell lines are not directly mitogenic for resting B cells, but synergize in an H-2-unrestricted manner with anti-Ig activated B cells to produce polyclonal proliferation but not antibody-forming-cell development; biochemical studies reveal the B cell co-stimulating factor present in antigen-stimulated T cell line supernatants is identical by phenyl Sepharose chromatography and isoelectric focusing (IEF) to EL4 supernatant BCGF-I. We thus conclude that normal T cells produce BCGF-I in response to antigenic stimulation. Analysis of the mechanism of BCGF-I production by antigen-stimulated T cells showed that optimum amounts of BCGF-I were obtained as quickly as 24 h post-stimulation, and that the factor producing cells in the T cell line investigated bore the Lyt-1+2- phenotype. As few as 10(4) T cells produced sufficient BCGF-I to support the proliferation of 5 X 10(4) purified anti-Ig activated B cells. Finally, the activation of normal T cell lines to produce BCGF-I required either antigen presented in the context of syngeneic antigen-presenting cells (APC) or interleukin 2 (IL-2).
Multiphoton Imaging of the Glomerular Permeability of Angiotensinogen
Authors: Daisuke Nakano, Hiroyuki Kobori, James L. Burford, Haykanush Gevorgyan, Saskia Seidel, Hirofumi Hitomi, Akira Nishiyama, Janos Peti-Peterdi
Journal: Journal of the American Society of Nephrology (2012)

Patients and animals with renal injury exhibit increased urinary excretion of angiotensinogen. Although increased tubular synthesis of angiotensinogen contributes to the increased excretion, we do not know to what degree glomerular filtration of systemic angiotensinogen, especially through an abnormal glomerular filtration barrier, contributes to the increase in urinary levels. Here, we used multiphoton microscopy to visualize and quantify the glomerular permeability of angiotensinogen in the intact mouse and rat kidney. In healthy mice and Munich-Wistar-Frömter rats at the early stage of glomerulosclerosis, the glomerular sieving coefficient of systemically infused Atto565-labeled human angiotensinogen (Atto565-hAGT), which rodent renin cannot cleave, was only 25% of the glomerular sieving coefficient of albumin, and its urinary excretion was undetectable. In a more advanced phase of kidney disease, the glomerular permeability of Atto565-hAGT was slightly higher but still very low. Furthermore, unlike urinary albumin, the significantly higher urinary excretion of endogenous rat angiotensinogen did not correlate with either the Atto565-hAGT or Atto565-albumin glomerular sieving coefficients. These results strongly suggest that the vast majority of urinary angiotensinogen originates from the tubules rather than glomerular filtration.
Survival with first-line bosentan in patients with primary pulmonary hypertension
Authors: V. V. McLaughlin
Journal: European Respiratory Journal (2005)

Primary pulmonary hypertension (PPH) is a progressive disease with high mortality. Administration of <i>i.v.</i> epoprostenol has demonstrated improved exercise tolerance, haemodynamics, and survival. The orally active, dual endothelin receptor antagonist bosentan improves exercise endurance, haemodynamics, and functional class over the short term. To determine the effect of first-line bosentan therapy on survival, this study followed 169 patients with PPH treated with bosentan in two placebo-controlled trials and their extensions. Data on survival and alternative treatments were collected from September 1999 (start of the first placebo-controlled study) to December 31, 2002. Observed survival up to 36 months was reported as Kaplan-Meier estimates and compared with predicted survival as determined for each patient by the National Institutes of Health Registry formula. Kaplan-Meier survival estimates were 96% at 12 months and 89% at 24 months. In contrast, predicted survival was 69% and 57%, respectively. In addition, at the end of 12 and 24 months, 85% and 70% of patients, respectively, remained alive and on bosentan monotherapy. Factors that predicted a worse outcome included World Health Organization Functional Class IV and 6-min walk distance below the median (358 m) at baseline. First-line bosentan therapy was found to improve survival in patients with advanced primary pulmonary hypertension.
A Major Gene Locus Links Early Onset Albuminuria with Renal Interstitial Fibrosis in the MWF Rat with Polygenetic Albuminuria
Authors: Angela Schulz, Dorothea Standke, Larisa Kovacevic, Martin Mostler, Peter Kossmehl, Monika Stoll, Reinhold Kreutz
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The development of renal interstitial fibrosis (RIF) represents an important step in the progression of chronic proteinuric nephropathies. The Munich Wistar Frömter (MWF) rat represents a valuable model to study the progression in proteinuric renal disease. MWF animals demonstrate a significant increase of urinary albumin excretion (UAE) and RIF compared with the spontaneously hypertensive rat (SHR) with low UAE. The aim of this study was to analyze the genetic basis and the relation between UAE and RIF by genetic linkage and quantitative trait loci (QTL) mapping analysis. The authors generated a backcross population between MWF and SHR including 215 male animals. UAE was determined in young backcross animals at 8 wk, and at 14 and 24 wk of age, respectively. RIF was evaluated by Sirius red staining of kidney sections and quantified by computer-assisted image analysis at 24 wk. Total genome scan analysis identified in total eight QTL linked to UAE and a major locus on chromosome 6. At this locus, homozygosity for the MWF allele exhibited a strong effect on UAE levels (threefold elevation) and displayed significant linkage already at 8 wk (logarithm of odds [LOD] = 4.3) with increasing significance at 14 and 24 wk (LOD = 7.8 and 10.1, respectively). In addition, this was the only QTL that was linked to the amount of RIF (P = 0.0009, LOD = 2.4). These data establish a genetic link between early onset albuminuria and progression of RIF at the QTL on RNO6. This study demonstrates the power of genetic linkage analysis for the dissection of physiologic pathways involved in renal disease progression.
Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival
Authors: David T. Denhardt, Masaki Noda, Anthony W. O’Regan, Dubravko Pavlin, Jeffrey S. Berman
Journal: Journal of Clinical Investigation (2001)

Matricellular proteinsOsteopontin (OPN) is a phosphorylated acidic glycoprotein that has been implicated in a number of physiological and pathological events, including maintenance or reconfiguration of tissue integrity during inflammatory processes.As such, it is required for stress-induced bone remodeling and certain types of cell-mediated immunity.It also acts in dystrophic calcification, coronary restenosis, and tumor cell metastasis.An RGD-containing protein, OPN exists both as an immobilized ECM molecule in mineralized tissues and as a cytokine in body fluids; it is not a significant part of typical nonmineralized ECM.OPN can engage a number of receptors, including the integrins α v (β 1 , β 3 , or β 5 ) and (α 4 , α 5 , α 8 , or α 9 )β 1 , and it may also be a ligand for certain variant forms of CD44, specifically v6 and/or v7, but possibly only in conjunction with a β 1 integrin (1).These receptors directly or indirectly activate cellular signaling pathways, allowing OPN to mediate cell-matrix, and possibly cell-cell, interactions.Several studies have demonstrated that OPN delivers a prosurvival, antiapoptotic signal to the cell.Here, we argue that OPN influences cellular functions in a unique manner, by mimicking key aspects of an ECM signal outside the confines of the ECM.We will explore this idea by reviewing recent data concerning OPN signaling and the consequences of OPN deficiency in several settings, notably inflammatory processes involving immune cells and bone cells.