tbuckley/cabot-search huggingface dataset:
Alveolar epithelial lining fluid cellularity, protein and endothelin-1 in children with congenital heart disease
Authors: J. Grigg, S. Kleinert, R.L. Woods, C.J. Thomas, P. Vervaart, J.L. Wilkinson, C.F. Robertson
Journal: European Respiratory Journal (1996)

This study applied bronchoalveolar lavage (BAL) to children with congenital heart disease (CHD) prior to elective cardiac catheterization (n = 48), to determine the influence of pulmonary blood flow and viral infection on the alveolar epithelial lining fluid (ELF) concentration of leucocytes, protein and endothelin-1 (ET-1). Lower respiratory tract (LRT) viral infection was defined as either a positive immunofluorescence for virus, or a virus cultured from the bronchoalveolar lavage fluid (BALF). Haemodynamic status was determined at cardiac catheterization. Normative data for BALF, but not ELF parameters, were obtained from 26 asymptomatic, noninfected normal children undergoing elective surgery. In the absence of LRT infection, the BALF macrophage, lymphocyte and neutrophil differential in CHD was not significantly different from the normal controls. In CHD, both increased pulmonary-to-systemic flow ratio (Q9p/Q9s) and increased pulmonary artery-to-left ventricular pressure ratio PAP/LVP were associated with a decrease in ELF protein (rs = -0.59; p &lt; 0.0001; and rs = -0.50; p &lt; 0.0001 respectively). A respiratory virus was isolated from the BALF in 8 (17%) of CHD children. Virus isolation was associated with an increased ELF total protein (p &lt; 0.05 vs no infection), a decreased alveolar macrophage differential count (p &lt; 0.01), and an increased neutrophil differential count (p &lt; 0.05). ET-1 was detected in the BALF of 83% of the noninfected CHD children compared to only 23% of the controls (p &lt; 0.001). ELF ET-1 concentrations did not correlate with haemodynamic status in CHD, but were up to 100 times higher than paired plasma levels. We conclude that, in congenital heart disease, both lower respiratory tract viral infection and increased pulmonary blood flow and/or pulmonary vascular pressure influence the alveolar milieu. High alveolar epithelial lining fluid concentrations of endothelin-1 occur in congenital heart disease, but the stimulus for pulmonary endothelin-1 production is unclear.
IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis
Authors: Jason R. Chan, Wendy Blumenschein, Erin Murphy, Caroline Diveu, Maria Wiekowski, Susan Abbondanzo, Linda Lucian, Richard Geissler, Scott Brodie, Alexa B. Kimball, Daniel M. Gorman, Kathleen Smith, Rene de Waal Malefyt, Robert A. Kastelein, Terrill K. McClanahan, Edward P. Bowman
Journal: The Journal of Experimental Medicine (2006)

Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor-dependent, but IL-17A-independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target.
Defective Processing Speed and Nonclinical Psychotic Experiences in Children: Longitudinal Analyses in a Large Birth Cohort
Authors: Maria Niarchou, Stanley Zammit, James Walters, Glyn Lewis, Michael John Owen, Marianne Bernadette van den Bree
Journal: American Journal of Psychiatry (2013)

Objective Psychotic experiences in children are associated with an elevated risk of developing psychosis. The authors investigated whether the pattern of cognitive deficits present in psychosis also exists in children with psychotic experiences within the general population. Method The authors examined the longitudinal relationships between key cognitive domains, selected a priori based on their association with schizophrenia, and onset of psychotic experiences in children from the Avon Longitudinal Study of Parents and Children and whether these associations were independent of one another. Results Lower performance in the domains of processing speed at age 8 years (odds ratio=1.24, 95% CI=1.12–1.36) and attention at age 11 (odds ratio=1.14, 95% CI=1.04–1.25) and decline of processing speed between the ages of 8 and 11 (odds ratio=1.29, 95% CI=1.15–1.45) were associated with higher risk of psychotic experiences at age 12. When adjusting for the other cognitive domains, processing speed at age 8 (odds ratio=1.20, 95% CI=1.09–1.33) was the measure most strongly associated with psychotic experiences. Conclusions Defective processing speed is a particularly strong predictor of psychotic experiences in children. Furthermore, the pattern of associations between cognition and psychotic experiences in children within the general population is similar to the one between cognition and schizophrenia. These findings have potentially important implications for understanding the pathogenesis of psychotic disorders and the specific deficits that seem to place children at higher risk of psychopathology.
Neuromuscular training strategies for preventing lower limb injuries: what's new and what are the practical implications of what we already know?: Table 1
Authors: Markus Hübscher, Kathryn M Refshauge
Journal: British Journal of Sports Medicine (2012)

Sports and recreation injuries are now known to be a significant public health problem. Lower limb injuries sustained during childhood and adolescence are associated with increased morbidity, including early development of osteoarthritis and long-term pain and disability;1 ,2 ultimately interfering with work, sports participation and a healthy level of physical activity.

In March 2010, we published a systematic review and meta-analysis (literature search conducted October 2008) on the effectiveness of neuromuscular training for prevention of sports injuries in athletes.3 Seven high-quality studies involving young male and female athletes (12–24 years) were included. Participants were engaged in organised sports, including basketball, volleyball, soccer, team handball, hockey and floorball. The pooled analyses revealed that multi-intervention exercises (comprising balance and agility training, stretching, plyometrics, running exercises, cutting and landing technique, strength training) significantly reduced the relative risk of lower limb injuries (relative risk reduction (RRR)=39%, 95% CI  23% to 51%), acute knee injuries (RRR=54%, 95% CI 24%  to 72%) and ankle sprain injuries (RRR=50%, 95% CI 21% to 69%).

Since the publication of our review, five key trials have been published that aimed to reduce the incidence of lower limb injuries in young basketball or soccer players (table 1).

View this table:

Table 1 
Key findings since publication of our previous systematic review



These studies are well designed with respect to important key criteria of internal validity and risk of bias, such as randomisation, allocation concealment, blinding of outcome assessors, statistical adjustment (eg, clustering and previous …
Doha Declaration has failed to deliver cheap drugs to developing countries, Oxfam says
Authors: Adrian O'Dowd
Journal: BMJ (2006)

Efforts to improve access to drugs for people living in poorer countries have failed despite a worldwide agreement designed to tackle the issue, it has been claimed. 

Oxfam has published a report on the fifth anniversary of the Doha Declaration, and claims that little has changed and in some cases things have worsened since the agreement was made dealing with the trade related aspects of intellectual property rights (TRIPS). 

The formal trade declaration, aimed at putting health before profits, has not worked, says the report, and in a debate held last week in London to coincide with the report launch, a motion saying “This house …
Asymmetric Paternalism to Improve Health Behaviors
Authors: George Loewenstein, Troyen Brennan, Kevin G. Volpp
Journal: JAMA (2007)

INDIVIDUAL BEHAVIOR PLAYS A CENTRAL ROLE IN THE DISease burden faced by society. Many major health problems in the United States and other developed nations, such as lung cancer, hypertension, and diabetes, are exacerbated by unhealthy behaviors. Modifiable behaviors such as tobacco use, overeating, and alcohol abuse account for nearly one-third of all deaths in the United States. Moreover, realizing the potential benefit of some of the most promising advances in medicine, such as medications to control blood pressure, lower cholesterol levels, and prevent stroke, has been stymied by poor adherence rates among patients. For example, by 1 year after having a myocardial infarction, nearly half of patients prescribed cholesterol-lowering medications have stopped taking them. Reducing morbidity and mortality may depend as much on motivating changes in behavior as on developing new treatments. Economics, as the social science discipline traditionally most closely tied to public policy, could be a key discipline in addressing behaviors that are potentially harmful to health. Yet conventional economics does not provide satisfactory policy solutions to problems caused by self-harmful behavior. Economics is premised on a rational choice perspective which, by assuming that individuals make optimal decisions given their information, resources, and preferences, in effect assumes away these problems. The main policy tools suggested by conventional economics, providing information or changing prices, only partially address these problems because they fail to exploit what is known about human motivation and behavior change. Responding in part to these limitations of conventional economics, the new field of behavioral economics has, over the last few decades, begun to import concepts from psychology. Behavioral economists have identified a number of decision biases and pitfalls in decision making that can help explain when and why individuals engage in selfharming behaviors that contribute to poor health outcomes. Insights from behavioral economics can contribute to solutions for public health problems such as medication nonadherence and sedentary lifestyles that have challenged clinicians and public health professionals for years. In this Commentary, we identify some key decision biases that ordinarily lead to self-harming behavior and show how they can be exploited in interventions to instead promote healthy behaviors.
Expression of human mammaglobin gene in pleural effusions of patients with malignant mesothelioma
Authors: A M Carletti
Journal: Thorax (2006)

Human mammaglobin (hMAM) is a 10 kd protein of unknown function originally identified through a differential screening approach aimed at the isolation of breast cancer related antigens. Accordingly, hMAM overexpression was demonstrated in breast cancers compared with non-malignant breast tissue. Based on these findings, the potential role of hMAM as a breast tumour marker has been extensively investigated.1 hMAM expression has recently been found in other tissues including lung cancer specimens and lung cancer cell lines.2 Thus, hMAM expression is no longer considered restricted to the mammary gland and the list of normal and/or malignant tissues in which hMAM is found is likely still to be incomplete. 

The aim of this study was to investigate the expression of hMAM transcripts in the pleural …
IL-1 receptor–associated kinase M is a central regulator of osteoclast differentiation and activation
Authors: Hongmei Li, Esteban Cuartas, Weiguo Cui, Yongwon Choi, Todd D. Crawford, Hua Zhu Ke, Koichi S. Kobayashi, Richard A. Flavell, Agnès Vignery
Journal: The Journal of Experimental Medicine (2005)

Osteoporosis is a serious problem worldwide; it is characterized by bone fractures in response to relatively mild trauma. Osteoclasts originate from the fusion of macrophages and they play a central role in bone development and remodeling via the resorption of bone. Therefore, osteoclasts are important mediators of bone loss that leads, for example, to osteoporosis. Interleukin (IL)-1 receptor (IL-1R)–associated kinase M (IRAK-M) is only expressed in cells of the myeloid lineage and it inhibits signaling downstream of IL-1R and Toll-like receptors (TLRs). However, it lacks a functional catalytic site and, thus, cannot function as a kinase. IRAK-M associates with, and prevents the dissociation of, IRAK–IRAK-4–TNF receptor–associated factor 6 from the TLR signaling complex, with resultant disruption of downstream signaling. Thus, IRAK-M acts as a dominant negative IRAK. We show here that mice that lack IRAK-M develop severe osteoporosis, which is associated with the accelerated differentiation of osteoclasts, an increase in the half-life of osteoclasts, and their activation. Ligation of IL-1R or TLRs results in hyperactivation of NF-κB and mitogen-activated protein kinase signaling pathways, which are essential for osteoclast differentiation. Thus, IRAK-M is a key regulator of the bone loss that is due to osteoclastic resorption of bone.
Reprogramming of human postmitotic neutrophils into macrophages by growth factors
Authors: Hiroto Araki, Naoyuki Katayama, Yoshihiro Yamashita, Hiroyuki Mano, Atsushi Fujieda, Eiji Usui, Hidetsugu Mitani, Kohshi Ohishi, Kazuhiro Nishii, Masahiro Masuya, Nobuyuki Minami, Tsutomu Nobori, Hiroshi Shiku
Journal: Blood (2004)
Orthotopic Liver Transplantation in a Patient With Amanita Poisoning
Authors: E. Steve Woodle
Journal: JAMA (1985)

Orthotopic liver transplantation in patients with acute toxic hepatitis has not, to our knowledge, been reported. Our recent experience with orthotopic liver transplantation in a 3-year-old girl with acute hepatic failure secondary to<i>Amanita</i>poisoning is described. Aspects of<i>Amanita</i>toxin-induced pathophysiology pertinent to orthotopic liver transplantation are discussed. The results in this case provide important implications for patients with fulminant hepatic failure secondary to other hepatotoxic agents in whom liver transplantation is considered. (<i>JAMA</i>1985;253:69-70)
Mucosal enzyme activity for butyrate oxidation; no defect in patients with ulcerative colitis.
Authors: E S Allan, S Winter, A M Light, A Allan
Journal: Gut (1996)

BACKGROUND: Butyrate is an important energy source for the colon and its metabolism has been reported to be defective in ulcerative colitis. One mechanism for defective butyrate metabolism in patients with ulcerative colitis could be an enzyme deficiency in the beta-oxidation pathway of butyrate. AIMS: This study was undertaken to measure the activity of each enzyme involved in the beta-oxidation pathway of butyrate in colonic epithelium. PATIENTS: Patients with ulcerative colitis (n = 33), Crohn9s colitis (n = 10), and control subjects with colorectal cancer or diverticular disease (n = 73) were studied. METHODS: Analysis was carried out using fluorometric and spectrophotometric techniques on homogenised epithelial biopsy specimens. RESULTS: Significantly increased butyryl CoA dehydrogenase activity was found in mucosa from patients with ulcerative colitis (33.2 (28.3, 38.1) mumol/g wet weight/min:mean (95% CI)) compared with activity in mucosa from control patients (24.3 (20.9, 27.7) mumol/g wet weight/min:mean (95% CI)) p &lt; 0.02. No significant increase in activity of the enzymes butyryl-CoA synthetase, crotonase or hydroxybutyryl-CoA dehydrogenase was found in patients with ulcerative colitis. In contrast the mucosal thiolase activity was significantly lower in those patients with quiescent colitis (3.21 (2.61, 3.81) mumol/g wet weight/min:mean (95% CI)) when compared with control mucosa (5.69 (5.09, 6.29) mumol/g wet weight/min:mean (95% CI)) p &lt; 0.001. However, mucosal thiolase activity increases with the age of the donor patient and differences in the age range of the patient groups probably account for this finding. CONCLUSIONS: This study shows no substantial deficiency of enzyme activity in the beta-oxidation pathway of butyrate in the mucosa of patients with ulcerative colitis in histological remission.
Molecular Detection of Early-Stage Laryngopharyngeal Squamous Cell Carcinomas
Authors: Stephane Temam, Jean Bénard, Christelle Dugas, Martine Trassard, Emmanuelle Gormally, Jean-Charles Soria, Sandrine Faivre, Bernard Luboinski, Patrick Marandas, Pierre Hainaut, Gilbert Lenoir, Li Mao, François Janot
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We sought to determine whether early-stage laryngopharyngeal squamous cell carcinomas (SCC) can be detected through molecular analysis of exfoliated cells collected with the use of a pharyngoesophageal brush (PEB). Experimental Design: Thirty-three patients with a single, untreated, early-stage (T1 or T2) SCC of the supraglottic larynx or pharynx underwent collection of cells with a PEB, followed by endoscopic biopsy of the tumor. PEB specimens were also collected from five healthy subjects. PEB samples and tumor tissue were examined for hypermethylation of p16INK4a (CDKN2) gene promoter CpG islands (assayed by methylation-specific PCR) and UT5085 tetranucleotide microsatellite instability (assayed by GeneScan analysis). PEB samples were also subjected to cytologic analysis. Results: Eight of 33 (24%) tumors exhibited a bandshift at UT5085, and 14 of 33 (42%) exhibited hypermethylation at the p16 promoter. Overall, 17 of 33 (52%) patients had at least one of the two markers in their tumor. Cytologic analysis of PEB samples revealed tumor in 4 of 33 (12%) patients; cytologic findings were normal in all five control subjects. Molecular analysis of PEB samples revealed tumor DNA in 13 of 17 (76%) patients with at least one of the two molecular markers in their tumor. Eight of 14 (57%) patients with p16 hypermethylation in their tumor and 8 of 8 (100%) patients with UT5085 microsatellite instability in their tumor had similar findings in the PEB samples. None of the PEB samples from the control subjects or patients with neither molecular marker in their tumor displayed abnormality. Conclusion: Molecular analysis of PEB samples holds promise for the early detection of early-stage laryngopharyngeal SCCs. New molecular markers need to be identified to increase the sensitivity of molecular screening.
Changes in endothelial cell mass, luminal volume and capillary number in the gravitational syndrome
Authors: M.M. MOURAD, S.P. BARTON, R. MARKS
Journal: British Journal of Dermatology (1989)

The histopathological changes in the skin of 31 patients with the gravitational syndrome and 10 normal control subjects were studied. To quantify the clinical severity of the syndrome, a new index of severity was used. Histometric evaluation of the cutaneous vasculature was performed on biopsies taken from the edge of the ulcers in the 31 patients and from the medical aspect of the lower legs in control subjects. Endothelial cell mass did not correlate with the clinical index of disease severity, suggesting that angiogenesis did not necessarily signal healing. The mean luminal volume appeared to be of greater prognostic value as there was a significant negative correlation of this parameter with the index of clinical severity. The degree of epidermal hyperplasia was found to be related to both the amount of inflammatory cell infiltrate present and the endothelial cell mass per unit tissue volume. The results also showed that the clinical index of disease severity was positively correlated to the mean epidermal thickness. The quantitative evaluation of biopsy material can be used to provide prognostic information in the gravitational syndrome.
Granulocyte pyruvate kinase in psoriasis vulgaris and psoriasis arthropathica
Authors: F. WASIK, JULIA JEDRZEJAK, MIECZYSLAWA MIKLASZEWSKA
Journal: British Journal of Dermatology (1987)

Journal Article Granulocyte pyruvate kinase in psoriasis vulgaris and psoriasis arthropathica Get access F. WASIK, F. WASIK Department of Dermatology, School of Medicine, Wroclaw, Poland Search for other works by this author on: Oxford Academic Google Scholar JULIA JEDRZEJAK, JULIA JEDRZEJAK Department of Dermatology, School of Medicine, Wroclaw, Poland Search for other works by this author on: Oxford Academic Google Scholar MIECZYSLAWA MIKLASZEWSKA MIECZYSLAWA MIKLASZEWSKA Department of Dermatology, School of Medicine, Wroclaw, Poland Mieczyslawa Miklaszewska, M.D., Department of Dermatology, School of Medicine, Chalubińskiego 1, 50‐368 Wroclaw, Poland. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 116, Issue 1, 1 January 1987, Pages 9–14, https://doi.org/10.1111/j.1365-2133.1987.tb05785.x Published: 01 January 1987
Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses
Authors: Liesbeth M. Kager, J. Daan de Boer, Paul Bresser, Jaring S. van der Zee, Sacha Zeerleder, Joost C.M. Meijers, Cornelis van 't Veer, Tom van der Poll
Journal: European Respiratory Journal (2012)

Intravenous administration of activated protein C (APC) inhibits coagulation and inflammation in the lungs of humans and animals. Investigations in rodents demonstrated that direct intrapulmonary delivery of APC also exerts anticoagulant and anti-inflammatory effects. The effect of intrabronchial administration of recombinant human (rh)APC on lipopolysaccharide (LPS)-induced haemostatic and inflammatory alterations in the bronchoalveolar space of humans was studied. Eight subjects received rhAPC via intrabronchial instillation by bronchoscope, while in a contralateral subsegment subjects received saline; all subjects were challenged bilaterally with LPS in the same lung subsegments. Four additional subjects received rhAPC (75 μg), with saline as a control in the contralateral subsegment, while they were bilaterally “challenged” with saline. After 6 h a bronchoalveolar lavage was performed and coagulation and inflammatory parameters were measured. rhAPC enhanced LPS-induced coagulation activation in the bronchoalveolar space, when compared with the control side. In addition, rhAPC amplified LPS-induced pro-inflammatory responses, as indicated by higher concentrations of cytokines and chemokines. rhAPC alone did not have procoagulant or pro-inflammatory effects. Locally administered rhAPC has unexpected procoagulant and pro-inflammatory effects in LPS-challenged lung subsegments. These data argue against a role for intrapulmonary delivery of rhAPC as a treatment strategy for lung inflammatory disorders in humans.
Brain networks in Huntington disease
Authors: David Eidelberg, D. James Surmeier
Journal: Journal of Clinical Investigation (2011)

Recent studies have focused on understanding the neural mechanisms underlying the emergence of clinical signs and symptoms in early stage Huntington disease (HD). Although cell-based assays have focused on cell autonomous effects of mutant huntingtin, animal HD models have revealed alterations in the function of neuronal networks, particularly those linking the cerebral cortex and striatum. These findings are complemented by metabolic imaging studies of disease progression in premanifest subjects. Quantifying metabolic progression at the systems level may identify network biomarkers to aid in the objective assessment of new disease-modifying therapies and identify new regions that merit mechanistic study in HD models.