tbuckley/cabot-search huggingface dataset:
Phenotype based treatment for wheezing in preschool children
Authors: Ayse Karakas, Engin Tutar, Sedat Oktem
Journal: European Respiratory Journal (2013)

Aim: to investigate the effectiveness of treatment for wheezing in preschool children based on ERS task force.

Material and Methods: Preschooler children with recurrent wheezing were classified as viral episodic wheeze (VEW) and multiple trigger wheeze (MTW) with respect to ERS task force and their treatments were arranged. Patients were evaluated at the beginning, at the end of the first month, and third month for the effectiveness of treatment by determining control levels according to the criteria in Global Initiative for Asthma Guideline for “asthma control levels”.

Results: 59 (56.7%) of 104 patients included in this study are boys and 45 (45.3%) of them are girls. 70 (67.3%) patients are classified as VEW and 34 (32.7%) as MTW. The mean age of VEW and MTW groups are 27.9±17.3 and 34.5±18.3, respectively. In MTW group, blood eosinophil levels and serum total IgE levels were found to be statistically significantly higher than VEW group. “The average numbers of symptom free days during 1 month before the treatment” in VEW and MTW groups were determined as statistically significantly lower compared to the 1st and 3rd months’ averages. In the 3rd month of the treatment, total control has been achieved in 81.4% of VEW group and in 76.5% of MTW group. Controller medications were changed in 7 (6.7%) cases because of insufficient control (2 cases (5.8%) MTW and 5 cases (7.1%) from VEW group).

Conclusion: Phenotype based classification which is a practical approach can be used in evaluation and treatment of preschool children with recurrent wheezing.

Reference: 

1.Brand PL et al. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J. 2008 Oct;32(4):1096-110.
Demographic Determinants of Hepatitis C Virus Seroprevalence Among Blood Donors
Authors: Edward L. Murphy
Journal: JAMA (1996)

<h3>Objective.</h3> —To measure demographic determinants of hepatitis C virus (HCV) seroprevalence among blood donors in the United States. <h3>Design.</h3> —Cross-sectional epidemiological study. <h3>Setting.</h3> —Five blood centers in different regions of the United States. <h3>Subjects.</h3> —A total of 862 398 consecutive volunteer blood donors with one or more nonautologous donations from March 1992 through December 1993. <h3>Methods.</h3> —Demographic data collection, serological screening with second-generation anti-HCV enzyme immunoassay, and confirmation with anti-HCV recombinant immunoblot. <h3>Results.</h3> —There were 3126 donors with at least one blood donation confirmed HCV-seropositive, for a crude prevalence of 3.6 per 1000. Age-specific HCV sero-prevalence rose from 0.5 per 1000 in donors younger than 20 years to a maximum of 6.9 per 1000 in donors aged 30 to 39 years and declined in older age groups. There was interaction between age and educational attainment, with 30- to 49-year-olds with less than a high school diploma at highest risk of HCV infection (odds ratio [OR], 33.0; 95% confidence interval [CI], 23.0 to 47.2 compared with those younger than 30 years with a bachelor's degree or higher degree). Other independent risk factors for HCV seropositivity included male sex (OR, 1.9; 95% CI, 1.8 to 2.1), black race (OR, 1.7; 95% CI, 1.6 to 1.9), Hispanic ethnicity (OR, 1.3; 95% CI, 1.1 to 1.5), previous blood transfusion (OR, 2.8; 95% CI, 2.5 to 3.1), and first/only time donor status (OR, 4.2; 95% CI, 3.9 to 4.5, compared with repeat donors). Seropositivity for human T-lymphotropic virus types I and II, human immunodeficiency virus, or hepatitis B core antigen was highly associated with HCV seropositivity (OR, 10.4; 95% CI, 9.6 to 11.4 for one vs no marker). <h3>Conclusions.</h3> —Despite a low overall HCV prevalence in blood donors in the United States, there is marked variation in HCV seroprevalence by demographic subgroup, even after controlling for prior blood transfusion, a recognized risk factor for HCV. Further study of the prevalence of other parenteral risk factors such as past injection drug use among blood donors is needed. (<i>JAMA</i>. 1996;275:995-1000)
Stable Myocardial-Specific AAV6-S100A1 Gene Therapy Results in Chronic Functional Heart Failure Rescue
Authors: Sven T. Pleger, Patrick Most, Matthieu Boucher, Stephen Soltys, J. Kurt Chuprun, Wiebke Pleger, Erhe Gao, Abhijit Dasgupta, Giuseppe Rengo, Andrew Remppis, Hugo A. Katus, Andrea D. Eckhart, Joseph E. Rabinowitz, Walter J. Koch
Journal: Circulation (2007)

Background— The incidence of heart failure is ever-growing, and it is urgent to develop improved treatments. An attractive approach is gene therapy; however, the clinical barrier has yet to be broken because of several issues, including the lack of an ideal vector supporting safe and long-term myocardial transgene expression. Methods and Results— Here, we show that the use of a recombinant adeno-associated viral (rAAV6) vector containing a novel cardiac-selective enhancer/promoter element can direct stable cardiac expression of a therapeutic transgene, the calcium (Ca 2+ )-sensing S100A1, in a rat model of heart failure. The chronic heart failure–rescuing properties of myocardial S100A1 expression, the result of improved sarcoplasmic reticulum Ca 2+ handling, included improved contractile function and left ventricular remodeling. Adding to the clinical relevance, long-term S100A1 therapy had unique and additive beneficial effects over β-adrenergic receptor blockade, a current pharmacological heart failure treatment. Conclusions— These findings demonstrate that stable increased expression of S100A1 in the failing heart can be used for long-term reversal of LV dysfunction and remodeling. Thus, long-term, cardiac-targeted rAAV6-S100A1 gene therapy may be of potential clinical utility in human heart failure.
Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels.
Authors: H F Dvorak, T M Sioussat, L F Brown, B Berse, J A Nagy, A Sotrel, E J Manseau, L Van de Water, D R Senger
Journal: The Journal of Experimental Medicine (1991)

Vascular permeability factor (VPF) is a highly conserved 34-42-kD protein secreted by many tumor cells. Among the most potent vascular permeability-enhancing factors known, VPF is also a selective vascular endothelial cell mitogen, and therefore has been called vascular endothelial cell growth factor (VEGF). Our goal was to define the cellular sites of VPF (VEGF) synthesis and accumulation in tumors in vivo. Immunohistochemical studies were performed on solid and ascites guinea pig line 1 and line 10 bile duct carcinomas using antibodies directed against peptides synthesized to represent the NH2-terminal and internal sequences of VPF. These antibodies stained tumor cells and, uniformly and most intensely, the endothelium of immediately adjacent blood vessels, both preexisting and those newly induced by tumor angiogenesis. A similar pattern of VPF staining was observed in autochthonous human lymphoma. In situ hybridization demonstrated VPF mRNA in nearly all line 10 tumor cells but not in tumor blood vessels, indicating that immunohistochemical labeling of tumor vessels with antibodies to VPF peptides reflects uptake of VPF, not endogenous synthesis. VPF protein staining was evident in adjacent preexisting venules and small veins as early as 5 h after tumor transplant and plateaued at maximally intense levels in newly induced tumor vessels by approximately 5 d. VPF-stained vessels were also hyperpermeable to macromolecules as judged by their capacity to accumulate circulating colloidal carbon. In contrast, vessels more than approximately 0.5 mm distant from tumors were not hyperpermeable and did not exhibit immunohistochemical staining for VPF. Vessel staining disappeared within 24-48 h of tumor rejection. These studies indicate that VPF is synthesized by tumor cells in vivo and accumulates in nearby blood vessels, its target of action. Because leaky tumor vessels initiate a cascade of events, which include plasma extravasation and which lead ultimately to angiogenesis and tumor stroma formation, VPF may have a pivotal role in promoting tumor growth. Also, VPF immunostaining provides a new marker for tumor blood vessels that may be exploitable for tumor imaging or therapy.
Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles
Authors: Michael H Jones, Carl Virtanen, Daisuke Honjoh, Tatsu Miyoshi, Yukitoshi Satoh, Sakae Okumura, Ken Nakagawa, Hitoshi Nomura, Yuichi Ishikawa
Journal: The Lancet (2004)
Peripheral Mechanism Involved in Response of Dogs' Cutaneous Veins to Local Temperature Change
Authors: MICHAEL M. WEBB-PEPLOE, JOHN T. SHEPHERD
Journal: Circulation Research (1968)

The cutaneous veins of the dog constrict and dilate with local cooling and warming, respectively. This response, which is dependent on the integrity of the adrenergic nerves, might be explained by an altered response of the smooth muscle to a given frequency of sympathetic nerve impulses or by local temperature receptors that initiate alterations in sympathetic nerve activity. In the lateral saphenous vein perfused at 42°, 27°, and 17°C, the constriction caused by stimulation of lumbar sympathetic nerves was 40%, 160%, and 200%, respectively, of that at 37°C; the constriction caused by norepinephrine at the same temperatures was 70%, 187%, and 318% of that at 37°C. Division of the dorsal spinal roots from L-1 to S-1 made no difference to the veno-constrictor response to local cooling. It is concluded that an alteration in the sensitivity of the smooth muscle to arriving sympathetic nerve impulses accounts for the venous responses to local temperature changes seen in the intact dog.
Palliative Sedation, Physician-Assisted Suicide, and Euthanasia: “Same, Same but Different”?
Authors: Bert Broeckaert
Journal: The American Journal of Bioethics (2011)

At least since the early 1990s palliative sedation has been an established option of last resort in specialized palliative care centers; in that sense, it could hardly be called a “relatively new p...
Sticking to Sugars at the Metastatic Site: Sialyltransferase ST6GalNAc2 Acts as a Breast Cancer Metastasis Suppressor
Authors: Christina M. Ferrer, Mauricio J. Reginato
Journal: Cancer Discovery (2014)

O-linked glycans on plasma membrane proteins are altered in cancer cells, leading to changes in cell adhesive properties and contributing to metastasis. Mechanisms of how these carbohydrates alter tumor spread remain vague. In this issue of Cancer Discovery, Murugaesu and colleagues, using an in vivo functional RNA interference metastasis screen, identified sialyltransferase ST6GalNAc2 as a novel metastasis suppressor gene. Aggressive estrogen receptor-negative breast cancers with reduced ST6GalNAc2 expression alter O-linked glycans on tumor cell surface, increasing soluble lectin galectin-3 binding and tumor cell clustering at metastatic sites.
Neutrophil attractant protein-1-immunoglobulin G immune complexes and free anti-NAP-1 antibody in normal human serum.
Authors: I Sylvester, T Yoshimura, M Sticherling, J M Schröder, M Ceska, P Peichl, E J Leonard
Journal: Journal of Clinical Investigation (1992)

After obtaining data indicating the presence of a neutrophil attractant protein-1 (NAP-1)-IgG complex in normal human serum, we developed sandwich ELISAs that could quantify NAP-1 and NAP-1-IgG in mixtures of the two moieties. The ELISA for free NAP-1 used a monoclonal capture antibody that did not bind NAP-1-IgG. The ELISA for NAP-1-IgG was based on omission of the anti-NAP-1 detection antibody (required for the free NAP-1 ELISA) and on interaction of phosphatase-conjugated anti-human IgG with the human NAP-1-IgG complex. Gel filtration of immunoaffinity-purified NAP-1-IgG showed that the bulk of the complex comprised a single IgG. Binding between NAP-1 and antibody is strong, since 8 M urea at neutral or alkaline pH did not release NAP-1. However, at pH 2.0 in 9 M urea approximately 15% of the total NAP-1 could be dissociated from the complex. NAP-1-IgG was detected in 18 of 26 sera from normal humans. The mean serum concentration was 58 ng of IgG-bound NAP-1/ml, with an SEM of 16 and a range from undetectable to 247 ng/ml. NAP-1-IgG concentrations in paired sera drawn at a 1-mo interval were remarkably constant. Using an ELISA for free NAP-1 with a detection limit of 200 pg/ml, we found no free NAP-1 in the 26 sera. Free anti-NAP-1-IgG autoantibody was found in 9 of 26 sera by direct ELISA. IgG anti-NAP-1 of all nine sera was polyclonal, comprising both kappa and lambda isotypes; predominant subclasses were IgG2 and IgG3. NAP-1-IgG did not compete with 125I-NAP-1 for binding to neutrophils, which suggests that IgG anti-NAP-1 is a molecular trap that prevents binding of NAP-1 to neutrophils after it diffuses from production sites into the circulation.
LTB<sub>4</sub>-induced Nasal Gland Serous Cell Secretion Mediated by Neutrophil Elastase
Authors: LARS-OLAF CARDELL, CARLOS AGUSTÍ, KIYOSHI TAKEYAMA, PÄR STJÄRNE, JAY A. NADEL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Local allergen challenge causes nasal hypersecretion and also causes local leukotriene (LT) release, including LTB4. Because LTB4 causes leukocyte recruitment, and because neutrophil elastase is a potent secretagogue, we examined the hypothesis that LTB4 causes nasal hypersecretion via neutrophil elastase. We developed a method for isolating and superfusing a nasal segment in dogs. Instillation of LTB4 into the nasal segment caused a time-dependent increase in the volume of airway fluid, in lysozyme secretion, and in the recruitment of neutrophils. ICI 200,355, a selective inhibitor of neutrophil elastase, prevented LTB4-induced nasal secretion and lysozyme secretion, but it had no effect on neutrophil recruitment. We conclude that LTB4 causes potent nasal secretion via release of elastase, and therefore LTB4 may play a major role in allergic nasal hypersecretion.
The Role of Sleep in Emotional Brain Function
Authors: Andrea N. Goldstein, Matthew P. Walker
Journal: Annual Review of Clinical Psychology (2014)

Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by long-standing clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (a) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep; (b) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning; and (c) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on posttraumatic stress disorder and major depression.
Normal physiology and retinal degeneration in the Drosophila visual system
Authors: Joseph E. O'Tousa
Journal: Progress in Retinal and Eye Research (1997)

The Drosophila genetic system has been exploited to identify and analyze many genes that are responsible for the specialized cellular processes and biochemical mechanisms of the photoreceptor cell. The results establish that disruption of many different cellular processes can trigger retinal degeneration. The rhodopsin gene family provides an example in which mutations are known to trigger retinal degeneration in both vertebrates and invertebrates. The Drosophila research has established that dominant rhodopsin mutations disrupt the protein maturation process. This review emphasizes the unique and powerful experimental approaches of Drosophila that are being applied towards understanding the many causes of retinal degeneration.
Are extra-fine particles from dry powder inhalers likely to improve lung deposition?
Authors: Doetie Gjaltema, Paul Hagedoorn, Henderik W. Frijlink, Anne H. De Boer
Journal: European Respiratory Journal (2014)

Rationale:  Differences between CFC- and HFA-MDIs include the particle size distribution of the aerosol and the discharge velocity of the aerosol. Because deposition of aerosol particles decreases rapidly in all lung sections with decreasing particle diameter below 1.5 μm, it is questionable whether there is any real advantage from administration of extra-fine particles without the benefit of a low delivery velocity. And although recent reviews have led to the conclusion that there is no convincing evidence yet for increased benefit from the use of extra-fine particles in asthmatic patients, a dry powder inhaler (DPI: Foster NEXThaler) with an extra-fine aerosol output has also now become available.   Methods:  Fine particle doses (FPDs) from Foster NEXThaler (F-N) measured with the Next Generation Impactor at 2, 4 and 6 kPa were compared with those from Symbicort Turbuhaler (S-TBH), Seretide Diskus (S-D) and Rolenium Elpenhaler (R-E) and evaluated in relation to the corresponding flow rates.   Results:  Flow rates corresponding with 4 kPa and delivered FPDs as percent of label claim at 4 kPa are summarised in the table.   Conclusion:  The FPD%
Simvastatin Induces Regression of Cardiac Hypertrophy and Fibrosis and Improves Cardiac Function in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy
Authors: R. Patel, S. F. Nagueh, N. Tsybouleva, M. Abdellatif, S. Lutucuta, H. A. Kopelen, M. A. Quinones, W. A. Zoghbi, M. L. Entman, R. Roberts, A. J. Marian
Journal: Circulation (2001)

Hypertrophic cardiomyopathy is a genetic disease characterized by cardiac hypertrophy, myocyte disarray, interstitial fibrosis, and left ventricular (LV) dysfunction. We have proposed that hypertrophy and fibrosis, the major determinants of mortality and morbidity, are potentially reversible. We tested this hypothesis in beta-myosin heavy chain-Q(403) transgenic rabbits.We randomized 24 beta-myosin heavy chain-Q(403) rabbits to treatment with either a placebo or simvastatin (5 mg. kg(-1). d(-1)) for 12 weeks and included 12 nontransgenic controls. We performed 2D and Doppler echocardiography and tissue Doppler imaging before and after treatment. Demographic data were similar among the groups. Baseline mean LV mass and interventricular septal thickness in nontransgenic, placebo, and simvastatin groups were 3.9+/-0.7, 6.2+/-2.0, and 7.5+/-2.1 g (P<0.001) and 2.2+/-0.2, 3.1+/-0.5, and 3.3+/-0.5 mm (P=0.002), respectively. Simvastatin reduced LV mass by 37%, interventricular septal thickness by 21%, and posterior wall thickness by 13%. Doppler indices of LV filling pressure were improved. Collagen volume fraction was reduced by 44% (P<0.001). Disarray was unchanged. Levels of activated extracellular signal-regulated kinase (ERK) 1/2 were increased in the placebo group and were less than normal in the simvastatin group. Levels of activated and total p38, Jun N-terminal kinase, p70S6 kinase, Ras, Rac, and RhoA and the membrane association of Ras, RhoA, and Rac1 were unchanged.Simvastatin induced the regression of hypertrophy and fibrosis, improved cardiac function, and reduced ERK1/2 activity in the beta-myosin heavy chain-Q(403) rabbits. These findings highlight the need for clinical trials to determine the effects of simvastatin on cardiac hypertrophy, fibrosis, and dysfunction in humans with hypertrophic cardiomyopathy and heart failure.
MyD88-mediated signals induce the bactericidal lectin RegIIIγ and protect mice against intestinal <i>Listeria monocytogenes</i> infection
Authors: Katharina Brandl, George Plitas, Bernd Schnabl, Ronald P. DeMatteo, Eric G. Pamer
Journal: The Journal of Experimental Medicine (2007)

Listeria monocytogenes is a food-borne bacterial pathogen that causes systemic infection by traversing the intestinal mucosa. Although MyD88-mediated signals are essential for defense against systemic L. monocytogenes infection, the role of Toll-like receptor and MyD88 signaling in intestinal immunity against this pathogen has not been defined. We show that clearance of L. monocytogenes from the lumen of the distal small intestine is impaired in MyD88−/− mice. The distal ileum of wild-type (wt) mice expresses high levels of RegIIIγ, which is a bactericidal lectin that is secreted into the bowel lumen, whereas RegIIIγ expression in MyD88−/− mice is nearly undetectable. In vivo depletion of RegIIIγ from the small intestine of wt mice diminishes killing of luminal L. monocytogenes, whereas reconstitution of MyD88-deficient mice with recombinant RegIIIγ enhances intestinal bacterial clearance. Experiments with bone marrow chimeric mice reveal that MyD88-mediated signals in nonhematopoietic cells induce RegIIIγ expression in the small intestine, thereby enhancing bacterial killing. Our findings support a model of MyD88-mediated epithelial conditioning that protects the intestinal mucosa against bacterial invasion by inducing RegIIIγ.
Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study
Authors: H Isomoto, S Shikuwa, N Yamaguchi, E Fukuda, K Ikeda, H Nishiyama, K Ohnita, Y Mizuta, J Shiozawa, S Kohno
Journal: Gut (2008)

<h3>Objective:</h3> Endoscopic submucosal dissection (ESD) has the advantage over conventional endoscopic mucosa resection, permitting removal of early gastric cancer (EGC) en bloc, but long-term clinical outcomes remain unknown. A follow-up study on tumour recurrence and survival after ESD was conducted. <h3>Method:</h3> ESD was performed for patients with EGC that fulfilled the expanded criteria: mucosal cancer without ulcer findings irrespective of tumour size; mucosal cancer with ulcer findings ⩽3 cm in diameter; and minute submucosal invasive cancer ⩽3 cm in size. 551 patients with 589 EGC lesions were enrolled. The patients underwent ESD and then received periodic endoscopic follow-up and metastatic surveys for 6–89 months (median, 30 months). The main outcome measures were resectability (en bloc or piecemeal resection), and curability (curative or non-curative). Complications were assessed, and factors related to each were analysed statistically. The overall and disease-free survival rates were estimated. <h3>Results:</h3> En bloc resection was achieved in 94.9% (559/589), and larger lesions were at higher risk of piecemeal resection. 550 of 581 lesions (94.7%) were deemed to have undergone curative resection. En bloc resection was the only significant contributor to curative ESD. Patients with non-curative resection developed local recurrence more frequently. The 5-year overall and disease-specific survival rates were 97.1% and 100%, respectively. <h3>Conclusion:</h3> Precise assessment of curability with successful one-piece resection may reduce tumour recurrence after ESD. The prognosis of EGC patients treated by ESD is likely to be excellent, though further longer follow-up studies are warranted.