tbuckley/cabot-search huggingface dataset:
Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma
Authors: Bruce Elliott, Richard A. Scolyer, Stefan Suciu, Serge Lebecque, Donata Rimoldi, Oliver Gugerli, Elena Musat, Raghwa N. Sharma, Danielle Lienard, Ulrich Keilholz, Alessandro Testori, Alexander Eggermont, Rona MacKie, Caroline Robert, Martin Cook, John F. Thompson, Eric Angevin, Alain Spatz
Journal: Clinical Cancer Research (2007)

In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation of mature DC-LAMP(+) DCs in SLNs was associated with local expansion of antigen-specific memory effector CTLs and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs.A total of 458 consecutive patients with micrometastatic melanoma within SLNs were eligible for analysis. The maximal density of mature DC-LAMP(+) DCs was evaluated by three independent observers and categorized into three classes (<100, 100 to <200, and >or=200/mm(2)).There was excellent interobserver reproducibility for maximum density of mature DC-LAMP(+) DC scores (kappa score = 0.82). There were differences in the maximal density scores and staining intensity according to the treating melanoma center (P < 0.001). The higher the mature DC density in the SLN is, the longer is the duration of survival [P = 0.047; hazard ratio, 0.70; 95% confidence interval, 0.50-1.00]. Adjusted by thickness and ulceration, the prognostic importance of DC density was lower (P = 0.36).This study is the first to report the prognostic value of DC-LAMP(+) DC counts in SLNs containing metastatic melanoma. Patients with a high density of mature DCs (>or=200/mm(2)) have the lowest risk of death. It also provides evidence that a lack of maturation in the SLNs is important in biological facilitation of melanoma progression.
Safety of Hymenoptera venom rush immunotherapy
Authors: J. Laurent, J. M. Smiejan, E. Bloch‐Morot, D. Herman
Journal: Allergy (1997)

We studied 97 consecutive patients who had received Hymenoptera venom rush immunotherapy in our department. There were 53 males and 44 females, whose mean age was 46 years (8–74 years). Most study patients had experienced severe anaphylaxis induced by a Hymenoptera sting: the reaction was Müller stage IV in 48 patients. Skin tests were positive for Vespula venom in 85 cases, Polistes venom in 23, and bee venom in 23. Radioallergosorbent test values exceeded 0.70 kIU/1 in 60 cases. Immunotherapy was performed with Vespula venom alone in 73 cases, bee venom alone in five cases, and both Vespula and bee venom in 19 cases. A cutaneous reaction was seen at the injection site in most patients. Four patients also had skin manifestations in areas remote from the injection site. Blood pressure elevation was seen in 11 patients, moderate hypotension in two, rhinitis in one, asthenia or headache in seven, visual disorders and vertigo in two, and transient dyspnea in two. Our protocol has proved very safe, epinephrine never being required in the 97 reported cases.
Regional Cerebral Blood Flow During Script-Driven Imagery in Childhood Sexual Abuse-Related PTSD: A PET Investigation
Authors: Lisa M. Shin, Richard J. McNally, Stephen M. Kosslyn, William L. Thompson, Scott L. Rauch, Nathaniel M. Alpert, Linda J. Metzger, Natasha B. Lasko, Scott P. Orr, Roger K. Pitman
Journal: American Journal of Psychiatry (1999)

The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD).Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition.In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus.The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.
Response of slowly adapting articular mechanoreceptors in the cat knee joint to alterations in intra-articular volume.
Authors: L Wood, W R Ferrell
Journal: Annals of the Rheumatic Diseases (1984)

Recordings were obtained from slowly adapting mechanoreceptors innervating the posterior aspect of the cat knee joint capsule. It was observed that, with rising intra-articular volume, initially both intra-articular pressure and the neural discharge increased. This increase was dependent on the rate of fluid accumulation within the joint. However, the joint nerve discharge invariably levelled out despite increasing intra-articular volume and pressure. This suggests that there exists some limit to capsular distension in the posterior joint region beyond which fluid is diverted to other areas of the knee joint.
Uveitis and tumour necrosis factor blockade in ankylosing spondylitis
Authors: L C Coates, D G McGonagle, A N Bennett, P Emery, H Marzo-Ortega
Journal: Annals of the Rheumatic Diseases (2007)

Anterior uveitis is the commonest extra-articular manifestation of ankylosing spondylitis (AS) and occurs in up to 40% of patients during the course of their disease.1 Uveitis associated with AS is typically anterior, unilateral and responsive to topical treatment.2 Tumour necrosis factor (TNF) blocking agents have been used in the treatment of uveitis refractory to conventional therapies but etanercept may be less effective in the treatment of uveitis in spondyloarthropathy (SpA) patients,3 possibly related to its alternative mode of action as a receptor blocker rather than antibody to TNF. Paradoxically they also seem to …
Bile acids with differing hydrophilic-hydrophobic properties do not influence cytokine production by human monocytes and murine Kupffer cells
Authors: A Bergamini, L Dini, L Baiocchi, L Cappannoli, L Falasca, F Bolacchi, M Capozzi, E Faggioli, A Nistri, A Salanitro, L Ventura, G Rocchi, M Angelico
Journal: Hepatology (1997)

Bile acids have been proposed to exert immunological effects of potential pathogenic or therapeutic relevance, yet the experimental evidence remains preliminary. We reexamined the effects of a variety of bile salts with differing hydrophilic-hydrophobic properties on the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) from monocytes and Kupffer cells. Monocytes from healthy human donors and Kupffer cells from 5-week-old mice were incubated for up to 18 hours with or without varying concentrations of bile salts and lipopolysaccharide (LPS). Monocyte viability was > or = 95% with up to 250 mumol/L sodium ursodeoxycholate and < or = 90% with 200 mumol/L chenodeoxycholate, decreasing sharply at higher concentrations. Kupffer cells were more vulnerable, particularly to chenodeoxycholate (viabilities of 25% and 0% at concentrations of 100 mumol/L and 200 mumol/L, respectively). In monocytes incubated in the presence of 20% fetal calf serum, neither ursodeoxycholate and chenodeoxycholate, nor a variety of other unconjugated and conjugated bile acids, tested up to their maximal noncytotoxic concentrations, influenced the IL-6 and TNF alpha production, at any level of LPS stimulation. Similar to monocytes, incubation of murine Kupffer cells with ursodeoxycholate and chenodeoxycholate did not influence cytokine release. In contrast, the addition of 10 nmol/L dexamethasone to monocytes significantly decreased TNF-alpha and IL-6 release (69 +/- 11% and 48 +/- 15%, respectively). When monocytes were incubated with 200 mumol/L chenodeoxycholate in the presence of lower concentrations of fetal calf serum (10% and 5%, respectively) a significant inhibition of cytokine release was observed, whereas incubation with ursodeoxycholate did not cause any effect. Flow cytometry using fluoresceinated LPS showed that chenodeoxycholate does not interact with the CD14 receptor, thus excluding the possibility of an interference with the LPS uptake by monocytes. Incubation with [14C]-chenodeoxycholate showed that the intracellular bile acid uptake was inversely related to the concentration of fetal calf serum, being negligible (< 3 fmol/cell) at the highest level. In conclusion, bile acids with widely different hydrophobicities are incapable of influencing the release of IL-6 and TNF alpha by monocytes and Kupffer cells, provided they are studied at noncytotoxic concentrations and in the presence of physiological amounts of proteins.
Abstract 4972: In vivo whole genome shRNA screen reveals novel targets to block cancer metastasis
Authors: Konstantin Stoletov, David Bond, Hon Sing Leong, Emma Woolner, Srijan Raha, Amy Robertson, Francis Wong, Andries Zijlstra, John D. Lewis
Journal: Cancer Research (2014)

Abstract The formation of invasive, rapidly growing metastatic lesions is a critical step in cancer metastasis, the cause of more than 90% of cancer deaths. Development of novel therapeutic approaches that block the invasion step of metastasis is one of the highest priorities for clinical cancer research. For this reason we completed the first genome-wide in vivo shRNA screen for genes that directly contribute to invasive metastatic lesion formation. Using state of the art intravital imaging, we identified over fifty novel regulators of invasive metastatic colony formation in vivo. Interactome analysis links these genes to key cellular processes including: transcriptional regulation of gene expression, mRNA processing and cytoskeletal remodeling. The target list was then prioritized based on clinical gene expression profiles that negatively correlated with key cancer endpoints including metastasis, cancer-specific and overall survival. Pharmacological and shRNA-mediated knockdown of the high priority targets in human cancer cell lines such as prostate cancer and melanoma specifically blocked cancer cell migration and invasion in vitro and in vivo. Moreover, shRNA-mediated knockdown of these genes blocked human cancer cell metastasis in the avian embryo and mouse preclinical models of metastasis. Finally, immunohistochemical analysis on clinical prostate cancer and melanoma tissue samples showed strong correlation with disease progression and metastasis. In summary, we have identified numerous novel genes that that are functionally involved in cancer invasion and metastasis that may serve as predictive markers for disease aggressiveness and represent exciting new pharmacological targets to block cancer invasion and metastasis. Citation Format: Konstantin Stoletov, David Bond, Hon Sing Leong, Emma Woolner, Srijan Raha, Amy Robertson, Francis Wong, Andries Zijlstra, John D. Lewis. In vivo whole genome shRNA screen reveals novel targets to block cancer metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4972. doi:10.1158/1538-7445.AM2014-4972
Effect of Hydrodynamics-Based Gene Delivery of Plasmid DNA Encoding Interleukin-1 Receptor Antagonist-Ig for Treatment of Rat Autoimmune Myocarditis
Authors: Hui Liu, Haruo Hanawa, Tsuyoshi Yoshida, Raafat Elnaggar, Manabu Hayashi, Ritsuo Watanabe, Ken Toba, Kaori Yoshida, He Chang, Yuji Okura, Kiminori Kato, Makoto Kodama, Hiroki Maruyama, Junichi Miyazaki, Mikio Nakazawa, Yoshifusa Aizawa
Journal: Circulation (2005)

Background— Interleukin-1 (IL-1) is a powerful and important cytokine in myocarditis. The purpose of this study was to evaluate the effect and possible mechanism of hydrodynamics-based delivery of the IL-1 receptor antagonist (IL-1RA)-immunoglobulin (Ig) gene for treatment of rat experimental autoimmune myocarditis (EAM). Methods and Results— On the day after immunization, rats were transfected with either pCAGGS encoding IL-1RA-Ig or pCAGGS encoding Ig alone. On day 17, IL-1RA-Ig gene therapy was effective in controlling EAM, as monitored by a decreased ratio of heart weight to body weight, reduced myocarditis areas, reduced gene expression of atrial natriuretic peptide in hearts, and improved cardiac function in echocardiographic and hemodynamic parameters. Examination of the expression of IL-1–related genes in purified cells from EAM hearts suggested that ectopic IL-1RA-Ig-acting target cells were αβT cells and noncardiomyocytic noninflammatory cells such as fibroblasts, smooth muscle cells, and endothelial cells. Therefore, we examined the effect of serum containing IL-1RA-Ig on the expression of immune-relevant genes within noncardiomyocytic cells cultured from EAM hearts or concanavalin A-stimulated lymphocytes derived from lymph nodes in EAM-affected rats. The expression of immunologic molecules (prostaglandin E synthase, cyclooxygenase-2, and IL-1β) in cultivated noncardiomyocytic cells and Th1 cytokines (IL-2 and IFN-γ) in lymphocytes was significantly decreased by the serum containing IL-1RA-Ig. Conclusions— EAM was suppressed by hydrodynamics-based delivery of plasmid DNA encoding IL-1RA-Ig. In addition, IL-1RA-Ig suppressed gene expression of prostaglandin synthases and IL-1 in noncardiomyocytic cells and Th1 cytokines in lymphocytes.
Roles of caudal-related homeobox gene Cdx1 in oesophageal epithelial cells in Barrett's epithelium development
Authors: H Kazumori, S Ishihara, Y Kinoshita
Journal: Gut (2009)

The mechanism of transformation to intestinal metaplasia in Barrett's oesophagus has not been clarified. We previously reported that bile acids activate the Cdx2 promoter via nuclear factor kappa B (NF-kappaB) and stimulate production of Cdx2 protein in oesophageal keratinocytes with a resulting production of intestinal type mucin. In addition to Cdx2, Cdx1 may play an important role in the development of Barrett's oesophagus. Therefore, we studied the direct effects of bile acids on the expression of Cdx1 as well as the precise mechanisms of Cdx1 expression in cultured oesophageal squamous epithelial cells. Furthermore, we investigated the relationship between Cdx1 and Cdx2 expression in cultured oesophageal squamous epithelial cells.A rat model of Barrett's oesophagus was produced by anastomosing the oesophagus and jejunum. The expression of Cdx1 was investigated by immunohistochemistry, while the response of that expression to bile acids was studied using a Cdx1 promoter luciferase assay. In addition, oesophageal squamous epithelial cells were transfected with a Cdx1 or Cdx2 expression vector, after which their possible transformation to intestinal-type epithelial cells was investigated.In our Barrett's rat model, the metaplastic epithelium and adjoining squamous epithelium strongly expressed Cdx1. Further, the bile acids mixture dose-dependently increased Cdx1 promoter activity and Cdx1 protein in oesophageal epithelial cells. Transfection of the Cdx1 expression vector in cultured oesophageal epithelial cells induced production of Cdx2 protein.Bile acid-induced sequential expression of Cdx1 followed by Cdx2 may have an important role in the development of Barrett's epithelium.
Assessment of component-resolved in vitro diagnosis of celeriac allergy
Authors: Kerstin Bauermeister, Barbara K. Ballmer-Weber, Merima Bublin, Philipp Fritsche, Kay-Martin O. Hanschmann, Karin Hoffmann-Sommergruber, Jonas Lidholm, Christina Oberhuber, Stefanie Randow, Thomas Holzhauser, Stefan Vieths
Journal: Journal of Allergy and Clinical Immunology (2009)
Traffic-related NO2 and the prevalence of asthma and respiratory symptoms in seven year olds
Authors: M Studnicka, E Hackl, J Pischinger, C Fangmeyer, N Haschke, J Kuhr, R Urbanek, M Neumann, T Frischer
Journal: European Respiratory Journal (1997)

The aim of this study was to determine whether outdoor nitrogen dioxide (NO2) was associated with the prevalence of asthma and respiratory symptoms. In eight nonurban communities, 843 children resident for a minimum of 2 yrs were studied. Since industrial sources of air pollution were at least 20 km away from the study communities, NO2 was considered to primarily indicate traffic-related air pollution. NO2 was recorded at central monitors, and the 3 yr mean exposure was calculated. Asthma and respiratory symptoms were assessed according to the International Study on Asthma and Allergy in Childhood. Prevalence of asthma at some time ("ever asthma") was associated with long-term NO2. In parallel with increasing levels of NO2 (community specific 3 yr mean 6.0-17.0 parts per billion (ppb)), asthma prevalence was 2.5, 1.4, 1.6, 2.3, 3.4, 3.6, 7.6 and 8.5%, respectively (p=0.002 for trend). The prevalence odds ratios (PORs) for "ever asthma", following adjustment for gender, age, parental education, passive smoke exposure, type of indoor heating, and parental asthma, were 1.28 (95% confidence interval (95% CI) 0.20-7.98), 2.14 (95% CI 0.40-11.3) and 5.81 (95% CI 1.27-26.5), when each of two communities with low, regular and high NO2, respectively, were compared with the two communities with very low NO2. For symptoms "wheeze" (adjusted PORs for increased NO2: 1.47, 1.23 and 2.27) and "cough apart from colds" (adjusted PORs for increased NO2: 1.49, 1.93 and 2.07), a similar trend was seen. In this study a significant relationship was observed between traffic-related nitrogen dioxide and the prevalence of asthma and symptoms. Whether this association is causal has to be tested in longitudinal studies.
Effect of mindfulness training on asthma quality of life and lung function: a randomised controlled trial
Authors: Lori Pbert, J Mark Madison, Susan Druker, Nicholas Olendzki, Robert Magner, George Reed, Jeroan Allison, James Carmody
Journal: Thorax (2012)

<h3>Background</h3> This study evaluated the efficacy of a mindfulness training programme (mindfulness-based stress reduction (MBSR)) in improving asthma-related quality of life and lung function in patients with asthma. <h3>Methods</h3> A randomised controlled trial compared an 8-week MBSR group-based programme (n=42) with an educational control programme (n=41) in adults with mild, moderate or severe persistent asthma recruited at a university hospital outpatient primary care and pulmonary care clinic. Primary outcomes were quality of life (Asthma Quality of Life Questionnaire) and lung function (change from baseline in 2-week average morning peak expiratory flow (PEF)). Secondary outcomes were asthma control assessed by 2007 National Institutes of Health/National Heart Lung and Blood Institute guidelines, and stress (Perceived Stress Scale (PSS)). Follow-up assessments were conducted at 10 weeks, 6 and 12 months. <h3>Results</h3> At 12 months MBSR resulted in clinically significant improvements from baseline in quality of life (differential change in Asthma Quality of Life Questionnaire score for MBSR vs control: 0.66 (95% CI 0.30 to 1.03; p&lt;0.001)) but not in lung function (morning PEF, PEF variability and forced expiratory volume in 1 s). MBSR also resulted in clinically significant improvements in perceived stress (differential change in PSS score for MBSR vs control: −4.5 (95% CI −7.1 to −1.9; p=0.001)). There was no significant difference (p=0.301) in percentage of patients in MBSR with well controlled asthma (7.3% at baseline to 19.4%) compared with the control condition (7.5% at baseline to 7.9%). <h3>Conclusions</h3> MBSR produced lasting and clinically significant improvements in asthma-related quality of life and stress in patients with persistent asthma, without improvements in lung function. <h3>Clinical Trial Registration Number</h3> Asthma and Mindfulness-Based Reduction (MBSR) Identifier: NCT00682669. clinicaltrials.gov.
REPORT of a CASE of HERNIA of the LUNG, with REMARKS
Authors: C. F. Wightman
Journal: BMJ (1898)

LUNG.'[THz BRIrfg 365 the mitral orifice measured 3A inches or less.If the measure- ment exceeded 3i inches (2 fingers), the stenosis was con- sidered doubtful, and neglected.The stenosed orifice ex- ceeded 24 inches (I finger) in circumference in io8 instances, and measured 24 inches (i finger) or less in 85.It is not clear from the statistics in which of tlle two catalogues 3 cases should be included.Of the 196 cases, I07 were females and 89 males.
GENETICS OF NON-INSULIN-DEPENDENT (TYPE-II) DIABETES MELLITUS
Authors: C. Ronald Kahn, M.D, David Vicent, M.D, Alessandro Doria, M.D., Ph.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Both genetic and environmental factors contribute to the etiology of non-insulin-dependent diabetes. The genetic component is heterogeneous and in some patients is probably complex, involving multiple genes. Specific genetic defects have been identified for rare monogenic forms of NIDDM: maturity-onset diabetes of the young, or MODY (which is due to glucokinase mutations in about 40% of families), syndromes of extreme insulin resistance (which often involve the insulin receptor), and diabetes-deafness syndromes (with defects in mitochondrial genes). In contrast, the genes involved in common forms of NIDDM are still uncertain. Mutations have been extensively searched in genes regulating insulin signaling and secretion. Some evidence of involvement has been produced for insulin-receptor substrate-1, glycogen synthase, the glucagon receptor, a ras-related protein (Rad), histocompatibility antigens, PC-1, and fatty acid binding protein, but the contribution of these genes to NIDDM is probably small. Other candidate genes (e.g. insulin, insulin receptor, glucose transporters) have been excluded as major diabetogenes. New insights are expected in the near future from the systematic scanning of the genome for linkage with NIDDM.