tbuckley/cabot-search huggingface dataset:
Familial Aggregation of Suicide Explained by Cluster B Traits: A Three-Group Family Study of Suicide Controlling for Major Depressive Disorder
Authors: Alexander McGirr, Martin Alda, Monique Séguin, Sophie Cabot, Alain Lesage, Gustavo Turecki
Journal: American Journal of Psychiatry (2009)

There is substantial evidence suggesting that suicide aggregates in families. However, the extent of overlap between the liability to suicide and psychiatric disorders, particularly major depressive disorder, remains an important issue. Similarly, factors that account for the familial transmission of suicidal behavior remain unclear. Thus, through direct and blind assessment of first-degree relatives, the authors conducted a family study of suicide by examining three proband groups: probands who committed suicide in the context of major depressive disorder, living depressed probands with no history of suicidal behavior, and psychiatrically normal community comparison probands.Participants were 718 first-degree relatives from 120 families: 296 relatives of 51 depressed probands who committed suicide, 185 relatives of 34 nonsuicidal depressed probands, and 237 relatives of 35 community comparison subjects. Psychopathology, suicidal behavior, and behavioral measures were assessed via interviews.The relatives of probands who committed suicide had higher levels of suicidal behavior (10.8%) than the relatives of nonsuicidal depressed probands (6.5%) and community comparison probands (3.4%). Testing cluster B traits as intermediate phenotypes of suicide showed that the relatives of depressed probands who committed suicide had elevated levels of cluster B traits; familial predisposition to suicide was associated with increased levels of cluster B traits; cluster B traits demonstrated familial aggregation and were associated with suicide attempts among relatives; and cluster B traits mediated, at least in part, the relationship between familial predisposition and suicide attempts among relatives. Analyses were repeated for severity of attempts, where cluster B traits also met criteria for endophenotypes of suicide.Familial transmission of suicide and major depression, while partially overlapping, are distinct. Cluster B traits and impulsive-aggressive behavior represent intermediate phenotypes of suicide.
The Proapoptotic Molecule BLID Interacts with Bcl-XL and Its Downregulation in Breast Cancer Correlates with Poor Disease-Free and Overall Survival
Authors: Constantinos G. Broustas, Jeffrey S. Ross, Qifeng Yang, Christine E. Sheehan, Rebecca Riggins, Anne-Michelle Noone, Bassem R. Haddad, Françoise Seillier-Moiseiwitsch, Bhaskar V.S. Kallakury, Bruce G. Haffty, Robert Clarke, Usha N. Kasid
Journal: Clinical Cancer Research (2010)

Abstract Purpose: BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer. Experimental Design: The interaction between BLID and Bcl-XL was examined using in vitro transcription/translation, coimmunoprecipitation, and immunoflourescence assays. The relationship between BLID mRNA expression and pathologic measures in breast cancer specimens (n = 55) was examined using the publicly available ONCOMINE microarray database. Immunohistochemistry was done using formalin-fixed, paraffin-embedded sections of 148 cases of invasive ductal breast carcinomas (IDC) and 58 cases of invasive lobular breast carcinomas, and breast tissue microarrays representing additional 437 cases (&amp;gt;85% IDC) with associated clinicopathologic database and long-term clinical follow-up (median 7 years). Results: BLID was found to interact with Bcl-XL, and the binding was enhanced in cancer cells exposed to doxorubicin or cisplatin. Exogenous expression of BLID correlated with activation of Bax and an increase in cytosolic cytochrome c. BLID mRNA expression was significantly reduced in grade 3 relative to grade 1 and 2 breast cancer (P = 0.023). Cytoplasmic BLID immunoreactivity was absent in IDC compared with invasive lobular breast carcinoma (P &amp;lt; 0.001). Lack of BLID expression was associated with younger age (median 40 years), African American ethnicity, tumor size, and triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative; all P &amp;lt; 0.005). Significant correlations were observed between BLID negativity and declines in overall, cause-specific, and local relapse-free survival (all P &amp;lt; 0.03). Multivariate analysis indicated that BLID is an independent prognostic factor of distant metastasis-free survival (hazard ratio, 0.302; 95% confidence interval, 0.160-0.570, P = 0.0002). Conclusion: BLID is a new binding partner of Bcl-XL and a significant prognostic factor in breast cancer. Clin Cancer Res; 16(11); 2939–48. ©2010 AACR.
Screening for Thyroid Disease in Children With IDDM
Authors: Malachi J McKenna, Raymonde Herskowitz, Joseph I Wolfsdorf
Journal: Diabetes Care (1990)

The aim of this study was to evaluate the usefulness of screening for thyroid disease by performing thyroid function tests and measuring thyroid autoantibodies in 371 children and adolescents with insulin-dependent diabetes mellitus (IDDM). We analyzed clinical data and results of serum thyroxine, triiodothyronine uptake, thyroid-stimulating hormone, and antibodies to thyroid microsomal antigen and thyroglobulin. Goiter was noted in 20% of subjects. Thyroid-specific autoantibody was positive in 19% of subjects. Twenty-seven subjects (7%) had thyroid dysfunction. Autoantibody testing identified subjects with thyroid dysfunction with a sensitivity of 50%, a specificity of 84%, a degree of misclassification of 17%, a positive predictive value of 13%, and a negative predictive value of 97%. We recommend that all children and adolescents be screened shortly after diagnosis of IDDM by determination of thyroid-stimulating hormone (measured by high-sensitivity assay) to identify thyroid dysfunction and by testing for antibody to thyroid microsomal antigen to characterize both risk of future thyroid dysfunction and the need for future testing.
Cyanide and uncoupling protein function: reply
Authors: W. Martinet, T. J.L. Van De Parre, G. R.Y. De Meyer
Journal: Cardiovascular Research (2008)

We would like to thank Dr Eduardo Rial for the interest in our study and acknowledge his critical comment that sodium cyanide is not an appropriate compound to mimic the thermogenic properties of uncoupling protein 2 (UCP2). UCP2 uncouples adenosine triphosphate (ATP) production from mitochondrial respiration and thereby converts the loss of potential energy in heat production.1 In our study, we describe cyanide as a ‘well-known uncoupler of mitochondrial respiration’,2 which assumes a similar mode of action as that of UCP2. As pointed out correctly by Dr Rial, sodium cyanide is not a classical uncoupling agent such as the carbonyl cyanide derivatives carbonyl …
Occupational asthma in an electronics factory.
Authors: P S Burge, W Perks, I M O'Brien, R Hawkins, M Green
Journal: Thorax (1979)

Workers in a modern electronics factory were surveyed by questionnaire and lung function testing to see if there was evidence of widespread work-related respiratory symptoms. Of the responding workers exposed to solder flux fumes on the shop floor, 22% had work-related breathlessness or wheeze or both. Exposed workers had a lower FEV1 and FVC than unexposed workers. Work-related rhinitis was also present in 22% of exposed workers. The most likely cause for these results is sensitivity to colophony fumes, released from solder flux during soldering. Levels of solder flux fume were below the threshold limit value in this factory during the survey.
Successful valve replacement for aortic incompetence in rheumatoid arthritis with vasculitis.
Authors: M Liew, D Wilson, D Horton, A Fleming
Journal: Annals of the Rheumatic Diseases (1979)

A patient with rheumatoid arthritis (RA), vasculitis, and aortic valve incompetence of the histologically nonspecific type is described. Valve replacement was undertaken, and an excellent haemodynamic result was achieved. Both arthritis and vasculitis subsequently remitted. Valve replacement can be successfully performed in RA despite active vasculitis.
Perceived key injury risk factors in World Cup alpine ski racing—an explorative qualitative study with expert stakeholders
Authors: Jörg Spörri, Josef Kröll, Günter Amesberger, Ollie M Blake, Erich Müller
Journal: British Journal of Sports Medicine (2012)

Background There is limited knowledge about key injury risk factors in alpine ski racing, particularly for World Cup (WC) athletes. Objective This study was undertaken to compile and explore perceived intrinsic and extrinsic risk factors for severe injuries in WC alpine ski racing. Methods Qualitative study. Interviews were conducted with 61 expert stakeholders of the WC ski racing community. Experts’ statements were collected, paraphrased and loaded into a database with inductively derived risk factor categories (Risk Factor Analysis). At the end of the interviews, experts were asked to name those risk factors they believed to have a high potential impact on injury risk and to rank them according to their priority of impact (Risk Factor Rating). Results In total, 32 perceived risk factors categories were derived from the interviews within the basic categories Athlete, Course, Equipment and Snow. Regarding their perceived impact on injury risk, the experts’ top five categories were: system ski, binding, plate and boot; changing snow conditions; physical aspects of the athletes; speed and course setting aspects and speed in general. Conclusions Severe injuries in WC alpine ski racing can have various causes. This study compiled a list of perceived intrinsic and extrinsic risk factors and explored those factors with the highest believed impact on injury risk. Hence, by using more detailed hypotheses derived from this explorative study, further studies should verify the plausibility of these factors as true risk factors for severe injuries in WC alpine ski racing.
A Generation Time Effect on the Rate of Molecular Evolution in Invertebrates
Authors: Jessica A. Thomas, John J. Welch, Robert Lanfear, Lindell Bromham
Journal: Molecular Biology and Evolution (2010)

The rate of genome evolution varies significantly between species. Evidence is growing that at least some of this variation is associated with species characteristics, such as body size, diversification rate, or population size. One of the strongest correlates of the rate of molecular evolution in vertebrates is generation time (GT): Species with faster generation turnover tend to have higher rates of molecular evolution, presumably because their genomes are copied more frequently and therefore collect more DNA replication errors per unit time. But the GT effect has never been tested for nonvertebrate animals. Here, we present the first general test of the GT effect in invertebrates, using 15 genes from 143 species spread across the major eumetazoan superphyla (including arthropods, nematodes, molluscs, annelids, platyhelminthes, cnidarians, echinoderms, and urochordates). We find significant evidence that rates of molecular evolution are correlated with GT in invertebrates and that this effect applies consistently across genes and taxonomic groups. Furthermore, the GT effect is evident in nonsynonymous substitutions, whereas theory predicts (and most previous evidence has supported) a relationship only in synonymous changes. We discuss both the practical and theoretical implications of these findings.
Influence of obesity on pulmonary function (PF) in severe asthmatic children
Authors: Verόnica Giubergia, Verόnica Aguerre, Silvia Caíno, Hebe Gonzalez Pena
Journal: European Respiratory Journal (2011)

While there have been reports in adults evaluating the effects of obesity on PF tests, in severe asthmatic children studies are scarce.   Aim:  To evaluate the influence of obesity on PF in children with asthma.   Methods:  39 children (41% male) with controlled severe asthma with and without obesity, and 22 non asthmatic obese patients (59% male) were included. Patients were divided according to asthma diagnosis (NIH guidelines) and to Body Mass Index (BMI) cut off (IOTF): Group 1 asthma with normal weight, G2 asthma with obesity and G3 obesity without asthma. Spirometry and plethysmography were performed in all patients. Considered parameters were FVC, FEV 1 , FEV 1 /FVC, FMMF, TLC (total lung capacity), FRC (functional residual capacity), RV (residual volume) and sGaw (specific airway conductance). BMI corrected for age and sex and BMI z-score were assessed. PF between G1, 2 and 3 were compared. (ANOVA. Pearson correlation)   Results:  Mean age (SD), G1: 12 (3), G2: 12 (3), G3: 11.8 (3) (NS).  A significant inverse correlation between BMI z-score and FRC (r -0.5, p 0.001) and RV (r -0.4, p 0.006) was found between asthmatic patients.   Conclusion:  Obesity might influence PF decreasing FRC and RV despite of asthma diagnosis.
Cl- secretion in a model intestinal epithelium induced by a neutrophil-derived secretagogue.
Authors: J L Madara, C Parkos, S Colgan, R J MacLeod, S Nash, J Matthews, C Delp, W Lencer
Journal: Journal of Clinical Investigation (1992)

A secreted product of activated neutrophils, NDS (neutrophil-derived secretagogue), elicits a short circuit current (Isc) in epithelial monolayers derived from the human intestinal cell line T84 (J. Clin. Invest. 1991. 87:1474-1477). Here, we identify and characterize the source of this Isc and examine associated signaling pathways. 125I efflux studies suggested that NDS activates an anion conductive channel. Bidirectional 22Na 36Cl flux studies showed that electrogenic Cl- secretion fully accounts for the NDS-induced Isc response. NDS behaved in many respects as a cAMP-mediated secretagogue: NDS did not further increase maximal cAMP-induced Cl- secretion; NDS potentiated Ca(2+)-mediated Cl secretion; and NDS elicited measurable 125I but not 86Rb effluxes. However, NDS did not elicit a detectable rise in intracellular cAMP. Such data suggest that NDS may elicit Cl- secretion by effecting distal events in the cAMP-mediated pathway. Data derived from cell volume assays of isolated guinea pig intestinal crypt cells indicated that NDS also directly elicits Cl- secretion from natural intestinal epithelia. Additionally, since NDS activity is released from PMN by stimuli normally present in the colonic lumen, since NDS is active when applied apically to this model intestinal epithelium, and since the NDS-elicited Isc response is indicative of electrogenic chloride secretion, we speculate NDS may contribute to the secretory diarrhea encountered in many patients with inflammatory intestinal disease.
Reciprocal expression of tumour-associated carbohydrate antigens (Tn/sTn) and nuclear factor-B serves as an indicator of the prognosis of oral squamous cell carcinoma
Authors: Chi-Yu Lin, Shin Nieh, Jacqueline Whang-Peng, Jaulang Hwang
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts To determine whether expression of tumour-associated carbohydrate antigens (Tn/sTn) and a representative inflammation marker, nuclear factor-B (NF-B), is related to the invasiveness of oral squamous cell carcinoma (OSCC) by correlating these markers with the well-established
Bronchial asthma: pathophysiological mechanisms and corticosteroids
Authors: Svend Norn, Paul Clementsen
Journal: Allergy (1988)

The clinical effects in asthma of corticosceroids can be ascribed to their strong anti‐inflammatory action. The pathophysiology of asthma is complex. A diversity of mediators and interactions between mediators and between mediators and various cell types enhances and maintains the inflammatory process in the airways resulting in severe asthma. This is a vicious circle. Penetration through the airway epithelium of allergens and other insulting particles trigger release of inflammatory mediators and neurotransmitters, which, by chemotaxis and activation of inflammatory cells, results in enhanced and prolonged mediator release. Several of these mediators possess tissue‐toxic properties enhancing the airway inflammation. The glucocorticoids have several points of action affecting both mediator release and accumulation and activation of inflammatory cells, which explains their favourable effect in asthma.
High Rate of BRAF and RET/PTC Dual Mutations Associated with Recurrent Papillary Thyroid Carcinoma
Authors: Ying C. Henderson, Thomas D. Shellenberger, Michelle D. Williams, Adel K. El-Naggar, Mitchell J. Fredrick, Kathleen M. Cieply, Gary L. Clayman
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, usually possesses BRAF mutation or rearranged in translation (RET)/PTC rearrangements. PTC usually possesses BRAF mutation or RET/PTC rearrangements. The mutation status of patients with recurrent PTC has never been characterized in a large population. Experimental Design: Mutation status was determined in a cohort of 54 patients with recurrent PTC and analyzed for clinicopathologic relationships. BRAF and ras mutations were determined by PCR and sequencing of genomic DNA. RET/PTC rearrangements were analyzed by reverse transcription-PCR. Results: BRAF mutation in exon 15 (V600E) was found in 42/54 (77.8%) recurrent PTC patients. The RET/PTC rearrangements were detected in 9 of 54 (16.7%) patients. In addition, 5 of 54 (9.3%) recurrent PTC patients had both a BRAF mutation and a RET/PTC rearrangement. The prevalence of tumors with dual mutations found in the recurrent population far exceeds the frequency historically reported for patients with primary PTC. Patients with dual mutations were significantly older (80% older than 45 years) than patients with a BRAF mutation alone (38% older than 45 years). Conclusions: Recurrent PTC is significantly associated with a predominant BRAF mutation. RET/PTC rearrangements, although commonly associated with primary PTCs in younger patients, are uncommonly found in recurrent PTC patients. In addition, the incidence of dual mutations was higher in patients with recurrent PTC than in those primary PTC, as reported by others.
Characterization of a spontaneous disease of white leghorn chickens resembling progressive systemic sclerosis (scleroderma).
Authors: M E Gershwin, H Abplanalp, J J Castles, R M Ikeda, J van der Water, J Eklund, D Haynes
Journal: The Journal of Experimental Medicine (1981)

University of California, Davis (UCD) line 200 White Leghorn Chickens spontaneously develop a syndrome that has many analogous features to human progressive systemic sclerosis. This syndrome is characterized by progressive involution of comb, dermal fibrosis, and distal polyarthritis. These three features occur within 6 wk after hatching, and are accompanied by a 40% mortality as a result of vaso-occlusive disease, with development of secondary infection of peripheral gangrenous lesions. Birds that survive greater than 2 mo after hatching progressively develop fibrosis of the esophagous and mononuclear infiltration of heart and kidney, with prominent occlusion of small and medium sized blood vessels. In addition, line 200 chickens develop rheumatoid factors, antinuclear antibodies, and antibodies to collagen, but do not have antibodies to thymocytes, DNA, or extractable nuclear antigens. Moreover, antinuclear antibodies when studied using HEp-2 cells as substrate demonstrate predominantly a speckled pattern. This syndrome of line 200 chickens is not detectable in F1 crosses to several UCD inbred lines. F1 X parental line BC1 backcrosses have an approximately 50% incidence of disease, suggesting that this syndrome is inherited as autosomal recessive. However, only 4% of F2 generation birds show abnormal symptoms, suggesting the presence of modifying genes. There is no appearance of IgG deposition, as determined by immunofluorescence, in either skin, blood vessels, esophagus, or heart. However, approximately 20% of chickens have a glomerulonephritis; this feature appears to be a terminal event and does not appear clinically significant. Although this syndrome of line 200 chickens has several features that are in sharp distinction to human scleroderma, the presence of common immunologic and pathologic denominators suggest that this spontaneous disease may be an appropriate model to develop a better understanding of autoimmune connective tissue diseases.
Effects of long-term administration of erythromycin on cytokine production in rat alveolar macrophages
Authors: Y Sugiyama, K Yanagisawa, SI Tominaga, S Kitamura
Journal: European Respiratory Journal (1999)

Low-dose long-term erythromycin treatment has recently been reported to be very effective in patients with chronic respiratory infection and inflammation. This effect of erythromycin was thought to be not antibacterial but anti-inflammatory. However, the exact mechanism of the effect of erythromycin has not yet been clarified. The aims of this study were to investigate the effects of erythromycin on cytokine production and its mechanisms of actions in rat alveolar macrophages. Using rats with or without administration of erythromycin for 3 months, the production of the cytokines tumour necrosis factor-or (TNF-alpha), cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2alpha by enzyme-linked immunosorbent assay and the expression of TNF-alpha and CINC-1 messenger ribonucleic acid (mRNA) by Northern blotting in rat alveolar macrophages were analysed. CINC-1 is the rat counterpart of human interleukin-8, and CINC-2alpha of human macrophage inflammatory peptide-2. Erythromycin reduced cytokine production and secretion when cytokines was induced by lipopolysaccharide treatment. Conversely, erythromycin slightly upregulated the expression of cytokine mRNA. These results suggest that erythromycin inhibits cytokine production and exhibits anti-inflammatory effects by means of a translational and/or posttranslational mechanism.