tbuckley/cabot-search huggingface dataset:
Predicting Non-Completion of Treatment for Latent Tuberculous Infection
Authors: Fred K. Shieh, Graham Snyder, C. Robert Horsburgh, John Bernardo, Claire Murphy, Jussi J. Saukkonen
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Treatment of latent tuberculosis (TB) infection (LTBI) is essential for the elimination of TB in the United States, but treatment is often not completed. Little is known about patients' reasons for not completing treatment. We hypothesized that certain health beliefs, lifestyle, and clinic- and regimen-related barriers to provision of care could predict non-completion of LTBI treatment.Methods: We administered a survey in English, Chinese, or Spanish to patients with LTBI at the first TB clinic visit. Using χ2 and logistic regression analysis, we assessed demographics, TB risk factors, and survey responses as predictors of non-completion of 6 mo of isoniazid.Results: 217 patients, 90% foreign-born, completed the survey, and 28.6% of which finished at least 6 mo of isoniazid under usual clinic conditions. Multivariate analysis identified two independent predictors of non-completion: low risk perception of progressing to active TB without LTBI treatment (odds ratio [OR], 0.31 [0.13–0.72], 95% confidence interval [CI]), p = 0.007, accounting for 20% of non-completers, and not wanting venipuncture (OR, 0.43 [0.22–0.85], 95% CI), p = 0.015, accounting for 37% of non-completers. Another 18% shared both predictors; thus these two predictors accounted for 75% of non-completers in total.Conclusions: Patients assess LTBI treatment risks and inconveniences relative to low perceived benefits at treatment outset. Predictors of LTBI treatment non-completion are identifiable at the first visit. Targeting TB high-risk individuals, minimizing inconveniences, further education, and use of diagnostic tests with improved specificity for TB may address these concerns.
VACCINATION AGAINST YELLOW FEVER WITH IMMUNE SERUM AND VIRUS FIXED FOR MICE
Authors: W. A. Sawyer, S. F. Kitchen, Wray Lloyd
Journal: The Journal of Experimental Medicine (1932)

1. After preliminary experiments in monkeys, 15 persons were actively immunized by a single injection of a dried mixture of living yellow fever virus, fixed for mice, and human immune serum, with separate injections of enough additional serum to make up the amount required for protection. 2. One person was similarly immunized by injecting immune serum and dried virus separately. 3. By titration of the sera of vaccinated persons in mice, it was shown that the immunity rose in a few weeks to a height comparable to that reached after an attack of yellow fever, and remained there throughout an observation period of 6 months. 4. Yellow fever virus could not be recovered from the blood of vaccinated persons or monkeys, except when the latter had received less than the minimal effective amount of immune serum. 5. Neutralization of yellow fever virus by immune serum took place very slowly in vitro at room temperature in our experiments, and could not have been an appreciable factor in vaccination with the serum virus mixtures. 6. A mixture of fixed virus and immune serum retained its immunizing power for 8 months when dried in the frozen state and sealed in glass. 7. It appears that the immunizing reaction after yellow fever vaccination was a part of a true infectious process, as was also the observed leucopenia.
Sodium channel genes in pain-related disorders: phenotype–genotype associations and recommendations for clinical use
Authors: Stephen G Waxman, Ingemar S J Merkies, Monique M Gerrits, Sulayman D Dib-Hajj, Giuseppe Lauria, James J Cox, John N Wood, C Geoffrey Woods, Joost P H Drenth, Catharina G Faber
Journal: The Lancet Neurology (2014)
Bcl-2 Inhibits Nuclear Homologous Recombination by Localizing BRCA1 to the Endomembranes
Authors: Corentin Laulier, Aurélia Barascu, Josée Guirouilh-Barbat, Gaëlle Pennarun, Catherine Le Chalony, François Chevalier, Gaëlle Palierne, Pascale Bertrand, Jean Marc Verbavatz, Bernard S. Lopez
Journal: Cancer Research (2011)

Genetic stability requires coordination of a network of pathways including DNA repair/recombination and apoptosis. In addition to its canonical anti-apoptotic role, Bcl-2 negatively impacts genome stability. In this study, we identified the breast cancer tumor suppressor BRCA1, which plays an essential role in homologous recombination (HR), as a target for Bcl-2 in the repression of HR. Indeed, ionizing radiation-induced BRCA1 foci assembly was repressed when Bcl-2 was expressed ectopically, in human SV40 fibroblasts, or spontaneously, in lymphoma t(14:18) cells and in HeLa and H460 cancer cell lines. Moreover, we showed that the transmembrane (TM) domain of Bcl-2 was required for both inhibition of BRCA1 foci assembly and the inhibition of HR induced by a double-strand break targeted into an intrachromosomal HR substrate by the meganuclease I-SceI. Fluorescence confocal microscopy, proximity ligation assay, and electron microscopy analyses as well as Western blot analysis of subcellular fractions showed that Bcl-2 and BRCA1 colocalized to mitochondria and endoplasmic reticulum in a process requiring the TM domain of Bcl-2. Targeting BRCA1 to the endomembranes depletes BRCA1 from the nucleus and, thus, accounts for the inhibition of HR. Furthermore, our findings support an apoptosis-stimulatory role for the cytosolic form of BRCA1, suggesting a new tumor suppressor function of BRCA1. Together, our results reveal a new mode of BRCA1 regulation and for HR in the maintenance of genome stability.
Laugier–Hunziker syndrome: a report of three cases and literature review
Authors: Wen-Mei Wang, Xiang Wang, Ning Duan, Hong-Liu Jiang, Xiao-Feng Huang
Journal: International Journal of Oral Science (2012)

Laugier–Hunziker syndrome (LHS) is an acquired pigmentary condition affecting lips, oral mucosa and acral area, frequently associated with longitudinal melanonychia. There is neither malignant predisposition nor underlying systemic abnormality associated with LHS. Herein, we present three uncommon cases of LHS with possibly new feature of nail pigmentation, which were diagnosed during the past 2 years. We also review the clinical and histological findings, differential diagnosis, and treatment of the syndrome in published literature.
Glucose-Regulated Protein 78 Controls Cross-talk between Apoptosis and Autophagy to Determine Antiestrogen Responsiveness
Authors: Katherine L. Cook, Ayesha N. Shajahan, Anni Wärri, Lu Jin, Leena A. Hilakivi-Clarke, Robert Clarke
Journal: Cancer Research (2012)

Abstract While more than 70% of breast cancers express estrogen receptor-α (ER+), endocrine therapies targeting these receptors often fail. The molecular mechanisms that underlie treatment resistance remain unclear. We investigated the potential role of glucose-regulated protein 78 (GRP78) in mediating estrogen resistance. Human breast tumors showed increased GRP78 expression when compared with normal breast tissues. However, GRP78 expression was reduced in ER+ breast tumors compared with HER2-amplifed or triple-negative breast tumors. ER+ antiestrogen-resistant cells and ER+ tumors with an acquired resistant antiestrogen phenotype were both shown to overexpress GRP78, which was not observed in cases of de novo resistance. Knockdown of GRP78 restored antiestrogen sensitivity in resistant cells, and overexpression of GRP78 promoted resistance in sensitive cells. Mechanistically, GRP78 integrated multiple cellular signaling pathways to inhibit apoptosis and stimulate prosurvival autophagy, which was dependent on TSC2/AMPK-mediated mTOR inhibition but not on beclin-1. Inhibition of autophagy prevented GRP78-mediated endocrine resistance, whereas caspase inhibition abrogated the resensitization that resulted from GRP78 loss. Simultaneous knockdown of GRP78 and beclin-1 synergistically restored antiestrogen sensitivity in resistant cells. Together, our findings reveal a novel role for GRP78 in the integration of cellular signaling pathways including the unfolded protein response, apoptosis, and autophagy to determine cell fate in response to antiestrogen therapy. Cancer Res; 72(13); 3337–49. ©2012 AACR.
Growth factor-like activity of gliadin, an alimentary protein: implications for coeliac disease
Authors: M. V Barone, A. Gimigliano, G. Castoria, G. Paolella, F. Maurano, F. Paparo, M. Maglio, A. Mineo, E. Miele, M. Nanayakkara, R. Troncone, S. Auricchio
Journal: Gut (2006)

<b>Background:</b> Gliadins, a family of wheat proteins, are central to the pathogenesis of celiac disease (CD). In addition to ‘immunogenic’ effects, gliadin directly affects cultured cells and intestine preparations, and produces damage in vivo, via a separate ‘toxic’ peptide, such as A-gliadin p31–43 (P31–43). <b>Aims:</b> Understanding the molecular mechanisms underlying direct non T-cell mediated effects of gliadin peptides, and assessing their potential role in promoting CD. <b>Method:</b> Gliadin effects were tested on a number of cell lines and on cultured mucosa samples by evaluating cytoskeleton rearrangements, endocytosis, proliferation and apoptosis. Standard biochemical methods were used to assess prolonged epidermal growth factor receptor (EGFR) activation. <b>Results:</b> Crude gliadin peptic-tryptic peptides (PTG], or P31–43 alone, fully reproduce the effects of epidermal growth factor (EGF] on actin cytosketon, cell cycle and cell proliferation of various cell lines. Inhibitor studies demonstrate the role of EGFR in the early response to gliadin exposure, pointing to activation of the EGFR pathway. Peptide P31–43 is not similar to any EGFR ligand, but can delay inactivation of the EGFR interfering with its endocytosis. Gliadin-induced delay of EGFR endocytosis in cultured intestinal biopsies, together with S-phase entry of epithelial intestinal cells, confirm a role for EGFR activation in CD. <b>Conclusion:</b> The ability of gliadin peptides to delay EGFR inactivation through interference with the endocytic pathway suggests a model where gliadin fragments amplify the effects of trace amounts of EGF, and possibly of other growth factors, by prolonging receptor activation. The results, using cultures of coeliac intestinal biopsies, highlight the role of the EGF pathway in establishing and maintaining the typical atrophic and proliferative alterations of the small intestine in CD.
Neural Autoantibody Clusters Aid Diagnosis of Cancer
Authors: Erika S. Horta, Vanda A. Lennon, Daniel H. Lachance, Sarah M. Jenkins, Carin Y. Smith, Andrew McKeon, Christopher Klein, Sean J. Pittock
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Clustering of neural autoantibodies in patients with paraneoplastic neurologic disorders may predict tumor type. A mathematical analysis of neural autoantibody clusters was performed in 78,889 patients undergoing evaluation for a suspected paraneoplastic autoimmune neurologic disorder. Tumor predictive autoantibody profiles were confirmed in sera from patients with histologically proven tonsillar cancer, thymoma, and lung cancer. Patients and Methods: Of note, 78,889 patient sera were tested for 15 defined neural autoantibodies (1.2 million tests). The observed and hypothesized frequencies of autoantibody clusters were compared and their tumor associations defined. A tumor validation study comprised serum from 368 patients with a variety of tumors (thymoma, lung, or tonsil). Results: Informative oncological associations included (i) thymoma in 85% of patients with muscle striational, acetylcholine receptor antibodies plus CRMP5 autoantibodies; (ii) lung carcinoma in 80% with both P/Q-type and N-type calcium channel antibodies plus SOX1-IgG; and (iii) in men, prostate carcinoma frequency more than doubled when striational and muscle AChR specificities were accompanied by ganglionic AChR antibody. In women, amphiphysin-IgG alone was associated commonly with breast carcinoma, but amphiphysin-IgG, coexisting with antineuronal nuclear autoantibody-type 1 or CRMP5-IgG, was associated with lung cancer (P &amp;lt; 0.0001). In the validation cohorts, many tumor-associated profiles were encountered that matched the clusters identified in the screening study (e.g., 15% of thymoma patients had striational, acetylcholine receptor antibodies plus collapsin response-mediator protein-5 autoantibodies). Conclusions: Neural autoantibodies commonly coexist in specific clusters that are identifiable by comprehensive screening. Signature autoantibody clusters may predict a patient's cancer risk and type. Clin Cancer Res; 20(14); 3862–9. ©2014 AACR.
An Outbreak of Conjunctivitis Due to Atypical<i>Streptococcus pneumoniae</i>
Authors: Michael Martin, John H. Turco, Michael E. Zegans, Richard R. Facklam, Samir Sodha, John A. Elliott, John H. Pryor, Bernard Beall, Dean D. Erdman, Yolanda Y. Baumgartner, Paul A. Sanchez, Joseph D. Schwartzman, José Montero, Anne Schuchat, Cynthia G. Whitney
Journal: New England Journal of Medicine (2003)

In February 2002, clinicians at the Dartmouth College Health Service recognized an outbreak of conjunctivitis; cultures of conjunctival swabs implicated Streptococcus pneumoniae. An investigation was begun to determine the extent of the outbreak, confirm the cause, identify modes of transmission, and implement control measures.
Comparative context analysis of codon pairs on an ORFeome scale
Authors: Gabriela Moura, Miguel Pinheiro, Raquel Silva, Isabel Miranda, Vera Afreixo, Gaspar Dias, Adelaide Freitas, José L Oliveira, Manuel AS Santos
Journal: Genome biology (2005)

Abstract Codon context is an important feature of gene primary structure that modulates mRNA decoding accuracy. We have developed an analytical software package and a graphical interface for comparative codon context analysis of all the open reading frames in a genome (the ORFeome). Using the complete ORFeome sequences of Saccharomyces cerevisiae , Schizosaccharomyces pombe , Candida albicans and Escherichia coli , we show that this methodology permits large-scale codon context comparisons and provides new insight on the rules that govern the evolution of codon-pair context.
Aldosterone-Induced Serum and Glucocorticoid-Induced Kinase 1 Expression Is Accompanied by Nedd4-2 Phosphorylation and Increased Na+ Transport in Cortical Collecting Duct Cells
Authors: Sandra Y. Flores, Dominique Loffing-Cueni, Elena Kamynina, Dorothée Daidié, Carole Gerbex, Sting Chabanel, Jean Dudler, Johannes Loffing, Olivier Staub
Journal: Journal of the American Society of Nephrology (2005)

Aldosterone plays a central role in Na+ homeostasis by controlling Na+ reabsorption in the aldosterone-sensitive distal nephron involving the epithelial Na+ channel (ENaC). Part of the effects of aldosterone is mediated by serum and glucocorticoid-induced kinase 1 (Sgk1), a Ser/Thr kinase whose expression is rapidly induced by aldosterone and that increases in heterologous expression systems ENaC cell surface abundance and activity. Previous work in Xenopus laevis oocytes suggested that Sgk1 phosphorylates specific residues (Ser212 and Ser328) on the ubiquitin-protein ligase Nedd4-2, an enzyme that directly interacts with ENaC and negatively controls channel density at the plasma membrane. It further indicated that phosphorylation of Nedd4-2 led to impairment of ENaC/Nedd4-2 interaction and consequently to more channels at the cell surface. These data suggested a novel mode of aldosterone-dependent action, yet this was not demonstrated formally in epithelial cells that physiologically express ENaC. Here it is shown, with the use of an anti-phospho-Ser328-mNedd4-2 antibody, that 2 to 6 h of aldosterone treatment induces an increase in Nedd4-2 phosphorylation, both in a mouse cortical collecting duct cell line (mpkCCDcl4) and in kidneys of adrenalectomized rats. This augmentation, which is accompanied by a raise in Sgk1 expression and transepithelial Na+ transport, is sensitive to phosphatidylinositol-3 kinase inhibition, as is Sgk1 phosphorylation and Na+ transport. Hence, these data provide evidence in cortical collecting duct cells in vitro and in vivo that Sgk1-dependent phosphorylation of Nedd4-2 is part of the aldosterone response.
Gastrin and the ultrastructure of G cells in the fasting rat.
Authors: N J Mortensen, J F Morris, C Owens
Journal: Gut (1979)

The effect of fasting on serum and antral gastrin concentrations and G cell ultrastructure in the rat has been examined using a radioimmunoassay and quantitative electron microscopy. Serum gastrin levels in fasting animals were markedly reduced and there was also a significant decrease in antral gastrin concentrations after 48 hours and 72 hours of fasting. This was associated with a significant fall in the granule content and cytloplasmic volume of individual G cells, at its greatest by 48 hours. A relative absence of electron dense granules in the Golgi zones of cells from animals fasted for 72 hours suggested a paucity of newly formed granules, but fasting produced no detectable change in the electron density of the granule population taken as a whole. The results indicate that, during fasting, release and then synthesis of gastrin is inhibited, so that granule stores and cell size diminish. The correlation between the granule content of G cells and the antral content of gastrin suggests that hormone release occurs by exocytosis, rather than by any change in the content of individual granules.
Comparative analysis of the predictive utility of clinical disease severity scores for non-cystic fibrosis bronchiectasis
Authors: Melissa McDonnell, Pieter Goeminne, Stefano Alberti, John Davison, Sara Lonni, Lucy Poppelwell, Waleed Salih, Alberto Pesci, Tom Fardon, Lieven Dupont, Adam Hill, Anthony De Soyza, James Chalmers
Journal: European Respiratory Journal (2014)

Background: Non-cystic fibrosis bronchiectasis is a multidimensional disease associated with increased morbidity and mortality. Two composite disease-specific clinical prediction tools have been developed and validated, the Bronchiectasis Severity Index (BSI) and FACED score; both objectively stratify patients into risk categories to predict the probability of mortality and other clinical outcomes.  Methods: The utility of the BSI and FACED to predict mortality and hospital admission rates across overall and risk-stratified groups in five international cohorts and combined meta-analysis was assessed using the area under the receiver operator characteristic curve (AUC). An AUC>0.8 is considered excellent.  Results: All cohorts totalled 1310 patients: median age 66 yrs (IQ range 57-75), 43.1% male, all-cause mortality 9.7%, hospitalisation rate 31.3%. Mortality rates ranged from 1.9%(Monza) to 16.6%(Leuven) with a range in hospitalisation from 26.6%(Dundee) to 45.3%(Newcastle). The AUC for BSI vs. FACED-predicted mortality was 0. 80 vs. 0.73(Edinburgh), 0.84 vs. 0.74(Dundee), 0.82 vs. 0.68(Newcastle) and 0.81 vs. 0.78(Leuven). The AUC for BSI vs. FACED-predicted hospitalisation was 0.88 vs. 0.70(Edinburgh), 0.82 vs. 0.63(Dundee), 0.80 vs. 0.56(Newcastle) and 0.88 vs. 0.63(Monza). Categorisation by risk in meta-analysis and individual cohorts showed the BSI to be superior to FACED in predicting both outcomes.  Conclusion: The BSI scored consistently higher than FACED across combined, total individual and risk-stratified patient groups with a higher discriminative ability in calculating the probability of mortality and hospital admissions in bronchiectasis patients.
On the Use of Stem-Pessaries
Authors: J. G. Black
Journal: BMJ (1887)

and quadriceps extensor, and is attached to the condyles of the femur and the tuberosities ofthetibia.The rectusfemorisand the vasti areattached, the rectus to the upper part, and the vasti to the sides, of the patella.From these, tendinous fibres pass across the patella, and become continu- ous with the ligamentum patellhT.In fact, the patella is regarded by many anatomists as a sesamoid bone developed in the tendon of the quadriceps extensor muscle, which is inserted into the tubercle of the tibia.The external and internal lateral ligaments are inserted nearer the back than the front of the knee-joint.Bearing these important noints in mind, I humbly submit that the
Interstitial fibrosis and growth factors.
Authors: J A Lasky, A R Brody
Journal: Environmental Health Perspectives (2000)

Interstitial pulmonary fibrosis (IPF) is scarring of the lung caused by a variety of inhaled agents including mineral particles, organic dusts, and oxidant gases. The disease afflicts millions of individuals worldwide, and there are no effective therapeutic approaches. A major reason for this lack of useful treatments is that few of the molecular mechanisms of disease have been defined sufficiently to design appropriate targets for therapy. Our laboratory has focused on the molecular mechanisms through which three selected peptide growth factors could play a role in the development of IPF. Hundreds of growth factors and cytokines could be involved in the complex disease process. We are studying platelet-derived growth factor because it is the most potent mesenchymal cell mitogen yet described, transforming growth factor beta because it is a powerful inducer of extracellular matrix (scar tissue) components by mesenchymal cells, and tumor necrosis factor alpha because it is a pleiotropic cytokine that we and others have shown is essential for the development of IPF in animal models. This review describes some of the evidence from studies in humans, in animal models, and in vitro, that supports the growth factor hypothesis. The use of modern molecular and transgenic technologies could elucidate those targets that will allow effective therapeutic approaches.
Folate and vitamin B-12 and risk of fatal cardiovascular disease: cohort study from Busselton, Western Australia
Authors: J. Hung
Journal: BMJ (2003)

To test the hypothesis that the incidence of fatal coronary heart disease and cardiovascular disease in a general population is related to serum and red cell folate and vitamin B-12 concentrations.Cohort study with follow up of 29 years.Busselton, Western Australia.1419 men and 1531 women aged 20 to 90 years, who were alive more than three years after their participation in the 1969 Busselton health survey. 2314 (78.4%) had no cardiovascular disease at the initial survey.Hazard ratios for fatal coronary heart disease and cardiovascular disease in men and women according to baseline concentrations of serum and red cell folate and serum vitamin B-12.213 men and 159 women died from coronary heart disease, and 342 men and 302 women died from cardiovascular disease. Serum and red cell folate concentrations showed a moderate positive correlation (r=0.26, P<0.001) but otherwise serum and red cell folate and serum B-12 concentrations were not strongly correlated with each other or with other standard risk factors. After age and standard risk factors were adjusted for, there was no independent association between folate and B-12 concentrations and death from coronary heart disease or cardiovascular disease in the full cohort or the subcohort with no cardiovascular disease at baseline. The multivariate adjusted hazard ratio for death from cardiovascular disease in the lowest versus the highest category of red cell folate concentration was 1.05 (95% confidence interval 0.77 to 1.43) in men and 1.10 (0.81 to 1.51) in women.These findings do not support the hypothesis that lower folate and B-12 concentrations increase the risk of fatal cardiovascular disease in a general population. The routine use of these vitamins for preventing cardiovascular disease should await evidence from clinical trials.