tbuckley/cabot-search huggingface dataset:
Clinical Findings and Lung Pathology in Children with Cystic Fibrosis
Authors: Refika Hamutcu, Jon M. Rowland, Monica V. Horn, Cornelia Kaminsky, Eithne F. MacLaughlin, Vaughn A. Starnes, Marlyn S. Woo
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Cystic fibrosis pulmonary disease is assessed by pulmonary function tests, arterial blood gases, and chest X-rays, but the correlation with lung pathology is unknown. We reviewed the clinical findings and lung pathology of 21 cystic fibrosis patients who had lung transplant. Pulmonary function tests, Brasfield scores, arterial blood gases, and age were correlated with lung pathology. All patients had severe Brasfield scores (9.0 ± 3.2), airways obstruction (FEV1 25.6 ± 5.6% predicted, FEF25–75% 11.0 ± 4.5% predicted), and hyperinflation (residual volume [RV] 341.8 ± 75.8% predicted). All patients were hypoxemic (PO2 64.2 ± 8.2 mm Hg), and 5 of 21 (24%) were hypercapneic (PCO2 > 50 mm Hg). Pulmonary function tests and Brasfield scores were within a narrow range, and did not allow correlation with lung pathology. Small airway density (airways < 2 mm/cm2) decreased with increasing age. There were no differences in small airways inflammation and fibrous narrowing between the hypercapneic and nonhypercapneic patients, but the percent of smallest airways (airways < 0.35 mm) was significantly lower in the hypercapneic group. We conclude that there is significant correlation between airway pathology and increased age and CO2 retention. We speculate that decreased small airway density in older patients and the decreased proportion of smallest airways in hypercapneic patients is caused by increased dilatation of small airways.
Weekly combination of non-pegylated liposomal doxorubicin and taxane in first-line breast cancer: wALT trial (phase I–II)
Authors: M S Rosati, C Raimondi, G Baciarello, P Grassi, S Giovannoni, E Petrelli, M L Basile, M Girolami, M Di Seri, L Frati
Journal: Annals of Oncology (2010)
Proteolysis of connexin43-containing gap junctions in normal and heat-stressed cardiac myocytes
Authors: J Laing
Journal: Cardiovascular Research (1998)

Objective: The present studies were performed to examine the degradation of connexin43-containing gap junctions by the lysosome or the proteasome in normal and heat-stressed cultures of neonatal rat ventricular myocytes. Methods: Primary cultures were prepared from neonatal rat ventricular myocytes. Connexin43 was detected by immunoblotting, immunofluorescence, or immunoprecipitation. Gap junction profiles were detected by transmission electron microscopy. Results: Immunoblots of whole cell lysates demonstrated increased levels of connexin43 in cultures treated with lysosomal inhibitors (chloroquine, leupeptin, E-64, or ammonium chloride) or proteasomal inhibitors (lactacystin or ALLN). Pulse-chase experiments showed that the half-life of connexin43 was 1.4 h in control cultures, but was prolonged to 2.0 or 2.8 h in cultures treated with chloroquine or lactacystin, respectively. Immunofluorescence and electron microscopy showed a significant increase in the number of gap junction profiles in myocytes treated with either chloroquine or lactacystin. Heat treatment of cultures (43.5°C for 30 min) produced a rapid loss of connexin43 as detected by immunoblotting or immunofluorescence. Heat-induced connexin43 degradation was prevented by simultaneous treatment with lactacystin, ALLN, or chloroquine. Connexin43 levels and distribution returned to normal by 3 h following a heat shock and were resistant to a subsequent repeat heat stress. The heat shock also led to production of HSP70 as detected by immunoblotting. Conclusions: These data suggest that Cx43 gap junctions in myocytes are degraded by the proteasome and the lysosome, that this proteolysis can be augmented by heat stress, and that inducible factors such as HSP70 may protect against Cx43 degradation.
Immunogenicity and Safety of a Combination Pneumococcal-Meningococcal Vaccine in Infants
Authors: Jim P. Buttery, Anna Riddell, Jodie McVernon, Tracey Chantler, Laura Lane, Jane Bowen-Morris, Linda Diggle, Rhonwen Morris, Anthony Harnden, Steven Lockhart, Andrew J. Pollard, Keith Cartwright, E. Richard Moxon
Journal: JAMA (2005)

OF IMMUNOgenic vaccines against major encapsulated pathogens of childhood has dramatically decreased the rates of invasive disease caused by Haemophilus influenzae type b, serogroup C Neisseria meningitidis, and Streptococcus pneumoniae in the developed countries fortunate enough to be able to afford the vaccines.Since the introduction of a monovalent serogroup C meningococcal glycoconjugate vaccine (MenC) into the UK routine immunization schedule in November 1999, group C meningococcal disease has decreased by 87% in the ages targeted for vaccination, with estimated vaccine efficacy of 90%. 1 Within 2 years of the introduction of a 7-valent pneumococcal glycoconjugate vaccine into the recommended infant schedule in the United States, there was
The Tumor Metastasis Suppressor Gene <i>Drg-1</i> Down-regulates the Expression of Activating Transcription Factor 3 in Prostate Cancer
Authors: Sucharita Bandyopadhyay, Ying Wang, Rui Zhan, Sudha K. Pai, Misako Watabe, Megumi Iiizumi, Eiji Furuta, Sonia Mohinta, Wen Liu, Shigeru Hirota, Sadahiro Hosobe, Taisei Tsukada, Kunio Miura, Yukio Takano, Ken Saito, Therese Commes, David Piquemal, Tsonwin Hai, Kounosuke Watabe
Journal: Cancer Research (2006)

The tumor metastasis suppressor gene Drg-1 has been shown to suppress metastasis without affecting tumorigenicity in immunodeficient mouse models of prostate and colon cancer. Expression of Drg-1 has also been found to have a significant inverse correlation with metastasis or invasiveness in various types of human cancer. However, how Drg-1 exerts its metastasis suppressor function remains unknown. In the present study, to elucidate the mechanism of action of the Drg-1 gene, we did a microarray analysis and found that induction of Drg-1 significantly inhibited the expression of activating transcription factor (ATF) 3, a member of the ATF/cyclic AMP-responsive element binding protein family of transcription factors. We also showed that Drg-1 attenuated the endogenous level of ATF3 mRNA and protein in prostate cancer cells, whereas Drg-1 small interfering RNA up-regulated the ATF3 expression. Furthermore, Drg-1 suppressed the promoter activity of the ATF3 gene, indicating that Drg-1 regulates ATF3 expression at the transcriptional level. Our immunohistochemical analysis on prostate cancer specimens revealed that nuclear expression of ATF3 was inversely correlated to Drg-1 expression and positively correlated to metastases. Consistently, we have found that ATF3 overexpression promoted invasiveness of prostate tumor cells in vitro, whereas Drg-1 suppressed the invasive ability of these cells. More importantly, overexpression of ATF3 in prostate cancer cells significantly enhanced spontaneous lung metastasis of these cells without affecting primary tumorigenicity in a severe combined immunodeficient mouse model. Taken together, our results strongly suggest that Drg-1 suppresses metastasis of prostate tumor cells, at least in part, by inhibiting the invasive ability of the cells via down-regulation of the expression of the ATF3 gene.
The safety of maximal exercise testing.
Authors: L Gibbons, S N Blair, H W Kohl, K Cooper
Journal: Circulation (1989)

Previous reports on the safety of exercise testing have been based on surveys from different testing facilities with a variety of testing protocols and patient types. From 1971 through 1987, 71,914 maximal exercise tests conducted in a population with a low prevalence of known coronary heart disease under uniform conditions at a single medical facility resulted in six major cardiac complications including one death. No complications have occurred in the past 10 years in 45,000 maximal tests. The overall cardiac complication rate in men and women is 0.8 complications per 10,000 tests with 95% confidence intervals of 0.3-1.9 complications per 10,000 tests. Maximal exercise testing appears safer than some previously published reports have suggested and seems to be getting safer with time.
An association between ADH protein levels and polymorphic nucleotide variation in the Adh gene of Drosophila melanogaster.
Authors: P Matthew, A Agrotis, A C Taylor, S W McKechnie
Journal: Molecular Biology and Evolution (1992)

Southern analysis of the Adh region of 212 Drosophila melanogaster lines collected from the Tahbilk winery revealed linkage disequilibrium between a 37-bp insertion [designated delta 2 by Kreitman (1983)] and the fast electrophoretic variant of alcohol dehydrogenase (ADH-F). Among these lines 34% contained the insert and encoded ADH-F, 33.5% encoded ADH-F and did not have the insert, and 32.5% encoded the slow electrophoretic variant of alcohol dehydrogenase (ADH-S). Strong linkage association between this insert and ADH-F is evident worldwide. Twenty-nine of the second chromosome lines were characterized for ADH protein quantity by using radial immunodiffusion. ADH quantity was estimated in both larvae and adult males raised in the presence and absence of alcohol supplement to each of two different food media. Analyses of variance indicated higher levels of ADH protein in larvae from lines with the insert (all ADH-F), compared with those without (both ADH-F and ADH-S), independent of either dietary alcohol or media type. No such difference in ADH quantity between insert- and noninsert-containing ADH-F lines was detected in adults, although the expected higher levels occurred in ADH-F lines compared with ADH-S lines. Given the high levels of linkage disequilibrium in the Adh region, these data suggest that either polymorphic nucleotide-site variants positively associated with delta 2 on the second chromosome or delta 2 itself increases larval levels of ADH protein.
Emergence of Pseudomonas aeruginosa strains producing metallo-β-lactamases of the IMP-15 and VIM-2 types in Mexico
Authors: F. Quinones-Falconi, M. Galicia-Velasco, P. Marchiaro, M.A. Mussi, V. Ballerini, A.J. Vila, A.M. Viale, K. Bermejo-Morales, A.S. Limansky
Journal: Clinical Microbiology and Infection (2009)
THE EFFECT OF HEAT, pH AND ORGANIC SOLVENTS ON THE ELECTRICAL IMPEDANCE AND PERMEABILITY OF EXCISED HUMAN SKIN
Authors: A. C. ALLENBY, J. FLETCHER, C. SCHOCK, T. F. S. TEES
Journal: British Journal of Dermatology (1969)

SUMMARY.— The permeability of excised human skin to dimethyl sulphoxide and the effects of this solvent on water permeability are described. The results of measurements of the electrical impedance of excised human skin both before and after chemical and heat treatments are also given. Stratum corneum is shown to undergo irreversible structural changes when heated above 65°C. or incubated in aqueous media at pH < 3 or > 9. Simultaneous measurements of water permeability and electrical impedance of skin samples subjected to treatments with dimethyl sulphoxide, detergents and surfactants show that there is a good correlation (coefficient ‐ 0·78) between the two quantities. Some organic solvents including aliphatic acids, bases, and neutral compounds are shown to produce large changes in electrical impedance, and hence, it is inferred, in water permeability. It is suggested that these changes are due to solution of skin components, loosening of the skin structure, and hence swelling and hydration of the skin. The solvent induced changes in water permeability provide an explanation for the accelerating effect of the solvents on the penetration rates of topically applied drugs.
Targeting EGFR signalling in chronic lung disease: therapeutic challenges and opportunities
Authors: Sabari Vallath, Robert E. Hynds, Laura Succony, Sam M. Janes, Adam Giangreco
Journal: European Respiratory Journal (2014)

Chronic respiratory diseases, including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD) and lung cancer, are the second leading cause of death among Europeans. Despite this, there have been only a few therapeutic advances in these conditions over the past 20 years. In this review we provide evidence that targeting the epidermal growth factor receptor (EGFR) signalling pathway may represent a novel therapeutic panacea for treating chronic lung disease. Using evidence from human patient samples, transgenic animal models, and cell and molecular biology studies we highlight the roles of this signalling pathway in lung development, homeostasis, repair, and disease ontogeny. We identify mechanisms underlying lung EGFR pathway regulation and suggest how targeting these mechanisms using new and existing therapies has the potential to improve future lung cancer, COPD and pulmonary fibrosis patient outcomes.
Secretin Effects on Cerebellar-Dependent Motor Learning in Schizophrenia
Authors: Amanda R. Bolbecker, William P. Hetrick, Jason K. Johannesen, Brian F. O’Donnell, Joseph E. Steinmetz, Anantha S. Shekhar
Journal: American Journal of Psychiatry (2009)

Pervasive cognitive deficits in schizophrenia are a major cause of disability among individuals with the disorder. One such deficit is the loss of effective associative learning, which is readily assessed via eye-blink conditioning procedures. The authors examined the efficacy of secretin, a hormonal agonist for the prototype group B G-protein-coupled receptors, in ameliorating eye-blink conditioning deficits in schizophrenia patients.Immediately following a pretreatment delay eye-blink conditioning recording session, 25 individuals with schizophrenia received either secretin (RG1068; 20 microg/kg [N=15]) or a saline placebo (20 microg/kg [N=10]) subcutaneously in a double-blind fashion. Comparison groups were formed by yoking pairs of subjects on the basis of performance during the pretreatment baseline eye-blink conditioning recording session, and thus 20 subjects underwent further analysis. Secretin was selected because eye-blink conditioning depends on the release of Purkinje cell inhibition on deep nuclei of the cerebellum and recent findings indicate that secretin is endogenously released in the cerebellum, where it acts as a retrograde messenger and neuromodulator on basket and Purkinje cells.Eye-blink conditioning was significantly improved at 2 and 24 hours after secretin administration but not after treatment with placebo. These results are consistent with evidence of intracellular signaling abnormalities in the pathophysiology of schizophrenia and indicate a possible role for secretin in modulating cerebellar-mediated classically conditioned learning.If cerebellar abnormalities in individuals with schizophrenia are associated with fundamental mechanisms and symptoms of the disorder, as suggested by the cognitive dysmetria model, then cerebellar-targeted treatments may provide a novel approach to treatment for schizophrenia.
Serum branched-chain amino acid to histidine ratio: a novel metabolomic biomarker of knee osteoarthritis
Authors: Guangju Zhai, Rui Wang-Sattler, Deborah J Hart, Nigel K Arden, Alan J Hakim, Thomas Illig, Tim D Spector
Journal: Annals of the Rheumatic Diseases (2010)

Objective There is a pressing need to develop reliable molecular biomarkers in osteoarthritis. The aim of the study was to identify novel serum biomarkers for osteoarthritis using a metabolomics approach. Methods A two-stage study design was utilised. 123 knee osteoarthritis cases and 299 controls were selected from the TwinsUK cohort as a discovery sample. 76 knee osteoarthritis cases and 100 controls from the Chingford Study were used as replication. Knee osteoarthritis was defined as either radiographic, medically diagnosed or total knee joint replacement due to primary osteoarthritis. All the subjects were unrelated white women. Their serum samples were assessed for targeted metabolite profiling by electrospray ionisation tandem mass spectrometry using the AbsoluteIDQ kit. 163 serum metabolites were assessed and their concentrations obtained. The ratios of metabolite concentrations as proxies for enzymatic reaction rates were calculated and tested for the association with knee osteoarthritis. Significance was assessed after adjustment for multiple testing (Bonferroni method) and potential confounders. Results In the discovery stage, the authors identified 14 ratios significantly associated with knee osteoarthritis with p≤1.9×10 −6 . Two of these 14 ratios were successfully confirmed in the replication stage—the ratios of valine to histidine and xleucine to histidine, with p=0.002. The significance remained after adjustment for age and body mass index. Conclusion This is the first serum-based metabolomic study of osteoarthritis in humans. The branched-chain amino acids to histidine ratio has potential clinical use as an osteoarthritis biomarker and shows the clinical potential of metabolomics.
Risk estimation in familial adenomatous polyposis using DNA probes linked to the familial adenomatous polyposis gene.
Authors: D J Koorey, G W McCaughan, R J Trent, N D Gallagher
Journal: Gut (1992)

The familial adenomatous polyposis gene has recently been assigned to the long arm of chromosome five through linkage to several 5q DNA probes. These probes can now be used to trace inheritance of the disease gene in affected families. In this study, DNA samples from 152 members of 10 Australian familial adenomatous polyposis families have been examined for restriction fragment length polymorphisms detected by DNA probes C11P11, ECB27, and YN5.48. Linkage analysis confirmed linkage between the familial adenomatous polyposis gene and each probe with a maximum combined LOD score of 2.82 for C11P11, 2.90 for ECB27 and 5.49 for YN5.48 all at a recombination fraction of zero. Risk estimates were determined for the 51 at risk individuals in these families based on their restriction fragment length polymorphism data alone or in addition by including the effect of age dependent penetrance. Thirty two of those at risk (63%) could be assigned specific high (greater than or equal to 95%) or low (less than or equal to 5%) risks of developing familial adenomatous polyposis on the basis of their probe results. When the effect of age dependent penetrance was included, 26 (51%) fell at the extremes of risk (greater than or equal to 99% or less than or equal to 1%). Such estimates provide a sound basis for planning sigmoidoscopic screening of at risk family members and will thus facilitate surveillance in familial adenomatous polyposis families.
Functional evaluation of sympathetic and parasympathetic system in Chagas' disease using dynamic exercise
Authors: LOURENÇO GALLO, JOSÉ MORELO FILHO, BENEDITO C MACIEL, JOSÉ A MARIN NETO, LUIZ E BARRETO MARTINS, EUCLYDES C LIMA FILHO
Journal: Cardiovascular Research (1987)

Ten normal subjects and 14 patients with chronic Chagas' disease (seven with and seven without heart disease) underwent dynamic exercise on a cycle ergometer. Heart rate (HR), pulmonary ventilation (V), oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ) were measured. Increasing workloads (25, 50, 100, and 150 W) were applied for 4 min and intercalated with resting periods. The main objective of this protocol was to analyse heart rate response in relation to the other cardiorespiratory variables in order to evaluate the functional conditions of the sympathetic and parasympathetic cardiac efferents. Analysis of the results showed that (a) the group of chagasic patients with heart disease had lower heart rates (p less than 0.05) than normal subjects during the initial 10 s (delta HR 0-10 s) of effort (fast component); (b) the difference between the normal subjects and chagasic patients without heart disease was not statistically significant; (c) the abnormalities in heart rate response were due to depression of parasympathetic efferent action on the sinus node; (d) the slow heart rate response (delta HR 1-4 min), which expresses the degree of sympathetic stimulation of the sinus node, was comparable in the three groups studied, thus showing unimpaired adrenergic responses during dynamic exercise in Chagas' disease; and (e) the V, VO2, VCO2, and RQ values were normal at all workloads in each group, suggesting that vagal dysfunction does not affect oxygen transport at these submaximal levels of dynamic exercise.
Four-drug combination chemotherapy (methotrexate, cyclophosphamide, hexamethylmelamine, and CCNU) for non-small cell bronchogenic carcinoma: a Cancer and Leukemia Group B study.
Authors: M Green, C Horton, M Spaulding, R T Silver, J Berenberg, B J Kennedy, T F Pajak, R Comis
Journal: Journal of Clinical Oncology (1983)

Ninety-eight evaluable patients with nonresectable regional or metastatic non-small cell bronchogenic carcinoma were treated with a four-drug combination chemotherapy program of methotrexate, cyclophosphamide, hexamethylmelamine, and CCNU (MCHC). Fifteen partial or complete responses (15%) were obtained, all but one of which occurred in good performance status (0-1) patients. While "responders lived longer than non-responders", this was due more to initial performance status among responding patients than to achievement of partial (greater than 50%) or complete disease regression. Evaluation of those patients with good performance status (PS 0-1), indicated no statistically significant differences in median survival time for complete response and partial response patients compared to patients with "improved" or "stable" disease status in this group. This combination of modestly active single agents produced disappointing results in our lung cancer population. A search for more active single agents in lung cancer is necessary.
Prevention Trials: Their Place in How We Understand the Value of Prevention Strategies
Authors: Graham A. Colditz, Philip R. Taylor
Journal: Annual Review of Public Health (2010)

Several key factors bear on the interpretation of prevention trials and observational studies that inform prevention strategies. These factors include the underlying disease process and aspects of the intervention: sustainability of behavior change, the time course of the intervention within the disease process, dose and duration of exposure needed to effect risk reduction, durability of the impact of intervention, and methodological problems in implementing and interpreting randomized trials and observational studies to evaluate prevention strategies. The question asked through an intent-to-treat analysis of a randomized controlled trial (RCT) differs from that in the observational setting. Furthermore, the long duration necessary to conduct prevention trials and the resulting lack of adherence to therapy can bias results toward the null. A broader range of approaches to evaluate prevention interventions and programs with improved knowledge synthesis and translation to public health practice will speed our progress toward achieving public health and prevention of chronic diseases.