tbuckley/cabot-search huggingface dataset:
Coexpression of Connexins 40 and 43 Enhances the pH Sensitivity of Gap Junctions
Authors: Hong Gu, Jose F. Ek-Vitorin, Steven M. Taffet, Mario Delmar
Journal: Circulation Research (2000)

Gap junctions are formed by oligomerization of a protein called connexin. Most cells express more than one connexin isotype. Atrial myocytes, for example, coexpress connexin (Cx) 40 and Cx43. The consequence of connexin coexpression on the regulation of gap junctions is not well understood. In the present study, we show that cells coexpressing Cx40 and Cx43 are more susceptible to acidification-induced uncoupling than those cells expressing only one connexin isotype. Xenopus oocytes were injected with mRNA for Cx40, Cx43, or a combination of both. Intracellular pH and junctional conductance were simultaneously measured while cells were progressively acidified by superfusion with a bicarbonate-buffered solution gassed with increasing concentrations of carbon dioxide. The data show that the pKa (ie, the pH at which junctional conductance decreased to 50% from maximum) shifted from approximately 6.7 when cells expressed only Cx40 or only Cx43 to approximately 7.0 when one of the oocytes was coexpressing both connexins. Truncation of the carboxyl terminal domains of the connexins caused the loss of pH sensitivity even after coexpression. The data are interpreted on the basis of previous studies from our laboratory that demonstrated heterodomain interactions in the regulation of Cx40 and Cx43 gap junctions. The possible implications of these findings on the regulation of native gap junctions that express both connexins remain to be determined.
Reporting on quality of life in randomised controlled trials: bibliographic study
Authors: C. Sanders, M. Egger, J. Donovan, D. Tallon, S. Frankel
Journal: BMJ (1998)

<b>Objectives</b> : To examine the frequency and quality of reporting on quality of life in randomised controlled trials. <b>Design</b> : Search of the Cochrane Controlled Trials Register 1980 to 1997 to identify trials from all disciplines, from oncology, and from cardiovascular medicine that reported on quality of life. Assessment of abstracts from articles published from 1993 to 1996. Assessment of a sample of full reports with a standardised instrument. <b>Main outcome measures</b> : Prevalence of reporting on quality of life. Conditions and interventions studied in trials reporting on quality of life. Quality of reporting on quality of life. <b>Results</b> : During 1980-97 reporting on quality of life increased from 0.63% to 4.2% for trials from all disciplines, from 1.5% to 8.2% for cancer trials, and from 0.34% to 3.6% for cardiovascular trials. Of 364 abstracts, 65% reported on drug interventions. Of a sample of 67 full reports, authors of 48 (72%) used 62 established quality of life instruments. In 15 reports (22%) authors developed their own measures, and in 2 (3%) methods were unclear. Response rates were given in 38 (57%), and complete reporting on all items and scales occurred in 31 (46%) <b>Conclusions</b> : Less than 5% of all randomised controlled trials reported on quality of life, and this proportion was below 10% even for cancer trials. A plethora of instruments was used in different studies, and the reporting of methods and results was often inadequate. Standards for the measurement and reporting of quality of life in clinical trials research need to be developed.
Non-enterobacterial endotoxins stimulate human coronary artery but not venous endothelial cell activation via Toll-like receptor 2
Authors: C ERRIDGE, C SPICKETT, D WEBB
Journal: Cardiovascular Research (2006)

To determine whether non-enterobacterial endotoxins, which are likely to constitute the majority of the circulating endotoxin pool, may stimulate coronary artery endothelial cell activation.Interleukin-8 secretion, monocyte adhesion, and E-selectin expression were measured in human umbilical vein endothelial cells (HUVECs) and coronary artery endothelial cells (HCAECs) challenged in vitro with highly purified endotoxins of common host colonisers Escherichia coli, Porphyromonas gingivalis, Pseudomonas aeruginosa, and Bacteroides fragilis. HCAECs but not HUVECs expressed Toll-like receptor (TLR)-2 and were responsive to non-enterobacterial endotoxins. Transfection of TLR-deficient HEK-293 cells with TLR2 or TLR4/MD2 revealed that while E. coli endotoxin utilised solely TLR4 to signal, the endotoxins, deglycosylated endotoxins (lipid-A), and whole heat-killed bacteria of the other species stimulated TLR2-but not TLR4-dependent cell-signalling. Blockade of TLR2 with neutralizing antibody prevented HCAEC activation by non-enterobacterial endotoxins. Comparison of each endotoxin with E. coli endotoxin in limulus amoebocyte lysate assay revealed that the non-enterobacterial endotoxins are greatly underestimated by this assay, which has been used in all previous studies to estimate plasma endotoxin concentrations.Circulating non-enterobacterial endotoxins may be an underestimated contributor to endothelial activation and atherosclerosis in individuals at risk of increased plasma endotoxin burden.
ACE inhibitors and hypoglycaemia
Authors: T.W. van Haeften, N. Kong, A. Bates, R.E.J. Ryder, MichaelD. Feher, Stephanie Amiel, AndrewP. Davie, I.H.M. Wildenborg, J. Veenstra, P.H.J. van der Voort, W.P. Verdegaal, J. Silberbusch, R.M.C. Herings, A. de Boer, B.H. Ch Stricker, H.G.M. Leufkens, A.J. Porsius
Journal: The Lancet (1995)
COX-2 expression during early lung squamous cell carcinoma oncogenesis
Authors: C. Mascaux, B. Martin, J-M. Verdebout, V. Ninane, J-P. Sculier
Journal: European Respiratory Journal (2005)

Cyclooxygenase (COX)-2 is implicated in the oncogenesis of many cancers, and COX-2 inhibitors are effective in preventing the development of tumours, such as in colon cancer. Its expression is increased in nonsmall cell lung cancer and is associated with poor prognosis. The present study assessed COX-2 expression in normal bronchial epithelium, as well as in all the putative precursors of squamous cell carcinomas. COX-2 expression was studied by immunohistochemistry in 106 biopsies collected during autofluorescence bronchoscopy in consecutive patients at high-risk for lung cancer. All biopsies corresponding to normal epithelium or low-grade lesions (lesions up to moderate dysplasia) did not show increased COX-2 expression. Lesions were positive for COX-2 in eight out of 14 severe dysplasia patients, eight out of 14 in situ carcinomas and five out of eight invasive carcinomas. A strong statistically significant difference in COX-2 expression was found between normal epithelium or low-grade lesions and high-grade lesions (severe dysplasia or worse). The positive and negative predictive values of COX-2 expression for high-grade lesion were 100% and 82.35%, respectively. In conclusion, bronchial precursors of squamous cell carcinoma showed increased cyclooxygenase-2 expression and were segregated into low- versus high-grade with a high positive predictive value. Thus, cyclooxygenase-2 appears as a potential early marker of squamous cell carcinoma.
Effects of isoproterenol on regional myocardial function, electrogram, and blood flow in conscious dogs with myocardial ischemia.
Authors: S F Vatner, R W Millard, T A Patrick, G R Heyndrickx
Journal: Journal of Clinical Investigation (1976)

The effects of coronary occlusion and of subsequent isoproterenol infusion were examined in conscious dogs. Left ventricular (LV) function was assessed by measurements of LV diameter, pressure, velocity and dP/dt/P, and regional myocardial function was assessed by measurements of segment length (SL) and velocity of SL shortening in normal, border, and ischemic zones. Regional myocardial function was measured from the same sites, along with intramyocardial electrograms and regional myocardial blood flow as determined by radioactive microspheres. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reductions and graded increases in ST segment elevation. Isoproterenol improved overall LV function, and function in the normal zone. Isoproterenol also improved function in 19 of 21 border-zone segments and in all moderately ischemic segments, while elevating further the ST segments. These changes were accompanied by increases in myocardial blood flow. In contrast, in severely ischemic segments, isoproterenol resulted in a deterioration of function, in that paradoxical motion occurred in segments previously akinetic during systole, while paradoxical motion was intensified in those segments in which it was already present. These changes were accompanied by further ST segment elevation but not by concurrent increases in blood flow. In addition, in 2 of 21 border zone segments, myocardial blood flow fell and these segments responded to isoproterenol with complete loss of function; paradoxical motion developed. Thus, in the conscious dog, a strong inotropic agent can improve function, even in the ischemic myocardium, as long as the required additional blood flow can be provided wither through primary or collateral channels.
Role of acrosomal matrix proteases in sperm-zona pellucida interactions
Authors: A. Honda
Journal: Human Reproduction Update (2002)

The roles of acrosomal matrix proteases in sperm–zona pellucida interactions have long been one of the most puzzling questions in mammalian fertilization. Of the acrosomal proteases identified, acrosin exhibits two distinct activities: (i) an enzymatic activity as a trypsin-like serine protease; and (ii) a lectin-like carbohydrate-binding activity. Thus, acrosin has been postulated to function both in the limited proteolysis of the zona pellucida, and in the maintenance of binding of acrosome-reacted sperm to the zona. However, analysis of acrosin-deficient mouse sperm demonstrates that this protein is not essential for sperm–zona pellucida interactions, including the sperm penetration of the zona pellucida. Acrosin is presumably involved in the limited proteolysis and/or processing of other proteins in the acrosome and on the membranes during the acrosome reaction at least in the mouse, although the serine protease system in mouse sperm is very different from those in sperm of other rodent species. It is concluded that membranous proteases rather than acrosomal proteases may play an important role(s) in the sperm–zona pellucida interactions.
Expression of the Bric-a-Brac Tramtrack Broad Complex Protein NAC-1 in Cervical Carcinomas Seems to Correlate with Poorer Prognosis
Authors: Shamima Yeasmin, Kentaro Nakayama, Masako Ishibashi, Atsuko Katagiri, Kouji Iida, Indri Nuryani Purwana, Naomi Nakayama, Kohji Miyazaki
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Recent studies have suggested a novel oncogenic role of a bric-a-brac tramtrack broad complex (also known as POZ) domain gene, NAC-1, in ovarian carcinomas. The aim of this study was to clarify the functional role of NAC-1 in human cervical carcinomas. Experimental Design: NAC-1 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. NAC-1 gene knockdown using small interfering RNA and a NAC-1 gene transfection system were used to asses NAC-1 function in cervical cancer in vivo. Results: Immunohistochemical and gene expression analysis revealed that NAC-1 is significantly overexpressed in cervical adenocarcinomas and adenosquamous carcinomas compared with squamous cell carcinomas. Patients with squamous cell carcinomas positive for NAC-1 expression who received radiotherapy had significantly shorter overall survival than peers whose tumors did not express NAC-1, and multivariate analysis showed that NAC-1 expression was an independent prognostic factor for overall survival after radiotherapy. Overexpressions of the NAC-1 gene stimulated cell proliferation in cervical carcinoma cells of the TCS, CaSki, and HeLa P3 lines, which do not have endogenous NAC-1 expression. NAC-1 gene knockdown inhibited cell growth and induced apoptosis in HeLa, HeLa TG, and ME180 cells, all of which overexpressed NAC-1. Conclusions: Our findings suggest that NAC-1 may play an important role in cervical carcinomas; moreover, these findings provide a rationale for future development of NAC-1–based therapy for cervical carcinomas that overexpress this candidate oncogene.
Illuminating the role of type I IFNs in colitis
Authors: Stefan Wirtz, Markus F. Neurath
Journal: Journal of Clinical Investigation (2005)

Recently, type I interferons IFN-α and IFN-β (IFN-α/β) have been evaluated in pilot clinical trials for the treatment of active ulcerative colitis. However, the underlying mechanisms that may contribute to a potential therapeutic effect are incompletely understood. A new study in this issue demonstrates a protective role for IFN-α/β, induced by activation of a Toll-like receptor 9–dependent pathway, in a rodent model of experimental colitis.
Retraction: A Genetically Enhanced Anaerobic Bacterium for Oncopathic Therapy of Pancreatic Cancer
Authors: Z. Li, J. Fallon, J. Mandeli, J. Wetmur, S. L. C. Woo
Journal: JNCI Journal of the National Cancer Institute (2010)

To the Editor: It was discovered that some of the micrographs in two papers we published [figure 4 in J Natl Cancer Inst 2008;100:1389–1400 (1), and figure 3 in Hum Gene Ther 2009;20:751–758 (2)] are apparently duplicated. This has been reported to the institutional research integrity committee by the authors and while the outcome of an investigation is pending, the undersigned co-authors respectfully request a retraction of both papers and sincerely apologize to our colleagues.

Background: A major obstacle in treatment of solid tumors is the inefficient delivery of therapeutic agents to the hypoxic cores. Hypoxia offers the potential for anaerobic bacteria colonization and tumor destruction by the bacteria, and dormant spores of wild-type Clostridium perfringens (Cp) germinate and proliferate within the hypoxic cores of pancreatic tumors in mice. However, the oncopathic effects of Cp were limited by host inflammatory responses and by Cp’s residual tolerance to oxygen, which caused toxic effects in animals.

Methods: Recombinant Cp strains in which superoxide dismutase, a major oxygen tolerance gene, was deleted (Cp/sod−) were constructed to enhance its selective growth in tumors. In addition, Panton-Valentine Leukocidin (PVL), an inflammation-suppressing gene from Staphylococcus aureus, was inserted into the Cp/sod− genome to enhance its oncopathic potency. The ability of the recombinant Cp strains to kill tumors was investigated in C57/BL6 mice bearing murine PANC02 tumors. Systemic and organ toxic effects were assessed by monitoring serum chemistries and histopathological examination. Statistical tests were two-sided.

Results: Cp/sod− showed reduced toxic effects compared with wild-type Cp when spores were administered intravenously into PANC02 tumor–bearing mice. Mice treated with Cp/sod−/PVL spores demonstrated a reduction in neutrophils and macrophages in tumors, logarithmically elevated growth of intratumoral bacteria, enhanced tumor necrosis, and substantially prolonged survival without apparent systemic and organ toxic effects, compared with mice treated with both wild-type Cp and Cp/sod− spores. Accordingly, 47% of Cp/sod−/PVL−treated mice (n = 15) achieved tumor-free survival for over 120 days, whereas all mice treated with Cp/sod− or phosphate-buffered saline (n = 10 per group) died within 50 days. The median survival for Cp/sod−/PVL−treated mice was 77 days (95% confidence interval [CI] = 45 to 120 days) and for Cp/sod−–treated mice was 30 days (95% CI = 23 to 36 days; P < .001).

Conclusions: Cp/sod−/PVL provides a prototype for a novel class of oncopathic microbes that may have potential for the safe and effective treatment of pancreatic cancer and other poorly vascularized tumors.
Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients.
Authors: E G Butchart, T Ashcroft, W C Barnsley, M P Holden
Journal: Thorax (1976)

An analysis is made of the results of pleuropneumonectomy for diffuse malignant pleural mesothelioma in 29 patients and a comparison is made with the results of non-surgical treatment in a further 17 patients. A system of tumour staging is proposed, and the results are correlated with tumour stage and with histological type. Pleuropneumonectomy does not appear materially to affect the course of the disease in cases of mixed epithelial and mesenchymal histological type. However, stage I cases of pure epithelial histological type appear to carry a better prognosis, especially those whose histological structure consists entirely of abundant oedematous mucoid stroma with loosely arranged tumour cells. It is suggested therefore that only epithelial cases should be subjected to pleuropneumonectomy. Means of reducing operative mortality are discussed and alternative methods of treatment described.
High Body Mass Index Increases the Risk for Osteonecrosis in Children With Acute Lymphoblastic Leukemia
Authors: Riitta A. Niinimäki, Arja H. Harila-Saari, Airi E. Jartti, Raija M. Seuri, Pekka V. Riikonen, Eija L. Pääkkö, Merja I. Möttönen, Marjatta Lanning
Journal: Journal of Clinical Oncology (2007)

Purpose The aim of the study was to determine the incidence of and clinical risk factors for radiographic osteonecrosis (ON) in children treated for acute lymphoblastic leukemia (ALL) using the Nordic ALL protocols. Patients and Methods Ninety-seven consecutive patients with childhood ALL were studied prospectively by magnetic resonance imaging (MRI) of the lower extremities at the end of the treatment. Results Twenty-three (24%) of the 97 patients had ON. Seven of the patients (30%) were symptomatic, and three patients (13%) required surgical interventions. Multiple logistic regression analysis showed that high body mass index (BMI; P = .04), female sex (P = .01), older age at diagnosis (P &lt; .001), and higher cumulative dexamethasone dose (P = .03) were independent risk factors for radiographic ON. The cumulative prednisone dose did not differ significantly between the patients with and without ON. The incidence of radiographic ON decreased significantly, from 36% to 7%, when the duration of dexamethasone exposure during the delayed-intensification phase was shortened from 3 to 4 weeks to 2 weeks with a taper (P = .001). Conclusion ON as determined by MRI was found to be a common complication in children and adolescents after treatment with the Nordic ALL protocols. Revision of the ALL protocols by shortening the single exposure to dexamethasone has diminished the risk for ON remarkably. High BMI was identified as a new significant risk factor for ON.
Double impact: Difficulties in treating patients with liver diseases from tuberculosis
Authors: Hoda Makhlouf, Nahed Makhlouf, Mohamed Metwally, Hebat Alla Rashed
Journal: European Respiratory Journal (2011)

Background:  Tuberculosis and liver disease are both endemic in many parts of the world. Many anti-TB drugs have hepatotoxic side effects and should be used cautiously during its use in liver disease patients.   Objectives:  To assess the frequency and risk factors of anti-TB-Drug-Induced-Hepatotoxicity (Anti-TB DIH) among patients with viral hepatitis and liver cirrhosis.  Patients & Methods: This prospective study included 26 TB patients of pulmonary and extrapulmonary TB associated with liver cirrhosis or viral hepatitis in addition to, 46 TB patients without liver disease as controls. All patients were followed up clinically and biochemically before and during their treatment.   Results:  Anti-TB-DIH was noticed in 30.8% patients with liver disease (46.2% and 15.4% in liver cirrhosis and viral hepatitis respectively; P=0.089) and in 8.7% of control group (P   Conclusion:  Anti-TB-DIH is common among patients with liver diseases and is more in patients with lower serum albumin while the presence of other co morbid diseases is only risk factor for DIH in TB patients without liver disease.
Recurrence of intracranial aneurysms in autosomal-dominant polycystic kidney disease
Authors: Mark M. Belz, Godela M. Fick-Brosnahan, Richard L. Hughes, David Rubinstein, Arlene B. Chapman, Ann M. Johnson, Kim K. Mcfann, William D. Kaehny, Patricia A. Gabow
Journal: Kidney International (2003)
Pharmacologic Unmasking of Epigenetically Silenced Genes in Breast Cancer
Authors: Kimberly Laskie Ostrow, Hannah Lui Park, Mohammad Obaidul Hoque, Myoung Sook Kim, Junwei Liu, Pedram Argani, William Westra, Wim Van Criekinge, David Sidransky
Journal: Clinical Cancer Research (2009)

Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of various cancers including breast cancer. Many epigenetically inactivated genes involved in breast cancer development remain to be identified. Therefore, in this study we used a pharmacologic unmasking approach in breast cancer cell lines with 5-aza-2'-deoxycytidine (5-aza-dC) followed by microarray expression analysis to identify epigenetically inactivated genes in breast cancer.Breast cancer cell lines were treated with 5-aza-dC followed by microarray analysis to identify epigenetically inactivated genes in breast cancer. We then used bisulfite DNA sequencing, conventional methylation-specific PCR, and quantitative fluorogenic real-time methylation-specific PCR to confirm cancer-specific methylation in novel genes.Forty-nine genes were up-regulated in breast cancer cells lines after 5-aza-dC treatment, as determined by microarray analysis. Five genes (MAL, FKBP4, VGF, OGDHL, and KIF1A) showed cancer-specific methylation in breast tissues. Methylation of at least two was found at high frequency only in breast cancers (40 of 40) as compared with normal breast tissue (0 of 10; P<0.0001, Fisher's exact test).This study identified new cancer-specific methylated genes to help elucidate the biology of breast cancer and as candidate diagnostic markers for the disease.
THE RELATION OF VEGETATIVE ACTIVITY OF BACTERIA TO PATHOGENICITY
Authors: Augustus R. Felty, Arthur L. Bloomfield
Journal: The Journal of Experimental Medicine (1924)

The experiments which have been reported show that distinct differences exist between relatively young cultures of bacteria and the same strains during the period of decline as regards invasive power and pathogenicity, and that these differences must be distinguished clearly from specific alterations in virulence such as those produced by animal passage. The exact interpretation of these observations is not, however, perfectly clear. We were inclined to believe that simple alterations in vegetative activity might account for the differences which have been described, but to what extent the results have been due to injury to the bacteria by products of culture growth it is impossible to say, and further work will be necessary to settle this point. At any rate the experiments seem to bear definitely on the problem of infection in as far as they show that purely temporary modifications See PDF for structure of growth activity whether or not brought about by specific injury lead to changes in invasiveness which are quite analogous to the test-tube phenomenon of lag. It has previously been shown that there exists in the upper air passages a mechanism by means of which foreign particles and bacteria can be eliminated within a few hours. It seems highly likely on the basis of the present work that bacteria entering in an inactive growth phase-for example dried in dust or perhaps from a chronic carrier-may be disposed of before activity can be resumed, whereas organisms introduced in the stage of active growth-as from a case of acute disease-may be able to take advantage of a portal of entry. It is further possible that these experiments may have some bearing on the genesis of epidemics, especially as regards the preepidemic phase, and these matters will be discussed at another time.