tbuckley/cabot-search huggingface dataset:
Aldosterone and Not Plasminogen Activator Inhibitor-1 Is a Critical Mediator of Early Angiotensin II/ <i>N</i> <sup>G</sup> -Nitro- <scp>l</scp> -Arginine Methyl Ester-Induced Myocardial Injury
Authors: Eveline M. Oestreicher, Diego Martinez-Vasquez, James R. Stone, Larus Jonasson, Weranuj Roubsanthisuk, Koji Mukasa, Gail K. Adler
Journal: Circulation (2003)

Background— Angiotensin II (Ang II) increases levels of aldosterone and plasminogen activator inhibitor-1 (PAI-1). Both aldosterone and PAI-1 seem to promote cardiovascular (CV) injury. Our objective was to determine the roles of PAI-1 and aldosterone in the development of myocardial and renal damage in a model with high Ang II and low nitric oxide (NO) availability, a pattern seen in patients with heart failure, diabetes mellitus, and arteriosclerosis. Methods and Results— Mice on a moderately high sodium diet were treated with the NO synthase inhibitor N G -nitro- l -arginine methyl ester (L-NAME) for 14 days plus Ang II during days 8 through 14. The roles of aldosterone and PAI-1 in the development of CV injury were assessed using the mineralocorticoid receptor antagonist spironolactone (0, 1.5, 15, and 50 mg · 100 g −1 · day −1 ) and PAI-1-deficient mice (PAI-1 −/− ). Ang II/L-NAME-treated mice showed glomerular ischemia, proteinuria, and necrosis of myocytes and vascular smooth muscle cells with an associated mixed inflammatory response, deposition of loose collagen, and neovascularization. Compared with saline-drinking mice, Ang II/L-NAME-treated mice had significantly increased heart to body weight (HW/BW) ratios, cardiac and renal damage assessed by histological examination, PAI-1 immunoreactivity, and proteinuria. Spironolactone treatment decreased PAI-1 immunoreactivity and reduced in a dose-dependent fashion cardiac and renal damage. PAI-1 −/− animals had a similar degree of CV injury as PAI-1 +/+ animals. Conclusions— Mineralocorticoid receptor antagonism, but not PAI-1 deficiency, protected mice from developing Ang II/L-NAME-mediated myocardial and vascular injury and proteinuria, suggesting that aldosterone, but not PAI-1, plays a key role in the development of early Ang II/L-NAME-induced cardiovascular injury.
Use of mortality rates and Hospital Activity Analysis as performance indicators of consultant staffing in thoracic medicine in Wales.
Authors: P D Davies
Journal: Thorax (1988)

An analysis of data from mortality rates and Hospital Activity Analysis has been used to determine potential "work loads" for respiratory diseases for each health authority in Wales. Mortality rates were generally higher in the authorities with fewer chest physicians in relation to the population. Three health authorities--West Glamorgan, Mid Glamorgan, and Clwyd--stood out as having a very much higher "work load" per chest physician than the other authorities. A fourth, Powys, had no chest physician. Analyses of this nature may be useful in assessing the requirements for medical staffing in any specialty within a region.
Post-transcriptional regulation of inducible nitric oxide synthase in chronic lymphocytic leukemia B cells in pro- and antiapoptotic culture conditions
Authors: A C Tiscornia, A Cayota, A I Landoni, C Brito, P Oppezzo, F Vuillier, C Robello, G Dighiero, R Gabús, O Pritsch
Journal: Leukemia (2003)
Ecto-5′-nucleotidase plays a role in the cardioprotective effects of heat shock protein 72 in ischemia–reperfusion injury in rat hearts
Authors: T Sakaguchi
Journal: Cardiovascular Research (2000)

Heat shock protein 72 (HSP72) is involved in the myocardial self-preservation system under several conditions such as ischemia-reperfusion injury or late preconditioning. However, its mechanism is not fully understood. Ecto-5'-nucleotidase is a key enzyme for synthesizing adenosine and plays an important role in ischemic preconditioning. In this study, we tested the hypothesis that ecto-5'-nucleotidase plays a role in the cardioprotection of HSP72.Rat hearts (H group, n=6) were transfected with HSP72 gene by an intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome complex. Control hearts (C group, n=6) were transfected with the beta-galactosidase gene. Following 30 min of normothermic ischemia, grafts were reperfused using Langendorff apparatus.The activity of ecto-5'-nucleotidase was significantly higher in H group than C group both before and after ischemia-reperfusion (H vs. C; 0.51+/-0.05 vs. 0.29+/-0.06, and 1.41+/-0.15 vs. 0.85+/-0.11 nmol/mg protein/min, P<0.05). H group also showed significant better functional recoveries than C group (P<0.05), as well as less creatine phosphokinase leakage (4.4+/-2.8 vs. 14.2+/-3.4 mU/min, P<0.05) and higher adenosine release (247.5+/-35.1 vs. 54.3+/-1.7 pmol/min, P<0.05). Administration of alpha,beta-methylene adenosine diphosphate (AMP-CP), an inhibitor of ecto-5'-nucleotidase, significantly diminished the tolerance to ischemia-reperfusion injury in H group (P<0.05).These results demonstrated that ecto-5'-nucleotidase activated by an overexpression of HSP72 attenuated ischemia-reperfusion injury in the rat myocardium. They suggest that ecto-5'-nucleotidase plays a role in the cardioprotective effects of HSP72 in rat hearts.
Continuous Caudal Analgesia
Authors: G. T. Johnson
Journal: BMJ (1954)

The Table summarizes the 14 cases of urethral valves which have been operated upon: clearly, the results leave a great deal to be desired.The older children are much more likely to survive than the infants, but this merely- indicates that the older children are suffering from a less severe obstruction and in no way contradicts the view that earlier diagnosis will lead to improved results.More careful attention to the urinary abnormalities of the " under- threes" is required if a significant proportion of children with this disease are to grow up to be healthy adults.ADDENDUM.-In the eight months which have elapsed since this paper was completed the survivors in the series reported have continued to thrive and five additional cases have been treated.Of these, two, aged 9 days and 11 weeks, died of renal failure before operative treatment of the obstruction had been completed; three, aged 3 weeks, 9 months, and 6 years, have made a satisfactory recovery.My thanks are due to Mr. Twistington Higgins and to other members of the staff of the Hospital for Sick Children, Great Ormond Street, for allowing me to treat their cases, and to Mr. N. Stidolph, of the Whittington Hospital, for inviting me to see the last of the series.Thanks
The Predictive Value of Kidney Allograft Baseline Biopsies for Long-Term Graft Survival
Authors: Katrien De Vusser, Evelyne Lerut, Dirk Kuypers, Yves Vanrenterghem, Ina Jochmans, Diethard Monbaliu, Jacques Pirenne, Maarten Naesens
Journal: Journal of the American Society of Nephrology (2013)

The effect of baseline histology and individual histologic lesions at the time of transplantation on long-term graft survival has been evaluated using different scoring systems, but the predictive capacity of these systems has not been adequately validated. All kidney recipients transplanted in a single institution between 1991 and 2009 who underwent a baseline kidney allograft biopsy at transplantation were included in this prospective study (N=548). All baseline biopsies were rescored according to the updated Banff classification, and the relationship between the individual histologic lesions and donor demographics was assessed using hierarchical clustering and principal component analysis. Survival analysis was performed using Cox proportional hazards analysis and log-rank testing. Mean follow-up time was 6.7 years after transplantation. Interstitial fibrosis, tubular atrophy, and glomerulosclerosis associated significantly with death-censored graft survival, whereas arteriolar hyalinosis and vascular intimal thickening did not. Notably, donor age correlated significantly with interstitial fibrosis, tubular atrophy, and glomerulosclerosis and associated independently with graft survival. On the basis of these findings, a novel scoring system for prediction of 5-year graft survival was constructed by logistic regression analysis. Although the predictive performance of previously published histologic scoring systems was insufficient to guide kidney allocation in our cohort (receiver operating characteristic area under the curve ≤0.62 for each system), the new system based on histologic data and donor age was satisfactory for prediction of allograft loss (receiver operating characteristic area under the curve = 0.81) and may be valuable in the assessment of kidney quality before transplantation.
STUDIES ON THE MECHANISM OF THE SHWARTZMAN PHENOMENON
Authors: Chandler A. Stetson, Robert A. Good
Journal: The Journal of Experimental Medicine (1951)

The inhibition of the Shwartzman phenomenon by nitrogen mustard and benzene has been confirmed and investigated further. This inhibition can be correlated with the leucopenia induced by these agents. Evidence is presented indicating that polymorphonuclear leucocytes play an essential role in the preparation of the skin for the Shwartzman phenomenon.
Suppressor cells in tolerance to contact sensitivity active against hapten-syngeneic and hapten-allogeneic determinants.
Authors: H N Claman, S D Miller, M S Sy
Journal: The Journal of Experimental Medicine (1977)

Genetic restrictions in generation and expression of hapten-specific suppressor cells for contact sensitivity were found. Dinitrophenol- (DNP) or trinitrophenol-modified mouse spleen cells (SC) induced suppressors in donors able to transfer suppression to normal recipients. When allogeneic DNP-SC were injected into BALB/c mice, cells were generated which were suppressive only in the allogeneic strain providing the DNP-SC. In contrast, when DNP-BALB/c-SC were injected into BALB/c mice, suppressors were generated which were active both in BALB/c and in allogeneic mice (e.g., CBA). This apparent absence of syngeneic major histocompability complex restriction may be explained by cross reactive T-cell receptors which are VH gene products.
LSC 2012 abstract - Phenotypic profiling of invading lung fibroblasts in 3D cell culture models
Authors: Bettina Oehrle, Gerald Burgstaller, Martin Irmler, Johannes Beckers, Oliver Eickelberg
Journal: European Respiratory Journal (2012)

Rationale: Fibroblasts exhibit an extraordinary capacity to undergo phenotypic changes during development and disease, both in vitro and in vivo. These changes include altered motility, migration or activation. Enhanced migratory capacity of primary lung fibroblasts (lfs) in IPF patients was found in vitro, but the underlying mechanisms remain elusive. The aim of this study was to decipher morphological, molecular and functional differences between invading (i) and non-invading (n-i) lfs in 3D cell culture models.  Methods/Results: We established a high-content 3D invasion model, enabling the separation of i from n-i lfs that allows the comparative analysis of parameters like morphology, invasion depth and protein/mRNA expression levels. Analysis revealed two significantly distinct subtypes. 7.62 % of untreated lfs invaded the collagen matrix. Invasion was augmented by TGFβ1 and EGF treatment. Gene expression analysis of i vs n-i lfs demonstrated significantly different expression profiles. Several markers, previously reported to be associated with IPF (MMP13 (ex. ratio=4.47), MMP3 (3.97), Osteopontin (1.45), Pten (0.34)) and genes of unknown function, were found deregulated in i lfs.  Conclusion: Lfs show two distinct subtypes in a 3D cell culture model. Gene expression profiling of i lfs revealed features highly similar to the (myo)fibroblast phenotype found in IPF. Our 3D invasion model constitutes a highly useful tool for high-content pharmacological screenings.
Antigen Presentation by Major Histocompatibility Complex Class I-B Molecules
Authors: S M Shawar, J M Vyas, J R Rodgers, R R Rich
Journal: Annual Review of Immunology (1994)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma
Authors: Angela B.Y. Hui, Alice Lin, Wei Xu, Levi Waldron, Bayardo Perez-Ordonez, Ilan Weinreb, Wei Shi, Jeff Bruce, Shao Hui Huang, Brian O'Sullivan, John Waldron, Patrick Gullane, Jonathan C. Irish, Kelvin Chan, Fei-Fei Liu
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Deregulation of miRNAs is associated with almost all human malignancies. Human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) has a significantly more favorable outcome compared with HPV-negative OPCs; however, the underlying mechanisms are not well understood. Hence, the objectives of this study were to determine whether miRNA expression differed as a function of HPV status and to assess whether such miRNAs provide prognostic value beyond HPV status. Methods: Global miRNA profilings were conducted on 88 formalin-fixed and paraffin-embedded (FFPE) OPC biopsies (p16-positive: 56; p16-negative: 32), wherein the expression levels of 365 miRNAs plus 3 endogenous controls were simultaneously measured using quantitative real-time (qRT)-PCR. Seven FFPE specimens of histologically normal tonsils were used as controls. Results: Overall, 224 miRNAs were expressed in more than 80% of the investigated samples, with 128 (57%) being significantly differentially expressed between tumor versus normal tissues (P &amp;lt; 0.05). Upregulated miR-20b, miR-9, and miR-9* were significantly associated with HPV/p16-status. Three miRNA sets were significantly associated with overall survival (miR-107, miR-151, miR-492; P = 0.0002), disease-free survival (miR-20b, miR-107, miR-151, miR-182, miR-361; P = 0.0001), and distant metastasis (miR-151, miR-152, miR-324-5p, miR-361, miR492; P = 0.0087), which retained significance even after adjusting for p16 status. The associated biologic functions of these miRNAs include immune surveillance, treatment resistance, invasion, and metastasis. Conclusion: We have identified several miRNAs, which associate with HPV status in OPC; furthermore, three candidate prognostic sets of miRNAs seem to correlate with clinical outcome, independent of p16 status. Furthermore, evaluations will offer biologic insights into the mechanisms underlying the differences between HPV-positive versus HPV-negative OPC. Clin Cancer Res; 19(8); 2154–62. ©2013 AACR.
Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration.
Authors: C P Armstrong, A L Blower
Journal: Gut (1987)

Two hundred and thirty five consecutive patients with a life threatening complication of peptic ulceration, who either died or required emergency surgery, have been studied over a 36 month period. Seventy eight of these high risk patients died; 25 at home, 19 in hospital without surgery and 34 postoperatively. Ninety eight patients had bleeding ulcers, 132 perforated ulcers and five had both bleeding and perforated ulcers. One hundred and forty one of these 235 patients (60%) were taking a non-steroidal anti-inflammatory drugs (NSAID) and the individual agents have been listed. The overall incidence of NSAID use in a hospital control group was 9.9%. The first sign of an ulcer was a life threatening complication in 58.2% of patients taking a NSAID. Nearly 80% of all ulcer related deaths occurred in patients using an anti-inflammatory agent. Patients using these drugs were older, with more pre-existing medical conditions and had larger ulcers than those not taking NSAIDs. The mortality associated with a peptic ulcer complication in patients taking a NSAID was more than twice that in patients with no such drug history. There appears to be a relationship between the development of a life threatening complication of peptic ulceration and NSAID ingestion. Much of the associated mortality and morbidity may be potentially avoidable.
Itraconazole-Induced Painful Neuropathy in a Man With Type 1 Diabetes
Authors: Rinki Singh, Tim Cundy
Journal: Diabetes Care (2005)

The antifungal agent itraconazole is considered safe in patients with diabetes (1,2) but has been associated with acute painful neuropathy in patients taking vincristine (3–5). We describe a patient with diabetic neuropathy who developed acute painful neuropathy with itraconazole therapy.

A 37-year-old man with poorly controlled type 1 diabetes of 19 years’ duration presented with an excematous rash affecting his lower abdomen. Skin scrapings grew C. albicans . Itraconazole (200 mg/day) was prescribed, but on the 4th day of treatment he developed acute bilateral leg weakness with stabbing pain in the hips and legs and difficulty walking. He …
Complete Histologic Remission after Sunitinib Neoadjuvant Therapy in T3b Renal Cell Carcinoma
Authors: Grégoire Robert, Grégoire Gabbay, Raphaël Bram, Hervé Wallerand, Colette Deminière, François Cornelis, Jean-Christophe Bernhard, Alain Ravaud, Philippe Ballanger
Journal: European Urology (2009)
Nationwide program for improving the care of diabetic patients in Israeli primary care centers
Authors: M Goldfracht, A Porath
Journal: Diabetes Care (2000)

To improve the effectiveness of primary care providers in Israel to monitor and control glycemic levels of diabetic patients.We designed a 2-year program to improve the effectiveness of primary care providers to administer diabetes care. The program was conducted by the largest Israeli health maintenance organization, which insures 60% of the population. Interventions included continuing medical education and establishing guidelines and diabetes registers in every clinic. A retrospective cohort study was conducted from 1995 to 1997 to evaluate the project's effect on the care of diabetic patients. One patient was randomly chosen for review from each of the physicians' updated diabetes registers. The same indicators and variables were collected for each year.The response rate was 72.7%. Nationwide, 876 physicians participated in the review. From 1995 to 1997, there was a statistically significant improvement in the prevalence of performing all of the parameters for monitoring the primary care of diabetic patients. The process parameters showed a considerable improvement: the prevalence of recording weight increased from 35% of the diabetic patients in 1995 to 60% in 1997: the prevalence of conducting foot inspections increased from 40 to 63%; the prevalence of conducting fundus examinations increased from 38.5 to 68.3%; and the prevalence of measuring HbAlc values increased from 30.6 to 69.9%. As a result, metabolic control significantly improved: the percentage of diabetic patients with HbAlc concentration >9% decreased from 33.2% in 1995 to 22.5% in 1997; the percentage of diabetic patients with HbAlc concentration <7.4% increased from 45.1 to 50.5%.A major intervention plan based on quality assurance principles can improve physicians' performance on a national scale without the use of punitive administrative measures.
The source of laterally transferred genes in bacterial genomes
Authors: Vincent Daubin, Emmanuelle Lerat, Guy Perrière
Journal: Genome biology (2003)

Laterally transferred genes have often been identified on the basis of compositional features that distinguish them from ancestral genes in the genome. These genes are usually A+T-rich, arguing either that there is a bias towards acquiring genes from donor organisms having low G+C contents or that genes acquired from organisms of similar genomic base compositions go undetected in these analyses.By examining the genome contents of closely related, fully sequenced bacteria, we uncovered genes confined to a single genome and examined the sequence features of these acquired genes. The analysis shows that few transfer events are overlooked by compositional analyses. Most observed lateral gene transfers do not correspond to free exchange of regular genes among bacterial genomes, but more probably represent the constituents of phages or other selfish elements.Although bacteria tend to acquire large amounts of DNA, the origin of these genes remains obscure. We have shown that contrary to what is often supposed, their composition cannot be explained by a previous genomic context. In contrast, these genes fit the description of recently described genes in lambdoid phages, named 'morons'. Therefore, results from genome content and compositional approaches to detect lateral transfers should not be cited as evidence for genetic exchange between distantly related bacteria.
Evaluation of a movement detector to measure daily activity in patients with chronic lung disease
Authors: B Schonhofer, P Ardes, M Geibel, D Kohler, PW Jones
Journal: European Respiratory Journal (1997)

This study was designed to evaluate the performance of movement detectors (pedometers) in measuring daily activity of patients with chronic lung disease. Three groups of subjects were studied: group 1: 25 patients with stable nonhypercapnic chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second (FEV1) = 47+/-9% predicted) studied twice, one month apart; group 2: 25 patients with chronic respiratory failure studied before and three months after nasal nocturnal mechanical ventilation; and group 3: 25 normal healthy subjects studied once. The median level of activity in the healthy subjects (group 3) was three times greater than in either group of patients (groups 1 and 2). Activity levels were not correlated with age, sex or employment status. The repeatability of the activity counts in the nonhypercapnic COPD patients was high (intraclass correlation coefficient=0.94) and in these patients activity correlated significantly with FEV1 (r=0.54, p=0.006). In the respiratory failure patients, daytime arterial carbon dioxide pressure (Pa,CO2) improved following nasal nocturnal mechanical ventilation (NMV) (pre NMV: 8.5+/-1.2 kPa; post NMV: 6.2+/-0.5 kPa), health status improved (p&lt;0.004) and daily movement count doubled (p&lt;0.0001). This increase correlated with change in Pa,CO2 (r-0.53, p=0.006), but not with improved health status. We conclude that motion detectors may provide repeatable measures of daily activity that are related to physiological impairment and improvement following treatment. Activity counts appear to be complementary to estimates of exercise limitation obtained using health questionnaires.