tbuckley/cabot-search huggingface dataset:
Mechanisms of Cardiac Depression Caused by Lipoteichoic Acids From <i>Staphylococcus aureus</i> in Isolated Rat Hearts
Authors: Ulrich Grandel, Michael Hopf, Michael Buerke, Katja Hattar, Martina Heep, Ludger Fink, Rainer M. Bohle, Siegfried Morath, Thomas Hartung, Soni Pullamsetti, Ralph T. Schermuly, Werner Seeger, Friedrich Grimminger, Ulf Sibelius
Journal: Circulation (2005)

Lipoteichoic acid (LTA) represents a major virulence factor in gram-positive sepsis.In the present study we perfused isolated rat hearts for 180 minutes with highly purified LTA from Staphylococcus aureus. A progressive decline of left ventricular contractile function paralleled by the expression of myocardial tumor necrosis factor-alpha (TNF-alpha) mRNA and protein as well as the release of TNF-alpha into the perfusate was observed in LTA-perfused hearts. Employment of an anti-TNF-alpha antibody completely prevented the loss in contractile function. When CD14, a prominent pathogen recognition receptor, was blocked by a specific antibody, induction of TNF-alpha mRNA and protein release as well as the associated cardiodepression was diminished in response to LTA. Synthesis of TNF-alpha protein was located to interstitial cells of LTA-challenged hearts as detected by immunohistochemistry. Besides progressive cardiodepression, coronary perfusion pressure (CPP) was moderately increased in LTA-perfused hearts. This was accompanied by the release of thromboxane A2 (TXA2) into the perfusate and the induction of cyclooxygenase (Cox)-2 mRNA and protein in the myocardium. Blocking of TXA2 by the nonspecific Cox inhibitor indomethacin, the thromboxane receptor antagonist daltroban, or the selective Cox-2 inhibitor NS-398 prevented the increase in CPP.LTA causes cardiac depression by activating myocardial TNF-alpha synthesis via CD14 and induces coronary vascular disturbances by activating Cox-2-dependent TXA2 synthesis. These phenomena may contribute to cardiac depression in gram-positive sepsis.
A possible contribution of lipocalin-2 to the development of dermal fibrosis, pulmonary vascular involvement and renal dysfunction in systemic sclerosis
Authors: T. Takahashi, Y. Asano, S. Noda, N. Aozasa, K. Akamata, T. Taniguchi, Y. Ichimura, T. Toyama, H. Sumida, Y. Kuwano, Y. Tada, M. Sugaya, T. Kadono, S. Sato
Journal: British Journal of Dermatology (2015)

Background Lipocalin-2 is an adipocytokine implicated in apoptosis, innate immunity, angiogenesis, and the development of chronic kidney disease. Objectives To investigate the role of lipocalin-2 in systemic sclerosis (SSc). Materials and methods Serum lipocalin-2 levels were determined by enzyme-linked immunosorbent assay in 50 patients with SSc and 19 healthy subjects. Lipocalin-2 expression was evaluated in the skin of patients with SSc and bleomycin (BLM)-treated mice and in Fli1-deficient endothelial cells by reverse transcriptase-real time polymerase chain reaction, immunoblotting and/or immunohistochemistry. Results Although serum lipocalin-2 levels were comparable between patients with SSc and healthy controls, the prevalence of scleroderma renal crisis was significantly higher in patients with SSc with elevated serum lipocalin-2 levels than in those with normal levels. Furthermore, serum lipocalin-2 levels inversely correlated with estimated glomerular filtration rate in patients with SSc with renal dysfunction. Among patients with SSc with normal renal function, serum lipocalin-2 levels positively correlated with skin score in patients with diffuse cutaneous SSc with disease duration of < 3 years and inversely correlated with estimated right ventricular systolic pressure in total patients with SSc. Importantly, in SSc lesional skin, lipocalin-2 expression was increased in dermal fibroblasts and endothelial cells. In BLM-treated mice, lipocalin-2 was highly expressed in dermal fibroblasts, but not in endothelial cells. On the other hand, the deficiency of transcription factor Fli1, which is implicated in SSc vasculopathy, induced lipocalin-2 expression in cultivated endothelial cells. Conclusions Lipocalin-2 may be involved in renal dysfunction and dermal fibrosis of SSc. Dysregulated matrix metalloproteinase-9/lipocalin-2-dependent angiogenesis due to Fli1 deficiency may contribute to the development of pulmonary arterial hypertension associated with SSc.
MG53 Constitutes a Primary Determinant of Cardiac Ischemic Preconditioning
Authors: Chun-Mei Cao, Yan Zhang, Noah Weisleder, Christopher Ferrante, Xianhua Wang, Fengxiang Lv, Yi Zhang, Ruisheng Song, Moonsun Hwang, Li Jin, Jiaojiao Guo, Wei Peng, Geng Li, Miyuki Nishi, Hiroshi Takeshima, Jianjie Ma, Rui-Ping Xiao
Journal: Circulation (2010)

Background— Ischemic heart disease is the greatest cause of death in Western countries. The deleterious effects of cardiac ischemia are ameliorated by ischemic preconditioning (IPC), in which transient ischemia protects against subsequent severe ischemia/reperfusion injury. IPC activates multiple signaling pathways, including the reperfusion injury salvage kinase pathway (mainly PI3K-Akt-glycogen synthase kinase-3β [GSK3β] and ERK1/2) and the survivor activating factor enhancement pathway involving activation of the JAK-STAT3 axis. Nevertheless, the fundamental mechanism underlying IPC is poorly understood. Methods and Results— In the present study, we define MG53, a muscle-specific TRIM-family protein, as a crucial component of cardiac IPC machinery. Ischemia/reperfusion or hypoxia/oxidative stress applied to perfused mouse hearts or neonatal rat cardiomyocytes, respectively, causes downregulation of MG53, and IPC can prevent ischemia/reperfusion-induced decrease in MG53 expression. MG53 deficiency increases myocardial vulnerability to ischemia/reperfusion injury and abolishes IPC protection. Overexpression of MG53 attenuates whereas knockdown of MG53 enhances hypoxia- and H 2 O 2 -induced cardiomyocyte death. The cardiac protective effects of MG53 are attributable to MG53-dependent interaction of caveolin-3 with phosphatidylinositol 3 kinase and subsequent activation of the reperfusion injury salvage kinase pathway without altering the survivor activating factor enhancement pathway. Conclusions— These results establish MG53 as a primary component of the cardiac IPC response, thus identifying a potentially important novel therapeutic target for the treatment of ischemic heart disease.
A Comparison of 2 Surgical Site Infection Monitoring Systems
Authors: Mila H. Ju, Clifford Y. Ko, Bruce L. Hall, Charles L. Bosk, Karl Y. Bilimoria, Elizabeth C. Wick
Journal: JAMA Surgery (2014)

IMPORTANCE Surgical site infection (SSI) has emerged as the leading publicly reported surgical outcome and is tied to payment determinations.Many hospitals monitor SSIs using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), in addition to mandatory participation (for most states) in the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN), which has resulted in duplication of effort and incongruent data.OBJECTIVE To identify discrepancies in the implementation of the NHSN and the ACS NSQIP at hospitals that may be affecting the respective SSI rates. DESIGN, SETTING, AND PARTICIPANTSA pilot sample of hospitals that participate in both the NHSN and the ACS NSQIP.INTERVENTIONS For each hospital, observed rates and risk-adjusted observed to expected ratios for year 2012 colon SSIs were collected from both programs.The implementation methods of both programs were identified, including telephone interviews with infection preventionists who collect data for the NHSN at each hospital. MAIN OUTCOMES AND MEASURESCollection methods and colon SSI rates for the NHSN at each hospital were compared with those of the ACS NSQIP. RESULTSOf 16 hospitals, 11 were teaching hospitals with at least 500 beds.The mean observed colon SSI rates were dissimilar between the 2 programs, 5.7% (range, 2.0%-14.5%)for the NHSN vs 13.5% (range, 4.6%-26.7%)for the ACS NSQIP.The mean difference between the NHSN and the ACS NSQIP was 8.3% (range, 1.6%-18.8%),with the ACS NSQIP rate always higher.The correlation between the observed to expected ratios for the 2 programs was nonsignificant (Pearson product moment correlation, ρ = 0.4465; P = .08).The NHSN collection methods were dissimilar among interviewed hospitals.An SSI managed as an outpatient case would usually be missed under the current NHSN practices. CONCLUSIONS AND RELEVANCEColon SSI rates from the NHSN and the ACS NSQIP cannot be used interchangeably to evaluate hospital performance and determine reimbursement.Hospitals should not use the ACS NSQIP colon SSI rates for the NHSN reports because that would likely result in the hospital being an outlier for performance.It is imperative to reconcile SSI monitoring, develop consistent definitions, and establish one reliable method.The current state hinders hospital improvement efforts by adding unnecessary confusion to the already complex arena of perioperative improvement.
Evaluation of a Breast Cancer Nomogram for Predicting Risk of Ipsilateral Breast Tumor Recurrences in Patients With Ductal Carcinoma in Situ After Local Excision
Authors: Min Yi, Funda Meric-Bernstam, Henry M. Kuerer, Elizabeth A. Mittendorf, Isabelle Bedrosian, Anthony Lucci, Rosa F. Hwang, Jaime R. Crow, Sheng Luo, Kelly K. Hunt
Journal: Journal of Clinical Oncology (2012)

Purpose Prediction of patients at highest risk for ipsilateral breast tumor recurrence (IBTR) after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The aim of our study was to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center to predict for risk of IBTR in patients with DCIS from our institution. Patients and Methods We retrospectively identified 794 patients with a diagnosis of DCIS who had undergone local excision from 1990 through 2007 at the MD Anderson Cancer Center (MDACC). Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients who had complete data. Results There was a marked difference with respect to tumor grade, prevalence of necrosis, initial presentation, final margins, and receipt of endocrine therapy between the two cohorts. The biggest difference was that more patients received radiation in the MDACC cohort (75% at MDACC v 49% at MSKCC; P &lt; .001). Follow-up time in the MDACC cohort was longer than in the MSKCC cohort (median 7.1 years v 5.6 years), and the recurrence rate was lower in the MDACC cohort (7.9% v 11%). The median 5-year probability of recurrence was 5%, and the median 10-year probability of recurrence was 7%. The nomogram for prediction of 5- and 10-year IBTR probabilities demonstrated imperfect calibration and discrimination, with a concordance index of 0.63. Conclusion Predictive models for IBTR in patients with DCIS who were treated with local excision are imperfect. Our current ability to accurately predict recurrence on the basis of clinical parameters alone is limited.
Translating the Chronic Care Model Into the Community
Authors: Gretchen A. Piatt, Trevor J. Orchard, Sharlene Emerson, David Simmons, Thomas J. Songer, Maria M. Brooks, Mary Korytkowski, Linda M. Siminerio, Usman Ahmad, Janice C. Zgibor
Journal: Diabetes Care (2006)

OBJECTIVE—To determine whether using the chronic care model (CCM) in an underserved community leads to improved clinical and behavioral outcomes for people with diabetes. RESEARCH DESIGN AND METHODS—This multilevel, cluster-design, randomized controlled trial examined the effectiveness of a CCM-based intervention in an underserved urban community. Eleven primary care practices, along with their patients, were randomized to three groups: CCM intervention (n = 30 patients), provider education only (PROV group) (n = 38), and usual care (UC group) (n = 51). RESULTS—A marked decline in HbA1c was observed in the CCM group (−0.6%, P = 0.008) but not in the other groups. The magnitude of the association remained strong after adjustment for clustering (P = 0.01). The same pattern was observed for a decline in non-HDL cholesterol and for the proportion of participants who self-monitor blood glucose in the CCM group (non-HDL cholesterol: −10.4 mg/dl, P = 0.24; self-monitor blood glucose: +22.2%, P &amp;lt; 0.0001), with statistically significant between-group differences in improvement (non-HDL cholesterol: P = 0.05; self-monitor blood glucose: P = 0.03) after adjustment. The CCM group also showed improvement in HDL cholesterol (+5.5 mg/dl, P = 0.0004), diabetes knowledge test scores (+6.7%, P = 0.07), and empowerment scores (+2, P = 0.02). CONCLUSIONS—These results suggest that implementing the CCM in the community is effective in improving clinical and behavioral outcomes in patients with diabetes.
The thyroid "microsomal" antibody revisited. Its paradoxical binding in vivo to the apical surface of the follicular epithelium.
Authors: E L Khoury, G F Bottazzo, I M Roitt
Journal: The Journal of Experimental Medicine (1984)

We have shown that thyroid monolayers derived from the glands of patients with autoimmune thyroid disease have immunoglobulin (Ig) bound to their surface. This appears to have been deposited in vivo rather than during preparation of the monolayers, a view supported by our finding of such deposits on the apical margin of follicular cells in sections cut from these glands and stained with conjugated anti-immunoglobulin. It is likely that these deposits represent specific binding of so-called "microsomal" autoantibodies to the surface of the thyroid cells in vivo since staining of partially disrupted follicles ("half-melons") with Hashimoto serum containing microsomal autoantibodies in the indirect immunofluorescence (IFL) test, localized the antigen on the apical surface of the cells lining the follicular cavity. Thus, paradoxically, although the antigen is relatively inaccessible, autoantibodies do reach and combine with the thyroid surface in vivo and may therefore play a role in pathogenesis.
Mycobacterium haemophilum cellulitis in a heart transplant recipient
Authors: Carrie Lederman, Joel L. Spitz, Brian Scully, Larry L. Schulman, Phyllis Della-Latta, Irene Weitzman, Marc E. Grossman
Journal: Journal of the American Academy of Dermatology (1994)

Mycobacterium haemophilum is an unusual pathogen that can infect the skin and underlying bone and joints of immunocompromised patients. I Infections have been reported in patients with kidney transplants.? lymphoma,1,3 bone marrow transplants, and, more recently, AIDS. IO-15 Cervical lymphadenitis developed in one child without immunodeficiency.l'' Most patients have multiple cutaneous nodules, abscesses, and ulcers. From 1990 to 1992, 13 cases of M. haemophilum infection were reported in New York City; only eight cases were reported in the rest of the United States.P The reservoir and mode of transmission of this infection are unknown. We describeM haemophilum cellulitis in a heart transplant recipient in an apparent clustering of cases in the New York City area.
Cerebral Perfusion and Aortic Stiffness Are Independent Predictors of White Matter Brain Atrophy in Type 1 Diabetic Patients Assessed With Magnetic Resonance Imaging
Authors: Saskia G.C. van Elderen, Anne Brandts, Jeroen van der Grond, Jos J.M. Westenberg, Lucia J.M. Kroft, Mark A. van Buchem, Johannes W.A. Smit, Albert de Roos
Journal: Diabetes Care (2011)

To identify vascular mechanisms of brain atrophy in type 1 diabetes mellitus (DM) patients by investigating the relationship between brain volumes and cerebral perfusion and aortic stiffness using magnetic resonance imaging (MRI).Approval from the local institutional review board was obtained, and patients gave informed consent. Fifty-one type 1 DM patients (30 men; mean age 44 ± 11 years; mean DM duration 23 ± 12 years) and 34 age- and sex-matched healthy control subjects were prospectively enrolled. Exclusion criteria comprised hypertension, stroke, aortic disease, and standard MRI contraindications. White matter (WM) and gray matter (GM) brain volumes, total cerebral blood flow (tCBF), total brain perfusion, and aortic pulse wave velocity (PWV) were assessed using MRI. Multivariable linear regression analysis was used for statistics, with covariates age, sex, mean arterial pressure, BMI, smoking, heart rate, DM duration, and HbA(1c).Both WM and GM brain volumes were decreased in type 1 DM patients compared with control subjects (WM P = 0.04; respective GM P = 0.03). Total brain perfusion was increased in type 1 DM compared with control subjects (β = -0.219, P < 0.05). Total CBF and aortic PWV predicted WM brain volume (β = 0.352, P = 0.024 for tCBF; respective β = -0.458, P = 0.016 for aortic PWV) in type 1 DM. Age was the independent predictor of GM brain volume (β = -0.695, P < 0.001).Type 1 DM patients without hypertension showed WM and GM volume loss compared with control subjects concomitant with a relative increased brain perfusion. Total CBF and stiffness of the aorta independently predicted WM brain atrophy in type 1 DM. Only age predicted GM brain atrophy.
Impact on patients of expanded, general practice based, student teaching: observational and qualitative study
Authors: John Benson, Thelma Quince, Arthur Hibble, Thomas Fanshawe, Jon Emery
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To compare patients9 enablement and satisfaction after teaching and non-teaching consultations. To explore patients9 views about the possible impact that increased community based teaching of student doctors in their practice may have on the delivery of service and their attitudes towards direct involvement with students. <b>Design</b> Observational study using validated survey instruments (patient enablement index—PEI, and consultation satisfaction questionnaire—CSQ) administered after teaching consultations and non-teaching consultations. Ten focus groups (two from each practice), comprising five with patients participating in prearranged teaching sessions and five with patients not participating in these. <b>Setting</b> Five general practices in west Suffolk and southern Norfolk, England, that teach student doctors on the Cambridge graduate medical course. <b>Participants</b> 240 patients attending teaching consultations (response rate 82%, 196 patients) and 409 patients attending non-teaching consultations (response rate 72%, 294 patients) received survey instruments. Ten focus groups with a total of 34 patients participating in prearranged teaching sessions and 20 patients not participating in these. <b>Main outcome measures</b> Scores on the patient enablement index and consultation satisfaction questionnaire, analysed at the level of all patients, allowing for age, sex, general practitioner, and practice, and at the level of the individual general practitioner teacher. Qualitative analysis of focus group data. <b>Results</b> Patients9 enablement or satisfaction was not reduced after teaching consultations compared with non-teaching consultations (mean difference in scores on the patient enablement index and consultation satisfaction questionnaire with adjustment for confounders 2.24% and 1.70%, respectively). This held true for analysis by all patients and by general practitioner teacher. Qualitative data showed that patients generally supported the teaching of student doctors in their practice. However, this support was conditional on receiving sufficient information about reasons for doctors9 absence, the characteristics of students, and the nature of teaching planned. Many patients viewed their general practice as different from hospital and expected greater control over students9 presence during their consultations. <b>Conclusions</b> Patients9 enablement and satisfaction are not impaired by students9 participation in consultations. Patients generally support the teaching of student doctors in their general practice but expect to be provided with sufficient information and to have a choice about participation, so they can give informed consent. Recognising this when organising general practice based teaching is important.
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Authors: J M Feldman, R Hilf
Journal: JNCI Journal of the National Cancer Institute (1985)

Journal Article Failure of Indomethacin To Inhibit Growth of the R3230AC Mammary Tumor in Rats Get access Jeffrey M. Feldman, Jeffrey M. Feldman Search for other works by this author on: Oxford Academic PubMed Google Scholar Russell Hilf Russell Hilf 6 6Address reprint requests to Dr. Hilf, at the Department of Biochemistry, Box 607, The University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 75, Issue 4, October 1985, Pages 751–756, https://doi.org/10.1093/jnci/75.4.751 Published: 01 October 1985 Article history Received: 10 January 1985 Accepted: 10 June 1985 Published: 01 October 1985
GeneChip analysis of human embryonic stem cell differentiation into hemangioblasts: an in silico dissection of mixed phenotypes
Authors: Shi-Jiang Lu, Jennifer A Hipp, Qiang Feng, Jason D Hipp, Robert Lanza, Anthony Atala
Journal: Genome biology (2007)

Microarrays are being used to understand human embryonic stem cell (hESC) differentiation. Most differentiation protocols use a multi-stage approach that induces commitment along a particular lineage. Therefore, each stage represents a more mature and less heterogeneous phenotype. Thus, characterizing the heterogeneous progenitor populations upon differentiation are of increasing importance. Here we describe a novel method of data analysis using a recently developed differentiation protocol involving the formation of functional hemangioblasts from hESCs. Blast cells are multipotent and can differentiate into multiple lineages of hematopoeitic cells (erythroid, granulocyte and macrophage), endothelial and smooth muscle cells.Large-scale transcriptional analysis was performed at distinct time points of hESC differentiation (undifferentiated hESCs, embryoid bodies, and blast cells, the last of which generates both hematopoietic and endothelial progenies). Identifying genes enriched in blast cells relative to hESCs revealed a genetic signature indicative of erythroblasts, suggesting that erythroblasts are the predominant cell type in the blast cell population. Because of the heterogeneity of blast cells, numerous comparisons were made to publicly available data sets in silico, some of which blast cells are capable of differentiating into, to assess and characterize the blast cell population. Biologically relevant comparisons masked particular genetic signatures within the heterogeneous population and identified genetic signatures indicating the presence of endothelia, cardiomyocytes, and hematopoietic lineages in the blast cell population.The significance of this microarray study is in its ability to assess and identify cellular populations within a heterogeneous population through biologically relevant in silico comparisons of publicly available data sets. In conclusion, multiple in silico comparisons were necessary to characterize tissue-specific genetic signatures within a heterogeneous hemangioblast population.