tbuckley/cabot-search huggingface dataset:
Effects of subendocardial ablation on anodal supernormal excitation and ventricular vulnerability in open-chest dogs.
Authors: P S Chen, P L Wolf, Y M Cha, B B Peters, S L Topham
Journal: Circulation (1993)

BACKGROUND In Langendorff-perfused hearts and in hearts on cardiopulmonary bypass, chemical ablation of the subendocardium of both ventricles decreases ventricular vulnerability to fibrillation. It was hypothesized that the effects of ablation are a result of the elimination of the subendocardial Purkinje fiber network. This hypothesis has been supported by recent observations that the supernormal excitability that is demonstrable in the Purkinje fibers is associated with arrhythmogenesis. METHODS AND RESULTS We tested this hypothesis on 10 open-chest dogs by evaluating the strength-interval curves of anodal and cathodal stimulation with the assistance of computerized mapping techniques. The ventricular fibrillation threshold was also determined. The same test was then performed after chemical ablation of the subendocardium of either the right ventricle (six dogs) or both ventricles (four dogs). Anodal supernormality was consistently demonstrated in all the dogs studied both before and after subendocardial ablation. The ventricular fibrillation thresholds were 23 +/- 5 mA both before and after right ventricular subendocardial ablation (p = NS). The ventricular fibrillation thresholds before and after biventricular subendocardial ablation were 25 +/- 3 and 22 +/- 10 mA, respectively (p = NS). CONCLUSIONS We conclude that 1) subendocardial ablation does not decrease ventricular vulnerability when the heart is in situ and is not on cardiopulmonary bypass and 2) anodal supernormal excitability can be demonstrated in ventricles without a subendocardial Purkinje fiber network.
Biochemical and molecular genetic characterization of a new variant prealbumin associated with hereditary amyloidosis.
Authors: M R Wallace, F E Dwulet, P M Conneally, M D Benson
Journal: Journal of Clinical Investigation (1986)

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant late-onset disorder characterized by the extracellular deposition of amyloid fibrils. In all cases studied these fibrils have been found to be composed of plasma prealbumin (transthyretin) containing a single amino acid substitution. Biochemical studies were conducted on amyloid from one patient and plasma prealbumin from his affected brother, both part of a large kindred from the Appalachian region of the United States. Sequence analysis of the amyloid subunit protein showed it to be prealbumin with about two-thirds of the molecules containing a substitution of alanine for threonine at position 60. Studies of the plasma prealbumin showed that the same substitution was present in 40-45% of the protein. Based on this substitution and the prealbumin cDNA sequence, a Pvu II restriction fragment length DNA polymorphism (RFLP) was predicted and demonstrated in DNA of both patients as well as other family members. This RFLP confirms the predicted DNA mutation responsible for the protein variant, and represents an accurate method for detection of this gene.
Opposing effects of the D70 mutation and the shared epitope in HLA-DR4 on disease activity and certain disease phenotypes in rheumatoid arthritis
Authors: N A Shadick, J E Heller, M E Weinblatt, N E Maher, J Cui, G Ginsburg, J Coblyn, R Anderson, D H Solomon, R Roubenoff, A Parker
Journal: Annals of the Rheumatic Diseases (2007)

Certain sequences present in the hypervariable region of human leucocyte antigen (HLA)-DRB1 known as the shared epitope (SE) are hypothesised to increase the risk of rheumatoid arthritis (RA), whereas alleles encoding aspartic acid at position 70 (D70 alleles) may have a protective effect.Patient HLA-DRB1 serotypes were assessed and the genotypes encoding the SE motif or the putatively protective D70 motif identified in a large RA cohort. Logistic regression was used to analyse associations of genotype with presence of disease, comorbidities and disease severity, and association between genotype and change in disease activity over time.The 689 patients enrolled had a mean (SD) age of 57.9 (13.7) years and mean (SD) disease duration of 15.3 (12.7) years. In a comparison with 482 ethnicity matched population-based controls, the D70 sequence exerted a strong protective effect (OR = 0.52, p<0.001) that remained significant when the SE at the same locus was accounted for (OR = 0.72, 95% CI 0.60 to 0.86, p<0.001). The SE assessed on all HLA-DRB1 serotypic backgrounds except DR1 was associated with RA susceptibility (additive OR = 2.43, p<0.001). Associations were found between SE and serum levels of rheumatoid factor (p<0.001, with correlation of 0.18) and anti-cyclic citrullinated peptide antibodies (p<0.001, with correlation of 0.25) but not with serum C-reactive protein.The D70 allele has a significant protective effect that is mitigated but still significant when the risk effect of the SE at the same locus is taken into account. The presence of the SE on DR4 is associated with greater RA susceptibility and certain disease-activity measures.
Differential diagnosis of focal pancreatitis and pancreatic cancer
Authors: T.M. van Gulik, T.M. Moojen, R. van Geenen, H. Obertop, D.J. Gouma, E.A.J. Rauws
Journal: Annals of Oncology (1999)

The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes and CP may develop into PAC. The aim of this study was tot analyze two sets of patients (group A and B) who were misdiagnosed to have either CP or PAC. The clinical and radiographical features of these patients were reviewed. Group A consisted of 22 patients (median age 54.5 years) who were referred with PAC after a previous diagnosis of PC. Eleven patients had a history of CP of > 12 mths (mean 40.2 mths) whereas in 11 patients, PAC became apparent within 12 mths (mean 4.9 mths) after the diagnosis of CP was made. The etiology of CP was alcohol abuse in 9 patients, pancreas divisum in 3 patients and was undefined in the remaining 10 patients. Imaging studies showed features of CP (parenchymal calcifications, irregularities and stenoses of the pancreatic duct wall). Pseudocysts were present in 13 patients. A mass lesion was detected in 13 patients. At the time of diagnosis, 20 patients had unresectable tumors and 2 patients underwent a Whipple resection which proved non-radical. Group B consisted of 14 patients (median age 53 years) who underwent a Whipple resection for a presumed PAC that on histopathology of the lesion proved to be CP. These patients accounted for 6% of all 220 patients who had undergone resection for PAC in the same period. Reassessment of clinical presentation and all imaging studies confirmed a high index of suspicion on PAC in these patients.In patients known with CP, misdiagnosis of PAC is a potential pitfall leading to delay of treatment. For any lesion suspicious of PAC an aggressive surgical approach is justified lest a potentially curable lesion is missed. As a consequence, there is at least a 5% chance of resecting a lesion based on CP, mimicking PAC.
Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle
Authors: Jason K. Kim, Ruth E. Gimeno, Takamasa Higashimori, Hyo-Jeong Kim, Hyejeong Choi, Sandhya Punreddy, Robin L. Mozell, Guo Tan, Alain Stricker-Krongrad, David J. Hirsch, Jonathan J. Fillmore, Zhen-Xiang Liu, Jianying Dong, Gary Cline, Andreas Stahl, Harvey F. Lodish, Gerald I. Shulman
Journal: Journal of Clinical Investigation (2004)

Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism by converting fatty acids into fatty acyl-CoA. To investigate the role of FATP1 in glucose homeostasis and in the pathogenesis of insulin resistance, we examined the effect of acute lipid infusion or chronic high-fat feeding on insulin action in FATP1 KO mice. Whole-body adiposity, adipose tissue expression of adiponectin, intramuscular fatty acid metabolites, and insulin sensitivity were not altered in FATP1 KO mice fed a regular chow diet. In contrast, FATP1 deletion protected the KO mice from fat-induced insulin resistance and intramuscular accumulation of fatty acyl-CoA without alteration in whole-body adiposity. These findings demonstrate an important role of intramuscular fatty acid metabolites in causing insulin resistance and suggest that FATP1 may be a novel therapeutic target for the treatment of insulin resistance and type 2 diabetes.
ACCF/AHA/AAP Recommendations for Training in Pediatric Cardiology. A Report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Clinical Competence (ACC/AHA/AAP Writing Committee to Develop Training Recommendations for Pediatric Cardiology)
Authors: Thomas P. Graham, Robert H. Beekman, Hugh D. Allen, J. Timothy Bricker, Michael D. Freed, Roger A. Hurwitz, Tim C. McQuinn, Richard M. Schieken, William B. Strong, Kenneth G. Zahka, Stephen P. Sanders, Steven D. Colan, Timothy M. Cordes, Mary T. Donofrio, Gregory J. Ensing, Tal Geva, Thomas R. Kimball, David J. Sahn, Norman H. Silverman, Mark S. Sklansky, Paul M. Weinberg, William E. Hellenbrand, Thomas R. Lloyd, James E. Lock, Charles E. Mullins, Jonathan J. Rome, David F. Teitel, Victoria L. Vetter, Michael J. Silka, George F. Van Hare, Edward P. Walsh, Thomas Kulik, Therese M. Giglia, Keith C. Kocis, Larry T. Mahoney, Steven M. Schwartz, Gil Wernovsky, David L. Wessel, Daniel J. Murphy, Elyse Foster, D. Woodrow Benson, H. Scott Baldwin
Journal: Circulation (2005)
Differences in proteoglycan deposition in the airways of moderate and severe asthmatics
Authors: L. Pini, Q. Hamid, J. Shannon, L. Lemelin, R. Olivenstein, P. Ernst, C. Lemière, J. G. Martin, M. S. Ludwig
Journal: European Respiratory Journal (2006)

Excess deposition of proteoglycans (PGs) has been described in the subepithelial layer of the asthmatic airway wall. However, less is known about deposition in the airway smooth muscle (ASM) layer, and whether the pattern of deposition is altered depending upon disease severity. Endobronchial biopsies were performed in patients with severe or moderate asthma (defined using American Thoracic Society criteria) and in control subjects. Biopsies were immunostained for the PGs biglycan, lumican, versican and decorin. PG deposition was measured in the subepithelial and ASM layers, the former by calculating the area of positive staining, and the latter by determining the percentage area stained using point counting. Immunostaining for PGs was prominent in biopsies from both moderate and severe asthmatics, compared with control subjects. While there was no difference in the amount of PG in the subepithelial layer between the two asthmatic groups, the percentage area of biglycan and lumican staining in the ASM layer was significantly greater in moderate versus severe asthmatics. Differences in the deposition of proteoglycans within the airway smooth muscle layer of moderate versus severe asthmatics potentially impact on the functional behaviour of the airway smooth muscle in these two groups of patients.
Targeted Inactivation of EGF Receptor Inhibits Renal Collecting Duct Development and Function
Authors: Zhao Zhang, Elena Pascuet, Pierre-Alain Hueber, LeeLee Chu, Daniel G. Bichet, Tang-Cheng Lee, David W. Threadgill, Paul Goodyer
Journal: Journal of the American Society of Nephrology (2010)

The ureteric bud (UB) expresses high levels of the EGF receptor (EGFR) during kidney development, but its function in this setting is unclear. Here, Egfr mRNA was abundant in medullary portions of the UB trunk but absent from the branching UB tips during embryogenesis. Homozygous Egfr knockout did not affect the pattern of UB arborization, but renal papillae were hypoplastic and exhibited widespread apoptosis of tubular cells. Because these EGFR-deficient mice die within 1 week of life, we targeted Egfr inactivation to the renal collecting ducts using Cre-lox technology with a Hoxb7-Cre transgene. This targeted inactivation of Egfr led to a thin renal medulla, and at 7 weeks of age, the mice had moderate polyuria and reduced urine-concentrating ability. At 30 to 33 weeks, water deprivation demonstrated a continued urine-concentrating defect despite similar levels of vasopressin between knockout mice and littermate controls. Taken together, these results suggest that unlike other tyrosine kinases expressed at the UB tip, EGFR functions primarily to drive elongation of the emerging collecting ducts and to optimize urine-concentrating ability.
Upregulation of neuroreceptors on CD4+ and CD8+ T cells promotes their anti-tumor function
Authors: Maria de Aquino, Thomas Hodo, Anil Shanker
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The nervous system can regulate the exacerbation of pro-inflammatory immune response predominantly in an immunosuppressive setting. Studies also suggest that glutamate, serotonin, dopamine, and substance P trigger immune responses such as cytokine secretion, integrin expression,
Glycometabolic State at Admission: Important Risk Marker of Mortality in Conventionally Treated Patients With Diabetes Mellitus and Acute Myocardial Infarction
Authors: Klas Malmberg, Anna Norhammar, Hans Wedel, Lars Rydén
Journal: Circulation (1999)

Background —The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study addressed prognostic factors and the effects of concomitant treatment and glycometabolic control in diabetic patients with myocardial infarction (AMI). Methods and Results —Of 620 diabetic patients with AMI, 306 were randomly assigned to a ≥24-hour insulin-glucose infusion followed by multidose subcutaneous insulin. Three hundred fourteen patients were randomized as controls, receiving routine antidiabetic therapy. Thrombolysis and β-blockers were administered when possible. Univariate and multivariate statistical analyses were applied to study predictors of long-term mortality. During an average follow-up of 3.4 years (range, 1.6 to 5.6 years), 102 patients (33%) in the intensive insulin group and 138 (44%) in the control group died ( P =0.011). Old age, previous heart failure, diabetes duration, admission blood glucose, and admission Hb A Ic were independent predictors of mortality in the total cohort, whereas previous AMI, hypertension, smoking, or female sex did not add independent predictive value. Metabolic control, mirrored by blood glucose and Hb A Ic , improved significantly more in patients on intensive insulin treatment than in the control group. β-Blockers improved survival in control subjects, whereas thrombolysis was most efficient in the intensive insulin group. Conclusions —Mortality in diabetic patients with AMI is predicted by age, previous heart failure, and severity of the glycometabolic state at admission but not by conventional risk factors or sex. Intensive insulin treatment reduced long-term mortality despite high admission blood glucose and Hb A Ic .
Letter by Dardas and Aaronson Regarding Article, “Impact of Implantable Cardioverter-Defibrillator, Amiodarone, and Placebo on the Mode of Death in Stable Patients With Heart Failure: Analysis From the Sudden Cardiac Death in Heart Failure Trial”
Authors: Todd F. Dardas, Keith D. Aaronson
Journal: Circulation (2010)
High occurrence of JAK2 V617 mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis
Authors: Renneville A, Quesnel B, Charpentier A, Terriou L, Crinquette A, Laï Jl, Cossement C, Lionne-Huyghe P, Rose C, Bauters F, Preudhomme C
Journal: Leukemia (2006)
Responses to Drug-Induced Myocardial Necrosis in Rats with Various Degrees of Arteriosclerosis
Authors: BERNARD C. WEXLER, GEORGE W. KITTINGER, JOSEPH T. JUDD
Journal: Circulation Research (1967)

Severe myocardial necrosis was produced in virgin Sprague-Dawley rats without preexisting arteriosclerosis and in breeder Sprague-Dawley rats with various degrees of arteriosclerosis by giving two subcutaneous injections of isoproterenol; the virgin rats received 50 mg/100 g and the breeder rats 25 mg/100 g body weight. Breeder rats withstood the stress and shock of myocardial necrosis with fewer untoward effects than the virgin animals. Changes in the thymus and adrenal glands also indicated that the arteriosclerotic breeder rats responded with a different pattern of adrenocortical activity. There were marked differences between the nonarteriosclerotic and arteriosclerotic rats in the fluctuation of serum transaminases and lactic dehydrogenase levels during the stress of myocardial necrosis. During the acute stages of myocardial necrosis there was intense activation of lipid metabolism with gross and microscopic evidence of intense fatty infiltration of the liver; during myocardial repair this lipid was removed concomitantly with reduction of hypercholesteremia. The dichotomy of response has been ascribed to the possibility that the preexisting arteriosclerosis in the breeder rats led to the development of increased collateral coronary artery circulation which afforded some degree of protection to the myocardium.
Vascular endothelial growth factor gene polymorphism and acute respiratory distress syndrome
Authors: A R L Medford
Journal: Thorax (2005)

<b>Background:</b> Non-cardiogenic pulmonary oedema is a characteristic feature of the acute respiratory distress syndrome (ARDS). The properties of vascular endothelial growth factor (VEGF) as a potent vascular permogen and mitogen have led to investigation of its potential role in this condition. Lower VEGF plasma levels have been linked to the presence of the T allele in the +936 CT polymorphism. We hypothesised that the presence of the T allele would be associated with the development and severity of ARDS. <b>Methods:</b> A cohort of 137 normal subjects, 117 ventilated patients with ARDS, and 103 "at risk" of ARDS were genotyped for the VEGF+936 CT polymorphism. The severity of physiological disturbance and mortality was determined in the ventilated cohorts. <b>Results:</b> The CT and TT genotype frequencies were increased in ARDS patients compared with both normal subjects (OR 2.01, 95% CI 1.13 to 3.58, p = 0.02) and those "at risk" (OR 2.05, 95% CI 1.02 to 2.20, p = 0.03). In patients with ARDS but not those "at risk", CT and TT genotypes were associated with a higher mean APACHE III score (80.9 (4.3) <i>v</i> 69.3 (2.9), p&lt;0.05). <b>Conclusion:</b> These data support a role for VEGF in the pathogenesis of ARDS and its associated physiological derangement.
Monensin turns on microtubule-associated translocation of secretory granules in cultured rat atrial myocytes.
Authors: H Iida, W M Barron, E Page
Journal: Circulation Research (1988)

We have studied the effect of monensin on microtubule-associated translocation of atrial secretory granules in 5-7-day-old cultures of atrial myocytes from adult rats. Atrial granules and microtubules were localized by immunofluorescent microscopy of myocytes double-labeled with primary antibodies against atrial natriuretic polypeptide (ANP) and alpha-tubulin. In control myocytes, fluorescence due to atrial granules was predominantly localized to the perinuclear region containing the Golgi complex. After exposure for 30 minutes to monensin (0.5-5.0 microM), myocytes transiently contained conspicuous linear arrays of atrial granules associated with cytoplasmic microtubules. Thereafter, ANP fluorescence accumulated in subsarcolemmal foci at the cell periphery, while perinuclear ANP fluorescence faded. The monensin-induced redistribution of atrial granules was observable in both serum-containing and serum-free media and was unaffected by reducing external Ca2+ to low values, by inhibition of sarcoplasmic reticulum Ca2+ release with ryanodine, or by both. The redistribution was prevented by pretreatment with nocodazole, which fragmented microtubules and scattered Golgi complexes and the associated atrial granules throughout the cytoplasm. Radioimmunoassay showed that monensin seemingly decreased the rate of ANP secretion into the medium from 0.15 to 0.11 fmol/(hr.myocyte). These results suggest that monensin turns on microtubule-associated translocation of atrial granules from the perinuclear areas to the cell periphery by modifying the interaction between microtubules and atrial granules. Monensin also promotes movement of atrial granules along the microtubules but does not accelerate the release of ANP.
Preclinical Evaluation of the Breast Cancer Cell-Binding Peptide, p160
Authors: Vasileios Askoxylakis, Sabine Zitzmann, Walter Mier, Keith Graham, Susanne Krämer, Frederic von Wegner, Rainer H.A. Fink, Manfred Schwab, Michael Eisenhut, Uwe Haberkorn
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Selective delivery of drugs into the target tissue is expected to result in high drug concentrations in the tissue of interest and therefore enhanced drug efficacy. To develop a peptide-based radiopharmaceutical, we investigated the properties of a peptide with affinity for human breast cancer, which has been selected through phage display. Experimental Design: The bioactivity of the p160 peptide (VPWMEPAYQRFL) was evaluated in vitro and in vivo. The specific binding to human breast cancer MDA-MB-435 cells was confirmed in competition experiments. Internalization of the peptide was investigated with confocal microscopy. Furthermore, the biodistribution of 131I-labeled p160 was studied in tumor-bearing mice. In vivo stability was evaluated at different periods after tracer administration using high-performance liquid chromatography analysis. Results: The binding of 125I-labeled p160 was inhibited up to 95% by the unlabeled peptide with an IC50 value of 0.6 μmol/L. In addition, 40% of the total bound activity was found to be internalized into the human breast cancer cells. Although a rapid degradation was seen, biodistribution studies in nude mice showed a higher uptake in tumor than in most of the organs. Perfusion of the animals caused a reduction of the radioligand accumulation in the healthy tissues, whereas the tumor uptake remained constant. A comparison of [131I]p160 with a 131I-labeled Arg-Gly-Asp peptide revealed a higher tumor-to-organ ratio for [131I]p160. Conclusions: p160 has properties that make it an attractive carrier for tumor imaging and the intracellular delivery of isotopes or chemotherapeutic drugs.
Response to: 'Conventional bronchoscopic techniques in sarcoidosis: not too far behind’ by Dhooria<i>et al</i>
Authors: Robert C Rintoul, Rawya Ahmed, Brendan Dougherty, Nicholas R Carroll
Journal: Thorax (2015)

We thank Dhooria et al 1 for their complimentary comments on our review article about linear endobronchial ultrasound.2 We congratulate them on their carefully performed randomised controlled trial comparing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in conjunction with transbronchial lung biopsies (TBLB) and endobronchial biopsies (EBB) with conventional non-ultrasound-guided transbronchial needle aspiration (cTBNA) in conjunction with TBLB and EBB for the diagnosis …