tbuckley/cabot-search huggingface dataset:
Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy.
Authors: A M Brillantes, P Allen, T Takahashi, S Izumo, A R Marks
Journal: Circulation Research (1992)

The molecular basis for the systolic and diastolic dysfunction characteristic of end-stage heart failure in humans remains poorly understood. It has been proposed that both abnormal calcium handling and defects in the contractile apparatus may contribute to the myocardial dysfunction. Two channels, the calcium release channel (CRC) or ryanodine receptor of the sarcoplasmic reticulum (SR), and the slow calcium channel or dihydropyridine receptor (DHPR) of the transverse tubule, play key roles in regulating intracellular calcium concentration and in excitation-contraction (E-C) coupling in the heart. The DHPR serves as the voltage sensor and plasma membrane calcium channel resulting in activation of the CRC during E-C coupling in heart muscle. In this study, we investigated the levels of CRC expression in several forms of end-stage heart failure in humans. A cardiac CRC cDNA was cloned from rabbit and used as a probe for Northern blot analyses to determine mRNA levels in the left ventricles of normal (n = 4) and cardiomyopathic (n = 34) human hearts from patients undergoing cardiac transplantation. Compared with normal patients, patients with ischemic cardiomyopathy (n = 18) showed a 28% decrease in CRC mRNA levels (p less than 0.025) and patients with idiopathic dilated cardiomyopathy (n = 14) a nonsignificant 12% increase. In these same hearts, alpha-actin levels were unchanged in end-stage heart failure, as has been previously reported. This is the first report indicating that the expression of the CRC mRNA is abnormal in end-stage human heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Sustained activation of nuclear factor kappa B and activator protein 1 in chronic heart failure
Authors: S Frantz
Journal: Cardiovascular Research (2003)

Objective: Innate immune response proteins such as inflammatory cytokines, inducible nitric oxide synthase, and toll like receptors are implicated in myocardial depression and left ventricular (LV) remodeling after myocardial infarction (MI). Although all these innate immunity proteins share the downstream activation of the transcription factor NF-κB (nuclear factor kappa B) and activator protein 1 (AP-1), the involvement of NF-κB and AP-1 in LV remodeling has not been demonstrated so far. Methods and results: Nuclear translocation of NF-κB and AP-1 was studied by electrophoretic mobility shift assays and ELISA 10 weeks after large experimental MI in rats, the chronic phase of LV remodeling. In the non-infarcted myocardium of MI rats, NF-κB and AP-1 were significantly activated (2.5-fold) as compared to sham-operated animals. Immunohistochemistry demonstrated NF-κB activation mainly in cardiac myocytes. Treatment with the ACE (angiotensin converting enzyme) inhibitor trandolapril led to a further 2-fold increase in the activation of NF-κB and AP-1 when compared to placebo-treated animals with the same MI size (P<0.001). Human failing hearts explanted at the time of heart transplantation exhibited marked nuclear translocation of NF-κB in cardiac myocytes when compared to control hearts. NF-κB as well as AP-1 were both significantly activated in congestive heart failure due to ischemic or dilated cardiomyopathy. Conclusion: In experimental and human heart failure, both NF-κB and AP-1 are chronically activated in cardiac myocytes. These findings suggest an important involvement of NF-κB and AP-1 in the cardiac remodeling process.
Distensibility and Water Content of Heart Muscle Before and After Injury
Authors: PETER F. SALISBURY, CECIL E. CROSS, P. ANDRE RIEBEN
Journal: Circulation Research (1960)

In open-chest dogs the circulation was carried on a heart-lung machine. The right heart and the left atrium were drained. A balloon was placed in the virtually bloodless left ventricle and filled with a known volume of air at the beginning of an experiment; left ventricular pressure was recorded after a steady state had become established. After this control observation, the preparation was exposed to experimental maneuvers, such as variation of the systemic flow rate or changes of the air volume in the balloon. At one or more later stages of the same experiment, the balloon was emptied, the heart was allowed to beat empty for several minutes, and the standard observation was again repeated. Comparison of left ventricular pressures from the initial and later observations showed that the diastolic pressure in the left ventricle increased in the course of the experiment even though other conditions were comparable. From this we conclude that experimental maneuvers injuring the heart muscle reduce its distensibility. The water content of injured hearts was abnormally elevated; myocardial edema is therefore not excluded as one of the mechanisms explaining the reduced distensibility of injured heart muscle.
Effects of High-Flux Hemodialysis on Clinical Outcomes
Authors: Alfred K Cheung, Nathan W Levin, Tom Greene, Lawrence Agodoa, James Bailey, Gerald Beck, William Clark, Andrew S Levey, John K Leypoldt, Daniel B Ornt, Michael V Rocco, Gerald Schulman, Steve Schwab, Brendan Teehan, Garabed Eknoyan
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for &gt;3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; <i>P</i> = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; <i>P</i> = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; <i>P</i> = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with &lt;3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation.
High Relaxivities and Strong Vascular Signal Enhancement for NaGdF<sub>4</sub> Nanoparticles Designed for Dual MR/Optical Imaging
Authors: Rafik Naccache, Pascale Chevallier, Jean Lagueux, Yves Gossuin, Sophie Laurent, Luce Vander Elst, Cornelia Chilian, John A. Capobianco, Marc‐André Fortin
Journal: Advanced Healthcare Materials (2013)

Near-infrared (NIR)-to-NIR upconverting NaY(Gd)F4 :Tm(3+) ,Yb(3+) paramagnetic nanoparticles (NPs) are efficiently detected by NIR imaging techniques. As they contain Gd(3+) ions, they also provide efficient "positive" contrast in magnetic resonance imaging (MRI). Water-dispersible small (≈25 nm, "S-") and ultrasmall (<5 nm diam., "US-") NaY(Gd)F4 :Tm(3+) ,Yb(3+) NPs are synthesized by thermal decomposition and capped with citrate. The surface of citrate-coated US-NPs shows sodium depletion and high Gd elemental ratios, as confirmed by a comparative X-ray photoelectron spectroscopy (XPS)/neutron absorption analysis study. US-NaGd0.745 F4 :Tm0.005 ,Yb0.25 NPs have hydrodynamic diameters close to that measured by TEM, with the lowest relaxometric ratios (r2 /r1 = 1.18) reported for NaGdF4 nanoparticle suspensions (r1 = 3.37 mM(-1) s(-1) at 1.4 T and 37 °C). Strong relaxivity peaks in the range of 20 (0.47 T) - 300 MHz (7.05 T) are revealed in nuclear magnetic resonance dispersion profiles, with high r2 /r1 ratios at increasing field strengths for S-NPs. This indicates the superiority of US-NPs over S-NPs for achieving high positive contrast at clinical MRI field strengths. I.-v. injected citrate-coated US-NPs evidence long blood retention times (>90 min) in mice. Biodistribution studies (48 h, 8 d) show elimination through the reticuloendothelial and urinary systems, similarly to other citrate-capped US-NP systems. In summary, upconverting NaY(Gd)F4 :Tm(3+) ,Yb(3+) nanoparticles have promising luminescent, relaxometric and blood-retention properties for dual MRI/optical imaging.
Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial
Authors: Martin E Gore, Cezary Szczylik, Camillo Porta, Sergio Bracarda, Georg A Bjarnason, Stéphane Oudard, Subramanian Hariharan, Se-Hoon Lee, John Haanen, Daniel Castellano, Eduard Vrdoljak, Patrick Schöffski, Paul Mainwaring, Alejandra Nieto, Jinyu Yuan, Ronald Bukowski
Journal: The Lancet Oncology (2009)
Isolation from individual A/J mice of anti-rho-azophenylarsonate antibodies bearing a cross-reactive idiotype.
Authors: A S Tung, A Nisonoff
Journal: The Journal of Experimental Medicine (1975)

Immuization of A/J mice with a KLH-p-azophenylarsonate conjugate induces the formation of antihapten antibodies, some of which share idiotypic specificity common to all recipients. The subpopulation carrying the idiotype generally comprises 20-70% of the total antibody content. Large quantities of antihapten antibody (occasionally over 100 mg) were obtained from individual mice through the induction of an ascites fluid. This facilitated isolation of antibodies with the cross-reactive idiotype by isoelectric focusing. Most of this subpopulation has pI values between 6.65 and 6.95 and essentially all is of the IgG1 subclass. Two peaks, near pI 6.7 and 6.9, were frequently observed. Upon refocusing, the protein artifact of the procedure, but indicates microheterogeneity. The antibodies in the two peaks were found to be idiotypically identical by measurements of cross-inhibition. Preliminary studies have indicated that it is feasible to initiate investigations of primary structure with antibodies from individual inbred mice.
Cd5 Maintains Tolerance in Anergic B Cells
Authors: Keli L. Hippen, Lina E. Tze, Timothy W. Behrens
Journal: The Journal of Experimental Medicine (2000)

Clonal anergy of autoreactive B cells is a key mechanism regulating tolerance. Here, we show that anergic B cells express significant surface levels of CD5, a molecule normally found on T cells and a subset of B-1 cells. Breeding of the hen egg lysozyme (HEL) transgenic model for B cell anergy onto the CD5 null background resulted in a spontaneous loss of B cell tolerance in vivo. Evidence for this included elevated levels of anti-HEL immunoglobulin M (IgM) antibodies in the serum of CD5(-/-) mice transgenic for both an HEL-specific B cell receptor (BCR) and soluble lysozyme. "Anergic" B cells lacking CD5 also showed enhanced proliferative responses in vitro and elevated intracellular Ca(2+) levels at rest and after IgM cross-linking. These data support the hypothesis that CD5 negatively regulates Ig receptor signaling in anergic B cells and functions to inhibit autoimmune B cell responses.
Drugs as Indicators of Hepatic Function
Authors: Robert A. Branch
Journal: Hepatology (1982)

It is well recognized that liver disease may influence the disposition of many drugs. Conversely, it has been suggested that knowledge of the disposition of a model drug might provide an index of certain aspects of hepatic function. This review discusses the physiology of drug disposition and indicates how recent progress in understanding the determinants of drug disposition has provided useful indices of individual aspects of hepatic function. Topics which are discussed are the interpretation of pharmacokinetic parameters as indices of hepatic function, including half-life clearance, and intrinsic clearance. Utilizing the "intact hepatocyte hypothesis" as an operational model, an approach is described that uses the pharmacokinetic disposition of high and low intrinsic clearance drugs following p.o. and i.v. administration to provide quantitative estimates of hepatic function, flow to functioning hepatocytes, and the extent of portasystemic shunting through the liver. Thus, the theoretical basis for quantitation of certain aspects of hepatic function are available. It remains to be determined whether these indices will provide clinically useful measures to follow the natural history of hepatic disease.
Renal Volume, Renin-Angiotensin-Aldosterone System, Hypertension, and Left Ventricular Hypertrophy in Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: Robert W Schrier
Journal: Journal of the American Society of Nephrology (2009)

<h3>Objective:</h3> To present an unusual case with complex management of acute motor-sensory axonal neuropathy (AMSAN) associated with systemic lupus erythematosus (SLE). <h3>Background:</h3> AMSAN is a variant of Guillian-Barré syndrome. The standard treatment is intravenous immunoglobulin (IVIg) or plasmapheresis. SLE is a multisystem autoimmune disease which is generally treated by immunosuppressant. The association of AMSAN and SLE is rarely reported. Herein, we described the clinical presentation and complex management in the case of AMSAN with SLE. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A previously healthy 72-year-old Caucasian man presented with rapidly progressive paraparesis and dysesthesia and bilateral knees and finger pain with morning stiffness. He had no history of recent fever, diarrhea or vaccination. Neurological examination showed complete quadriplegia and areflexia. Hyperesthesia was noted in all extremities. Cranial nerves were intact. Pain with passive movement and tenderness were noted in knees and joints of the fingers. Other systemic examination was normal. Blood work showed elevated erythrocyte sedimentation rate, antinuclear antibody, and anti-dsDNA titer. Antineutrophil cytoplasmic antibody and paraneoplastic antibodies were negative. Cerebrospinal fluid showed albuminocytologic dissociation. Nerve conduction study was suggestive for acute diffuse axonal sensorimotor polyneuropathy (motor predominant). Initially, the patient was treated by IVIg without significant response. Because the patient met the systemic lupus international collaborating clinic diagnostic criteria for SLE, intravenous methylprednisolone and cyclophosphamide were given. Joint pain was resolved. The motor strength was slowly improving. Ganglioside antibody panel reported positive GD1b antibody with negative GM1, GD1a and GQ1b. Ten days later, the weakness started worsening. After plasmapheresis, the patient was stabilized, then slowly improving. The outcome at 3 and 6 months will be presented at the conference. <h3>Conclusions:</h3> The association of AMSAN and SLE is poorly understood. Combination of IVIg and/or plasmapheresis with immunosuppression may benefit in AMSAN associated with SLE. <b>Disclosure:</b> Dr. Thakolwiboon has nothing to disclose. Dr. Karukote has nothing to disclose.
Prevention of Falls in Community-Dwelling Older Adults: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2012)

Update of the 1996 U.S. Preventive Services Task Force (USPSTF) recommendation statement on counseling to prevent household and recreational injuries, including falls.The USPSTF reviewed new evidence on the effectiveness and harms of primary care-relevant interventions to prevent falls in community-dwelling older adults. The interventions were grouped into 5 main categories: multifactorial clinical assessment (with or without direct intervention), clinical management (with or without screening), clinical education or behavioral counseling, home hazard modification, and exercise or physical therapy.The USPSTF recommends exercise or physical therapy and vitamin D supplementation to prevent falls in community-dwelling adults aged 65 years or older who are at increased risk for falls. (Grade B recommendation)The USPSTF does not recommend automatically performing an in-depth multifactorial risk assessment in conjunction with comprehensive management of identified risks to prevent falls in community-dwelling adults aged 65 years or older because the likelihood of benefit is small. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of the circumstances of prior falls, comorbid medical conditions, and patient values. (Grade C recommendation).
The Value of Information and the Ethics of Personal-Genomic Screening
Authors: Peter H. Schwartz
Journal: The American Journal of Bioethics (2009)

Click to increase image sizeClick to decrease image size Acknowledgment This work was supported in part by a grant from Richard M. Fairbanks Foundation to the Indiana University Center for Bioethics on “Predictive Health Research Ethics and Regulation.” Thanks to Amy Gilbert and Eva Jackson for research assistance.
Assessment of Differentiation and Progression of Hepatic Tumors Using Array-Based Comparative Genomic Hybridization
Authors: Doris Steinemann, Britta Skawran, Thomas Becker, Marcel Tauscher, Anja Weigmann, Luzie Wingen, Sarah Tauscher, Tanja Hinrichsen, Sabine Hertz, Peer Flemming, Jacobus Flik, Birgit Wiese, Hans Kreipe, Peter Lichter, Brigitte Schlegelberger, Ludwig Wilkens
Journal: Clinical Gastroenterology and Hepatology (2006)
Obstructive sleep apnoea, insulin resistance and sleepiness
Authors: M. S M Ip
Journal: Thorax (2008)

Our understanding of obstructive sleep apnoea (OSA) has advanced much beyond that of the condition being a noisy breathing abnormality during sleep which classically presents with daytime sleepiness, to a condition with numerous potentially significant downstream sequelae and multisystem manifestations. The relationship between OSA and metabolic dysfunction is a moving target. Cross sectional studies have provided suggestive evidence for an independent relationship between OSA and adverse glucose metabolism, while supportive longitudinal data and interventional data from randomised controlled trials are still lacking.1 Recently, data from the Sleep Heart Health Study again confirmed the independent association between sleep disordered breathing and impaired glucose metabolism in normal weight and overweight/obese individuals.2 In this issue of Thorax , the study of Barcelo and colleagues3 suggested that the presence/absence of daytime sleepiness determined the presence/absence of increased insulin resistance in OSA, and that continuous positive airway pressure (CPAP) treatment decreased insulin resistance in sleepy subjects but had no effect in non-sleepy subjects (see page 946) . Their findings showed a pattern analogous to the previously reported phenomenon regarding OSA and elevated blood pressure, whereby the severity of daytime sleepiness in OSA predicted a blood pressure lowering response to CPAP treatment.4 5

Excessive daytime sleepiness has always been considered as one of the cardinal symptoms of OSA, and it is usually improved by effective treatment of OSA. However, it has also been well recognised that excessive daytime sleepiness is not universally present in OSA …
Echolucent carotid plaques predict future coronary events in patients with coronary artery disease
Authors: Osamu Honda, Seigo Sugiyama, Kiyotaka Kugiyama, Hironobu Fukushima, Shinichi Nakamura, Shunichi Koide, Sunao Kojima, Nobutaka Hirai, Hiroaki Kawano, Hirofumi Soejima, Tomohiro Sakamoto, Michihiro Yoshimura, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2004)
The micrornas as biomarkers in knee osteoarthritis
Authors: Y. M. Pers, F. Djouad, I. Duroux-Richard, F. Apparailly, D. Noel, C. Jorgensen
Journal: Annals of the Rheumatic Diseases (2010)

Among the new biomarkers associated with rheumatoid arthritis (RA), we describe the microRNA (miRNAs). miRNAs are small RNAs of 21–23 nucleotides able to inhibit gene expression. The objectives of this work are to identify the original miRNAs as biomarkers in two different chronic bone and joint diseases, osteoarthritis (OA) and RA.

Serum samples and fresh …
Sputum sol phase proteins and elastase activity in patients with clinically stable bronchiectasis.
Authors: P Lloberes, E Montserrat, J M Montserrat, C Picado
Journal: Thorax (1992)

Inflammatory and proteolytic activity occurs in sputum from patients with stable purulent bronchiectasis and has been proposed as the main pathogenetic mechanism of the disease. This study was designed to define further the role of inflammation and proteolysis in bronchiectasis.Neutrophil elastase activity, sputum concentrations of the serum derived inhibitors alpha 1 antiproteinase and alpha 2 macroglobulin, and the sputum to serum ratios of albumin and C reactive protein concentration were measured in 26 patients with bronchiectasis.Free elastase activity was found in 15 sputum samples. A trend to higher proteolytic and inflammatory activity was found between mucoid and purulent sputum samples, suggesting that inflammatory and proteolytic activities are related to the macroscopic degree of purulence. Purulent sputum had a high sputum to serum ratio of C reactive protein, suggesting local production or active transport of this protein into bronchial secretions. C reactive protein was more sensitive than albumin in detecting a higher degree of inflammation in elastase positive samples.The finding of greater concentrations of alpha 2 macroglobulin in purulent and elastase positive samples than in mucopurulent, mucoid and elastase negative sputum samples suggests that this inhibitor may have a role in the proteolysis-antiproteolysis balance in bronchial secretions.