tbuckley/cabot-search huggingface dataset:
A4.5 Do High Molecular Weight Adiponectin Levels Associate with Radiographic Progression in early Rheumatoid Arthritis and Hand Osteoarthritis?
Authors: IR Klein-Wieringa, SN Andersen, JC Kwekkeboom, L Herb-v.Toorn, AHM van der Helm-van Mil, I Meulenbelt, TWJ Huizinga, M Kloppenburg, REM Toes, A Ioan-Facsinay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adipose tissue can secrete many different soluble factors (adipokines) influencing whole body metabolism. Some of these adipokines, such as adiponectin, have been shown to influence radiographic progression in osteoarthritis (OA) and rheumatoid arthritis (RA). In RA patients, total adiponectin (totAPN) levels in serum associate positively with radiographic progression, which suggestes an adverse effect on disease. Intruiguingly, in patients with hand OA, high totAPN levels in serum associated with a decreased relative risk for radiographic progression, suggesting a benificial effect on disease. Adiponectin is a pleiotropic adipokine, which consists of several isoforms. Of these isoforms, high molecular weight adiponectin (hmwAPN) has been described as one of the most biologically active and its effect on radiographic progression in RA and hand OA is unknown. <h3>Objective</h3> Therefore, we explored the possibility that the association between totAPN and disease progression is primarily mediated by the hmwAPN isoform. <h3>Methods</h3> Concentrations of hmwAPN and totAPN were determined in baseline plasma of 324 RA patients from the Early Arthritis Cohort (EAC) and in baseline sera of 164 hand OA patients from the Genetics Arthrosis and Progression (GARP) study. The association between levels of hmwAPN and totAPN with radiographic progression were determined using a multivariate normal regression model (EAC cohort) or by generalised estimated equations (GARP cohort). Adjustments were made for age, gender, treatment strategy and Body Mass Index (BMI). <h3>Results</h3> In RA patients totAPN associated positively with radiographic progression (Sharp van der Heijde scores) (association estimate 3.65, p = 0.002), whereas in patients with hand OA, totAPN associated negatively with radiographic progression (joint space narrowing (JSN)) (Odds 0.24/Odds 0.21, p = 0.002/p = 0.002 two highest tertiles compared to the lowest tertile). HmwAPN on the other hand, did not associate significantly with radiographic progression in patients with hand OA or RA, although in patients with RA we did observe a trend towards a positive association (association estimate 1.53 p = 0.07) upon correcting for age, gender and treatment strategy. This trend was lost after further adjustment for BMI. Similar results were obtained when joint space narrowing (JSN) was used as outcome measurement. <h3>Conclusions</h3> Our data further substantiate the connexion between APN-levels and radiographic progression in rheumatic disease and indicate that the differential effects associated between totAPN and radiographic progression in either in RA and hand OA is not mediated by (a selective effect of) hmwAPN.
Enhanced autophagy ameliorates cardiac proteinopathy
Authors: Md. Shenuarin Bhuiyan, J. Scott Pattison, Hanna Osinska, Jeanne James, James Gulick, Patrick M. McLendon, Joseph A. Hill, Junichi Sadoshima, Jeffrey Robbins
Journal: Journal of Clinical Investigation (2013)

Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryABR120G mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryABR120G hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryABR120G mice and the Atg7-crossed CryABR120G mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryABR120G cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions.
Late Na+Current Inhibition by Ranolazine Reduces Torsades de Pointes in the Chronic Atrioventricular Block Dog Model
Authors: Gudrun Antoons, Avram Oros, Jet D.M. Beekman, Markus A. Engelen, Marien J.C. Houtman, Luiz Belardinelli, Milan Stengl, Marc A. Vos
Journal: Journal of the American College of Cardiology (2010)
Coming now to a chest clinic near you
Authors: Charlotte E Bolton, Andrew Bush
Journal: Thorax (2013)

Premature birth means that instead of being fluid-filled and non-functional for many weeks, the immature lungs are gas-filled and have to support respiration. Often they are exposed to iatrogenic positive not physiological negative pressure expansion, infections, fluid overload and potentially hazardous treatments such as systemic steroids. Hence the respiratory sequelae of a premature birth need to be a major focus as more and more immature infants survive. Novel treatments, in particular, ‘gentle’ ventilator strategies (low mean airway pressures, faster rates), antenatal corticosteroids and inhaled surfactant have transformed the nature of the respiratory impairment from the traditional bronchopulmonary dysplasia (BPD) which was primarily an airways disease to ‘new’ BPD, more related to arrested alveolar development. However, our focus has long been on short term morbidity and mortality. As a community we have been particularly bad at following these young people up and appreciating their ongoing problems and risks. Specifically, paediatricians have sighed with relief when these children are no longer oxygen dependent, and have failed to keep these children under review. Furthermore, as we recently documented adult chest physicians rarely make enquiries about early life events.1 So survivors of prematurity are apt to disappear into a modern-day black hole.

In part, the problem may have arisen because of lack of appreciation of normal lung growth and the consequences of disease. There are three key stages which need to be optimal for long term lung health. First, lung growth in utero, ensuring the child is delivered with normally developed lungs, and second, the rate of lung growth in childhood, both determine whether the child will reach the full potential plateau at age 20–25 years.2 The airway generations are laid down by 16 weeks and primitive gas exchanging units develop from around 24 weeks of …
500 years later: Henry VIII, leg ulcers and the course of history
Authors: CR Chalmers, EJ Chaloner
Journal: Journal of the Royal Society of Medicine (2009)

In 1509, at the age of 18 years, Henry VIII ascended the throne of England and the recent 500th anniversary of this event has prompted a resurgence of interest in his life, politics and health. Henry was a fascinating character: initially blessed with good looks and stature; tremendous sporting prowess; a renaissance scholar revered by his subjects as ‘Bluff King Hal’. However, over the course of his 38-year reign, he underwent a dramatic personal metamorphosis to become a despotic, cruel and tyrannical sovereign, vile of temper and cursed by his deteriorating health and his ‘sorre legge’.1 While the changes in his character undoubtedly mirrored the pressures and political machinations of the day, it is interesting to reflect on the impact that persistent ulceration would have had on his life, personality and political administration. Five hundred years later, with the advent of vascular surgery and a modern understanding of the factors inherent in ulceration, it is also possible to reconsider the underlying aetiology of his leg ulcers.

Henry himself was keenly interested in medicine. He founded the Royal College of Physicians in 15182 and amalgamated The Barbers Company of London and the Guild (or Fellowship) of Surgeons to form the Company of Barber-Surgeons3 in 1540 (Figure 1). His administration passed seven separate Acts of Parliament aimed at regulating and licensing medical practitioners, legislature that required no further amendment for 300 years.4 Guided by Sir Thomas More, the Under-Sherriff of London, Henry presided over great improvements in public health; installing public water supplies and sewers, and implementing segregation and crude disinfection during epidemics of plaque and sweating-sickness.5 Henry also personally prepared medicines in the form of salves and ointments from compounds such as ground pearls and white lead for the treatment of his friends and, later, for himself:6 ‘An Oyntment devised by the kinges Majesty made at Westminster. And devised at Grenwich to take away inflammations and to cease payne and heale ulcers called gray plaster.’



Figure 1

Henry VIII and the Barber-Surgeons. This large work was commissioned from Hans Holbein the Younger to commemorate the grant of a royal charter to the Company of Barbers and the Guild of Surgeons on their merger in 1540. Henry is shown wearing his famous ...
Microbial Contamination of Shellfish: Prevalence, Risk to Human Health, and Control Strategies
Authors: R. J. Wittman, G. J. Flick
Journal: Annual Review of Public Health (1995)

There has been significant concern in recent times about the safety of molluscan shellfish for human consumption. Despite extensive efforts to assure a safe supply of molluscan shellfish, the number of cases of disease and death are still great enough to cause concern among the public. The number of cases of illness and death associated with the ingestion of shellfish falls in the lower end of the range of other similar microbial pathogen-related foodborne disease. Disease and deaths due to viruses and naturally occurring bacteria are now of greatest concern because they are the most often cited casusative agents. The greatest risk of disease or death due to shellfish consumption is among the population with underlying health conditions who choose to consume raw shellfish. Control strategies to limit shellfish-borne disease should focus upon disease and death caused by viruses and naturally occurring bacteria among at-risk populations.
Activation of Tubular Epithelial Cells in Diabetic Nephropathy and the Role of the Peroxisome Proliferator–Activated Receptor-γ Agonist
Authors: Sydney C.W. Tang, Joseph C.K. Leung, Loretta Y.Y. Chan, Anita W.L. Tsang, Kar Neng Lai
Journal: Journal of the American Society of Nephrology (2006)

The effects of advanced glycation end products (AGE) in the form of glycated albumin (GA) on the proinflammatory phenotype of cultured renal proximal tubular epithelial cells (PTEC) and the therapeutic potential of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist were studied. Human PTEC were exposed to medium alone or supplemented with albumin or GA with or without previous addition of rosiglitazone (0.1 to 0.5 microM). Exposure to GA (up to 0.5 mg/ml) but not the equivalent dose of neat albumin significantly upregulated both mRNA and protein expression of IL-8 and soluble intercellular adhesion molecule-1 (sICAM-1) in a dose- and time-dependent manner. Using immunohistochemistry, ICAM-1 signals were detected in the tubular epithelia and peritubular capillaries in association with AGE deposition and leukocyte infiltration, whereas IL-8 staining was localized in the tubular epithelia of human diabetic kidney biopsies. Also in a dose-dependent manner, GA (0.5 mg/ml) but not albumin caused nuclear translocation of NF-kappaB and activation of mitogen-activated protein kinase (MAPK) p44/p42 and signal transducer and activator of transcription (STAT-1). Inhibition of these pathways with pyrrolidine dithiocarbamate, PD 98059, and fludarabine, respectively, attenuated GA-induced IL-8 secretion. Rosiglitazone dose-dependently attenuated GA-induced IL-8 and ICAM-1 signals in PTEC and completely abolished GA-induced STAT-1 signals but had no effect on NF-kappaB and MAPK activation. These findings suggest that AGE stimulate renal tubular expression of adhesion molecule and chemokine that together may account for the transmigration of inflammatory cells into the interstitial space during diabetic tubulopathy. Such proinflammatory phenotype may be partially modified by PPAR-gamma ligation through STAT-1 inhibition independent of NF-kappaB transcriptional activity and MAPK signaling.
Hyponatremia in the rat in the absence of positive water balance.
Authors: M Gowrishankar, C B Chen, S Cheema-Dhadli, A Steele, M L Halperin
Journal: Journal of the American Society of Nephrology (1997)

The purpose of this report is to determine the mechanisms that lead to hyponatremia when isotonic saline was the only fluid infused into rats given antidiuretic hormone (ADH), and what might minimize the degree of this hyponatremia. Normal rats were deprived of food and water for the 24-hr study period. They received an infusion of isotonic saline to expand their extracellular fluid (ECF) volume with and without exogenous ADH administration (N = 8 in each of the four groups). Similar studies were also carried out in 32 rats fed a low electrolyte diet for 72 hr before the experiment. An additional control group was fed the low electrolyte diet supplemented with sodium (Na), potassium (K), and chloride (Cl). Hyponatremia developed over 24 hr in rats fed their usual diet if treated with ADH and isotonic saline (fall, 13 +/- 2 mM, P < 0.01). The hyponatremia was caused by negative balance for Na + K salts. Hyponatremia did not develop after the saline + ADH treatment if rats were pretreated for 3 days with a low electrolyte diet. Two factors were required to develop this hyponatremia--generation of electrolyte-free water as a result of the excretion of a large quantity of Na + K salts at a high concentration in the urine, and prevention of the excretion of this electrolyte-free water by ADH. Increasing the avidity for Na reabsorption by the kidney prevented this type of hyponatremia from developing.
Court allows US human embryonic stem cell research to continue, for now
Authors: J. H. Tanne
Journal: BMJ (2010)

The US Court of Appeals for the District of Columbia permanently lifted an injunction on 28 September imposed by a lower court prohibiting federal funding of human embryonic stem cell research. The ruling allows research to continue while the lower court considers the lawsuit that charges federal funding for human embryonic stem cell research is prohibited.

The injunction was issued on 23 August by Judge Royce Lamberth of the lower court, the US District Court for the District of Columbia ( BMJ 26 August, doi:10.1136/bmj.c4689). It called for a halt …
Biliary Cystic Tumors: Clinicopathological Features
Authors: Yasuni Nakanuma, Hiroko Ikeda, Yasunori Sato, Kenichi Harada, Koichi Nakamura, Yoh Zen
Journal: Liver Cancer (2009)

Several types of biliary cystic tumors or tumorous lesions have been reported (Nakanuma et al., 2000; Portman and Nakanuma, 2006). Currently, with advanced imaging techniques, increasing numbers of cystic diseases including rare types are being found, and their clinicopathological features are now being characterized (Okuda, 2001). Hepatobiliary cystadenoma and cystadenocarcinoma are a prototype of biliary cystic tumors, and intraductal papillary neoplasm of the bile duct, particularly with cystic dilatation, is a recently proposed disease entity (Chen et al., 2001). However, the exact definition and clinicopathological features of these biliary cystic tumors, particularly for differential diagnosis, remain to be established because the number of cases is small. While the cystic lesions themselves are rather easily detectable by imaging modalities, an exact diagnosis based on pathological characteristics is needed at present. In this chapter, the clinicopathological features of biliary cystic tumors, such as their walls being lined by biliary or other epithelial cells, are reviewed. The tumors can be divided into non-neoplastic and neoplastic categories. The former includes hamartomatous lesions or developmental anomalies. Recently, diagnostic criteria for intraductal papillary mucinous neoplasm (IPMN) and mucinous cystadenoma and cystadeno-carcinoma, which are also called mucinous cystic neoplasm of the pancreas (pancreatic MCN), have been established with reference to the presence of communication with the duct system and also the presence of ovarian-like stroma in the cystic walls (Longnecker et al., 2000; Zamboni et al., 2000). Recent studies showed that two similar types of neoplastic diseases are also present in the hepatobiliary system (Chen et al., 2001; Zen et al., 2006b; Abraham et al., 2002, 2003). In this review, these biliary cystic tumors are discussed and compared with pancreatic cystic tumors from the standpoint of their clinicopathological similarities. Solitary hepatic cyst, polycystic liver, and cystic dilatation of the bile duct will not be discussed here.
Effect of autonomic nervous system modulation on retrograde atrioventricular nodal conduction in the human heart
Authors: M. A. SADR-AMELI, M. SHENASA, P. LACOMBE, G. FAUGERE, R. NADEAU
Journal: Cardiovascular Research (1987)

Although the influence of the autonomic nervous system on anterograde atrioventricular nodal conduction is well established, its effect on retrograde atrioventricular nodal conduction has not been examined systematically. Since retrograde atrioventricular nodal conduction in subjects with normal anterograde conduction may vary from intact retrograde conduction to complete retrograde block when assessed during ventricular pacing, in this study patients with (a) intact retrograde atrioventricular nodal conduction (group 1) were studied during parasympathetic (vagal) stimulation by carotid sinus pressure and during sympathetic inhibition (propranolol 0.2 mg.kg-1 intravenously) and (b) retrograde atrioventricular nodal block (group 2) were studied during vagal blockade (atropine 0.04 mg.kg-1 intravenously) and during sympathetic stimulation (isoproterenol 1-4 micrograms.min-1 infusion). In both groups changes in sinus cycle length and anterograde atrioventricular nodal conduction were measured. In group 1 vagal stimulation by carotid sinus pressure in 20 patients caused the cycle length at which retrograde atrioventricular nodal block was induced to be significantly lengthened from a mean(SD) of 375(59) to 451(51) ms in six patients; caused complete retrograde block in 10 patients; and had no effect in four patients. Sympathetic inhibition by propranolol in another 15 patients delayed the onset of pacing induced retrograde atrioventricular nodal block from a mean(SD) of 340(60) to 418(80) ms in 11 patients; caused complete retrograde atrioventricular nodal block in three patients; and had no effect in one patient. In group 2 vagal blockade by atropine caused a 1:1 retrograde response during ventricular pacing up to a mean(SD) cycle length of 470(135) ms in six out of eight patients. The infusion of isoproterenol caused the retrograde atrioventricular nodal block to be abolished and 1:1 conduction to be resumed up to a ventricular pacing mean(SD) cycle length of 364(57) ms in six out of eight patients. It is concluded that (a) the autonomic nervous system modulates retrograde atrioventricular nodal conduction in a similar manner to its anterograde counterpart and (b) that since retrograde atrioventricular nodal conduction was reversible after the administration of either atropine or isoproterenol retrograde atrioventricular nodal block may be dynamic (physiological) rather than fixed (anatomical) in nature.
Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations
Authors: P Gorello, G Cazzaniga, F Alberti, M G Dell'Oro, E Gottardi, G Specchia, G Roti, R Rosati, M F Martelli, D Diverio, F Lo Coco, A Biondi, G Saglio, C Mecucci, B Falini
Journal: Leukemia (2006)
B-1b Cells Secrete Atheroprotective IgM and Attenuate Atherosclerosis
Authors: Sam M. Rosenfeld, Heather M. Perry, Ayelet Gonen, Thomas A. Prohaska, Prasad Srikakulapu, Sukhdeep Grewal, Deepanjana Das, Chantel McSkimming, Angela M. Taylor, Sotirios Tsimikas, Timothy P. Bender, Joseph L. Witztum, Coleen A. McNamara
Journal: Circulation Research (2015)

Rationale: B cells contribute to atherosclerosis through subset-specific mechanisms. Whereas some controversy exists about the role of B-2 cells, B-1a cells are atheroprotective because of secretion of atheroprotective IgM antibodies independent of antigen. B-1b cells, a unique subset of B-1 cells that respond specifically to T-cell–independent antigens, have not been studied within the context of atherosclerosis. Objective: To determine whether B-1b cells produce atheroprotective IgM antibodies and function to protect against diet-induced atherosclerosis. Methods and Results: We demonstrate that B-1b cells are sufficient to produce IgM antibodies against oxidation-specific epitopes on low-density lipoprotein both in vitro and in vivo. In addition, we demonstrate that B-1b cells provide atheroprotection after adoptive transfer into B- and T-cell deficient ( Rag1 −/− Apoe −/− ) hosts. We implicate inhibitor of differentiation 3 (Id3) in the regulation of B-1b cells as B-cell–specific Id3 knockout mice (Id3 BKO Apoe −/− ) have increased numbers of B-1b cells systemically, increased titers of oxidation-specific epitope–reactive IgM antibodies, and significantly reduced diet-induced atherosclerosis when compared with Id3 WT Apoe −/− controls. Finally, we report that the presence of a homozygous single nucleotide polymorphism in ID3 in humans that attenuates Id3 function is associated with an increased percentage of circulating B-1 cells and anti–malondialdehyde-low-density lipoprotein IgM suggesting clinical relevance. Conclusions: These results provide novel evidence that B-1b cells produce atheroprotective oxidation-specific epitope–reactive IgM antibodies and protect against atherosclerosis in mice and suggest that similar mechanisms may occur in humans.