tbuckley/cabot-search huggingface dataset:
Ambulatory Electrocardiographic Evidence of Transmural Dispersion of Repolarization in Patients With Long-QT Syndrome Type 1 and 2
Authors: Matti Viitasalo, Lasse Oikarinen, Heikki Swan, Heikki Väänänen, Kathy Glatter, Päivi J. Laitinen, Kimmo Kontula, Hal V. Barron, Lauri Toivonen, Melvin M. Scheinman
Journal: Circulation (2002)

Transmural dispersion of repolarization (TDR) may be related to the genesis of torsade de pointes (TdP) in patients with the long-QT (LQT) syndrome. Experimentally, LQT2 models show increased TDR compared with LQT1, and beta-adrenergic stimulation increases TDR in both models. Clinically, LQT1 patients experience symptoms at elevated heart rates, but LQT2 patients do so at lower rates. The interval from T-wave peak to T-wave end (TPE interval) is the clinical counterpart of TDR. We explored the relationship of TPE interval to heart rate and to the presence of symptoms in patients with LQT1 and LQT2.We reviewed Holter recordings from 90 genotyped subjects, 31 with LQT1, 28 with LQT2, and 31 from unaffected family members, to record TPE intervals by use of an automated computerized program. The median TPE interval was greater in LQT2 (112+/-5 ms) than LQT1 (91+/-2 ms) or unaffected (86+/-3 ms) patients (P<0.001 for all group comparisons), and the maximal TPE values differed as well. LQT1 patients showed abrupt increases in TPE values at RR intervals from 600 to 900 ms, but LQT2 patients did so at RR intervals from 600 to 1400 ms (longest RR studied). Asymptomatic and symptomatic patients showed similar TDRs.TDR is greater in LQT2 than in LQT1 patients. LQT1 patients showed a capacity to increase TDR at elevated heart rates, but LQT2 patients did so at a much wider rate range. The magnitude of TDR is not related to a history of TdP.
Repair of the Injured Adult Heart Involves New Myocytes Potentially Derived From Resident Cardiac Stem Cells
Authors: David Angert, Remus M. Berretta, Hajime Kubo, Hongyu Zhang, Xiongwen Chen, Wei Wang, Barbara Ogorek, Mary Barbe, Steven R. Houser
Journal: Circulation Research (2011)

The ability of the adult heart to generate new myocytes after injury is not established.Our purpose was to determine whether the adult heart has the capacity to generate new myocytes after injury, and to gain insight into their source.Cardiac injury was induced in the adult feline heart by infusing isoproterenol (ISO) for 10 days via minipumps, and then animals were allowed to recover for 7 or 28 days. Cardiac function was measured with echocardiography, and proliferative cells were identified by nuclear incorporation of 5-bromodeoxyuridine (BrdU; 7-day minipump infusion). BrdU was infused for 7 days before euthanasia at days 10, 17, and 38 or during injury and animals euthanized at day 38. ISO caused reduction in cardiac function with evidence of myocyte loss from necrosis. During this injury phase there was a significant increase in the number of proliferative cells in the atria and ventricle, but there was no increase in BrdU+ myocytes. cKit+ cardiac progenitor cells were BrdU labeled during injury. During the first 7 days of recovery there was a significant reduction in cellular proliferation (BrdU incorporation) but a significant increase in BrdU+ myocytes. There was modest improvement in cardiac structure and function during recovery. At day 38, overall cell proliferation was not different than control, but increased numbers of BrdU+ myocytes were found when BrdU was infused during injury.These studies suggest that ISO injury activates cardiac progenitor cells that can differentiate into new myocytes during cardiac repair.
Promoter Hypermethylation of Multiple Genes in Sputum Precedes Lung Cancer Incidence in a High-Risk Cohort
Authors: Steven A. Belinsky, Kieu C. Liechty, Frederick D. Gentry, Holly J. Wolf, Justin Rogers, Kieu Vu, Jerry Haney, Tim C. Kennedy, Fred R. Hirsch, York Miller, Wilbur A. Franklin, James G. Herman, Stephen B. Baylin, Paul A. Bunn, Tim Byers
Journal: Cancer Research (2006)

Abstract A sensitive screening approach for lung cancer could markedly reduce the high mortality rate for this disease. Previous studies have shown that methylation of gene promoters is present in exfoliated cells within sputum prior to lung cancer diagnosis. The purpose of the current study is to conduct a nested case-control study of incident lung cancer cases from an extremely high-risk cohort for evaluating promoter methylation of 14 genes in sputum. Controls (n = 92) were cohort members matched to cases (n = 98) by gender, age, and month of enrollment. The comparison of proximal sputum collected within 18 months to &amp;gt;18 months prior to diagnosis showed that the prevalence for methylation of gene promoters increased as the time to lung cancer diagnosis decreased. Six of 14 genes were associated with a &amp;gt;50% increased lung cancer risk. The concomitant methylation of three or more of these six genes was associated with a 6.5-fold increased risk and a sensitivity and specificity of 64%. This is the first study to prospectively examine a large panel of genes for their ability to predict lung cancer and shows the promise of gene promoter hypermethylation in sputum as a molecular marker for identifying people at high risk for cancer incidence. (Cancer Res 2006; 66(6): 3338-44)
A novel mouse model of lipotoxic cardiomyopathy
Authors: Hsiu-Chiang Chiu, Attila Kovacs, David A. Ford, Fong-Fu Hsu, Ricardo Garcia, Pilar Herrero, Jeffrey E. Saffitz, Jean E. Schaffer
Journal: Journal of Clinical Investigation (2001)

Inherited and acquired cardiomyopathies are associated with marked intracellular lipid accumulation in the heart. To test the hypothesis that mismatch between myocardial fatty acid uptake and utilization leads to the accumulation of cardiotoxic lipid species, and to establish a mouse model of metabolic cardiomyopathy, we generated transgenic mouse lines that overexpress long-chain acyl-CoA synthetase in the heart (MHC-ACS). This protein plays an important role in vectorial fatty acid transport across the plasma membrane. MHC-ACS mice demonstrate cardiac-restricted expression of the transgene and marked cardiac myocyte triglyceride accumulation. Lipid accumulation is associated with initial cardiac hypertrophy, followed by the development of left-ventricular dysfunction and premature death. Terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling staining and cytochrome c release in transgenic hearts suggest that cardiac myocyte death occurs, in part, by lipid-induced programmed cell death. Taken together, our data demonstrate that fatty acid uptake/utilization mismatch in the heart leads to accumulation of lipid species toxic to cardiac myocytes. This novel mouse model will provide insight into the role of perturbations in myocardial lipid metabolism in the pathogenesis of inherited and acquired forms of heart failure.
Manganese Is Essential for Neuronal Health
Authors: Kyle J. Horning, Samuel W. Caito, K. Grace Tipps, Aaron B. Bowman, Michael Aschner
Journal: Annual Review of Nutrition (2015)

The understanding of manganese (Mn) biology, in particular its cellular regulation and role in neurological disease, is an area of expanding interest. Mn is an essential micronutrient that is required for the activity of a diverse set of enzymatic proteins (e.g., arginase and glutamine synthase). Although necessary for life, Mn is toxic in excess. Thus, maintaining appropriate levels of intracellular Mn is critical. Unlike other essential metals, cell-level homeostatic mechanisms of Mn have not been identified. In this review, we discuss common forms of Mn exposure, absorption, and transport via regulated uptake/exchange at the gut and blood-brain barrier and via biliary excretion. We present the current understanding of cellular uptake and efflux as well as subcellular storage and transport of Mn. In addition, we highlight the Mn-dependent and Mn-responsive pathways implicated in the growing evidence of its role in Parkinson's disease and Huntington's disease. We conclude with suggestions for future focuses of Mn health-related research.
The effect of anti-reactional drugs on complement components in the type II, erythema nodosum leprosum, reaction
Authors: V. N. SEHGAL, V. SHARMA, V. K. SHARMA
Journal: British Journal of Dermatology (1988)

Seventeen patients with the type II (erythema nodosum leprosum) (ENL) reaction were studied. They received multidrug therapy and also the anti‐reactional drugs prednisolone clofazimine or chloroquin, and we measured serum levels of complement components before treatment and after the reaction had subsided. Factor B was significantly elevated after treatment with each of the three drugs. C3 levels were significantly increased after treatment, the largest change being in patients treated with clofazimine. In these patients there was also a concomitant decrease in C3d levels. This suggests that clofazimine has complement modulating activity and we would recommend it as the drug of choice in treatment of the ENL reaction.
Tissue distribution of beta 3-adrenergic receptor mRNA in man.
Authors: S Krief, F Lönnqvist, S Raimbault, B Baude, A Van Spronsen, P Arner, A D Strosberg, D Ricquier, L J Emorine
Journal: Journal of Clinical Investigation (1993)

Expression of mRNA for beta 1-, beta 2-, and beta 3-adrenergic receptors (beta 1-, beta 2-, and beta 3-AR) was investigated in human tissues. beta 1- and beta 2-AR mRNA distribution correlated with that of the cognate receptors established by pharmacological studies. beta 3-AR transcripts were abundant in infant perirenal brown adipose tissue, characterized by the presence of uncoupling protein (UCP) mRNA. In adult whole adipose tissues, beta 3-AR mRNA levels were high in deep deposits such as perirenal and omental, and lower in subcutaneous. In these deposits, UCP mRNA levels paralleled those of beta 3-AR. However, isolated omental and subcutaneous adipose cells, enriched in white adipocytes, expressed beta 3-AR but no UCP transcripts. beta 3-AR mRNA was highly expressed in gallbladder, and to a much lower extent in colon, independently of UCP mRNA. Quadriceps or abdominal muscles, heart, liver, lung, kidney, thyroid, and lymphocytes did not express intrinsic beta 3-AR mRNA. This study demonstrates that substantial amounts of brown adipocytes exist throughout life in adipose deposits, which are generally classified as white. These deposits are the main sites of beta 3-AR expression, which also occurs in gallbladder and colon. beta 3-AR may thus be involved in the control of lipid metabolism, possibly from fat assimilation in the digestive tract, to triglyceride storage and mobilization in adipose tissues.
Obscure clinical implication of occult hepatitis B virus infection by perinatal transmission despite prophylaxis with hepatitis B vaccination and HBIG
Authors: Chien-Hsieh Chiang, Yen-Hsuan Ni
Journal: Journal of Hepatology (2012)

Dear Editor:We are much interested in the article by Shahmoradi et al. pub-lished in the Journal of Hepatology [1]. In the cross-sectionalreport, the authors investigated the serum samples of 75 childrenborn to hepatitis B surface antigen (HBsAg)-positive mothers.Hepatitis B virus (HBV) DNA could be detected in 21 (28%) outof 75 children previously immunized by a dose of HBIG and threestandard injections of hepatitis B vaccines. All were positive forantibody to hepatitis B surface antigen (anti-HBs), while only 5(24%) were positive for antibody to hepatitis B core antigen(anti-HBc). There are some issues to be addressed.Almost all babies who acquired HBV infection through perina-tal transmission were born to mothers with positive hepatitis B eantigen (HBeAg) [2]. HBeAg can cross the placenta and helpestablish the infectivity [3]. HBeAg, viral load, and metabolicfactors may entangle each other to foster the perinatal transmis-sion [4]. However, this article did not elucidate the associationbetween the risk of occult HBV infection and these three factors.The relatively higherprevalence of occult HBV infection in thisstudy is not consistent with our ﬁndings in Taiwan [5], where theprevalence of occult HBV infection was about 0.1% (3/2954)under the 25-year infant universal vaccination program coverage.One possible explanation is that the polymerase chain reactionused in this report was too sensitive to avoid false positive results[1]. Besides, the detection of HBV DNA in this study might be tooearly for anti-HBc levels to be measurable [6]. HBV genotyping isanother concern. Occult HBV infection in Taiwan is mainly geno-type C [5], rather than genotype D as in North of Iran [1]. We alsodo not know how long the positive HBV DNA status would persistin these cases.We agree that mother-to-infant transmission is not com-pletely blocked by immunoprophylaxis [7]. Although the emerg-ing escape mutants caused some concern, less infectivity ofG145R, recombinant vaccine use, and mutant loss with olderage seem to decrease the mutant prevalence in an immunizedpopulation over time [8]. In addition to the risk of transmissionby blood transfusion, individuals with occult HBV infection areat risk of reactivation when they receive chemotherapy or immu-nosuppressive therapy [6]. However, whether the clinical out-come of occult HBV infection is signiﬁcant or not remainsunclear since most people with occult HBV infection have anormal liver function.In conclusion, a long-term follow-up study is mandatory todeﬁne the clinical signiﬁcance of occult HBV infection causedby perinatal transmission if any.Conﬂict of interestThe authors declared that they do not have anything to discloseregarding funding or conﬂict of interest with respect to thismanuscript.References
Health System Costs of Out-of-Hospital Cardiac Arrest in Relation to Time to Shock
Authors: Anouk P. van Alem, Marcel G.W. Dijkgraaf, Jan G.P. Tijssen, Rudolph W. Koster
Journal: Circulation (2004)

Background— Early defibrillation results in higher admission rates and healthcare costs. This study determined the healthcare resources used and related medical costs after out-of-hospital cardiac arrest (OHCA) in relation to time to shock. We assessed the incremental healthcare costs per life gained from reduction in time to shock of 2, 4, and 6 minutes. Methods and Results— Clinical and costs data of patients in witnessed OHCA with ventricular fibrillation as initial rhythm were collected. Each patient’s time to shock was estimated and assigned to 1 of 3 categories: ≤7 minutes (early), 7 to 12 minutes (intermediate), and &gt;12 minutes (late). Incremental cost-effectiveness analysis and Monte Carlo simulation compared scenarios of reduction in time to shock of 2, 4, and 6 minutes. Six-month survival was 22%. Mean prehospital, in-hospital, and posthospital costs in the first half-year after OHCA were €559, €6869 and €666. Mean costs were €28 636 per survivor and €2384 per nonsurvivor. Among patients shocked early (n=24), 46% survived, with costs averaging €20 253. Of the intermediate group (n=149), 26% survived, with costs averaging €31 467. Among patients shocked late (n=135), 13% survived, with costs averaging €27 781. The point estimates of the incremental cost-effectiveness ratios of reduction of time to shock of 2, 4, and 6 minutes compared with baseline were €17 508, €14 303, and €12 708 per life saved, respectively. Conclusions— Costs per survivor were lowest with the shortest time to shock because of shorter stay in the intensive care unit. Reducing the time to defibrillation increases the healthcare costs by an acceptable amount according to current standards and is economically attractive.
Exploratory differential gene expression analysis in microarray experiments with no or limited replication
Authors: Alexander V Loguinov, I Saira Mian, Chris D Vulpe
Journal: Genome biology (2004)

We describe an exploratory, data-oriented approach for identifying candidates for differential gene expression in cDNA microarray experiments in terms of alpha-outliers and outlier regions, using simultaneous tolerance intervals relative to the line of equivalence (Cy5 = Cy3). We demonstrate the improved performance of our approach over existing single-slide methods using public datasets and simulation studies.
Deficient production of IL-1 receptor antagonist and IL-6 coupled to oxidative stress in cryopyrin-associated periodic syndrome monocytes
Authors: Sonia Carta, Sara Tassi, Laura Delfino, Alessia Omenetti, Salvatore Raffa, Maria Rosaria Torrisi, Alberto Martini, Marco Gattorno, Anna Rubartelli
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To determine whether dysregulated production of cytokines downstream of interleukin (IL)-1 participates in the pathophysiology of cryopyrin-associated periodic syndromes (CAPS). <h3>Methods</h3> Primary monocytes from patients with CAPS, unstimulated or after stimulation with lipopolysaccharide (LPS) and other Toll-like receptor (TLR) agonists, were examined for signs of stress and production of IL-1β, IL-1 receptor antagonist (IL-1Ra) and IL-6 in comparison with monocytes from patients with autoimmune diseases and from healthy donors. <h3>Results</h3> Unstimulated CAPS monocytes showed mild signs of stress including elevated levels of reactive oxygen species and fragmented mitochondria. Stress signs were worsened by TLR stimulation and eventually led to protein synthesis inhibition with strong impairment of production of cytokines downstream of IL-1, such as IL-1Ra and IL-6. These defects were not detected in monocytes from autoimmune patients and healthy donors. <h3>Conclusions</h3> The stress state of LPS-stimulated CAPS monocytes and the consequent inhibition of translation are likely to be responsible for the impaired production of IL-1Ra and IL-6. The deficient secretion of these cytokines coupled with increased IL-1β release explains the severity of the IL-1-related clinical manifestations and the predominant implication of innate immunity in CAPS.
Optimal Calcium Intake
Authors: Robert P. Heaney
Journal: JAMA (1994)

IT HAS BEEN a decade since the 1984 Consensus Development Conference on Osteoporosis first suggested that increased intake of calcium might help prevent osteoporosis. Osteoporosis affects more than 25 million people in the United States and is the major underlying cause of bone fractures in postmenopausal women and the elderly. Previous surveys have revealed that the US population experiences more than 1.5 million fractures annually at a cost in excess of $10 billion per year to the health care system. Two important factors that influence the occurrence of osteoporosis are optimal peak bone mass attained in the first two to three decades of life and the rate at which bone is lost in later years. Adequate calcium intake is critical to achieving optimal peak bone mass and modifies the rate of bone loss associated with aging. A number of publications have addressed the possible role of calcium intake in the
Trends in 5- and 10-year Survival After Diagnosis with Childhood Hematologic Malignancies in the United States, 1990–2004
Authors: Dianne Pulte, Adam Gondos, Hermann Brenner
Journal: JNCI Journal of the National Cancer Institute (2008)

Advances in the treatment of childhood hematologic malignancies have led to improvements in survival for several of these conditions during the past few decades, but most population-based survival data available to date refer only to patients diagnosed up to the mid-1990s.We used period analysis to assess trends in 5- and 10-year survival in US patients younger than 15 years of age at diagnosis with four hematologic malignancies--acute lymphoblastic leukemia, acute non-lymphoblastic leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma--over three recent 5-year intervals, 1990-1994, 1995-1999, and 2000-2004, using data on a total of 6957 patients from the Surveillance, Epidemiology, and End Results database. Expected survival for 2005-2009 was estimated by modeling from trends in the preceding intervals.Major improvements in 5- and 10-year relative survival between 1990-1994 and 2000-2004 were seen for acute lymphoblastic leukemia (from 80.2% to 87.5% and from 73.4% to 83.8%, respectively), acute non-lymphoblastic leukemia (from 41.9% to 59.9% and from 38.7% to 59.1%, respectively), and non-Hodgkin lymphoma (from 76.6% to 87.7% and from 73.0% to 86.9%, respectively). For those diagnosed with Hodgkin lymphoma, 5- and 10-year survival rates for the 1990-1994 period were 96.1% and 94.4%, respectively, and these rates did not change substantially in the later time periods. Projected 10-year survival rates for children diagnosed in the 2005-2009 period were 88.0% for acute lymphoblastic leukemia, 63.9% for acute non-lymphoblastic leukemia, 90.6% for non-Hodgkin lymphoma, and 94.3% for Hodgkin lymphoma.Application of period analysis to a population-based study of childhood hematologic malignancies reveals ongoing increases in survival for three of the four common childhood hematologic malignancies.
Amygdala Activity During Autobiographical Memory Recall in Depressed and Vulnerable Individuals: Association With Symptom Severity and Autobiographical Overgenerality
Authors: Kymberly D. Young, Greg J. Siegle, Jerzy Bodurka, Wayne C. Drevets
Journal: American Journal of Psychiatry (2015)

In healthy individuals, autobiographical memory recall is biased toward positive and away from negative events, while the opposite is found in depressed individuals. This study examined amygdala activity during autobiographical memory recall as a putative mechanism underlying biased memory recall and depressive symptoms in currently depressed adults and two vulnerable populations: individuals remitted from depression and otherwise healthy individuals at high familial risk of developing depression. Identification of such vulnerability factors could enable interception strategies that prevent depression onset.Sixty healthy control subjects, 45 unmedicated currently depressed individuals, 25 unmedicated remitted depressed individuals, and 30 individuals at high familial risk of developing depression underwent functional MRI while recalling autobiographical memories in response to emotionally valenced cue words. Amygdala reactivity and connectivity with anatomically defined amygdala regions were examined.During positive recall, depressed participants exhibited significantly decreased left amygdala activity and decreased connectivity with regions of the salience network compared with the other groups. During negative recall, control subjects had significantly decreased left amygdala activity compared with the other groups, while depressed participants exhibited increased amygdala connectivity with the salience network. In depressed participants, left amygdala activity during positive recall correlated significantly with depression severity (r values >-0.38) and percent of positive specific memories recalled (r values >0.59).The results suggest that left amygdala hyperactivity during negative autobiographical recall is a trait-like marker of depression, as both vulnerable groups showed activity similar to the depressed group, while amygdala hypoactivity during positive autobiographical recall is a state marker of depression manifesting in active disease. Treatments targeting amygdala hypoactivity and blunted salience during positive autobiographical recall could exert antidepressant effects.