tbuckley/cabot-search huggingface dataset:
Nonuniform Ca2+ transients in arrhythmogenic Purkinje cells that survive in the infarcted canine heart
Authors: P Boyden
Journal: Cardiovascular Research (2003)

Objective and methods: In this study, we investigated whether Ca2+ transients are altered in Purkinje cell aggregates dispersed from the subendocardium overlying the infarcted zone of the left ventricle (IZPCs) 48 h after coronary artery occlusion. To do so, we combined epifluorescent imaging with microelectrode recordings of IZPCs and normal canine Purkinje cell aggregates (NZPCs). Results: NZPCs respond to an action potential (AP) by a small Ca2+ transient at the cell surface immediately after the AP upstroke followed by a large [Ca2+] transient, which propagates to the cell core. In addition, focal Ca2+ waves can originate spontaneously later during the AP or during the diastolic interval (Circ Res 2000;86:448–55) and then propagate throughout the aggregate as 'cell-wide Ca2+ waves'. Electrically-evoked Ca2+ transients in IZPCs arose significantly faster than those in NZPCs, and showed substantial spatiotemporal nonuniformity within an IZPC aggregate as well as between IZPC aggregates. IZPCs showed, hitherto undetected, low amplitude, micro Ca2+ transients (extent ≤5 μm) at a fivefold higher incidence than in NZPCs. Micro Ca2+ transients appeared to meander over distances ≤100 μm and reduced the local Ca2+ transient of the next paced beat. Micro Ca2+ transients nearly always preceded the cell-wide Ca2+waves, which occurred more frequently in IZPCs than in NZPCs and caused non-driven electrical activity of the Purkinje aggregate. Conclusions: Micro Ca2+ transients preceded cell-wide Ca2+ waves so often that it is probable that micro Ca2+ transients induced cell-wide Ca2+ waves. Cell-wide Ca2+ waves, in turn, clearly elicited spontaneous APs. We propose that the high incidence of micro Ca2+ transients in IZPCs is a fundamental element of the abnormal Ca2+ handling of diseased Purkinje cells, underlying arrhythmias originating in the subendocardial Purkinje network post myocardial infarction.
Endoplasmic reticulum Ca2+ depletion induces endothelial cell apoptosis independently of caspase-12
Authors: T NAKANO, H WATANABE, M OZEKI, M ASAI, H KATOH, H SATOH, H HAYASHI
Journal: Cardiovascular Research (2005)

Apoptosis of endothelial cells is considered an initial step in the development of atherosclerosis. Recent studies have indicated that depletion of the endoplasmic reticulum (ER) Ca(2+) content plays an important role in apoptosis. Caspase-12 is a key signal in ER stress-induced apoptosis. However, it is not known whether the depletion of ER Ca(2+) is linked to caspase-12 signalling in endothelial cells. Here we have investigated the interaction of Ca(2+) signalling and caspase-12 cleavage in apoptosis of endothelial cells.Cytosolic Ca(2+) concentration ([Ca(2+)](i)) of primary porcine aortic endothelial cells was measured using fura-2/AM. Apoptosis was assessed by DNA fragmentation, and cleavage of caspase-12 using Western blotting techniques.Thapsigargin (5 microM), an inhibitor of the ER Ca(2+)-ATPase, depleted ER Ca (2+) content, increased [Ca(2+)](i), cleaved caspase-12, and induced apoptosis. Bradykinin (10 nM) also increased [Ca(2+)](i) but did not cleave caspase-12 or induce apoptosis. However, when intracellular Ca(2+) was chelated with BAPTA/AM (100 microM), bradykinin caused ER Ca(2+) depletion and apoptosis without accompanying caspase-12 cleavage. A non-selective caspase inhibitor, z-VAD.fmk (100 microM), inhibited apoptosis and cleavage of caspase-12 stimulated by thapsigargin, while a calpain inhibitor, MDL 28170 (120 microM), inhibited caspase-12 cleavage but not apoptosis.Thus, increases in intracellular Ca(2+) concentration are not sufficient for the induction of apoptosis in endothelial cells, and ER Ca(2+) depletion appears to induce apoptosis independently of caspase-12.
Risk factors for pulmonary disease due to culture‐positive M. tuberculosis or nontuberculous mycobacteria in South African gold miners
Authors: P. Sonnenberg, J. Murray, J.R. Glynn, R Glyn Thomas, P Godfrey-Faussett, S Shearer
Journal: European Respiratory Journal (2000)

The aim of this study was to determine risk factors for disease due to nontuberculous mycobacteria (NTM) compared to those due to Mycobacterium tuberculosis in South African gold miners with pulmonary mycobacterial disease. A case/control study comparing tuberculosis and NTM cases amongst all patients with a positive sputum mycobacterial culture in 1995 was carried out. The 51 cases of disease due to NTM and 425 tuberculosis cases were similar with regard to age, education, home region, smoking habits and percentage of CD4 cells. After adjustment for confounders, those with NTM were more likely to have had previous tuberculosis treatment (odds ratio (OR) 3.61; 95% confidence interval (CI) 1.9-6.9), have worked longer underground (p-value for trend=0.05) or have evidence of silicosis (OR 12.6; 95% CI 2.2-71) and were less likely to drink regularly (OR 0.12; 95% CI 0.02-0.93) than patients with tuberculosis. In patients with disease due to NTM, 35.3% were human immunodeficiency virus-positive compared with 48.8% of tuberculosis patients (p=0.2) and an estimated 21% overall in the mines at the time of the study. Previous tuberculosis treatment, silicosis and duration of underground work are even more strongly associated with disease due to nontuberculous mycobacteria than with tuberculosis. Attempts to reduce the incidence of all pulmonary mycobacterial disease in this community should address recognized risk factors and ensure that those with tuberculosis are diagnosed, treated and cured.
Transurethral Resection and Surveillance of Bladder Cancer Supported by 5-Aminolevulinic Acid-Induced Fluorescence Endoscopy
Authors: Martin Kriegmair, Dirk Zaak, Helmut Stepp, Herbert Stepp, Reinhold Baumgartner, Ruth Knuechel, Alfons Hofstetter
Journal: European Urology (1999)
The articular manifestations of progressive systemic sclerosis (scleroderma).
Authors: M Baron, P Lee, E C Keystone
Journal: Annals of the Rheumatic Diseases (1982)

<b>Introduction:</b> A method for the collection of lining fluid from small airways non-invasively has been developed, the PExA method (Particles in Exhaled Air). The exhaled particles are mainly composed of surfactant, and the most abundant phospholipid is di-palmitoylphosphocholine (DPPC) and the most abundant lung-specific protein is surfactant protein A (SP-A). <b>Methods:</b> 200 participants (mean age 53 years, range 40-66) in the Gothenburg part of the European Respiratory Community Health Survey (ERCHS- III) were examined with the PExA method, spirometry and FENO. PExA samples were analyzed for SP-A and albumin using ELISA, and the major phospholipids using GC-MS-MS. <b>Results:</b> 36 subjects reported physician diagnosed asthma, the majority had mild disease and no alterations of SP-A, albumin or phospholipid pattern in PExA samples. Subjects reporting an asthma attack the last year (n=17) had increased levels of PC 16:0/18:2 (11.3 vs 10.2 %SI, p=0.01) and decreased levels of albumin (6.8 vs 5.6 wt%, p=0.03) in PExA samples, compared to healthy subjects. In the whole group, the levels of DPPC were correlated with FENO (rs=0.3, p=0.03), and weakly with the FEV1/FVC ratio (rs=0.17, p=0.02). Smokers had increased levels of DPPC compared to non-smokers (9.9 vs 11.4 wt%, p= 0.02) and PC16:0/18:2 (28.3 vs 25.1 %SI, p=0.05). <b>Conclusions:</b> In subjects with a recent asthma attack, the levels of PC16:0/18:2 was increased, plausibly a result of increased leakage from plasma. One may speculate that the increase in DPPC in smokers may have a protective function against the inhaled toxic cigarette fume.
Onco-Nephrology: An Invitation to a New Field
Authors: Kevin W. Finkel, Scott C. Howard
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: Kidney disease is common in patients with cancer and includes disorders that occur in people without cancer as well as entities that are unique to people with cancer, such as tumor lysis syndrome. However, as the field of oncology hasdevelopedareasofincreasingsubspecializationandthearrayof treatment options with novel agents has expanded, the need has been created for a new field: onco-nephrology. Such a necessity resultsfromseveralfactors.First,certainrenaldisordersareunique to patients with cancer, related either to therapy or the malignancy itself. Paraneoplastic glomerulonephritis, posthematopoietic stem-cell transplantation microangiopathy and sinusoidal obstruction syndrome, and kidney injury from graft-versus-host disease are prime examples. Therefore, it is a requirement that nephrologistsbeknowledgeableabouttheseuniquedisorders.Second, many patients with cancer are now cared for at comprehensive cancer centers where nephrologists have become integral members of treatment teams. Nephrologists must provide expertiseintheevaluationandmanagementofacuteandchronickidney disease, fluid and electrolyte disorders, and the use of various extracorporeal therapies in patients with cancer. Third, the presence of acute and chronic kidney disease in patients with cancer can adversely affect treatment and outcome. Patients with cancer are at increased risk of developing acute kidney injury (AKI) 1 ; survival rates are significantly lower in patients with cancer and AKI compared with patients with similar disease severity who do not have cancer. 2 In patients with chronic kidney disease (CKD), therapeutic doses may need to be reduced (thus decreasing the so-called killing effect), or some promising agents may need to be omitted altogether. Fourth, given that the prevalence of both cancer and CKD are high, a growing number of patients require the expertise of onco-nephrologists, who must be knowledgeable about the array of new chemotherapeutic agents and their potential effects on kidney function. The hypertension, CKD, and proteinuria that are associated with the use of antivascular endothelial growth factor (anti-VEGF) agents are examples. 3 Onconephrology in general, and the effects of anti-VEGF agents in particular, provide fertile ground for both clinical and basic research. Understanding the effects of anti-VEGF therapy has led to more insight into the function of the glomerular filter and the pathogenesis of preeclampsia. Onco-nephrologists must also be awareoftheeffectsofvariousdialyticmodalitiesondrugclearance.
Pulmonary vascular disorders in portal hypertension
Authors: P Herve, D Lebrec, F Brenot, G Simonneau, M Humbert, O Sitbon, P Duroux
Journal: European Respiratory Journal (1998)

The wide spectrum of pulmonary vascular disorders in liver disease and portal hypertension ranges from the hepatopulmonary syndrome characterized by intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary hypertension), in which pulmonary vascular resistance is elevated. Since hepatopulmonary syndrome and portopulmonary hypertension have been reported in patients with nonhepatic portal hypertension, the common factor that determines their development must be portal hypertension. The clinical presentations are very different, with gas exchange impairment in the hepatopulmonary syndrome and haemodynamic failure in portopulmonary hypertension. The severity of hepatopulmonary syndrome seems to parallel the severity of liver failure, whereas no simple relationship has been identified between hepatic impairment and the severity of portopulmonary hypertension. Resolution of hepatopulmonary syndrome is common after liver transplantation, which has an uncertain effect in portopulmonary hypertension. The pathophysiology of both syndromes may involve vasoactive mediators and angiogenic factors.
Analysis of Tumor Metabolism Reveals Mitochondrial Glucose Oxidation in Genetically Diverse Human Glioblastomas in the Mouse Brain In Vivo
Authors: Isaac Marin-Valencia, Chendong Yang, Tomoyuki Mashimo, Steve Cho, Hyeonman Baek, Xiao-Li Yang, Kartik N. Rajagopalan, Melissa Maddie, Vamsidhara Vemireddy, Zhenze Zhao, Ling Cai, Levi Good, Benjamin P. Tu, Kimmo J. Hatanpaa, Bruce E. Mickey, José M. Matés, Juan M. Pascual, Elizabeth A. Maher, Craig R. Malloy, Ralph J. DeBerardinis, Robert M. Bachoo
Journal: Cell Metabolism (2012)
Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study
Authors: Lisa B Signorello, John J Mulvihill, Daniel M Green, Heather M Munro, Marilyn Stovall, Rita E Weathers, Ann C Mertens, John A Whitton, Leslie L Robison, John D Boice
Journal: The Lancet (2010)
Authors’ response to Murray<i>et al</i>
Authors: Amelia O Clive, Brennan C Kahan, Nick A Maskell
Journal: Thorax (2014)

We thank Murray et al for their interest and complementary comments regarding the LENT score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type).1 We are pleased they felt it would be a beneficial addition to multidisciplinary team discussions.

We agree with their observation that the survival differences between cell types may reflect different stages of disease at presentation with malignant pleural effusion (MPE) or the availability of subsequent effective therapies for some of the underlying tumour types. However, when designing the LENT score we chose to use the cell types themselves rather than …
Personal Protection From Blood-Sucking Arthropods
Authors: Carroll N. Smith
Journal: JAMA (1966)

This symposium will be concerned primarily with methods which the individual can use to protect himself from disease-bearing insects and other invertebrates. Much of the time we will be talking about materials he can apply to his skin or clothing to repel these pests. In order to explain the elements of insect behavior that repellents must overcome, we will devote some time to a discussion of the factors that attract mosquitoes to their hosts and induce mosquitoes to bite. Since repellents are actually used to alleviate annoyance from insect bites more often than to prevent disease, we will discuss cutaneous responses to insects. We have also included a discussion of a novel method of insect control. An eighth contribution to this symposium, entitled "Protection From Ticks, Fleas, Chiggers, and Leeches" by Harry K. Gouck, has already been published in the<i>Archives of Dermatology</i>(<b>93</b>:112-113 [Jan] 1963). <h3>Protection from Disease</h3>
Injuries sustained by users and non-users of gum shields in local rugby union.
Authors: D C Jennings
Journal: British Journal of Sports Medicine (1990)

This study was undertaken because of the high number of orofacial injuries and the complacent attitude of local rugby union players to the wearing of gum shields in spite of encouragement and advice to do so.Amongst non-users there seemed to be an attitude that injuries are inevitable.This apathy and cavalier attitude to unnecessary injury needs to be changed.These injuries can be almost totally avoided
Recurrent miscarriage: aetiology, management and prognosis
Authors: T C Li, M Makris, M Tomsu, E Tuckerman, S Laird
Journal: Human Reproduction Update (2002)

Recurrent miscarriage (RM) is a heterogeneous condition. A large number of studies has recently been published, yet many of them have conflicting conclusions. The various aetiological factors, management, prognostic features and outcomes of a subsequent pregnancy in women with RM are reviewed.
Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis
Authors: Madhav C. Menon, Peter Y. Chuang, Zhengzhe Li, Chengguo Wei, Weijia Zhang, Yi Luan, Zhengzi Yi, Huabao Xiong, Christopher Woytovich, Ilana Greene, Jessica Overbey, Ivy Rosales, Emilia Bagiella, Rong Chen, Meng Ma, Li Li, Wei Ding, Arjang Djamali, Millagros Saminego, Philip J. O’Connell, Lorenzo Gallon, Robert Colvin, Bernd Schroppel, John Cijiang He, Barbara Murphy
Journal: Journal of Clinical Investigation (2014)

Fibrosis underlies the loss of renal function in patients with chronic kidney disease (CKD) and in kidney transplant recipients with chronic allograft nephropathy (CAN). Here, we studied the effect of an intronic SNP in SHROOM3, which has previously been linked to CKD, on the development of CAN in a prospective cohort of renal allograft recipients. The presence of the rs17319721 allele at the SHROOM3 locus in the donor correlated with increased SHROOM3 expression in the allograft. In vitro, we determined that the sequence containing the risk allele at rs17319721 is a transcription factor 7–like 2–dependent (TCF7L2-dependent) enhancer element that functions to increase SHROOM3 transcription. In renal tubular cells, TGF-β1 administration upregulated SHROOM3 expression in a β-catenin/TCF7L2–mediated manner, while SHROOM3 in turn facilitated canonical TGF-β1 signaling and increased α1 collagen (COL1A1) expression. Inducible and tubular cell–specific knockdown of Shroom3 markedly abrogated interstitial fibrosis in mice with unilateral ureteric obstruction. Moreover, SHROOM3 expression in allografts at 3 months after transplant and the presence of the SHROOM3 risk allele in the donor correlated with increased allograft fibrosis and with reduced estimated glomerular filtration rate at 12 months after transplant. Our findings suggest that rs17319721 functions as a cis-acting expression quantitative trait locus of SHROOM3 that facilitates TGF-β1 signaling and contributes to allograft injury.
Opioid Dose and Risk of Road Trauma in Canada
Authors: Tara Gomes, Donald A Redelmeier, David N Juurlink, Irfan A Dhalla, Ximena Camacho, Muhammad M Mamdani
Journal: JAMA Internal Medicine (2013)

Use of opioids may predispose drivers to road trauma, yet the effect of opioid dose on this association is unknown.We conducted a population-based nested case-control study of patients aged 18 to 64 years who received at least 1 publicly funded prescription for an opioid from April 1, 2003, through March 31, 2011. Cases were defined as having an emergency department visit related to road trauma. Patients without road trauma served as a control group matched to cases by age, sex, index year, prior road trauma, and a disease risk index. We compared the risk of road trauma among patients treated with doses of opioids ranging from very low to very high (<20 to ≥200 morphine equivalents daily). In a subgroup analysis, we stratified our analysis by driver status.Among 549 878 eligible adults, we identified 5300 cases with road trauma and matched an equal number of controls. Multivariate adjustment yielded no significant association between escalating opioid dose and odds of road trauma (adjusted odds ratio ranged between 1.00 and 1.09). However, a significant association between opioid dose and road trauma was observed among drivers. Compared with very low opioid doses, drivers prescribed low doses had a 21% increased odds of road trauma (adjusted odds ratio, 1.21 [95% CI, 1.02-1.42]); those prescribed moderate doses, 29% increased odds (1.29 [1.06-1.57]); those prescribed high doses, 42% increased odds (1.42 [1.15-1.76]); and those prescribed very high doses, 23% increased odds (1.23 [1.02-1.49]).Among drivers prescribed opioids, a significant relationship exists between drug dose and risk of road trauma. This association is distinct and does not appear with passengers, pedestrians, and others injured in road trauma.
Blood Culture Time to Positivity in Febrile Infants With Bacteremia
Authors: Eric A. Biondi, Matthew Mischler, Karen E. Jerardi, Angela M. Statile, Jason French, Rianna Evans, Vivian Lee, Clifford Chen, Carl Asche, Jinma Ren, Samir S. Shah
Journal: JAMA Pediatrics (2014)

Blood cultures are often obtained as part of the evaluation of infants with fever and these infants are typically observed until their cultures are determined to have no growth. However, the time to positivity of blood culture results in this population is not known.To determine the time to positivity of blood culture results in febrile infants admitted to a general inpatient unit.Multicenter, retrospective, cross-sectional evaluation of blood culture time to positivity. Data were collected by community and academic hospital systems associated with the Pediatric Research in Inpatient Settings Network. The study included febrile infants 90 days of age or younger with bacteremia and without surgical histories outside of an intensive care unit.Blood culture growing pathogenic bacteria.Time to positivity and proportion of positive blood culture results that become positive more than 24 hours after placement in the analyzer.A total of 392 pathogenic blood cultures were included from 17 hospital systems across the United States. The mean (SD) time to positivity was 15.41 (8.30) hours. By 24 hours, 91% (95% CI, 88-93) had turned positive. By 36 and 48 hours, 96% (95% CI, 95-98) and 99% (95% CI, 97-100) had become positive, respectively.Most pathogens in febrile, bacteremic infants 90 days of age or younger hospitalized on a general inpatient unit will be identified within 24 hours of collection. These data suggest that inpatient observation of febrile infants for more than 24 hours may be unnecessary in most infants.
Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus.
Authors: J W Yoon, P R McClintock, T Onodera, A L Notkins
Journal: The Journal of Experimental Medicine (1980)

Plaque purification of the M variant of encephalomyocarditis (EMC) virus resulted in the isolation of two stable variants: one diabetogenic and designated D and the other nondiabetogenic and designated B. When the D variant was inoculated into SJL/J male mice, hypoinsulinemia and hyperglycemia developed in > 90% of the animals. In contrast, none of the mice inoculated with the B variant developed diabetes. Histologic examination of pancreata from mice infected with the D variant revealed insulitis and necrosis of beta cells, whereas islets from mice infected with the B variant showed little, if any, change. When islets were assayed for infectious virus, approximately 10 times more virus was recovered from animals inoculated with the D as compared with the B variant. Moreover, approximately 60% of islet cells from mice infected with the D variant contained viral antigens when stained with fluorescein-labeled anti-EMC virus antibody, whereas < 5% of islet cells from animals infected with the B variant contained viral antigens. Co-infection experiments showed that the induction of diabetes by the D variant was inhibited by the B variant. When the B and D variants were mixed together at B:D ratios of 1, 9, and 99, diabetes developed in 60, 11, and 0% of the mice, respectively. Tissue-culture experiments revealed that the B variant induced considerably more interferon than the D variant, and studies in animals showed that interferon appeared earlier and in greater amounts in the circulation of mice infected with the B as compared with the D variant. These studies suggest that the induction of interferon by the B variant is, at least in part, responsible for the inhibition of diabetes by the D variant.