tbuckley/cabot-search huggingface dataset:
Determinants and Within-Person Variability of Urinary Cadmium Concentrations among Women in Northern California
Authors: Robert B. Gunier, Pamela L. Horn-Ross, Alison J. Canchola, Christine N. Duffy, Peggy Reynolds, Andrew Hertz, Erika Garcia, Rudolph P. Rull
Journal: Environmental Health Perspectives (2013)

Cadmium (Cd) is a toxic metal associated with increased morbidity and mortality. Urinary Cd (U-Cd) concentration is considered a biomarker of long-term exposure.Our objectives were to evaluate the within-person correlation among repeat samples and to identify predictors of U-Cd concentrations.U-Cd concentrations (micrograms per liter) were measured in 24-hr urine samples collected from 296 women enrolled in the California Teachers Study in 2000 and a second 24-hr sample collected 3-9 months later from 141 of the participants. Lifestyle and sociodemographic characteristics were obtained via questionnaires. The Total Diet Study database was used to quantify dietary cadmium intake based on a food frequency questionnaire. We estimated environmental cadmium emissions near participants' residences using a geographic information system.The geometric mean U-Cd concentration was 0.27 µg/L and the range was 0.1-3.6 µg/L. The intraclass correlation among repeat samples from an individual was 0.50. The use of a single 24-hr urine specimen to characterize Cd exposure in a case-control study would result in an observed odds ratio of 1.4 for a true odds ratio of 2.0. U-Cd concentration increased with creatinine, age, and lifetime pack-years of smoking among ever smokers or lifetime intensity-years of passive smoking among nonsmokers, whereas it decreased with greater alcohol consumption and number of previous pregnancies. These factors explained 42-44% of the variability in U-Cd concentrations.U-Cd levels varied with several individual characteristics, and a single measurement of U-Cd in a 24-hr sample did not accurately reflect medium- to long-term body burden.
Inhibition of diabetic nephropathy by a decoy peptide corresponding to the “handle” region for nonproteolytic activation of prorenin
Authors: Atsuhiro Ichihara, Matsuhiko Hayashi, Yuki Kaneshiro, Fumiaki Suzuki, Tsutomu Nakagawa, Yuko Tada, Yukako Koura, Akira Nishiyama, Hirokazu Okada, M. Nasir Uddin, A.H.M. Nurun Nabi, Yuichi Ishida, Tadashi Inagami, Takao Saruta
Journal: Journal of Clinical Investigation (2004)

We found that when a site-specific binding protein interacts with the "handle" region of the prorenin prosegment, the prorenin molecule undergoes a conformational change to its enzymatically active state. This nonproteolytic activation is completely blocked by a decoy peptide with the handle region structure, which competitively binds to such a binding protein. Given increased plasma prorenin in diabetes, we examined the hypothesis that the nonproteolytic activation of prorenin plays a significant role in diabetic organ damage. Streptozotocin-induced diabetic rats were treated with subcutaneous administration of handle region peptide. Metabolic and renal histological changes and the renin-Ang system components in the plasma and kidneys were determined at 8, 16, and 24 weeks following streptozotocin treatment. Kidneys of diabetic rats contained increased Ang I and II without any changes in renin, Ang-converting enzyme, or angiotensinogen synthesis. Treatment with the handle region peptide decreased the renal content of Ang I and II, however, and completely inhibited the development of diabetic nephropathy without affecting hyperglycemia. We propose that the nonproteolytic activation of prorenin may be a significant mechanism of diabetic nephropathy. The mechanism and substances causing nonproteolytic activation of prorenin may serve as important therapeutic targets for the prevention of diabetic organ damage.
Successful treatment of posttransplantation lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8+ T-cell restoration
Authors: Pierluigi Porcu, Charles F. Eisenbeis, Ronald P. Pelletier, Elizabeth A. Davies, Robert A. Baiocchi, Sameek Roychowdhury, Srinivas Vourganti, Gerard J. Nuovo, William L. Marsh, Amy K. Ferketich, Mitchell L. Henry, Ronald M. Ferguson, Michael A. Caligiuri
Journal: Blood (2002)
Adverse Outcomes After Noncardiac Surgery in Patients With Diabetes
Authors: Chun-Chieh Yeh, Chien-Chang Liao, Yi-Cheng Chang, Long-Bin Jeng, Horng-Ren Yang, Chun-Chuan Shih, Ta-Liang Chen
Journal: Diabetes Care (2013)

To investigate whether diabetes affects perioperative complications or mortality and to gauge its impact on medical expenditures for noncardiac surgeries.With the use of reimbursement claims from the Taiwan National Health Insurance system, we performed a population-based cohort study of patients with and without diabetes undergoing noncardiac surgeries. Outcomes of postoperative complications, mortality, hospital stay, and medical expenditures were compared between patients with and without diabetes.Diabetes increased 30-day postoperative mortality (odds ratio 1.84 [95% CI 1.46-2.32]), particularly among patients with type 1 diabetes or uncontrolled diabetes and patients with preoperative diabetes-related comorbidities, such as eye involvement, peripheral circulatory disorders, ketoacidosis, renal manifestations, and coma. Compared with nondiabetic control patients, coexisting medical conditions, such as renal dialysis (5.17 [3.68-7.28]), liver cirrhosis (3.59 [2.19-5.88]), stroke (2.87 [1.95-4.22]), mental disorders (2.35 [1.71-3.24]), ischemic heart disease (2.08 [1.45-2.99]), chronic obstructive pulmonary disease (1.96 [1.29-2.97]), and hyperlipidemia (1.94 [1.01-3.76]) were associated with mortality for patients with diabetes undergoing noncardiac surgery. Patients with diabetes faced a higher risk of postoperative acute renal failure (3.59 [2.88-4.48]) and acute myocardial infarction (3.65 [2.43-5.49]). Furthermore, diabetes was associated with prolonged hospital stay (2.30 [2.16-2.44]) and increased medical expenditures (1.32 [1.25-1.40]).Diabetes increases postoperative 30-day mortality, complications, and medical expenditures in patients undergoing in-hospital noncardiac surgeries.
Vasoactive intestinal peptide concentrations and immunocytochemical studies in rectal biopsies from patients with inflammatory bowel disease.
Authors: C O'Morain, A E Bishop, G P McGregor, A J Levi, S R Bloom, J M Polak, T J Peters
Journal: Gut (1984)

Vasoactive intestinal polypeptide (VIP)-containing nerves and VIP content of endoscopic rectal biopsies from 47 patients with inflammatory bowel disease and 17 normal controls were examined by immunocytochemistry and radioimmunoassay. Immunocytochemistry revealed a consistent increase in, and abnormal appearance of, VIP nerves in patients with Crohn9s disease not only those with rectal involvement but also patients with no histological evidence of rectal disease. Normal control biopsies contained 1.64 +/- 0.39 pmol VIP/mg protein as compared with 3.43 +/- 1.24 pmol VIP/mg protein in tissue from patients with rectal Crohn9s disease and 5.37 +/- 1.23 pmol VIP/mg protein in those with Crohn9s disease without rectal involvement. Ten of the 17 biopsies examined from ulcerative colitics showed a normal pattern of VIP innervation. Examination of the conventional histology of these biopsies showed that only areas with obvious active proctitis had increased VIP nerves and, unlike the appearance in Crohn9s disease, these nerves had a normal morphology. The VIP content of these biopsies was similar to that of the controls; 1.34 +/- 0.37 pmol/mg protein.
Assessment of functional disorders in asthmatic children comparing parameters of simple spirometry with plethysmography
Authors: Richard Kraemer
Journal: European Respiratory Journal (2013)

Rational.  Lung function (LF) testing is considered as hallmark to get objectivity of functional deficits and their severity. The question is whether simple spirometry is an appropriate tool for that purpose in asthmatic children.   Objectives.  Selectivity to detect abnormal  in asthmatic children comparing spirometric with plethysmographic parameters.   Methods.  An asthma database was prospectively built-up during the past 3 years comprising  measurements of 168 children (98 males, 70 females). Target parameters of spirometry were forced expiratory indices (FEV 1 , MEF 50 ), those of plethysmography functional residual capacity (FRC pleth ), and effective total airway resistance (sR tot ). Data were analysed as standard deviation scores (SDS) using reference equations.   Results.  Normal  were found in 11.8% of patients. 19.8% presented with pulmonary hyperinflation (FRC pleth  >2 SDS), 22.7% with bronchial obstruction (sR tot >2 SDS), and 48.2% with bronchial obstruction and pulmonary hyperinflation. A small group of 9.4% presented only with a decrease of MEF 50 , considered as “small airway dysfunction. Best detection rate of abnormal LF was found for sR tot  (72.3%) followed by MEF 50  (51.6%). FEV 1  was abnormal only in 14.7% of patients, especially with a very low rate in patients with pulmonary hyperinflation (6.9% and those with both pulmonary hyperinflation and bronchial obstruction (23.1%).   Conclusions.  The assessment of lung function disorders in asthmatic children should not be based on spirometry only, because airway patency is not well reflected by flow-volume curves in children, especially when pulmonary hyperinflation is present.
Pulmonic Valve Insufficiency: A Common Cause of Transient Diastolic Murmurs in Renal Failure
Authors: JULIO E. PÉREZ
Journal: Annals of Internal Medicine (1985)

To study the transient diastolic murmur associated with renal failure, we used Doppler echocardiography to characterize flow across the semilunar valves in 10 patients on chronic hemodialysis with a diastolic murmur (group A), 26 patients on chronic hemodialysis without murmurs (group B), and 15 healthy persons (group C). Nine patients in group A had pulmonic valve insufficiency that encompassed 77 ± 21% (SD) of diastole with peak regurgitant flow velocities of 1.7 ± 0.3 m/s. Doppler-calculated mean pulmonary artery pressure in 8 of them was 43 ± 7 mm Hg before dialysis and 20 ± 12 mm Hg afterward (p < 0.001). Dialysis reduced the duration of pulmonic insufficiency to 10 ± 16% of diastole and lowered peak regurgitant flow velocities to 0.2 ± 0.2 m/s (p < 0.001 for each). Three patients in group B had aortic valve insufficiency and 3 had pulmonic valve insufficiency like that in group A. Three persons in group C had mild pulmonic valve insufficiency. Thus, transient diastolic murmurs associated with pulmonic valve insufficiency are not uncommon in patients with renal failure; they are related to fluid overload, are diminished by extracellular fluid removal, and reflect correctable pulmonary hypertension.
Total Artificial Heart Implantation— Eligibility Criteria
Authors: Robert J. Levine
Journal: JAMA (1984)

"What do you think of Barney Clark's great sacrifice—his willingness to serve as a subject of risky research so near the end of his life?" My response surprised the journalist who asked me this question shortly after the implantation of a total artificial heart in Dr Clark. "Considering the alternatives, as I understand the alternatives available to him," I replied, "I think he made an easily understandable choice. He chose a chance of life over a certainty of death. That does not sound like a sacrifice to me." In the September issue of the<i>Archives of General Psychiatry</i>, Berenson and Grosser<sup>1</sup>present a careful account of Dr Clark's relevant experiences before and after he received his artificial heart; it is particularly rich in neuropsychiatric detail. From this report we learn that Dr Clark wanted first and foremost an improvement in his physical condition. Even before he knew of the
Location, location, location: important for jet-lagged circadian loops
Authors: Mary Harrington
Journal: Journal of Clinical Investigation (2010)

It is now believed that frequent jet lag or shifts of daily rhythms caused by rotating shift work can lead to deleterious health outcomes. Indeed, many serious health problems, including breast cancer, stroke, and cardiovascular disease, have been linked to an occupational history of shift work. This has heightened interest in better understanding the biological responses to jet lag and shift work, with the hope that this will pave the way to developing compounds that can help people avoid their negative health consequences. In this context, a report in this issue of the JCI takes us to a new level of understanding of the molecular control of the resetting of the multitude of internal biological clocks disrupted in a mouse model of jet lag.
Mixed lineage kinase 3 mediates release of C‐X‐C motif ligand 10–bearing chemotactic extracellular vesicles from lipotoxic hepatocytes
Authors: Samar H. Ibrahim, Petra Hirsova, Kyoko Tomita, Steven F. Bronk, Nathan W. Werneburg, Stephen A. Harrison, Val S. Goodfellow, Harmeet Malhi, Gregory J. Gores
Journal: Hepatology (2015)

Mixed lineage kinase 3 (MLK3) deficiency reduces macrophage‐associated inflammation in a murine model of nonalcoholic steatohepatitis (NASH). However, the mechanistic links between MLK3 activation in hepatocytes and macrophage‐driven inflammation in NASH are uncharted. Herein, we report that MLK3 mediates the release of (C‐X‐C motif) ligand 10 (CXCL10)‐laden extracellular vesicles (EVs) from lipotoxic hepatocytes, which induce macrophage chemotaxis. Primary mouse hepatocytes (PMHs) and Huh7 cells were treated with palmitate or lysophosphatidylcholine (LPC). Released EVs were isolated by differential ultracentrifugation. LPC treatment of PMH or Huh7 cells induced release of EVs, which was prevented by either genetic or pharmacological inhibition of MLK3. Mass spectrometry identified the potent chemokine, CXCL10, in the EVs, which was markedly enriched in EVs isolated from LPC‐treated hepatocytes versus untreated cells. Green fluorescent protein (GFP)‐tagged CXCL10 was present in vesicular structures and colocalized with the red fluorescent protein (RFP)‐tagged EV marker, CD63, after LPC treatment of cotransfected Huh‐7 cells. Either genetic deletion or pharmacological inhibition of MLK3 prevented CXCL10 enrichment in EVs. Treatment of mouse bone‐marrow–derived macrophages with lipotoxic hepatocyte‐derived EVs induced macrophage chemotaxis, an effect blocked by incubation with CXCL10‐neutralizing antisera. MLK3‐deficient mice fed a NASH‐inducing diet had reduced concentrations of total plasma EVs and CXCL10 containing EVs compared to wild‐type mice. Conclusions : During hepatocyte lipotoxicity, activated MLK3 induces the release of CXCL10‐bearing vesicles from hepatocytes, which are chemotactic for macrophages. (H epatology 2016;63:731–744)
Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection
Authors: Yanick J Crow, Andrea Leitch, Bruce E Hayward, Anna Garner, Rekha Parmar, Elen Griffith, Manir Ali, Colin Semple, Jean Aicardi, Riyana Babul-Hirji, Clarisse Baumann, Peter Baxter, Enrico Bertini, Kate E Chandler, David Chitayat, Daniel Cau, Catherine Déry, Elisa Fazzi, Cyril Goizet, Mary D King, Joerg Klepper, Didier Lacombe, Giovanni Lanzi, Hermione Lyall, María Luisa Martínez-Frías, Michèle Mathieu, Carole McKeown, Anne Monier, Yvette Oade, Oliver W Quarrell, Christopher D Rittey, R Curtis Rogers, Amparo Sanchis, John B P Stephenson, Uta Tacke, Marianne Till, John L Tolmie, Pam Tomlin, Thomas Voit, Bernhard Weschke, C Geoffrey Woods, Pierre Lebon, David T Bonthron, Chris P Ponting, Andrew P Jackson
Journal: Nature Genetics (2006)
Early Onset and Progression of Left Ventricular Remodeling After Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy
Authors: Willem G. van Dockum, Aernout M. Beek, Folkert J. ten Cate, Jurrien M. ten Berg, Olga Bondarenko, Marco J.W. Götte, Jos W.R. Twisk, Mark B.M. Hofman, Cees A. Visser, Albert C. van Rossum
Journal: Circulation (2005)

Background— Alcohol septal ablation (ASA) reduces left ventricular outflow tract (LVOT) pressure gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM), which leads to left ventricular remodeling. We sought to describe the early to midterm changes and modulating factors of the remodeling process using cardiac MRI (CMR). Methods and Results— CMR was performed at baseline and 1 and 6 months after ASA in 29 patients with HOCM (age 52±16 years). Contrast-enhanced CMR showed no infarct-related hyperenhancement outside the target septal area. Septal mass decreased from 75±23 g at baseline to 68±22 and 58±19 g ( P &lt;0.001) at 1- and 6-month follow-up, respectively. Remote, nonseptal mass decreased from 141±41 to 132±40 and 111±27 g ( P &lt;0.001), respectively. Analysis of temporal trends revealed that septal mass reduction was positively associated with contrast-enhanced infarct size and transmural or left-sided septal infarct location at both 1 and 6 months. Remote mass reduction was associated with infarct location at 6 months but not with contrast-enhanced infarct size. By linear regression analysis, percentage remote mass reduction correlated significantly with LVOT gradient reduction at 6-month follow-up ( P =0.03). Conclusions— Left ventricular remodeling after ASA occurs early and progresses on midterm follow-up, modulated by CMR infarct size and location. Remote mass reduction is associated with infarct location and correlates with reduction of the LVOT pressure gradient. Thus, myocardial hypertrophy in HOCM is, at least in part, afterload dependent and reversible and is not exclusively caused by the genetic disorder.
The most intense running periods in English FA Premier League soccer matches
Authors: M Di Mascio, PS Bradley
Journal: British Journal of Sports Medicine (2011)

The aim of this study was to examine the most intense periods of high-intensity running during elite soccer matches. Elite players ( n =100) were analysed using a multi-camera computerised tracking system. Total high-intensity running distance (speed ≥19.8 km·h -1 ) and that covered in the most intense 5-min period were quantified during games. High-intensity running was performed for ∼3% of total time but this doubled (p&lt;0.05) during intense periods (8.4±2.7 vs 16.4±4.6 s). Recovery time between high-intensity running bouts was ∼70 s during the game but declined (p&lt;0.05) to ∼30 s during intense periods (70.8±25.7 vs 33.3±19.7 s). The distance of each discrete high-intensity running bout increased (p&lt;0.05) ∼13% during intense periods compared to the game average (6.7±1.8 vs 5.8±0.6 m). Central defenders covered less (p&lt;0.05) high-intensity running during intense periods compared to full backs, wide midfielders and attackers (4.3±0.8 vs 6.0±1.1, 6.1±1.8 and 5.6±1.3%), and performed less frequent (p&lt;0.05) bouts of high-intensity running than full backs and wide midfielders (14±5 vs 20±6 and 21±6). Central defenders had a greater recovery time (p&lt;0.05) than all other positional roles. No differences were evident between playing positions for maximum running speed and average distances of high-intensity running. These results show that high-intensity running is reduced following the most intense period of the game and that this trend is highly dependent on positional role. These findings have implications for developing conditioning drills and performance tests that closely mimic intense periods during soccer match-play.
P132 MYELOID-DERIVED SUPPRESSOR CELLS MEDIATE IMMUNOTOLERANCE IN CHRONIC HEPATITIS B (CHB) THROUGH ARGININE DEPRIVATION
Authors: L.J. Pallett, M. Haniffa, A. Schurich, U. Gill, N. Davies, M. Jover-Cobos, A. Das, R. Gilson, I. Ghosh, P.T. Kennedy, A. Bertoletti, M.K. Maini
Journal: Journal of Hepatology (2014)
Efficacy of captopril in postponing nephropathy.
Authors: M Hjelm
Journal: BMJ (1991)

prospective or retrospectivc -representative of the majority of' births is clearly difficult.Because of the large numb11hcr of births in lower age groups and the tiny proportion of these which wvill be affected by Down's svndrome, only a very large study could pn)vide sufficient cases for evalluation (although cost could presumably be redLuced by conducting this study in one of the regions alreadv providing the triple test on the NHS) In commenting on Cuckle et al's article I did not intend to suggest that netitrophil alkaline phosphatase activity will not prove to be a highly valuable additional marker- only that it may have been premature in a leaflet sent directly to pregnant women to contrast the efficiencv of the triple and triple plus tests before all of the necessary evidence is in.
Inhibition of Dipeptidyl Peptidase IV Improves Metabolic Control Over a 4-Week Study Period in Type 2 Diabetes
Authors: Bo Ahrén, Erik Simonsson, Hillevi Larsson, Mona Landin-Olsson, Hlin Torgeirsson, Per-Anders Jansson, Madeléne Sandqvist, Peter Båvenholm, Suad Efendic, Jan W. Eriksson, Sheila Dickinson, David Holmes
Journal: Diabetes Care (2002)

OBJECTIVE—Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1–degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study. RESEARCH DESIGN AND METHODS—A total of 93 patients (61 men and 32 women), aged 64 ± 9 years (means ± SD) and with BMI 27.3 ± 2.7 kg/m2, entered the study. Fasting blood glucose was 8.5 ± 1.5 mmol/l, and HbA1c was 7.4 ± 0.7%. Before and after treatment with NVP DPP728 at 100 mg × 3 (n = 31) or 150 mg × 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal). RESULTS—Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P &amp;lt; 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA1c was reduced to 6.9 ± 0.7% in the combined active treatment groups (P &amp;lt; 0.001). Laboratory safety and tolerability was good in all groups. CONCLUSIONS—We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.