tbuckley/cabot-search huggingface dataset:
Cystatin C deficiency in human atherosclerosis and aortic aneurysms
Authors: Guo-Ping Shi, Galina K. Sukhova, Anders Grubb, Anique Ducharme, Luis H. Rhode, Richard T. Lee, Paul M. Ridker, Peter Libby, Harold A. Chapman
Journal: Journal of Clinical Investigation (1999)

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-β1. The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease.
The Impact of Natural Selection on an ABCC11 SNP Determining Earwax Type
Authors: J. Ohashi, I. Naka, N. Tsuchiya
Journal: Molecular Biology and Evolution (2010)

A nonsynonymous single nucleotide polymorphism (SNP), rs17822931-G/A (538G>A; Gly180Arg), in the ABCC11 gene determines human earwax type (i.e., wet or dry) and is one of most differentiated nonsynonymous SNPs between East Asian and African populations. A recent genome-wide scan for positive selection revealed that a genomic region spanning ABCC11, LONP2, and SIAH1 genes has been subjected to a selective sweep in East Asians. Considering the potential functional significance as well as the population differentiation of SNPs located in that region, rs17822931 is the most plausible candidate polymorphism to have undergone geographically restricted positive selection. In this study, we estimated the selection intensity or selection coefficient of rs17822931-A in East Asians by analyzing two microsatellite loci flanking rs17822931 in the African (HapMap-YRI) and East Asian (HapMap-JPT and HapMap-CHB) populations. Assuming a recessive selection model, a coalescent-based simulation approach suggested that the selection coefficient of rs17822931-A had been approximately 0.01 in the East Asian population, and a simulation experiment using a pseudo-sampling variable revealed that the mutation of rs17822931-A occurred 2006 generations (95% credible interval, 1,023–3,901 generations) ago. In addition, we show that absolute latitude is significantly associated with the allele frequency of rs17822931-A in Asian, Native American, and European populations, implying that the selective advantage of rs17822931-A is related to an adaptation to a cold climate. Our results provide a striking example of how local adaptation has played a significant role in the diversification of human traits.
Exertion induced rhabdomyolysis of the long head of the triceps
Authors: J-N Goubier, O Silbermann Hoffman, C Oberlin
Journal: British Journal of Sports Medicine (2002)

The case is reported of bilateral rhabdomyolysis of the long head of the triceps following intensive exercise in a 30 year old male weightlifter. The diagnosis was based on myalgias localised to one muscle and raised levels of muscle enzymes. Magnetic resonance imaging helped to locate the site and extent of muscular involvement. Treatment consisted of complete rest and adequate intravenous perfusion to allow clearance of the clinical and biological abnormalities and prevent renal involvement.
Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates
Authors: Lucia Friedli, Ephron S. Rosenzweig, Quentin Barraud, Martin Schubert, Nadia Dominici, Lea Awai, Jessica L. Nielson, Pavel Musienko, Yvette Nout-Lomas, Hui Zhong, Sharon Zdunowski, Roland R. Roy, Sarah C. Strand, Rubia van den Brand, Leif A. Havton, Michael S. Beattie, Jacqueline C. Bresnahan, Erwan Bézard, Jocelyne Bloch, V. Reggie Edgerton, Adam R. Ferguson, Armin Curt, Mark H. Tuszynski, Grégoire Courtine
Journal: Science Translational Medicine (2015)

Fundamental differences in the anatomy and function of the corticospinal tract support enhanced recovery of leg and hand function after lateralized spinal cord injury in primates compared to rodents, emphasizing the importance of primate models for spinal cord repair therapies.
Use of Descriptive Terms in Medical Records—Reply
Authors: Joseph R. Berger
Journal: JAMA Neurology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Temperature perturbation studies of sarcoplasmic reticulum from malignant hyperthermia pig muscle.
Authors: T E Nelson, D E Bee
Journal: Journal of Clinical Investigation (1979)

The effects of varying temperatures from 25 degrees to 37 degrees C on calcium binding characteristics of sarcoplasmic reticulum from malignant hyperthermia-susceptible (MHS) and control pig muscle were examined. Two groups of MHS pigs were included: those with high susceptibility to malignant hyperthermia (MHS group) and a cross-bred, less susceptible group (MHX). At 25 degrees C, calcium binding was lower for MHS than for controls and MHX. As temperature was increased by 2 degrees C jumps, calcium binding decreased in all sarcoplasmic reticulum fractions. At 35 degrees C a sharp decrease in calcium binding occurred in the MHS and MHX fractions. The sharp decrease in calcium binding at 35 degrees C differentiated the MHS and MHX fractions from controls. The initial velocity (Vi) for calcium binding was lower in MHS fractions between 25 degrees and 35 degrees C when compared with MHX and controls. All fractions had increased Vi values as temperature increased from 25 degrees to 35 degrees C. From 35 degrees to 39 degrees Vi for controls increased markedly. In contrast, Vi for the MHX fraction decreased as temperature exceeded 35 degrees C. These temperature effects on calcium binding characteristics of sarcoplasmic reticulum from MHS and MHX muscle may be indicative of a membrane transition that impairs calcium binding.
The effect of alcohol ingestion on exhaled nitric oxide
Authors: DH Yates, SA Kharitonov, RA Robbins, PS Thomas, PJ Barnes
Journal: European Respiratory Journal (1996)

The concentration of nitric oxide (NO) is increased in the exhaled air of patients with inflammatory lung diseases, including asthma, possibly reflecting cytokine-mediated chronic airway inflammation. Endogenous NO is generated from L-arginine by the action of several types of NO synthase (NOS). NOS have structural similarities with cytochrome P450 reductases. Alcohol decreases exhaled NO in animals, but this has not previously been investigated in man. We studied the effect of alcohol ingestion in nine asthmatic and 12 normal subjects, measuring the peak concentration of exhaled NO using a modified chemiluminescence analyser. A significant decrement in NO occurred in asthmatic patients (mean +/- SEM before ethanol 204 +/- 58 to 158 +/- 59 parts per billion (ppb) after ethanol; p &lt; 0.02), without significant change in the normal subjects (122 +/- 14 to 114 +/- 15 ppb). Thus, in our study, alcohol decreased exhaled nitric oxide in asthmatic subjects but not in normal individuals. This may reflect preferential action on inducible nitric oxide synthase which is expressed in asthmatic airways. An inhibitory effect of ethanol on inducible nitric oxide synthase may contribute towards the effect of alcohol in asthma.
Cardiovascular and neuropsychiatric risks of varenicline: a retrospective cohort study
Authors: Daniel Kotz, Wolfgang Viechtbauer, Colin Simpson, Onno C P van Schayck, Robert West, Aziz Sheikh
Journal: The Lancet Respiratory Medicine (2015)

BackgroundVarenicline is an effective pharmacotherapy to aid smoking cessation. However, its use is limited by continuing concerns about possible associated risks of serious adverse cardiovascular and neuropsychiatric events. The aim of this study was to investigate whether use of varenicline is associated with such events.MethodsIn this retrospective cohort study, we used data from patients included in the validated QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients aged 18–100 years (registered for longer than 12 months before data extraction) who received a prescription of nicotine replacement treatment (NRT; reference group), bupropion, or varenicline. We excluded patients if they had used one of the drugs during the 12 months before the start date of the study, had received a prescription of a combination of these drugs during the follow-up period, or were temporary residents. We followed patients up for 6 months to compare incident cardiovascular (ischaemic heart disease, cerebral infarction, heart failure, peripheral vascular disease, and cardiac arrhythmia) and neuropsychiatric (depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders (primary outcomes).FindingsWe identified 164 766 patients who received a prescription (106 759 for nicotine replacement treatment; 6557 for bupropion; 51 450 for varenicline) between Jan 1, 2007, and June 30, 2012. Neither bupropion nor varenicline showed an increased risk of any cardiovascular or neuropsychiatric event compared with NRT (all hazard ratios [HRs] less than 1. Varenicline was associated with a significantly reduced risk of ischaemic heart disease (HR 0·80 [95%CI 0·72–0·87]), cerebral infarction (0·62 [0·52–0·73]), heart failure (0·61 [0·45–0·83]), arrhythmia (0·73 [0·60–0·88]), depression (0·66 [0·63–0·69]), and self-harm (0·56 [0·46–0·68]).InterpretationVarenicline does not seem to be associated with an increased risk of documented cardiovascular events, depression, or self-harm when compared with NRT. Adverse events that do not come to attention of general practitioners cannot be excluded. These findings suggest an opportunity for physicians to prescribe varenicline more broadly, even for patients with comorbidities, thereby helping more smokers to quit successfully than do at present.FundingEgton Medical Information Systems, University of Nottingham, Ministry of Innovation, Science and Research of the German Federal State of North Rhine-Westphalia, Cancer Research UK, Medical Research Council, Commonwealth Fund.
Zoned Out: Functional Mapping of Stromal Signaling Microenvironments in the Thymus
Authors: Howard T. Petrie, Juan Carlos Zúñiga-Pflücker
Journal: Annual Review of Immunology (2007)

All hematopoietic cells, including T lymphocytes, originate from stem cells that reside in the bone marrow. Most hematopoietic lineages also mature in the bone marrow, but in this respect, T lymphocytes differ. Under normal circumstances, most T lymphocytes are produced in the thymus from marrow-derived progenitors that circulate in the blood. Cells that home to the thymus from the marrow possess the potential to generate multiple T and non-T lineages. However, there is little evidence to suggest that, once inside the thymus, they give rise to anything other than T cells. Thus, signals unique to the thymic microenvironment compel multipotent progenitors to commit to the T lineage, at the expense of other potential lineages. Summarizing what is known about the signals the thymus delivers to uncommitted progenitors, or to immature T-committed progenitors, to produce functional T cells is the focus of this review.
Prediction of peak oxygen uptake in chronic fatigue syndrome.
Authors: R Mullis, I T Campbell, A J Wearden, R K Morriss, D J Pearson
Journal: British Journal of Sports Medicine (1999)

OBJECTIVES: To establish a simple, valid, and acceptable method of predicting peak oxygen uptake (VO2peak) in patients with chronic fatigue syndrome (CFS), which could provide a basis for subsequent exercise prescription at an appropriate intensity as part of a clinical rehabilitation programme. METHODS: A total of 130 patients who met UK research criteria for CFS were taken from consecutive referrals for chronic fatigue to the University Department of Medicine at Withington Hospital, Manchester. VO2peak was determined using an incremental graded exercise test to exhaustion. Respiratory gas exchange, work rate, and heart rate were monitored throughout. RESULTS: In all patients, VO2peak was found to correlate strongly and significantly with peak work rate (WRpeak) during testing (r2 = 0.88, p&lt;0.001). In patients who exercised for longer than two minutes (n = 119), regression analysis established the relation as Vo2peak = 13.1 x WRPpeak + 284, where VO2 is given in ml/min and WR in W. The mean error between the measured VO2peak and the predicted value was 10.7%. The relation between increase in work rate and oxygen uptake across the group was highly significant (r2 = 0.87, p&lt;0.001), and given as VO2increase = 12.0 x WRincrease, this value being similar to that expected for healthy individuals. Almost all (97%) subjects reported no exacerbation of symptoms after maximal exercise testing. CONCLUSIONS: Using a simple to administer maximal exercise test on a cycle ergometer, it is possible to predict accurately the VO2peak of a patient with CFS from peak work rate alone. This value can then be used as an aid to setting appropriate exercise intensity for a rehabilitation programme. The increase in VO2 per unit increase in workload was consistent with that expected in healthy individuals, suggesting that the physiological response of the patients measured here was not abnormal. Contrary to the belief of many patients, maximal exercise testing to the point of subjective exhaustion proved to be harmless, with no subjects suffering any lasting deterioration in their condition after assessment.
A new gold standard for assessing CT in early CF lung disease
Authors: Tim Rosenow, Wieying Kuo, Marleen de Bruijne, Conor Murray, Harm Tiddens, Stephen Stick
Journal: European Respiratory Journal (2014)

Background: Chest computed tomography (CT) is an important tool to assess early cystic fibrosis (CF) structural lung disease, particularly early in life where no validated outcome measures exist. Current CF-CT scoring systems show poor agreement between observers in infants <3 yrs. CT scores must be reliable if they are to be validated as outcome measures.

Aim: To determine the repeatability of a quantitative scoring system for chest CT scans early in life.

Methods: Twenty-five volumetric CT scans from the AREST CF cohort obtained at age 1 or 3 yrs were scored by two observers using PRAGMA (Perth-Rotterdam Annotated Grid Morphometry Analysis). Briefly, a square grid was overlaid on 10 equidistant slices. Each cell was annotated according to whether it contained bronchiectasis, other abnormalities or healthy lung only, expressed as a proportion of the total lung for bronchiectasis (%Bx) or any lung abnormality (%Disease). This analysis was then repeated two months later by one observer. Repeatability was assessed using intraclass correlation coefficients (ICC).

Results: %Bx ranged from 0-3.9 (median 0.23) and %Disease ranged from 0-6.9 (median 1.04). ICCs for inter-observer reliability were 0.77 (good agreement) for %Bx and 0.65 (good agreement) for %Disease. For intra-observer reliability, ICCs were 0.79 (good agreement) for %Bx and 0.71 (good agreement) for %Disease.

Conclusion: Inter- and intra-observer agreement were high for PRAGMA, suggesting that this new method is more reliable in young children than the present gold standard. The biological relevance of this new scoring system will be further assessed in the AREST CF cohort by comparing outcomes with other markers of early CF lung disease.
Effects of Advanced Glycation End Products on Cytosolic Ca2+ Signaling of Cultured Human Mesangial Cells
Authors: PAOLO MENÈ, CARMEN PASCALE, ANNA TETI, SILVIA BERNARDINI, GIULIO A. CINOTTI, FRANCESCO PUGLIESE
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Advanced glycation end product (AGE) accumulation in a high glucose (HG) environment is thought to mediate some of the vascular complications of diabetes. Transmembrane signaling of contractile cells is generally inhibited by HG, with implications for systemic and target organ hemodynamics. In the kidney, glomerular mesangial cells grown in HG media are hyporesponsive to the effects of vasoconstrictor agents, possibly explaining the hyperfiltration and increased capillary pressure that eventually lead to diabetic glomerulopathy. To verify whether AGE binding to specific mesangial receptors could mediate these effects of HG, cultured human mesangial cells (HMC) were exposed to in vitro glycated bovine serum albumin (BSA) for 60 min at 37°C before measurement of cytosolic Ca 2+ ([Ca 2+ ] i ) by microfluorometric techniques in monolayers or single cells. AGE-BSA (2 mg/ml) reduced Ca 2+ release from intracellular stores by 1 μM angiotensin II from peak [Ca 2+ ] i levels of 843 ± 117 to 390 ± 50 nM in monolayers and from 689 ± 68 to 291 ± 36 nM in individual cells ( P &lt; 0.05). Nonglycated BSA and BSA exposed to 250 mM glucose-6-phosphate for 30 d in the presence of 250 mM aminoguanidine (AMGD), an inhibitor of nonenzymatic glycation, had no effect on the angiotensin II-induced [Ca 2+ ] i spike (peak 766 ± 104 and 647 ± 87 nM, monolayers/single cells, respectively, P = NS). AGE also inhibited store-operated Ca 2+ influx through plasma membrane channels, assessed by addition of 1 to 10 mM extracellular Ca 2+ to cells previously held in Ca 2+ -free media (control 339 ± 46/593 ± 51, +AGE-BSA 236 ± 25/390 ± 56, +AMGD 483 ± 55/374 ± 64 nM [Ca 2+ ] i , monolayers/single cells at 10 mM Ca 2+ , respectively; +AGE-BSA, P &lt; 0.05 versus control). Contrary to HG, AGE-BSA did not translocate protein kinase C isoforms α, ξ, and δ to the plasma membrane. Culture of HMC in HG supplemented with 1 mM AMGD prevented downregulation of [Ca 2+ ] i signaling. These data suggest that glycated macromolecules or matrix components may inhibit transmembrane Ca 2+ signaling of glomerular cells through binding to a specific AGE receptor, thus mediating some of the known functional effects of HG on the kidney.
Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM)
Authors: B. Castagneto, M. Botta, E. Aitini, F. Spigno, D. Degiovanni, O. Alabiso, M. Serra, A. Muzio, R. Carbone, R. Buosi, V. Galbusera, E. Piccolini, L. Giaretto, L. Rebella, M. Mencoboni
Journal: Annals of Oncology (2007)
Long-term Use of Statins and Risk of Renal Cell Carcinoma: A Population-based Case–Control Study
Authors: Anton Pottegård, Peter Clark, Søren Friis, Jesper Hallas, Lars Lund
Journal: European Urology (2015)

Use of statins has been suggested to protect against renal cell carcinoma (RCC); however, studies have typically been underpowered, and the results are conflicting.To determine whether the use of statins is associated with a reduced risk of RCC using high-quality registry data.We conducted a nationwide case-control study based on all histologically verified cases of RCC in Denmark between 2002 and 2012 (n=4606) matched 1:10 to cancer-free controls. Data on drug use, comorbidity, and educational level were obtained from Danish nationwide prescription, patient, and demographic registries.Odds ratios (ORs) and 95% confidence intervals (CIs) for RCC associated with long-term use (≥5 yr) of statins were estimated using conditional logistic regression, adjusting for potential confounders.The adjusted OR for RCC associated with long-term use of statins was 1.06 (95% CI, 0.91-1.23). Analyses stratified by duration of statin use, type of statin, and patient characteristics all yielded ORs close to unity, except for a slightly increased OR for RCC associated with long-term statin use among women (OR: 1.25; 95% CI, 0.96-1.62). The main limitation of our study was lack of information on lifestyle factors, notably obesity, which may have biased the risk estimates upward.Our study does not support an important chemopreventive effect of long-term statin use against RCC. The marginally increased and statistically insignificant risk estimates can readily be interpreted as a null finding, considering the lack of control for obesity and other lifestyle risk factors.Previous studies have shown that the use of cholesterol-lowering drugs (statins) may protect against renal cancer. In a large study including all Danish renal cancers during an 11-yr period, we found no evidence of such an effect.
Increased Expression of Cyclooxygenase-2 Mediates Enhanced Contraction to Endothelin ET <sub>A</sub> Receptor Stimulation in Endothelial Nitric Oxide Synthase Knockout Mice
Authors: Yingbi Zhou, Srabani Mitra, Saradhadevi Varadharaj, Narasimham Parinandi, Jay L. Zweier, Nicholas A. Flavahan
Journal: Circulation Research (2006)

The aim of this study was to determine whether prolonged loss of NO activity, in endothelial NO synthase knockout (eNOS(-/-)) mice, influences endothelin (ET) ETA receptor-mediated smooth muscle contraction and, if so, to define the underlying mechanism(s). In isolated endothelium-denuded abdominal aortas, contractions to the selective ETA receptor agonist ET-1(1-31) were significantly increased in aortas from eNOS(-/-) compared with wild-type (WT) mice. In contrast, contractions to the alpha1-adrenergic agonist phenylephrine or the thromboxane (TX) A2 analog U-46619 were similar between eNOS(-/-) and WT mice. Immunofluorescent and Western blot analysis demonstrated that the aortic expression of ETA receptors was decreased in eNOS(-/-) compared with WT mice. Contractions evoked by ET-1(1-31), but not phenylephrine, were reduced by inhibition of cyclooxygenase-2 (COX-2) (indomethacin or celecoxib) or of TXA2/prostaglandin H2 receptors (SQ-29548). After COX inhibition, contractions to ET-1(1-31) were no longer increased and were actually decreased in eNOS(-/-) compared with WT aortas. Western blot analysis revealed that endothelium-denuded abdominal aortas express COX-2, but not COX-1, and that expression of COX-2 was significantly increased in eNOS(-/-) compared with WT mice. Contractions to the COX substrate arachidonic acid were also increased in eNOS(-/-) aortas. Furthermore, ET-1(1-31) but not phenylephrine stimulated production of the TXA2 metabolite TXB2, which was increased in eNOS(-/-) compared with WT aortas. Therefore, COX-2 plays a crucial and selective role in ETA-mediated smooth muscle contraction. Furthermore, COX-2 expression is increased in eNOS(-/-) mice, which overcomes a reduced expression of ETA receptors and enables a selective increase in contraction to ETA receptor stimulation.