tbuckley/cabot-search huggingface dataset:
Nondipping and Its Relation to Glomerulopathy and Hyperfiltration in Adolescents With Type 1 Diabetes
Authors: Torun B. Torbjörnsdotter, Georg A. Jaremko, Ulla B. Berg
Journal: Diabetes Care (2004)

OBJECTIVE—To determine whether there is a relation between dipping/nondipping status and end-organ damage (measured as renal glomerulopathy) and long-term renal function in order to predict the development of nephropathy in normoalbuminuric patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—Analysis of renal biopsy and ambulatory blood pressure measurements was done in relation to renal function tests performed during a 10-year period. Forty unselected patients (16 girls), with a mean age of 17.7 years and a mean duration of 10.7 years, were studied. The renal biopsies were examined by electron microscopy. Ambulatory blood pressure was monitored (Space Labs 90 207). Systolic nondippers were defined as a &amp;lt;7%, diastolic nondippers as a &amp;lt;14%, and mean arterial blood pressure (MAP) nondippers as a &amp;lt;12% fall in blood pressure during the night. Renal function was evaluated every other year by clearances of inulin (glomerular filtration rate [GFR]) and para-amino hippurate (effective renal plasma flow [ERPF]), and filtration fraction (GFR/ERPF) was calculated. Overnight urinary albumin excretion rate and long-term mean HbA1c were measured. RESULTS—MAP (27% of the patients) and diastolic nondippers (12%) had a significantly thicker basement membrane; larger mesangial matrix volume fraction; and higher long-term GFR, nighttime heart rate, and mean HbA1c than dippers. CONCLUSIONS—Nondipping status was related to more renal morphological changes and long-term hyperfiltration in normoalbuminuric adolescents and young adults, despite a short duration of type 1 diabetes. Nondipping status may be an early predictor of later nephropathy.
In situ studies of protein aggregation kinetics with multiparametric and superresolution imaging
Authors: Gabriele Kaminski Schierle, Claire Michel, Eric Rees, Dorothea Pinotsi, Clemens Kaminski
Journal: Molecular Neurodegeneration (2013)

Misfolding and aggregation of peptides and proteins is a characteristic of many neurodegenerative disorders, including Parkinson’s (PD) and Alzheimer’s disease (AD). Their common feature is that normally unstructured and soluble proteins misfold and aggregate into insoluble amyloid fibrils, which make up the deposits in the brains of patients suffering from these devastating illnesses. A key requirement to gain insight into molecular mechanisms of disease and to progress in the search for therapeutic intervention is a capability to image the aggregation process and structure of ensuing fibrils in situ.

We have recently reported that amyloid proteins that are associated with protein misfolding diseases, including PD, AD and various other types of amyloidosis develop an intrinsic fluorescence in the visible range [1,2]. The discovery of intrinsic amyloid fluorescence has enabled the process of amyloid formation from disease-relevant polypeptides to be monitored in a label-free manner and with high specificity [2,3]. I will show here how specific and sensitive in vivo probes of amyloid structures can be developed using external fluorophores covalently attached to the amyloid backbone. Such external fluorophores can participate in Forster resonance energy transfer (FRET) with intrinsic energy states of amyloid structures if present, providing a readout in the form of a reduced fluorescence lifetime of the external fluorophores. I will provide an overview on the application of all-optical techniques to inform on the aggregation state of α-synuclein (relevant to PD), amyloid β and Tau (relevant to AD) in vitro, in live cells and model organisms. Multiparametric microscopy permits us to follow the kinetics of amyloid oligomerisation in vivo and correlate the appearance of aggregates with phenotypes of disease [1]. Using direct stochastic optical reconstruction microscopy, dSTORM, we are able to probe, in cells, the morphology of the ensuing aggregates with a resolution better than 20 nm [4]. We are able to distinguish different types of structures, including oligomeric assemblies and mature fibrils, and observe a number of morphological differences between the species formed in vitro and in vivo, which may be significant in the context of disease.
Systematic Review of Herbs and Dietary Supplements for Glycemic Control in Diabetes
Authors: Gloria Y. Yeh, David M. Eisenberg, Ted J. Kaptchuk, Russell S. Phillips
Journal: Diabetes Care (2003)

To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes.We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale.A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported.There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.
Long-Term Prognosis of Individuals With Right Precordial ST-Segment–Elevation Brugada Syndrome
Authors: Lars Eckardt, Vincent Probst, Jeroen P.P. Smits, Eric Schulze Bahr, Christian Wolpert, Rainer Schimpf, Thomas Wichter, Pierre Boisseau, Achim Heinecke, Günter Breithardt, Martin Borggrefe, Herve LeMarec, Dirk Böcker, Arthur A.M. Wilde
Journal: Circulation (2005)

Background— Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death as a result of ventricular fibrillation. Controversy exists with regard to risk stratification and therapeutic management, particularly in asymptomatic individuals. Methods and Results— A total of 212 individuals (mean age, 45±6 years) with a type 1 Brugada ECG pattern were studied. Of these, 123 (58%) were asymptomatic, 65 (31%) had ≥1 syncope of unknown origin, and 24 (11%) had to be resuscitated because of ventricular fibrillation. In 125 individuals (59%), a spontaneous type 1 ECG was recorded. In the remaining, drug challenge with a class I antiarrhythmic agent unmasked a Brugada ECG. The mean ST elevation was 2.3±1.2 mm in symptomatic patients and 1.9±1.5 mm in asymptomatic individuals ( P =0.04). During a mean follow-up of 40±50 months, 4 of the 24 patients (17%) with aborted sudden cardiac death and 4 of 65 (6%) with a prior syncope had a recurrent arrhythmic event, whereas only 1 of 123 asymptomatic individuals (0.8%) had a first arrhythmic event. Four of 9 patients with arrhythmic events during follow-up were not inducible during programmed electrical stimulation. A previous history of aborted sudden death or syncope and the presence of a spontaneous type 1 ECG were predictors of adverse outcome. Conclusions— The present study reports data on a large population of individuals with a type 1 Brugada ECG pattern with the longest follow-up reported so far. A very low incidence of severe arrhythmic events, particularly in asymptomatic individuals, was found during follow-up. In the presence of very few arrhythmic events on follow-up, programmed electrical stimulation showed very little accuracy in predicting outcome.
Nephrin TRAP Mice Lack Slit Diaphragms and Show Fibrotic Glomeruli and Cystic Tubular Lesions
Authors: Maija Rantanen, Tuula Palmén, Anu Pätäri, Heikki Ahola, Sanna Lehtonen, Eva A[Combining Ring Above]ström, Thomas Floss, Franz Vauti, Wolfgang Wurst, Patrizia Ruiz, Dontscho Kerjaschki, Harry Holthöfer
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The molecular mechanisms maintaining glomerular filtration barrier are under intensive study. This study describes a mutant Nphs1 mouse line generated by gene-trapping. Nephrin, encoded by Nphs1, is a structural protein of interpodocyte filtration slits crucial for formation of primary urine. Nephrintrap/trap mutants show characteristic features of proteinuric disease and die soon after birth. Morphologically, fibrotic glomeruli with distorted structures and cystic tubular lesions were observed, but no prominent changes in the branching morphogenesis of the developing collecting ducts could be found. Western blotting and immunohistochemical analyses confirmed the absence of nephrin in nephrintrap/trap glomeruli. The immunohistochemical staining showed also that the interaction partner of nephrin, CD2-associated protein (CD2AP), and the slit-diaphragm-associated protein, ZO-1α −, appeared unchanged, whereas the major anionic apical membrane protein of podocytes, podocalyxin, somewhat punctate as compared with the wild-type (wt) and nephrinwt/trap stainings. Electron microscopy revealed that >90% of the podocyte foot processes were fused. The remaining interpodocyte junctions lacked slit diaphragms and, instead, showed tight adhering areas. In the heterozygote glomeruli, approximately one third of the foot processes were fused and real-time RT-PCR showed >60% decrease of nephrin-specific transcripts. These results show an effective nephrin gene elimination, resulting in a phenotype that resembles human congenital nephrotic syndrome. Although the nephrintrap/trap mice can be used to study the pathophysiology of the disease, the heterozygous mice may provide a useful model to study the gene dose effect of this crucial protein of the glomerular filtration barrier.
Translational Medicine Policy Issues in Infectious Disease
Authors: Robin Fears, Jos W. M. van der Meer, Volker ter Meulen
Journal: Science Translational Medicine (2010)

The European Academies Science Advisory Council has published a series of reports on infectious disease policy issues, analyzing priorities for building the science base as part of public health strategy. Among current challenges facing the European Union are the needs to tackle antibiotic resistance, promote vaccine innovation, prepare for the emergence of novel zoonoses, and integrate research approaches to human and animal health. The scientific community must help public policy-makers to address the organization, balance, and sustainability of research funding and infrastructure; encourage the creation of a more supportive regulatory environment for translational medicine; and evaluate new models for public-private partnership to facilitate innovation.
Diagnostic strategies for suspected pulmonary embolism
Authors: A.B. Donkers-van Rossum
Journal: European Respiratory Journal (2001)

Pulmonary embolism often remains a difficult diagnosis for the clinician, particularly in patients with comorbidity factors. This is in contrast with the availability of effective treatment, which should be prescribed as soon as possible. To date, there is still no ideal diagnostic test that is accurate, safe, readily available and cost-effective. Recent technical advances in computed tomography, magnetic resonance imaging and laboratory findings have raised new possibilities in the diagnosis of pulmonary embolism. This review covers the performance of different diagnostic tests, and focuses on the advantages and limitations of single diagnostic tests and the clinical usefulness of these tests in diagnostic strategies.
49 OSTEOPONTIN IS A NOVEL THERAPEUTIC TARGET IN PATIENTS WITH ALCOHOLIC HEPATITIS
Authors: O. Morales, M. Dominguez, E. Juez, M. Moreno, R. Miquel, J.J. Lozano, J. Colmenero, J.C. García-Pagán, V. Arroyo, P. Ginès, J. Caballería, R. Bataller
Journal: Journal of Hepatology (2010)
Measurement of Hymenoptera Venom Specific IgE by the Immulite 3gAllergy in Subjects with Negative or Positive Results by Immunocap
Authors: Mineaki Watanabe, Hirokuni Hirata, Naruo Yoshida, Taichi Shiobara, Tatsuya Yokoyama, Takeshi Fukuda
Journal: Journal of Allergy and Clinical Immunology (2013)
Oxygen Sensing by Arterial Chemoreceptors Depends on Mitochondrial Complex I Signaling
Authors: M. Carmen Fernández-Agüera, Lin Gao, Patricia González-Rodríguez, C. Oscar Pintado, Ignacio Arias-Mayenco, Paula García-Flores, Antonio García-Pergañeda, Alberto Pascual, Patricia Ortega-Sáenz, José López-Barneo
Journal: Cell Metabolism (2015)
Predialysis systolic blood pressure correlates strongly with mean 24-hour systolic blood pressure and left ventricular mass in stable hemodialysis patients.
Authors: P J Conion, J J Walshe, S K Heinle, S Minda, M Krucoff, S J Schwab
Journal: Journal of the American Society of Nephrology (1996)

This study used a 24-h ambulatory blood pressure (ABP) monitor to study the relationship between dialysis room-measured blood pressures (BP) and mean 24-h systolic and diastolic ambulatory BP (SABP and DABP) with left ventricular mass (LV) in a group of 35 stable hemodialysis patients. Predialysis and postdialysis systolic and diastolic blood pressure data were collected for the 12 dialysis treatments before the wearing of the ABP device, and the means of these values are reported. All patients were maintained on the same antihypertensive medications for 3 months before the study and had a stable hematocrit value of 30 +/- 3% during this time period. There was no difference detected between daytime and nighttime ABP. SABP was a mean of 4.7 mm Hg below predialysis systolic BP (P = 0.004) and DABP was a mean of 3.7 mm Hg below predialysis diastolic BP. There was a strong correlation between SABP and predialysis systolic BP (r = 0.67, P = 0.0001); however, postdialysis diastolic BP correlated better with DABP than did predialysis diastolic BP. In addition, LV mass correlated with SABP (r = 0.35, P = 0.03) and predialysis systolic BP (r = 0.35, P = 0.03). There was no apparent correlation between either pre- or postdialysis diastolic BP with LV mass. It was concluded that predialysis systolic BP and postdialysis diastolic BP correlates strongly with SABP and DABP. Furthermore, predialysis systolic BP correlates with LV mass in hemodialysis patients. If the deleterious effects of hypertension in this patient population are to be avoided, it is the predialysis systolic BP that needs to be controlled: It is insufficient to be satisfied with good postdialysis BP control, if patients are hypertensive before beginning dialysis.
DNA Hypomethylation and Ovarian Cancer Biology
Authors: Martin Widschwendter, Guanchao Jiang, Christian Woods, Hannes M. Müller, Heidi Fiegl, Georg Goebel, Christian Marth, Elisabeth Müller-Holzner, Alain G. Zeimet, Peter W. Laird, Melanie Ehrlich
Journal: Cancer Research (2004)

Abstract Hypomethylation of some portions of the genome and hypermethylation of others are very frequent in human cancer. The hypomethylation often involves satellite 2 (Sat2) DNA in the juxtacentromeric (centromere-adjacent) region of chromosome 1. In this study, we analyzed methylation in centromeric and juxtacentromeric satellite DNA in 115 ovarian cancers, 26 non-neoplastic ovarian specimens, and various normal somatic tissue standards. We found that hypomethylation of both types of satellite DNA in ovarian samples increased significantly from non-neoplastic toward cancer tissue. Furthermore, strong hypomethylation was significantly more prevalent in tumors of advanced stage or high grade. Importantly, extensive hypomethylation of Sat2 DNA in chromosome 1 was a highly significant marker of poor prognosis (relative risk for relapse, 4.1, and death, 9.4) and more informative than tumor grade or stage. Also, comparing methylation of satellite DNA and 15 5′ gene regions, which are often hypermethylated in cancer or implicated in ovarian carcinogenesis, we generally found no positive or negative association between methylation changes in satellite DNA and in the gene regions. However, hypermethylation at two loci, CDH13 (at 16q24) and RNR1 (at 13p12), was correlated strongly with lower levels of Sat2 hypomethylation. The CDH13/Sat2 epigenetic correlation was seen also in breast cancers. We conclude that satellite DNA hypomethylation is an important issue in ovarian carcinogenesis as demonstrated by: (a) an increase from non-neoplastic tissue toward ovarian cancer; (b) an increase within the ovarian cancer group toward advanced grade and stage; and (c) the finding that strong hypomethylation was an independent marker of poor prognosis.
Cross-sectional and longitudinal associations between circulating leptin and knee cartilage thickness in older adults
Authors: Oliver P Stannus, Yuelong Cao, Benny Antony, Leigh Blizzard, Flavia Cicuttini, Graeme Jones, Changhai Ding
Journal: Annals of the Rheumatic Diseases (2013)

To investigate cross-sectional and longitudinal associations between serum leptin levels and knee cartilage thickness in older adults.A prospective cohort of 163 randomly selected subjects (mean 63 years, range 52-78, 46% women) was studied. Knee cartilage thickness at medial tibial, lateral tibial, femoral and patellar sites was determined using T1-weighted fat-suppressed MRI. Serum leptin levels were measured by radioimmunoassay. Radiographic osteoarthritis, body fat (%), trunk fat (%), weight and height were measured, and body mass index (BMI) was calculated.Cross-sectionally, serum levels of leptin were negatively associated with femoral (β: -0.013, 95% CI -0.022 to -0.003), medial tibial (β: -0.009, 95% CI -0.018 to -0.001), lateral tibial (β: -0.012, 95% CI -0.021 to -0.003) and patellar (β: -0.014, 95% CI -0.026 to -0.002) cartilage thickness after adjustment for covariates. Moreover, BMI, trunk fat and total body fat were negatively associated with cartilage thickness, and the significant associations disappeared after further adjustment for leptin. Longitudinally, both baseline leptin and change in leptin were associated with greater changes in medial tibial cartilage thickness (β: -0.004, 95% CI -0.007 to -0.001 and β: -0.009, 95% CI -0.018 to -0.001, respectively) in multivariable analyses.Serum levels of leptin are independently and consistently associated with reduced cartilage thickness cross-sectionally and longitudinally. In addition, the associations between adiposity measures and cartilage thickness are mediated by leptin, suggesting leptin may play a key role in cartilage thinning.
Rebamipide, a novel antiulcer agent, attenuates Helicobacter pylori induced gastric mucosal cell injury associated with neutrophil derived oxidants.
Authors: M Suzuki, S Miura, M Mori, A Kai, H Suzuki, D Fukumura, M Suematsu, M Tsuchiya
Journal: Gut (1994)

The effect of rebamipide, a novel antiulcer compound, on Helicobacter pylori activated neutrophil dependent in vitro gastric epithelial cell injury was investigated. Luminol dependent chemiluminescence (ChL), which detects toxic oxidants from neutrophils exhibited a 12-fold increase when the bacterial suspension of H pylori was added to the isolated human neutrophils. This change was significantly attenuated by rebamipide at a concentration less than 1 mM, showing that rebamipide may inhibit oxidant production from H pylori elicited neutrophils. To assess whether rebamipide attenuates gastric mucosal injury, we tested its inhibitory action on H pylori induced gastric mucosal damage associated with neutrophils in vitro. Rabbit gastric mucosal cells were monolayered in culture wells and coincubated with human neutrophils and H pylori, and the cytotoxicity index was then calculated. Cultured gastric cells were significantly damaged when they were incubated with human neutrophils activated by H pylori. This cellular damage was attenuated by rebamipide in a dose-dependent manner. Furthermore, spectrophotometrical measurement showed that rebamipide (1 mM) inhibits urease activity by 21.7%. As monochloramine (an oxidant yielded by reaction of neutrophil derived chlorinated oxidant and ammonia) is proposed as an important toxic molecule in this model, the current findings suggest that the preventive effect of rebamipide on H pylori elicited neutrophil induced gastric mucosal injury may result from its inhibitory actions on the neutrophilic oxidative burst as well as H pylori derived urease activity.
Somatic Mutations of <i>JAK1</i> and <i>JAK3</i> in Acute Leukemias and Solid Cancers
Authors: Eun Goo Jeong, Min Sung Kim, Hyo Kyung Nam, Chang Ki Min, Seok Lee, Yeun Jun Chung, Nam Jin Yoo, Sug Hyung Lee
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The aim of this study was to see whether JAK1, JAK3, and TYK2 genes are altered in human cancers. Experimental Design: We analyzed 494 tissues from 186 acute adulthood leukemias, 30 multiple myelomas, and 278 common solid cancers, including 90 breast, 47 gastric, 47 colon, 47 lung, and 47 hepatocellular carcinomas by single-strand conformation polymorphism analysis. Results: Overall, we found six JAK1 mutations (four in acute leukemias, one in a lung carcinoma, and one in a breast carcinoma) and three JAK3 mutations (two in breast carcinomas and one in a gastric carcinoma). Of note, three JAK1 mutations were an identical p.V658F mutation, which is homologous to JAK2 p.V617F mutation. We also found two other JAK1 mutations that occurred at very close sites (p.T782M and p.L783F). We found three of the four leukemias with JAK1 mutations expressed mutated JAK1 at the mRNA level. For JAK3 mutations, one of them was JAK3 p.V715I that is homologous to the JAK1 p.L783F. These recurrent mutations in identical and homologous sites suggest a possibility that alterations of these amino acids might be important for tumor pathogenesis. With respect to the cancer types, T-acute lymphoblastic leukemia (T-ALL) showed the highest incidence of the mutations (3 of 11; 27.3%). Conclusion: Our data indicate that both JAK1 and JAK3 mutations occur in common human cancers and that JAK1 mutation in T-ALL is a frequent event. The data suggest that some of the JAK1 and JAK3 mutations may to be functional and contributes to cancer development, especially to T-ALL development.
NEUROPATHY, AGRANULOCYTOSIS, AND HEPATO-TOXICITY FOLLOWING IMIPRAMINE THERAPY
Authors: MORTON MILLER
Journal: American Journal of Psychiatry (1963)

Bilateral peroneal nerve palsy, agranulocytosis, and hepato-toxicity following imipramine administration, with improvement after cessation of the drug, were observed. Laboratory tests seemed to rule out other possible sources of the symptoms noted. The 5 previously reported cases of motor neuropathy appearing during imipramine therapy are similar in that they all involved elderly persons, and were restricted to the lower extremities. Complete remission of neurologic symptoms is not universal. Considering recent experience with thalidomide, the large variety of neurotoxic side effects seen with imipramine would merit caution in the use of this agent in pregnancy.