tbuckley/cabot-search huggingface dataset:
Association between heparan sulfate proteoglycan excretion and proteinuria after renal transplantation.
Authors: I Stefanidis, B Heintz, G Stöcker, C Mrowka, H G Sieberth, H D Haubeck
Journal: Journal of the American Society of Nephrology (1996)

The aim of the study presented here was to investigate whether, in patients showing immediate graft function after renal transplantation, cold-ischemia and reperfusion lead to damage of the glomerular basement membrane and consequently to a loss of heparan sulfate proteoglycans. Loss of these heparan sulfate proteoglycans is a major cause of proteinuria. Time-dependent changes in urinary excretion rates of heparan sulfate proteoglycans but also of total protein, albumin, low- and high-molecular-weight proteins were analyzed quantitatively and by polyacrylamid-gel-electrophoresis in eight patients. Immediately after renal transplantation, severe proteinuria with an excretion rate of up to 251 +/- 108 mg/min was apparent and rapidly declined within 24 h to 4.11 +/- 2.80 mg/min. The gel-electrophoretic pattern showed a nonselective glomerular and tubular proteinuria. The excretion rate of heparan sulfate proteoglycan was increased in this initial reperfusion phase (up to 7 h), most probably because of ischemia- and reperfusion-induced damage of the glomerular basement membrane. The initial nonselective glomerular proteinuria disappeared within 48 h, changing to a mild selective glomerular proteinuria. In this second phase (7 to 48 h), lower levels of heparan sulfate proteoglycan excretion were observed (0.54 +/- 0.54 microgram/min versus 1.66 +/- 1.93 micrograms/min, P < 0.05). However, during the repair process of the glomerular basement membrane, heparan sulfate proteoglycan is synthesized de novo, leading to an increasing heparan sulfate proteoglycan content of the glomerular basement membrane. This second phase is paralleled by the change from a nonselective to a selective glomerular proteinuria. In the third phase, when the heparan sulfate proteoglycan content of the glomerular basement membrane normalizes, glomerular proteinuria was abolished in most of the patients.
Genomic disorders ten years on
Authors: James R Lupski
Journal: Genome Medicine (2009)

It is now becoming generally accepted that a significant amount of human genetic variation is due to structural changes of the genome rather than to base-pair changes in the DNA. As for base-pair changes, knowledge of gene and genome function has been informed by structural alterations that convey clinical phenotypes. Genomic disorders are a class of human conditions that result from structural changes of the human genome that convey traits or susceptibility to traits. The path to the delineation of genomic disorders is intertwined with the evolving technologies that have enabled the resolution of human genome analyses to continue increasing. Similarly, the ability to perform high-resolution human genome analysis has fueled the current and future clinical implementation of such discoveries in the evolving field of genome medicine.
Synthetic Inhibitors of Platelet Glycoprotein IIb/IIIa in Clinical Development
Authors: Marc Verstraete
Journal: Circulation (2000)

Activation of the platelet glycoprotein (GP IIb/IIIa) receptor on the platelet surface is the final pathway of platelet aggregation, regardless of the initiating stimulus. Inhibitors of GP IIb/IIIa receptors include monoclonal antibodies (abciximab) against this receptor and peptidic and nonpeptidic synthetic specific receptor blockers. Abciximab exchanges between and binds to platelets for as long as 2 weeks, whereas synthetic GP IIb/IIIa inhibitors inhibit ex vivo platelet aggregation for only a few hours after the end of infusion, but some have the advantage of also being orally active. In the secondary prevention of atherothrombosis, large-scale trials were successfully conducted with aspirin, dipyridamole, ticlopidine, and clopidogrel. In the first large-scale trials with GP IIb/IIIa inhibitors, abciximab was investigated. In aggregate, synthetic GP IIb/IIIa inhibitors, combined with aspirin and heparin, were shown to reduce ischemic events in patients with high- and low-risk coronary intervention, stents, unstable angina, and non-Q-wave infarction. With short-term use of synthetic GP IIb/IIIa inhibitors, there is no suppression of clinical evident restenosis 6 months after the end of treatment. With the doses currently used, bleeding occurs more often with the synthetic GP IIb/IIIa inhibitors (used for 3 days) than with abciximab (used for 12 hours), but there are no direct comparisons between these drugs.
Hyperhomocysteinemia After an Oral Methionine Load Acutely Impairs Endothelial Function in Healthy Adults
Authors: M.F. Bellamy, I.F.W. McDowell, M.W. Ramsey, M. Brownlee, C. Bones, R.G. Newcombe, M.J. Lewis
Journal: Circulation (1998)

Background —Elevated plasma homocysteine is a risk factor for arteriosclerosis, but a cause-and-effect relationship remains to be fully established. Endothelial dysfunction, an early event in the atherogenic process, has been shown to be associated with hyperhomocysteinemia in experimental and human studies. To further establish a direct relationship between changes in plasma homocysteine and endothelial dysfunction, we investigated whether moderate hyperhomocysteinemia induced by an oral methionine load would acutely impair flow-mediated endothelium-dependent vasodilatation in healthy adults. Methods and Results —Twenty-four healthy volunteers completed a randomized crossover study in which an oral methionine load (0.1 g/kg) was administered on 1 of 2 study days, 7 days apart. At each visit, plasma homocysteine and brachial artery endothelium-dependent and -independent dilatation were measured at baseline and at 4 hours. To further elucidate the temporal relationship between methionine, homocysteine, and endothelial function, an oral methionine load was administered in 10 subjects on a separate visit, and the time courses of plasma methionine, homocysteine, and flow-mediated brachial artery dilatation were measured at baseline and after 1, 2, 3, 4, and 8 hours. After oral methionine, plasma homocysteine increased from 7.9±2.0 μmol/L at baseline to 23.1±5.4 μmol/L at 4 hours ( P &lt;0.0001, n=24) and was associated with a decrease in flow-mediated brachial artery dilatation from 0.12±0.09 to 0.06±0.09 mm ( P &lt;0.05). The time course of the impairment of flow-mediated vasodilatation mirrored the time course of the increase in homocysteine concentration. Conclusions —Oral methionine loading raises plasma homocysteine and impairs flow-mediated endothelium-dependent vasodilatation. This supports the view that homocysteine may promote vascular disease by inducing endothelial dysfunction.
Megakaryocytopoietic cytokines in autoimmune thrombocytopenic purpura
Authors: Ibrahim C. Haznedaroglu, Nilgün M. Sayinalp, Osman I. Özcebe, Oktay Özdemir, Semra V. Dündar, Şerafettin Kirazli
Journal: American Journal of Hematology (1995)
Primary angioplasty is cost-minimizing compared with pre-hospital thrombolysis for patients within 60 min of a percutaneous coronary intervention center
Authors: Jacques Machecourt, Eric Bonnefoy, Gérald Vanzetto, Pascal Motreff, Stéphanie Marlière, Alain Leizorovicz, Benoit Allenet, Jean Michel Lacroute, Jean Cassagnes, Paul Touboul
Journal: Journal of the American College of Cardiology (2005)
THE SIGNIFICANCE OF INDUCED FORESTOMACH TUMORS
Authors: D. B. Clayson, F. Iverson, E. A. Nera, E. Lok
Journal: The Annual Review of Pharmacology and Toxicology (1990)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
CONCERNING A POLYVALENT ANTIGEN FOR THE COMPLEMENT FIXATION TEST FOR STREPTOCOCCUS VIRIDANS INFECTION
Authors: T. W. Hastings
Journal: The Journal of Experimental Medicine (1914)

1. Streptococcus viridans is of extremely low virulence for white mice and rabbits. 2. The serum of rabbits, after a series of intravenous injections of dead or living Streptococcus viridans, is poor in complement fixative substance (fixateur of Besredka) for Streptococcus viridans. 3. Antigens prepared from several strains of Streptococcus viridans are relatively poor in fixable substance. 4. The technique of complement fixation tests for infection with Streptococcus viridans is so laborious and difficult that the method will not be available for general clinical work.
Metabolic control of type I (insulin dependent) diabetes after pancreas transplantation.
Authors: G Pozza, E Bosi, A Secchi, P M Piatti, J L Touraine, A Gelet, A E Pontiroli, J M Dubernard, J Traeger
Journal: BMJ (1985)

A study was conducted of the circadian hormonal and metabolic patterns of 10 type I (insulin dependent) uraemic diabetic patients after pancreas and renal transplantation. A single 24 hour profile was obtained in each patient following as closely as possible his or her normal daily routine two to 15 months after transplantation. None of the patients were using insulin at the time of the study. Compared with a group of six normal subjects the transplant recipients had mildly raised blood glucose concentrations, hyperinsulinaemia between meals and at night, delayed postprandial insulin peaks, mild hyperketonaemia, and normal blood lactate and plasma glucagon concentrations. The findings showed that successful pancreas transplantation results in disappearance of the need for insulin and return to normal or near normal of the metabolic abnormalities of diabetes. The minor differences observed in comparison with normal hormonal and metabolic homoeostasis were probably due to intrinsic (reduced islet mass, denervation, peripheral hormone delivery) and environmental (immunosuppression, relatively impaired renal function) factors.
Brick1 Is an Essential Regulator of Actin Cytoskeleton Required for Embryonic Development and Cell Transformation
Authors: Beatriz Escobar, Guillermo de Cárcer, Gonzalo Fernández-Miranda, Alberto Cascón, José J. Bravo-Cordero, María C. Montoya, Mercedes Robledo, Marta Cañamero, Marcos Malumbres
Journal: Cancer Research (2010)

Brick1 (Brk1) is the less-studied component of the Wave/Scar pathway involved in the branched nucleation of actin fibers. The clinical relevance of Brk1 is emphasized by correlative data showing that Von Hippel-Lindau (VHL) patients that also lose the BRK1 gene are protected against the development of tumors. This contrasts with recent evidence suggesting that the Wave complex may function as an invasion suppressor in epithelial cancers. Here, we show that the downregulation of Brk1 results in abnormal actin stress fiber formation and vinculin distribution and loss of Arp2/3 and Wave proteins at the cellular protrusions. Brk1 is required for cell proliferation and cell transformation by oncogenes. In addition, Brk1 downregulation results in defective directional migration and invasive growth in renal cell carcinoma cells as well as in other tumor cell types. Finally, genetic ablation of Brk1 results in dramatic defects in embryo compaction and development, suggesting an essential role for this protein in actin dynamics. Thus, genetic loss or inhibition of BRK1 is likely to be protective against tumor development due to proliferation and motility defects in affected cells.
Obesity in Elderly Subjects
Authors: Etty Osher, Naftali Stern
Journal: Diabetes Care (2009)

Although the negative impact of high BMI on the risk of death from all-cause mortality is now well established, there is an apparent decline in the relative added risk of obesity with increasing age (1,2). This has led some experts to conclude that obesity should not necessarily be viewed as a disease in individuals older than 55 years. If such shift in the approach to adiposity during the latter phases of life is prematurely accepted, it may not only discourage attempted weight loss in older subjects, but also promote nutritional and lifestyle indulgence, which is presently difficult enough to overcome. It is the purpose of the present commentary to briefly outline the full spectrum of obesity-related hardships in the elderly. In our opinion, obesity-induced complications amount to real disease, which gravely affects quality of life and limits effective lifespan.

The incidence of hypertension, diabetes, and the metabolic syndrome intensifies with age, and aging per se is closely linked to increased prevalence of most of the abnormalities contributing to the metabolic syndrome (3). The incidence of the metabolic syndrome rises with increasing BMI, and a broader waist circumference is more common in men older than 65 years than in younger age-groups (3). The occurrence of the metabolic syndrome reaches peak levels in the 6th decade for men and the 7th decade for women, and a decline is noted only in the 8th decade for men and for some women in different ethnic groups (3). As recently outlined by the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research, older age and obesity are two of the most powerful risk factors for uncontrolled hypertension (4), and high blood pressure, in turn, is a major determinant of mortality and stroke incidence, particularly in senior years. BMI …
Complete recovery from an unusual cause of coma
Authors: Jörgen M. P. Rovers, Elisabeth S. Louwerse, C. Peter C. de Jager
Journal: Intensive Care Medicine (2007)

The Case Discussion format is intended to describe instructive cases in the field of intensive care medicine in a stepwise manner, allowing each step to be commented or discussed.This format might help to delineate the different steps of clinical reasoning in intensive care and highlight the important messages conveyed by the case
Comparison of Two Interferon-γ Assays and Tuberculin Skin Test for Tracing Tuberculosis Contacts
Authors: Sandra M. Arend, Steven F. T. Thijsen, Eliane M. S. Leyten, John J. M. Bouwman, Willeke P. J. Franken, Ben F. P. J. Koster, Frank G. J. Cobelens, Arend-Jan van Houte, Ailko W. J. Bossink
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Background: The tuberculin skin test (TST) has low specificity. QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB are based on interferon (IFN)-γ responses to Mycobacterium tuberculosis–specific antigens. A novel in-tube format of QFT-G (QFT-GIT) offers logistical advantages.Objective: To compare TST, QFT-GIT, and T-SPOT.TB in bacillus Calmette-Guérin unvaccinated contacts and correlate results with measures of recent exposure.Methods: When a supermarket employee with smear-positive tuberculosis had infected most close contacts, a contact investigation among more than 20,000 customers was performed. We recruited subjects randomly on the day of TST administration (n = 469) and subjects with TST of more than 0 mm on the day of TST reading (n = 316). QFT-GIT and T-SPOT.TB were performed. Demographic data and measures of exposure were collected. TST results were analyzed at a cutoff of 10 or 15 mm. Blood tests were interpreted following the manufacturers' criteria and by varying cutoff levels.Results: Among 785 study participants, TST results were associated with age, whereas positive IFN-γ responses were significantly associated with cumulative shopping time, most markedly for QFT-GIT. Among participants with a TST of 15 mm or greater, sensitivity of QFT-GIT and T-SPOT.TB was 42.2 and 51.3%, respectively. Interassay agreement was 89.6% (κ = 0.59). By varying cutoff values, agreement between the IFN-γ assays was optimal at 93.6% (κ = 0.71) using a cutoff of 0.20 IU/ml for QFT-GIT and 13 spots for T-SPOT.TB.Conclusions: Blood test results were associated with exposure, whereas the TST was not. A possible lack of sensitivity of IFN-γ assays in detecting individuals with TST of 15 mm or greater, despite negative bacillus Calmette-Guérin vaccination status, warrants further investigation into alternative cutoff values.
Vitamin D3 Metabolism in Human Glioblastoma Multiforme: Functionality of CYP27B1 Splice Variants, Metabolism of Calcidiol, and Effect of Calcitriol
Authors: Britta Diesel, Jens Radermacher, Matthias Bureik, Rita Bernhardt, Markus Seifert, Jörg Reichrath, Ulrike Fischer, Eckart Meese
Journal: Clinical Cancer Research (2005)

Abstract Purpose: A better understanding of the vitamin D3 metabolism is required to evaluate its potential therapeutic value for cancers. Here, we set out to contribute to the understanding of vitamin D3 metabolism in glioblastoma multiforme. Experimental Design: We did nested touchdown reverse transcription-PCR (RT-PCR) to identify CYP27B1 splice variants and real-time RT-PCR to quantify the expression of CYP27B1. A cell line was treated with calcitriol to determine the effect on the expression of CYP27B1, 1α,25-dihydroxyvitamin D3-24-hydroxylase (CYP24), and vitamin D3 receptor (VDR). We generated three antibodies for the specific detection of CYP27B1 and splice variants. High-performance TLC was done to determine the endogenous CYP27B1 activity and the functionality of CYP27B1 splice variants. Using WST-1 assay, we determined the effect of vitamin D3 metabolites on proliferation. Results: We report a total of 16 splice variants of CYP27B1 in glioblastoma multiforme and a different expression of CYP27B1 and variants between glioblastoma multiforme and normal tissues. We found preliminary evidence for enzymatic activity of endogenous CYP27B1 in glioblastoma multiforme cell cultures but not for the functionality of the splice variants. By adding calcitriol, we found a proliferative effect for some cell lines depending on the dose of calcitriol. The administration of calcitriol led to an elevated expression of CYP27B1 and CYP24 but left the expression of the VDR unaltered. Conclusions: Our findings show that glioblastoma multiforme cell lines metabolize calcidiol. In addition, we show various effects mediated by calcitriol. We found a special vitamin D3 metabolism and mode of action in glioblastoma multiforme that has to be taken into account in future vitamin D3–related therapies.
ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile
Authors: Adrian Wiestner, Andreas Rosenwald, Todd S. Barry, George Wright, R. Eric Davis, Sarah E. Henrickson, Hong Zhao, Rachel E. Ibbotson, Jenny A. Orchard, Zadie Davis, Maryalice Stetler-Stevenson, Mark Raffeld, Diane C. Arthur, Gerald E. Marti, Wyndham H. Wilson, Terry J. Hamblin, David G. Oscier, Louis M. Staudt
Journal: Blood (2003)
Anti-proteasome autoantibodies contribute to anti-nuclear antibody patterns on human larynx carcinoma cells
Authors: E Feist, M Brychcy, G Hausdorf, B Hoyer, K Egerer, T Dorner, U Kuckelkorn, G-R Burmester
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Autoantibodies to the 20S proteasome represent an unspecific but common serological phenomenon in patients with systemic autoimmune diseases. Interestingly, a high prevalence of these antibodies have been observed in patients with connective tissue diseases, where anti-nuclear antibodies (ANAs) serve as an important diagnostic screening test. <b>Objective:</b> To disclose interference of anti-proteasome antibodies with known ANA patterns. <b>Methods:</b> Anti-proteasome antibodies were isolated for comprehensive immunofluorescence analyses. The immunofluorescence pattern of human anti-proteasome antibodies was compared with a panel of monoclonal and polyclonal reference antibodies, and colocalisation was analysed using confocal microscopy. <b>Results:</b> Anti-proteasome antibodies clearly contributed to the ANA patterns of their respective serum samples from patients with different rheumatic disorders. In addition to the nuclear pattern, proteasomal staining was also detectable in the cytoplasm, at the endoplasmic reticulum and perinuclear regions showing features overlapping with other known autoantibodies such as those to mitochondria. The specificity of anti-proteasome antibodies was proved by competition experiments and by colocalisation with monoclonal reference antibodies in confocal microscopy. <b>Conclusion:</b> In ANA diagnostics, interference of anti-proteasome antibodies will have to be taken into account, especially in the differentiation of anti-cytoplasmatic autoantibodies.
Genetic Determinants of Aggressive Breast Cancer
Authors: Alejandra C. Ventura, Sofia D. Merajver
Journal: Annual Review of Medicine (2007)

The development and spread of breast and other human cancers are caused by the overexpression, mutation, and/or deletion of specific genes that drive these events. Finding genetic and molecular differences between cancerous and healthy cells can reveal the genetic determinants of cancer. This knowledge results in a better understanding of the carcinogenic process and improved predictive power, with implications for identifying new drug targets, designing novel therapies, and improving preclinical and clinical studies. We review the concepts of biomarker, genetic marker, and genetic determinant in cancer, with particular focus on the most aggressive and lethal form of breast cancer, termed inflammatory breast cancer (IBC). Using IBC as an example, we describe in detail the approaches to identify the genes that are responsible for-and not merely associated with-this disease.
R219K polymorphism of the ABCA1 gene and its modulation of the variations in serum high-density lipoprotein cholesterol and triglycerides related to age and adiposity in white versus black young adults. The bogalusa heart study
Authors: Sathanur R Srinivasan, Shengxu Li, Wei Chen, Eric Boerwinkle, Gerald S Berenson
Journal: Metabolism (2003)
The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate
Authors: Raymond Vanholder, Eva Schepers, Anneleen Pletinck, Evi V. Nagler, Griet Glorieux
Journal: Journal of the American Society of Nephrology (2014)

A growing number of publications supports a biologic effect of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. However, the use of unrealistically high free concentrations of these compounds and/or inappropriately low albumin concentrations may blur the interpretation of these results. Here, we performed a systematic review, selecting only studies in which, depending on the albumin concentration, real or extrapolated free concentrations of indoxyl sulfate and p-cresyl sulfate remained in the uremic range. The 27 studies retrieved comprised in vitro and animal studies. A quality score was developed, giving 1 point for each of the following criteria: six or more experiments, confirmation by more than one experimental approach, neutralization of the biologic effect by counteractive reagents or antibodies, use of a real-life model, and use of dose–response analyses in vitro and/or animal studies. The overall average score was 3 of 5 points, with five studies scoring 5 of 5 points and six studies scoring 4 of 5 points, highlighting the superior quality of a substantial number of the retrieved studies. In the 11 highest scoring studies, most functional deteriorations were related to uremic cardiovascular disease and kidney damage. We conclude that our systematic approach allowed the retrieval of methodologically correct studies unbiased by erroneous conditions related to albumin binding. Our data seem to confirm the toxicity of indoxyl sulfate and p-cresyl sulfate and support their roles in vascular and renal disease progression.