tbuckley/cabot-search huggingface dataset:
Upper airway.4: Sarcoidosis of the upper respiratory tract (SURT)
Authors: R. P. Baughman, E. E. Lower, T. Tami
Journal: Thorax (2010)

A patient is described who developed right side hemineglect after a right cerebellar lesion. This spatial disorder was interpreted as a secondary effect of a deficit of the motor organisation in the right hemispace due to left frontal diaschisis. The pathological base may be the interruption of a highly integrated system which includes the lateral cerebellum and the contralateral frontal lobe.
Surveillance for Breast Cancer After Childhood Cancer
Authors: Aliki J. Taylor
Journal: JAMA (2009)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Expression of mdr1 and mdr3 Multidrug-resistance Genes in Human Acute and Chronic Leukemias and Association With Stimulation of Drug Accumulation by Cyclosporine
Authors: H. Herweijer, P. Sonneveld, F. Baas, K. Nooter
Journal: JNCI Journal of the National Cancer Institute (1990)

We determined the expression levels of the mdr1 and mdr3 multidrug-resistance genes (also known as PGY1 and PGY3, respectively) in peripheral blood cells from 69 adult patients with acute and chronic leukemias, using an RNase protection assay. Expression of mdr1 was found in samples from patients with acute nonlymphocytic leukemia (13 of 17), chronic myelocytic leukemia (CML, chronic phase, 10 of 10; blast crisis, three of four), acute lymphocytic leukemia (ALL, eight of 11), B-cell chronic lymphocytic leukemia (B-CLL, 17 of 17), hairy cell leukemia (HCL, one of two), and T-cell prolymphocytic leukemia (one of one), but not in B-cell prolymphocytic leukemia (B-PLL, 0 of seven). Expression of mdr3 was only detected in samples from B-cell lymphocytic leukemias: CML, lymphoid blast crisis (one of one), B-cell ALL (two of two), B-CLL (17 of 17), B-PLL (seven of seven), and HCL (two of two). In vitro drug uptake studies by on-line flow cytometry showed that in leukemia cells expressing either mdr1 or mdr3 , the steady-state accumulation of daunorubicin could be significantly increased by addition of cyclosporine and, to a lesser extent, by verapamil. Because cyclosporine and verapamil are known as inhibitors of the mdr1 -encoded P-glycoprotein drug-efflux pump, and because the mdr1 and mdr3 genes are highly homologous, our data suggest that the mdr3 gene encodes a functional drug pump in B-cell lymphocytic leukemias. The results of this study may have implications for clinical therapy for acute or chronic leukemias expressing the mdr1 or mdr3 gene, in particular, treatment with combinations of cytotoxic drugs plus agents that reverse multidrug resistance. Since mdr1 and mdr3 are frequently expressed in untreated as well as treated leukemia, such combination therapy should be considered for untreated patients as well as treated patients.
An mRNA based IP-10 release assay for LTBI combining RT-qPCR and dried blood spots
Authors: Thomas Blauenfeldt, Jesper Bonde, Sidse Graff, Niels Seersholm, Christoph Lange, Jan Heyckendorf, Morten Ruhwald
Journal: European Respiratory Journal (2014)

Introduction: 

IP-10 is an immunodiagnostic biomarker for latent TB (LTBI) expressed at levels 100 fold higher than IFN-γ. We compared mRNA and protein expression patterns of IP-10 and IFN-γ in whole blood stimulated with M.Tb specific antigens, and show proof-of-principle detecting LTBI using an mRNA based IP-10 release assay on dried blood spots (DBS).

Method: 

Blood from 27 TB patients, 9 healthy IGRA positive and 96 controls was stimulated in QuantiFERON tubes. mRNA was detected at 8h and protein levels at 20h. In a subgroup of 5 patients, both levels were determined at 2 hour intervals for 48h. mRNA expression was assessed using RT-qPCR and protein levels using ELISA.

Results: 

IP-10 mRNA is stable and readily detected from whole blood as well as DBS. Assay reproducibility was very high (CV% <1). The kinetics of IP-10 and IFN-γ expression were comparable, with IP-10 levels substantially higher than IFN-γ. IP-10 mRNA levels were detectable at 4h and peaked at 8h, protein levels plateaued at 18h. IP-10 mRNA and protein release were comparable for LTBI and TB. The diagnostic accuracy was high (area under ROC curve; 0.93) and both mRNA and protein based methods yielded sensitivity of 86% (31/36) with a specificity of 96% (92/96).

Discussion: 

Given the shorter incubation time, mRNA based IP-10 release assays enables a fast workflow. Compared to protein-based assays, molecular detection is more accurate and optimal for automation, suggesting that next generation IGRA assays could be developed from this blueprint.

This study is ongoing and for the conference, we will present a larger cohort.
A comparative longitudinal quality of life study using the Spitzer quality of life index in a randomized multicenter phase III trial (FFCD 9102): chemoradiation followed by surgery compared with chemoradiation alone in locally advanced squamous resectable thoracic esophageal cancer
Authors: F. Bonnetain, O. Bouché, P. Michel, C. Mariette, T. Conroy, D. Pezet, B. Roullet, J.-F. Seitz, B. Paillot, P. Arveux, C. Milan, L. Bedenne
Journal: Annals of Oncology (2006)
Analysis of the influence of <i>PTPN22</i> gene polymorphisms in systemic sclerosis
Authors: LM Diaz-Gallo, P Gourh, J Broen, C Simeon, V Fonollosa, N Ortego-Centeno, S Agarwal, MC Vonk, M Coenen, G Riemekasten, N Hunzelmann, R Hesselstrand, FK Tan, JD Reveille, S Assassi, FJ García-Hernandez, P Carreira, MT Camps, A Fernandez-Nebro, P Garcia de la Peña, T Nearney, D Hilda, MA González-Gay, P Airo, L Beretta, R Scorza, A Herrick, J Worthington, A Pros, I Gómez-Gracia, L Trapiella, G Espinosa, I Castellvi, T Witte, F de Keyser, M Vanthuyne, MD Mayes, TRDJ Radstake, FC Arnett, J Martin, B Rueda
Journal: Annals of the Rheumatic Diseases (2010)

Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes.3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc.The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected)=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected)=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected)=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1).The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.
Chronic Prenatal Hypoxia Induces Epigenetic Programming of PKCε Gene Repression in Rat Hearts
Authors: Andrew J. Patterson, Man Chen, Qin Xue, Daliao Xiao, Lubo Zhang
Journal: Circulation Research (2010)

Epidemiological studies demonstrate a clear association of adverse intrauterine environment with an increased risk of ischemic heart disease in adulthood. Hypoxia is a common stress to the fetus and results in decreased protein kinase C epsilon (PKCepsilon) expression in the heart and increased cardiac vulnerability to ischemia and reperfusion injury in adult offspring in rats.The present study tested the hypothesis that fetal hypoxia-induced methylation of cytosine-phosphate-guanine dinucleotides at the PKCepsilon promoter is repressive and contributes to PKCepsilon gene repression in the heart of adult offspring.Hypoxic treatment of pregnant rats from days 15 to 21 of gestation resulted in significant decreases in PKCepsilon protein and mRNA in fetal hearts. Similar results were obtained in ex vivo hypoxic treatment of isolated fetal hearts and rat embryonic ventricular myocyte cell line H9c2. Increased methylation of PKCepsilon promoter at SP1 binding sites, -346 and -268, were demonstrated in both fetal hearts of maternal hypoxia and H9c2 cells treated with 1% O(2) for 24 hours. Whereas hypoxia had no significant effect on the binding affinity of SP1 to the unmethylated sites in H9c2 cells, hearts of fetuses and adult offspring, methylation of both SP1 sites reduced SP1 binding. The addition of 5-aza-2'-deoxycytidine blocked the hypoxia-induced increase in methylation of both SP1 binding sites and restored PKCepsilon mRNA and protein to the control levels. In hearts of both fetuses and adult offspring, hypoxia-induced methylation of SP1 sites was significantly greater in males than in females, and decreased PKCepsilon mRNA was seen only in males. In fetal hearts, there was significantly higher abundance of estrogen receptor alpha and beta isoforms in females than in males. Both estrogen receptor alpha and beta interacted with the SP1 binding sites in the fetal heart, which may explain the sex differences in SP1 methylation in the fetal heart. Additionally, selective activation of PKCepsilon restored the hypoxia-induced cardiac vulnerability to ischemic injury in offspring.The findings demonstrate a direct effect of hypoxia on epigenetic modification of DNA methylation and programming of cardiac PKCepsilon gene repression in a sex-dependent manner, linking fetal hypoxia and pathophysiological consequences in the hearts of adult offspring.
Yellow nail syndrome associated with mental retardation in two siblings
Authors: M. KAMATANI, A. RAI, H. HEN, K. HAYASHI, T. AOKI, K. UMEYAMA, J. TAKEBAYASHI
Journal: British Journal of Dermatology (1978)

Two siblings with yellow nail syndrome and mental retardation are described. In addition to nail changes, the younger brother was found to have congenital lymphoedema and idiopathic pleural effusion, and the elder brother, lymphoedema praecox. They had in common a history of respiratory tract infections. Their intelligence quotient as measured by the Suzuki-Binet tests was 30% and 70%, respectively.
Nutritional influences on metal toxicity: cadmium as a model toxic element.
Authors: M R Fox
Journal: Environmental Health Perspectives (1979)

The nutrient quality of the diet has been shown repeatedly to be a significant factor in modifying the response of man and animals to toxic element exposure. Deficiencies of several essential nutrients have been shown to exacerbate the effects of cadmium and supplements of such nutrients have been shown to ameliorate the toxicity. Thus the effects of exposure to a toxic element, such as cadmium, may vary, depending on interactions with other elements which are present in the diet in different concentrations.
Vaccine-Mediated Immunotherapy Directed against a Transcription Factor Driving the Metastatic Process
Authors: Andressa Ardiani, Sofia R. Gameiro, Claudia Palena, Duane H. Hamilton, Anna Kwilas, Thomas H. King, Jeffrey Schlom, James W. Hodge
Journal: Cancer Research (2014)

Numerous reports have now demonstrated that the epithelial-to-mesenchymal transition (EMT) process is involved in solid tumor progression, metastasis, and drug resistance. Several transcription factors have been implicated as drivers of EMT and metastatic progression, including Twist. Overexpression of Twist has been shown to be associated with poor prognosis and drug resistance for many carcinomas and other tumor types. The role of Twist in experimental cancer metastases has been principally studied in the 4T1 mammary tumor model, where silencing of Twist in vitro has been shown to greatly reduce in vivo metastatic spread. Transcription factors such as Twist are generally believed to be "undruggable" because of their nuclear location and lack of a specific groove for tight binding of a small molecule inhibitor. An alternative approach to drug therapy targeting transcription factors driving the metastatic process is T-cell-mediated immunotherapy. A therapeutic vaccine platform that has been previously characterized consists of heat-killed recombinant Saccharomyces cerevisiae (yeast) capable of expressing tumor-associated antigen protein. We report here the construction and characterization of a recombinant yeast expressing the entire Twist protein, which is capable of inducing both CD8(+) and CD4(+) Twist-specific T-cell responses in vivo. Vaccination of mice reduced the size of primary transplanted 4T1 tumors and had an even greater antitumor effect on lung metastases of the same mice, which was dependent on Twist-specific CD8(+) T cells. These studies provide the rationale for vaccine-induced T-cell-mediated therapy of transcription factors involved in driving the metastatic process.
Clinical outcomes of ethnic minority women in MA.17: a trial of letrozole after 5 years of tamoxifen in postmenopausal women with early stage breast cancer
Authors: B. Moy, D. Tu, J.L. Pater, J.N. Ingle, L.E. Shepherd, T.J. Whelan, P.E. Goss
Journal: Annals of Oncology (2006)
Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in germany: A 20-year multicenter study
Authors: Manfred Wiese, Frieder Berr, Michael Lafrenz, Heiner Porst, Ute Oesen
Journal: Hepatology (2000)

From August 1978 until March 1979, 14 batches of anti-D immune globulin contaminated with hepatitis C virus (HCV) genotype 1b (20,000-480,000 copies/dose) from a single erythrocyte donor had been administered for prophylaxis of rhesus isoimmunization throughout East Germany. All 2,867 women involved had been recalled after January 12, 1979 for repeated screening of alanine transaminase (ALT). They were prospectively followed in regional centers. We have reexamined a cohort of 1,018 women (median age 24, range 16-38 years at infection) on follow-up for 20 years in 9 representative centers. Within 6 months after anti-D administration, 10% of these women had no evidence of disease and 90% had acute hepatitis C (n = 917) including 49% with symptomatic and 22% with icteric course. After 20 years, 85% of the 917 affected women still tested positive for HCV antibodies (among them 3% responded to interferon treatment) and 55% were positive for HCV RNA (among them 7% were nonresponders to interferon and 3% were apparent HCV carriers). Only 4 (0.4%) had overt cirrhosis. Two (0.2%) died of superinfected fulminant hepatitis B or alcoholism and cirrhosis, respectively. Histology obtained in 44% of the viremic women showed hepatitis of minimal to moderate grade in 96%, portal fibrosis in 47%, and septal fibrosis in 3% of the cases. In conclusion, formerly healthy young women, without hepatic comorbidity, may clear HCV (1b) infection in half of the cases or develop mild chronic hepatitis C with low risk of progression to cirrhosis within 20 years.
Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome.
Authors: T J Gregory, W J Longmore, M A Moxley, J A Whitsett, C R Reed, A A Fowler, L D Hudson, R J Maunder, C Crim, T M Hyers
Journal: Journal of Clinical Investigation (1991)

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung injury and damage to the alveolar type II cells. This study sought to determine if endogenous surfactant is altered in ARDS. Bronchoalveolar lavage was performed in patients at-risk to develop ARDS (AR, n = 20), with ARDS (A, n = 66) and in normal subjects (N, n = 29). The crude surfactant pellet was analyzed for total phospholipids (PL), individual phospholipids, SP-A, SP-B, and minimum surface tension (STmin). PL was decreased in both AR and A (3.48 +/- 0.61 and 2.47 +/- 0.40 mumol/ml, respectively) compared to N (7.99 +/- 0.60 mumol/ml). Phosphatidylcholine was decreased in A (62.64 +/- 2.20% PL) compared to N (76.27 +/- 2.05% PL). Phosphatidylglycerol was 11.58 +/- 1.21% PL in N and was decreased to 6.48 +/- 1.43% PL in A. SP-A was 123.64 +/- 20.66 micrograms/ml in N and was decreased to 49.28 +/- 21.68 micrograms/ml in AR and to 29.88 +/- 8.49 micrograms/ml in A. SP-B was 1.28 +/- 0.33 micrograms/ml in N and was decreased to 0.57 +/- 0.24 micrograms/ml in A. STmin was increased in AR (15.1 +/- 2.53 dyn/cm) and A (29.04 +/- 2.05 dyn/cm) compared to N (7.44 +/- 1.61 dyn/cm). These data demonstrate that the chemical composition and functional activity of surfactant is altered in ARDS. Several of these alterations also occur in AR, suggesting that these abnormalities occur early in the disease process.
SMAL: A Resource of Spontaneous Mutation Accumulation Lines
Authors: W. Wei, L.-W. Ning, Y.-N. Ye, S.-J. Li, H.-Q. Zhou, J. Huang, F.-B. Guo
Journal: Molecular Biology and Evolution (2014)

Mutation is the ultimate source of genetic variation and evolution. Mutation accumulation (MA) experiments are an alternative approach to study de novo mutation events directly. We have constructed a resource of Spontaneous Mutation Accumulation Lines (SMAL; http://cefg.uestc.edu.cn/smal), which contains all the current publicly available MA lines identified by high-throughput sequencing. We have relocated and mapped the mutations based on the most recent genome annotations. A total of 5,608 single base mutations and 540 other mutations were obtained and are recorded in the current version of the SMAL database. The integrated data in SMAL provide detailed information that can be used in new theoretical analyses. We believe that the SMAL resource will help researchers better understand the processes of genetic variation and the incidence of disease.
Direct studies on the control of the renal microcirculation.
Authors: R J Roman, P K Carmines, R Loutzenhiser, J D Conger
Journal: Journal of the American Society of Nephrology (1991)

Recent advances in videomicroscopy combined with the development of several innovative in vivo and in vitro preparations now allow for direct study of the renal microcirculation. Blood flow in vasa recta capillaries of the rat can be studied by using video-microscopy, and changes in the flow of red blood cells in the renal cortex and papilla can be continuously monitored by using laser-Doppler flowmetry. All elements of the renal microcirculation can be visualized with the in vitro perfused juxtamedullary nephron or hydronephrotic kidney preparations. Pressures, blood flows, and vascular diameters in individual vessels can be directly measured in these preparations. Renal arterioles can be microdissected from the kidneys of several species and cannulated and pressurized in vitro for the study of pressure-diameter relationships and vascular responses to different agonists. In addition, membrane potentials and intracellular ion concentrations can now be measured in isolated renal arterioles by using microelectrodes and fluorescence microscopy. Thus, it is possible to study the control of renal vascular tone at all levels of integration from signal transduction in isolated cells to direct analysis of the regulation of hemodynamics in different regions of the microcirculation of the kidney in intact animals.
Developing a strategic research framework for Sport and Exercise Medicine
Authors: Louis J Holtzhausen, Gert J van Zyl, Marietjie M Nel
Journal: British Journal of Sports Medicine (2014)

Background/aim Sport and Exercise Medicine (SEM) is a young, fast growing discipline. The need to broaden its evidence base has been established. The aim of the study was to compile a research-based strategic framework for the development of a sustainable research programme in SEM at a South African university. Methods A literature review, internal document analysis, semistructured interviews with role players within the university and a Delphi process utilising a panel of international and national experts in research and SEM, were applied. Results were analysed and categorised regarding foundational aspects and operational components to create a sustainable research programme in SEM. Results The foundational level of the framework consists of points of departure, premises and resources. Points of departure regarding SEM, the university, management, research and sustainability were identified. The premises for the research programme are relevance, currency, flexibility, implementability and a scientific base. Internal, institutional and external resources required by the programme were identified. The operational level was developed according to the W.K. Kellogg programme logic model. It consists of academic and management inputs; a central hub of activities which drives the programme; desired financial, human and academic outputs, and long-term qualitative and quantitative outcomes. The third level represents a sustainable research programme which is constantly monitored and reviewed. Conclusions The strategic framework provides guidelines for the development and sustainable management of an SEM research programme. It will make a substantial contribution to the research, further development, and ultimately the status of SEM in South Africa.