tbuckley/cabot-search huggingface dataset:
Peroxiredoxin1 Prevents Excessive Endothelial Activation and Early Atherosclerosis
Authors: Janka Kisucka, Anil K. Chauhan, Ian S. Patten, Ayce Yesilaltay, Carola Neumann, Richard A. Van Etten, Monty Krieger, Denisa D. Wagner
Journal: Circulation Research (2008)

The peroxiredoxin (Prdx) family of antioxidant enzymes uses redox-active cysteines to reduce peroxides, lipid hydroperoxides, and peroxynitrites. Prdx1 is known to be important to protect red blood cells against reactive oxygen species and in tumor prevention. In this study, the role of Prdx1 in inflammation, thrombosis, and atherosclerosis was investigated. Using intravital microscopy, we showed that the number of leukocytes rolling per minute in unstimulated veins was increased by 2.5-fold in Prdx1(-/-) compared to Prdx1(+/+) mice. In Prdx1(-/-) mice, 50% of leukocytes rolled at a velocity <10 mum/sec compared with 10% in Prdx1(+/+) mice, suggesting that adhesion molecule density on the endothelium may have been increased by Prdx1 deficiency. Indeed, endothelial P-selectin, soluble P-selectin, and von Willebrand factor in plasma were increased in Prdx1(-/-) mice compared to Prdx1(+/+) mice, indicating elevated Weibel-Palade body release. In contrast to this excessive endothelial activation, Prdx1(-/-) platelets showed no sign of hyperreactivity, and their aggregation both in vitro and in vivo was normal. We also examined the role of Prdx1 in the apoE(-/-) murine spontaneous model of atherosclerosis. Prdx1(-/-)/apoE(-/-) mice fed normal chow developed larger, more macrophage-rich aortic sinus lesions than Prdx1(+/+)/apoE(-/-) mice, despite similar amounts and size distributions of cholesterol in their plasma lipoproteins. Thus, Prdx1 protects against excessive endothelial activation and atherosclerosis, and the Prdx1(-/-) mice could serve as an animal model susceptible to chronic inflammation.
PTTG Overexpression Promotes Lymph Node Metastasis in Human Esophageal Squamous Cell Carcinoma
Authors: Shuang Yan, Cuiqi Zhou, Xiaomin Lou, Zefen Xiao, Hongxia Zhu, Qifeng Wang, Yihua Wang, Ning Lu, Shun He, Qimin Zhan, Siqi Liu, Ningzhi Xu
Journal: Cancer Research (2009)

Human pituitary tumor transforming gene (PTTG) overexpression correlates with metastasis in multiple tumors, and yet its molecular mechanisms of action remain elusive. We detected PTTG overexpression in 66% (111 of 169) of primary esophageal squamous cell carcinoma (ESCC) tumor tissues by in situ hybridization. PTTG overexpression correlated with lymph node metastasis (P < 0.05). Ectopic PTTG overexpression in a representative ESCC cell line, EC9706, increased in vitro cell migration and invasion and promoted in vivo lymph node metastasis. Suppressing PTTG expression by siRNA decreased cell motility in both PTTG-HA/EC9706 and KYSE150 cells. By using mass spectrometric analysis, we identified that PTTG up-regulated S100A4 and galectin-1 secretion and down-regulated tissue inhibitor of metalloproteinase-2 secretion to the culture media. PTTG induced S100A4 and galectin-1 mRNA and protein expression as assessed by Western blot and reverse transcription-PCR. Attenuating galectin-1 expression by siRNA constrained PTTG-HA/EC9706 cell motility (P < 0.05). PTTG activated E-box transcription and induced c-Myc protein expression in EC9706 cells, which in turn may act on an E-box motif within the galectin-1 promoter. Chromatin immunoprecipitation assays further confirmed specific c-Myc binding to galectin-1 promoter. PTTG-induced galectin-1 transactivation and expression were mediated by c-Myc, and both inductions were suppressed by c-Myc RNAi cotranfection. These findings elucidate the molecular mechanisms of PTTG overexpression in promoting tumor metastasis, whereby up-regulated PTTG modulates expression and secretion of metastasis-related factors to facilitate cell motility.
Trends in Reported Incidence of Primary Malignant Brain Tumors in Children in the United States
Authors: Malcolm A. Smith, Boris Freidlin, Lynn A. Gloeckler Ries, Richard Simon
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The reported incidence of primary malignant brain tumors among children in the United States increased by 35% during the period from 1973 through 1994. The purpose of our study was twofold: 1) to determine whether the reported incidence rates for this period are better represented by a linear increase over the entire period (“linear model”) or, alternatively, by a step function, with a lower rate in the years preceding 1984–1985 and a constant higher rate afterward (“jump model”); and 2) to identify the specific brain regions and histologic subtypes that have increased in incidence. Methods: Incidence data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period from 1973 through 1994 for primary malignant brain tumors in children were used to model the number of cases in a year as a random variable from a Poisson distribution by use of either a linear model or a jump model. Results/Conclusions: The increase in reported incidence of childhood primary malignant brain tumors is best explained by the jump model, with a step increase in incidence occurring in the mid-1980 s. The brain stem and the cerebrum are the primary sites for which an increase in tumor incidence has been reported. The increase in reported incidence of low-grade gliomas in the cerebrum and the brain stem (unaccompanied by an increase in mortality for these sites) supports the substantial contribution of low-grade gliomas to the overall increase in reported incidence for childhood brain tumors. Implications: The significantly better fit of the data to a jump model supports the hypothesis that the observed increase in incidence somehow resulted from changes in detection and/or reporting of childhood primary malignant brain tumors during the mid-1980 s. [J Natl Cancer Inst 1998;90:1269–77]
Does PCMH “Work”?—The Need to Use Implementation Science to Make Sense of Conflicting Results
Authors: George L. Jackson, John W. Williams
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
CD11b tunes tolerance
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

![Graphic][1] 

TH17 cells thrive and react to the OVA antigen in mice lacking CD11b. The immune system takes its cues from antigen-presenting cells (APCs) to either go on the offensive against a foreign enemy or to stand down and tolerate a harmless threat. Ehirchiou et al. (page 

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Molecular diagnosis of vascular access device-associated infection in children being treated for cancer or leukaemia
Authors: M.R. Millar, G. Johnson, M. Wilks, R. Skinner, S. Stoneham, B. Pizer, S. Hemsworth, A. Fogarty, C. Steward, R. Gilbert, E.M. Hennessy
Journal: Clinical Microbiology and Infection (2008)
Primary Crohn's disease of the colon and rectum
Authors: J. S. Cornes, M. Stecher
Journal: Gut (1961)

Crohn's disease of the large bowel has been increasingly recognized and this paper presents a clinical and pathological study of 45 patients in whom the disorder was confined entirely to the large intestine. The clinical and pathological factors are contrasted with those of 86 patients with regional ileitis and of 200 patients with ulcerative colitis. Compared with regional ileitis the disease occurred in an older age group, had a different sex distribution, and a higher incidence of perianal and rectovaginal fistulae. A high incidence of recurrent disease following surgical treatment, found in the patients with regional ileitis, was not found in the patients with primary Crohn's disease of the large intestine. The incidence of the disease relative to ulcerative colitis was approximately 6%. The disease had the same sex distribution as ulcerative colitis but occurred in an older age group. The disease was usually of gradual onset and continuous course, and periods of freedom lasting a month or more were uncommon. The patients came to surgery much earlier than patients with ulcerative colitis.
Use of Rapamycin Slows Progression of Cardiac Transplantation Vasculopathy
Authors: Donna Mancini, Sean Pinney, Daniel Burkhoff, John LaManca, Silviu Itescu, Elizabeth Burke, Niloo Edwards, Mehmet Oz, Andrew R. Marks
Journal: Circulation (2003)

Background— Cardiac transplantation vasculopathy is the leading cause of late death in heart transplantation recipients. Rapamycin is an immunosuppressant drug with potent antiproliferative and antimigratory effects. We investigated whether rapamycin could prevent progression of graft vasculopathy in 46 patients (age, 54±10 years; 4.3±2.3 years after transplantation) with severe disease. Methods and Results— At annual cardiac catheterization, patients were randomly assigned to treatment with rapamycin (n=22) versus continued current immunosuppression (n=24). Clinical characteristics including recipient age and sex, underlying cause of congestive heart failure, donor age and sex, and ischemic time were recorded. Cardiac catheterization was graded with the use of a semiquantitative scale and repeated annually. Clinically significant adverse events were defined as death, need for angioplasty or bypass surgery, myocardial infarction, and a &gt;25% worsening of the catheterization score. These events were monitored as primary study end points. Anti-HLA class I and II antibody production and lymphocyte growth assays were measured with each biopsy. Patients selected for rapamycin had azathioprine or mycophenolate mofetil discontinued and were given rapamycin. Outcomes were compared by means of log-rank analysis. There were no significant differences in baseline characteristics. Duration of follow-up was comparable (rapamycin, 689±261; control, 630±207 days; NS). In the rapamycin group, 3 patients reached primary end points versus 14 patients in the control group ( P &lt;0.001). There was no difference in baseline or subsequent anti-HLA class I or II antibody production. Conclusions— In this patient cohort with cardiac vasculopathy, treatment with rapamycin slowed disease progression probably by its antiproliferative and antimigratory effects.
Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma
Authors: Robert J. Clifford, Jinghui Zhang, Daoud M. Meerzaman, Myung-Soo Lyu, Ying Hu, Constance M. Cultraro, Richard P. Finney, Jenny M. Kelley, Sol Efroni, Sharon I. Greenblum, Cu V. Nguyen, William L. Rowe, Sweta Sharma, Gang Wu, Chunhua Yan, Hongen Zhang, Young-Hwa Chung, Jeong A. Kim, Neung Hwa Park, Il Han Song, Kenneth H. Buetow
Journal: Hepatology (2010)

Primary liver cancer is the third most common cause of cancer-related death worldwide, with a rising incidence in Western countries. Little is known about the genetic etiology of this disease. To identify genetic factors associated with hepatocellular carcinoma (HCC) and liver cirrhosis (LC), we conducted a comprehensive, genome-wide variation analysis in a population of unrelated Asian individuals. Copy number variation (CNV) and single nucleotide polymorphisms (SNPs) were assayed in peripheral blood with the high-density Affymetrix SNP6.0 microarray platform. We used a two-stage discovery and replication design to control for overfitting and to validate observed results. We identified a strong association with CNV at the T-cell receptor gamma and alpha loci (P < 1 × 10(-15)) in HCC cases when contrasted with controls. This variation appears to be somatic in origin, reflecting differences between T-cell receptor processing in lymphocytes from individuals with liver disease and healthy individuals that is not attributable to chronic hepatitis virus infection. Analysis of constitutional variation identified three susceptibility loci including the class II MHC complex, whose protein products present antigen to T-cell receptors and mediate immune surveillance. Statistical analysis of biologic networks identified variation in the "antigen presentation and processing" pathway as being highly significantly associated with HCC (P = 1 × 10(-11)). SNP analysis identified two variants whose allele frequencies differ significantly between HCC and LC. One of these (P = 1.74 × 10(-12)) lies in the PTEN homolog TPTE2.Combined analysis of CNV, individual SNPs, and pathways suggest that HCC susceptibility is mediated by germline factors affecting the immune response and differences in T-cell receptor processing.
Ex vivo culture of the intestinal epithelium: strategies and applications
Authors: Marc Leushacke, Nick Barker
Journal: Gut (2014)

Limited pools of resident adult stem cells are critical effectors of epithelial renewal in the intestine throughout life. Recently, significant progress has been made regarding the isolation and in vitro propagation of fetal and adult intestinal stem cells in mammals. It is now possible to generate ever-expanding, three-dimensional epithelial structures in culture that closely parallel the in vivo epithelium of the intestine. Growing such organotypic epithelium ex vivo facilitates a detailed description of endogenous niche factors or stem-cell characteristics, as they can be monitored in real time. Accordingly, this technology has already greatly contributed to our understanding of intestinal adult stem-cell renewal and differentiation. Transplanted organoids have also been proven to readily integrate into, and effect the long-term repair of, mouse colonic epithelia in vivo, establishing the organoid culture as a promising tool for adult stem cell/gene therapy. In another exciting development, novel genome-editing techniques have been successfully employed to functionally repair disease loci in cultured intestinal stem cells from human patients with a hereditary defect. It is anticipated that this technology will be instrumental in exploiting the regenerative medicine potential of human intestinal stem cells for treating human disorders in the intestinal tract and for creating near-physiological ex vivo models of human gastrointestinal disease.
Effects of continuous vs. interval aerobic training on PetCO2 response during graded exercise test in patients with coronary artery disease
Authors: Eneas Rocco, Danilo Marcelo Prado, Alexandre Silva, Jaqueline Lazzari, Pedro Bortz, Debora Rocco, Amanda Campolin, Carla Rosa, Valter Furlan
Journal: European Respiratory Journal (2011)

Background:  Previous studies have demonstrated in patients with coronary artery disease (CAD) that lower values in end-tidal CO2 pressure (PetCO2) during graded exercise test (GET) have been associated with ventilation perfusion (V/Q) mismatch.   Purpose:  1) to evaluate the effects of the continuos (CT) and interval aerobic training (IT) on PetCO2 responses during GET in CAD patients; and 2) examine the relationships between PetCO2 at ventilatory anaerobic threshold (PetCO2VAT) and cardiorespiratory parameters after interventions.   Methods:  37 patients with CAD (59.7±1.7 years) were divided into 2 groups: CT (n=20; 28.1±1 kg/m 2 ) and IT (n=17; 28.5±1 kg/m 2 ). All patients performed a GET on treadmill to determine VAT and peak oxygen consumption (VO2 peak).   Results:  CT and IT groups showed increased in relative aerobic fitness (ΔVO2peak = 4.1± 0.4 and 4.4±0.3 ml/kg/min CT and IT, respectively; p  Significant relationships were observed to: 1) CT (PetCO2VAT and VO2peak r=0.49; PetCO2VAT and VEVCO2VAT r= -0.80; P=0.01); and 2) IT (PetCO2VAT and VO2peak r=0.39; PetCO2VAT and VEVCO2VAT r= -0.45; P=0.01).   Conclusion:  CT and IT demonstrated the same responsiveness in increase PetCO2 values during GET in CAD patients. These results suggest that the factors related to both an increased cardiorespiratory fitness and ventilatory efficiency after interventions may be responsible to increased PetCO2 during GET.
Regulation of perfluorooctanoic acid-induced peroxisomal enzyme activities and hepatocellular growth by adrenal hormones
Authors: Jaideep Thottassery, Lloyd Winberg, Jihan Youssef, Michael Cunningham, Mostafa Z. Badr
Journal: Hepatology (1992)

A wide variety of compounds, including hypolipidemic drugs, plasticizers and other industrial chemicals, have been found to cause liver enlargement and hepatic peroxisome proliferation by mechanisms that are unclear. Although thyroid and sex hormones have been shown to modulate the hepatic response to these chemicals, the role of adrenal hormones in these phenomena is not clear, and a few studies have produced conflicting data. Therefore this study was undertaken to investigate the role of adrenal hormones in hepatomegaly and peroxisomal enzyme induction caused by peroxisomal proliferators and to further delineate the interrelationship between these parameters. Because adrenalectomy alters hepatic drug metabolism, we have used the nonmetabolizable proliferator perfluorooctanoic acid. Our data show that hepatomegaly caused by perfluorooctanoic acid depends on corticosterone, the major glucocorticoid in rodents. Liver growth caused by perfluorooctanoic acid appears to be predominantly hypertrophic in nature, and DNA synthesis in response to perfluorooctanoic acid predominates in periportal regions of the liver lobule. Data also show that although induction of peroxisomal beta-oxidation by perfluorooctanoic acid is independent of adrenal hormones, induction of catalase is dependent on the presence of these hormones. This study supports the contention that induction of activities of various peroxisomal enzymes is controlled by different regulatory mechanisms.
Anchoring pockets in human histocompatibility complex leukocyte antigen (HLA) class I molecules: analysis of the conserved B ("45") pocket of HLA-B27.
Authors: S E Buxton, R J Benjamin, C Clayberger, P Parham, A M Krensky
Journal: The Journal of Experimental Medicine (1992)

Dissection of the peptide binding grooves of seven subtypes of human histocompatibility leukocyte antigen (HLA)-B27 into the six specificity pockets defined by the 2.6-A structure of HLA-A*0201 revealed just one pocket, the B ("45") pocket, that is conserved among all the HLA-B27 subtypes. Functional studies of mutant HLA-B*2705 molecules with point substitutions in residues of the B pocket show that this structure, and the glutamine residue at position 45 in particular, plays a critical role in cell surface expression, peptide binding, and in the presentation of both exogenous and endogenous peptides by HLA-B*2705. We predict that the B pocket of HLA-B*2705 interacts with an amino acid side chain that anchors peptides in the binding groove, and that this peptide motif is present in most endogenously processed peptides that bind to all seven subtypes of HLA-B27.
Challenge food industry to improve Scots' diet, says review
Authors: Bryan Christie
Journal: BMJ (2006)

No progress in reducing childhood obesity despite increased awareness 334newsroundup Childhood obesity is increasing and becoming a serious health problem, but the US government has cancelled a Centers for Disease Control programme called Verb, which had produced documented successes, says the US Institute of Medicine, a part of the National Academies of Sciences.The CDC's programme was a five year social marketing campaign to promote physical activity in children aged 9-13 years.Evaluation showed that the programme had positive results, but funding was discontinued and will end this month.The programme's website (www.verbnow.com) encourages children to find activities in their own city or town.According to the institute's latest report the rate of obesity for children in the US has increased from 16.0% in 2002 to 17.1% in 2004 and is projected to reach to 20% in 2010."The remarkable and unexpected rise in obesity among our children and youth in a relative short timespan is one of the 21st century's most critical public health challenges," said Dr Jeffrey Koplan, chairman of the committee that produced the institute's report.
Blocking acid, boosting T cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

![Graphic][1] 

Chloroquine gets soluble antigens out of endosomes (right) and into the cytoplasm (left).Intracellular antacids boost cytotoxic T cell responses, according to a study on 

[page 817][2]. Accapezzato and colleagues show that an inhibitor that prevents endosome
IQ in childhood and vegetarianism in adulthood: 1970 British cohort study
Authors: Catharine R Gale, Ian J Deary, Ingrid Schoon, G David Batty
Journal: BMJ (2006)

To examine the relation between IQ in childhood and vegetarianism in adulthood.Prospective cohort study in which IQ was assessed by tests of mental ability at age 10 years and vegetarianism by self-report at age 30 years.Great Britain.8170 men and women aged 30 years participating in the 1970 British cohort study, a national birth cohort.Self-reported vegetarianism and type of diet followed.366 (4.5%) participants said they were vegetarian, although 123 (33.6%) admitted eating fish or chicken. Vegetarians were more likely to be female, to be of higher social class (both in childhood and currently), and to have attained higher academic or vocational qualifications, although these socioeconomic advantages were not reflected in their income. Higher IQ at age 10 years was associated with an increased likelihood of being vegetarian at age 30 (odds ratio for one standard deviation increase in childhood IQ score 1.38, 95% confidence interval 1.24 to 1.53). IQ remained a statistically significant predictor of being vegetarian as an adult after adjustment for social class (both in childhood and currently), academic or vocational qualifications, and sex (1.20, 1.06 to 1.36). Exclusion of those who said they were vegetarian but ate fish or chicken had little effect on the strength of this association.Higher scores for IQ in childhood are associated with an increased likelihood of being a vegetarian as an adult.
The Effects of Hexamethonium on Certain Manifestations of Congestive Heart Failure
Authors: ROBERT T. KELLEY, EDWARD D. FREIS, THOMAS F. HIGGINS
Journal: Circulation (1953)

Hypotensive doses of hexamethonium were administered intravenously to 19 patients with various types of heart disease in congestive failure. Clinical improvement as judged by the usual methods was seen in most cases. Intracardiac or pulmonary artery pressures paralleled the fall of arterial pressures following hexamethonium in four patients with hypertensive heart disease in congestive failure. It is suggested that hexamethonium, by reducing the total peripheral resistance and by a redistribution of blood volume, may interrupt the vicious cycle of heart failure.