tbuckley/cabot-search huggingface dataset:
Abstract 2017: Demethylation of HIC1 gene sensitizes thyroid cancer cells to TRAIL-induced apoptosis
Authors: Abdul K. Siraj, Maha Al-Rasheed, Azhar Husain, Prashant Bavi, Abdul Rahman Al Nuaim, Saif Al-Deen S. Alsobhi, Fouad Al-Dayel Fouad Al-Dayel, Shahab Uddin, Khawla S. Al-Kuraya
Journal: Cancer Research (2011)

Abstract Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration. It serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers. Several genes have been shown to be epigenetically inactivated in a wide range of tumors and most neoplasms show hypermethylation of one or more genes. Concurrent methylation status of the CpG islands of 24 genes were determined in 40 PTC cases and in a panel of PTC cell lines, using methylation specific PCR. Seven genes demonstrated a relatively high frequency of aberrant methylation: RASF1 (95%), HIC1 (55%), GSTP1 (26%), P14 (25%), TMS1 (24%), DCR1 (17%) and SERF (15%). Five genes (BRACA1, P15INK4B, MGMT, BLU and APC) showed a low frequency (2-6%) of methylation, and no methylation was detected for the remaining twelve genes (P16INK4A, APAF1, FANCF, FAS, MINT25, P73, MLH1, DAPK, RARB, CASP8, E-Cadherin and SOC1. Statistical analysis demonstrated that frequency of methylated and unmethylated HIC1 was significant (p &amp;lt;0.05). Further clinical analysis demonstrated significant association of only HIC1 methylation with: age of patients, stage of disease and expression of HIC1 IHC data (p = &amp;lt;0.0001, &amp;lt;0.0173 and &amp;lt; 0.0448; respectively). HIC1 has been shown to be hypermethylated in different cancers and confers bad prognosis. HIC1 is a tumor suppressor gene which encodes a transcriptional repressor with five Kruppel-like Cys2-His2 zinc fingers in the C terminus and a protein-protein interaction domain called the BTB/POZ domain at the N terminus. Analysis of BCPAP-1 and TPC1 (papillary thyroid cell lines) revealed that they are completely methylated for HIC1 gene. Treatment of methylated thyroid cell line with the methyltransferase inhibitor, 5-aza-2’deoxy-cytidine, resulted in partial demethylation and re-expression of HIC1 gene, suggesting the role of methylation in silencing of the gene. We further evaluated the role of HIC1 gene after demethylation for apoptosis. After demethylation of HIC1 gene with 5-aza-2’deoxy-cytidine we treated our PTC cell lines with increasing doses of TRAIL and evaluated its response by Annexin/PI dual staining. We found that after demethylation of HIC1 there was increase in percentage apoptosis following increasing doses of TRAIL suggesting that HIC1 gene plays a major role in inducing apoptosis in PTC. In conclusion, HIC1 methylation may be a promising molecular marker to predict patient outcome in PTC, and may be used as therapeutic demethylating target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2017. doi:10.1158/1538-7445.AM2011-2017
TOMATO LEAVES AND DERMATITIS
Authors: Malcolm MacKay
Journal: JAMA (1918)

<h3>To the Editor:</h3> —I notice in an article on "Dermatitis Lycopersicum Esculentum (Tomato Plant)" by Dr. E. S. Lain (The Journal, Oct. 5, 1918, p. 1114) that after a brief search he was unable to find the tomato plant mentioned as a cause of skin eruption. In Norman Walker's "Introduction to Dermatology," Edition 6, p. 109, it says, "The following are some plants and woods which have been proved to cause dermatitis... tomato leaves (<i>Lycopersicum escu</i><i>latum</i>)."
Adipocyte Modulation of High-Density Lipoprotein Cholesterol
Authors: YuZhen Zhang, Fiona C. McGillicuddy, Christine C. Hinkle, Sean O'Neill, Jane M. Glick, George H. Rothblat, Muredach P. Reilly
Journal: Circulation (2010)

Adipose harbors a large depot of free cholesterol. However, a role for adipose in cholesterol lipidation of high-density lipoprotein (HDL) in vivo is not established. We present the first evidence that adipocytes support transfer of cholesterol to HDL in vivo as well as in vitro and implicate ATP-binding cassette subfamily A member 1 (ABCA1) and scavenger receptor class B type I (SR-BI), but not ATP-binding cassette subfamily G member 1 (ABCG1), cholesterol transporters in this process.Cholesterol efflux from wild-type, ABCA1(-/-), SR-BI(-/-), and ABCG1(-/-) adipocytes to apolipoprotein A-I (apoA-I) and HDL3 were measured in vitro. 3T3L1 adipocytes, labeled with (3)H-cholesterol, were injected intraperitoneally into wild-type, apoA-I transgenic, and apoA-I(-/-) mice, and tracer movement onto plasma HDL was monitored. Identical studies were performed with labeled wild-type, ABCA1(-/-), or SR-BI(-/-) mouse embryonic fibroblast adipocytes. The effect of tumor necrosis factor-alpha on transporter expression and cholesterol efflux was monitored during adipocyte differentiation. Cholesterol efflux to apoA-I and HDL3 was impaired in ABCA1(-/-) and SR-BI(-/-) adipocytes, respectively, with no effect observed in ABCG1(-/-) adipocytes. Intraperitoneal injection of labeled 3T3L1 adipocytes resulted in increased HDL-associated (3)H-cholesterol in apoA-I transgenic mice but reduced levels in apoA-I(-/-) animals. Intraperitoneal injection of labeled ABCA1(-/-) or SR-BI(-/-) adipocytes reduced plasma counts relative to their respective controls. Tumor necrosis factor-alpha reduced both ABCA1 and SR-BI expression and impaired cholesterol efflux from partially differentiated adipocytes.These data suggest a novel metabolic function of adipocytes in promoting cholesterol transfer to HDL in vivo and implicate adipocyte SR-BI and ABCA1, but not ABCG1, in this process. Furthermore, adipocyte modulation of HDL may be impaired in adipose inflammatory disease states such as type 2 diabetes mellitus.
Survival From Out-of-Hospital Cardiac Arrest After Chest Compression–Only CPR
Authors: Rudolph W. Koster
Journal: JAMA (2011)

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
Benefits and Risks of Solitary Islet Transplantation for Type 1 Diabetes Using Steroid-Sparing Immunosuppression
Authors: M. Arthur Charles, Jean-Louis Selam
Journal: Diabetes Care (2004)

The report by Hirshberg et al. (1) describes the National Institutes of Health (NIH) experience in islet-only transplantation using the medical indication of severe hypoglycemia. Although the report details islet transplantation, there was little hypoglycemic information. Because of the potential side effects comparing the medical indication and the treatment, we have scientific, educational, and ethical concerns.

The first concern is the relative morbidity and mortality between severe hypoglycemia and islet transplantation. The mortality associated with severe hypoglycemia is unclear, but estimates show that 0–4% of type 1 diabetic patients …
Abstract 4924: Dysregulated transcriptional mechanisms that control crypt cell maturation: A mechanism that contributes to stem cell overpopulation during colon cancer development
Authors: Jayasree Padmanabhan, Greg Gonye, Tao Zhang, Bruce M. Boman
Journal: Cancer Research (2012)

Abstract Our goal is to determine how transcriptional regulatory mechanisms that control crypt cell maturation in normal colonic epithelium, when dysregulated, lead to maturation arrest, tumor stem cell (SC) overpopulation and colorectal cancer (CRC) development. Accordingly, we studied changes in maturation during colon cancer development caused by APC mutations. Quantitative mapping of crypt cell subpopulations was done on colon tissues from FAP patients using markers for stem cells (SC), proliferating cells, cell-cycle arrest, and apoptosis. In normal human colon, mapping defined the sequential transitions in colonic crypts that enterocyte subpopulations undergo during their maturation from stem-to-proliferating-to-differentiated-to-apoptotic cells, illustrating the point that maturation is a process involving both proliferation and differentiation. In normal-appearing (heterozygous-mutant) and adenomatous (homozygous-mutant) FAP crypts, SC and proliferating cell subpopulations increasingly expanded towards the crypt top, while differentiated/apoptotic subpopulations in the upper crypt contracted, indicating that crypt cell maturation becomes progressively delayed. These data indicate that there are coordinated mechanisms that regulate maturation of crypt cells in normal crypts which become dysregulated in premalignant crypts. To investigate possible transcriptional regulation of a network of genes underlying maturation, we used bioinformatic tools to identify (i) genes that are co-expressed in the proliferating cell population and (ii) transcriptional regulatory elements (TREs) statistically enriched in the promoter regions among those genes. Computational analysis revealed (i) a specific cassette of sixty-six genes that are co-expressed with the markers used for mapping the proliferating cell population in the lower colonic crypt and (ii) eleven TREs that are significantly enriched in the promoter regions among genes in this gene set. Quantitative PCR and immunohistochemistry was then used to validate that the transcription factors (TFs), which correspond to the common TREs, are differentially expressed along the normal crypt axis and in normal colonic epithelium versus malignant colon tissues. Our results indicate that dysregulation of a transcriptional regulatory network contributes to delayed crypt cell maturation, SC overpopulation, and initiation and promotion of CRC. Accordingly, restoring maturation by targeting transcriptional pathways that control expression of multiple genes involved in crypt cell maturation may be a therapeutically effective approach to CRC treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4924. doi:1538-7445.AM2012-4924
Reliability of Measurements of Tricyclic Levels
Authors: Robert L. Bank
Journal: JAMA (1984)

To the Editor.—  In regard to the letter Toxic Tricyclic Antidepressant Levels and the ECG, 1 several remarks are pertinent. In a previous discussion inThe Journal, 2 the reliability of tricyclic antidepressant serum levels were questioned. The laboratory procedures (gas or liquid chromatography) for measuring tricyclics are complicated, and specimen collection procedures also can be problematic. 3 Also, studies using known standards and split samples have revealed troublesome interlaboratory and intralaboratory differences in reporting tricyclic levels. 4,5 The patient described by Johnson and associates 1 had an initial doxepin level of 1,230 ng/mL with no ECG changes. While it may be correct to conclude that this case is an exception to the rule that tricyclic levels over 1,000 ng/mL are associated with QRS prolongation, the alternative possibility of laboratory error must be considered. Another group of investigators using serum spiked with a known quantity of amitriptyline plus nortriptyline have reported
Insulinoma in a 94-year-old Woman: Long-term Therapy with Verapamil
Authors: Jan S Ulbrecht, Ralph Schmeltz, Jerome H Aarons, Douglas A Greene
Journal: Diabetes Care (1986)

Several drugs can be used to control hypoglycemia caused by insulin-secreting pancreatic tumors but none are reliably efficacious or free of side effects. We report the case of a woman with an insulinoma who refused surgical intervention and was successfully treated with the Ca2+-channel blocker verapamil.
Formation of vitamin A lipid droplets in pancreatic stellate cells requires albumin
Authors: N Kim, W Yoo, J Lee, H Kim, H Lee, Y-S Kim, D-U Kim, J Oh
Journal: Gut (2009)

<h3>Objective:</h3> Quiescent pancreatic stellate cells (PSCs) store vitamin A as cytoplasmic lipid droplets, and, when activated by profibrogenic stimuli, they transform into myofibroblast-like cells characterised by the loss of vitamin A droplets. Activation of stellate cells is central to fibrogenesis, but the mechanism for the formation of vitamin A droplets and its relationship to stellate cell activation remain unclear. <h3>Methods:</h3> With use of cultured PSCs, an attempt was made to characterise the function of albumin endogenously expressed in stellate cells. <h3>Results:</h3> Albumin is endogenously expressed in quiescent PSCs, localised in cytoplasmic lipid droplets, and its levels are markedly reduced after stellate cell activation. Continuous albumin expression in stellate cells is sufficient to maintain their fat-storing phenotype even after cell passages and renders cells resistant to the activating effects of transforming growth factor β (TGFβ). Forced expression of albumin in PSCs after passage 2 (activated PSCs) induced the re-appearance of lipid droplets and phenotypic changes, which were previously reported with retinol treatment. Retinol increases albumin synthesis in activated PSCs and the suppression of albumin expression using small interfering RNA (siRNA) abolishes retinol-induced effects. <h3>Conclusions:</h3> The data demonstrate a novel role for albumin in the formation of cytoplasmic vitamin A lipid droplets in stellate cells, and suggest that albumin may have a direct influence on stellate cell activation.
Neurocognitive Endophenotypes in a Multiplex Multigenerational Family Study of Schizophrenia
Authors: Raquel E. Gur, Vishwajit L. Nimgaonkar, Laura Almasy, Monica E. Calkins, J. Daniel Ragland, Michael F. Pogue-Geile, Stephen Kanes, John Blangero, Ruben C. Gur
Journal: American Journal of Psychiatry (2007)

Objective: Genetic factors contribute to the development of schizophrenia where cognitive dysfunction is a hallmark. The purpose of this article was to examine computerized neurocognitive measures as candidate endophenotypic markers of liability for schizophrenia in a genetically informative cohort. Method: European Americans from 35 multiplex multigenerational families (N=349) and healthy participants (N=154) underwent clinical assessments and neurocognitive measurements and provided blood samples. The neurocognitive measures included performance (accuracy and speed) from a computerized battery that assessed abstraction/mental flexibility; attention; verbal, face, and spatial memory; spatial processing; sensorimotor processing; and emotion intensity discrimination. Results: Probands, relatives, and comparison subjects differed from each other in performance. Probands demonstrated greatest impairment relative to comparison subjects, followed by family members. Liability for schizophrenia affected the speed-accuracy tradeoff differently for specific neurocognitive domains. Significant heritability estimates were obtained for accuracy of verbal, facial, and spatial memory and spatial and emotion processing. For speed, estimates of heritability were significant for abstraction/mental flexibility, attention, face memory, and spatial and sensorimotor processing. Conclusions: In a multigenerational multiplex design, the authors demonstrated that neurocognitive measures are associated with schizophrenia, differentiate unaffected relatives from comparison subjects, and may have significant presumed heritability. Therefore, they are endophenotypes suitable for genetic studies. Accuracy and speed can be differentially sensitive to presumed genetic liability.
Genetic variation in the serotonin receptor gene affects immune responses
Authors: Omri Snir, Espen Hesselberg, Petra Amoudrouz, Lars Klareskog, Lars Alfredsson, Izabella Zarea-Ganji, Anca I Catrina, Leonid Padyukov, Vivianne Malmström, Maria Seddighzadeh
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objective</h3> The function of the 5-HT2A receptor in the periphery is still largely unknown, but an increasing body of evidence shows effects of this receptor on immune responses. Rheumatoid arthritis (RA) is a common chronic inflammatory disease resulting from the complex interaction between genes and environment. Recently, the authors demonstrated that a haplotype in HTR2A, composed of the protective alleles of two SNPs (rs6314 and rs1328674) in HTR2A, is associated with protection against RA (Seddighzadeh, 2010). Our objective was to investigate whether presence of a RA-associated serotonin receptor 2A (HTR2A) haplotype (ie, TC) affect T cell and monocyte function. <h3>Materials and methods</h3> Patients with established RA (n=379) were genotyped for two SNPs in the <i>HTR2A</i> locus, rs6314 and rs1328674, and a haplotype was defined for each individual. PBMCs from 23 patients with or without the RA-associated TC-haplotype were selected for functional studies and cultured with and without a selective HTR2A agonist (2, 5-Dimethoxydimethoxy-4-iodoamphetamine, DOI). The authors targeted either T cells or monocytes for stimulation with staphylococcal enterotoxin B (SEB) and lipopolysaccharide (LPS), respectively. Following stimulation, the authors assessed cytokine levels intracellularly via FACS and in supernatants via CBA. <h3>Results</h3> Upon stimulation, T cells from TC-carrier patients produced more proinflammatory cytokines (TNFá, IFNã and IL-17) and monocytes produced higher levels of TNFá compared to patients carrying the non-TC haplotype. TC carriers also displayed greater inhibition of cytokine production through stimulation of the serotonin receptor 2 using the agonist DOI. <h3>Conclusion</h3> Our data demonstrate that association of RA with a distinct serotonin receptor haplotype has functional impact by affecting the immunological phenotype of T cells and monocytes.
Independent relationship of left atrial size and mortality in patients with heart failure: an individual patient meta‐analysis of longitudinal data (MeRGE Heart Failure)
Authors: Andrea Rossi, Pier Luigi Temporelli, Miguel Quintana, Frank L. Dini, Stefano Ghio, Graham S. Hillis, Allan L. Klein, Nina Ajmone Marsan, David L. Prior, Cheuk Man Yu, Katrina K. Poppe, Robert N. Doughty, Gillian A. Whalley
Journal: European Journal of Heart Failure (2009)
PWE-121 Does chromoendoscopy allow avoidance of duodenal biopsy in coeliac disease?: Abstract PWE-121 Table 1
Authors: M Kurien, K E Evans, I Chalkiadakis, M F Hale, D S Sanders
Journal: Gut (2012)

<h3>Introduction</h3> Chromoendoscopy is increasingly being used to detect, localise and characterise mucosal abnormalities seen at gastrointestinal endoscopy. The endoscopic features of coeliac disease may be difficult to recognise and are reported to lack sensitivity and/or specificity. Thus many UK centres undertake routine duodenal biopsy or have a low threshold for duodenal biopsy in order to ensure detection of patients with coeliac disease. Other than one Italian investigator group there has been limited work evaluating the role of duodenal dye spray in patients undergoing endoscopy. We aimed to determine if dye spray improved identification of characteristic endoscopic markers of coeliac disease and whether this would enhance a biopsy avoidance strategy. <h3>Methods</h3> Patients undergoing oesophogastroduodenoscopy (OGD) with duodenal biopsies were prospectively recruited between January and November 2011. Four experienced endoscopists undertook the endoscopic examinations, with endoscopic findings reported both before and after the use of indigo carmine dye spray in the second part of the duodenum (D2). Endoscopic markers reported suggestive of coeliac disease included reduction or absence of duodenal folds, scalloping, mosaic pattern, visible blood vessels and nodularity of the duodenal folds. Thereafter, in accordance with the current gold standard four duodenal biopsies were taken and histology compared with reported endoscopic findings. <h3>Results</h3> 83 patients were recruited (55 female: 28 male, median age 49 years). Of these, 33 (40%) had coeliac disease (24 newly diagnosed, nine previously treated) and 50 were controls. Three of the treated coeliac patients had persistent Marsh 3a–3c changes. In patients with coeliac disease (n=33), endoscopic features of coeliac disease were identified in 16/33 (48%) of patients. The addition of dye spray in D2 accentuated these features but only highlighted endoscopic markers in two further cases (18/33, 55%), which was not statistically significant (p=0.81). However, a significant difference was identified when comparing endoscopic markers in the coeliac group with the control group (p&lt;0.001), both before and after the use of dye spray (Abstract PWE-121 table 1). Sensitivity, specificity, positive and negative predictive values of chromoendoscopy to detect coeliac disease were 55%, 100%, 100% and 77% respectively. <h3>Conclusion</h3> The preliminary data from this study suggests there is no additional benefit of using dye spray in patients with suspected coeliac disease. Our data suggests that our current practice of a low threshold for duodenal biopsy may still be the optimal way of diagnosing patients with coeliac disease due to the low sensitivity of endoscopic markers. <h3>Competing interests</h3> None declared.