tbuckley/cabot-search huggingface dataset:
HG-01 * MGMT PROMOTER METHYLATION STATUS AND miRNA-181 FAMILY EXPRESSION AS PROGNOSTIC MARKERS IN GLIOBLASTOMA PATIENTS
Authors: L. Bie, C. Hua, G. Zhao, Y. Li
Journal: Neuro-Oncology (2015)

BACKGROUND: The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. The miRNA-181 family is the important role of radio- and chemo-resistant in glioblastoma (GBM) patients. Our research is to analyze the prognostic significance of MGMT promoter methylation status and miRNA-181 family expression in a group of GBM patients treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated. METHODS: Sixty-three patients with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and miRNA-181 family. We examined methylation status of MGMT promoter by methylation-specific real-time PCR. MiRNA-181 family expression was assessed qPCR. Overall and progression-free survival was calculated according to the Kaplan–Meier method. RESULTS: The MGMT gene promoter was found to be methylated in 29 patients (46.0%) and unmethylated in 34 patients (54.0%). MGMT methylation status was significant correlated with response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MiRNA-181c and miR-181d expression were the predictive markers in GBM patients prognosis (p < 0.05). MiRNA-181c and miRNA-181d were down-regulated in patients who responded to RT/TMZ (p = 0.032; p = 0.017, respectively) in comparison to patients with poor prognosis. Analyses of possible correlation between miRNA-181d expression and MGMT promoter methylation status were positive. CONCLUSIONS: Our results support the hypothesis that MGMT promoter methylation status may be a predictive biomarker in the treatment of patients with GBM. In addition, our data indicate for the first time that expression levels of miRNA-181c and miRNA-181d could serve as a predictive marker of response to RT/TMZ therapy in GBM patients. Moreover, these data suggest that miRNA-181d is a potential role to regulate MGMT promoter methylation status.
Cholesterol Emboli after Coronary Bypass Surgery
Authors: Rolf Dario Frank, Joachim Velden
Journal: New England Journal of Medicine (2011)

Five weeks after uneventful coronary-artery bypass grafting, an 81-year-old woman presented to the hospital with a serum creatinine level of 493 μmol per liter (5.6 mg per deciliter). Her kidney function had remained stable throughout her hospital stay for the surgery, and her serum creatinine level on discharge had been 106 μmol per liter (1.2 mg per deciliter), with an estimated glomerular filtration rate of 46 ml per minute per 1.73 m2 of body-surface area. Physical examination of her legs and feet now revealed extensive livedo reticularis (Panel A) and cyanosis of the toes (Panel B). A differential blood count . . .
Abstract 2633: Single nucleotide polymorphisms in one carbon metabolism genes are associated with methylation patterns and plasma metabolites in high risk smokers based on gender
Authors: Kristina G. Flores, Christine A. Stidley, Maria A. Picchi, Amanda J. Mackey, Sally P. Stabler, Tim Byers, Marianne Berwick, Steven A. Belinsky, Shuguang Leng
Journal: Cancer Research (2012)

Abstract Lung cancer is the leading cause of cancer related deaths and most lung cancers are detected at a late stage. Gene promoter hypermethylation is now regarded as a promising biomarker to identify early risk and progression of lung cancer. The one carbon metabolism pathway is postulated to affect DNA methylation because it is necessary for the generation of S-adenosyl methionine or (SAM), the methyl donor for cellular DNA methylation reactions, through complex interactions with metabolites including folate, homocysteine, and methionine. This study investigated the association of single nucleotide polymorphisms (SNPs) in one carbon metabolism related genes with DNA promoter hypermethylation in sputum cell DNA from current and former smokers in the Lovelace Smokers Cohort (n=907). The association of SNPs with methylation was analyzed by logistic regression using gender specific high and low methylation cutoffs from a 12 gene methylation panel as the outcome. SNPs in the cystathionine beta-synthase (CBS) and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) genes were found to be statistically associated with methylation in a gender specific fashion (CBS SNP, OR=4.9; CI: 1.98, 12.2, p=.0006 in males) and (MTRR SNP, OR= 0.57, CI: 0.42, 0.77, p=0.0003 in females). Plasma homocysteine levels and the ratio of homocysteine to cystathionine increased in male samples with heterozygous or homozygous minor alleles of the CBS SNP compared to male samples with homozygous common alleles (n=86). This study suggests that SNPs in the CBS and MTRR genes are associated with methylation patterns in smokers by gender. The CBS SNP may be important in regulating plasma homocysteine and cystathionine levels that could theoretically mediate the aberrant DNA methylation in smokers at high risk to develop lung cancer. Grant Support: This work is supported by K01CA128823 NCI (Flores) and R01CA097356 NCI (Belinsky). 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 2633. doi:1538-7445.AM2012-2633
Reevaluating “Made in America” — Two Cost-Containment Ideas from Abroad
Authors: Gerard F. Anderson, Amber Willink, Robin Osborn
Journal: New England Journal of Medicine (2013)

Two cost-containment pricing strategies from abroad could be adapted to the U.S. health care context: a bundled-payment system from Germany and volume-driven pricing adjustment from Japan. These promising policies would not require large-scale reform.
Abstract 4866: The atypical kinase SgK223 is a novel mediator of cell invasion in pancreatic cancer
Authors: Carole M. Tactacan, Emily S. Humphrey, Andrew V. Biankin, Roger J. Daly
Journal: Cancer Research (2012)

Abstract Pancreatic cancer still remains one of the most aggressive and lethal of human cancers, with a lack of effective treatments contributing to its poor prognosis and high mortality. Perturbations in tyrosine kinase signaling are characteristic of many human cancers. In order to detect aberrant protein tyrosine phosphorylation events in pancreatic cancer, and to subclassify pancreatic cancer cell lines based on their tyrosine phosphorylation patterns, tryptic digests from a wide panel of pancreatic cancer cell lines were subjected to anti-phosphotyrosine immunoprecipitation, then analysed by liquid chromatography coupled with tandem mass spectrometry (MS/MS). Proteins were ranked according to differences in median phosphorylation levels across the cell line panel, and those that exhibited significantly variable phosphorylation levels were selected as candidates for further evaluation as biomarkers and therapeutic targets. One candidate identified by this approach was SgK223, a 175 kDa atypical kinase with substitutions in the DFG motif of its kinase domain. Since this is one of the conserved motifs critical for full catalytic activity, SgK223 may be catalytically inactive. Western blotting revealed that SgK223 protein expression varied across the panel, with a subset of pancreatic cancer lines exhibiting overexpression relative to normal human pancreatic duct epithelial (HPDE) cells. To further interrogate the role of SgK223 in pancreatic cancer, SgK223 was overexpressed in HPDE cells. This resulted in an elongated cell morphology and increased cellular migration and invasion in transwell assays, with no effect on cellular proliferation or Erk and Akt activity. MS/MS analysis determined that SgK223 was phosphorylated on tyrosine residues 159 and 413. Since the former is a candidate Stat3 binding site, we characterised Stat3 signalling in this model. SgK223 overexpression led to enhanced Stat3 tyrosine phosphorylation and transcriptional activity. These data identify a role for SgK223 as a mediator of cell invasion in pancreatic cancer, and support the use of MS-based phosphoproteomic profiling as an effective discovery tool for cancer-associated signaling proteins. 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 4866. doi:1538-7445.AM2012-4866
Developmentally regulated responsiveness to transforming growth factor-β is correlated with functional differences between human adult and fetal primitive hematopoietic progenitor cells
Authors: SFA Weekx, J Plum, P Van Cauwelaert, M Lenjou, G Nijs, M De Smedt, M Vanhove, P Muylaert, DR Van Bockstaele, ZN Berneman, H-W Snoeck
Journal: Leukemia (1999)
Mimicry of Physiological Urinary FDG Excretion
Authors: Te-Chun Hsieh, Shung-Shung Sun, Yu-Chin Wu, Kuo-Yang Yen, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2010)

Skeletal muscle metastases are rare and usually occur with various malignancies at more advanced stages. FDG PET/CT has been known as a useful tool to detect these lesions because of the character of whole-body scanning and superior contrast between malignant and normal tissues, except in areas with abundant physiological FDG radioactivity, such as the urinary system. We present a patient with esophageal squamous cell carcinoma and an incidental, rare finding of psoas muscle metastasis that was initially omitted because of the similarity of its distribution to physiological urinary FDG excretion in the ureter.
Ga-67 Uptake in a Corpus Luteum Cyst
Authors: HITOYA OHTA, TOMOO KOMIBUCHI
Journal: Clinical Nuclear Medicine (1998)

Ga-67 scintigraphy was performed in a 25-year-old woman with fever of unknown origin to search for an infectious focus. Abnormal Ga-67 uptake was recognized in the pelvis, and a CT scan showed a cystic mass consistent with the Ga-67 uptake. Gynecologic examination revealed the mass to be a corpus luteum cyst. The fever still continued, but follow-up Ga-67 scintigraphy and CT showed no abnormal findings. This case suggested that corpus luteum cyst should be considered in the differential diagnosis of pelvic Ga-67 uptake.
Fulminant Hepatic Failure
Authors: Charles Trey, Leslie Lipworth, Thomas C. Chalmers, Charles S. Davidson, Leonard S. Gottlieb, Hans Popper, Stuart J. Saunders
Journal: New England Journal of Medicine (1968)

Analysis of the first 150 cases collected from 73 centers reporting to the Fulminant Hepatic Failure Surveillance Study showed that 80 patients had presumable viral hepatitis, of whom 62 died. Of 41 patients who had recent surgery, 36 died. In 35 patients massive liver necrosis developed less than three weeks after halothane anesthesia, and 27 (77 per cent) of these had multiple exposures to halothane. The risk from halothane is small, but this complication was present in nearly one quarter of the cases reported in our study. When the use of halothane is desired, multiple exposure should be avoided, if possible. Moreover, postoperative fever after exposure to halothane, otherwise "unexplained," is an important warning sign, and should be thoroughly investigated and taken into consideration when further exposure to this anesthetic is contemplated. The physician prescribing halothane must balance need against risk.
KIDNEY DEPTH EVALUATION USING TONNESEN FORMULA AS COMPARED TO ULTRASOUND.
Authors: Doina E. Tanasescu, Kenneth Resser, Bob McLurkin, David E. Brown, Mitchell Komaiko, Michael B. Brachman, Lalitha Ramanna, Alan D. Waxman
Journal: Clinical Nuclear Medicine (1986)

Tanasescu, Doina E.; Resser, Kenneth; McLurkin, Bob; Brown, David E.; Komaiko, Mitchell; Brachman, Michael B.; Ramanna, Lalitha; Waxman, Alan D. Author Information
Tc-99m Pertechnetate Scintigraphy for the Detection of Ileal Duplication
Authors: I Peksoy, B Caner, G Kale, Z Akcören, C F Bekdik
Journal: Clinical Nuclear Medicine (1998)

A 6-month-old boy with rectal bleeding was admitted to the hospital. Two months before admission he had melena. On admission, a suspicious abdominal mass was palpated and the hemoglobin was 8.3 g/dl. Abdominal ultrasonography was not diagnostic. Abdominal scintigraphy with Tc-99m pertechnetate showed an abnormal tubular shaped area of increased radioactivity filling the entire abdomen and was highly suggestive of intestinal duplication. At operation, 55 cm of ileal duplication was resected. Histologic examination revealed that the duplication was lined by gastric mucosa. Preoperative abdominal Tc-99m pertechnetate scintigraphy was essential to making the diagnosis of ileal duplication.
Abstract 2423: B7-H3 contributes to increased metastatic potential of melanoma cells by interfering with the expression of metastasis-related genes
Authors: Marit K. Nygren, Christina Tekle, Yih-Wen Chen, Alexandr Kristian, Jahn Marthin Nesland, Gunhild Mari Mælandsmo, Øystein Fodstad
Journal: Cancer Research (2011)

Abstract Metastatic malignant melanoma is a disease with a long time survival rate of only 5%. Since there is no effective treatment for advanced melanoma, detection of molecular markers involved in tumor progression and drug resistance can hopefully provide new insight in therapeutically aspects of this disease. We have been studying B7-H3 – a glycosylated transmembrane protein which has been shown to play a role in cancer progression through its immunoregulatory properties. B7-H3 is highly expressed in melanoma cell lines as well as in clinical melanoma specimens, and we have previously demonstrated a role of the protein in chemoresistance. Thus, in this study, we wanted to investigate the possible function of B7-H3 in melanoma metastasis development. We found that short hairpin RNA silencing of B7-H3 reduced the migratory potential as well as the matrigel-invasiveness of the malignant melanoma cells in vitro. In an in vivo experimental metastasis model, silencing of B7-H3 increased the symptom-free survival of nude mice and rats significantly, this in parallel with a lower fraction mice having microscopically detectable metastasis compared to control mice. The brain was the predominant organ with metastases and a clear difference between the nude mice injected with B7-H3 expressing cells and B7-H3 knock down cells was observed, with 10/14 and 6/17 mice having brain tumors, respectively. Furthermore, we found the expression of several metastasis-associated proteins, such as MMP-2, TIMP1 and TIMP2 to be regulated by B7-H3. In addition, the secretion of IL-8 was markedly reduced in the B7-H3 knock down cells as well as the phosphorylation of Stat3. Interestingly, activated Stat3 is known to play a role in brain metastasis. Taken together, our findings suggest that B7-H3 might be a potential therapeutic target for anti-metastasis therapy in human melanoma. 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 2423. doi:10.1158/1538-7445.AM2011-2423
Oral cholera vaccine raises hopes
Authors: Z. Kmietowicz
Journal: BMJ (1997)

Researchers in Vietnam have produced a cheap and effective oral vaccine against cholera, reducing the incidence of the disease in an endemic area of the country by 60%.

To test the efficacy of an oral killed cholera vaccine that had been produced locally the Vietnamese team performed an open field trial in 22 653 households in the central coastal city of Hue ( Lancet 1997;349:231-5). They found that the number of cases of cholera during an outbreak …
Beyond the VA Crisis — Becoming a High-Performance Network
Authors: David J. Shulkin
Journal: New England Journal of Medicine (2016)

Interview with Dr. Ashish Jha on lessons from the recent Veterans Health Administration crisis and future directions at the VA. (04:55)Download The Veterans Health Administration plans to evolve its current troubled system into a high-performance network based on a foundation of timely access and the integration of private-sector providers to ensure the best achievable outcomes for all enrolled veterans.
Book: Telepsychiatry and e-Mental Health
Authors: Kristina Fišter
Journal: BMJ (2003)

The earliest reports of telepsychiatry (defined in this book as “the delivery of health care and the exchange of information for purposes of providing psychiatric services across distances”) date from the late 1950s, when an interactive television link was used in Nebraska, United States, to connect a teaching hospital department of psychiatry with a state institution. Today, e-mental health (“mental health services provided through any form of electronic medium, most commonly via the internet or telephony”) is practised in most Western countries and delivered widely in different ways around the world.​world.




Figure 1



Eds Richard Wootton, Peter Yellowlees, Paul McLaren

Royal Society of Medicine Press, £24.95/$39.95, pp 368 ISBN 1 8531 549 7 www.rsmpress.co.uk/bkwootton3.htm

Rating: ★ ★ ★ ★




This book is one of the first to examine this field comprehensively. It is an interesting and ultimately important read for patients seeking valid sources of education and self help, and for all mental health professionals, whether practising or considering using telepsychiatry and the internet.

The contributors are experienced practitioners of telepsychiatry from a wide range of clinical and academic centres in Australia, Europe, and north America. They discuss various technologies and approaches, real life experiences, economic challenges, legal and ethical aspects, experimental ideas, and future trends.

Telepsychiatry and e-mental health are a reality of the e-21st century. e-mental health services will never replace face to face care, nor does the book in any way suggest that they should. But the benefits that they can provide mean that they look set to be increasingly integrated into face to face programmes. In particular they can ensure that mental health care becomes more accessible and affordable for those who are at present out of direct reach of such services, whether that is because they are bed bound, phobic or paranoid, living in a remote area, or even in prison.

This book is bursting with useful information, practical ideas, advice, and up to date international references on technical, clinical, economic, and legal issues for both mental health professionals and patients. It offers a comprehensive overview of the current state of telepsychiatry and e-mental health and a valuable insight into the future of this exciting and developing field.
Hyperplastic Nodules and Adenomas of Exocrine Pancreas in Azaserine-Treated Rats2
Authors: Daniel S. Longnecker, Barbara G. Crawford
Journal: JNCI Journal of the National Cancer Institute (1974)

Long-term studies of the carcinogenicity of azaserine in rats were undertaken to develop a model of adenocarcinoma of the pancreas. Rats were treated for 6 weeks to 6 months with once or twice weekly intraperitoneal azaserine injections. Single doses were 5–25 mg/kg; total doses were 120–300 mg/kg. All of 18 rats autopsied 3½, 6, or 8 months after initiation of treatment had nodular groups of atypical exocrine cells which seemed to represent hyperplastic foci, and 3 rats had small exocrine adenomas. No malignant tumors were found. One of 6 control rats contained 1 hyperplastic nodule in exocrine pancreas.
THU0505 Characterization of Phenotype and Immunoglobulin Genes of Autoreactive B Cells in SjÖGren's Syndrome
Authors: P. Efthimiou, S. Kadavath, A. Bhatta, E. Charles, L. Dustin
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Characteristic changes in the distribution of peripheral B cell subsets and differences in use of immunoglobulin-variable region genes are features of Sjögren9s Syndrome (SS). Studies on Hepatitis C virus infected (HCV+) mixed Cryoglobulinemia (MC) patients have revealed B cell clonal expansion expressing stereotypical Rheumatoid Factor (RF) encoded by the immunoglobulin genes VH1-69 and Vk 3-20. G6 antibody specific for VH1-69 can identify the RF- expressing B cells in HCV+MC patients.Since some SS patients have been known to develop lymphomas bearing VH1-69 encoded antibodies, we hypothesized that SS patients might have clonal expansions of VH1-69-bearing B cells. <h3>Objectives</h3> Identify B lymphocyte characteristics in patients with Sjogren9s syndrome <h3>Methods</h3> We obtained blood samples from 13 patients diagnosed with SS at a teaching hospital rheumatology clinic, serving a large inner city population. Further processing of the blood samples from these patients was done at Rockefeller University and the Peripheral Blood Mononuclear Cells (PBMCs) were cryopreserved. Fluorescent- labeled Ro/SS-A (52,60kDA) and La-SS-B antigens were obtained. The purpose was to label B cells that make SS-A antibody so they could be seen by flow cytometry. <h3>Results</h3> Preliminary flow cytometric analysis of B cells in 8 of the blood samples showed a B cell phenotype different from that seen in HCV-associated MC. The memory B cells were high in CD-21, unlike those seen in HCV-associated MC. Few VH1-69 + B cells were seen in 4/8 patients analyzed. The other blood samples showed very few cells binding SS-A. <h3>Conclusions</h3> Unraveling the association between autoimmunity and lympoproliferation in SS patients will have clinical value, and B cell gene expression data may be able to predict susceptibility to lymphoma in these individuals. The abnormally expanded B cells should be studied at the transcriptional, proteomic and functional levels. The lack of direct comparison between the B cell repertoire in the blood and that in the parotids and/or minor salivary glands has prevented drawing of firm conclusions. The long term goal would be to clone, sequence and characterize autoantibodies produced in SS. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5796