tbuckley/cabot-search huggingface dataset:
Transplantation of highly purified peripheral blood CD34+ cells from HLA-mismatched parental donors in 14 children: evaluation of early monitoring of engraftment
Authors: C Peters, S Matthes-Martin, G Fritsch, W Holter, T Lion, V Witt, P Höcker, G Fischer, K Dieckmann, R Handgretinger, T Klingebiel, H Gadner
Journal: Leukemia (1999)
UNDERUTILIZATION OF STATIN THERAPY AFTER A CARDIOVASCULAR EVENT OR DIABETES DIAGNOSIS IN THREE REAL-WORLD DATA SYSTEMS
Authors: Deborah Kim, Yi Peng, Suying Li, Jill Hardin, Anne Beaubrun, Katherine Mues, Brian Bradbury, Keri Monda, Paul Muntner, Robert Rosenson, Charles Herzog
Journal: Journal of the American College of Cardiology (2016)
LEPTOSPIRAL MYOCARDITIS MIMICKING ACUTE ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Dharmaraj Karthikesan, Huan Yean Kang, Ahmad Shukri Saad, Kai Soon Liew, Noor Hafis Md Tob, Song Weng Khoo, Wan Faizal Wan Rahimi Shah, Omar Ismail
Journal: Journal of the American College of Cardiology (2016)
EPIG-11THE IMPLICATION OF CpG island AND SPINT2 HYPERMETHYLATION IN BOTH IDH1 WILD-TYPE AND MUTANT ADULT DIFFUSE GLIOMAS
Authors: Fei Liu, Reshmi Chowdhury, Tie Li, Sichen Li, Huytram Nguyen, Bowen Wei, Arthur P. Chou, Jean K. Reiss, Reema R. Mody, Linda M. Liau, Phioanh L. Nghiemphu, William H. Yong, Timothy Cloughesy, Albert Lai
Journal: Neuro-Oncology (2015)

BACKGROUND: IDH1/2 mutation and associated glioma CpG island methylator phenotype (G-CIMP) is associated with glioma prognosis. G-CIMP is defined as CpG islands hypermethylated in IDH1/2 mutant (IDH1/2MUT) gliomas. G-CIMP thus excludes hypermethylated CpG islands shared between IDH1/2MUT and IDH1/2 wildtype (IDH1/2WT) gliomas. These shared hypermethylated CpG islands may be important in gliomagenesis. We aimed to determine whether a set of CpG islands are hypermethylated in both IDH1/2MUT and IDH1/2WT gliomas and its functional implications. METHODS: Methylation profiling was performed using reduced representation bisulfite sequencing. Unsupervised clustering identified a novel sets of hypermethylated CpG islands shared between IDH1/2MUT and IDH1/2WT tumors. Targeted bisulfite sequencing of selected genes was used to confirm this novel set of hypermethylated CpG islands. SPINT2 was identified as a candidate hypermethylated tumor suppressor gene. SPINT2 DNA methylation and gene expression were measured in glioma samples. To assess regulation of SPINT2 expression by methylation, DNMT1 was knockdown and SPINT2 promoter activity was measured by luciferase assay. SPINT2 tumor suppressive function was investigated in vitro. RESULTS: A group of CpG islands were found hypermethylated in both IDH1/2MUT and IDH1/2WT gliomas compared with normal brain (designated as Glioma Total CpG island Methylator, GT-CIM). Nine candidate genes within GT-CIM were confirmed by target bisulfite sequencing. Within GT-CIM, the cell motility gene SPINT2 mRNA level was significantly lower in the hypermethylated glioblastomas as compared to the hypomethylated ones. DNMT1 knockdown restored SPINT2 expression. In the luciferase assay, SPINT2 promoter activity was reduced by DNA methylation. Over-expression of SPINT2 inhibited the glioma cells migration and invasion in vitro. CONCLUSIONS: We identified a set of CpG islands hypermethylated in all gliomas, termed GT-CIM. Within GT-CIM, we found that SPINT2 is regulated by DNA methylation, and its overexpression suppresses tumor cell migration and invasion. Further studies on GT-CIM and its related genes are warranted.
FRI0329 Free light chains of immunoglobulins in serum as biomarkers of activity in systemic lupus erythematosus
Authors: Z. Hrncir, M. Drahosova, T. Soukup, J. Toms
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The molecules of immunoglobulins (Ig) include two identical heavy and two identical light chains. More light than heavy chains of Ig are produced under physiological conditions, and so free light chains (FLC) may be detected in biological fluids, especially in serum. Systemic lupus eryhtematosus (SLE) is associated with polyclonal activation of B cells, and proportional elevation of FLC kappa and FLC lambda values in serum should be expected in active form of SLE. <h3>Objectives</h3> To explore the changes of serum concentration of FLC kappa and FLC lambda as putative biomarkers of SLE disease activity in a prospective, comparative, and cross-over study. <h3>Methods</h3> Eighty-three adult SLE pts (ACR/1982, updated 1997) and 33 age- and sex-matched healthy controls were enrolled; concomitant infection, monoclonal gammopathy and renal failure in SLE pts were excluded. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K): a score ≥ 6 was considered clinically important. FLC kappa and FLC lambda in serum were analysed by quantitative nephelometric assay (Freelite, The Binding Site Group, Birmingham, UK) and compared against SLEDAI-2K score and serological biomarkers IgG, C3, C4 (Beckman Coulter), "total" ANA/IF (DIA SORIN, USA) in maximal titre, anti-dsDNA/IFCL (INOVA, USA) in maximal titre, and antinucleosome Abs/ELISA (EUROIMMUN, BRD). The data obtained were statistically processed using Medcalc-Statistical Software progamme. <h3>Results</h3> Serum concentration of FLC kappa, FLC lambda and total FLC kappa+FLC lambda in 22 SLE with SLEDAI-2K ≥ 6, and also in 61 SLE with SLEDAI-2K &lt; 6 was significantly higher against healthy controls (p=0.003- &lt; 0.001) except FLC lambda in SLE with SLEDAI-2K &lt; 6 (p &gt; 0.05). In SLE with SLEDAI-2K ≥ 6 the concentration of FLC kappa, FLC lambda and FLC kappa+FLC lambda was always significantly higher than in SLE with SLEDAI-2K &lt; 6 (p &lt; 0.001). In total group of 83 SLE was found significant correlation (p &lt; 0.001) between SLEDAI-2K score and FLC kappa (r = 0.56), FLC lambda (r = 0.58), and FLC kappa+FLC lambda (r = 0.62); FLC analysis against serological biomarkers under study demonstrated a strong correlation namely between antinucleosome Abs and FLC kappa (r = 0.59), FLC lambda (r = 0.53) and FLC kappa+FLC lambda (r = 0.59). <h3>Conclusions</h3> The data obtained are suggesting that investigation of FLC values in serum should be useful as biomarkers of SLE disease activity, but further studies are necessary. <b>Disclosure of Interest</b>: Z. Hrncir Grant/research support from: PRVOUK P37-08, M. Drahosova Grant/research support from: PRVOUK P37-08, T. Soukup: None Declared, J. Toms: None Declared
Abstract 3482: Hypoxia induces translational regulation of lymphangiogenic growth factors
Authors: Barbara H. Garmy-Susini, Francoise Pujol, Loic Van den Berghe, Anne-Catherine Prats
Journal: Cancer Research (2011)

Abstract Hypoxia is a major condition for induction of angiogenesis during tumor development, nevertheless its role in lymphangiogenesis remain unclear. In this study, we investigate the role of hypoxia in the translational regulation of lymphangiogenic growth factors. The majority of cellular stresses such as hypoxia leads to an inhibition of mRNA translation in cell by the classical cap-dependent mechanism. However, several mRNAs are translated by an alternative mechanism mediated by internal ribosome entry sites (IRESs) located in their 5’ untranslated regions. We found IRES elements in mRNAs of lymphangiogenic growth factors such as VEGFA and FGF2, and demonstrated that hypoxia is able to activate IRES-mediated mRNA translation both in vitro and in vivo. Interestingly, our recent data demonstrated a strong induction of VEGFA and FGF2 IRES activities in vivo in pancreas adenocarcinoma CAPAN-1, that correlates with development of hypoxia area and lymphangiogenesis in primary tumors. Such an activation is not observed with the viral EMCV IRES used as a control, indicating a translational activation in response to tumoral hypoxia could be specific of angiogenic/lymphangiogenic factors IRESs. We are interested in the translational control of more specific of lymphangiogenic growth factors, VEGFC and VEGFD. We've shown, in CAPAN-1 model, that VEGFC and VEGFD translation correlates with hypoxia area development in vivo. To determine the presence of IRESs in VEGFC and -D mRNAs, we cloned the 5’ untranslated regions of murine and human VEGF-C and -D mRNAs in bicistronic lentivectors. First data suggest the presence of an IRES VEGFC and -D mRNAs. In further investigations, our purpose is to demonstrate that the process of IRES-dependent translation plays a pivotal role in the hypoxic response, and should lead to induction of lymphangiogenic factors, including VEGFC and VEGFD. Thus, cell proteins able to activate IRESs, called IRES trans-acting factors (ITAFs), would be crucial protagonists in the lymphangiogenesis process and potential taget for anti-angiogenic therapy. 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 3482. doi:10.1158/1538-7445.AM2011-3482
Abstract 850: Selenium compounds activate ATM-dependent DNA damage response via the mismatch repair protein hMLH1 in colorectal cancer cells
Authors: Yongmei Qi, Norberta W. Schoene, Frederick M. Lartey, Wen-Hsing Cheng
Journal: Cancer Research (2011)

Abstract Epidemiological and animal studies indicate that selenium supplementation suppresses risk of colorectal and other cancers. The majority of colorectal cancers are characterized by a defective DNA mismatch repair (MMR). Here, we have employed the MMR-deficient HCT 116 colorectal cancer cells and the MMR-proficient HCT 116 cells with hMLH1 complementation to investigate the role of hMLH1 in selenium-induced DNA damage response, a tumorigenesis barrier. The ATM (ataxia telangiectasia mutated) protein responds to clastogens and initiates DNA damage response. We show that hMLH1 complementation sensitizes HCT 116 cells to methylseleninic acid, methylselenocysteine, and sodium selenite via reactive oxygen species and facilitates the selenium-induced oxidative 8-oxoguanine damage, DNA breaks, G2/M checkpoint response, and ATM pathway activation. Pretreatment of the hMLH1-complemented HCT 116 cells with the antioxidant N-acetylcysteine or 2,2,6,6-tetramethylpiperidine-1-oxyl or the ATM kinase inhibitor KU55933 suppresses hMLH1-dependent DNA damage response to selenium exposure. Selenium treatment stimulates the association between hMLH1 and hPMS2 proteins, a heterodimer critical for functional MMR, in a manner dependent on ATM and reactive oxygen species. Taken together, the results suggest a new role of selenium in mitigating tumorigenesis by targeting the MMR pathway, whereby the lack of hMLH1 renders the HCT 116 colorectal cancer cells resistant to selenium-induced DNA damage response. 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 850. doi:10.1158/1538-7445.AM2011-850
Endovascular Stent–Graft Placement for the Treatment of Acute Aortic Dissection
Authors: Michael D. Dake, Noriyuki Kato, R. Scott Mitchell, Charles P. Semba, Mahmood K. Razavi, Takatsugu Shimono, Tadanori Hirano, Kan Takeda, Isao Yada, D. Craig Miller
Journal: New England Journal of Medicine (1999)

The standard treatment for acute aortic dissection is either surgical or medical therapy, depending on the morphologic features of the lesion and any associated complications. Irrespective of the form of treatment, the associated mortality and morbidity are considerable.
Case 22-2008
Authors: Martin S. Hirsch, Alfred DeMaria, Pamela W. Schaefer, John A. Branda
Journal: New England Journal of Medicine (2008)

A 52-year-old woman was admitted to this hospital because of fever and confusion. The patient was first taken to the emergency department of another hospital, where she was reported to be lethargic and disoriented. Several hours later, a tonic–clonic seizure occurred, and she was transferred to this hospital. The patient lived in a rural area of Massachusetts and had been bitten by mosquitoes. MRI scans showed multiple bilateral lesions in the brain that were hyperintense. On the fourth hospital day, the result of a diagnostic test was received.
Abstract 1549: Regulation of inflammation and tumor growth by the novel XL313 cryptic ECM element
Authors: Jacquelyn J. Ames, Desiree P. Nugent, Liangru Contois, Jennifer M. Caron, Peter C. Brooks
Journal: Cancer Research (2011)

Abstract Experimental evidence suggests that multiple cell types within the tumor microenvironment such as fibroblast, endothelial cells and inflammatory cells contribute to tumor growth. Recent evidence indicates that biomechanical alterations in the structural integrity of ECM proteins may result in exposure of cryptic regulatory elements that play roles in differentially controlling cell signaling pathways. Therefore, exposure of cryptic regulatory sites may function as biomechanical switches, allowing various cell populations to respond in distinct ways to localized structural alterations within the tumor microenvironment. Thus, identifying and characterizing biomechanical ECM switches may provide selective new therapeutic targets to regulate tumor progression. In this regard, triple helical collagen has numerous RGD containing cryptic integrin binding sites. However, it is not known whether all these cryptic RGD elements are functionally redundant or whether distinct flanking sequences may convey differential control of cellular behavior. To examine potential functional differences between distinct RGD containing cryptic sites, we generated a series of Mabs directed to synthetic RGD containing peptides found within type-I collagen. One Mab termed XL313 selectively recognized a cryptic element containing the amino acid sequence RGDKGE, but failed to bind other RGD containing sites. Mab XL313 failed to recognize intact triple helical collagen, but did bind proteolytically cleaved collagen. Importantly, Mab XL313 significantly (P&amp;lt;0.05) inhibited B16F10 melanoma tumor growth by greater than 50%. Given the possibility that inflammation may contribute to tumor development, we examined the impact of the XL313 epitope on growth factor induced inflammation. Our studies suggest that the XL313 cryptic site may regulate inflammation as Mab XL313 significantly (P&amp;lt;0.05) inhibited inflammation / CAM thickening in the chick embryo model. Collectively, our studies suggest that the XL313 biomechanical ECM switch may represent an important new therapeutic target for the control of tumor growth and inflammation. 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 1549. doi:10.1158/1538-7445.AM2011-1549
Case 21-1998
Authors: Nesli Basgoz, Matthew Frosch
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 32-year-old woman was admitted to the hospital because of paresthesias and pharyngeal spasms.The patient had been in excellent health until 68 days earlier, when she was bitten by a dog in Nepal. She received only first aid. The wound healed uneventfully. Thereafter, she was well until two days before admission, when she began to have severe “shooting pains” in the left arm, followed by numbness in the bitten area. A physician in an emergency room prescribed acetaminophen–codeine and a nonsteroidal antiinflammatory drug. Mild headache, low-grade fever, malaise, nausea, and vomiting followed, and during the two . . .
Abnormal Red-Cell Calcium Pump in Patients with Idiopathic Hypercalciuria
Authors: Giuseppe Bianchi, Giuseppe Vezzoli, Daniele Cusi, Tiziana Cova, Attilio Elli, Laura Soldati, Grazia Tripodi, Maurizio Surian, Ercole Ottaviano, Patrizio Rigatti, Sergio Ortolani
Journal: New England Journal of Medicine (1988)

Idiopathic hypercalciuria is a common disorder whose inheritance suggests an enzyme abnormality in calcium transport. We measured calcium-magnesium-ATPase activity in erythrocytes from 38 patients (mean age [+/- SEM], 40 +/- 2.1 years) with idiopathic hypercalciuria (24-hour urinary calcium excretion greater than or equal to 0.1 mmol per kilogram of body weight) and a history of multiple calcium oxalate kidney stones. As compared with 41 healthy controls, the patients with hypercalciuria had increased erythrocyte-membrane calcium-magnesium-ATPase activity (64.2 +/- 2.19 vs. 51.6 +/- 1.91 nmol of ATP split per milligram per minute; P less than 0.01) and increased sodium-potassium pump activity (6866 +/- 233 vs. 6096 +/- 228 mumol of sodium per liter of red cells per hour; P less than 0.05). No significant difference between the two groups was found in erythrocyte sodium-potassium cotransport, sodium-lithium countertransport, or potassium content. In 66 patients with kidney stones (38 with hypercalciuria and 28 with normal calcium excretion), 24-hour urinary calcium excretion correlated with calcium-magnesium-ATPase activity (r = 0.46, P less than 0.001). Erythrocyte calcium-magnesium-ATPase activity remained unchanged in eight subjects studied after four months on a low-calcium diet. A study of 30 healthy families found significant correlations between mean values in parents and those in offspring for calcium-magnesium-ATPase (r = 0.68, P less than 0.001) and urinary calcium excretion (r = 0.45, P less than 0.02), with no significant correlations between parents with respect to these measures (r = 0.27 and r = 0.08, respectively). We conclude that abnormalities in erythrocyte calcium-magnesium-ATPase activity may represent an inherited defect in calcium transport related to the cause of idiopathic hypercalciuria.
Abstract 2343: Overexpression of uPAR in the murine oral squamous cell carcinoma cell line AT84
Authors: Synnøve Magnussen, Stine Haustreis, Lars Uhlin-Hansen, Jan-Olof Winberg, Gunbjorg Svineng
Journal: Cancer Research (2010)

Abstract Cancers of the oral cavity are associated with bad prognosis and have been so for the last 20-30 years. Almost half of the patients diagnosed with oral squamous cell carcinoma (SCC) will die from the disease. When comparing oral SCC to its counterpart in skin, one of the main features that differ between the two is the ability of the oral SCC to metastasize. A prerequisite for metastasis is the capability to invade the surrounding tissue and penetrate into the nearest blood- or lymphatic vessel. This initial step in metastasis requires several extracellular matrix degrading enzymes. One such enzyme is uPA (urokinase-type plasminogen activator), involved in pericellular proteolysis, where high levels are known to be correlated to bad prognosis in several cancers. Pro-uPA binds to its extracellularly located receptor uPAR. Upon binding, pro-uPA is cleaved and activated, and ample evidence shows that binding of uPA triggers uPAR-mediated cellular signalling. Being that uPAR has no membrane spanning domain, the signal transduction has to be mediated through one or several membrane partners. uPARs role in the regulation of cell adhesion, migration and proliferation have been dedicated to its interplay with membrane partners such as integrins, chemokine receptors, EGFR, G-protein coupled receptors and caveolin. To better understand the role of uPAR in the metastasis of oral SCCs, a mouse oral SCC cell line, AT84, was stably transfected with uPAR. AT84 was initially obtained from a spontaneously originating oral SCC of the C3H mouse (Lou et al., 2003; Schultz-Hector and Haghayegh, 1993). Characterization of these cell lines with respect to adhesion, migration, invasion, and effects on gene expression and activation of other proteolytic enzymes will be presented. Lou, E., R.M. Kellman, R. Hutchison, and E.J. Shillitoe. 2003. Clinical and pathological features of the murine AT-84 orthotopic model of oral cancer. Oral Dis. 9:305-12. Schultz-Hector, S., and S. Haghayegh. 1993. Beta-fibroblast growth factor expression in human and murine squamous cell carcinomas and its relationship to regional endothelial cell proliferation. Cancer Res. 53:1444-9. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2343.
682 APPARENT DIFFUSION COEFFICIENT DETERMINED TARGET RESPONSE AT DIFFUSION-WEIGHTED MRI IS AN INDEPENDENT PREDICTOR OF OUTCOME IN HEPATOCELLULAR CANCER PATIENTS TREATED WITH TRANSARTERIAL CHEMOEMBOLIZATION
Authors: V. Vandecaveye, K. Michielsen, F. De Keyzer, W. Laleman, M. Komuta, K. Op de Beeck, T. Roskams, F. Nevens, C. Verslype, G. Maleux
Journal: Journal of Hepatology (2013)
SAT0159 Clinical Features of Japanese Patients with Vasculo- BehÇEt’S Disease: A Multicenter Study by BehÇEt’S Disease Research Committee, MHLW
Authors: M. Takeno, H. Ideguchi, A. Suda, R. Watanabe, H. Kikuchi, H. Nagafuchi, M. Kuwana, K. Saito, S. Hirohata, Y. Ishigatsubo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Vascular lesion is one of most critical manifestations in patients with Behçet's disease (BD), whereas there are some regional differences in the clinical features. <h3>Objectives</h3> This study characterizes clinical features and therapeutic approaches in Japanese vasculo-BD patients. <h3>Methods</h3> We retrospectively analyzed clinical data of 105 BD patients (male 71, female 34) with vascular lesions from 6 institutes which belong to Behçet's Disease Research Committee, Ministry of health, labor, and Welfare, Japan. All patients met the Japan Diagnostic Criteria (2003), and presented with more than one vascular lesions in arteries and veins, but superficial thrombophlebitis was not included as vascular involvement. <h3>Results</h3> The diagnosis of BD in the enrolled patients was made at 35.5 years old, while the initial vascular event appeared at 42.7 years old. Frequency of HLA-B51 positive was lower in vasculo-BD patients (41%) than the others (51%). Eye involvement and epididymitis were less frequent in vasculo-BD patients, whereas intestinal lesions were more commonly found. The vascular lesions were distributed in the venous system (71%), the arterial system (31%) and the pulmonary vessels (25%), all of which were determined by imaging modalities including contrast CT, angiography, ultrasonography, pulmonary perfusion scan, MRI, and PET. As treatment, corticosteroids and immunosuppressants such as MTX, cyclosporine, and azathioprine were used in 73% and 35%, respectively, whereas 18 patients (17%) had surgical operation. Of 5 patients treated with Infliximab, 2 patients received endovascular or surgical intervention for the vascular lesions, resulting in improvement. Any anticoagulant and/or anti-platelet agents were used in 82.9 % of patients, including warfarin in 58.1% and aspirin 49.5%. These agents-related bleeding events were found 9 times in 8 patients, all of them were minor and recovered after discontinuation of the agents. Eight patients have died, and 4 of them were associated with vascular involvement including hemoptysis in 2 patients who did not receive anticoagulant and anti-platelet agents. <h3>Conclusions</h3> The present study shows that the distribution of vascular lesions and therapeutic approaches in Japanese BD patients were similar with those from other countries according to previous reports. However, our data suggest that fatal pulmonary bleeding caused by anticoagulant and anti-platelet agents is rare in Japanese BD patients, though these agents are commonly used in Japan. <h3>Disclosure of Interest</h3> None Declared