tbuckley/cabot-search huggingface dataset:
Abstract 300: Blockage of OPN induction via HGF/cMET signaling in multiple myeloma cells suppresses both MMP9 expression and RUNX2 expression of BMSCs associating with bone erosion of MM patients
Authors: Woo June Jung, Kwang-Sung Ahn, JIyeon Ryu, Soyoung Park, Juwon Park, Chansu Lee, Eunkyung Bae, Sung-Soo Yoon
Journal: Cancer Research (2012)

Abstract Dynamic interaction between multiple myeloma cells (MM) and bone marrow stromal cells plays critical roles in progression of MM. Hepatocyte growth factor (HGF), one of these factors, as a c-Met ligand, activates mitogenic activation protein kinase (MAPK). OPN binds with integrins and CD44 variants and activates cell signaling involved in invasiveness, angiogenesis and bone remodeling. Increasing lines of evidence provide that HGF and OPN, respectively, associate with the progression of MM. However, the role of HGF in MM largely remains unknown. In bone marrow serum of MM patients, HGF expression correlated with OPN expression (p=0,0095), suggesting that HGF derived from bone marrow stromal cells stimulates OPN expression in MM cells. Firstly, we found that expression levels of OPN in HFG-treated MM cells (fraction of CD138+ cells) obtained from MM patients was higher than either HFG-treated bone marrow stromal cells or HFG-treated MM cells (fraction of CD138- cells). Also, induction of DKK1 by HGF, suggesting the inhibition of osteogenesis, was found in U266 cells and RPMI8226, Both HGF-mediated MAPK and PI3K/AKT results in activating NF-kB and increasing OPN expression and DKK1. Those expressions were effectively down-regulated in U266 cells transfected with shRNA c-MET. RUNX2 mRNA and MMP-9 mRNA was increased in bone marrow stromal cells (BMSCs) treated with OPN. In addition, combined cMET inhibitor and PI3K inhibitor effectively inhibited the RUNX2 and the MMP9 mRNA expression in both OPN alone treatment and co-treatment with OPN and HGF in BMSCs. Taken together, since Induction of OPN and DKK1 by HGF in MM cells could be one of the major factors for the progression of MM through interaction of MM cells and BMSCs, blockage of HGF/cMET signaling leading to increasing levels of OPN and DKK1 may help to prevent from progressing bone erosion of MM patients. 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 300. doi:1538-7445.AM2012-300
Tc-99m MDP Scan in Medullary Carcinoma of the Thyroid With Bone Marrow Invasion
Authors: S Turpin, H Villeneuve
Journal: Clinical Nuclear Medicine (1998)

A 63-year-old woman was admitted for bone pain in her spine and right shoulder. She had been treated previously for medullary carcinoma of the thyroid, associated with MEN2A. Radiographs of her spine and shoulders were normal. Tc-99m MDP bone scan demonstrated diffuse increased uptake in the skeleton, consistent with bone marrow invasion. Neoplastic infiltration by medullary carcinoma of the thyroid was confirmed by bone marrow biopsy. To the authors' knowledge, this is the first case of Tc-99m MDP 'superscan' in medullary carcinoma of the thyroid.
Left Ventricular Aneurysm of Uncertain Etiology with Recurrent Ventricular Arrhythmias
Authors: William C. Maloy, Jack E. Arrants, Broadus F. Sowell, Grady H. Hendrix
Journal: New England Journal of Medicine (1971)

VENTRICULAR aneurysm is encountered in 2 to 3 per cent of routine autopsy cases in most medical centers.1 The frequency after myocardial infarction is much higher and varies from 10 to 38 per cent depending upon definition.2 3 4 5 Ventricular aneurysms of congenital or uncertain etiology are much rarer but have been reported in several articles especially in African natives.6 7 8 At least three cases of surgical removal of left ventricular aneurysms because of intractable ventricular arrhythmias were noted in a review of the literature.9 10 11 These were in elderly patients who most probably had coronary arteriosclerotic heart disease. In the young woman described . . .
Distribution of Antibody to Hepatitis A Antigen in Urban Adult Populations
Authors: Wolf Szmuness, Jules L. Dienstag, Robert H. Purcell, Edward J. Harley, Cladd E. Stevens, Doris C. Wong
Journal: New England Journal of Medicine (1976)

To investigate the prevalence and distribution of antibody to hepatitis A antigen we tested 947 randomly selected people in the Greater New York City area; 45 per cent were antigen positive, as determined by the immune adherence method. Antibody was detected two to three times more frequently in lower social classes (72 to 80 per cent) than in middle and upper-middle classes (18 to 30 per cent). The rate of antibody detection was strongly correlated with age; the prevalence gradually increased throughout adulthood and reached its peak level in people 50 years of age and older. Those with serologic evidence of past exposure to hepatitis B virus were significantly more often antibody positive than those without such evidence (61 vs. 40 per cent; P less than 0.001). Very few of the positive subjects had had hepatitis. The prevalence of this antibody varies among different population groups, increases with age, decreases with rise in socioeconomic status, is independent on sex and race, and correlates with serologic evidence of hepatitis B virus infections.
Abstract 3087: Regulation of p53 stability and activity by ribosomal protein S27a
Authors: Xiao-Xin Sun, Tiffany DeVine, Mushui Dai
Journal: Cancer Research (2011)

Abstract Ribosomal proteins (RPs) play a critical role in tightly coordinating p53-dependent cell cycle checkpoint with ribosomal biogenesis. A number of RPs, including L5, L11, L23, L26, and S7, specifically bind to MDM2 and inhibit MDM2-mediated p53 ubiquitination and degradation, leading to p53 activation, in response to nucleolar stress triggered by the perturbation of ribosomal biogenesis. Here, we report S27a, a ribosomal protein from small subunit of ribosome and synthesized as an ubiquitin C-terminal extension protein (CEP80), as a novel MDM2 regulator. S27a interacts with MDM2 at the central acidic domain of MDM2 and suppresses MDM2-mediated p53 ubiquitination, leading to p53 activation and cell cycle arrest. Knockdown of endogenous S27a significantly attenuated p53 activation by treatment with a low dose (5 nM) of actinomycin D (Act D), which specifically inhibits RNA polymerase I activity leading to inhibition of rRNA synthesis and perturbation of ribosomal biogenesis, suggesting that S27a is a non-redundant MDM2 regulator in response to nucleolar stress. Interestingly, we also show that MDM2 ubiquitinates S27a, leading to protesomal degradation of S27a, in response to Act D treatment, suggesting that MDM2, in turn, controls S27a levels in response to nucleolar stress. Taken together, our results reveal that S27a regulates p53 activity in response to nucleolar stress via a novel and dynamic interplay between S27a and MDM2. 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 3087. doi:10.1158/1538-7445.AM2011-3087
Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting
Authors: Rudolph M. Navari, Matti Aapro
Journal: New England Journal of Medicine (2016)

One of the most important changes in cancer treatment in recent decades has been the development of treatment regimens that greatly reduce the incidence and intensity of nausea and vomiting. The most effective regimens and how they work are reviewed.
AB0488 Etanercept down regulate serum chemokines in patients with rheumatoid arthritis
Authors: P.A. Klimiuk, S. Sierakowski, I. Domyslawska, J. Chwiecko
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chemokines promote leukocyte traffic into the synovium, leading to the initiation and progression of the rheumatoid arthritis (RA). <h3>Objectives</h3> The aim of the study was to determine the effects of etanercept, a soluble tumour necrosis factor receptor (sTNFr), on the serum chemokines levels in patients with active RA. <h3>Methods</h3> Patients were treated with 50mg of subcutaneous injection of etanercept per week and methotrexate (10-25mg/week). Serum levels of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at months 0, 3, 6, 9 and at month 12, prior to injection. <h3>Results</h3> Three months treatment with etanercept diminished serum concentrations of IL-8, RANTES and MCP-1 (p&lt;0.05, p&lt;0.01 and p&lt;0.001, respectively). Subsequent etanercept administrations prolonged decrease in serum chemokines levels and in the case of IL-8 even intensified the reduction of its concentration in serum. These changes were accompanied by significant decrease of disease activity score (DAS28) (in all cases p&lt;0.001). Prior to the first etanercept administration serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) and DAS28. Following next drug injection such associations were less or not significant. <h3>Conclusions</h3> Therapy with etanercept and MTX, not only caused a clinical improvement, but also diminished serum chemokines levels in RA patients. Further treatment with etanercept sustained chemokines suppression. <h3>Disclosure of Interest</h3> None Declared
Prevention of Rheumatic Fever by Treatment of Previous Streptococcal Infections
Authors: Robert Chamovitz, Francis J. Catanzaro, Chandler A. Stetson, Charles H. Rammelkamp
Journal: New England Journal of Medicine (1954)

RHEUMATIC fever can be prevented by adequate treatment of the preceding streptococcal respiratory infection.1 , 2 Most therapeutic regimens thus far recommended require either frequent oral medication for at least a week or multiple parenteral injections. A disadvantage of oral therapy is that it places the responsibility of maintaining treatment on the patient. In the majority of cases the symptoms of the streptococcal infection subside within three to five days, and the patient may then haphazardly take the medication or discontinue it completely. The physician can ensure adequate therapy for the prevention of rheumatic fever by the parenteral administration of penicillin. Since . . .
AT-48 * A PHASE 1 TRIAL OF CARBOXYAMIDOTRIAZOLE OROTATE (CTO) IN COMBINATION WITH BEVACIZUMAB FOR ADULT PATIENTS WITH RECURRENT MALIGNANT GLIOMA POST-BEVACIZUMAB FAILURE
Authors: T. Ranjan, k. B. Peters, G. Vlahovic, J. Watts, S. Dutton, S. Boulton, E. Lipp, J. Herndon, P. Healy, E. Miller, H. Friedman, R. Karmali, A. Desjardins
Journal: Neuro-Oncology (2014)

CTO, an oral inhibitor of non-voltage-dependent calcium signaling, modulates several pathways, including EGFR, MEK, RAS, HDAC, HSP90, WNT/B-catenin, Akt, ERK, VEGF and Bcr-Abl. A recent Phase I safety study (NCT01107522) in advanced solid tumors, including glioblastoma, demonstrated a safe toxicity profile and responses to CTO. Primary objective is to assess the maximum tolerated dose, dose limiting toxicity (DLT) and activity of CTO when combined with Bevacizumab among patients with recurrent malignant glioma (WHO grade III or IV) post Bevacizumab failure. CTO dose escalation follows a classical 3 + 3 design at a dosage ranging from 225-642mg/m2/day. Bevacizumab is being administered intravenously at 10mg/kg every 2 weeks. Pharmacokinetic sampling is performed during cycle 1 at each dose level. MRI of the brain is evaluated at baseline and then every 8 weeks using RANO criteria. To date, 11 patients have been enrolled. Of the eight evaluable patients, seven have WHO grade IV and one has WHO grade III glioma. Median age at enrollment is 54 (32-66) years with the average KPS of 80% (60-90%) in five female and three male patients. Of the three patients treated at dose level 1 of CTO (225mg/m2/day), two have completed 4 cycles and demonstrated CAI (the active moiety of CTO in plasma) levels of 2317 and 361 ng/ml. Of the three patients treated at the dose level 2 (293mg/m2/day), one experienced DLT with Grade 3 fatigue and hypertension. Three additional patients are being enrolled at dose level 2. Two patients died due to progression of tumor within 30 days of coming off study. The most frequently recorded adverse events were constipation, fatigue, nausea, vomiting, hypertension, proteinuria, hypokalemia and dizziness. CTO at a dose of 225mg/m2/day given in combination with Bevacizumab is safe and tolerable. Dose escalation is ongoing.
AB0196 Increased Plasma Soluble Urokinase Plasminogen Activator Receptor Level in Systemic Sclerosis with Impaired Microvascular Abnormalities and Fibrosis
Authors: A. Balog, N. Legány, G. Toldi, J.H. Distler, C. Beyer, B. Szalay, L. Kovács, B. Vásárhelyi
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Urokinase-type plasminogen activator receptor (uPAR) is a key component of the fibrinolytic system involved in extracellular matrix remodeling and angiogenesis. Novel animal models supported the key role of uPAR not only in fibrosis but also in systemic sclerosis (SSc)-related microvascular abnormalities. The aim of this study was to investigate plasma soluble uPAR (suPAR) levels in SSc, and their association with organ specific progression. <h3>Methods</h3> suPAR concentrations were measured by ELISA in SSc patient (n=83) and in healthy controls (n=29). Simultaneously, CRP and ESR were assessed. Detailed clinical data including skin, lung, heart and microvascular characteristics were evaluated at sampling. <h3>Results</h3> suPAR values were higher in SSc patients than in controls. Subgroup analysis showed higher suPAR values in diffuse cutaneous- than in limited cutaneous SSc and correlated with anti-Scl-70+. suPAR levels also associated with pulmonary function test parameters of fibrosis, presence of microvascular lesions (e.g. Raynaud phenomenon, naifold capillaroscopic abnormalities and digital ulcers) and arthritis. <h3>Conclusions</h3> Our data indicate that suPAR might be a valuable early diagnostic marker of SSc which also correlates with disease severity and progression. <h3>Disclosure of Interest</h3> None declared
Immunophenotyping Versus Morphological Evaluation Of Fresh and Stabilized Cerebrospinal Fluid As Diagnostic Tool For CNS Involvement In Childhood Acute Lymphoblastic Leukemia
Authors: Edwin Sonneveld, Christian M. Zwaan, Alita J van der Sluijs-Gelling, Valerie de Haas, Rob Pieters, Vincent H.J. van der Velden
Journal: Blood (2013)
Perforated gastric diverticulum with bleeding
Authors: M. Ho, A. Teoh, S. Liu, P. Chiu, S. Wong, E. Ng
Journal: Endoscopy (2013)

A 42-year-old man presented with a 3-day history of epigastric pain and tarry stools. On physical examination the hemodynamics were stable, and the patient had a pallor and mild epigastric tenderness. Blood tests revealed a hemoglobin level of 7.7 g/dL, and a chest X-ray showed a rim of free gas under the diaphragm. On abdominal computed tomography, focal dilatation was noted over the greater curve of the stomach, exaggerated by the presence of organized debris with hyperdensities suspicious of blood or food particles ([Fig. 1]). In view of his stable condition, the patient was treated conservatively. However, on follow-up esophagogastroduodenoscopy (EGD) 2 weeks later, a 4-cm outpouching, containing small amounts of coffee-ground substances and food residue, was noted on the greater curvature of the stomach ([Fig. 2]). Overall, the features were suggestive of a gastric diverticulum that had previously bled and was perforated. The patient underwent laparoscopic-stapled diverticulectomy, and pathological examination revealed gastric mucosal herniations without muscular coating, compatible with a false diverticulum of the stomach.
Abstract 2819: Serum parietal cell antibodies, gastrin G17 concentration and risk of gastric cancer: A 15 year prospective assessment
Authors: Mark Roth, You-Lin Qiao, Farin Kamangar, Jin-Hu Fan, Lena Diaw, Jian-Song Ren, Philip R. Taylor, Carol A. Giffen, Sanford M. Dawsey, Christian C. Abnet
Journal: Cancer Research (2010)

Abstract Background: We conducted a prospective nested case-cohort analysis within a high-risk Chinese population to determine if baseline serum PCAs or gastrin was associated with an increased risk of gastric or esophageal cancer during 15 years of follow-up. Methods: The study included 200 cases of gastric cardia adenocarcinoma (GCA), 200 gastric non-cardia adenocarcinomas (GNCA), 100 esophageal squamous cell carcinomas (ESCC), and a 400 person subcohort of the Linxian General Population Nutritional Intervention Trial cohort. Serum PCA and gastrin G17 concentrations were measured using enzyme-linked immunosorbent assays. Mean sample concentrations were calculated by averaging duplicate optical density measures. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs), using case-cohort models. Models assessed high PCA (Q4 vs Q1) or low gastrin G17 (Q1 vs Q4) and cancer risk. H. pylori status and pepsinogen serology were previously determined (Kamangar et al. Br J. Ca 2007, Ren et al. Gut 2009). Results: The average time from baseline to cancer diagnosis was 8.1 years. Serum PCA concentrations were non-significantly lower in those who developed GCA than in the subcohort, and were inversely associated with GCA risk. Serum gastrin G17 concentrations were significantly lower in those who developed GNCA than in the subcohort, and were inversely associated with GNCA risk. Neither serum PCA nor gastrin G17 concentration was associated with ESCC risk. These associations were independent of gender, age, smoking, serum pepsinogen I and II concentrations, and H. pylori status. PCA concentration, median (IQR)PwilcoxonPCA Q4 vs Q1PtrendSubcohort (N= 424)0.84 (0.26-5.8)---ESCC (N=95)1.02 (0.32-6.3)0.231.28 (0.65-2.53)&amp;gt;0.5Cardia (N=193)0.59 (0.23-3.2)0.0700.53 (0.30-0.93)0.013Noncardia (N=193)0.85 (0.27-5.4)0.830.76 (0.42-1.35)&amp;gt;0.5 G17 concentration median (IQR)PwilcoxonG17 Q1 vs Q4PtrendSubcohort (N= 424)3.16 (0.78-8.33)-- ESCC (N=95)3.23 (0.57-10.39)0.731.06 (0.55-2.03)0.91Cardia (N=193)3.23 (0.87-6.89)0.681.54 (0.83-2.87)0.30Noncardia (N=193)2.20 (0.30-5.70)0.00203.72 (1.83-7.57)0.00020 Conclusion: High serum parietal cell antibodies were associated with a decreased risk of GCA, and low serum gastrin G17 levels were associated with an increased risk of GNCA in this high-risk population. 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 2819.
Rendezvous technique using bronchoscopy and gastroscopy to close a tracheoesophageal fistula by placement of an over-the-scope clip
Authors: Sudheer Vinnamala, Buddhavarapu Murthy, Jitendra Parmar, Nikhil Bhasin, Pratima Verma, Colin Melville, Jayan Mannath
Journal: Endoscopy (2014)

A 23-year-old man with polytrauma was admitted to the intensive care unit for level 3 postoperative support. His medical history included VATER syndrome [1] with corrective surgery for the tracheoesophageal fistula (TEF). Ventilatory support according to ARDSNet criteria in the acute phase was complicated by a persistent air leak and significant gastric distension, raising the possibility of a residual TEF. An initial gastroscopy failed to show a fistulous opening. A Ryle's tube for gastric air drainage and nasojejunal tube for enteral feeding were left in situ. Flexible bronchoscopy through the endotracheal tube showed a flap with access to the esophagus from the bronchial tree just above the carina, confirming the clinical suspicion of a TEF.
Seven Years of Remission in a Type I Diabetic Patient: Influence of cyclosporin and regular exercise
Authors: Veikko A Koivisto, Marjatta Leirisalo-Repo, Pertti Ebeling, Juha A Tuominen, Mikael Knip, Ulla Turunen, Thomas Mandrup-Poulsen, Risto Pelkonen
Journal: Diabetes Care (1993)

Objective— To analyze factors contributing to a long-term remission in a patient with type I diabetes. Research Design and Methods— The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow-up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and β-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects. Results— Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr. Conclusions— In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr.
Comparative Features and Course of Ulcerative and Granulomatous Colitis
Authors: Donald J. Glotzer, Richard C. Gardner, Harvey Goldman, H. Richard Hinrichs, Howard Rosen, Louis Zetzel
Journal: New England Journal of Medicine (1970)

The course of 95 patients was reviewed to evaluate criteria used to distinguish ulcerative and granulomatous colitis and to determine the effects of operation. Histologic criteria useful in separation of the two forms of colitis were the depth of mucosal ulceration and inflammation and the presence of sinus tracts and granulomas. The presence of microscopic sinuses or granulomas (or both) correlated significantly with clinical features considered those of granulomatous colitis, and their absence with clinical features of ulcerative colitis (p less than 0.005), but there was overlap in about a quarter of the cases. Patients with clinical and microscopical features considered typical of granulomatous colitis tended to require more ileostomy revisions, but the long-term course after total colectomy and ileostomy was similar for both forms of colitis. The distinction between ulcerative and granulomatous colitis has been too sharply drawn, and the unfavorable prognosis commonly ascribed to the granulomatous form is not proved.
Multiple testing correction in linear mixed models
Authors: Jong Wha J. Joo, Farhad Hormozdiari, Buhm Han, Eleazar Eskin
Journal: Genome biology (2016)

Multiple hypothesis testing is a major issue in genome-wide association studies (GWAS), which often analyze millions of markers. The permutation test is considered to be the gold standard in multiple testing correction as it accurately takes into account the correlation structure of the genome. Recently, the linear mixed model (LMM) has become the standard practice in GWAS, addressing issues of population structure and insufficient power. However, none of the current multiple testing approaches are applicable to LMM. We were able to estimate per-marker thresholds as accurately as the gold standard approach in real and simulated datasets, while reducing the time required from months to hours. We applied our approach to mouse, yeast, and human datasets to demonstrate the accuracy and efficiency of our approach. We provide an efficient and accurate multiple testing correction approach for linear mixed models. We further provide an intuition about the relationships between per-marker threshold, genetic relatedness, and heritability, based on our observations in real data.