tbuckley/cabot-search huggingface dataset:
AB0197 Endothelial dysfunction in a mouse model of SLE: A role for tumor necrosis factor-α?:
Authors: A. Virdis, C. Tani, S. Vagnani, E. Duranti, S. Bombardieri, M. Mosca
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is characterized by a reduced endothelium-dependent relaxation. These alteration have been associated with an early occurrence of traditional cardiovascular risk factors as well as to disease related factors such as inflammation and autoantibodies. <h3>Objectives</h3> In the present study we aimed to assess the endothelial function on mesenteric resistance arteries in a mouse model of SLE (NZB/W F1) (mSLE) at different disease stages; the endothelial dysfunction (ED) reversibility with anti- tumor necrosis factor (TNF)-α was also investigated. <h3>Methods</h3> Twenty 8 weeks old female mSLE were subdivided in 4 groups and monitored for 24-hours proteinuria as disease progression parameter; each group was sacrificed at 12, 18, 24 and 30 weeks of age respectively. Small arteries were studied on a pressurized myograph. E-D relaxation was assessed by infusion of acetylcholine (Ach), NO availability and inflammation were assessed by repeating Ach under the nitric oxide synthase (NOS) inhibitor L-NAME (100 μmol/l) and infliximab (Ifx, monoclonal anti-TNF-α antibody, 100 μmol/l), respectively. C56BL/6J (mC) mice were sacrificed and analyzed at the same age as controls. <h3>Results</h3> In mSLE, we observed a decline in relaxation to Ach from 18 weeks of age and a further worsening at 30. The inhibitory effect of L-NMMA on Ach was reduced at 18 and progressively blunted up to 30 weeks; interestingly, ED appeared simultaneously to a significant increase in 24-hours proteinuria (mean 0.39±0.1 at 12 weeks versus 5.8±3.4 at 18 weeks of age, p=0.02). Interestingly, Ifx normalized the relaxation to Ach at 18 and 24 weeks of age but, after that age period, Ifx was no more effective. In mC, maximal relaxation to Ach significantly started to decline at 30 weeks of age with a concomitant reduction of the inhibitory effect of L-NMMA on Ach. Ifx failed to affect the response to Ach at any time. The response to sodium nitroprusside (SNP) was preserved among mC but started to decline at 30 weeks of age in mSLE <h3>Conclusions</h3> In this mouse model of SLE we observed a progressive ED caused by a reduced NO availability starting from 18 weeks of age which occurred earlier than in control mice and was concomitant with lupus disease activity. While in mC, ED is related with ageing, in mSLE the inflammatory disease appears to play a role in the development of ED. ED is initially reversed with TNF-alpha blocking but this effect seems to disappear when age-and disease- related vascular structural alterations occur. These data suggest a possible involvement of TNF- alpha on the accelerated atherosclerosis observed in SLE patients <h3>Disclosure of Interest</h3> None Declared
Treatment of 171 Patients with Pulmonary Tuberculosis Resistant to Isoniazid and Rifampin
Authors: Marian Goble, Michael D. Iseman, Lorie A. Madsen, Dennis Waite, Lynn Ackerson, C. Robert Horsburgh
Journal: New England Journal of Medicine (1993)

The frequency of infection with multidrug-resistant Mycobacterium tuberculosis is increasing. We reviewed the clinical courses of 171 patients with pulmonary disease due to M. tuberculosis resistant to rifampin and isoniazid who were referred to our hospital between 1973 and 1983. The patients' records were analyzed retrospectively. Their regimens were selected individually and preferably included three medications that they had not been given previously and to which the strain was fully susceptible.
A Trial of Goal-Oriented Hemodynamic Therapy in Critically Ill Patients
Authors: Luciano Gattinoni, Luca Brazzi, Paolo Pelosi, Roberto Latini, Gianni Tognoni, Antonio Pesenti, Roberto Fumagalli
Journal: New England Journal of Medicine (1995)

Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal levels may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index.
PTH-008 Safety And Efficacy Of Balloon Sphincteroplasty Using Controlled Radial Expansion (cre) Balloon During Endoscopic Retrograde Cholangio Pancreatography In The Management Of Large Common Bile Duct (cbd) Stones: A District General Hospital Experience
Authors: DK Hanumantharaya, T Barnes, J Hunt, M Asante
Journal: Gut (2014)

<h3>Introduction</h3> Extraction of large (&gt;1 cm) CBD stones at ERCP is often difficult despite adequate sphincterotomy. Failure of extraction of stones warrants repeat ERCPs and also referral to advanced techniques such as extracorporeal shock wave lithotripsy which is not readily available in UK centres. We believe that balloon sphincteroplasty is a safe and effective procedure which is underutilised. We describe a large district general hospital experience of use of balloon sphincteroplasty in a cohort of elderly patients. <h3>Methods</h3> All patients who underwent balloon sphincteroplasty since June 2012 at Princess Royal Hospital, Bromley were identified from endoscopy database. Patients demographics, sedation dose, size of balloon sphincteroplasty, success rate of CBD stones clearance and complications were examined. <h3>Results</h3> A Total of 29 patients underwent balloon sphicteroplsty. 8 (27%) of these patients had previous unsuccessful attempt at ERCP removal of stones. All patients had sphincterotomy prior to sphincteroplasty. Mean age of patients was 72 years. There were 20 female and 9 male patients. Mean dose of Midazolam was 4 mg and Fentanyl 75 mg. Mean size of the CBD stones in these patients was 13 mm (range 10–20 mm). 8 patients had large peri-ampullary diverticulum (6 patients had ampulla at the edge of diverticulam, one &lt;5 mm). Balloon sphincterotoplasty using Boston Scientific CRE balloon was performed. Mean size of balloon sphincteroplasty was 14 mm (range 10–20 mm and median 15 mm). Stone retrieval basket was used in 6 patients. Complete extraction of CBD stones was documented in 28 of 29 (97%) patients. One patient developed uncomplicated pancreatitis who recovered with conservative management. One patient had minor bleeding which settled spontaneously. None of the patients had perforations. Stone clearance was incomplete in one patient due to to a small proximal stone floated up in to the left hepatic duct. On median follow up of 6 months 1 patient underwent repeat ERCP for recurrence of stones. <h3>Conclusion</h3> In our district general hospital cohort of elderly patients, Balloon sphincteroplasty was found to be safe and effective procedure in extraction of large common bile duct stones. Complete extraction of CBD stones was achieved in 97% of patients. One patient had mild pancreatitis, one had mild bleeding and there was no of perforations observed. Balloon sphincteroplasty was particularly useful in patients with peri-ampullary divericulm in whom a generous sphincterotomy could be risky. Balloon sphincteroplasty had prevented the further need for ERCP, and its associated cost and morbidity. <h3>Reference</h3> Maydeo A, Bhandari S, et al., <i>Endoscopy</i> 2007; 39 (11) <h3>Disclosure of Interest</h3> None Declared.
422 THE IMPACT OF DECREASING LEVELS OF SERUM HBsAg ON HBsAg SEROCLEARANCE IN CHRONIC HEPATITIS B
Authors: S. Nagaoka, H. Yatsuhashi, Y. Kugiyama, S. Bekki, R. Sasaki, S. Hashimoto, M. Ohtani, S.K. Bae, A. Saeki, S. Abiru, A. Komori
Journal: Journal of Hepatology (2013)
'False-Positive' Uptake of FDG in a Hepatic Adenoma
Authors: PRATUL M. PATEL, HALUK ALIBAZOGLU, AMJAD ALI, ERNEST FORDHAM, GREGORY LAMONICA
Journal: Clinical Nuclear Medicine (1997)

Positron emission tomography using F-18 FDG is becoming a very useful test in the evaluation of many tumors because of its high sensitivity and specificity. However, on rare occasions, it may be difficult to differentiate a neoplasm from a benign lesion. This article describes increased metabolic activity in a hepatic mass found on a routine follow-up CT examination of the abdomen in a 41-year-old woman with a history of bilateral breast carcinoma. Based on an elevated differential uptake ratio of 4.2, the lesion was thought to be consistent with a metastatic tumor. The hepatic mass was removed surgically and proved to be a hepatic adenoma.
Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity
Authors: Byung-Cheol Lee, Myung-Sunny Kim, Munkyong Pae, Yasuhiko Yamamoto, Delphine Eberlé, Takeshi Shimada, Nozomu Kamei, Hee-Sook Park, Souphatta Sasorith, Ju Rang Woo, Jia You, William Mosher, Hugh J.M. Brady, Steven E. Shoelson, Jongsoon Lee
Journal: Cell Metabolism (2016)
Power Doppler Sonography Versus Tc-99m DMSA Scintigraphy for Diagnosing Acute Pyelonephritis in Children
Authors: SERGEY BYKOV, LEONID CHERVINSKY, VLADISLAV SMOLKIN, RAFI HALEVI, IZAK GARTY
Journal: Clinical Nuclear Medicine (2003)

Purpose This study assessed the role of renal power Doppler ultrasonography (PDU) to identify acute pyelonephritis (APN) and to determine whether PDU can replace Tc-99m DMSA renal scintigraphy in the diagnosis of APN in children. Methods A prospective study was conducted in 40 infants and young children (78 kidneys were evaluated) with a mean age of 25.9 months (range, 1 to 68 months) who were hospitalized with a first episode of high fever and bacteruria, possibly APN. All children were examined by PDU and Tc-99m DMSA within the first 3 days after admission. Patients with congenital abnormalities, hydronephrosis, and urinary reflux were excluded. Results Twenty-seven of the 78 kidneys appeared abnormal on Tc-99m DMSA, and 20 of them were abnormal on PDU. Fifty-one of 78 kidneys were normal on Tc-99m DMSA, and 3 of 51 appeared diseased on PDU. The accuracy of PDU was 87%, sensitivity was 74%, and specificity was 94%. The positive predictive and negative predictive values were both 87%. When considering the numbers of lesions in 27 kidneys with positive Tc-99m DMSA studies (38 lesions), PDU did not disclose 16 lesions (false-negative results). Thus, the sensitivity of PDU for diagnosing lesions of APN decreased to 58%. Conclusions A positive PDU finding should obviate the use of Tc-99m DMSA in patients thought to have possible APN. However, because of a large number of false-negative results (26%) and underestimation of the number of pyelonephritic lesions (low sensitivity of 58%), PDU cannot replace Tc-99m DMSA in the diagnosis of APN in children.
Abstract 4846: Manipulation of autophagy during tumor cell killing regulates the growth of neighboring tumor cells
Authors: Jacqueline Thorburn, Michael Morgan, Andrew Thorburn
Journal: Cancer Research (2012)

Abstract Many anti-cancer agents induce macroautophagy (hereafter “autophagy”) and it is widely thought that autophagy can regulate tumor chemosensitivity. Most work in this area asks if autophagy increases or decreases tumor cell killing. Using a targeted anti-cancer agent (DT-EGF, an EGF receptor-targeted diphtheria toxin), we demonstrated that autophagy can also control the characteristics of dying glioma cells. DT-EGF induces autophagy in glioma cells, however this autophagy has little impact on whether or not the cells die. Instead its major effect is to determine how the cells die. When autophagy is allowed, the cells die by a non-apoptotic mechanism that has little caspase activation, whereas if autophagy is inhibited, the glioma cells die by inducing caspase-dependent apoptosis. Here, we present data showing that the effects of this switch in death mechanism change the growth of other tumor cells that did not die in response to the drug. By mixing DT-EGF-sensitive and DT-EGF-resistant cells such that 99% of the tumor cells in the population die, we found that manipulation of autophagy in the dying cells affects the growth rates of the surviving 1% of tumor cells. If caspase-dependent apoptosis is allowed by inhibiting autophagy, the surviving tumor cells grow faster to repopulate the tumor. Conversely if autophagy is allowed in the dying cells, the resistant cells grow more slowly. We propose that cancer therapy should take account not just of how many tumor cells are killed but also the way that they are killed and that manipulating autophagy during cancer treatment could be used to improve outcomes by regulating the mechanism of tumor cell death as well as the amount of tumor cell death. 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 4846. doi:1538-7445.AM2012-4846
Urine may be better than milk for 'biopharming'
Authors: A. Berger
Journal: BMJ (1998)

Scientists in the United States have produced mice that can produce urine rich in human growth hormone.

The scientists, from the Department of Agriculture in Maryland, have produced the mice by replacing the protein coding region of a gene that is expressed only in the epithelial cells lining the bladder with the genetic sequence that codes for human growth hormone ( Nature BioTechnology 1997;16:75-9).

The next step will be to see if larger farm animals can be similarly modified to produce human proteins. If such technology is developed, the commercial production of biologically useful proteins from the urine of genetically modified farm animals could become a viable option.

Three body fluids-milk, blood, and urine-have been suggested as potentially suitable media for protein production in genetically modified animals. So far, proteins have been produced from both milk and blood. The most recent example of this was Polly, the genetically cloned sheep that has been designed to produce human factor IX in her milk.

However, only female animals can be used for protein production in milk, and the process also depends on lactation taking place. Protein production in urine should therefore confer several advantages over production in milk: not only could the whole herd be used, but production …
Abstract LB-91: Identification and feasibility test of novel methylation biomarkers for stool DNA-based colorectal cancer screening
Authors: Sungwhan An, TaeJeong Oh, YoungHo Moon, Nayoung Kim, Seung-Hoon Lee, Nam Kyu Kim, Hyun Cheol Chung, HyunIl Oh
Journal: Cancer Research (2010)

Abstract Aberrant DNA methylation event is known to be early and frequent process in tumorigenesis and could therefore serve as a convenient biomarker for early detection of cancers. For the identification of novel methylation markers we compared each methylation profiles in super normal tissues (n=2) of healthy individuals and primary tumors and their matched normal appearing adjacent tissues (non-tumor) from colorectal cancer patients (n=12) relative to that of common reference DNA through genome-wide CpG microarray analysis following methylated DNA enrichment with a minimum size of methyl binding domain. Unsupervised hierarchical clustering of with entire methylation pattern data successfully discriminated normal, match-paired normal and primary tumors. We then statistically selected novel methylation candidates showing high frequency of methylation in primary tumor samples and intermediate in non-tumor but no methylation in supernormal tissues for early detection and confirmed in colorectal cancer cell lines by quantitative pyrosequencing-based methylation assay. For final candidates with high specificity, we selected 4 genes, GABRA1, gt-SD, gt-SI, gt-SO which showed a low methylation level in 2 healthy normal tissues. All of 4 genes appeared to be much more frequently hypermethylated in primary tumors than in non-tumor tissues in pyrosequencing assay. For the applicability into non-invasive sample we analyzed methylation status of 4 genes in stool DNAs obtained from patients with colorectal cancer (n=106) and healthy volunteers (n=10) by modified two-round nested MSP for improving analytic sensitivity. The sensitivity and specificity of each of 4 genes were estimated as 50.5% to 60.2% and 85.7% to 100%, respectively. The sensitivity of the four-gene panel was 88.7% (94/106) and its specificity was 80.0% (2/10) in detecting colorectal cancer with stool DNA. Consequently, 4 novel genes have a great potential in noninvasive stool DNA testing for colorectal cancer screening. Further large-scale clinical validation will be needed for clinical setting. 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 LB-91.
The effect of tetrathiomolybdate on endothelial progenitor cells in patients at high risk for breast cancer recurrence.
Authors: S. Jain, J. A. Cohen, M. M. Ward, J. O'Loughlin, M. Boeck, N. Wiener, E. Chuang, T. Cigler, A. Moore, D. Donovan, C. Lam, M. E. Cobham, S. E. Schneider, P. J. Christos, M. E. Lane, R. Baergen, V. Mittal, S. Rafii, L. T. Vahdat
Journal: Journal of Clinical Oncology (2011)

1054 Background: Bone marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. Tetrathiomolybdate (TM), an oral copper-depleting compound, inhibits angiogenesis and maintains tumor dormancy. This study explores the effect of TM on EPCs in patients (pts) at high risk for breast cancer recurrence. Methods: This phase II study enrolled pts with stage III, stage IV without evidence of disease (NED) breast cancer, and stage II if triple negative (TN). Only concomitant hormone therapy was allowed. Pts received induction TM 180 mg daily followed by 100 mg daily to maintain ceruloplasmin (Cp) level < 17 mg/dL (target for copper depletion). TM was continued for 24 months (mo), or until relapse or toxicity, with an extension study for additional 24 mo in selected pts. We monitored EPCs (CD45dim/CD133+), Cp, CEA and CA15-3 at baseline (BL) and monthly. EPCs were quantitated from peripheral blood mononuclear cells by flow cytometry. Median BL EPCs was compared to subsequent time points by Wilcoxon signed-rank. Results: 41 pts (29 adjuvant, 12 stage 4 NED, 11 TN) were enrolled and 802 cycles of TM were administered. Median age was 51 years (29-64). Median tumor size was 3.6 cm (1.2-7) and number of positive lymph nodes was 9 (0-42). Median BL Cp level was 29 mg/dL (20-47). 61% pts were adequately copper depleted, by a median time of 1 mo. Four pts discontinued treatment before reaching target. Median BL EPCs/mL was 712 (0-3332). EPCs significantly decreased from BL in copper depleted pts, p=0.03 at 12 mo. Only grade 3/4 toxicity was hematologic: neutropenia in 18 cycles (2.2%), febrile neutropenia in 1 cycle, anemia in 1 cycle. All resolved in 5-13 days with TM held and resumed at a lower dose. Sixteen pts discontinued therapy because of toxicity (3), patient preference (4), inability to copper deplete (2) and disease progression (7). In pts with recurrence, a marked rise in EPCs preceded overt relapse and a tumor marker rise by at least 2 mo. Conclusions: TM is a well-tolerated copper chelator that may contribute to maintaining EPCs below baseline in copper-depleted pts. Further, the rise in EPCs prior to overt relapse in pts with recurrent disease may signify a potential surrogate marker for early relapse.
ASSOCIATION BETWEEN OBESITY AND POSTOPERATIVE ATRIAL FIBRILLATION IN PATIENTS UNDERGOING CARDIAC SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Adrian V. Hernandez, Roop Kaw, Vinay Pasupuleti, Pouya Bina, John P.A. Ioannidis, Hector Bueno, Eric Boersma
Journal: Journal of the American College of Cardiology (2013)
Increase in Salmonella enterica serovar Paratyphi A infections in Phnom Penh, Cambodia, January 2011 to August 2013
Authors: E Vlieghe, T Phe, B De Smet, C H Veng, C Kham, D Sar, J van Griensven, K Lim, S Thai, J Jacobs
Journal: Eurosurveillance (2013)

We report an increased number of Salmonella enterica Paratyphi A infections in adults in Cambodia. Between January 2011 and August 2013, 71 S. Paratyphi A isolates were recovered from blood cultures, representing a 44-fold increase compared to July 2007 to December 2010, while monthly numbers of cultures did not change. Infections with S. Typhi increased two-fold in the same period. Most cases came from the capital Phnom Penh. These findings warrant epidemiological investigation to support public health measures.
Positive Selection on a Regulatory Insertion–Deletion Polymorphism in<i>FADS2</i>Influences Apparent Endogenous Synthesis of Arachidonic Acid
Authors: Kumar S. D. Kothapalli, , Kaixiong Ye, Maithili S. Gadgil, Susan E. Carlson, Kimberly O. O’Brien, Ji Yao Zhang, Hui Gyu Park, Kinsley Ojukwu, James Zou, Stephanie S. Hyon, Kalpana S. Joshi, Zhenglong Gu, Alon Keinan, J.Thomas Brenna
Journal: Molecular Biology and Evolution (2016)

Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion–deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product–precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice.
Evidence That Dyslexia May Represent the Lower Tail of a Normal Distribution of Reading Ability
Authors: Sally E. Shaywitz, Michael D. Escobar, Bennett A. Shaywitz, Jack M. Fletcher, Robert Makuch
Journal: New England Journal of Medicine (1992)

Dyslexia is now widely believed to be a biologically based disorder that is distinct from other, less specific reading problems. According to this view, reading ability is considered to follow a bimodal distribution, with dyslexia as the lower mode. We hypothesized that, instead, reading ability follows a normal distribution, with dyslexia at the lower end of the continuum.