tbuckley/cabot-search huggingface dataset:
Complication Rates of Endoscopic Polypectomy in Relation to Polyp Characteristics and Techniques
Authors: W. K. Choo, J. Subhani
Journal: Gut (2011)

<h3>Introduction</h3> Endoscopic polypectomy (EP) could reduce colorectal cancer incidence by 76–90%. Quoted rates of major complications in EPs were low, often less than 1%. We aimed to examine our complication rates in relation to the characteristics of polyps removed and techniques employed. <h3>Methods</h3> We retrospectively reviewed 2106 EPs performed on 1252 consecutive patients over a 3.5-year period between January 2006 and June 2009. EP techniques and polyp morphology, site and size were examined. EP data were matched with data on readmissions post-endoscopy. Serious complications were defined as events leading to readmission within a 14-day period. χ<sup>2</sup>-test and Fishers Exact Analysis were used in significance testing. <h3>Results</h3> Majority of our EPs were done with colonoscopy (94%) while 6% were done with flexible sigmoidoscopy. Thirteen patients or 23 (1.1%) polypectomies had complications within 14 days. None of our complications involved perforation, 10 (0.47%) had bleeding and 4 (0.19%) had post-polypectomy syndromes. Our bleeding rate was 1:211, lower than the national standard of 1:100. No deaths were reported within the study period. Majority of polyps removed were sessile in morphology (77%) with another 23% being pedunculated. Over 80% of polyps resected were 10 mm or less. The number of polyps removed fell with increasing size. Only 2% of polyps removed were larger than 30 mm, largest being 80 mm (2 polyps). Complication rates rose from 1% in the smallest group (1–10 mm) to 4.9% in the largest (&gt;31 mm) but the rise was not statistically significant (p=0.067). We performed more EPs in the descending colon, sigmoid colon and rectum (70%) than in the rest of the colon but found fewer complications in these groups compared to ascending and transverse colon polypectomies (p=0.002). The latter groups had a higher tendency of developing post-polypectomy syndrome and bleeding. We performed 1163 (55%) snares, 783 (37%) hot biopsies and 164 (8%) endoscopy mucosal resections (EMR). Complication rates in snare polypectomies were not significantly different from that of hot biopsies (p=0.64). However, EMR had significantly more complications compared to snares (p=0.045) and hot biopsies (p=0.026). <h3>Conclusion</h3> We achieved lower bleeding rates than that published nationally. Hot biopsy did not carry a higher risk although EMR did. Polyp size was an important risk factor although statistical significance was not met. Ascending and transverse colon polypectomies carried the highest risks of complications. Patients should be made aware of this risk prior to their procedure. We would include the rates of minor complications in a longer follow-up in future studies. <h3>Competing interests</h3> None.
E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin
Authors: Craig MacKay, Eilís Carroll, Adel F.M. Ibrahim, Amit Garg, Gareth J. Inman, Ronald T. Hay, Arno F. Alpi
Journal: Cancer Research (2014)

Abstract The genotoxin cisplatin is commonly used in chemotherapy to treat solid tumors, yet our understanding of the mechanism underlying the drug response is limited. In a focused siRNA screen, using an siRNA library targeting genes involved in ubiquitin and ubiquitin-like signaling, we identified the E3 ubiquitin ligase HOIP as a key regulator of cisplatin-induced genotoxicity. HOIP forms, with SHARPIN and HOIL-1L, the linear ubiquitin assembly complex (LUBAC). We show that cells deficient in the HOIP ligase complex exhibit hypersensitivity to cisplatin. This is due to a dramatic increase in caspase-8/caspase-3–mediated apoptosis that is strictly dependent on ATM-, but not ATR-mediated DNA damage checkpoint activation. Moreover, basal and cisplatin-induced activity of the stress response kinase JNK is enhanced in HOIP-depleted cells and, conversely, JNK inhibition can increase cellular resistance to cisplatin and reverse the apoptotic hyperactivation in HOIP-depleted cells. Furthermore, we show that HOIP depletion sensitizes cancer cells, derived from carcinomas of various origins, through an enhanced apoptotic cell death response. We also provide evidence that ovarian cancer cells classified as cisplatin-resistant can regain sensitivity following HOIP downregulation. Cumulatively, our study identifies a HOIP-regulated antiapoptotic signaling pathway, and we envisage HOIP as a potential target for the development of combinatorial chemotherapies to potentiate the efficacy of platinum-based anticancer drugs. Cancer Res; 74(8); 2246–57. ©2014 AACR.
Diagnosis and management of adult onset Still's disease
Authors: P Efthimiou
Journal: Annals of the Rheumatic Diseases (2005)

Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology that is responsible for a significant proportion of cases of fever of unknown origin and can also have serious musculoskeletal sequelae.To assess and synthesise the evidence for optimal diagnosis and management of AOSD.The key terms, adult onset Still's disease, AOSD, adult Still's disease, ASD, Still's disease were used to search Medline (1966-2005) and PubMed (1966-2005) for all available articles in the English language. Clinically relevant articles were subsequently selected. Bibliographies, textbooks, and websites of recent rheumatology conferences were also assessed.Data on diagnosis and treatment of AOSD are limited in the medical literature and consist mainly of case reports, small series, and modest scale retrospective studies. Diagnosis is clinical and requires exclusion of infectious, neoplastic, and other autoimmune diseases. Laboratory tests are non-specific and reflect heightened immunological activity. Treatment comprises non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive drugs (methotrexate, leflunomide, gold, azathioprine, cyclosporin A, cyclophosphamide), and intravenous gammaglobulin. The recent successful application of biological agents (anti-tumour necrosis factor, anti-interleukin (IL)1, anti-IL6), often in combination with traditional immunosuppressive drugs, has been very promising.AOSD often poses a diagnostic and therapeutic challenge and clinical guidelines are lacking. The emergence of validated diagnostic criteria, discovery of better serological markers, and the application of new biological agents may all provide the clinician with significant tools for the diagnosis and management of this complex systemic disorder.
Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells
Authors: Daisuke Uchida, Tomitaro Onoue, Nasima-Mila Begum, Nobuyuki Kuribayashi, Yoshifumi Tomizuka, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto
Journal: Molecular Cancer (2009)

We have demonstrated that the stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4 system is involved in the establishment of lymph node metastasis in oral squamous cell carcinoma (SCC). Chemotherapy is a powerful tool for the treatment of oral cancer, including oral SCC; however, the effects of chemotherapeutic agents on the expression of CXCR4 are unknown. In this study, we examined the expression of CXCR4 associated with the chemotherapeutic agents in oral cancer cells. The expression of CXCR4 was examined using 3 different chemotherapeutic agents; 5-fluorouracil, cisplatin, and vesnarinone (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2-(1H)-quinolinone) in B88, a line of oral cancer cells that exhibits high levels of CXCR4 and lymph node metastatic potential. Of the 3 chemotherapeutic agents that we examined, only vesnarinone downregulated the expression of CXCR4 at the mRNA as well as the protein level. Vesnarinone significantly inhibited lymph node metastasis in tumor-bearing nude mice. Moreover, vesnarinone markedly inhibited 2.7-kb human CXCR4 promoter activity, and we identified the transcription factor, Krüppel-like factor 2 (KLF2), as a novel vesnarinone-responsive molecule, which was bound to the CXCR4 promoter at positions -300 to -167 relative to the transcription start site. The forced-expression of KLF2 led to the downregulation of CXCR4 mRNA and impaired CXCR4 promoter activity. The use of siRNA against KLF2 led to an upregulation of CXCR4 mRNA. These Results indicate that vesnarinone downregulates CXCR4 via the upregulation of KLF2 in oral cancer.
Early dynamics of hepatitis B virus in chimeric mice carrying human hepatocytes monoinfected or coinfected with genotype G
Authors: Masaya Sugiyama, Yasuhito Tanaka, Tomoyuki Sakamoto, Isao Maruyama, Takashi Shimada, Satoru Takahashi, Tomoyuki Shirai, Hideaki Kato, Masataka Nagao, Yuzo Miyakawa, Masashi Mizokami
Journal: Hepatology (2007)

Of the 8 genotypes of HBV (genotypes A-H), genotype G is unique in that it has an insertion in the core gene and two stop codons in the precore region preventing the synthesis of hepatitis B e antigen. Most individuals with genotype G are coinfected with other genotypes, typically genotype A. Mice with severe combined immunodeficiency disease carrying human hepatocytes were infected with HBV particles propagated in Huh7 cells in culture. Mice monoinfected with genotype G did not raise detectable HBV DNA in serum, although products of the core gene emerged 4 to 8 weeks after inoculation. When they were superinfected with genotype A at week 10, however, HBV DNA of genotype A developed, which was replaced almost completely by that of genotype G within 10 weeks. Such a rapid takeover was also observed in mice initially infected with genotype A or C and superinfected with genotype G. Similar viral dynamics occurred in mice simultaneously coinfected with genotypes G and A. Takeover was markedly enhanced in mice inoculated with a serum passage containing genotype G with a trace of genotype A. Coinfection of mice with genotypes G and A induced abundant cellular steatosis along with increased fibrosis in the liver, which was not detected in mice monoinfected with genotype A or G. Conclusion: Genotype G can monoinfect chimeric mice at very low levels, and its replication increases maredly when coinfected with other genotypes. Coinfection with genotype G could enhance fibrosis under immunocompromised states. (HEPATOLOGY 2007;45:929–937.)
Studies in Clinical Shock and Hypotension
Authors: FELIX E. TRISTANI, JAY N. COHN
Journal: Circulation (1970)

Renal blood flow was measured by the indicator-dilution technic in 17 patients with shock related to sepsis, myocardial infarction, pulmonary embolism, or pancreatitis. Renal blood flow averaged 225 ml/min/kidney, the renal plasma transit time was prolonged to an average of nearly three times normal, and the renal fraction of cardiac output was reduced to an average of 10.6%. A direct relationship between renal vascular resistance and systematic nonrenal vascular resistance suggested that renal vasocontriction was a manifestation of a more generalized vasoconstrictor process. Since rapid infusion of dextran in patients with normal central venous pressure relaxed renal vasoconstriction and tended to increase the renal fraction, inadequate venous return apparently is an important factor in the reduced renal blood flow in shock. None of the vasoactive drugs used were effective in restoring normal renal perfusion. The vasoconstrictor drugs (norepinephrine, metaraminol, and angiotensin) increased arterial pressure and renal vascular resistance without significantly altering renal blood flow. Isoproterenol and dopamine increased renal blood flow by an average of 26%, but the renal fraction of cardiac output often decreased further. Renal blood flow was increased by an average of 67% during renal arterial infusion of acetylcholine or hydralazine. It is concluded that shock is associated with preferential diversion of blood flow away from the renal bed. Although plasma volume expansion and vasoactive drug therapy may improve perfusion, renal hypoperfusion often persists.
Investigation into the impact of abatacept on sleep quality in patients with rheumatoid arthritis, and the validity of the MOS-Sleep questionnaire Sleep Disturbance Scale
Authors: G. Wells, T. Li, P. Tugwell
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> To assess the impact of abatacept on sleep quality in patients with rheumatoid arthritis (RA), and the validity of the sleep disturbance scale of the Medical Outcomes Study Sleep Questionnaire (MOS-Sleep). <h3>Methods</h3> Data from two randomised, double-blind, placebo-controlled abatacept trials (Abatacept Trial in Treatment of Antitumor necrosis factor IN adequate responders (ATTAIN) and Abatacept in Inadequate responders to Methotrexate (AIM)) were analysed. Sleep quality was assessed using the MOS-Sleep. Changes in the Sleep Disturbance Scale were assessed according to clinical responses (including American College of Rheumatology (ACR) and Disease Activity Score 28 C-reactive protein criteria). Correlations between sleep disturbance and patient-reported outcomes were assessed. The sensitivity to change of sleep disturbance was assessed by calculating the standardised response means (SRMs). <h3>Results</h3> 258 abatacept- and 133 placebo-treated patients in ATTAIN and 433 abatacept- and 219 placebo-treated patients in AIM were analysed. In ATTAIN, mean improvements to month 6 were significantly greater for patients treated with abatacept than for placebo patients in sleep disturbance (11.3 vs 2.9, p&lt;0.001), sleep adequacy (9.0 vs 0.6, p&lt;0.05), somnolence (10.5 vs 1.6, p&lt;0.001) and Sleep Problems Index (SPI) I (9.5 vs 1.4, p&lt;0.0001) and II (9.8 vs 2.1, p&lt;0.001); mean improvements in AIM to year 1 were statistically significant for sleep disturbance (12.9 vs 8.9, p&lt;0.05) and SPI I (9.4 vs 6.7, p&lt;0.05) and II (10.4 vs 7.3, p&lt;0.05). Associations between mean improvements in sleep disturbance and clinical responses were statistically significant (3.8, 12.7, 18.0, p&lt;0.001 and 5.0, 11.5, 15.7, p&lt;0.001 for European League Against Rheumatism responses, none, moderate and good in ATTAIN and AIM, respectively; 10.2, 14.4, 22.8, p=0.007 and 10.9, 14.9, 17.7, p=0.006 for ACR 20, 50 and 70 responses in ATTAIN and AIM, respectively). SRMs for sleep disturbance were 0.38 (ATTAIN) and 0.19 (AIM). <h3>Conclusions</h3> Abatacept treatment provides significant improvements in multiple aspects of sleep in patients with RA. The Sleep Disturbance Scale of the MOS-Sleep shows validity, reliability and sensitivity to change.
Acute eosinophilic pneumonia associated with 2009 influenza A (H1N1)
Authors: E. J. Jeon, K. H. Kim, K. H. Min
Journal: Thorax (2010)

Acute eosinophilic pneumonia (AEP) is a cause of acute respiratory failure, and differs from other eosinophilic pneumonias by its acute onset, presence of fever and acute hypoxaemia. Cases of 2009 influenza A (H1N1) virus infection have included rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the case of a young patient who showed dyspnoea, fever and rapid radiological progression and was simultaneously diagnosed with AEP and 2009 influenza A (H1N1) infection, which was diagnosed by using bronchoalveolar lavage (BAL). We suggest that 2009 influenza A (H1N1) virus should be considered as a cause of AEP, and BAL can provide further information, especially in patients with severe lower respiratory disease.
Abstract 4782: Genome-wide chromatin profiling in bladder and prostate cancers
Authors: Sohyoung Kim, Lyuba Varticovski, Qizong Lao, Songjoon Baek, Myong-Hee Sung, Lars Grøntved, Michael L. Nickerson, Bethtrice Thompson, Dan Theodorescu, Michael Dean, Gordon H. Hager
Journal: Cancer Research (2015)

Abstract Mutations in a few driver genes can cause cancer, and a main goal of cancer genome analysis has been the identification of these cancer genes. Recent findings, however, indicate that deregulation of enhancers can play a major role in carcinogenesis. In this study, we aim to understand how enhancer networks evolve during cancer initiation and progression and to identify epigenetic states that are predictive of cancer stage and drug response. We surveyed 15 bladder cell lines, including the T24 lineage (T24, T24T, FL, and SL) and the UMUC3 lineage (UMUC3 and LUL2), and 10 prostate cancer cell lines including BPH1, DU145 and LNCap. These cell lines display different tumorigenic and metastatic potentials, and thus present a model for cancer progression and development of castration-resistance. DNase-seq was performed to map genome-wide regulatory profiles in these cells. The enhancers detected as DNase I hypersensitivity sites (DHSs) showed large-scale changes in the chromatin accessibility landscape during the acquisition of tumorigenic and metastatic phenotypes. Selective sets of gained or lost DHSs were identified. Among the changes during the T24 to T24T transition, the loss of DHSs was remarkable. Some of these DHSs were found near genes that are in the downstream response to HDACs. Induction of expression by the HDAC inhibitor, Na butyrate, was correlated with DNase-seq signal for these genes. Gene Ontology (GO) enrichment analysis also indentified a set of genes neighboring lost DHSs that belong to the focal adhesion class in GO category. This study identified a set of DHSs that were associated with cancer progression in bladder and prostate cancer, and the potential clinical application of the identified DHSs will be discussed. Citation Format: Sohyoung Kim, Lyuba Varticovski, Qizong Lao, Songjoon Baek, Myong-Hee Sung, Lars Grøntved, Michael L. Nickerson, Bethtrice Thompson, Dan Theodorescu, Michael Dean, Gordon H. Hager. Genome-wide chromatin profiling in bladder and prostate cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4782. doi:10.1158/1538-7445.AM2015-4782
Prospects for new compounds tiosemikarbazonami class to create drugs with antituberculosis activity
Authors: Galina Mozhokina, Nataliya Elistratova, Irina Solovieva
Journal: European Respiratory Journal (2014)

Perspective way of increase of efficiency of treatment of tuberculosis is creation of antitubercular preparations on the basis of chemical modification of known structures. New compoundfrom a classtiosemikarbazonami Phs-205(Ltd.Pharmasyntez) showed high anti-tuberculosis activity concerning strains of Mycobacterium tuberculosis (MBT) human types.  The aim: to study the efficacy and safety of anti-TB compound Phs-205 in comparison with the drug perhlozonom in the model of TB in mice.  Material and methods . Investigations were carried out on 80 white non- linear mice, which were infected with Mycobacterium tuberculosis strain H37Rv. Treatment of animals started at day 16 after infection. Phs- 205 was tested at three doses (10, 20, 30 mg / kg), perhlozon - 20 mg / kg.The effectiveness of chemotherapy was assessed by the survival of mice, the definition of weighted indices of internal organs, the results of pathomorphological and microbiological studies. For estimates of the general toxicity of Phs- 205 and perhlozona determined in the blood content of biochemicalindicators.  Results of studies. It was established that Phs- 205 at 30 mg / kg has the most pronounced therapeutic and a protectiveeffects: to reduce mortality, reduce the volume of lung area affected tuberculous inflammation, a significant reduction of the isolation of MBT of the lungs.Biochemical studies have shown a more pronounced toxic effects on the performance perhlozona protein and lipid metabolism.  Conclusion. Compound Phs-205 is promising to create a new anti-tuberculosis drug.
African-American Women Have Higher Initial HbAlc Levels in Diabetic Pregnancy
Authors: William L. Holcomb, Dorothea J. Mostello, Gustavo F. Leguizamon
Journal: Diabetes Care (2001)

OBJECTIVE— African-American women with diabetes are at greater risk for poor glycemic control outside of pregnancy. We evaluated the effect of race on glycemic control in a racially mixed population of women with diabetes entering prenatal care. RESEARCH DESIGN AND METHODS— HbAlc levels along with demographic data were collected at the first prenatal visit from a group of 234 women with preexisting diabetes. We applied logistic multivariate analysis to identify factors associated with HbAlc levels above the median for the group. RESULTS— The median HbAlc level for the group was 8%. HbAlc levels were 8.7 ± 2.0% in African-Americans and 7.7 ± 1.5% in Caucasians (P &amp;lt; 0.001). African-American racial designation was significantly and independently associated with high HbAlc when controlled for maternal age, parity, White classification, diabetes type, education, marital status, obesity, insurance type, and first trimester entry into care. The effect of race was confined to the nonobese patients, for whom the adjusted odds ratio for African-American race as a predictor of high HbAlc was 8.15 with a 95% CI of 2.41-27.58 (P = 0.001). CONCLUSIONS— We found a clear racial disparity in glycemic control among women entering prenatal care with preexisting diabetes. This study demonstrates that there generally is need for better glycemic control among reproductive-age women with diabetes, but especially among those who are African-American.
Molecular Identification and Functional Characterization of a Mitochondrial Sulfonylurea Receptor 2 Splice Variant Generated by Intraexonic Splicing
Authors: Bin Ye, Stacie L. Kroboth, Jie-Lin Pu, Jason J. Sims, Nitin T. Aggarwal, Elizabeth M. McNally, Jonathan C. Makielski, Nian-Qing Shi
Journal: Circulation Research (2009)

Rationale : Cardioprotective pathways may involve a mitochondrial ATP-sensitive potassium (mitoK ATP ) channel but its composition is not fully understood. Objective : We hypothesized that the mitoK ATP channel contains a sulfonylurea receptor (SUR)2 regulatory subunit and aimed to identify the molecular structure. Methods and Results : Western blot analysis in cardiac mitochondria detected a 55-kDa mitochondrial SUR2 (mitoSUR2) short form, 2 additional short forms (28 and 68 kDa), and a 130-kDa long form. RACE (Rapid Amplification of cDNA Ends) identified a 1.5-Kb transcript, which was generated by a nonconventional intraexonic splicing (IES) event within the 4th and 29th exons of the SUR2 mRNA. The translated product matched the predicted size of the 55-kDa short form. In a knockout mouse (SUR2KO), in which the SUR2 gene was disrupted, the 130-kDa mitoSUR2 was absent, but the short forms remained expressed. Diazoxide failed to induce increased fluorescence of flavoprotein oxidation in SUR2KO cells, indicating that the diazoxide-sensitive mitoK ATP channel activity was associated with 130-kDa–based channels. However, SUR2KO mice displayed similar infarct sizes to preconditioned wild type, suggesting a protective role for the remaining short form-based channels. Heterologous coexpression of the SUR2 IES variant and Kir6.2 in a K + transport mutant Escherichia coli strain permitted improved cell growth under acidic pH conditions. The SUR2 IES variant was localized to mitochondria, and removal of a predicted mitochondrial targeting sequence allowed surface expression and detection of an ATP-sensitive current when coexpressed with Kir6.2. Conclusions : We identify a novel SUR2 IES variant in cardiac mitochondria and provide evidence that the variant-based channel can form an ATP-sensitive conductance and may contribute to cardioprotection.