tbuckley/cabot-search huggingface dataset:
Regression of extranodal natural killer/T-cell lymphoma, nasal type with denileukin diftitox (Ontak<sup>®</sup>) and bexarotene (Targretin<sup>®</sup>): report of a case
Authors: K. Kerl, C. Prins, L. Cerroni, L.E. French
Journal: British Journal of Dermatology (2006)

Journal Article Regression of extranodal natural killer/T‐cell lymphoma, nasal type with denileukin diftitox (Ontak®) and bexarotene (Targretin®): report of a case Get access K. Kerl, K. Kerl Department of Dermatology, Geneva University Medical School, 24 rue Micheli‐du‐Crest, CH‐1211 Geneva 14, Switzerland *Department of Dermatology, University Medical School Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar C. Prins, C. Prins Department of Dermatology, Geneva University Medical School, 24 rue Micheli‐du‐Crest, CH‐1211 Geneva 14, Switzerland *Department of Dermatology, University Medical School Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar L. Cerroni, L. Cerroni Department of Dermatology, Geneva University Medical School, 24 rue Micheli‐du‐Crest, CH‐1211 Geneva 14, Switzerland *Department of Dermatology, University Medical School Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar L.E. French L.E. French Department of Dermatology, Geneva University Medical School, 24 rue Micheli‐du‐Crest, CH‐1211 Geneva 14, Switzerland *Department of Dermatology, University Medical School Graz, Austria Lars E. French. E‐mail: lars.french@medecine.unige.ch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 5, 1 May 2006, Pages 988–991, https://doi.org/10.1111/j.1365-2133.2006.07151.x Published: 01 May 2006 Article history Accepted: 12 September 2005 Published: 01 May 2006
Human right and left colon differ in epithelial cell apoptosis and in expression of Bak, a pro-apoptotic Bcl-2 homologue
Authors: L U Liu, P R Holt, V Krivosheyev, S F Moss
Journal: Gut (1999)

<h3>BACKGROUND</h3> Propensity to colonic neoplasia differs between the right and left colon. <h3>AIMS</h3> To examine whether this difference may be related to regional differences in epithelial apoptosis, in expression of a proapoptotic regulatory protein, Bak, and in proliferation. <h3>PATIENTS</h3> Individuals with no history of colorectal neoplasia. <h3>METHODS</h3> Archival blocks of colorectal tissues were immunostained for proliferating cells (antibody to Ki-67 antigen), and Bak expression (polyclonal antiserum). Cells containing DNA strand breaks, a marker of apoptosis, were identified by terminal deoxyuridine nucleotidyl nick end labelling (TUNEL). <h3>RESULTS</h3> There were fewer TUNEL positive epithelial cells in the right colon (mean 1.2 (SE 0.1)% of all epithelial cells) than the left colon (2.2 (0.1)%, p&lt;0.0001) or rectum (2.2 (0.3)%, p&lt;0.05). Bak expression was less common in the right colon (mean 46 (2.3)% of epithelial cells immunoreactive) than the left colon (66 (2.7)%, p&lt;0.0001), or rectum (67 (2.3)%, p&lt;0.001). Bak expression and TUNEL positivity were highly positively correlated (p&lt;0.0001). In contrast to apoptosis, mean whole crypt proliferation labelling index was similar throughout the colorectum (right colon: 15.6 (3.2)%; left colon: 13.5 (1.2)%; rectum: 13.3 (2.3)%). <h3>CONCLUSION</h3> The percentage of proliferating colonic epithelial cells is constant throughout the colon, but fewer epithelial cells undergo Bak mediated apoptosis in the right than in the left colon or rectum. This suggests that colonocytes may be lost by methods other than apoptosis in the right colon.
UK guidelines on the management of variceal haemorrhage in cirrhotic patients
Authors: Dhiraj Tripathi, Adrian J Stanley, Peter C Hayes, David Patch, Charles Millson, Homoyon Mehrzad, Andrew Austin, James W Ferguson, Simon P Olliff, Mark Hudson, John M Christie
Journal: Gut (2015)

These updated guidelines on the management of variceal haemorrhage have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines which this document supersedes were written in 2000 and have undergone extensive revision by 13 members of the Guidelines Development Group (GDG). The GDG comprises elected members of the BSG liver section, representation from British Association for the Study of the Liver (BASL) and Liver QuEST, a nursing representative and a patient representative. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. The nature of variceal haemorrhage in cirrhotic patients with its complex range of complications makes rigid guidelines inappropriate. These guidelines deal specifically with the management of varices in patients with cirrhosis under the following subheadings: (1) primary prophylaxis; (2) acute variceal haemorrhage; (3) secondary prophylaxis of variceal haemorrhage; and (4) gastric varices. They are not designed to deal with (1) the management of the underlying liver disease; (2) the management of variceal haemorrhage in children; or (3) variceal haemorrhage from other aetiological conditions.
Cardiac death in a patient with adult-onset Still's disease treated with the interleukin 1 receptor inhibitor anakinra
Authors: P. J Ruiz, E. Masliah, T. A Doherty, A. Quach, G. S Firestein
Journal: Annals of the Rheumatic Diseases (2006)

We report a case of adult-onset Still’s disease (AOSD) with rapid deterioration of cardiac function when treated with recombinant human interleukin (IL) 1 receptor antagonist. Pro-inflammatory cytokines such as IL 1 and tumour necrosis factor (TNF) have been implicated in the pathogenesis of cardiac dysfunction, partly because of their negative inotropic activities in vitro and in vivo.1–3 This concept led to clinical trials evaluating the utility of TNF inhibitors in patients with congestive heart failure. Surprisingly, TNF blockade considerably increased the incidence of cardiac death. On the basis of these observations, TNF inhibitors are usually discontinued in patients with cardiac dysfunction.4,5 However, there is no information on the risks of other cytokine inhibitors.

A 29-year-old woman with a 4-year history …
Abstract B22: Potential combinatorial strategies to overcome drug resistance in BRAF-mutant melanoma
Authors: Nicholas A. Dompe, Eva Lin, Jing Peng, Grace Chan, Grace Chan, Grace Chan, Janet Tien, Mark Merchant, Richard Bourgon, Jeffrey Settleman, Timothy Wilson, Richard M. Neve
Journal: Clinical Cancer Research (2015)

Abstract RAF and MEK inhibitors are used to target malignant melanomas harbouring BRAF V600E mutations, but resistance to these therapies remains a significant challenge. Here we conducted a screen of 450 secreted peptides to identify possible cell-autonomous or microenvironment-driven mechanisms of resistance to RAF and MEK inhibitors in ten melanoma cell lines. We identified multiple receptor tyrosine kinase (RTK)-mediated resistance mechanisms and show that drug-resistance in vitro was driven by mechanisms predicted by the screen and that co-targeting FGFR and BRAF prevents tumour regrowth in vivo. We also found that cells can become resistant to rational combinations of targeted inhibitors in a serial manner, again predicted by the screen. In many cases resistance is mediated by reactivation of MAPK-signalling, however, there is also evidence for non-MAPK-dependent mechanisms of resistance once these are exhausted. These data reveal multiple, defined mechanisms of resistance as well as highlight potential challenges of overcoming therapeutic resistance in a highly adaptive tumour type. Citation Format: Nicholas A. Dompe, Eva Lin, Jing Peng, Grace Chan, Grace Chan, Grace Chan, Janet Tien, Mark Merchant, Richard Bourgon, Jeffrey Settleman, Timothy Wilson, Richard M. Neve. Potential combinatorial strategies to overcome drug resistance in BRAF-mutant melanoma. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B22.
Causal Relationship Between Stressful Life Events and the Onset of Major Depression
Authors: Kenneth S. Kendler, Laura M. Karkowski, Carol A. Prescott
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Stressful life events are associated with the onset of episodes of major depression. However, exposure to stressful life events is influenced by genetic factors, and these factors are correlated with those that predispose to major depression. The aim of this study was to clarify the degree to which stressful life events cause major depression. METHOD: The authors assessed the occurrence of 15 classes of stressful life events and the onset of DSM-III-R major depression over a 1-year period in female twins ascertained from a population-based registry. The sample contained 24,648 person-months and 316 onsets of major depression. Stressful life events were individually rated on contextual threat and dependence (the degree to which the stressful life event could have resulted from the respondent’s behavior). The nature of the relationship between stressful life events and major depression was tested by 1) discrete-time survival analysis examining the relationship between dependence and the depressogenic effect of stressful life events and 2) a co-twin control analysis. RESULTS: While independent stressful life events were significantly associated with onsets of depression, when level of threat was controlled, the association was significantly stronger for dependent events. The odds ratio for onset of major depression in the month of a stressful life event was 5.64 in all subjects, 4.52 within dizygotic pairs, and 3.58 within monozygotic pairs. CONCLUSIONS: Stressful life events have a substantial causal relationship with the onset of episodes of major depression. However, about one-third of the association between stressful life events and onsets of depression is noncausal, since individuals predisposed to major depression select themselves into high-risk environments.
Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications
Authors: A. Italiano, M.-C. Saint-Paul, F.-X. Caroli-Bosc, E. François, A. Bourgeon, D. Benchimol, J. Gugenheim, J.-F. Michiels
Journal: Annals of Oncology (2005)
Lifestyle Intervention for Pre-Diabetic Neuropathy
Authors: A. Gordon Smith, James Russell, Eva L. Feldman, Jonathan Goldstein, Amanda Peltier, Sheldon Smith, Jouhaina Hamwi, Donald Pollari, Billie Bixby, James Howard, J. Robinson Singleton
Journal: Diabetes Care (2006)

The purpose of this study was to evaluate intraepidermal nerve fiber density (IENFD) as a sensitive measure of neuropathy change in patients with neuropathy associated with impaired glucose tolerance (IGT) receiving lifestyle intervention based on that used in the Diabetes Prevention Program.We performed 3-mm skin biopsies with measurement of IENFD at the distal leg and proximal thigh at baseline and after 1 year in 32 subjects with IGT. Each received individualized diet and exercise counseling as a standard of care. Nerve conduction studies, quantitative sensory testing, quantitative sudomotor axon reflex testing, and the Michigan Diabetic Neuropathy score were performed, and a visual analog pain scale was completed. Two-hour oral glucose tolerance tests (OGTTs) following the American Diabetes Association guidelines were performed, and serum lipid levels were measured at baseline and 1 year later.Baseline distal IENFD was 0.9 +/- 1.2 fibers/mm and proximal IENFD was 4.8 +/- 2.3 fibers/mm. Baseline distal IENFD correlated with fasting glucose (P < 0.001) and OGTT (P < 0.01). After 1 year of treatment, there was a 0.3 +/- 1.1-fiber/mm improvement in distal IENFD and a 1.4 +/- 2.3-fiber/mm improvement in proximal IENFD (P < 0.004). The change in proximal IENFD correlated with decreased neuropathic pain (P < 0.05) and a change in sural sensory amplitude (P < 0.03).These findings indicate that diet and exercise counseling for IGT results in cutaneous reinnervation and improved pain. Skin biopsy was the most sensitive measure of neuropathy change over 1 year. IENFD should be included as an end point in future neuropathy trials.
Male infertility, impaired spermatogenesis, and azoospermia in mice deficient for the pseudophosphatase Sbf1
Authors: Ron Firestein, Peter L. Nagy, Megan Daly, Phil Huie, Marco Conti, Michael L. Cleary
Journal: Journal of Clinical Investigation (2002)

Pseudophosphatases display extensive sequence similarities to phosphatases but harbor amino acid alterations in their active-site consensus motifs that render them catalytically inactive. A potential role in substrate trapping or docking has been proposed, but the specific requirements for pseudophosphatases during development and differentiation are unknown. We demonstrate here that Sbf1, a pseudophosphatase of the myotubularin family, is expressed at high levels in seminiferous tubules of the testis, specifically in Sertoli’s cells, spermatogonia, and pachytene spermatocytes, but not in postmeiotic round spermatids. Mice that are nullizygous for Sbf1 exhibit male infertility characterized by azoospermia. The onset of the spermatogenic defect occurs in the first wave of spermatogenesis at 17 days after birth during the synchronized progression of pachytene spermatocytes to haploid spermatids. Vacuolation of the Sertoli’s cells is the earliest observed phenotype and is followed by reduced formation of spermatids and eventual depletion of the germ cell compartment in older mice. The nullizygous phenotype in conjunction with high-level expression of Sbf1 in premeiotic germ cells and Sertoli’s cells is consistent with a crucial role for Sbf1 in transition from diploid to haploid spermatocytes. These studies demonstrate an essential role for a pseudophosphatase and implicate signaling pathways regulated by myotubularin family proteins in spermatogenesis and germ cell differentiation.
Species-Specific Differences in Positive and Negative Regulatory Elements in the Renin Gene Enhancer
Authors: Qi Shi, Thomas A. Black, Kenneth W. Gross, Curt D. Sigmund
Journal: Circulation Research (1999)

Abstract —A distal transcriptional enhancer has been previously reported upstream of the mouse renin gene. A homologous sequence is also present upstream of the human renin gene, but the mouse and human renin enhancers differ markedly in their ability to activate transcription of a renin promoter. Although the 2 enhancers share high homology in their 202-bp promoter distal portions, their 40-bp proximal portions are heterogeneous. Chimeric enhancers were used to test the role of the 40-bp segment (m40) of the enhancer by using transient transfection analysis in mouse kidney renin-expressing As4.1 cells. Deletion of m40 from the mouse renin enhancer or its addition to the human renin enhancer did not significantly change transcriptional activity when placed close to a mouse or human renin promoter. However, when placed further upstream of a renin promoter, the same deletion and substitution markedly altered enhancer activity. Electrophoretic gel mobility shift analysis identified 2 elements, a and b, in m40 that specifically bound nuclear proteins from As4.1 cells. Mutagenesis and transient transfection analysis revealed that element b accounts for the function of m40 and that element a antagonizes the positive influence of element b. Gel competition and supershift analysis revealed that nuclear factor-Y, a ubiquitous CAAT-box binding protein, binds to element a. Sequence analysis revealed that the human renin enhancer has a natural loss-of-function mutation in element b that affects its ability to transactivate when placed far upstream of a promoter. Reversion of the human renin element b to match the mouse sequence restored transactivation of the enhancer in mouse As4.1 cells. These data suggest that element b cooperates with the rest of the enhancer to maintain full enhancer activity, whereas element a may regulate enhancer activity. Sequence differences in these elements may explain the functional differences in the mouse and human renin enhancer sequences.
Induction of inflammation as a possible mechanism of probiotic effect in atopic eczema–dermatitis syndrome
Authors: Mirva Viljanen, Emma Pohjavuori, Tari Haahtela, Riitta Korpela, Mikael Kuitunen, Annikki Sarnesto, Outi Vaarala, Erkki Savilahti
Journal: Journal of Allergy and Clinical Immunology (2005)
Vascular Endothelial Growth Factor Receptors in Human Mesangium in Vitro and in Glomerular Disease
Authors: STEPHEN THOMAS, JOHANN VANUYSTEL, GABRIELLA GRUDEN, VERÓNICA RODRÍGUEZ, DAVINA BURT, LUIGI GNUDI, BARRY HARTLEY, GIANCARLO VIBERTI
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Mesangial cell proliferation and growth factor over-expression are characteristic features of several glomerular diseases. Vascular endothelial growth factor (VEGF), a potent mitogen, is expressed in podocytes in the glomerulus, and VEGF receptors (flt-1, KDR, and neuropilin-1) are present on endothelial cells and other cell types. This study examined whether human mesangial cells (HMC) express VEGF receptors in vitro and ex vivo and evaluated the effect of VEGF on HMC proliferation. All receptor types were detected in HMC in vitro by immunofluorescence and Western blotting. VEGF 165 induced a dose-responsive increase in 3 H-thymidine incorporation (25 ng/ml VEGF 165 : 2.3-fold increase; 50 ng/ml: 3.8-fold; 100 ng/ml: 4.8-fold; 200 ng/ml: 3.4-fold; P = 0.016) and in cell number (50 ng/ml VEGF 165 : 1.2-fold increase; 100 ng/ml: 1.6-fold; 200 ng/ml: 1.4-fold; P = 0.005), effects prevented by an anti-VEGF 165 polyclonal neutralizing antibody (100 μg/ml). The proliferative effect was confirmed by a tetrazolium dye-based assay (100 ng/ml VEGF 165 : 1.4-fold increase). In ex vivo experiments, VEGF receptors in biopsy material from normal and diseased kidneys were detected by immunohistochemistry. No mesangial flt-1 receptor staining was seen in normal renal cortical tissue samples, and only weak mesangial KDR staining was detected. In contrast, mesangial flt-1 and KDR receptor staining were both clearly seen in biopsy samples from proliferative renal diseases. In conclusion, flt-1, KDR, and neuropilin-1 are present on cultured HMC, and VEGF 165 induces HMC proliferation. In addition, the flt-1 and KDR receptors are expressed in the mesangium in mesangioproliferative disease.
CUDC-101, a Multitargeted Inhibitor of Histone Deacetylase, Epidermal Growth Factor Receptor, and Human Epidermal Growth Factor Receptor 2, Exerts Potent Anticancer Activity
Authors: Cheng-Jung Lai, Rudi Bao, Xu Tao, Jing Wang, Ruzanna Atoyan, Hui Qu, Da-Gong Wang, Ling Yin, Maria Samson, Jeffrey Forrester, Brian Zifcak, Guang-Xin Xu, Steven DellaRocca, Hai-Xiao Zhai, Xiong Cai, William E. Munger, Mitchell Keegan, Carmen V. Pepicelli, Changgeng Qian
Journal: Cancer Research (2010)

Receptor tyrosine kinase inhibitors have recently become important therapeutics for a variety of cancers. However, due to the heterogeneous and dynamic nature of tumors, the effectiveness of these agents is often hindered by poor response rates and acquired drug resistance. To overcome these limitations, we created a novel small molecule, CUDC-101, which simultaneously inhibits histone deacetylase and the receptor kinases epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in cancer cells. Because of its integrated histone deacetylase inhibition, CUDC-101 synergistically blocked key regulators of EGFR/HER2 signaling pathways, also attenuating multiple compensatory pathways, such as AKT, HER3, and MET, which enable cancer cells to escape the effects of conventional EGFR/HER2 inhibitors. CUDC-101 displayed potent antiproliferative and proapoptotic activities against cultured and implanted tumor cells that are sensitive or resistant to several approved single-targeted drugs. Our results show that CUDC-101 has the potential to dramatically improve the treatment of heterogeneous and drug-resistant tumors that cannot be controlled with single-target agents. Further, they provide a framework to create individual small molecules that simultaneously antagonize multiple biochemically distinct oncogenic targets, suggesting a general paradigm to surpass conventional, single-target cancer therapeutics. Cancer Res; 70(9); 3647-56. (c)2010 AACR.
Seasonal variation in fitness in a women's National League hockey squad
Authors: E Jones, A McGregor
Journal: British Journal of Sports Medicine (2010)

Regular fitness assessments are crucial in monitoring the efficacy of a training programme, judging return to play after injury and motivating athletes. The data can be used by practitioners to track differences in fitness at specific time points in the season or between playing positions. This study presents three seasons of test data in an elite women's squad, covering their promotion from National Division 1 to Premier League Status. Injury-free players were tested at the start of the preseason (PRE), start of competition (COMP1), midseason break (XMAS) and the start of second competition phase (COMP2) for the 2007-2008, 2008-2009 and 2009-2010 seasons. Test battery comprised speed (0-5 m, 0-30 m), repeated sprint (8×56 m off 40 s rolling clock) and the yo-yo intermittent recovery test level 1. Aerobic conditioning improved from PRE to COMP1 to XMAS and was maintained (2007-2008), improved (2008-2009) or declined (2009-2010) in the second half of the season. The lowest levels were seen in the 2007-2008 season. Trends in the speed data are difficult to elicit due to missing data points. Repeated sprint performance was lowest at PRE and improved to COMP1 in all three seasons. A decline was evident between XMAS and COMP2. Improvements in aerobic conditioning from the 2007 to the 2008 season reflect the onset of a squad training intervention. There were no further improvements on promotion to the Premier League. A general increase in aerobic conditioning from preseason to the Christmas break is likely indicative of 5-6 months' conditioning. Fitness levels over the midseason break show maintenance in aerobic and repeated sprint performance in the 2008-2009 season. In 2009-2010, a decline was evident in both these parameters, probably due to the inclement weather negatively affecting training patterns and/or poor adherence to the training programme.