tbuckley/cabot-search huggingface dataset:
Macrophage‐Derived Delta‐like Protein 1 Enhances Interleukin‐6 and Matrix Metalloproteinase 3 Production by Fibroblast‐like Synoviocytes in Mice With Collagen‐Induced Arthritis
Authors: Chiyoko Sekine, Toshihiro Nanki, Hideo Yagita
Journal: Arthritis & Rheumatology (2014)

We previously reported that blockade of the Notch ligand delta-like protein 1 (DLL-1) suppressed osteoclastogenesis and ameliorated arthritis in a mouse model of rheumatoid arthritis (RA). However, the mechanisms by which joint inflammation were suppressed have not yet been revealed. This study was undertaken to determine whether DLL-1 regulates the production of RA-related proinflammatory cytokines.Joint cells from mice with collagen-induced arthritis (CIA) and mouse fibroblast-like synoviocytes (FLS) were cultured with or without stimuli in the presence of neutralizing antibodies against Notch ligands, and the production of proinflammatory cytokines was determined by enzyme-linked immunosorbent assay. The expression of Notch receptors and ligands on mouse joint cells was determined by flow cytometry.The production of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by mouse joint cells with or without stimulation was suppressed by DLL-1 blockade. DLL-1 blockade also suppressed the levels of IL-6 and matrix metalloproteinase 3 (MMP-3) in the joint fluid in a mouse model of RA. However, the production of tumor necrosis factor α and IL-1β was not suppressed by DLL-1 blockade. The production of IL-6 and MMP-3 by mouse FLS was enhanced by DLL-1 stimulation as well as Notch-2 activation. Among joint cells, DLL-1 was not expressed on mouse FLS but was expressed on macrophages.These results suggest that the interaction of DLL-1 on mouse joint macrophages with Notch-2 on mouse FLS enhances the production of IL-6 and MMP-3. Therefore, suppression of IL-6, GM-CSF, and MMP-3 production by DLL-1 blockade might be responsible for the amelioration of arthritis in a mouse model of RA.
NK-92 cells transduced with retroviral vectors encoding marker genes and class I MHC suppression genes for improved use in adoptive cellular immunotherapy
Authors: T. Radosevich, S. Kisselev, C. Link
Journal: Journal of Clinical Oncology (2004)

2592 Background: Human NK-92 cells have a natural killer phenotype and exhibit high cytotoxicity towards targets lacking class I MHC expression. They are currently being tested for use in adoptive cellular immunotherapy and bone marrow purging to augment autologous stem cell transplant. One problem encountered in initial clinical trials employing adoptive cellular immunotherapy involves the generation of host cytotoxic T lymphocyte (CTL) responses to the transplanted cells limiting their effectiveness in vivo. Methods: LXSN based retroviruses encoding green fluorescent protein (GFP), and two separate class I MHC suppression genes (Herpes simplex virus (HSV) ICP47 and Human Cytomegalovirus (HCMV) US11) were constructed and used to transduce NK-92 cells. Stable populations of transgenic NK-92 cells were selected either in media containing a neomycin homologue or by fluorescent cell sorting for GFP encoding vectors. Populations were then analyzed for class I MHC expression or GFP fluorescence using anti-class I MHC antibodies and flow cytometry. Results: NK-92 cells transduced with ICP47 and US11 encoding retroviruses expressed 52% and 32% less class I MHC respectively. The levels of cell surface class I MHC expression observed remained consistent over 8 months in culture. Current work focuses on determining whether the decrease in class I MHC expression noted is significant enough to abrogate a host CTL response. Modified NK-92 cells expressing GFP were transduced with additional retroviruses encoding the class I suppression genes and populations of fluorescent cells expressing reduced cell surface class I MHC were isolated. In these dual transduced populations, class I MHC expression was reduced by 53% and 83% for ICP47 and US11 respectively. The modified NK-92 cells were tested against a panel of class I MHC positive and negative target cell lines and only minimal alterations of NK-92 cytotoxicity were observed. Conclusions: These results demonstrate the potential to improve cells used for adoptive cellular immunotherapy by the incorporation of multiple transgenes encoding beneficial traits. No significant financial relationships to disclose.
Molecular Mechanisms of Right Ventricular Failure
Authors: Sushma Reddy, Daniel Bernstein
Journal: Circulation (2015)

An abundance of data has provided insight into the mechanisms underlying the development of left ventricular (LV) hypertrophy and its progression to LV failure. In contrast, there is minimal data on the adaptation of the right ventricle (RV) to pressure and volume overload and the transition to RV failure. This is a critical clinical question, because the RV is uniquely at risk in many patients with repaired or palliated congenital heart disease and in those with pulmonary hypertension. Standard heart failure therapies have failed to improve function or survival in these patients, suggesting a divergence in the molecular mechanisms of RV versus LV failure. Although, on the cellular level, the remodeling responses of the RV and LV to pressure overload are largely similar, there are several key differences: the stressed RV is more susceptible to oxidative stress, has a reduced angiogenic response, and is more likely to activate cell death pathways than the stressed LV. Together, these differences could explain the more rapid progression of the RV to failure versus the LV. This review will highlight known molecular differences between the RV and LV responses to hemodynamic stress, the unique stressors on the RV associated with congenital heart disease, and the need to better understand these molecular mechanisms if we are to develop RV-specific heart failure therapeutics.
Abstract #LB-168: Differences in in vitro azacitidine and decitabine activities in non-small cell lung cancer
Authors: Aaron Nguyen, Paul Hollenbach, Antonio Luna-Moran, Helen Brady, Carla Heise, Kyle MacBeth
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The azanucleosides 5-azacytidine (azacitidine; Vidaza; AZA) and 2\#8217;-deoxy-5-azacytidine (decitabine; Dacogen; DAC) are DNA methyltransferase (DNMT) inhibitors that have shown clinical benefit in the treatment of myelodysplastic syndromes (MDS) and are approved by the Food and Drug Administration for the treatment of MDS. While AZA has demonstrated the ability to significantly extend overall survival in MDS patients, DAC failed to show a survival benefit over conventional therapy in a similar trial. The different outcomes of these late-stage clinical studies suggest that AZA and DAC may have different modes of action. To better understand the mechanism of action of these two drugs, we examined the effects of AZA and DAC in a panel of cancer cell lines. We found that AZA and DAC differentially affected the viability of many cell lines, with the greatest difference exhibited in non-small cell lung cancer (NSCLC) cells. Of the six NSCLC lines tested, all were sensitive to AZA (EC50 of 1-6 \#956;M) while only one was sensitive to DAC (EC50 of 5 \#956;M). Both inhibitors caused DNMT1 depletion and DNA demethylation in these cells; however, only AZA induced histone-H2AX phosphorylation (a marker of DNA damage) and PARP cleavage (a marker of cell death), suggesting that mechanisms in addition to, or other than DNA hypomethylation, are important for AZA-mediated reduction of NSCLC cell viability. Consistent with these results, AZA-treated, but not DAC-treated, cells were positive for AnnexinV staining, indicative of cells undergoing apoptosis. Cell cycle analysis indicated that AZA induced an accumulation of cells in the sub-G1 phase whereas DAC mainly caused an increase of cells in G2/M. Gene expression analysis of AZA- and DAC-treated cells revealed strikingly different profiles, with many genes distinctly regulated by each drug. Collectively, these results in NSCLC cell lines suggest that besides the common activities of AZA and DAC on DNMT depletion and DNA hypomethylation, these drugs differ in other aspects, including regulation of gene expression and induction of apoptosis.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-168.
Results of Buck Screw Fusion in Grade I Spondylolisthesis
Authors: A V Bonnici, S R Koka, D J Richards
Journal: Journal of the Royal Society of Medicine (1991)

The results of posterolateral screw fixation using the Buck technique performed on 24 patients with painful isthmic spondylolysis and up to grade I spondylolisthesis in the lumbar spine are reported. The average age at operation was 29 years and average follow-up was 5 years with a range of 13 months to 12 years. Operations were performed for persistent disabling low back pain. At review 21 patients were either free of pain or complained of only occasional backache and discomfort. All but two patients were satisfied with the operation and rated the result as excellent or good. It is concluded that Buck screw fixation is a safe and reliable method of treatment for painful Grade I spondylolisthesis due to isthmic spondylolysis in the young active adult with a low complication rate.
Dose Intensive Induction Followed By Allogeneic Stem Cell Transplantation More Than Doubles Progression-Free and Overall Survival In “Double-Hit” Lymphoma (DHL)
Authors: Christina Howlett, Andre Goy, Tania Zielonka, Andrew L Pecora, Tatyana Feldman, Scott D Rowley, Michele L. Donato, Mary Timberg, Gabriella Gadaleta, David H. Vesole, Pritish M Bhattacharyya, Kar Fai Chow, Raihan Faroqui, Maria Rosario, Anthony R Mato
Journal: Blood (2013)
CAT (COPD assessment test) in the initial assessment for pulmonary rehabilitation program
Authors: Ipek Candemir, Nilgun Mendil, Pinar Ergun, Dicle Kaymaz, Ezgi Utku, Filiz Tasdemir, Nurcan Egesel
Journal: European Respiratory Journal (2013)

AIM: COPD Assessment Test (CAT) containing 8 questions, is recently introduced instrument to evaluate health-related quality of life in COPD. We aimed to examine association between CAT and health-related quality of life, exercise capacity and lung function test in the initial assessment for pulmonary rehabilitation program.

METHOD: 22 stable COPD patients (1 female) were enrolled. Sensation of dysnea was assessed with MRC dyspnea scale, health related quality of life with CAT and S.George Respiratory Questionnaire (SGRQ), daily living activities with London Chest Daily Living Scale (LCDL) and exercise capacity with Incremental Shuttle Walking Test (ISWT) and Endurance Shuttle Walking Test (ESWT). Lung function tests and ages were also recorded.

RESULTS: Parameters of patients are summarized in Table 1.

View this table:

Table1: Parameters





There were positive correlations between CAT and MRC dysnea scale (p:0,01), SGRQ activity, impact and total scores (p values:0.03,0.005,0.002,0.009;respectively), LCDL scale self-care, physical, leisure and total scores (p:0.03,0.005,0.002,0,003; respectively). There were no associations between CAT and %FEV1, %FVC, and exercise capacity.

CONCLUSION: The study demonstrated that CAT is as feasible, practical and reliable as other tests in determining the sensation of dyspnea, quality of life, and daily living activity in initial assessment of COPD patients admitted to PR program.
Phase II Study of a Combination of Irinotecan and Cisplatin Against Metastatic Gastric Cancer
Authors: Narikazu Boku, Atsushi Ohtsu, Yasuhiro Shimada, Kuniaki Shirao, Shigeki Seki, Hiroshi Saito, Yuh Sakata, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A phase II study of a combination chemotherapy regimen of cisplatin (CDDP) and irinotecan (CPT-11) was conducted to assess its efficacy and feasibility in patients with metastatic gastric cancer. PATIENTS AND METHODS: Eligibility criteria included the following: (1) histologically proven gastric cancer with measurable metastatic lesions, (2) performance status of 2 or less, (3) age of 75 years or younger, (4) one or no prior chemotherapy regimens, (5) adequate bone marrow, liver, renal, and cardiac functions, and (6) written informed consent. The treatment consisted of CPT-11 (70 mg/m 2 ) on day 1 and day 15 and CDDP (80 mg/m 2 ) on day 1, repeated every 4 weeks. RESULTS: Forty-four patients were entered onto the study. The overall response rate was 48% (21 of 44 patients, 95% confidence interval [CI], 33% to 63%) and included one complete remission (2%). The response rate of the patients who had not received prior chemotherapy was 59% (17 of 29 patients, 95% CI, 39% to 77%). The median survival time was 272 days for all patients and 322 days for the 29 patients who had not received prior chemotherapy. Grade 4 neutropenia was observed in 25 patients (57%), and grade 3 or 4 diarrhea was observed in nine patients (20%). Other adverse reactions were mild. No treatment-related deaths occurred. CONCLUSION: This combination chemotherapy regimen is active and well tolerated. It may be an appropriate regimen for future phase III trials.
Safety of tiotropium in renally impaired patients
Authors: Donald Tashkin, Norbert Metzdorf, Christoph Hallmann, Michael Könen-Bergmann, Katrin Kupas, Ronald Dahl
Journal: European Respiratory Journal (2014)

Background:  Tiotropium is primarily renally excreted. Adverse events (AEs) including fatal AEs (FAEs), were analyzed by renal impairment in placebo-controlled trials of once-daily tiotropium HandiHaler 18 µg (HH) or Respimat 5 µg (R5).   Methods:  Fifteen HH and 7 R5 studies* estimating baseline creatinine clearance (Cockroft-Gault) included 10,805 evaluable patients in total. AE incidence rate ratios (IRR; tiotropium/placebo) were determined for renal impairment subgroups (normal ≥90, mild ≥60, moderate ≥30, severe    Results:  95% confidence intervals (CI) of the IRRs for AEs and serious AEs (SAEs) included or were close to 1, and IRR did not correlate with worsening renal function for both HH and R5 (Table). IRR of FAEs did not increase with decreasing renal function. Selected system organ classes (fatal cardiac disorders, general disorders) did not show consistent IRR trends. Results for severe renal impairment were limited due to low patient numbers (n=52).   Conclusions:  Incidence of AEs, SAEs or FAEs with tiotropium (HH or R5) showed no association with mild-to-moderately impaired renal function.  *Reference list on request.  Funded by Boehringer Ingelheim.
Fine Structure of Dividing Cells and of Nondividing, Differentiating Cells of Nickel Sulfide-Induced Rhabdomyosarcomas&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: C Bruni, J N Rust
Journal: JNCI Journal of the National Cancer Institute (1975)

Cells of nickel sulfide-induced rhabdomyosarcomas were studied with the electron microscope. Cells in the proliferative compartment were mononucleate and exhibited neither myofilaments nor other features of normal muscle cell differentiation. Cells in the nonproliferative compartment had myofilaments and differentiated similarly to the normal fetal and early postnatal muscle cells. The tumor cells did not differentiate beyond the initial stage of formation of triads and of the smooth endoplasmic reticulum. Transitional forms between undifferentiated and differentiated tumor cells were observed. Only a fraction of the progeny of the dividing cells seemed to differentiate; the remaining fraction did not and remained in the proliferative cell compartment as stem cells. The ratio between these cells and the descendants of the dividing cells that, by differentiation, became part of the nonproliferative cell compartment was a factor in the growth of the rhabdomyosarcomas. The pattern of fetal differentiation of the rhabdomyosarcomas was analogous to that of diethylnitrosamine-induced hepatomas studied previously in this laboratory.
Brain Correlates of the Interaction Between<i>5-HTTLPR</i>and Psychosocial Stress Mediating Attention Deficit Hyperactivity Disorder Severity
Authors: Dennis van der Meer, Pieter J. Hoekstra, Marcel Zwiers, Maarten Mennes, Lizanne J. Schweren, Barbara Franke, Dirk J. Heslenfeld, Jaap Oosterlaan, Stephen V. Faraone, Jan K. Buitelaar, Catharina A. Hartman
Journal: American Journal of Psychiatry (2015)

The serotonin transporter 5-HTTLPR genotype has been found to moderate the effect of stress on severity of attention deficit hyperactivity disorder (ADHD), with stronger effects of stress in carriers of the short allele than in individuals homozygous for the long allele. The underlying neurobiological mechanism of this gene-environment interaction in ADHD is unknown. The authors aimed to determine whether 5-HTTLPR moderates the effect of stress on brain gray matter volume and, if so, which brain regions mediate the effect of this gene-environment interaction on ADHD severity. Structural MRI, 5-HTTLPR genotype, and stress exposure questionnaire data were available for 701 adolescents and young adults participating in the multicenter ADHD cohort NeuroIMAGE study (from 385 families; 291 with ADHD, 78 with subthreshold ADHD, 332 healthy comparison subjects; 55.8% male; average age: 17.0 years). ADHD symptom count was determined through multi-informant questionnaires. For the analysis, a whole-brain voxel-based morphometry approach was combined with mediation analysis. Stress exposure was associated with significantly less gray matter volume in the precentral gyrus, middle and superior frontal gyri, frontal pole, and cingulate gyrus in S-allele carriers compared with participants homozygous for the l-allele. The association of this gene-environment interaction with ADHD symptom count was mediated by gray matter volume in the frontal pole and anterior cingulate gyrus. 5-HTTLPR genotype moderates the effect of stress on brain regions involved in social cognitive processing and cognitive control. Specifically, regions important for cognitive control link this gene-environment interaction to ADHD severity.
Anti-tumour necrosis factor therapy in patients with impaired renal function
Authors: A. J Hueber, A. Tunc, G. Schett, B. Manger
Journal: Annals of the Rheumatic Diseases (2007)

Renal insufficiency is a common comorbidity in patients with inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis. Decreased renal function is a limiting factor for the use of non-steroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs. Therefore, the availability of therapeutic alternatives would improve our treatment options for these patients. For tumour necrosis factor α (TNFα) inhibitors, no data about their use in patients with impaired renal function are available, because it has been an exclusion criterion in all major clinical trials.

We therefore retrospectively analysed all patients from our institution who had increased serum creatinine levels before or during treatment with TNFα antagonists. All patients with a serum creatinine ⩾1.1 mg/dl and treatment with infliximab, etanercept or adalimumab were included. We were able to identify nine patients with rheumatoid arthritis, one patient with …
Demonstration of Natural Antibodies in Normal Rabbit Serum With Similar Specificity Pattern as Mouse Natural Killer Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A Grönberg, M Hansson, R Kiessling, B Andersson, K Kärre, J Roder
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Demonstration of Natural Antibodies in Normal Rabbit Serum With Similar Specificity Pattern as Mouse Natural Killer Cells Get access Alvar Grönberg, Alvar Grönberg Search for other works by this author on: Oxford Academic PubMed Google Scholar Mona Hansson, Mona Hansson Search for other works by this author on: Oxford Academic PubMed Google Scholar Rolf Kiessling, Rolf Kiessling 5 5Address reprint requests to Dr. Kiessling. Search for other works by this author on: Oxford Academic PubMed Google Scholar Birger Andersson, Birger Andersson Search for other works by this author on: Oxford Academic PubMed Google Scholar Klas Kärre, Klas Kärre Search for other works by this author on: Oxford Academic PubMed Google Scholar John Roder John Roder Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 5, May 1980, Pages 1113–1119, https://doi.org/10.1093/jnci/64.5.1113 Published: 01 May 1980 Article history Received: 31 January 1979 Revision received: 19 September 1979 Accepted: 16 October 1979 Published: 01 May 1980
Low prevalence of invasive bacterial infection in febrile infants under 3 months of age with enterovirus infection
Authors: A. Martínez Planas, C. Muñoz Almagro, C. Luaces Cubells, A. Noguera Julián, L. Selva, J. Pou Fernández, J. J. García García
Journal: Clinical Microbiology and Infection (2011)
Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients.
Authors: V R Grann, K S Panageas, W Whang, K H Antman, A I Neugut
Journal: Journal of Clinical Oncology (1998)

PURPOSE Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy. METHODS A Markov model was developed to determine the survival, quality of life, and cost-effectiveness of prophylactic surgical procedures. The probabilities of developing breast and ovarian cancer were based on literature review among women with the BRCA1 or BRCA2 gene and mortality rates were determined from Surveillance, Epidemiology, and End Results (SEER) data for 1973 to 1992. The costs for hospital and ambulatory care were estimated from Health Care Financing Administration (HCFA) payments in 1995, supplemented by managed care and fee-for-service data. Utility measures for quality-adjusted life-years (QALYs) were explicitly determined using the time-trade off method. Estimated risks for breast and ovarian cancer after prophylactic surgeries were obtained from the literature. RESULTS For a 30-year-old woman, according to her cancer risks, prophylactic oophorectomy improved survival by 0.4 to 2.6 years; mastectomy, by 2.8 to 3.4 years; and mastectomy and oophorectomy, by 3.3 to 6.0 years over surveillance. The QALYs saved were 0.5 for oophorectomy and 1.9 for the combined procedures in the high-risk model. Prophylactic surgeries were cost-effective compared with surveillance for years of life saved, but not for QALYs. CONCLUSION Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life. Prophylactic surgery is cost-effective for years of life saved compared with other medical interventions that are deemed cost-effective.
Laxative Induced Diarrhoea-A Neglected Diagnosis
Authors: A Duncan, A J Morris, A Cameron, M J Stewart, W G Brydon, R I Russell
Journal: Journal of the Royal Society of Medicine (1992)

A laxative screening service was established and offered to gastroenterologists in hospitals covering the West and Central belt of Scotland. The prevalence of laxative induced diarrhoea was assessed in two populations and was found to be 4% in new patients presenting to a gastroenterology clinic with diarrhoea and 20% in patients already under investigation of chronic idiopathic diarrhoea. A high rate of missed diagnosis of laxative induced diarrhoea (71%) and a low request rate (eight per annum) confirm the low clinical awareness of this diagnosis. We found potential savings of 80% of the cost of investigations subsequently ordered which could have been avoided by performing laxative screens on all patients presenting with diarrhoea. The introduction of such a screening policy is recommended as a cost-effective measure.