tbuckley/cabot-search huggingface dataset:
T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut
Authors: Sylvia Brugman, Kerstin Schneeberger, Merlijn Witte, Mark R Klein, Bartholomeus van den Bogert, Jos Boekhorst, Harro M Timmerman, Marianne L Boes, Michiel Kleerebezem, Edward ES Nieuwenhuis
Journal: Gut Microbes (2014)

Dysbiosis of the intestinal microbial community is considered a risk factor for development of chronic intestinal inflammation as well as other diseases such as diabetes, obesity and even cancer. Study of the innate and adaptive immune pathways controlling bacterial colonization has however proven difficult in rodents, considering the extensive cross-talk between bacteria and innate and adaptive immunity. Here, we used the zebrafish to study innate and adaptive immune processes controlling the microbial community. Zebrafish lack a functional adaptive immune system in the first weeks of life, enabling study of the innate immune system in the absence of adaptive immunity. We show that in wild type zebrafish, the initial lack of adaptive immunity associates with overgrowth of Vibrio species (a group encompassing fish and human pathogens), which is overcome upon adaptive immune development. In Rag1-deficient zebrafish (lacking adaptive immunity) Vibrio abundance remains high, suggesting that adaptive immune processes indeed control Vibrio species. Using cell transfer experiments, we confirm that adoptive transfer of T lymphocytes, but not B lymphocytes into Rag1-deficient recipients suppresses outgrowth of Vibrio. In addition, ex vivo exposure of intestinal T lymphocytes to Rag1-deficient microbiota results in increased interferon-gamma expression by these T lymphocytes, compared to exposure to wild type microbiota. In conclusion, we show that T lymphocytes control microbial composition by effectively suppressing the outgrowth of Vibrio species in the zebrafish intestine.
Age dependent changes in myosin ATPase activity in the myocardium of spontaneously hypertensive rats
Authors: R V SHARMA, J P McELDOON, R C BHALLA
Journal: Cardiovascular Research (1986)

Journal Article Age dependent changes in myosin ATPase activity in the myocardium of spontaneously hypertensive rats Get access R V SHARMA, R V SHARMA From the Department of Anatomy and the Cardiovascular Center. University of Iowa, College of Medicine, Iowa City, Iowa, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar J P McELDOON, J P McELDOON From the Department of Anatomy and the Cardiovascular Center. University of Iowa, College of Medicine, Iowa City, Iowa, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar R C BHALLA R C BHALLA From the Department of Anatomy and the Cardiovascular Center. University of Iowa, College of Medicine, Iowa City, Iowa, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 20, Issue 1, January 1986, Pages 52–60, https://doi.org/10.1093/cvr/20.1.52 Published: 01 January 1986
Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles
Authors: Nicole YP Souren, Pavlo Lutsik, Gilles Gasparoni, Sascha Tierling, Jasmin Gries, Matthias Riemenschneider, Jean-Pierre Fryns, Catherine Derom, Maurice P Zeegers, Jörn Walter
Journal: Genome biology (2013)

Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes.Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences.Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies.
Angiotensin II Type 2 Receptor Stimulation
Authors: Elena Kaschina, Aleksandra Grzesiak, Jun Li, Anna Foryst-Ludwig, Melanie Timm, Franziska Rompe, Manuela Sommerfeld, U. Rudolf Kemnitz, Caterina Curato, Pawel Namsolleck, Carsten Tschöpe, Anders Hallberg, Mathias Alterman, Thomas Hucko, Ingo Paetsch, Thore Dietrich, Bernhard Schnackenburg, Kristof Graf, Björn Dahlöf, Ulrich Kintscher, Thomas Unger, U. Muscha Steckelings
Journal: Circulation (2008)

Background— This study is the first to examine the effect of direct angiotensin II type 2 (AT 2 ) receptor stimulation on postinfarct cardiac function with the use of the novel nonpeptide AT 2 receptor agonist compound 21 (C21). Methods and Results— Myocardial infarction (MI) was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with C21 (0.01, 0.03, 0.3 mg/kg per day IP) was started 24 hours after MI and was continued until euthanasia (7 days after MI). Infarct size was assessed by magnetic resonance imaging, and hemodynamic measurements were performed via transthoracic Doppler echocardiography and intracardiac Millar catheter. Cardiac tissues were analyzed for inflammation and apoptosis markers with immunoblotting and real-time reverse transcription polymerase chain reaction. C21 significantly improved systolic and diastolic ventricular function. Scar size was smallest in the C21-treated rats. In regard to underlying mechanisms, C21 diminished MI-induced Fas-ligand and caspase-3 expression in the peri-infarct zone, indicating an antiapoptotic effect. Phosphorylation of the p44/42 and p38 mitogen-activated protein kinases, both involved in the regulation of cell survival, was strongly reduced after MI but almost completely rescued by C21 treatment. Furthermore, C21 decreased MI-induced serum monocyte chemoattractant protein-1 and myeloperoxidase as well as cardiac interleukin-6, interleukin-1β, and interleukin-2 expression, suggesting an antiinflammatory effect. Conclusions— Direct AT 2 receptor stimulation may be a novel therapeutic approach to improve post-MI systolic and diastolic function by antiapoptotic and antiinflammatory mechanisms.
Investigation of the diffusion abnormality index as a new imaging biomarker for early assessment of brain tumor response to radiation therapy
Authors: Reza Farjam, Christina I. Tsien, Felix Y. Feng, Diana Gomez-Hassan, James A. Hayman, Theodore S. Lawrence, Yue Cao
Journal: Neuro-Oncology (2013)

Diffusion MRI, although having the potential to be a biomarker for early assessment of tumor response to therapy, could be confounded by edema and necrosis in or near the brain tumors. This study aimed to develop and investigate the ability of the diffusion abnormality index (DAI) to be a new imaging biomarker for early assessment of brain metastasis response to radiation therapy (RT). Patients with either radiosensitive or radioresistant brain metastases that were treated by whole brain RT alone or combined with bortezomib as a radiation sensitizer had diffusion-weighted (DW) MRI pre-RT and 2 weeks (2W) after starting RT. A patient-specific diffusion abnormality probability function (DAProF) was created to account for abnormal low and high apparent diffusion coefficients differently, reflecting respective high cellularity and edema/necrosis. The DAI of a lesion was then calculated by the integral of DAProF-weighted tumor apparent diffusion coefficient histogram. The changes in DAI from pre-RT to 2W were evaluated for differentiating the responsive, stable, and progressive tumors and compared with the changes in gross tumor volume and conventional diffusion metrics during the same time interval. In lesions treated with whole brain RT, the DAI performed the best among all metrics in predicting the posttreatment response of brain metastases to RT. In lesions treated with whole brain RT + bortezomib, although DAI was the best predictor, the performance of all metrics worsened compared with the first group. The ability of DAI for early assessment of brain metastasis response to RT depends upon treatment regimes.
Fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease: 5-year follow-up
Authors: Marco Contoli, Simonetta Baraldo, Brunilda Marku, Paolo Casolari, John A. Marwick, Graziella Turato, Micaela Romagnoli, Gaetano Caramori, Marina Saetta, Leonardo M. Fabbri, Alberto Papi
Journal: Journal of Allergy and Clinical Immunology (2010)
LABORATORY DIAGNOSIS OF THE ATOPIC CONDITION: EVALUATION OF A POSSIBLE METHOD BASED ON HUMAN SERUM COMPLEMENT CONSUMPTION
Authors: L. BERRENS
Journal: Allergy (1975)

Purified house dust allergen has been employed for screening the susceptibility to inactivation of haemolytic complement in the blood serum of atopic individuals and control subjects. Though the atopic sera displayed a tendency to higher susceptibility, no practical distinction was possible from the sera of patients with various forms of chronic pulmonary disease, extrinsic allergic alveolitis, or urticaria. CH50 and C4 levels were unrelated to allergen-sensitivity of haemolytic complement, nor was there a correlation with the titers of naturally-occurring sheep red cell haemolysins. Although blood group specificity within the ABO system was distributed over the patients as expected for the normal population, the titers of A- and B-type antibodies displayed a trend to correlate with the allergen-sensitivity of fluid phase complement.
TPI ASM8 Decreases Inflammatory Markers and Improves Airway Responsiveness in Asthmatics
Authors: R. Pageau, G. Gauvreau, R. Seguin, D. Carballo, H. D'Anjou, H. Campbell, R. Watson, M. Parry-Billings, K. Killian, P. Renzi
Journal: Journal of Allergy and Clinical Immunology (2011)
Arsenic Trioxide Sensitizes Human Glioma Cells, but not Normal Astrocytes, to TRAIL-Induced Apoptosis via CCAAT/Enhancer-Binding Protein Homologous Protein–Dependent DR5 Up-regulation
Authors: Eun Hee Kim, Mi Jin Yoon, Seung U. Kim, Taeg Kyu Kwon, Seonghyang Sohn, Kyeong Sook Choi
Journal: Cancer Research (2008)

Abstract The current study shows that treatment of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–resistant glioma cells with a combination of TRAIL and subtoxic doses of arsenic trioxide (As2O3) induces rapid apoptosis. Whereas TRAIL-mediated proteolytic processing of procaspase-3 was partially blocked in glioma cells, treatment with As2O3 efficiently recovered TRAIL-induced activation of caspases. We also found that As2O3 treatment of glioma cells significantly up-regulated DR5, a death receptor of TRAIL. Furthermore, suppression of DR5 expression by small interfering RNA (siRNA) inhibited As2O3/TRAIL-induced apoptosis of U87MG glioma cells, suggesting that DR5 up-regulation is critical for As2O3-induced sensitization of glioma cells to TRAIL-mediated apoptosis. Our results also indicate that an increase in CCAAT/enhancer binding protein homologous protein (CHOP) protein levels precedes As2O3-induced DR5 up-regulation. The involvement of CHOP in this process was confirmed by siRNA-mediated CHOP suppression, which not only attenuated As2O3-induced DR5 up-regulation but also inhibited the As2O3-stimulated TRAIL-induced apoptosis. These results therefore suggest that the CHOP-mediated DR5 up-regulation, brought about by As2O3, stimulates the TRAIL-mediated signaling pathway. This in turn leads to complete proteolytic processing of caspase-3, which is partially primed by TRAIL in glioma cells. In contrast to human glioma cells, astrocytes were very resistant to the combined administration of As2O3 and TRAIL, demonstrating the safety of this treatment. In addition, As2O3-mediated up-regulation of CHOP and DR5, as well as partial proteolytic processing of procaspase-3 by TRAIL, was not induced in astrocytes. Taken together, the present results suggest that the combined treatment of glioma cells with As2O3 plus TRAIL may provide an effective and selective therapeutic strategy. [Cancer Res 2008;68(1):266–75]
COMPARISON OF FOUR-DIMENSIONAL ECHOCARDIOGRAPHY AND TWO-DIMENSIONAL ECHOCARDIOGRAPHY IN ASSESSMENT OF FETAL CARDIAC FUNCTION: AN IN VIVO STUDY
Authors: David J. Sahn, Meihua Zhu, Eriko Shimada, Cole Streiff, Sumito Kimura, Muhammad Ashraf
Journal: Journal of the American College of Cardiology (2014)
Breast Cancer Cells Stimulate Neutrophils to Produce Oncostatin M: Potential Implications for Tumor Progression
Authors: Marisa M. Queen, Randall E. Ryan, Ryan G. Holzer, Cynthia R. Keller-Peck, Cheryl L. Jorcyk
Journal: Cancer Research (2005)

Abstract Tumor-associated and tumor-infiltrating neutrophils (TAN) and macrophages (TAM) can account for as much as 50% of the total tumor mass in invasive breast carcinomas. It is thought that tumors secrete factors that elicit a wound-repair response from TAMs and TANs and that this response inadvertently stimulates tumor progression. Oncostatin M is a pleiotropic cytokine belonging to the interleukin-6 family that is expressed by several cell types including activated human T lymphocytes, macrophages, and neutrophils. Whereas oncostatin M can inhibit the proliferation of breast cancer cells in vitro, recent studies suggest that oncostatin M may promote tumor progression by enhancing angiogenesis and metastasis. In addition, neutrophils can be stimulated to synthesize and rapidly release large quantities of oncostatin M. In this article, we show that human neutrophils secrete oncostatin M when cocultured with MDA-MB-231 and T47D human breast cancer cells. Neutrophils isolated from whole blood or breast cancer cells alone express little oncostatin M by immunocytochemistry and ELISA, but neutrophils express and release high levels of oncostatin M when they are cocultured with breast cancer cells. In addition, we show that granulocyte-macrophage colony-stimulating factor produced by breast cancer cells and cell-cell contact are both necessary for the release of oncostatin M from neutrophils. Importantly, neutrophil-derived oncostatin M induces vascular endothelial growth factor from breast cancer cells in coculture and increases breast cancer cell detachment and invasive capacity, suggesting that neutrophils and oncostatin M may promote tumor progression in vivo.
High dose-intensity of irinotecan administered every 3 weeks in advanced cancer patients: a feasibility study.
Authors: Y Merrouche, J M Extra, D Abigerges, R Bugat, G Catimel, E Suc, M Marty, P Hérait, M Mahjoubi, J P Armand
Journal: Journal of Clinical Oncology (1997)

PURPOSE To assess, on a multicenter basis, the feasibility of treating advanced cancer patients with high-dose irinotecan. PATIENTS AND METHODS Thirty-five patients who met the usual phase I criteria (26 men and nine women) were included. Primary tumor sites were colon, head and neck, unknown primary, kidney, liver, and others. All had been previously treated. Irinotecan was given at the maximum-tolerated dose (MTD) (600 mg/m2) or the level below (500 mg/m2) as a 30-minute infusion once every 3 weeks. RESULTS Eighteen patients were entered in the four participating centers at the MTD of 600 mg/m2. This dose level was clearly shown not to be feasible: 14 patients (78%) had grade 3 to 4 neutropenia, with febrile episodes in 11 patients; grade 3 to 4 diarrhea was observed in nine patients; and one toxic death occurred. Subsequently, 17 not heavily pretreated patients were included at 500 mg/m2 and carefully monitored. The safety of this dose level was considered acceptable: 41% of patients had grade 3 to 4 neutropenia, 24% experienced grade 3 to 4 diarrhea, and no febrile granulocytopenia or toxic death occurred. Six partial responses were documented in metastatic colorectal cancer, all in patients who had previously received conventional chemotherapy, four in patients who had exhibited progressive disease under fluorouracil (5FU)-based chemotherapy. CONCLUSION We plan to study the higher dose-intensity 500-mg/m2 level on good-risk and carefully monitored patients. This could enlarge the spectrum of tumors sensitive to irinotecan and improve the already good results observed in colorectal cancers.
Orphan Nuclear Receptor Nur77 Is Involved in Caspase-independent Macrophage Cell Death
Authors: Sung Ouk Kim, Koh Ono, Peter S. Tobias, Jiahuai Han
Journal: The Journal of Experimental Medicine (2003)

Activation-induced cell death in macrophages has been observed, but the mechanism remains largely unknown. Activation-induced cell death in macrophages can be independent from caspases, and the death of activated macrophages can even be triggered by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD). Here, we show that this type of macrophage death can occur in the septic mouse model and that toll-like receptor (TLR)-2 or TLR4 signaling is required in this process. We conclude that Nur77 is involved in the macrophage death because Nur77 expression correlates with cell death, and cell death is reduced significantly in Nur77-deficient macrophages. The extracellular signal–regulated kinase pathway, which is downstream of TLR2 or TLR4, and myocyte-specific enhancer binding factor 2 (MEF2) transcription factor activity, which is up-regulated by zVAD, are required for Nur77 induction and macrophage death. Reporter gene analysis suggests that Nap, Ets, Rce, and Sp1 sites in the Nur77 promoter are regulated by TLR4 signaling and that MEF2 sites in the Nur77 promoter are regulated by zVAD treatment. MEF2 transcription factors are constitutively expressed and degraded in macrophages, and zVAD increases MEF2 transcription factor activity by preventing the proteolytic cleavage and degradation of MEF2 proteins. This paper delineates the dual signaling pathways that are required for Nur77 induction in macrophages and demonstrates a role of Nur77 in caspase-independent cell death.
HIV/TB co-morbidity epidemiology in Siberian Federal District 2008-2010
Authors: Svetlana Naryshkina, Elena Pushkareva, Sergey Medvedev
Journal: European Respiratory Journal (2012)

The epidemiological situation with HIV infection is diverse for each region in Siberian Federal District (SFO). An increase in HIV prevalence was registered in these areas in different years and currently it varies considerably. Since 2001, the Irkutsk region, which has reached rate of 1196.8 per 100 000 population in 2010, occupies the “leading” position among other SFO territories. The lowest prevalence of HIV infection in 2010 was registered in the Republic of Tyva (15.1 per 100 000 people, respectively).  Purpose: The assessment of TB-HIV co-morbidity epidemiological situation in 2008-2010 in the SFO.  Methods: A retrospective analysis of annual report forms from territories of SFO and the analysis of personified registration cards of coinfected patients.  Results: The incidence of tuberculosis varies slightly in the SFO in 2008-2010: 132.9, 129.2 and 121.5 per 100 thousand population, respectively, without difference in tendencies of situations. Noticeable increase by 1.5 times in new TB-HIV cases registration pertains to period of 2008 to 2010 (2008 - 1573 patients, 2010 - 2318), with growth of the reservoir of infection in 2,3 times. Proportion of patients with TB/HIV in the penitentiary system is in the range of 6.3% to 52.6% for the different region. The proportion of patients with co-infection among TB patients exceeds 5% threshold in five territories and it continues to grow (data 2008-2010): Irkutsk region - 15.9%, Kemerovo region - 10,0-15,3%, Republic of Buryatia – 9,6-14,9%, Altaiski Kray - 5,5-10,8%, Zabaikalski Kray - 5,9-8,3%.  Conclusions: Further deterioration of epidemiological indicators of TB-HIV co-morbidity demonstrates the demand to improve TB-HIV Control programs, including prevention.
mTOR Co-Targeting in Cetuximab Resistance in Head and Neck Cancers Harboring PIK3CA and RAS Mutations
Authors: Zhiyong Wang, Daniel Martin, Alfredo A. Molinolo, Vyomesh Patel, Ramiro Iglesias-Bartolome, Maria Sol Degese, Lynn Vitale-Cross, Qianming Chen, J. Silvio Gutkind
Journal: JNCI Journal of the National Cancer Institute (2014)

Cetuximab, a monoclonal blocking antibody against the epidermal growth factor receptor EGFR, has been approved for the treatment of squamous cell carcinomas of the head and neck (HNSCC). However, only few patients display long-term responses, prompting the search for cetuximab resistance mechanisms and new therapeutic options enhancing cetuximab effectiveness. Cetuximab-sensitive HNSCC cells were retro-engineered to express PIK3CA and RAS oncogenes. These cells and HNSCC cells harboring endogenous PIK3CA and RAS oncogenes were xenografted into mice (n = 10 per group) and studied for their biochemical, antitumor, antiangiogenic, and antilymphangiogenic responses to cetuximab and mTOR targeting agents. All P values are two-sided. Cetuximab treatment of PIK3CA- and RAS-expressing HNSCC xenografts promoted an initial antitumor response, but all tumors relapsed within few weeks. In these tumors, cetuximab did not decrease the activity of mTOR, a downstream signaling target of EGFR, PIK3CA, and RAS. The combined administration of cetuximab and mTOR inhibitors exerted a remarkably increased antitumor activity, particularly in HNSCC cells that are resistant to cetuximab as a single agent. Indeed, cotargeting mTOR together with cetuximab caused a rapid tumor collapse of both PIK3CA- and RAS-expressing HNSCC xenografts (P < .001), concomitant with reduced proliferation (P < .001) and lymphangiogenesis (P < .001). The presence of PIK3CA and RAS mutations and other alterations affecting the mTOR pathway activity in HNSCC could be exploited to predict the potential resistance to cetuximab, and to select the patients that may benefit the most from the concomitant administration of cetuximab and PI3K and/or mTOR inhibitors as a precision molecular therapeutic option for HNSCC patients.
Vascular Endothelial Growth Factor and Angiogenesis
Authors: Ann Hoeben, Bart Landuyt, Martin S. Highley, Hans Wildiers, Allan T. Van Oosterom, Ernst A. De Bruijn
Journal: Pharmacological Reviews (2004)

Angiogenesis is a hallmark of wound healing, the menstrual cycle, cancer, and various ischemic and inflammatory diseases. A rich variety of pro- and antiangiogenic molecules have already been discovered. Vascular endothelial growth factor (VEGF) is an interesting inducer of angiogenesis and lymphangiogenesis, because it is a highly specific mitogen for endothelial cells. Signal transduction involves binding to tyrosine kinase receptors and results in endothelial cell proliferation, migration, and new vessel formation. In this article, the role of VEGF in physiological and pathological processes is reviewed. We also discuss how modulation of VEGF expression creates new therapeutic possibilities and describe recent developments in this field.