tbuckley/cabot-search huggingface dataset:
Curcumin inhibition of JNKs prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease through suppressing mitochondria dysfunction
Authors: Jing Pan, Hui Li, Jian-Fang Ma, Yu-Yan Tan, Qin Xiao, Jian-Qing Ding, Sheng-Di Chen
Journal: Translational Neurodegeneration (2012)

Curcumin,a natural polyphenol obtained from turmeric,has been implicated to be neuroprotective in a variety of neurodegenerative disorders although the mechanism remains poorly understood. The results of our recent experiments indicated that curcumin could protect dopaminergic neurons from apoptosis in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The death of dopaminergic neurons and the loss of dopaminergic axon in the striatum were significantly suppressed by curcumin in MPTP mouse model. Further studies showed that curcumin inhibited JNKs hyperphosphorylation induced by MPTP treatment. JNKs phosphorylation can cause translocation of Bax to mitochondria and the release of cytochrome c which both ultimately contribute to mitochondria-mediated apoptosis. These pro-apoptosis effect can be diminished by curcumin. Our experiments demonstrated that curcumin can prevent nigrostriatal degeneration by inhibiting the dysfunction of mitochondrial through suppressing hyperphosphorylation of JNKs induced by MPTP. Our results suggested that JNKs/mitochondria pathway may be a novel target in the treatment of PD patients.
Membrane androgen receptor activation triggers down-regulation of PI-3K/Akt/NF-kappaB activity and induces apoptotic responses via Bad, FasL and caspase-3 in DU145 prostate cancer cells
Authors: Natalia Papadopoulou, Ioannis Charalampopoulos, Vasileia Anagnostopoulou, Georgios Konstantinidis, Michael Föller, Achilleas Gravanis, Konstantinos Alevizopoulos, Florian Lang, Christos Stournaras
Journal: Molecular Cancer (2008)

Abstract Background Recently we have reported membrane androgen receptors-induced apoptotic regression of prostate cancer cells regulated by Rho/ROCK/actin signaling. In the present study we explored the specificity of these receptors and we analyzed downstream effectors controlling survival and apoptosis in hormone refractory DU145-prostate cancer cells stimulated with membrane androgen receptor-selective agonists. Results Using membrane impermeable conjugates of serum albumin covalently linked to testosterone, we show here down-regulation of the activity of pro-survival gene products, namely PI-3K/Akt and NF-κB, in DU145 cells. Testosterone-albumin conjugates further induced FasL expression. A FasL blocking peptide abrogated membrane androgen receptors-dependent apoptosis. In addition, testosterone-albumin conjugates increased caspase-3 and Bad protein activity. The actin cytoskeleton drug cytochalasin B and the ROCK inhibitor Y-27632 inhibited FasL induction and caspase-3 activation, indicating that the newly identified Rho/Rock/actin signaling may regulate the downstream pro-apoptotic effectors in DU145 cells. Finally, other steroids or steroid-albumin conjugates did not interfere with these receptors indicating testosterone specificity. Conclusion Collectively, our results provide novel mechanistic insights pointing to specific pro-apoptotic molecules controlling membrane androgen receptors-induced apoptotic regression of prostate cancer cells and corroborate previously published observations on the potential use of membrane androgen receptor-agonists as novel anti-tumor agents in prostate cancer.
Chest-Tube Insertion
Authors: Shelly P Dev, Bartolomeu Nascimiento, Carmine Simone, Vincent Chien
Journal: New England Journal of Medicine (2007)

The insertion of a pleural chest tube is often done in a setting where immediate action is required. Nonetheless, adherence to sterility, analgesia, sound technique, and safety are always warranted. Indications The most common indications for chest-tube drainage are: Pneumothorax that is recurrent, persistent, under tension, or bilateral; any pneumothorax in a patient on positive-pressure ventilation; hemothorax; recurrent or symptomatic large pleural effusion; empyema; and chylothorax. Contraindications There are relative contraindications, mainly based on hematologic abnormalities such as bleeding diatheses or coagulopathy. Blood products or coagulation factors may need to be transfused in order to reduce the . . . .
Inhibition of NF-κB–Mediated Signaling by the Cyclin-Dependent Kinase Inhibitor CR8 Overcomes Prosurvival Stimuli to Induce Apoptosis in Chronic Lymphocytic Leukemia Cells
Authors: Emilio Cosimo, Alison M. McCaig, Luke J.M. Carter-Brzezinski, Helen Wheadon, Michael T. Leach, Karine Le Ster, Christian Berthou, Emilie Durieu, Nassima Oumata, Hervé Galons, Laurent Meijer, Alison M. Michie
Journal: Clinical Cancer Research (2013)

Chronic lymphocytic leukemia (CLL) is currently incurable with standard chemotherapeutic agents, highlighting the need for novel therapies. Overcoming proliferative and cytoprotective signals generated within the microenvironment of lymphoid organs is essential for limiting CLL progression and ultimately developing a cure.We assessed the potency of cyclin-dependent kinase (CDK) inhibitor CR8, a roscovitine analog, to induce apoptosis in primary CLL from distinct prognostic subsets using flow cytometry-based assays. CLL cells were cultured in in vitro prosurvival and proproliferative conditions to mimic microenvironmental signals in the lymphoid organs, to elucidate the mechanism of action of CR8 in quiescent and proliferating CLL cells using flow cytometry, Western blotting, and quantitative real-time PCR.CR8 was 100-fold more potent at inducing apoptosis in primary CLL cells than roscovitine, both in isolated culture and stromal-coculture conditions. Importantly, CR8 induced apoptosis in CD40-ligated CLL cells and preferentially targeted actively proliferating cells within these cultures. CR8 treatment induced downregulation of the antiapoptotic proteins Mcl-1 and XIAP, through inhibition of RNA polymerase II, and inhibition of NF-κB signaling at the transcriptional level and through inhibition of the inhibitor of IκB kinase (IKK) complex, resulting in stabilization of IκBα expression.CR8 is a potent CDK inhibitor that subverts pivotal prosurvival and proproliferative signals present in the tumor microenvironment of CLL patient lymphoid organs. Our data support the clinical development of selective CDK inhibitors as novel therapies for CLL.
Epicardial adipose stem cell sheets results in greater post-infarction survival than intramyocardial injections
Authors: H. Hamdi, V. Planat-Benard, A. Bel, E. Puymirat, R. Geha, L. Pidial, H. Nematalla, V. Bellamy, P. Bouaziz, S. Peyrard, L. Casteilla, P. Bruneval, A. A. Hagege, O. Agbulut, P. Menasche
Journal: Cardiovascular Research (2011)

Intramyocardial injections of cells can damage tissue and enhance dissociation-induced cell death. We assessed whether epicardial delivery of cell sheets could overcome these issues in a rat model of chronic myocardial infarction. Eighty-two rats that had undergone coronary ligation and simultaneous harvest of fat tissue to yield the adipose-derived stromal cell (ADSC) fraction were randomized 1 month after infarction to receive injections of either control medium (n= 24) or 10 × 106 autologous ADSC (n= 37) or the epicardial deposit, onto the infarcted area, of a trilayered ADSC sheet (10 × 106, n= 21) prepared by culturing cells on temperature-sensitive dishes. Some treated rats received green fluorescent protein labelled ADSC. Survival, function, and cell engraftment were blindly assessed after 2 months. Prior to implantation, cell sheets and suspended cells were assessed for the expression of extracellular matrix constituents and molecules involved in angiogenesis and cardiac remodelling. The survival rate of rats receiving the cell sheets was significantly higher than after cell injections (73 vs. 41%, P = 0.01). This correlated with the absence of left ventricular (LV) remodelling in the cell sheet group, as end-diastolic volume only increased by 2.8% compared with baseline [95% confidence interval (CI): −18.7%; +30.0%, P = 0.81] vs. increases of 25.9% (−0.4%; +59.2%, P = 0.05) and 51.2% (+18.6%; +92.8, P = 0.001) in the cell and medium injection groups, respectively. Sheets also resulted in a greater cell engraftment possibly related to the greater expression of extracellular matrix constituents. The better preservation of LV geometry afforded by ADSC sheets is associated with increased survival and engraftment, which supports the concept of an epicardial delivery of cell-seeded biomaterials.
Skin reactivity to neuropeptides in atopic dermatitis
Authors: A. GIANNETTI, G. GIROLOMONI
Journal: British Journal of Dermatology (1989)

Adults with atopic dermatitis (AD), with respiratory atopy only and healthy non-atopic controls were given intradermal injections of substance P (SP), neurokinin A (NKA), neurotensin (NT), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and histamine into the normal-appearing skin on the back. The weal and flare responses were evaluated after 3, 5 and 15 min and the areas calculated using an automatic image analyser. With the three different concentrations used (1,3 and 30 pmols) a statistically significant (P < 0·05) reduction in both the weal and flare response to SP, NKA, NT and histamine and a reduced flare to CGRP was observed only in AD patients. Among those with AD there was no uniformity of response to the individual neuropeptide and in general the more severely affected showed a lower reactivity. Dose-response relationships were evaluated for SP and NT (10–320 pmols) in AD and healthy controls. In AD dose-response curves and time-course relationships were similar to controls, but at significantly reduced levels. The itch response to the neuropeptides and histamine was not different in atopics and controls. We suggest that this hyporesponsiveness in AD is the result of natural tachyphylaxis of the target structures (mast cells and blood vessels) and possibly due to a higher availability of neuropeptides in the skin or to a primary abnormal sensitivity of the blood vessels and mast cells to these peptides.
Outcome of Watchful Waiting in Asymptomatic Severe Mitral Regurgitation
Authors: Raphael Rosenhek, Florian Rader, Ursula Klaar, Harald Gabriel, Marcel Krejc, Daniel Kalbeck, Michael Schemper, Gerald Maurer, Helmut Baumgartner
Journal: Circulation (2006)

The management of asymptomatic severe mitral regurgitation remains controversial. The aim of this study was to evaluate the outcome of a watchful waiting strategy in which patients are referred to surgery when symptoms occur or when asymptomatic patients develop left ventricular (LV) enlargement, LV dysfunction, pulmonary hypertension, or recurrent atrial fibrillation.A total of 132 consecutive asymptomatic patients (age 55+/-15 years, 49 female) with severe degenerative mitral regurgitation (flail leaflet or valve prolapse) were prospectively followed up for 62+/-26 months. Patients underwent serial clinical and echocardiographic examinations and were referred for surgery when the criteria mentioned above were fulfilled. Overall survival was not statistically different from expected survival either in the total group or in the subgroup of patients with flail leaflet. Eight deaths were observed. Thirty-eight patients developed criteria for surgery (symptoms, 24; LV criteria, 9; pulmonary hypertension or atrial fibrillation, 5). Survival free of any indication for surgery was 92+/-2% at 2 years, 78+/-4% at 4 years, 65+/-5% at 6 years, and 55+/-6% at 8 years. Patients with flail leaflet tended to develop criteria for surgery slightly but not significantly earlier. There was no operative mortality. Postoperative outcome was good with regard to survival, symptomatic status, and postoperative LV function.Asymptomatic patients with severe degenerative mitral regurgitation can be safely followed up until either symptoms occur or currently recommended cutoff values for LV size, LV function, or pulmonary hypertension are reached. This management strategy is associated with good perioperative and postoperative outcome but requires careful follow-up.
Klebsiella respiratory infection community acquired
Authors: Safa Hafaied, Nawel Chaouch, Sawsen Bacha, Sonia Habibech, Hajer Racil, S. Cheikh Rouhou, Mourad Zarrouk, Abdellatif Chabbou
Journal: European Respiratory Journal (2013)

Klebsiella respiratory infection (KRI) is usually contracted at hospital, but rarely community acquired. To describe clinical and evolution features of KRI we analyzed all respiratory infections due to klebsiella hospitalized in our department between 2005 and 2012. During this period 29 patients mean aged 59,39 years were enrolled, among them 71,4% were smokers and 25% were alcoholic. No risk factor of klebsiella infection was found in 6 cases. KRI was associated to bronchiectasis in 11 cases, COPD in 6 cases, asthma in 3 cases, immunodepression in 6 cases. KRI reveled lung cancer in 7 cases and sarcoidosis in 1 case. Respiratory infection consists in pneumonia (17 cases), bronchitis (10 cases) or suppuration (2 case). Pleural effusion was associated to pneumonia in 4 cases. Klebsiella was identified by sputum culture in 25 cases, bronchial aspiration in 4 cases. All Klebsiella strains were ESBL negative. Treatment was based on 1 antibiotic in 16 cases and 2 antibiotics in 13 cases. Lobectomy was indicated in 1 case because of pulmonary suppuration. Outcome was favorable in 23 cases, 3 patients died because of respiratory failure, 3 patients had Klebsiella colonization.  Although KRI could be seen in patients with normal condition mostly they happens in underlying respiratory disease especially lung cancer which should be always kept in mind.
Alveolar Macrophages from Atopic Asthmatics, But Not Atopic Nonasthmatics, Enhance Interleukin-5 Production by CD4 + T Cells
Authors: CHIBING TANG, JENNIFER M. ROLLAND, XUN LI, CHRISTOPHER WARD, ROS BISH, E. HAYDN WALTERS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Recent studies have demonstrated that different antigen-presenting cell (APC)-related factors in the microenvironment of a T cell may determine its profile and quantity of cytokine expression and production. We have therefore examined the effects of alveolar macrophages and peripheral blood monocytes on interleukin (IL)-5 production by peripheral blood CD4+ T cells from atopic people with asthma (AA), atopic people without asthma (AN), and nonatopic normal subjects (N). In response to allergen stimulation, IL-5 production was significantly enhanced by the addition of monocytes to CD4+ cell cultures in AA and AN patients (p < 0.05 and 0.01, respectively), but not in N subjects. In mitogen-stimulated CD4+ cell plus monocyte cocultures, there was a small increase in IL-5 production in all three groups (p < 0.05 for AN). In contrast, the addition of alveolar macrophages to parallel cultures significantly amplified IL-5 production only in AA patients (p < 0.05 or 0.01). Furthermore, IL-5 production by CD4+ cells in alveolar macrophage cocultures, stimulated by allergen or mitogen, was higher than that in monocyte cocultures in AA patients (p < 0.05). Conversely, in AN and N subjects, the IL-5 values for alveolar macrophage cocultures were lower than those for peripheral blood monocytes. In blocking studies, antibodies against IL-1alpha, IL-1beta, IL-6, or tumor necrosis factor-alpha differentially suppressed macrophage-enhanced IL-5 production (p < 0.05 for IL-1beta and IL-6) and expression of the activation marker CD25 (p < 0.05 for IL-1alpha and IL-6) by allergen-stimulated CD4+ cells in AA patients. These observations suggest that alveolar macrophages influence the quantity of IL-5 production by T cells in the airways and, as a consequence, the development of asthma in atopic individuals.
Capsaicin Is a Novel Blocker of Constitutive and Interleukin-6–Inducible STAT3 Activation
Authors: Manisha Bhutani, Ashutosh K. Pathak, Asha S. Nair, Ajaikumar B. Kunnumakkara, Sushovan Guha, Gautam Sethi, Bharat B. Aggarwal
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Capsaicin, a constituent of green and red peppers, has been linked with suppression of tumorigenesis through a mechanism that is not well understood. Because the transcription factor signal transducer and activator of transcription 3 (STAT3) has been closely linked with tumorigenesis, we investigated the effect of this vanilloid on the STAT3 pathway in human multiple myeloma cells. Experimental Design: The effect of capsaicin on both constitutive and interleukin-6–induced STAT3 activation, associated protein kinases, and STAT3-regulated gene products involved in proliferation, survival and angiogenesis, cellular proliferation, and apoptosis in multiple myeloma cells was investigated. Results: We found that capsaicin inhibited constitutive activation of STAT3 in multiple myeloma cells in a dose- and time-dependent manner, with minimum effect on STAT5. Capsaicin also inhibited the interleukin-6–induced STAT3 activation. The activation of Janus-activated kinase 1 and c-Src, implicated in STAT3 activation, was also inhibited by the vanilloid, with no effect on extracellular signal-regulated kinase 1/2 activation. Pervanadate reversed the capsaicin-induced down-regulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Capsaicin down-regulated the expression of the STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, and vascular endothelial growth factor. Finally, capsaicin induced the accumulation of cells in G1 phase, inhibited proliferation, and induced apoptosis, as indicated by caspase activation. Capsaicin also significantly potentiated the apoptotic effects of Velcade and thalidomide in multiple myeloma cells. When administered i.p., capsaicin inhibited the growth of human multiple myeloma xenograft tumors in male athymic nu/nu mice. Conclusion: Overall, these results suggest that capsaicin is a novel blocker of the STAT3 activation pathway, with a potential role in the prevention and treatment of multiple myeloma and other cancers.
Decaffeinated Coffee and Glucose Metabolism in Young Men
Authors: James A. Greenberg, David R. Owen, Allan Geliebter
Journal: Diabetes Care (2009)

OBJECTIVE The epidemiological association between coffee drinking and decreased risk of type 2 diabetes is strong. However, caffeinated coffee acutely impairs glucose metabolism. We assessed acute effects of decaffeinated coffee on glucose and insulin levels. RESEARCH DESIGN AND METHODS This was a randomized, cross-over, placebo-controlled trial of the effects of decaffeinated coffee, caffeinated coffee, and caffeine on glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) levels during a 2-h oral glucose tolerance test (OGTT) in 11 young men. RESULTS Within the first hour of the OGTT, glucose and insulin were higher for decaffeinated coffee than for placebo (P &amp;lt; 0.05). During the whole OGTT, decaffeinated coffee yielded higher insulin than placebo and lower glucose and a higher insulin sensitivity index than caffeine. Changes in GIP could not explain any beverage effects on glucose and insulin. CONCLUSIONS Some types of decaffeinated coffee may acutely impair glucose metabolism but less than caffeine.
FEASIBILITY AND SAFETY OF SAME DAY DISCHARGE AFTER IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IMPLANTATION: A SINGLE CENTER EXPERIENCE
Authors: Saba Darda, Yazan Khouri, Sachin Jain, Rony Gorges, Mershed Al Samara, Michael Shaw, Christian Machado
Journal: Journal of the American College of Cardiology (2011)
Should There be Intervention to Alter Serum Lipids in Children?
Authors: A M Mauer
Journal: Annual Review of Nutrition (1991)

Background Iriformation Supporting Intervention  376 Population Studies  377 Vascular Lesions During Childhood and Adolescence   378 Diet a.nd Ser�m Lipfd Relationshi ps   . .   379 �enetlc. P�;dlsposltlon     380 Trackmg . . . . ... . . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......... . . . . . . . . . . . . . .. . . . . . . . ... 380 Current Serum Values in US Children .....     381 Current Dietary Patterns in US Children    382 Response to Dietary Intervention . ....     382 Future Studies   384 Conclusions and Recommendations   385
Repeated Aerosol Delivery of Carboxyl-terminal Modulator Protein Suppresses Tumor in the Lungs of K-<i>ras</i><sup>LA1</sup> Mice
Authors: Soon-Kyung Hwang, Hwang-Tae Lim, Arash Minai-Tehrani, Eun-Sun Lee, Jongmin Park, Seung Bum Park, George R. Beck, Myung-Haing Cho
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Difficulties in achieving long-term survival of patients with lung cancer treated with conventional therapies suggest that novel approaches are required. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.To investigate the repeated effect of carboxyl-terminal modulator protein (CTMP) on multistage lung tumorigenesis. In this study, we addressed this question by studying the effects of lentivirus-based CTMP in the lungs of 9- and 13-week-old K-ras(LA1) mice, a model of lung cancer.An aerosol of lentivirus-based CTMP was delivered into 9- and 13-week-old K-ras(LA1) mice, a model of lung cancer, through a nose-only inhalation system twice a week for 4 weeks. The effects of CTMP on lung cancer progression and Akt-related signals were evaluated.Long-term repeated delivery of CTMP effectively reduced tumor progression in the lungs at different stages of development. Lentiviral-CTMP inhibited protein synthesis and cell cycle and altered Akt signaling pathway in the lungs of 9-week-old K-ras(LA1) mice, and increased apoptosis was observed in the lungs of 13-week-old K-ras(LA1) mice.Long-term repeated viral delivery of CTMP may provide a useful tool for designing lung tumor treatment.
Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function
Authors: Paolo Serafini, Kristen Meckel, Michael Kelso, Kimberly Noonan, Joseph Califano, Wayne Koch, Luigi Dolcetti, Vincenzo Bronte, Ivan Borrello
Journal: The Journal of Experimental Medicine (2006)

Phosphodiesterase-5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) are agents currently in clinical use for nonmalignant conditions. We report the use of PDE5 inhibitors as modulators of the antitumor immune response. In several mouse tumor models, PDE5 inhibition reverses tumor-induced immunosuppressive mechanisms and enables a measurable antitumor immune response to be generated that substantially delays tumor progression. In particular, sildenafil, down-regulates arginase 1 and nitric oxide synthase–2 expression, thereby reducing the suppressive machinery of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs) recruited by growing tumors. By removing these tumor escape mechanisms, sildenafil enhances intratumoral T cell infiltration and activation, reduces tumor outgrowth, and improves the antitumor efficacy of adoptive T cell therapy. Sildenafil also restores in vitro T cell proliferation of peripheral blood mononuclear cells from multiple myeloma and head and neck cancer patients. In light of the recent data that enzymes mediating MDSC-dependent immunosuppression in mice are active also in humans, these findings demonstrate a potentially novel use of PDE5 inhibitors as adjuncts to tumor-specific immune therapy.
Adalimumab and Infliximab Are Equally Effective for Crohn's Disease in Patients Not Previously Treated With Anti–Tumor Necrosis Factor-α Agents
Authors: Christine Kestens, Martijn G.H. van Oijen, Charlotte L.J. Mulder, Ad A. van Bodegraven, Gerard Dijkstra, Dirk de Jong, Cyriel Ponsioen, Bas A.C. van Tuyl, Peter D. Siersema, Herma H. Fidder, Bas Oldenburg
Journal: Clinical Gastroenterology and Hepatology (2013)