tbuckley/cabot-search huggingface dataset:
MAPK/ERK1/2 kinase regulates the cytokine loop between Interleukin-6 (IL6) and Macrophage inflammatory protein alpha (MIP-1 a) in myeloma-stromal cell in-vitro model
Authors: Ramadevi Nimmanapalli, Elvira Gerbino, William Dalton, Melissa Alsina
Journal: Cancer Research (2004)

1755   Myeloma-stromal cell interactions facilitate the development of bone disease, tumor growth, survival and drug resistance. We have shown that IL-6 stimulates myeloma cell adhesion through a Mip-1a dependent mechanism and that the effects of IL6 on MIP-1a expression are enhanced by adhesion to extra cellular matrix protein fibronectin (FN) however the signal transduction pathways involved in this cytokine loop are poorly understood. To study these pathways, we developed an in-vitro model of myeloma-stromal cell interactions. We used the myeloma cell line 8226 and human bone marrow stromal cell line (HS-5) to mimic bone marrow microenvironment. Adhesion of 8226 cells to HS-5 induced secretion of MIP-1a and a neutralizing antibody to IL6 blocked this effect. To explore the signal transduction pathways involved in this cytokine loop, we examined signaling pathways down stream from IL6. Western blot analysis showed that the survival and proliferation signaling pathways AKT/protein kinase B (PKB), mitogen activated protein kinase family (MAPK) and STAT-3 are activated when myeloma cells (8226) are adhered to HS-5 cells. PD98059 a MAPK/ERK kinase inhibitor attenuated myeloma cell adhesion to HS-5 and reduced MIP-1a protein expression and gene expression but had no effect on IL6 expression. However the AG490 JAK2 inhibitor and the PI3/AKT kinase inhibitor LY294002 had no effect on MIP-1a secretion. By blocking IL6 signaling using IL6 neutralizing antibody, Mip-1a secretion, MAPK/ERK kinase and STAT-3 activation were reduced. Together these results suggest that regulation of MIP-1a by IL6 is through MAPK pathway. By blocking Mip-1a signaling using Mip-1a neutralizing antibody, secretion of IL6 and ERK1/2 activity were reduced. This result indicates that the secreted MIP-1a in turn enhances IL6 secretion. In summary, we showed that adhesion of myeloma cells to BM stromal cells stimulates expression and secretion of IL6 and Mip-1a. IL6 stimulates myeloma cell expression and secretion of Mip-1a by enhancing Erk1/2 kinase activity. Understanding the signaling involved in Mip-1a induced IL6 secretion should provide insight into the complex loop between soluble factors and cell-cell contact mediating myeloma-stromal cell interactions and provides potential novel targets for therapies that would interfere with these interactions.
Protoesome inhibitor induces apoptosis in primary effusion lymphoma
Authors: Shahab Uddin, Azhar Hussain, Naif Al-Jomah, Mehar Sultana, Maqbool Ahmed, Khawla Al-Kuraya
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

1449 

Proteosome inhibition is a novel approach for treating malignancy and has been approved for clinical use. The proteosome is the primary proteolytic mechanism in eukaryotic cells and inhibition of its catalytic activity initiates a cascade of events affecting cell cycle and apoptotic activities. These activities ultimately lead to cell cycle arrest and apoptosis in malignant cells however, the normal counterpart of these cells are spared. In this study, we used a panel of primary effusion lymphoma cell lines (BC1, BC3, BCBL1 and HBL6) to study the effects of proteosome inhibitor, MG132 on cell proliferation and apoptosis. Our data showed that proteosome inhibitor MG132 decreased cell viability as well as induced apoptosis in a dose dependent manner ranging from 0.5-10μM. Furthermore, treatment with 2.5μM MG132 for 24hours induced 41% apoptosis in BC1, 51% in BC3, 41% in BCBL1 and 48% in HBL6 cell lines as detected by annexinV/PI dual staining. S-phase kinase-associated protein 2 (skp-2) is a proto-oncogene and over expressed in various types of tumors. We sought to determine the role of Skp-2 following proteosome inhibition in PELs. MG132 treatment of PEL cell lines resulted in down-regulation of SKP-2 protein in a dose dependent manner whereas the expression of p-27 was up-regulated demonstrating an inverse relationship between these two proteins. Furthermore, MG132 treatment of PELs led to conformational changes in Bax protein and translocation to the mitochondria leading to the loss of mitochondrial membrane potential with subsequent release of cytochrome c from mitochondria into cytosol. Cytochrome c release caused activation of caspase-3 followed by polyadenosin-5 -diphosphate-ribose polymerase (PARP) cleavage. In addition, proteosome inhibitor treatment also caused down-regulation of inhibitor of apoptosis protein, XIAP. Taken together, our findings show that proteosome inhibition causes down-regulation of skp-2, up-regulation of p-27, inhibition of proliferation as well as caspase-dependent apoptosis in primary effusion lymphoma cells suggesting a role of proteosome inhibitors in the treatment of these aggressive cancers.
Ready-to-Use Supplementary Food Supplements Improve Endothelial Function, Hemoglobin and Growth in Tanzanian Children with Sickle Cell Anaemia: The Vascular Function Intervention Study (V-FIT), a Random Order Crossover Trial
Authors: Sharon E. Cox, Julie Makani, Gurishaeli Walter, Selemani Mtunguja, Beatrice A Kamala, Elizabeth Ellins, Charles RJ Newton, Fenella J. Kirkham, Andrew M Prentice, Julian P Halcox
Journal: Blood (2014)
Recent Investigations of &lt;sc&gt;l&lt;/sc&gt;- and &lt;sc&gt;d&lt;/sc&gt;-Amino Acid Oxidases&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Alton Meister, Daniel Wellner, Sara Jo Scott
Journal: JNCI Journal of the National Cancer Institute (1960)

Journal Article Recent Investigations of l- and d-Amino Acid Oxidases Get access Alton Meister, Alton Meister Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel Wellner, Daniel Wellner Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts Search for other works by this author on: Oxford Academic PubMed Google Scholar Sara Jo Scott Sara Jo Scott Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 24, Issue 1, January 1960, Pages 31–49, https://doi.org/10.1093/jnci/24.1.31 Published: 01 January 1960 Article history Received: 03 September 1959 Published: 01 January 1960
Abstract 967: Parathyroidectomy Reduces Cardiovascular Events And All-cause Mortality In Renal Hyperparathyroidism
Authors: Jose Lima, Valeria Costa-Hong, Vanda Jorgetti, Luis Henrique W Gowdak, Rosa Maria A Moyses, Eduardo M Krieger
Journal: Circulation (2007)

Background: Secondary hyperparathyroidism (SHPT) and its associated abnormalities in mineral metabolism increase the risk of cardiovascular morbidity and death in chronic kidney disease (CKD). The effect of parathyroidectomy (PTX) on the incidence of major cardiovascular events in CKD patients with SHPT is unknown. We tested the hypothesis that PTX reduces the incidence of cardiovascular complications and death in CKD patients with severe SHPT scheduled for PTX, comparing the outcome of patients treated or not treated by surgery. Methods: The study comprised 118 CKD patients with SHPT on maintenance hemodialysis, unresponsive to medical treatment, and scheduled for PTX. Patients underwent comprehensive cardiovascular evaluations at baseline. They were followed up until death, occurrence of major cardiovascular events, or kidney transplantation. Results: No deaths related to surgery occurred. After a median follow-up of 30 months, 50 patients (42.4%) had undergone PTX while 68 (57.9%) had not. The groups were comparable in terms of age, sex, race, parathyroid hormone (PTH), calcium, phosphate, calcium x phosphate product, and all major cardiovascular variables, except diastolic blood pressure. PTX was associated with a reduced incidence of major cardiovascular events (log-rank= 0.02) and overall mortality (log-rank= 0.001). Cox proportional multivariate analysis showed that variables significantly and independently associated with events were PTX (RR=2.36, CI 1.11–6.32, p=0.02) and age (RR=1.07, IC 1.02–1.14, p=0.009). All-cause mortality was related to PTX (RR=2.34, CI 1.25–5.14, p=0.007) and hematocrit (RR=1.15, CI 1.03–1.29, p=0.01). Conclusion: PTX confers protection against future major cardiovascular events and death in select CKD patients with severe refractory SHPT.
A Comparative Analysis Of Next-Generation Sequencing and Real-Time Quantitative PCR For Minimal Residual Disease Detection In Follicular Lymphomas
Authors: Christiane Pott, Luigia Monitillo, Elisa Genuardi, Barbara Mantoan, Heiko Trautmann, Michael Kneba, Monika Brüggemann, Malek Faham, Marco Ladetto
Journal: Blood (2013)
Abstract 19306: Myocardial Strain Predicts Adverse Cardiac Events in Patients Treated with Anthracyclines
Authors: Mohammed T Ali, Evin Yucel, Souhila Bouras, Marielle Scherrer-Crosbie
Journal: Circulation (2014)

Introduction: When the cardiotoxicity of anthracyclines is associated with symptoms or with an impaired left ventricular ejection fraction (LVEF), it is often not responsive to heart failure treatment. Identifying individuals at high risk for major adverse cardiac events (MACE) before the initiation of chemotherapy, especially in patients with hematological malignancies who have high MACE occurrence, may decrease cardiotoxicity. Although decreased baseline LVEF is predictive of MACE, it is a rare occurrence. We compared pre-chemotherapy global longitudinal strain (GLS) and LVEF to stratify patients at high risk for anthracycline-induced cardiac toxicity. Methods: Patients with hematological cancers treated with anthracyclines who had a pre-chemotherapy echocardiogram between January 2009 and June 2011 at MGH were recruited. Basic demographic data, end-diastolic and end-systolic LV dimensions, LVEF, and GLS (Tomtec Imaging System) were measured. MACE were defined as cardiac death or hospital admission for ...
Low cerebellar metabolism in medicated patients with chronic schizophrenia
Authors: N D Volkow, A Levy, J D Brodie, A P Wolf, R Cancro, P Van Gelder, F Henn
Journal: American Journal of Psychiatry (1992)

Because of the frequent association of cerebellar structural defects with schizophrenia, the authors reanalyzed the metabolic brain images of patients with chronic schizophrenia to assess if they had abnormalities in cerebellar metabolism. They used carbon-11-2-deoxyglucose and positron emission tomography to study 18 medicated patients with chronic schizophrenia and 12 normal comparison subjects. Patients with schizophrenia showed significantly lower absolute and relative metabolism in the cerebellum than normal subjects.
How Negative are We to the Idea of Suicide Prevention?
Authors: H G Morgan, M O Evans
Journal: Journal of the Royal Society of Medicine (1994)

Assessment of attitudes amongst health care professionals to suicide prevention reveals a considerable degree of doubt with regards to its feasibility and appropriateness. The various professional groups may vary considerably in the degree of negative attitudes which they exhibit. Such findings suggest that there is an urgent need to ensure that health care professionals are fully informed about the key facts concerning suicide and preventive strategies. Key elements of clinical practice and service organization with regards to suicide prevention are discussed.
Estrogen Receptor Gene Polymorphisms and Lung Adenocarcinoma Risk in Never-Smoking Women
Authors: Kuan-Yu Chen, Chin-Fu Hsiao, Gee-Chen Chang, Ying-Huang Tsai, Wu-Chou Su, Yuh-Min Chen, Ming-Shyan Huang, Fang-Yu Tsai, Shih-Sheng Jiang, I-Shou Chang, Chih-Yi Chen, Chao A. Hsiung, Chien-Jen Chen, Pan-Chyr Yang
Journal: Journal of Thoracic Oncology (2015)
Was the vasectomy necessary after all? [letter]
Authors: Hoy Am
Journal: BMJ (1986)

Dr. Lloyd Nicholass personal paper (1 March p. 604) provides the profession with a useful warning against treating serious disease as mere routine.  However the practical issue he raises of fertility after orchidectomy and postoperative radiotherapy is also important.  Many children have been fathered by men in this group.  Although patients with previous testicular tumors may be subfertile they should not be regarded as irretrievably sterile.  Aspermia induced by low dose radiation recovers as a function of both time and dose.  With modern sharp beam linear accelerators and appropriate shielding testicular dosage should be in the 0.2-1.5 Gy range.  In Dr. Nicholass case his vasectomy almost certainly was necessary.  (full text)
Abstract 9583: Remote Preconditioning Has a Powerful Antiarrhythmic Effect Independent of the Reperfusion Injury Salvage Kinase Pathways
Authors: Joan Dow, Boris Z Simkhovich, Anil Bhandari, Robert A Kloner
Journal: Circulation (2011)

Background: There is continuing need for non pro-arrhythmic antiarrhythmic therapies for life threatening ventricular arrhythmias associated with myocardial ischemia/reperfusion. A new form of endogenous cardio-protection, remote ischemic preconditioning (RPC) showed promise for reducing myocardial infarct size, but its effect on ventricular arrhythmias is largely unknown. The purpose of this study was to determine the effects of RPC on arrhythmias in a non-infarct producing model. Methods: Anesthetized open chest rats were exposed to 5 minutes of proximal left coronary artery occlusion and 10 minutes of reperfusion. Rats were either untreated controls (Ctrl, n=17) or received RPC (n=14) with 5 minutes bilateral femoral occlusions followed by 5 minutes of reperfusion times 3, started 30 minutes before coronary occlusion. Reperfusion arrhythmias were quantitated and in some rats Western Blot Analysis for pAKT and p-p70S6 kinase were studied. Results: Ischemic risk zone (blue dye technique) was similar in Ctrl (35% of LV) and RPC (32%) as were heart rate and blood pressure throughout the study. At reperfusion, onset of ventricular tachycardia (VT) was delayed in RPC group (45.8 ± 17.1 sec; mean + SEM) versus Ctrl (11.5 ± 3.3 sec; p=0.04). The number of episodes of VT was 18.1 ± 5.1 in Ctrl versus 5.2 ± 1.7 in the RPC group (p=0.01) and duration of VT was 67.2 ± 13.2 sec in Ctrl versus 24.9 ± 11.1 sec in RPC (p=0.019). Sustained VT (≥ 10 sec) occurred in 12 controls and 4 RPC rats (p=0.03); and duration of sustained VT was 40.2 ± 9.9 sec in Ctrl versus 14.6 ± 7.2 sec in RPC (p=0.03). Ventricular fibrillation occurred in 3 controls and 1 RPC rat. Mean number of ventricular premature beats was 38.2 ± 11.4 in Ctrl and 14.1 ± 3.1 in RPC rats (p=0.04). At the end of reperfusion p-Akt level in the risk area in control hearts was 2 times higher compared to the non-ischemic area, and was not different from its level in the risk area in the RPC hearts. In addition, the risk area in both Ctrl and RPC hearts demonstrated no difference in the p-p70S6 kinase level. Conclusion: Remote ischemic preconditioning of the lower limbs induced a powerful delay in/and reduction in ischemia/reperfusion induced ventricular arrhythmias, but without evoking the reperfusion injury salvage kinase pathway.
Abstract 13716: Dipeptidyl Peptidase-4 Inhibitor Improved Exercise Capacity in Association With Switching to Oxidative Skeletal Muscle Fiber Type in Mice With Post-infarct Heart Failure
Authors: Yoshihiro Masaki, Shintaro Kinugawa, Takashi Yokota, Shouji Matsushima, Arata Fukushima, Shingo Takada, Takaaki Furihata, Tomoyasu Kadoguchi, Ryoichi Katsuyama, Koichi Okita, Hiroyuki Tsutsui
Journal: Circulation (2013)

Background:  Exercise capacity is reduced in heart failure (HF) largely due to the impairment of skeletal muscle function. Glucagon-like peptide-1 (GLP-1), one of the incretin hormons, has been shown to improve exercise tolerance in HF patients. However, the effects of dipeptidyl peptidase (DPP)-4 inhibitor on the exercise capacity and skeletal muscle characteristics have not been elucidated in HF.   Methods and Results:  Myocardial infarction (MI) was created in male C57BL/6J mice (n=20) by ligating the left coronary artery, and sham operation was performed (n=20). They were further divided into 2 groups of the treatment with or without DPP-4 inhibitor, MK-0626 (1 mg/kg/day) for 4 weeks. MK-0626 significantly inhibited plasma DPP-4 activity by 42 % and increased plasma active GLP-1 levels by 171 %. MK-0626 did not affect infarct size from MI and MI+MK-0626 mice (53±2 vs 56±3 %,  p =NS) and left ventricular function evaluated by echocardiography. In contrast, exercise capacity, measured by treadmill test with expired gas analysis, was reduced in MI mice compared to sham mice (work 17±1 vs 29±1 J,  p  2  140±5 vs 161±3 mL/kg/min,  p  2  158±3 mL/kg/min) without affecting skeletal muscle weight. A shift toward fast twitch myosin fiber type was observed in the skeletal muscle from MI mice, and this change was reversed by MK-0626, expressed as the increase in type I fiber from 14 to 24 % and the decrease in type IIb fiber from 25 to 19 %. Citrate synthase activity was significantly reduced in the skeletal muscle from MI mice by 71 % and this decrease was ameliorated in MI+MK-0626 by 175 %. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) gene expression and protein level were significantly reduced (gene expression 56 % and protein levels 64 %) in the skeletal muscle from MI mice and these changes were normalized in MI+MK-0626. These effects of MK-0626 on skeletal muscle fiber type and mitochondrial function were not observed in sham mice.   Conclusions:  The administration of MK-0626 into MI mice improved exercise capacity and normalized the skeletal muscle fiber type switch. DPP-4 inhibitor may be a novel therapeutic agent against skeletal muscle dysfunction in HF.
Women's health: women's health is a global issue
Authors: N. Craft
Journal: BMJ (1997)

All over the world, women live longer than men, up to 12 years longer in the Russian Federation. However, while women live longer, they are not necessarily living better, healthier lives. In developing countries, communicable diseases, together with childbirth-related illnesses, account for most morbidity among women. In the developed world, too, women report experiencing higher levels of physical and psychological morbidity. While women risk contracting the same endemic diseases as men, both biological and social factors may increase exposure or worsen the effects. The following are discussed as affecting women more than men, regardless of where they live: poverty, birth rates and aging populations, gender, violence against women, and lack of research about women. Issues affecting women in the developing world and in poorer areas of the developed world include education, lack of autonomy, legal status, preference for sons, traditional practices, lack of access to health care, work and environmental health hazards, and unequal human rights. Women's health in the developed world is also considered.
Adalimumab in Juvenile Rheumatoid Arthritis
Authors: Paolo Sfriso, Francesca Ravaioli
Journal: New England Journal of Medicine (2008)

To the Editor: Lovell et al. (Aug. 21 issue)1 report that adalimumab seems to be effective in the treatment of children with juvenile rheumatoid arthritis. However, interpretation of their results is difficult, given the medication-withdrawal design of the trial. During the open-label lead-in phase, patients who had a response to the drug were preselected and children who could not tolerate it were excluded. The double-blind phase was therefore enriched with patients who had a response to the drug, and the treatment effects observed may be larger than those seen in an unselected population. The evaluation of safety also raises some concerns. Since all the patients initially received adalim umab, how can we rule out a carryover effect that might have masked the true incidence of adverse events?2 The authors highlight the ethical issues associated with denying active treatment during a double-blind phase of placebo-controlled trials in pediatric populations. However, failure to appropriately estimate the potential benefit and side effects might be of even more concern. We believe that the assertion that “the openlabel lead-in approach is generalizable to clinical practice” must be considered with caution.
Trans-10,cis-12 conjugated linoleic acid (CLA) induces a G1 cell cycle arrest in HT-29 human colon cancer cells
Authors: Jung H. Park, Han J. Cho, Jae B. Park, Yung H. Choi, Jae-Yong Lee
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3897 

A commercially available mixture of CLA isomers reduces the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine. CLA is a collective term used to denote one or more positional and geometric isomers of octadecadienoic acid with cis -9, trans -11 and trans -10, cis -12 CLA being the principal isomers. Our previous in vitro studies have shown that trans -10, cis -12 CLA inhibited the growth of HT-29 cells, whereas cis -9, trans -11 CLA had no effect on the cell growth. In the present study, to examine the effects of the CLA isomers on cell cycle and cell cycle regulatory proteins, HT-29 cells were treated with various concentrations (0 –4 μM) of the individual CLA isomers. Results from DNA flow cytometric analysis revealed that trans -10, cis -12 CLA induced a G1 arrest, whereas cis -9, trans -11 CLA had no effect on the cell cycle. Western blot analysis of total cell lysates revealed that trans -10, cis -12 CLA did not alter the protein expression of either cyclin A, D, and E or cyclin-dependent kinase (CDK) 2 and 4. However, trans -10, cis -12 CLA substantially increased the protein expression and mRNA accumulation of the CDK inhibitor p21Cip1/WAF1. Trans -10, cis -12 CLA decreased phosphorylated retinoblastoma protein (Rb) levels without any change in total Rb protein levels. In vitro kinase assay by using Histone H1 as a substrate showed that CDK 2 activities were markedly decreased by trans -10, cis -12 CLA. These results indicate that CLA inhibits the growth of colon cancer cells by inducing a G1 cell cycle arrest. Induction of p21Cip1/WAF1 may be one of the mechanisms by which CLA inhibits cell cycle progression in HT-29 cells. Supported by grant No. [R01-1999-000-00166-0 (2003)] from the Basic Research Program of the Korea Science & Engineering Foundation.
LP21 : The macrophage activation markers soluble CD206 And CD163 predict mortality in patients with liver cirrhosis and acute-on-chronic liver failure (ACLF)
Authors: H. Groenbaek, S. Rødgaard-Hansen, N.K. Aagaard, V. Arroyo, S. Moestrup, E. Garcia, H. Vilstrup, H.J. Møller
Journal: Journal of Hepatology (2015)
Similar process exists in general practice
Authors: F A O'Driscoll
Journal: BMJ (1994)

EDITOR,—The proposed two stage NHS complaints procedure1 already, in effect, operates for complaints in general practice. Many practices have in house, informal procedures, and many family health services authorities have informal conciliatory procedures. These broadly equate with stage I of the proposed procedure.14 The proposed stage II or panel review equates with the current formal, service committee procedure. Thus not only have Professor Alan Wilson and his colleagues …