tbuckley/cabot-search huggingface dataset:
Dual level of interactions between calcineurin and PKC-ε in cardiomyocyte stretch
Authors: F VINCENT, N DUQUESNES, C CHRISTOV, T DAMY, J SAMUEL, B CROZATIER
Journal: Cardiovascular Research (2006)

Myocardial stretch activates a number of interconnected pathways including the protein kinase C (PKC) pathway that in turn activates mitogen activated protein kinases (MAPK), leading to gene expression stimulation and ventricular hypertrophy. A role of calcineurin has also been shown during hypertrophy. The goal of our study was to look for a possible interconnection between PKC and calcineurin in myocardial stretch.Neonatal rat cardiomyocytes were cultured for 5 days and a 15% stretch was applied. Expression of MAPK and PKC-epsilon was evaluated by Western blot analysis. The specific role of PKC-epsilon was evaluated by transfection of cardiomyocytes with a specific inhibitor peptide. Calcineurin and PKC-epsilon complex formation and co-localization were evaluated by co-immunoprecipitation and by immunolocalization.The PKC isoform involved in stretch-induced ERK and JNK activations was PKC-epsilon. We show here that calcineurin is also found to be involved in the stretch response and that calcineurin and PKC-epsilon co-operate at 2 levels during stretch. First, stretch-induced translocation of PKC-epsilon from the cytosolic to the membrane fraction was inhibited by calcineurin inhibitors, indicating that calcineurin was necessary for PKC-epsilon activation induced by stretch. A second level of interaction was the formation of a calcineurin-PKC-epsilon complex, which increased during stretch. Immunofluorescent studies indicated that, after stretch, calcineurin and PKC-epsilon were co-localized at the level of the perinuclear membrane. These results may have a major relevance in vivo since we also found similar PKC-epsilon-calcineurin complexes in the phase of thoracic aortic stenosis in rats during which heart failure develops.Calcineurin appears to be necessary for stretch-induced PKC-epsilon activation after which the phosphatase and the kinase are co-localized in a complex at the level of the perinuclear membrane where they may finely regulate the phosphorylation of their target proteins.
SHOX mutations in dyschondrosteosis (Leri-Weill syndrome)
Authors: Valérie Belin, Veronica Cusin, Géraldine Viot, Delphine Girlich, Annick Toutain, Anne Moncla, Michel Vekemans, Martine Le Merrer, Arnold Munnich, Valérie Cormier-Daire
Journal: Nature Genetics (1998)
Changes in synovial tissue Jak-STAT expression in rheumatoid arthritis in response to successful DMARD treatment
Authors: J G Walker, M J Ahern, M Coleman, H Weedon, V Papangelis, D Beroukas, P J Roberts-Thomson, M D Smith
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis (IA). <b>Objective:</b> To examine the effect of successful disease-modifying antirheumatic drug (DMARD) treatment on the expression of Jak-STAT in a cohort of patients with active rheumatoid arthritis. <b>Methods:</b> Synovial tissue biopsy specimens from 16 patients with active rheumatoid arthritis, taken before and after initiation of DMARD treatment, were examined for the presence of janus kinase (Jak)3, signal transducer and activator of transcription (STAT)1, STAT4 and STAT6 expression using immunohistochemistry. <b>Results:</b> Successful treatment with DMARDs results in reduction in STAT1 expression in the lining, and STAT1 and STAT6 in the sublining of rheumatoid arthritis synovial tissue. Although the overall expression of STAT4 and Jak3 was not significantly altered by DMARD treatment, there was a significant reduction in the expression of the STAT4 and Jak3 bright cells, thought to be an activated dendritic cell subpopulation. <b>Conclusion:</b> Results show that Jak3, STAT1, STAT4 expression and STAT6 sublining expression decrease in response to successful treatment of rheumatoid arthritis with standard DMARDs. Therefore, altering the expression of these pathways may represent an alternative treatment option, either through promoting up-regulation of inhibitory pathways, or suppressing inflammatory paths.
Bradykinin Contributes to the Vasodilator Effects of Chronic Angiotensin-Converting Enzyme Inhibition in Patients With Heart Failure
Authors: Fraser N. Witherow, Ahmed Helmy, David J. Webb, Keith A.A. Fox, David E. Newby
Journal: Circulation (2001)

Background Bradykinin, an endogenous vasodilator peptide, is metabolized by ACE. The aims of the present study were to determine the doses of B9340, a bradykinin receptor antagonist, that inhibit vasodilatation to exogenous bradykinin and to assess the contribution of bradykinin to the maintenance of basal vascular tone in patients with heart failure receiving chronic ACE inhibitor therapy. Methods and Results Forearm blood flow was measured using bilateral venous occlusion plethysmography. On three occasions in a double-blind randomized manner, 8 healthy volunteers received intrabrachial infusions of placebo or B9340 (at 4.5 and 13.5 nmol/min). On each occasion, placebo or B9340 was coinfused with bradykinin (30 to 3000 pmol/min) and substance P (4 to 16 pmol/min). B9340 caused no change in basal FBF but produced dose-dependent inhibition of the vasodilatation to bradykinin ( P &lt;0.001) but not substance P. The effects of bradykinin antagonism were studied in 17 patients with NYHA grade II through IV heart failure maintained on chronic ACE inhibitor therapy. Incremental doses of B9340, but not HOE-140, produced a dose-dependent vasoconstriction ( P =0.01). After withdrawal of ACE inhibitor therapy, B9340 produced no significant change in forearm blood flow. After reinstitution of therapy, B9340 again resulted in vasoconstriction ( P &lt;0.03). Conclusions B9340 is a potent and selective inhibitor of bradykinin-induced vasodilatation. Bradykinin does not contribute to the maintenance of basal peripheral arteriolar tone in healthy humans or patients with heart failure but contributes to the vasodilatation associated with chronic ACE inhibitor therapy in patients with heart failure via the B 1 receptor.
Targeting Ceramide Metabolism--a Strategy for Overcoming Drug Resistance
Authors: A. Senchenkov, D. A. Litvak, M. C. Cabot
Journal: JNCI Journal of the National Cancer Institute (2001)

Inherent or acquired drug resistance, which frequently characterizes cancer cells, is caused by multiple mechanisms, including dysfunctional metabolism of the lipid second messenger ceramide. Ceramide, the basic structural unit of the sphingolipids, plays a role in activating cell death signals initiated by cytokines, chemotherapeutic agents, and ionizing radiation. Recent discoveries about the metabolism of ceramide suggest that this agent may have an important influence on the effectiveness of various cancer therapeutics. In particular, the cytotoxic effect of chemotherapy is decreased when generation of ceramide is impaired but is increased when the degradation of ceramide is blocked. Herein, we review the mechanisms of resistance to chemotherapeutic agents in terms of ceramide metabolism.
Transgenic Mouse Model of Ventricular Preexcitation and Atrioventricular Reentrant Tachycardia Induced by an AMP-Activated Protein Kinase Loss-of-Function Mutation Responsible for Wolff-Parkinson-White Syndrome
Authors: Jasvinder S. Sidhu, Yadavendra S. Rajawat, Tapan G. Rami, Michael H. Gollob, Zhinong Wang, Ruiyong Yuan, A.J. Marian, Francesco J. DeMayo, Donald Weilbacher, George E. Taffet, Joanna K. Davies, David Carling, Dirar S. Khoury, Robert Roberts
Journal: Circulation (2004)

We identified a gene (PRKAG2) that encodes the gamma-2 regulatory subunit of AMP-activated protein kinase (AMPK) with a mutation (Arg302Gln) responsible for familial Wolff-Parkinson-White (WPW) syndrome. The human phenotype consists of ventricular preexcitation, conduction abnormalities, and cardiac hypertrophy.
N.H.S. Superannuation Scheme
Authors: R. J. Carr
Journal: BMJ (1971)

1ll carcinoma patients the serum calcium was raised to around the 16 mg/100 ml level and that the classical symptoms of hyper- calcaemia were present; there were no skeletal metastases.It would appear that the low incidence of the hypercalcaemic syndrome in Locks's series and its absence in the Jersey study would tend to support the comments of Drs.von Wichert and Mitchell-Heggs.-Iam, etc.,
RESPONSIVENESS OF GERMFREE MICE IN MIXED LEUKOCYTE CULTURE
Authors: Michael B. Widmer, Paul M. Sondel, Fritz H. Bach
Journal: The Journal of Experimental Medicine (1972)

Conventional (cv) and germfree (gf) mice are able to give a good proliferative response to allogeneic cells in the mixed leukocyte culture (MLC) test, while the response to xenogeneic stimulating cells has been in question. Previous studies by others have suggested only a low MLC response in cv animals and none in gf ones. We have found that both cv and gf animals can give a good MLC response to xenogeneic as well as allogeneic cells. These findings are of importance for our understanding of both MLC stimulation and response.
Sunitinib Acts Primarily on Tumor Endothelium rather than Tumor Cells to Inhibit the Growth of Renal Cell Carcinoma
Authors: Dan Huang, Yan Ding, Yan Li, Wang-Mei Luo, Zhong-Fa Zhang, John Snider, Kristin VandenBeldt, Chao-Nan Qian, Bin Tean Teh
Journal: Cancer Research (2010)

Sunitinib is a broad-spectrum small-molecule inhibitor of receptor tyrosine kinases (RTK) that serves as the present standard of care for first-line therapy of advanced clear cell renal cell carcinoma (ccRCC). A full understanding of the targets and mechanism of action of sunitinib in ccRCC treatment remains incomplete. In this study, we evaluated several tumor cell and endothelial targets of sunitinib and investigated which RTK(s) may specifically contribute to its therapeutic effects. Microarray expression profiling and Western blot analysis revealed that among known sunitinib targets, only platelet-derived growth factor receptor-beta and vascular endothelial growth factor receptor-2 (VEGFR-2) were overexpressed in ccRCCs relative to normal tissues. Sunitinib was unable to inhibit survival or proliferation of ccRCC cells at pharmacologically relevant concentrations (approximately 0.1 micromol/L) that inhibit RTK targets. In contrast, sunitinib inhibited endothelial cell proliferation and motility at the same concentrations by suppressing VEGFR-2 signaling. Moreover, whereas sunitinib inhibited the growth of ccRCC xenograft tumors and decreased tumor microvessel density as soon as 12 hours after treatment, sunitinib showed no significant effects on tumor cell proliferation or apoptosis up to 72 hours after treatment. Our findings indicate that sunitinib inhibits ccRCC growth primarily through an antiangiogenic mechanism and not through direct targeting of ccRCC tumor cells.
SCAI/ACC/AHA Expert Consensus Document: 2014 Update on Percutaneous Coronary Intervention Without On-Site Surgical Backup
Authors: Gregory J. Dehmer, James C. Blankenship, Mehmet Cilingiroglu, James G. Dwyer, Dmitriy N. Feldman, Timothy J. Gardner, Cindy L. Grines, Mandeep Singh
Journal: Circulation (2014)
Double blind, placebo controlled trial of magnesium carbonate in chronic pyrophosphate arthropathy
Authors: M. Doherty, P. A. Dieppe
Journal: Annals of the Rheumatic Diseases (1983)

Unlike the situation with urate crystals in gout, there is at present no definitive treatment to prevent formation or enhance dissolution of CPPD crystals in patients with pyrophosphate arthropathy.In vitro studies, however, have shown that magnesium exerts a solubilising, growth inhibitory effect on CPPD crystals,' and the possibility
STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS
Authors: Oswald T. Avery, James M. Neill
Journal: The Journal of Experimental Medicine (1924)

1. Anaerobically grown pneumococci rapidly form peroxide upon exposure to molecular oxygen. 2. The peroxide-forming activity of pneumococci varies with different strains, and with the age of the cell. 3. Peroxide production by pneumococcus can proceed under conditions of reaction and temperature that do not permit active growth and multiplication of the cell.
Controversial topics in tuberculosis
Authors: J.A. Caminero, A. Torres
Journal: European Respiratory Journal (2004)

Tuberculosis (TB) is certainly the disease that has provoked the most damage to mankind throughout history. It has caused death and disease for perhaps >20,000 yrs 1 and, as a rule, has affected the poorest strata of society. Such a long time of common life with men has endowed Mycobacterium tuberculosis , the causal agent, with the best adaptation among all known human pathogens. Therefore, it has remained in a quiescent state within a large number of individuals, generating neither symptoms nor disease, but surviving and awaiting more suitable conditions to attack 2. Today, it isestimated that one-third of the global population, around 2,000 million people 3, lives with this microorganism, knownas Koch's bacillus, and represents the largest reservoirof healthy, infected carriers for any given infectious disease. It is disconcerting that, at the onset of a new millennium and after so numerous and significant developments of the last century, one has to admit that TB remains the major infectious disease by the number of healthy infectedpersons in the …
Bronchial fistulae in ARDS patients: management with an extracorporeal lung assist device
Authors: M. Hommel, M. Deja, V. von Dossow, K. Diemel, C. Heidenhain, C. Spies, S. Weber-Carstens
Journal: European Respiratory Journal (2008)

Patients with bronchial tree lesions feature, in particular, a high risk for developing bronchial fistulae after surgical repair when the clinical situation is complicated by acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mechanical ventilation is needed. The current authors hypothesised that extracorporeal carbon dioxide removal would significantly decrease inspiratory airway pressures, thus promoting the protection of surgical bronchial reconstruction. Four patients were studied after surgical reconstruction of bronchial fistulae in whom ALI/ARDS developed and mechanical ventilation with positive end-expiratory pressure was required. Gas exchange, tidal volumes, airway pressures, respiratory frequency, vasopressor and sedation requirements were analysed before and after initiation of a pumpless extracorporeal lung assist device (pECLA; NovaLung®, Talheim, Germany). Initiation of pECLA treatment enabled a reduction of inspiratory plateau airway pressures from 32.4 to 28.6 cmH 2 O (3.2 to 2.8 kPa), effectively treated hypercapnia (from 73.6 to 53.4 mmHg (9.8 to 7.1 kPa)) and abolished respiratory acidosis (from pH 7.24 to 7.41). All patients survived and were discharged to rehabilitation clinics. In patients after surgical bronchial reconstruction that was complicated by acute lung injury/acute respiratory distress syndrome, use of pumpless extracorporeal carbon dioxide removal was safe and efficient. Initiation of a pumpless extracorporeal lung assist device enabled a less invasive ventilator management, which may have contributed to healing of surgical bronchial repair.
STELLATE GANGLION INFILTRATION IN ORGANIC PSYCHOSES OF LATE LIFE
Authors: JOSEPH HABER
Journal: American Journal of Psychiatry (1955)

The results of stellate ganglion infiltration in 8 patients, suffering from psychosis with cerebral arteriosclerosis or senile psychosis, are discussed. The rationale of this treatment is presented and a number of papers dealing with the effect of this method are briefly reviewed. Six patients who were in an advanced state of organic mental deterioration showed only temporary or moderate improvement. Two patients in the early phase of senile organic psychosis showed marked improvement. One remains improved to date (1 year after completion of treatment), while the improvement of the other patient lasted for 3 months. The tentative conclusions arrived at were that while stellate ganglion infiltration is not of great benefit to patients in the advanced stages of senile psychoses it seems to have good results in patients in the early phase of psychoses of late life. Although we had only 2 cases in this group, the results seem encouraging enough to explore the value of stellate ganglion infiltration in such patients. The technique used is simple and complications did not occur.
Regression of idiopathic thrombocytopenic purpura after endoscopic mucosal resection of gastric mucosa associated lymphoid tissue lymphoma
Authors: M Noda, N Mori, K Nomura, K Kojima, S Mitsufuji, I Yamane, S Misawa, T Okanoue
Journal: Gut (2004)

Recent reports have suggested an association between Helicobacter pylori infection and both gastric mucosa associated lymphoid tissue (MALT) lymphoma and thrombocytopenic purpura. Although treatments eradicating H pylori lead to regression of these diseases in some cases, the exact mechanisms are still controversial. This case report describes a patient with thrombocytopenic purpura accompanied by an early stage gastric MALT lymphoma. Endoscopic mucosal resection of the lesion in this patient led to dramatic regression of thrombocytopenic purpura, and t(11;18)(q21;q21), which means resistance more likely to H pylori eradication therapy, was confirmed by fluorescence in situ hybridisation. There is no evidence of recurrence and his platelet count is within normal limits after 24 months of follow up. This is the first case report describing regression of thrombocytopenic purpura after mucosal resection of a gastric MALT lymphoma. We suggest that while some cases of thrombocytopenic purpura may be induced by H pylori, others may be due to an autoreactive antibody produced by MALT lymphoma B cells.
Phase II study of cilengitide in the treatment of refractory or relapsed high-grade gliomas in children: A report from the Children's Oncology Group
Authors: T. J. MacDonald, G. Vezina, C. F. Stewart, D. Turner, C. R. Pierson, L. Chen, I. F. Pollack, A. Gajjar, M. W. Kieran
Journal: Neuro-Oncology (2013)

Cilengitide, an αv integrin antagonist, has demonstrated activity in recurrent adult glioblastoma (GBM). The Children's Oncology Group ACNS0621 study thus evaluated whether cilengitide is active as a single agent in the treatment of children with refractory high-grade glioma (HGG). Secondary objectives were to investigate the pharmacokinetics and pharmacogenomics of cilengitide in this population. Cilengitide (1800 mg/m2/dose intravenous) was administered twice weekly until evidence of disease progression or unacceptable toxicity. Thirty patients (age range, 1.1–20.3 years) were enrolled, of whom 24 were evaluable for the primary response end point. Toxicity was infrequent and mild, with the exception of one episode of grade 2 pain possibly related to cilengitide. Two intratumoral hemorrhages were reported, but only one (grade 2) was deemed to be possibly related to cilengitide and was in the context of disease progression. One patient with GBM received cilengitide for 20 months and remains alive with continuous stable disease. There were no other responders, with median time to tumor progression of 28 days (range, 11–114 days). Twenty-one of the 24 evaluable patients died, with a median time from enrollment to death of 172 days (range, 28–325 days). The 3 patients alive at the time of this report had a follow-up time of 37, 223, and 1068 days, respectively. We conclude that cilengitide is not effective as a single agent for refractory pediatric HGG. However, further study evaluating combination therapy with cilengitide is warranted before a role for cilengitide in the treatment of pediatric HGG can be excluded.
Perineal massage in labour and prevention of perineal trauma: randomised controlled trial
Authors: G. Stamp
Journal: BMJ (2001)

To determine the effects of perineal massage in the second stage of labour on perineal outcomes.Randomised controlled trial.At 36 weeks' gestation, women expecting normal birth of a singleton were asked to join the study. Women became eligible to be randomised in labour if they progressed to full dilatation of the cervix or 8 cm or more if nulliparous or 5 cm or more if multiparous. 1340 were randomised into the trial.Massage and stretching of the perineum during the second stage of labour with a water soluble lubricant.rates of intact perineum, episiotomies, and first, second, third, and fourth degree tears.pain at three and 10 days postpartum and pain, dyspareunia, resumption of sexual intercourse, and urinary and faecal incontinence and urgency three months postpartum.Rates of intact perineums, first and second degree tears, and episiotomies were similar in the massage and the control groups. There were fewer third degree tears in the massage group (12 (1.7%) v 23 (3.6%); absolute risk 2.11, relative risk 0.45; 95% confidence interval 0.23 to 0.93, P<0.04), though the trial was underpowered to measure this rarer outcome. Groups did not differ in any of the secondary outcomes at the three assessment points.The practice of perineal massage in labour does not increase the likelihood of an intact perineum or reduce the risk of pain, dyspareunia, or urinary and faecal problems.
B-Type Natriuretic Peptide in Type 2 Diabetes
Authors: Liu Chung, Agnès Georges, Jean Benoit Corcuff, Laurence Bordenave, Henri Gin, Vincent Rigalleau
Journal: Diabetes Care (2005)

Cardiac ventricles release B-type natriuretic peptide (BNP) in response to volume expansion and pressure overload; therefore, BNP concentration may be used as a biochemical marker of cardiac failure (1). BNP levels are high in diabetic subjects with left ventricular dysfunction (2). Because the diagnosis of cardiac failure may be an emergency (3), it is important to know whether the timing of BNP measurement (before or after a meal) affects the result. The effect of renal failure is also an important practical issue, since 25–40% of diabetic subjects have diabetic nephropathy. This study was designed to …
Standardization of the Chromium-51 Release, Cell-Mediated Cytotoxicity Assay: Cryopreservation of Mouse Effector and Target Cells2
Authors: Howard T. Holden, Robert K. Oldham, John R. Ortaldo, Ronald B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1977)

Utilizing controlled cryopreservation techniques, we were able to standardize the 51Cr release cytotoxicity assay and thereby ensured reliable comparisons between results obtained on different days. Optimal conditions for freezing of both effector and target cells were quite similar. Dimethyl sulfoxide (DMSO) at a concentration of 7.5-10.0% was employed as the cryoprotective agent and cells were frozen at the rate of -1 degrees C/minute. The handling procedures for the cells before and after freezing were important. Factors affecting recovery of functional reactivity were related to toxicity of DMSO for the cells, the osmotic stress placed upon the cells as the DMSO was being removed after thawing, the handling temperature of the freshly thawed cells, and the susceptibility of cells to mechanical damage immediately after thawing. The recovery of lymphocytes after freezing was about 70%; the recovery of cytotoxicity was around 85%. Syngeneic cytotoxic reactivity induced by inoculation with the Moloney strain of murine sarcoma virus was cryopreserved, as were allogeneic cytotoxicity and natural cytotoxic reactivity. Multiple tests employing effector cells from the same frozen pool gave reproducible results; the standard error of the mean percent cytotoxicity was less than 1.5%. Cryopreserved target cells gave decreased day-to-day variability in susceptibility to lysis, since the same population of cells could be employed in each assay. These results demonstrated conclusively that we can now have a constant source of effector cells and target cells, which can be used from assay to assay as an internal standard.