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MMC
Selected AbstractsIndirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorptionACTA PHYSIOLOGICA, Issue 2 2009A. Bajor Abstract Aim:, The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III-generated voltage was related to the degree of BAM quantified by the 75SeHCAT test. Methods:, We used a multi-channel intestinal infusion system to simultaneously measure jejunal pressure and PD. Saline passing calomel half-cells was infused into the jejunum and subcutaneously. Pressure and PD were recorded in the fasting state and after a test meal. Results:, In the absence of motor activity, jejunal PD was not significantly different from zero in either group. During MMC phase III, PD reached significantly higher mean and peak levels in BAM patients. The product of MMC phase III length multiplied by voltage, over 3 h, was also significantly higher in BAM patients (controls: median 307 mV × cm, range 70,398; BAM: median 511, range 274,2271, P < 0.01). This value was also significantly correlated with the degree of BAM as reflected by the 75SeHCAT test (P < 0.05). Conclusion:, Phase III induced jejunal secretion may be upregulated in BAM patients, resulting in overload of colonic reabsorption capacity. [source] Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probeENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2003S.M. Attia Abstract The topoisomerase II (topo II) inhibitors etoposide (VP-16) and merbarone (MER) were investigated with the in vivo micronucleus test (MN test) combined with fluorescence in situ hybridization (FISH) using the mouse minor satellite DNA probe to discriminate MN of clastogenic and aneugenic origin. All experiments were performed with male (102/ElxC3H/El) F1 mice bred in the mouse colony of the GSF Research Center. The sample size per experimental group was five animals and 2,000 polychromatic erythrocytes (PCE) were scored per animal from coded slides in the conventional MN test. A separate set of coded slides was used for the FISH analysis. All treatments consisted of single intraperitoneal injections. Colchicine (COL, 3 mg/kg) and mitomycin (MMC, 1 mg/kg) were used as a positive control aneugen and clastogen, respectively, and these compounds produced the expected responses. A dose of 1 mg/kg VP-16 induced 3.44% MNPCE (compared to the concurrent solvent control of 0.37%, P < 0.001) and of these 39.9% (1.4% MNPCE) showed one or more fluorescent signals. MER (7.5,60 mg/kg) increased the MNPCE frequencies in a dose-dependent manner, with 15 mg/kg being the lowest positive dose. At the highest dose of 60 mg/kg of MER, a total of 4.26% MNPCE were found (compared to 0.31% in the concurrent solvent control, P < 0.001) and of these 46.2% (2.0% MNPCE) contained one or more fluorescent signals. The data demonstrate that VP-16 and MER induced both clastogenic and aneugenic events despite their different modes of topo II inhibition. Environ. Mol. Mutagen. 41:99,103, 2003. © 2003 Wiley-Liss, Inc. [source] Micronuclei and chromatid buds are the result of related genotoxic eventsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2001Luis Serrano-García Abstract Chromatin buds (CHB), broken eggs, or budding cell nuclei are structures similar to micronuclei (MN) in shape, structure, and size, which are linked to the main nuclei of cells by a thread or stalks of chromatin. They have been observed in numerous cell types and there are reports of their existence relating them with MN or with genotoxic events. However, there is no systematic study reporting their frequency and no experiment has been done to ascertain whether they are really induced by genotoxins. Furthermore, they have been discarded as genotoxic events with the argument that they are not formed in dividing cells. Studies are presented here that indicate that CHB can be considered as genotoxic events and that their origin is comparable to that of MN. Bromodeoxyuridine (BrdU) was used to label proliferating lymphocytes, which were later identified by means of an immunohistochemical method, using the H2O2,DAB stain. The results show that CHB are consistently formed where MN are seen. CHB were induced by the clastogen mitomycin C (MMC) as well as by the aneuploidogen colcemid, with frequencies similar to MN in both cases, and to multinucleated cells in the case of colcemid. CHB occur in lymphocytes of smokers with frequencies similar to those of MN, and we found that the infection with Taenia solium metacestodes induced a comparable increase of both MN and CHB frequency in lymphocytes from pigs. Environ. Mol. Mutagen. 38:38,45, 2001 © 2001 Wiley-Liss, Inc. [source] A salvage treatment for solid liver metastasis after radical resection of Klatskin tumourHPB, Issue 4 2003Yuji Nakagawa Background Long-term survival has not been described following surgical resection for liver metastasis after radical resection of an advanced hilar bile duct carcinoma (Klatskin tumour). One such patient who developed liver metastasis after radical treatment for stage IVA (pTNM) hilar cholangiocarcinoma has survived 5.5 years after resection of the liver metastasis followed by chemotherapy. Case report A 50-year-old man developed a solid liver metastasis in segment VIII 17 months after radical resection of a stage IVA (pT3 pN1 M0) Klatskin tumour followed by postoperative radiotherapy (54 Gy) and systemic chemotherapy (oral UFT 450 mg/day plus intravenous cisplatin 20 mg on 5 consecutive days each month). The patient is alive at 7 years after the primary resection followed by resection of the liver metastasis plus further systemic chemotherapy comprising oral UFT combined with intravenous adriamycin (ADM) and mitomycin C (MMC). Conclusion Aggressive salvage resection surgery can be an effective component of a multidisciplinary treatment regimen, even for a postoperative liver metastasis that developed after radical resection of an advanced Klatskin tumour, provided that the metastasis is solid and has not failed local-regional control. [source] Modelling the behaviour of an embankment on soft clay with different constitutive modelsINTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 10 2006M. Karstunen Abstract The paper investigates the effect of constitutive models on the predicted response of a simplified benchmark problem, an embankment on soft soil. The soft soil is assumed to have the properties of POKO clay from Finland and five different constitutive models are used to model the deposit. Two of the models are isotropic models, i.e. the Modified Cam Clay model and the Soft-Soil model. The other models are recently proposed constitutive models that account for plastic anisotropy. The S-CLAY1 and S-CLAY1S models are embedded in a standard elasto-plastic framework and account for anisotropy via a rotational hardening law. In addition, the S-CLAY1S model accounts for bonding and destructuration. In contrast, the Multilaminate Model for Clay (MMC) accounts for plastic anisotropy by utilizing so-called multilaminate framework. The results of numerical simulations show that accounting for anisotropy results in notable differences in the predicted settlements and horizontal movements compared to the predictions using the isotropic models. There are also significant differences in the K0 predictions by the different constitutive models and this has a significant impact on the results. Copyright © 2006 John Wiley & Sons, Ltd. [source] Circulation dynamics of Mediterranean precipitation variability 1948,98INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 15 2003A. Dünkeloh Abstract Canonical correlation analysis is used to identify main coupled circulation,rainfall patterns and to relate recent variability and trends of Mediterranean precipitation to large-scale circulation dynamics. Analyses are based on geopotential heights (500 and 1000 hPa levels) for the North Atlantic,European area (National Centers for Environmental Prediction,National Center for Atmospheric Research reanalysis) and on highly resolved (0.5° × 0.5° ) monthly rainfall grids (Climatic Research Unit, Norwich) selected for the Mediterranean area during the 1948,98 period. Combining monthly analyses with similar characteristics to seasonal samples yields winter (October,March), spring (April,May) and summer (June,September) types of coupled variability; a particular autumn type for the whole Mediterranean does not occur on the monthly time scale. Coupled patterns specifically linked to one or two seasons include an east Atlantic jet (EA-Jet) related pattern for summer and a Mediterranean meridional circulation (MMC) pattern for winter and spring. The most important pattern recurring with dynamical adjustments throughout the whole year reflects the seasonal cycle of the Mediterranean oscillation (MO), which is linked (with seasonal dependence) to the Northern Hemisphere teleconnection modes of the Arctic oscillation (AO) and North Atlantic oscillation (NAO). Winter rainfall trends of the recent decades marked by widespread decreases in the Mediterranean area and by opposite conditions in the southeastern part are linked to particular changes over time in several of the associated circulation patterns. Thus, different regional rainfall changes are integrated into an overall interrelation between Mediterranean rainfall patterns and large-scale atmospheric circulation dynamics. Copyright © 2003 Royal Meteorological Society [source] Prophylactic intravesical instillation of mitomycin C and cytosine arabinoside for prevention of recurrent bladder tumors following surgery for upper urinary tract tumors: A prospective randomized studyINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2001Naotaka Sakamoto Abstract Background: A recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract is not rarely observed. A prospective randomized study was conducted to examine the significance of prophylactic intravesical instillation of mitomycin C (MMC) and cytosine arabinoside (Ara-C) to prevent recurrent bladder tumors after surgery for superficial transitional cell carcinoma of the upper urinary tract. Methods: The patients were randomized into an instillation group, who received postoperative intravesical instillation of MMC (20 mg) and Ara-C (200 mg) 28 times over a period of 2 years, and a non-instillation group. The non-recurrence rate was then compared between the groups. Results: Of the 27 patients registered, 25 patients (13 with instillation and 12 without instillation) were able to be evaluated, with a median follow-up period of 45 months. The non-recurrence rate of bladder tumors in the instillation group was higher than that in the non-instillation group. Although the difference was not statistically significant, the P -value (P = 0.079) demonstrated a strong trend. When any possible bias was allowed for a multivariate analysis, the difference was almost significant (P = 0.0567). No patients withdrew from this study due to any side-effects. Conclusion: The postoperative instillation of MMC and Ara-C may be a useful approach for reducing the recurrence of bladder tumors after surgery for upper urinary tract tumors. [source] Effects of a 5-HT3 antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imagingALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010L. Marciani Aliment Pharmacol Ther 2010; 32: 655,663 Summary Background, 5-HT3 antagonists have been shown to be effective in relieving the symptoms of irritable bowel syndrome with diarrhoea (IBS-D). Using a recently validated magnetic resonance imaging (MRI) method, we have demonstrated reduced fasting small bowel water content (SBWC) in IBS-D associated with accelerated small bowel transit. We hypothesized that slowing of transit with ondansetron would lead to an increase in SBWC by inhibiting fasting motility. Aim, To assess the effects of ondansetron compared with placebo in healthy volunteers on SBWC and motility in two different groups of subjects, one studied using MRI and another using manometry. Methods, Healthy volunteers were given either a placebo or ondansetron on the day prior to and on the study day. Sixteen volunteers underwent baseline fasting and postprandial MRI scans for 270 min. In a second study, a separate group of n = 18 volunteers were intubated and overnight migrating motor complex (MMC) recorded. Baseline MRI scans were carried out after the tube was removed. Results, Fasting SBWC was markedly increased by ondansetron (P < 0.0007). Ondansetron reduced the overall antroduodenal Motility Index (P < 0.04). The subjects who were intubated had significantly lower fasting SBWC (P < 0.0002) compared with the group of subjects who were not intubated. Conclusions, The 5-HT3 receptor antagonism increased fasting small bowel water. This was associated with reduced fasting antroduodenal Motility Index which may explain the clinical benefit of such drugs. [source] The influence of citalopram on interdigestive gastrointestinal motility in manALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010P. Janssen Aliment Pharmacol Ther 2010; 32: 289,295 Summary Background, Administration of 5-hydroxytryptamine (5HT) and selective 5HT receptor ligands modifies interdigestive motility in animals and in man. Aim, To study the effect of citalopram, a selective 5-HT reuptake inhibitor, on interdigestive motility in man. Methods, In 20 healthy subjects, antroduodenojejunal motor activity was studied manometrically. Basal interdigestive motor activity was recorded until the passage of two activity fronts. Ten minutes after the second activity front, placebo or 20 mg of citalopram was administered intravenously in a double-blind randomized fashion. Recording continued until the passage of two more activity fronts had occurred. Results, Administration of citalopram induced a premature small intestinal phase 3 after 35 ± 6.4 min, compared to 120 ± 17 min after placebo P < 0.01. Citalopram shortened MMC cycle length at the expense of phase 1 and phase 2 and significantly increased the motility index during phase 2 in the antrum and the small intestine. Conclusions, In the interdigestive state in man, intravenous administration of the selective 5-HT reuptake inhibitor citalopram induces a premature intestinal phase 3 and suppresses gastric activity fronts. Phase 2 motility is stimulated both in the stomach and in the small bowel after citalopram. These data suggest that 5HT is involved in the control of interdigestive motility. [source] Development of High Strength Magnesium Based MMC Reinforced with SiC Particles for Satellite Structure ApplicationsMATERIALWISSENSCHAFT UND WERKSTOFFTECHNIK, Issue 4 2003B. Landkof Abstract The appearance of Metal Matrix Composites has opened a new area in structural design. The possibility of tailoring mechanical properties of structural metals reinforced with particles or fibers into specific spacecraft applications is very appealing. This paper deals with such a MMC, which is based on a magnesium alloy matrix and SiC reinforcement. The technology used is a commercial semi-solid die-casting, which promises a cost-effective solution. The results of the first stage of this research are discussed with a focus on the satellite structure design application. The next steps of this investigation are also presented. [source] Providers and Staff Respond to Medicaid Managed Care: The Unintended Consequences of Reform in New MexicoMEDICAL ANTHROPOLOGY QUARTERLY, Issue 1 2005LOUISE LAMPHERE In 1997 a new Medicaid managed care (MMC) program called Salud! was implemented by the State of New Mexico. This article serves as an introduction to a special issue of Medical Anthropology Quarterly that assesses the unintended consequences of this reform and its impact on providers and staff who work in clinics, physician offices, and emergency rooms where Medicaid patients are served. MMC fused state and corporate bureaucracies, creating a complex system where enrollment and access was difficult. The special issue focuses on providers' responses to these new structures, including ways in which staff buffer the impact of reform and the role of the discourses of medical necessity and accountability in shaping the way in which MMC functions. [source] De Facto Disentitlement in an Information Economy: Enrollment Issues in Medicaid Managed CareMEDICAL ANTHROPOLOGY QUARTERLY, Issue 1 2005LESLIE LÓPEZ This article discusses enrollment issues in New Mexico's Medicaid managed care (MMC) system and seeks to illuminate reasons for persistent problems reported by workers and clients. It argues that between 1997 and 2000, the MMC and welfare reforms raised enrollment barriers by complicating and dehumanizing the system, thus "technically disenfranchising" workers and clients. Specifically, the new system increased the need for professional, in-person enrollment assistance precisely when the state decreased its provision of it. Some aspects of the State Child Health Insurance Program (SCHIP) reforms indirectly aggravated those same problems, and though they also significantly lowered barriers in some areas, overall the new system was plagued with preexisting barriers as well as new, unmet needs that produced "de facto disentitlement" to health services. [source] Long-term ethanol exposure causes human liver cancer cells to become resistant to mitomycin C treatment through the inactivation of bad-mediated apoptosis,MOLECULAR CARCINOGENESIS, Issue 8 2010Ching-Shui Huang Abstract The aim of this study was to test whether long-term ethanol consumption confers therapeutic resistance to human liver cancer patients infected with hepatitis B virus (HBV). Chronic ethanol-treated cells were established by consecutively culturing a human hepatocellular carcinoma cell line, Hep 3B, which contains integrated HBV sequences, for 20,40 passages with or without 10,mM ethanol (designated as E20,E40 and C20,C40, respectively). Flow cytometry analysis demonstrated that a growth promoting effect of long-term ethanol treatment was induced in the E40 cells through preferential acceleration of S-phase in these cells. Lower protein expression levels of p16, p21/Cip1, and p27/Kip1 were detected in the ethanol-treated E40 cells. We further demonstrated that long-term ethanol-treated E40 cells develop drug resistance in response to mitomycin C (MMC) treatment (>8,µM). Immunoblot analysis revealed that caspase-8-mediated mitochondrial apoptotic signals (such as Bad) were inactivated in the MMC-resistant E40 cells. Immunoprecipitation experiments demonstrated that the sequestration of phosphorylated Bad (Ser-112) through its binding with 14-3-3 was detected more profoundly in the MMC-resistant E40 cells. Next, we examined the therapeutic efficacy of MMC (10,mg MMC/kg body weight, three times per week) in severe combined immunodeficient (SCID) mice bearing E40- and C40-xenografted tumors. Significant reductions (>3-fold) in tumor growth were detected in MMC-treated C40-xenografted mice. In vivo and in vitro studies demonstrated that AKT- and extracellular signal-regulated kinase (ERK)-mediated survival factors inhibited the Bad-induced mitochondrial apoptotic signals that were involved in E40 tumor cells and that conferred resistance to MMC. © 2010 Wiley-Liss, Inc. [source] Alterations of intestinal motor responses to various stimuli after Nippostrongylus brasiliensis infection in rats: role of mast cellsNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2000J. Gay Nippostrongylus brasiliensis infection induces jejunal mastocytosis associated with enteric nerve remodelling in rats. The aim of this study was to evaluate the intestinal motility responses to meals and to neurotransmitters involved in the control of gut motility (acetylcholine (carbachol), substance P and neurokinin A) in both control and N. brasiliensis -infected rats 30 days post-infection. All rats were equipped with NiCr electrodes in the jejunum to record myoelectrical activity. The duration of disruption of the jejunal migrating myoelectrical complexes (MMC) induced by the different stimuli was determined. Meal ingestion and substance P administration disrupted the MMC pattern for similar durations in the two groups. Carbachol and neurokinin A induced a significantly longer MMC disruption in post-infected rats than in controls (125 ± 8.3 vs. 70 ± 6 min for carbachol 100 ,g kg,1 and 51 ± 4 vs. 40 ± 2 for neurokinin A 50 ,g kg,1). The enhanced motor response in postinfected rats was reduced by previous mast cell stabilization with ketotifen or mast cell degranulation with compound BrX 537 A. In conclusion, the increased intestinal motor reactivity to carbachol and neurokinin A in post- N. brasiliensis -infected rats depends upon intestinal mast cell hyperplasia and degranulation. [source] Chemokine and cytokine expression in murine intestinal epithelium following Nippostrongylus brasiliensis infectionPARASITE IMMUNOLOGY, Issue 2 2002Anne Rosbottom Summary Infection of mice with the nematode parasite Nippostrongylus brasiliensis results in a well characterized intestinal mastocytosis with intraepithelial migration of mucosal mast cells (MMC). The molecules mediating this response are unknown. We examined expression of several putative mast cell chemoattractants in intestinal epithelium following N. brasiliensis infection. Expression of the chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1,(MIP-1,), RANTES (regulated on activation normal T-cell expressed and secreted), fractalkine, and thymocyte expressed chemokine (TECK); and the cytokines stem cell factor (SCF) and transforming growth factor ,1 (TGF,1), was constitutive and no alteration was detected following infection. MCP-1 expression was also constitutive but at much lower levels and increased expression was detected on days 7 and 14 postinfection. Expression of MCP-1 in whole jejunum was at much higher levels than in epithelium. Constitutive expression of MCP-1, MIP-1, and TGF,1 was also detected in cultured bone marrow-derived homologues of MMC. In an intestinal epithelial cell line (CMT-93), there was constitutive expression of SCF, TGF,1, fractalkine and MCP-1. The results show that, in vivo, epithelium is a potentially important source of mast cell chemoattractants. [source] Evaluation of antioxidant and antimicrobial properties of Soymida febrifuga leaf extractsPHYTOTHERAPY RESEARCH, Issue 7 2008Boreddy Srinivas Reddy Abstract The present study was designed to evaluate the antioxidant and antimicrobial properties of hexane (LH), methanol (LM) and aqueous (LA) extracts of Soymida febrifuga (Maliaceae) leaves, which is a traditional folk medicine in India. No pharmacological evaluation of this plant (except antiplasmodial activity) has been reported to date. Antioxidant activity of different extracts was evaluated by DPPH free radical scavenging activity, taking total phenolic content (TPC) as an index. Antimicrobial activity was tested against six bacterial and five fungal strains using the agar hole diffusion method and the minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) were determined for all the test organisms against the extracts. The results showed that the methanol and aqueous extracts of leaf had a higher antioxidant activity and total phenolic content than the hexane extract. The antioxidant activity and TPC of the extracts were highly correlated. Extracts also showed several degrees of antimicrobial activity against different microbes. The methanol extract was more potent against Aspergillus fumigatus and Candida tropicana. The lowest MIC values obtained for LM, LA and LH were 78, 156, 625 µg/mL against A. fumigatus, C. tropicana and C. albicans, respectively. Hence, this study confirms that Soymida febrifuga leaves possess potent antioxidant and antimicrobial activity. Copyright © 2008 John Wiley & Sons, Ltd. [source] Determination of total urinary mercury by on-line sample microwave digestion followed by flow injection cold vapour inductively coupled plasma mass spectrometry or atomic absorption spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2002M. Bettinelli The total mercury content in urine was determined by inductively coupled plasma mass spectrometry with the so-called cold vapour method after on-line oxidative treatment of the sample in a microwave oven (FI-MW-CV-ICPMS). Use of a KBr/KBrO3 mixture, microwave digestion, and the final oxidation with KMnO4, assure the complete recovery of the organic forms of Hg which would be difficult to determine otherwise if using only the CV-ICPMS apparatus. Quantitative recoveries were obtained for phenyl Hg chloride (PMC), dimethyl Hg (DMM), Hg acetate (MA) and methyl Hg chloride (MMC). Use of automatic flow injection microwave systems (FI-MW) for sample treatment reduces environmental contamination and allows detection limits suitable for the determination of reference values. Since no certified reference materials were commercially available in the concentration ranges of interest, the accuracy of the proposed procedure has been assessed by analysing a series of urine samples with two independent techniques, ICP-MS and AAS. When using the FI-MW-CV-ICP-MS technique, the detection limit was assessed at 0.03µg/L Hg, while with FI-MW-CV-AAS it was 0.2µg/L Hg. The precision of the method was less than 2,3% for FI-MW-CV-ICP-MS and about 3,5% for FI-MV-CV-AAS at concentrations below 1µg/L Hg. These results show that ICP-MS can be considered as a "reference technique" for the determination of total urinary Hg at very low concentrations, such as are present in non-exposed subjects. Copyright © 2002 John Wiley & Sons, Ltd. [source] Synchronization of enteric neuronal firing during the murine colonic MMCTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Nick J. Spencer DiI (1,1,didodecyl-3,3,3,,3,-tetramethylindocarbecyanine perchlorate) retrograde labelling and intracellular electrophysiological techniques were used to investigate the mechanisms underlying the generation of spontaneously occurring colonic migrating myoelectric complexes (colonic MMCs) in mice. In isolated, intact, whole colonic preparations, simultaneous intracellular electrical recordings were made from pairs of circular muscle (CM) cells during colonic MMC activity in the presence of nifedipine (1,2 ,m). During the intervals between colonic MMCs, spontaneous inhibitory junction potentials (IJPs) were always present. The amplitudes of spontaneous IJPs were highly variable (range 1,20 mV) and occurred asynchronously in the two CM cells, when separated by 1 mm in the longitudinal axis. Colonic MMCs occurred every 151 ± 7 s in the CM and consisted of a repetitive discharge of cholinergic rapid oscillations in membrane potential (range: 1,20 mV) that were superimposed on a slow membrane depolarization (mean amplitude: 9.6 ± 0.5 mV; half-duration: 25.9 ± 0.7 s). During the rising (depolarizing) phase of each colonic MMC, cholinergic rapid oscillations occurred simultaneously in both CM cells, even when the two electrodes were separated by up to 15 mm along the longitudinal axis of the colon. Smaller amplitude oscillations (< 5 mV) showed poor temporal correlation between two CM cells, even at short electrode separation distances (i.e. < 1 mm in the longitudinal axis). When the two electrodes were separated by 20 mm, all cholinergic rapid oscillations and IJPs in the CM (regardless of amplitude) were rarely, if ever, coordinated in time during the colonic MMC. Cholinergic rapid oscillations were blocked by atropine (1 ,m) or tetrodotoxin (1 ,m). Slow waves were never recorded from any CM cells. DiI labelling showed that the maximum projection length of CM motor neurones and interneurones along the bowel was 2.8 mm and 13 mm, respectively. When recordings were made adjacent to either oral or anal cut ends of the colon, the inhibitory or excitatory phases of the colonic MMC were absent, respectively. In summary, during the colonic MMC, cholinergic rapid oscillations of similar amplitudes occur simultaneously in two CM cells separated by large distances (up to 15 mm). As this distance was found to be far greater than the projection length of any single CM motor neurone, we suggest that the generation of each discrete cholinergic rapid oscillation represents a discreet cholinergic excitatory junction potential (EJP) that involves the synaptic activation of many cholinergic motor neurones simultaneously, by synchronous firing in many myenteric interneurones. Our data also suggest that ascending excitatory and descending inhibitory nerve pathways interact and reinforce each other. [source] Expression and role of E-cadherin and CD103,7 (,E,7 integrin) on cultured mucosal-type mast cells,APMIS, Issue 2 2005TATSUYA TEGOSHI Mucosal-type mast cells (MMC) in the respiratory and/or gut epithelium play pivotal roles in the development of allergic inflammation and nematode clearance. To determine the role of E-cadherin and ,E,7 integrin in MMC localization to the epithelium, we analyzed the epithelial binding of two types of mouse bone marrow-derived mast cells: S3-BMMC, which developed in medium containing stem cell factor (SCF) plus IL-3, and S39T-BMMC, which developed with SCF, IL-3, IL-9 and TGF-,1. The latter cells were more similar to mature MMC than the former in terms of mouse mast cell protease (mMCP)-1 expression. FACS analyses revealed that S3-BMMC expressed E-cadherin and ,7 integrin but not ,E integrin, whereas S39T-BMMC expressed ,E,7 integrin as well as E-cadherin. Mn2+ promoted adhesion of S39T-BMMC to the monolayer of E-cadherin+F9 cells. The adhesion was suppressed significantly by the combined addition of blocking antibodies against integrin ,E and E-cadherin, whereas either blocking antibody alone failed to do so. S3-BMMC adhesion was suppressed by E-cadherin blocking antibody but not by ,E blocking antibody. These results suggested that E-cadherin and ,E,7 integrin, which are expressed on MMC-analog S39T-BMMC, play an important role in mast cell-epithelial cell interaction through homophilic as well as heterophilic binding to the epithelial E-cadherin molecule. [source] Breaking T cell tolerance against self type II collagen in HLA,DR4,transgenic mice and development of autoimmune arthritisARTHRITIS & RHEUMATISM, Issue 7 2010Tsvetelina Batsalova Objective To establish a new animal model in DRB1*0401 (DR4),transgenic mice in which T cell tolerance to self type II collagen (CII) can be broken and allow for the development of autoimmune arthritis, to investigate the role of posttranslational modifications of the CII259,273 epitope in the induction and breaking of tolerance of DR4-restricted T cells, and to characterize DR4-restricted T cell recognition of the immunodominant CII259,273 epitope. Methods DR4-transgenic mice expressing either the entire human CII protein (HuCII) or only the immunodominant T cell epitope of heterologous CII (MMC) in joint cartilage were established on different genetic backgrounds, and susceptibility to collagen-induced arthritis (CIA) was tested. Results HuCII mice displayed stronger T cell tolerance to heterologous CII than did MMC mice. On the B10 background, arthritis developed only in MMC mice with a defective oxidative burst. However, MMC mice on the C3H background were susceptible to arthritis also with a functional oxidative burst. Significant recall responses in tolerized mice were detected only against the nonglycosylated CII259,273 epitope. Recognition of the CII259,273 epitope was heterogeneous, but the majority of T cells in DR4 mice specifically recognized the nonglycosylated side chain of lysine at position 264. Conclusion It is possible to break tolerance to self CII and induce arthritis in DR4 mice. However, arthritis susceptibility is tightly controlled by the genetic background and by the source of the transgenic element for expressing the heterologous CII peptide as a self CII protein in the joint. In contrast to CIA in Aq -expressing mice, the nonglycosylated CII259,273 epitope is clearly immunodominant in both tolerized and nontolerized DR4 mice. [source] Evaluation of genotoxic effects in human peripheral blood leukocytes following an acute in vitro exposure to 900 MHz radiofrequency fieldsBIOELECTROMAGNETICS, Issue 4 2005O. Zeni Abstract Human peripheral blood leukocytes from healthy volunteers have been employed to investigate the induction of genotoxic effects following 2 h exposure to 900 MHz radiofrequency radiation. The GSM signal has been studied at specific absorption rates (SAR) of 0.3 and 1 W/kg. The exposures were carried out in a waveguide system under strictly controlled conditions of both dosimetry and temperature. The same temperature conditions (37.0,±,0.1 °C) were realized in a second waveguide, employed to perform sham exposures. The induction of DNA damage was evaluated in leukocytes by applying the alkaline single cell gel electrophoresis (SCGE)/comet assay, while structural chromosome aberrations and sister chromatid exchanges were evaluated in lymphocytes stimulated with phytohemagglutinin. Alterations in kinetics of cell proliferation were determined by calculating the mitotic index. Positive controls were also provided by using methyl methanesulfonate (MMS) for comet assay and mitomycin-C (MMC), for chromosome aberration, or sister chromatid exchange tests. No statistically significant differences were detected in exposed samples in comparison with sham exposed ones for all the parameters investigated. On the contrary, the positive controls gave a statistically significant increase in DNA damage in all cases, as expected. Thus the results obtained in our experimental conditions do not support the hypothesis that 900 MHz radiofrequency field exposure induces DNA damage in human peripheral blood leukocytes in this range of SAR. Bioelectromagnetics 26:258,265, 2005. © 2005 Wiley-Liss, Inc. [source] Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumor drug potency in a human adenocarcinoma cell line,BIOELECTROMAGNETICS, Issue 8 2002M.J. Ruiz-Gómez Abstract The resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA-2/1cch. The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P,<,0.01), exhibiting 6.1% of survival at 47.5 ,g/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 ,g/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P,<,0.001). Cisplatin showed a significant reduction in the % of survival (44.2,39.1%, P,<,0.05) at 25 Hz and 47.5 ,g/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA-2/1cch, with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation. Bioelectromagnetics 23:578,585, 2002. © 2002 Wiley-Liss, Inc. [source] On-line adaptive metabolic flux analysis: Application to PHB production by mixed microbial culturesBIOTECHNOLOGY PROGRESS, Issue 2 2009Joăo Dias Abstract In this work, an algorithm for on-line adaptive metabolic flux analysis (MFA) is proposed and applied to polyhydroxybutyrate (PHB) production by mixed microbial cultures (MMC). In this process, population dynamics constitutes an important source of perturbation to MFA calculations because some stoichiometric and energetic parameters of the underlying metabolic network are continuously changing over time. The proposed algorithm is based on the application of the observer-based estimator (OBE) to the central MFA equation, whereby the role of the OBE is to force the accumulation of intracellular metabolites to converge to zero by adjusting the values of unknown network parameters. The algorithm was implemented in a reactor equipped with on-line analyses of dissolved oxygen and carbon dioxide through respirometric and titrimetric measurements. The oxygen and carbon dioxide fluxes were measured directly, whereas acetate, PHB, and sludge production fluxes were estimated indirectly using a projection of latent structures model calibrated a priori with off-line measurements. The algorithm was implemented in a way that the network parameters associated with biosynthesis were adjusted on-line. The algorithm proofed to converge exponentially with the steady state error always below 1 mmol/L. The estimated fluxes passed the consistency index test for experimental error variances as low as 1%. The comparison of measured and estimated respiratory coefficient and of the theoretical and estimated yield of sludge on acetate further confirmed the metabolic consistency of the parameters that were estimated on-line. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Analysis of progression and survival after 10 years of a randomized prospective study comparing mitomycin-C and bacillus Calmette-Guérin in patients with high-risk bladder cancerBJU INTERNATIONAL, Issue 4 2007Truls Gĺrdmark OBJECTIVE To report the 10-year follow-up of a study randomizing between instillations of bacillus Calmette-Guérin (BCG) and mitomycin-C (MMC) for treating high-risk and not muscle-invasive urinary bladder cancer to assess progression, the need for more aggressive treatment and survival (cancer-specific and overall), as many of the published studies comparing different treatments for disease that is not muscle-invasive have a short follow-up. PATIENTS AND METHODS Between 1987 and 1992, 261 patients were included; they had frequently recurring Ta/T1G1,G2, T1G3 or primary Tis-dysplasia. The patients were randomized to treatment with either 40 mg of MMC or 120 mg of BCG (Danish strain 1331) given weekly for 6 weeks, then monthly up to a year and finally every third month for a further year. The 250 evaluable patients were followed using hospital files and national registers on causes of death. RESULTS The median follow-up for survivors was 123 months. The disease progressed in 58 (23%) of the patients, 34 in the MMC group and 24 in the BCG group (P = 0.26). Of the 140 patients who died, 68 were in the BCG and 72 in the MMC group (log-rank P = 0.98); most (95, 68%) died from other causes. CONCLUSION Based on the follow-up of the present patients it cannot be concluded that the drugs originally administered, MMC or BCG, differed in their effect on progression, need for subsequent treatment or survival. [source] Gene expression of anti- and pro-apoptotic proteins in malignant and normal plasma cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2009Michel Jourdan Summary The survival of malignant plasma cells is a key event in disease occurrence, progression and chemoresistance. Using DNA-microarrays, we analysed the expression of genes coding for 58 proteins linked with extrinsic and intrinsic apoptotic pathways, caspases and inhibitor of apoptosis proteins. We considered six memory B cells (MBC), seven plasmablasts (PPC), seven bone marrow plasma cells (BMPC) and purified myeloma cells (MMC) from 92 newly-diagnosed patients. Forty out of the 58 probe sets enabled the separation of MBC, PPC and BMPC in three homogeneous clusters, characterized by an elevated expression of TNFRSF10A, TNFRSF10B, BCL2A1, CASP8, CASP9 and PMAIP1 genes for MBC, of FAS, FADD, AIFM1, BIRC5, CASP CASP2, CASP3 and CASP6 for PPC and of BCL2, MCL1, BID, BIRC3 and XIAP for BMPC. Thus, B cell differentiation was associated with change of expression of pro-apoptotic and anti-apoptotic genes. Regarding MMC, the major finding was TRAIL upregulation that might be counteracted by a high osteoprotegerin production by BM stromal cells and a decreased expression of FAS, APAF1 and BNIP3 compared to normal BMPC. Out of the 40 genes, CASP2 and BIRC5 expression in MMC had adverse prognosis in two independent series of previously-untreated patients. [source] Effects of sepsis on mast cells in rat dura mater: influence of L -NAME and VIPBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2001F Tore The influence of lipopolysaccharide (LPS)-induced sepsis on the various mast cell phenotypes of rat dura mater were examined both by immunohistochemical and biochemical methods. Three different populations of mast cells were identified in control rats: connective tissue type mast cells (CTMC) which contain rat mast cell protease1 (RMCP1), histamine, serotonin and heparin, mucosal type mast cells (MMC) which contain RMCP2, histamine and serotonin, and intermediate type which contains both RMCP1 and RMCP2 and probably various proportions of amines and heparin. LPS (25 mg kg,1 i.p.) caused changes in the proportions of the various types of mast cells. The number of MMC and intermediate type mast cells significantly increased and the number of mast cells immunopositive for both heparin and serotonin significantly decreased. Biochemical analysis showed that the histamine concentration of dura increased while its serotonin concentration decreased. While vasoactive intestinal peptide (VIP) (25 ng kg,1 i.p.) appears to potentiate LPS effects on dura mater mast cells, non-selective inhibition of nitric oxide (NO) synthase by Ng -nitro- L -arginine methyl ester (L -NAME) (30 mg kg,1 i.p.) did not influence sepsis-induced mast cell changes. These findings suggest that mast cells of dura mater may play a role in brain protection during sepsis. British Journal of Pharmacology (2001) 134, 1367,1374; doi:10.1038/sj.bjp.0704412 [source] Macrophage Colony-stimulating Factor (M-CSF) Prevents Infectious Death Induced by Chemotherapy in Mice, While Granulocyte-CSF Does NotCANCER SCIENCE, Issue 4 2002Takao Hidaka To clarify the effect of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced infection, we estimated the effect of those CSFs on a mouse model under severe myelosuppression. First, we established an animal model in which 48.9% (22/45) of C3H/Hej mice died of sepsis related to severe myelosuppression after intraperitoneal administration of a single dose (9 mg/kg) of mitomycin C (MMC). G-CSF or M-CSF was administered to this model on various administration schedules after chemotherapy, and the effect of those CSFs on survival rates, peripheral blood granulocyte counts, expression of adhesion molecules (CD11a, CD11b, CD18) on granulocytes and granulocyte function (phagocytosis and superoxide anion production) were examined. In all G-CSF administration groups, peripheral blood granulocyte counts were increased, but improvements in expression of adhesion molecules such as CD11a and CD18, and granulocyte function were less marked and survival rates were not unproved. Meanwhile, when M-CSF was administered from 1 to 7 days after chemotherapy, granulocyte and platelet counts were increased, and moreover, expression of adhesion molecules and granulocyte function were markedly improved. Furthermore, the survival rate was significantly improved to 77.8% (28/36) compared with the MMC group (P<0.05). Positive rate of blood culture examination at 7 days after chemotherapy in the M group was 0%, and was significantly lower than that in the G group (40%) and the MMC group (40%) (P<0.05). These results demonstrated that it is important not only to increase the granulocyte counts, but also to improve granulocyte functions for preventing infection under myelosuppression after chemotherapy. [source] 2143: Corneal keratocyte population after laser subepithelial keratectomy (LASEK) with mitomycin C (MMC): 3 months vs 15 months comparisonACTA OPHTHALMOLOGICA, Issue 2010P CANADAS SUAREZ Purpose To study corneal keratocyte population after LASEK with mitomycin C (MMC) 15 months vs 3 months after surgery Methods Sixty eyes were included in this study, all of them treated with LASEK with intraoperative 0.02% MMC, divided into 2 groups. 32 eyes had LASEK performed 3 months before, versus 28 in the 15 months post-op group. Keratocyte density was examined by using confocal microscopy in the anterior, mid and posterior stroma in both groups, and the mean density was compared with a control group of healthy eyes Results Keratocyte density in the anterior stroma was 16993,75+ 8001,7 cells/mm3 and 18529,1 + 2917,7 cells/mm3(p=0,3) in the 3 months and in the 15 months groups respectively, in the mid stroma it was 30783,3+ 9300 cells/mm3 in the 3 months and 20754,7 + 3615,3 cells/mm3 in the 15 months groups (p= 0,0001) and 30286,75+ 8321 cells/mm3and 19994+ 3085,9 cells/mm3 (p= 0,0001) in the posterior stroma in the 3 months and in the 15 months groups respectively. The comparison between the average densities through the whole cornea showed statistically significant difference between the 3 months vs 15 months group and 3 months vs normals, but it was not statistically significant different between 15 months vs normals Conclusion The changes in the corneal keratocyte population after LASEK + MMC seen in the early post-op, seem to change towards the normal values 15 months after the procedure. [source] 2144: LASEK with MMC vs femtosecond sub-Bowmann keratomileusis to correct myopic astigmatism: a pilot studyACTA OPHTHALMOLOGICA, Issue 2010MA TEUS Purpose To evaluate the safety and efficacy of LASEK and Femtosecond sub-Bowmann Keratomileusis (FSBK) in the correction of myopic astigmatism Methods Prospective, masked study of consecutive eyes, with myopic astigmatism higher than 1.5D. MMC was used in LASEK eyes if ablation > 50 microns. Visual results were evaluated three months post-op Results 252 eyes were analyzed, 125 LASEK and 127 FSBK. Preoperative sphere and cylinder was similar in both groups (p=0.1). Safety and Efficacy indexes were 1.01 vs 1.02 and 0.90 vs 0.88 in LASEK and FSBK groups, respectively (p=0.8 and 0.3) Conclusion LASEK and FSBK achieve comparable visual results when used to correct myopic astigmatism at 3 months follow-up [source] Mitomycin-C-augmented deep sclerectomy in patients with primary open-angle glaucoma and exfoliation glaucoma: a 1-year prospective studyACTA OPHTHALMOLOGICA, Issue 1 2010Minna Ollikainen ABSTRACT. Purpose:, To investigate the efficacy and safety of mitomycin C (MMC)-augmented deep sclerectomy with implant (DSCI) in patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG). Methods:, A total of 68 eyes of 68 patients with POAG and ExG were enrolled consecutively to undergo DSCI with MMC (0.4 mg/ml for 2 min). The intraocular pressure (IOP), number of antiglaucoma medications, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser goniopunctures and complications were compared postoperatively. Surgery was considered as a complete success when IOP was < 18 mmHg without antiglaucoma medication. Results:, Preoperatively, the mean IOPs were 23.1 ± 5.8 and 25.4 ± 8.3 mmHg, and 13.8 ± 6.1 and 11.2 ± 5.6 mmHg in the POAG and ExG groups, respectively, at 12 months. 77.4% and 75.7% of surgeries were a complete success in the POAG and ExG groups, respectively [not significant (NS)]. Five patients (16.1%) in the POAG group but none in the ExG group (0%) were receiving antiglaucoma medication at 12 months (NS). Nd:YAG laser goniopuncture was performed in 29.0% of eyes in the POAG group and in 55.6% of eyes in the ExG group (p = 0.047). Postoperatively, choroidal detachment occurred in 16.1% of eyes in the POAG group and in 10.8% of eyes in the ExG group (NS). We encountered no serious complications related to MMC use. Conclusion:, DS with MMC augmentation appears to be equally effective in ExG and POAG patients in lowering IOP to target levels, at least in the short term, with few immediate postoperative complications. [source] | ||||||||||||||||||||||||||||