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Marked Alterations (marked + alteration)
Selected AbstractsDecreased expression and promoter methylation of the menin tumor suppressor in pancreatic ductal adenocarcinomaGENES, CHROMOSOMES AND CANCER, Issue 5 2009Ilaria Cavallari Loss of menin, a tumor suppressor coded by the MEN1 gene, is a key factor in the pathogenesis of multiple endocrine neoplasia type I and in a percentage of sporadic endocrine tumors of the pancreas and parathyroid glands. This study investigated expression of the menin protein in the normal exocrine pancreas and in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic tumor. Immunofluorescence (IF) analyses showed that menin is expressed at high levels in normal acinar and duct cells. Examination of 24 clinical samples of PDAC revealed a pronounced decrease in menin expression in all tumors examined. To identify alterations underlying this defect, we searched for disruption and epigenetic silencing of the MEN1 gene. Analysis of nine laser-microdissected tumors revealed loss of heterozygosity of intragenic (one tumor) or adjacent (three tumors) MEN1 microsatellite markers. Methylation of CpG sites in the MEN1 promoter was documented in five of 24 tumors. IF analyses also revealed low to undetectable menin expression in the PDAC cell lines MiaPaCa-2 and Panc-1. Ectopic expression of menin in these cells resulted in a marked alteration of the cell cycle, with an increase in the G1/S+G2 ratio. These findings represent the first evidence that the MEN1 gene is a target of mutation and methylation in PDAC and that menin influences the cell cycle profile of duct cells. © 2009 Wiley-Liss,Inc. [source] Generation of cortactin floxed mice and cellular analysis of motility in fibroblastsGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 9 2009Shinji Tanaka Abstract Cortactin is an F-actin binding protein that has been suggested to play key roles in various cellular functions. Here, we generated mice carrying floxed alleles of the cortactin (Cttn) gene (Cttnflox/flox mice). Expression of Cre recombinase in mouse embryonic fibroblasts (MEFs) isolated from Cttnflox/flox embryos depleted cortactin within days, without disturbing F-actin distribution and localization of multiple actin-binding proteins. Cre-mediated deletion of Cttn also did not affect cell migration. To obtain mice with a Cttn null allele, we next crossed Cttnflox/flox mice with transgenic mice that express Cre recombinase ubiquitously. Western blot and immunocytochemical analysis confirmed complete elimination of cortactin expression in MEFs carrying homozygously Cttn null alleles. However, we found no marked alteration of F-actin organization and cell migration in Cttn null-MEFs. Thus, our results indicate that depletion of cortactin in MEFs does not profoundly influence actin-dependent cell motility. genesis 47:638,646, 2009. © 2009 Wiley-Liss, Inc. [source] Hemorheologic profile in systemic sclerosis: Role of NOS3 ,786T>C and 894G>T polymorphisms in modulating both the hemorheologic parameters and the susceptibility to the diseaseARTHRITIS & RHEUMATISM, Issue 7 2006Cinzia Fatini Objective Microvascular disorders are relevant in systemic sclerosis (SSc). Hyperviscosity, due to alterations of blood cells and plasma components, may play a role in the pathogenesis of microcirculatory disorders. An impaired availability of nitric oxide, related to polymorphisms in NOS3, the gene for endothelial cell nitric oxide synthase, might influence erythrocyte deformability. We undertook this study to investigate the hemorheologic profile in SSc and the role of NOS3 polymorphisms in modulating the hemorheologic status of SSc patients. Methods We studied 113 consecutive SSc patients (75 with limited cutaneous SSc [lcSSc] and 38 with diffuse cutaneous SSc [dcSSc]) and 113 healthy controls. The hemorheologic profile was obtained by assessing whole blood viscosity (WBV; at shear rates of 0.512 and 94.5 seconds,1), plasma viscosity (PLV; at a shear rate of 94.5 seconds,1), and erythrocyte deformability index (DI). We determined NOS3 polymorphisms by molecular analysis. Results A marked alteration of hemorheologic parameters was found both in patients with lcSSc and in those with dcSSc compared with controls (P < 0.0001). In multivariate analysis, rheologic variables were significantly associated with the disease (for WBV at a shear rate of 94.5 seconds,1, odds ratio [OR] 5.4, 95% confidence interval [95% CI] 1.4,19.9, P = 0.01; for PLV, OR 2.8, 95% CI 1.2,6.5, P = 0.01; for DI, OR 3.9, 95% CI 1.4,10.8, P = 0.007), and NOS3 ,786C and 894T alleles significantly affected the DI (for ,786C allele, OR 2.3, 95% CI 1.01,5.4, P = 0.04; for 894T allele, OR 2.2, 95% CI 1.01,4.8, P = 0.04). The simultaneous presence of the ,786C and 894T alleles represented a susceptibility factor for SSc (OR 2.8, 95% CI 1.4,5.7, P = 0.004). Conclusion Our findings document an altered rheologic profile in SSc and demonstrate a relationship between this alteration and NOS3 polymorphisms, thus shedding light on a potential novel mechanism influencing the microcirculation in this disease. [source] Classification of hydrological regimes of northern floodplain basins (Peace,Athabasca Delta, Canada) from analysis of stable isotopes (,18O, ,2H) and water chemistryHYDROLOGICAL PROCESSES, Issue 2 2007Brent B. Wolfe Abstract We used stable isotopes (,18O and ,2H) and water chemistry to characterize the water balance and hydrolimnological relationships of 57 shallow aquatic basins in the Peace-Athabasca Delta (PAD), northern Alberta, Canada, based on sampling at the end of the 2000 thaw season. Evaporation-to-inflow ratios (E/I) were estimated using an isotope mass-balance model tailored to accommodate basin-specific input water compositions, which provided an effective, first-order, quantitative framework for identifying water balances and associated limnological characteristics spanning three main, previously identified drainage types. Open-drainage basins (E/I < 0·4; n = 5), characterized by low alkalinity, low concentrations of nitrogen, dissolved organic carbon (DOC) and ions, and high minerogenic turbidity, include large, shallow basins that dominate the interior of the PAD and experience frequent or continuous river channel connection. Closed-drainage basins (E/I , 1·0; n = 16), in contrast, possess high alkalinity and high concentrations of nitrogen, DOC, and ions, and low minerogenic turbidity, and are located primarily in the relict and infrequently flooded landscape of the northern Peace sector of the delta. Several basins fall into the restricted-drainage category (0·4 # E/I < 1·0; n = 26) with intermediate water chemistries and are predominant in the southern Athabasca sector, which is subject to active fluviodeltaic processes, including intermittent flooding from riverbank overflow. Integration of isotopic and limnological data also revealed evidence for a new fourth drainage type, mainly located near the large open-drainage lakes that occupy the central portion of the delta but within the Athabasca sector (n = 10). These basins were very shallow (<50 cm deep) at the time of sampling and isotopically depleted, corresponding to E/I characteristic of restricted- and open-drainage conditions. However, they are limnologically similar to closed-drainage basins except for higher conductivity and higher concentrations of Ca2+ and Na+, and lower concentrations of SiO2 and chlorophyll c. These distinct features are due to the overriding influence of recent summer rainfall on the basin water balance and chemistry. The close relationships evident between water balances and limnological conditions suggest that past and future changes in hydrology are likely to be coupled with marked alterations in water chemistry and, hence, the ecology of aquatic environments in the PAD. Copyright © 2006 John Wiley & Sons, Ltd. [source] Occurrence of oxidative impairments, response of antioxidant defences and associated biochemical perturbations in male reproductive milieu in the Streptozotocin-diabetic ratINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2007B. Shrilatha Summary Oxidative stress is implicated to play a vital role in the pathogenesis of various diabetic complications. While reproductive dysfunction is a well recognized consequence of diabetes mellitus, the underlying mechanisms are poorly understood. The present study aims to obtain insights into the incidence, extent and progression of oxidative impairments in testis and epididymal sperm (ES) in streptozotocin (STZ)-induced diabetic rat during early and progressive phase. Adult rats (CFT-Wistar strain) rendered diabetic by an acute dose of STZ (60 mg/kg bw, i.p.) were examined for induction of hyperglycaemia at 72 h, followed by the assessment of oxidative impairments in testis and ES over a 6-week period. Oxidative damage was ascertained by measuring the malondialdehyde levels, reactive oxygen species (ROS) generation, alterations in antioxidant defences and extent of protein oxidation. STZ induced a significant (2.5-fold) increase in blood glucose levels. In diabetic rats, both testis and ES showed enhanced status of lipid peroxidation measured as increased TBARS and ROS from week 2 onwards. These impairments in testis were consistent, progressive and accompanied by marked alterations in antioxidant defences and elevated protein carbonyls. Varying degree of reduction in the specific activities of antioxidant enzymes was evident in testis and ES, while the activity of glutathione- S -transferase (GST) was significantly elevated. Reduced glutathione (GSH) and vitamin E levels were consistently reduced in testis. Lipid dysmetabolism measured in terms of increased cholesterol, triglycerides and phospholipids was evident only beyond week 2 in diabetic testis. Taken together, these results indicate that the testis and ES are indeed subjected to significant oxidative stress in the STZ-diabetic rat both during early as well as progressive phase. It is hypothesized that oxidative impairments in testis which develop over time may at least in part contribute towards the development of testicular dysfunction eventually leading to testicular degeneration which culminates in reduced fertility during the progressive phase of STZ-induced diabetes in adult rats. [source] Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exerciseJOURNAL OF INTERNAL MEDICINE, Issue 3 2005Y. JAMMES Abstract. Objectives., Because the muscle response to incremental exercise is not well documented in patients suffering from chronic fatigue syndrome (CFS), we combined electrophysiological (compound-evoked muscle action potential, M wave), and biochemical (lactic acid production, oxidative stress) measurements to assess any muscle dysfunction in response to a routine cycling exercise. Design., This case,control study compared 15 CFS patients to a gender-, age- and weight-matched control group (n = 11) of healthy subjects. Interventions., All subjects performed an incre-mental cycling exercise continued until exhaustion. Main outcome measures., We measured the oxygen uptake (Vo2), heart rate (HR), systemic blood pressure, percutaneous O2 saturation (SpO2), M-wave recording from vastus lateralis, and venous blood sampling allowing measurements of pH (pHv), PO2 (PvO2), lactic acid (LA), and three markers of the oxidative stress (thiobarbituric acid-reactive substances, TBARS, reduced glutathione, GSH, and ascorbic acid, RAA). Results., Compared with control, in CFS patients (i) the slope of Vo2 versus work load relationship did not differ from control subjects and there was a tendency for an accentuated PvO2 fall at the same exercise intensity, indicating an increased oxygen uptake by the exercising muscles; (ii) the HR and blood pressure responses to exercise did not vary; (iii) the anaerobic pathways were not accentuated; (iv) the exercise-induced oxidative stress was enhanced with early changes in TBARS and RAA and enhanced maximal RAA consumption; and (v) the M-wave duration markedly increased during the recovery period. Conclusions., The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress together with marked alterations of the muscle membrane excitability. These two objective signs of muscle dysfunction are sufficient to explain muscle pain and postexertional malaise reported by our patients. [source] Electrocardiographic Changes Due to Pyridoxine DeficiencyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2003EDUARDO MALMIERCA A young woman presented with marked alterations in the ECG without cardiological symptoms or evidence of structural heart disease after further evaluation. There was evidence of vitamin deficiency and the ECG normalized after 10 days of treatment with vitamins. Similar alterations have been described in several experimental studies with rats, but this is the first case reported in humans. (PACE 2003; 26:1289,1291) [source] A prospective, randomized-controlled clinical trial to evaluate bone preservation using implants with different geometry placed into extraction sockets in the maxillaCLINICAL ORAL IMPLANTS RESEARCH, Issue 1 2010Mariano Sanz Abstract Aim: The primary objective of this study was to determine the association between the size of the void established by using two different implant configurations and the amount of buccal/palatal bone loss that occurred during 16 weeks of healing following their installation into extraction sockets. Material and methods: The clinical trial was designed as a prospective, randomized-controlled parallel-group multicenter study. Adults in need of one or more implants replacing teeth to be removed in the maxilla within the region 15,25 were recruited. Following tooth extraction, the site was randomly allocated to receive either a cylindrical (group A) or a tapered implant (group B). After implant installation, a series of measurements were made to determine the dimension of the ridge and the void between the implant and the extraction socket. These measurements were repeated at the re-entry procedure after 16 weeks. Results: The study demonstrated that the removal of single teeth and the immediate placement of an implant resulted in marked alterations of the dimension of the buccal ridge (43% and 30%) and the horizontal (80,63%) as well as the vertical (69,65%) gap between the implant and the bone walls. Although the dimensional changes were not significantly different between the two-implant configurations, both the horizontal and the vertical gap changes were greater in group A than in group B. Conclusions: Implant placement into extraction sockets will result in significant bone reduction of the alveolar ridge. To cite this article: Sanz M, Cecchinato D, Ferrus J, Pjetursson EB, Lang NP, Jan L. A prospective, randomized-controlled clinical trial to evaluate bone preservation using implants with different geometry placed into extraction sockets in the maxilla. Clin. Oral Impl. Res. 21, 2009; 13,21. [source] Ridge alterations following tooth extraction with and without flap elevation: an experimental study in the dogCLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2009Mauricio G. Araújo Abstract Background: Different approaches were advocated to preserve or improve the dimension and contour of the ridge following tooth extraction. In some of studies, socket ,flapless extraction' apparently had a successful outcome. Aim: The objective of the present experiment was to compare hard tissue healing following tooth extraction with or without the prior elevation of mucosal full-thickness flaps. Material and methods: Five mongrel dogs were used. The two second mandibular premolars (2P2) were hemi-sected. The mesial roots were retained. By random selection the distal root in one side was removed after the elevation of full-thickness flaps while on the contralateral side, root extraction was performed in a flapless procedure. The soft tissue wound was closed with interrupted sutures. After 6 months of healing, the dogs were euthanized and biopsies were sampled. From each experimental site, four ground sections , two from the mesial root and two from the healed socket , were prepared, stained and examined in the microscope. Results: The data showed that the removal of a single tooth (root) during healing caused a marked change in the edentulous ridge. In the apical and middle portions of the socket site minor dimensional alterations occurred while in the coronal portion of the ridge the reduction of the hard tissue volume was substantial. Similar amounts of hard tissue loss occurred during healing irrespective of the procedure used to remove the tooth was, i.e. flapless or following flap elevation. Conclusion: Tooth loss (extraction) resulted in marked alterations of the ridge. The size of the alveolar process was reduced. The procedure used for tooth extraction , flapless or following flap elevation , apparently did not influence the more long-term outcome of healing. [source] | ||||||||||