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Selected AbstractsRole of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinomaPATHOLOGY INTERNATIONAL, Issue 10 2003Hua-Chuan Zheng To investigate the role of PTEN and matrix metalloproteinase-7 (MMP-7) expression in tumorigenesis and progression of gastric carcinoma, their expression in 113 gastric carcinomas was studied by immunohistochemistry. Microvessel density (MVD) was counted using the anti-CD34 antibody. The expressions of PTEN and MMP-7, and MVD were compared with the clinicopathological parameters of tumors, and the relationship between PTEN and MMP-7 expression and MVD was analyzed. It was found that PTEN was expressed less frequently in primary gastric carcinoma cells than in adjacent epithelial cells (P < 0.05), whereas this was reversed for MMP-7 (P < 0.05). PTEN expression was negatively correlated with invasion, metastasis, growth pattern, Lauren's classification and histological classification (P < 0.05). Matrix metalloproteinase-7 expression was positively associated with tumor size, Borrmann's classification, invasive depth, metastasis and TNM staging (P < 0.05), but negative with PTEN expression (P < 0.05). A positive correlation of MVD with tumor size, invasive depth, metastasis and TNM staging was found (P < 0.05). Microvessel density depended on decreased PTEN expression and increased MMP-7 expression (P < 0.05). The results of the present study suggested that down-regulated PTEN expression and up-regulated MMP-7 expression were greatly implicated in tumorigenesis and progression of gastric carcinoma. Close correlation between PTEN on MMP-7 expression provided a novel insight into the regulatory effects of PTEN on MMP-7 expression in gastric carcinoma. [source] Comparative analysis of ATP-binding cassette (ABC) transporter gene expression levels in peripheral blood leukocytes and in liver with hepatocellular carcinomaCANCER SCIENCE, Issue 6 2004Mohsen A. Moustafa ATP-binding cassette (ABC) transporters comprise a superfamily of similar proteins involved in transmembrane transport of various substances. ABC transporter family members in the liver participate in bile formation and lipid metabolism. In order to assess whether peripheral blood leukocytes (PBL) are available as a surrogate for determination of the expression of ABC transporter genes in the liver, we compared ABC transporter gene expression levels in PBL with those in liver tissues from patients with hepatocellular carcinoma (HCC). We measured ABCA1, A2, B1-B4, C1°C5, G1 and G2 gene expression levels in PBL, and cancerous and non-cancerous portions of liver from patients with hepatocellular carcinoma by means of real time reverse-transcription (RT)-PCR. We could not detect ABCC5 expression in any tissue of the liver. Close correlations between ABCA2, C1 and 67 in PBL and in non-tumor tissues of the liver were found. Compared with the non-tumor part, HCC tissue expressed lower levels of ABCA1, B4 and G2. We think monitoring of ABCA2, C1 and G7 gene expression levels in PBL will be useful for selection of anti cancer agents and monitoring of drug resistance of HCC. Administration of chemotherapeutic agents which are substrates of ABCA1, B4 and G2 should be effective for the treatment of HCC. (Cancer Sci 2004; 95: 530,536) [source] P73 The magnitude of contact allergy responses can be quantified with imaged perfusionCONTACT DERMATITIS, Issue 3 2004Bolli Bjarnason Objective:, The objective of this study was to determine whether the magnitude of the perfusion of the contact hypersensitivity response as measured by the laser Doppler perfusion imaging (LDPI) technique was associated with immunological parameters implicated in the pathogenesis of the disease. Methods:, Urushiol was applied on one of the forearms of volunteers for 48 hours while the other forearm served as a control. Twenty-four hours later, measurements of perfusion of the patch test sites were performed with the LDPI technique. To determine whether there was a correlation with immunological parameters associated with human contact hypersensitivity, suction blisters were produced at the test sites. Blister fluid was removed and examined for the cytokine interleukin-8 (IL-8). Results:, There was an extremely close correlation between the magnitude of the contact hypersensitivity response as measured by the imaged perfusion and the level of IL-8 in the blister fluid (r = 1.00). Compared to subjects with visually positive urushiol reactions, patients who failed to develop urushiol contact hypersensitivity despite repeated exposures to that substance had both greatly diminished perfusion and blister fluid IL-8 levels. Conclusion:, The results indicate that LDPI is a sensitive method of quantifying contact hypersensitivity reactions in humans and that the magnitude of the measurements with this technique correlates extremely well with cutaneous cytokine levels that have been implicated in the immunopathogenesis of contact hypersensitivity. [source] Migration of hawksbill turtles Eretmochelys imbricata from Tortuguero, Costa RicaECOGRAPHY, Issue 3 2005Sebastian Troëng The hawksbill turtle Eretmochelys imbricata is a widely distributed and critically endangered species that feeds on sponges and fills an important ecological role in the coral reef ecosystem. At Tortuguero, Costa Rica, trend analyses indicate considerable decline in nesting estimated at 77.2,94.5% between 1956 and 2003, as a result of excessive turtle fishing. We analyzed flipper tag returns, satellite telemetry and genetic samples to determine movements and habitat use of adult female Tortuguero hawksbills. Tag returns and satellite telemetry show hawksbills migrate to foraging grounds in Nicaragua and Honduras. Genetic analysis indicates the hawksbills may also migrate to Cuban, Puerto Rican, and possibly Mexican waters. We conclude hawksbills represent an internationally shared resource. There is a close correlation between tag recapture sites, hawksbill foraging grounds and coral reef distribution. Caribbean coral reef decline may reduce food availability and negatively impact hawksbill turtles. Conversely, hawksbill decline may shift the balance on coral reefs by reducing predation pressure on sponges and hence make coral reefs less resilient to natural and anthropogenic threats. Strategies aiming to conserve hawksbills and coral reefs must consider both the extensive hawksbill migrations and the close relationship between the species and the coral reef ecosystem. [source] Gender differences in genetic damage induced by the tobacco-specific nitrosamine NNK and the influence of the Thr241Met polymorphism in the XRCC3 geneENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005Courtney E. Hill Abstract The rapid increase in adenocarcinoma of the lung and mortality amongst women strongly suggests that gender differences exist in sensitivity to certain tobacco carcinogens. In the current study, we performed the mutagen-sensitivity assay, with the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to test the hypothesis that women are more sensitive to the genotoxic effects of NNK than men. Chromosome aberration (CA) frequencies in peripheral blood lymphocytes (PBLs) from 99 patients were evaluated before and after in vitro exposure to NNK. Because the Thr241Met polymorphism in the DNA-repair gene XRCC3 is associated with increased risk of tobacco-related cancers, especially among women, we also tested the hypothesis that individuals who inherit the homozygous variant 241Met allele are more sensitive to the genotoxic effects of NNK. CA frequency was significantly higher 1 hr after NNK treatment in women, compared with men (P = 0.02). When smoking and gender were considered together, a significant interaction was observed. PBLs from female smokers had significantly higher frequencies of NNK-induced CA, compared with female nonsmokers 1 hr after treatment (P = 0.02). We observed no overall effect of the Thr241Met polymorphism on NNK-induced CA in men, women, smokers, or nonsmokers. Overall, our data indicate that women are more sensitive to the genotoxic effects of NNK than men. Because in past years smoking among women has increased, and in view of the close correlation between NNK exposure and adenocarcinoma of the lung, our data provide a plausible explanation for the recent increase in the incidence of this cancer among women. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source] Intracellular Calcium Increase in Epileptiform Activity: Modulation by Levetiracetam and LamotrigineEPILEPSIA, Issue 7 2004Antonio Pisani Summary:,Purpose: Alterations in neuronal calcium (Ca2+) homeostasis are believed to play an essential role in the generation and propagation of epileptiform events. Levetiracetam (LEV) and lamotrigine (LTG), novel antiepileptic drugs (AEDs), were tested on epileptiform events and the corresponding elevations in intracellular Ca2+ concentration ([Ca2+]i) recorded from rat neocortical slices. Methods: Electrophysiological recordings were performed from single pyramidal neurons from a slice preparation. Spontaneous epileptiform events consisting of long-lasting, repetitive paroxysmal depolarization shifts (PDSs) and interictal spike activity were induced by reducing the magnesium concentration from the solution and by adding bicuculline and 4-aminopyridine. Simultaneously, microfluorimetric measurements of [Ca2+]i were performed. Optical imaging with Ca2+ indicators revealed a close correlation between Ca2+ transients and epileptiform events. Results: Both LEV and LTG were able to reduce both amplitude and duration of PDSs, as well as the concomitant elevation in [Ca2+]i, in a dose-dependent fashion. Whole-cell patch-clamp recordings from isolated neocortical neurons revealed that LEV significantly reduced N-, and partially P/Q-type high-voltage-activated (HVA) Ca2+ currents, whereas sodium currents were unaffected. Interestingly, the inhibitory effects of LEV were mimicked and occluded by LTG or by a combination of ,-conotoxin GVIA and ,-agatoxin IVA, selective blockers of N- and P/Q-type HVA channels, respectively, suggesting a common site of action for these AEDs. Conclusions: These results demonstrate that large, transient elevations in neuronal [Ca2+]i correlate to epileptiform discharges. The antagonistic effects of LEV and LTG on [Ca2+]i overload might represent the basis for their anticonvulsant efficacy and could preserve neuronal viability. [source] High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B,cell discrimination of monomeric proteinsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2005Wanli Liu Abstract Although early studies have shown a close correlation between epitope density and epitope-specific humoral immune responses, few attempts have been made to quantitatively compare the antigenic and immunogenic differences between protein molecules bearing low or high degrees of epitope density, nor have studies quantitatively investigated the mechanism of B,cell discrimination of monomeric antigens. In this study, we prepared glutathione S-transferase (GST) fusion proteins bearing various copies of the M2e epitope from the influenza virus M2,protein [GST-(M2e)8, GST-(M2e)4 and GST-(M2e)1], which were used to detect and compare the real-time kinetic binding with M2e-specific mAb by surface plasma resonance. Our data show clearly that fusion proteins bearing higher M2e epitope density resulted in higher average avidity for M2e-specific mAb. Furthermore, it was observed that fusion proteins bearing high M2e epitope density could induce polyclonal antibodies (pAb) with enhanced an average affinity constant (KA) for M2e epitope peptide compared to fusion proteins bearing low epitope density. The average KA of pAb induced by GST-(M2e)8 (3.08 × 108,M,1 or 9.96 × 108,M,1) was up to two orders of magnitude greater than the average KA of pAb induced by GST-(M2e)1 (2.00 × 106,M,1 or 3.43 × 106,M,1). Thus, the data presented here demonstrate that high epitope density in a single protein molecule significantly enhances antigenicity and immunogenicity. These findings enrich our knowledge of how epitope density might relate to the recognition, activation and antibody production processes of epitope-specific immature B,cells. [source] Modeling of Environmental Degradation in Fatigue-Life Prediction of Near-, Titanium Alloy IMI 834 under Complex High-Temperature Loading Conditions,ADVANCED ENGINEERING MATERIALS, Issue 6 2003R.G. Teteruk The crack propagation model successfully applies to life-prediction of near-,-titanium alloy IMI 834 under complex high-temperature fatigue-loading conditions. The predictive capabilities of the model can be attributed to the close correlation of the model with the relevant damage mechanisms (among them environmental degradation under varying conditions) and micro-structural processes. The Figure shows an SEM image of a typical crack-initiation site for a test run at 400,°C. [source] Modulation of oat arginine decarboxylase gene expression and genome organization in transgenic Trypanosoma cruzi epimastigotesFEBS JOURNAL, Issue 3 2006María P. Serra We have previously demonstrated that wild-type Trypanosoma cruzi epimastigotes lack arginine decarboxylase (ADC) enzymatic activity as well as its encoding gene. A foreign ADC has recently been expressed in T. cruzi after transformation with a recombinant plasmid containing the complete coding region of the oat ADC gene. In the present study, upon modulation of exogenous ADC expression, we found that ADC activity was detected early after transfection; subsequently it decreased to negligible levels between 2 and 3 weeks after electroporation and was again detected ,,4 weeks after electroporation. After this period, the ADC activity increased markedly and became expressed permanently. These changes of enzymatic activity showed a close correlation with the corresponding levels of ADC transcripts. To investigate whether the genome organization of the transgenic T. cruzi underwent any modification related to the expression of the heterologous gene, we performed PCR amplification assays, restriction mapping and pulse-field gel electrophoresis with DNA samples or chromosomes obtained from parasites collected at different time-points after transfection. The results indicated that the transforming plasmid remained as free episomes during the transient expression of the foreign gene. Afterwards, the free plasmid disappeared almost completely for several weeks and, finally, when the expression of the ADC gene became stable, two or more copies of the transforming plasmid arranged in tandem were integrated into a parasite chromosome (1.4 Mbp) bearing a ribosomal RNA locus. The sensitivity of transcription to ,-amanitin strongly suggests involvement of the protozoan RNA polymerase I in the transcription of the exogenous ADC gene. [source] Prediction of temporal gene expressionFEBS JOURNAL, Issue 22 2002Metabolic optimization by re-distribution of enzyme activities A computational approach is used to analyse temporal gene expression in the context of metabolic regulation. It is based on the assumption that cells developed optimal adaptation strategies to changing environmental conditions. Time-dependent enzyme profiles are calculated which optimize the function of a metabolic pathway under the constraint of limited total enzyme amount. For linear model pathways it is shown that wave-like enzyme profiles are optimal for a rapid substrate turnover. For the central metabolism of yeast cells enzyme profiles are calculated which ensure long-term homeostasis of key metabolites under conditions of a diauxic shift. These enzyme profiles are in close correlation with observed gene expression data. Our results demonstrate that optimality principles help to rationalize observed gene expression profiles. [source] Soil parent materials and the pottery of Roman Galilee: A comparative studyGEOARCHAEOLOGY: AN INTERNATIONAL JOURNAL, Issue 4 2002Moshe Wieder The paper presents a comparative micromorphological analysis of the range of soil materials used to make the pottery of the hilly Galilee during the Roman period, and the ceramic products made from these materials. The four soil units that served as raw material for most of the pottery made in this period and region are examined along with pottery derived from each of them. For each soil unit, the soil characteristics and processes are described, followed by a presentation of the micromorphological characteristics of the soil material and those of the pottery made from that material. The contribution of the aeolian dust component to the soil materials is discussed as well as the identification of the tempering materials (nonplastics or other soil materials) added to the pottery paste. The study demonstrates the close correlation in microfabric between the pottery and original soil materials, sheds light on the raw material selection and modification practices of the potters of Roman Galilee, and has significant implications for provenance studies, using chemical analysis, on the pottery of this period and region. © 2002 Wiley Periodicals, Inc. [source] Haemophilia and thrombophilia: an unexpected association!HAEMOPHILIA, Issue 4 2004Y. Dargaud Summary., In patients with haemophilia, a close correlation is usually observed between the clinical expression of the disease and plasmatic factor VIII/factor IX clotting activity. However, some patients experience milder bleeding phenotypes than others, although they exhibit a similar biological profile. The high prevalence of some inherited thrombophilia risk factors offers the possibility of a co-inheritance in haemophilic patients which could influence the phenotypic expression of the disease. Rare thrombotic complications occurring in haemophiliacs could also be facilitated by the co-inheritance of modifier genes. The majority of thrombotic events occurring in haemophiliacs are in relation to clotting factor infusions or central venous catheters. Concerning surgical situations, in the absence of therapeutic recommendations, postoperative thromboprophylaxis is not systematically performed in haemophiliacs. However, substitutive treatment more or less completely corrects the coagulation defect and makes the venous thrombosis risk closer to the control population. It should be emphasized that haemophilia does not fully protect against venous thromboembolic disease. Patients with haemophilia very infrequently experience thrombotic events. Thus, the management of thrombotic complications occurring in haemophilic patients should be discussed in each case according to the precipitating risk factors, the clinical context and the thrombo-haemorrhagic balance of the patient with respect to a particular clinical situation. [source] A note on estimating urban roof runoff with a forest evaporation modelHYDROLOGICAL PROCESSES, Issue 8 2008J. H. C. Gash Abstract A model developed for estimating the evaporation of rainfall intercepted by forest canopies is applied to estimate measurements of the average runoff from the roofs of six houses made in a previous study of hydrological processes in an urban environment. The model is applied using values of the mean rates of wet canopy evaporation and rainfall derived previously for forests and an estimate of the roof storage capacity derived from the data collected in the previous study. Although the model prediction is sensitive to the value of storage capacity, close correlation between the modelled and measured runoff indicates that the model captures the essential processes. It is concluded that the process of evaporation from an urban roof is sufficiently similar to that from a forest canopy for forest evaporation models to be used to give a useful estimate of urban roof runoff. Copyright © 2007 John Wiley & Sons, Ltd. [source] Interleukin-10 expression significantly correlates with minor CD8+ T-cell infiltration and high microvessel density in patients with gastric cancerINTERNATIONAL JOURNAL OF CANCER, Issue 8 2006Teruhisa Sakamoto Abstract We aimed to investigate the relationships between interleukin-10 (IL-10) expression and both the clinicopathological findings and prognoses in patients with gastric cancer and to compare IL-10 expression with microvessel (MV) density and CD8+ T lymphocyte infiltration to evaluate its effects on angiogenesis and immune responses in gastric cancer. IL-10 expression was determined in gastric cancer patients by reverse transcription-polymerase chain reaction (RT-PCR) or immunohistochemical procedures. Two of 7 normal gastric tissues showed IL-10 mRNA expression, while its expressions were confirmed in all advanced gastric carcinoma tissues examined (n = 11) by RT-PCR. Immunohistochemical staining demonstrated that IL-10 expression was detected in 52 (47.7%) of 109 cases. There was a close correlation between IL-10 expression and MV density. IL-10 expression inversely correlated with CD8+ T-lymphocyte infiltration. The prognoses of patients whose tumors expressed IL-10 were significantly worse than those of patients whose tumors did not express IL-10. Multivariate analysis indicated IL-10 expression was an independent prognostic factor. IL-10 might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric cancer. © 2005 Wiley-Liss, Inc. [source] Carotenoids/vitamin C and smoking-related bladder cancerINTERNATIONAL JOURNAL OF CANCER, Issue 3 2004J. Esteban Castelao Abstract Previous epidemiological studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results, especially with respect to the role of cigarette smoking as a possible modifier of the diet-bladder cancer association. A population-based case-control study was conducted in nonAsians of Los Angeles, California, which included 1,592 bladder cancer patients and an equal number of neighborhood controls matched to the index cases by sex, date of birth (within 5 years) and race between January 1, 1987 and April 30, 1996. Information on smoking, medical and medication history, and intake frequencies of food groups rich in preformed nitrosamines, vitamins A and C and various carotenoids, were collected through in-person, structured interviews. Beginning in January 1992, all case patients and their matched control subjects were asked for a blood sample donation at the end of the in-person interviews for measurements of 3- and 4-aminobiphenyl (ABP) hemoglobin adducts, and glutathione S -transferases M1/T1/P1 (GSTM1/T1/P1) and N -acetyltransferase-1 (NAT1) genotypes. Seven hundred seventy-one (74%) case patients and 775 (79%) control subjects consented to the blood donation requests. In addition, all case patients and matched control subjects were asked to donate an overnight urine specimen following caffeine consumption for measurements of cytochrome P4501A2 (CYP1A2) and N -acetyltransferase-2 (NAT2) phenotypes. Urine specimens were collected from 724 (69%) case patients and 689 (70%) control subjects. After adjustment for nondietary risk factors including cigarette smoking, there were strong inverse associations between bladder cancer risk and intake of dark-green vegetables [p value for linear trend (p) = 0.01], yellow-orange vegetables (p = 0.01), citrus fruits/juices (p = 0.002) and tomato products (p = 0.03). In terms of nutrients, bladder cancer risk was inversely associated with intake of both total carotenoids (p = 0.004) and vitamin C (p = 0.02). There was a close correlation (r = 0.58, p = 0.0001) between intakes of total carotenoids and vitamin C in study subjects. When both nutrients were included in a multivariate logistic regression model, only total carotenoids exhibited a residual effect that was of borderline statistical significance (p = 0.07 and p = 0.40 for total carotenoids and vitamin C, respectively). Cigarette smoking was a strong modifier of the observed dietary effects; these protective effects were confined largely to ever smokers and were stronger in current than ex-smokers. Smokers showed a statistically significant or borderline statistically significant decrease in 3- and 4-aminobiphenyl (ABP)-hemoglobin adduct level with increasing intake of carotenoids (p = 0.04 and 0.05, respectively). The protective effect of carotenoids on bladder cancer seemed to be influenced by NAT1 genotype, NAT2 phenotype and CYP1A2 phenotype; the association was mainly confined to subjects possessing the putative NAT1 -rapid, NAT2-rapid and CYP1A2-rapid genotype/phenotype. The carotenoid-bladder cancer association was not affected by the GSTM1, GSTT1 and GSTP1 genotypes. © 2004 Wiley-Liss, Inc. [source] Evaluation of a clinical examination skills training course in an undergraduate pharmacy programmeINTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 4 2008Dr. Andy Wearn senior lecturer, director Objective To introduce and evaluate a short clinical examination skills course in a BPharm programme. The study objectives were to assess needs, explore attitudes, record perceived competence requirements and assess the value of physical examination skills learning. Setting BPharm programme in Auckland, New Zealand. Participants were students enrolled in years 3 and 4 of the programme (2003). Method The design was a longitudinal, dual cohort, educational intervention evaluation using a self-completed questionnaire. An examination skills component was added to the fourth year of the pharmacy programme. Year 3 and 4 students were recruited, and completed the questionnaire at two points. Year 3 students were sampled one year before and soon after the skills sessions. Year 4 students were sampled after the sessions and 18 months later (once registered). The questionnaire sought their attitudes towards clinical skills training and practical relevance for future practice, and evaluated their learning experience. Key findings Response rates at the four points were 42,67%. Year 3 students identified a similar set of appropriate skills to those actually taught in year 4. Overall, attitudes to introducing examination skills learning were positive at all points. At follow-up, both cohorts agreed more strongly that examination skills training should be core (significantly for registered pharmacists versus year 3, P < 0.006). Measuring manual blood pressure was deemed the most difficult skill. All taught skills were used in practice except for respiratory rate; most used were body mass index (BMI), temperature and peak flow measurement. Conclusions There was a close correlation between what was offered in the course, what students felt they needed to learn and what was relevant in practice. Once registered, pharmacists were aware of their limitations and level of competence in relation to clinical skills. The small changes in attitudinal scores appear to reflect maturity and experience. The study design allowed us to adapt the educational component to student need. Health professional educators need to be aware of and respond to changes in professional scopes of practice. [source] Predictive value of renal histological changes for postoperative renal function improvement in children with congenital ureteropelvic junction stenosisINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2002Ahmet Erbagci Abstract Background: The aim of this study was to evaluate the relationship between renal function, as measured by diuretic radionuclide renography, and the outcome of pyeloplasty. A study was designed to evaluate renal parenchymal biopsy specimens derived from children undergoing corrective surgery for ureteropelvic junction (UPJ) stenosis, and compare these to preoperative and postoperative renal function status. Methods: Thirty-five children with congenital unilateral UPJ stenosis were evaluated. In addition to all conventional diagnostic procedures for UPJ stenosis, differential renal functional (DRF) activity was assessed in each of these children by obtaining 99mTc diethylenetriaminepentaacetic acid renogram curves. All children underwent dismembered pyeloplasty, and follow-up renogram evaluation was conducted 6 and 12 months after surgical repair. Biopsy specimens from renal cortical regions obtained during the surgical correction of UPJ stenosis were evaluated, and changes in renal histology were graded from I to V according to their severity. Spearman's correlation test was used to compare the histological evaluation results and the basal, 6- and 12-month follow-up DRF findings. A Wilcoxon paired test was used to evaluate statistical differences between values. Results: The findings showed a positive correlation between the severity of histological changes and DRF activity. All kidneys (22) with a DRF activity value of < 40% preoperatively demonstrated at least grade III changes when biopsy specimens were examined. Of children with a DRF activity value > 40% (13), only three showed severe histological changes. Histological grades were correlated between basal (r = ,0.4; P = 0.019), 6-month (r = 0.54; P = 0.002) and 12-month (r = 0.54; P = 0.02) findings. In the Wilcoxon paired test, there was a statistically significant difference between basal and 6-month values (P < 0.05), and also between basal and 12-month values (P < 0.01). There was no statistically significant difference between 6- and 12-month values (P > 0.20). Conclusion: Comparative evaluation of postoperative renal function with DRF activity and renal parenchymal histological alterations revealed a close correlation in terms of renal function improvement potential following reconstructive surgery in children with UPJ stenosis. [source] Do the Left Atrial Substrate Properties Correlate with the Left Atrial Mechanical Function?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2008A Novel Insight from the Electromechanical Study in Patients with Atrial Fibrillation Background: The atrial substrate is the determinant of occurrence and maintenance of atrial fibrillation (AF), which can induce remodeling of atrial function and structure. This study investigated the relationship between the left atrial (LA) substrate properties and LA mechanical function. Methods: Forty-four consecutive patients (50.3 ± 10.7 years old, 33 men) who presented with sinus rhythm during echocardiographic study before receiving catheter ablation for AF were enrolled. The LA diameter, LA volume, ratio of early and late transmitral filling flow velocities (E/A), LA appendage flow velocity, and transmitral velocity-time integral (VTI) were measured by the echocardiography. The LA empty fraction (LAEF), which was obtained via dividing the difference between maximal and minimal LA volume by maximal LA volume, was calculated as a parameter of the global LA contractile function. The LA global contact voltage mapping (NavX system) was performed before pulmonary vein isolation. Results: Mean LA voltage and LA low voltage zone index (LVZ index, area with voltage < 0.5 mV, divided by total LA surface area) showed significant correlation with LA diameter and volume, but only the LA LVZ index showed significant correlation with A-wave velocity, transmitral A-wave VTI, and LAEF (r =,0.340, ,0.411, ,0.426; P = 0.024, 0.006, 0.005, respectively). We divided the LA LVZ index into three groups (< 10%, 10,20%, > 20%). The LAEF got worse and the transmitral A-wave VTI percentage (divided by transmitral VTI) decreased as LA LVZ index increased. Conclusions: The LA substrate properties showed close correlation with LA size, but only the LA LVZ index correlated with the LA mechanical function. [source] Predictors of cardiac events in high-risk patients undergoing emergency surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009A. OSCARSSON Background: The aim of this study was to determine the incidence of myocardial damage and left ventricular myocardial dysfunction and their influence on outcome in high-risk patients undergoing non-elective surgery. Methods: In this prospective observational study, 211 patients with American Society of Anesthesiologists classification III or IV undergoing emergent or urgent surgery were included. Troponin I (TnI) was measured pre-operatively, 12 and 48 h post-operatively. Pre-operative N-terminal fragment of B-type natriuretic peptide (NT-proBNP), as a marker for left ventricular systolic dysfunction, was analyzed. The diagnostic thresholds were set to TnI >0.06 ,g/l and NT-proBNP >1800 pg/ml, respectively. Post-operative major adverse cardiac events (MACE), 30-day and 3-months mortality were recorded. Results: Elevated TnI levels were detected in 33% of the patients post-operatively. A TnI elevation increased the risk of MACE (35% vs. 3% in patients with normal TnI levels, P<0.001) and 30-day mortality (23% vs. 7%, P=0.003). Increased concentrations of NT-proBNP were seen in 59% of the patients. Elevated NT-proBNP was an independent predictor of myocardial damage post-operatively, odds ratio, 6.2 [95% confidence interval (CI) 2.1,18.0] and resulted in an increased risk of MACE (21% vs. 2.5% in patients with NT-proBNP ,1800 pg/ml, P<0.001). Conclusion: Myocardial damage is common in a high-risk population undergoing unscheduled surgery. These results suggest a close correlation between myocardial damage in the post-operative period and increased concentration of NT-proBNP before surgery. The combinations of TnI and NT-proBNP are reliable markers for monitoring patients at risk in the peri-operative period as well as useful tools in our risk assessment pre-operatively in emergency surgery. [source] Cytoprotection by bcl-2 gene transfer against ischemic liver injuries together with repressed lipid peroxidation and increased ascorbic acid in livers and serumJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2004Shinobu Yanada Abstract The maximum gene exhibition was shown to be achieved at 48 h after transfection with human bcl-2 (hbcl-2) genes built in an SV40 early promoter-based plasmid vector and HVJ-liposome for cultured rat hepatocytes. The similar procedure of hbcl-2 transfection was therefore conducted for livers in rats via the portal vein, and after 48 h followed by post-ischemic reperfusion (I/R) operation for some hepatic lobes. The I/R-induced hepatic injuries were in situ observed as both cell morphological degeneration and cellular DNA strand cleavages around capillary vessels of the ischemic liver lobes as detected by HE stain and TUNEL assay, and were biochemically observed as release of two hepatic marker enzymes AST and ALT into serum. All the I/R-induced injuries examined were appreciably repressed for rats transfected with hbcl-2; hbcl-2 was expressed in hepatocytes around the capillaries of ischemic regions such as the median lobe and the left lobe, but scarcely around those of non-ischemic regions. Thus cytoprotection against I/R-induced injuries may be attributed to the I/R-promoted expression of transferred hbcl-2 genes. The possibility was examined firstly by methylphenylindole method, which showed that I/R-enhanced lipid peroxidation in the reference vector-transfected livers were markedly repressed in the hbcl-2 -transfected livers. Contents of ascorbic acid (Asc) in serum and livers of hbcl-2 -transfected rats were enriched, unexpectedly, versus those of non-transfected rats, and were as abundant as 1.90-fold and 1.95- to 2.60-fold versus those in the pre-ischemic state, respectively. After I/R, an immediate decline in serum Asc occurred in hbcl-2 -transfectants, and was followed by prompt restoration up to the pre-ischemic Asc levels in contrast to the unaltered lower Asc levels in non-transfectants except a transient delayed increase. Hepatic Asc contents were also diminished appreciably at the initial stage after I/R in the ischemic lobes of hbcl-2 -transfectants, which however retained more abundant Asc versus non-transfectants especially at the initial I/R stage when scavenging of the oxidative stress should be most necessary for cytoprotection. The results showed a close correlation between cytoprotection by exogenously transferred hbcl-2 and repressive effects on the lipid peroxidation associated with Asc consumption or redistribution. © 2004 Wiley-Liss, Inc. [source] Cleavage of p130Cas in anoikisJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2004Lin Wei Abstract p130Cas is a multifunctional signaling adaptor protein. It integrates and relays signals generated from a variety of extracellular stimuli and regulates a number of cellular activities including cell death. In this study, we analyzed the regulation and function of p130Cas in anoikis, a type of apoptosis caused by disruption of cell-matrix interactions. We found that p130Cas was specifically cleaved during anoikis in anoikis-sensitive epithelial cells, but not in anoikis-resistant tumor cells. There is a close correlation between p130Cas cleavage and anoikis. Furthermore, we found that the cleavage of p130Cas, as well as another focal adhesion component FAK, is different from that of caspase substrate PARP and spectrin. Although caspases and calpain were found to be involved in the cleavage of p130Cas, there appear to be other unidentified proteases that are mainly responsible for the cleavage of p130Cas, particularly at the early stage of anoikis. Overexpression of the p130Cas cleavage product induced apoptosis. Taken together, these data suggest that there are novel proteases involved in the cleavage of p130Cas during anoikis, which may be functionally involved in the onset of anoikis. p130Cas may have a dual role in the regulation of anoikis. On one hand, it mediates a survival signal from cell-matrix interactions when cells are attached to the extracellular matrix. On the other hand, it participates in executing cell death when cell-matrix interactions are disrupted. These observations provide new insights into the understanding of the function of p130Cas and the molecular mechanism of anoikis. © 2003 Wiley-Liss, Inc. [source] JNK phosphorylates the HSF1 transcriptional activation domain: Role of JNK in the regulation of the heat shock responseJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2001Jeonghyeon Park Abstract The role of c-Jun NH2 -terminal kinase (JNK) signaling cascade in the stress-inducible phosphorylation of heat shock factor 1 (HSF1) was investigated using known agonists and antagonists of JNK. We showed that treatment of HeLa cells with MG132, a proteasome inhibitor and known JNK activator, caused the transcriptional activation domain of HSF1 to be targeted and phosphorylated by JNK2 in vivo. Dose-response and time course studies of the effects of heat shock and anisomycin treatment showed a close correlation of the activation of JNK and hyperphosphorylation of HSF1. SB203580 inhibited JNK at the 100 ,M concentration and significantly reduced the amount of hyperphosphorylated HSF1 upon heat shock or anisomycin treatment. SB203580 and dominant-negative JNK suppress hsp70 promoter-driven reporter gene expression selectively at 45°C but not at 42°C heat stress, suggesting that JNK would be preferentially associated with the protective heat shock response against severe heat stress. The possibility that JNK-mediated phosphorylation of HSF1 may selectively stabilize the HSF1 protein and confers protection to cells under conditions of severe stress is discussed. J. Cell. Biochem. 82: 326,338, 2001. © 2001 Wiley-Liss, Inc. [source] Using the Acetabulum to Estimate Age at Death of Adult Males,JOURNAL OF FORENSIC SCIENCES, Issue 2 2006Carme Rissech Ph.D. ABSTRACT: The acetabular region is often present and adequately preserved in adult human skeletal remains. Close morphological examination of the 242 left male os coxae from the identified collection of Coimbra (Portugal) has enabled the recognition of seven variables that can be used to estimate age at death. This paper describes these variables and argues their appropriateness by analyzing the correlation between these criteria and the age, the intra- and interobserver consistence, and the accuracy in age prediction using Bayesian inference to estimate age of identified specimens. Results show significant close correlation between the acetabular criteria and age, nonsignificant differences in intra- and interobserver test, and 89% accuracy in Bayes prediction. Obtained estimated age of the specimens had similar accuracy in all ages. These results indicate that these seven variables, based on the acetabular area, are potentially useful to estimate age at death for adult specimens. [source] Clinicopathological study of scirrhous hepatocellular carcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2006Mina Kurogi Abstract Background and Aims:, Scirrhous hepatocellular carcinoma (SHCC) is characterized by diffuse fibrosis of the tumor, however, its clinicopathological features are not fully clarified. This study aimed to clarify the clinicopathological features of SHCC. Methods:, Among 546 consecutively resected HCC without preoperative anticancer therapies, 25 SHCC were selected for the study and compared with 521 cases without scirrhous as the control. Results:, SHCC accounted for 4.6% of cases. On diagnostic imagings, SHCC was frequently misdiagnosed as cholangiocarcinoma (CC), combined HCC-CC or metastatic carcinoma. Overall survival rate was significantly higher than the control. The average (±SD) tumor size of SHCC was 3.4 ± 1.8 cm without significant difference to the control. The majority of SHCC (88%) were located close to the liver capsule. SHCC was characterized by stellate fibrosis (84%), no encapsulation (100%), no necrosis and hemorrhage (100%), intratumoral portal tracts (80%), remarkable lymphocyte infiltration (84%), clear cell change (84%), and hyaline bodies (52%). The number of ,-smooth muscle actin-positive myofibroblast-like cells (activated stellate cells) in the tumor was about three times more than that in the control. Regarding the developmental mechanism of scirrhous change, a close correlation with unique tumor location and activation of stellate cells was suggested. Conclusion:, SHCC presents with characteristic clinicopathological features and the recognition of SHCC is important for both clinicians and pathologists. [source] Free-radical 4-nitrophenylation of thieno[2,3- b]pyridine.JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 6 2001Part 3: Consideration of mechanistic, selectivity factors involved in the substitution process A 1:1 geometrically oriented encounter complex between thieno[2,3-b]pyridine (1) and 4-nitrophenyldia-zoacetate (2) is proposed to account for the dominant formation (ca. 64%) of the 2-isomer in the mixture of 4-nitrophenyl-l isomers obtained previously. A mechanism involving one-electron transfer from 1 to 2 plus fragmentation of 2· into 4-nitrophenyl free radical, N2, and acetate ion is invoked. Formation of other isomers is discussed. It is noted that there is a close correlation between orientational rules plus mechanisms of reaction for numerous free-radical substitutions (SR) with SN reactions of alkyllithiums on furan, thiophene, N -alkylpyrroles, pyridine, and their condensed aromatic molecules, including 1, as substrates. Also isomeric selectivities for SE, SN, and SR substitutions into 1 were shown to be qualitatively consistent with one another. While SE reactions occur largely at position 3 and then at 2, SN and SR reactions occur either at 2 or 6. Selectivity for positions 4 or 5 is small or zero. [source] Molecularly defined (L)-lactic acid oligomers and polymers: Synthesis and characterizationJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 18 2008Kenichi Takizawa Abstract The synthesis of (L)-lactide oligomers from dimer to 64mer via an exponential growth strategy is described. By careful selection of orthogonal protective groups, the synthesis were conducted using a t -butyldimethylsilyl (TBDMS) ether as the protective group of the hydroxyl group and benzyl (Bn) ester as the protective group of the carboxylic acid group. The yields of both the deprotection steps and coupling reactions using 1,3-dicyclohexylcarbodiimide or 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride were high (70,100%) and the absence of a requirement for conducting the majority of reactions under an inert atmosphere permitted a robust and efficient synthetic strategy to be developed. This allowed monodisperse dimer, tetramer, octamer, 16mer, 32mer, and 64mer materials to be prepared in gram quantities and fully characterized using mass spectrometry and size exclusion chromatography. Evaluation of the thermal and physical properties using thermogravimetric analysis, differential scanning calorimetry, and small angle X-ray scattering demonstrated a close correlation between the molecular structure of the well-defined Poly(lactide) oligomers and their physical properties. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5977,5990, 2008 [source] Negative Thermal Expansion and Correlated Magnetic and Electrical Properties of Si-Doped Mn3GaN CompoundsJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 3 2010Ying Sun The negative thermal expansion (NTE) and correlated magnetic and electrical transport properties of Mn3GaxSi1,xN were investigated. For pure Mn3GaN, there is a large NTE effect corresponding to the antiferromagnetic to paramagnetic transition. Very interestingly, when partial Ga was replaced by Si, the NTE properties around the magnetic transition were changed. The NTE temperature range was broadened to ,T=148 K for Mn3Ga0.75Si0.25N and the linear thermal expansion coefficient was estimated as ,=,1.4 × 10,5 K,1 (272,420 K). Accordingly, the resistivity also showed a decrease from 327 to 395 K with temperature. With a further increasing Si content to x=0.5, the magnetic transition still occured, but the NTE effect did not appear. After careful observation, an anomaly was found at around 350 K in a,T, ,,T, and DSC curves of Mn3Ga0.5Si0.5N, respectively. This phenomenon strongly implies the close correlation among lattice, spin, and charge in this series materials. [source] Validation of a brief symptom questionnaire (ReQuest in Practice) for patients with gastro-oesophageal reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2008G. RUBIN Summary Background, A clinical need exists for a means of assessing symptom control in patients with gastro-oesophageal reflux disease. The ReQuest questionnaire has been extensively validated for symptom assessment in both erosive and non-erosive gastro-oesophageal reflux disease but was designed for research purposes. We derived a shorter version (ReQuest in Practice) that would be more convenient for clinical practice. Aim, To validate ReQuest in Practice in patients suffering from gastro-oesophageal reflux disease. Methods, Multicentre, non-interventional, crossover comparison. Patients completed ReQuest in Practice followed by ReQuest or vice versa. Before and after a planned endoscopy, patients completed the health-related quality of life questionnaire GERDyzer. Internal consistency and the Intraclass Correlation Coefficient were calculated. Construct validity was evaluated by correlation with ReQuest and GERDyzer. Results, There was high internal consistency of ReQuest in Practice (Cronbach's alpha: 0.9) and a high Intraclass Correlation Coefficient of 0.99. The measurement error of ReQuest in Practice was 4.1. High correlation between ReQuest in Practice and ReQuest (Spearman correlation coefficient: 0.9) and GERDyzer (Spearman correlation coefficient: 0.8) demonstrated construct validity. Conclusions, ReQuest in Practice was proven to be valid and reliable. Its close correlation with ReQuest makes it a promising tool to guide the clinical management of patients across the full spectrum of both erosive and non-erosive gastro-oesophageal reflux disease. [source] Palaeontologic and biogeochemical characterization of the Cyrtograptus lundgreni event in the black shales of eastern Mid-Sardinia, ItalyLETHAIA, Issue 2 2006Paola Pittau A succession of biotic and geochemical changes that occurred during the Cyrtograptus lundgreni Event (Late Wenlock) have been recorded from the ,pelagic' black-shales in the Goni section, eastern mid-Sardinia, Italy. The studied interval encompasses the Cyrtograptus rigidus to Pristiograptus dubius-Gothograptus nassa zones. The fossil association includes graptolites, chitinozoans and microplankton i.e. probable linings of agglutinated foraminifera and radiolaria capsular membranes. Analysis of the chitinozoan distribution revealed a succession of several chitinozoan associations with low species diversity and dominated by opportunistic species. Three chitinozoan faunal turnovers and three extinction events have been recorded. Two of them coincide with graptolite extinctions whereas one probably is of local significance. Disappearance of the chitinozoan and microplankton associations occurred during four consecutive graptolite zones. Geochemical data (trace elements analysis) showed significantly higher (up to c. 100%) values for Co and Cd in the sedimentary organic matter (SOM) than in the whole rock samples. Possible relationships between peaks of metal enrichment, the major faunal changes among chitinozoans, extinction events among chitinozoans and graptolites and, to a certain extent, oceanic events may be inferred. The first extinction datum is older that those occurring in Gotland, Sweden and Thüringen, Germany and is so far considered to be of local significance. The second extinction datum of Sardinia can be matched with Datum 1 of Gotland and Thüringen. A close correlation between the third extinction datum of Sardinia and Datum 2 of Thüringen and Gotland reinforces the importance of these events at global scale. [source] Genetic similarity of polyploids: a new version of the computer program POPDIST (version 1.2.0) considers intraspecific genetic differentiationMOLECULAR ECOLOGY RESOURCES, Issue 5 2009JÜRGEN TOMIUK Abstract For evolutionary studies of polyploid species estimates of the genetic identity between species with different degrees of ploidy are particularly required because gene counting in samples of polyploid individuals often cannot be done, e.g., in triploids the phenotype AB can be genotypically either ABB or AAB. We recently suggested a genetic distance measure that is based on phenotype counting and made available the computer program POPDIST. The program provides maximum-likelihood estimates of the genetic identities and distances between polyploid populations, but this approach is not informative for populations within species that only differ in their allele frequencies. We now close this gap by applying the frequencies of shared ,bands' in both populations to Nei's identity measure. Our simulation study demonstrates the close correlation between the band-sharing identity and the genetic identity calculated on the basis of gene frequencies for any degree of ploidy. The new extended version of POPDIST (version 1.2.0) provides the option of choosing either the maximum-likelihood estimator or the band-sharing measure. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||