Home About us Contact
|
Home About us Contact | ||
|
|
||
Multistep Process (multistep + process)
Selected AbstractsENDOSCOPIC DIAGNOSIS OF INTRAEPITHELIAL SQUAMOUS NEOPLASIA IN HEAD AND NECK AND ESOPHAGEAL MUCOSAL SITESDIGESTIVE ENDOSCOPY, Issue 2006Manabu Muto In the multistep process of squamous epithelial carcinogenesis, squamous epithelial dysplasia has been considered to be a preinvasive stage of squamous cell carcinoma. If we could distinguish a dysplasia at high risk, such lesions could be targets for local treatment such as endoscopic mucosal resection to avoid the transformation to invasive carcinoma. Narrow-band imaging, a new optical technology, is useful to identify the cancerous lesion compared to conventional white light image. In addition, narrow-band imaging combined with magnifying endoscopy makes it possible to visualize the changes of microvascular architecture occurring in the epithelium. To evaluate whether these endoscopic findings are reliable to diagnose a dysplasia at high risk, a prospective study on the basis of the standards for reporting diagnostic accuracy initiative is needed. If endoscopic assessment of intraepithelial squamous neoplasia is reliable, it would be of benefit to the patients' outcome and improve cost effectiveness of care because of the avoidance of developing invasive carcinoma and the reduction of unnecessary biopsies. [source] A Guide to Understanding and Developing Performance-Level DescriptorsEDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 4 2008Marianne Perie There has been much discussion recently about why the percentage of students scoring Proficient or above varies as much as it does on state assessments across the country. However, most of these discussions center on the leniency or rigor of the cut score. Yet, the cut score is developed in a standard-setting process that depends heavily on the definition for each level of performance. Good performance-level descriptors (PLDs) can be the foundation of an assessment program, driving everything from item development to cut scores to reporting. PLDs should be written using a multistep process. First, policymakers determine the number and names of the levels. Next, they develop policy definitions specifying the level of rigor intended by each level, regardless of the grade or subject to which it is applied. Finally, content experts and education leaders should supplement these policy definitions with specific statements related to the content standards for each assessment. This article describes a process for developing PLDs, contrasts that with current state practice, and discusses the implication for interpreting the word "proficient," which is the keystone of No Child Left Behind. [source] Targeting leukocyte trafficking to inflamed skin , still an attractive therapeutic approach?EXPERIMENTAL DERMATOLOGY, Issue 1 2007Thomas M. Zollner Abstract:, Research into leukocyte trafficking and its therapeutic exploitation appears to be a multistep process, just like the trafficking cascade itself. The initial euphoria evoked by an early understanding of the trafficking steps was followed by considerable disappointment following the clinical failure of the first selectin antagonist Cylexin (CY-1503), a sialyl LewisX mimetic. The research area recovered and identified additional attractive pharmacological targets such as chemokine receptors and integrins. However, after lack of efficacy in anti-chemokine trials and the fatalities associated with anti VLA-4 therapy (Tysabri), the question arose again whether targeting leukocyte trafficking is really promising or whether such a complex, multistep process with many redundant and/or functionally overlapping molecules is simply too challenging to deal with. In this article, we delineate some pros and cons of this approach followed by a brief update on where we stand in the field and where we might move in the future. [source] The activation of gelsolin by low pHFEBS JOURNAL, Issue 20 2003The calcium latch is sensitive to calcium but not pH Gelsolin is a multidomain and multifunction protein that nucleates the assembly of filaments and severs them. The activation of gelsolin by calcium is a multistep process involving many calcium binding sites that act to unfold the molecule from a tight structure to a more loose form in which three actin-binding sites become exposed. Low pH is also known to activate gelsolin, in the absence of calcium and this too results in an unfolding of the molecule. Less is known how pH-activation occurs but we show that there are significant differences in the mechanisms that lead to activation. Crucially, while it is known that the bonds between G2 and G6 are broken by co-operative occupancy of calcium binding sites in both domains [Lagarrique, E., Maciver, S. K., Fattoum, A., Benyamin, Y. & Roustan, C. (2003) Eur. J. Biochem. 270, 2236,2243.], pH values that activate gelsolin do not result in a weakening of the G2-G6 bonds. We report the existence of pH-dependent conformational changes within G2 and in G4,6 that differ from those induced by calcium, and that low pH overrides the requirement for calcium for actin-binding within G4,6 to a modest extent so that a Kd of 1 µm is measured, compared to 30,40 nm in the presence of calcium. Whereas the pH-dependent conformational change in G2 is possibly different from the change induced by calcium, the changes measured in G4,6 appear to be similar in both calcium and low pH. [source] Human telomerase catalytic subunit gene re-expression is an early event in oral carcinogenesisHISTOPATHOLOGY, Issue 1 2004B Luzar Aims:, Detection of telomerase catalytic subunit (hTERT) mRNA has been used as a surrogate marker for estimation of telomerase activity. The exact role and timing of telomerase re-activation, a key enzyme implicated in cellular immortalization and transformation, in the multistep process of oral carcinogenesis is still unknown. The aim was to test the hypothesis that (i) quantitative rather than qualitative differences exist in the level of hTERT mRNA expression between normal oral mucosa, different grades of oral epithelial abnormalities and squamous cell carcinomas of the oral cavity, and that (ii) hTERT gene re-expression is an important, probably early event in oral carcinogenesis. Methods and results: The relative quantity of hTERT mRNA was analysed in 45 frozen oral epithelia representing different morphological stages of oral carcinogenesis classified according to the Ljubljana classification and in 37 oral squamous cell carcinomas, using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. hTERT mRNA was not detected in normal or reactive hyperplastic oral epithelia, but was present in 43% of atypical hyperplasias (premalignant lesions), 60% of intraepithelial carcinomas and 68% of oral squamous cell carcinomas. Statistical analysis revealed two groups of oral epithelial changes, with significant differences in the levels of hTERT mRNA expression: 1, normal and reactive hyperplastic oral epithelium, and 2, atypical hyperplasia, intraepithelial carcinomas and squamous cell carcinomas. Conclusion:, These data suggest that hTERT gene re-expression represents an early event in the multistep process of oral carcinogenesis, already detectable at the stage of precancerous oral epithelial changes. Nevertheless, other genetic aberrations appear to be necessary for progression of oral epithelial abnormalities towards invasive squamous cell carcinoma. [source] The diagnosis of dysplasia and malignancy in Barrett's oesophagusHISTOPATHOLOGY, Issue 2 2000REVIEW Barrett's metaplasia is associated with an increased risk for adenocarcinoma. Adenocarcinoma develops through a multistep process characterized by defects in genes and morphological abnormalities. The early morphological changes of the process are called ,dysplasia'. Dysplasia is defined as an unequivocal neoplastic (premalignant) transformation confined within the basement membrane. For most Western pathologists malignancy is defined as invasion and characterized by a breach through the basement membrane. Japanese pathologists rely on cytological atypia and complex branching of crypts. Cytological and architectural abnormalities allow identification of dysplasia on routinely stained sections. A distinction is made between low- and high-grade dysplasia. The differential diagnosis between low-grade dysplasia and reactive changes can be difficult. Therefore a second opinion is strongly recommended, not only for high-grade dysplasia but also for low-grade. Immunohistochemistry for p53 and flow cytometry for detection of aneuploidy can support the diagnosis. Identification of dysplasia and malignancy depends on the number of biopsy samples examined. The minimum number of biopsies required has not yet been determined and depends partly on the length of the metaplastic segment. It has been proposed to sample with four quadrant biopsies at 20-mm intervals. New endoscopic techniques can increase the diagnostic yield. Endoscopically visible lesions increase the risk of finding malignancy. The time sequence for the progression of dysplasia is not known but progression from low- to high-grade and cancer has been shown to occur over a period of years although it may not be inevitable. [source] Shock tube study of 1,3,5-triazine dissociation and relaxation and relaxation of pyrazineINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2010Hui Xu The three-body dissociation of 1,3,5-triazine (s-triazine, s-C3H3N3 , 3HCN) has been observed in incident shock waves with the laser-schlieren technique. The experiments use 5% triazine/Kr and cover 1630,2350 K for 100,600 Torr. These experiments show dissociation rates with strong falloff and a slight but fully expected pressure dependence. The dissociation is without secondary reaction save for a possible, but rather unlikely, contribution from the isomerization HCN , HNC. Electronic structure calculations of the transition-state properties (G3B3, HL1, Eo = 84.6 kcal/mol) are used to construct a Rice,Ramsperger,Kassel,Marcus (RRKM) model whose fit to the rate measurements suggests a ,,E,down of 1200 cm,1. However, a seemingly better fit is achieved using the barrier of 81 kcal/mol proposed by Dyakov et al. (J. Phys. Chem. A 2007, 111, 9591,9599). With this barrier k, (s,1) = 5.3 × 1016 exp(,86.6(kcal/mol)/RT), and the fit now accepts the more routine ,,E,down = 126(T/298)0.9. It seems the dissociation most likely occurs by a direct, one-step, "triple" dissociation to 3HCN, although the present experiments cannot rule out a multistep process. Vibrational relaxation of the triazine was also examined in 5% and 20% mixtures with Kr over 770,1500 K for pressures between 6 and 14 Torr. Relaxation is very fast, with a slight inverse temperature dependence, P, rising from 100 to 200 ns-atm over the full temperature range. Integrated gradients are in good accord with calculated total changes in density, indicating a single exponential relaxation. A separate investigation of relaxation in the related molecule pyrazine (500,1300 K, in 1% and 5% in Kr, between 13 and 66 Torr) is included. Again relaxation is rapid, but here the temperature dependence seems more normal, the relaxation times decreasing slightly with temperature. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 211,220, 2010 [source] Kinetic characterization of a transient reaction by degeneration of the precursor mechanism: Application to the synthesis of 3,4-diazabicyclo[4.3.0]- non-2-eneINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 5 2006H. Delalu The rate of the oxidation of N -amino-3-azabicyclo[3.3.0]octane by chloramine has been studied by GC and HPLC between pH 10.5 and 13.5. The second-order reaction exhibits specific acid catalysis. The formation of N,N,-azo-3-azabicyclo[3.3.0]octane or 3,4-diazabicyclo[4.3.0]non-2-ene is pH, concentration, and temperature dependent. In alkaline media, the exclusive formation of 3,4-diazabicyclo[4.3.0]non-2-ene is observed. Kinetic studies show that the oxidation of N -amino-3-azabicyclo[3.3.0]octane by chloramine is a multistep process with the initial formation of a diazene-type intermediate, which is converted by hydroxide ions into 3,4-diazabicyclo[4.3.0]non-2-ene. Because it was not possible to follow the rate of change of the intermediate concentration, to determine the kinetics of 3,4-diazabicyclo[4.3.0]non-2-ene formation, a procedure based on the degeneration of the precursor process was adopted. An appropriate mathematical treatment allowed a quantitative interpretation of all the phenomena observed over the given pH interval. The activation parameters were determined. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 327,338, 2006 [source] Protein Import Into MitochondriaIUBMB LIFE, Issue 3-5 2001Stefan A. Paschen Abstract Most mitochondrial proteins are encoded by the nuclear genome and thus have to be imported into mitochondria from the cytosol. Protein translocation across and into the mitochondrial membranes is a multistep process facilitated by the coordinated action of at least four specialized translocation systems in the outer and inner membranes of mitochondria. The outer membrane contains one general translocase, the TOM complex, whereas three distinct translocases are located in the inner membrane, which facilitates translocation of different classes of preproteins. The TIM23 complex mediates import of matrix-targeted preproteins with N -terminal presequences, whereas hydrophobic preproteins with internal targeting signals are inserted into the inner membrane via the TIM22 complex. The OXA translocase mediates the insertion of preproteins from the matrix space into the inner membrane. This review focuses on the structural organization and function of the import machinery of the model organisms of Saccharomyces cerevisiae and Neurospora crassa . In addition, the molecular basis of a new human mitochondrial disorder is discussed, the Mohr-Tranebjaerg syndrome. This is the first known disease, which is caused by an impaired mitochondrial protein import machinery leading to progressive neurodegeneration. [source] Proliferative drive and liver carcinogenesis: Too much of a good thing?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2009Narci C Teoh Abstract There have been innumerable studies published in the attempt to identify gene expression signatures in hepatocellular carcinoma (HCC). When all the regulators and targets of the differentially expressed genes are analyzed from larger studies, the most striking theme is upregulation of mitosis-promoting and cell proliferation genes in HCC compared with ,liver-specific gene clusters' in non-tumorous tissue. A major limitation of expression profiling is that it only provides a ,snapshot' of what is an evolving process and thus cannot distinguish the differences in gene expression that are primary effectors of dysregulated growth from those that represent downstream consequences. The development of HCC in a chronically diseased liver, often referred to as hepatocarcinogenesis, is a multistep process characterized by the progressive accumulation and interplay of genetic alterations causing aberrant growth, malignant transformation of liver parenchymal cells, followed by vascular invasion and metastasis. This review will discuss HCC precursor lesions, draw on the ,proliferation cluster' genes highlighted from HCC expression profiling studies, relate them to a selection of regulatory networks important in liver regeneration, cell cycle control and their potential significance in the pathogenesis of HCC or primary liver cancer. [source] The tumor suppressor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factorJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2009Satoshi Otani MD Abstract Background/Aims Hepatocarcinogenesis is a multifactorial, multistep process that involves the activation of oncogenes or the inactivation of tumor suppressor genes throughout the different stages of hepatocellular carcinoma (HCC) progression. NPRL2 is one of the candidate tumor suppressor genes identified on chromosome 3p21.3, a region which frequently contains genetic abnormalities found in the early stages of the development of various human cancers. In the current study, we aimed to evaluate NPRL2 expression in HCC and to explore the prognostic significance of NPRL2. Method We investigated NPRL2 mRNA expression in 70 HCC specimens, using quantitative real-time reverse transcription polymerase chain reaction analysis, and the correlation between NPRL2 expression and clinicopathologic parameters. Results NPRL2 mRNA was found to be expressed equally in both HCC tissues and corresponding non-cancerous liver tissues. However, higher NPRL2 expression correlated significantly with tumor size (P,=,0.0062) and serum PIVKA-II levels (P,=,0.0002). Univariate and multivariate analyses revealed that higher NPRL2 mRNA expression was an independent prognostic factor for overall survival (risk ratio 0.39; P,<,0.0001). Conclusion Our results suggest that NPRL2 mRNA expression has prognostic significance for the survival of patients with HCC. J. Surg. Oncol. 2009;100:358,363. © 2009 Wiley-Liss, Inc. [source] INK4a-ARF mutations in skin carcinomas from UV irradiated hairless miceMOLECULAR CARCINOGENESIS, Issue 4 2004N. Soufir Abstract To characterize further the role of the INK4a-ARF locus in the multistep process of skin carcinogenesis, we performed a mutational analysis of this locus in skin lesions from hairless mice either irradiated with UVB alone or with a solar simulator delivering UVA,+,B. INK4a-ARF mutations were present in five of 57 squamous cell carcinomas (9%), but no mutation was detected in precancerous lesions. All mutations were C:G,>,T:A transitions located at dipyrimidic sites, the hallmark of UVB mutagenesis. Three mutations affected only the p19ARF reading frame, whereas two mutations affected only the p16INK4a transcript. This study demonstrates for the first time UV-induced mutations of INK4a-ARF that occur in a small percentage in late stages skin tumors. © 2004 Wiley-Liss, Inc. [source] A multistep process for the dispersal of a Y chromosomal lineage in the Mediterranean areaANNALS OF HUMAN GENETICS, Issue 4 2001P. MALASPINA In this work we focus on a microsatellite-defined Y-chromosomal lineage (network 1.2) identified by us and reported in previous studies, whose geographic distribution and antiquity appear to be compatible with the Neolithic spread of farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it with respect to other lineages associated with the same movements by other authors, examine its diversity by means of tri- and tetranucleotide loci and discuss the implications in reconstructing the spread of this group of chromosomes in the Mediterranean area. Our results define a tripartite phylogeny within HG 9 (Rosser et al. 2000), with the deepest branching defined by alleles T (Haplogroup Eu10) or G (Haplogroup Eu9) at M172 (Semino et al. 2000), and a subsequent branching within Eu9 defined by network 1.2. Population distributions of HG 9 and network 1.2 show that their occurrence in the surveyed area is not due to the spread of people from a single parental population but, rather, to a process punctuated by at least two phases. Our data identify the wide area of the Balkans, Aegean and Anatolia as the possible homeland harbouring the largest variation within network 1.2. The use of recently proposed tests based on the stepwise mutation model suggests that its spread was associated to a population expansion, with a high rate of male gene flow in the Turkish,Greek area. [source] Junctional adhesion molecule C mediates leukocyte adhesion to rheumatoid arthritis synoviumARTHRITIS & RHEUMATISM, Issue 10 2008Bradley J. Rabquer Objective Leukocyte infiltration into the rheumatoid arthritis (RA) synovium is a multistep process in which leukocytes leave the bloodstream and invade the synovial tissue (ST). Leukocyte transendothelial migration and adhesion to RA ST requires adhesion molecules on the surface of endothelial cells and RA ST fibroblasts. This study was undertaken to investigate the role of junctional adhesion molecule C (JAM-C) in mediating leukocyte recruitment and retention in the RA joint. Methods Immunohistologic analysis was performed on RA, osteoarthritis (OA), and normal ST samples to quantify JAM-C expression. Fibroblast JAM-C expression was also analyzed using Western blotting, cell surface enzyme-linked immunosorbent assay, and immunofluorescence. To determine the role of JAM-C in leukocyte retention in the RA synovium, in vitro and in situ adhesion assays and RA ST fibroblast transmigration assays were performed. Results JAM-C was highly expressed by RA ST lining cells, and its expression was increased in OA ST and RA ST endothelial cells compared with normal ST endothelial cells. JAM-C was also expressed on the surface of OA ST and RA ST fibroblasts. Furthermore, we demonstrated that myeloid U937 cell adhesion to both OA ST and RA ST fibroblasts and to RA ST was dependent on JAM-C. U937 cell migration through an RA ST fibroblast monolayer was enhanced in the presence of neutralizing antibodies against JAM-C. Conclusion Our results highlight the novel role of JAM-C in recruiting and retaining leukocytes in the RA synovium and suggest that targeting JAM-C may be important in combating inflammatory diseases such as RA. [source] CCAAT/enhancer binding protein-, promotes the survival of intravascular rat pancreatic tumor cells via antiapoptotic effectsCANCER SCIENCE, Issue 11 2007Yasuhito Shimizu A transcriptional factor, CCAAT/enhancer binding protein-, (C/EBP-,), regulates a variety of cell functions in normal and neoplastic cells. Although the involvement of C/EBP-, in metastasis has been demonstrated clinicopathologically in several types of human cancer, the mechanism by which it functions during the multistep process of metastasis remains largely unknown. We investigated the role of C/EBP-, in the intravascular step of hematogenous metastasis in a rat pancreatic tumor cell line, AR42J-B13, as this step profoundly affects metastatic efficiency. C/EBP-,-transfected AR42J-B13 (,B13) cells acquired considerable resistance against serum toxicity, which was primarily mediated by apoptosis in vitro. Upregulated expression of Bcl-2 and Bcl-xL was seen in ,B13 cells. Enhanced early survival of intraportally injected ,B13 cells in the BALB/c nu/nu male mice liver, detected by the mRNA of a vector-specific gene, was observed. Nick-end labeling analysis of the tumor-injected liver revealed significantly lower rates of apoptosis among intravascular ,B13 tumor cells than among empty vector-transfected AR42J-B13 (mB13) cells. Finally, intrasplenically injected ,B13 cells established a larger number of colonies in the liver than did the mB13 cells. These findings suggest that C/EBP-, may enhance hematogenous metastasis and its antiapoptotic effects may promote the survival of intravascular tumor cells. (Cancer Sci 2007; 98: 1706,1713) [source] Differential mitogenic responses of human macrovascular and microvascular endothelial cells to cytokines underline their phenotypic heterogeneityCELL PROLIFERATION, Issue 3 2001I. Lang A variety of growth factors promote the complex multistep process of angiogenesis. The mitogenic activity of vascular endothelial growth factors (VEGFs) and placental growth factors (PlGFs), known as cytokines acting predominantly on endothelial cells, was tested on human umbilical vein endothelial cells (HUVEC) and microvascular endothelial cells (MIEC) and compared with the potency of the universally acting basic fibroblast growth factor (FGF-2). The cells were seeded at different cell numbers and incubated with various doses of growth factors for a period of 24,72 h in culture medium ± serum. Proliferation was determined by measuring the optical density after staining the cells with the tetrazolium salt WST-1. VEGF121 and VEGF165 increased the number of HUVEC and MIEC at low and high seeding densities various doses and incubation times. The efficiency of FGF-2 was less pronounced at high seeding densities of the cells under serum-free conditions. PlGF-1 and PlGF-2 stimulated mitogenesis on HUVEC only at low cell numbers and after a short incubation time by 125 ± 3% and 102 ± 5% (P < 0.001), respectively. Longer incubation times with the lower seeding density in the absence of FCS did not induce a significant stimulatory effect of the PlGFs. MIEC responded stronger to all growth factors. In particular under serum free conditions, PlGF-1 and PlGF-2 effectively stimulated cell proliferation by 247 ± 54% (P < 0.01) and 288 ± 40% (P < 0.05) at low cell numbers, and by 81 ± 13% (P < 0.05) and 49 ± 13% (P < 0.01), respectively, at high cell numbers. The addition of fetal calf serum caused a reduced proliferative response of all growth factors on both cell types related to the controls. In conclusion, MIEC and HUVEC differ in their proliferative response to VEGFs, PlGFs and FGF-2. [source] | ||||||||||||||||