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Various Markers (various + marker)
Selected AbstractsArchitectural changes in the developing human brain based on the matrix cell theoryCONGENITAL ANOMALIES, Issue 3 2002Yasuhiro Nakamura ABSTRACT, Architectural changes in the developing human brain are discussed based on the matrix cell theory. Neural stem cells/matrix cells with self-renewing ability and multipotency exist in the developing human brain in vivo. The brain development is divided into three stages and the cell differentiation is time regulated. Immunohistochemical distribution of various markers for brain development is summarized and categorized along with differentiation lineages. Particularly, the existence of glial fibrillary acidic protein is re-evaluated in the developing human brain. The commonly used terms and concepts "radial glial fiber" or "subventricular zone" are also re-evaluated. [source] Human remyelination promoting antibody inhibits apoptotic signaling and differentiation through Lyn kinase in primary rat oligodendrocytesGLIA, Issue 15 2010J. Watzlawik Abstract Purpose: Human remyelination promoting IgM mAbs target oligodendrocytes (OLs) and function in animal models of multiple sclerosis (MS). However, their mechanism of action is unknown. This study seeks to identify the cellular mechanism of action of a recombinant human IgM on OL survival. Methods: Binding of rHIgM22 to the surface of rat OLs was studied by co-localization with various markers. RHIgM22-mediated effects on apoptotic signaling in OLs, differentiation markers, and signaling molecules were detected by Western blotting and immunoprecipitation. Results: RHIgM22 co-localized with integrin ,3 but not other integrin ,-chains in OLs. Downstream of integrin ,3 we identified Src family kinase (SFK) Lyn as a key player of rHIgM22-mediated actions in OLs. Lyn immunoprecipitated in a complex together with integrin ,v,3 and PDGF,R. Lyn expression was 9-fold up-regulated and Lyn activation was 3-fold higher inrHIgM22-treated OL cultures compared with controls. RHIgM22 inhibited apoptotic signaling by greater than 10-fold reduction of caspase-3 and capsase-9 cleavage and reduced by 4-fold expression of differentiation markers MBP and MOG in OLs. SFK inhibitors PP2 and SU6656 inhibited Lyn activity and restored caspase-cleavage in OLs. A human IgM that did not promote remyelination and medium wereused as controls. Conclusions: rHIgM22 prevented apoptotic signaling andinhibited OL differentiation by Lyn implying thatIgM-mediated remyelination is due toprotection of OPC and OLs rather than promotion of OPC differentiation. © 2010 Wiley-Liss, Inc. [source] Alcohol inhibition of neurogenesis: A mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse modelHIPPOCAMPUS, Issue 5 2010Stephanie A. Morris Abstract Adolescents diagnosed with an alcohol use disorder show neurodegeneration in the hippocampus, a region important for learning, memory, and mood regulation. This study examines a potential mechanism by which excessive alcohol intake, characteristic of an alcohol use disorder, produces neurodegeneration. As hippocampal neural stem cells underlie ongoing neurogenesis, a phenomenon that contributes to hippocampal structure and function, we investigated aspects of cell death and cell birth in an adolescent rat model of an alcohol use disorder. Immunohistochemistry of various markers along with Bromo-deoxy-Uridine (BrdU) injections were used to examine different aspects of neurogenesis. After 4 days of binge alcohol exposure, neurogenesis was decreased by 33 and 28% at 0 and 2 days after the last dose according to doublecortin expression. To determine whether this decrease in neurogenesis was due to effects on neural stem cell proliferation, quantification of BrdU-labeled cells revealed a 21% decrease in the dentate gyrus of alcohol-exposed brains. Cell survival and phenotype of BrdU-labeled cells were assessed 28 days after alcohol exposure and revealed a significant, 50% decrease in the number of surviving cells in the alcohol-exposed group. Reduced survival was supported by significant increases in the number of pyknotic-, FluoroJade B positive-, and TUNEL-positive cells. However, so few cells were TUNEL-positive that cell death is likely necrotic in this model. Although alcohol decreased the number of newborn cells, it did not affect the percentage of cells that matured into neurons (differentiation). Thus, our data support that in a model of an adolescent alcohol use disorder, neurogenesis is impaired by two mechanisms: alcohol-inhibition of neural stem cell proliferation and alcohol effects on new cell survival. Remarkably, alcohol inhibition of neurogenesis may outweigh the few dying cells per section, which implies that alcohol inhibition of neurogenesis contributes to hippocampal neurodegeneration in alcohol use disorders. © 2009 Wiley-Liss, Inc. [source] Assessment of Markers for Identifying Patients at Risk for Life-Threatening Arrhythmic Events in Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2005YOUICHI AJIRO M.D. Introduction: Risk stratification for life-threatening arrhythmic events in Brugada syndrome is not yet established. The aim of the present study was to examine the usefulness of various markers in predicting life-threatening arrhythmic events in the Brugada syndrome. Methods and Results: Forty-six patients with Brugada-type ECGs were categorized into the symptomatic (n = 28) and asymptomatic (n = 18) groups. Statistical analyses were performed with respect to the usefulness of the following markers: SCN5A mutation, pharmacologic challenge, ventricular fibrillation (VF) inducibility by programmed electrical stimulation, and late potential (LP) by signal-averaged ECG (SAECG). Comparison between the two groups revealed a significant difference only in LP positivity (92.6% vs 47.1%, P = 0.0004). The symptomatic group had significantly lower RMS40, longer LAS40, and longer fQRSd compared with the asymptomatic group. A significant difference was noted, especially RMS40. The positive predictive value, negative predictive value, and predictive accuracy when setting a cutoff value of 15 ,V were 92.0%, 78.9%, and 86.4%, respectively. Furthermore, patients with an RMS40 value <15 ,V (n = 25) showed significantly higher rates of VF recurrence compared with patients with an RMS40 value , 15 ,V (n = 19, P = 0.047). Conclusion: Regarding risk stratification for identifying high-risk patients in Brugada syndrome, only LP by SAECG was shown to be useful, suggesting the importance of RMS40 in predicting the history of life-threatening arrhythmic events and the recurrence of VF. [source] Xanthine oxidase inhibitor allopurinol attenuates the development of diabetic cardiomyopathyJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Mohanraj Rajesh Abstract In this study, we investigated the effect of the xanthine oxidase (XO) inhibitor, allopurinol (ALP), on cardiac dysfunction, oxidative-nitrosative stress, apoptosis, poly(ADP-ribose) polymerase (PARP) activity and fibrosis associated with diabetic cardiomyopathy in mice. Diabetes was induced in C57/BL6 mice by injection of streptozotocin. Control and diabetic animals were treated with ALP or placebo. Left ventricular systolic and diastolic functions were measured by pressure,volume system 10 weeks after established diabetes. Myocardial XO, p22phox, p40phox, p47phox, gp91phox, iNOS, eNOS mRNA and/or protein levels, ROS and nitrotyrosine (NT) formation, caspase3/7 and PARP activity, chromatin fragmentation and various markers of fibrosis (collagen-1, TGF-,, CTGF, fibronectin) were measured using molecular biology and biochemistry methods or immunohistochemistry. Diabetes was characterized by increased myocardial, liver and serum XO activity (but not expression), increased myocardial ROS generation, p22phox, p40phox, p47phox, p91phox mRNA expression, iNOS (but not eNOS) expression, NT generation, caspase 3/7 and PARP activity/expression, chromatin fragmentation and fibrosis (enhanced accumulation of collagen, TGF-,, CTGF and fibronectin), and declined systolic and diastolic myocardial performance. ALP attenuated the diabetes-induced increased myocardial, liver and serum XO activity, myocardial ROS, NT generation, iNOS expression, apoptosis, PARP activity and fibrosis, which were accompanied by improved systolic (measured by the evaluation of both load-dependent and independent indices of myocardial contractility) and diastolic performance of the hearts of treated diabetic animals. Thus, XO inhibition with ALP improves type 1 diabetes-induced cardiac dysfunction by decreasing oxidative/nitrosative stress and fibrosis, which may have important clinical implications for the treatment and prevention of diabetic cardiomyopathy and vascular dysfunction. [source] Validity of FibroScan values for predicting hepatic fibrosis stage in patients with chronic HCV infectionJOURNAL OF DIGESTIVE DISEASES, Issue 2 2009Ryosuke TAKEMOTO OBJECTIVE: The aim of this study was to validate the FibroScan system compared with liver histology and serum markers for the diagnosis of hepatic fibrosis. We also tried to determine the cut-off levels and assess the feasibility of using FibroScan values to predict the fibrosis stage. METHODS: In 44 patients with HCV infection, liver stiffness was evaluated by FibroScan, serum fibrosis markers and a liver biopsy. Associations between these indices were also analyzed. RESULTS: FibroScan values showed a good correlation with serum levels of type IV collagen, hyaluronic acid and procollagen-III-peptide, and with the platelet count. Compared with liver histology, the FibroScan values increased proportionally with the progression of the histological fibrosis stage. Advanced fibrosis (F3 or F4) could be efficiently predicted by a FibroScan cut-off value of 15 kPa. The FibroScan sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 100%, 73.9%, 77.8%, 100%, and 86.4%, respectively. CONCLUSION: FibroScan values gave a good correlation with various markers of fibrosis and increased proportionally with the progression of the hepatic fibrosis stage. A FibroScan value of 15 kPa was found to be a significant separation limit for differentiating advanced fibrosis stages (F3 and F4) from the milder stages (F0,F2). FibroScan values are clinically useful for predicting the fibrosis stages and helpful in managing interferon therapy in patients with chronic hepatitis C. [source] Quantification of expression levels of cellular differentiation markers does not support a general shift in the cellular phenotype of osteoarthritic chondrocytesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2003Pia Margarethe Gebhard Abstract Many studies have shown increased anabolic activity in osteoarthritic cartilage and have suggested changes in the cellular phenotypes of articular chondrocytes. Most of these studies relied on non-quantitative technologies, which did not allow the estimation of the relative importance of the different differentiation phenomena. In the present study, we developed and used quantitative PCR assays for collagen types I, II(total), IIA, III, and X as marker genes indicating cellular synthetic activity (collagen type II) as well as differentiation pattern of chondrocytes (collagen types I, IIA, III, and X) and quantified these genes in normal, early degenerative, and late stage osteoarthritic cartilage in parallel. At first sight, our results confirmed previously published data showing hardly any expression of collagen genes in normal and significantly enhanced expression in osteoarthritic cartilage. This included collagen types II, III, and IIA, but also collagen types I(,1) and X. However, if one considers the ratios of the various markers of chondrocytic differentiation in comparison to collagen type II, the main synthetic product of differentiated chondrocytes, no shift in the cellular phenotype was detectable. In fact, expression ratios remained constant or were even decreased in osteoarthritic cartilage. Our results confirm that normal adult human articular chondrocytes display hardly any expression activity of the collagen types investigated, whereas osteoarthritic chondrocytes show very increased synthetic activity. The largely unchanged ratios of collagen subtypes investigated indicate that no general shift in the cellular phenotype does occur in osteoarthritic cartilage as suggested by previous investigations. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Influence of anesthesia on immune responses and its effect on vaccination in children: review of evidencePEDIATRIC ANESTHESIA, Issue 5 2007J.N. SIEBERT MD Summary Anesthesia and surgery exert immunomodulatory effects and some authors argue that they may exert additive or synergistic influences on vaccine efficacy and safety. Alternatively, inflammatory responses and fever elicited by vaccines may interfere with the postoperative course. There is a lack of consensus approach among anesthesiologists to the theoretical risk of anesthesia and vaccination. Few studies have assessed the influence of anesthesia and surgery on pediatric vaccine responses. We have undertaken an extensive review of articles published in English between 1970 and 2006 meeting the criteria: measurement of immune parameters following general anesthesia in children. By searching the major medical databases (OVID Medline, PubMed, ISI Web of Science) and references cited in the articles themselves, among 277 articles obtained none examined directly the influence of anesthesia/surgery on vaccine responses. Only 16 original reports assessed the influence of several anesthetic agents on various markers of immunity including lymphocyte numbers and functions. These results are reinterpreted here in view of our current understanding of the immune mechanisms underlying vaccine efficacy and adverse events. We conclude that the immunomodulatory influence of anesthesia during elective surgery is both minor and transient (around 48 h) and that the current evidence does not provide any contraindication to the immunization of healthy children scheduled for elective surgery. However, respecting a minimal delay of 2 days (inactivated vaccines) or 14,21 days (live attenuated viral vaccines) between immunization and anesthesia may be useful to avoid the risk of misinterpretation of vaccine-driven adverse events as postoperative complications. [source] Fluorescent protein fusions to a human immunodeficiency virus monoclonal antibody reveal its intracellular transport through the plant endomembrane systemPLANT BIOTECHNOLOGY JOURNAL, Issue 7 2008Sarah L. Irons Summary In order to further understand the production and intracellular trafficking of pharmaceutical proteins in plants, the light and heavy chains (LC and HC) of the human immunodeficiency virus neutralizing monoclonal antibody 2G12 were fused to fluorescent proteins [Venus and monomeric red fluorescent protein (mRFP)] to enable the visualization of their passage through the plant cell. Co-expression of LC and HC with various markers of the endomembrane system demonstrated that LC fusions were found in mobile punctate structures, which are likely to be pre-vacuolar compartments (PVCs) as a proportion of the LC fusions were found to be located in the vacuole. In addition, apoplast labelling was also observed with a 2G12LC-RFP fusion. The HC fusion expressed alone was found only in the endoplasmic reticulum (ER). When the LC and HC fusions were expressed together, they were found to co-locate to larger punctate structures, which were morphologically distinct from any observed on expression of LC or HC alone. These structures appeared to be in close association with the ER and their labelling partially overlapped with PVC marker fluorescence, but no increase in apoplast labelling was observed. Co-immunoprecipitation data demonstrated that the presence of the fluorescent proteins did not affect the assembly of the antibody, and also showed the association of BiP with the antibody chains. The antigen-binding activity of the Venus-fused 2G12 antibody was confirmed by enzyme-linked immunosorbent assay. [source] Roles of perinatal problems on adolescent antisocial behaviors among children born after 33 completed weeks: a prospective investigationTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 10 2008Yoko Nomura Background:, There is uncertainty about the extent to which mildly sub-optimal perinatal characteristics among individuals born near-term (>33 weeks of gestation) are associated with various subsequent childhood problems, including antisocial behavior. There is even more uncertainty about whether the pathway to antisocial behavior differs by gender. Methods:, A sample of 1689 infants, born near-term, was followed from birth for over 30 years. Using structural equation modeling (SEM), the study evaluated hypothesized mechanisms linking perinatal problems to antisocial behavior, mediated through the following variables in early and later childhood: neurological abnormalities at age 1; hearing, speech, and language problems at age 3; cognitive function at age 4; and academic performance at age 7. Childhood problems were assessed by trained research clinicians, blind to perinatal status. An ,antisocial behavior' variable was created, based on retrospective self-report of six antisocial incidences assessed in adulthood. Results:, Path coefficients showed that birthweight, head circumference, and Apgar scores were indirectly associated with antisocial behavior in the presence of one or more of the following: neurological abnormalities, abnormality in language, speech, and hearing, cognitive function, or academic performance. We found gender differences only in the associations between hearing and IQ and between language perception and IQ. Poor academic performance was associated with antisocial behavior in both boys and girls. Conclusion:, Our hypothesis, that perinatal problems may progress to antisocial behavior when mediated by various markers of early childhood problems, was confirmed. Adverse perinatal events need to be considered in identifying infants who are at risk for academic problems and antisocial behavior, even when the infant is born relatively close to term (i.e., >33 weeks). Poor academic performance, which is indirectly influenced by a variety of neurological and cognitive problems during the perinatal period, infancy, and early childhood appear to increase antisocial behavioral problems in both girls and boys. [source] Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis,THE JOURNAL OF PATHOLOGY, Issue 2 2007Y Hori Abstract Renal cell carcinoma (RCC) is more frequently observed in patients on dialysis than in patients with normal renal function. However, the mechanism underlying carcinogenesis in RCC patients on dialysis is still unclear. We hypothesized that oxidative stress affects patients on dialysis and generates new neoplasms, and therefore analysed the correlation between the influences of various markers of oxidative stress and carcinogenesis in those patients. We evaluated the immunohistochemical expression of oxidative stress markers, such as iNOS, 8-OHdG, and COX-2 in 42 cases on dialysis and 51 cases with normal renal function as a control. The methylation status of p16INK4a, p14ARF, VHL, and RASSF1A was analysed together with clinicopathological factors. Histologically, the papillary type was observed more frequently in dialysis RCC than in sporadic RCC. Immunohistochemically, overexpression of iNOS (p < 0.0001) and COX-2 (p = 0.0002) was more frequently observed in dialysis RCC. Furthermore, the 8-OHdG labelling index was significantly higher in dialysis RCC than in sporadic RCC. Hypermethylation of p16INK4a was more frequently found in dialysis RCC (p < 0.05). However, no significant correlations between oxidative stress markers and DNA hypermethylation status were observed. The overexpression of iNOS, COX-2, and 8-OHdG in dialysis RCC suggests that patients on dialysis are affected by oxidative stress and that this effect plays an important role in the genesis of dialysis RCC. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Functional characterization of hypertrophy in chondrogenesis of human mesenchymal stem cellsARTHRITIS & RHEUMATISM, Issue 5 2008Michael B. Mueller Objective Mesenchymal stem cells (MSCs) are promising candidate cells for cartilage tissue engineering. Expression of cartilage hypertrophy markers (e.g., type X collagen) by MSCs undergoing chondrogenesis raises concern for a tissue engineering application for MSCs, because hypertrophy would result in apoptosis and ossification. To analyze the biologic basis of MSC hypertrophy, we examined the response of chondrifying MSCs to culture conditions known to influence chondrocyte hypertrophy, using an array of hypertrophy-associated markers. Methods Human MSC pellet cultures were predifferentiated for 2 weeks in a chondrogenic medium, and hypertrophy was induced by withdrawing transforming growth factor , (TGF,), reducing the concentration of dexamethasone, and adding thyroid hormone (T3). Cultures were characterized by histologic, immunohistochemical, and biochemical methods, and gene expression was assessed using quantitative reverse transcription,polymerase chain reaction. Results The combination of TGF, withdrawal, a reduction in the level of dexamethasone, and the addition of T3 was essential for hypertrophy induction. Cytomorphologic changes were accompanied by increased alkaline phosphatase activity, matrix mineralization, and changes in various markers of hypertrophy, including type X collagen, fibroblast growth factor receptors 1,3, parathyroid hormone,related protein receptor, retinoic acid receptor ,, matrix metalloproteinase 13, Indian hedgehog, osteocalcin, and the proapoptotic gene p53. However, hypertrophy was not induced uniformly throughout the pellet culture, and distinct regions of dedifferentiation were observed. Conclusion Chondrogenically differentiating MSCs behave in a manner functionally similar to that of growth plate chondrocytes, expressing a very similar hypertrophic phenotype. Under the in vitro culture conditions used here, MSC-derived chondrocytes underwent a differentiation program analogous to that observed during endochondral embryonic skeletal development, with the potential for terminal differentiation. This culture system is applicable for the screening of hypertrophy-inhibitory conditions and agents that may be useful to enhance MSC performance in cartilage tissue engineering. [source] A comprehensive review of biomarkers in psoriasisCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2009R. Rashmi Summary Psoriasis is a common, chronic skin disorder, the pathogenesis of which is incompletely understood. Results from various clinical and experimental studies indicate that psoriasis is a complex, multifactorial disease with a genetic predisposition. Factors such as climate, physical trauma, drug, stress and infections (Streptococcus, human immunodeficiency virus) are known to trigger psoriasis. The success of treatment of psoriasis with T-cell depletion and antitumour necrosis factor (TNF)-, treatment is explained by the involvement of T cells and TNF- , in the pathogenesis of psoriasis. The biochemical basis for the pathogenesis of psoriasis can be attributed to both overexpression and underexpression of certain proteins in psoriatic lesions. The anomalies in protein expression can be classified as abnormal keratinocyte differentiation, keratinocyte hyperproliferation and inflammation. Oxidative stress (OS) and increased free-radical generation have been linked to skin inflammation in psoriasis. The review presents evidence for various markers of psoriasis that can be targeted for effective treatment, including biomarkers of inflammation, keratinocyte hyperproliferation and abnormal differentiation, and stress. [source] | |||||||||||||