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Reliable Marker (reliable + marker)
Selected AbstractsWT1 Is Not a Reliable Marker to Distinguish Reactive from Neoplastic Astrocyte Populations in the Central Nervous SystemBRAIN PATHOLOGY, Issue 6 2010T. David Bourne MD Abstract A diagnostic difficulty in neuropathology practice is distinguishing reactive from neoplastic astrocyte populations. This is particularly true in small biopsy samples that lack evidence of increased cellularity or mitotic activity, microvascular proliferation, or necrosis. We performed the current study to validate the previously reported finding that in the central nervous system, the expression of WT1 is limited to neoplastic astrocytes. We retrospectively studied WT1 protein expression by immunohistochemistry (IHC) in 100 formalin-fixed, paraffin-embedded brain tissue samples consisting of 3 normal control tissues, 44 cases of reactive gliosis, 49 gliomas and 4 lesions suspicious for glioma. In normal human cortex, WT1 staining was restricted to vascular endothelium. Most cases of reactive gliosis (82%) showed at least focal WT1 positivity, and analysis of specimens with electrode monitoring lesions showed an inverse relationship between WT1 expression intensity and the number of days from electrode placement to tissue resection. All glioma samples (100%) and all cases suspicious for glioma (100%) showed at least focal WT1 positivity. Our results likely differ from those in the prior report because of differences in tissue fixation and IHC methodology. Thus, our findings indicate that WT1 expression alone is not a reliable feature to distinguish reactive from neoplastic astrocytes. [source] Effect of Normal Saline Infusion on the Diagnostic Utility of Base Deficit in Identifying Major Injury in Trauma PatientsACADEMIC EMERGENCY MEDICINE, Issue 12 2006Richard Sinert DO Abstract Background Base deficit (BD) is a reliable marker of metabolic acidosis and is useful in gauging hemorrhage after trauma. Resuscitation with chloride-rich solutions such as normal saline (NS) can cause a dilutional acidosis, possibly confounding the interpretation of BD. Objectives To test the diagnostic utility of BD in distinguishing minor from major injury after administration of NS. Methods This was a prospective observational study at a Level 1 trauma center. The authors enrolled patients with significant mechanism of injury and measured BD at triage (BD-0) and at four hours after triage (BD-4). Major injury was defined by any of the following: injury severity score of ,15, drop in hematocrit of ,10 points, or the patient requiring a blood transfusion. Patients were divided into a low-volume (NS < 2L) and a high-volume (NS , 2L) group. Data were reported as mean (±SD). Student's t- and Wilcoxon tests were used to compare data. Receiver operating characteristic (ROC) curves tested the utility of BD-4 in differentiating minor from major injury in the study groups. Results Four hundred eighty-nine trauma patients (mean age, 36 [± 18] yr) were enrolled; 82% were male, and 34% had penetrating injury. Major-(20%) compared with minor-(80%) injury patients were significantly (p = 0.0001) more acidotic (BD-0 mean difference: ,3.3 mmol/L; 95% confidence interval [CI] =,2.5 to ,4.2). The high-volume group (n = 174) received 3,342 (±1,821) mL, and the low-volume group (n = 315) received 621 (±509) mL of NS. Areas under the ROC curves for the high-volume (0.63; 95% CI = 0.52 to 0.74) and low-volume (0.73; 95% CI = 0.60 to 0.86) groups were not significantly different from each other. Conclusions Base deficit was able to distinguish minor from major injury after four hours of resuscitation, irrespective of the volume of NS infused. [source] Brain Natriuretic Peptide Levels and Response to Cardiac Resynchronization Therapy in Heart Failure PatientsCONGESTIVE HEART FAILURE, Issue 5 2006Reynolds M. Delgado MD The authors used brain natriuretic peptide (BNP) as a reliable marker to identify nonresponders to cardiac resynchronization therapy (CRT) in patients with advanced heart failure. The study included 70 patients with left ventricular dysfunction (mean ejection fraction, 21±4%) and left bundle branch block (QRS duration, 164±25 milliseconds) treated with CRT. The authors reviewed data on New York Heart Association functional class, baseline ejection fraction, sodium, creatinine, QRS duration, and BNP levels 3 months before and after CRT therapy. The authors compared results of 42 patients who survived (973+192 days) after CRT implantation (responders) to those of 28 patients (nonresponders) who either expired (n=21) or underwent heart transplantation (n=5) or left ventricular assist device implantation (n=2) after an average of 371+220 days. Mean BNP levels after 3 months of CRT decreased in responders from 758±611 pg/mLto 479±451 pg/mL (P=.044), while in nonresponders there was increase in BNP levels from 1191 ±466 pg/mL to 1611 ±1583; P=.046. A rise in BNP levels was associated with poor response (death or need for transplantation or left ventricular assist device and impaired long-term outcome), which makes it a good predictor to identify such patients. [source] p27Kip1 Expression and grading of breast cancer diagnosed on cytological samplesDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2004Giancarlo Troncone M.D. Abstract The progressive reduction in p27Kip1 (p27) protein immunohistochemical staining with increasing histological grading is a well-established finding occurring in breast cancer, and its role as diagnostic complement and prognostic marker has been thoroughly evaluated. To clarify whether this test may be applied to breast cytopathology, we performed p27 immunostaining on fresh fine-needle cytology (FNC) samples from 10 benign and 40 malignant breast lesions. On average, p27 immunostaining was significantly lower in carcinomas than in benign lesions (P < 0.005). In particular, among carcinomas, p27 immunostaining progressively reduced from well-to poorly differentiated lesions (G1 vs. G2, P < 0.05; G1 vs. G3, P < 0.001; G2 vs. G3; P < 0.001). A similar trend was noted in a subgroup of 20 matched FNCs and histological samples of breast carcinomas, when p27 immunostaining on FNCs was stratified according to the histological grading (G1 vs. G2, P = 0.18; G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05). In addition, p27 immunostaining on FNCs showed a good positive correlation with that on histology (Spearman R = 0.58; P < 0.01), with a diagnostic concordance between samples of 85%, by using the standard 50% positive cell cutoff. Taken in concert, our data suggest that p27 immunostaining is a reliable marker of tumor cell differentiation in breast cytopathology as well as in histopathology. Accordingly, staining FNCs for p27 may be an useful complement in addition to cytological grading in the preoperative assessment of breast cancer. Diagn. Cytopathol. 2004;30:375,380. © 2004 Wiley-Liss, Inc. [source] Heat Shock Protein-27 Is Upregulated in the Temporal Cortex of Patients with EpilepsyEPILEPSIA, Issue 12 2004Hans-J Bidmon Summary:,Purpose: Heat shock protein-27 (HSP-27) belongs to the group of small heat shock proteins that become induced in response to various pathologic conditions. HSP-27 has been shown to protect cells and subcellular structures, particularly mitochondria, and serves as a carrier for estradiol. It is a reliable marker for tissues affected by oxidative stress. Oxidative stress and related cellular defence mechanisms are currently thought to play a major role during experimentally induced epileptic neuropathology. We addressed the question whether HSP-27 becomes induced in the neocortex resected from patients with pharmacoresistant epilepsy. Methods: Human epileptic temporal neocortex was obtained during neurosurgery, and control tissue was obtained at autopsy from subjects without known neurologic diseases. The tissues were either frozen for Western blot analysis or fixed in Zamboni's fixative for the topographic detection of HSP-27 at the cellular level by means of immunohistochemistry. Results: HSP-27 was highly expressed in all epilepsy specimens and in the cortex of a patient who died in the final stage of multiple sclerosis (positive control), whereas only low amounts of HSP-27 were detectable in control brains. In epilepsy patients, HSP-27 was present in astrocytes and in the walls of blood vessels. The intracortical distribution patterns varied strongly among the epilepsy specimens. Conclusions: These results demonstrate that HSP-27 becomes induced in response to epileptic pathology. Although the functional aspects of HSP-27 induction during human epilepsy have yet to be elucidated, it can be concluded that HSP-27 is a marker for cortical regions in which a stress response has been caused by seizures. [source] Intralesional bovine papillomavirus DNA loads reflect severity of equine sarcoid diseaseEQUINE VETERINARY JOURNAL, Issue 4 2010R. HARALAMBUS Summary Reasons for performing study: Sarcoids are nonmetastasising, yet locally aggressive skin tumours that constitute the most frequent neoplasm in equids. Infection by bovine papillomaviruses types 1 and 2 (BPV-1, BPV-2) has been recognised as major causative factor in sarcoid pathogenesis, but a possible correlation of intralesional virus load with disease severity has not been established thus far. Hypothesis: Given the pathogenic role of BPV-1 and BPV-2 in sarcoid disease, we suggest that intralesional viral DNA concentration may reflect the degree of affection. Methods: Severity of disease was addressed by recording the tumour growth kinetics, lesion number and tumour type for 37 sarcoid-bearing horses and one donkey. Viral load was estimated via quantitative real-time PCR (qPCR) of the E2, E5, L1 and L2 genes from the BPV-1/-2 genome for one randomly selected lesion per horse and correlated with disease severity. Results: Quantitative PCR against E2 identified viral DNA concentrations ranging from 0,556 copies/tumour cell. Of 16 horses affected by quiescent, slowly growing single tumours or multiple mild-type lesions, 15 showed a viral load up to 1.4 copies per cell. In stark contrast, all equids (22/22) bearing rapidly growing and/or multiple aggressive sarcoids had a viral load between 3 and 569 copies per cell. Consistent results were obtained with qPCR against E5, L1 and L2. Conclusions: While tumours of the same clinical type carried variable virus load, confirming that viral titre does not determine clinical appearance, we identified a highly significant correlation between intralesional viral load and disease severity. Potential relevance: The rapid determination of BPV viral load will give a reliable marker for disease severity and may also be considered when establishing a therapeutic strategy. [source] Influence of clinical factors on the haemolysis marker haptoglobinEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2006G. F. Körmöczi Abstract Background, Plasma haptoglobin determination is clinically used as parameter for haemolysis. To date, however, the influence of the mode of haemolysis (extravascular vs. intravascular) and of nonhaemolytic conditions on haptoglobin concentration and its reliability as a haemolysis marker remain poorly defined. Materials and methods, In a total of 479 individuals, the influence of haemolytic and nonhaemolytic conditions on plasma haptoglobin levels was investigated. Results, All studied types of haemolytic disease (n = 16) were associated with markedly decreased plasma haptoglobin levels, without significant differences between intravascular vs. predominantly extravascular haemolysis. Diminished haptoglobin values were also observed in patients with liver cirrhosis, which normalized after liver transplantation. In contrast, markedly increased haptoglobin levels were found in patients with inflammation. In patients with haemolysis and a concomitant acute-phase response, however, haemolysis-dependent haptoglobin depletion was not attenuated. Interestingly, patients with a strongly positive direct antiglobulin test or high cold agglutinin titre but no further evidence for haemolysis had normal haptoglobin values. Likewise, anaemia owing to bone marrow failure, acute gastrointestinal or chronic diffuse blood loss, and end-stage kidney disease were associated with normal haptoglobin levels. Conclusions, Plasma haptoglobin depletion is a reliable marker for the instant diagnosis of accelerated red cell destruction irrespective of the site of haemolysis or the presence of inflammation. The capacity of this parameter to predict haemolysis appears to be limited in patients with liver cirrhosis and decreased haptoglobin production only. [source] 8-isoprostane increases scavenger receptor A and matrix metalloproteinase activity in THP-1 macrophages, resulting in long-lived foam cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2004H. Scholz Abstract Background, Oxidative stress is a key factor in atherogenesis, in which it is closely associated with the inflammation and formation of bioactive lipids. Although 8-isoprostane is regarded as a reliable marker of oxidative stress in vivo, the pathogenic role of this F2 -isoprostane in atherogenesis is far from clear. Based on the important role of foam cells in the initiation and progression of atherosclerosis we hereby examined the ability of 8-isoprostane to modulate oxidized (ox)LDL-induced foam cell formation and the function of these cells, particularly focusing on the effect on matrix degradation. Methods and results, 8-isoprostane (10 µM) augmented the oxLDL-induced (20 µg mL,1) lipid accumulation of THP-1 macrophages evaluated by Oil-Red-O staining and lipid mass quantification (colourimetric assay). Additionally, 8-isoprostane induced the expression of the scavenger receptor A type 1 (MSR-1) [mRNA and protein level], assessed by RT-PCR and Western blotting, respectively. Moreover, 8-isoprostane counteracted the oxLDL-induced apoptosis of these cells, involving both mitochondrial-protective and caspase-suppressive mechanisms. Along with these changes, 8-isoprostane increased the oxLDL-induced gene expression of matrix metalloproteinase (MMP)-9 and its endogenous inhibitor [i.e. tissue inhibitor of MMP (TIMP)-1] accompanied by enhanced total MMP activity. Conclusions, We show that 8-isoprostane increases foam cell formation at least partly by enhancing MSR-1 expression and by inhibiting apoptosis of these cells, inducing long-lived foam cells with enhanced matrix degrading capacity. Our findings further support a role for 8-isoprostane not only as a marker of oxidative stress in patients with atherosclerotic disorders, but also as a mediator in atherogenesis and plaque destabilization. [source] Cancer-associated genodermatoses: a personal historyEXPERIMENTAL DERMATOLOGY, Issue 9 2006Walter H. C. Burgdorf Abstract:, Cancer-associated genodermatoses are a group of genetic disorders inherited in an autosomal-dominant fashion in which unique cutaneous findings are a reliable marker for the risk of developing internal malignancies. The historical, clinical and dermatopathological aspects of basal cell nevus syndrome, Muir,Torre syndrome, Cowden syndrome, Carney complex and Birt,Hogg,Dubé syndrome are reviewed in a personal and informal fashion. The latest advances in the molecular genetics of the disorders are also summarized. [source] Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infectionHEPATOLOGY, Issue 4 2001Heike Bantel Hepatitis C virus (HCV) infection is a major cause of liver disease characterized by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis has been implicated in the pathogenesis, although it is unclear whether proteases of the caspase family as the central executioners of apoptosis are involved and how caspase activation contributes to liver injury. In the present study, we measured the activation of effector caspases in liver biopsy specimens of patients with chronic HCV infection. The activation of caspase-3, caspase-7, and cleavage of poly(ADP-ribose)polymerase (PARP), a specific caspase substrate, were measured by immunohistochemistry and Western blot analysis by using antibodies that selectively detect the active truncated, but not the inactive precursor forms of the caspases and PARP. We found that caspase activation was considerably elevated in liver lobules of HCV patients in comparison to normal controls. Interestingly, the immunoreactive cells did yet not reveal an overt apoptotic morphology. The extent of caspase activation correlated significantly with the disease grade, i.e., necroinflammatory activity. In contrast, no correlation was observed with other surrogate markers such as serum transaminases and viral load. In biopsy specimens with low activity (grade 0) 7.7% of the hepatocytes revealed caspase-3 activation, whereas 20.9% of the cells stained positively in grade 3. Thus, our results suggest that caspase activation is involved in HCV-associated liver injury. Moreover, measurement of caspase activity may represent a reliable marker for the early detection of liver damage, which may open up new diagnostic and therapeutic strategies in HCV infection. [source] Spectral analysis of electrocorticographic activity during pharmacological preconditioning and seizure induction by intrahippocampal domoic acidHIPPOCAMPUS, Issue 8 2010P.M. Sawant Abstract Previously we have shown that low-dose domoic acid (DA) preconditioning produces tolerance to the behavioral effects of high-dose DA. In this study, we used electrocorticography (ECoG) to monitor subtle CNS changes during and after preconditioning. Young adult male Sprague-Dawley rats were implanted with a left cortical electrode, and acute recordings were obtained during preconditioning by contralateral intrahippocampal administration of either low-dose DA (15 pmoles) or saline, followed by a high-dose DA (100 pmoles) challenge. ECoG data were analyzed by fast Fourier transformation to obtain the percentage of baseline power spectral density (PSD) for delta to gamma frequencies (range: 1.25,100 Hz). Consistent with previous results, behavioral analysis confirmed that low-dose DA preconditioning 60 min before a high-dose DA challenge produced significant reductions in cumulative seizure scores and high level seizure behaviors. ECoG analysis revealed significant reductions in power spectral density across all frequency bands, and high-frequency/high-amplitude spiking in DA preconditioned animals, relative to saline controls. Significant correlations between seizure scores and ECoG power confirmed that behavioral analysis is a reliable marker for seizure analysis. The reduction ofpower in delta to gamma frequency bands in contralateral cortex does not allow a clear distinction between seizure initiation and seizure propagation, but does provide objective confirmation that pharmacological preconditioning by DA reduces network seizure activity. © 2009 Wiley-Liss, Inc. [source] Follicle-stimulating hormone and oestradiol levels during perimenopause in a cohort of Japanese womenINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2008M. Yamada Summary Context:, There had been a lack of longitudinal studies regarding follicle-stimulating hormone (FSH) and oestradiol (E2) during perimenopause for non-Caucasian populations. Objective:, To investigate FSH and E2 levels during perimenopause in a Japanese cohort. Design and setting:, The Adult Health Study is a longitudinal population-based study. Perimenopausal women from this study cohort were followed between 1993 and 2003. Participants and main outcome measures:, Non-menopausal women, aged 47,54 years, were measured in terms of FSH and E2 levels every 6 months. For 89 women whose FSH and E2 levels were measured within 3 months from their final menstrual period (FMP), trends of FSH and E2 within 21 months of FMP were investigated at 6-month intervals. Results:, Follicle-stimulating hormone and E2 levels within 3 months from FMP showed wide ranges. Neither FSH nor E2 levels differed by age, weight or duration of amenorrhoea. Although FSH increased and E2 decreased during perimenopause, FSH and E2 levels at a single time point were found to not be a reliable marker of biological menopause, as hormone levels in and between the subjects showed wide variation and any trend in one individual was not necessarily one directional. Conclusions:, Among Japanese women who had natural menopause around the age of 50, hormone levels in and between individuals showed wide variation throughout perimenopause with a converged biochemical menopausal pattern characterised by high FSH and low E2 at about 2 years after FMP. [source] Bladder smooth muscle cell phenotypic changes and implication of expression of contractile proteins (especially caldesmon) in rats after partial outlet obstructionINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2003SEIJI MATSUMOTO Abstract Background: The purpose of the present study was to investigate morphological changes in bladder smooth muscle of rats with partial outlet obstruction. We investigated smooth muscle cell phenotypic changes and implication of synthetic phenotype in contractility decrease and bladder compliance after bladder outlet obstruction. Methods: Partial bladder outlet obstruction was introduced in female rats. Bladder were removed at 1, 3, 6, 10 and 20 weeks after the obstruction. Temporal pattern of changes in bladder mass, light microscopic pathogenesis and phenotypic expression of the bladder smooth muscle cells in the electron micrographs were investigated. Expression of contractile protein was also investigated by the immunoblotting method. Results: Marked increase in bladder mass with marked thickening of smooth muscle layer was observed at 1 week after obstruction. The ratio of myocytes exhibiting contractile and synthetic phenotypes was almost constant until 6 weeks after the obstruction, but thereafter, synthetic phenotypes gradually increased and the ratio (synthetic/contractile phenotype) was 1.5-fold at 20 weeks after the obstruction. Caldesmon was most markedly expressed after the obstruction among contractile proteins examined by the immunoblotting method. Conclusion: Phenotypic changes were confirmed in bladder smooth muscle, and the decrease of the ratio of contractile phenotype was observed after long-term obstruction of the bladder outlet. Among the contractile proteins in the bladder smooth muscle cell, caldesmon was considered a reliable marker for predicting the pathogenetic conditions of the bladder. [source] Rapid assessment of the sex of codling moth Cydia pomonella (Linnaeus) (Lepidoptera: Tortricidae) eggs and larvaeJOURNAL OF APPLIED ENTOMOLOGY, Issue 4 2009I. Fuková Abstract Two different methods were tested to identify the sex of the early developmental stages of the codling moth Cydia pomonella (Linnaeus) (Lepidoptera: Tortricidae) with a WZ/ZZ (female/male) sex chromosome system. First, it was shown that the sex of all larval stages can be easily determined by the presence or absence of sex chromatin, which is formed by the female-specific W chromosome in interphase nuclei. This trait can also be used to identify the sex of newly hatched larvae but it does require care and accuracy. Secondly, a new sexing technique was developed based on a molecular marker of the codling moth W chromosome. Flanking regions of an earlier described W-specific sequence (CpW2) were isolated and sequenced and a 2.74 kb sequence (CpW2- EcoRI), specific for the W chromosome, was obtained. Several PCR tests were conducted, which confirmed that the CpW2- EcoRI sequence is a reliable marker for the sex identification in codling moth samples of different geographical origin. In addition, a fragment of a codling moth gene, period (Cpper) was isolated and sequenced. Results of southern hybridization of the Cpper probe with female and male genomic DNA suggested that the Cpper gene is located on the Z chromosome. Then a multiplex PCR assay was developed, which co-amplified the CpW2- EcoRI sequence to identify the W chromosome and the Z-linked Cpper sequence, which served as a positive control of accurate processing of tested samples. The multiplex PCR provides an easy and rapid identification of the sex of embryos and early larval instars of the codling moth. [source] Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosisJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2007Alicja Bauer Abstract Primary biliary cirrhosis (PBC) is an autoimmune liver disease with unknown etiology. Patients with PBC have antimitochondrial autoantibodies (AMA) and additionally 50% of them have antinuclear antibodies (ANA). A 15,amino acid fragment (DRKASPPSGLWSPAY) from the C-terminal part of the nuclear envelope glycoprotein gp210 has been proposed as one of the antigenic targets for ANA. The aim of this work was to develop an immunoenzymatic assay for determination of gp210 autoantibodies using for its binding a synthetic pentadecapeptide derived from the gp210 amino acid sequence and to determine level of these autoantibodies in sera of patients with PBC and other autoimmune liver diseases from Poland. Polystyrene microtitration plates coated with the synthetic peptide were consecutively incubated with diluted sera, anti-human immunoglobulin G (IgG) antibodies conjugated with horseradish peroxidase, and with tetramethylobenzidine. Optical density (OD) was read at 450 nm. The mean values of the intra- and interassay of variation coefficients of the test were 4.1 and 10.2%, respectively. Anti-gp210 was detected in 44% of PBC patients and in 6% of patients with PSC. The results were negative for healthy blood donors and other controls. The specificity of the test was 99%, so the anti-gp-210 autoantibodies estimated on DRKASPPSGLWSPAY can be a reliable marker of PBC. J. Clin. Lab. Anal. 21:227,231, 2007. © 2007 Wiley-Liss, Inc. [source] Lifespan extension by dietary restriction is not linked to protection against somatic DNA damage in Drosophila melanogasterAGING CELL, Issue 3 2009Ursula Edman Summary Dietary restriction (DR) has been shown to robustly extend lifespan in multiple species tested so far. The pro-longevity effect of DR is often ascribed to an increase in cellular defense against somatic damage, most notably damage by reactive oxygen species (ROS), considered a major cause of aging. Especially irreversible damage to DNA, the carrier of genetic information, is considered a critical causal factor in aging. Using a recently developed transgenic Drosophila melanogaster model system harboring a lacZ-plasmid construct that can be recovered in E. coli, spontaneous DNA mutation frequency in flies under DR and ad libitum conditions are measured. Three different DR conditions, imposed by manipulating levels of different types of yeast sources, were tested in females and males of two lacZ reporter gene lines. Feeding with the ROS producer paraquat at 1 mM resulted in a rapid accumulation of somatic mutations, indicating that the frequency of mutations at the lacZ locus is a reliable marker for increased oxidative stress. However, none of the DR conditions altered the accumulation of spontaneous mutations with age. These results suggest that the beneficial effects of DR are unlikely to be linked to protection against oxidative somatic DNA damage. [source] Enhanced hippocampal F2 -isoprostane formation following kainate-induced seizuresJOURNAL OF NEUROCHEMISTRY, Issue 5 2001Manisha Patel We attempted to obtain evidence for the occurrence of oxidant injury following seizure activity by measuring hippocampal F2 -isoprostanes (F2 -IsoPs), a reliable marker of free radical-induced lipid peroxidation. Formation of F2- IsoPs esterified in hippocampal phospholipids was correlated with hippocampal neuronal loss and mitochondrial aconitase inactivation, a marker of superoxide production in the kainate model. F2 -IsoPs were measured in microdissected hippocampal CA1, CA3 and dentate gyrus (DG) regions at various times following kainate administration. Kainate produced a large increase in F2 -IsoP levels in the highly vulnerable CA3 region 16 h post injection. The CA1 region showed small, but statistically insignificant increases in F2 -IsoP levels. Interestingly, the DG, a region resistant to kainate-induced neuronal death also showed marked (2.5,5-fold) increases in F2 -IsoP levels 8, 16, and 24 h post injection. The increases in F2 -Isop levels in CA3 and DG were accompanied by inactivation of mitochondrial aconitase in these regions. This marked subregion-specific increase in F2 -Isop following kainate administration suggests that oxidative lipid damage results from seizure activity and may play an important role in seizure-induced death of vulnerable neurons. [source] Immunohistochemical study of syndecan-1 down-regulation and the expression of p53 protein or Ki-67 antigen in oral leukoplakia with or without epithelial dysplasiaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2003Hideo Kurokawa Abstract Background:, Leukoplakia is an oral pre-cancerous lesion that sometimes develops into squamous cell carcinoma. Therefore, leukoplakia with epithelial dysplasia is useful for studying carcinogenesis at the cellular level. The purpose of this study was to evaluate a potential association between the loss of syndecan-1 expression and the expression of p53 protein and Ki-67 antigen, and to identify reliable markers for predicting malignant changes in oral leukoplakia with epithelial dysplasia. Methods:, Changes in the expression of syndecan-1, p53, and Ki-67 were examined immunohistochemically in 43 cases of oral leukoplakia with or without epithelial dysplasia. The subjects were categorized as: none, 13 cases; mild dysplasia, 5 cases; moderate dysplasia, 17 cases; and severe dysplasia, 8 cases. The expression of these molecules in normal oral epithelia (22 cases) was also investigated. Results:, Strong syndecan-1 expression was observed on the surface of keratinocytes in normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. In normal epithelium, p53 and Ki-67 appeared mainly in the basal cell layer, while they were more widely distributed in leukoplakia. Specifically, significant changes were observed in the labeling index of p53 and Ki-67 in leukoplakia as epithelial dysplasia progressed from mild to moderate or severe. Conclusion:, Our results reveal that overexpression of p53 protein and Ki-67 antigen, and down-regulation of syndecan-1 expression in the lower part of the epithelium, are associated with dysplastic changes. Therefore, the down-regulation of syndecan-1 expression may be the most important reliable marker for dysplastic changes. [source] Cystatin C as a marker of renal function immediately after liver transplantationLIVER TRANSPLANTATION, Issue 2 2006Gianni Biancofiore To verify whether cystatin C may be of some use as a renal function marker immediately after orthotopic liver transplantation (OLT), we compared serum cystatin C (SCyst), serum creatinine (Scr), and creatinine clearance (Ccr) levels with the glomerular filtration rate (GFR). On postoperative days 1, 3, 5, and 7, SCyst and Scr was measured in simultaneously drawn blood samples, whereas Ccr was calculated using a complete 24-hour urine collection. The GFR was determined on the same days by means of iohexol plasma clearance (I-GFR). The correlation between 1/SCyst and I-GFR was stronger than that of 1/Scr or Ccr (P< 0.01). In the case of moderate reductions in I-GFR (80-60 mL/minute/1.73 m), Scr remained within the normal range, whereas the increase in Scyst was beyond its upper limit; for I-GFR reductions to lower levels (59-40 mL/minute/1.73 m), Scr increased slightly, whereas Scyst was twice its upper normal limit. When we isolated all of the I-GFR values on days 3, 5, and 7 that were ,30% lower than that recorded on the first postoperative day, SCyst(P< 0.0001) and Scr (P< 0.01) levels were increased, whereas Ccr remained unchanged (P= 0.09). Receiver operating characteristic (ROC) area-under-the-curve analysis showed that the diagnostic accuracy of Scyst was better than that of Scr and Ccr. Scyst levels of 1.4, 1.7, and 2.2 mg/L respectively predicted I-GFR levels of 80, 60, and 40 mL/minute/1.73 m. In conclusion, cystatin C is a reliable marker of renal function during the immediate post-OLT period, especially when the goal is to identify moderate changes in GFR. Liver Transpl 12:285,291, 2006. © 2006 AASLD. [source] Glycated albumin levels predict long-term survival in diabetic patients undergoing haemodialysisNEPHROLOGY, Issue 4 2008KOUSUKE FUKUOKA SUMMARY: Aim: Glycated albumin (GA) is recognized as a reliable marker for monitoring glycemic control particularly in patients with end-stage renal disease (ESRD). Here, we investigated the impact of GA levels on long-term survival in diabetic patients with ESRD. Methods: We enrolled ESRD patients with diabetic nephropathy into our single-centre prospective follow-up study (n = 98, 66 men and 32 women; age 68.2 12.3 years) with a mean follow-up period of 47.7 months. All patients had started haemodialysis between December 1992 and November 2003. They were categorized into two groups according to their GA levels at the initiation of haemodialysis; GA < 29% (low-GA group; n = 54) and GA 29% (high-GA group; n = 44). Results: Between low-GA and high-GA groups, there were no significant differences in various clinical parameters except GA and HbA1c levels. The cumulative survival rate of low-GA group was significantly higher than that of high-GA group (P = 0.034, log,rank test). After adjustment for age, sex, total cholesterol, C-reactive protein and albumin, high-GA was a significant predictor of survival (hazard ratio 1.042 per 1.0% increment of GA, 95% CI 1.014,1.070, P < 0.05), but not in the case with HbA1c. Cox proportional hazard model demonstrated that high-GA group was a significant predictor for cardiovascular death (hazard ratio 2.971 (1.064,8.298), P = 0.038). Conclusion: We conclude that poor glycemic control (GA 29%) before starting haemodialysis is associated with increased cardiovascular morbidity and shortened survival in diabetic patients with ESRD. [source] The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilageORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 1 2005G Shen Structured Abstract Author , Shen G Objective , This review was compiled to explore the role of type X collagen in growth, development and remodeling of articular cartilage by elucidating the linkage between the synthesis of this protein and the phenotypic changes in chondrogenesis and the onset of endochondral ossification. Design , The current studies closely dedicated to elucidating the role of type X collagen incorporating into chondrogenesis and endochondral ossification of articular cartilage were assessed and analyzed to allow for obtaining the mainstream consensus on the bio-molecular mechanism with which type X collagen functions in articular cartilage. Results , There are spatial and temporal correlations between synthesis of type X collagen and occurrence of endochondral ossification. The expression of type X collagen is confined within hypertrophic condrocytes and precedes the embark of endochondral bone formation. Type X collagen facilitates endochondral ossification by regulating matrix mineralization and compartmentalizing matrix components. Conclusion , Type X collagen is a reliable marker for new bone formation in articular cartilage. The future clinical application of this collagen in inducing or mediating endochondral ossification is perceived, e.g. the fracture healing of synovial joints and adaptive remodeling of madibular condyle. [source] Procalcitonin is a reliable marker of severe systemic infection in neutropenic haematological patients with mucositis,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Loredana Sarmati First page of article [source] Impact of acute cellular rejection on coagulation and fibrinolysis biomarkers within the immediate post-operative period in pediatric liver transplantationPEDIATRIC TRANSPLANTATION, Issue 3 2010Jun Mimuro Mimuro J, Mizuta K, Kawano Y, Hishikawa S, Hamano A, Kashiwakura Y, Ishiwata A, Ohmori T, Madoiwa S, Kawarasaki H, Sakata Y. Impact of acute cellular rejection on coagulation and fibrinolysis biomarkers within the immediate post-operative period in pediatric liver transplantation. Pediatr Transplantation 2010:14: 396,376. © 2009 John Wiley & Sons A/S. Abstract:, We studied restoration of the coagulation and fibrinolysis system in pediatric patients following liver transplantation and biomarkers of blood coagulation and fibrinolysis for suspecting the occurrence of acute cellular rejection. Coagulation activity recovered rapidly within two days following transplantation, but it took approximately 21,28 days for full recovery of the coagulation and fibrinolysis factors synthesized in the liver. PAI-1 levels were significantly higher in patients at the time of acute cellular rejection compared with levels after control of AR, and levels on days 14 and 28 in patients without AR. Plasma protein C and plasminogen levels at the time of rejection were significantly lower than those on day 14 in patients without AR. Statistical analysis suggested that an increase in plasma PAI-1 at a single time point in the post-operative period is a reliable marker among the coagulation and fibrinolysis factors for suspecting the occurrence of acute cellular rejection. These data suggested that appropriate anticoagulation may be required for 14 days after liver transplantation in order to avoid vascular complications and measurement of plasma PAI-1 levels may be useful for suspecting the occurrence of acute cellular rejection in pediatric patients following liver transplantation. [source] Patent ductus arteriosus flow patterns in the treatment of congenital diaphragmatic herniaPEDIATRICS INTERNATIONAL, Issue 4 2009Shinya Okamoto Abstract Background:, Congenital diaphragmatic hernia (CDH) mortality still remains high, due to lung hypoplasia and persistent pulmonary hypertension of the neonate (PPHN). Effective management of PPHN and time of operation are quite important to the improvement of CDH treatment. In order to determine the optimal time for operation, we monitored PPHN with cardiac ultrasound. Methods:, PPHN was assessed with three parameters: patent ductus arteriosus flow patterns (PDAFP), %left ventricular diameter at diastole, and left ventricular fraction of shortening (LVFS). Four patients with an antenatal diagnosis were treated under this protocol. Diaphragm repair was performed when PDAFP became left to right shunt dominant and the pre- and postoperative course was analyzed with regular chart reviews. Results:, The alveolar-arterial oxygen difference levels of four patients were 590, 335, 613 and 530 mmHg, and operations were carried out when the patients were 2, 2, 3 and 2 days old, respectively. In three of the four patients (all except case 3) the PDAFP changed from right to left shunt dominant or bidirectional (BD), to left to right shunt dominant within 48 h. The %left ventricular diameter at diastole was relatively stable around the time of operation. The LVFS of all patients decreased after the operation. Only the LVFS of case 3 decreased temporarily to less than 30% (which indicates poor left ventricular function) but recovered. No patients needed extracorporeal membrane oxygenation support. All patients survived the procedure and were extubated. Case 3, who took 10 days to become left to right shunt dominant after the operation, needed home oxygenation therapy for 10 months. Conclusions:, PDAFP was a reliable marker of PPHN on a high-frequency oscillatory ventilator to determine the optimal time for the operation for CDH. The optimal time for operation is supposed to be the time when PDAFP become left to right shunt dominant. [source] Is procalcitonin a reliable marker for the diagnosis of infected pancreatic necrosis?ANZ JOURNAL OF SURGERY, Issue 7 2004Nadir Yonetci Background: Infected necrosis in acute pancreatitis is the main factor in determining the prognosis of the disease. Early and accurate diagnosis of infected pancreatic necrosis might decrease mortality. The aim of the present study is to identify a reliable marker for the onset infection in three different experimentally induced pancreatitis models. Methods: Ninety female Wistar albino rats were randomly divided into nine groups. In three different experimental models, including cerulein induced acute oedematous pancreatitis (AEP), sterile pancreatic necrosis due to taurocholate-induced acute pancreatitis (SPN) and infected pancreatic necrosis taurocholate-induced acute pancreatitis (IPN). Serum levels of procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor a (TNF-,), interleukin 6 (IL-6) and interleukin 8 (IL-8), amylase were measured. The degree of pancreatic damage also evaluated pathologically. Results: Procalcitonin levels were increased significantly in AEP, SPN and IPN compared to control groups (P < 0.05). PCT and IL-6 level were the highest in the IPN group (P < 0.05). Serum amylase, CRP, TNF-,, IL-2, and IL-8 levels were similar between IPN and SPN groups (P > 0.05), but higher than in other groups. The results of histological evaluation also correlated with the advent of the disease. Conclusion: Procalcitonin and IL-6 acts as reliable acute phase reactant in an experimental model of AEP, SPN and IPN in the rat. PCT and IL-6 combination might be surrogate marker of infected pancreatic necrosis and should be preferred to other markers assay especially in severe pancreatitis. [source] Expression of Cell Death-Associated Proteins in Neuronal Apoptosis Associated with Pontosubicular Neuron NecrosisBRAIN PATHOLOGY, Issue 3 2001Christine Stadelmann Expression of apoptosis-associated proteins p53, bcl-2, bax, and caspase-3/CPP32, activation of caspase-3, and modification of proteins via poly(ADP-ribosyl)ation was studied in pontosubicular neuron necrosis (PSN), a form of perinatal brain damage revealing the morphological hallmarks of neuronal apoptosis. Immunoreactivity for p53 was completely absent. The majority of cells stained with the bax and procaspase-3 antibodies did not show morphological signs of apoptosis. In contrast, an antibody against activated caspase-3 almost exclusively stained cells with apoptotic morphology. Poly(ADP-ribosyl)ated proteins were only rarely detected in cells with apoptotic morphology. The expression patterns of bax, procaspase-3, bcl-2, and p53 in PSN were similar to that found in age-matched control brains. However, activated caspase-3 and poly-ADP-ribosylated proteins were exclusively found in apoptotic cells. These data indicate that detection of active caspase-3 is a reliable marker for apoptosis in formalin-fixed human tissue, and that neuronal apoptosis in pontosubicular neuron necrosis is accompanied by a pronounced activation of caspase-3. [source] Reduced in vivo oxidative stress following 5-methyltetrahydrofolate supplementation in patients with early-onset thrombosis and 677TT methylenetetrahydrofolate reductase genotypeBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005Antonio Coppola Summary The protective role of folate in vascular disease has been related to antioxidant effects. In 45 patients with previous early-onset (at age <50 years) thrombotic episodes and the 677TT methylenetetrahydrofolate reductase genotype, we evaluated the effects of a 28d-course (15 mg/d) of 5-methyltetrahydrofolate (MTHF) on homocysteine metabolism and on in vivo generation of 8-iso-prostaglandin F2, (8-iso-PGF2,), a reliable marker of oxidative stress. At baseline, patients' fasting total homocysteine (tHcy) was 11·5 ,mol/l (geometric mean) and urinary excretion of 8-iso-PGF2, was 304 pg/mg creatinine, with the highest metabolite levels in the lowest quartile of plasma folate distribution (P < 0·05). After 5-MTHF supplementation, plasma folate levels increased approximately 13-fold (P < 0·0001 versus baseline); tHcy levels (6·7 ,mol/l, P < 0·0001) and urinary 8-iso-PGF2, (254 pg/mg creatinine, P < 0·001) were both significantly lowered, their reduction being proportional to baseline values (r = 0·98 and r = 0·77, respectively) and maximal in patients with the lowest pre-supplementation folate levels (P < 0·05). The effects on folate (P < 0·0001) and tHcy (P = 0·0004) persisted for at least up to 2 months after withdrawing 5-MTHF. In parallel with long-lasting tHcy-lowering effects, a short-course 5-MTHF supplementation reduces in vivo formation of 8-iso-PGF2, in this population, supporting the antioxidant protective effects of folate in vascular disease. [source] Cancer chronotherapy: Principles, applications, and perspectivesCANCER, Issue 1 2003Marie-Christine Mormont Ph.D. Abstract BACKGROUND Cell physiology is regulated along the 24-hour timescale by a circadian clock, which is comprised of interconnected molecular loops involving at least nine genes. The cellular clocks are coordinated by the suprachiasmatic nucleus, a hypothalamic pacemaker that also helps the organism adjust to environmental cycles. The rest-activity rhythm is a reliable marker of the circadian system function in both rodents and humans. This circadian organization is responsible for predictable changes in the tolerability and efficacy of anticancer agents, and possibly also may be involved in tumor promotion or growth. METHODS Expected least toxic times of chemotherapy were extrapolated from experimental models to human subjects with reference to the rest-activity cycle. The clinical relevance of the chronotherapy principle (i.e., treatment administration as a function of rhythms) has been investigated previously in randomized multicenter trials. RESULTS In the current study, chronotherapeutic schedules were used to safely document activity of the combination of oxaliplatin, 5-fluorouracil, and leucovorin against metastatic colorectal carcinoma and to establish new medicosurgical management for this disease, and were reported to result in unprecedented long-term survival. CONCLUSIONS Chronotherapy concepts appear to offer further potential to improve current cancer treatment options as well as to optimize the development of new anticancer or supportive agents. Cancer 2003;97:155,69. © 2003 American Cancer Society. DOI 10.1002/cncr.11040 [source] Large cava septi pellucidi in schizophrenic patients, alcoholics, head-traumatized, and normal individuals: morpholgical features and forensic implications.ACTA NEUROPSYCHIATRICA, Issue 1 2006A postmortem study Background:, The enlarged cava septi pellucidi (CSP = 6 mm in length) have been reported as a reliable marker of an underlying neuropsychiatric disease or disorder. Differences in the dimensions of cava longer than 6 mm associated with a neuropsychiatric impairment could be of possible clinical and forensic significance. Methods:, We obtained 479 brains from autopsied persons (310 males and 169 females, aged 22,89 years) and observed that 110 brains (75 males and 35 females) had CSP, of which the length of CSP was equal to or longer than 6 mm on 69 (49 males and 20 females) of them. These cava were classified into four groups depending on the past medical histories of the autopsied person: five without neuropsychiatric history (asymptomatic CSP), 25 schizophrenic patients, 22 alcoholics, and 17 with a past head trauma (symptomatic CSP). Results:, The linear parameters of CSP (i.e. length, width) of the symptomatic and asymptomatic groups were measured and were statistically analyzed. Analysis revealed that the cava in the group of schizophrenic patients were significantly longer and wider. Conclusions:, Discriminant function analysis was used to derive a mathematical formula to classify CSP into one of the groups obtained based on width measurements of the cavum. [source] Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxisCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009E. Ono Abstract Background Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. However, pathological evidence of the association between inflammatory mediators and human anaphylaxis is insufficient. Objective The aim of this study was to better understand the relationship between in vivo production of inflammatory mediators and the pathogenesis of anaphylaxis. We also sought to evaluate mast cell activation in anaphylaxis. Methods We measured the concentrations of various inflammatory mediators in urine samples, which were collected from 32 anaphylactic patients during the onset of anaphlaxis and during clinical remission, 21 patients with asthma on acute exacerbation and 15 healthy control subjects. Blood and urine specimens were collected from the patients after provocation test. Urinary leukotriene E4 (LTE4), 9,, 11,-prostaglandin F2 (9,, 11,-PGF2), eosinophil-derived neurotoxin (EDN) and leukotriene B4 glucuronide (LTBG) concentrations were determined by enzyme immunoassay, and the activity of plasma platelet-activating factor acetylhydrolase and serum tryptase concentration were measured using commercially available kits. Results Significantly higher concentrations of urinary LTE4 and 9,, 11,-PGF2, which immediately decreased during clinical remission, were observed in the anaphylactic patients than in asthmatic patients on acute exacerbation and healthy control subjects. Concentrations of EDN and LTBG were not significantly different among the anaphylactic patients, asthmatic patients on acute exacerbation and healthy subjects. There was a significant correlation between urinary LTE4 and 9,, 11,-PGF2 concentrations in the anaphylactic patients (r=0.672, P=0.005, n=32). In addition, LTE4 concentration in patients with anaphylactic shock is significantly elevated compared with that in patients without anaphylactic shock. Conclusions This is a report on the significant increase in urinary LTE4 and 9,, 11,-PGF2 concentrations during anaphylaxis. Urinary LTE4 and 9,, 11,-PGF2 concentrations may be a reliable marker of endogenous production of inflammatory mediators associated with anaphylaxis. [source] | |||||||||||||||||||||||||||||||