New Markers (new + marker)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Primary predictors of preterm labour

François Goffinet
Spontaneous preterm birth accounts for 60% of all preterm births in developed countries. With the increase in multiple pregnancies, induced preterm birth and the progress in neonatal care for extremely preterm neonates, spontaneous preterm birth for singleton pregnancies in developed countries has probably decreased over the past 30 years. This decrease is likely to be related to better prenatal care for all pregnant women because the recognition of primary risk factors in early or late pregnancy remains a basic part of prenatal care. The failure to distinguish between induced and spontaneous preterm labour in most population-based studies makes it difficult to interpret results with respect to the primary predictors of preterm labour. Many such primary predictors of preterm labour have been used over the past 20,30 years. These include individual factors, socio-economic factors, working conditions and obstetric and gynaecological history. Risk scores have been proposed in order to produce these data. Unfortunately, the predictive value of these scores, especially their specificity, is poor, mainly because all of these factors are indirect. We still cannot identify the mechanisms that lead to preterm labour and birth. New markers more directly related to preterm labour have recently been proposed, some of which relate to direct causes of preterm labour such as cervical ultrasound measurement, fetal fibronectin (FFN), salivary estriol, serum CRH and bacterial vaginosis. Several of these have predictive values, which are potentially useful for clinical practice. Nonetheless, pregnant women in developed countries are already closely monitored throughout pregnancy. Before proposing new screening tests to be applied systematically to all pregnant women, their advantages and drawbacks must be fully evaluated. [source]

Regional Response of Myocardial Acceleration During Isovolumic Contraction During Dobutamine Stress Echocardiography: A Color Tissue Doppler Study and Comparison with Angiocardiographic Findings

Linda B. Pauliks M.D.
Background: Color tissue Doppler imaging permits noninvasive quantitation of regional wall motion. In experimental studies, a new marker, the slope of the isovolumic contraction wave, isovolumic acceleration (IVA) was more insensitive to ventricular loading conditions than myocardial velocities. This study compared the regional response IVA to dobutamine stress echocardiography to angiographic findings. Methods: The Myocardial Doppler in Stress Echocardiography (MYDISE) study prospectively recruited 149 consecutive patients with chest pain for dobutamine stress tissue Doppler echocardiography prior to coronary angiography. This color tissue Doppler database was analyzed for IVA in 1192 basal and mid segments at rest and again at peak stress. Angiographic findings were compared to IVA and peak systolic velocities (PSV) in corresponding cardiac segments. The diagnostic accuracy of IVA to predict coronary artery stenosis was determined using cut-off values for three representative segments and with the MYDISE diagnostic model including eight segments. Results: Regional IVA increased in a dose-dependent manner during dobutamine infusion. The response was blunted in the supply territory of stenosed coronary artery branches. IVA performed slightly better than PSV as single marker for coronary artery stenosis. A diagnostic model incorporating IVA and PSV was 85,95% accurate (area under receiver operating characterstic curves). Conclusions: Regional changes of isovolumic acceleration during dobutamine stress echocardiography reflect regional wall motion and can be used to predict coronary artery stenosis with similar accuracy as a model based on systolic myocardial velocities. As a single marker, IVA performed better than myocardial velocities. (ECHOCARDIOGRAPHY, Volume 22, November 2005) [source]

Urine tested positive for ethyl glucuronide after trace amounts of ethanol

ADDICTION, Issue 12 2009
Annette Thierauf
ABSTRACT Aim Ethyl glucuronide (EtG) is used commonly as a marker for the detection of non-compliance of patients in alcohol withdrawal therapy in psychiatric hospitals in Europe and in work-place monitoring programmes in the United States. With the increased use of this new marker, questions related to an unintentional uptake of ethanol resulting in detectable EtG concentrations have been discussed. The aim of this study was to determine the concentration ranges of EtG and ethyl sulphate (EtS) after the consumption of very small amounts of ethanol (1 and 3 g), which are more likely to be incidental than intended. Methods Drinking experiments with ethanol amounts of 1 and 3 g, respectively, were performed on a total of 31 volunteers. EtG and EtS analysis in urine was performed by electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), and creatinine concentration was determined using the Jaffé reaction. Furthermore, data obtained from this experimentation were then compared to data from literature. Results and conclusions The maximum concentration of EtG normalized to creatinine after the uptake of 1 g and 3 g of ethanol was found to be 0.32 mg/l and 1.53 mg/l, respectively, and 0.15 mg/l and 1.17 mg/l for EtS; these peak concentrations are considered to be positive by many laboratories testing urine for ethanol conjugates in work-place testing progammes. [source]

Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T cells

Malgorzata Kisielow
Abstract Lymphocyte activation gene 3 (LAG-3/CD223) is a CD4 homolog known to be selectively expressed in activated T and NK cells. It is thought to have a negative regulatory function in T cells. With the help of new monoclonal antibodies against mouse LAG-3, we show that LAG-3 surface expression is not limited to activated T and NK cells but is also found on activated B cells. Induction of B cell surface expression is T cell dependent and mediated by a soluble factor. The majority of LAG-3 on B cell surface is endogenously produced, even though soluble LAG-3 is present in the culture supernatants and can be passively absorbed. As B cells express LAG-3 in a T cell dependent manner and not when activated by Toll-like-receptor agonists alone, we propose LAG-3 as a new marker of T cell induced B cell activation. [source]

Interleukin-17 as a new marker of severity of acute hepatic injury

Yuki Yasumi
Aim:, To determine cytokines associated with the progression of acute hepatic injury (AHI), we comprehensively evaluated the serum levels of 17 cytokines. Methods:, We simultaneously measured serum levels of 17 cytokines on admission using a newly developed suspension array protein assay system in 51 patients with AHI, including 15 conventional AHI (CAHI), 15 severe AHI (SAHI) and 21 fulminant hepatic failure (FHF). Results:, Interleukin (IL)-6, IL-8 and IL-17 levels were significantly different among the three disease types as determined by one-way analysis of variance, and only the IL-17 level showed a significant elevation in SAHI and FHF than in CAHI. Namely, the IL-17 levels in SAHI and FHF patients were 4.4 (2.0,11.0) (mean [1 .s.d. range]) and 5.6 (2.0,18.5) pg/mL, respectively, whereas all CAHI patients showed levels lower than the lower limit of detection (2.0 pg/mL). In multiple regression analysis for each factor of model for end-stage liver disease (MELD) score, only IL-10 level was selected as the significant independent variable for total bilirubin level, only IL-17 level for prothrombin time, and TNF-, and IL-1, levels for creatinine level. Conclusion:, These data suggest the usefulness of serum IL-17 level in evaluating the severity of AHI, thus emphasizing the necessity for the basic investigation of the pathological role of IL-17 in acute hepatitis. [source]

RM2 antigen (,1,4-GalNAc-disialyl-Lc4) as a new marker for prostate cancer

Seiichi Saito
Abstract Although prostate-specific antigen (PSA) has been widely used for early detection of prostate cancer, PSA has problems with specificity and prediction of pathological stage. Therefore, a new marker for prostate cancer is urgently required. We examined expression of a novel carbohydrate antigen, ,1,4-GalNAc-disialyl-Lc4, defined by the monoclonal antibody RM2, in prostate cancer using 75 cases of radical prostatectomy specimens. RM2 immunoreactivity was negative to weak in all benign glands, and weak to moderate in high-grade prostatic intraepithelial neoplasia. In prostatic adenocarcinoma, RM2 immunoreactivity was negative to weak (lower expression) in 20 cases, and moderate to strong (higher expression) in 55 cases. A clear difference of RM2 expression level was observed between Gleason patterns 3 and ,4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern ,4, high Gleason score (,8), larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure-free survival was significantly lower in the higher expression group. However, no significant relationship was observed between RM2 expression level and preoperative serum PSA. Western blot analysis in prostate cancer cell lines PC3 and LNCap revealed that major 49-kDa and minor 39-kDa glycoproteins were common to both cells, but there was an increase of 59- and 125-kDa glycoproteins unique to LNCap and an increase of 88- and 98-kDa glycoproteins unique to PC3. RM2 antigen is a new histological marker for prostate cancer that may reflect the Gleason grading system. Identification of the glycoproteins carrying the RM2 antigen will provide new insights into the properties of prostate cancer. © 2005 Wiley-Liss, Inc. [source]

Enterocytin: A new specific enterocyte marker bearing a B30.2-like domain

Stéphane Parnis
Enterocyte differentiation is correlated to the expression of specific proteins which only a few of them are identified. In this study, we characterize a new marker of enterocyte differentiation using monoclonal antibodies. We showed that small intestinal enterocytes specifically express a new 47 kDa protein named Enterocytin. Expression of this protein increase along the crypt-villus axis and it is concentrated in the terminal web, lateral plasma membrane domain, and nucleus membrane of mature enterocytes. A 1.8-kb cDNA of Enterocytin was isolated by expression cloning from a cDNA library of rabbit small intestine. The amino acid sequence obtained shows an N-terminal region with a coiled-coil structure and a B30.2-like domain in the C-terminus region. By co-transfection and immunoprecipitation procedures on Cos cells, it was observed that the coiled-coil domain is involved in the homodimerization of Enterocytin. In the human intestine, a similar 47 kDa protein was detected, exclusively in the small intestinal enterocytes. In addition, expression of this protein in Caco2 cells is correlated with the state of differentiation of these cells. The restricted expression of Enterocytin in the intestine and its localization in mature cells suggest that it may contribute to the differentiation processes and maintenance of the enterocytic polarity. J. Cell. Physiol. 198: 441,451, 2004© 2003 Wiley-Liss, Inc. [source]

Pigment epithelium-derived factor as a new marker of metabolic syndrome in Caucasian population

D. Stejskal
Abstract Authors present that serum pigment epithelium derived factor (PEDF) is an independent marker of metabolic syndrome in Caucasianpopulation. PEDF was measured with new ELISA sandwich test. J. Clin. Lab. Anal. 24:17,19, 2010. © 2010 Wiley-Liss, Inc. [source]

,-trace protein, a new marker of GFR, may predict the early prognostic stages of patients with type 2 diabetic nephropathy

Mami Kobata
Abstract The relationship between serum levels of ,-trace protein (BTP) or serum creatinine (s-Cr) and the prognostic stages of type 2 diabetic nephropathy was determined. Serum samples from 174 patients with type 2 diabetes were obtained from Juntendo University Hospital, Tokyo, and Juntendo Urayasu Hospital, Chiba, Japan. They were classified into four groups according to the Report of the Ministry of Health and Welfare of Japan (1991, p 251,256) as follows: Stage I (normoalbuminuric stage), Stage II (microalbuminuric stage), Stage IIIA (macroalbuminuric stage without renal dysfunction), Stage IIIB (macroalbuminuric stage with renal dysfunction), and Stage IV (renal failure stage). Among these patients, 68 were Stage I, 29 Stage II, 32 Stage IIIA, 17 Stage IIIB, and 28 Stage IV. Levels of serum BTP were measured using the nephelometric assay on a BNA II analyzer (Dade Behring Diagnostics, Marburg, Germany). The mean levels of serum BTP in Stage IIIA were significantly higher than those in Stage I or II (P<0.00001, P<0.002, respectively). However, the mean levels of s-Cr in Stage IIIA were not significantly higher than that in Stage I or II. In conclusion, serum BTP was a good marker for the identification of early renal impairment in type 2 diabetes. J. Clin. Lab. Anal. 18:237,239, 2004. © 2004 Wiley-Liss, Inc. [source]

Selection of glycoprotein IIb/IIIa inhibitors for upstream use in patients with diabetes experiencing unstable angina or non-ST segment elevation myocardial infarction.

What have we learned in the last 10 years?
Summary Coronary disease accounts for the majority of deaths among patients with diabetes and the thrombotic milieu accelerated by diabetes results in unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) or death. Upstream use of a glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor with percutaneous coronary intervention (PCI) as part of an early invasive approach is preferred. However substantial numbers of patients present to rural or non-teaching hospitals without immediate access to a catheterization laboratory. Enhanced GP IIb/IIIa receptor mobilization, TXA2 production and platelet activation together present an extensive thrombotic challenge that may not be overcome with current doses of GP IIb/IIIa inhibitors when used without PCI. Heterogeneity of platelet aggregometric analysis may have identified GP IIb/IIIa doses used in clinical trials that may not fully overcome the thrombotic challenge in patients with diabetes. GUSTO-IV ACS failed to demonstrate a difference in mortality when used without PCI. The PURSUIT trial provided evidence that eptifibatide decreases death or non-fatal myocardial infarction (MI) in the main group and in the diabetic subgroup. Reductions in this primary endpoint were driven by the reduction in non-fatal MI. The PRISM and PRISM-PLUS trials demonstrated a reduction in death, MI or refractory ischaemia at 48 h or 7 days in the main cohort but not specifically in patients with diabetes. Data supporting use of GP IIb/IIIa inhibitors are inconsistent, raising the question of whether these agents should be used at all without PCI. Variability in experimental methodology of platelet aggregometry and selection of anticoagulant used during dose finding studies may have generated doses that are insufficient to overcome the thrombotic burden. A new marker of active inflammation, sCD40L is found to be upregulated at subtherapeutic doses of GP IIb/IIIa inhibitors, suggesting that rebound inflammatory processes may partially account for absence of clear evidence of benefit with some GP IIb/IIIa inhibitors in patients with diabetes experiencing UA/NSTEMI. [source]

Expression of PGP 9.5 in granular cell nerve sheath tumors: an immunohistochemical study of six cases

Meera Mahalingam
Background: Protein gene product 9.5 (PGP 9.5) is expressed in brain at 20 to 50 times the levels detected in other organs. Immunohistochemical studies reveal this protein is localized to both central and peripheral neurons. Recently, PGP 9.5 is reported to be a useful marker for cellular neurothekeomas. Herein we test whether PGP 9.5 is a new marker for granular cell nerve sheath tumors. Material and Methods: An immunohistochemical analysis for PGP 9.5 expression was carried out on all cases with the diagnosis of granular cell nerve sheath tumor seen over a 2-year period. In addition, we compared expression of PGP 9.5 with other accepted markers for neuroectodermal tumors including anti-S-100 protein and NKI/C3 monoclonal antibodies. Results: Six granular cell nerve sheath tumors were diagnosed in over 80,000 dermatopathology specimens in the two-year period. These cases were all positive for PGP 9.5 as well as for S-100 protein and NK1/C3. Conclusion: These findings identify PGP 9.5 as a new immunohistochemical marker for use in the diagnosis of granular cell tumors. They also strengthen the histogenetic relationship between granular cell nerve sheath tumors and tumors of Schwann cell or perineurial origin. [source]

Genome-wide expression analysis of intra- and extraarticular connective tissue

Richard V. Pearse II
Abstract In comparison to extraarticular ligaments and tendons, the intraarticular ligaments such as the anterior and posterior cruciates exhibit different biochemical, biomechanical, and viscoelastic properties and most importantly, differential abilities to heal after surgical repair. Little is known about the underlying basis for these differences, in large measure due to the paucity of molecular markers distinguishing different classes of tendons and ligaments. To date, there has been no systematic analysis of gene expression differences between different types of connective tissues. We used Affymetrix expression arrays to analyze the differences in gene expression levels between the anterior cruciate, posterior cruciate, and medial collateral ligaments, the patellar and Achilles tendons and the synovium. We have identified five clusters of gene cohorts displaying similar expression patterns. These clusters group into three categories including: (1) genes that are strongly expressed in all connective tissues compared to the synovium control tissue; (2) genes that distinguish intraarticular connective tissues from extraarticular connective tissues; and (3) a group of genes expressed in common by the patellar tendon and the synovium. Our analysis identifies a new marker of tendons and ligaments (fibin2), demonstrates molecular diversity between subtypes of tendons and ligaments, and indicates that the primary molecular subdivision among dense regular connective tissues is intra- versus extraarticular rather than ligament versus tendon. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 427,434, 2009 [source]

Ethyl Glucuronide in Hair Compared With Traditional Alcohol Biomarkers,A Pilot Study of Heavy Drinkers Referred to an Alcohol Detoxification Unit

ALCOHOLISM, Issue 5 2009
Gudrun Høiseth
Background:, Traditional biomarkers for heavy alcohol use include serum carbohydrate-deficient transferrin (CDT), the enzymes aspartate aminotranserase (AST), and alanine aminotransferase (ALT) as well as gamma-glutamyl transferase (GGT). Measurement of the nonoxidative ethanol metabolite, ethyl glucuronide (EtG) in hair, has been proposed as a new marker with superior qualities. The aim of this study was to investigate the sensitivity of EtG in hair to detect heavy alcohol use compared with CDT, AST, ALT, and GGT. We also wanted to study the quantitative relation between alcohol intake and the different biomarkers. Methods:, Sixteen patients with a history of heavy alcohol use over the previous 3 months were recruited directly after admission to a withdrawal clinic. They were thoroughly interviewed about their drinking pattern as well as relevant diseases and use of medicines or drugs. Serum was sampled and analyzed for %CDT, AST, ALT, and GGT. Hair samples were collected and analyzed for EtG. Results:, The mean estimated daily intake (EDI) over the previous 3 months was 206 ± 136 g pure alcohol. All patients fulfilled the criteria for heavy alcohol use. The sensitivity to detect heavy alcohol use was 64% for %CDT, 67% for AST, 67% for ALT, 93% for GGT, and 94% for EtG. There was no correlation between the quantitative values of EDI and %CDT, AST, ALT, and GGT. There was a positive, statistically significant correlation between EDI and the level of EtG in hair. Conclusions:, In this study, EtG in hair and GGT showed the best sensitivity to detect heavy alcohol use and there was a positive correlation between EDI and the concentrations of EtG in hair. Before giving recommendations for clinical practice, further studies should be carried out on larger materials and populations with a wider range of alcohol intake. [source]

Immunological Detection of in Vitro Formed Phosphatidylethanol,An Alcohol Biomarker,With Monoclonal Antibodies

ALCOHOLISM, Issue 6 2008
Antti E. Nissinen
Background:, Phosphatidylethanol (PEth) is a promising new marker for detecting long-term alcohol abuse with excellent sensitivity and specificity. Current methods are based on the high performance liquid chromatography,mass spectrometric method and therefore require high levels of expertise and expensive instrumentation. This study was designed to generate PEth-specific monoclonal antibodies for PEth immunoassay development. Methods:, C57/BL6 mice were immunized with PEth in 3 different carriers, mouse serum albumin, mouse high-density lipoproteins, and human low-density lipoprotein (LDL). Mouse splenocytes were fused with a mouse myeloma cell line using the hybridoma technique. Mouse IgM-producing cell lines were selected by limiting dilutions. Binding characteristics of the anti-PEth antibodies were studied using luminometric immunoassays and sequence analysis of the variable region mRNA sequences of the antibodies. Produced antibodies were purified by chromatographic methods. PEth was detected with these antibodies in fluorescence immunoassay and flow cytometric analysis. Results:, We generated monoclonal cell lines (2B1 and 2E9) that produce IgM antibodies binding specifically to PEth but not to structurally or chemically similar phospholipids, such as phosphatidylcholine, phosphatidic acid, and cardiolipin. We show here that these anti-PEth antibodies can be used to detect PEth in a fluorescent PEth assay and FACS analysis of human red blood cell samples spiked with PEth. Conclusions:, The present study shows that PEth-specific monoclonal antibodies can be generated using traditional hybridoma technique. Immunogenicity of PEth was enhanced using human LDL as an immunization carrier. The generated monoclonal anti-PEth antibodies, 2B1 and 2E9 bind to PEth in fluid phase and in biological membranes. [source]

Sentinel lymph node as a new marker for therapeutic planning in breast cancer patients

Marco Gipponi MD
Abstract Background and Objectives Literature review suggests that the sentinel lymph node (sN) represents a reliable predictor of axillary lymph node status in breast cancer patients; however, some important issues, such as the optimisation of the technique for the intraoperative identification of the sN, the role of intraoperative frozen section examination of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla, still require further confirmation. The authors aimed (1) to assess the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, (2) to determine the accuracy and usefulness of intraoperative frozen section examination of the sN in order to perform a one-stage surgical procedure, and (3) to define how the sN might modulate the therapeutic planning in different stages of disease. Materials and Methods From October 1997 to June 2001, 334 patients with early-stage (T1,2 N0 M0) invasive mammary carcinoma underwent sN biopsy; the average age of patients was 61.5 years (range, 39,75 years). In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed. Results In the whole group, the sN was identified in 326 of 334 patients (97.6%), and 105 of 326 patients (37.3%) had positive axillary lymph nodes (pN+). In 9 of 105 pN+ patients, the definitive histologic examination of the sN did not show metastases but these were detected in non-sN, thus giving an 8.6% false-negative rate, a negative predictive value of 94.5% (156/165), and an accuracy of 96.5% (252/261). As regards the specific contribution of the two different techniques used in the identification of the sN, the detection rate was 73.8% (113/153) with Patent Blue-V alone, 94.1% (144/153) with RGS alone, and 98.7% (151/153) with Patent Blue-V combined with RGS (P,<,0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93,95% sensitivity; 100% specificity; 95,97% negative predictive value, and 97,98% accuracy) whichever of the three procedures was adopted (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). Intraoperative frozen section examination was performed in 261 patients, who had at least one sN identified, out of 267 patients who underwent complete axillary dissection; 170 patients had histologically negative sN (i.o. sN,) and 91 patients histologically positive sN (i.o. sN+). All 91 i.o. sN+ were confirmed by definitive histology, whereas in 14 of 170 i.o. sN, patients (8.2%) metastases were detected at definitive histology. As regards the correlation between the size of sN metastasis, the primary tumour size, and the status of non-sN in the axilla, micrometastases were detected at final histology in 23 patients and macrometastases in 82 patients. When only micrometastases were detected, the sN was the exclusive site of nodal metastasis in 20 of 23 patients (86.9%) while in 3 patients with tumour size larger than 10 mm micrometastases were detected also in non-sN. Macrometastases were never detected in pT1a breast cancer patients; the sN was the exclusive site of these metastases in 30 patients (36.6%), while in 52 patients (63.4%) there were metastases both in sN and non-sN. Conclusions Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, because of the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar whichever method is used. The intraoperative frozen section examination proved to be rather accurate in predicting the actual pathologic status of the sN, with a negative predictive value of 91.8%; in 35% of patients it allowed sN biopsy and axillary dissection to be performed in a one-stage surgical procedure. Finally, specific clinical and histopathologic features of the primary tumour and sN might be used to tailor the loco-regional and systemic treatment in different clinical settings, such as in ductal carcinoma in-situ (DCIS), early-stage invasive breast cancer, and patients with large breast cancer undergoing neo-adjuvant CT for breast-saving surgery as well as elderly patients with operable breast cancer. J. Surg. Oncol. 2004;85:102,111. © 2004 Wiley-Liss, Inc. [source]

Monoclonal antibody against rat podocyte-derived macrophagic cells reacts with crescent-forming cells in an experimental model

NEPHROLOGY, Issue 5 2003
SUMMARY: The origin of crescent-forming cells in crescentic glomerulonephritis has not been clarified in spite of the application of monoclonal antibodies (mAbs) against glomerular epithelial cells or monocytes/macrophages. This study was undertaken to characterize the cellular composition of crescents using a new marker, mAb OS-3, produced against macrophagic cells derived from podocytes in normal rat glomerular culture. Monoclonal antibody OS-3 was confirmed to be reactive with some normal epithelial cells of Bowman's capsule. Female Wistar Kyoto rats were injected with rabbit antiglomerular basement membrane (GBM) serum and killed at 2 h, 1, 3, 7, 14 days and 2 months, respectively. The mAb OS-3-positive cells were segmentally observed in glomeruli at 3 days, increased at 14 days, but decreased at 2 months. These cells lacked reactivity with antipodocalyxin in double immunofluorescence (IF) staining. In immunoelectron microscopy of a glomerulus on day 3 and 7, however, reaction products were observed within cells located on the outer surface of the GBM, which were considered to be podocyte in terms of its localization. In conclusion, we have shown a possibility that damaged podocytes partly constitute crescent-forming cells with phenotypic changes, visualized by positive staining with mAb OS-3. We propose a novel concept of crescent formation, suggesting that crescents may be partly composed of phenotypically changed cells, which could not be detected by typical markers for glomerular epithelial cells or monocytes/macrophages. [source]

CD109, a new marker for myoepithelial cells of mammary, salivary, and lacrimal glands and prostate basal cells

Masaki Hasegawa
The CD109 gene encodes a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Herein it is shown that CD109 is highly expressed in myoepithelial cells of mammary, salivary, and lacrimal glands; and in prostate basal cells. The anti-CD109 antibody generated by the authors was available for formalin-fixed paraffin section, and it strongly stained myoepithelial cells and basal cells but not ductal, acinar, and secretory cells in these glands. CD109 expression was negative in examined breast ductal carcinomas and prostate adenocarcinomas. These findings indicate that CD109 is a useful marker for the diagnosis of invasive breast and prostate carcinomas. [source]

Nestin expression as a new marker in malignant peripheral nerve sheath tumors

Satoko Shimada
Malignant peripheral nerve sheath tumor (MPNST) can be difficult to diagnose because it lacks specific immunohistochemical markers. S-100, which is a useful marker of MPNST, has limited diagnostic utility. Recent studies suggest that nestin, which is an intermediate filament protein, is expressed in neuroectodermal stem cells. The diagnostic utility of immunostains for nestin and three other neural markers (S-100, CD56 and protein gene product 9.5 (PGP 9.5)) were evaluated in 35 cases of MPNST and in other spindle cell tumors. All MPNST cases were strongly positive for nestin and had cytoplasmic staining. Stains for S-100, CD56, and PGP 9.5 were positive in fewer cases (17/35, 11/35, and 29/35 cases, respectively), and had less extensive staining. Nestin was negative in 10/10 leiomyomas, and weak nestin expression was seen in 10/10 schwannomas, 3/10 neurofibromas, 2/8 synovial sarcomas, 2/10 liposarcomas, 4/7 carcinosarcomas and 3/7 malignant fibrous histiocytomas. In contrast, strong nestin positivity was seen in 10/10 rhabdomyosarcomas, 15/19 leiomyosarcomas, and 9/9 desmoplastic melanomas. Nestin is more sensitive for MPNST than other neural markers and immunostains for nestin in combination with other markers could be useful in the diagnosis of MPNST. [source]

Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma,

W Vermi
Abstract The homeostatic chemokine CXCL13 is preferentially produced in B-follicles and is crucial in the lymphoid organ development by attracting B-lymphocytes that express its selective receptor CXCR5. Follicular dendritic cells (FDCs) have been identified as the main cellular source of this chemokine in lymphoid organs. Recently, genome-wide approaches have suggested follicular CD4 T-helper cells (THF) as additional CXCL13 producers in the germinal centre and the neoplastic counterpart of THF (CD4+ tumour T-cells in angioimmunoblastic T-cell lymphoma) retains the capability of producing this chemokine. In contrast, no data are available on CXCL13 expression on FDC sarcoma (FDC-S) cells. By using multiple approaches, we investigated the expression of CXCL13 at mRNA and protein level in reactive and neoplastic FDCs. In reactive lymph nodes and tonsils, CXCL13 protein is mainly expressed by a subset of FDCs in B-cell follicles. CXCL13 is maintained during FDC transformation, since both dysplastic FDCs from 13 cases of Castleman's disease and neoplastic FDCs from ten cases of FDC-S strongly and diffusely express this chemokine. This observation was confirmed at mRNA level by using RT-PCR and in situ hybridization. Of note, no CXCL13 reactivity was observed in a cohort of epithelial and mesenchymal neoplasms potentially mimicking FDC-S. FDC-S are commonly associated with a dense intratumoural inflammatory infiltrate and immunohistochemistry showed that these lymphocytes express the CXCL13 receptor CXCR5 and are mainly of mantle zone B-cell derivation (IgD+ and TCL1+). In conclusion, this study demonstrates that CXCL13 is produced by dysplastic and neoplastic FDCs and can be instrumental in recruiting intratumoural CXCR5+ lymphocytes. In addition to the potential biological relevance of this expression, the use of reagents directed against CXCL13 can be useful to properly identify the origin of spindle cell and epithelioid neoplasms. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

S100-, serum protein,a new marker in the diagnosis and monitoring of Langerhans cell histiocytosis?

S. Ugurel
No abstract is available for this article. [source]

A novel promoter polymorphism in the gene encoding complement component 5 receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three independent populations

K. C. Barnes
Summary Background The inflammatory functions of complement component 5 (C5) are mediated by its receptor, C5R1, which is expressed on bronchial, epithelial, vascular endothelial and smooth muscle cells. A susceptibility locus for murine allergen-induced airway hyper-responsiveness was identified in a region syntenic to human chromosome 19q13, where linkage to asthma has been demonstrated and where the gene encoding C5R1 is localized. Objective The aim of this study was to screen for novel polymorphisms in the C5R1 gene and to determine whether any identified polymorphisms are associated with asthma and/or atopy and whether they are functional. Methods Single-nucleotide polymorphism (SNP) detection in the gene encoding C5R1 was performed by direct sequencing. Genotyping was performed in three populations characterized for asthma and/or atopy: (1) 823 German children from The Multicenter Allergy Study; (2) 146 individuals from Tangier Island, Virginia, a Caucasian isolate; and (3) asthma case,parent trios selected from 134 families (N=783) in Barbados. Functional studies were performed to evaluate differences between the wild-type and the variant alleles. Results We identified a novel SNP in the promoter region of C5R1 at position ,245 (T/C). Frequency of the ,245C allele was similar in the German (31.5%) and Tangier Island (36.3%) populations, but higher in the Afro-Caribbean population (53.0%; P=0.0039 to <0.0001). We observed no significant associations between the ,245 polymorphism and asthma or atopy phenotypes. Upon examination of the functional consequences of the ,245T/C polymorphism, we did not observe any change in promoter activity. Conclusion This new marker may provide a valuable tool to assess the risk for C5a-associated disorders, but it does not appear to be associated with asthma and/or atopy. [source]

Increases in collagen type I synthesis in asthma: the role of eosinophils and transforming growth factor-b,

A. Nomura
Summary Background Collagen type I is one of the major deposits in thickening of the reticular basement membrane of asthma. Objective and Methods In this study, we assessed turnover of collagen type I in asthma by measuring procollagen type I C-terminal peptide (PICP) and collagen type I C-terminal telopeptide (ICTP) in induced sputum. Results PICP but not ICTP was found to be significantly higher in asthma subjects than in normal volunteers (P < 0.05). In asthma, PICP was inversely correlated with %FEV1.0 (r = ,0.539), and its levels significantly increased upon exacerbation (P < 0.05), indicating that collagen synthesis increases during asthma exacerbation. Additionally, PICP was found to significantly correlate with eosinophil counts in sputum (r = 0.539), indicating that eosinophils stimulate collagen turnover. Because eosinophils can produce TGF-,, a potent stimulator of collagen synthesis, we immunocytochemically examined TGF-,-positive cells in sputum. TGF-,-positive cells significantly correlated with eosinophil counts (r = 0.811) and PICP (r = 0.569), suggesting that TGF-, released from eosinophils is involved in collagen synthesis. Conclusions The results of the present study suggest that collagen synthesis is stimulated in asthmatic airways by eosinophils through TGF-,, while collagen degradation is not, and that PICP in sputum can act as a new marker for airway inflammation in asthma. [source]

Autoantibodies against CD28 are associated with atopic diseases

K. Neuber
Summary The B7-1/B7-2-CD28/CTLA-4 pathway is crucial in regulating T cell activation and tolerance. Autoantibodies to surface molecules on lymphocytes have already been described in various immune conditions, such as autoimmune diseases, infections and blood transfusions. The objective of this study was to test sera from healthy individuals and from patients for association of CD28 autoantibodies with inflammatory and non-inflammatory diseases. First, CD28 was obtained by digestion of CD28-Ig fusion protein with trypsin. The cleavage products were separated by sodium dodecyl sulphate,page gel electrophoresis. Additionally, a CD28/GST fusion protein was expressed in Escherichia coli and was used to establish an enzyme-linked immunosorbent assay for detection of autoantibodies against CD28. Sera from healthy individuals (n = 72) and patients with different inflammatory and non-inflammatory skin diseases (n = 196) were tested for the presence of autoantibodies against CD28. Using mixed lymphocyte reaction (MLR), purified autoantibodies against CD28 were tested for their effects on CTLA-4-Ig-induced T cell anergy. In this study, for the first time, we describe the existence of autoantibodies against CD28 in humans which are associated with atopic diseases, e.g. allergic rhinitis and asthma. These antibodies stimulate T cells and overcome the CTLA-4-Ig-induced anergy of T cells in an MLR. The existence of autoantibodies against CD28, which may have a T cell-stimulating function, has been shown. The data indicate that autoantibodies against CD28 could be a new immunological mechanism in allergic inflammation. Additionally, autoantibodies against CD28 could be an important new marker to discriminate between atopic diseases and other inflammatory skin diseases. [source]

Role of intratumoral lymphatic vessels in the lymph node dissemination of laryngopharyngeal squamous cell carcinoma

Adolfo Hinojar-Gutiérrez MD
Abstract Background The development of new markers for lymphatic endothelium allowed the study of intratumoral lymphatic microcirculation, as well as its association with lymph node metastasis. Methods In all, 120 patients with laryngopharyngeal squamous cell carcinoma (LPSCC) without previous treatment were retrospectively studied. The immunohistochemical determination of PA2.26 antigen/podoplanin was used to assess intratumoral lymphatic vessels (ILVs) in the primary tumor. Results Multivariate analysis revealed that lymph node metastasis was associated with tumor location (p = .001), differentiation grade (p = .02), and ILV (p = .013). Hypopharyngeal and supraglottic locations, poor grade of differentiation, and ILV, respectively, increased the risk of developing lymph node metastasis 13.5-, 4.7-, 5.2-, and 3.2-fold. Conclusions In our series, the presence of ILV in the primary tumor was an independent risk factor for the development of lymph node metastasis. The incorporation of ILV assessment into routine clinicopathological study might improve the evaluation of patients with LPSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source]

Bone disease in multiple myeloma: new markers, new treatments

D. Joshua
No abstract is available for this article. [source]

Histogenesis of Abrikossoff tumour of the oral cavity

F Haikal
Abstract:, Background:, Abrikossoff or granular cell tumour (GCT) is a relatively rare neoplasia, benign in most of the cases. It may occur in any part of the human body, but it has an oral location in 70% of the cases. Its origin has been discussed for decades, and it is not yet definitively determined. Immunohistochemical techniques suggest its origin in the Schwann cells, while more recent studies with new markers indicate an origin related to neuroendocrine cells. Objective:, Contribute to the clarification of histogenesis of oral Abrikossoff tumour studying immunohistochemical marking of 11 oral Brazilian cases. Materials and methods:, Samples of tissues from the oral mucosa, tongue and lips placed in paraffin blocks, from eleven patients with a histopathological diagnosis of benign GCT were studied. Four different anti-serums (S-100, vimentin, PGP9.5 and ENE) were used for immunoperoxydase technique. Results:, A clear positivity for S-100 protein and vimentin was observed, with markers indicating origin from the Schwann cells. Less intense positivity was found in some cases, for ENE and PGP9.5, which suggests a neuroendocrine origin. Conclusions:, The results obtained suggest an origin from Schwann cells, but also arise the possibility of neuroendocrine origin. New methods and more specific immunohistochemical markers are needed to elucidate the origin of the Abrikossoff tumour. [source]

Identification of novel single nucleotide polymorphisms within the NOTCH4 gene and determination of association with MHC alleles

R. Tazi-Ahnini
Summary Mapping of disease susceptibility loci within the MHC has been partly hampered by the high degree of polymorphism of the HLA genes and the high level of linkage disequilibrium (LD) between markers within the MHC region. It is therefore important to identify new markers and determine the level of LD between HLA alleles and non-HLA genes. The NOTCH4 gene lies at the centromeric end of the MHC class III region, approximately 335 kb telomeric of the DRB1 locus. The encoded protein is an oncogene that is important in regulating vascular development and remodelling. A recent report has linked polymorphisms within NOTCH4 with risk of developing schizophrenia. We have investigated if coding polymorphisms exist within this gene and have identified three single nucleotide polymorphisms; a synonomous T to C transition at +1297 (HGBASE accession number SNP000064386), a synonomous A to G transition at +3061 (SNP000064387) and an A to G transition at +3063 which results in a replacement of glycine with aspartic acid at amino acid 279 (SNP000064388). The allele frequencies of +1297T, +3061A and +3063G were 0.65, 0.66 and 0.66, respectively. Linkage disequilibrium was detected both between these markers and with MHC alleles. These findings can be used in the fine mapping of disease susceptibility alleles within the MHC. [source]

Modulation of white adipose tissue proteome by aging and calorie restriction

AGING CELL, Issue 5 2010
Adamo Valle
Summary Aging is associated with an accrual of body fat, progressive development of insulin resistance and other obesity comorbidities that contribute to decrease life span. Caloric restriction (CR), which primarily affects energy stores in adipose tissue, is known to extend life span and retard the aging process in animal models. In this study, a proteomic approach combining 2-DE and MS was used to identify proteins modulated by aging and CR in rat white adipose tissue proteome. Proteomic analysis revealed 133 differentially expressed spots, 57 of which were unambiguously identified by MS. Although CR opposed part of the age-associated protein expression patterns, many effects of CR were on proteins unaltered by age, suggesting that the effects of CR on adipose tissue are only weakly related to those of aging. Particularly, CR and aging altered glucose, intermediate and lipid metabolism, with CR enhancing the expression of enzymes involved in oxalacetate and NADPH production, lipid biosynthesis and lipolysis. Consistently, insulin-, and ,3-adrenergic receptors were also increased by CR, which denotes improved sensitivity to lipogenic/lipolytic stimuli. Other beneficial outcomes of CR were an improvement in oxidative stress, preventing the age-associated decrease in several antioxidant enzymes. Proteins involved in cytoskeleton, iron storage, energy metabolism and several proteins with novel or unknown functions in adipose tissue were also modulated by age and/or CR. Such orchestrated changes in expression of multiple proteins provide insights into the mechanism underlying CR effects, ultimately allowing the discovery of new markers of aging and targets for the development of CR-mimetics. [source]

Noxp20 and Noxp70, two new markers of early neuronal differentiation, detected in teratocarcinoma-derived neuroectodermic precursor cells

M. Boucquey
Abstract The murine 1C11 cell line, derived from F9 pluripotent teratocarcinoma cells, exhibits features of a bipotential neuronal precursor as it converts into serotonergic or catecholaminergic neurons under appropriate induction. In order to point out molecular markers expressed in this early neuroectodermic commitment, we used a cDNA subtractive hybridization method. The 105 different isolated cDNAs represented 75 known genes, expressed sequence tags (EST) or genomic fragments. A majority of known proteins encoded by these sequences are involved in cellular mobility or migration. We characterized two sequences showing identities with ESTs and we called them Noxp20 and Noxp70. The Noxp20 transcript encodes a putative protein with a predicted caspase recruitment domain and the Noxp70 transcript encodes a putative protein displaying a Zn-finger domain. Consistent with their roles in neuronal cell development, in situ hybridization showed that Noxp20 and Noxp70 are over-expressed in brain. At embryonic days 12 and 15, Noxp20 is strongly expressed in the ventricular and intermediate zones of the brain and of the spinal cord. At embryonic day 15, Noxp70 was found to be strongly expressed in the ventricular zone around the telencephalic ventricle, and to a lower extent in the thalamus and hypothalamus. At post-natal day 10, Noxp20 mRNA was detected in the dentate gyrus, the hippocampus, the cerebellum and the olfactory bulb. [source]

Detection of Recent Ethanol Intake With New Markers: Comparison of Fatty Acid Ethyl Esters in Serum and of Ethyl Glucuronide and the Ratio of 5-Hydroxytryptophol to 5-Hydroxyindole Acetic Acid in Urine

ALCOHOLISM, Issue 5 2005
K Borucki
Background: At present, recent ethanol consumption can be routinely detected with certainty only by direct measurement of ethanol concentration in blood or urine. Because ethanol is rapidly eliminated from the circulation, however, the time span for this detection is in the range of hours. Several new markers have been proposed to extend the detection interval, but their characteristics have not yet justified their use in routine clinical practice. We therefore investigated three new markers and compared their kinetics and sensitivities: (1) fatty acid ethyl esters (FAEEs) in serum, (2) ethyl glucuronide (EtG) in urine, and (3) the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid (5-HTOL/5-HIAA) in urine. Methods: Seventeen healthy men participated in a drinking experiment. Blood and urine samples were collected twice daily on three consecutive days and once daily on days 4 and 5. Ethanol concentration was determined by gas chromatography, FAEE levels, by gas chromatography with mass spectrometry, EtG concentration, by liquid chromatography-tandem mass spectrometry, and 5-HTOL/5-HIAA ratio, by high-performance liquid chromatography. Results: The peak serum ethanol concentrations of the subjects ranged from 5.4 to 44.7 mmol/liter (mean ± SD, 30.1 ± 9.1 mmol/liter). In the case of the serum ethanol determination, 100% sensitivity was reached only immediately after the end of the drinking experiment, and in the case of FAEE levels and 5-HTOL/5-HIAA ratio, it tested for 6.7 hr after the end of the ethanol intake. Thereafter, these latter parameters declined until 15.3 hr (FAEEs) and 29.4 hr (5-HTOL/5-HIAA), subsequently remaining in a stable range until 78.5 hr without further decrease. In contrast, EtG concentration showed 100% sensitivity until 39.3 hr and thereafter decreased, falling to below the limit of quantification of 0.1 mg/liter at 102.5 hr. Conclusion: After moderate drinking, EtG in the urine proved to be a superior marker of recent ethanol consumption in healthy subjects. This is because EtG is a direct ethanol metabolite, it occurs in the urine only when ethanol has been consumed, and its sensitivity remains at the level of 100% for 39.3 hr. [source]