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Austin, TX, United States

Tozzoli R.,Clinical Pathology Laboratories
Autoimmunity Reviews | Year: 2014

The antiphospholipid syndrome (APS) is an autoimmune disease defined by the co-occurrence of clinical and serological symptoms [presence of at least one of the antiphospholipid autoantibodies (aPL), such as anti-cardiolipin (aCL) IgG/IgM and anti-β2glycoprotein I (aβ2GPI) IgG/IgM]. The measurement of these autoantibodies constitutes the first-line approach for the diagnosis of APS. Recently the advent of multiplex proteomic technologies seems to be an optimal solution for the parallel detection of autoantibodies (IgG, IgA, IgM) related to APS. The BioPlex 2200 is an automated commercial platform based on the multi-analyte profiling technology that allows the detection of different types of autoantibodies, particularly ANA, ENA, dsDNA, PR3, MPO, GBM. We performed firstly a study to evaluate the diagnostic accuracy of this analytical system in a group of APS patients. The BioPlex system showed a good diagnostic accuracy for all test evaluated, very similar to that of the other established commercial singleplex immunoassays. In our study, the simultaneous detection of aCL and aβ2GPI of IgA isotype in addition to IgG and IgM isotypes did not increase the diagnostic sensitivity for APS. The good diagnostic accuracy, the high level of automation, and the high throughput make this multiplex platform a very useful and practical tool for the laboratory diagnosis of aPL in daily practice. © 2013 Elsevier B.V. Source

Apple F.S.,Clinical Pathology Laboratories | Apple F.S.,University of Minnesota | Ler R.,Hennepin County Medical Center | Murakami M.M.,Hennepin County Medical Center
Clinical Chemistry | Year: 2012

BACKGROUND: Between-assay comparability of 99th percentiles for cardiac troponin concentrations has not been assessed systematically in a single population for a large number of assays. METHODS: We determined 99th percentiles for 19 cardiac troponin assays in heparin plasma samples from a population of 272 and 252 presumably healthy males and females, respectively. The assays evaluated included 1 cardiac troponin T (cTnT) assay from Roche and 18 cTnI assays from Abbott, Alere, Beckman, bioMerieux, Instrumentation Laboratory, Ortho-Clinical Diagnostics, Singulex, Siemens, and Roche. Five of these assays were categorized as high-sensitivity, 9 as sensitive-contemporary, and 5 as point-of-care (POC) assays. RESULTS: For high-sensitivity cTnI (hs-cTnI) assays 99th percentiles varied from 23 to 58 ng/L. At least 80% of individuals had measurable hs-cTnI, whereas only 25% had measurable high-sensitivity cTnT. All highsensitivity cardic troponin assays had 99th percentiles that were 1.2-2.4-fold higher in males than females. For the 9 sensitive-contemporary cTnI assays, 99th percentiles varied from 12 to 392 ng/L, and only the Beckman assay gave measurable concentrations in a substantial portion of the population (35% vs ≤6% for the others). Seven of these 9 assays had 1.3-5.0-fold higher 99th percentiles for males than females. For 5 cTnI POC assays, 99th percentiles varied from < 10 to 40 ng/L. The Instrumentation Laboratory assay gave measurable results in 27.8% of study participants vs ≤6% for the others. Correlations were generally poor among assays. CONCLUSIONS: Among cardiac troponin assays 99th percentile concentrations appear to differ. Highsensitivity assays provide measurable cardiac troponin results in a substantially greater fraction of presumably healthy individuals. © 2012 American Association for Clinical Chemistry. Source

Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.Leukemia advance online publication, 12 April 2016; doi:10.1038/leu.2016.67. © 2016 Macmillan Publishers Limited Source

Yamamoto S.,National Defense Medical College | Tsuda H.,Clinical Pathology Laboratories | Takano M.,National Defense Medical College | Tamai S.,National Defense Medical College Hospital | Matsubara O.,National Defense Medical College
Modern Pathology | Year: 2012

ARID1A is a recently identified tumor suppressor gene that is mutated in 50% of ovarian clear-cell carcinomas. This mutation is associated with loss of ARID1A protein expression as assessed by immunohistochemistry. The present study aimed at determining the timing of the loss of ARID1A protein expression during the development of ovarian clear-cell carcinoma and assessing its relevance in correlation to PIK3CA gene mutations. A total of 42 clear-cell carcinoma cases with adjacent putative precursor lesions (endometriosis-associated carcinoma cases (n28) and (clear-cell) adenofibroma-associated carcinoma cases (n14)) were selected and subjected to immunohistochemical analysis for ARID1A protein expression and direct genomic DNA sequencing of exons 9 and 20 of the PIK3CA gene. ARID1A immunoreactivity was deficient in 17 (61%) of the 28 endometriosis-associated carcinomas and 6 (43%) of the 14 adenofibroma- associated carcinomas. Among the precursor lesions adjacent to the 23 ARID1A-deficient carcinomas, 86% of the non-atypical endometriosis (12 of 14) and 100% of the atypical endometriosis (14 of 14), benign (3 of 3), and borderline (6 of 6) clear-cell adenofibroma components were found to be ARID1A deficient. In contrast, in the 19 patients with ARID1A-intact carcinomas, all of the adjacent precursor lesions retained ARID1A expression regardless of their types and cytological atypia. Analysis of 22 solitary endometrioses and 10 endometrioses distant from ARID1A-deficient carcinomas showed that all of these lesions were diffusely immunoreactive for ARID1A. Among the 42 clear-cell carcinomas, somatic mutations of PIK3CA were detected in 17 (40%) tumors and majority (71%) of these were ARID1A-deficient carcinomas. These results suggest that loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development, similar to the pattern of PIK3CA mutation recently reported by our group, and frequently coexists (not mutually exclusive) with PIK3CA mutations. © 2012 USCAP, Inc. All rights reserved. Source

Hasebe T.,Clinical Pathology Laboratories
Expert Opinion on Therapeutic Targets | Year: 2013

Introduction: Existing pathological diagnostic protocols for breast cancer do not fully reflect the biological characteristics of tumor stromata. To improve the pathological diagnosis of breast cancer, a new pathological diagnostic method capable of assessing the degree of breast cancer malignancy based on the histological features of the tumor stroma is needed. Areas covered: The presence of a fibrotic focus (FF), which consists of fibroblasts or collagen fibers, and the presence of atypical tumor-stromal fibroblasts are significantly associated with nodal metastasis or distant-organ metastasis in patients with invasive ductal carcinoma (IDC) of the breast. FF is the only factor that is significantly associated with an increase in tumor angiogenesis. The importance of FF and atypical tumor-stromal fibroblasts clearly indicates that the malignant potential of IDC does not depend only on the biological characteristics of the tumor cell, but also on those of the tumor stroma. Expert opinion: The biological characteristics of fibroblasts forming an FF or atypical tumor-stromal fibroblasts probably differ from those of fibroblasts located outside an FF or ordinary tumor-stromal fibroblasts. Thus, similar to tumor cells, the heterogeneity of tumor-stromal fibroblasts probably influences the outcome of patients with IDC of the breast. © 2013 Informa UK, Ltd. Source

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