GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Leukemia Research, Elsevier BV, Vol. 116 ( 2022-05), p. 106818-
    Type of Medium: Online Resource
    ISSN: 0145-2126
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 752396-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2010
    In:  Annals of Diagnostic Pathology Vol. 14, No. 3 ( 2010-6), p. 168-172
    In: Annals of Diagnostic Pathology, Elsevier BV, Vol. 14, No. 3 ( 2010-6), p. 168-172
    Type of Medium: Online Resource
    ISSN: 1092-9134
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
    detail.hit.zdb_id: 1440011-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    Online Resource
    Online Resource
    Elsevier BV ; 2017
    In:  Annals of Diagnostic Pathology Vol. 29 ( 2017-08), p. 23-27
    In: Annals of Diagnostic Pathology, Elsevier BV, Vol. 29 ( 2017-08), p. 23-27
    Type of Medium: Online Resource
    ISSN: 1092-9134
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1440011-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Journal of Virology, American Society for Microbiology, Vol. 93, No. 8 ( 2019-04-15)
    Abstract: Gammaherpesviruses are ubiquitous pathogens that are associated with B cell lymphomas. In the early stages of chronic infection, these viruses infect naive B cells and subsequently usurp the B cell differentiation process through the germinal center response to ensure latent infection of long-lived memory B cells. A unique feature of early gammaherpesvirus chronic infection is a robust differentiation of irrelevant, virus-nonspecific B cells with reactivities against self-antigens and antigens of other species. In contrast, protective, virus-specific humoral responses do not reach peak levels until a much later time. While several host factors are known to either promote or selectively restrict gammaherpesvirus-driven germinal center response, viral mechanisms that contribute to the irrelevant B cell response have not been defined. In this report we show that the expression and the enzymatic activity of the gammaherpesvirus-encoded conserved protein kinase selectively facilitates the irrelevant, but not virus-specific, B cell responses. Further, we show that lack of interleukin-1 (IL-1) receptor attenuates gammaherpesvirus-driven B cell differentiation and viral reactivation. Because germinal center B cells are thought to be the target of malignant transformation during gammaherpesvirus-driven lymphomagenesis, identification of host and viral factors that promote germinal center responses during gammaherpesvirus infection may offer an insight into the mechanism of gammaherpesvirus pathogenesis. IMPORTANCE Gammaherpesviruses are ubiquitous cancer-associated pathogens that usurp the B cell differentiation process to establish life-long latent infection in memory B cells. A unique feature of early gammaherpesvirus infection is the robust increase in differentiation of B cells that are not specific for viral antigens and instead encode antibodies that react with self-antigens and antigens of other species. Viral mechanisms that are involved in driving such irrelevant B cell differentiation are not known. Here, we show that gammaherpesvirus-encoded conserved protein kinase and host IL-1 signaling promote irrelevant B cell responses and gammaherpesvirus-driven germinal center responses, with the latter thought to be the target of viral transformation.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1495529-5
    detail.hit.zdb_id: 80174-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2848-2848
    Abstract: BACKGROUND: Sézary syndrome and mycosis fungoides are two clinically distinct neoplasias of CD4-positive skin-resident T-cells that share remarkable morphologic and immunophenotypic similarities, commonly referred together as cutaneous T-cell lymphoma (CTCL). Prognostic clinical staging in CTCL requires flow cytometric quantitation of peripheral blood tumor cells (Sézary cells), based on aberrant loss of CD7 and/or CD26 within the CD4-positive T-cell compartment. Unfortunately, similar T-cell populations are frequently encountered in reactive conditions, creating uncertainty in the diagnostic interpretation. We recently reported a flow cytometric strategy to assess T-cell clonality using a single antibody (JOVI-1) against one of 2 mutually exclusive T-cell receptor beta constant (TRBC) regions randomly selected during T-cell receptor gene rearrangement. We hereby applied this strategy to a diagnostic Sézary cell flow cytometry panel, resulting in rapid, accurate and unequivocal identification and quantitation of clonal CD4-positive T-cells. METHODS: We studied 33 peripheral blood specimens from 24 patients with CTCL, and 28 specimens from patients with no clinical or laboratory evidence of T-cell malignancy. A routine Sézary cell flow cytometry panel (CD2/CD3/CD4/CD5/CD7/CD8/CD26/CD45) was modified to include a fluorescent labeled antibody against TRBC1. Gated CD4 T-cells were studied to identify discrete subsets lacking CD7, CD26 or both, in addition to other immunophenotypic abnormalities. Within each subset, clonality was defined as a dominant TRBC1-positive or TRBC1-negative population greater than 85%, or a dominant abnormal TRBC1-dim population, as previously described. RESULTS: Peripheral blood specimens from patients with CTCL showed subsets of CD4-positive T-cells lacking CD7 (median=35%; range 1.6% to 96%) or CD26 expression (median=54%; range 6.6% to 98%). Fifteen (45%) of these specimens had other identifiable phenotypic abnormalities, including decreased CD2, CD3, CD4 or CD5. Patients without a T-cell malignancy also had CD4-positive T-cells lacking CD7 (median=13%; range 0.5% to 38%) or CD26 expression (median=9.4%; range 0.7% to 30%), albeit to a lesser extent compared to CTCL patients (p 〈 0.01 and p 〈 0.0001 for CD7 and CD26, respectively). One febrile infant showed loss of CD2 on a small T-cell subset. Discrete CD4-positive T-cell subsets with monotypic TRBC expression were identified in 24 specimens (73%) from patients with CTCL (Figure A), ranging from 30 to12,000 cells/µL (median=632). Importantly, no TRBC-restricted CD4-positive T-cells were detected in any of the 28 patients without a T-cell malignancy. Nine specimens from CTCL patients without a TRBC-restricted subset were reviewed based on morphologic, immunophenotypic and clinical features, yielding no definitive evidence of Sézary cells. Absolute numbers of TRBC-restricted T-cells correlated with numbers of Sézary cells estimated based on lack of CD7 or CD26 expression (R=0.99), or absence of both antigens (R=0.7) (Figure B). However, all cases with no detectable clonal TRBC-restricted T-cells showed significant absolute numbers of CD4-positive T-cells lacking CD7 or CD26 (mean=208 cells/µL, range=22 to 1,078 cells/µL), resulting in common diagnostic uncertainties based on quantitation of these subsets. A narrower gating strategy on these same patients based on the combined loss of CD7 and CD26 yielded lower numbers of abnormal cells (mean=51 cells/µL, range=2 to 556 cells/µL), but grossly underestimated the number of TRBC-restricted CD4-positive T-cells by more than 500 cells/µL in 6 patients with CTCL (Figure B). CONCLUSIONS: A single anti-TRBC1 antibody added to a routine Sézary cell flow cytometry assay provides a rapid, simple and low-cost approach to query for clonality within immunophenotypically distinct CD4 T-cell subsets, eliminating the need for a separate T-cell clonality assay. Diagnostic uncertainties and quantitative biases resulting from immunophenotypic overlaps between Sézary cells and reactive T-cells are virtually resolved. Direct quantitation of clonal CD4 T-cells based on TRBC1 restriction is a biologically sound strategy for blood staging in CTCL, effectively overcoming the limitations and uncertainties of staging by immunophenotypic analysis based on current guidelines. Figure Disclosures Horna: MorphoSys AG: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1316-1316
    Abstract: BACKGROUND Bone marrow examination is essential in diagnosis, staging and monitoring of various hematologic disorders. The aspirate smears and core biopsy are complementary samples; current clinical benchmarks recommend an optimal core sample length of at least 15-20 mm. We assessed the core length in 2 cross-sectional cohorts from 2001 and 2011 in 32 academic medical centers from the US and Canada, the first such study to date. METHODS After IRB approval, participants collected data from pathology reports (including the preprocessing length) and measured aggregate postprocessing and evaluable marrow length using a uniform validated methodology on 100 consecutive marrow samples in 2001 and 2011 at each institution. Deidentified data was centralized at Roswell Park Cancer Institute (RPCI) and centers were anonymized. A total of 6374 samples were accepted for statistical analysis, performed using SAS (v. 9.4 or higher; SAS Institute, Cary, NC) at RPCI. Relationship between core length and NCCN status, geographic location, gender, age, and staging was assessed using the PROC MIXED and PROC GLIMMIX procedure using a random center effect and a nominal significance level of 0.05. RESULTS The study cohort included 56% men and 44% women, mean age 51 (range, 1-102) years, 88% adults (³18) and 12% children ( 〈 18). The two most common clinical indications were acute leukemia/myeloid neoplasms and lymphoma staging (Fig 1). A core biopsy was obtained in 90% of 2001 and in 95% of 2011 samples. Most cores were unilateral (85%); bilateral sampling decreased from 10% to 4% between 2001 and 2011. An aspirate specimen was received in the pathology department in 86% of the cases; however, a clot section was prepared in only 56% of the cases. Preprocessing core length (PreCL; n=3141) documentation in pathology reports was missing in 9 centers for both years; in 3 centers it was available only for one year; its mean (standard deviation) was 16.9 (9.9) mm, decreasing from 2001 to 2011 [17.7 (11.9) to 16.2 (8); p=0.002]. Postprocessing core length (PostCL; n=5742) mean (SD) was 14.2 (8.5) mm, significantly shorter in women than in men (p 〈 0.001), longer in bilateral than unilateral (p 〈 0.001) and in staging than in non-staging samples (p 〈 0.001), in children than adults (NS), and in 2001 than 2011 samples [14.3 (9.4) v. 14.2 (7.6); p=0.144]. Evaluable marrow space length (EML; n=5617) mean (SD) was 10.7 (7.5) mm and decreased from 2001 to 2011 [10.9 (8.5) to 10.6 (6.6); p=0.002]. Ninety-one samples (1.6%) with measureable PostCL were entirely devoid of evaluable marrow. PostCL was 15% shorter than PreCL. The EML measured 24% less than the PostCL and 33% less than the PreCL. Lymphoma staging samples (n=1222) were obtained from adults (96%) and children (4%); of these, only 45% and 28% reached the PostCL of 15 mm and 20 mm, respectively. Lymphoma involvement rate was 16%, 25%, 32%, 30%, and 23% when PostCL was 〈 5, 5-10, 11-14, 15-20, and ³20 mm, respectively (Fig 2). There was no significant difference of PostCL mean based on geographic region or NCCN status. PostCL mean ranged from 8.8 to 29.6 mm and its median was ³15 mm in only 12 of 23, 9 of 32, and 2 of 32 centers for PreCL, PostCL, and EML, respectively (Fig 3). When compared to current benchmarks, only 53%, 38%, and 22% of all samples were ³15 mm and only 30%, 19%, and 10% were ³20 mm for PreCL, PostCL, and EML, respectively. CONCLUSIONS Current benchmarks for bone marrow core biopsy adequacy are met in only a minority of cases. Samples from women were shorter than from men. Bilateral sampling decreased and PreCL and EML diminished significantly between 2001 and 2011, while PostCL showed only minimal decrease. This discrepancy may be due to technical differences. Although staging cores were longer than non-staging ones, most did not meet the benchmarks. The wide variability among different centers suggests significant institutional differences and lack of standardization in bone marrow sampling. Over a third of all centers did not record preprocessing length, an important parameter which may guide operator assessment of adequacy at the bedside. PostCL and/or EML can be measured by the pathologist and integrated in the report to document adequacy. In staging samples, a minimal marrow space sampling should be required to avoid understaging. Consensus definition of an inadequate core biopsy is currently lacking but would be desirable for uniform pathology reporting, clinical protocols and management. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2018
    In:  American Journal of Clinical Pathology Vol. 150, No. suppl_1 ( 2018-09-21), p. S101-S102
    In: American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 150, No. suppl_1 ( 2018-09-21), p. S101-S102
    Type of Medium: Online Resource
    ISSN: 0002-9173 , 1943-7722
    RVK:
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2944-0
    detail.hit.zdb_id: 2039921-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    In: American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 150, No. 5 ( 2018-10-01), p. 393-405
    Type of Medium: Online Resource
    ISSN: 0002-9173 , 1943-7722
    RVK:
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2944-0
    detail.hit.zdb_id: 2039921-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  American Journal of Clinical Pathology Vol. 154, No. 5 ( 2020-10-13), p. 683-691
    In: American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 154, No. 5 ( 2020-10-13), p. 683-691
    Abstract: Distinguishing between T-cell and natural killer (NK)–cell neoplasms could be difficult given their overlapping immunophenotype. In this study, we investigated whether a flow cytometry assay with cytoplasmic staining for CD3 could be used for this purpose. Methods Flow cytometry immunophenotyping was performed on 19 surface CD3 (sCD3)–negative mature T-cell neoplasms, 10 sCD3-positive mature T-cell neoplasms, 13 mature NK-cell neoplasms, and 19 normal controls. In addition to routine antibody panels (CD2, sCD3, CD4, CD5, CD7, CD8, CD16, CD45, CD56, CD57, CD94, CD158a, CD158b, CD158e, NKG2A TCRγ/δ), cytoplasmic staining for a monoclonal CD3 antibody (clone SK7/Leu-4) was assessed in all cases. A molecular study for T-cell receptor (TCR) gene rearrangement and an immunohistochemical study for TCRβ were performed. Results Our data showed all T-cell neoplasms were uniformly positive for cytoplasmic CD3 (cCD3) regardless of sCD3 expression, whereas 85% of NK-cell neoplasms completely lacked cCD3 expression. The 2 cases with classic NK-cell immunophenotype but partial cCD3 expression showed no molecular genetic features of T-cell lineage by TCR gene rearrangement studies. Conclusions Uniform cCD3 positivity and homogeneous cCD3 negativity highly suggest T-cell and NK lineage, respectively. When partial cCD3 expression is encountered, additional confirmatory studies should be pursued for the most accurate lineage assignment.
    Type of Medium: Online Resource
    ISSN: 0002-9173 , 1943-7722
    RVK:
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2944-0
    detail.hit.zdb_id: 2039921-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    In: American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 161, No. 6 ( 2024-06-03), p. 609-624
    Abstract: VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable. Methods To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review. Results Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases. Conclusions Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context.
    Type of Medium: Online Resource
    ISSN: 0002-9173 , 1943-7722
    RVK:
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2944-0
    detail.hit.zdb_id: 2039921-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...