43 results on '"Abruzzo, L V"'
Search Results
2. Extramedullary BCR-ABL1-negative myeloid leukemia in a patient with chronic myeloid leukemia and synchronous cytogenetic abnormalities in Philadelphia-positive and -negative clones during imatinib therapy
- Author
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Quintás-Cardama, A, Kantarjian, H, Abruzzo, L V, and Cortes, J
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- 2007
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3. A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome
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Quintás-Cardama, A, Abruzzo, L V, Giles, F J, Jorgensen, J, Cortes, J, Sarriera, J E, Kantarjian, H, and Verstovsek, S
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- 2006
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4. Association of 3q21q26 syndrome and late-appearing Philadelphia chromosome in acute myeloid leukemia
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Quintás-Cardama, A, Gibbons, D L, Cortes, J, Bobadilla, D, Slovak, M L, Kantarjian, H, and Abruzzo, L V
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- 2008
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5. The activation profile of tumour-associated reactive T-cells differs in the nodular and diffuse patterns of lymphocyte predominant Hodgkinʼs disease
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Lin, P, Medeiros, L J, Wilder, R B, Abruzzo, L V, Manning, J T, and Jones, D
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- 2004
6. EBV-ASSOCIATED CD30-POSITIVE B-CELL LARGE CELL LYMPHOMA WITH ANAPLASTIC FEATURES INVOLVING SKIN AT A CATHETER SITE IN A PATIENT WITH AIDS.
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Kauffman, C. L., Medeiros, L. J., Kumar, D., and Abruzzo, L. V.
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- 1997
7. Expression and regulation of macrophage inflammatory protein-1 alpha by murine alveolar and peritoneal macrophages.
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VanOtteren, G M, Standiford, T J, Kunkel, S L, Danforth, J M, Burdick, M D, Abruzzo, L V, and Strieter, R M
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- 1994
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8. Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance
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Jain, P., primary, Javdan, M., additional, Feger, F. K., additional, Chiu, P. Y., additional, Sison, C., additional, Damle, R. N., additional, Bhuiya, T. A., additional, Sen, F., additional, Abruzzo, L. V., additional, Burger, J. A., additional, Rosenwald, A., additional, Allen, S. L., additional, Kolitz, J. E., additional, Rai, K. R., additional, Chiorazzi, N., additional, and Sherry, B., additional
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- 2011
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9. The clinical significance of chromosome 17p deletion in chronic lymphocytic leukemia: A study of 180 consecutive patients
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Tam, C. S., primary, Wierda, W., additional, O'Brien, S. M., additional, Lerner, S., additional, Abruzzo, L. V., additional, Ferrajoli, A., additional, Kantarjian, H. M., additional, and Keating, M. J., additional
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- 2008
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10. Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas
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Abruzzo, L. V., Thornton, A. J., Liebert, M., Grossman, H. B., Evanoff, H., Westwick, J., Strieter, R. M., and Kunkel, S. L.
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Carcinoma, Transitional Cell ,Urologic Neoplasms ,Base Sequence ,Tumor Necrosis Factor-alpha ,Interleukin-8 ,Molecular Sequence Data ,Enzyme-Linked Immunosorbent Assay ,Blotting, Northern ,Gene Expression Regulation, Neoplastic ,Tumor Cells, Cultured ,Humans ,RNA, Messenger ,RNA, Neoplasm ,Carcinoma, Renal Cell ,Research Article - Abstract
Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha. All cell lines expressed high levels of IL-8 mRNA on stimulation with either IL-1 beta or TNF-alpha, but not lipopolysaccharide; one expressed the gene constitutively. The authors selected one transitional cell carcinoma cell line (UM-UC-9) and one renal cell carcinoma cell line (UM-RC-5) for further study. Both displayed a time- and dose-dependent increase in steady-state levels of IL-8 mRNA in response to IL-1 beta and TNF-alpha. Specific mRNA was detectable by 1 hour after stimulation. Secretion of antigenic IL-8 measured by enzyme-linked immunosorbent assay into culture supernatants reflected the kinetics of mRNA expression. Because heat-inactivated TNF-alpha failed to induce synthesis of IL-8 mRNA, and cycloheximide augmented TNF-alpha-induced synthesis, IL-8 expression appears to be a stimulus-specific primary induction phenomenon. As with other inflammatory mediators whose mRNA contains a 3' AU-rich sequence (eg, IL-2, TNF-alpha), the half-life of IL-8 mRNA was short, less than 1 hour. Our data suggest that secretion of IL-8 by malignant cells may partly account for the inflammatory infiltrates associated with some malignant neoplasms.
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- 1992
11. Association of 3q21q26 syndrome and late-appearing Philadelphia chromosome in acute myeloid leukemia
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Quintás-Cardama, A, primary, Gibbons, D L, additional, Cortes, J, additional, Bobadilla, D, additional, Slovak, M L, additional, Kantarjian, H, additional, and Abruzzo, L V, additional
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- 2007
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12. Differences in gene expression between B-cell chronic lymphocytic leukemia and normal B cells: a meta-analysis of three microarray studies
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Wang, J., primary, Coombes, K. R., additional, Highsmith, W. E., additional, Keating, M. J., additional, and Abruzzo, L. V., additional
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- 2004
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13. Atypical Multidrug Resistance: Breast Cancer Resistance Protein Messenger RNA Expression in Mitoxantrone-Selected Cell Lines
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Ross, D. D., primary, Yang, W., additional, Abruzzo, L. V., additional, Dalton, W. S., additional, Schneider, E., additional, Lage, H., additional, Dietel, M., additional, Greenberger, L., additional, Cole, S. P. C., additional, and Doyle, L. A., additional
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- 1999
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14. Enhancer activity of upstream hypersensitive site 2 of the chicken beta-globin cluster is mediated by GATA sites.
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Abruzzo, L V, primary and Reitman, M, additional
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- 1994
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15. Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma.
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Alonsozana, E L C, Stamberg, J, Kumar, D, Jaffe, E S, Medeiros, L J, Frantz, C, Schiffer, C A, O’Connell, B A, Kerman, S, Stass, S A, Abruzzo, L V, Alonsozana, E L, and O'Connell, B A
- Subjects
LYMPHOMAS ,CHROMOSOME abnormalities - Abstract
Malignant lymphomas often have complex, nonrandom chromosomal abnormalities. Hepatosplenic gammadelta T cell lymphoma (gammadelta TCL) is an unusual post-thymic T cell lymphoma that primarily involves liver and spleen, often in young adult males. Few cases have had cytogenetic analysis. We report a consistent isochromosome 7q [i(7q)] abnormality in three cases of hepatosplenic gammadelta TCL, one with i(7q) as the sole abnormality at presentation. Three patients, 15-, 37- and 65-year-old males, presented with hepatosplenomegaly and fevers. Histopathologic, immunophenotypic, and molecular genetic studies supported the diagnosis. Spleen, liver, and bone marrow contained sinusoidal infiltrates of atypical lymphoid cells of T cell immunophenotype. PCR performed on two cases demonstrated clonal T cell receptor gamma gene rearrangements. Cytogenetic analysis of bone marrow showed i(7q) as the sole abnormality at presentation in one case. The second case showed i(7q) in addition to two normal chromosomes 7, and other structural and numerical abnormalities. The third case showed i(7q) and a deletion in the long arm of chromosome 11. These findings support the proposal that i(7q) represents the primary nonrandom cytogenetic abnormality in hepatosplenic gammadelta TCL, and plays a role in its pathogenesis. [ABSTRACT FROM AUTHOR]
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- 1997
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16. Cytogenetic findings in mantle cell lymphoma cases with a high level of peripheral blood involvement have a distinct pattern of abnormalities.
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Onciu, M, Schlette, E, Medeiros, L J, Abruzzo, L V, Keating, M, and Lai, R
- Abstract
We compared conventional cytogenetic findings in mantle cell lymphomas (MCLs) having an absolute peripheral lymphocytosis of more than 10,000/microL (>10 x 10(9)/L) at diagnosis ("leukemic"; n = 30) with those in cases having no or minimal lymphocytosis ("nodal"; n = 19). Only cases positive for t(11;14) were included for study. Forty-six cases (94%) had abnormalities in addition to t(11;14). The most frequent abnormalities involved chromosome 13 (26 cases [53%]), followed by chromosomes 1, 3, 7, 8, 9, 10, 12, 15, 17, and 21 (11-18 cases [22%-37%]). There was no difference in the number of aberrations between the 2 groups. Abnormalities of chromosomes 17, 21, and 22 were more frequent, and breakpoints involving 8q24, 9p22-24, and 16q24 were found exclusively in leukemic MCL. Chromosome 17 aberrations involved were structural (breakpoints involving 17p13, 17p11.2, 17q) in leukemic MCL but were only numeric in nodal MCL. Thus, leukemic MCL differs from nodal MCL in their cytogenetic profiles, which may contribute to the clinical presentation.
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- 2001
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17. Hepatosplenic gamma/delta T-cell lymphoma in bone marrow. A sinusoidal neoplasm with blastic cytologic features.
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Vega, F, Medeiros, L J, Bueso-Ramos, C, Jones, D, Lai, R, Luthra, R, and Abruzzo, L V
- Abstract
We report 8 cases of hepatosplenic T-cell lymphoma (HSTCL) involving bone marrow and correlate histologic findings with disease progression. Immunophenotypic analysis demonstrated mature, aberrant gamma/delta T-cell immunophenotypes. Isochromosome 7q was identified in 4 cases; 1 case showed the t(7;14)(q34;q13). Seven of 7 cases tested had monoclonal TCR gamma gene rearrangements. The initial diagnostic bone marrow biopsy specimens were hypercellular with a frequently subtle, predominantly sinusoidal infiltrate of atypical small to medium-sized lymphoid cells. In all cases, aspirate smears at diagnosis and in subsequent specimens contained malignant cells that resembled blasts, some with fine cytoplasmic granules. With progression, the pattern of HSTCL in bone marrow biopsy specimens became increasingly interstitial, and the neoplastic cells became larger. In aspirate smears, the proportion of blasts increased. Seven patients died; 1 was lost to follow-up. Autopsy performed on 1 patient demonstrated malignant cells within vascular channels in all organs sampled, with relatively little tumor formation, resembling intravascular lymphoma at these sites. HSTCL often can be recognized in bone marrow by its unique combination of a sinusoidal pattern in core biopsy specimens and blastic cytology in aspirate smears.
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- 2001
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18. A novel four-color PCR assay to assess T-cell receptor gamma gene rearrangements in lymphoproliferative lesions.
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Vega, F, Medeiros, L J, Jones, D, Abruzzo, L V, Lai, R, Manning, J, Dunmire, V, and Luthra, R
- Abstract
We describe a novel 4-color polymerase chain reaction (PCR) assay combined with GeneScan analysis to assess for T-cell receptor gamma chain gene (TCRgamma) rearrangements and evaluate its usefulness in 86 lymphoproliferative lesions. In this assay, each variable region (Vgamma) family primer is 5' end-labeled with a different fluorescent dye, allowing determination of the Vgamma family involved in each TCRgamma rearrangement. PCR products were analyzed by capillary electrophoresis. We detected clonal TCRgamma rearrangements in 60 (98%) of 61 T-cell lymphomas, 2 (15%) of 13 B-cell lymphomas, and 3 (25%) of 12 reactive lesions. These results compared favorably with conventional PCR methods using denaturing gradient gel electrophoresis, which revealed clonal TCRgamma rearrangements in 37 (90%) of 41 T-cell lymphomas, 1 (25%) of 4 B-cell lymphomas, and 2 (25%) of 8 reactive lesions. This 4-color PCR assay is at least equivalent to conventional PCR methods and is convenient, allows accurate size determination of TCRgamma rearrangements, and identifies the specific Vgamma family involved, providing more specific information about TCRgamma rearrangement.
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- 2001
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19. Chronic Lymphocytic Leukemia Associated with t(14;18)(q32;q21)
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Tang, G., Sargent, R. L., L. Jeffrey Medeiros, and Abruzzo, L. V.
20. Significantly Increased Detection Rate of High Risk Cytogenomic Markers by Interphase FISH on Enriched Plasma Cells
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Muddasani, R., Zhao, M., Abruzzo, L. V., You, J. M., L. Jeffrey Medeiros, Lovshe, D., and Lu, G.
21. Del(20q) in Patients with Chronic Lymphocytic Leukemia Is Associated with Prior Chemotherapy, Atypical Morphology, ZAP70 Expression, and Unmutated IGHV Genes
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Yin, C. C., Lu, G., L. Jeffrey Medeiros, Feng, X., Keating, M. J., and Abruzzo, L. V.
22. Retroperitoneal follicular dendritic cell sarcoma presenting as secondary amyloidosis.
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Chiaramonte MF, Lee D, Abruzzo LV, Heyman M, and Bass BL
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- Adult, Humans, Male, Retroperitoneal Neoplasms diagnostic imaging, Retroperitoneal Neoplasms pathology, Sarcoma diagnostic imaging, Sarcoma pathology, Tomography, X-Ray Computed, Amyloidosis complications, Liver Diseases complications, Retroperitoneal Neoplasms complications, Sarcoma complications
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- 2001
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23. Primary follicular large cell lymphoma of the testis in a child.
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Lu D, Medeiros LJ, Eskenazi AE, and Abruzzo LV
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, B-Lymphocytes chemistry, B-Lymphocytes pathology, Biomarkers, Tumor analysis, Child, Cyclophosphamide administration & dosage, DNA, Neoplasm analysis, Doxorubicin administration & dosage, Humans, Immunohistochemistry, Lymphoma, Follicular chemistry, Lymphoma, Follicular therapy, Male, Neoplasm Proteins analysis, Orchiectomy, Polymerase Chain Reaction, Prednisone administration & dosage, Testicular Neoplasms chemistry, Testicular Neoplasms therapy, Treatment Outcome, Vincristine administration & dosage, Lymphoma, Follicular pathology, Testicular Neoplasms pathology
- Abstract
Primary follicular lymphoma of the testis in childhood is extremely rare. To our knowledge, only 5 cases have been reported to date. We report a case in a 6-year-old boy who presented with painless right scrotal enlargement. Right radical orchiectomy revealed a follicular large cell lymphoma with diffuse areas confined to the testis and epididymis, clinical stage IE. Immunohistochemical stains demonstrated that the neoplastic cells were of B-cell lineage, positive for CD10, CD20, CD79a, and BCL-6. Staining for CD21 accentuated networks of dendritic reticulum cells within the nodules. The cells were negative for BCL-2, p53, and T-cell antigens. There was no evidence of the t(14;18) detected by polymerase chain reaction. The data suggest that follicular lymphoma of the testis in children has a different pathogenesis than follicular lymphoma in adults.
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- 2001
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24. Primary paratesticular lymphoma: a report of 2 cases and review of literature.
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Vega F, Medeiros LJ, and Abruzzo LV
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- Adult, Biomarkers, Tumor metabolism, Epididymis metabolism, Epididymis surgery, Humans, Immunoenzyme Techniques, Lymphoma, B-Cell metabolism, Lymphoma, B-Cell surgery, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse surgery, Male, Middle Aged, Spermatic Cord metabolism, Spermatic Cord surgery, Testicular Neoplasms metabolism, Testicular Neoplasms surgery, Epididymis pathology, Lymphoma, B-Cell pathology, Lymphoma, Large B-Cell, Diffuse pathology, Spermatic Cord pathology, Testicular Neoplasms pathology
- Abstract
Non-Hodgkin lymphoma arising in the paratesticular organs without testicular involvement is rare. In most previously reported cases, the classification systems that were used are now outdated and/or immunologic studies were not done. We report the clinical and pathologic features of 2 cases of non-Hodgkin lymphoma arising in the epididymis and the spermatic cord. Patient 1 was a 35-year-old man who presented with a painless scrotal mass. Patient 2 was a 61-year-old man who presented with a right inguinal mass. Orchiectomy performed in both patients revealed a mass confined to the epididymis in patient 1 and to the spermatic cord in patient 2. Histologic examination in both cases revealed diffuse large cell lymphoma, and immunohistochemical studies supported B-cell lineage. Subsequent staging studies showed no other site of disease in patient 1 and an isolated mass anterior to the right psoas muscle in patient 2. Malignant lymphoma involving testicular adnexal structures without involvement of the testis is extremely uncommon. To our knowledge, only 6 cases confined to the epididymis and 12 cases confined to the spermatic cord have been reported previously.
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- 2001
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25. Identifying differentially expressed genes in cDNA microarray experiments.
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Baggerly KA, Coombes KR, Hess KR, Stivers DN, Abruzzo LV, and Zhang W
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- Analysis of Variance, Computational Biology, Glioma genetics, Humans, Models, Statistical, Regression Analysis, Tumor Cells, Cultured, Gene Expression Profiling statistics & numerical data, Oligonucleotide Array Sequence Analysis statistics & numerical data
- Abstract
A major goal of microarray experiments is to determine which genes are differentially expressed between samples. Differential expression has been assessed by taking ratios of expression levels of different samples at a spot on the array and flagging spots (genes) where the magnitude of the fold difference exceeds some threshold. More recent work has attempted to incorporate the fact that the variability of these ratios is not constant. Most methods are variants of Student's t-test. These variants standardize the ratios by dividing by an estimate of the standard deviation of that ratio; spots with large standardized values are flagged. Estimating these standard deviations requires replication of the measurements, either within a slide or between slides, or the use of a model describing what the standard deviation should be. Starting from considerations of the kinetics driving microarray hybridization, we derive models for the intensity of a replicated spot, when replication is performed within and between arrays. Replication within slides leads to a beta-binomial model, and replication between slides leads to a gamma-Poisson model. These models predict how the variance of a log ratio changes with the total intensity of the signal at the spot, independent of the identity of the gene. Ratios for genes with a small amount of total signal are highly variable, whereas ratios for genes with a large amount of total signal are fairly stable. Log ratios are scaled by the standard deviations given by these functions, giving model-based versions of Studentization. An example is given.
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- 2001
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26. Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines.
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Ross DD, Yang W, Abruzzo LV, Dalton WS, Schneider E, Lage H, Dietel M, Greenberger L, Cole SP, and Doyle LA
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- Blotting, Northern, Blotting, Southern, Breast Neoplasms genetics, Colonic Neoplasms drug therapy, Colonic Neoplasms metabolism, Fibrosarcoma drug therapy, Fibrosarcoma metabolism, Humans, Multiple Myeloma drug therapy, Multiple Myeloma metabolism, Neoplasm Proteins genetics, RNA, Messenger analysis, RNA, Neoplasm analysis, Stomach Neoplasms drug therapy, Stomach Neoplasms metabolism, Tumor Cells, Cultured, Up-Regulation, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Drug Resistance, Multiple genetics, Drug Resistance, Neoplasm genetics, Gene Expression Regulation, Neoplastic, Mitoxantrone pharmacology, Neoplasm Proteins biosynthesis
- Abstract
Background: Human cancer cell lines grown in the presence of the cytotoxic agent mitoxantrone frequently develop resistance associated with a reduction in intracellular drug accumulation without increased expression of the known drug resistance transporters P-glycoprotein and multidrug resistance protein (also known as multidrug resistance-associated protein). Breast cancer resistance protein (BCRP) is a recently described adenosine triphosphate-binding cassette transporter associated with resistance to mitoxantrone and anthracyclines. This study was undertaken to test the prevalence of BCRP overexpression in cell lines selected for growth in the presence of mitoxantrone., Methods: Total cellular RNA or poly A+ RNA and genomic DNA were isolated from parental and drug-selected cell lines. Expression of BCRP messenger RNA (mRNA) and amplification of the BCRP gene were analyzed by northern and Southern blot hybridization, respectively., Results: A variety of drug-resistant human cancer cell lines derived by selection with mitoxantrone markedly overexpressed BCRP mRNA; these cell lines included sublines of human breast carcinoma (MCF-7), colon carcinoma (S1 and HT29), gastric carcinoma (EPG85-257), fibrosarcoma (EPF86-079), and myeloma (8226) origins. Analysis of genomic DNA from BCRP-overexpressing MCF-7/MX cells demonstrated that the BCRP gene was also amplified in these cells., Conclusions: Overexpression of BCRP mRNA is frequently observed in multidrug-resistant cell lines selected with mitoxantrone, suggesting that BCRP is likely to be a major cellular defense mechanism elicited in response to exposure to this drug. It is likely that BCRP is the putative "mitoxantrone transporter" hypothesized to be present in these cell lines.
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- 1999
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27. A multidrug resistance transporter from human MCF-7 breast cancer cells.
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Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, and Ross DD
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- ATP Binding Cassette Transporter, Subfamily G, Member 2, ATP-Binding Cassette Transporters biosynthesis, ATP-Binding Cassette Transporters chemistry, Adenosine Triphosphate metabolism, Amino Acid Sequence, Animals, Breast Neoplasms, Cell Survival drug effects, Cloning, Molecular, DNA Primers, Female, Gene Library, Humans, Molecular Sequence Data, Phylogeny, RNA, Messenger genetics, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Reverse Transcriptase Polymerase Chain Reaction, Software, Transfection, Tumor Cells, Cultured, ATP-Binding Cassette Transporters genetics, Antineoplastic Agents toxicity, Daunorubicin pharmacokinetics, Drug Resistance, Multiple, Neoplasm Proteins, Transcription, Genetic
- Abstract
MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 655-aa [corrected] member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.
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- 1998
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28. Quantitative measurement of telomerase activity in lymphadenopathy: correlation with histologic features and human immunodeficiency virus-1 infection.
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Strovel JW, Abruzzo LV, Highsmith WE, and Stamberg J
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- Biopsy, DNA Primers chemistry, Electrophoresis, Polyacrylamide Gel, HIV Infections pathology, Hodgkin Disease enzymology, Humans, Lymph Nodes enzymology, Lymph Nodes pathology, Lymphoma, AIDS-Related enzymology, Polymerase Chain Reaction, Tumor Cells, Cultured enzymology, Tumor Cells, Cultured pathology, HIV Infections enzymology, HIV-1, Hodgkin Disease pathology, Lymphoma, AIDS-Related pathology, Telomerase analysis
- Abstract
Telomerase is a ribonucleoprotein that uses its internal RNA component as a template for synthesis of telomeric DNA on the ends of chromosomes after each round of cell division. It is expressed in approximately 90% of all human cancers tested to date, as well as in most immortal cell lines. Recently, telomerase activity was detected in normal proliferating lymphoid tissue and in non-Hodgkin's lymphomas (NHLs) by use of the telomeric repeat amplification protocol assay, a qualitative measure of telomerase activity. In this study, we modified the assay to measure quantitatively the telomerase activity in lymph node biopsy specimens obtained from patients with lymphadenopathy. The lymph nodes either contained benign reactive changes, were involved by NHL of B-cell lineage, or were involved by Hodgkin's disease. Telomerase activity was detected in all of our samples, benign as well as malignant. The levels of activity were unaffected by the patient's human immunodeficiency virus-1 status. Although the specimens involved by NHLs showed a range in telomerase activity from low to high, the levels did not correlate strictly with the histologic grade according to the Working Formulation. All of the cases of Hodgkin's disease also expressed telomerase activity, and the levels were similar regardless of histologic subtype. Our results showed that telomerase activity was expressed in both benign and malignant lymphoproliferative processes.
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- 1998
29. Epstein-Barr virus-related posttransplantation lymphoproliferative disorder involving pancreas allografts: histological differential diagnosis from acute allograft rejection.
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Drachenberg CB, Abruzzo LV, Klassen DK, Bartlett ST, Johnson LB, Kuo PC, Kumar D, and Papadimitriou JC
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- Acute Disease, Adult, Diagnosis, Differential, Female, Follow-Up Studies, Herpesviridae Infections virology, Herpesvirus 4, Human genetics, Humans, Immunohistochemistry, In Situ Hybridization, Lymphoproliferative Disorders virology, Male, Pancreas pathology, Pancreas virology, Postoperative Complications virology, RNA, Viral analysis, Transplantation, Homologous, Tumor Virus Infections virology, Graft Rejection pathology, Herpesviridae Infections diagnosis, Herpesvirus 4, Human isolation & purification, Lymphoproliferative Disorders diagnosis, Pancreas Transplantation, Postoperative Complications diagnosis, Tumor Virus Infections diagnosis
- Abstract
The clinical and pathological features of acute pancreas allograft rejection and involvement of the graft by posttransplantation lymphoproliferative disorders (PTLD) overlap. Because the treatment is diametrically opposite in these two types of lesions, an accurate diagnosis is essential. The histological features in pancreas allograft needle biopsy specimens (n=7) and pancreatectomies (n=4) from four patients with Epstein-Barr virus (EBV)-related PTLD were compared with the material from 14 patients who did not develop PTLD after 12 to 58 months of follow-up and whose biopsy specimens (n=10) and pancreatectomies (n=10) showed rejection-related heavy or atypical inflammatory infiltrates. Features typical of rejection included most (>75%) being of mixed small and large, activated-appearing T lymphocytes, a smaller component of mature plasma cells, and variable numbers of eosinophils. Cytologically atypical cells were always a minority (< 10%). The inflammation involved the septal spaces with proportional involvement of the exocrine tissue, veins, ducts, and arteries. The inflammation was particularly targeted against the acini and was associated with acinar cell damage. Features characteristic of PTLD were nodular and expansile infiltrates, composed of a significant proportion of atypical, plasmacytoid B cells (40% to 70% of the infiltrate); Reed-Sternberg-like cells were noted in two patients. The infiltrates involved the parenchyma randomly with no apparent affinity for the acinar tissue. Extensive infiltration of the peripancreatic soft tissues was common. Arterial walls were not involved in PTLD unless there was concurrent acute vascular rejection. Features identified in both conditions were foci of necrosis and infiltration of venous walls with associated endotheliitis. Samples with concurrent PTLD and acute rejection showed combinations of these features. In situ hybridization for EBER (Epstein-Barr-encoded RNAs) was positive only in the samples from patients with PTLD. Based on the assessment of morphological differences and the selective use of relatively simple ancillary techniques, PTLD can be correctly diagnosed even in small tissue samples such as needle biopsy specimens. An early diagnosis will lead to the appropriate treatment.
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- 1998
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30. Primary hepatic low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) associated with primary biliary cirrhosis.
- Author
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Prabhu RM, Medeiros LJ, Kumar D, Drachenberg CI, Papadimitriou JC, Appelman HD, Johnson LB, Laurin J, Heyman M, and Abruzzo LV
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- Female, Humans, Liver pathology, Liver Cirrhosis, Biliary pathology, Liver Neoplasms pathology, Lymphoma, B-Cell pathology, Lymphoma, B-Cell, Marginal Zone pathology, Middle Aged, Liver Cirrhosis, Biliary complications, Liver Neoplasms complications, Lymphoma, B-Cell complications, Lymphoma, B-Cell, Marginal Zone complications
- Abstract
We describe a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the liver of a patient with early-stage primary biliary cirrhosis (PBC). The patient, a 62-year old woman, presented with abnormal liver function tests, a positive antimitochondrial antibody titer (1:160), and a liver mass. The resected mass, 6.0 x 5.0 x 4.0 cm, had the features of MALT-type lymphoma. The neoplastic cells were small lymphoid cells of B-cell lineage that surrounded reactive lymphoid follicles and infiltrated bile ductules to form lymphoepithelial lesions. The uninvolved liver had histologic evidence of early stage PBC, characterized by segmental duct destruction with granulomata and an inflammatory infiltrate in the portal triads composed of lymphocytes, plasma cells, and occasional eosinophils. A periportal lymph node showed histologic features of the hyaline-vascular type of Castleman's disease, without evidence of malignant lymphoma. Low-grade B-cell lymphomas of the MALT type rarely arise in the liver and, to our knowledge, have not been reported previously in association with PBC. The association in this case suggests that chronic antigenic stimulation as a result of PBC induced the accumulation of acquired MALT, which subsequently transformed to low-grade B-cell lymphoma.
- Published
- 1998
31. Posttransplantation lymphoproliferative disorder associated with OKT3 and decreased antiviral prophylaxis in pancreas transplant recipients.
- Author
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Keay S, Oldach D, Wiland A, Klassen D, Schweitzer E, Abruzzo LV, Kumar D, and Bartlett S
- Subjects
- Acyclovir administration & dosage, Adult, Antiviral Agents administration & dosage, Antiviral Agents therapeutic use, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Ganciclovir administration & dosage, Humans, Immunosuppressive Agents therapeutic use, Lymphoproliferative Disorders chemically induced, Lymphoproliferative Disorders drug therapy, Male, Muromonab-CD3 therapeutic use, Treatment Outcome, Immunosuppressive Agents adverse effects, Lymphoproliferative Disorders etiology, Muromonab-CD3 adverse effects, Pancreas Transplantation adverse effects
- Abstract
Between September 1994 and October 1995, we diagnosed and treated four cases of early onset posttransplantation lymphoproliferative disorder (PTLD) occurring within 62 days of pancreas transplantation. The development of PTLD was associated with both a significantly higher total muromonab-CD3 (OKT3) dose and a lack of ganciclovir/acyclovir prophylaxis, but it was not associated with the total dose of antithymocyte globulin or cytomegalovirus serostatus. All four patients were treated aggressively and survived without evidence of recurrent PTLD more than 1.5 years later. We conclude that the use of a high total dose of OKT3 puts pancreas transplant recipients at increased risk for early onset PTLD, while ganciclovir/acyclovir prophylaxis may help to prevent this disorder; however, if early onset PTLD does occur in these patients, aggressive therapy can lead to a favorable outcome.
- Published
- 1998
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32. Histologically discordant lymphomas with B-cell and T-cell components.
- Author
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Abruzzo LV, Griffith LM, Nandedkar M, Aguilera NS, Taubenberger JK, Raffeld M, Stass SA, Abbondanzo SL, and Jaffe ES
- Subjects
- Adult, Aged, Aged, 80 and over, Base Sequence, Bone Marrow chemistry, Bone Marrow pathology, Bone Marrow Neoplasms chemistry, Bone Marrow Neoplasms diagnosis, Bone Marrow Neoplasms pathology, Burkitt Lymphoma diagnosis, Burkitt Lymphoma pathology, DNA Primers analysis, DNA Primers chemistry, DNA Primers genetics, DNA, Neoplasm analysis, DNA, Neoplasm chemistry, DNA, Neoplasm genetics, DNA, Viral analysis, DNA, Viral chemistry, DNA, Viral genetics, Female, Genotype, Herpesvirus 4, Human genetics, Herpesvirus 4, Human isolation & purification, Humans, Immunophenotyping, Lymph Nodes chemistry, Lymph Nodes pathology, Lymphoma, B-Cell diagnosis, Lymphoma, B-Cell virology, Lymphoma, T-Cell diagnosis, Lymphoma, T-Cell virology, Male, Middle Aged, Neoplasms, Multiple Primary diagnosis, Neoplasms, Multiple Primary virology, Neoplasms, Second Primary diagnosis, Neoplasms, Second Primary virology, Skin chemistry, Skin pathology, Skin Neoplasms chemistry, Skin Neoplasms diagnosis, Skin Neoplasms pathology, Spleen chemistry, Spleen pathology, Splenic Neoplasms chemistry, Splenic Neoplasms diagnosis, Splenic Neoplasms pathology, Lymphoma, B-Cell pathology, Lymphoma, T-Cell pathology, Neoplasms, Multiple Primary pathology, Neoplasms, Second Primary pathology
- Abstract
We describe the clinical, histologic, immunophenotypic, and genotypic features of five cases of histologically discordant lymphomas with B-cell and T-cell components. Three patients presented with B-cell lymphoma; T-cell lymphoma subsequently developed. One patient presented with T-cell lymphoma; B-cell lymphoma subsequently developed. One patient presented with synchronous B-cell and T-cell lymphomas. There were three men and two women. The median age at the initial diagnosis of lymphoma was 66 years. The mean interval between the development of the two lymphomas was 83 months. All patients died of disease. The mean survival was 96 months after the initial diagnosis of lymphoma and 14 months after the diagnosis of the histologically discordant lymphoma. Epstein-Barr virus was found in two cases--the B-cell lymphoma in the patient who presented with synchronous lymphomas, and the subsequent T-cell lymphoma in one of the patients who presented with B-cell lymphoma. Based on the results of immunophenotypic and genotypic analyses, these cases likely represent the occurrence of two distinct lymphoid neoplasms rather than histologic progression of the same neoplastic clone. Furthermore, a subset of these cases are Epstein-Barr virus-associated.
- Published
- 1997
- Full Text
- View/download PDF
33. Correlation of light microscopic, immunocytochemical and ultrastructural cytomorphology of anaplastic large cell Ki-1 lymphoma, an activated lymphocyte phenotype. A case report.
- Author
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Papadimitriou JC, Abruzzo LV, Bourquin PM, and Drachenberg CB
- Subjects
- Biopsy, Needle, Child, Humans, Lymphoma, Large-Cell, Anaplastic ultrastructure, Male, Palatal Neoplasms ultrastructure, T-Lymphocytes immunology, Lymphocyte Activation, Lymphoma, Large-Cell, Anaplastic immunology, Lymphoma, Large-Cell, Anaplastic pathology, Palatal Neoplasms immunology, Palatal Neoplasms pathology
- Abstract
Background: Anaplastic large cell Ki-1 lymphoma has been proposed to be a neoplasm of activated lymphocytes, mostly of T-cell origin., Case: A previously healthy 12-year-old boy presented with a two-month history of a rapidly growing hard palate mass that involved the nasal cartilage and extended to the floor of the right orbit. By light microscopy (LM) the aspirates were very cellular, containing single, pleomorphic cells and occasional cellular aggregates. The cells showed distinct polarity, with the large, anaplastic nucleus at one end and the tapering cytoplasm, including a prominent paranuclear halo (or "hof"), at the other end ("hand mirror" appearance). The cytoplasmic border showed prominent ruffling, concentrated at the two poles of the cells and corresponding to the areas of the protopod and uropod. Immunocytochemically (ICC) the cells were positive for Ki-1, epithelial membrane antigen and UCHL-1, all of which showed both membrane positivity along with Golgi area staining. LCA showed variable membrane staining. Ultrastructurally (electron microscopy [EM]) the polarity was recapitulated, with an eccentric, horseshoe-shaped nucleus partially enclosing a prominent Golgi complex with associated centrosomes and asymmetric plasma membrane ruffling., Conclusion: All three levels of examination (LM, ICC and EM) revealed tumor cell features corresponding to the phenotype of the activated lymphocyte. These features are characteristic, thus allowing the diagnosis of Ki-1 anaplastic lymphoma by fine needle aspiration cytology.
- Published
- 1996
- Full Text
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34. B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus.
- Author
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Abruzzo LV, Schmidt K, Weiss LM, Jaffe ES, Medeiros LJ, Sander CA, and Raffeld M
- Subjects
- Blotting, Southern, Clone Cells, DNA, Viral analysis, Genes, Immunoglobulin, Herpesvirus 4, Human genetics, Humans, Immunoblastic Lymphadenopathy pathology, Immunophenotyping, In Situ Hybridization, Lymph Nodes pathology, Lymphoma, B-Cell immunology, Male, Middle Aged, RNA, Viral analysis, Gene Rearrangement, B-Lymphocyte, Herpesvirus 4, Human pathogenicity, Immunoblastic Lymphadenopathy complications, Lymphoma, B-Cell genetics, Tumor Virus Infections complications
- Abstract
We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.
- Published
- 1993
35. Anti-i causing acute hemolysis following a negative immediate-spin crossmatch.
- Author
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Judd WJ, Steiner EA, Abruzzo LV, Davenport RD, Oberman HA, Pehta JC, and Nance SJ
- Subjects
- Female, Humans, Isoantibodies physiology, Middle Aged, Blood Grouping and Crossmatching methods, Hemolysis immunology, I Blood-Group System immunology, Transfusion Reaction
- Abstract
A unique case of acute hemolysis following transfusion of red cells (RBCs) that were found compatible by immediate-spin (IS) crossmatch technique is reported. Screening tests for unexpected antibodies, using low-ionic-strength saline (LISS), 10 minutes' incubation at 37 degrees C, and anti-IgG, were nonreactive; however, 1 transfused unit was found crossmatch incompatible by indirect antiglobulin technique (IAT). An anti-i (titer 512 at 4 degrees C) that was not an autoantibody was identified in the patient's serum. Unlike the incriminated donor RBCs, most I+ RBCs did not react by LISS-IAT. Variable reactivity was seen with ficin-treated I+ RBCs, and there was marked hemolysis of iadult and icord RBCs. In marked contrast, dominant Lu(a-b-) RBCs, with reduced expression of i, did not react by any test method; nor did autologous I+, Lu(b+) RBCs. The in vivo clinical significance of this anti-i was confirmed by monocyte monolayer assay and RBC survival studies. The patient's i antigen may have been altered, by either chemotherapy or disease, and lacked part of the i antigen-mosaic. Her antibody was directed at epitopes of i that were absent from her RBCs. Those i epitopes missing from her RBCs are also absent on dominant Lu(a-b-) RBCs. This anti-i represents a unique cause of an acute hemolytic transfusion reaction. It also represents a case of acute immune-mediated hemolysis following transfusion of IS crossmatch-compatible blood when screening tests for unexpected antibodies are nonreactive. Because of the rarity of such cases (less than 1/200,000 RBC units transfused), modifications to pretransfusion testing protocols are not proposed.
- Published
- 1992
- Full Text
- View/download PDF
36. T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy.
- Author
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Abruzzo LV, Jaffe ES, Cotelingam JD, Whang-Peng J, Del Duca V Jr, and Medeiros LJ
- Subjects
- Acute Disease, Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biopsy, Bone Marrow pathology, Child, Cytogenetics, Female, Histocytochemistry, Humans, Immunophenotyping, Leukemia, Myeloid drug therapy, Leukemia, Myeloid pathology, Lymph Nodes pathology, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Eosinophilia complications, Leukemia, Myeloid etiology, Myeloproliferative Disorders etiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications
- Abstract
Three patients with T-cell lymphoblastic lymphoma and peripheral blood eosinophilia are reported. At the time of diagnosis, all patients had lymphadenopathy, and one had a mediastinal mass. Lymph node biopsies revealed lymphoblastic lymphoma admixed with a variable number of mature eosinophils. Immunophenotypic studies demonstrated that each lymphoma had an immature T-cell immunophenotype. Bone marrow biopsies were hypercellular with myeloid hyperplasia and eosinophilia but were negative for lymphoma. All patients received multiagent chemotherapy; one patient achieved a complete remission, and two patients had partial remissions. All patients subsequently developed a myeloid malignancy. Two died of acute myeloid leukemia within 18 months of the diagnosis of lymphoblastic lymphoma. The third patient relapsed with a lymphoma that had histologic and immunophenotypic features of both T-cell lymphoblastic lymphoma and granulocytic sarcoma and also developed a poorly defined myeloproliferative disorder. These findings suggest that T-cell lymphoblastic lymphoma associated with eosinophilia may represent a distinct clinico-pathologic entity with a high risk of subsequent myeloid neoplasia.
- Published
- 1992
- Full Text
- View/download PDF
37. Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas.
- Author
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Abruzzo LV, Thornton AJ, Liebert M, Grossman HB, Evanoff H, Westwick J, Strieter RM, and Kunkel SL
- Subjects
- Base Sequence, Blotting, Northern, Enzyme-Linked Immunosorbent Assay, Humans, Interleukin-8 genetics, Interleukin-8 metabolism, Molecular Sequence Data, RNA, Messenger drug effects, RNA, Neoplasm drug effects, Tumor Cells, Cultured, Carcinoma, Renal Cell metabolism, Carcinoma, Transitional Cell metabolism, Gene Expression Regulation, Neoplastic drug effects, Interleukin-8 biosynthesis, Tumor Necrosis Factor-alpha pharmacology, Urologic Neoplasms metabolism
- Abstract
Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha. All cell lines expressed high levels of IL-8 mRNA on stimulation with either IL-1 beta or TNF-alpha, but not lipopolysaccharide; one expressed the gene constitutively. The authors selected one transitional cell carcinoma cell line (UM-UC-9) and one renal cell carcinoma cell line (UM-RC-5) for further study. Both displayed a time- and dose-dependent increase in steady-state levels of IL-8 mRNA in response to IL-1 beta and TNF-alpha. Specific mRNA was detectable by 1 hour after stimulation. Secretion of antigenic IL-8 measured by enzyme-linked immunosorbent assay into culture supernatants reflected the kinetics of mRNA expression. Because heat-inactivated TNF-alpha failed to induce synthesis of IL-8 mRNA, and cycloheximide augmented TNF-alpha-induced synthesis, IL-8 expression appears to be a stimulus-specific primary induction phenomenon. As with other inflammatory mediators whose mRNA contains a 3' AU-rich sequence (eg, IL-2, TNF-alpha), the half-life of IL-8 mRNA was short, less than 1 hour. Our data suggest that secretion of IL-8 by malignant cells may partly account for the inflammatory infiltrates associated with some malignant neoplasms.
- Published
- 1992
38. Lymphoblastic lymphoma presenting in cutaneous sites. A clinicopathologic analysis of six cases.
- Author
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Sander CA, Medeiros LJ, Abruzzo LV, Horak ID, and Jaffe ES
- Subjects
- Adult, B-Lymphocyte Subsets pathology, Child, Chromatin ultrastructure, Cytoplasm ultrastructure, Female, Follow-Up Studies, Forehead pathology, Head and Neck Neoplasms pathology, Humans, Immunophenotyping, Male, Neoplasm Staging, Scalp pathology, Skin pathology, T-Lymphocyte Subsets pathology, Facial Neoplasms pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Skin Neoplasms pathology
- Abstract
Six patients with malignant lymphoma of lymphoblastic type involving cutaneous sites at time of diagnosis are presented. Skin sites of the head and neck were involved in all patients and included the scalp (three patients), forehead (two patients), and malar region of the face (one patient). Two patients also had additional sites of skin disease (neck, breast, and anterior trunk). In two patients the skin was the predominant site of disease, whereas in the remaining patients staging workup revealed generalized lymphoma. The histologic findings in each patient were typical of lymphoblastic lymphoma; the neoplastic cells were small with blastic nuclear chromatin. In three patients the neoplastic cells were convoluted, and in three they were nonconvoluted. Immunophenotypically, four lymphomas were of pre-B cell type, and two lymphomas were of T cell type. There was no correlation between histologic features and the immunophenotype. Since the majority of lymphoblastic lymphomas are of T cell type, the predominance of pre-B cell tumors involving the skin may suggest that pre-B cell neoplasms have a predilection for cutaneous involvement. In further support of this hypothesis, both lymphomas that appear to have arisen in the skin had a pre-B cell immunophenotype.
- Published
- 1991
- Full Text
- View/download PDF
39. Stimulated urothelial cells produce cytokines and express an activated cell surface antigenic phenotype.
- Author
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Liebert M, Wedemeyer G, Abruzzo LV, Kunkel SL, Hammerberg C, Cooper KD, and Grossman HB
- Subjects
- Blotting, Northern, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Fluorescent Antibody Technique, Humans, In Vitro Techniques, Antigens, Surface analysis, Cystitis immunology, Cytokines metabolism, Ureter cytology
- Published
- 1991
40. Blood use during extracorporeal membrane oxygenation.
- Author
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McCoy-Pardington D, Judd WJ, Knafl P, Abruzzo LV, Coombes KR, Butch SH, and Oberman HA
- Subjects
- Bilirubin blood, Erythrocyte Transfusion, Hemoglobins analysis, Humans, Infant, Infant, Newborn, Blood Banks, Blood Transfusion, Extracorporeal Membrane Oxygenation mortality
- Abstract
An analysis of the transfusion records of 91 neonatal patients subjected to extracorporeal membrane oxygenation (ECMO) is reported. Mean daily blood usage was 250 mL of red cells (RBCs), 80 mL of fresh-frozen plasma, and 2 units of platelets. Average time on ECMO was 4.6 days. Group O or ABO type-specific RBCs and group AB or ABO type-specific plasma products and platelets were transfused. RBCs were not washed, and neither RBCs nor other components were tested for anticytomegalovirus (CMV) or irradiated. No cases of posttransfusion CMV infection or graft-versus-host disease were observed. Hemolysis in eight patients was traced to occlusions in the ECMO circuit. All but three patients survived ECMO. Contrary to a previous report, an active ECMO program for neonatal patients imposes a minimal burden on the hospital transfusion service.
- Published
- 1990
- Full Text
- View/download PDF
41. Immunoregulation by natural killer cells.
- Author
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Abruzzo LV, Mullen CA, and Rowley DA
- Subjects
- Animals, Antibody Formation drug effects, Female, Hemolytic Plaque Technique, Immune Tolerance, Immunization, Immunoglobulin M analysis, Interferons physiology, Killer Cells, Natural drug effects, Mice, Mice, Inbred C3H, Neoplasm Transplantation, Poly I-C pharmacology, Killer Cells, Natural immunology
- Abstract
Polyinosinic-polycytidilic acid (poly (I:C], a synthetic analog of viral double-stranded RNA (dsRNA), activates natural killer (NK) cells and inhibits induction or promotes termination of the primary IgM response in vivo. Suppression of responses was reproduced in vivo by interferons (IFN) which activate NK cells and in vitro by cells enriched for NK cells. The likelihood that NK cells may be involved in the normal regulation of IgM responses is supported by the following observations: immunization itself induces NK activity at times appropriate to account for termination, NK cells activated by immunization suppress in vitro, mice with high NK activity induced by immunization with one antigen have reduced responses to immunization with a second antigen, and mice with induced loss of NK activity fail to down-regulate IgM antibody responses normally.
- Published
- 1986
- Full Text
- View/download PDF
42. In vitro and in vivo interaction between murine fibrosarcoma cells and natural killer cells.
- Author
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Laybourn KA, Hiserodt JC, Abruzzo LV, and Varani J
- Subjects
- Animals, Antibodies, Monoclonal, Cell Line, Cytotoxicity, Immunologic, Glycosphingolipids immunology, Laminin physiology, Mice, Poly I-C immunology, Receptors, Immunologic metabolism, Receptors, Laminin, Fibrosarcoma immunology, G(M1) Ganglioside, Immunity, Innate, Killer Cells, Natural immunology, Lung Neoplasms immunology
- Abstract
Murine fibrosarcoma cells were examined for sensitivity to killing by natural killer (NK) and natural cytotoxic lymphocytes from mouse spleens. These tumor cell lines were sensitive to killing by effector cells which were nonadherent to plastic or nylon wool, Thy-1 negative, asialo-GM1 negative, and present in the spleens of beige mice, nude mice, and A/J mice, as well as in the spleens of normal syngeneic and allogeneic control mice. This indicates that the cytotoxic effects were due to natural cytotoxic lymphocytes rather than to NK lymphocytes, T-cells, or macrophages. Although the fibrosarcoma cells were not killed in vitro by endogenous NK cells, these tumor cells were able to "cold target" compete for Yac-1 (an NK-sensitive target) killing and to bind to asialo-GM1-positive, nonadherent spleen lymphocytes in a target cell binding assay. This suggests that the fibrosarcoma cells were recognized by NK cells. In addition, these cell lines were killed in a 4-h NK cytotoxicity assay by polyinosinic-polycytidylic acid-activated effector lymphocytes. The interaction between NK cells and the murine fibrosarcoma cells may have in vivo significance. When syngeneic mice were treated with anti-asialo-GM1 serum to eliminate NK activity and then given i.v. injections of the fibrosarcoma cells, many more lung tumors developed than in control animals. The structural basis for the recognition of the murine fibrosarcoma cells by the NK effector cells is not known. However, laminin may be involved. When the fibrosarcoma cells, which have receptors for the laminin molecule, were preincubated with laminin, they were reduced in their ability to compete for the killing of Yac-1 cells by the NK effectors and had reduced capacity to bind to NK cells in a target cell binding assay.
- Published
- 1986
43. Homeostasis of the antibody response: immunoregulation by NK cells.
- Author
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Abruzzo LV and Rowley DA
- Subjects
- Animals, Antibody-Producing Cells immunology, Cells, Cultured, Homeostasis, Killer Cells, Natural radiation effects, Lymphocyte Cooperation, Mice, Poly I-C immunology, Spleen immunology, Antibody Formation, Killer Cells, Natural immunology, Lymphocytes immunology
- Abstract
When injected into mice, the synthetic double-stranded polynucleotide poly(inosinic) X poly(cytidylic) acid induces high natural killer (NK) cell activity within 4 to 12 hours. Induction of NK activity in mice immunized 2 or 3 days previously, or the addition of NK cells to cultures immunized in vitro 2 or 3 days previously, promotes early termination of the ongoing primary immunoglobulin M antibody response. A target for NK cells is a population of accessory cells that has interacted with antigen and is necessary for sustaining the antibody response. The inference is strong that NK cells induced normally by immunization also terminate the usual antibody response in vivo by elimination of antigen-exposed accessory cells.
- Published
- 1983
- Full Text
- View/download PDF
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