33 results on '"Theil, K. S."'
Search Results
2. UPD1p indicates the presence of MPL W515L mutation in RARS-T, a mechanism analogous to UPD9p and JAK2 V617F mutation
- Author
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Szpurka, H, Gondek, L P, Mohan, S R, Hsi, E D, Theil, K S, and Maciejewski, J P
- Published
- 2009
- Full Text
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3. 400 cGy TBI with fludarabine for reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation
- Author
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Sobecks, R M, Dean, R, Rybicki, L A, Chan, J, Theil, K S, Macklis, R, Andresen, S, Kalaycio, M, Pohlman, B, Ferraro, C, Cherni, K, Sweetenham, J, Copelan, E, and Bolwell, B J
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- 2008
- Full Text
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4. Influence of killer immunoglobulin-like receptor/HLA ligand matching on achievement of T-cell complete donor chimerism in related donor nonmyeloablative allogeneic hematopoietic stem cell transplantation
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Sobecks, R M, Ball, E J, Askar, M, Theil, K S, Rybicki, L A, Thomas, D, Brown, S, Kalaycio, M, Andresen, S, Pohlman, B, Dean, R, Sweetenham, J, Macklis, R, Bernhard, L, Cherni, K, Copelan, E, Maciejewski, J P, and Bolwell, B J
- Published
- 2008
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5. Single nucleotide polymorphism arrays complement metaphase cytogenetics in detection of new chromosomal lesions in MDS
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Gondek, L P, Tiu, R, Haddad, A S, O'Keefe, C L, Sekeres, M A, Theil, K S, and Maciejewski, J P
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- 2007
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6. Survival of AML patients receiving HLA-matched sibling donor allogeneic bone marrow transplantation correlates with HLA-Cw ligand groups for killer immunoglobulin-like receptors
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Sobecks, R M, Ball, E J, Maciejewski, J P, Rybicki, L A, Brown, S, Kalaycio, M, Pohlman, B, Andresen, S, Theil, K S, Dean, R, and Bolwell, B J
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- 2007
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7. Building Entrustable Professional Activities In Residency Training: Peripheral Blood Smear And Body Fluid Analysis
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Theil, K S, primary, Nakashima, M O, additional, Ondrejka, S L, additional, and Cotta, C V, additional
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- 2020
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8. TP53 mutations in myeloid malignancies are either homozygous or hemizygous due to copy number-neutral loss of heterozygosity or deletion of 17p
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Jasek, M, primary, Gondek, L P, additional, Bejanyan, N, additional, Tiu, R, additional, Huh, J, additional, Theil, K S, additional, O'Keefe, C, additional, McDevitt, M A, additional, and Maciejewski, J P, additional
- Published
- 2009
- Full Text
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9. UPD1p indicates the presence of MPL W515L mutation in RARS-T, a mechanism analogous to UPD9p and JAK2 V617F mutation
- Author
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Szpurka, H, primary, Gondek, L P, additional, Mohan, S R, additional, Hsi, E D, additional, Theil, K S, additional, and Maciejewski, J P, additional
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- 2008
- Full Text
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10. Use of single nucleotide polymorphism (SNP) array karyotyping to detect clonal chromosomal abnormalities in myelodysplastic syndrome (MDS) and refractory anemia with ringed sideroblasts (RARS)
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Ghazal, T., primary, Haddad, A. S., additional, Gondek, L. P., additional, Theil, K. S., additional, Sekeres, M. A., additional, Lichtin, A., additional, and Maciejewski, J. P., additional
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- 2008
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11. The influence of early transplantation, age, GVHD prevention regimen, and other factors on outcome of allogeneic transplantation for CML following BuCy.
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Copelan, E A, Penza, S L, Theil, K S, Elder, P J, Bechtel, T P, Tighe, M B, Ezzone, S A, Scholl, M D, Belt, P S, Young, D C, and Avalos, B R
- Subjects
TRANSPLANTATION of organs, tissues, etc. ,GRAFT versus host disease ,METHOTREXATE ,CYCLOSPORINE - Abstract
Results in 164 patients who underwent allogeneic marrow transplantation following busulfan and cyclophosphamide over a 15 year period were analyzed. Age (median 37, range 14–66 years) did not significantly affect the incidence of graft-versus-host disease (GVHD), but patients who received methotrexate with cyclosporine had a significantly lower incidence (P = 0.002) of chronic GVHD compared to those who received methylprednisolone with cyclosporine. Hepatic veno-occlusive disease (VOD) occurred less frequently in chronic phase patients (P = 0.002) and in those transplanted shortly after diagnosis (P = 0.001). Five year leukemia-free survival (LFS) for the entire group was 49% (95% CI 41–57%). For 102 patients who underwent transplantation in chronic phase, results were significantly improved by transplantation at a short interval following diagnosis, particularly within 3 months (P = 0.01), by the use of methotrexate and not corticosteroids for GVHD prevention (P = 0.03), and by use of HLA-identical sibling donors (P = 0.01). Age was not a significant adverse prognostic factor and transplantation was successfully performed in individuals up to age 66. Allogeneic transplantation in CML, including older patients and those with unrelated donors, can be most safely and effectively performed shortly after diagnosis. Bone Marrow Transplantation (2000) 26, 1037–1043. [ABSTRACT FROM AUTHOR]
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- 2000
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12. TEL/AML-1 fusion gene
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Jamil, A., Theil, K. S., Kahwash, S., Ruymann, F. B., and Klopfenstein, K. J.
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- 2000
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13. Malignant conversion of human cells by antisense cDNA to a putative tumor suppressor gene.
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Li, D, Yan, H, Chen, J, Casto, B C, Theil, K S, and Milo, G E
- Abstract
A cell line, SCC83-01-82, derived from a human oral squamous carcinoma, was non-tumorigenic in nude mice, a characteristic of premalignant cells. Conversion of these cells to a tumorigenic phenotype with chemical mutagens did not increase mutations in hot spots or other conserved regions of p53 or H-ras genes. Investigation of the tumorigenic conversion using an expression library resulted in isolation of a previously unidentified gene, CATR1, located on the long arm of chromosome 7 at band approximately q31-32. Evidence for the involvement of this gene in conversion to tumorigenicity was demonstrated by introduction of a eukaryotic expression CATR1 construct into SCC83-01-82 cells. Transfection with the antisense construct reduced the expression of CATR1 in tumors formed by the transfected cells, suggesting that the antisense suppression of endogenous CATR1 expression appeared to be sufficient for tumorigenic conversion. These results are consistent with previous reports of cytogenetic analyses of tumors, that 7q31-32 contains a gene(s) with tumor suppressor activity; CATR1 is a candidate for this putative suppressor gene.
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- 1996
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14. Hypocupremia and bone marrow failure.
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Haddad AS, Subbiah V, Lichtin AE, Theil KS, and Maciejewski JP
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- Adult, Anemia complications, Bone Marrow Examination, Cell Lineage, Copper blood, Copper metabolism, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Pancytopenia diagnosis, Pancytopenia etiology, Peripheral Nervous System Diseases etiology, Anemia diagnosis, Bone Marrow abnormalities, Bone Marrow pathology, Copper deficiency
- Abstract
Copper deficiency associated with neurological disorders is a well-documented condition. However, hypocupremia is less often recognized as a cause of cytopenias or bone marrow failure. We report an illustrative series of three new cases of bi-lineage cytopenia associated with copper deficiency. We have analyzed clinical features of current and historical cases to identify clues that could facilitate application of appropriate laboratory testing and heighten the level of clinical suspicion. By maintaining an appropriately high level of suspicion for potential copper deficiency and obtaining a serum copper level, bone marrow failure due to this condition can be correctly diagnosed and treated. We suggest that copper deficiency be included in the differential diagnosis of reversible causes of bone marrow failure syndromes including myelodysplastic syndrome.
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- 2008
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15. Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B Study.
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Mrózek K, Prior TW, Edwards C, Marcucci G, Carroll AJ, Snyder PJ, Koduru PR, Theil KS, Pettenati MJ, Archer KJ, Caligiuri MA, Vardiman JW, Kolitz JE, Larson RA, and Bloomfield CD
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- Adult, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins genetics, Female, Humans, Male, Middle Aged, Prospective Studies, RUNX1 Translocation Partner 1 Protein, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors genetics, Chromosome Inversion, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 8, Proto-Oncogene Proteins, Translocation, Genetic
- Abstract
Purpose: To prospectively compare cytogenetics and reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), aberrations characteristic of core-binding factor (CBF) acute myeloid leukemia (AML), in 284 adults newly diagnosed with primary AML., Patients and Methods: Cytogenetic analyses were performed at local laboratories, with results reviewed centrally. RT-PCR for AML1/ETO and CBFbeta/MYH11 was performed centrally., Results: CBF AML was ultimately identified in 48 patients: 21 had t(8;21) or its variant and AML1/ETO, and 27 had inv(16)/t(16;16), CBFbeta/MYH11, or both. Initial cytogenetic and RT-PCR analyses correctly classified 95.7% and 96.1% of patients, respectively (P =.83). Initial cytogenetic results were considered to be false-negative in three AML1/ETO-positive patients with unique variants of t(8;21), and in three CBFbeta/MYH11-positive patients with, respectively, an isolated +22; del(16)(q22),+22; and a normal karyotype. The latter three patients were later confirmed to have inv(16)/t(16;16) cytogenetically. Only one of 124 patients reported initially as cytogenetically normal was ultimately RT-PCR-positive. There was no false-positive cytogenetic result. Initial RT-PCR was falsely negative in two patients with inv(16) and falsely positive for AML1/ETO in two and for CBFbeta/MYH11 in another two patients. Two patients with del(16)(q22) were found to be CBFbeta/MYH11-negative. M4Eo marrow morphology was a good predictor of the presence of inv(16)/t(16;16)., Conclusion: Patients with t(8;21) or inv(16) can be successfully identified in prospective multi-institutional clinical trials. Both cytogenetics and RT-PCR detect most such patients, although each method has limitations. RT-PCR is required when the cytogenetic study fails; it is also required to determine whether patients with suspected variants of t(8;21), del(16)(q22), or +22 represent CBF AML. RT-PCR should not replace cytogenetics and should not be used as the only diagnostic test for detection of CBF AML because of the possibility of obtaining false-positive or false-negative results.
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- 2001
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16. Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrophy (SMA) carrier with two SMN1 copies on one chromosome.
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Mailman MD, Hemingway T, Darsey RL, Glasure CE, Huang Y, Chadwick RB, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Schafer RW, Abuelo DN, Reich EW, Theil KS, Burghes AH, de la Chapelle A, and Prior TW
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- Autoradiography, Base Sequence, Chromosome Mapping, Cyclic AMP Response Element-Binding Protein, DNA Primers, Haplotypes, Humans, In Situ Hybridization, Fluorescence, Mutation, RNA-Binding Proteins, SMN Complex Proteins, Survival of Motor Neuron 1 Protein, Chromosomes, Human, Pair 5, Genetic Carrier Screening, Muscular Atrophy, Spinal genetics, Nerve Tissue Proteins genetics
- Abstract
We have analyzed the survival motor neuron gene (SMN1) dosage in 100 parents of children with homozygous SMN1 deletions. Of these parents, 96 (96%) demonstrated the expected one-copy SMN1 carrier genotype. However, four parents (4%) were observed to have a normal two-copy SMN1 dosage. The presence of two intact SMN1 genes in the parent of an affected child indicates either the occurrence of a de novo mutation event or a situation in which one chromosome has two copies of SMN1, whereas the other is null. We have separated individual chromosomes from two of these parents with two-copy SMN1 dosage by somatic cell hybridization and have employed a modified quantitative dosage assay to provide direct evidence that one parent is a two-copy/ zero-copy SMN1 carrier, whereas the other parent had an affected child as the result of a de novo mutation. These findings are important for assessing the recurrence risk of parents of children with spinal muscular atrophy and for providing accurate family counseling.
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- 2001
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17. The partial nontandem duplication of the MLL (ALL1) gene is a novel rearrangement that generates three distinct fusion transcripts in B-cell acute lymphoblastic leukemia.
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Whitman SP, Strout MP, Marcucci G, Freud AG, Culley LL, Zeleznik-Le NJ, Mrózek K, Theil KS, Kees UR, Bloomfield CD, and Caligiuri MA
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- Alternative Splicing genetics, Blotting, Southern, Chromosome Breakage, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 9 genetics, Exons, Histone-Lysine N-Methyltransferase, Humans, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins genetics, Recombinant Fusion Proteins genetics, Repetitive Sequences, Nucleic Acid, Reverse Transcriptase Polymerase Chain Reaction, Translocation, Genetic, Tumor Cells, Cultured, Burkitt Lymphoma genetics, DNA-Binding Proteins genetics, Gene Rearrangement, Proto-Oncogenes, RNA, Messenger genetics, Transcription Factors
- Abstract
A partial nontandem duplication (PNTD) of mixed lineage leukemia (MLL) gene is described in B-cell acute lymphoid leukemia without structural cytogenetic abnormalities at 11q23 and 9p22. A duplicated portion of MLL is interrupted by the insertion of a region of 9p22 that includes the 3'-end of the AF9 gene. The PNTD encodes: (a) a PNTD transcript; (b) a partial tandem duplication of MLL; and (c) a chimeric transcript fusing MLL to the 3'-end of AF9, mimicking the t(9;11)(p22;q23) and expressed 1024-fold higher than the other two. The MLL PNTD, therefore, contributes toward leukemogenesis through simultaneous production of fusion transcripts that are otherwise encoded by three distinct genetic defects.
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- 2001
18. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study.
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Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, and Appelbaum FR
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- Acute Disease, Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Chromosomes, Human ultrastructure, Combined Modality Therapy, Cytarabine administration & dosage, Female, Humans, Idarubicin administration & dosage, Leukemia, Myeloid drug therapy, Leukemia, Myeloid mortality, Leukemia, Myeloid therapy, Life Tables, Male, Middle Aged, Remission Induction, Risk, Survival Analysis, Translocation, Genetic, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, Aneuploidy, Chromosome Aberrations, Karyotyping, Leukemia, Myeloid genetics
- Abstract
The associations of cytogenetics with complete remission (CR) rates, overall survival (OS), and outcomes after CR were studied in 609 previously untreated AML patients younger than 56 years old in a clinical trial comparing 3 intensive postremission therapies: intensive chemotherapy, autologous transplantation (ABMT), or allogeneic bone marrow transplantation (alloBMT) from matched related donors. Patients were categorized into favorable, intermediate, unfavorable, and unknown cytogenetic risk groups based on pretreatment karyotypes. CR rates varied significantly (P <.0001) among the 4 groups: favorable, 84% (95% confidence interval [CI], 77%-90%); intermediate, 76% (CI, 71%-81%); unfavorable, 55% (CI, 48%-63%); and unknown, 54% (CI, 33%-74%). There was similar significant heterogeneity of OS (P <.0001), with the estimated relative risk of death from any cause being 1.50 (CI, 1.10-2.05), 3. 33 (CI, 2.43-4.55), and 2.66 (CI, 1.59-4.45) for the intermediate, unfavorable, and unknown risk groups, respectively, compared with the favorable group. In multivariate analyses, the effects of cytogenetic risk status on CR rate and OS could not be explained by other patient or disease characteristics. Among postremission patients, survival from CR varied significantly among favorable, intermediate, and unfavorable groups (P =.0003), with significant evidence of interaction (P =.017) between the effects of treatment and cytogenetic risk status on survival. Patients with favorable cytogenetics did significantly better following ABMT and alloBMT than with chemotherapy alone, whereas patients with unfavorable cytogenetics did better with alloBMT. Cytogenetic risk status is a significant factor in predicting response of AML patients to therapy; however, to tighten treatment correlates within genetically defined AML subsets, a significantly larger leukemia cytogenetic database is warranted.
- Published
- 2000
19. Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia.
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Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS, Krahe R, Ruutu T, Knuutila S, Bloomfield CD, and Caligiuri MA
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- Adult, Amino Acid Sequence, Artificial Gene Fusion, Base Sequence, Chromosome Mapping, DNA, Complementary, Histone-Lysine N-Methyltransferase, Humans, Male, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein, Rho Guanine Nucleotide Exchange Factors, Chromosomes, Human, Pair 11, DNA-Binding Proteins genetics, Guanine Nucleotide Exchange Factors genetics, Leukemia, Myelomonocytic, Acute genetics, Proto-Oncogenes, Transcription Factors
- Abstract
We have identified a gene at 11q23, telomeric to MLL, that encodes a guanine nucleotide exchange factor (GEF). This gene is transcribed into a 9.5-kb mRNA containing a 4.6-kb ORF. By Northern analysis, it was found to be expressed in all human tissues examined including peripheral blood leukocytes, spleen, prostate, testis, ovary, small intestine, colon, and minimally in thymus. Analysis of the predicted protein sequence indicates that it has strong homology to several members of the family of Rho GEFs that includes such oncogenes as Dbl, Vav, Tiam, and Bcr. A patient with primary acute myeloid leukemia (AML) and a karyotype of 51,XY,+8,+19,+3mar was found to have the 5' end of MLL at exon 6 fused in-frame with the 3' end of almost the entire ORF of this gene, which we named LARG for leukemia-associated Rho GEF. Transcriptional orientation of both genes at 11q23 is from centromere to telomere, consistent with other data that suggest the MLL-LARG fusion resulted from an interstitial deletion rather than a balanced translocation. LARG does not appear to have any homology with other MLL partner genes reported thus far. Thus, LARG represents an additional member of the GEF family and a novel MLL fusion partner in acute myeloid leukemia.
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- 2000
- Full Text
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20. HER-2/neu amplification and overexpression in endometrial carcinoma.
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Rolitsky CD, Theil KS, McGaughy VR, Copeland LJ, and Niemann TH
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- Adenocarcinoma, Clear Cell diagnosis, Adenocarcinoma, Clear Cell genetics, Adenocarcinoma, Clear Cell metabolism, Adenocarcinoma, Clear Cell mortality, Adult, Aged, Aged, 80 and over, Carcinoma, Endometrioid diagnosis, Carcinoma, Endometrioid genetics, Carcinoma, Endometrioid metabolism, Carcinoma, Endometrioid mortality, Chromosomes, Human, Pair 17 genetics, Endometrial Neoplasms diagnosis, Endometrial Neoplasms genetics, Female, Gene Amplification, Gene Expression, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Middle Aged, Prognosis, Proto-Oncogene Mas, Receptor, ErbB-2 genetics, Survival Rate, Endometrial Neoplasms metabolism, Endometrial Neoplasms mortality, Receptor, ErbB-2 biosynthesis
- Abstract
HER-2/neu is a proto-oncogene associated with poor prognosis in women with breast and ovarian carcinoma. The significance of HER-2/neu in endometrial carcinoma is less clearly established. The authors compared HER-2/neu gene amplification using fluorescence in situ hybridization and protein overexpression using immunohistochemistry with survival in patients with endometrial carcinoma. Fluorescence in situ hybridization and immunohistochemical staining were performed on 72 formalin-fixed, paraffin-embedded endometrial carcinoma specimens. Vysis combination HER-2/neu and centromere 17 probe mixture was applied to isolated tumor cell nuclei. A minimum of 200 nuclei were scored for each specimen using standard signal enumeration criteria. A specimen was considered amplified with 5% or greater amplified nuclei. Tissue sections were immunostained with polyclonal antibody against p185erb-2 transmembrane glycoprotein. Immunohistochemical reactivity was scored on a three-tiered scale. HER-2/neu gene amplification and protein overexpression were detected in 15 of 72 (21%) and 12 of 72 (17%) of the specimens, respectively, with 2 cases of normal copy overexpression and 5 cases of amplification without overexpression. Both amplification and overexpression were associated with higher grade tumors. Amplification was associated with clear cell and serous subtypes (p = 0.002), and overexpression with only clear cell type (p = 0.006). Using the proportional hazards model of survival, amplification was found to have significant negative predictive value beyond stage, grade, and cell type (p = 0.002). HER-2/neu gene amplification as detected by fluorescence in situ hybridization in archival material has significant prognostic value.
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- 1999
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21. Familial eosinophilia: clinical and laboratory results on a U.S. kindred.
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Lin AY, Nutman TB, Kaslow D, Mulvihill JJ, Fontaine L, White BJ, Knutsen T, Theil KS, Raghuprasad PK, Goldstein AM, and Tucker MA
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- Adolescent, Adult, Aged, Antibodies, Helminth analysis, Child, Chromosome Banding, Chromosome Disorders, Chromosome Inversion, Chromosomes, Human, Pair 10, Family Characteristics, Female, Granulocyte-Macrophage Colony-Stimulating Factor blood, Humans, Interleukin-3 blood, Interleukin-5 blood, Karyotyping, Male, Middle Aged, Pedigree, United States, Chromosome Aberrations genetics, Eosinophilia genetics
- Abstract
We describe a five-generation kindred with familial eosinophilia (FE; MIM131400), characterized by the occurrence of sustained eosinophilia of unidentifiable cause in multiple relatives. The inheritance pattern is consistent with an autosomal dominant pattern. Among 52 related subjects studied, 19 were affected and 33 were unaffected. Ten unaffected spouses were also evaluated. Four subjects with sustained eosinophilia were diagnosed with cardiac abnormalities and two of them also had neurologic symptoms. In comparison with the unaffected or spouses, evaluation of complete blood counts showed that the affected relatives had, as expected, significantly higher white cell (P < 0.005) and absolute eosinophil counts (P < 0.001) and lower red cell counts (P < 0.05). Evaluation of serum cytokine levels (IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GMCSF) and serology for parasitic helminth infection demonstrated no differences between the affected and unaffected individuals; no individuals studied had serologic evidence for parasitic infection. There were also no differences in anti-nuclear antibody, serum cobalamin (vitamin B12) level, immunoglobulin level, leukocyte alkaline phosphatase, rheumatoid factor, HLA analysis, and stool findings for ova and parasites. Among eight affected persons who had peripheral blood or bone marrow karyotype analysis, two carried the same chromosome abnormality, a pericentric inversion of chromosome 10, inv (10) (p11.2q21.2). A gene mapping study is currently underway to study the underlying genetic mechanism(s) of this syndrome.
- Published
- 1998
22. Localization of FCGR1 encoding Fcgamma receptor class I in primates: molecular evidence for two pericentric inversions during the evolution of human chromosome 1.
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Maresco DL, Blue LE, Culley LL, Kimberly RP, Anderson CL, and Theil KS
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- Animals, Humans, In Situ Hybridization, Fluorescence, Macaca mulatta, Pan troglodytes, Papio, Species Specificity, Chromosome Inversion, Chromosomes, Human, Pair 1, Evolution, Molecular, Primates genetics, Receptors, IgG genetics
- Abstract
The human high-affinity receptor for immunoglobulin G, FcgammaRI (FCGR1), is encoded by a family of three genes that share over 95% sequence homology. Curiously, the three genes in this recently duplicated gene family flank the centromere of human chromosome 1, with FCGR1B located at 1p12 and both FCGR1A and FCGR1C located at 1q21. We have previously speculated that a pericentric inversion could account for the separation of the genes in the FCGR1 family and explain their current chromosomal location. Here we present evidence, obtained through fluorescence in situ hybridization analysis, that in the rhesus monkey (Macaca mulatta) and baboon (Papio papio) FCGR1 is located adjacent to the centromere on the chromosomal arm with greatest homology to human 1p, whereas in the chimpanzee (Pan troglodytes) it is located adjacent to the centromere on the chromosomal arm with greatest homology to human 1q. The separation of the FCGR1 gene family in humans suggests that the location of a second pericentric inversion, known to distinguish the human from the chimpanzee chromosome 1, is within the FCGR1 gene family. This finding refines the assignment of homology between the human and chimpanzee chromosomes 1.
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- 1998
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23. Expression, exon-intron organization, and chromosome mapping of the human sodium iodide symporter.
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Smanik PA, Ryu KY, Theil KS, Mazzaferri EL, and Jhiang SM
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- Base Sequence, Biological Transport physiology, Blotting, Northern, Breast chemistry, Breast metabolism, Breast physiology, Carrier Proteins analysis, Carrier Proteins physiology, Chromosomes, Human, Pair 19, Colon chemistry, Colon metabolism, Colon physiology, Female, Gene Amplification, Humans, In Situ Hybridization, Iodides metabolism, Ion Transport, Membrane Proteins analysis, Membrane Proteins physiology, Ovary chemistry, Ovary metabolism, Ovary physiology, Polymerase Chain Reaction, Sodium metabolism, Thyroid Gland chemistry, Thyroid Gland metabolism, Thyroid Gland physiology, Thyroid Neoplasms chemistry, Thyroid Neoplasms metabolism, Thyroid Neoplasms physiopathology, Carrier Proteins genetics, Chromosome Mapping, Exons, Introns, Membrane Proteins genetics, Symporters
- Abstract
The active iodide uptake of the thyroid gland in humans is mediated by the human sodium iodide symporter (hNIS). In this report, we show that hNIS expression was detected primarily in thyroid tissue, but also in breast, colon, and ovary tissues. Expression of hNIS is greatly reduced in thyroid tumors compared to normal thyroid tissue. Among tumor tissues, hNIS expression appears to be variable, consistent with the variable response to radioiodide treatment observed for thyroid carcinomas. The coding region of hNIS is interrupted by 14 introns, and the nucleotide sequence of each exon-intron junction is reported. Using this information, an alternatively spliced form of hNIS was identified. Finally, the chromosome location of the hNIS gene was mapped to chromosome 19p.
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- 1997
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24. Aberrant expression of CD19 as a marker of monocytic lineage in acute myelogenous leukemia.
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Tisone JA, Bohman JE, Theil KS, and Brandt JT
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- Adult, Aged, Antibodies, Monoclonal, Antigens, CD19 immunology, Female, Humans, Immunophenotyping, Leukemia, Myeloid, Acute immunology, Male, Middle Aged, Antigens, CD19 biosynthesis, Gene Expression Regulation, Leukemic, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology
- Abstract
Immunophenotypic analysis plays a critical role in the diagnosis and classification of acute leukemia. Certain characteristic immunophenotypic patterns have emerged that aid in the classification of acute myelogenous leukemia (AML). We describe a unique pattern of expression of CD19, a B cell-associated cell surface antigen, in cases of AML. We reviewed 59 cases of de novo AML to determine the pattern of CD19 expression in cases of AML using three different CD19 monoclonal antibodies, including B4 (Lytic), B4 89B (Coulter, Miami, Fla) and SJ25-C1 (GenTrak, Plymouth Meeting, Pa). We confirmed the known relationship between CD19 expression and t(8;21)-positive AML M2; in these cases, CD19 was detected with all three antibodies. We also found a unique pattern of CD19 expression in cases of AML with a substantial monocytic-monoblastic component. In 6 of 12 cases of AML M4 or M5, CD19 expression was evident only with the B4 (Lytic) antibody; CD19 expression was not observed using B4 89B or SJ25-C1. We did not observe any recurring chromosomal abnormalities in these cases of CD19-positive AML M4/M5; furthermore, none of these cases demonstrated a t(8;21). Using CD11b, CD14, and other myeloid markers, we found that AML M4 and AML M5 were characterized by dual populations of blasts. With the exception of a case of AML M4 eo, cases of AML M4 were associated with one population of blasts lacking both CD11b and CD14 and a second population with one or both of these antigens. Cases of AML M5 also had dual populations of blasts, but in contrast with AML M4, each population expressed CD11b, CD14, or both. Our findings suggest that specific immunophenotypic patterns, including the unique pattern of CD19 expression with the B4 (Lytic) monoclonal antibody, may prove useful in classifying cases of AML M4 and M5.
- Published
- 1997
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25. The three genes of the human FCGR1 gene family encoding Fc gamma RI flank the centromere of chromosome 1 at 1p12 and 1q21.
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Maresco DL, Chang E, Theil KS, Francke U, and Anderson CL
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- 3T3 Cells, Animals, Base Sequence, Blotting, Southern, CHO Cells, Cell Line, Centromere, Chromosome Mapping, Chromosomes, Artificial, Yeast, Cricetinae, DNA, Gene Dosage, Humans, Hybrid Cells, In Situ Hybridization, Fluorescence, Mice, Molecular Sequence Data, Oligonucleotide Probes, Chromosomes, Human, Pair 1, Receptors, IgG genetics
- Abstract
The high-affinity receptor for immunoglobulin G, Fc gamma RI (FCGR1), is encoded by a family of three genes within humans that share over 98% of DNA sequence homology. Efforts to define the location of the FCGR1 genes within chromosome 1 have been made to determine if they are tightly linked to the five other FCGR genes present at 1q23. Our results, obtained through both fluorescence in situ hybridization analysis of human cells and Southern analysis of cell lines containing 1p and 1q, show instead that the three genes flank the centromere of chromosome 1 at bands 1p12 and 1q21. FCGR1B was found at 1p12, whereas both FCGR1A and FCGR1C were localized to 1q21. This places the FCGR1 gene family within a large pericentric linkage group which is conserved between humans and mice. We hypothesize that the three FCGR1 genes were separated by a pericentric inversion known to have occurred on human chromosome 1, which relocated FCGR1A and FCGR1C to the long arm and left FCGR1B positioned on the short arm. We have also performed FCGR1 gene copy number experiments which indicate the existence of three FCGR1 genes within the human genome.
- Published
- 1996
- Full Text
- View/download PDF
26. HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.
- Author
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Scott AA, Head DR, Kopecky KJ, Appelbaum FR, Theil KS, Grever MR, Chen IM, Whittaker MH, Griffith BB, and Licht JD
- Subjects
- Acute Disease, Antigens, Differentiation, Myelomonocytic analysis, Antigens, Differentiation, T-Lymphocyte analysis, Base Sequence, CD56 Antigen, Cell Differentiation drug effects, Cytotoxicity, Immunologic, Diagnostic Errors, Humans, Immunophenotyping, Leukemia immunology, Leukemia therapy, Leukemia, Promyelocytic, Acute immunology, Molecular Sequence Data, Receptors, IgG analysis, Receptors, Retinoic Acid genetics, Sialic Acid Binding Ig-like Lectin 3, Tretinoin pharmacology, Antigens, CD analysis, HLA-DR Antigens analysis, Killer Cells, Natural immunology, Leukemia diagnosis, Leukemia, Promyelocytic, Acute diagnosis
- Abstract
We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer (NK) cells. From a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML), we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+, CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated (CD56) antigens in each case, whereas reverse transcription polymerase chain reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases shared unique morphologic features (deeply invaginated nuclear membranes, scant cytoplasm with fine azurophilic granularity, and finely granular Sudan black B and myeloperoxidase cytochemical reactivity) that were remarkably similar to those of acute promyelocytic leukemia (APL); particularly the microgranular variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2 cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript. All cases tested (6/20), including the case with t(11;17), failed to differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA. Four of 6 cases tested showed functional NK cell-mediated cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16- acute leukemias and normal CD56+, CD16- NK precursor cells. Using a combination of panning and multiparameter flow cytometric sorting, we identified a normal CD56+, CD33+, CD16- counterpart cell at a frequency of 1% to 2% in the peripheral blood of healthy individuals. Our studies suggest that this form of acute leukemia may arise from transformation of a precursor cell common to both the myeloid and NK cell lineages; thus we propose the designation myeloid/NK acute leukemia. Recognition of this new leukemic entity will be important in distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL.
- Published
- 1994
27. Spontaneous development of a chromosomal translocation 5;14 in an Epstein-Barr-virus-associated B-cell lymphoma in a SCID mouse.
- Author
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Glaser R, Theil KS, Bonneau RH, Sheridan JF, Vasquez M, and Allen CM
- Subjects
- Animals, Antigens, Viral biosynthesis, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 5, DNA-Binding Proteins biosynthesis, Epstein-Barr Virus Nuclear Antigens, Female, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Herpesvirus 4, Human genetics, Humans, Immunoglobulin G biosynthesis, Lymphoma, B-Cell immunology, Mice, Mice, SCID, Neoplasm Transplantation immunology, Tumor Cells, Cultured, Tumor Virus Infections immunology, Antibodies, Viral biosynthesis, Genes, Immunoglobulin genetics, Herpesvirus 4, Human immunology, Lymphoma, B-Cell genetics, Translocation, Genetic, Tumor Virus Infections genetics
- Abstract
C.B-17 SCID mice were inoculated with human peripheral blood leukocytes (PBLs) from normal Epstein-Barr virus (EBV)-seropositive and -seronegative donors. Confirmation of a functioning human immune response was demonstrated by the detection of human antibody after inoculation with rotavirus, tetanus toxoid, or EBV. One group of animals inoculated with PBLs from an EBV-seropositive donor developed immunoblastic lymphomas approximately 9 weeks after transplantation. Confirmation of the species and sex of origin of the tumor cells was established using a spontaneous cell line prepared from the tumor. At passage I, the tumor-cell line (AGTI) showed 15% of the metaphases with a translocation involving chromosomes 5 and 14. A lymphoblastoid cell line (AGLCL) established from the same PBLs from the same donor at the time of inoculation of the mice had a normal female karyotype. The AGLCL and a clone of AGTI cells were analyzed for rearrangement of immunoglobulin heavy chain (IgH) genes; both cell lines showed rearrangement of both IgH alleles. The results outlined in this report suggest that a spontaneous chromosomal translocation involving chromosome 14 occurred in normal PBLs in the SCID mouse.
- Published
- 1993
- Full Text
- View/download PDF
28. An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation.
- Author
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Downing JR, Head DR, Curcio-Brint AM, Hulshof MG, Motroni TA, Raimondi SC, Carroll AJ, Drabkin HA, Willman C, and Theil KS
- Subjects
- Adolescent, Adult, Base Sequence, Child, Child, Preschool, Chromosome Disorders, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 8, Core Binding Factor Alpha 2 Subunit, Female, Gene Expression, Humans, Infant, Male, Molecular Sequence Data, Neoplasm Proteins genetics, Oligodeoxyribonucleotides chemistry, Polymerase Chain Reaction, RNA, Messenger genetics, RNA, Neoplasm genetics, Recombinant Proteins genetics, Chromosome Aberrations diagnosis, DNA-Binding Proteins, Leukemia, Myeloid, Acute genetics, Proto-Oncogene Proteins, Transcription Factors, Translocation, Genetic
- Abstract
The 8;21 translocation is one of the most common chromosomal translocations in acute myelogenous leukemia (AML), accounting for 40% of pediatric AML with French-American-British (FAB)-M2 morphology. The chromosomal breakpoints have recently been identified at the molecular level and shown to involve the AML1 gene on chromosome 21 and the ETO gene on chromosome 8. Translocation results in the consistent fusion of these genes on the der(8) chromosome, resulting in the production of a novel chimeric gene and message. Using oligonucleotide primers derived from the AML1 and ETO cDNAs, we were able to amplify a specific fusion transcript from 26 of 26 patients with t(8;21) by a reverse transcriptase polymerase chain reaction (PCR) approach. DNA fragments of identical size were generated from each case including two with complex translocations. Studies on the sensitivity and specificity of this approach show that PCR analysis can be used as a rapid, accurate, and sensitive means for detecting this chromosomal abnormality, and for following the patients' response to therapy.
- Published
- 1993
29. Rapid diagnosis of cytomegalovirus in the cerebrospinal fluid of a patient with AIDS-associated polyradiculopathy.
- Author
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Marmaduke DP, Brandt JT, and Theil KS
- Subjects
- Adult, Cerebrospinal Fluid microbiology, Cytomegalovirus Infections complications, Female, Humans, Immunoenzyme Techniques, Polyradiculoneuropathy cerebrospinal fluid, Polyradiculoneuropathy microbiology, Acquired Immunodeficiency Syndrome complications, Cytomegalovirus isolation & purification, Cytomegalovirus Infections cerebrospinal fluid, Polyradiculoneuropathy complications
- Abstract
Polyradiculopathy is an uncommon but serious neurologic disorder that can complicate the course of the acquired immunodeficiency syndrome. We report a case in which the presence of cytomegalovirus was detected in cerebrospinal fluid by immunoperoxidase staining. In addition, large atypical cells with flocculogranular cytoplasmic inclusions were present. These cells were found to be positive for cytomegalovirus by immunoperoxidase staining. Rapid diagnosis by this method permitted early intervention with ganciclovir.
- Published
- 1991
30. Abnormalities of leukocyte histograms resulting from microorganisms.
- Author
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Marshall BA, Theil KS, and Brandt JT
- Subjects
- Adult, Blood Cell Count instrumentation, Blood Cell Count methods, Candida, Electronics, Medical instrumentation, Female, Humans, Infant, Male, Middle Aged, Staphylococcus epidermidis, Blood microbiology, Leukocyte Count, Leukocytes pathology
- Abstract
The authors report a series of 13 patients seen in their laboratory during October 1985 to August 1988 in which the presence of bacterial, fungal, or malarial parasites visible on peripheral smear was correlated with an abnormal leukocyte histogram. Samples submitted for complete blood count and differential counts were analyzed with Coulter S-Plus VI (seven specimens) or S-Plus STKR (six specimens) instrumentation. Organisms visualized on the Wright-stained peripheral smears included Histoplasma capsulatum (two), Candida sp. (four), Plasmodium sp. (three), and Staphylococcus sp. (four). Two patients had a diagnosis of acquired immune deficiency syndrome (AIDS); intravascular catheters were present in five other patients. In all cases the leukocyte histograms were abnormal. The instrument flagged abnormalities of the R1 region in four patients and multiple regions in nine patients. Similar flags were produced by the in vitro addition of bacteria or fungi to whole blood. These studies document that the presence of microorganisms in the peripheral blood can result in spurious white blood cell (WBC) counts or electronic differentials. The authors' findings indicate that the possibility of circulating organisms should be considered when abnormal WBC flags are detected with Coulter instrumentation.
- Published
- 1990
- Full Text
- View/download PDF
31. Hairy cell leukemia involving an inguinal hernial sac.
- Author
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Melaragno MJ, Theil KS, Marsh WL, Sedmak DD, and Bouroncle BA
- Subjects
- Adult, Hernia, Inguinal diagnosis, Hernia, Inguinal surgery, Humans, Leukemia, Hairy Cell diagnosis, Leukemia, Hairy Cell surgery, Male, Neoplasm Invasiveness, Spleen pathology, Splenectomy, Hernia, Inguinal pathology, Leukemia, Hairy Cell pathology
- Abstract
A 37-year-old man with hairy cell leukemia was found incidentally to have a right inguinal hernia. Microscopic examination of the resected herniorrhaphy specimen disclosed dense transmural infiltration by hairy cells. Electron-microscopic and immunoperoxidase studies confirmed the presence of surface cytoplasmic projections and B cell phenotype, respectively, of the infiltrating cells. This case is, to our knowledge, the first reported instance of hairy cell leukemia involving a hernial sac and demonstrates the capacity of hairy cells to infiltrate unexpected soft-tissue sites.
- Published
- 1990
- Full Text
- View/download PDF
32. Comparison of Papanicolaou's and Wright-Giemsa stains in the examination of body fluids for Hodgkin's disease.
- Author
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Wilson MS, Theil KS, Goodwin RA, and Brandt JT
- Subjects
- Adult, Aged, Diagnosis, Differential, Evaluation Studies as Topic, Hodgkin Disease diagnosis, Humans, Lymphoma, Non-Hodgkin diagnosis, Lymphoma, Non-Hodgkin pathology, Male, Middle Aged, Azure Stains, Body Fluids cytology, Hodgkin Disease pathology, Phenothiazines, Staining and Labeling methods
- Abstract
We reviewed 36 body fluid specimens from 18 patients with Hodgkin's disease (HD) to characterize the cytologic features of HD as seen in Wright-Giemsa (WG)-stained cytocentrifuge preparations, and to compare diagnostic agreement between WG- and Papanicolaou-stained samples. Slides were examined independently by two pathologists without knowledge of the original diagnosis, and were classified as either positive, inconclusive, or negative for malignant cells. There was diagnostic agreement between both methods in 35 (97%) of 36 samples. Features in cytocentrifuged WG-stained specimens that were most helpful in recognizing HD included mirror image nuclei in typical Reed-Sternberg cells and an axis of symmetry in polylobate Reed-Sternberg variants, with even distribution of the nuclear material within the cytoplasm.
- Published
- 1988
33. Testicular stromal tumor with myofilaments: ultrastructural comparison with normal gonadal stroma.
- Author
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Greco MA, Feiner HD, Theil KS, and Mufarrij AA
- Subjects
- Adult, Humans, Male, Microscopy, Electron, Middle Aged, Testicular Neoplasms pathology, Cytoskeleton ultrastructure, Testicular Neoplasms ultrastructure, Testis ultrastructure
- Abstract
The ultrastructural features of two testicular stromal tumors were compared with those of normal gonadal stroma. The two patients with tumor were 28 and 48 years old and had no endocrine abnormalities. No metastases or recurrences occurred after 32 and 12 months of follow-up, respectively. The tumors were composed of bundles of oval to spindle-shaped cells. Ultrastructurally, intracytoplasmic myofilaments were characteristic of the tumor cells, which resembled the contractile peritubular and interfollicular cells of normal testis and ovary. In normal testicular tissue, an intertubular mesenchymal cell may differentiate into a peritubular contractile cell or into an interstitial (Leydig) cell. Therefore, testicular stromal tumors with myofilaments may originate from an intertubular mesenchymal cell that is capable of differentiating into a cell with contractile elements.
- Published
- 1984
- Full Text
- View/download PDF
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