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H Ratech

Publications and source records attributed to H Ratech.

At least 37 records · Page 2Linked to original sources
PubMed1993

Genotypic divergence precedes clinical dissemination in a case of synchronous bilateral B-cell malignant lymphoma of the testes.

Malignant lymphoma of the testis occurs bilaterally more often than any other tumor type. We report the case of a 62-year-old man who presented with synchronous, bilateral, testicular malignant lymphomas without clinical or radiologic evidence of extratesticular disease. The patient received no therapy other than bilateral orchiectomy and subsequently developed widespread disease 6 months later. Southern blot DNA analysis was performed on the initial orchiectomy samples for immunoglobulin (Ig) gene rearrangements. These genotypic analyses showed different clonal rearrangements in the Ig heavy chain JH region but identical clonal rearrangements in the Ig light chain C Kappa region. To our knowledge this is the first genotypic demonstration of a common clonal origin in synchronous, bilateral, testicular malignant lymphomas. We interpret these findings as molecular evidence that the patient's malignant lymphoma was already disseminated at initial presentation, although it was clinically undetectable at that time.

Antigens, CD↗
PubMed1993

Sensitive detection of clonal antigen receptor gene rearrangements in non-Hodgkin's malignant lymphoma with an anchored polymerase chain reaction-based strategy.

The identification of minimal residual disease (MRD) in non-Hodgkin's malignant lymphoma is of immediate clinical relevance. Although several polymerase chain reaction (PCR)-based strategies are currently available, they all share serious technical or theoretic limitations with respect to their ability to detect the broad spectrum of mature B-cell neoplasia. We report a new strategy based on anchored PCR that does not rely on a particular chromosomal translocation or VH consensus sequence. It can yield the complete DNA sequence of the immunoglobulin heavy chain variable region (VHDJH). The assay is capable of detecting one neoplastic cell among 10(3)-10(4) normal cells with high specificity and has the potential to greatly expand the variety of B-cell malignant neoplasms that can be studied.

Amino Acid Sequence↗
PubMed1992

Rapid cloning of rearranged immunoglobulin heavy chain genes from human B-cell lines using anchored polymerase chain reaction.

A general method to obtain the variable region DNA sequence of the immunoglobulin heavy chain using anchored polymerase chain reaction is described. Based on this DNA sequence, clone-specific oligonucleotides were designed to anneal to the complementarity determining regions. These were used to identify the original B-cell clone in serial dilutions of polyclonal lymph node DNA with high specificity and sensitivity. This method should be useful for studying minimal residual disease in B-cell neoplasia.

Amino Acid Sequence↗
PubMed1990

Small malignant melanomas: clinicopathologic correlation and DNA ploidy analysis.

Among the various clinical and histologic criteria used to differentiate between benign and malignant melanocytic neoplasms, emphasis has been placed on the size of the lesion. Malignant melanomas, when diagnosed, are usually larger than 6 mm in diameter whereas most acquired melanocytic nevi tend to be smaller. We tested this size criterion with a retrospective clinicopathologic study of 30 proliferations of atypical melanocytes within the epidermis and dermis that measured less than 6 mm in diameter. Nineteen cases fulfilled all 15 established histologic criteria for the diagnosis of malignant melanoma. The remaining 11 cases fulfilled 14 of 15 criteria. Four of eight of these small malignant melanomas analyzed by multiparameter flow cytometry were aneuploid (DNA ploidy index less than or equal to 0.9 or greater than or equal to 1.1). The sex ratio, race, and anatomic sites associated with these small melanomas were similar to those described in patients with malignant melanomas larger than 6 mm in diameter. Furthermore, one melanoma metastasized to a regional lymph node and another recurred. We conclude that small malignant melanomas less than 6 mm in diameter can have histologic features, DNA abnormalities, clinical presentations, and biologic potentials similar to larger lesions.

Adult↗
PubMed1990

HLA-DR expression in B-cell non-Hodgkin's malignant lymphomas: a multiparameter flow cytometry study.

Ten cases of reactive follicular hyperplasia and 31 cases of B-cell non-Hodgkin's malignant lymphoma were studied using multiparameter flow cytometry. A bimodal distribution for HLA-DR expression, but not for surface immunoglobulin or B cell-specific antigens CD19 and CD20, was observed commonly in mixed cell type and infrequently in non-mixed cell type B-cell malignant lymphomas. On the basis of HLA-DR distribution alone, 31 cases of B-cell malignant lymphomas of low, intermediate, and high grades could be separated into mixed and non-mixed cell types, with only two misclassifications (P = 0.0001). Exceptionally, one case of malignant lymphoma, follicular and diffuse, mixed-cell type had a unimodal HLA-DR distribution, and one case of malignant lymphoma, diffuse, large noncleaved cell type had a bimodal HLA-DR distribution. In all cases of malignant lymphoma, follicular, mixed-cell type studied, low HLA-DR was correlated with small cells, and high HLA-DR was correlated with large cells. In contrast, HLA-DR expression and cell size were not as directly correlated in cases of malignant lymphoma, diffuse, mixed-cell type. These observations suggest that most, but not all, cases of B-cell malignant lymphomas of the mixed cell type can be separated from other B-cell lymphomas on the basis of HLA-DR distribution.

Adolescent↗
PubMed1989

A clinicopathologic study of malignant lymphomas of the nose, paranasal sinuses, and hard palate, including cases of lethal midline granuloma.

Malignant lymphomas of the nose, paranasal sinuses, and hard palate show marked clinicopathologic, immunologic, and prognostic diversity. The clinical features and pathologic spectrum of these lesions were studied in 20 cases (11 female and 9 male cases) with a mean age of 51 years at initial presentation. Malignant lymphomas of the large cell type were most frequently encountered (11/20). The next largest category was malignant lymphoma, diffuse, mixed small and large cell type (six of 20). Two thirds, 13 of 20 cases, had morphologic features suggestive of peripheral T-cell lymphomas. Necrosis, an angiocentric growth pattern, and epitheliotropism were found in nine, eight, and three cases, respectively. Of ten cases immunophenotyped on fresh-frozen or fixed, paraffin-embedded tissue sections, eight had a T-cell phenotype and two had a B-cell phenotype. Of 17 patients with sufficient follow-up data, ten are alive (median follow-up 33 months) and seven are dead (median survival 12 months). Patients with clinical Stages IE and IIE did not have a superior 5-year survival to those with more advanced disease. Histologic type also did not correlate with survival but this may be due to the aggressive histologic grade of the majority of cases and the retrospective nature of this study. The authors conclude that, despite the overall high-grade histologic type, the pathologic spectrum of malignant lymphomas involving this anatomic region is broad. Furthermore, some cases do not fit well into the National Cancer Institute (NCI) Working Formulation but more closely resemble the histologic features of peripheral T-cell lymphomas described in Japan.

Adult↗
PubMed1989

Surface immunoglobulin light chain restriction in B-cell non-Hodgkin's malignant lymphomas.

Twenty-four control cases of reactive follicular hyperplasia (RFH) and 28 cases of B-cell non-Hodgkin's malignant lymphoma (ML) were evaluated for surface immunoglobulin (sIg) light chain expression with flow cytometry. Because there was no significant difference between the distribution of the ML kappa/lambda ratios for which kappa/lambda greater than 1 compared with those ML lambda/kappa ratios for which lambda/kappa greater than 1 using the Kolmogorov-Smirnov statistic, the authors treated kappa/lambda and lambda/kappa data symmetrically. By transforming all kappa/lambda ratios to maximum ratios, that is, Rmax = max (kappa/lambda, lambda/kappa), so that all resulting ratios were at least one, the authors defined a new statistic for evaluating sIg light chain restriction. There was a highly significant difference for equality of distribution of the data using the Mann-Whitney test (P less than 0.0001). By choosing cut-points based on the Rmax statistic, the authors were able to separate the RFH and ML cases with sensitivity = 0.96 +/- 0.07 (95% confidence) and with specificity = 0.91 +/- 0.11 (95% confidence). These point estimates of sensitivity and specificity appear to be promising for the clinical utility of the Rmax statistic, even for cases of B-cell ML with discordantly low expression of sIg light chains. The Rmax statistic will facilitate the comparison of data between different laboratories because it does not require prior assignment of cut-points and can be made using a simple nonparametric test.

Adolescent↗
PubMed1989

Pathologic findings in adenosine deaminase deficient-severe combined immunodeficiency. II. Thymus, spleen, lymph node, and gastrointestinal tract lymphoid tissue alterations.

Eight autopsies of patients with adenosine deaminase deficient-severe combined immunodeficiency disease (ADA-SCID) were reviewed with special emphasis on the lymphoid tissues. The thymus histology in five cases was remarkably uniform, whether or not prior ADA enzyme replacement or immunologic reconstitution therapy had been administered. Lymph nodes and spleens in all cases examined showed a residual nonlymphoid architectural framework corresponding to usual T and B cell zones found in normals. The development of an extranodal, monoclonal IgA lambda B cell immunoblastic lymphoma as a terminal event in one patient after several years of successful ADA enzyme replacement therapy through multiple red blood cell transfusions is described. In another patient with long-term ADA enzyme replacement, a terminal autoimmune hemolytic anemia developed. Autopsy revealed severe deposits of iron in the B cell zones of the lymph nodes, which is an unusual location. In addition, iron deposits outlined the splenic trabeculae, as well as the ring fibers and bridging fibers of the splenic sinuses.

Adenosine Deaminase↗
PubMed1989

Improved detection of aneuploidy in malignant melanoma using multiparameter flow cytometry for S100 protein and DNA content.

DNA aneuploidy has been demonstrated to be an independent parameter of prognostic significance in malignant melanomas. In order to improve the detection of DNA aneuploidy in malignant melanomas, and to minimize diploid non-tumor cells in the sample, we developed a two-color staining strategy for S100 protein and DNA content in paraffin embedded samples. The ability to detect aneuploidy, defined as DNA ploidy index less than or equal to 0.90 or greater than or equal to 1.10, in 37 stage I malignant melanoma samples by flow cytometry analysis was significantly improved from 10.8% of cases using traditional one-color analysis for DNA content only (propidium iodide) to 32.4% of cases using two-color analysis for simultaneous measurement of both DNA (propidium iodide) and S100 protein (fluorescein conjugated antibody) (Chi-square with Yates' correction; p less than 0.05). The largest increase in sensitivity was found in level I and II melanomas less than or equal to 0.76 mm in thickness. In addition, we report the new observation that multiple S100 protein-positive subpopulations were found significantly more frequently in malignant melanomas (23/37 cases) than in compound melanocytic nevi (5/22 cases) (Chi-square with Yates' correction; p less than 0.01). These findings suggest that there is a previously unsuspected degree of tumor heterogeneity even in thin, presumably early, malignant melanomas.

Aneuploidy↗
PubMed1988

Immunoarchitecture of the "pseudofollicles" of well-differentiated (small) lymphocytic lymphoma: a comparison with true follicles.

Some human malignant lymphomas of the B-cell type have morphologic and immunologic similarities to follicles seen in nonneoplastic reactive lymph nodes. In contrast, a peculiar, vaguely nodular pattern of growth called "pseudonodules" or "pseudofollicular proliferation centers," which is morphologically distinguishable from "true" follicles, is seen in malignant lymphoma, well-differentiated (small) lymphocytic type (WDL). To characterize the cellular components of "pseudofollicles," we undertook a detailed, comparative immunohistologic study of the architectural relationship and distribution of T cells, B cells, and follicular dendritic reticulum cells (DRCs) in reactive follicles, neoplastic follicles, and pseudofollicles. We report several observations on the presence of DRCs and T-cell subset topography in pseudofollicles. Immunohistologic staining for the C3d complement receptor on DRCs revealed that DRC networks associated with "true" follicles were present in all cases of reactive follicular hyperplasia (RFH) and malignant lymphoma, nodular, poorly differentiated lymphocytic type (PDL) studied. Surprisingly, DRC networks were also identified in 8 of 23 cases of WDL. Although the size distribution of DRC network diameters was nearly identical in RFH and PDL, the sizes were markedly diminished in WDL. Immunohistologic staining for Leu 3+ and Leu 2+ T-cell subsets confirmed cellular arrangements in RFH and PDL reported by others. In only 2 of 23 cases of WDL could T cells localized to "pseudofollicles" in frozen tissue sections be identified in a nonrandom arrangement.

Adolescent↗
PubMed1988

Extranodal non-T-cell lymphoblastic lymphoma in adults. A report of two cases.

Typical adult cases of malignant lymphoma, diffuse, lymphoblastic type (MLLB), are of the T-cell immunophenotype and occur as mediastinal masses. The authors report two unusual adult cases with initial extranodal sites of involvement and non-T-cell immunophenotype that were originally misclassified. One patient presented with a right submaxillary salivary gland mass and the other presented with a T7-8 spinal cord compression resulting from a vertebral body tumor. A lymphoblastic leukemic phase developed in both patients after 15 months and 5 months, respectively. The bone marrow blasts of both patients had positive results for cluster designation (CD) 10, CD19, HLA-DR, and terminal deoxynucleotidyl transferase. Because both extranodal sites of presentation and non-T-cell immunophenotype are unusual in adult MLLB, these features may have contributed to the original misclassification of these lesions.

Adult↗
PubMed1988

Differential expression of adenosine deaminase isozymes in acute leukemia.

Total adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities were measured in cell samples from 13 cases of de novo acute leukemia and from three cases of chronic myeloid leukemia in blast crisis (CMLBC). These cases could be separated into lymphoid and nonlymphoid types on the basis of enzyme activity, with two misclassifications. However, PNP activity added little or no discriminatory information. Analysis for expression of the various molecular weight (mol wt) ADA isozymes, ADA1 (40 Kd) and ADA2 (110 Kd), revealed that ADA2 was expressed exclusively in nonlymphoid cells whereas ADA1 was found in both lymphoid and nonlymphoid cell types. Identification of ADA2 divided these leukemia cases into lymphoid and nonlymphoid types with no misclassifications (P = .0002; Fisher's exact test). Acute nonlymphoblastic leukemia (ANLL) with a monocytic component tended to have a greater percentage of ADA2 than ANLL without a monocytic component. These studies suggest that ADA2 may be a novel biochemical marker for an immature nonlymphoid cell.

Adenosine Deaminase↗
PubMed1987

Epstein-Barr-virus-related malignant B cell lymphoplasmacytic lymphoma following allogeneic bone marrow transplantation for aplastic anemia.

The development of B cell lymphoma has been reported to occur in recipients of a variety of organ transplants, including some patients who have received an allogeneic bone marrow graft. In this report, we describe a patient with severe aplastic anemia who developed a malignant B cell lymphoplasmacytoid proliferation 48 days after undergoing allogeneic marrow transplantation from her HLA-matched MLC-nonreactive brother. Immunologic studies showed this malignancy to be a mixed polyclonal and monoclonal proliferation in donor cells. Virologic studies documented Epstein Barr infection of the cells. A review of the literature suggests that graft-versus-host disease and treatment of this complication by antithymocyte globulin are related to the development of the EBV-related malignancy in the EBV-infected B cells of the developing bone marrow graft.

Adult↗
PubMed1985

Enzymatic differences between chronic lymphocytic leukemia and prolymphocytic leukemia.

Chronic lymphocytic leukemia and prolymphocytic leukemia of the B-cell immunophenotype are closely related disorders, but differ in their cytomorphologic and clinical features. In an attempt to differentiate further between these two forms of leukemia, we measured adenosine deaminase and purine nucleoside phosphorylase activities by using a linked-enzyme spectrophotometric assay on peripheral-blood leukemic cells from seven patients with chronic lymphocytic leukemia, three patients with prolymphocytic leukemia, and one patient with prolymphocytoid transformation of chronic lymphocytic leukemia. By using discriminant analysis, we were able to distinguish the two groups only on the basis of purine nucleoside phosphorylase activity (F1,9; p less than 0.001). The purine nucleoside phosphorylase activity in leukemic cells with prolymphocytic cytomorphology was significantly elevated (mean = 58.6 nM/min/mg protein) compared to the activity in leukemic cells with lymphocytic cytomorphology (mean = 25.6 nM/min/mg protein). There was only one patient with chronic lymphocytic leukemia who was assigned to the prolymphocytic leukemia group on the basis of her purine nucleoside phosphorylase activity. Our study suggests that purine nucleoside phosphorylase activity in leukemic cells may be useful in the distinction of prolymphocytic leukemia from chronic lymphocytic leukemia, and that it may be an enzymatic marker for the early detection of prolymphocytoid transformation of chronic lymphocytic leukemia.

Adenosine Deaminase↗
PubMed1985

Effects of deoxycoformycin in mice. III. A murine model reproducing multi-system pathology of human adenosine deaminase deficiency.

Adult AKR/J mice were treated with 10 micrograms/g or 100 micrograms/g 2'-deoxycoformycin, an adenosine deaminase inhibitor with chemotherapeutic potential. The thymus and adrenal glands were decreased in weight more than any other organ. Histologic and cytofluorographic analyses indicated preferential depletion of peanut-agglutinin-positive, cortical thymocytes, as well as acute, dose-dependent damage to the adrenal cortex and medulla. The effect of 2'-deoxycoformycin on the thymus was proven to be independent of the adrenal glands by use of adrenalectomized mice. Dose-dependent liver necrosis, hemolysis, and leukemoid reactivity were observed. These findings illustrate a differential sensitivity of thymocyte subpopulations and suggest, in addition, preferential sensitivity of certain nonlymphoid tissues to 2'-deoxycoformycin administered in vivo.

Adenosine Deaminase↗
PubMed1985

Pathologic findings in adenosine deaminase-deficient severe combined immunodeficiency. I. Kidney, adrenal, and chondro-osseous tissue alterations.

The authors have reviewed the autopsies of 8 patients with adenosine-deaminase-deficient severe combined immunodeficiency disease (ADA-SCID). Several new findings in nonlymphoid organs, including kidney and adrenal gland, and chondro-osseous tissue indicate the multisystem nature of this disorder. Examination of renal tissue in 7 of 8 cases showed mesangial sclerosis. This was confirmed in 3 cases by electron microscopy. One case, treated with multiple erythrocyte partial exchange transfusions for several years, had no mesangial sclerosis. Six of 8 cases showed adrenal-gland cortical sclerosis. Chondro-osseous tissue from vertebrae and costochondral junctions of 4 cases examined showed typical alterations previously reported in ADA-SCID such as short growth plates with few proliferating and some hypertrophic chondrocytes. The authors report the new observations of necrotic chondrocytes, as well as large amounts of cellular debris. These changes were not observed in the 2 other patients examined, who received bone marrow or multiple partial exchange transfusions. The distribution and severity of these lesions, their relationship to ADA replacement therapy, and their homology to mice treated with a potent ADA inhibitor suggests that, in addition to lymphoid dysfunction, disordered nucleoside metabolism due to absent ADA activity in ADA-SCID may be the cause of diverse multi-system pathologic changes in tissues which continue to differentiate or mature after birth.

Adenosine Deaminase↗
PubMed1984

Effects of deoxycoformycin in mice. II. Differences between the drug sensitivities and purine metabolizing enzymes of transplantable lymphomas of varying immunologic phenotypes.

Transplantable BALB/c and AKR lymphomas of different cell surface immunologic phenotypes have distinctive patterns of response to the ADA inhibitor DCF in vivo and in vitro. BAL 9, a lymphoma of the Lyt-1+,2+ T cell phenotype, was the most sensitive to DCF in vivo, and its DNA synthesis was inhibited more than 95% when cultured in the presence of dAr and DCF in vitro. This was correlated with a 10-fold increase in dATP content. The ADA and AMPDA activities were both high. Two lymphomas of the Lyt-1-,2+ T cell phenotype, BAL 5 and AKTB - lt , as well as two B cell phenotype lymphomas, A20 .3 and AKTB -lb, were all moderately inhibited in their in vivo growth if enough DCF was administered. However, their DNA synthesis in vitro was only inhibited 8 to 24% by dAr and DCF, there was only a twofold increase in the accumulation of dATP, and ADA and AMPDA activities were both low in the two BALB/c lymphomas tested. BAL 13, the only lymphoma of the Lyt-1+,2- phenotype examined, was completely resistant to DCF in vivo and in vitro. When cultured in the presence of dAr and DCF there was a transient increase in dATP content, followed by an abrupt decline. AMPDA activity was five to seven times greater than in the other lymphomas tested. ADA activity was moderate. The activities of 5' nucleotidase and of adenosine kinase were low and approximately equal in all the BALB/c lymphomas. These results suggest that the response to DCF by lymphomas of various immunologic phenotypes can be correlated with their nucleoside metabolism. The sensitivity of BAL 9 and the resistance of BAL 13 to DCF are correlated with their tendency to accumulate dATP and with their AMPDA and ADA activity ratios. The moderate sensitivity to DCF in vivo of the other T and B cell lymphomas, however, could not be clearly explained by any of the in vitro parameters thus far investigated, and this suggests that mechanisms inhibiting lymphoma proliferation other than dATP accumulation may be operating.

Adenosine Deaminase↗