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E S Jaffe

Publications and source records attributed to E S Jaffe.

At least 325 records · Page 18Linked to original sources
PubMed1983

Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms.

Immunoglobulin genes in their germ-line form are separated DNA subsegments that must be joined by means of recombinations during B-cell development. Individual immunoglobulin-gene rearrangements are specific for a given B cell and its progeny. We show that the detection of such gene rearrangements by Southern hybridization provides a sensitive marker for both clonality and B-cell lineage within lymphoid tissues lacking expression of definitive surface phenotypes. We have used these genetic markers in three ways: to establish a diagnosis of lymphoma in a neoplastic disorder of uncertain cell type, to show that some lymphomas that were previously classified as being of T-cell type in fact contain monoclonal B cells, and to detect clonal B-cell populations within lymphomatous tissues of uncertain immunotype and within an atypical lymphofollicular hyperplasia having no other clonal surface markers. These sensitive and unique indicators of clonality located directly at the DNA level are capable of providing insights into the cellular origin, early detection, and natural history of neoplasia.

B-Lymphocytes↗
PubMed1983

The human T-cell leukemia-lymphoma virus in the southeastern United States.

The human T-cell leukemia-lymphoma virus (HTLV) is a recently described RNA tumor virus associated with human T-cell malignant neoplasms. In two geographic areas, Japan and the Caribbean basin, clusters of adult T-cell leukemia-lymphoma are "sentinel diseases" and have suggested an underlying prevalence of HTLV infection in both family members of the index cases and in the population. Four cases of lymphoma from the United States are described as illustrative of the sentinel disease. Serological studies of families and of a small population sample suggest that HTLV infection is endemic in certain parts of the southeastern United States at rates similar to those seen in Caribbean blacks but at a lower rate than that observed in southwestern Japan.

Adult↗
PubMed1983

Malignant lymphoma and erythrophagocytosis simulating malignant histiocytosis.

Six patients with malignant lymphoma are described, in whom a syndrome that mimicked malignant histiocytosis clinically and pathologically developed as a terminal event. The clinical course was characterized by hepatosplenomegaly, fever, and a rapid fall in all hematologic counts. Survival from onset of this syndrome was less than six weeks. Pathologically, activation of benign histiocytes with marked erythrophagocytosis was seen throughout the reticuloendothelial system. Disseminated lymphoma was also evident but was grossly and microscopically segregated from the erythrophagocytic process. Immunologic and cytochemical studies in two cases indicated the lymphomas to be of peripheral T cell origin, whereas the phagocytic cells had markers characteristic of histiocytes. A likely mechanism for this syndrome is the production of lymphokines (macrophage-activating factors) by neoplastic T lymphocytes.

Adolescent↗
PubMed1983

Rearrangement and expression of immunoglobulin genes and expression of Tac antigen in hairy cell leukemia.

The origin and exact stage of differentiation of the neoplastic cells that comprise hairy cell leukemia have remained uncertain. As Ig heavy and light chain genes must both undergo a DNA rearrangement during B-cell development but rarely do so within other hematopoietic lineages, we examined these genes in this leukemia. The neoplastic cells of all eight cases demonstrated rearranged heavy and light chain genes and, in two cases examined, contained the corresponding mRNA for heavy and light chain Ig. Consistent with this B-cell genotype, all cases displayed cell surface HLA-DR and B-cell-associated antigens. Unexpectedly, all cases demonstrated cell surface Tac antigen, which previously had been restricted predominantly to select T-cell malignancies and activated T cells. Prior studies suggested that the anti-Tac monoclonal antibody recognized a peptide associated with the binding of interleukin 2 (T-cell growth factor) in such T cells. Immunoprecipitation with anti-Tac and NaDodSO4/polyacrylamide gel electrophoresis revealed an antigen on leukemic hairy cells with a Mr of 53,000-57,000, identical in size to the receptor on activated T cells. This apparent biphenotypic status might reflect a transformation-associated expression of the Tac antigen in this leukemia. Alternatively, hairy cell leukemia may be a malignancy of a unique stage of normal B-cell differentiation in which the Tac antigen is expressed.

Antibodies, Monoclonal↗
PubMed1983

Monoclonal antibodies directed against human lymphoid, monocytic, and granulocytic cells: reactivities with other tissues.

Monoclonal antibodies (MAbs) reactive with lymphoid cells are not necessarily specific for lymphoid tissues. Forty MAbs with varying degrees of specificity in lymphoid tissue were tested against a wide battery of nonlymphoid human tissues. Cross-reactivity was identified in 18 of 41 antibodies tested. Based on their reactivities, the MAbs were classified in three groups: (1) antibodies with wide reactivities in normal nonlymphoid tissues, i.e., anti-Leu 4, anti-Leu M1, OKT9, anti-HLA-Dr, anti-Leu M2, Mo-2 (Coulter), anti-Leu 7, BA-1, BA-2, BA-3, J5, and A1G3; (2) antibodies with limited reactivities in nonlymphoid tissues (one or two tissues), i.e., OKT6, anti-Leu 10, Mo-1 (BRL), Mo-2 (BRL); and (3) antibodies without cross reactivities in nonlymphoid tissues, i.e., anti-Leu 1, anti-Leu 2a, anti-Leu 3a, OKT3, OKT10, 3A1, anti-Leu 8, TA-1, Lyt 3, B1, B2, OKMo-1, anti-Leu M3, T200. The reactions can be attributed to the presence of a similar, if not identical, epitope in related or different molecules.

Antibodies, Monoclonal↗
PubMed1983

Lymphocyte subsets in normal human lymphoid tissues.

A series of B, T, natural killer (NK) cell, and monocyte-specific monoclonal antibodies was used to determine the localization of lymphocyte subpopulations in frozen tissue sections of human lymph node, spleen, tonsil, and thymus by means of an immunohistochemical technic. In thymus, most cortical thymocytes reacted with Leu 1, Leu 2a, Leu 3a, Leu 4, Lyt 3, OKT3, and OKT6 antibodies. Except for OKT6, Leu 2a, and Leu 3a, these antibodies also reacted with medullary thymocytes. The majority (70-80%) of medullary thymocytes reacted with Leu 3a and a smaller fraction (20-30%) with Leu 2a antibody. The staining pattern of thymic medulla approximates the staining pattern of peripheral T cells. In peripheral lymphoid tissues, the majority of cells in the paracortical region of lymph node and in the periarteriolar sheath of spleen stained with Leu 1, Leu 4, OKT3, and Lyt 3 antibodies. Staining with Leu 3a and Leu 2a identified 60-80% and 20-40% of total T cells, respectively, as defined by Lyt 3 positivity. In addition, a substantial number of Leu 3a+ and Leu 7+ cells were found in the germinal centers of secondary follicles. This finding supports the importance of these subsets of lymphocytes in regulation of the human immune response. Leu 2a+ cells were rare in tissues with prominent follicular hyperplasia, but appeared in considerable number in the red pulp of spleen. In the mantle zone of lymphoid follicles, the majority of lymphocytes were positive for IgM, IgD, and B1. Approximately 60-70% of these cells bore kappa chain and 30-40% lambda chain immunoglobulin. The extracellular substance in germinal centers was positive for B1, IgG, IgM, kappa, and lambda. The majority of germinal center cells appeared to contain no surface or cytoplasmic immunoglobulins. Small mononuclear cells bearing OKM1 marker were abundant in the marginal zone of white pulp and in the red pulp of spleen but, rarely were observed in other portions of lymphoid tissues. OKM1 also reacted with granulocytes. Leu 7+ (NK) cells were rare in the thymus, but frequent in the GC of secondary follicles. The distribution of Leu 7+ cells did not correspond to staining with Lyt 3 and Leu 2a.

Antibodies, Monoclonal↗
PubMed1983

Utility of monoclonal antibodies directed against B and T lymphocytes and monocytes in paraffin-embedded sections.

Monoclonal antibodies reactive with B and T lymphocytes, monocytes, and granulocytes were applied to B-5-, Bouin's-, or formalin-fixed paraffin-embedded sections. Most antigens were destroyed or masked by fixation or embedding procedures, or both. However, T200, an antigen present in all lymphoid and hematopoietic cells, and Leu M1, an antigen in granulocytes, were well preserved in formalin-fixed tissues. Leu 1 and BA-1, antigens present on T and B lymphocytes, respectively, were preserved in Bouin's-fixed specimens. With careful selection of fixatives, identification of some T and B lymphocytes and granulocytes by monoclonal antibodies in paraffin-embedded specimens is possible.

Animals↗
PubMed1983

Hairy cell leukemia: a B cell neoplasm with a unique antigenic phenotype.

A panel of B, T, and monocyte antibodies was used to study the phenotype of hairy cell leukemia. It was found that the neoplastic cells had monoclonal surface immunoglobulins and, in addition, reacted with B1, HLA-DR, Leu 10, and Tac. Most of the above markers are features of B cell lymphocytes. However, Tac is a monoclonal antibody normally reactive with activated T lymphocytes. All other antibodies reactive with T cells were negative. An additional unexpected finding was intranuclear reactivity in 4/5 cases with an antibody to TdT. TdT enzymatic activity was not demonstrable by biochemical assay. All five cases were nonreactive with monocyte antibodies. The findings support the concept that hairy cell leukemia is of B cell lineage but demonstrates an unusual phenotype not seen in other normal or neoplastic B lymphocytes.

Adult↗
PubMed1983

A comparison of ABC, unlabeled antibody and conjugated immunohistochemical methods with monoclonal and polyclonal antibodies--an examination of germinal center of tonsils.

Staining of lymphoid tissues with anti-immunoglobulin antibodies often is complicated by heavy interstitial staining and potential unwanted binding through Fc receptors. This problem is aggravated in the germinal center because of an unusually intense extracellular staining. In an attempt to examine a variety of staining methods, we found both poly- or monoclonal antibodies produced satisfactory results only if a suitable method was employed, such as a two-step or three-step avidinbiotin-peroxidase complex (ABC) method. Other staining technics for example, indirect conjugate or four-layer PAP methods, failed to provide a clean background. The use of F(ab')2 fragments did not significantly improve the staining quality, indicating that the role of the Fc receptors in inducing nonspecific staining is not significant in acetone-fixed frozen tissues. Germinal centers also were studied with a panel of monoclonal and polyclonal anti-Ig antibodies, and the results indicated that the number of surface or cytoplasmic Ig-positive cells in the germinal center is variable from one follicle to another. IgG+ cells are generally sparse (less than 10%) and are scattered in the light zone of follicles. IgA+ cells constitute about 0-10% of the total cell population and tend to be distributed randomly either in the dark or light zones. IgM+ and IgD+ cells may be scanty (less than 10%) or abundant (50-70%). The IgM+ and IgD+ cells tend to localize in the dark zone of the follicles. The results indicate that, depending on the stage of differentiation or transformation of the germinal center, s-Ig or c-Ig expression is highly variable.

Animals↗
PubMed1983

Terminal deoxynucleotidyl transferase in non-Hodgkin's lymphoma.

To investigate the specificity of terminal deoxynucleotidyl transferase (TdT) as a marker for lymphoblastic lymphoma in the non-Hodgkin's lymphomas, the authors assayed malignant cells from 142 patients with non-Hodgkin's malignant lymphoma, as well as cells from normal lymphoid tissue controls. Neoplastic cells from all 25 patients with lymphoblastic lymphoma were TdT positive. Of the remaining 117 patients with malignant lymphoma of other histologic subtypes, only one patient, with diffuse, large cell immunoblastic lymphoma, had TdT-positive cells. This patient's cells had positive results only by the enzyme assay and were TdT-negative by both immunofluorescence and immunoperoxidase assays. Of 56 patients whose cells were studied by both enzyme assay and an immunoassay method for TdT detection, a discordant result was obtained only on cells from the previously mentioned patient with large cell immunoblastic lymphoma. To determine the optimal immunoassay method, the authors studied malignant cells from 24 patients with non-Hodgkin's lymphoma for the presence of TdT by three different methods: immunofluorescence, peroxidase-antiperoxidase, and avidin-biotin-complex immunoperoxidase. Fifteen of the 24 patients had lymphoblastic lymphoma. The avidin-biotin-complex method produced superior staining, with no false-negative results. False-negative results were seen with both the immunofluorescence and peroxidase-antiperoxidase methods. Other advantages of the avidin-biotin-complex method included a marked decrease in background and non-specific staining and the ability to use higher dilutions of antisera.

Clinical Enzyme Tests↗
PubMed1983

Epidemiology of human T-cell leukemia/lymphoma virus.

Human T (thymus-derived)-cell leukemia/lymphoma virus (HTLV) is the first retrovirus consistently isolated from humans. Seroepidemiologic testing for antibodies to HTLV document the following. (1) HTLV is associated with a spectrum of mature T-cell lymphoreticular neoplasms. (2) HTLV is strongly associated with clusters of adult T-cell leukemia in Japan and a related syndrome, lymphosarcoma T-cell leukemia in the Caribbean. (3) Virus-positive infections from other areas of the world share similar clinicopathologic features, with some overlap with cutaneous T-cell lymphoma (CTCL). Antibodies to HTLV are lacking in most persons with CTCL. (4) Virus-associated malignancy clusters in geographic areas where HTLV infection is prevalent, and virus positivity varies by country, region within country, age, and possibly race and sex. Although preliminary, the epidemiologic data suggest that HTLV is etiologically linked to a specific subtype of mature T-cell malignancy.

Adult↗
PubMed1983

The human T-cell leukemia/lymphoma virus, lymphoma, lytic bone lesions, and hypercalcemia.

The human T-cell lymphoma (HTL) virus is a type C RNA tumor virus isolated from patients with malignancies of mature T cells. We report three patients with peripheral T-cell lymphoma, hypercalcemia, and antibodies to HTL virus. One patient presented with idiopathic hypercalcemia of 6 months' duration, two with striking lytic bone lesions, and two with circulating malignant lymphocytes. Malignant cells from all patients had surface markers characteristic of thymic-derived lymphocytes (T cells), and all patients had natural serum antibodies to disrupted HTL virus and to one or both viral structural proteins p19 and p24. Patients with adult peripheral T-cell lymphomas, particularly those that present with hypercalcemia and lytic bone lesions, may have antibodies to the type C RNA human tumor virus, HTL virus.

Adult↗
PubMed1983

Diversity of immunological phenotypes of lymphoblastic lymphoma.

Eleven cases of lymphoblastic malignancy, presenting as lymphoma, were investigated for immunological and differentiation markers prior to the onset of therapy. Biopsy specimens exhibited the typical morphological features of lymphoblastic lymphoma (convoluted T-cell lymphoma). Intranuclear terminal deoxynucleotidyl transferase was detected in the neoplastic cells from each case by indirect antibody staining of cytocentrifuge preparations. Eight cases were T-cell type as evidenced by unsensitized sheep erythrocyte rosette formation and staining with the monoclonal antibody OKT11. Three T-cell cases were OKT4 positive, two were OKT8 positive, and none were positive with both OKT4 and OKT8. Three cases failed to react with any monoclonal antibodies specific for T-cells and did not form unsensitized sheep erythrocyte rosettes or stain for surface immunoglobulin. However, these three cases were Ia positive and J5 (common acute lymphoblastic leukemia antigen) positive. Cells from two of these erythrocyte rosette-negative, Ia-positive, common acute lymphoblastic leukemia-positive cases contained intracytoplasmic mu heavy chains and were therefore of pre-B-cell phenotype. These cases were histologically indistinguishable from the T-cell cases. However, clinically, they were distinguished by the absence of mediastinal masses and by a clinical presentation as isolated lytic lesions of bone in two of the three. OKT9 and OKT10 stained neoplastic cells from T-cell, as well as pre-B-lymphoblastic, lymphoma. Although morphologically homogeneous, lymphoblastic lymphomas are comprised of an immunologically diverse group of neoplasms which include cells of "common" and "mature" thymocyte, non-T, non-B, and pre-B phenotypes and are closely related to the cells of acute lymphoblastic leukemia. In addition, intratumor heterogeneity was observed in most instances and may reflect growth or differentiation differences between subpopulations of individual neoplastic clones.

Adolescent↗
PubMed1983

The human T-cell leukemia/lymphoma virus associated with American adult T-cell leukemia/lymphoma.

The human T-cell leukemia/lymphoma virus (HTLV) is a novel type-C retrovirus isolated from patients with T-lymphoproliferative malignancies. Thirteen cases of HTLV-associated malignancy from US centers were studied in detail. Ten of these cases share common clinical features and define a typical virus-associated adult T-cell leukemia/lymphoma (ATL). All ten patients presented with Ann Arbor stage IV lymphoma because of skin involvement, bone marrow involvement, or lymphomatous leptomeningitis. Lymphadenopathy occurred in 7 of 10 patients at presentation, and the malignant cells were cytologically pleomorphic. Leukemia occurred in 60% of the patients at presentation. Hypercalcemia was found initially in two-thirds of the patients, with lytic bone lesions or positive bone scans in 7 of 10. Complete remission occurred in 40%, but all have relapsed. These cases closely resemble those virus-positive cases of adult T-cell leukemia/lymphoma (ATL) reported from Japan and the Caribbean. Three additional virus-positive patients had atypical presentations and diagnoses (acute lymphocytic leukemia, Sézary's syndrome, leukemic reticuloendotheliosis), usually with less aggressive clinical courses and atypical demographic and laboratory features. Presence of HTLV serum antibodies in cases of ATL (with hypercalcemia and circulating malignant cells) appears to define a distinct clinicopathologic entity that may occur in geographic clusters.

Adult↗
PubMed1982

Predictability of immunologic phenotype by morphologic criteria in diffuse aggressive non-Hodgkin's lymphomas.

Diffuse aggressive non-Hodgkin's lymphomas are immunologically and morphologically heterogeneous. Morphologic subclassifications have been proposed with a presumptive relationship to immunologic phenotype. Six histologic types were studied, four of presumed follicular origin (large cleaved, large non-cleaved, mixed follicular center cell, and blastic) and two of presumed nonfollicular origin (pleomorphic pyroninophilic and pleomorphic convoluted). Two of these follicular subtypes were found to be associated with the frequent presence of B-cell markers; large non-cleaved, six of seven; and blastic, four of six. However, four of nine T-cell lymphomas were misclassified as lesions of follicular center cell type, indicating the difficulty of distinguishing some convoluted cells of T-cell lymphoma from irregularly cleaved cells of follicular lymphoma. Pleomorphic pyroninophilic or B-immunoblastic morphology was associated with B-cell markers in only two of six cases; two additional cases had T-cell markers, one had histiocytic markers and in one case, no markers were demonstrable. Thus, this morphology may reflect a common pathway of transformed lymphoid cells. Some cases of T-cell origin could be recognized by the striking pleomorphic convoluted histology (three of five cases) but morphologic overlap with pleomorphic B-cell tumors, particularly transformed nodular lymphomas, posed a problem. This histopathologic subclassification correctly predicted immunologic phenotype in only 61% of cases, suggesting that in diffuse non-Hodgkin's lymphomas, histologic appearance alone may not be a reliable indicator of immunologic surface markers.

Adult↗