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Biomedical subjects

E S Jaffe

Publications and source records attributed to E S Jaffe.

At least 307 records · Page 17Linked to original sources

Phenotypic expression of T lymphocytes in thymus and peripheral lymphoid tissues.

The pattern of expression of cell surface antigens and their relationship to the sequence of T-cell differentiation were delineated by the application of a series of monoclonal antibodies against T cells on tissue sections. The morphologic features and location of T-cell differentiation can be categorized into four stages: 1) subcapsular thymocytes, 2) cortical thymocytes, 3) medullary thymocytes, and 4) peripheral T cells. Phenotypically, on the basis of reactivity with monoclonal antibodies, T cells could be separated into two groups: immature and mature T cells. All stages of T cells expressed T200, Lyt 3, Leu 1, OKT3, Leu 9, and TA1, although staining intensities varied between thymic cortex and medulla. Mature T cells (medullary thymocytes and peripheral T cells) stained more intensely than immature T cells for some antigens, such as Leu 1, OKT3, and Leu 9, and, therefore, probably have a greater antigen density. Immature T cells, exemplified by subcapsular and cortical thymocytes, were characterized by the expression of Tdt, Leu M3, OKT6, OKT9, J5, BA-2, OKT10, and usually coexpressed both helper (T4/Leu 3a) and suppressor (T8/Leu 2a) antigens. With further maturation, medullary thymocytes and peripheral T cells lost reactivity for the above-mentioned markers, acquired A1G3 and Leu 8, and segregated into either T4+/Leu 3a+ or T8+/Leu 2a+ cells. A subpopulation of T cells in germinal centers differs from the majority of peripheral T cells by virtue of an absence of expression of Leu 8/A1G3. This histologically localized subset of T cells may be responsible for the mediation of helper function within the germinal center.

Animals↗

Phenotypic expression of Hodgkin's and Reed-Sternberg cells in Hodgkin's disease.

The phenotypic expression of Hodgkin's and Reed-Sternberg (H-RS) cells was determined by analysis with a panel of monoclonal antibodies and peanut agglutinin (PNA) by an immunohistochemical technique. Seven antibodies, including T200, anti-HLA-DR, anti-Leu 10, A1G3, anti-Tac, OKT9, and anti-Leu M1, were found to react with a great majority of H-RS cells. In some cases, H-RS cells also bound PNA. Other antibodies, including those highly specific for T cells (eg, Lyt 3) and B cells (eg, B1, anti-Leu 14) were consistently negative. The results argue against the derivation of H-RS cells from T or B lymphocytes. The H-RS cells were also negatively stained with antibodies which react with monocytes (OKM1, Mo-2, 63D-3), follicular dendritic cells (DRC-1), and natural killer/killer cells (Leu 7, Leu 11a, B73.1). The presence of Leu M1 and Tac in H-RS cells is of interest. Anti-Leu M1 positivity was seen in all 20 of Hodgkin's disease (HD) cases tested and should provide a very useful reagent for differential diagnosis of HD from other reactive and neoplastic conditions. Tac normally is present only on activated T cells. The presence of Tac in H-RS cells may reflect expression of T-cell growth factor receptor or a closely related protein during a stage of neoplastic transformation. Although the nature of the neoplastic cell of HD cannot be determined by these studies, they are consistent with an origin from interdigitating reticulum cells. Both H-RS cells and interdigitating reticulum cells have a similar antigenic phenotype (Leu M1+, T200+, HLA-DR+, Leu 10+, A1G3+, and OKT9+) and a similar pattern of lysosomal enzyme activity.

Antibodies, Monoclonal↗

Immunologic phenotypes of diffuse, aggressive, non-Hodgkin's lymphomas. Correlation with clinical features.

The immunologic phenotypes of 59 cases of diffuse, aggressive, non-Hodgkin's lymphomas were determined using a battery of immunologic and cytochemical techniques. Included were cases of diffuse, large cell "histiocytic," mixed cell, undifferentiated non-Burkitt's. Burkitt's lymphoma, lymphoblastic lymphoma, and mycosis fungoides/Sézary's syndrome were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunologic phenotypes. The immunotype could be determined in 57/59 (97%) cases tested: 31 of 59 cases (53%) were B-cell type, 25 of 59 (42%) were peripheral T-cell type, and one was true histiocytic. Two cases had no detectable markers and were called "null cell." This relatively high frequency of peripheral T-cell lymphomas in an American series previously has not been observed and may be a result of progressive improvements in immunologic techniques. Monoclonal anti-T cell antibody staining was performed in 11 T-cell cases and corroborated the findings using spontaneous E-rosette formation. Eight of the T-cell lymphomas had a helper cell phenotype whereas one had a suppressor cell phenotype and two could not be subclassified. All B-cell lymphomas in this series possessed monoclonal surface immunoglobulin detected by direct immunofluorescence of viable cells. Enzyme cytochemistry profiles only partially correlated with immunotype and were not believed to be helpful in the determination of specific phenotypes. There were no significant differences between the B-cell and T-cell diffuse aggressive lymphomas with respect to sex, constitutional symptoms, stages, sites of extranodal involvement, complete remission rate, or survival when they were studied prior to the initiation of aggressive therapy. Although immunotyping can be successfully performed in essentially all cases of diffuse, aggressive non-Hodgkin's lymphomas, to date, the authors have been unable to demonstrate that immunotype alone has an independent prognostic effect.

B-Lymphocytes↗

Acute megakaryoblastic leukemia in childhood.

Routine morphologic and cytochemical study of the leukemic cells of a 13-month-old child did not permit definitive determination of either a lymphoid or a myeloid cell origin. However, ultrastructural cytochemical analysis revealed platelet peroxidase (PPO) reactivity. The malignant cells expressed PPO in both unfixed and fixed preparations. PPO was observed in the perinuclear space and reticulum but not in the Golgi saccules. In a 1% glutaraldehyde, 1% formaldehyde solution known to inhibit PPO but not myeloperoxidase, no reaction product was observed. The demonstration of PPO activity in these undifferentiated cells established their megakaryoblastic lineage. Further studies including DNA flow cytometry confirmed that these cells were megakaryoblasts. This study demonstrates that megakaryoblastic malignancy may occur as an acute leukemia of childhood and emphasizes the value of ultrastructural cytochemistry in cases of acute leukemia which defy routine classification. Abnormalities of chromosome 21 were present in our patient as in four previous cases of megakaryoblastic leukemia in childhood. The nonrandomness of chromosome 21 involvement in this disease should therefore be considered.

Acute Disease↗

Non-Hodgkin's lymphomas. Application of the International Classification of Diseases for Oncology (ICD-O) to the Working Formulation.

International Classification of Diseases for Oncology (ICD-O) code numbers for the non-Hodgkin's lymphomas (NHL) are assigned to the new Working Formulation (WF). This will facilitate the coding of NHL cases by registrars and pathologists by providing a ready means of translation of terms utilized in most of the existing classification schemes. Additional code numbers and synonyms are suggested to accommodate all of the terms in the six major classification systems currently in use and to permit the coding of immunologic cell type when appropriate tests have been performed. To demonstrate how the assignment of these code numbers can be useful, over 8000 incidence cases from the Surveillance, Epidemiology and End Results (SEER) Program (1977-1980) were coded according to the WF groups and the data analyzed. The prognostic significance of the three major groups in the WF is confirmed for each group in the SEER data and comparisons are discussed with the NCI study.

Actuarial Analysis↗

Thymoma: lymphoid and epithelial components mirror the phenotype of normal thymus.

Six thymomas were studied with monoclonal and polyclonal antisera and an immunohistochemical technique to characterize the lymphocytic and epithelial components of the tumor. The T lymphocytes had characteristics of thymocytes, and cortico medullary differentiation was demonstrated within all tumors, regardless of histologic appearance. Cortical thymocytes were positive with anti-terminal deoxynucleotidyl transferase, OKT6, and OKT10, all of which failed to stain medullary thymocytes. Conversely, A1G3 stained medullary thymocytes exclusively. Epithelial cells reacted with A2B5, an antibody that identifies cells of neuroendocrine origin. Epithelial cell processes were also positive with anti-p19, a monoclonal antibody directed against the internal protein of HTLV, which also reacts with normal thymic epithelium. No correlation was found in the distribution of epithelial cells with evidence of cortical and medullary thymocyte differentiation. However, the components of the tumor mirrored the normal cellular and structural components of the thymus.

Antibodies, Monoclonal↗

Leu M1 and peanut agglutinin stain the neoplastic cells of Hodgkin's disease.

It has been suggested that the malignant cells of Hodgkin's disease (HD), Reed-Sternberg cells, and their mononuclear variants may be related to cells of the monocyte-histiocyte system. To test this hypothesis, 20 cases of HD were tested with nine antibodies, monoclonal or polyclonal, that normally react with cells of monocytic/histiocytic/granulocytic lineages, as well as PNA, which binds to histiocytes directly. Only two reagents, Leu M1 and PNA bound to the neoplastic cells in 20/22 and 13/22 cases tested, respectively. Leu M1 was the most sensitive reagent and was negative in only two cases of lymphocyte predominant HD. Leu M1 also could be employed in routinely fixed and processed formalin or B5-fixed tissue. This antibody, which was negative in 27 cases of non-Hodgkin's lymphoma, including 12 peripheral T-cell lymphomas, should prove to be of value in differential diagnosis of HD and morphologically similar reactive and neoplastic lymphoid lesions.

Antibodies, Monoclonal↗

Immunologic methods in cytology: definitive diagnosis of non-Hodgkin's lymphomas using immunologic markers for T- and B-cells.

The cytologic diagnosis of malignant lymphoma can be extremely difficult because the cytologic features of the malignant cells in small cell and mixed small and large cell lymphomas may be indistinguishable from those of reactive lymphoid cells. In addition, large cell lymphoma can be difficult to distinguish from undifferentiated carcinoma in cytologic specimens. Using the avidin-biotin immunoperoxidase technic and antibodies to the B-cell markers alpha, gamma, and mu heavy chains and kappa and lambda light chains, to the T-cell markers Leu-1, Leu-2a, and Leu-3a, to the lymphoid marker T200, to TdT, and to Leu-M3, the authors studied 35 cytologic specimens including pleural, cerebrospinal, and ascites fluids and fine-needle aspirations. Immunologic staining allowed them to make a definitive diagnosis of lymphoma or reactive effusion in every case studied and resulted in a significant modification of the morphologic diagnosis in over 50% of cases. In 16 cases the lymphoid cells were monoclonal B-cells: ten expressing IgM kappa; four expressing IgM lambda; one expressing IgA kappa; and one expressing kappa without demonstrable heavy chain expression. Although there are no good markers of monoclonality for T-cells, the authors were able to make a positive diagnosis in two cases of T-cell lymphoid malignancies by the expression of an aberrant phenotype on the malignant cells. The expression of TdT confirmed the diagnosis in one case of common ALL and one lymphoblastic lymphoma. In a patient with a "null cell" large cell lymphoma, the expression of T200 on the malignant cells ruled out the possibility of carcinoma. In 15 cases the marker studies indicated a reactive lymphoid proliferation. The authors conclude that immunologic markers are very useful in the cytologic diagnosis of lymphoma.

Adolescent↗

The pathologic spectrum of adult T-cell leukemia/lymphoma in the United States. Human T-cell leukemia/lymphoma virus-associated lymphoid malignancies.

The human T-cell leukemia/lymphoma virus (HTLV) is a novel Type-C retrovirus isolated from patients with post-thymic T-cell malignancies. Thirteen patients diagnosed in the United States were identified as having antibodies to HTLV and a typical clinicopathologic syndrome characteristic of adult T-cell leukemia/lymphoma as described in Japan. The most characteristic diagnostic feature in our series was the presence of highly pleomorphic and lobated lymphoid cells in the peripheral blood. Also notable was acid phosphatase activity which was partially tartrate-resistant in the neoplastic cells. The pathologic spectrum of the associated lymphomas was broad and encompassed several diffuse histologic subtypes in the Rappaport classification, the working formulation, and the classification of the Japanese lymphoma study group. However, differences in survival could not be correlated with differences in histologic subtype. All patients presented with Ann Arbor Stage IV lymphoma. Other common clinical features were generalized lymphadenopathy, hepatosplenomegaly, skin and peripheral blood involvement, hypercalcemia, and lytic bone lesions. The clinical course was aggressive with a median survival of 9 months. In two-third of patients with cutaneous involvement, epidermal infiltration resembling Pautrier microabscesses was observed. However, most cases can be readily distinguished from mycosis fungoides/Sézary syndrome on clinical and epidemiologic grounds. The presence of HTLV-antibodies in patients with lymphoid malignancies appears to define a distinct clinicopathologic syndrome which tends to occur in geographic clusters. Adult T-cell leukemia/lymphoma is favored as the diagnostic term for this clinicopathologic entity.

Adult↗

Inflammatory pseudotumor of the spleen.

Two examples of an unusual splenic inflammatory pseudotumor are reported. Splenectomy followed detection of a mass lesion by CT scan in one case, and in the other, the pseudotumor was an unexpected and incidental pathologic finding. Despite the alarming gross appearance of these lesions, microscopic features were unequivocally inflammatory and benign. To our knowledge, this entity has not been described previously in the spleen.

Aged↗

NIH conference. T-cell lymphoproliferative syndrome associated with human T-cell leukemia/lymphoma virus.

Human T-cell leukemia/lymphoma virus is a unique family of T-cell tropic, human, type-C retroviruses. The discovery of this class of retroviruses provides the first proven link between retroviruses and cancer in humans. This virus is endemic in certain parts of the world, including the southeastern United States, and is associated with the development of adult T-cell leukemia/lymphoma, a fulminant lymphoproliferative disorder frequently accompanied by opportunistic infections and hypercalcemia. Over the last few years, major advances have been made in understanding the clinical, epidemiologic, molecular biologic, and immunologic features of this unique class of human RNA tumor viruses.

Acquired Immunodeficiency Syndrome↗

Low-grade lymphomas. Expression of developmentally regulated B-cell antigens.

A series of low-grade B-cell lymphomas was analyzed for a battery of immunologic determinants by flow cytometry and immunohistochemistry. Histologically distinctive subclasses of these lymphomas, well-differentiated lymphocytic (WDL), intermediately differentiated lymphocytic (IDL), and follicular center cell (FCC) lymphoma, were found to be readily distinguishable by their expression of immunologic determinants that are known to be developmentally regulated in normal B cells. Although all cases expressed monoclonal surface immunoglobulin (sIg), HLA-DR, and the surface membrane proteins recognized by antibodies B1 (p32) and BA1, staining with other monoclonal antibodies revealed unique immunologic phenotypes for each subclass: WDL p65 (Leu 1)+, p24 (BA2)-; IDL p65+, p24+; FCC p65-, p24-. Additionally, the fluorescence intensities (number of determinants per cell) obtained for sIg, BA-1, and B1, but not HLA-DR, were significantly different among the three lymphoma subclasses. The relative fluorescence intensities of each of these three markers followed the same pattern: FCC greater than IDL greater than WDL. Taken together, these distinguishing features suggest that low-grade B-cell lymphomas represent arrested, and possibly sequential, stages of B-cell differentiation.

Antibodies, Monoclonal↗

Phenotypic expression of B-lymphocytes. 2. Immunoglobulin expression of germinal center cells.

With a sensitive and specific immunohistochemical technique, immunoglobulin expression was examined in germinal centers with frozen and paraffin-embedded tissues. The majority of cells positive for surface immunoglobulin (IgM and IgD) were confined to the dark zone of the germinal center, while the cells positive for cytoplasmic immunoglobulin (IgM and IgG) were found in the light zone. There were considerable numbers of germinal center cells without identifiable immunoglobulin. The results, in conjunction with previous in vitro and in vivo B-cell activation studies, indicate that centroblasts (noncleaved cells) are formed during early stages of B-cell differentiation. Centroblasts further mature into centrocytes.

Antibody-Producing Cells↗

Phenotypic expression of B-lymphocytes. 1. Identification with monoclonal antibodies in normal lymphoid tissues.

Marker expression is highly variable among different stages of B-cell activation. In peripheral lymphoid tissues, architecturally and cytologically three or four types of B cells can be identified, thus allowing an investigation of cellular surface or cytoplasmic phenotypes. Mantle zone lymphocytes of follicles are phenotypically similar, if not identical, to peripheral blood B-lymphocytes and express the following markers: B1, B2, BA-1, HLA-DR, Leu 10, A1G3, Leu 8, and T200. The germinal center is composed of two main populations, centroblasts and centrocytes which express the following markers: B1, BA-2, J5, OKT9, HLA-DR, Leu 10, and T200. This phenotype is similar to that of activated B cells or pre-B cells. Although membranous OKT10 is present in cortical thymocytes, the presence of cytoplasmic OKT10 appears to be a useful marker for plasma cells, terminally differentiated B cells, which also express A1G3 and T200. This study also revealed that a subpopulation of T cells in the germinal center express different markers (A1G3-/Leu 8-) as compared with that of most T cells in the T-dependent zone (A1G3+/Leu 8+).

Animals↗

An effective therapy for both undifferentiated (including Burkitt's) lymphomas and lymphoblastic lymphomas in children and young adults.

We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt's lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2-16 yr) and 34 young adults 17-35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt's lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

In vivo administration of purified Jurkat-derived interleukin 2 in mice.

Pure human interleukin 2 (IL-2), produced by the T-cell lymphoma Jurkat, was injected in mice to study the serum half-life, toxicity, and in vivo immunological effects of IL-2. The serum half-life (t1/2) of Jurkat IL-2 in mice appeared to have two components: (a) a rapid initial phase with t1/2 of approximately 2 min during which most of the exogenous IL-2 was cleared from the serum; and (b) a second, slower component with t1/2 of about 9 min. Mice given injections i.p. or i.v. with pure Jurkat IL-2, at doses comparable on a microgram/kg basis to contemplated doses for humans, showed no signs of toxicity on the basis of serial measurements of weight, serum liver and kidney chemistries, or histology of lymphoid and vital organs. Jurkat IL-2 had no effect on the rate of growth or survival of mice with an established s.c. methylcholanthrene-induced fibrosarcoma, but Jurkat IL-2 used in conjunction with in vitro-resensitized and IL-2-expanded specific immune splenocytes prolonged survival of mice with disseminated FBL-3 tumor. This survival prolongation was highly significant when compared to treatment with Jurkat IL-2 alone (p = less than 0.001) or an equivalent number of in vitro-resensitized and expanded cells alone (p = 0.004). Treatment of mice with i.p. Jurkat IL-2 subsequent to secondary immunization with allogeneic tumor enhanced by more than 5-fold the splenocyte cytotoxicity for alloantigen measured 7 days later. Thus, purified human IL-2 derived from the Jurkat cell line has a short half-life in mice with no apparent toxicity at large doses. In vivo efficacy of human IL-2 was demonstrated in increasing alloantigen responsiveness and in increasing the efficacy of transferred expanded immune lymphocytes in the FBL-3 lymphoma model.

Animals↗