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Biomedical subjects

E S Jaffe

Publications and source records attributed to E S Jaffe.

At least 343 records · Page 19Linked to original sources

Objective regressions of T- and B-cell lymphomas in patients following treatment with anti-thymocyte globulin.

We have conducted a clinical trial utilizing anti-thymocyte globulin (ATG) for the treatment of patients with non-Hodgkin's lymphomas. Six patients were treated; 50% reductions in tumor mass of short duration were observed in one patient with a T-cell lymphoma and two patients with B-cell lymphomas. In vitro assays have been performed in an attempt to study the reactivity and potential mechanism of antitumor action of the ATG. The ATG bound to essentially all normal blood mononuclear leukocytes as well as tumor cells from patients with T-, B-, or null cell lymphomas demonstrating its lack of specificity. Furthermore, complement-mediated lysis of normal mononuclear leukocytes, normal T- or B-cells, and tumor cells from two unresponsive patients were all comparable; moreover, since this lysis occurred only at concentrations of ATG that are not attainable in vivo, it is unlikely that complement-mediated cytotoxicity accounts for the responses observed. Peripheral blood lymphocyte counts and total erythrocyte rosettes did decrease during ATG treatment. Thus, objective tumor responses in both B- and T-cell non-Hodgkin's lymphomas can be achieved with a very nonspecific antiserum although significant toxicity resulted. Whether the magnitude or duration of response can be increased with monoclonal antibodies remains to be determined. Future success with serotherapy might require use of either a battery of different monoclonal antibodies or a single monoclonal antibody that can deliver radioisotopes, chemotherapy, or toxins to the tumor cells.

Adolescent↗

Polyarteritis nodosa, hairy cell leukemia and splenosis.

Appendiceal vasculitis and splenosis in a young women provided pathologic evidence that a systemic necrotizing vasculitis preceded the onset of hairy cell leukemia by at least six years. As in other patients who have had both diseases, florid polyarteritis nodosa developed during the course of the malignancy. However, the antecedent vasculitis, as well as the coincidence of these rare diseases, indicate that systemic vasculitis does not necessarily result from hairy cell leukemia as previously reported and suggest that the two diseases might share a common pathogenesis or predisposing factor.

Adult↗

NIH conference. A multidisciplinary approach to non-hodgkin's lymphomas.

Epidemiologic studies show that non-Hodgkin's lymphomas tend to develop after prolonged antigenic stimulation, after loss of normal regulation of lymphoid proliferation, or especially after both processes. Study of these tumors in vitro has greatly increased understanding of their pathophysiology and has provided a conceptual framework for their morphologic diversity. Lymphomas are now understood to be expanded clones of their normal counterparts. The anatomic location, phenotypic characteristics, proliferative capacity, and functional capabilities of the neoplasm often reflect those of the equivalent normal cells. If neoplastic transformation can occur at any stage of lymphoid differentiation, then it is theoretically possible that neoplastic lymphocytes may respond, or could be induced, to normal regulatory influences. Further study of selective cytotoxicity may reveal exploitable differences among lymphocytic subpopulations and permit more rational choices of therapy. Of major aid to future clinical trials should be the recent consensus on nomenclature by an international panel of experts.

Adolescent↗

Distribution of complement receptor subtypes in non-Hodgkin's lymphomas of B-cell origin.

Surface receptors specific for either the C4b (CR1) or C3d (CR2) component of complement were examined on the neoplastic cells from 30 cases of non-Hodgkin's lymphoma of B-cell origin and on cells derived from 9 normal lymphoid tissues. Lymphocyte suspensions from non-neoplastic peripheral blood, tonsils, and lymph node contained three categories of complement receptor lymphocytes (CRL): cells with receptors for both C4b and C3d (CR1+, CR2+); cells with receptors for C4b but not C3d (CR1+, CR2-), and cells with receptors for C3d but not C4b (CR1-, CR2+). The mean of the proportion of total CRL expressing receptors only of C3d (CR1-, CR2+) was 0.35 for non-neoplastic tissues and 0.28 for malignant lymphomas of follicular center cell (FCC) origin. However, the proportion of cells with this phenotype was significantly higher in well differentiated lymphocytic lymphomas (WDL) and chronic lymphocytic leukemia (CLL) (0.65) and in intermediately differentiated lymphocytic lymphomas (IDL) (0.59). Histologic compartmentalization of the CRL subtypes was observed in frozen sections of normal lymphoid tissue. CR1+ cells were present in lymphoid follicles interfollicular areas, and in splenic red pulp. CR2+ cells were confined to lymphoid follicles. These findings strongly suggest that complement receptor phenotypes may be useful markers of B-cell differentiation.

B-Lymphocytes↗

Induction of complement receptors in human cell lines derived from undifferentiated lymphomas.

Two Epstein-Barr nuclear antigen-negative cell lines, EW36 and CA46, derived from human undifferentiated lymphomas were exposed to the methylxanthines theophylline and 3-isobutyl-1-methylxanthine. Both compounds markedly increased the proportion of cells which bears complement receptors, whereas other surface markers such as surface immunoglobulin and IgG Fc receptors were unchanged. The inducing agents, hexamethylene bisacetamide and diethylsulfoxide, had a similar effect, but other compounds known to alter intracellular cyclic AMP had no effect on surface markers. The expression of complement receptors first appeared at 8 to 10 hours and was dependent upon the continued presence of theophylline in the tissue culture medium. Other effects of the methylxanthine derivatives tested included inhibition of DNA synthesis and a reduction in mean cellular volume. However, inhibition of growth per se did not result in complement receptor induction. These data suggest that the differentiation agents active in this system may be useful tools in the study of human lymphoid malignancies.

Cell Differentiation↗

Resolution of longstanding protein-losing enteropathy in a patient with intestinal lymphangiectasia after treatment for malignant lymphoma.

In 1956 we evaluated a patient who had a debilitating disease of a 2 yr duration, characterized by recurrent vomiting, diarrhea, cachexia, massive edema, hypoproteinemia, and dilated intestinal lymphatics. During our initial evaluation of this patient, we observed that 42% of her circulating protein pool was lost into her gastrointestinal tract daily, whereas normal gastrointesinal loss of protein does not exceed 1.6%. Her disease appeared to represent a classic example of intestinal lymphangiectasia. She was treated symptomatically for 13 yr with essentially no change. In 1969 the patient developed a stage IV diffuse, undifferentiated (non-Burkitt's) malignant lymphoma. Using immunoperoxidase staining, the neoplastic cells were found to contain cytoplasmic IgMKappa, suggesting that the lymphoma had a monoclonal B-cell origin. She was successfully treated with cyclophosphamide, vincristine, and prednisone. Shortly after the initiation of this systemic combination chemotherapy, her serum protein concentration returned to normal, her edema resolved, and she was cured of gastrointestinal symptoms. Moreover, repeat studies revealed that her protein loss had fallen to only 2%. The simultaneous cure of both the intestinal lymphangiectasia and lymphoma with combination chemotherapy suggests new relationships between these conditions as well as new possibilities for the treatment of acquired forms of intestinal lymphangiectasis associated with overwhelming gastrointestinal protein loss.

Adult↗

Diffuse large cell lymphomas (reticulum cell sarcomas, histiocytic lymphomas). Correlation of morphologic features with functional markers.

Electron microscopic findings in 15 cases of diffuse large cell lymphoma were correlated with other morphologic features, surface immunotype and cytoplasmic immunoglobulin content. Immunologically, the cases were: B cell, 8; null, 4; T cell, 2; and H cell (true histiocytic), 1. Ultrastructurally, all B cell and three null lymphomas were characterized by an abundance of polyribosomes and segments of rough endoplasmic reticulum. Concentric rough endoplasmic reticulum was observed in 4 cases of B cell lymphoma containing cytoplasmic immunoglobulin and in a null lymphoma. In 1 case of B cell lymphoma, the diastase-sensitive, periodic-acid-Schiff-positive cytoplasm showed evidence of widely dispersed monoparticulate glycogen granules. The two T cell lymphomas contained hyperlobulated or single round nuclei, and abundant smooth to rough endoplasmic reticulum. One null lymphoma appeared to share the ultrastructural features of T cell convoluted nuclei and the cytoplasmic organelles of myeloid precursor cells. The H cell lymphoma had features of monocytic-macrophagic differentiation. The large cell lymphomas, a morphologically and functionally heterogeneous group, were represented predominantly in this series by neoplasms with follicular center cells or early plasma cells.

Antigens, Neoplasm↗

Non-Hodgkin's lymphomas in leukemic phase: clinicopathologic correlations.

A leukemic phase occurred in 30 (14 percent) of 214 patients with non-Hodgkin's lymphoma. To determine the significance of peripheral blood involvement in each type of NHL, patients were subdivided according to a modified Rappaport classification. Each histologic subtype presented a homogeneous clinical picture which differed from that seen in other histologic subtypes. Of particular note was the recognition of two distinctive cytologic and clinical subtypes within the category of nodular lymphoma, poorly differentiated lymphocytic lymphoma (NPDL). In one subtype, the predominant cells had cytologic features akin to those of lymphoblasts. In these cases, although the interval to peripheral blood involvement was variable, the median leukemic survival was only two months. In contrast in conventional NPDL the median leukemic survival was 43+ months, and peripheral blood involvement did not appear to exert an independent effect on prognosis. In diffuse large cell lymphomas the median leukemic survival was 0.5 months, with peripheral blood involvement appearing as a terminal event associated with unresponsive disease in multiple sites. The recognition of adult lymphoblastic lymphoma as a clinicopathologic entity with a high risk of leukemic conversion, 100 percent in this study, is also confirmed.

Adolescent↗

Malignant lymphomas as tumours of the immune system.

Malignant lymphomas have traditionally been classified on solely morphological grounds. With new immunological and cytochemical techniques, it has been possible to characterize normal cells of the T-lymphocyte, B-lymphocyte, and monocyte-macrophage system. Application of these methodologies to malignant lymphomas has established their nature as neoplasms of the immune system. Within the B-lymphocyte system it is possible to identify subpopulations responsible for Burkitt's tumour, follicular (nodular) lymphomas, lymphocytic lymphomas of intermediate differentiation and well differentiated lymphocytic lymphomas. The T-lymphocyte system includes lymphoblastic lymphomas, mycosis fungoides, and Sezary's syndrome. Large-cell lymphomas are diverse, but the majority are tumours of transformed lymphocytes, usually of the B-lymphocyte system. The precise nature of the neoplastic cells of Hodgkin's disease (i.e., Reed-Sternberg cells and their mononuclear counterparts) has not yet been established. Despite previous suggestions of a B-lymphocyte or T-lymphocyte origin, recent studies with in vitro cultivation have strongly suggested derivation from the monocyte-macrophage system.

Antibodies, Neoplasm↗

A comparison between combination chemotherapy and total body irradiation plus combination chemotherapy in non-Hodgkin's lymphoma.

Thirty-nine untreated patients with either lymphocytic or nodular mixed/nodular histiocytic non-Hodgkin's lymphoma, stage II--IV, were randomized to treatment with total body irradiation (TBI), 100 rads in 10 fractions over 12 days, plus combination chemotherapy with either cyclophosphamide, vincristine and prednisone (CVP) or cyclophosphamide, vincristine, procarbazine and prednisone (C-MOPP) or to treatment with combination chemotherapy (CVP or C-MOPP) alone. Remission rate and duration was comparable for both treatment groups; thus the use of both treatment modalities ab initio provides no therapeutic advantage.

Adult↗

Immunologic aspects and pathology of the malignant lymphomas.

Malignant lymphomas have traditionally been classified on solely morphologic grounds. With new immunologic and cytochemical techniques, it has been possible to characterize normal cells of the T-lymphocytic, B-lymphocytic, and monocyte-macrophage systems. Application of these methodologies to malignant lymphomas has established their nature as neoplasmas of the immune system. Within the B-lymphocytic system it is possible to identify subpopulations responsible for Burkitt's tumor, follicular (nodular) lymphomas, lymphocytic lymphomas of intermediate differentiation and well differentiated lymphocytic lymphomas. The T-lymphocytic system includes lymphoblastic lymphomas, mycosis fungoides, and Sezary's syndrome. Large cell lymphomas are diverse but the majority are tumors of transformed lymphocytes, usually of the B-lymphocytic system. The precise nature of the neoplastic cells of Hodgkin's disease, i.e., Reed-Sternberg cells and their mononuclear counterparts, has not yet been established. Despite previous suggestions of a B-lymphocytic or T-lymphocytic origin, recent studies utilizing in vivo cultivation have strongly suggested derivation from the monocyte-macrophage system.

Adolescent↗

Acute lymphoblastic leukemia--hand mirror cell variant: a detailed cytological and ultrastructural study with an analysis of the immunologic surface markers.

Acute lymphoblastic leukemia was observed in a 22-year-old white female patient and was manifested by normal palelet counts, 50--60% hand mirror cells (HMC) in the bone marrow, and prolonged survival without treatment. The characteristic neoplastic cell had a nucleus within the "mirror" portion and a cytoplasmic uropod forming the "handle" portion. The presence of acid phosphatase and beta-glucuronidase activity suggested that the cell was a T cell lymphoblast. However, extensive immunologic surface marker studies indicated the cells were non-T, non-B. Terminal transferase activity further supported the lymphoid nature of the cell. The hand mirrow cells were considered a real phenomenon since they were demonstrated on phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy. The cells did not grow in tissue culture and cytogenetics revealed a normal female karyotype. From the above observations, the HMC is a lymphoblast with morphological, cytochemical, and immunological features which may differentiate it from the usual cell in acute lymphoblastic leukemia. Therefore, cases involving increased numbers of hand mirror cells in the bone marrow and acute lymphoblastic leukemia require further investigation to elucidate the full importance of this cell. This study represents the first attempt to investigate this cell in detail.

Binding Sites↗