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Biomedical subjects

J Cossman

Publications and source records attributed to J Cossman.

At least 109 records · Page 6Linked to original sources
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

Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2.

Transferrin is required by many cells for growth. Mitogen-induced T lymphocyte proliferation is dependent on the presence of both interleukin 2 (IL-2; T-cell growth factor) and transferrin, even though resting lymphocytes do not have receptors for either. Exposure to mitogen (phytohemagglutinin) alone is sufficient to induce transient appearance of IL-2 receptors on lymphocytes. Using monoclonal antibodies to the IL-2 receptor and to the transferrin receptor, we examined those signals required for transferrin receptor induction during T lymphocyte proliferation. Our study has revealed that (i) monocytes, or a monocyte substitute such as the phorbol ester tetradecanoylphorbol 13-acetate, are required for transferrin receptor expression after mitogen exposure; (ii) the presence of IL-2 receptors is necessary for transferrin receptor induction; (iii) antibody to the IL-2 receptor inhibits thymidine incorporation (DNA synthesis) in lymphocytes, but only if administered before transferrin receptors have appeared; and (iv) antitransferrin receptor antibody inhibits DNA synthesis but has minimal effect on IL-2 receptor expression. Thus, IL-2 receptor induction leads to transferrin receptor induction and subsequent initiation of DNA synthesis. These data indicate that IL-2 stimulates T lymphocyte proliferation, at least in part, by induction of transferrin receptors on these cells.

Antibodies, Monoclonal↗
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

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

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

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↗
PubMed1983

Association of the human type C retrovirus with a subset of adult T-cell cancers.

To determine whether the human T-cell lymphoma-leukemia virus (HTLV) is associated with particular cancers, patient sera were surveyed for HTLV-specific antibodies. An association was seen with aggressive cancers of mature T-cells, specifically Japanese adult T-cell leukemia (ATL) and T-cell lymphosarcoma cell leukemia (TLCL), a similar cancer of Caribbean blacks. Ninety to 100% of these patients possessed HTLV-specific antibody. Forty-seven and 20% of relatives of ATL and TLCL patients, respectively, and 12 and 4% of healthy donors from ATL and TLCL endemic areas were also antibody positive. Visceral organ involvement, hypercalcemia, and skin manifestation, features of ATL and TLCL, were often seen in other antibody-positive patients. Childhood cancers, most cutaneous T-cell and all non-T-cell leukemias and lymphomas, myeloid leukemias, Hodgkin's disease, and solid tumors were not associated with HTLV. Healthy United States donors and European patients with non-malignant diseases were antibody negative. HTLV is thus associated with a subtype of adult T-cell leukemia-lymphoma, clustered in viral endemic areas, with apparent racial and geographic predilection.

Adult↗
PubMed1982

Role of the thymus in directing the development of a subset of B lymphocytes.

In an effort to evaluate the role of the thymus in influencing the development of Lyb-5- B lymphocytes, mice expressing both the xid and nu gene defects were studied. Mice expressing either of these defects respond to both trinitrophenylated Brucellus abortus and lipopolysaccharide; whereas mice with the combined defect show markedly suppressed responses. The other abnormalities included: (a) greater than 80 percent diminution of serum Ig levels; (b) significant increase in the number of sIgM+ sIgD- B lymphocytes; (c) reduced expression of IgD on sIgD+ cells; and (d) a strikingly abnormal histology of their lymphoid tissue. Because nu/nu mice that do not express the xid defect appear relatively normal, it would suggest that the development of Lyb-5- B lymphocytes require a thymic influence for normal maturation, whereas, Lyb-5+ B lymphocytes are relatively independent of such influences.

Animals↗
PubMed1982

Heterogeneity of complement receptor expression on surface immunoglobulin-bearing cells from neonatal and adult mice.

The ontogeny of acquisition of complement receptors (CR) on splenic B lymphocytes from mice of varying ages was examined. Reagents used for the identification of CR included antibody- and complement-coated erythrocytes (EAC), bacteria (BAC) and bacteria treated with complement alone (BC). When whole mouse serum used as the source of complement both EAC and BAC failed to bind to human erythrocytes (C3b receptor-negative), showed binding to Raji and Daudi cells (C3d receptor) and formed rosettes with human neutrophils (C3bi receptor). Therefore these reagents bore C3d and C3bi, but not intact C3b. Although EAc and BAC detected nearly equal percentages of CR lymphocytes in adult mice, BAC bound to a higher percentage of neonatal lymphocytes (8-12%) than did EAC (1-3%). The ability of BAC to detect EAC-negative lymphocytes among neonatal spleen lymphocytes appeared to be due to the increased sensitivity of this bacterial reagent for binding to CR. Further evidence of this enhanced sensitivity was that BAC were less inhibitable than EAC by soluble antigen-antibody-complement complexes.

Animals↗
PubMed1982

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↗
PubMed1981

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↗
PubMed1981

Factors predicting long-term survival in diffuse mixed, histiocytic, or undifferentiated lymphoma.

Clinical and histopathologic material from 151 cases of diffuse mixed, diffuse histiocytic, and diffuse undifferentiated non-Burkitt's lymphomas have been reviewed to determine the factors that predict long-term survival. Median survival of all patients was 34 mo with 43% alive at 70 mo. Factors associated with a poor prognosis include: male sex, constitutional symptoms, advanced stage, bone marrow involvement, huge (greater than 10 cm) abdominal masses with gastrointestinal involvement, hepatic involvement, hemoglobin greater than 12 g/dl, or serum LDH greater than 250 U. The best prediction of a given patient's survival was defined by a set of four variables, which includes sex, symptoms, bone marrow status, and the presence or absence of a huge abdominal mass with gastrointestinal involvement. In contrast, classification of these patients according to the histopathologic categories of Rappaport of Strauchen did not define patient groups with significant differences in survival, nor did these categories correlate with the previously described clinical factors. Knowledge of the distribution of these prognostic factors in any clinical trial is needed before therapeutic results can be compared. In addition, such data may define subsets of patients for whom current therapy is inadequate and conversely those patients for whom current therapy yields excellent long-term survival.

Abdominal Neoplasms↗
PubMed1980

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↗