PubMed Health⌕ Search

Biomedical subjects

S M Hsu

Publications and source records attributed to S M Hsu.

At least 109 records · Page 6Linked to original sources

L&H variants of Reed-Sternberg cells express sialylated Leu M1 antigen.

Anti-Leu M1 generally does not stain the lymphocytic and histiocytic (L&H) variants of Reed-Sternberg cells in the lymphocyte predominant type of Hodgkin's disease. However, the authors found that after neuraminidase treatment for removal of sialic acid, the L&H cells in more than half of the cases studied could be stained by anti-Leu M1. This result strongly suggests that L&H cells differ from the Reed-Sternberg cells in other types of Hodgkin's disease in their unique capacity to sialylate the 150-kd Leu M1 antigen.

Antigens↗

Phenotypes and phorbol ester-induced differentiation of human histiocytic lymphoma cell lines (U-937 and SU-DHL-1) and Reed-Sternberg cells.

Hodgkin's mononuclear cells, Reed-Sternberg (H-RS) cells, and U-937 and SU-DHL-1 histocytic cell lines were induced to differentiate by phorbol ester in cultures. The phenotypes of cells were determined by a panel of antibodies specific for monocytes, histiocytes, and interdigitating reticulum cells. Before induction, SU-DHL-1 cells and H-RS cells expressed similar markers, such as HeFi-1, 2H9, 1A2, and 1E9. In addition, SU-DHL-1 cells were also stained by Tac and Leu M5. Other monocyte markers, including OK M1, Co Mo2, BRL Mo1, BRL Mo2, and Leu M3 were consistently negative in both types of cells. After induction, SU-DHL-1 cells conserved the same phenotype, but H-RS cells became negative for HeFi-1, 1A2, and 2H9. The U-937 cells expressed Leu M1 and Co Mo2 and became positive for Leu M5, OK M1, Co Mo2, BRL Mo2, 2H9, and 1E9 after phorbol ester induction. The U-937 cells did not express HeFi-1 or 1A2. The marker expression of H-RS cells, SU-DHL-1 cells, and U-937 cells were compared with those of histiocytes or interdigitating reticulum cells in lymphoid tissues and with neoplastic cells in true histiocytic lymphoma and malignant histiocytosis. It is concluded that SU-DHL-1, U-937, and H-RS cells are derived from or most closely related to fixed histiocytes, free histiocytes, and interdigitating reticulum cells, respectively. Our study further confirms the diagnosis of SU-DHL-1 as true histiocytic lymphoma but reveals that U-937 is a case of malignant histiocytosis rather than the previously diagnosed histiocytic lymphoma. The phenotypes and induction properties of SU-DHL-1 cells are quite different from those of U-937 cells, which suggests that true histiocytic lymphoma and malignant histiocytosis are two distinct disease entities.

Antibodies, Monoclonal↗

Expression of interleukin-1 in Reed-Sternberg cells and neoplastic cells from true histiocytic malignancies.

Interleukin-1, a peptide produced by monocytes, histiocytes, and interdigitating reticulum cells, plays an important role in the regulation of immune function. In this styde, we examined the production of interleukin-1 in 115 patients with a variety of human lymphomas by using a rabbit anti-interleukin-1 antibody and the immunoperoxidase technique. Interleukin-1 was detected in Reed-Sternberg cells from 20 patients with Hodgkin's disease as well as in neoplastic cells from 9 patients with true histiocytic lymphoma or malignant histiocytosis. In the other 86 cases, which included T- and B-cell lymphomas, no interleukin-1 could be detected. This result indicates a close relationship between Hodgkin's disease and true histiocytic malignancies and provides additional evidence to support our hypothesis that Reed-Sternberg cells are related to interdigitating reticulum cells.

Animals↗

Granulomas in sympathetic ophthalmia and sarcoidosis. Immunohistochemical study.

Monoclonal antibodies were used to identify cells that form choroidal granulomas and Dalen-Fuchs nodules in sympathetic ophthalmia as well as the granulomas of sarcoid. Immunohistochemical analysis of frozen sections of fresh human tissues obtained after enucleation (sympathetic ophthalmia) and lung biopsy (sarcoid) was performed by the avidin-biotin-peroxidase complex method. The majority of the inflammatory cells within these lesions were identical and were composed mainly of cells originating from bone marrow-derived monocytes (reticuloendothelial system) probably representing immunologically stimulated granulomas. This study suggests possible immune phenomena that may take part in the pathogenesis of sympathetic ophthalmia and provides some insights into the possible mechanism of formation of choroidal granulomas and Dalen-Fuchs nodules in this disease.

Antibodies, Monoclonal↗

Immunohistochemistry and electron microscopy of choroidal infiltrates and Dalen-Fuchs nodules in sympathetic ophthalmia.

An immunohistological study using monoclonal antibodies directed at specific membrane antigens of various inflammatory cells was carried out in order to evaluate the identity and topographic localization of the immuno-competent cells in an enucleated eye from a 6-year-old black patient with a three-month history of sympathetic ophthalmia. Correlative light and transmission electron microscopic examination of serial sections was also performed. The data demonstrated that the predominant cells within the choroidal infiltrate were T-lymphocytes (Leu 1+). T-cell subset analysis disclosed that most of these cells harbored specific antigenic determinants of the helper phenotype (Leu 3a+). A smaller proportion of the T cells demonstrated the specific determinants of the suppressor subtype (Leu 2a+). The helper/suppressor ratio varied slightly and ranged in most areas of the choroid between 3:1 and 4:1. Additionally, approximately 15% of the infiltrating lymphocytes harbored the Leu 14+ determinant specific for B cells. The latter were located in the outer choroid adjacent to the sclera. Very few natural killer (NK) cells (Leu 7+) were identified throughout the choroid. The granulomatous foci in the choroid were composed mainly of epithelioid cells and histiocytes expressing the OKM1+ and M221+ antigenic determinants on their membranes and demonstrating a high cytoplasmic nonspecific esterase activity (ANAE+). Within the Dalen-Fuchs nodules, similar to the choroidal nodules, there was a predominance of histiocytes and epithelioid cells (OKM1+, M221+, ANAE+), a few T-helper cells (Leu 1+, Leu3a+) and some OKM1-, M221- cells whose origin could not be determined. These findings were corroborated by electron microscopic observations of serial sections. Careful light and electron microscopic studies disclosed breaks in Bruch's membrane underlying some of Dalen-Fuchs nodules. In our opinion, these observations may be interpreted as the demonstration that Dalen-Fuchs' nodules and the choroidal granulomatous foci could be formed by identical cells of similar function and origin.

Child↗

Pathologic and immunologic characterization of malignant lymphoma in Taiwan. With special reference to retrovirus-associated adult T-cell lymphoma/leukemia.

One hundred four cases of malignant lymphomas, including 90 cases of non-Hodgkin's lymphoma, 5 cases of histiocytic malignancy, and 9 cases of Hodgkin's disease were analyzed pathologically and immunologically using a panel of monoclonal and conventional antibodies for T-, B-, histiocyte, and Hodgkin's neoplastic cells. Our results revealed a high frequency of T-cell lymphoma (42.3%), a low percentage of follicular lymphoma (10.5%), and Hodgkin's disease (8.7%) in Taiwan. More than half of the malignant lymphomas belonged to the high-risk unfavorable group. Peripheral T-cell lymphomas (33 cases) showed characteristic clinical and histologic features, which can sometimes be confused with Hodgkin's disease. Monoclonal antibodies Leu-M1 and 2H9 were an important aid for their differential diagnosis. Five of the 33 peripheral T-cell lymphomas were positive for antibody to adult T-cell lymphoma/leukemia (ATL) virus associated antigen (ATLA). Four patients were from the northeast coast of Taiwan, I-Lan county. Five (4.8%) were diagnosed as true histiocytic malignancies, including two true histiocytic lymphoma and three malignant histiocytosis. Two cases each of large cell lymphoma and immunoblastic lymphoma showed no identifiable marker expression. The distribution of lymphoproliferative disorders in Taiwan is similar to that in Japan but much different from western countries.

Adolescent↗

Malignant lymphoma in patients with the Wiskott-Aldrich syndrome.

The type and incidence of malignant lymphoma developing in patients with the Wiskott-Aldrich syndrome being followed at the National Cancer Institute (NCI) between the years 1966 and 1982 was evaluated. Histologic material from lymphoid tissue was available for review on 24 of the 50 Wiskott-Aldrich patients followed by the Metabolism Branch of the NCI. In 17 patients, specimens were obtained by biopsy performed for diagnosis of lymphoid mass lesions, and in 16 patients autopsy specimens were reviewed. In 9 of the 24 patients a diagnosis of malignant lymphoma was made. A distinct preponderance of non-Hodgkin's lymphoma (NHL) over Hodgkin's disease (HD) with a ratio 8:1 was observed, and the overall incidence of malignant lymphoma in all 50 patients was 18%. The most common histologic subtype of NHL was large cell immunoblastic. In all but one patient the diagnosis of lymphoma was made antemortem, most often presenting in extranodal sites or the brain. Involvement of peripheral lymph nodes was conspicuous by its absence. Immunoperoxidase staining for kappa and lambda chain immunoglobulin and lysozyme was negative in the four cases studied, failing to provide supportive evidence for a B-cell or true histiocytic origin for the tumor cells. Histologic subtypes of lymphoma commonly observed in childhood, such as Burkitt's lymphoma and lymphoblastic lymphoma, were not observed. Despite treatment with combination chemotherapy in some patients, there were no long-term remissions and median survival was less than one year following the diagnosis of lymphoma.

Adolescent↗

Phenotypic expression of B lymphocytes. III. Marginal zone B cells in the spleen are characterized by the expression of Tac and alkaline phosphatase.

The marginal zone of the spleen contains lymphocytes with an intermediate morphologic form between small lymphocytes and plasmablasts. The majority of cells can be stained by B cell monoclonal antibodies including B1, Leu-14, and Leu-12. The most significant finding is the expression of an interleukin 2 receptor (Tac) and an enzyme-alkaline phosphatase by the marginal zone B lymphocytes. The Tac antigen is not normally present in B cells, but can be found in a portion of in vitro-activated B lymphocytes. In conjunction with other evidence, the marginal zone B lymphocytes may represent the activated B cells in the early stages of B cells differentiation. Alternatively, the Tac-positive, marginal zone B lymphocytes may be a discrete subpopulation of activated B cells.

Alkaline Phosphatase↗

Production and characterization of a monoclonal antibody that binds Reed-Sternberg cells.

A murine monoclonal antibody, termed HeFi-1, was produced after immunization with the L428 Hodgkin's disease tissue culture cell line. HeFi-1 selectively stained only the Reed-Sternberg or Hodgkin's cells in 18 of 18 cases of Hodgkin's disease, including the nodular sclerosis, mixed cellularity, and lymphocyte-depleted histologic subtypes. HeFi-1 did not stain any cells in normal lung, brain, salivary gland, thyroid, gall bladder, pancreas, liver, testis, breast, endometrium, or kidney. Rare large cells at the edge of the lymphoid follicles were stained in normal tonsil, colon, and hyperplastic thymus. There was no staining of any cells in 14 cases of B cell non-Hodgkin's lymphoma; however, the malignant cells in three of 11 cases of non-Hodgkin's lymphoma which appeared to express T cell markers were also stained with HeFi-1. Tissue culture cell lines including the T cell acute lymphocytic leukemia lines MOLT4 and CEM, the histiocytic cell line U-937, and the amniotic cell line WISH were not stained. Seven Epstein Barr virus (EBV)-positive lymphoblastoid cell lines were stained with HeFi-1, but there was no staining of three EBV+ African Burkitt's lymphoma cell lines or three EBV- American Burkitt's cell lines. HeFi-1 did not block the ability of the L428 cells to stimulate a mixed lymphocyte reaction or function as accessory cells for mitogen-induced human T cell proliferative responses. Modulation of the HeFi-1 cell surface antigen on the L428 cells was not observed. HeFi-1 specifically immunoprecipitated a cell surface protein of approximately 120,000 daltons from both the L428 and EBV+ lymphoblastoid cell lines. HeFi-1 monoclonal antibody should prove useful not only in the diagnosis, staging, and potential therapy of Hodgkin's disease, but also for determining the cell of origin of the Reed-Sternberg cell.

Animals↗

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↗

Curative intravenous adoptive immunotherapy of Meth A murine sarcoma. A histologic and immunohistochemical assessment.

Intravenous administration of 1.5 X 10(8) syngeneic spleen cells from immune animals resulted in the complete eradication of established Meth A soft tissue sarcomas in (C57BL/6 X BALB/c) F1 mice. In mice receiving a single injection of immune spleen cells 4 days after tumor implantation in the abdominal wall, the tumors continued to grow for approximately 1 week before undergoing regression. This delay before adoptive immunity is expressed is thought to represent the time needed for the passively transferred cells to give rise to a host response of sufficient magnitude to destroy the tumor. None of the mice receiving a similar number of control spleen cells were cured of their sarcomas. Successful therapy was dependent upon the transfer of viable, immune T lymphocytes and required prior irradiation of the tumor-bearing host in order to remove suppressor T cells. Utilizing sequential histologic and immunohistochemical techniques, we attempted to characterize the cellular events of tumor regression. The earliest histologic difference between animals treated with immune and nonimmune lymphocytes was in the number of lymphocytes detected at the perimeter of the tumor in specifically immunized mice on day 6. There was also a striking difference between animals treated with immune versus nonimmune lymphocytes in the intensity and timing of the acute inflammatory response beginning on day 8. The "front" of immunologically mediated tumor destruction appeared at the lateral and deep borders of the implanted sarcomas and progressed inward. During the period of active tumor regression T lymphocytes reactive with a biotinylated mouse anti-Thy 1.2 monoclonal antibody were increased in frozen sections of tumors in mice receiving immune cells relative to the controls. During the first 3 weeks following adoptive transfer of lymphocytes, T cells reactive with Lyt-1 biotinylated mouse monoclonal antibody (helper/inducer phenotype) outnumbered their Lyt-2 (suppressor/cytotoxic) counterparts in frozen sections of tumor from both specifically immunized and control mice. By the end of the 4th week of the experiment, the sarcomas were completely eradicated in all mice receiving immune cells. The previous tumor beds were occupied by collections of lipid-laden macrophages, lymphocytes, plasma cells, and fibroblasts. Despite vigorous but delayed acute and chronic inflammatory responses at the tumor perimeters in the control mice, these tumors all progressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Immunohistochemical characterization of intrathyroid lymphocytes in Graves' disease. Interstitial and intraepithelial populations.

The phenotypic cell surface markers of the lymphocytes present in thyroid tissue from four patients with Graves' disease were quantitatively analyzed using the avidin-biotin immunoperoxidase technique. As control specimens, normal perinodular tissues from three patients who had benign thyroid nodules resected were also studied. In contrast to normal thyroid tissue, which contained very few T cells and no B cells, thyroid tissue of all four patients with Graves' disease contained a lymphocytic infiltrate, and this could be divided into two populations of lymphocytes. The first population was located in the follicular epithelium and expressed a cytotoxic-suppressor T cell marker (Leu2a). On the average, these cells were 4.2 times as numerous in Graves' tissues as in normal tissues (p less than 0.05). Most of these cells did not express Leu1, a pan-T cell marker. The second population was found in the interstitial tissues, often within lymphoid aggregates, and 70 to 83 percent of the cells expressed Leu1. The majority of these cells expressed a helper-inducer T cell marker, Leu3a; Leu3a/Leu2a ratios within aggregates ranged from 1.9 to 2.1. The number of B cells present was small, ranging from 5.8 to 12.1 percent of the interstitial lymphocytes. These findings are consistent with the involvement of both helper-inducer and suppressor-cytotoxic T cells in a localized autoimmune reaction directed, at least in part, against the thyroid follicular epithelial cells.

Autoimmune Diseases↗

Identification of bromodeoxyuridine in malignant and normal cells following therapy: relationship to complications.

During a clinical Phase I study of bromodeoxyuridine (BUdR) as a radiation sensitizer we identified the normal and malignant cells that incorporated the BUdR. BUdR was infused for up to 14 days and the in vivo incorporation of BUdR into DNA was assessed using an immunohistochemical technique and a monoclonal antibody directed against BUdR. BUdR was identified in 50% of breast cancer cells and 10% of cells in a malignant melanoma. BUdR was also found in the basal layer of the normal epidermis and in 50% of cells in the marrow. The incorporation of BUdR into cells in the epidermis and marrow may produce the phototoxicity and myelosuppression observed in patients treated with BUdR. Sequential biopsies from a breast cancer taken prior to and following radiotherapy suggested that cells that incorporated BUdR may have been selectively killed by the radiation. The immunohistochemical technique used to identify BUdR appeared to be useful for studies of in vivo and in vitro cell proliferation.

Bone Marrow↗

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↗