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Biomedical subjects

S S Xie

Publications and source records attributed to S S Xie.

17 recordsLinked to original sources

Immunosuppression of triptolide and its effect on skin allograft survival.

In this study the immunosuppressive properties of triptolide were evaluated. Triptolide was found to inhibit skin allograft rejection in a dose-dependent manner. This inhibitory effect was time dependent. Triptolide at 0.1 mg/kg/day significantly prolonged the graft survival when triptolide was given for 9 days after transplantation, but not before transplantation. In vitro studies showed that triptolide markedly suppressed cytotoxic T-lymphocyte (CTL) induction and mixed lymphocyte reaction (MLR) at concentrations ranging from 0.08 to 10 ng/ml. The inhibition on MLR was also significant when triptolide was added to the cultures at 36 h after initial incubation. Furthermore, exogenous IL-2 did not reverse this inhibitory effect of triptolide. Our results suggest that triptolide inhibits lymphocyte activation at a relatively late stage, and its effect on immune response is not exerted through altering IL-2 production.

Animals

Russell bodies consist of heterogenous glycoproteins in B-cell lymphoma cells.

The phenotypic expression of Russell bodies (RB) in the tumor cells of two patients with different types of B-cell lymphoma and of one patient with plasma cell myeloma were examined. In both B-cell lymphomas, the RBs reacted consistently with anti-Leu 8 and anti-immunoglobulin M. The RBs in one case also reacted with other monoclonal antibodies, including anti-CD5, CD19, CD22, and CD25. The membranes of most of the tumor cells containing RBs did not stain. In the myeloma, the RBs reacted only with anti-immunoglobulin, and the myeloma cells expressed no surface antigens associated with B lymphocytes. This finding suggests that RBs do not form in cells that can transport glycoproteins to the cell membrane, but rather occur as a result of defective transport or process of certain glycoproteins by plasmacytoid cells.

Antibodies, Monoclonal

Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma.

Thrombomodulin (TM) is a glycoprotein of molecular weight 75,000 kd that is normally present in restricted numbers of cells, including endothelial and mesothelial cells. In this study, the authors tested the possibility of using anti-TM to facilitate the diagnosis of mesothelioma. All of the 31 mesotheliomas and the two mesothelioma cell lines (MS-1 and MS-2) tested were stained positively with anti-TM. The specificity of anti-TM staining in mesothelioma cells was further confirmed by in situ hybridization of MS-1 cells with a TM-specific probe. The expression of TM in MS-1 cells was increased markedly when these cells were induced by 12-0-tetradecanyl phorbol 13-acetate (TPA) to differentiate. The expression of TM in mesothelioma cells, however, did not correlate with any particular phase of the cell cycle. In an attempt to differentiate pleural mesothelioma from pulmonary adenocarcinoma, the authors compared the expression of TM, carcinoembryonic antigen (CEA), and Leu M1 in these two types of tumors. Only four of 48 (8%) pulmonary adenocarcinomas were stained positively by antibodies to TM. Therefore, immunohistochemical staining with antibodies to TM yielded 100% sensitivity and 92% specificity for diagnosis of mesothelioma. All of the mesotheliomas stained negatively for CEA and Leu M1, except for one, which showed minimal focal positivity for Leu M1. In contrast, 79% and 60% of adenocarcinomas stained positively for CEA and Leu M1, respectively. These findings suggest that immunocytochemical staining with anti-TM should be added to the battery of tests to increase the diagnostic sensitivity and specificity for differentiating mesothelioma from pulmonary adenocarcinoma.

Adenocarcinoma

Functional heterogeneity and pathogenic significance of interleukin-6 in B-cell lymphomas.

A possible autocrine effect of interleukin-6 (IL-6) on the growth and differentiation of the tumor cells of 55 B-cell lymphomas was examined. Interleukin-6 was detected in a few types of B-cell lymphomas, including polymorphic immunocytoma (PI), small lymphocytic lymphoma (SLL), and immunoblastic lymphoma (IBL) with or without plasmacytoid differentiation. In PI and in IBL with plasmacytoid differentiation (IBL-P), IL-6 was detected only in immunoglobulin-containing plasmacytoid cells, and it was absent from most proliferating (Ki-67/PCNA-positive) lymphoma cells. In SLL, IL-6 was not observed in lymphoplasmacytoid cells; instead, IL-6 was observed in transformed (Ki-67/PCNA-positive) tumor cells in proliferation centers. The lymphoplasmacytoid cells in SLL exhibited a phenotype (IL-6/glutathione-S-transferase-pi [GST-pi]-negative), different from that of normal plasma cells (IL-6-negative/GST-pi-positive) and from the plasmacytoid cells (IL-6/GST-pi-positive) in PI and IBL-P. In IBL without obvious plasmacytoid differentiation, IL-6 was detected in most tumor cells that were highly proliferative (Ki-67/PCNA-positive). In this study, IL-6 was undetectable in most lymphomas related to follicular centers, in lymphoblastic lymphoma, in small noncleaved cell lymphomas of the Burkitt and non-Burkitt types, and in diffuse large cell lymphoma. This finding is compatible with a previous finding that IL-6 mRNA was absent from follicular center cells in reactive lymphoid tissues. The functions of IL-6 in these lymphomas may be quite diverse. It appears that IL-6, as an autocrine factor, is responsible for the plasmacytoid differentiation of lymphoma cells in IP and some IBL (IBL-P). The differentiation of lymphoplasmacytoid lymphoma cells in SLL, however, may not be mediated by an autocrine IL-6 mechanism. Interleukin-6 may provide a growth signal, rather than acting as a differentiation factor, for some IBL cells and for some transformed tumor cells in proliferation centers in SLL.

Cell Differentiation

Interleukin-6, but not interleukin-4, is expressed by Reed-Sternberg cells in Hodgkin's disease with or without histologic features of Castleman's disease.

Hodgkin's disease (HD) is a neoplastic disease that is characterized by unbalanced and/or unregulated cytokine production. Information accumulated in our own and other laboratories indicates that the cytokines interleukin-1 (IL-1), IL-5, IL-9, tumor necrosis factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), and transforming growth factor-beta (TGF-beta) are secreted by Hodgkin's and Reed-Sternberg (H-RS) cells. These and perhaps additional cytokines are likely to be responsible for the unique histopathologic and clinical alterations seen in patients with HD. In this study, we confirmed that IL-6 is produced by cultured H-RS cells as well as by H-RS cells in tissues. By using an enzyme-linked immunosorbent assay, we found that approximately 2 to 10 ng/ml of IL-6 was secreted by cultured H-RS cells (10(6) cells/ml). In tissues, we were able to immunolocalize IL-6 in the cytoplasm in 10 to 30% of H-RS cells by using rabbit polyclonal and mouse monoclonal anti-IL-6 antibodies. There was no correlation among the IL-6 staining intensity, number of H-RS cells stained, and the degree of plasma cell infiltration. However, in 3 of 17 cases studied, a large number (60%) of H-RS cells were positive for IL-6, and in these patients, abundant plasma cells were present. In one patient, the involved lymph node also showed histologic features similar to those of Castleman's disease. In this patient, we noted abundant IL-6 expression not only in H-RS cells, but also in most reactive histiocytes. The cultured H-RS cells did not express functional receptors for IL-6, and exogenously added IL-6 did not induce proliferation of these cells. We also conducted studies with specific anti-IL-4 antibodies, which did not show IL-4 production by H-RS cells in both cultures and tissues. In tissues, only rare IL-4 positive lymphoid cells or dendritic cells were identified. Thus, the study demonstrated that adequate amounts of IL-6 are required for an abundant plasma cell reaction, and that an additional source of IL-6 from histiocytes is essential for the formation of Castleman's disease-like changes in lymph nodes involved by HD. Furthermore, IL-4 is not likely to be responsible for the T-lymphocyte reaction in tissues, by a mechanism distinct from that in T-cell-rich B-cell lymphomas.

Aged

Correlation of c-fos/c-jun expression with histiocytic differentiation in Hodgkin's Reed-Sternberg cells. Examination in HDLM-1 subclones with spontaneous differentiation.

The c-fos proto-oncogene, which is the normal homolog of the transforming gene carried by murine osteogenic sarcoma viruses, interacts with the protein product of another proto-oncogene, c-jun, to form a heterodimer that can recognize and bind to a specific sequence of nucleotides in the DNA. The expression of c-fos and c-jun is linked to the proliferation of certain cells and the differentiation of others, including those of monomyelocyte lineage. The authors used two cultured Hodgkin's Reed-Sternberg (H-RS) cell lines, KM-H2 and HDLM-1, and their single-cell clones to study the correlation of c-fos/c-jun expression with cell differentiation in H-RS cells. Within 48 hours after induction with phorbol ester (TPA), both parent lines exhibited markedly increased expression of c-fos/c-jun. The expression returned to the preinduction level after 96 hours, however, and the cells retained their differentiated status. The transitory increase in c-fos/c-jun expression suggests that binding of these proteins to a specific promoter in the nucleus triggers a cascade of events that result in cell differentiation. Expression of these proteins may not be required for the cells to maintain their differentiation. The authors selected three groups of sublines of HDLM-1 cells based on their degree of spontaneous cytologic differentiation. The first group, without obvious differentiation, showed a c-fos/c-jun expression pattern similar to that of the parent line. The second group, with moderate differentiation, had a high degree of expression, which decreased on treatment with TPA. The third group, which had morphologic features resembling those of histiocytes, expressed minimal amounts of c-fos/c-jun, irrespective of TPA treatment. These findings provide further evidence that c-fos/c-jun expression is related to differentiation of H-RS cells, and that these proteins are not byproducts of TPA induction. Expression of c-fos/c-jun also was noted in a subpopulation of H-RS cells in tissues; and this expression also was enhanced when these cells were treated with TPA in culture. These findings indicate that H-RS cells can differentiate to become mature-appearing cells in tissues.

Adult

[Preparation of rotundine-chitosan gelled granules and their drug-release tests].

The paper described a delivery system prepared from granulation of a chitosan solution containing rotundine in a coagulating bath and examined the effects of the ratios of rotundine: chitosan, crosslinking agents and molecular weight of chitosan on the analgesic release rate. It was shown that the rotundine (56.7%)-chitosan (Mw:5.70 x 10(5) degree of deacetylation: 72.4%) gelled granules in an artificial gastroenteric juice (pH 1.0 and 7.2) have T50 of 40 and 180 min respectively, and the total release time sustained over 540 min.

Alkaloids

[Enhancing effect of kang shuai sen fang on immune functions of mice].

In this report the authors studied the effects of kang shuai sen fang (KSSF) on the immune functions of mice. The results indicated that KSSF was able to enhance the proliferation response of spleen cells of mice to Con A and LPS. At the dosage of 400 mg/kg.d, KSSF could stimulate the production of plague forming cells (PFC), the DTH response induced by allogeneic splenocytes. The mixed lymphocyte reaction was much stronger in the drug-receiving group than that in the control group. Further study indicated that KSSF was able to enhance the activities of cytotoxic T lymphocyte and the production of interleukin 2.

Adjuvants, Immunologic

Application of target-specific drug immunoconjugates to experimental bone marrow replacement therapy in mice.

Immunoconjugates whose cytotoxic component consists of a phytopeptide are often used as purging agents in bone marrow replacement therapy. Less popular are drug immunoconjugates containing a small molecular weight cytotoxic drug attached to the target-specific conjugand via an appropriate spacer molecule. High target specificity, resistance of the drug to intralysosomal proteases and, once cleaved from the spacer, ready exist of the drug from the lysosome are among the advantages drug immunoconjugates hold over phytotoxin immunoconjugates. The cytotoxic drug daunomycin attached via an acid-sensitive spacer to monoclonal antibody of appropriate specificity was shown to purge murine bone marrow of contaminating tumor cells without affecting its hematopoietic potential. Lethally irradiated mice reconstituted with syngeneic bone marrow from which contaminating lymphoma cells had been removed survived indefinitely. Furthermore, lymphoma-bearing mice, provided they were sufficiently irradiated to eliminate tumor cells in situ, were successfully reconstituted with fully allogeneic bone marrow from which potentially graft-versus-host-reactive T-cells had been purged.

Animals

Cultured Reed-Sternberg cells HDLM-1 and KM-H2 can be induced to become histiocytelike cells. H-RS cells are not derived from lymphocytes.

Two Hodgkin's Reed-Sternberg cell (H-RS) lines, HDLM-1 and KM-H2, have phenotypes and functional properties very similar to those of H-RS cells in tissues. These two types of cells were induced to differentiate with a combination of phorbol ester, retinoic acid, and extracellular matrix. The induced cells displayed the morphology of histiocytes or histiocytelike cells, with a small, round or oval, eccentric nucleus and abundant cytoplasm. In ultrastructural studies, many cytoplasmic projections and rugae were observed. These induced cells exhibited abundant cytoplasmic lysosomal enzymes, such as esterase, acid phosphatase, alpha 1-antitrypsin, or lysozyme. The histiocytic nature of these induced cells was further confirmed by the increased expression of many monocyte/histiocyte markers, including CD11b, CD11c, CD13, CD14, CD15, CD33, CD68, Mac387, and 1E9. In functional tests, the induced cells were shown to produce interleukin-1, tumor necrosis factor, macrophage colony-stimulating factor, and/or prostaglandin E2. Phagocytosis was detected in less than 5% to 10% of the cells when Candida albicans was added to cultures. The results strongly suggest that H-RS cells are related to cells of histiocyte lineage.

Adult

[Immunoregulatory effect of polysaccharide of Acanthopanax senticosus (PAS). I. Immunological mechanism of PAS against cancer].

The effect of PAS against cancer and its immunoregulatory function were studied. The results indicated that PAS was able to inhibit tumor growth and prolong the survival time of tumor-bearing mice significantly at the dose of 100 mg/kg/day, ip. In addition, PAS was also able to increase the response of murine spleen cells to Con A and LPS, the amount of IgM and IgG PFC in murine spleen and the DTH response induced by BSA. These results indicate that the inhibitory effect of PAS on tumor growth is related to the enhanced immune response.

Animals

Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin.

Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice.

Animals

[Thy-1 antigen].

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Animals