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Biomedical subjects

T Han

Publications and source records attributed to T Han.

At least 181 records · Page 10Linked to original sources

Combinations of methotrexate (COP or CHOP) in the treatment of previously untreated and treated lymphomas.

A regimen consisting of two courses of methotrexate (MTX) with leucovorin rescue followed 1 week later by cyclophosphamide, vincristine, and prednisone (MTX-COP) was studied in ten patients with disseminated diffuse non-Hodgkin's lymphoma who had had no prior chemotherapy. A similar regimen with the addition of doxorubicin (MTX-CHOP) was used for patients who had had previous chemotherapy: 11 with diffuse non-Hodgkin's lymphoma and two with Hodgkin's disease. The response rate to initial MTX administration was 55%, and the clinical onset of effect was usually observed within 48 hours. Responses were observed in previously treated and untreated patients. The remission rate was 100% with both regimens. There were seven complete remissions with MTX-COP and six with MTX-CHOP. The median durations of remission were 23 and 13 months, respectively; median survival was not reached in either group. MTX was well-tolerated by both groups of patients without serious toxic effects. Overall, significantly more hematologic toxicity was observed in previously treated patients; however, no life-threatening toxic effects were observed in either group. The incorporation of MTX and other antimetabolites into schedules of chemotherapy for previously treated and untreated patients with non-Hodgkin's lymphoma is well tolerated and deserved further exploration.

Adult↗

The presence of monoclonal cytoplasmic immunoglobulins in leukemic B cells from patients with chronic lymphocytic leukemia.

It has generally been assumed that CLL B cells do not contain cytoplasmic immunoglobulin (Cylg), although these cells express surface membrane immunoglobulin (Smlg). The present study, in which Smlg and Cylg determinations were performed simultaneously using leukemia B cells from 20 patients with CLL, demonstrates that Cylg staining was detectable in each CLL cell population examined and that the intensity of cytoplasmic immunofluorescent staining in each instance was moderate to strong. Both Smlg and Cylg light chain determinations indicated monoclonality in all 20 cases. The heavy chain class of Smlg and Cylg in each CLL cell population was not uniformly comparable, however. The majority (15 cases) of CLL B cells contained mu heavy chain Cylg and mu and delta heavy chain Cylg was demonstrated in the remaining 6 cases. In contrast, the Smlg phenotypes appeared heterogeneous with both gamma and alpha chain determinants found associated with mu or mu and delta chains on the same leukemia cell populations. This apparent polyclonal Smlg staining pattern was most likely due to nonspecific adsorption of the patient's own serum Ig by Fc receptors on CLL B cells. It is concluded that the great majority of CLL B cells contain detectable Cylg and that Cylg determination is superior to Smlg phenotyping in documenting the monoclonality of CLL.

B-Lymphocytes↗

The influence of histologic type on survival in non-Hodgkin's lymphoma.

Histologic groups in 231 cases of malignant lymphoma were correlated with survival data at 100 months from the time of initiation of the study. Patients in the first two decades of life fared comparably with adults, but those over 60 years of age showed a poorer survival trend. Seven favorable and four unfavorable histopathologic groups were found with collective median survivals of 83 and 16 months, respectively (P less than 0.001). The favorable group included three follicular classes (cleaved, mixed, and large noncleaved) and four diffuse classes (small lymphocytic, cleaved, Burkitt non-cleaved, and convoluted lymphocytic). The unfavorable group consisted of four diffuse classes (plasmacytoid lymphocytic, mixed, and small and large non-cleaved). The group of 88 patients with follicular lymphoma had significantly longer overall survival than the group of 143 patients with diffuse lymphomas. No significant differences in survival were noted within three grades of follicular involvement. The favorable and unfavorable diffuse lymphomas had collective median survivals of 82 and 16 months, respectively (P = 0.01). Significant survival differences due to pattern of nodal involvement (P = 0.01) were found in patients with mixed and large non-cleaved cell lymphomas, but not in those with cleaved cell lymphomas. The group with large cleaved cells had significantly longer survival than those with large non-cleaved cells. Patients with mixed and large non-cleaved cell lymphomas of the same nodal pattern had similar survival data.

Adolescent↗

Marker profiles of human leukemia and lymphoma cell lines.

By means of the multiple marker analysis, a total of 55 human leukemia-lymphoma cell lines which included 15 T-cell, 30 B-cell, four myelomonocytic-cell, and six non-T, non-B cell lines was characterized for their marker profiles. The multiple markers used included a number of cell surface markers as detected by either rosette or immunofluorescence tests, enzyme assays, cytogenetic analysis, and certain functional assay. Based on the criteria previously defined it was found that all the cell lines were proved to represent original leukemia-lymphoma of ALL, AML, CLL, CML in blastic phase or variety of lymphomas. The monoclonality, a "frozen" state at a specific state of differentiation-maturation, and cytogenetic marker in each leukemia-lymphoma cell line were remarkable common properties and were stable for years of cultivation. Similar, if not identical, general characteristics were observed in the study on 344 cases of uncultured fresh leukemia-lymphomas by the multiple marker analysis. While no single marker specific to any type of tumor was found, the study offers not only a basis for better understanding of the biology of leukemia-lymphoma but also an insight into normal hematopoietic cell differentiation in man.

Antigens, Neoplasm↗

Immunoregulatory T cell function in multiple myeloma.

Multiple myeloma is a malignancy characterized by uncontrolled monoclonal B cell differentiation and immunoglobulin production. In most instances, there is concomitant reduction in polyclonal differentiation and immunoglobulin synthesis both in vivo and in vitro. In in vitro pokeweed mitogen-induced B cell differentiation assays, proliferation and polyclonal immunoglobulin secretion optimally requires T cell help and can be inhibited both by monocytes and suppressor T cells. Helper function and monocyte-mediated suppression are relatively radio-resistant whereas T suppressor function is sensitive to 2,000 rad x-irradiation. We have examined myeloma T cell subset function in this assay using recombinations of isolated patient and normal B cells, T cells, and T cell subsets. Monocytes were removed by a carbonyl iron ingestion technique, normal and myeloma T cells were fractionated on the basis of Fc receptors for immunoglobulin (Ig) G (Tgamma) or IgM (Tmu or T non-gamma), and proliferation and IgG secretion after co-culture determined by [(3)H]thymidine incorporation and radio-immunoassay, respectively. Myeloma B cells demonstrate quantitatively and qualitatively normal blastogenic responses and are appropriately regulated by either autologous or allogeneic T helper and suppressor subsets. Despite normal proliferation, however, myeloma B cells remain deficient in subsequent differentiation and immunoglobulin secretion even when co-cultured in the absence of monocytes or suppressor T cells and the presence of normal helper cells. Myeloma T cell populations, in contrast, are entirely normal in helper capacity over a range of T:B ratios but are markedly deficient in radiosensitive and concanavalin A-induced suppressor activity. T suppressor cell dysfunction in multiple myeloma is apparently due to a deficit in the T non-gamma suppressor subset, whereas Tgamma cells, although proportionately reduced, are functionally normal. This unique T suppressor deficit reflects the heterogeneity of suppressor mechanisms in this disease and may represent a compensatory response to the monoclonal proliferation or the involvement of regulatory T cells in the pathogenesis of the malignancy.

Antigens, Surface↗

Indomethacin-mediated enhancement of lymphocyte response to mitogens in healthy subjects and lung cancer patients.

Indomethacin (prostaglandin synthetase inhibitor) was found to be capable of enhancing the mitogen-induced lymphocyte proliferative responses of healthy subjects and patients with lung cancer. A whole-blood culture technique was used. Indomethacin had no mitogenic activity. We observed a greater enhancement of lymphocyte response by indomethacin in weak responders as compared with strong responders in healthy subjects and lung cancer patients. A greater enhancement was also noted in lung cancer patients with active disease as compared with lung cancer patients in remission. In a separated cell culture system, the indomethacin exerted no effect on purified T cells in the absence of monocytes, while this agent exerted its enhancement effect on T lymphocyte response in the presence of autologous monocytes of lung cancer patients. This suggests that monocytes (suppressor cells) may secrete prostaglandins, which are responsible for the impairment of T lymphocyte response in lung cancer patients.

Adult↗

Malignant lymphoma of pre-T-cell type terminating in acute myelocytic leukemia. A case report with enzymic and immunologic marker studies.

We report a case of a T-zone malignant lymphoma of a cervical lymph node developing in a 25-year-old man. Only 14% of the marrow was originally involved, but within two months massive, leukemic dissemination ensued. The blast cells were unable to bind sheep erythrocytes (E) but expressed human thymus leukemia antigen (HTLA) and common ALL-stem-cell (cALL) antigen and had high terminal deoxynucleotidyl transferase (TdT) and acid phosphatase activity. These findings suggest a malignant lymphoproliferative disorder of pre-T-cell type. Complete remission was achieved with intensive chemotherapy. Two months later, acute myelomonocytic leukemia was diagnosed; at this time, over 90% of the blast cells were peroxidase, sudan black, and chloracetate-esterase positive. Consistent with loss of high TdT activity and HTLA and cALL antigens, 86% of the blasts now expressed Ia-like antigens. Cytogenetic studies demonstrated hyperdiploidy. Reports of granulocytic leukemia in lymphoma are reviewed in the context of the above findings and the hypothesis that a leukemogenic factor affects a multipotential stem cell.

Acid Phosphatase↗

Role of suppressor cells in depression of T lymphocyte proliferative response in untreated and treated Hodgkin's disease.

The present study was undertaken to elucidate the type and the role of suppressor cells on T lymphocyte response to PHA in untreated and treated patients with Hodgkin's disease. The mean value of peripheral blood T lymphocyte response to PHA in untreated or treated patients was lower than that in healthy subjects. However, the difference was not statistically significant. There was no significant difference in T lymphocyte response between localized and generalized stage or between different cell types in both active and remission Hodgkin's disease patients. The mean T lymphocyte response to PHA of active patients without systemic symptoms (A), on the other hand, was significantly higher than that of active patients with systemic symptoms (B). The mean value of T lymphocyte response in the presence of monocyte-enriched E- cells was significantly lower, whereas the mean value in the presence of monocyte-depleted E- cells was only moderately lower than that in the absence of these non-T cells in active patients. The mean value of PHA response of T lymphocytes with monocyte-enriched or monocyte-depleted E- cells was only slightly lower than PHA response without these cells in remission patients. No suppressor cell activity of T cells was observed in both active and remission patients. The only significant difference in the suppressor cell activity of monocyte-enriched E- cells on the T lymphocyte response to PHA was observed between localized and generalized stage in patients with active disease. Unlike peripheral blood monocyte-enriched E- cells, the splenic monocyte-enriched E- cells possessed no significant suppressor cell activity on the splenic T lymphocyte response to PHA in active Hodgkin's disease patients. These observations suggest that the depression of in vitro cell-mediated immunity seen in patients with active Hodgkin's disease may be due to the non-specific suppression of T lymphocyte response by monocytes, in addition to a possibly intrinsic defect of T lymphocytes.

Adult↗

Appraisal of aspiration cytology in management of Hodgkin's disease.

The value of aspiration cytology in the management of Hodgkin's disease is shown in this study of 228 patients and 403 aspirations; 385 from lymph nodes and 18 from extranodal masses. In all patients the initial diagnosis was established on surgical biopsy. Aspirates were helpful in staging, defining extension of unusual radiation fields, and in recognizing residual disease and relapses after therapy. Adequate material was obtained in 80% of aspirations. The diagnosis of Hodgkin's disease could not be established in the adequate cytologic sample in 9.9% of cases. In 5.5%, the diagnosis was that of benign reactive hyperplasia and in 4.4%, non-Hodgkin's lymphoma. Unsatisfactory material was usually obtained from nodes less than 1 cm in diameter or from residual lesions following radiation or chemotherapy. Only 14 of 93 such lesions proved to have active disease during follow up. There were no significant complications. Characteristics of the varied aspects of aspirated tumor cells found in Hodgkin's disease are described.

Adolescent↗

Splenic T and B lymphocytes and their mitogenic response in untreated Hodgkin's disease.

The splenic T and B cell distribution in 79 patients with untreated Hodgkin's disease was quite similar to that in 15 control patients with non-Hodgkin's lymphoma or carcinoma. The mean T lymphocyte percentage was slightly higher in involved spleens than in uninvolved spleens of patients with Hodgkin's disease. There was no significant difference in the T and B cell distribution between tumor area and tumor-free area of the same spleens of Hodgkin's disease patients. Splenic T and B cell distribution did not correlate well with the clinical features of Hodgkin's disease. The splenic T cell percentage was significantly lower than that of the peripheral blood T cell percentage (P less than 0.05), while the splenic B cell percentage was significantly higher than peripheral blood B cell percentage (P less than 0.01) in 13 patients with untreated Hodgkin's disease. The splenic T lymphocyte response to PHA was significantly higher than the peripheral blood T lymphocyte response (P less than 0.05), and the splenic B lymphocyte response to PHA, in the presence of irradiated autologous splenic T lymphocytes, was also significantly higher than the peripheral blood B lymphocyte response (P less than 0.05) in 8 and 6 patients with untreated Hodgkin's disease, respectively. Since the control splenic cells, utilized in this study were obtained not from patients with non-neoplastic disease, but from patients with neoplastic disease other than Hodgkin's disease, our data are not conclusive, but only suggestive of normal T and B cell distribution and function in uninvolved spleens of patients with untreated Hodgkin's disease.

Adolescent↗

Malignant lymphoma with a high content of epithelioid histiocytes: report of T-cell variant of so-called Lennert lymphoma and review of the literature.

The present report describes the first case of well-differentiated nodular lymphocytic lymphoma evolving into Lennert lymphoma of T-cell origin. A 58-year-old white female developed malignant lymphoma, well-differentiated, lymphocytic type, nodular, with focal bone marrow involvement (stage IV) in May 1975. She received 16 cycles of cyclophosphamide and prednisone combination chemotherapy which was completed in October 1976. A complete remission was achieved. In December 1976, she relapsed and was treated with cyclophosphamide, vincristine, bleomycin, and prednisone until May 1977. Lymphadenopathy decreased until August 1978, but then increased again. Biopsy of an axillary lymph node was interpreted as Lennert lymphoma. She received methotrexate, cyclophosphamide, vincristine, adriamycin, and prednisone beginning in September 1978. When last seen in November 1979, she was in partial remission. Lymphoid cells obtained from lymph node which was involved with Lennert lymphoma consisted of 93% standard E-rosettes and 83% gravity E-rosettes. Cytoplasmic immunoglobulin on frozen sections was negative, but acid phosphatase (ACP) and alpha-naphthyl acetate esterase reactions were strongly positive. These findings support a T-cell proliferation in Lennert lymphoma. A review of the literature reveals only four cases of Lennert lymphoma of T-cell origin.

Drug Therapy, Combination↗

Expression of MLR-S in human myeloid, monocytic and erythroid cell differentiation.

The present study describes a comparative study of MLR-S of various stages of fresh and cultured normal or leukemic myeloid, monocytic and erythroid cells. "One-way" MLR was performed, using a slightly modified whole blood method. Fresh leukemic myeloblasts from patients with acute myelocytic leukemia or chronic myelocytic leukemia, in blastic crisis possess a strong MLR-S whereas fresh granulocytes from patients with chronic myelocytic leukemia or from healthy subjects possess no MLR-S. Cultured leukemic myeloblasts from KG-1 or ML-1 cell line possess a very strong or a moderate MLR-S, whereas cultured leukemic promyelocytes from HL-60 cell line possess little or no MLR-S. Fresh leukemic erythroblasts or cultured leukemic erythroblasts from K-562 cell line exert a strong MLR-S whereas fresh erythrocytes exert no MLR-S. Cultured monoblasts from HPL-SK-1 or Murray cell line possess a very strong MLR-S whereas fresh monocytes from healthy subjects or from a patient with chronic monocytic leukemia possess a moderate MLR-S. These observations clearly indicate that there is a good correlation between the MLR-S and the cell differentiation stage. Observations in the present study also support the hypothesis that the MLR-S is a differentiation antigen which is completely lost by the terminal stage of myeloid or erythroid cell maturation or partially lost by the terminal stage of monocytic cell maturation.

Cell Line↗

Establishment and characterization of human B-lymphocytic lymphoma cell lines (BALM-3, -4 and -5); intraclonal variation in the B-cell differentiation stage.

This study describes the establishment of three non-Burkitt B-lymphoma cell lines (BALM-3, BALM-4 and BALM-5) originating from the pleural effusion of a patient with a poorly differentiated diffuse lymphocytic lymphoma. The cells of BALM-3, -4 and -5 exhibited a number of properties which distinguish them from the usual B-cell type lymphoblastoid cell lines. Thus, they lacked the Epstein-Barr virus genome and had abnormal chromosome constitutions including a 14q+ marker. The presence of the identical surface immunoglobulin isotypes (gamma and chi chain determinants), and Ia-like B-cell-associated antigen in the cultured cells and in the "fresh" lymphoma cells in vivo was demonstrated. These findings strongly suggested that these cell lines have B-cell characteristics and were derived from the original tumor cell population. BALM-5 cells, however, showed somewhat different growth, cell surface marker profile and functional characteristics compared to those of BALM-3, and -4 cells. These variations suggest that the BALM-5 cells were probably at different stages of B-cell maturation than those of BALM-3 and -4, even though all three cell lines (established in three separate flasks) originated from the cells of the same pleural effusion of a lymphoma with monoclonal B-cell characteristics.

Antigens, Surface↗

In vitro functional studies of mononuclear cells in patients with CLL: evidence for functionally normal T lymphocytes and monocytes and abnormal B lymphocytes.

In vitro functional studies of mononuclear cells from 34 patients with B-cell type CLL were investigated and the results of these studies were as follows: 1) The T lymphocytes from patients with CLL were capable of responding normally to PHA or PWM, of inducing allogeneic normal B lymphocytes to respond to these mitogens and of stimulating normally to allogeneic lymphocytes in "one-way" mixed lymphocyte reaction; 2) The monocytes from these patients were capable of enhancing the T lymphocyte response to mitogens and of stimulating normally to allogeneic lymphocytes; and 3) The leukemic B lymphocytes were incapable of responding to mitogens even in the presence of normal T lymphocytes and their enhancer cell activity on T lymphocyte response or their stimulating capacity on allogeneic lymphocytes was depressed. These observations suggest that the T lymphocytes and monocytes from patients with CLL are functionally normal while the leukemic B lymphocytes from these patients are functionally abnormal.

Adult↗