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Biomedical subjects

M Ichimaru

Publications and source records attributed to M Ichimaru.

At least 163 records · Page 9Linked to original sources

Changes of adult T cell leukemia cell surface antigens at relapse or at exacerbation phase after chemotherapy defined by use of monoclonal antibodies.

Surface phenotypes of leukemic cells from six patients with adult T cell leukemia (ATL) were analyzed by the use of monoclonal antibodies, both at the time of initial diagnosis and at either relapse or exacerbation phase after chemotherapy. Changes of cell surface antigens were observed in four of the six cases. The majority of the leukemic cells of these patients were reactive with anti-Leu-1 and anti-Leu-3a, but unreactive with anti-Leu-2a and MAS 036c monoclonal antibodies at the time of initial diagnosis, indicating that ATL cells are of peripheral inducer/helper T cell origin. In three cases, the Leu-1 antigen disappeared at relapse or at exacerbation phase, and in one of these cases, a small percentage of ATL cells became reactive with MAS 036c, which identifies cortical thymocyte antigen. ATL cells of one other case did not have Leu-1 antigen from the start, but gained Leu-2a antigen at exacerbation phase and became double-labeled cells (Leu-2a+, 3a+), which is known to be a feature of thymocytes. Thus, it appeared that ATL cells sometimes change their surface phenotype to that of an earlier stage of T cell differentiation at relapse or at exacerbation phase. Chronic myelocytic leukemia (CML) cells also usually change to immature cells at blastic crisis involving morphological change. However, this morphological change was not so prominent in the ATL cases studied, except one, in which typical ATL cells with nuclear indentation changed to large immature cells with basophilic cytoplasm at relapse.

Adult↗

Preparation of polyamine antibody and its use in enzyme immunoassay of spermine and spermidine with beta-D-galactosidase as a label.

An enzyme immunoassay for polyamines is described which uses beta-galactosidase labeled spermine and antiserum raised in rabbits against spermine-bovine serum albumin synthesized by coupling spermine to mercaptosuccinylated bovine serum albumin with a bifunctional cross-linker, N-(gamma-maleimidobutyryloxy)-succinimide. The lower limit of detection by this assay, which involves a double antibody technique for the separation of antibody-bound and free antigen, was 1 ng of spermine per tube. The anti-spermine serum showed 88% cross-reaction with spermidine but only 0.13% with putrescine, 0.08% with 1,3-diaminopropane, and 0.04% with cadaverine. The method has been used to measure serum polyamine levels in healthy subjects and cancer patients, in whom mean concentrations of 58.1 ng/ml and 94.8 ng/ml (as spermine), were respectively noted. This enzyme immunoassay is specific, accurate and easy to perform, and appears suitable for routine clinical use.

Animals↗

Establishment and characterization of 10 cell lines derived from patients with adult T-cell leukemia.

By using human T-cell growth factor (TCGF), 10 cell lines were established from tissue samples of 10 patients with adult T-cell leukemia (ATL). Three cell lines were adapted to growth in medium lacking TCGF. The surface markers of all cell lines were characteristic of inducer/helper T cells, i.e., OKT3+, OKT4+, OKT6-, OKT8-, OKIa1+, and human Lyt2+ and Lyt3+, except that one cell line was OKT3-. The expression of the viral antigen was examined during establishment of 8 of the 10 cell lines. The viral antigen was not expressed in leukemic cells before cultivation. In 5 lines, the viral antigen was detected by immunofluorescent staining after a short period of cultivation. However, 3 cell lines, ATL-6A, ATL-9Y, and ATL-1K did not express the viral antigen during short-term culture: the ATL-6A and ATL-9Y cell lines became positive for the viral antigen after 5 and 2 months of cultivation, respectively; the ATL-1K cell line remained antigen-negative throughout a culture period of 13 months. Southern blot hybridization assay showed that all of the cell lines, including the viral antigen-negative ATL-1K cell line, contained the viral genome. Thus, the retrovirus was associated with all 10 cell lines established from ATL patients, but there was a heterogeneity in the expression time of the retroviral antigen in leukemic cells maintained in vitro. Our findings suggested that the expression of the viral antigen was not required for maintenance of the leukemic state in vivo and for growth of leukemic cells in vitro.

Antigens, Surface↗

[Combination chemotherapy using peplomycin for the treatment of non-Hodgkin's lymphoma including adult T cell leukemia].

Peplomycin containing combination chemotherapy with cyclophosphamide, hydroxy-daunomycin, oncovin and prednisone (CHOP-P) was performed in one patient with ATL and 8 patients with advanced diffuse lymphoma. CHOP-PM combination chemotherapy plus MTX was applied to 6 patients resistant to CHOP-P regimen. The overall complete remission rate was 53%, and 67% in non-T cell type and 50% in T cell type. However, only one patient out of 4 ATL patients showed complete response. Toxicities such as transient fever, myelotoxicities, G-I tract symptoms, hair loss and interstitial pneumonitis, were observed. Only in one out of 4 patients suspected drug-induced pneumonitis by peplomycin was observed. This regimen including peplomycin is considered to be one of the useful combination chemotherapies for diffuse lymphoma, especially non-T cell type and some of T cell type, except ATL.

Adult↗

Adult T-cell leukemia-lymphoma-related diseases in the Nagasaki District.

The clinical, hematological and pathological features of the adult T-cell leukemia (ATL)-related diseases and their cell membrane phenotypes in the Nagasaki district, one of the ATL-endemic areas, were delineated to compare them with those of adult T-cell leukemia-lymphoma (ATLL). In addition, the participation of ATL virus (ATLV) in the ATL-related diseases was investigated on the basis of a study of ATLV-associated antigen (ATLA) and anti-ATLA antibody. ATLA and/or anti-ATLA antibody could be detected in the ATL-related diseases, including persistent T-lymphocytosis with morphologically abnormal T-lymphocytes, T-cell chronic lymphocytic leukemia (T-CLL) of helper T-cells, T-cell malignant lymphoma of the skin, some seronegative helper T-cell malignant lymphomas and monomorphic T-cell leukemia with round nuclei. These results suggest that those cases in the Nagasaki district, though clinically different from each other, might be the same T-lymphoproliferative disease of possible viral etiology associated with ATLV. On the other hand, persistent T-lymphocytosis seems to be an infectious condition caused by ATLV and partly a preclinical stage of ATLL in view of the clinicohematological features.

Aged↗

Adult T-cell leukemia-associated antigen (ATLA) and anti-ATLA antibodies in patients with Hodgkin's disease in the Nagasaki District.

Seven patients with Hodgkin's disease in the Nagasaki district were examined for adult T-cell leukemia-associated antigen (ATLA), a human retrovirus-associated antigen, and anti-ATLA antibodies. Anti-ATLA antibody reactivity with the ATLA-positive cultured cells from an ATL patient was demonstrated in four (57.1%) of seven patients. This suggests that infection by a human retrovirus may be closely associated with Hodgkin's disease in the Nagasaki district. However, ATLA could not be induced in the cultured mononuclear cells taken from biopsied lymph nodes of the three patients examined. Hence, it is necessary to collect more direct evidence in the search for a viral etiology of Hodgkin's disease.

Antibodies, Viral↗

[Clinical features of adult T-cell leukemia].

Adult T-cell leukemia (ATL) is T-cell leukemic non Hodgkins' malignant lymphoma; 73 percent of 199 non Hodgkins' lymphomas were of T-cell origin, and 58 percent of these T-cell lymphomas were ATL in Nagasaki, Japan. ATL cells are mostly characteristic in the specific nuclear indentations. These cells have a commonly helper T-cell phenotype on the reaction to the Leu series monoclonal antibody, and the cells showed a suppressor function to normal B-cell differentiation by PWM. Miscellaneous infections, probably due to T-cell disfunction have been frequently experienced in ATL. Pulmonary infections, especially interstitial pneumonitis, were characteristic. Bone destraction through osteocrast proliferation was suggested to be the main cause of hypercalcemia. Many cases with familiar disposition have been found in ATL and T-ML, and 3 siblings having ATL and T-ML were presented. ATLA antibody was positive in all cases of ATL and 63 percent of T-ML. Positive rate of ATLA antibody in healthy spouses and siblings of ATL and T-ML patients was high. ATLA (antigen) on the mononuclear cells of almost all the ATL and ATLA antibody positive T-ML was positive. Peripheral blood mononuclear cells of 2 cases of mycosis fungoides were also positive for ATLA. Probably pre ATL cases with low grade leukocytosis and the presence of ATL cell like lymphocytes and positive rate of ATLA antibody and antigen of these cases were presented. By the chromosome study of 14 cases of ATL, chromosome aberrations of No. 2, 3 and 18 were frequently observed.

Adolescent↗

[Effect of human lymphoblast interferon in adult T-cell leukemia and non-Hodgkin's lymphoma].

Four patients with adult T-cell leukemia (ATL) and 4 patients with non-Hodgkin's lymphoma were treated with alpha-type interferon (Human Lymphoblastoid Interferon: HLBI). Treatment regimen consisted of 3 to 12 million units (MU) of HLBI given intramuscularly once daily. The total dose varied from 36 to 520 MU. Complete remissions were obtained in one of 4 patients with ATL and one of 3 patients with B-cell lymphoma. A partial remission was yielded in one patient with B-cell lymphoma. An overall response rate (CR + PR) was 37.5%. Toxicity included flu-like symptoms, myelosuppression, G-I tract symptoms, fatigue, high fever and hepatic disturbance. On the basis of this study, we have concluded that HLBI is effective for the treatment of ATL and B-cell lymphoma.

Adult↗

A study of leukemic cell migration by an agarose plate method.

By means of inducing random migration of leukemic cells in human peripheral blood by an agarose plate method, a study was made to see how migration distance and cell morphology after migration differed with the type of leukemia. After 3 days of incubation, the distance of random migration in cells of lymphocytic leukemia patients was on the average 0.41 mm for the cells of 13 patients with adult T-cell leukemia/lymphoma and 0.03 mm for the cells of four patients with chronic lymphocytic leukemia which were all of B-cell origin. Thus leukemic cells of T-cell origin migrated farther than those of B-cell origin. In the cases of myelocytic leukemia, the distance of random migration was on the average 0.54 mm for the cells of five patients with acute myelocytic leukemia, 2.42 mm for the cells of three patients with acute myelomonocytic leukemia, 1.69 mm for the cells of four patients with chronic myelocytic leukemia at blastic crisis and 3.78 mm for the cells of one patient with chronic monocytic leukemia. Thus, cells of monocyte origin migrated quite well. Migrating cells differing from cells of smear samples retained their original natural morphology and were considered to serve as an aid in the differentiation of types of leukemia.

Adult↗

Clinical, hematologic, and pathologic features of leukemic T-cell lymphoma.

Cells obtained from malignant lymph nodes and the peripheral blood of 106 patients with non-Hodgkin's lymphomas were examined for T- and B-cell characteristics. Surprisingly, 79 cases were of the T-cell type on the basis of spontaneous rosette formation with sheep erythrocytes (E-rosettes). Of the remaining cases, 15 were B-cell in nature (monoclonal S-Ig positive), seven were non T-, non B-cell and four cases were undetermined. Forty-nine (62.0%) of the T-cell malignancies were of a leukemic variety, characterized by pleomorphism in the peripheral blood cell size, and histological appearance. Most of the leukemic T-cells showed obvious lymphocytic differentiation, with condensed nuclear chromatin and scant cytoplasm, although in many of the cases, the lymphomatous infiltrate was dominated by large or pleomorphic lymphoid cells. All tumors were of a diffuse variety, and on histologic examination included a mixed type (21 cases), PDLL forms (15 cases), a large lymphoid cell type (eight cases), and WDLL forms (five cases). Although the mixed type with a pleomorphic lymphoid infiltrate was distinctive, there has been considerable variation from case to case. Clinically this unusual t-cell, leukemic variety of non-Hodgkin's lymphomas primarily involved middle-aged and elderly subjects, and was characterized by wide spread organ invasion (preferentially to the liver, spleen and skin), resistance to chemotherapy, and a poor prognosis. A mediastinal mass was not observed in all cases. The patients had a median survival of only ten months.

Adolescent↗

Antibodies to adult T-cell leukemia-virus-associated antigen (ATLA) in sera from patients with ATL and controls in Japan: a nation-wide sero-epidemiologic study.

A nation-wide sero-epidemiologic survey of adult T-cell leukemia virus (ATLV), detected es anti-ATLA (ATLV-associated antigen), was made in Japan. Sera from adult donors in 15 different locations were screened for anti-ATLA. High incidences (6 to 37%) of antibody-positive donors were found in seven regions, one in northern Japan, and the others in southwestern regions. These areas are ATLV-endemic areas corresponding to ATL-endemic areas. Examination of sera from healthy donors aged 6 to 80 years in ATL-endemic areas showed an age-dependent increase of seropositive donors with a maximum of about 30% at 40 years of age. Anti-ATLA was found in all but two of 142 patients with ATL. Anti-ATLA-positive patients with ATL were mainly found in ATLV-endemic areas, and only a few in ATL-nonendemic areas. Six patients with cutaneous T-cell lymphoma in ATLV-nonendemic areas gave a negative reaction for anti-ATLA. The geometric mean titer of anti-ATLA of patients with ATL was higher than that of healthy donors.

Adult↗