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Biomedical subjects

N Asou

Publications and source records attributed to N Asou.

At least 109 records · Page 6Linked to original sources

Rearrangements of T-cell antigen receptor delta chain gene in hematologic neoplasms.

Rearrangements of the T-cell antigen receptor (TCR) delta chain gene were studied in primary neoplastic cells from 137 patients with leukemia or lymphoma. TCR delta gene rearrangements or deletions were observed in all 50 T-cell neoplasms: 5 of 8 CD3- T-cell neoplasms showed rearrangements, whereas biallelic deletion of TCR delta gene was the most common pattern in CD3+ T-cell neoplasm (39 of 42 patients). Rearrangements of TCR delta gene were also detected in 23 of 40 immature B-cell leukemias, including 22 of 25 patients with rearrangements of TCR gamma gene, 2 of 17 mature B-cell neoplasms, and 3 of 30 myeloid leukemias. Thus, TCR delta gene rearrangement or deletion is always found in T-cell neoplasms and is frequently found in immature B-cell leukemias associated with TCR gamma gene rearrangement. Furthermore, TCR delta gene rearrangements associated with the germline configuration of the TCR beta, gamma, and immunoglobulin heavy chain genes were observed in two immature T-cell leukemias, suggesting that TCR delta gene rearrangements precede TCR gamma and beta gene rearrangements. These results indicate that an analysis of TCR delta gene rearrangement provides potential tools to establish the clonality of immature T-cell neoplasms and to identify the normal stages of lymphocyte differentiation.

Antigens, CD↗

[Relapse of gingival tumor during hematological remission in acute promyelocytic leukemia].

A 56-year-old man was admitted to the hospital in April, 1986, with the chief complaint of fatigue. The diagnosis of acute promyelocytic leukemia (APL) was made based on the proliferation of atypical promyelocytes in the bone marrow. No gingival swelling was found on admission. A complete remission was achieved by the BHAC-DMP therapy and maintained by the consolidation therapy and the intensification therapy. In July, 1987, he noticed a solitary gingival tumor around the left lower second molar. The biopsy showed the massive infiltration of leukemic cells, despite the hematological remission. Combination chemotherapy was not effective but the tumor disappeared by irradiation. A hematological relapse occurred in November, 1987, but the second complete remission was achieved by the AB-triple V therapy. He died because of the second hematological relapse in July, 1988. Along with the wide use of intensive chemotherapy for acute leukemia, tumor forming leukemia during the hematological remission, as seen in this case, would be increasing. Thus, we should not overlook any newly formed tumor in the treatment of leukemia.

Aclarubicin↗

["AB-Triple V" therapy of relapsed or refractory acute myelogenous leukemia].

Sixteen adults with acute myelogenous leukemia (AML) in relapse or refractory to conventional therapy were treated with AB-Triple V therapy. This regimen consists of aclarubicin, behenoyl cytosine arabinoside, etoposide, vincristine, and vinblastine or vindesine. Patients who obtained complete remission (CR) were then given monthly three courses of AB-Triple V therapy, and further courses of AB-triple V therapy every three months. Eleven of the 16 patients entered CR, three were no response, and two died early after initial AB-Triple V therapy. Among 11 patients who achieved CR, 7 are alive and in CR during 1 to 13 months, one died of hepatic failure, and three patients died of infection in CR. Systemic arthralgia following the administration of vinblastine were frequently observed. These results indicate that this salvage therapy are useful relapsed or refractory AML. Therefore, the role of this combination chemotherapy as a part of the initial post-remission therapy needs to be evaluated.

Aclarubicin↗

Polyclonal integration of HTLV-I proviral DNA in lymphocytes from HTLV-I seropositive individuals: an intermediate state between the healthy carrier state and smouldering ATL.

We have studied 15 individuals (aged 14-74 years) with antibodies to HTLV-I in their serum and random integration of HTLV-I proviral DNA in their peripheral blood lymphocytes. All but one of these patients suffered from a variety of non-specific complaints which did not correspond to those of adult T-cell leukemia (ATL). All of them were born in Kyushu and Okinawa which are endemic areas for HTLV-I infection; 25% of their family members were also seropositive for HTLV-I. The only haematological abnormality in these patients was the presence of few atypical lymphoid cells in the peripheral blood. The CD4/CD8 ratios were normal but the proportion of Tac positive cells was slightly higher than normal. These individuals with polyclonal integration of HTLV-I proviral DNA seem to represent an intermediate state between smouldering ATL (monoclonal integration) and healthy HTLV-I carriers (with antibodies but no detectable HTLV-I proviral DNA). Patients with this intermediate state of HTLV-I infection may be at risk to progress to ATL. The natural history of HTLV-I infection in humans leading to the development of ATL is reviewed in the light of these new findings.

Adolescent↗

Clinical study on the serum levels of immunosuppressive acidic protein in patients with adult T-cell leukemia.

Serum levels of immunosuppressive acidic protein (IAP) were measured in patients with adult T-cell leukemia (ATL) in order to clarify its significance in this disease. The mean levels in patients with both acute (854 +/- 404 micrograms/ml) and chronic ATL (439 +/- 103 micrograms/ml) were significantly higher than in sera of healthy controls (367 +/- 104 micrograms/ml). However, mean levels in patients with smoldering ATL, healthy T-cell lymphotropic virus type 1 (HTLV-1) carriers and healthy controls showed no differences. Levels in crisis in chronic and smoldering ATL were similar to those in patients with acute ATL. Serial measurements of serum IAP in a number of patients revealed that the levels reflected each patient's clinical course, suggesting a potential for use in evaluating the effects of chemotherapy.

Deltaretrovirus Infections↗

Gene rearrangements of T cell receptor beta and gamma chains in HTLV-I infected primary neoplastic T cells.

Rearrangements of T cell receptor beta and gamma chain (T beta and T gamma) genes were analyzed by Southern blot method in samples from 30 patients with adult T cell leukemia (ATL) and 17 patients with non-ATL T cell neoplasms. The DNA probes used were the constant and joining region of T beta gene and the joining region of T gamma gene. Rearranged bands of T beta gene on one or both allelic chromosomes were detected in all neoplastic T cells, even those of smoldering ATL, in which only a small percentage of peripheral blood T cells were detected as leukemic. T gamma gene was rearranged in the cells of all but one patient, the exception being one ATL patient. In order to test whether any given variable region (V) of T beta gene was expressed in ATL cells, two functionally rearranged V beta sequences of ATL were compared with a V beta sequence from T cells acute lymphoblastic leukemia cells. No significant homologies were noted among the three deduced gene product amino acid sequences, confirming that T beta molecules of ATL cells contained no specific structures in common. The observed heterogeneity of T beta and T gamma gene rearrangements in ATL cells further supported these findings.

Amino Acid Sequence↗

Adult T cell leukemia cell lines that originated from primary leukemic clones also had a defect of expression of CD3-T cell receptor complex.

Surface phenotypes and genotypes of six T cell lines established from four patients with adult T cell leukemia (ATL) were compared with those of fresh ATL cells. The surface antigen densities of CD3 and T cell receptor (TCR) complex examined by OKT3 and WT-31 mAbs on fresh ATL cells were low. But three IL-2-dependent cell lines, SKT-2, SKT-5, and ATL-17-2, established from three patients expressed a high density of CD3-TCR complex on their surfaces. On the contrary, three other cell lines (SKT-1A, SKT-1B, and MMT-2), established from two other patients, expressed a low density of CD3-TCR complex. Genotypic analysis of TCR beta chain (T beta) gene and integration sites of the proviral genome of human T cell lymphotropic virus type 1 demonstrated that SKT-1A, SKT-1B, and MMT-2 were derived from the original leukemic clones. These apparent associations between a defect of expression of CD3-TCR complex and identical genotypes of fresh and cultured cells suggest that the defect of expression of CD3-TCR complex may play a key role for development of ATL.

Adult↗

Autocrine stimulation of interleukin 1 beta in acute myelogenous leukemia cells.

A significant increase in CD25 antigen-positive cells by IL-1 was observed in cells of a patient with M7 acute myelogenous leukemia. Basal proliferation and expression of CD25 antigen by the M7 leukemic cells were inhibited by addition of anti-IL-1 beta antibody in a dose-dependent manner, but not by rabbit anti-IL-1 alpha antibody. Culture supernatants of these leukemic cells contained IL-1 activity, which was specifically inhibited by addition of anti-IL-1 beta antibody, and Northern blot analysis detected intracellular IL-1 beta mRNA. These results indicated that autocrine secretion of IL-1 beta was involved in proliferation of some myelogenous leukemic cells.

Antigens, Surface↗

T cell gamma chain gene rearrangement without T cell receptor beta chain gene rearrangement in two cases of non-Hodgkin's lymphoma.

We report two patients with non-Hodgkin's lymphoma whose neoplastic cells had rearranged T cell gamma chain (T gamma) genes, and had the germ line DNA of T cell receptor beta chain (T beta) and immunoglobulin genes. Surface marker analysis of the neoplastic cells revealed that leukemic cells from one patient were derived from common thymocytes, while in the other patient the clonality and cell lineage could not be identified, probably due to the low percentage of neoplastic cells in the specimen. No phenotypic changes were observed after cultivation with phorbol myristate acetate, except for induction of Tac antigens on cells of one patient. Leukemic cells with only the T gamma gene rearrangement are thought to be precursor T cells that differentiate into mature T cells following T beta gene rearrangement. This suggests that such T cells with only the T gamma gene rearrangement exist among common thymocytes.

Aged↗

T cell gamma gene rearrangements in hematologic neoplasms.

Rearrangements of the T cell gamma (T gamma) gene were studied in primary neoplastic cells from 75 patients with leukemia or lymphoma. T gamma gene rearrangements were observed in 19 of 21 T cell neoplasms; 14 of 21 immature B cell leukemias, including 4 out of 5 patients with rearrangements of both immunoglobulin heavy-chain (JH) and T cell receptor beta chain (T beta) genes; none out of 16 nonlymphoid leukemias. Thus, T gamma gene rearrangement is frequently found in immature B cells and is not always found in T cells showing T beta gene rearrangement, but it is not detected in nonlymphoid cells. Furthermore, T gamma gene rearrangement in cells with the germline configuration of the JH and T beta genes was observed. These results indicate that the detection of T gamma gene rearrangement does not allow a clear assignment to a particular lineage. However, an analysis of T gamma gene rearrangement provides a further potential tool to establish the lymphoid cellular origin and clonality of hematologic neoplasms and identify the normal stages of lymphocyte differentiation.

B-Lymphocytes↗

Genotypic analysis of lymph node cells from patients with phenotypically undetermined cell lymphoma.

Rearrangements of immunoglobulin (Ig) heavy chain (JH) and T cell receptor beta chain (T beta) genes of lymph node cells from 28 patients with malignant lymphoma were studied. Fourteen of 28 patients were diagnosed as undetermined cell lymphomas, since a marked predominance of cells expressing a single light chain of Ig or T cell associated antigens was not demonstrated by phenotypic analysis. Of these patients, JH gene rearrangements were observed in 8 patients, whereas T beta gene rearrangements were detected in 9 patients. Although bigenotypes were seen and cell lineage was not determined in three cases, these results indicate that demonstration of Ig and T beta gene rearrangements is a powerful tool to determine cell lineage and clonality of lymphoma cells that do not express definitive surface phenotypes. Interestingly, 12 of 14 lymphoma cells whose lineage had been determined by phenotypic analysis showed rearrangements of two alleles; however, only single allelic gene rearrangement was observed in 11 of 14 lymph node cells from phenotypically undetermined cell lymphoma.

Genotype↗

HTLV-I seroprevalence in patients with malignancy.

Since many malignancies often occur in patients with smoldering type adult T-cell leukemia (ATL) (5 of 18 cases in this report), the relationship between HTLV-I (human T-cell leukemia virus type I) infection, which is closely associated with ATL, with other malignancies in an HTLV-I endemic area was examined. Among the 394 patients with malignancies and who had not had blood cell transfusions, 61 (15.5%) tested positive for HTLV-I antibody. The prevalence was significantly higher in males older than age 40 years and females of all ages compared to age- and sex-matched healthy individuals. The overall seroprevalence (26.1%) in 291 patients with malignancies and who had had blood cell transfusions was higher than that of those who had not had blood transfusions. There was no significant correlation between the site of malignancy and antibody prevalence. These results suggest the possibility that development of malignancy may contribute to expression of latent HTLV-I infection and that HTLV-I infection may contribute to the risk of other malignancies.

Adolescent↗

Human urinary megakaryocyte colony-stimulating factor in thrombopoietic disorders.

The level of urinary Meg-CSF activity in patients with various thrombopoietic disorders was studied. Five out of eight patients with idiopathic thrombocytopenic purpura had megakaryocytic hyperplasia in the marrow and increased Meg-CSF activity in the urine. Urinary Meg-CSF activity in patients with polycythaemia vera and essential thrombocythaemia was normal. There was a significant inverse correlation between urinary Meg-CSF activity and peripheral blood platelet count but not bone marrow megakaryocyte mass. There was a significant increase of urinary Meg-CSF activity during the period of thrombocytopenia after chemotherapy in patients with acute leukaemia who were in complete remission. The timing of maximal Meg-CSF levels corresponded to the nadirs of platelet counts. These results support the concept that Meg-CSF may play a significant role in the regulation of megakaryopoiesis and/or thrombopoiesis in vivo.

Blood Platelet Disorders↗

Absolute neutrophilia in adult T cell leukemia.

The numbers of neutrophils and platelets and the serum calcium (Ca) levels were examined in 12 patients with lymphoma-type adult T cell leukemia (ATL) and 35 patients with leukemic-type ATL. The same parameters were also studied in 17 patients with non-Hodgkin's lymphoma and 22 patients with acute lymphocytic leukemia as controls. The numbers of neutrophils and the serum Ca levels were significantly higher in leukemic-type ATL (P less than 0.01) and lymphoma-type ATL (P less than 0.05) than in the controls. However, no statistically significant correlation between the numbers of neutrophils and the levels of serum Ca in ATL was observed. Thus, these two abnormal clinical features might be caused by different humoral factors.

Adult↗