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Biomedical subjects

M Kozuru

Publications and source records attributed to M Kozuru.

At least 55 records · Page 3Linked to original sources
PubMed1989

Rearrangement of T-cell receptor delta chain gene as a marker of lineage and clonality in T-cell lymphoproliferative disorders.

We analyzed the rearrangement of T-cell receptor (TcR) delta chain gene in 88 cases of lymphoproliferative disorders; 31 acute lymphoblastic leukemias/lymphoblastic lymphomas (ALL/LBL); 27 adult T-cell leukemias/lymphomas, 9 angioimmunoblastic lymphoadenopathies (AILD); 10 T-cell lymphomas (non-Hodgkin's lymphoma); and 11 Hodgkin's disease. All of 9 T-ALL/LBL cases, of which 4 cases have neither beta nor gamma gene rearrangement, had a new rearranged band of TcR delta locus. Ten of 16 B-lineage ALL/LBL had rearranged band(s) or deletion of TcR delta locus. The rearranged bands were recognized in 2 cases of AILD and 1 case of T-cell lymphoma. All cases of adult T-cell leukemias/lymphomas, 4 of AILD, 4 of T-cell lymphoma, and 8 of Hodgkin's disease had deleted TcR delta locus. Heterogeneous findings of TcR delta locus analysis were observed in AILD, T-cell lymphoma, and Hodgkin's disease. In 16 cases with TcR delta rearrangement, the J delta 1 region was frequently used and the J delta 2 region was rearranged in one AILD. It is suspected that J delta 3 was used in one T-ALL/LBL. There was no correlation between the phenotypic pattern of CD3, CD4, CD8 in T-cell disorders and the rearrangement of the TcR delta gene. These findings suggest that the newly identified TcR delta chain gene rearranges at a very early stage of T-cell ontogeny; prior to the other TcR genes and perhaps at almost the same stage with CD7 expression. The TcR delta gene is useful in assessing clonality for the most immature T-cell neoplasms not showing rearrangement of the other TcR genes. This gene is not lineage specific; however, when used in conjunction with immunoglobulin heavy chain gene, it may be a useful tool to distinguish lymphoid lineage of ALL/LBL.

Gene Rearrangement, T-Lymphocyte↗
PubMed1989

The possible mode of escape of adult T-cell leukaemia cells from antibody-dependent cellular cytotoxicity.

Antibody-dependent cellular cytotoxicity (ADCC) was measured using 51Cr-labelled ATL derived cell lines as the target, peripheral mononuclear cells (PMNCs) from disease-free persons as the effector cells and heat-inactivated serum from patients with ATL or the IgG purified from this. The release of 51Cr was not usually demonstrated in the HTLV-1 non-producing ATL derived cell line (MT-1), but was evident in the HTLV-1 producing ATL derived cell lines (KT 252 and IT 607). The 51Cr-labelled MT-1 cells after induction of HTLV-1 retrovirus by 5-iodo-2'-deoxyuridine (IdUr), showed a remarkable target sensitivity in the ADCC assay. On the other hand, the 51Cr-labelled MT-1 cells after culture with IdUr and ATL patient's serum, had no ADCC sensitivity. The fresh ATL cells immediately separated from ATL patient's blood did not express HTLV-1 virus in the cell and had no ADCC sensitivity as the target. Based on these findings, an antigenic modulation on the ATL cell surface by ATL patient's serum is considered to be the possible mode of escape of ATL cells from ADCC.

Adult↗
PubMed1989

Dual rearrangement of immunoglobulin and T-cell receptor genes in blast crisis of CML.

Dual rearrangement of immunoglobulin and T-cell antigen receptor (beta, delta) genes was demonstrated in a case of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in blast crisis. The blast cells, showing L2 morphology and high activity of TdT, expressed pre-B cell (CD19+, Ia+) and myeloid (CD13+, CD34+) surface antigens but lacket T-cell antigens (CD2-, CD7-). Cytogenetic studies on bone marrow and peripheral blood revealed the Phl chromosome in all metaphases analyzed, majority of which also had the additional chromosome changes, +8, +10, +21. Furthermore, molecular analysis of the breakpoint cluster region (bcr) on chromosome 22 showed a rearrangement, confirming the CML origin of the blast cells.

Blast Crisis↗
PubMed1989

[Impaired superoxide production by neutrophils in myelodysplastic syndrome: correlation with bone marrow karyotype].

Superoxide (O2-) production by neutrophils was examined in 21 patients with myelodysplastic syndrome (MDS), including 13 with primary MDS (p-MDS) and 8 with therapy-related MDS (t-MDS). O2-production of MDS patients was significantly less than that of healthy controls (2.81 +/- 3.51 vs 6.19 +/- 2.41 nmol/min/10(6) PNMs, p less than 0.005). Although no relationship between pathogenesis (primary or therapy related), FAB type and levels of O2- production was observed, O2- production of 11 patients with abnormal bone marrow karyotypes was significantly reduced than that of 10 other patients with normal karyotypes. Furthermore, five t-MDS patients with monosomy for all or part of chromosome no. 7 (-7 or 7q-) showed the lowest level of O2- production, which was significantly different from the level in the patients with other abnormal karyotypes (0.61 +/- 0.29 vs 1.80 +/- 0.31, p less than 0.001). These results suggest that the long arm of chromosome no. 7 may in part play an important role for O2- production by neutrophils.

Adult↗
PubMed1988

Regulation of erythropoietin and burst-promoting activity production in patients with aplastic anemia and iron deficiency anemia.

To clarify the control mechanism of production of erythropoietic growth factors in anemic states, we compared erythropoietin (Epo) and burst-promoting activity (BPA) in patients with aplastic anemia and iron deficiency anemia, using in vitro erythroid progenitor assays. Although serum levels of Epo activity increased in the presence of anemia, the rise was more marked in patients with aplastic anemia. BPA was high only in the sera of aplastic anemia patients. Serum levels of BPA of patients with aplastic anemia negatively correlated with hemoglobin concentrations, while those of patients with iron deficiency anemia did not correlate. In 2 patients with aplastic anemia who responded well to androgen therapy, serum levels of Epo activity and BPA decreased after the hemopoiesis had recovered. These results suggest that serum levels of BPA do not rise in response to anemia only. The elevated BPA levels in sera in cases of aplastic anemia are probably related to a reduction in the number of hemopoietic stem cells. Moreover, we observed that BPA in bone-marrow-conditioned medium (BMCM) from patients with severe aplastic anemia increased more than in the BMCM from patients with severe iron deficiency anemia. Therefore, our findings suggest that the enhanced BPA production depends on a decrease in hemopoietic precursors rather than the anemic state.

Adolescent↗
PubMed1986

Periodical appearance of erythropoietin-independent erythropoiesis in chronic myelogenous leukemia with cyclic oscillation.

A patient with Ph1-positive chronic myelogenous leukemia (chronic phase) had a cyclic oscillation in white blood cells, platelets and percent saturation of transferrin. The cycle comprised about 70 days. The number of circulating granulocyte-macrophage colony-forming units (CFU-GM) oscillated with the same phase, while that of bone marrow CFU-GM and erythroid colony-forming units (CFU-E) oscillated in a reverse phase. At the nadir, we observed an abnormal increase in bone marrow endogenous CFU-E (e-CFU-E). An erythropoietin (Epo) dose-response curve of CFU-E showed a high Epo-sensitivity. Anti-Epo rabbit serum did not inhibit the e-CFU-E colony formation. This indicates that Epo-independent erythropoiesis occurs periodically at the nadir. It is suggested that the interactions between the abnormal stem cell and the hematopoietic regulating system cause cyclic oscillation.

Adult↗
PubMed1986

[A phase II study of epirubicin in acute leukemia: a cooperative group study].

A new doxorubicin analogue, epirubicin (EPI), has been evaluated in 11 institutions throughout Japan in a phase II study in patients with acute leukemia. A total of 41 patients were entered into this study between January 1983 and July 1985, and 34 were considered evaluable. Two patients were added for evaluation of toxicity. There were 25 males and 9 females with a median age of 43 years. Of the 34 evaluable patients, 24 had previously been treated with intensive combination chemotherapy, 21 with anthracyclines. The remaining ten were previously untreated patients. Underlying diseases were acute lymphocytic leukemia (ALL) in 15, acute non-lymphocytic leukemia (ANLL) in 17 and blastic crisis of chronic myelogenous leukemia (CML/BC) in 2. EPI was administered intravenously in two schedules, a high-dose regimen consisting of 24 to 60 mg/m2/day for 3 to 5 days and a low-dose regimen involving 11-17 mg/m2/day for 5 to 8 days. Responses were obtained in 5 (33.3%) of 15 patients with ALL, 3 of these attaining complete remission, 2 (11.8%) of 17 patients with ANLL and one (50.0%) of 2 patients with CML/BC. Out of the 21 patients who had received previous anthracyclines, 4 (19.1%) attained responses. Also, responses were obtained in 23.5% with the higher doses as well as 24% with the lower doses. The remission duration of responders was 1, 1, 3, 3, 3, 16+, 17 and 26 weeks, respectively. The major non-hematologic toxicity was stomatitis which occurred in 15 patients, in 11 of whom the symptoms were severe (Grade 3 or 4). This stomatitis was thought to be the dose limiting factor. On the basis of the above observations, we concluded that EPI was active against acute leukemia, especially ALL. Stomatitis was considered to be the dose-limiting factor, especially in the high-dose regimen. Toxicity was tolerable in the low-dose regimen.

Acute Disease↗
PubMed1986

[Clinical investigation of the therapeutic effects of cefmenoxime in the treatment of infections complicated by hematological diseases].

Therapeutic effects on cefmenoxime hemihydrochloride (CMX, Bestcall), a new synthetic cephem antibiotic, were examined in the treatment of various infections complicated with hematological diseases. The number of patients treated with CMX was 37 including 5 cases of sepsis or suspected sepsis, 14 cases of pneumonia or suspected pneumonia, 5 cases of upper respiratory diseases, 2 cases of urinary tract infections and 11 cases of other infections. All of these infections were complicated with hematological diseases: Acute leukemia, 13 cases; chronic myelocytic leukemia, 1 case; adult T cell leukemia, 3 cases; malignant lymphoma, 8 cases; Hodgkin's disease, 2 cases and myeloma, 3 cases. CMX were administered by a single intravenous injection or by a drip infusion. The dose was between 2 and 6 grams per day. Good to excellent clinical results were obtained in 25 out of 37 cases, total effective rate of 67.6%. No clinical side effects or abnormal laboratory findings attributable to CMX were observed except for light diarrhea in 2 cases. By the clinical investigation, it was demonstrated that CMX was one of safe and effective antibiotics for treating infections in the compromised hosts complicated with hematological diseases.

Acute Disease↗
PubMed1983

Case report of adult T-cell leukemia with preceding long-standing cutaneous involvement.

This report documents an unusual case of adult T-cell leukemia (ATL) with a preceding phase of long-standing cutaneous involvement. After nine months of an aleukemic phase, characteristic leukemic cells of ATL, possessing inducer/helper phenotype without helper function, had appeared. In addition, antibodies to ATL virus-associated antigen (ATLA) were found in the serum of the patient and her family. The patient died after an 18-month clinical course due to generalized cytomegalovirus infection in spite of strong chemotherapy. At autopsy, leukemic involvement was restricted to the skin. We postulate that ATL may originate not only from the lymph nodes but also from the skin.

Aged↗