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T Machii

Publications and source records attributed to T Machii.

At least 73 records · Page 4Linked to original sources

Association of protein tyrosine phosphorylation with B cell differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA).

We have assessed whether tyrosine protein kinase (TPK) is involved in B cell differentiation. In vitro phosphorylation of an endogenous substrate in B cell leukemias showed that leukemic B cells at different stages of differentiation had specific endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. To clarify the relationship between TPK and the process of B cell differentiation, we studied protein tyrosine phosphorylation in two kinds of leukemic B cells, which showed distinct responses to TPA (12-O-tetradecanoylphorbol-13-acetate) in B cell differentiation. TPA-treated leukemic B cells from patients with B cell chronic lymphocytic leukemia (B-CLL) differentiated into cytoplasmic immunoglobulin (clg)+ plasmacytoid cells, while TPA-treated leukemic B cells from patients with hairy cell leukemia (HCL) did not differentiate into clg+ cells, but showed a peculiar morphological change, spreading. Untreated B-CLL cells and HCL cells showed similar TPK activities and tyrosine protein phosphorylation. When treated with TPA, enhanced phosphorylation was seen in B-CLL cells, while a clear reduction in phosphorylation was found in HCL cells. However, using 4-hydroxycinnamide derivatives which reduce TPK activity, we found that only the reduction of TPK activity did not lead HCL cells to spreading. These data suggest that protein tyrosine phosphorylation and/or dephosphorylation might be involved in B cell differentiation, but only the change of TPK activity in HCL cells is not sufficient to induce effects.

B-Lymphocytes↗

[Mycotic liver and spleen abscesses successfully treated by intraportal and intrahepatosplenic arterial administration of antimycotic drugs in two cases with acute leukemia].

Case 1. A 34-year-old male was admitted in July, 1986 with a diagnosis of AML (M2). Two courses of BHAC-DMP regimen induced complete remission in October, while marked pyrexia resistant to antibiotics remained. An ultrasonography (US) and computed tomography (CT) revealed multiple liver and spleen abscesses suspected of mycotic etiology. Administration of amphotericin B (AMPH-B) by intravenous injection was difficult owing to its severe side effect. Multiple abscesses increased in the size and number despite treatment with Miconazole (MCZ) and Ketoconazole. Exploratory laparotomy was performed with splenectomy, and splenic specimens were found to contain Candida organisms. Soon AMPH-B was administered through a catheter inserted into the portal vein at the same time. A side effect by AMPH-B was tolerable and his fever resolved to normal in 2 weeks after institution of this therapy, and the sizes of abscesses were markedly reduced. The patient remained in remission through 23 months, free of fungal infection. Case 2. A 23-year-old female was admitted for relapse of ALL (L2), in April, 1987. Reinduction therapy with BHAC-L-AVP achieved again in May but fever unresponsive to antibiotics occurred. Since multiple liver-spleen abscesses were showed by US and CT suspected mycotic etiology, antimycotic therapy with Miconazole and AMPH-B was performed but clinical findings were deteriorated. AMPH-B was administered through a catheter inserted into the hepatic artery for two weeks, following into the splenic artery for a week. Splenic abscesses were resolved in a week and liver abscesses were markedly reduced at three weeks after initiation of intra-arterial antifungal treatment. Through the analysis of these case studies we confirmed the usefulness of intraportal and intrahepatosplenic arterial administration of AMPH-B.

Abscess↗

Inhibition of human natural killer activity by antiserum against vitamin D-binding protein, a group-specific component (Gc).

An anti-Gc antiserum (anti-Gc) was prepared by immunizing rabbits with purified Gc, a major vitamin D-binding protein in human serum. Gc is expressed on the surfaces of a small proportion of resting T cells and almost all B cells are natural killer (NK) cells. We investigated the effects of anti-Gc on NK activity of normal peripheral blood lymphocytes. Both anti-Gc and purified IgG isolated from anti-Gc prominently inhibited human NK activity in vitro. Inhibition of anti-Gc was dependent on the concentration of the antiserum employed. Competition assay showed that purified Gc significantly blocked the inhibitory effect of anti-Gc. The inhibition of NK activity in the cells treated with anti-Gc was restored time-dependently by being cultured in anti-Gc free medium. Anti-Gc-treated NK cells retained their capacity to bind to target cells. These findings suggest that mGc is associated with the process of the NK cytolysis on the post-binding cytolytic phase.

Cytotoxicity Tests, Immunologic↗

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on leukemic cells from chronic B cell leukemia.

It is not clear whether cells from various chronic B cell leukemias including B-chronic lymphocytic leukemia (CLL), CLL in prolymphocytoid transformation (CLL-PLT), B-prolymphocytic leukemia (PLL), and hairy cell leukemia (HCL) simply represent different stages of a single B cell differentiation pathway. Furthermore, it is not known whether cells from any given B cell leukemia are characterized by the same population during the differentiation process. Differentiation of various B cell leukemic cells was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and the resulting changes in their morphology, cytoplasmic immunoglobulin (clg), and cytochemistry were evaluated. With respect to peculiar morphological change, i.e. extending long thin processes (spreading) and the appearance of clg, each sample showed different responses. According to these two indices samples were classified into three groups; spread+ clg- samples (one case of CLL-PLT, all HCL), spread+ clg+ samples (one of CLL, one of CLL-PLT), and spread- clg+ samples (a majority of CLL, one of CLL-PLT, and all PLL). Unexpectedly, both CLL and CLL-PLT consisted of heterogenous populations as to the reactivity to TPA. In the process of TPA-induced differentiation in CLL cells, features similar to those of HCL cells were not found. Since three different TPA-induced response patterns were observed in each chronic B cell leukemia type, it was not possible to sequentially assign each of these leukemias along a single B cell differentiation pathway. In order to explain this result, we introduced the hypothesis that these groups might be divided into different lineages in B cell differentiation. Since TPA-induced spreading cells were present in the B cell fraction of normal peripheral blood mononuclear cells, this morphological change should not be associated with malignant transformation.

B-Lymphocytes↗

[Hairy cell leukemia of European-American type with dual T and B-cell phenotype].

A 46-year-old woman was admitted because of palpitation and conjunctival jaundice. Physical examination revealed hepatosplenomegaly and purpura without lymphadenopathy. Blood count showed 4.7 g/dl hemoglobin with increased reticulocytosis. The platelet count was 1.5 X 10(4)/microliters and the leukocyte count was 6,000/microliters with 17% abnormal mononuclear cells (hairy cells). Hairy cells had nuclei of frequently folded shape and abundant cytoplasma with irregular edges on blood films. The hair-like cytoplasmic projections of the cells were clearly seen under the phase-contrast microscopy. Hairy cells were strongly positive for tartrate resistant acid phosphatase. Bone marrow aspiration was unsuccessful. The biopsy specimens showed small patchy and scattering infiltrations by hairy cells. Surface marker studies of hairy cells revealed that they were strongly positive for SmIg (IgG kappa). They also reacted with alpha B 1, alpha Tac, alpha Leu-M 5 monoclonal antibodies and a rabbit anti-hairy cell serum (alpha HC-M). 53% of hairy cells were shown to react with alpha B 1 and alpha OKT 11 simultaneously by double labelling. The southern blot analysis of peripheral blood mononuclear cells showed IgH chain genes rearrangement and germ line patterns of T-cell receptor genes. Hemolysis was promptly disappeared after blood transfusion. Moreover, the red blood cells, platelets and leukocytes have spontaneously returned to normal levels with disappearance of circulating hairy cells and palpable spleen one year after admission.

B-Lymphocytes↗

Inhibition against CFU-C and CFU-E colony formation by soluble factor(s) derived from hairy cells.

The inhibitory effect by hairy cell conditioned medium (HCCM) on the growth of granulocyte and erythrocyte colony forming cells was studied in vitro. The percent inhibition of CFU-C formation by HCCM from four hairy cell leukemia (HCL) patients ranged from 36% to 76%, while no inhibition was observed with conditioned medium (CM) obtained from three B-cell chronic lymphocytic leukemia (B-CLL) patients nor from two normal controls. HCCM inhibited specially the growth of rG-CSF responding stem cells. The hairy cell-derived colony inhibitory factor from HCCM was nondialyzable, fairly stable to heat treatment, and trypsin sensitive. Its maximal inhibitory activity against granulopoiesis was observed in the fractions of 5,000 to 6,000 daltons. Moreover HCCM inhibited CFU-E colony formation but not BFU-E. These results indicate that hairy cells produce a factor that inhibits granulopoiesis and erythropoiesis in vitro. This factor may play a role in neutropenia and anemia observed in HCL.

Culture Media↗

New cell line from hairy-cell leukemia: confirmation of leukemic cell origin by karyotype and Ig gene analysis.

A hairy-cell leukemia (HCL) line, BNBH-I, was established from the peripheral blood of a 40-year-old male patient with HCL in a relatively stable clinical phase after splenectomy. The cells have since been growing continuously for more than 2 years. Their cell surface immunoglobulin (sIg) was identical with that found on the surface of freshly isolated leukemic cells, consisting of IgG-kappa. The BNBH-I cells were more mature than the original hairy cells in their degree of B-cell differentiation, as reflected by a decrease in sIg expression together with the appearance of some cytoplasmic Ig (cIg)+ cells, loss of EA gamma-rosette formation and reactivity with monoclonal antibody (MAb) FMC7, and an increase in the proportion of MAb PCA-I+ cells. The BNBH-I cells possessed the antigen recognized by Leu-M5, a highly specific MAb for HCL. Epstein-Barr virus nuclear antigen (EBNA) was present. Both the freshly isolated leukemic cells and the cell line had the 14q+ involving q32 chromosomal abnormality, and their Ig gene rearrangements were also identical. Following exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA), both the freshly isolated leukemic cells and the BNBH-I cells adhered to culture dishes and extended long, thin processes, a phenomenon characteristic of HCL. These results indicate that the BNBH-I line was derived from the leukemic hairy cells.

Adult↗

B cell lymphoma showing clinicopathological features of malignant histiocytosis.

This report describes a case of B cell lymphoma, the clinicopathological features of which are quite similar to those of malignant histiocytosis. The clinical features included fever, anemia, and marked hepatosplenomegaly without lymphadenopathy. Histological findings revealed diffuse and noncohesive proliferation of cytologically atypical cells and benign-appearing histiocytes in the splenic red pulp, where the erythrophagocytosis was frequently found. Immunological studies, however, revealed a B cell nature of proliferating atypical cells. Accordingly, the histology of this patient was interpreted as a neoplastic proliferation of B cells accompanied by marked proliferation and activation of the histiocytes.

B-Lymphocytes↗

OKM1-positive T-cell leukemias. Relationships among morphologic features, phenotype, and functional activities.

The morphologic features, phenotype, and functions of OKM1+ leukemic T-cells were studied. The leukemic T-cells in two patients with chronic lymphocytic leukemia (CLL) had specific features of large granular lymphocytes (LGL), and those in two patients with acute lymphocytic leukemia (ALL) had L2 morphologic characteristics. The phenotype of the leukemic cells from one patient with CLL was OKM1+, ER+, OKT3+, OKT4+, OKT8-, OKIa1-, IgGFc receptor (EA gamma)+, Leu-7+, Leu-11b+, and anti-Tac-. The cells had antibody-dependent cell-mediated cytotoxicity (ADCC), but no natural killer (NK) activity. They had a definitive helper effect on pokeweed mitogen-induced normal B-cell differentiation. The leukemic cells from the other patient with CLL were Leu-7-, and Leu-11b-, and lacked both ADCC and NK activity. The leukemic cells in the two patients with ALL were ER+, OKM1+, Leu-7-, and Leu-11-, and did not have any cytotoxicity. One was EA gamma +, and the other was EA gamma -. These findings suggest that OKM1+ leukemic T-cells consist of at least two subgroups: (1) T-cells with the morphologic features of LGL; and (2) those with a lymphoblastic morphologic type. In either case, the phenotype is novel and suggests the emergence of a small, distinct lymphocyte subset.

Acid Phosphatase↗

Distribution of Gc protein (vitamin D binding protein) on the surfaces of normal human lymphocytes and leukemic lymphocytes.

Distribution of membrane-bound Gc protein (mGc) in normal lymphocyte subpopulations and leukemic lymphocytes was studied using a rabbit antiserum specific to Gc protein. Forty to fifty percent of the normal peripheral blood mononuclear cells were stained with anti-Gc antiserum by membrane immunofluorescence, and almost all of the B cells (B1+) and NK cells (Leu 11+) were mGc-positive. Only a few resting T cells (T3+) reacted with anti-Gc, but mGc appeared in a significant number of the T cells after activation by PHA. The distribution of mGc on leukemic lymphocytes of various types nearly corresponded to that in normal lymphocyte subpopulations.

B-Lymphocytes↗

Association of specific tyrosine phosphorylation with stages of B-cell differentiation in human lymphoid leukemias.

In vitro protein phosphorylation in various types of human fresh lymphoid leukemic cells (C-ALL, B-CLL, HCL and PCL: B-cell lineage and T-ALL, ATL and T-CLL: T-cell lineage) were studied. In cases of B-CLL and HCL, tyrosine protein kinase (TPK) activity was at least 5-fold higher than that in other cases of B- and T-cell lineages. B-cell leukemic cells at various differentiation stages had different endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. The P-tyr-containing proteins of 68K, 59K and 56K were detected commonly in all the cases of B-cell lineage. The phosphorylated protein of 32K was present only in cases of PCL. On the other hand, in T-ALL and ATL, the major substrate in tyrosine phosphorylation was 58K. These results suggest that the characterization of in vitro tyrosine phosphorylation provides a new means not only to distinguish T- and B-lymphoid leukemia, but also to differentiate stages of lymphoid development.

B-Lymphocytes↗

Serum immunosuppressive acidic protein in adult T-cell leukaemia (ATL).

The availability of serum immunosuppressive acidic protein (IAP) as a marker of subtypes of adult T-cell leukaemia (ATL) was examined. Serum IAP levels were measured in 34 patients with ATL (18 typical, 9 atypical and 7 smoldering), 7 healthy carriers of ATLA antibody and 53 healthy controls. The mean value of serum IAP was significantly higher in patients with typical ATL (897.8 +/- 502.4 micrograms/ml) than in those with atypical ATL (426.7 +/- 106.6 micrograms/l), smoldering ATL (310.0 +/- 51.3 micrograms/ml), healthy carriers of ATLA antibody (302.9 +/- 39.5 micrograms/ml) and normal controls (350.5 +/- 73.2 micrograms/ml). Serial determinations of IAP revealed that the level was correlated with the clinical course in patients with ATL; there was a difference in the prognosis of patients with high and normal levels of IAP (P less than 0.05). Thus, routine measurement of serum IAP seems useful in differentiating typical, atypical and smoldering ATL and also in evaluating the prognosis of patients.

Adult↗

Phenotypical heterogeneity of Japanese adult T-cell leukaemia.

The leukaemic cells of 11 patients with Japanese adult T-cell leukaemia (ATL) were characterized in terms of phenotype employing various monoclonal antibodies against T-cell surface antigens. The leukaemic cells of all ATL patients except patient no. 11 displayed the phenotype OKT4+/OKT8-. However, the % of OKT3+ cells varied from 3 to 98. In 1 case, cells with phenotype OKT4+/OKT8+, which is characteristic of T-cells at an early stage of differentiation, were found. These results suggest that some ATL cells may be in an immature differentiation stage. Among the 11 patients, 2 with unusual ATL cell phenotypes (1 case with OKT3- cells and 1 case with Ia+/EAC+ cells) showed spontaneous regression of leukaemic cells. Characterization of leukaemic cells from a larger number of ATL patients may demonstrate a significant relationship between cell phenotype and prognosis.

Aged↗