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Biomedical subjects

M Ichimaru

Publications and source records attributed to M Ichimaru.

At least 127 records · Page 7Linked to original sources

T lymphomas associated with human T-cell leukemia-lymphoma virus may show phenotypic and functional differences from adult T-cell leukemias.

We report phenotypic and functional characterization of lymph node cells from 27 patients with T lymphoma from the Nagasaki district of Japan. Nagasaki is one of several areas where adult T-cell leukemia is endemic, and sera from 18 of 23 patients examined (78.3%) were positive for antibody to adult T-cell leukemia-associated antigen. The majority of cases (24 of 27) showed the Leu-2a-, 3a+, MASO36c- phenotype similar to adult T-cell leukemia, but seemed to be subdivided into four groups according to the presence or absence of Leu-1 antigen and the receptor for sheep erythrocytes (SRBC). Eleven cases had both Leu-1 antigen and the receptor for SRBC (E-RFC+, Leu-1+, 2a-, 3a+), but 6 cases lacked Leu-1 antigen (E-RFC+, Leu-1-, 2a-, 3a+), 4 cases lacked receptors for SRBC (E-RFC-, Leu-1+, 2a-, 3a+), and 3 cases lacked both of these markers (E-RFC-, Leu-1-, 2a-, 3a+). The effects of lymph node T cells on pokeweed mitogen (PWM)-induced normal B-cell differentiation was studied in 10 cases. Lymph node T cells of 5 cases showed helper activity without any suppressor activity, and 2 cases showed suppressor activity with almost no detectable helper activity, similar to adult T-cell leukemia cells. Two other cases lacked particular functional effects. These results suggest the possibility that Leu-3a+ T-cell lymphoma may be functionally subdivided into at least two types, a helper type and a suppressor (adult T-cell leukemia) type.

Adolescent↗

CFU-C abnormalities and cytochemical defects in bone marrow of adult patients during remission of acute leukemia.

Twenty-three adult patients in complete remission (CR) from acute leukemia were investigated for the steady-state bone marrow (BM) CFU-C concentration and the cytochemical findings of neutrophils and monocytes. There was considerable variation in CFU-C concentrations among patients. Patients with abnormality high or low values tended to relapse earlier. Repeated assays revealed constant CFU-C values in individual long-term cases of remission (4 cases). One case of M4 (myelomonocytic) and the case of M5b (monocytic) leukemia revealed a complete lack of nonspecific esterase activity in CR monocytes as well as initial leukemic promonocytes; they also showed abnormally high or low concentrations of CFU-C and relapsed early. This finding suggests that hematopoiesis in CR bone marrow occurs from abnormal stem cells common to initial, acute leukemic clones in such cases.

Acute Disease↗

A comparative study of immunological and cytochemical profiles between adult and childhood acute lymphoblastic leukemias (ALLs): heterogeneity in adult common ALL.

To investigate the biological differences between adult and childhood acute lymphoblastic leukemia (ALL), leukemic blasts from 33 patients with ALL (22 adults and 11 children) and from 11 patients in the lymphoid crisis of chronic myeloid leukemia (CML) were studied using cytochemical and immunological markers and also by the outcome of their treatment. The cytochemical studies showed that blasts from seven of the adult ALL patients were dense-granular-positive (DG-positive) for beta-glucuronidase, whereas the blasts from the children were negative except for one (with T-ALL). In the adults with common ALL (cALL), survival of patients DG-positive for this enzyme were significantly shorter than that of eight patients with a scattered granular pattern (p less than 0.05). The mean ratio between the percentage of blasts positive for cALL antigen (cALLA) to that of blasts positive for terminal deoxynucleotidyl transferase (TdT) in the adult group with cALL (0.6 +/- 0.3) was significantly lower (p less than 0.01) than in the group of children with cALL (1.1 +/- 0.2) or in the lymphoid-crisis group (1.5 +/- 1.0). These findings indicate that adult cALL consists of two distinct subpopulations, one with less differentiated phenotype (cALL-/TdT+) and the other with more (cALL+/TdT+). In contrast, the blast cells in childhood cALL and some patients in lymphoid crisis had a relatively homogeneous population with the latter phenotypes. The results suggest that the clonotypic cells in adult ALL, particularly in cALL, appear to be more immature than those in childhood ALL. The beta-glucuronidase patterns indicate a further heterogeneity in adult ALL.

Adolescent↗

Lymphoid crisis with T-cell phenotypes in a patient with Philadelphia chromosome negative chronic myeloid leukaemia.

A case of Philadelphia (Ph1) chromosome negative chronic myeloid leukaemia (CML) developed lymphoid crisis. Immunological marker studies disclosed that the lymphoid cells were sheep erythrocyte-rosetting-, Leu-1+, Leu-5+, OKT-4+, OKT-8+, common ALL antigen-, HLA-DR-, cytoplasmic and surface immunoglobulin-, MAS 036C(antithymocyte)+ (after in vitro culture) and terminal deoxynucleotidyl transferase-, indicating T-cell phenotypes, probably of common thymocytes. Cytochemical staining also demonstrated immature T-cell characters: dot-positivity for acid phosphatase and beta-glucuronidase, and negative for acid alpha-naphthyl acetate esterase. All bone marrow metaphases exhibited normal karyotypes. Our observation suggests that the neoplastic features of a common stem cell for myeloid and lymphoid cell lines are very similar in Ph1 positive and negative CMLs, and that the stem cell can differentiate towards T-lineage.

Adult↗

Low-dose cytosine arabinoside regimen induced a complete remission with normal karyotypes in a case with hypoplastic acute myeloid leukaemia with No. 8-trisomy: in vitro and in vivo evidence for normal haematopoietic recovery.

Complete remission was achieved in a case of hypoplastic acute myeloid leukaemia with chromosomal aberration of No. 8-trisomy by giving very low dose of cytosine arabinoside (ara-C), 10 mg (7 X 5 mg/m2)/d, by 24 h continuous intravenous infusion for 20 d. We observed a definite cytoreduction phase in the bone marrow (BM) before normal haematopoiesis resumed. The remission BM showed only normal karyotypes in all metaphases examined. Granulocyte/macrophage colonies and erythroid bursts recovered sufficiently in numbers and cytogenetic study on single colonies and bursts revealed only normal karyotypes. These observations provide evidence that a low dose ara-C regimen can induce remission by cytoreduction which diverts the growth advantage from the leukaemic clone to the normal clones.

Chromosomes, Human, 6-12 and X↗

Adult T cell leukemia with atypical surface phenotypes: clinical correlation.

The leukemic cells of 57 patients with adult T cell leukemia (ATL) were analyzed for their immunologic surface markers. Forty-four cases showed normal mature inducer/helper T cell phenotype (typical group: E-RFC+, Leu-1+, 2a-, 3a+ MASO36c-), but the other 13 cases showed unusual surface phenotypes (variant group) and could be subdivided into several groups (V1 to V5). Four cases had absent or low Leu-1 positivity (V1: E-RFC+, Leu-1-, 2a-, 3a+, MASO36c-), while two other cases with low Leu-1 positivity had both Leu-2a and 3a, a characteristic of cortical thymocytes, but were unreactive with MASO36c (V2: E-RFC+, Leu-1-, 2a+, 3a+, MASO36c-). Three cases lacked both Leu-2a and 3a despite having other T cell markers (V3: E-RFC+, Leu-1+, 2a-, 3a-, MASO36c-). The next three cases had low rosette-forming ability with sheep RBCs (V4: E-RFC-, Leu-1- approximately +, 2a- approximately +, 3a+, MASO36c-). Interestingly, one other case showed high reactivity against anti-Leu-7, which is believed to be one of the monoclonal antibodies directed against natural killer cells (V5: E-RFC+, Leu-1+, 2a-, 3a+, 7+, MASO36c-). Clinical and hematologic differences between the typical group and variant group were investigated, and it was found that the variant group (excluding V5) have statistically significant (P less than .002) higher serum lactic dehydrogenase (LDH) activity. The overall survival in the variant group was worse than in the typical group, but it was not quite statistically significant (P = .072). The median survival time was eight months for typical cases and only four months for variant cases; six cases died within two months. The V5 case was unusual not only because the patient's leukemic cells have Leu-7 antigen but also because she survived more than nine years after initial diagnosis. There seems to be some correlation between phenotypic diversity of ATL cells and prognosis.

Adult↗

Cytochemistry of acute promyelocytic leukemia (M3): leukemic promyelocytes exhibit heterogeneous patterns in cellular differentiation.

Cytochemical investigation of leukemic promyelocytes from 25 cases of acute promyelocytic leukemia (M3) disclosed two major cellular differentiation categories: (1) the pure neutrophilic (N) type (16 cases) with strong myeloperoxidase (MPO) and naphthol-ASD chloroacetate esterase (Es-chl), but lacking the monocytic enzyme NaF-sensitive alpha-naphthyl butyrate esterase (Es-b), and (2) the mixed neutrophilic/monocytoid (N/M) type (seven cases) with strong Es-b as well as strong MPO, all cases exhibiting Es-dual (Es-b + Es-chl) positive cells. Two more cases with unusual phenotypes were noted: one with intense lysozyme activity but without Es-b and the other with toluidine blue-methachromasia and negative MPO. Promyelocytes from the control group, consisting of nine cases of t(8;21) M2 AML and ten cases with normal bone marrow, lacked such cytochemical heterogeneity. HL-60, an M3 cell line that can be induced to differentiate toward monocytic lineage in vitro, was almost negative for Es-b in the uninduced condition. Cytogenetically, eight cases of N type and five of N/M type had the t(15;17) abnormality. Thus at least two differentiation patterns were observed in M3 leukemia with fidelity (N type) and infidelity (N/M type) for normal granulocytic differentiation. In this series, there was no statistically significant difference in clinical features (remission rate and survival) between the two types. Our study suggests that the development of M3 leukemia is not exclusively restricted to the neutrophilic pathway, but more heterogeneously related to myelomonocytic differentiation.

Adolescent↗

Preleukemic state of adult T cell leukemia: abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus.

We report the clinical, hematologic, and immunologic features of 18 preleukemic adult T cell leukemia (pre-ATL) cases with abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus (HTLV/ATLV). The patients were from the Nagasaki district, which is one of the most endemic areas of ATL in Japan. Pre-ATL is a subclinical T cell abnormality differing from ATL. It is characterized by an insidious onset and appearance of abnormal T lymphocytes (10% to 40%) in the peripheral blood without clinical symptoms except for a few cases transiently presenting fever, skin eruptions, and slight lymphadenopathies. Most abnormal T lymphocytes were small and mature with incised or lobulated nuclei and formed E rosettes with sheep RBCs. Virologic and biomolecular analysis revealed that all cases were infected with HTLV, and proviral DNA was integrated in host lymphocytes from 12 of the 14 cases examined. Furthermore, the lymphocyte populations, including abnormal T lymphocytes, were monoclonal with respect to the site of the provirus integration. Abnormal T lymphocytosis persisted from one to more than seven years in six cases, three of which developed ATL after a one- to five-year pre-ATL stage, whereas abnormal T lymphocytes spontaneously decreased in the other seven patients. However, HTLV-infected monoclonal lymphocytes were detected in four cases examined, even after most of the abnormal T lymphocytes had disappeared. Moreover, the same clonally provirus-integrated lymphocytes persisted in two of four cases not only during the course of abnormal lymphocytosis, but also in the subsequent almost-normal blood. These results indicate that the majority of the cases were in a pre-ATL state with a potential to develop ATL.

Adult↗

Oral transmission of human T-cell leukemia virus type-I into a common marmoset (Callithrix jacchus) as an experimental model for milk-borne transmission.

To obtain experimental support for possible milk-borne infection of human T-cell leukemia virus type-I (HTLV-I), short-term-cultured viral antigen-positive lymphocytes obtained from peripheral blood of adult T-cell leukemia lymphoma complex (ATLL) patients were inoculated into the oral cavity of two adult common marmosets (Callithrix jacchus) in amounts comparable to those of HTLV-I-carrying cells fed to a baby in the milk of seropositive mothers. One of the animals seroconverted 2.5 months after the first inoculation. Cultures of peripheral blood mononuclear leukocytes of the marmoset revealed HTLV-I antigen expression in cells, indicating the establishment of oral infection of HTLV-I in an adult marmoset. The cell number deduced to be responsible for the infection was 5.6 X 10(7) cells (used in the first 2 inoculations). The results suggest that the concept of milk-borne infection of HTLV-I from a seropositive mother to her child is plausible.

Administration, Oral↗

Oral infection of a common marmoset with human T-cell leukemia virus type-I (HTLV-I) by inoculating fresh human milk of HTLV-I carrier mothers.

To obtain definitive evidence that milk-borne infection plays a critical role in the endemy or mother-to-child transmission of human T-cell leukemia virus type-I (HTLV-I), we inoculated concentrated fresh human milk cells obtained from HTLV-I carrier mothers into the oral cavity of a common marmoset (Callithrix jacchus). Twenty-eight milk samples were collected (5-10 ml each) from 17 carrier mothers in the first week after delivery. Cells in the milk were centrifuged down and resuspended in 1/10 vol of the milk fluid. The concentrated cell suspensions were successively inoculated into the oral cavity of a common marmoset. The marmoset was found to be seroconverted by indirect immunofluorescence assay at 2.5 months after the first inoculation of the milk (3.5 X 10(8) cells in total), and was later confirmed to be infected with HTLV-I by the detection of viral antigen expression in short-term cultures of its peripheral blood T-lymphocytes. The results strongly support the working hypothesis that milk-borne infection plays a significant role in the mother-to-child transmission of HTLV-I.

Animals↗

Effects of atomic bomb radiation on the differentiation of B lymphocytes and on the function of concanavalin A-induced suppressor T lymphocytes.

The differentiation of peripheral blood B lymphocytes into immunoglobulin-producing cells (Ig-PC) by pokeweed mitogen (PWM) and the function of concanavalin A (Con A)-induced suppressor T lymphocytes were examined to elucidate the late effects of atomic bomb radiation. A total of 140 individuals, 70 with an exposure dose of 100 rad or more and an equal number with an exposure dose of 0 rad matched by sex and age, were selected from the Nagasaki Adult Health Study (AHS) sample. Both the differentiation of peripheral blood B lymphocytes into Ig-PC by PWM and the function of Con A-induced suppressor T lymphocytes tended to be more depressed in the exposed group than in the control group, but a statistically significant difference could not be observed between the two groups. The function of Con A-induced suppressor T lymphocytes tended to decrease with age, but a statistical significance was detected only for percentage suppression against IgM-PC.

Adult↗