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Biomedical subjects

J Akatsuka

Publications and source records attributed to J Akatsuka.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Effective combination therapy by recombinant erythropoietin and cepharanthin in a girl with refractory anemia].

A 3-year-old girl was admitted with a one-month history of a tendency to bleed to Jikei Kashiwa hospital in May, 1992. She developed pancytopenia as follows; hemoglobin: 8.6 g/dl, red blood cell: 316 x 10(4)/microliters, reticulocyte: 9,480/microliters, white blood cell: 2,500/microliters (neutrophil: 400/microliters) and platelet count: 2.7 x 10(4)/microliters. Her bone marrow was hypoplastic, but was so dysplastic in 3 cell-lines as to be diagnosed as hypoplastic refractory anemia. After two courses of methylprednisolone pulse therapy followed by oral prednisolone therapy which were not effective and were supplemented by blood transfusions, the treatment of 20mg/day oral Cepharanthin, a biscoclaurine alkaloid, and intravenous recombinant human erythropoietin (rhEPO) twice a week at dose of 6,000 U/week was initiated in January, 1993. About 3 months later she showed a steady rise in hemoglobin concentration (from 4.1 to 11.9 g/dl) and platelet count (from 4,000 to 39,000/microliters). Although the rhEPO was tapered and ceased in September, 1993, her hemoglobin concentration has ranged from 11.0 to 11.9 g/dl and her platelet count from 30,000 to 40,000/microliters by giving her Cepharanthin and low dose prednisolone.

Alkaloids↗
PubMed1993

Neurofibromatosis type 1 and childhood cancer.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) are prone to develop malignancy, particularly malignant schwannoma and glioma in adults. METHODS: To assess the risk for childhood malignancy in NF1, 26,084 patients with cancer younger than 15 years of age registered from 1969 to 1989 in the Japan Children's Cancer Registry were reviewed. The incidence of NF1 in each type of cancer was compared with that in the Japanese population. RESULTS: Fifty-six children with cancer had NF1 in the national registry. The incidence of NF1 (0.21%) was 6.45 times that of the expected estimated rate of 1 per 3000 in the Japanese population. These tumors tended to be type and site specific. The NF1 incidence was extremely high in optical nerve glioma (12.5%), other central nervous system gliomas (0.9%), and malignant schwannoma (31.4%). For nonneural tumors, NF1 incidence was increased in rhabdomyosarcoma (1.36%), particularly those in urogenital organs, and in myelogenous leukemia (0.27%). Epithelial carcinomas were not observed in the group of patients with NF1. CONCLUSION: The risk for glioma and malignant schwannoma increases in children and adults with NF1. Moreover, the risk for two childhood malignancies, myelogenous leukemia and rhabdomyosarcoma, increases in children with NF1. The NF1 gene seems to increase the risk not only for neural tumors but also for some non-neural tumors in an age-specific, organ-dependent pattern of carcinogenesis.

Adolescent↗
PubMed1993

High frequency of etoposide (VP-16)-related secondary leukemia in children with non-Hodgkin's lymphoma.

PATIENTS AND METHODS: We report patients who were treated for non-Hodgkin's lymphoma (NHL) or Ki-1 antigen-positive (Ki-1) lymphoma with a T-8801 protocol that included etoposide (VP-16) and behenoylcytosine arabinoside. RESULTS: Secondary acute myeloid leukemia (AML) developed in 5 of 38 NHL and Ki-1 lymphoma patients, and the cumulative risk at 4 years was 18.4%. The median time from the initiation of the chemotherapy to the development of AML was 21 months (range, 13-30). Four patients had a FAB M5 morphology, and one had FAB M2. In four of five examined cases, chromosomal alterations involving the long arm of chromosome 11 were demonstrated at the time of development of AML. None of the 46 NHL patients who we treated with another protocol (B-8801), using significantly higher cumulative doses of VP-16 than in the case of the patients with T-8801 and a different schedule of VP-16 administration, developed secondary AML. CONCLUSIONS: The risk of secondary AML possibly related to the use of VP-16 given twice weekly.

Adolescent↗
PubMed1993

Prediction of engraftment after peripheral blood stem cell transplantation by CD34-positive cells in grafts.

A total of 91 peripheral blood stem cell collections were performed in 26 children with various malignant tumors and peripheral blood stem cell transplantations (PBSCT) were performed in 15 of the children. There was a positive correlation between logarithm of total CD34+ cells/kg and logarithm of colony-forming unit-granulocyte macrophage (CFU-GM)/kg (r = 0.86). The time elapsed until the white blood cells (WBC) exceeded 1000/microL was related to both CFU-GM (r = 0.67) and CD34+ cell count (r = 0.60). The number of days elapsed until platelet count exceeded 5 x 10(4)/microL was not related to the logarithm of CFU-GM count/10(5) per kg transfused (r = 0.47), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.73). The number of days elapsed until the reticulocytes exceeded 10% was not related to the logarithm of CFU-GM count/10(5) per kg (r = 0.52), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.91). Although CD34+ cell counts correlated with the number of CFU-GM, bone marrow regeneration rates in three lineages were predicted more accurately by the number of CD34+ cells transfused than by the number of CFU-GM. These results suggest that measurement of the CD34+ cell count may be useful in predicting bone marrow regeneration rate after PBSCT.

Adolescent↗
PubMed1993

Establishment of a neuroblastoma cell line and induction of lymphokine-activated killer (LAK) activity against the autologous neuroblastoma cell line.

We have established a new human neuroblastoma (NB) cell line from the bone marrow of a 1-year-old boy with NB, termed JK-NB1, which showed constant growth for as long as 17 months or more, similar phenotype to those of other reported NB cell lines, colony formation in liquid and methylcellulose culture, N-myc amplification, high expression of N-CAM, and NSE production. We have tried to induce LAK cell activity with peripheral blood mononuclear cells (PBMCs) from the patient against the autochthonous JK-NB cells. PBMCs from the patient proliferated up to 20-fold in the presence of interleukin-2 (IL-2) after 9 days of incubation, and LAK activity increased up to 24.7-fold and killed all of the JK-NB1 cells. In contrast, IL-2 alone or PBMCs from the patient or a healthy adult donor had little effect on the growth of NB cells. These data suggest that it is possible to induce LAK cell activity in PBMCs from the patient against autologous as well as allogenic NB cells, and provide a rational base for the clinical use of IL-2 as one of the treatments for NB.

Adrenal Gland Neoplasms↗
PubMed1992

A deletional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin Tokyo (beta 220/216).

A novel spectrin variant carrying a truncated beta-chain and designated Spectrin Tokyo (beta 220/216) is presented. It was associated with elliptocytosis and moderate uncompensated hemolysis. The dimer self-association was reduced. An increase of the alpha I 74-Kd fragment was detected upon partial trypsin digestion. Analysis of cDNA and genomic DNA showed a 1-base deletion in codon 2059 (GCC AGC-->GCA GCT; Ala-Ser-->Ala-Ala) that belongs to exon X of spectrin beta-gene. A missense sequence extended down to (new) codon 2075. Serine 2060, a potential phosphorylation site, was replaced by alanine. The shortened beta-chain failed to undergo phosphorylation in vitro. Spectrin Tokyo shared the same stop codon, overlapping normal codons 2076 and 2077 (CTG AAA), as Spectrin Nice (beta 220/216), which is caused by a dinucleotide insertion in codon 2046 and contains 2076 amino acids. However, for some reason, Spectrin Tokyo had a lower incorporation level into the membrane than Spectrin Nice.

Base Sequence↗
PubMed1992

Establishment and characteristics of a T-cell acute lymphoblastic leukemia cell line, JK-T1, with a chromosomal translocation between 8q24 and 14q13.

A human leukemia cell line, JK-T1, was established from the bone marrow of a 10-year-old boy with T-cell acute lymphoblastic leukemia. The origin of the leukemic cell line, JK-T1, was demonstrated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. Karyotypic analysis revealed 46,XY,del(6)(q?),t(8;14)(q24;q13),der(9)t(9;?)(q34;?). In JK-T1, neither rearrangement nor amplification of the c-myc gene was observed apparently because the breakpoint of chromosome 14 was not q11 but q13. JK-T1 was independent of interleukin 2 (IL-2) because of little production of IL-2, little IL-2 receptor (CD25) on the surface, and no response to exogenous IL-2. JK-T1 had lymphocyte function associated antigen-1 (LFA-1) (CD11a, CD18) on its surface and could adhere to the hematologic stromal layer. These characteristics of JK-T1 cell line are considered to be useful not only for evaluating the role of t(8;14) but also in studying the adhesion molecules of leukemia.

Bone Marrow Cells↗
PubMed1992

BUN/Cr ratio as an index of gastrointestinal bleeding mass in children.

Determining the site and severity of blood loss is important in the management of children with gastrointestinal (GI) bleeding. Blood urea nitrogen (BUN) and serum creatinine (Cr) were measured on the day of hospitalization and the ratio of BUN/Cr was calculated in 11 children with 16 episodes of upper GI bleeding and 49 with lower GI bleeding. There was a significant difference between the two GI bleeding groups with regard to BUN/Cr ratio (p less than 0.001). When the ratio was 30 or above, the specificity of upper GI bleeding was 98% with a sensitivity of 68.8%. A linear relationship was found between the BUN/Cr ratio and delta Hb (delta Hb = 0.08 x BUN/Cr +/- 0.8 g/dl) for bleeding originating from the upper GI tract. This study confirms that measurement of the BUN/Cr ratio is useful for localizing the source of bleeding to the upper GI tract and also demonstrates its usefulness as an estimation of the severity of blood loss from the upper GI tract.

Adolescent↗
PubMed1992

Analysis of leukemic cell activity with a simple acridine orange staining method.

Leukemic cells from 28 patients with acute lymphoblastic leukemia (ALL) were supravitally stained with acridine orange (AO). Based on the staining characteristics of their cells, the patients were divided into an orange cell-dominant group (15 patients) and a green cell-dominant group (13 patients). The prognosis was better in the former than in the latter group. Orange cells which had high RNA contents were observed, while the proportion of dividing cells was high. Supravital staining with AO is a very simple and useful method for assessing the metabolic activity of leukemic cells in ALL; this method may thus be useful in assessing the prognosis of these patients.

Acridine Orange↗
PubMed1992

[The measurement of erythrocyte zinc protoporphyrin/heme ratio in various anemias in childhood].

The measurement of erythrocyte zinc protoporphyrin (ZPP) with a hematofluorometer is known to be a simple and cost-effective method to screen iron deficiency and lead poisoning. We measured ZPP on blood samples from 201 children suffering from various diseases, which revealed that ZPP has better sensitivity and specificity for identifying iron deficiency than serum ferritin and percent transferrin saturation. ZPP levels in various anemias were also measured. ZPP rose markedly (> 200 mumol/mol heme) in untreated iron deficiency anemia and returned to normal in 3-4 months since the initiation of iron therapy. Moderate elevation of ZPP was observed in acute leukemia (at onset and during induction therapy), MDS, aplastic anemia and some other anemic conditions. These findings suggest that erythrocyte ferrochelatase may be unexpectedly affected in anemias even except lead poisoning.

Anemia↗
PubMed1992

[Platelet-derived microparticles].

The presence of platelet fragments or platelet-derived microparticles (MP) in blood is of great interest, because it could be used as a marker for increased destruction or activation of platelets followed by their aggregation and vesiculation. In addition to early electronmicroscopic observations, a variety of methods to detect MP in plasma and serum have been developed, including immunoelectrophoresis, radioimmunoassay and the immunofluorescence test using flow cytometric analysis. In these techniques, monoclonal antibodies directed against platelet membrane specific antigens, such as glycoprotein (GP) IIb/IIIa or GP I b, have been used to distinguish platelet microparticles from other components. From basic and clinical investigations, MP has proved to be increased in some physiological and pathological conditions, including blood clotting, thrombin and collagen-induced activation of platelets, mechanical trauma of platelets, and immune-mediated platelet destruction. Furthermore, it has been shown that a significant part of platelet procoagulant activity resides on these small vesicles (MP), released from the platelet plasma membrane, on activation.

Biomarkers↗
PubMed1992

[Abnormalities of beta spectrin with hereditary elliptocytosis in mother and child].

It is generally considered that abnormality of the erythrocyte membrane skeleton co elliptocytes. There are, however, few reports of beta spectrin variants. We found a new variant of beta spectrin in a child and her mother. This report is the first case of abnormality of beta spectrin in Japan. The propositus was an 8 month-old girl who was first examined by us in 1988. On laboratory findings, she showed anemia, increased reticulocyte count and decreased haptoglobin concentration. Both peripheral blood smears of patient and her mother showed typical elliptocytosis and they were diagnosed as hereditary elliptocytosis. SDS-PAGE patterns of the red cell membranes of the propositus and her mother were characterized by the presence of an abnormal component migrating immediately below the spectrin chains. We confirmed that the abnormal spectrin appeared clearly at the expense of normal beta chain. The abnormal spectrin (M.W. 216,000d) makes up 16% of the total beta chain. The inheritance of our case was autosomal dominant. The present case is considered as a new spectrin variant.

Adult↗
PubMed1991

Infectious complications in childhood leukemia.

Since children with acute leukemia have prolonged periods of severe neutropenia due to the disease itself or its intensive chemotherapy, they often develop life-threatening infectious complications. A protected environment and prophylactic antibiotics for patients with severe neutropenia have been shown to decrease the incidence of infectious morbidity. In spite of the high mortality rate of infections, on the other hand, their diagnosis is not well established because the percentage of microbiological detectability by blood culture is low. The differentiation of infections may be possible by using some supplementary measures and particular laboratory parameters. Febrile neutropenic patients with leukemia should promptly receive empiric treatment with combinations of two or three broad-spectrum antibiotics that are bactericidal and synergistic toward the presumed pathogens, or with antifungal drugs if patients are resistant to antibiotics, as well as supportive measures such as granulocyte transfusion, intravenous gamma-globulin and granulocyte colony-stimulating factor.

Anti-Bacterial Agents↗
PubMed1991

Late effects of childhood acute leukemia and its treatment.

Late effects of childhood acute leukemia and its treatment were studied in 776 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.

Adolescent↗
PubMed1991

[Requirements of diagnostic criteria for aplastic anemia in children].

As a general rule, diagnostic criteria of aplastic anemia in children are the same as adult criteria. However, blood counts of normal children show wide age-related variation, therefore we must establish a system of adjustment for diagnosis of aplastic anemia in children. The data of children with aplastic anemia visiting our institutes from 1966 to 1990 were evaluated for this study. RBC below 350 x 10(4)/microliters, WBC below 4,000/microliters or neutrophils below 1,500/microliters, platelets below 8 x 10(4)/microliters, reticulocytes below 4 x 10(4)/microliters and lymphocytes over 60% were seemed to satisfy the diagnostic criteria of aplastic anemia proposed by the Study Group of hemopoietic Disorders sponsored by the Ministry of Health and Welfare of Japan. Fifteen children (4.6%) did not meet these criteria and as such were diagnosed as atypical aplastic anemia. Thirteen of them were in a pre-aplastic state and developed typical aplastic anemia within 6 months to 8 years after the initial diagnosis. Clinical findings of these patients showed the decrease in number of megakaryocytes and committed stem cells in bone marrow. Three of these patients developed acute non-lymphocytic leukemia, and 2 of them were diagnosed as Fanconi's anemias.

Adolescent↗
PubMed1991

Treatment of acute lymphoblastic leukemia in the Tokyo Children's Cancer Study Group--preliminary results of L84-11 protocol.

The Tokyo Children's Cancer Study Group (TCCSG) has performed prospective randomized controlled studies since 1984 for childhood acute lymphoblastic leukemia (ALL). Four hundred and ninety-eight newly diagnosed patients were treated with 5 different regimens designated as S1, S2 for a standard risk group (SRG), H1 and H2 for a high risk group (HRG) and HEX for an extremely high risk group of patients. We added intermediate-dose methotrexate as early intensification therapy in the S2 and H2 groups to reduce extramedullary and medullary relapses. Event-free survival of all patients at 4 years 6 months from the start of this regimen (median follow-up period 32 months) was 67.5%. The CNS relapse rate was significantly decreased to 2.2% compared to previously reported studies and our own experience. There were some unexpected complications of the CNS such as myelopathy and/or leukoencephalopathy. For the SRG early ID-MTX seemed to be useful to improve the prognosis, but triple intrathecal injections (TIT) should be limited in number. The 24Gy cranial irradiation (CRX) was effective but possibly excessive for the HRG. As evidenced by the success of the HEX group regimen, more intensive multi-drug consolidation in the early post-remission phase might be necessary to improve further the prognosis and to make it possible to shorten the treatment periods.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Detection of antigenic determinants of autoantibodies in idiopathic thrombocytopenic purpura using anti-platelet monoclonal antibodies and flow cytometry in whole blood].

To detect antigenic sites of platelet-bound autoantibodies in chronic ITP, whole blood or platelet-rich plasma from patients was stained with monoclonal antibodies (MoAbs) directed against platelet membrane glycoproteins (GPs) and with FITC-conjugated anti-mice IgG in an unwashed system followed by flow cytometric analysis. Platelets were identified by light-scattering profile and the amount of anti GP MoAb bound to platelets was measured and expressed as mean fluorescence intensity. This system enabled to quantitate the amount of intact GPs on platelet surface, regardless of activation of platelet. As a result, decreased amount of platelet-bound anti GPIIb/IIIa MoAb was noted in 5 of 22 patients with chronic ITP comparing to those with normal subjects. On the contrary, none of these patients revealed any demonstrable decrease in the amount of anti GPIb MoAb binding. From these observations, we suggest that the decreased MoAb binding to platelets in these five patients indicates the binding of autoantibody directed toward antigenic determinants, which are on or close to the epitope of this MoAb.

Adolescent↗