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Y Sonoda

Publications and source records attributed to Y Sonoda.

At least 19 recordsLinked to original sources
PubMed1995

Homozygous deletion of the MTS1/p16 and MTS2/p15 genes and amplification of the CDK4 gene in glioma.

Loci on chromosome 9p are frequently deleted in several malignant tumors, suggesting the presence of putative tumor suppressor genes. The MTS1/p16 and MTS2/p15 genes on 9p are considered to be candidates. Binding of p15 and p16 cell cycle-regulatory proteins to the cyclin dependent protein kinase CDK4 inhibits CDK4/cyclin D dependent phosphorylation of retinoblastoma protein. We analysed the DNAs from 37 gliomas of several grades of malignancy for allelic loss of chromosome 9p and aberrations of the MTS1/p16 and MTS2/p15 genes. We detected losses of one allele and homozygous deletions at loci, including those of the MTS1/p16 and MTS2/p15 genes, in 10 and 3 tumors, respectively. However, we did not detect any tumor-specific mutation in the two genes. The CDK4 gene was amplified in two malignant gliomas without homozygous deletion of the MTS1/p16 and MTS2/p15 genes and one malignant glioma with an allelic loss of the genes. These data suggest that aberrations of the genes coding for components of the cell cycle-regulatory system occurred in at least 15 of 37 gliomas.

Alleles↗
PubMed1995

Loss of heterozygosity at 11p15 in malignant glioma.

Deletions of loci on chromosome 11p have been found frequently in several malignant tumors including gliomas, suggesting the presence of tumor suppressor genes. We analyzed 38 gliomas [26 malignant gliomas (grades III and IV) and 12 less malignant gliomas (grade I and II)] for loss of heterozygosity using microsatellite sequences on 11p as polymorphic markers. Loss of heterozygosity was found in 8 of 26 malignant gliomas (31%) but not in the less malignant gliomas. In the region with loss of heterozygosity, loci on 11p15.5-pter were commonly deleted. Our results suggest that a putative tumor suppressor gene involved in malignant progression of gliomas is located in an approximately 21-cM region on 11p15.5-pter.

Base Sequence↗
PubMed1995

Synergistic effects of stem cell factor and interleukin 6 or interleukin 11 on the expansion of murine hematopoietic progenitors in liquid suspension culture.

The synergistic effects of stem cell factor (SCF) in combination with other growth factors including interleukin (IL)-6, IL-11, IL-3, GM-CSF, G-CSF, IL-1 alpha and interferon-gamma (IFN-gamma) on the expansion of murine hematopoietic progenitors were studied in a short-term liquid suspension culture system. Bone marrow (BM) cells obtained 2 days after 5-fluorouracil (5-FU) injection were cultured for up to 18 days in serum-containing and serum-free cultures in the presence of combinations of various cytokines. The numbers of nucleated cells, total colony-forming cells (CFC), mixed-colony forming units (CFU-Mix) and high-proliferative potential colony-forming cells (HPP-CFC) before and after liquid suspension cultures were measured in the presence of different combinations of cytokines. Combinations of SCF with IL-11, IL-6 or IL-1 alpha markedly increased the numbers of total CFC, CFU-Mix and HPP-CFC. A combination of SCF and IL-3 also expanded the number of total CFC; however, the fold increase was smaller than those of SCF plus IL-11, IL-6 or IL-1 alpha. Three or four factor combinations including SCF with IL-3, IL-6 and IL-11 did not yield increased numbers of total CFC over that supported by SCF plus either IL-6 or IL-11. The addition of IFN-gamma to the culture containing SCF plus IL-11 resulted in a decrease of the expansion efficiency. However, this difference is not statistically significant. In contrast, the addition of IFN-gamma to the cultures containing SCF plus IL-6 did not affect the expansion efficiency. Interestingly, the addition of IL-1 alpha in the culture containing SCF plus IL-3 significantly increased the number of HPP-CFC over that supported by SCF plus IL-3 (p < 0.01). In contrast, IL-1 alpha did not significantly affect the expansion efficiency in the presence of SCF plus IL-6 or IL-11. These results suggest that combinations of SCF plus either IL-6 or IL-11 or a combination of SCF, IL-3 and IL-1 alpha can most effectively expand murine hematopoietic progenitors derived from day-2 post-5-FU BM cells in vitro.

Animals↗
PubMed1995

Contralateral early blink reflex in patients with HTLV-I associated myelopathy/tropical spastic paraparesis.

Thirty-two Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were studied by means of the electrically elicited blink reflex and three responses (R1, R2, R3) were registered. 69% of the patients displayed a uni- or bilateral crossed R1 response (R1k) as compared to 11% in the control group. A positive correlation between R1k and an exaggerated jaw jerk reflex was found in the patients. Central abnormalities of the nervous system with diminished presynaptic inhibition acting in the interneuronal input of the brainstem of HAM/TSP patients was the most likely cause. It could lead to the unmasking of crossed trigemino-facial pathway reflex which is present in the normal population from birth. These results strongly support the supraspinal involvement of the central nervous system (CNS) in HAM/TSP more than usually thought.

Action Potentials↗
PubMed1995

Lanosterol 14 alpha-demethylase (cytochrome P-45014DM): modulation of its enzyme activity by cholesterol feeding.

Regulation of the activity of lanosterol 14 alpha-demethylase (cytochrome P-45014DM) by dietary cholesterol was studied in rats. In male rats fed a 3% cholesterol diet for 1 and 4 weeks, the activity of 24,25-dihydrolanosterol 14 alpha-demethylase was decreased in the liver. The cytochrome P-45014DM protein content detected by immunoblotting was also decreased by cholesterol feeding. These results demonstrate that dietary cholesterol acts as a repressive factor for lanosterol 14 alpha-demethylase. Further, the activity was enhanced by preincubation with phosphatase of the enzyme solution from both the control and cholesterol fed rats at the same rate. This result suggests that regulation of the activity involves phosphorylation of this enzyme.

Animals↗
PubMed1995

[Peripheral blood stem cell collection with high dose etoposide].

Peripheral blood stem cells (PBSC) were collected from 24 patients who were treated with high dose etoposide. Studied patients included one with acute lymphoblastic leukemia, 4 with acute myeloid leukemia (AML), 1 with myelodysplastic syndrome, 13 with lymphoma, 1 with malignant histiocytosis, 2 with myeloma, and 4 with testicular tumor. Etoposide was infused at a dose of 500 mg/m2 for 4 days, followed by subcutaneous injection of recombinant human granulocyte-colony stimulating factor from the nadir of leukocyte. PBSC were collected by processing 15-20 liters of blood apheresis in the recovery phase of chemotherapy. In all patients, the number of CFU-GM collected per aphereresis ranged from 0.01 to 59.4 x 10(5)/kg, and more than 5 x 10(5)/kg CFU-GM were collected in 19 of the patients (73%). All leukemia patients treated along with our protocols have remained in complete remission, but one patient with AML relapsed within 1 month after the treatment. Ten lymphoma patients were assessable for antitumor effect, and complete response (CR) was observed in 2, partial response (PR) was 7, and no change (NC) in one patient. Two patients with myeloma were classified to be NC. Three of the 4 patients with testicular tumor were PR, and the other one was NC. Eleven patients subsequently underwent PBSCT. The number of days required to achieve an absolute granulocyte count of 0.5 x 10(9)/l was 7 to 11 days, with a mean of 8.6.

Adult↗
PubMed1995

[Treatment of spastic paraparesis with botulinum toxin with reference to beneficial effects, disease severity and long-term treatment].

We administered local botulinum toxin injections on the leg adductors of 12 patients with spastic paraparesis (9 patients with HAM, 2 patients with spinal spastic paraparesis, 1 patient with an identified degenerative disease). Two of them were wheelchair-bound and the other patients could walk with or without help. The patients were assessed by the time to walk 10 m and the spasticity score which was derived from the degree of muscle tone and spasm frequency of leg adductors. After the initial injection, 7 of the 12 patients improved spasticity scores and 8 of the 10 patients could walk 10 m within a shorter time. The time to walk 10 m was markedly shortened in moderate cases. However, one patient complained of leg weakness and the time to walk 10 m was prolonged. Five of the 12 patients received injections 3 to 7 times, and were followed up for a mean of 16.2 months. In 4 of the 5 patients, repeated injections could maintain the improvement of spasticity score and time to walk 10 m. However, injection was discontinued in one patient because of leg weakness. The other side effects were pain and swelling at the injected site and dysarthria. However, these side effects were slight and transient and did not require treatment. No other systemic side effects were observed. In conclusion, the beneficial effects of botulinum injections to spastic paraparesis were (1) improvement of objective symptoms in mild cases, (2) improvement of ADL in moderate cases, and (3) improvement of objective symptoms and ease of nursing care in severe cases. Furthermore, we confirmed the long-term efficacy and safety of botulinum toxin.

Adult↗
PubMed1994

Synergistic actions of stem cell factor and other burst-promoting activities on proliferation of CD34+ highly purified blood progenitors expressing HLA-DR or different levels of c-kit protein.

We studied the synergistic effects of stem cell factor (SCF) and other burst-promoting activities (BPAs) such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-9 on proliferation of human peripheral blood-derived highly purified progenitors. SCF, IL-3, GM-CSF, and IL-9 showed significant BPA when CD34+HLA-DR+ cells were used as the target population. IL-3 exerted the most potent BPA, and GM-CSF supported approximately 40% to 70% of the erythroid burst-forming units that are responsive to IL-3. SCF and IL-9 showed much weaker BPA than that of IL-3 or GM-CSF. Combinations of IL-3 with other BPAs did not show synergistic actions supporting erythroid-burst formation. However, GM-CSF showed a significant additive effect with IL-9 or SCF. When CD34+c-kithigh cells were used as the target, SCF showed a much stronger BPA. Also, a distinct additive effect between SCF and IL-3 or GM-CSF on erythrocyte-containing mixed colony formation was observed. On the other hand, when CD34+c-kitlow cells were used as the target, SCF, IL-3, and GM-CSF could express BPA. In contrast, IL-9 alone failed to support erythroid-burst formation. Because CD34+c-kithigh cells weakly expressed CD34 antigen, these cells appeared to be more mature progenitors than CD34+c-kitlow cells. These results suggest that IL-9 acts on more mature progenitors than those of SCF, IL-3, or GM-CSF and that the primary target of SCF is multipotential progenitors at the very early stage of development.

Animals↗
PubMed1994

Posterolateral extradural approach for lateral thoracic meningocele--case report.

A 26-year-old female presented with a lateral thoracic meningocele associated with neurofibromatosis. The development of the thoracic meningocele was documented on serial chest roentgenograms. Magnetic resonance imaging and three-dimensional bone computed tomography scans were particularly useful to identify organic changes in the surrounding structures and the osseous orifice of the dural sac, respectively. The large thoracic meningocele was successfully treated through the posterolateral extradural approach in combination with resection of the adjacent ribs and cerebrospinal fluid drainage from the dural sac.

Adult↗
PubMed1994

[Successful collection of peripheral blood stem cells mobilized by high-dose etoposide for patients with chemotherapy-resistant and/or poor prognostic testicular cancer].

Clinical effects of peripheral blood stem cell autotransplantation (PBSCT) after ultra high-dose chemotherapy were evaluated in patients with chemotherapy-resistant and/or poor prognostic testicular cancer. Four patients with testicular cancer, who had high-risk malignancy, were treated with high-dose etoposide (500 mg/m2 x 4 days) in order to collect peripheral blood stem cells. After the administration of high-dose etoposide, rG-CSF (250 micrograms/body) was administered from nadir state. Blood mononuclear cells were collected using a Fenwall CS-3000 blood cell separator. Fractions enriched for stem cells were obtained by discontinuous Percoll gradient centrifugation and were stored in liquid nitrogen using patient's sera and DMSO. The mean number of peripheral blood granulocyte-macrophage-colony-forming units (CFU-GM) collected by one apheresis was 22.3 x 10(5)/kg body weight. In addition, CFU-GM more than 2.0 x 10(5)/kg body weight could be collected in each apheresis, which was though to be sufficient dosis to perform PBSCT in safe, based upon our previous studies. All the patients were treated by a combination of cisplatin (20 mg/m2 x 5 days), etoposide (100 mg/m2 x 5 days) and bleomycin (15 mg x 3 days). Three patients responded to BEP therapy and obtained a CR, however, remaining 1 patient failed to achieve CR, who was later treated by ultrahigh-dose chemotherapy including carboplatin (200 mg/m2 x 4 days), etoposide (250 mg/m2 x 4 days) and cyclophosphamide (50 mg/kg x 2 days) followed by PBSCT. He responded to this therapy and obtained a CR for 10 months. The results suggested the method was promising for patients with chemotherapy-resistant and/or poor prognostic testicular cancer.

Adult↗
PubMed1994

[Ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer].

This is a report of 45-year-old man with advanced nonseminomatous germ cell tumor (stage IIIB2: embryonal carcinoma, yolk sac tumor, seminoma), who had relapse after PVB (cisplatin, vinblastine, bleomycin) chemotherapy. Peripheral blood stem cells (PBSCs) were taken by two consecutive apheresis using a CS-3000 blood separator after high-dose chemotherapy of cytarabine and mitoxantrone. In total, 6.4 x 10(5)/kg of granulocytic cells (CFU-GM) was collected. He was treated with ultra high-dose chemotherapy consisting of carboplatin (800 mg/m2), etoposide (1,000 mg/m2) and cyclophosphamide (100 mg/kg) from day 1, followed by peripheral blood stem cell autotransplantation (PBSCT) on day 9. We transfused 2.4 x 10(5)/kg CFU-GM, which was enough number of stem cells for safe PBSCT. No serious side effects or complications were encountered. The patient achieved partial remission for more than two months. However, he died of respiratory dysfunction caused by metastatic lung cancer 5 months later. It was thought that ultra high-dose chemotherapy with PBSCT might be a new therapy for refractory testicular cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[A phase III trial of subcutaneous administration of rhG-CSF in aplastic anemia].

To evaluate the efficacy and safety of subcutaneous administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in aplastic anemia (AA), 21 patients were given a daily subcutaneous dose of 200 micrograms/m2 of KRN8601 for 4 weeks. When the blood neutrophil count did not reach 2,000/microliters within 2 weeks, the dose was increased to 400 micrograms/m2. A marked neutrophilic response was obtained in all 9 patients with non-severe AA and in 9 out of the 12 patients with severe AA, yielding a response rate of 85.7%. Adverse effects included lumbago in one patient and elevation of serum enzyme levels in 6 patients, but did not prohibit further treatment. These results suggest that subcutaneous administration of KRN8601 is safe and useful in improving neutropenia in AA.

Adolescent↗
PubMed1994

[A phase III trial of subcutaneous administration of rhG-CSF in the myelodysplastic syndromes].

To evaluate the safety and efficacy of subcutaneous administration of recombinant human granulocyte colony-stimulating factor in the myelodysplastic syndromes (MDS), 20 patients were given a daily dose of 50 micrograms/m2 of KRN8601 for 4 weeks. When the blood neutrophil count did not reach 2,000/microliters within 2 weeks, the dose was increased to 100 micrograms/m2. A marked neutrophilic response was obtained in 17 of the 18 evaluable patients (94.4%), irrespective of the MDS disease type. Five patients showed a platelet increase, 3 of which also showed an erythroid improvement. To maintain neutrophil levels greater than 1,000/microliters, 12 patients were treated with KRN8601 for 4 weeks. A dose of 25 to 50 micrograms/m2 3-4 times a week served to this end in 8 patients and 100 micrograms/m2 three times a week or daily in the remaining 4 patients. One patient with RAEB progressed to acute myeloid leukemia 8 weeks after KRN8601. The treatment was well-tolerated in the majority of patients with no severe toxicities. These results suggest that subcutaneous administration of KRN8601 is safe and useful in the treatment of cytopenias in MDS.

Adult↗
PubMed1993

Human interleukin-4 inhibits proliferation of megakaryocyte progenitor cells in culture.

We studied the effects of recombinant human interleukin-4 (rhIL-4) on megakaryocyte colony formation from enriched hematopoietic progenitors. IL-4 strongly inhibited pure and mixed megakaryocyte colony formation in a dose-dependent manner. Formation of erythroid bursts, eosinophil colonies, and erythrocyte-containing mixed colonies was not affected by the addition of IL-4 as reported previously (Sonoda Y, et al; Blood 75:1615, 1990). Delayed addition experiments suggested that IL-4 acts on an early stage of proliferation of megakaryocyte progenitors. Neutralizing antibodies (antisera) prepared against transforming growth factor beta, tumor necrosis factor alpha, interferon alpha (IFN alpha), and IFN gamma did not affect the inhibitory effects of IL-4 on pure and mixed megakaryocyte colony formation. In addition, the inhibitory effects of IL-4 was also seen in serum-free cultures and in cultures containing highly enriched CD34+, HLA-DR+ cells as a target population. These results indicate that IL-4 may function as one of the negative regulators in human megakaryocytopoiesis in vitro.

Adult↗
PubMed1993

Multilineage response in aplastic anemia patients following long-term administration of filgrastim (recombinant human granulocyte colony stimulating factor).

The present multicenter study was undertaken to confirm whether filgrastim/recombinant human granulocyte colony stimulating factor (rhG-CSF) could mobilize residual multipotential stem cells by its G0-shortening effect in patients with aplastic anemia (AA) and induce a multilineage response. Twenty-seven patients with acquired severe or moderate AA received long-term administration (2 to 12+ months) of rhG-CSF in doses from 100 to 400 micrograms/body/day by s.c. injection or 250 to 1,500 micrograms/body/day by i.v. infusion. Twenty-six out of the 27 evaluable patients showed a substantial increase in neutrophils associated with a recovery of myeloid precursors in bone marrow within one month of therapy. Interestingly, 10 out of the 27 patients showed a dramatic improvement in severe anemia after two to ten months of therapy. Moreover, severe thrombocytopenia improved after two to four months of therapy in three out of these ten patients accompanied by a significant increase in megakaryocytes in bone marrow. Clonal cultures of bone marrow cells revealed a recovery in myeloid as well as erythroid precursors in most of these ten patients. In two patients who showed a trilineage response, mixed and megakaryocyte colony formations also recovered. These results suggest that long-term administration of rhG-CSF mobilizes myeloid, erythroid, megakaryocyte and multipotential progenitor cells and induces a multilineage response in some patients with AA.

Adolescent↗
PubMed1993

[Successful collection of peripheral blood stem cells mobilized by a combination of G-CSF with high-dose Ara-C or high-dose etoposide].

The author evaluated the effectiveness of a combination of G-CSF with high-dose Ara-C (HD Ara-C) or high-dose etoposide based on the collection of peripheral blood stem cells (PBSC) during the recovery phase from myelosuppression in 17 patients with various types of hematopoietic malignancies. Following therapy with HD Ara-C or HD etoposide, G-CSF (250 micrograms/body) was administered from the nadir state and blood mononuclear cells were collected using a CS-3000 by processing 15 litres of blood at each apheresis. Stem cell-enriched fractions obtained from discontinuous Percoll gradients were collected and stored in liquid nitrogen. The mean numbers of granulocyte-macrophage colony-forming units (CFU-GM) obtained by the first apheresis were 10.9 x 10(5)/kg after chemotherapy with HD Ara-C and 13.4 x 10(5)/kg after HD etoposide therapy, respectively. In 14 out of the 17 first apheresis, more than 2 x 10(5) CFU-GM/kg were collected. Serial apheresis was performed in seven patients, at intervals ranging from 21-79 days, and the progenitor yield in the second apheresis decreased in five patients. These results suggest that the use of either HD Ara-C or HD etoposide induces an effective mobilization of PBSC and enables large scale collection of PBSC for autotransplantation.

Acute Disease↗
PubMed1993

[Peripheral blood stem cell transplantation in adult patients].

We reported the experience of peripheral blood stem cell transplantation (PBSCT) performed in adult patients with hematological malignancies and solid tumors. After myelosuppressive chemotherapy, peripheral blood stem cells were collected using a Blood Cell Separator (CS-3000) during bone marrow recovery and subsequently cryopreserved in 17 patients (9: malignant lymphoma; 2: ALL; 2: AML; 2: multiple myeloma; 2: solid tumors). In 28 apheresis cases, the collected number of granulocyte/macrophage progenitors (CFU-GM) was more than 5 x 10(5)/kg BW in 17 apheresis cases and ranged between 2 and 5 x 10(5)/kg BW in 4 of such cases. Eleven patients (7: malignant lymphoma; 1: ALL; 1: AML; 1: multiple myeloma; 1: neuroblastoma) underwent PBSCT following myeloablative chemotherapy. The infused number of CFU-GM ranged between 0.6 and 18.1 x 10(5)/kg BW. In 7 patients, more than 5 x 10(5) CFU-GM/kg BW were infused. The median time to reach 500 neutrophils/microliter or 50,000 platelets/microliter was 10 (range: 8-17) and 20 (range: 8-63) days, respectively. One patient died from sepsis before hematologic recovery occurred. Eight patients are alive with no evidence of active disease for 7-19 months after PBSCT. When the infused number of CFU-GM is more than 2 x 10(5)/kg BW, PBSCT following myeloablative chemotherapy seems to be safe and useful treatment.

Adolescent↗