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T Ninomiya

Publications and source records attributed to T Ninomiya.

At least 91 records · Page 5Linked to original sources
PubMed1991

Synergistic effect of recombinant interferon-gamma and interleukin-3 on the growth of immature human hematopoietic progenitors.

Purified peripheral blood hematopoietic progenitors from children in early remission from cancer respond to recombinant human interleukin-3 (IL-3), but not to granulocyte colony-stimulating factor (G-CSF). With these purified cells as a target, we studied the effect of recombinant human interferon-gamma (IFN-gamma) on progenitor growth, using both liquid-suspension limiting dilution assay (LDA) and regular methylcellulose culture of progenitors. We found that in LDA with IL-3, IFN-gamma directly stimulated the growth of blood progenitors in a dose-dependent manner with single-hit kinetics, whereas IFN-gamma suppressed the growth of G-CSF-supported progenitors obtained from bone marrow. The stimulatory effect was also observed in methylcellulose culture, but the addition of antibodies for G-CSF, granulocyte-macrophage CSF, IL-1 alpha, IL-1 beta, IL-6, or tumor necrosis factor did not result in a decrease of the colony number, supporting further the possible direct effect of IFN-gamma on progenitor growth. These results suggest that the inhibitory effect of IFN-gamma on hematopoietic progenitors is limited to those in an advanced stage of maturation. IFN-gamma may be one of the essential lymphokines upregulating the growth of human hematopoietic progenitor cells.

Blood Component Removal↗
PubMed1991

Effectiveness of high-dose MCNU therapy and hematopoietic stem cell autografts treatment of childhood acute leukemia/lymphoma with high-risk features.

Clinical and pharmacokinetic studies were performed regarding the toxicity of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) with other drugs, in conjunction with a peripheral blood stem cell autograft (PBSCT), for treating 26 children with acute leukemia or lymphoma associated with high-risk features. In the early phase of the study, MCNU (300 to 500 mg/m2) was administered with cytosine arabinoside (Ara-C) (1.6 to 16 g/m2), etoposide (VP-16) (0.8 to 1.6 g/m2), cyclophosphamide (CY) (100 to 200 mg/kg), or busulfan (16 mg/kg). No acute toxicity was noticed after this high-dose therapy. The dose-limiting factor of the regimens was significant but reversible interstitial pneumonitis (IP). In a subsequent trial with an MCNU/VP-16/Ara-C/CY (MCVAC) regimen in which the dose of MCNU was reduced, the risk of IP diminished. This study is still in progress, but the clinical response has so far been encouraging. Fifteen of 26 children are alive and well in unmaintained complete remission (CR) with a median follow-up period of 11 months (range, 3 to 34 months) after transplantation. This MCNU-based regimen without total body irradiation (TBI) is especially important in children to avoid the serious sequelae of irradiation. Our results justify a broader clinical trial to evaluate the effects of the MCVAC regimen followed by PBSCT.

Adolescent↗
PubMed1991

A simplified and rapid limiting dilution assay of T lymphocytes.

We report here the development of an alternative limiting dilution assay (LDA) of T lymphocytes (T cells). Blood mononuclear cells were first stimulated for 60 hr with PHA and then cultured in microwells in the presence of recombinant interleukin-2 without feeder cells. After 4 days of culture, wells were scored for proliferation. Clonal expansion of T cells followed the single-hit model of the Poisson distribution. The progenitor frequency (f) in the mononuclear cells and E-rosette-positive cells from normal donors were 0.082 +/- 0.025 (n = 12) and 0.236 +/- 0.029 (n = 5), respectively, but this was markedly decreased in patients who underwent marrow-ablative chemotherapy and autografts with blood hematopoietic stem cells. This LDA system should be of value in routine use for the evaluation of T cell proliferative activities.

Bone Marrow Transplantation↗
PubMed1991

Nucleosides influence the myelination of dorsal root ganglion cells in vitro; a quantitative comparison.

alpha-Modified minimal essential medium (alpha MEM) is the most useful commercial medium for survival and myelin formation of dorsal root ganglia (DRGs). When components of alpha MEM are compared with those of other commercial media, nucleosides are found only in alpha MEM. We examined the effects of nucleosides on myelin formation in rat DRG cultures. When myelin formation was viewed quantitatively, cultures using alpha MEM with nucleosides yielded 2- to 3-fold more myelin segments than cultures using alpha MEM without nucleosides.

Animals↗
PubMed1991

Impaired production of burst promoting activity by blood mononuclear cells from chronic uremic patients.

The ability of blood mononuclear cells (MNC) to produce burst promoting activity (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells from uremic patients, with or without hemodialysis, was consistently lower than that of 17 normal donors (mean 64%, P less than 0.01). Coculture of MNC with recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five of 31 patients received in vivo treatment with rEpo (1,500 units x3/week) and showed therapeutic benefit, but in all patients the BPA production remained low. On the other hand, in four patients who were on a hemodialysis protocol and subsequently underwent renal transplantation, impaired BPA production was resolved quickly, and at the same time the number of circulating BFU-E and the hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA production was not observed in patients receiving continuous ambulatory peritoneal dialysis. These observations suggest that decreased production of BPA may play a role in the development of anemia associated with chronic uremic patients, and the correction of BPA production by the improvement of hemodialysis procedure may result in more effective therapy with rEpo for those patients.

Adult↗
PubMed1991

Early infectious complications after peripheral blood stem cell autografts in children.

Seventeen children underwent marrow-ablative high-dose chemotherapy with peripheral blood stem cell autografts and were studied retrospectively to determine the type, frequency, and outcomes associated with infectious complications 3 months postgraft. The patients were kept in isolated rooms with a laminar air flow facility, but no decontamination procedures, such as gut sterilization with nonabsorbable antibiotics, nonmicrobial diet, and skin cleansing, were used. They were under their mothers' daily care to maintain good psychological conditions. After the completion of marrow-ablative chemotherapy and the infusion of stem cells, the absolute granulocyte count exceeded 0.5 x 10(9)/liter with a mean of 17.9 days (range 6-65 days). Fifteen patients developed a total of 16 febrile episodes during the first 4 week period, and the confirmed diagnoses were mucositis (12), enterocolitis (nine), septicemia (four), central venous catheter-associated infection (three), pneumonia (one), perianal abscess (one), and possible invasive fungal infection (one). All episodes were successfully treated with parenteral antibiotic therapy, and no patient died of infectious complications. The observations suggest that high-dose chemotherapy can be performed safely with simple and efficient patient management protocol followed by peripheral blood stem cell autografts.

Adolescent↗
PubMed1991

[Peripheral blood stem cell autografts (PBSCT) in the treatment of 30 children with acute leukemias and lymphoma].

Thirty children (1-16 y.o.; median, 10 y.o.) with acute leukemia or non-Hodgkin's lymphoma (NHL) associated with high-risk features underwent high-dose chemotherapy without total body irradiation and peripheral blood stem cell autografts (PBSCT). Eighteen patients had acute lymphoblastic leukemia (ALL), 6 had acute non-lymphoblastic leukemia (ANLL), 2 had mixed-lineage leukemia and 4 had NHL. Twelve patients with two or more high-risk features (WBC greater than 10 x 10(4)/microliter, T- or B-phenotypes, infancy, massive organ infiltration, or induction failure) underwent PBSCT in 1st CR. Twelve patients underwent PBSCT in 2nd CR, and 4 in the subsequent remission greater than or equal to 3rd CR). Two patients were treated at refractory relapse. After PBSCT the number of days required to achieve a granulocyte count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l was 6.39 (median, 13) and 9-427 (median, 16), respectively. The disease-free survival rate was 6/12 in 1st CR group (6-41 mo) and 6/16 in the patients who underwent PBSCT in 2nd or subsequent remission (2-35 mo). The data justify the incorporation of PBSCT in the design of salvage protocol for children with leukemias or NHL. However, the application of the procedure as part of initial therapy in patients still remaining in 1st CR should be regarded as highly experimental and deserve further clarification.

Acute Disease↗
PubMed1991

Retrospective analysis of late intensification therapy with high-dose methotrexate for standard-risk acute lymphoblastic leukemia in childhood (CCLSG-S811 study). The Children's Cancer and Leukemia Study Group.

Using the CCLSG-S811 protocol for children with standard-risk acute lymphoblastic leukemia (ALL), late intensification therapy (LIT) with high-dose methotrexate (HD-MTX) was conducted without randomization. Of 118 eligible patients, 114 attained complete remission and 82 maintained continuous complete remission (CCR) for at least 3 years, completing the entire S811 regimen. Among the latter, 74 patients received LIT with HD-MTX between 2-3 years after CCR onset. MTX (2,000 mg/m2 per dose per week) was administered by 24 h infusion and three doses were given every 12 weeks. Leucovorin rescue (15 mg/m2 i.v.) every 6 h was initiated 12 h after the end of MTX infusion for seven doses. As regular maintenance chemotherapy, intermittent (Regimen A) or continuous (Regimen B) MTX plus 6-mercaptopurine (6MP) combined with pulses of prednisolone and vincristine was administered (Koizumi S, Fujimoto T, Takeda T, et al. Cancer 1988; 61: 1292-1300). Retrospective analysis revealed that patients on Regimen A who started LIT earlier (within 2 years of CCR onset (n = 23)) showed a higher rate of event-free survival (EFS) at 8 years (95.5% +/- 4.4%, mean +/- S.E.) than patients who started LIT later (2.5 years after CCR onset (n = 18, 66.2% +/- 11.3%, p less than 0.01)). In addition, the superiority of four or five courses of the LIT (n = 39) as compared to 2 or 3 courses (n = 35) was noted for both regimens. The data suggest that early and aggressive LIT with HD-MTX may improve the long-term survival of childhood ALL patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Effects of recombinant human G-CSF, GM-CSF, IL-3, and IL-1 alpha on the growth of purified human peripheral blood progenitors.

The effects of recombinant products of granulocyte colony-stimulating factors (G-CSF), granulocyte/macrophage CSF (GM-CSF), human interleukin-3 (IL-3), and interleukin-1 (IL-1) were studied using purified target cell populations from patients undergoing peripheral blood stem cell transplantation after myeloablative therapy. Cells were subjected to combined purification procedures including negative selection with a panel of monoclonal antibodies (CD2, 3, 5, 10, and 20). The purified cells were enriched for HLA-DR+ (51% to 71%) and My-10+ (CD34; 37% to 54%) and had a plating efficiency of up to 20%. In the liquid-suspension limiting dilution clonal assay (LDA), purified progenitors responded directly to IL-3 by proliferation with single-hit kinetics. The ability of GM-CSF to support progenitor growth was inferior to that of IL-3, and the cells were virtually unresponsive when cultured with G-CSF, supporting the notion that these blood-derived progenitors belong to a primitive population of hematopoietic progenitor cells. The results obtained in simultaneous methycellulose cultures (MC) showed the same trend and provided additional information on the ability of GM-CSF and IL-3 to support erythroid progenitor growth. The combination of IL-3 plus G-CSF, but not IL-3 plus GM-CSF, resulted in a synergistic increase in colony number. IL-1 alpha increased both the size and number of colonies when added to IL-3 or G-CSF. Study of this enriched progenitor cell population in MC and LDA represents an excellent model for the investigation of myeloid and erythroid differentiation and for evaluating the influence of various cytokines on human hematopoiesis.

Antigens, CD↗
PubMed1990

[Optimal methods for peripheral blood progenitor assay and its relevance in the blood cell autotransplantation].

Methylcellulose culture study revealed that the potency of recombinant granulocyte-colony stimulating factor (G-CSF) or granulocyte/macrophage (GM)-CSF to support the growth of purified target cell populations from peripheral blood of patients undergoing peripheral blood stem cell (PBSC) autotransplantation was inferior to that of PHA-stimulated lymphocyte conditioned medium (PHA-LCM) or interleukin-3 (IL-3). In liquid-suspension limiting dilution assay the cells responded directly to IL-3 by proliferation with single-hit kinetics. Hence, optimal culture for PBSC should include the use of PHA-LCM or IL-3. Further study disclosed a linear relationship between the number of CFU-GM infused into the patients and days required to achieve a granulocyte count above 0.5 x 10(9)/l.

Adolescent↗
PubMed1990

[Autografts with peripheral blood stem cells].

This paper reports a clinical and laboratory experience of peripheral blood stem cell (PBSC) autografts at a single institute. Twenty-eight children with various types of cancer underwent a total of 90 leukaphereses to collect PBSC and 17 of them subsequently received marrow-ablative therapy and PBSC autografts. We found that frozen-thawed progenitor dose is important in determining the rate of hematopoietic recovery after transplantation; in 11 patients who received more than 1 x 10(5) CFU-GM/kg, the granulocyte count reached to 0.5 x 10(9)/L in two weeks. With conditioning chemotherapy without total body irradiation, 6 of 14 patients with high-risk acute leukemia or non-Hodgkin's lymphoma have survived disease-free 3 to 25 months posttransplant. This approach may have a potential to induce prolonged remission-interval and ultimate cure.

Adolescent↗
PubMed1990

[Experiences in general anesthesia of patients with scoliosis presupposed to have difficulties in airway maintenance].

We experienced general anesthesia of two patients with cerebral palsy presupposed to have difficulties in tracheal intubation by reason of scoliosis. Case 1 is a 26-year-old woman. Chest X-ray photography and respiratory sounds in both pulmonary areas indicated neither airway stricture nor respiratory distress, but severe scoliosis presupposed difficult tracheal intubation. However, under the impression of possible intubation obtained by preoperative laryngoscopy, orotracheal intubation was tried with rapid induction. Epiglottis deviation to the left noted upon developing larynx made the glottis direct invisible, but some compression of cricoid from outside barely succeeded in intubation. The fixation of the endotracheal tube found much difficulties in its proper positioning so as to make stethoscopy uniform in both pulmonary areas, but trial rotations of the tube both in various directions and at various depths barely managed to find a position of uniform stethoscopy in both pulmonary areas, in which position the tube was fixed as proper positioning. Anesthesia was performed by nitrous oxide.oxygen.halothane; peroperative hemodynamics remained stable and arterial blood gas analysis presented no problems. Case II is a 16-year-old man. Resting respiration presented stridor and chest X-ray photography indicated scoliosis and laryngeal stricture. Patient's lack in the degree of cooperation made laryngoscopy impossible. Thus, in view of a high possibility of difficult tracheal intubation, orotracheal intubation was tried under the control of spontaneous respiration. While the intubation was being carried out by means of a stylet without developing larynx, severe bronchostriction was palpable at the point when the tube barely passed through the glottis, making the intubation impossible. However, the tube barely managed to be inserted while rotating with the stylet being extracted. Anesthesia was carried out by nitrous oxide.oxygen.halothane; peroperative hemodynamics underwent no remarkable change and arterial blood gas analysis presented no problems.

Adolescent↗
PubMed1990

Molecular analysis of T cell receptor and CD3 genes in CD3- large granular lymphocytes (LGLs): evidence for the existence of CD3- LGLs committed to the T cell lineage.

Seven patients with CD3- lymphoproliferative disorder of granular lymphocytes (LDGL) were analyzed for rearrangement of the T cell receptor (TCR) delta and alpha as well as gamma and beta genes. Among those patients six showed the germline configuration of all known rearranging TCR genes. Two analyzed patients of them lacked CD3-gamma transcripts and expressed nonfunctional TCR-beta transcripts. Meanwhile, TCR-delta gene rearrangement accompanied by expression of full-length TCR-delta transcripts was observed in one patient with CD3- LDGL. In addition, the cells from this patient transcribed the CD3-gamma gene which is one of the earliest events restricted to cells committed to the T cell lineage. These findings indicate that CD3- LGLs include not only cells belonging to the NK cell lineage but also precursor cells committed to the T cell lineage.

Antigens, Differentiation, T-Lymphocyte↗