Biomedical subjects

T Ninomiya

Publications and source records attributed to T Ninomiya.

At least 109 records · Page 6Linked to original sources

PubMed1990

[Evaluation of BPA secretory ability from blood mono-nuclear cells in uremic patients after renal transplantation or rEpo treatment].

Conditioned media (CM) of phyto-hemagglutinin-stimulated lymphocytes from chronic uremic patients were studied for burst promoting activity (BPA), using methylcellulose cultures with cord blood cells as a target population. Renal transplantation procedure was followed by a prompt rise of BPA, as well as the number of blood burst-forming unit erythroid (BFU-E) and hemoglobin levels, while no change in BPA and blood BFU-E number was observed in patients receiving rEpo and recovering from anemia. Thus, low BPA secretion from blood cells may have a role in the development of anemia in uremic patients.

Adult↗

PubMed1989

Cell-mediated suppression of human hematopoiesis: evaluation by limiting-dilution analysis of hematopoietic progenitors.

We have used limiting-dilution clonal analysis (LDA) in microwells to study the inhibitory effects of T lymphocytes (T-cells) or natural killer (NK) cells on human marrow progenitor cell growth. In four subjects with normal hematopoiesis, the growth of progenitors showed single-hit kinetics both before and after T-cell removal, indicating that, in the presence of colony-stimulating activity, T-cell have no effect on progenitor growth. In a patient with marrow hypoplasia associated with thymoma, hypogammaglobulinemia, and an increased number of suppressor T-cells (Good's syndrome), the progenitor growth deviated from linearity, demonstrating the presence of cells with suppressor activity. After T-cells were removed from this sample, the progenitor growth showed single-hit kinetics. The suppressive action of E-rosette-positive cells with NK or cytotoxic activities was also suggested in a patient with severe combined immune deficiency and in a patient with T gamma lymphocytosis. Poor progenitor-cell growth in three other patients with aplastic anemia was not significantly altered by T-cell removal. Thus, LDA of human hematopoietic progenitors is useful for evaluating cell-mediated interactions affecting hematopoiesis. This method may facilitate elucidation of mechanisms of myelosuppression in clinical settings.

Anemia, Aplastic↗

PubMed1989

Selection of mouse preimplantation embryos carrying exogenous DNA by polymerase chain reaction.

A polymerase chain reaction (PCR) system to detect transgenes in mouse preimplantation embryos was employed so that transgenic embryos could be selected before they were transferred to recipient mice. The selection system involves bisection of morulae, selection of the half-morulae containing target sequences within 7 hr, and culture and transfer of the sister half-morulae. PCR analysis of morulae derived from transgenic mice confirmed that the PCR system was reliable. However, five of 41 implanted embryos derived from PCR-positive morulae did not contain the transgenes. Also, one of 28 implanted embryos from PCR-negative morulae were transgenic. The selection system was applied to fertilized mouse eggs into which pSV2-gpt-gE1A DNA was injected. The injected DNA was detected in 30 of 84 morulae derived from the microinjected eggs. All seven implanted embryos developed from PCR-negative morulae had no detectable amount of transgenes, and one of two successfully implanted embryos from PCR-positive morulae was transgenic.

Animals↗

PubMed1989

Immunohistochemical localization of the alpha and beta subunits of S-100 protein in pleomorphic adenoma of the salivary glands.

The immunohistochemical expression of the alpha and beta subunits of S-100 protein in reactive, modified and transformed of myoepithelial cells, salivary pleomorphic was investigated using monoclonal antibodies. With S-100 alpha, normal salivary glands showed strong staining in serous acinar cells and moderate to slight staining in ductal segments, and with S-100 beta staining was slight or negative in acinar cells, but strong in nerve fibres. In pleomorphic salivary adenomas, the immunohistochemical distribution of S-100 alpha and beta proteins indicated great variation in the tumour cells. Some neoplastic cells gave similar staining for both S-100 alpha and beta, others were strongly positive for S-100 alpha and stained only slightly for S-100 beta, or vice versa. Yet other cells were positive for S-100 alpha and negative for S-100 beta, or vice versa. Pleomorphic salivary adenomas were classified both by histopathological criteria and by their staining pattern for S-100 alpha and beta proteins. Great heterogeneity in S-100 alpha and beta protein expression was found in individual tumour cells of both ductal and myoepithelial origin, and no regular pattern was identified. The cellular origin of salivary pleomorphic adenomas is discussed in terms of S-100 alpha and beta protein immunohistochemistry. Pleomorphic adenoma cells may be transformed from reserve cells into tumour cells displaying biologic properties of myoepithelial cells, ductal cells, or a mixture of both.

Adenoma, Pleomorphic↗

PubMed1989

Branchial cleft cysts. Histologic and immunohistochemical aspects.

8 cases of branchial cleft cysts and 1 case of branchiogenic carcinoma were examined immunohistochemically for detectable keratin, immunoglobulins (IgG, IgA, IgM), carcinoembryonic antigen (CEA), factor VIII related antigen (Factor VIII RGA), and lysozyme. Lectin binding patterns were also determined. Histologically, cystic lining epithelia were classified into stratified squamous epithelium without keratinization, columnar epithelium with or without cilia, or a mixture of both. Almost all of the cases indicated accompanying lymphoid structures with germinal centers. Keratin expression in epithelial cells was slightly positive, and lectin binding affinities in them were similar to those of oral squamous epithelium. CEA was found on the surface border of columnar epithelial cells, but cystic epithelia in most of the cases were devoid of lysozyme. Endothelial cells of capillary vessels showed positive binding by UEA-1 lectin and the presence of factor VIII RAG. In the lymphoid structures, there were scattered strongly positive lysozyme-staining cells as well as a few lymphocytes bearing IgG, IgA, or IgM.

Adult↗

PubMed1989

Sustained cytopenia after leukapheresis for collection of peripheral blood stem cells in small children.

Marked and persistent cytopenia was observed in two 3-year-old children with cancer, after lymphopheresis to collect peripheral blood stem cells (PBSC) for autotransplantation after high-dose chemotherapy. This finding suggests that PBSC are a major component of the hematopoietic cells in small children and, hence, that special care is necessary in the construction of a protocol for collection of stem cells from young children.

Child, Preschool↗

PubMed1989

In vivo dose-response effect of recombinant human granulocyte colony-stimulating factor on increase in granulocytes after peripheral blood stem cell autotransplantation.

The in vivo dose-response potential of recombinant human granulocyte colony-stimulating factor (rG-CSF) in facilitating reconstitution of granulopoiesis was evaluated in an 11-year-old girl who received autotransplantation of peripheral blood stem cells (PBSC) after marrow-ablative therapy for relapsing acute lymphoblastic leukemia. The recovery of hematopoiesis was slow when a small number of progenitors were collected and reinfused into the patient, but administration of rG-CSF led to significant dose-dependent increase in peripheral blood granulocytes.

Blood Transfusion, Autologous↗

PubMed1989

CD3-negative lymphoproliferative disease of granular lymphocytes containing Epstein-Barr viral DNA.

Lymphoproliferative disease of granular lymphocytes (LDGL) is a heterogeneous disorder and the pathogenesis is likely to be complex. Some patients with chronic active EBV (CAEBV) infection also have LDGL. To investigate the relationship between EBV infection and the pathogenesis of LDGL, we conducted a survey for EBV DNA sequences by Southern blot analysis of DNA obtained from the peripheral blood of seven patients with LDGL, including one with CAEBV infection. Interestingly, EBV DNA was detected in the sample from the patient with CAEBV infection, and in the samples from four other patients with CD3-LDGL. Moreover, a single band for the joined termini of the EBV genome was demonstrated in two samples, suggesting a clonal disorder of those LDGL. These findings strongly suggest that EBV may play a pathogenic role in some cases of LDGL.

Adolescent↗

PubMed1989

Myoepitheliomas and myoepithelial adenomas of salivary gland origin. Immunohistochemical evaluation of filament proteins, S-100 alpha and beta, glial fibrillary acidic proteins, neuron-specific enolase, and lactoferrin.

Immunohistochemical identification of keratin proteins (TK, KL1 and PKK1), vimentin, myosin, S-100 protein (using polyclonal antiserum) and S-100 alpha and beta subunits, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), lactoferrin, and lysozyme was made in myoepitheliomas, myoepithelial adenomas, and clear cell adenomas of salivary gland origin. Myoepithelioma cells were divided into two types: plasmacytoid cells, which showed great heterogeneity in terms of keratins and S-100 alpha and beta proteins and a lack of GFAP, NSE, lactoferrin, and lysozyme in most the cells, and fibrous and dendritic tumor cells, which displayed variable staining for keratin and S-100 alpha and beta proteins. Myoepithelial adenomas were composed of small-, intermediate-, and large-sized spindle cells that showed irregular positive reactions for keratins and S-100 alpha and beta. Immunohistochemical deposition of S-100 protein was restricted strongly to the dendritic cells present in hyalinous and myxomatous areas. Clear cell adenomas revealed uniformly slight staining of keratins and S-100 proteins, and negative staining or rarely positivity for GFAP, NSE, lactoferrin, and lysozyme. When the immunohistochemical deposition of these proteins was compared between normal glands and myoepithelial tumors, heterogeneity of expression of keratins, S-100 proteins, GFAP, and NSE was notable in the tumors. Progenitor cells of several kinds of myoepithelioma were suggested to be intercalated reserve cells, which are thought to be the same cell that gives rise to pleomorphic adenoma of salivary glands.

Adenoma↗

PubMed1989

[Recovery kinetics of hematopoiesis after peripheral blood stem cell autotransplantation].

Hematopoietic recovery kinetics was evaluated in five children with therapy-refractory cancers who received peripheral blood stem cell autotransplantation (PBSCT) following marrow-ablative chemotherapy. Four children received graft containing more than 1.5 X 10(4) CFU-GM/kg and days required to achieve granulocyte counts of greater than 0.5 X 10(9)/l were 6, 10, 13, and 18, respectively. One patient received 0.9 X 10(4) CFU-GM/kg, but, recovery of granulopoiesis was retarded (greater than 30 days). The days required to achieve platelet count of greater than 50 X 10(9)/l were 12, 15, 16, 195, and greater than 240, respectively. Transient decrease of blood cell counts developed 3 to 5 weeks after transplantation and thereafter, the recovery of hematopoiesis became stable. With the use of a large number of progenitors, PBSCT seems to be safe and effective new type of stem cell rescue operation as an alternative to bone marrow transplantation.

Acute Disease↗

PubMed1989

[Rapid and complete hematopoietic reconstitution following peripheral blood stem cell autotransplantation in a child with T cell acute lymphoblastic leukemia].

Rapid and complete hematopoietic reconstitution was achieved in a child with T cell acute lymphoblastic leukemia who was autografted with peripheral blood stem cells (PBSC). A large number of PBSC was collected by two courses of 3-4 hour-lasting lymphopheresis during early remission induced by the second-line chemotherapy and then cryopreserved in liquid nitrogen. A myeloid progenitor cell dose of 203 X 10(4) CFU-GM/kg body weight was reinfused to the patient following marrow-ablative chemotherapy (MCNU 600 mg/m2, cytosine arabinoside 6 g/m2, etoposide 300 mg/m2, cyclophosphamide 160 mg/kg). Neutrophil count reached 0.5 X 10(9)/l by day + 7 and platelet count reached 20 X 10(9)/l by day + 9. Thereafter, white blood cell count continued to increase and reached a maximum of 38 X 10(9)/l on day + 14. Thus, the rapid recovery of hematopoiesis minimised marrow aplasia-related risks. This approach of stem cell rescue operation can be applied to the treatment of children with cancer, who otherwise have no hope to be cured, as an alternative to bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Peripheral blood stem cell autotransplantation in treatment of childhood cancer.

The levels of circulating hematopoietic progenitor cells were measured sequentially in eight children receiving chemotherapy for acute leukemia or neuroblastoma. Significant increases in the progenitor levels (up to 50-fold in CFU-GM numbers) were observed during post-chemotherapy cytopenia in all cases, but differences among individuals in the kinetics of recovery of less committed progenitors (CFU-mix) contrasted with the synchronized-mode of expansion of committed progenitors (CFU-GM). Peripheral blood cells were collected by repeated continuous-flow leukaphereses from three of the children during post-chemotherapy expansion of the progenitor pool and were cryopreserved after fractionation procedures. Infusion of these stored cells into the patients after marrow-ablative chemotherapy established trilineage hematopoiesis. This use of stem cell rescue should be useful as an alternative to bone marrow transplantation and extends the application of cure-oriented salvage therapy to childhood cancers.

Blood Cell Count↗

PubMed1989

Isolation and storage of peripheral blood hematopoietic stem cells for autotransplantation into children with cancer.

Peripheral blood stem cells (PBSC) were collected for autotransplantation by a total of 46 continuous-flow leukaphereses in 17 children with various types of cancer in whom the stem-cell pool had been expanded by chemotherapy. As the cells collected by leukapheresis were contaminated with many visible cell clumps, platelets, and erythrocytes, they were separated from the platelet-rich plasma (PRP) by slow-speed centrifugation and fractionated on a discontinuous gradient of Percoll. All the hematopoietic progenitors (CFU-GM, CFU-GEMM) in the starting samples were recovered at the interface of 40% and 60% Percoll solutions largely free of other cellular components and with a substantial reduction in volume. The separation and freezing procedures could be completed within three hours after obtaining cells by leukapheresis. After their fractionation and storage, these PBSC were shown to be able to reconstitute normal hematopoiesis in ten children with poor prognosis leukemia or neuroblastoma for whom no HLA-compatible marrow donors were available and who had been subjected to marrow-ablative therapy. This separation procedure is simple, efficient, and readily available and can be used for children as a routine procedure for PBSC autotransplantation.

Adolescent↗

PubMed1989

[Interstitial pneumonitis following high-dose MCNU].

We describe a 11-year-old boy with NHL, who developed interstitial pneumonitis following high-dose MCNU with autologous peripheral stem cell transfusion. Non-productive cough, malaise and progressive dyspnea on exertion were noticed 7 weeks after high-dose MCNU (600 mg/kg) treatment, and chest X-ray revealed a bibasilar reticular pattern. Arterial blood was hypoxemic and pulmonary function showed the development of a restrictive ventilatory effect and a reduced diffusing capacity for carbon monoxide (DLCO). Clinical Symptoms were resolved after 3 courses of m-PSL pulse therapy and 6 months prednisolone, but an isolated reduction in DLCO has been present. This case suggests that pulmonary toxicity is a dose limiting factor for MCNU treatment.

Antineoplastic Agents↗

PubMed1989

[Comparative study on in vitro lymphocytotoxicity and mitogenicity of different antilymphocyte globulin (ALG) preparations].

The lymphocytotoxicity and mitogenicity between six different ALG preparations on the clinical use world wide were compared. No significant difference in the lympholytic activity was observed between preparations and 100% cell lysis was achieved at a concentration of 50 micrograms/ml in the presence of complement. On the other hand, four preparations now in use in European countries and USA showed variable mitogenic activities on lymphocytes in the absence of complement, whereas two ALGs used in Japan did not. As the stimulatory effects of ALG on lymphocytes may contribute to the clinical outcome in the treatment of severe aplastic anemia (Kawano et al, 1988), these date can explain the poor clinical results of ALG therapy with those two preparations in Japan. Careful measures should be paid in the construction of treatment protocol and selection of ALG preparations to yield the best results.

Antilymphocyte Serum↗

PubMed1988

Comparison of intermittent or continuous methotrexate plus 6-mercaptopurine in regimens for standard-risk acute lymphoblastic leukemia in childhood (JCCLSG-S811). The Japanese Children's Cancer and Leukemia Study Group.

From 1981 to 1983, 131 previously untreated patients with acute lymphoblastic leukemia (ALL) standard-risk group were entered to the protocol JCCLSG-S811. Of 119 eligible patients, 115 (96.6%) attained complete remission by treatment with prednisone (PRD) plus vincristine (VCR) or vindesine (VDS). After preventive central nervous system (CNS) therapy including 18 Gy cranial irradiation and three doses of intrathecal methotrexate (MTX), the patients were assigned randomly to the two maintenance chemotherapies, Regimen A and Regimen B. Regimen A (intermittent regimen) consisted of PRD (120 mg/m2/day by mouth for 5 days) plus 6-mercaptopurine (6MP) (175 mg/m2/day by mouth for 5 days) plus VCR (2.0 mg/m2 intravenously) alternating biweekly with MTX (225 mg/m2 intravenously). Regimen B (continuous regimen) consisted of 6MP (50 mg/m2/day by mouth) plus MTX (20 mg/m2/week by mouth) combined with pulses of PRD and VCR (the same dosages as Regimen A) every 4 weeks. As the late intensification therapy (LIT), five courses of high-dose MTX (2000 mg/m2 per dose per week intravenously for three doses every 12 weeks) with leucovorin rescue were administered to all patients who were in continuous complete remission (CCR) for more than 2 years. Sixty and 55 patients, respectively, were registered in Regimen A and B. The CCR rates in Regimen A and B were 75.1% +/- 5.8% (mean +/- 1 SE) and 49.7% +/- 7.3% (P less than 0.01) at 4 years, and 72.1% +/- 6.3% and 49.7% +/- 7.3% (P less than 0.05) at 5 years, respectively. In Regimen B, CNS and testicular relapses increased after 3 years of CCR. In addition, the patients in Regimen B had a much higher incidence of infections than Regimen A. The LIT did not seem to have important effects on the duration of CCR. From these data we conclude that the intermittent cyclic regimen of 6MP and MTX may be more effective as compared to the continuous administration of these drugs in the maintenance chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Myelin formation in rat dorsal root ganglion cultured in a serum-free medium: influence of various culture media on myelin formation.

Survival and myelination in dorsal root ganglion culture were observed using 6 kinds of modified commercial serum-free media: MEM, neMEM, alpha-MEM, DMEM, F12 medium and DF medium (see Materials and Methods). The results showed that the survival rates of dorsal root ganglia cultured in alpha-MEM and DF medium are the highest and that the rates of myelinated ganglia are the highest when alpha-MEM is used as culture medium, as compared with other serum-free media.

Animals↗

PubMed1988

Immunoreactive prolactin in lesions and tumours of salivary glands.

The prolactin binding in obstructive lesions and tumours of salivary glands was described by use of the immunohistochemical PAP technique. Normal salivary glands had prolactin binding cells in the striated ducts only. Chronic obstructive lesions of submandibular glands showed negative immunoreaction for prolactin binding in ductal cells, but positive staining of the luminal surface of ductal segments. In pleomorphic adenomas, occasional neoplastic cells located along the luminal borders of tubular, ductal, or of duct-like epithelial structures were strongly reactive with anti-prolactin and 26.5% of cases pleomorphic adenoma were positive for anti-prolactin. Adenoid cystic carcinoma exhibited positive prolactin binding on the luminal surface of some of tumour foci, but not in the rest of the tumour. Warthin's tumour was devoid of detectable prolactin binding.

Humans↗