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Biomedical subjects

T Fujisaki

Publications and source records attributed to T Fujisaki.

At least 55 records · Page 3Linked to original sources
PubMed1996

Granulocyte colony-stimulating factor-induced mobilization of peripheral blood stem cells for autologous and allogeneic transplantation. Fukuoka Bone Marrow Transplantation Group.

Peripheral blood stem and progenitor cells (PBSC and PBPC), which circulate at very low levels during steady-state hematopoiesis, show a transient but marked increase during hematologic recovery from marrow-suppressive chemotherapy. To ensure rapid and sustained hematologic engraftment after autologous PBSC transplantation, sufficient PBSC or PBPC must be infused. To confirm the utility of granulocyte colony-stimulating factor (G-CSF) in chemotherapy-induced PBSC mobilization, we investigated the effect of G-CSF on PBSC mobilization in leukemia and lymphoma patients. The study design was such that PBSC mobilization with and without G-CSF was assessed in the same patients. The results indicate that PBSC mobilization can be enhanced significantly when G-CSF is given during the recovery phase postchemotherapy. Interestingly, progenitor cells of different lineages could be mobilized by G-CSF. We subsequently investigated the effect of increasing G-CSF dose on PBSC mobilization during steady-state hematopoiesis in healthy adult donors. The results indicate that not only committed but also primitive progenitor cells are mobilized into the circulation in a dose-and time-dependent manner when G-CSF at 5, 10, or 15 micrograms/kg was given on each of 5 days and leukapheresis was performed on day 6. From our data we estimate that sufficient PBSC for engraftment after allogeneic PBSC transplantation can be collected on day 5 of administration of G-CSF at 10 micrograms/kg and by 10-1 leukapheresis on days 5 and 6. Furthermore, we found that some G-CSF-mobilized PBSC retained their self-renewal capability. These observations suggest that hematopoietic stem cells for allogeneic PBSC transplantation can be mobilized by short-term administration of relatively high-dose G-CSF.

Animals↗
PubMed1996

Deficient cerebellar long-term depression, impaired eyeblink conditioning, and normal motor coordination in GFAP mutant mice.

Mice devoid of glial fibrillary acidic protein (GFAP), an intermediate filament protein specifically expressed in astrocytes, develop normally and do not show any detectable abnormalities in the anatomy of the brain. In the cerebellum, excitatory synaptic transmission from parallel fibers (PFs) or climbing fibers (CFs) to Purkinje cells is unaltered, and these synapses display normal short-term synaptic plasticity to paired stimuli in GFAP mutant mice. In contrast, long-term depression (LTD) at PF-Purkinje cell synapses is clearly deficient. Furthermore, GFAP mutant mice exhibited a significant impairment of eyeblink conditioning without any detectable deficits in motor coordination tasks. These results suggest that GFAP is required for communications between Bergmann glia and Purkinje cells during LTD induction and maintenance. The data support the notion that cerebellar LTD is a cellular mechanism closely associated with eyeblink conditioning, but is not essential for motor coordination tasks tested.

Animals↗
PubMed1996

Generation of human natural killer cells from peripheral blood CD34+ cells mobilized by granulocyte colony-stimulating factor.

We studied the generation of human natural killer (NK) cells from CD34+ cells that were isolated from peripheral blood stem cells (PBSC) mobilized by granulocyte colony-stimulating factor (g-CSF). The isolated CD34+ cells were cultured in the presence of a combination of interleukin-1 (IL-1alpha), IL-2, and stem cell factor for 5 weeks without marrow stroma. We found that the CD34+ cells isolated from G-CSF-mobilized PBSC (G-CSF/PBSC) could differentiate into a population of NK cells which were CD56+(bright)/CD3- and showed morphologic characteristics of large granular lymphocytes. Immunophenotypic analysis of the NK cells thus generated showed that a small proportion of them expressed CD2, CD8 and CD16 surface markers and approximately half of them coexpressed CD7. This NK population exhibited cytotoxic activity against a NK-sensitive cell line, K562. These observations suggest that CD34+ cells from G-CSF/PBSC contain precursors of NK cells that can differentiate into functional NK cells.

Adult↗
PubMed1996

G-CSF-induced mobilization of peripheral blood stem cells from healthy adults for allogeneic transplantation.

We investigated a dose-escalation effect of G-CSF (5, 10, and 15 micrograms/kg) on mobilization of committed and primitive hemopoietic progenitor cells, including CFU-GM, BFU-E, and long-term culture-initiating cells (LTC-IC) in addition to CD34+ cells and yields of progenitor cells in PBSC harvests obtained by leukapheresis of healthy adult donors. Results indicate that the mobilization of these progenitor cells is both dose and time dependent. Despite the very small number of healthy donors studied, it is estimated from our data that a sufficient number of CD34+ cells for allogeneic PBSC transplant (PBSCT) could be collected using a 5 day administration of 10 micrograms/kg of G-CSF to normal adult donors. Adverse effects include general fatigue and bone pain in most of the donors and fever and headache in some. These symptoms were well tolerated in most instances. Laboratory test abnormalities, including transient thrombocytopenia, increased platelet aggregation, and increased serum levels of some liver enzymes, were induced by G-CSF administration, but all were reversible within a short time. These observations suggest that hemopoietic stem cells for allogeneic PBSCT can be mobilized by short-term administration of a relatively high-dose G-CSF.

Adult↗
PubMed1996

[Condylar movement in patient with skeletal mandibular prognathism during maximum opening and closing movement before and after surgery].

Condylar movement of patients with mandibular prognathism who received sagittal splitting ramus osteotomy (SSRO) was investigated using computer aided diagnostic axiography (CADIAX). Linear and angular parameters were used to evaluate the maximum opening and closing paths of the condyle projected on the sagittal plane. The motion paths of six subjects with mandibular prognathism (MP group) were examined immediately before surgery and during the retention period. The results were compared with the recording from six normal subjects (control group). The results were as follows: (1) The average change in the maximum translating distance of the condyle in the retention period was 99.4 +/- 14.5% of the presurgical value on right side and 97.8 +/- 20.8% on the left side. The difference was not significant. (2) The shape of the opening translating curve of the MP group was flatter than that of the control group, however, no significant differences were found between the pre- and postsurgical curves of the MP group. (3) The coordination between the maximum opening and closing paths of the control group was fairly stable and smooth. However, although some improvement was observed, the paths of the MP group were unstable even after surgical treatment and large individual variations were observed.

Adult↗
PubMed1995

Functional brain block preparation of the rat auditory cortex.

To maintain neural functions in brain block preparations of the rat auditory cortex in vitro, a pressurized oxygenated medium was injected into the blocks. Distribution of indigo carmine contained in the injection medium indicated that a columnar region of 1-2 mm in diameter was homogeneously perfused from the white matter to the pial surface. Stimulation of cortical layers just above the white matter produced supragranular field potentials of two negative peaks. They represented antidromic and postsynaptic activities, of which only the latter was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). The depth profile and temperature-dependency of field potentials in the blocks were very similar to those recorded in usual slice preparations. The responses in blocks were recorded stably for several hours. The functional brain block preparation may be a useful tool for analyses of neocortical neural networks in vitro.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Effects of Bestatin on hematopoiesis in long-term human bone marrow cultures.

The effects of Bestatin (Ubenimex, UBX) on normal hematopoiesis were investigated using long-term bone marrow cultures (LTBMC) to determine whether it might enhance hematopoiesis over a long period, as well as induce the release of cytokines. LTBMC were inoculated with 0.1 or 1.0 microgram/ml of UBX at the onset of culture and was added at each weekly medium change. The cellularity and the content of the progenitors in nonadherent layer were examined each week for 5 weeks; those from the adherent layer were examined at week 5. The number of the nucleated mature cells and that of the myeloid progenitors from the nonadherent layer increased significantly (approximately two-fold) following treatment with UBX vs controls. The total number of colonies and the number of myeloid progenitors, but not that of erythroid progenitors, from the adherent layer increased significantly (about 1.5-fold) following treatment with 1.0 microgram/ml UBX. The level of interleukin-6 (IL-6) in the culture supernatants was significantly increased one day after the addition of 1.0 microgram/ml UBX. Findings indicate that UBX stimulated both the production of mature cells and myeloid progenitors on normal hematopoiesis in LTBMC. This was mediated by an indirect action via IL-6 production.

Aminopeptidases↗
PubMed1995

Quantitative analysis of AML1/ETO transcripts in peripheral blood stem cell harvests from patients with t(8;21) acute myelogenous leukaemia.

Peripheral blood stem cells (PBSC) have been used increasingly for haemopoietic reconstitution after marrow-ablative chemotherapy in patients with acute leukaemia because of the possibility that there is a lower risk of leukaemic contamination. We have developed a titration assay using a competitive reverse transcriptase polymerase chain reaction (RT-PCR) which is able to estimate the number of AML1/ETO transcripts so that minimal residual disease (MRD) can be monitored quantitatively in patients with t(8;21) acute myelogenous leukaemia (AML). Using a qualitative RT-PCR method, AML1/ETO transcripts could be detected in all samples from 15 first PBSC harvests and 11 second PBSC harvests obtained from 15 patients with t(8;21) AML. With our competitive RT-PCR assay, the number of AML1/ETO transcripts was found to be lower in the second PBSC harvest than that in the first in every individual. Furthermore, MRD in PBSC harvests was less than that in the corresponding bone marrow obtained on the day of PBSC collection in the individual patients studied. In 10 patients who received autologous blood stem cell transplantation (ABSCT), we could not find a relationship between the number of AML1/ETO transcripts in the infused PBSC harvests and the clinical outcome after ABSCT. The present study clearly indicates that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukaemic cells, the degree of leukaemic contamination may decrease as chemotherapy is repeated. The mobilization of PBSC by repeated chemotherapy may provide an advantageous source of haemopoietic stem cells for ABSCT.

Adolescent↗
PubMed1995

[A case of toxoplasmosis with dermatomyositis].

We report a case of dermatomyositis (DM) in a 15-year-old female with toxoplasmosis after ingestion of raw bovine liver. Facial erythema and cervical lymphadenopathy preceded myalgia and muscle weakness of the extremities. The diagnostic criteria of DM was fulfilled because of symmetrical and proximal dominant muscle weakness, elevation of myogenic enzyme (CPK, GOT, LDH, myoglobin, aldorase), myogenic pattern of electromyogram, skeletal muscle biopsy showing interstitial myositis with mild destruction of muscle fiber, and facial erythema. Immunological findings showed IgG anti-toxoplasma antibody to be 1340 IU/ml and IgM to be 7.0 (Cut off index 0.7), suggesting acute toxoplasmosis. Treatment with prednisolone for DM and acetylspiramycin for toxoplasmosis was successful. Toxoplasmosis should be considered as a possibility in patients with myositis.

Adolescent↗
PubMed1995

Malignant histiocytosis derived from a common histiocyte clone in a patient with chronic Epstein-Barr virus infection.

Epstein-Barr virus (EBV) has a particular propensity for B lymphocytes, but in a few cases it seems to play a role in histiocytic disorders and EVB DNA has been identified in histiocytes. To determine what kind of cell proliferate clonally, we studied a patient with malignant histiocytosis that developed after chronic EBV infection. Polymerase chain reaction (PCR) for lymphocyte-defined membrane antigen (LYDMA) of EBV, a marker of monoclonality, double stainings of cell markers (B, T lymphocytes; histiocytes), and in situ hybridization for EBV were performed in tissues obtained in 1987 and 1990 before the appearance of malignant histiocytosis and in 1991 after the disease was diagnosed. PCR for LYDMA from multiple samples during the disease showed the same single band, indicating that chronic EBV infection and malignant histiocytosis were caused by the same single virion. We also found a single terminal repeat band of EBV which supports this finding. In the studies of double stainings, EBV was present in histiocytes of the non-neoplastic early stage, and in the neoplastic cells of malignant histiocytosis. The histiocyte, infected with EBV, clonally expanded to result in malignant histiocytosis.

Adolescent↗
PubMed1995

Granulocyte colony-stimulating factor mobilizes primitive hematopoietic stem cells in normal individuals.

We studied the hematopoietic activity of peripheral blood stem cells (PBSC) mobilized by recombinant human granulocyte colony-stimulating factor (G-CSF) using semisolid and long-term culture systems (LTC) in 5 normal individuals. Following 2 or 3 daily subcutaneous injections of G-CSF (filgrastim; 1.5 micrograms/kg), not only committed progenitors including CFU-GM, BFU-E, and CFU-Mix, but also long-term culture initiating cells (LTC-IC) were increased in the peripheral blood. When the cells derived from CFU-GM, BFU-E and CFU-Mix colonies were replated for secondary colony formation, a minor fraction of CFU-GM and CFU-Mix colonies formed after 3 days of G-CSF stimulation in vivo could produce secondary colonies. Moreover, the replating capacity of primary colonies from 5-week-old LTC initiated after 3 days of G-CSF stimulation was increased compared to that from 5-week-old LTC initiated in a 'steady-state'. These observations indicate that G-CSF can mobilize very primitive progenitors (LTC-IC) along with committed progenitors into the circulation and suggest that some of these G-CSF-mobilized progenitors may retain self-renewal capacity.

Adult↗
PubMed1995

In vitro chemosensitivity assay for human osteosarcoma using tumor xenografts.

The authors have established an in vitro chemosensitivity assay for human osteosarcoma. To overcome the difficulty of maintaining primary osteosarcoma cells in culture, biopsy or surgical specimens were transplanted directly into athymic nude mice and early generation xenografts were used for in vitro scintillation assay. These xenografts enabled a large number of viable tumor cells to be obtained even from small biopsy specimens. As a result, this system afforded a workable assay in 21 (62%) of 34 osteosarcomas tested and enabled the assay of numerous drugs at 4 different concentrations. Reproducibility of the assay can be checked by using serially transplanted xenografts. Retrospectively, the in vitro results were compared with the histologic response of the resected tumor in 18 patients who had received preoperative chemotherapy. The true positive rate, true negative rate, and predictive accuracy were 40%, 100%, and 66.7%, respectively. The authors suggest that this system provides a valid tool to determine which drugs are ineffective in individual osteosarcoma patients and thus may allow more efficient therapy.

Animals↗
PubMed1994

[A comparative study of imipenem/cilastatin sodium BID vs QID in the treatment of infections associated with hematopoietic disorders].

Using the envelope method, we allocated 125 patients with infections accompanied by hematopoietic disorders into two groups treated with imipenem/cilastatin sodium (IPM/CS) at a daily dose of 1 g/1 g b.i.d. (group BID) or 0.5 g/0.5 g q.i.d. (group QID), and obtained the following results. 1. In group BID, ANLL was observed in 25 patients; ALL in 6; and NHL in 12. In group QID, ANLL was observed in 27 patients; ALL in 7; and NHL in 13. 2. In group BID, efficacy rates were 54.5% (6/11) in sepsis, 63.0% (17/27) in fever of undetermined origin and 50.0% (4/8) in pneumonia, thus the overall efficacy was 61.8% (34/55). In group QID, efficacy rates were 66.7% (4/6) in sepsis, 76.0% (19/25) in fever of undetermined origin and 35.7% (5/14) in pneumonia, thus the over all was 61.1% (33/54). No significant difference in response rates were observed between the two groups. 3. Bacteriologically, 22 bacterial strains were isolated in group BID and 21 21 strains, in group QID. The eradication rates after treatment with IPM/CS was 100% in group BID and 66.7% in group QID. 4. Side effects were observed in 8 patients in group BID and 3 in group QID. Laboratory examination revealed abnormal values in 9 patients in group BID and 6 in group QID. However, all of the side effects disappeared after the suspension or discontinuation of IPM/CS. The efficacies of IPM/CS therapy for severe infections in patients with hematopoietic disease were similar between 1 g/1 g b.i.d. and 0.5 g/0.5 g q.i.d. groups.

Adult↗
PubMed1993

Effects of methyl mercury in postnatal developing rats.

Rats on Postnatal Days 1 (PD 1), 14 (PD 14), and 35 (PD 35) were orally administered 0, 2.60, 3.64, 5.10, 7.14, and 10 mg/kg/day of methyl mercury chloride (MMC) for 10 consecutive days. Mercury (Hg) accumulation in the brain of the rats treated with 10 mg/kg/day of MMC for 10 consecutive days was highest in PD-14 rats, followed by PD-35 and PD-1 rats. Hg accumulations in the liver and kidney were lowest in PD-1 rats and increased markedly with development in postnatal phase. The effect of MMC treatment on body weight change was most severe in PD-35 rats. The body weight loss began on Day 5 in PD-35 rats and on Day 10 in PD-14 rats treated with 10 mg/kg/day of MMC, but not in PD-1 rates under the same treatment. The phenomenon of hindlimb-crossing was induced on Day 11 in PD-14 rats and on Day 14 in PD-35 rats treated with 10 mg/kg/day of MMC, but was not observed in PD-1 rats. The deficit of rotarod performance was apparent only at the dose of 7.14 mg/kg/day of MMC in PD-35 rats, whereas rotarod performance was dose-dependently inhibited by MMC treatment in PD-14 rats, and lowered even at the dose of 2.6 mg/kg/day of MMC. However, the performance was gradually restored to the control level by 1 month except in rats given 7.14 mg/kg/day of MMC. These findings indicated that the Hg distribution and the effects of MMC treatment on body weight gain and motor coordination were different among the rat postnatal developing phases.

Age Factors↗
PubMed1993

[Exercise test to predict postoperative complications in patients with impairment of pulmonary function].

We studied the prediction of postoperative complications in patients whose predicted postoperative FEV1.0% and/or %VC were below fifty. Preoperative exercise tests were performed in 88 cases mainly old patients of age or with impaired pulmonary function; 57 were lobectomies, 10 were bilobectomies and 21 were pneumonectomies. Predicted postoperative FEV1.0% and/or %VC were below fifty in 29 cases consisting of 12 lobectomies, one bilobectomy and 16 pneumonectomies. Among these 29 patients, thirteen suffered postoperative complications (A group) and sixteen did not (B group). All five cases of operative death (death within 30 days after operation) were included in the A group. The prediction of postoperative complications in cases of which pred. postope, FEV1.0% and %VC were fifty or over (C group) was also studied. The results were as follows; (1) The percentage of complications among A and B groups was higher than that among C group but no statistical difference could be found. (2) In the A group, the number of pred. postope. FEV1.0% and/or %VC had little correlation to complications. (3) Statistical differences between A and B group were found in submax VO2 (p < 0.05), VO2/VE at AT (p < 0.001) and VCO2/VE at submaximal exercise (p < 0.001). (4) Cardiac output ratio of maximal exercise to rest had marked correlation to complications (p < 0.001) in C group but had no correlation in the A and B groups. (5) The three items of A and B groups, submax VO2 < 500 ml/min/m2, VO2/VE at AT < 40 ml/l and submax VCO2/VE < 25 ml/l, showed high correlation to operative death (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗