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Biomedical subjects

K Sunami

Publications and source records attributed to K Sunami.

At least 37 records · Page 2Linked to original sources
PubMed2000

Granulocyte colony-stimulating factor and lineage-independent modulation of VLA-4 expression on circulating CD34+ cells.

Although the use of allogeneic transplants of peripheral blood stem/progenitor cells (PBSCs) is increasing, the precise mechanism of PBSC mobilization has not yet been fully clarified. We examined the expression of some adhesion molecules on CD34+ cells from steady-state bone marrow (BM), granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCs, and cytotoxic drugs plus G-CSF-mobilized PBSCs. Irrespective of mobilization method, very late antigen (VLA)-4 expression on circulating CD34+ cells was significantly lower than on steady-state BM CD34+ cells. To elucidate the influence of lineage commitment on VLA-4 expression of circulating CD34+ cells, we analyzed VLA-4 expression on different subsets of CD34+ cells with or without CD33, CD38, CD5, or CD10 antigens, or Glycophorin A in G-CSF-mobilized PBSCs and steady-state BM from related donors, using 3-color flow cytometry. VLA-4 on circulating CD34+ subsets was less expressed than on each corresponding subset of steady-state BM CD34+ cells. Furthermore, VLA-4 positive rates showed no significant difference among the CD34+ subsets. Finally, the data comparing CD34+ cells from steady-state and G-CSF-mobilized PBSCs revealed no differences in terms of VLA-4 expression. These data suggest that reduced expression of VLA-4 may be a result of peripheralization of CD34+ cells from bone marrow, which occurs in a G-CSF- and lineage-independent fashion.

Anti-Allergic Agents↗
PubMed2000

[Prevention of hepatitis B flare-up using lamivudine in a patient with non-Hodgkin's lymphoma after allogeneic bone marrow transplantation].

A 22-year-old man with non-Hodgkin's lymphoma (B-cell lymphoblastic lymphoma, Stage IVA) received chemotherapy and radiation therapy and achieved complete remission. He was admitted for allogeneic bone marrow transplantation (BMT) using a graft from his completely HLA-matched mother. Although he had HBV infection, allogeneic BMT was performed because he still had normal liver function and strongly requested the procedure. He developed both acute and chronic GVHD after the procedure, but showed no liver damage related to HBV. Treatment with lamivudine (150 mg/day) was started because the HBV-DNA level increased gradually after allogeneic BMT. Although the HBV-DNA then decreased gradually and there was no evidence of severe liver damage, the patient died following relapse of NHL. It seems that in this case, treatment of HBV with lamivudine may have prevented serious liver damage after allogeneic BMT. Therefore, allogeneic BMT may be done safely in patients with HBV infection if lamivudine is administered.

Adult↗
PubMed2000

Allogeneic peripheral blood stem cell transplantation in 23 adult patients with hematologic malignancies: a single-center experience.

We describe a single-center experience of 23 consecutive patients (median age, 35 years) with hematologic malignancies who received allogeneic peripheral blood stem cell transplants (alloPBSCTs) from HLA-identical siblings. Ten patients had standard-risk disease and 13 had high-risk disease. Twenty-one patients received alloPBSCT as a primary transplant, and the remaining 2, with high-risk disease, as a second transplant after posttransplantation relapse. All donors received daily subcutaneous injections of granulocyte colony-stimulating factor at a dose of 10 microg/kg, and peripheral blood stem cells were collected by 1 to 3 aphereses. Median numbers of CD34+ and CD3+ cells infused were 5.8 x 10(6)/kg (range, 1.3-19.7 x 10(6)/kg) and 4.9 x 10(8)/kg (range, 1.9-8.6 x 10(8)/kg), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and methotrexate (18 patients) or CyA and methylprednisolone (5 patients). Rapid hematologic engraftment was observed in 20 of the 23 patients. Median days to absolute neutrophil counts >0.5 x 10(9)/L and platelet counts >20 x 10(9)/L were 12 (range, 9-18 days) and 14 (range, 10-128 days), respectively. Acute GVHD of grade 2-4 was observed in 6 of 20 evaluable patients (30%) and extensive chronic GVHD in 8 of 15 evaluable patients (53%). Ten of the 23 patients (44%) were surviving in continuous complete remission 191 to 1492 days (median, 643 days) posttransplantation. Treatment-related death within 100 days posttransplantation was observed in 6 of the 23 patients (26%). Six of the 23 patients (26%) developed relapse at a median 81 days (range, 38-160 days) posttransplantation. Further study is needed to assess the precise benefits of alloPB-SCT compared with allogeneic bone marrow transplantation.

Adolescent↗
PubMed2000

Successful engraftment of allogeneic peripheral blood stem cell transplant after nonmyeloablative preparative regimen with cytarabine and cyclophosphamide: report of 2 cases.

We report our experience with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) following a nonmyeloablative conditioning regimen consisting of cytarabine (8 g/m2) and cyclophosphamide (120 mg/kg) in the treatment of 2 patients aged 50 and 55 years with refractory chronic myelomonocytic leukemia and chronic myeloid leukemia in accelerated phase, respectively. Our nonmyeloablative regimen was well tolerated by older patients at high risk of regimen-related toxicity by the conventional conditioning regimen but was immunosuppressive enough to achieve mixed chimerism. After allo-PBSCT, we monitored chimerism in these patients by fluorescence in situ hybridization using X- and Y-specific probes and polymerase chain reaction-based analysis of a variable number of tandem repeats. We found that full chimerism and graft-versus-leukemia (GVL) effects could be induced in these patients by donor lymphocyte infusions and withdrawal of posttransplantation immunosuppressive therapy. Our observations suggest that a nonmyeloablative conditioning regimen can establish mixed chimerism and that donor lymphocyte infusion may induce GVL effects in older patients at high risk of regimen-related toxicity.

Cyclophosphamide↗
PubMed1999

Involvement of nitric oxide in aminoglycoside vestibulotoxicity in guinea pigs.

Involvement of nitric oxide (NO) has been reported in physiological and pathological conditions in the inner ear. Recently, the presence of nitric oxide synthase (NOS) was demonstrated in the vestibular epithelium. In this study we used nicotinamide adenine dinucleotide phosphate-diapholase staining to monitor NOS activity during degeneration of guinea pig vestibular epithelia affected by streptomycin. Increased NOS activity was observed in affected epithelia in a dose- and time-dependent manner and a NOS inhibitor could protect hair cells from apoptosis. Additionally, cycloheximide significantly reduced NOS activity and the occurrence of apoptosis. These findings suggest that NO is involved in the degenerative process of vestibular epithelia caused by aminoglycosides.

Aminoglycosides↗
PubMed1999

Glutamate toxicity induced degeneration of outer hair cells with a temporal increase of nitric oxide production in the guinea pig cochlea.

The aim of this study was to examine the roles of glutamate (GLU) toxicity and involvement of nitric oxide (NO) in the pathogenesis of cochlear degeneration. We examined guinea pig cochleae following chronic exposure to GLU. Trypan blue extrusion and transmission electron microscopy were performed to evaluate degeneration in the organ of Corti. In parallel, nitric oxide synthase (NOS) activity was demonstrated by histochemical staining of NADPH diapholase. GLU treatment caused time-dependent degeneration of outer hair cells (OHCs) in conjunction with a temporal increase of NOS activity in the organ of Corti. This suggests that GLU may be involved in OHC degeneration under toxic conditions, with NO production possibly playing a role in this process.

Animals↗
PubMed1999

Delayed postoperative CSF rhinorrhea of intrasellar arachnoid cyst.

CSF rhinorrhea due to a transsphenoidal approach usually follows accidental or intentional arachnoid opening. We report a patient with an intrasellar arachnoid cyst, who developed delayed onset of CSF rhinorrhea. A sixty-two-year-old man presented with bitemporal type visual field defect for the last 3 years. With the diagnosis of arachnoid cyst or Rathke's cleft cyst, based on MRI findings of intra-and supra-sellar cyst with CSF intensity, he successfully underwent transsphenoidal surgery without evidence of intra-operative CSF leakage. He developed CSF rhinorrhea one week later. This needed another operation for sellar floor repair. The pathomechanism of this delayed onset is explained as follows. Incomplete or oneway communication of subarachnoid space to cyst cavity, unrecognized during surgery, might cause delayed onset of CSF rhinorrhea. By using MRI, identification of the residual gland, which was compressed posteriorly, is useful for differentiating an arachnoid cyst from other cystic lesions. In highly suspect cases, even without evidence of intra-operative CSF leakage, peri-operative measures to prevent occurrence of postoperative CSF rhinorrhea are required.

Arachnoid Cysts↗
PubMed1999

MRI findings and clinical manifestations in Rathke's cleft cyst.

We retrospectively analysed patients with histologically proven Rathke's cleft cyst (RCC) in relation to the clinical manifestations and MRI findings, in particular, of cyst size and intensity in order to obtain an insight into their growing mechanisms, clinical presentations and their management. Eleven patients with RCC were divided into two groups based on T1 weighted images(WI). The A group consisted of 4 patients with cyst of low intensity in T1 WI. The age averaged 64.5 years. Their initial complaints were visual field defects(VFD). Their complaints were rather insidious. The maximum cyst size averaged 27.8+/-2.4 mm. The B group consisted of 7 patients with cyst of iso- or high-intensity in T1 WI. Two patients in the B group showed mixture of low and high and iso- and high-intensity, suggesting the presence of bleeding at the onset of symptoms or growing mechanism of the cysts. In the B group the age averaged 39.9 years, being lower than that in the A group. (P=0.0140 with Mann-Whitney's U test) The 5 patients out of 7 showed headache of insidious type or acute onset and the 3 showed a fluctuation of the VFD. The average size was 21.7+/-3.5 mm and smaller than that of the A group. (P=0.0298 with Mann-Whitney's U test) Our study has shown that the cyst with iso-to high intensity on T1 WI may cause clinical symptoms with a smaller size than cysts of the low intensity. In the former cyst pattern the onset and growing mechanism may be related to bleeding. The patients with this pattern are more likely to have acute and/or fluctuation of clinical presentations. Knowing these various clinical manifestations based on MRI pattern will be of help in following and managing patients with RCC.

Adult↗
PubMed1999

Cystine protects cochlear outer hair cells against glutamate toxicity.

We previously reported that long-term exposure to glutamate (Glu) induced death of cochlear outer hair cells (OHCs). However, the mechanisms of OHC death induced by Glu were unclear. In the central nervous system, Glu is known to interfere with a cystine-Glu antiporter, leading to a decrease in cystine uptake and reducing the intracellular glutathione level. We therefore investigated the effect of cystine supplementation on degeneration of OHCs caused by long-term exposure to Glu. Supplementation of cystine significantly decreased the number of dying OHCs. These findings suggest that a cystine-Glu interaction may be involved in the mechanism of OHC degeneration caused by Glu.

Analysis of Variance↗
PubMed1999

[Stem cell transplantation in multiple myeloma].

High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) has brought about high complete remission rates (about 40%), reduction of transplant-related toxicity in the patients with multiple myeloma, and it has spread rapidly. Moreover, it has demonstrated that overall survival times of high-dose chemotherapy with ASCT are significantly more extended than conventional chemotherapy. The indications of transplantation should be determined on the basis of various prognostic factors and sensitivity of the induction chemotherapy, and it is important that a therapeutic strategy should take the timing of ASCT into consideration before induction therapy. However, some problems of tumor cell contamination in the peripheral stem progenitor graft and its contribution to relapse have arisen. Some new trials including positive selection of CD34+ cells within its grafts and double auto-transplantation are ongoing to solve these problems. If the patient is under 50 years of age and an HLA identical donor is available, an allogeneic bone marrow transplantation (allo-BMT) may be considered. However, the indication of allo-BMT should be carefully selected because the transplant-related mortality is high (about 40%), and allo-BMT is not superior to ASCT in overall survival. New trials with nonablative hematopoietic stem cell transplantation with donor lymphocyte infusions (DLI) to induce a graft-versus-myeloma (GVM) effect are awaited.

Antineoplastic Agents↗
PubMed1998

Apoptosis of guinea pig cochlear hair cells following chronic aminoglycoside treatment.

Although aminoglycosides have been investigated for their cochleotoxicity, it has still not been determined whether apoptosis or necrosis results in cochlear hair cell death following aminoglycoside treatment. To study possible mechanisms of cell death, we used in situ DNA break-labeling to examine guinea pig cochleae affected by Kanamycin ototoxicity. Chronic kanamycin treatment induced DNA fragmentation that was detectable in both outer and inner hair cells, suggesting the occurrence of apoptosis. These findings suggest that apoptosis achieves deletion of affected hair cells without disrupting tissue architecture in the organ of Corti.

Animals↗
PubMed1998

MRI prediction of fibrous pituitary adenomas.

The transsphenoidal approach is a less invasive and safer procedure for removing pituitary adenomas. However, this procedure becomes extremely difficult when the tumour consistency is fibrous as encountered in about 10% of pituitary adenomas. In this study, we investigated predicting factors of tumour consistency in magnetic resonance images (MRIs). MRIs of two groups, twenty-one soft and five firm (fibrous) adenomas, were retrospectively evaluated and compared in respect of tumour consistency. To compare the two groups objectively, tumour densities on MRI films and percentage of collagen content on operative specimens were expressed as numerical data using NIH-image. The relationships between collagen content and T1-weighted images, T2-weighted images, grade of enhancement effect, and heterogeneity of enhancement were investigated. Signal intensities on T1-weighted images were not correlated with tumour consistency, whereas those on T2-weighted images were significantly correlated with the percentage of collagen content. Adenomas, showing lower signal intensities on T2-weighted images, contained more collagen. On enhanced images, homogeneously enhanced adenomas tended to include more collagen, even though the grade of enhancement effect showed only weak correlation with the tumour hardness. MRIs give us useful information on tumour consistency. Adenomas may be firm and fibrous if they show low signal intensities on T2-weighted images and homogeneous enhancement. To remove such tumours, a long sized and small-calibred ultrasonic aspirators applicable to transsphenoidal approach must be prepared and multistaged operations may be more than likely needed.

Adenoma↗
PubMed1998

Trisomy 12 and t(14;18) in B-cell chronic lymphocytic leukemia.

We report a case of B-cell chronic lymphocytic leukemia (B-CLL) in which trisomy 12 and t(14;18)(q32;q21) were simultaneously detected in the same leukemic clone. Southern blot analysis showed that the BCL2/IgJH rearrangement occurred at the major breakpoint region in the hot spot of the BCL2 gene. Double color fluorescence in situ hybridization analysis using multiple probes indicated that clonal B-cell with t(14;18) represented a subpopulation of the total leukemic cells and that trisomy 12 followed t(14;18) as the cytogenetic aberration in the development of B-CLL. Our findings suggests that both the t(14;18) and the trisomy are secondary chromosomal changes in the leukemogenesis of B-CLL.

Blotting, Southern↗
PubMed1998

Graft rejection and recovery of host-derived hematopoiesis after allogeneic bone marrow transplantation: relation to conditioning with high dose etoposide and total body irradiation.

Engraftment failure following allogeneic bone marrow transplantation (BMT) is rare in patients with acute leukemia, after frequent conditioning with marrow-lethal chemoradiotherapy. We evaluated the efficacy of a preparatory regimen consisting of fractionated total body irradiation (TBI) (12 Gy in six fractions) and high dose etoposide (60 mg/kg) administered as an 8-h infusion for allogeneic BMT in 16 consecutive patients with acute leukemia. Although 14 patients showed complete and sustained engraftment, the remaining two patients rejected bone marrow grafts from HLA-identical sibling donors and showed subsequent recovery of host-derived hematopoiesis. Despite the limited number of patients, this observation suggests that the immunosuppressive potential of etoposide may be inferior to that of cyclophosphamide (CY) and that etoposide as an alternative to CY as an antileukemic and immunosuppressive agent in allogeneic BMT may increase the risk of graft rejection.

Acute Disease↗
PubMed1998

Dose-dependent response of vestibular hair cells of guinea pigs following streptomycin ototoxiation.

Although the involvement of apoptosis has been suggested in the loss of vestibular hair cells due to aminoglycosides, dose-dependent effects of aminoglycosides have not been determined. We therefore examined dose-dependent effects of streptomycin on the degeneration of hair cells of guinea pig ampullar cristae using TUNEL stain and Hoechst nuclear stain. Streptomycin induced apoptosis of hair cells in a dose-dependent manner. Even following high-dose applications, most of the affected cells showed apoptotic features. Apoptosis may therefore play a predominant role in the deletion of vestibular hair cells affected by aminoglycosides.

Animals↗
PubMed1998

Role of amino acids in cochlear degeneration: deprivation of cystine induces death of cochlear hair cells of guinea pigs in vitro.

Redox regulation reportedly plays a role in maintaining cochlear homeostasis. However, little is known about the roles of oxidation-reduction systems in the cochlea. We examined the role of the cystine/cysteine oxidation-reduction system in survival of cochlea hair cells in vitro. The survival of hair cells was evaluated in cochlea specimens following incubation with the medium supplemented with various concentrations of cystine. Dying hair cells were detected by the trypan blue extrusion method. The rates of cell death for both outer and inner hair cells increased significantly with a decrease in the concentration of cystine. In addition, the rate of cell death of IHCs tended to be higher than that of OHCs. These findings suggest that the cystine/cysteine system might be required for maintenance of homeostasis in cochlear hair cells, especially in IHCs.

Animals↗
PubMed1998

Role of amino acids in cochlear degeneration: morphological changes in cochlear outer hair cells following glutamate application.

Glutamate is an excitatory neurotransmitter in the cochlea and has toxic effects on the organ of Corti in various pathological conditions. The toxic effects of glutamate have not been determined in detail. In this study, we examined morphological changes in the organ of Corti of guinea pigs following local application of glutamate. Morphological changes were noted in outer hair cells. Degeneration of outer hair cells was found 24 h after glutamate treatment. The extent of degeneration depended on exposure time. Inner hair cells did not exhibit any degeneration. In addition, no degenerative changes were detected in nerve endings attached to hair cells. These findings suggest that outer hair cells are the initial site of degeneration caused by application of excess glutamate to the inner ear.

Animals↗