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Biomedical subjects

Y Kiyama

Publications and source records attributed to Y Kiyama.

At least 19 recordsLinked to original sources
PubMed2004

Mediastinal emphysema and bilateral pneumothoraces with chronic GVHD in patients after allogeneic stem cell transplantation.

It is difficult to treat lung complications caused by chronic graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). We retrospectively analyzed the characteristics of five patients with mediastinal emphysema (ME) and bilateral pneumothoraces (BP) caused by chronic lung GVHD after allo-SCT. Four of these patients had undergone unrelated SCT, and three had had HLA-identical unrelated donors. All patients received total body irradiation (TBI) during conditioning. Immunosuppressive agents were administered as GHVD prophylaxis, but two patients developed acute GVHD and all the five developed chronic GVHD. The onset of lung complications was 99-1915 days (median, 202 days) after SCT. The onset of ME and BP was 6-48 days (median, 23 days) after the onset of lung complications. Immunosuppressive agents were initially beneficial on the lung complications, but the patients later showed no response to therapy, and all died from respiratory failure 7-195 days (median, 28 days) after the development of ME and BP. The results suggest that these complications progress rapidly, are resistant to treatment, and have a poor prognosis. It is therefore important to start prophylaxis and treatment as early as possible.

Adolescent↗
PubMed2001

Re-treatment of relapsed indolent B-cell lymphoma with rituximab.

The purpose of this study was to investigate the toxicity and the efficacy of re-treatment with rituximab, a chimeric mouse human anti-CD20 monoclonal antibody, in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (NHL) who responded to rituximab in the previous phase I or phase II study. Thirteen patients with relapsed B-cell NHL, each of whom was confirmed to have Revised European-American Lymphoma Classification type II, 1-6 histology (indolent B-NHL), enrolled in this re-treatment study. All were re-treated with rituximab at 375 mg/m2 weekly for 4 consecutive weeks. Rituximab re-treatment was well tolerated with no grade 3/4 nonhematological toxicities, similar to that of the initial treatment. No patients developed detectable human anti-chimeric antibody. Partial responses were observed in 5 of 13 patients (38%; 95% confidence interval [CI], 14% to 68%); 6 patients showed stable disease and 2 showed progressive disease. Overall survival rate was 93% at 19 months of median follow-up after rituximab re-treatment. Median progression-free survival (PFS) after the re-treatment was 5.1 months (95% CI, 4.1 to 5.6 months), and the median PFS after the initial treatment was 8.2 months (95%CI, 5.9 to 11.3 months). Although rituximab re-treatment induced prolonged depletion of normal peripheral blood B cells in all patients, no significant decrease in serum immunoglobulin or complement level was observed. In conclusion, rituximab re-treatment was well tolerated, and it may produce a prolonged PFS in some patients with indolent B-cell NHL who showed initial response to rituximab.

Adult↗
PubMed2001

Enhancement of hippocampal LTP, reference memory and sensorimotor gating in mutant mice lacking a telencephalon-specific cell adhesion molecule.

Telencephalin (TLCN) is a cell adhesion molecule selectively expressed in the telencephalon of the mammalian brain. The mutant mice lacking TLCN had no detectable abnormalities in their neural development and synaptic structures. Ablation of TLCN increased the hippocampal long-term potentiation and its saturation level. The TLCN mutation selectively enhanced the performance of the radial maze and water-finding tasks, learning tasks with appetitive reinforcers, but not the contextual fear conditioning and Morris water maze tasks with aversive stimuli for conditioning. Furthermore, the TLCN mutant mice showed an increase of prepulse inhibition of the acoustic startle response. These results suggest that TLCN is a determinant of the dynamic range of synaptic plasticity and plays roles in reward-motivated learning and memory and sensorimotor gating.

Animals↗
PubMed2001

Roles of the glutamate receptor epsilon2 and delta2 subunits in the potentiation and prepulse inhibition of the acoustic startle reflex.

We examined the regulation of the acoustic startle response in mutant mice of the N-methyl-D-aspartate (NMDA)- and delta-subtypes of the glutamate receptor (GluR) channel, which play important roles in neural plasticity in the forebrain and the cerebellum, respectively. Heterozygous mutant mice with reduced GluRepsilon2 subunits of the NMDA receptor showed strongly enhanced startle responses to acoustic stimuli. On the other hand, heterozygous and homozygous mutation of the other NMDA receptor GluRepsilon subunits exerted no, or only small effects on acoustic startle responses. The threshold of the auditory brainstem response of the GluRepsilon2-mutant mice was comparable to that of the wild-type littermates. The primary circuit of the acoustic startle response is a relatively simple oligosynaptic pathway located in the lower brainstem, whilst the expression of GluRepsilon2 is restricted to the forebrain. We thus suggest that the NMDA receptor GluRepsilon2 subunit plays a role in the regulation of the startle reflex. Ablation of the cerebellar Purkinje cell-specific delta2 subunit of the GluR channel exerted little effect on the acoustic startle response but resulted in the enhancement of prepulse inhibition of the reflex. Because inhibition of the acoustic startle response by a weak prepulse is a measure of sensorimotor gating, the process by which an organism filters sensory information, these observations indicate the involvement of the cerebellum in the modulation of sensorimotor gating.

Acoustic Stimulation↗
PubMed1998

Attenuation of focal ischemic brain injury in mice deficient in the epsilon1 (NR2A) subunit of NMDA receptor.

The role of glutamate neurotoxicity in cerebral ischemia has long been advocated but still remains controversial, because various glutamate receptor (GluR) antagonists showed inconsistent protective efficacy in brain ischemia models. To address this central issue of ischemic brain damage more directly, we used mutant mice deficient in the GluRepsilon1 (NR2A) subunit of NMDA receptor with or without additional heterozygous mutation in the GluRepsilon2 (NR2B) subunit. Those mutant mice, as well as their littermates, were subjected to focal cerebral ischemia by introducing a 6-0 nylon suture from left common carotid artery. Brain injury volumes after 2 hr of suture insertion, as evaluated by 2,3,5-triphenyltetrazolium chloride staining at 24 hr after ischemia, revealed significantly smaller injury size in GluRepsilon1 subunit knock-out mice compared with their wild-type littermates. The reduction in injury volume was not attributable to differences in body temperature or in blood flow during ischemia. Additional heterozygous GluRepsilon2 subunit disruption did not result in further reduction in injury volume. These data directly demonstrate relevance of NMDA receptor-mediated tissue injury after brain ischemia and provide evidence that GluRepsilon1 subunit is involved in these injurious mechanisms.

Animals↗
PubMed1998

Increased thresholds for long-term potentiation and contextual learning in mice lacking the NMDA-type glutamate receptor epsilon1 subunit.

The NMDA-type glutamate receptor (GluR) channel, composed of the GluRepsilon and GluRzeta subunits, plays a key role in synaptic plasticity in the CNS. The mutant mice lacking the GluRepsilon1 subunit exhibited a reduction in hippocampal long-term potentiation (LTP), but a stronger tetanic stimulation restored the impairment and the saturation level of LTP was unaltered. These results suggest an increase of threshold for LTP induction in the GluRepsilon1 mutant mice. After a series of backcrosses we established a GluRepsilon1 mutant mouse line with a 99.99% pure C57BL/6 genetic background. The performance of the mutant mice in tone- and context-dependent fear conditioning tests was comparable with that of the wild-type mice. However, a significant difference in the extent of contextual learning became apparent when the chamber exposure time before footshock was shortened. Furthermore, there was a significant difference in freezing responses immediately after footshock on the conditioning day between the wild-type and mutant mice, and the difference was not restored by longer chamber exposure in contrast to the contextual learning on the next day of the conditioning. These results suggest that the GluRepsilon1 subunit of the NMDA receptor channel is a determinant of thresholds for both hippocampal LTP and contextual learning and plays differential roles in two forms of contextual fear memories.

Animals↗
PubMed1998

[Treatment of aplastic anemia with anti-thymocyte globulin and cyclosporine].

Antithymocyte globulin (ATG) is an effective immunosuppressive therapy for aplastic anemia (AA). We administered ATG combined with cyclosporine (CyA), to 9 patients (4 men and 5 women; median age, 55 years). AA was severe in 8 patients and moderate in 1. The ATG and CyA regimen was the initial treatment for 3 patients, but sequential treatment for the other 6, who were refractory to other agents. Peripheral T lymphocytes, including CD4-positive and CD8-positive cells, decreased rapidly after treatment. Although 1 patient died of pulmonary hemorrhage during the 6-month period following treatment with this combined regimen, 3 showed a favorable response, 2 moderate response, and 3 no response at all. Adverse drug reactions, including transient fever and rash, were not severe. These findings suggested that ATG and CyA in combination are a safe and effective immunosuppressive regimen for initial and refractory patients with AA.

Adult↗
PubMed1997

A translocation t(8;14) and c-myc gene rearrangement associated with the histological transformation of B-cell acute lymphocytic leukemia (FAB-L2) into Burkitt's type (FAB-L3) leukemia.

We report a case of B-cell acute lymphocytic leukemia which showed histological transformation from an FAB-L2 into a Burkitt's type (FAB-L3). Both leukemias had identical immunoglobulin heavy-chain joining gene and kappa light-chain joining gene rearrangements, indicating the clonal identity of the two leukemias. A chromosomal analysis of leukemia cells on the onset indicated normal karyotype, whereas that of the transformed FAB-L3 showed t(8;14)(q24;q32). Furthermore, the proto-oncogene c-myc was in the germline configuration in the initial leukemia but in the rearranged configuration after transformation. Presence of t(8;14)(q24;q32) and the c-myc gene rearrangement after transformation suggested that the chromosomal translocation followed by the activation of the c-myc proto-oncogene might be involved in the Burkitt's type transformation of the FAB-L2 leukemic clone, but not in the leukemogenesis of the initial FAB-L2 leukemia.

Adolescent↗
PubMed1997

[Positive seroconversion syphilis in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation].

An acute lymphocytic leukemia patient underwent allogeneic bone marrow transplantation (BMT) from a sibling who was serologically positive for syphilis. After the donor was administered antibiotic therapy, the titration of treponema pallidum hemagglutination (TPHA) decreased from x1260 to x320. Thereafter, the graft consisting of mononuclear cells was transplanted. TPHA of the recipient turned positive on day +63, but became negative 1.5 years after BMT. Although the cause of the seroconversion of TPHA seemed to be the contamination of treponema to the graft, the adoptive transfer could not be ruled out as an another possible cause.

Adult↗
PubMed1996

Locations of local anesthetic dibucaine in model membranes and the interaction between dibucaine and a Na+ channel inactivation gate peptide as studied by 2H- and 1H-NMR spectroscopies.

To study the molecular mechanisms of local anesthesia, locations of local anesthetic dibucaine in model membranes and the interactions of dibucaine with a Na+ channel inactivation gate peptide have been studied by 2H- and 1H-NMR spectroscopies. The 2H-NMR spectra of dibucaine-d9 and dibucaine-d1, which are deuterated at the butoxy group and at the 3 position in its quinoline ring, respectively, have been observed in multilamellar dispersions of the lipid mixture composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine. 2H-NMR spectra of deuterated palmitic acids incorporated, as a probe, into the lipid mixture containing cholesterol have also been observed. An order parameter, SCD, for each carbon segment was calculated from the observed quadrupole splittings. Combining these results, we concluded that first, the butoxy group of dibucaine is penetrating between the acyl chains of lipids in the model membranes, and second, the quinoline ring of dibucaine is located at the polar region of lipids but not at the hydrophobic acyl chain moiety. These results mean that dibucaine is situated in a favorable position that permits it to interact with a cluster of hydrophobic amino acids (Ile-Phe-Met) within the intracellular linker between domains III and IV of Na+ channel protein, which functions as an inactivation gate. To confirm whether the dibucaine molecule at the surface region of lipids can really interact with the hydrophobic amino acids, we synthesized a model peptide that includes the hydrophobic amino acids (Ac-GGQDIFMTEEQK-OH, MP-1), the amino acid sequence of which corresponds to the linker part of rat brain type IIA Na+ channel, and the one in which Phe has been substituted by Gln (MP-2), and measured 1H-NMR spectra in both phosphate buffer and phosphatidylserine liposomes. It was found that the quinoline ring of dibucaine can interact with the aromatic ring of Phe by stacking of the rings; moreover, the interaction can be reinforced by the presence of lipids. In conclusion, we wish to propose that local anesthesia originates from the pi-stacking interaction between aromatic rings of an anesthetic molecule located at the polar headgroup region of the so-called boundary lipids and of the Phe in the intracellular linker between domains III and IV of the Na+ channel protein, prolonging the inactivated state and consequently making it impossible to proceed to the resting state.

Amino Acid Sequence↗
PubMed1996

[Treatment of refractory hematologic malignancies by combination of cytarabine ocfosfate and etoposide].

We attempted a combination chemotherapy with cytarabine ocfosfate (SPAC) and etoposide for myelodysplastic syndrome (MDS), and acute non-lymphocytic leukemia developing after a prior history of MDS (MDS/ANLL). SPAC and etoposide were administered orally at the dose of 200 mg/day and 25 mg/day for 14 days, as standard regimen. Two cases complete remission (CR), 4 of partial remission (PR) were obtained among 9 patients. The plasma concentration of cytarabine (Ara-C) reached a plateau at around 4.5 ng/ml during the treatment period from the 7th to the 14th day, and it was detectable with a gradual decrease until the 28th day in spite of the last administration of SPAC on the 14th day. It is suggested that this combination chemotherapy is useful against MDS, MDS/ANLL and other resistant leukemia, especially in elderly patients who can not be treated by intensive combination chemotherapy.

Acute Disease↗
PubMed1996

[Two cases of relapse or refractory germ cell tumor who had been treated with combination chemotherapy of cisplatin and carboplatin].

We tried a combination chemotherapy with cisplatin (CDDP) and carboplatin (CBDCA) (CDDP/CBDCA regimen) as salvage therapy for 2 cases with recurrent or refractory Germ Cell Tumor (GCT). Case 1 was a 29-year-old man with 2nd relapsed embryonal carcinoma and seminoma originating from testis. Case 2 was a 23-year-old man with primary refractory embryonal carcinoma and yolk sac tumor originating from mediastinum. CDDP and CBDCA were administered at the dose of 120 mg/m2 and 350 mg/m2 on day 1, and vinblastin was administered at the dose of 10 mg/body on day 2. In one of two cases, a complete response was obtained. Non-hematologic toxicity of CDDP/CBDCA regimen was tolerable. It is suggested that this combination chemotherapy is useful for GCT recurrence.

Adult↗
PubMed1995

Differential expression of two zebrafish emx homeoprotein mRNAs in the developing brain.

The complete amino-acid sequences of two zebrafish emx homeoproteins containing a homeodomain homologous to that of the Drosophila empty spiracles head gap gene product have been determined by cloning and sequencing of cDNAs. The zebrafish emx1 and emx2 homeoproteins consist of 233 and 247 amino acids, respectively. The zebrafish emx1 and emx2 mRNAs are present at 12 h after fertilization, when the presumptive brain is in a simple tubular structure, and before first primary neurons appear. During brain development, the emx1 mRNA is localized in the dorsal telencephalon, whereas the emx2 mRNA is distributed in the dorsal telencephalon, parts of the diencephalon and the otocyst. The differential expression patterns of the two emx homeoprotein mRNAs may define the subdivisions of the zebrafish telencephalon.

Amino Acid Sequence↗
PubMed1995

[Germ cell tumor].

Germ cell tumor (GCT) is chemotherapy-sensitive, and with the development of a cisplatin combined regimen, the majority of patients can now be cured. Seventy percent to 80% of patients with advanced GCT have a lasting complete response to a cisplatin combined regimen, while 20 to 30% of these patients are refractory to the therapy. Refractory GCT patients need more effective and intense therapy. In order to overcome the conventional dose chemotherapy results, high-dose chemotherapy backed by autologous hematopoietic stem cell transplantation (AHSCT), has been applied to patients with GCT who have relapsed after achieving a complete response by first-line chemotherapy or to those in whom disease progression or the failure to achieve CR had occurred after initial and/or ifosfamide combined salvage therapy. The therapy with a high-dose combination of CBDCA (Carboplatin), VP-16 (Etoposide) and CPM (Cyclophosphamide) or IFM (Ifosfamide), supported with AHSCT is administered to the advanced GCT patients. The response rate (CR+PR) ranges from 40 to 78% by reported groups averaging about 50%, and disease-free survival is possible in about half the survivors thus far. Treatment related morbidity and mortality are observed, but are tolerable with the above dosage. Thanks to the technical development of collecting hematopoietic stem cells using either bone marrow or peripheral blood, and hematopoietic growth factor to lessen hematologic toxicities and obtain early hematological recovery, this method can be performed more safely. High-dose chemotherapy with AHSCT may well become more effective in patients with resistant GCT by a new combination of synergistic drugs or multicycle transplants.

Adult↗
PubMed1995

Comparison of peripheral blood stem cells mobilized with granulocyte colony-stimulating factor with or without prior standard-dose chemotherapy in patients with malignancy.

We studied the effect of granulocyte colony-stimulating factor on the magnitude of peripheral blood stem cell mobilization in patients with malignancy. The leukapheresis products mobilized with granulocyte colony-stimulating factor alone at a steady state (a period of full hematopoietic recovery) (group 1) were compared with those obtained after cytotoxic chemotherapy using granulocyte colony-stimulating factor (group 2). In group 1, six patients underwent six courses of stem cell collection with a median of 20 l leukapheresis. In group 2, 10 patients underwent 12 courses of stem cell collection with a median of 10 l leukapheresis. Median yields of group 1 vs. group 2 were mononuclear cells (x 10(9)), 21.9 vs. 11.6; CD34+ cells (x 10(6)/l), 14.5 vs. 17.1; colony-forming unit for granulocyte-macrophage (/ml), 223 vs. 1193; burst-forming unit for erythroid (/ml), 29 vs. 71; colony-forming unit for erythroid (/ml), 42 vs. 29; colony-forming unit for megakaryocyte (/ml), 26 vs. 59. While there were no statistically significant differences in the number of CD34+ cells between the two groups, granulocyte-macrophage-committed progenitor cells were more enriched in the apheresis products of group 2. The correlation between CD34+ cells and colony-forming unit for granulocyte-macrophage was poor. Our results demonstrate that granulocyte colony-stimulating factor can mobilize a sufficient number of progenitor cells into the peripheral blood for stem cell transplantation with or without prior chemotherapy.

Adolescent↗
PubMed1994

Evaluation of mixed chimaerism and origin of bone marrow derived fibroblastoid cells after allogeneic bone marrow transplantation.

We assessed the origin of bone marrow derived fibroblastoid cells (BMF) in long-term cultures of 13 samples obtained from nine patients after allo-BMT by polymerase chain reaction (PCR) amplification of MCT118, one of the variable number of tandem repeats regions (VNTR). BMF showed a complete recipient pattern in nine samples obtained from seven patients; however, a recipient-predominant mixed chimaeric pattern was detected in BMF from four patients. Also, two of the four patients died with bone marrow hypoplasia. These data suggest that mixed chimaeric pattern of BMF may be correlated with bone marrow hypoplasia.

Adult↗