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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 487 records · Page 27Linked to original sources
PubMed1995

[Proton MR spectroscopy of the brain in patients with congenital myotonic dystrophy].

Volume selective proton MR spectroscopy (1H-MRS) of the brain was performed on a 1.5T magnet in five patients with congenital muscular dystrophy (CMyD), 46 healthy children, and one healthy adult. Peaks of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were observed in both patients and control groups on 1H-MRS, but lactate was not observed. 1H-MRS revealed an increase in the ratio of NAA/Cho and NAA/Cr, and a decrease in Cho/Cr ratio with age in control subjects. In patients with CMyD, the values of NAA/Cho ratio did not increase with age. The values of NAA/Cr ratio decreased with age. The values of Cho/Cr ratio decreased with age in both patient and control groups. At age more than 4 years, the values of NAA/Cho and NAA/Cr ratios were lower in patients with CMyD than in controls. The values of Cho/Cr ratio did not differ between CMyD and controls. These results suggest that in patients with CMyD, there is an NAA decrease and a developmental disorder of neurons in the brain.

Adolescent↗
PubMed1995

[Intensive and high-dose chemotherapy with peripheral blood stem cell transfusion for pediatric malignant brain tumor].

In this study, the newly developed marrow-rescue therapy during myelosuppression is utilized. In this therapy, peripheral blood stem cell transfusion (PBSCT) is administered following high-dose chemotherapy. Harvest of peripheral blood stem cells (PBSC) during myelosuppression following marrow-ablative chemotherapy is a safe, reliable procedure in children with leukemia. And administration of these cryopreserved PBSC is useful in reducing myelosuppression following intensive/ultra high-dose chemotherapy. In this study, several courses of intensive chemotherapy (1 course: VP-16 300mg/m2 x 5 days + carboplatin 400-500mg/m2 x 3 days) and one course of ultra-high dose chemotherapy (1 course: VP-16 400mg/m2 x 8 days + carboplatin 800mg/m2 x 5 days + MCNU 250, 200mg/m2 x each day) with PBSC transfusion were applied in four cases of pediatric malignant brain tumors (2 cases of medulloblastoma, one case of pineoblastoma and anaplastic ependymoma) after surgical reduction. With PBSC transfusion, myelosuppression following high-dose chemotherapy could be overcome without serious complication in all cases. Three cases showed complete remission and one showed partial remission after the operation and intensive chemotherapy. However, CSF dissemination appeared in two cases and they died 20 and 28 months after the onset respectively. Intensive/ultra high-dose chemotherapy with PBSC transfusion is a safe procedure in children with malignant brain tumors. This procedure may enable the postponement of radiation for pediatric malignant brain tumor cases under three years of age.

Age of Onset↗
PubMed1995

[Therapeutic results of non-small cell lung cancer in stage III: combined synchronous irradiation with bronchial artery infusion of CDDP].

The present series consisted of 55 patients with non-small cell lung cancer in stage III who underwent radiotherapy from 1986-1989. They were divided into two groups: 35 patients with combined concurrent bronchial artery infusion (BAI) of CDDP (50 mg) and unevenly fractionated radiotherapy (combined group) and 20 with evenly fractionated irradiation (radiation group). The combined therapy was expected to achieve higher local control of disease. The rationale for the combined regime was based on the effects of CDDP, which causes cytostasis following intra-arterial infusion, and increased radiosensitivity from unevenly fractionated irradiation just after BAI. The radiotherapy group was considered a control in this study. The results of the combined group were limited to no CR, PR in 33 patients and NC in two with a period of 30 +/- 13 days for 50% reduction of tumor, superior to the radiation group. There was no difference between the two groups in the rate of local recurrence (combined group: 63%). The combined group showed 28 months of MST in cause-specific survival, a significant difference. Survival rates were 71% at one year, 27% at three years, and 15% at five years, including three survivors without recurrence. Stage III a patients in the combined group showed a better outcome than stage III b patients in the same group, and stage III a patients in the radiation group. Although radiation pneumonitis as a fatal side effect was noted in one patient of the combined group, the combined therapy presented here seemed to improve the prognosis of locally advanced lung cancer if properly indicated.

Aged↗
PubMed1995

A novel system for small bowel preservation--cavitary two-layer (University of Wisconsin solution/perfluorochemical) cold storage method.

Organ preservation is very important to accomplish successful organ transplantation. Unlike the kidney, liver, pancreas or heart, the preservation method of the small bowel has not been established yet. In this study, we tested 24-48hr-preservation of rat small bowel by a cavitary two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) cold storage method (two-layer method (group 1)) in heterotopic rat segmental small bowel transplant model, and compared it with simple cold storage method in UW (group 3). In an attempt to clarify that the oxygenation of the graft by the two-layer method allows for 48hr-preservation, a cavitary two-layer method without oxygen bubbling (group 2) was also examined. The 7 day survival rates after 24hr-preservation were 100%, 67% and 86% for group 1, 2 and 3, respectively. On the other hand, the 7 day survival rates for group 1, 2 and 3 after 48hr-preservation were 86%, 20% and 0%, respectively. Histological studies of grafts preserved by the two-layer method (group 1) for 48hrs on the 7th day posttransplant showed almost normal architecture of the intestinal mucosa. This study demonstrated that the oxygenation of the small bowel during preservation by the cavitary two-layer method using UW allows for 48hr-preservation of rat small bowel. This method is simple and reliable and holds promise for clinical small bowel transplantation.

Animals↗
PubMed1995

The mechanism of action of the two-layer cold storage method in canine pancreas preservation--protection of pancreatic microvascular endothelium.

We have demonstrated that oxygenation of a pancreas during preservation by a two-layer method leads continued ATP production to maintain cellular integrity and produces an extended period of preserved pancreatic viability. The aim of this study is to examine the effect of ATP vs. oxygenation per se on viability of nonparenchymal cell (vascular endothelium), using 2.4 dinitrophenol, an uncoupler of mitochondrial oxidative phosphorylation. Mongrel dogs of both sexes, weighing 12-18kg were used. Under general anesthesia, a left lobectomy of the pancreas was performed. The segmental pancreas graft was autotransplanted immediately (group 1; control) or after 48-hour preservation (group 2; simple cold storage method with Euro-Collins' solution [EC], group 3; two-layer cold storage method using EC, group 4; two-layer cold storage method using EC with 0.2 mM DNP), and the remainder of the pancreas was excised at the time of autotransplantation. Graft viability was judged from graft survival after transplantation. A K-value of intravenous glucose tolerance test more than 1.0 at 2 weeks after transplantation was considered graft survival. Tissue concentration of ATP was determined after preservation using high-performance liquid chromatography. Viability of vascular endothelium was examined using trypan-blue perfusion/fixation test after preservation. Nuclear staining by trypan blue in eosin-counterstaining sections was indicative of loss of cell viability. Pancreatic tissue perfusions, which reflect pancreatic microcirculation, were also measured using H2 clearance technique after 30 to 240 min of reperfusion. Graft survival rates in groups 1, 2, 3 and 4 were 5/5, 0/4, 4/4 and 0/3 respectively. ATP tissue concentration was significantly higher in group 3 compared with group 2 (7.91 +/- 1.21 [n = 4] vs. 1.21 +/- 0.31 [n = 4] mumol/g dry weight, p < 0.01). DNP caused a significant decrease in tissue ATP in group 4 (0.61 +/- 0.07 [n = 3] vs. 7.91 +/- 1.21 [n = 4] mumol/g dry weight, p < 0.01). The percentage of nuclear trypan blue uptake of nonparenchymal cells in group 3 was significantly lower than group 2 (11.29 +/- 3.71 [n = 3] vs. 26.41 +/- 1.66 [n = 3] %, p < 0.01), and DNP (group 4) increased trypan blue uptake (30.10 +/- 4.08 [n = 3] vs. 11.29 +/- 3.71 [n = 3] %, p < 0.01). Tissue perfusions after 2hr-reperfusion in group 3 were significantly higher than group 2 (68.64 +/- 8.62 [n = 5] vs. 45.56 +/- 12.84 [n = 5] ml/min/100g, p < 0.01). Moreover, DNP (group 4) caused a significant decrease in pancreatic tissue perfusions (28.84 +/- 9.09 [n = 5] vs. 68.64 +/- 8.62 [n = 5] ml/min/100g. p < 0.001). It was clear that the two-layer method (group 3) protected microvascular endothelium against cold ischemic damage and inhibition of ATP production using DNP (group 4) caused endothelial damage, microcirculatory disturbance after reperfusion and consequently loss of graft viability. We conclude that microvascular endothelium of the pancreas graft is protected against cold ischemic injury by maintaining ATP tissue levels during preservation by the two-layer method. This is one of the mechanisms of action of the two-layer method in successful pancreas preservation.

Adenosine Triphosphate↗
PubMed1995

MR of childhood-onset dentatorubral-pallidoluysian atrophy.

MR findings in a 14-year-old boy with progressive myoclonic epilepsy, who was diagnosed as having dentatorubral-pallidoluysian atrophy by DNA analysis, were compared with those of his father, who had adult-onset dentatorubral-pallidoluysian atrophy. Besides showing severe brain atrophy, especially of the brain stem tegmentum and cerebellum, MR showed diffuse periventricular hyperintensity on T2-weighted images. As compared with the proband, the father had a mild case.

Adolescent↗
PubMed1995

Detection of dihydrotestosterone (DHT) doping: alterations in the steroid profile and reference ranges for DHT and its 5 alpha-metabolites.

Dihydrotestosterone (DHT), a biologically active metabolite of testosterone, may be misused in sports to benefit from its anabolic and psychotropic effects. After DHT application, a significant increase of the glucuronides of DHT and its metabolites can be expected for a certain time period depending upon dose, formulation, route of administration, and in case of percutaneous administration the chainlength of the ester. DHT and its metabolites can be monitored by gas-chromatography/mass spectrometry (GC/MS) after enzymatic hydrolysis and trimethylsilylation. To investigate the extent of the alteration of the urinary steroid profile after DHT application, timely controlled experiments have been performed with: a) oral application of [16,16,17-2H3]-DHT, and b) sublingual application of a 25 mg dose of DHT. In the experiment with [16,16,17-2H3]-DHT within 24 hours about 44% of the applied dose was recovered after hydrolysis with beta-glucuronidase from E. coli as di- or tri-deuterated 5 alpha-androstane glucuronides: androsterone (33.2%), 5 alpha-androsta-ne-3 alpha,17 beta-diol (2.5%), 5 alpha-androstane-3 beta, 17 beta-diol (0.9%), DHT (7.2%). Hydrolysis with beta-glucuronidase/arylsulfatase from Helix Pomatia resulted in a about 10% higher yield except for DHT. In the study with sublingual application of 25 mg of DHT the extent of the recovery of DHT and its metabolites was in the same range as for the deuterated DHT. The urinary glucuronide concentrations of DHT, androsterone (AND), 5 alpha-androstane-3 alpha, 17 beta-diol (5 alpha A3 alpha D) and 5 alpha-androstane-3 beta,17 beta-diol (5 alpha A3 beta D) and their ratios to etiocholanolone (ETIO), 5 beta-androstane-3 alpha, 17 beta-diol (5 beta A3 alpha D) and epitestosterone (EPIT) were increased for up to 48 hours after application. For doping control purposes concentrations of DHT, 5 alpha A3 alpha D, 5 alpha A3 beta D and ratios of 5 alpha-metabolites to non 5 alpha-metabolites such as DHT/ETIO, DHT/EPIT, 5 alpha A3 alpha D/5 beta A3 alpha D, 5 alpha A3 beta D/5 beta A3 alpha D, and AND/ETIO outside the reference ranges are a proof for DHT application. Reference ranges for Asian and Caucasian male and female athletes are calculated from data bases of the Asian Games 1994, the previous Asian Games 1990 and the routine doping control samples of Caucasian athletes measured in Cologne 1994. At the occasion of the 1994 Asian Games in Hiroshima alterations in the concentrations and ratios of the DHT depending parameters for outside there reference ranges have been found and have been sanctioned on this basis by the Medical Commission of the Organisation of Olympic Council of Asia (OCA).

Adult↗
PubMed1994

A substrate of ecto-protein kinase is microtubule-associated protein 1B in cortical cell cultures undergoing synaptogenesis.

Synapse formation between cultured rat cortical neurons is inhibited by the continuous application of K-252b, an ecto-protein kinase inhibitor, which cannot permeate the cell membrane. In order to identify the phosphorylated membrane proteins which are necessary for synapse formation, endogenous substrates for ecto-protein kinase activity were investigated. To detect phosphorylation of proteins containing extracellular domains, [gamma-33P]ATP was applied to the medium for brief periods. Proteins were then separated by SDS polyacrylamide gel electrophoresis and detected by autoradiography. Some bands showed immediate phosphorylation and this phosphorylation was suppressed by the addition of K-252b to the medium. We examined partial amino acid sequences of these substrates. The band with the highest molecular weight, whose phosphorylation was strongly inhibited by K-252b, was identified as microtubule-associated protein (MAP) 1B. These results suggest the possibility that the phosphorylation of extracellular domains of MAP1B is involved in synaptogenesis between cortical neurons.

Adenosine Triphosphate↗
PubMed1994

Defective T cells from gld mice play a pivotal role in development of Thy-1.2+B220+ cells and autoimmunity.

The gld mouse represents a fascinating animal model of autoimmune disease, which is characterized by massive development of Thy-1.2+B220+ CD4-CD8- cells. These cells thus have double positive markers for T and B cells, but are double negative for CD4 and CD8 markers and are thus designated DN cells in the present context. An additional important feature in gld mice is a defect in expression of Fas ligand. To investigate the regulatory role of bone marrow-derived cells for the development of these DN cells and of gld autoimmunity, we constructed chimeric mice transplanted with fetal liver cells or fetal thymus from gld mice into nonirradiated severe combined immunodeficient (SCID) mice. These chimeric mice regenerated, developed both these DN cells and the gld autoimmune syndrome and also generalized lymphoproliferative disorders. However, when fetal liver cells from both gld and non-gld mice (C57BL/10 Thy-1.1 mice) were co-transplanted into SCID mice, the development of DN cells was apparently inhibited. Further, this inhibition was also seen in SCID mice that had been grafted with both gld and non-gld fetal thymus revealing the pivotal role played by T cells in development of DN cells. When B cells purified from non-gld (C3H+/+) mice were transplanted into SCID mice grafted with gld fetal thymus, the development of DN cells was not inhibited. Taken together, these findings indicate that T cells from non-gld mice inhibit the expression of gld features, e.g., lymphoproliferation, immune-based nephritic disease, and autoantibody production. These findings also suggest that the Fas ligand is selectively expressed on T cells.

Animals↗
PubMed1994

Vitamin D-dependent rickets type II: regulation of human osteocalcin gene expression in cells with defective vitamin D receptors by 1,25-dihydroxyvitamin D-3, retinoic acid, and triiodothyronine.

The vitamin D receptor (VDR) is a nuclear transcription factor which binds to the vitamin D response element (VDRE) of the human osteocalcin gene and regulates its expression. Humans with VDR gene mutations, ever among those with the same point mutation in their VDR gene, demonstrate clinical heterogeneity. In addition, in some patients with these mutations, rickets has not recurred following cessation of therapy during follow-up ranging from 6 to 24 years. While important, it is likely that the VDR protein is not the sole factor in the development of rickets. To try to understand these clinical findings, the complex formed between the VDRE and one or more proteins in the nuclear extracts of cultured skin fibroblasts treated with 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3), retinoic acid (RA), and/or triiodothyronine (T3) was investigated since such complexes are likely to precede the transcription of the VDR gene. Complex formation in the control cells with an intact VDR was increased by treatment with either 0.1 nM, 1 nM, 10 nM 1,25(OH)2D3, 100 nM RA, or 100 nM T3; however, combinations of these compounds did not produce an additive effect. In cells of affected patients, 1,25(OH)2D3, RA, or T3 increased complex formation, while no combination had an additive effect. These results indicate that 1,25(OH)2D3, RA, and T3 play a role in the regulation of bone remodeling through modulating the formation of protein complexes on the VDRE. Therefore, the clinical observations in patients with a VDR mutation might be explained at least in part by the overlapping control of osteocalcin expression by 1,25(OH)2D3, RA and T3.

Base Sequence↗
PubMed1994

Astrocytic contribution to functioning synapse formation estimated by spontaneous neuronal intracellular Ca2+ oscillations.

Glial contribution to in vitro synaptic function was investigated in a neuron-glia co-culture system by monitoring spontaneous oscillations of intracellular Ca2+ in neurons. Rat cortical neurons, grown stably on a cortical astrocyte monolayer, extended neurites resulting in marked functional synapse formation. Little synapse formation was observed in neuronal co-culture with meningeal fibroblasts or endothelial cells. Aged astrocytes in vitro (C35) were found to attenuate synaptic development, while young astrocytes (C5) markedly promoted synaptic function. C5 and C35 astrocyte media conditioned yielded no significant synaptogenic effect, indicating diffusible factor(s) are not responsible for our observation. Modulation of astrocytic proliferation and differentiation by gliostatin, a glial growth inhibitor, or dibutyryl cAMP affected neuronal synaptic function on the co-cultures. Site-specific analysis in homologous and heterologous neuron-astrocyte co-cultures among cortex, hippocampus, septum, and striatum revealed that homologous combinations of neurons and astrocytes derived from identical brain regions elicited the largest number of synchronizing neurons. These results suggest that in vivo neuronal synaptic function essentially requires the participation of adjacent astrocytes, which is site-specific and age-dependent.

Animals↗
PubMed1994

Endoglycoceramidase treatment inhibits synchronous oscillations of intracellular Ca2+ in cultured cortical neurons.

Gangliosides are major components of nerve cell membranes and are especially rich in synaptic areas. In order to evaluate the role of endogenous gangliosides in synapse formation, endoglycoceramidase (EGCase) was used to remove oligosaccharides of gangliosides from the cell surface. We have reported previously that synapse formation between cultured rat cerebral cortical neurons can be estimated by the synchronous oscillation of synaptic activity monitored by fura-2 calcium imaging. Continuous application of endoglycoceramidase (EGCase) together with its activator protein dose-dependently decreased the frequency of synchronous oscillations without any morphological changes in neurons and their neurites. The result suggests that oligosaccharides liberated from glycosphingolipids on cultured cortical cell surface with EGCase are important for synapse formation between cortical neurons.

Animals↗
PubMed1994

Tianeptine decreases both serotonin transporter mRNA and binding sites in rat brain.

In situ hybridization histochemistry and quantitative autoradiography were used to evaluate the effects of repeated administration of the serotonin reuptake enhancer, tianeptine. Tianeptine (10 mg/kg twice daily, for 14 days) significantly reduced both the expression of serotonin transporter mRNA and serotonin transporter binding sites labeled by [3H]paroxetine in rat dorsal raphe nucleus. In median raphe nucleus, tianeptine did not change either expression of serotonin transporter mRNA or binding. This effect, which is similar to a reported effect for serotonin reuptake inhibitors, may help to explain the antidepressant effect of tianeptine.

Animals↗