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Biomedical subjects

K Miyasaka

Publications and source records attributed to K Miyasaka.

At least 91 records · Page 5Linked to original sources

CTLA-4 gene polymorphism may modulate disease in Japanese multiple sclerosis patients.

Multiple sclerosis (MS) is widely believed to have a T-cell-mediated autoimmune etiology. The CTLA-4 gene is a strong candidate for involvement in autoimmune diseases because it plays an important role in the termination of T-cell activation. To examine the genetic association of the CTLA-4 gene locus with MS, we analyzed the CTLA-4 gene exon 1 A/G polymorphism in 74 Japanese MS patients and 93 controls. We also investigated the possible interactions of the CTLA-4 gene polymorphism with clinical course and severity, with MRI findings, with another genetic marker-HLA antigens, and with oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). The CTLA-4 exon 1 polymorphism was similar between MS patients and controls. Conversely, clinical disability was significantly more severe in AA homozygous patients than in the other patients, and the allele frequency and the phenotype frequency of the A allele were significantly higher in patients with severe-grade MRI findings of cerebral white matter than in patients with mild-grade MRI findings. The allele frequency and the phenotype frequency of the A allele were significantly higher in patients with OCB than in patients without. This CTLA-4 polymorphism may modulate the prognosis of patients with MS and may be relevant to generation of OCB in the CSF.

Abatacept↗

Expression of cholecystokinin type A receptor gene correlates with DNA demethylation during postnatal development of rat pancreas.

Cholecystokinin stimulates pancreatic amylase secretion, gallbladder contraction, and pancreatic growth, etc. by binding with high affinity to a cholecystokinin type A receptor (CCKAR). To better understand the expression of CCKAR mRNA in terms of tissue specificity and postnatal development, we determined the methylation status of BssHII sites (5'-B sites) in the rat CCKAR gene promoter. The 5'-B sites in adult pancreas expressing CCKAR mRNA were much less extensively methylated than those in fetal pancreas not expressing the mRNA. In brain, liver, and kidney of adult rats not expressing CCKAR mRNA, the 5'-B sites were methylated. In pancreas, the demethylation level of the sites increased at 21 days after birth. Concomitant with the DNA demethylation level in the 5'-B sites, the mRNA level rose rapidly in 21 days. These results demonstrate that methylation and expression of the CCKAR gene reveal a good inverse correlation.

Animals↗

Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active form of vitamin D, exerts an immunosuppressive effect and can completely prevent experimental autoimmune encephalomyelitis (EAE). 1,25(OH)2D3 exerts most of its actions only after it has bound to its specific nuclear receptors. To investigate the possible role of vitamin D receptor gene (VDRG) polymorphism in susceptibility to or disease-modulation of MS, we evaluated 77 Japanese patients with 'conventional' MS and 95 controls. A VDRG allelic polymorphism was assessed by Bsm1 endonuclease restriction after specific PCR amplification. Genotypic polymorphism was clearly defined as BB (absence of restriction site on both alleles), bb (presence of restriction site on both alleles), or Bb (heterozygous). We found overexpression of the b allele (92.9 vs. 84.2%: P=0.0138) and homozygote bb (85.7 vs. 71.6%; P=0.0263) in MS patients compared with controls. The results indicate for the first time an association of MS with VDRG polymorphism, which may be involved in pathogenesis of MS, or in the linkage disequilibrium of VDRG to another pathogenic gene loci. The role of VDR gene polymorphism should be further studied in other populations, and the distribution of other polymorphism, such as Apa I, Taq I, should be also analyzed to confirm another susceptibility gene for MS and to obtain more adequate strategies for treatment of MS.

Adolescent↗

Comparison between observation policy and fractionated stereotactic radiotherapy (SRT) as an initial management for vestibular schwannoma.

PURPOSE: To compare the use of an observation policy with that of stereotactic radiotherapy (SRT) for treatment of vestibular schwannoma. METHODS AND MATERIALS: The study group consisted of 27 patients who underwent observation as an initial treatment (observation group) and 50 who received SRT (SRT group). The mean follow-up period was 35 months and 31 months, respectively. Stereotactic radiotherapy consisted of small-field fractionated radiotherapy (36-44 Gy in 20-22 fractions over 6 weeks) with or without a subsequent 4-Gy single irradiation boost. RESULTS: Actuarial tumor control rate of the SRT group was significantly better than that of the observation group (p < 0.0001). The mean growth was 3.87 mm/year in the observation group and -0.75 mm/year in the SRT group (p < 0.0001). Eleven patients (41 %) in the observation group and 1 (2 %) in the SRT group received salvage therapy (p < 0.001). There was no difference in the actuarial Gardner and Robertson's class preservation curves for 5 years after the initial presentation. CONCLUSION: Stereotactic radiotherapy using a fractionated schedule provides a better tumor control rate and a similar rate of deterioration for hearing levels compared to an observation policy. Initial SRT may be a reasonable alternative to a wait-and-see policy.

Adolescent↗

Preirradiation evaluation and technical assessment of involved-field radiotherapy using computed tomographic (CT) simulation and neoadjuvant chemotherapy for intracranial germinoma.

PURPOSE: To investigate the importance of preirradiation mental and endocrinological evaluation, and the effectiveness of involved-field radiotherapy following neoadjuvant chemotherapy. METHODS AND MATERIALS: Following etoposide and cisplatin with or without ifosfamide, 13 patients with nondisseminated disease received involved-field irradiation of 24 Gy in 12 fractions within 3 weeks and 2 patients with disseminated germinoma received 24 Gy craniospinal irradiation (CSI). CT simulation was used to cover the tumor bed. RESULTS: Full-scale intelligence quotient (IQ) tests given at the time of the initial radiotherapy showed less than 90 in 7 of 11 patients who had tumors involving the neurohypophyseal region, but the 4 patients who had solitary pineal tumors showed higher scores. Panhypopituitarism was observed in 9 patients with tumors involving the neurohypophyseal region. All patients are alive without disease, with a median follow-up period of 40 months. No in-field relapse was noted after the involved-field radiotherapy. One patient experienced a recurrence outside of the planning target volume. CONCLUSION: Decline of neurocognitive and endocrine functions were often seen in patients with tumors involving the hypophyseal region, but not in patients with solitary pineal germinoma before radiotherapy. Involved-field radiotherapy using 24 Gy is effective with the help of CT simulation and neoadjuvant chemotherapy.

Adolescent↗

Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors.

A systemic administration of cholecystokinin (CCK) increases gastric vagal afferent activity via type A CCK receptors (CCKAR). In the present study, the response of gastric vagal afferent activity to an intravenous administration of CCK was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which lack CCKAR, and compared with its control strain, Long-Evans Tokushima Otsuka (LETO) rats. The intravenous administration of 300 pmol kg(-1) and 3 nmol kg(-1) of CCK elicited dose-dependent increases in the gastric vagal afferent activity in LETO rats. The responses were not influenced by the pretreatment with L-365,260, a type B CCK receptor (CCKBR) antagonist, while they were significantly diminished by pretreatment with MK-329, a CCKAR antagonist. After pretreatment with MK-329, 3 nmol kg(-1) (but not 300 pmol kg(-1)) of CCK still elicited a small but significant increase in the activity. In the OLETF rats, both 300 pmol kg(-1) and 3 nmol kg(-1) of CCK produced small increases in the vagal afferent activity, and the responses were not influenced by pretreatment with either L-365,260 or MK-329. In addition, the systemic administration of CCK did not change gastric motility in the OLETF rats, indicating that the response of the vagal afferent activity in OLETF rats was independent of the gastric motility change. These results demonstrate that neither CCKAR nor CCKBR contributes to the response of the afferent activity of the gastric vagal nerve to a systemic administration of CCK in OLETF rats, suggesting an involvement of novel (non-A, non-B) CCK receptors.

Animals↗

MRI of the brain in the Kearns-Sayre syndrome: report of four cases and a review.

We report brain MRI findings in four patients with typical Kearns-Sayre syndrome (KSS) and correlate them with clinical manifestations. MRI was interpreted as normal in two patients; cerebral and cerebellar atrophy was seen in the other two. On T2-weighted spin-echo images, two patients had high-signal lesions bilaterally in subcortical white matter, thalamus and brain stem. In one patient, the white matter lesion extended into the deep cerebral white matter and the cerebellum was also affected. The other also had bilateral high-signal lesions in the globus pallidus. There was little correlation between neurological deficits and MRI findings. A review of the literature revealed that 10 of the 13 patients with typical KSS previously studied had bilateral subcortical white-matter lesions on T2-weighted images; at least 7 also had high-signal lesions in the brain stem, globus pallidus, thalamus or cerebellum. Although MRI may be normal or show atrophy, the characteristic finding in KSS is a combination of the high-signal foci in subcortical cerebral white matter and in the brain stem, globus pallidus or thalamus.

Adolescent↗

Radiographic evaluation of the lumbosacral disc height.

OBJECTIVE: To establish criteria for the radiographic evaluation of narrowing of the L5-S1 disc height, which varies widely with transition of the L5 vertebra. DESIGN AND PATIENTS: Nondegenerated disc heights of L3-4 to L5-S1 and the thickness and length of the L5 transverse process were measured on plain radiographs of the lumbar spine in 166 outpatients, aged 18-35 years (mean 26.3 years), in whom at least the L3-4 and L5-S1 discs both showed normal signal intensity on magnetic resonance imaging. The level of the iliac crest was recorded semiquantitatively. The disc height was expressed as a percentage of the L3-4 disc height, namely "relative disc height". The ratio of disc height to the sagittal diameter of the overlying vertebral body was termed the "disc height index". RESULTS AND CONCLUSION: The relative disc height and disc height index of L5-S1 showed strong negative correlations with two anatomic variables, which were the relative thickness of the transverse process and the level of the iliac crest (P<0.0001). The results of linear regression analysis suggest that narrowing of the L5-S1 disc height can be evaluated on plain radiographs alone in relation to these anatomic variables.

Adolescent↗

The effect of left-to-right shunting on coronary oxygenation during extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Blood perfusion to the coronary artery (CA) during venoarterial (VA) extracorporeal membrane oxygenation (ECMO) was examined to determine whether it was receiving highly oxygenated ECMO blood or desaturated blood from the pulmonary circulation of diseased lungs. METHODS: In the first experiment, left ventricle output and oxygen saturation in the left ventricle (LV) and CA were measured in dogs placed on VA ECMO. In the second experiment, dogs with an artificial subclavian-pulmonary artery shunt were placed on VA ECMO at 100 mL/kg/min, and oxygen saturation was measured as the shunt flow increased. RESULTS: Without an artificial shunt, a substantial portion of coronary perfusion was found to be supplied by the left ventricle (54 + 30%), even at a high ECMO flow rate of 100 mL/kg/min and low LV output (22+/-17%) relative to ECMO flow. With a shunt, oxygen saturation in the CA was more than 95%, even when shunt flow was only 7.5% of ECMO flow and output from the left ventricle was less than 25% of the ECMO flow rate. CONCLUSIONS: These results suggest that an excessive "lung rest" strategy during VA ECMO may produce suboptimal coronary oxygenation possibly leading to myocardial damage. The presence of a small left-to-right shunt may prevent coronary hypoxia.

Animals↗

Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptor.

Cholecystokinin (CCK) is one of the most abundant neurotransmitter peptides in the brain. As OLETF rats lack CCK-A receptor because of a genetic abnormality, we examined whether learning and memory were impaired in these animals using an elevated eight-arm radial maze. After the completion of a radial maze study, the animals were sacrificed for histological examination of the brain. In some animals, long-term potentiation (LTP) in the hippocampus was measured. In the radial maze, the level of activity (seconds/entry) and the time remaining in the arms were significantly longer in OLETF rats. The number of errors was also significantly higher, and that of the correct choices was significantly lower in OLETF rats compared to the controls (LETO rats). The LTP of the population spike was significantly lower in the OLETF than in the LETO rats. No histological abnormalities were observed. From these observations, we concluded that learning and memory functions were impaired in the OLETF rats.

Animals↗

Three-dimensional movement of a liver tumor detected by high-speed magnetic resonance imaging.

OBJECTIVE: Three-dimensional (3D) movement of a spherical liver tumor during respiration was investigated with magnetic resonance imaging (MRI) using a high-speed sequence. METHODS: A marker was placed on the surface of the patient as a reference of distance. Repetition time (TR) was 7.7 ms, echo time (TE) was 4.2 ms, flip angle was 20 degrees, section thickness was 8 mm, and a 256 x 128 matrix was used. The acquisition time was 1.0 s followed by an interval of 0.5 s. The 20 tumor contours extracted during 30 s were superimposed on sagittal and coronal MR images. RESULTS: The maximum value of tumor edge location was 3.9 cm in the cranio-caudal direction, 2.3 cm in the ventro-dorsal direction, and 3.1 cm in the lateral direction. The mean length of tumor displacement observed was 2.1 cm in the cranio-caudal direction, 0.8 cm in the ventro-dorsal and 0.9 cm in the left-right direction, respectively. The locus of the center of the tumor contour in the sagittal cross section was inclined at 23 degrees and in the coronal cross section was inclined at 18 degrees to the cranio-caudal axis of body. CONCLUSION: In conclusion, 3D movement of a spherical liver tumor was detected using rapid MRI sequential examinations. Magnetic resonance imaging has a potential to improve the accuracy of the planning target volume of a liver tumor.

Humans↗

Small-field fractionated radiotherapy with or without stereotactic boost for vestibular schwannoma.

PURPOSE: To assess the efficacy and toxicity of small-field fractionated radiotherapy with or without stereotactic boost (SB) for vestibular schwannomas. METHODS AND MATERIALS: Thirty-nine patients with vestibular schwannoma were treated with irradiation between March 1991 and February 1996. Extra-meatal tumor diameters were under 30 mm. Thirty-three patients received small-field fractionated radiotherapy followed by SB. Basic dose schedule was 44 Gy in 22 fractions over 5 1/2 weeks plus 4 Gy in one session. Six patients received small-field fractionated radiotherapy only (40-44 Gy in 20-22 fractions over 5-5 1/2 weeks or 36 Gy in 20 fractions over 5 weeks).dash;p > RESULTS: Follow-up ranged from 6 to 69 months (median, 24 months). Tumors decreased in size in 13 cases (33%), were unchanged in 25 (64%), and increased in one (3%). The actuarial 2-year tumor control rate was 97%. Fifteen patients had useful hearing (Gardner-Robertson class 1-2) and 25 patients had testable hearing (class 1-4) before irradiation. The 2-year actuarial rates of useful hearing preservation (free of deterioration from class 1-2 to class 3-5) were 78%. The 2-year actuarial rates of any testable hearing preservation (free of deterioration from class 1-4 to class 5) were 96%. No permanent facial and trigeminal neuropathy developed after irradiation. The 2-year actuarial incidences of facial and trigeminal neuropathies were 8% and 16%, respectively. CONCLUSIONS: Small-field fractionated radiotherapy with or without SB provides excellent short-term local control and a relatively low incidence of complications for vestibular schwannoma, although further follow-up is necessary to evaluate the long-term results.

Actuarial Analysis↗

Combination of EDTA conditioner and phenyl-P/HEMA self-etching primer for bonding to dentin.

OBJECTIVES: The purpose of this study was to examine a new bonding system, combining an ethylenediaminetetraacetic acid (EDTA) conditioner and the 2-methacryloyloxyethyl phenyl phosphoric acid (Phenyl-P)/2-hydroxyethyl methacrylate (HEMA) self-etching primer with a dumbbell-shaped specimen for tensile test. METHODS: Bovine dentin was prepared with a 180-grit paper, conditioned with EDTA, primed with Phenyl-P/HEMA and applied with a light-cured bonding agent, then trimmed to the dumbbell-shaped specimen. After storage in water at 37 degrees C for one day, the tensile bond strength was measured and the hybridization was evaluated by scanning electron microscopy (SEM). RESULTS: When the demineralized dentin with EDTA was primed with 1 wt% Phenyl-P in 30 wt% aqueous HEMA for 10 s, the highest tensile bond strength (22 MPa) was obtained. The SEM views showed that the fractured surface after the tensile test was due to cohesive failure in the cured resin and the 1 micron-hybridized dentin was identified. When the concentration of Phenyl-P and the priming period were increased, tensile bond strength significantly decreased and adhesive failure appeared on the fractured surface. SIGNIFICANCE: Combining the EDTA conditioner and Phenyl-P/HEMA primer afforded high-quality hybridization and good bond strength. This bonding system was promising for bonding resin to human dentin.

Acid Etching, Dental↗

Role of radiotherapy for mucoepidermoid carcinoma of salivary gland.

This report analyzes 61 patients with mucoepidermoid carcinomas of the salivary gland treated by surgery alone or by surgery plus radiotherapy. Local control for all 61 patients at 5 and 10 years was achieved for 88.8 and 79.7% of the cases. Although the rate of positive surgical margin was higher in patients treated with surgery and radiotherapy (radiotherapy group) than in patients treated by surgery alone (surgery group), the local control rates of the two groups showed no statistically significant differences. There was no local recurrence in seven patients receiving post-operative radiotherapy above 55 Gy while there were three local relapses among 17 patients receiving 55 Gy or lower doses (P < 0.05). The 5- and 10-year actual survival rates were 73.4 and 63.3% respectively. Histopathologic subtype of mucoepidermoid carcinomas correlated with regional lymph node involvement and survival. There were no differences in the local control and survival rates of patients with major salivary gland tumors and patients with minor salivary gland tumors. Radiotherapy using 55 Gy or more combined with operation achieved local control and survival rates comparable with complete resection of tumors even if a positive surgical margin was more frequent in the radiotherapy groups.

Adolescent↗

Diagnosis of spinal cord ependymoma and astrocytic tumours with magnetic resonance imaging.

Ependymoma and astrocytic tumours, both originating from the glial tissue, constitute the majority of intramedullary spinal cord tumours. The purpose of this study is to evaluate the diagnostic ability of magnetic resonance imaging (MRI) in these two types of intramedullary spinal cord tumours. MRI findings of 17 ependymomas and 11 astrocytic tumours of the spinal cord were reviewed. Pre-contrast T(1)-weighted images revealed abnormal enlargement of the spinal cord in all cases. Peritumoural cyst formation was noted in 14 ependymomas (82%) and four astrocytic tumours (36%). Evidence of haemorrhage was identified in five (29%) ependymomas and one (9%) astrocytic tumour. Gadolinium-MRI (Gd-MRI) revealed marked enhancement in 11 ependymomas (65%), while six ependymomas showed irregular, partial or no enhancement. Five of these six ependymomas had evidence of prior haemorrhage. Eight astrocytic tumours (73%) were enhanced on Gd-MRI and the pattern of enhancement was more irregular or partial than that of ependymomas. Two pilocytic astrocytomas showed marked ring-like enhancement. In conclusion, detection of haemorrhage and Gd-MRI will help to differentiate these two types of tumours. Further study will be needed to elucidate the relationship between the histological subtypes of the tumours and MRI findings. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗

Effect of temporary hepatic venous occlusion on hepatic arterial embolization. An experimental study.

RATIONALE AND OBJECTIVES: The authors evaluated the effect of hepatic venous occlusion on hepatic arterial embolization in rats. METHODS: A Lipiodol-Iopamidol mixture was injected into the proper hepatic artery in rats during clamping the right side of the hepatic venous confluence. The distribution of Lipiodol-Iopamidol mixture in the sinusoids was analyzed by histological examination with en bloc silver impregnation. The extent of the distribution of Lipiodol-Iopamidol mixture was compared in sinusoids with hepatic venous occlusion and in sinusoids without hepatic venous occlusion. RESULTS: Lipiodol-Iopamidol mixture was more widely distributed in the lobules with hepatic venous occlusion than in the lobules without occlusion. CONCLUSIONS: Hepatic venous occlusion may enhance the effect of hepatic arterial embolization using Lipiodol emulsions and could be useful in the treatment of hepatocellular carcinoma.

Animals↗