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Biomedical subjects

Y Ohtsuka

Publications and source records attributed to Y Ohtsuka.

At least 91 records · Page 5Linked to original sources
PubMed1998

Dystrophin acts as a transplantation rejection antigen in dystrophin-deficient mice: implication for gene therapy.

Duchenne muscular dystrophy is a lethal and common X-linked recessive disease caused by a defect in dystrophin. Normal myoblast transplantation and dystrophin gene transfer have been expected to correct the deficiency in the muscles, but their clinical application has been hampered by the limited preservation of dystrophin-positive myofibers. In this study we investigated the mechanism for immunologic rejection of normal C57BL/10 (B10) myoblasts transplanted into dystrophin-deficient mdx mice, an animal model of Duchenne muscular dystrophy. We found that mdx mice develop CTL specific for dystrophin itself, which were CD8 dominant and restricted by H-2Kb. We identified several antigenic peptides derived from dystrophin that bind to H-2Kb and are recognized by the mdx anti-B10 CTL. Immunologic tolerance against dystrophin was successfully induced by i.v. injection of these peptides before B10 myoblast transplantation, which resulted in sustained preservation of dystrophin-expressing myofibers in mdx mice. These results demonstrate that dystrophin is antigenic in dystrophin-deficient mice and that immunologic regimen would be necessary to achieve the persistent expression of introduced dystrophin in the muscles of dystrophin-deficient individuals.

Amino Acid Sequence↗
PubMed1998

Functional characteristics and the complete primary structure of ascidian gelsolin.

The body wall of the ascidian is composed of unusual multi-nucleated smooth muscle cells enriched with thin actin filaments containing troponin-tropomyosin which run along the longitudinal cell axis without being organized into striated structures. We purified an actin-binding protein of 80 kDa, tentatively termed 80K protein, from the body wall muscle of ascidian, Halocynthia roretzi, and characterized the functional properties and molecular structures. In the presence of Ca2+, the 80K protein accelerated the initial phase of actin polymerization, namely the nucleation process, decreased the level of polymerization at the steady state, caused marked reduction in viscosity of an F-actin solution, and fragmented F-actin filaments, while in the absence of Ca2+, it remained associated with F-actin without severing the filaments. The interaction of the 80K protein with actin was inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2). When actin was polymerized in the presence of acrosome actin bundles from horseshoe crab sperm, the 80K protein inhibited the growth of actin filaments at the barbed end but not at the pointed end, indicating that the 80K protein functions as a barbed-end capping protein. In order to characterize the molecular structure of the 80K protein, cDNAs encoding this protein were isolated from the lambda gt11 cDNA library of the ascidian muscle by using a monoclonal antibody (AS23) specific for this protein and the entire sequence was determined. The deduced peptide sequence showed about 44% homology in amino acid residues with the human gelsolin sequence, and in addition, 6 repeating segments were observed in the sequence of the 80K protein as has been described in the gelsolin sequence. These results indicate strongly that the 80K protein belongs to the gelsolin family.

Actins↗
PubMed1998

Shinrin-yoku (forest-air bathing and walking) effectively decreases blood glucose levels in diabetic patients.

The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels.

Baths↗
PubMed1998

A severe case of Moebius syndrome with calcification on the fourth ventricular floor.

We report the case of a Japanese girl with a severe type of Moebius syndrome. Her morphological features were a mask-like face, limitation of horizontal eye movements, severe bulbar palsy, multiple and bilateral arthrogryposis including the elbow, knee, and ankle joints, and clubfeet. After birth, her general condition became worse because of repeated apneic spells and aspiration pneumonias due to dysphagia. She finally required tracheotomy. Computed tomography (CT) of the brain revealed minute calcifications on the fourth ventricle floor; this may have been due to severe damage to the brain stem. It is most likely that the various manifestations in our patient were due to disturbance of the blood supply to arteries perfusing the brain stem and to some other arteries, at a critical stage of fetal development.

Abnormalities, Multiple↗
PubMed1998

Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior.

Advanced neuroblastoma and malignant liver tumor are representative childhood cancers for which combined chemotherapy including cisplatin and doxorubicin is routinely performed. The prognosis of patients with tumors which develop multiple drug resistance (MDR) is unfavorable. To elucidate the role of multidrug resistance-associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) in the clinical behavior of the tumors, we examined 42 neuroblastomas and 10 malignant liver tumors for the expressions of MRP and cMOAT by quantitative RNA-polymerase chain reaction (PCR). The amplification and expression of N-myc oncogene in the neuroblastomas were also investigated. We found a close association between MRP and N-myc expression in each neuroblastoma sample but no significant relationship between MRP expression and the patients' outcome. The forced expression of N-myc failed to enhance the expression of MRP in N-myc transfected neuroblastoma cell lines. cMOAT was rarely expressed in the neuroblastomas, but was frequently expressed in the malignant liver tumors. The expression of MRP and cMOAT in the childhood liver tumors was more common and higher, especially in advanced cases with a poor outcome, than that observed in normal liver or in 9 hepatocellular carcinomas from adult patients. The enhanced expression of these genes might be characteristic of childhood malignant liver tumors and related to their clinical chemoresistance.

ATP-Binding Cassette Transporters↗
PubMed1998

Long-term follow-up of childhood epilepsy associated with tuberous sclerosis.

PURPOSE: To study the clinical and electroencephalographic (EEG) characteristics of patients whose epilepsy is associated with tuberous sclerosis, with special reference to their clinical course. METHODS: We investigated the electroclinical and radiologic features of 38 patients with epilepsy associated with tuberous sclerosis. RESULTS: Eleven patients showed only generalized epilepsy, and 10 showed only localization-related epilepsy throughout their clinical course. Among the other 17 cases, the nature of the epilepsy changed between generalized and localization-related epilepsies during the clinical course. A shift from generalized to localization-related epilepsies was more common than the reverse. Seventeen had West syndrome (WS), three had Lennox-Gastaut syndrome (LGS), and eight had epilepsies that evolved from WS to LGS. Tonic spasms, mostly in series, were seen in all 28 patients with generalized epilepsy. Eleven of the 28 patients had partial seizures and tonic spasms in the same period. Six of them showed "simultaneous seizures," consisting of tonic spasms in series and a partial seizure. Partial seizures were the main seizure type in 27 patients with localization-related epilepsy, but three of them also showed tonic spasms that included "simultaneous seizures." Ictal EEGs revealed multiple active foci in the same period that could shift during the clinical course. Neither the location nor number of tubers was related to the clinical course. As for seizure outcome, 12 (32%) of 38 patients were free from seizures at follow-up. CONCLUSIONS: In epilepsies associated with tuberous sclerosis, there may be an interrelation between generalized and localization-related epilepsies, as well as one between generalized and partial seizures.

Child↗
PubMed1998

Analysis of ictal EEGs of epilepsy associated with tuberous sclerosis.

PURPOSE: To investigate the significance of cortical pathology of tonic spasms in patients with tuberous sclerosis. METHODS: The subjects were 38 patients with epilepsy associated with tuberous sclerosis. We analyzed ictal EEGs of tonic spasms and partial seizures by means of video-EEG monitoring for a total of 763 tonic spasms in 20 patients and 107 partial seizures in 15 patients. We also investigated the relation between partial seizures and magnetic resonance imaging (MRI) findings of these patients. RESULTS: Ictal EEG patterns of tonic spasms were divided into generalized and focal patterns. Thirteen patients had only generalized patterns, whereas seven had both patterns. In five patients who had focal ictal patterns of tonic spasms and partial seizures, the location of focal patterns corresponded with the location of onset of partial seizures. Focal discharges were seen immediately before, after, and in the middle of tonic spasms in series in 13 patients. The location of focal discharges also corresponded with the location of the onset of partial seizures in 10 of the 13 patients. Regarding partial seizures, four patients had multiple active epileptogenic foci during the same period, and two others had shifting epileptogenic foci with increasing age. CONCLUSIONS: These findings indicate that cortical pathology plays an important role in the occurrence not only of partial seizures but also of tonic spasms in patients with tuberous sclerosis.

Adult↗
PubMed1998

West syndrome and its related epileptic syndromes.

The purpose of this project was to study the relationship between West syndrome (WS) and its related epileptic syndromes, and reconsider the nosological limits of WS. The electroclinical features of 45 patients who experienced spasms in series were investigated, as well as some features not common in patients with WS. All patients were mentally retarded. The patients were divided into three groups: Group 1 consisted of 12 patients with refractory epilepsies with onset in early infancy, group 2 consisted of 5 patients with symptomatic localization-related epilepsies associated with spasms in series, and group 3 consisted of 28 patients with generalized epilepsies who had spasms in series after age 2 years. Partial seizures were the dominant symptom throughout the clinical course and spasms in series associated with atypical hypsarrhythmia appeared transiently during infancy in a significant number of the patients in group 1. In group 2, complex partial seizures (CPS) were the main seizure type and hypsarrhythmia was not observed during the clinical course. The EEGs in group 3 patients showed diffuse slow spike-waves or multifocal epileptic discharges in all but 1 patient. The EEG of the remaining patient still showed hypsarrhythmia at age 8 years. Therefore, group 1 patients should be classified as having WS although cortical mechanisms play a critical role in the occurrence of their seizures. Group 2 patients should be considered as having a type of localization-related epilepsy even though they share a similar pathophysiological mechanism with group 1. In group 3, 1 patient whose EEG still showed hypsarrhythmia was classified as having WS. The other patients should be classified as having generalized epilepsies other than WS.

Adolescent↗
PubMed1998

A case of chronic graft-versus-host disease following living-related donor kidney transplantation.

A 25-year-old man with a 2.5-year history of maintenance hemodialysis underwent a living-related donor (father) kidney transplantation. He was free from acute rejection, but 8 months after the kidney transplantation, he complained of malaise and fever which were accompanied by eruptions on the face, fingers, and hips which resembled symptoms seen in patients suffering from systemic vasculitis. Skin biopsy findings were compatible with those of chronic graft-versus-host disease (GVHD). The human leukocyte antigen (HLA) family study disclosed that the donor's HLA haplotype was homozygous and identical to one of the recipient's HLA haplotypes which indicated that the host would not resist engraftment. On the basis of these findings, a diagnosis of chronic GVHD was made, and increasing doses of immunosuppressants resulted in a resolution of these symptoms. Our report is the first describing GVHD that developed in a patient undergoing related-donor kidney transplantation.

Adult↗
PubMed1998

Chronic oral antigen exposure induces lymphocyte migration in anaphylactic mouse intestine.

Persistent diarrhea, vomiting, and dehydration are symptoms often seen in patients suffering from food allergy after chronic antigen exposure; however, the precise mechanisms involved have not been well defined. In an effort to clarify the mechanisms of the chronic intestinal changes attributable to genuine IgE-mediated anaphylactic reactions induced by orally administered antigen, a mouse model was established by s.c. implantation of a murine hybridoma capable of producing monoclonal anti-trinitrophenyl IgE antibody, and the morphologic and immunologic changes occurring in the intestine upon chronic antigen exposure were investigated. In the early stage after ingestion of the antigen, diarrhea and noticeable infiltration of mast cells as well as eosinophils into the lamina propria were observed. A substantial increase in serum histamine levels as well as an increase in leukotriene C4 synthesis in the jejunal mucosa were observed 1 h after antigen challenge. Also, the synthesis of leukotriene B4 was significantly elevated for up to 9 h after antigen challenge. The expression of both intercellular adhesion molecule-1 (ICAM-1) on mucosal vascular endothelial cells and IAd on epithelial cells was markedly enhanced, and noticeable infiltration of eosinophils and lymphocytes was also confirmed in the mouse model after chronic antigen exposure. These findings suggest that oral antigen exposure induces anaphylactic reactions in the intestine mediated by mast cells and eosinophils in response to the IgE-antigen complex in the early phase, and also induces lymphocyte migration after chronic antigen exposure.

Administration, Oral↗
PubMed1998

An immunocytochemical study for lysosomal cathepsins B and D related to the intracellular degradation of titanium at the bone-titanium interface.

The morphological relationship between titanium and lysosomal proteinases, cathepsins B and D, at the bone-titanium interface using titanium-coated plastic implants placed for 28 days in the tibiae of 6-week-old rats was immunocytochemically investigated by the colloidal immunogold-silver method. Under light microscopy the titanium layer appeared to make direct contact with the bone and one or a few layers of slender cells were interposed between the bone and titanium. Ultrastructurally, the titanium came in contact with the bone or the slender cell layer through a 20 to 40 nm thin amorphous zone. The slender cells at the bone-titanium interface consisted of two types; one was an osteoblast type with glycogen granules which was found along the newly-formed bone facing titanium layer. The other was a fibroblast type which came in contact with the titanium layer and occasionally endocytosed the detached titanium fragments. In addition, some of the slender cells also showed degenerative changes. Immunocytochemically, cathepsins B and/or D were sometimes colocalized in some phagolysosomes with titanium fragments. These findings suggested that the fibroblast types at the bone-titanium interface may act as scavengers to remove both cell debris and titanium by means of some endocytotic ability, and lysosomal cathepsins also developed in response to the endocytosed titanium. The osteoblast type also appears to show a high degree of osteogenic activity around the titanium-coated plastic implants.

Animals↗
PubMed1998

[The impact of low calcium dialysate (1.25 mmol/l; LCD) on bone metabolism in CAPD patients].

The aim of this study was to evaluate the influence of LCD on bone metabolism, and assess the indication of LCD. Fourteen patients on CAPD (m = 8, f = 6) were converted to LCD following over 1 year on standard calcium dialysate (1.75 mmol/l; SCD) treatment, and followed for 1 year. The biochemical measurements included plasma levels of Ca, P, ALP, and i-PTH. The bone mineral density (BMD) was evaluated using dual energy x-ray absorptiometry. Ca-carbonate and calcitriol were administered to maintain plasma Ca levels within the normal range. The patients were divided into three groups on the basis of the i-PTH levels just before the conversion to LCD. Group 1; n = 5, i-PTH < 65. Group 2; n = 5, 65 < or = i-PTH < 200. Group 3; n = 4, 200 < or = i-PTH (pg/ml). Mean BMD Z scores decreased significantly in group 3. Mean serum i-PTH significantly increased in all groups. These results suggest that LCD is effective for treating adynamic bone disease, which is seen in high frequency in patients undergoing peritoneal dialysis. However, these results also pointed to the disadvantage of worsening the secondary hyperparathyroidism. In conclusion, LCD should be used carefully in patients whose i-PTH levels are high, because of the possibility of bone mineral loss.

Adult↗
PubMed1997

Sensitive determination of sulpiride in human plasma by high-performance liquid chromatography.

We developed a simple, sensitive and reliable method for the determination of sulpiride, a specific antipsychotic drug, in human plasma using high-performance liquid chromatography. A structurally related benzamide, tiapride, was used as the internal standard. A Sep-Pak C18 cartridge was used to extract a sample from 1 ml of plasma. The extract was dissolved in methylene chloride, and then back-extracted with 0.01 M hydrochloric acid. The aqueous layer was put on a octadecylsilica column with a mobile phase of 50% acetonitrile in 0.01 M phosphate buffer (pH 3.0). A fluorescence detector with excitation at 300 nm and emission at 365 nm was used for detection. The calibration curve was linear in the concentration range of 10-1500 ng/ml, and the lower limit of detection was 1 ng/ml. We used this method to examine plasma levels of sulpiride in 14 inpatients being treated with sulpiride for 6 months. The determined plasma levels were 70.1-1121.2 ng/ml, and the correlation between daily dose and plasma concentration was positive. This simple, reliable method is expected to be put to good use in forensic and hospital laboratories.

Adult↗
PubMed1997

Physical effects of negative air ions in a wet sauna.

The physical effects of negative air ions on humans were determined in an experimental sauna room equipped with an ionizer. Thirteen healthy persons took a wet sauna bath (dry bulb temperature 42 degrees C, relative humidity 100%, 10 min exposure) with or without negative air ions. The subjects were not told when they were being exposed to negative air ions. There were no differences in the moods of these persons or changes in their blood pressures between the two saunas. The surface temperatures of the foreheads, hands, and legs in the sauna with negative ions were significantly higher than those in the sauna without ions. The pulse rates and sweat produced in the sauna with ions were significantly higher than those in the sauna without ions. The results suggest that negative ions may amplify the effects on humans of the sauna.

Adult↗
PubMed1997

Detection of tumor thrombus in children using color Doppler ultrasonography.

Color Doppler ultrasonography (CDUS), which provides information regarding both the tissue and the blood flow simultaneously in real time, is a relatively new and noninvasive technique for the evaluation of organ perfusion. The authors investigated the usefulness of CDUS in the detection of tumor thrombus in 34 children who had malignant tumor (21 neuroblastomas, 2 Wilms' tumors, 5 hepatoblastomas, 2 rhabdomyosarcomas, and 4 others) who underwent CDUS between April 1992 and March 1995 in our department. The CDUS showed tumor thrombus in four patients (11.8%). Three thrombi (in one patient each with neuroblastoma, Wilms' tumor, and hepatoblastoma) were situated in the inferior vena cava, and one (in a patient who had hepatoblastoma) in the portal vein. Each tumor thrombus was monitored and followed up using CDUS every month during the entire clinical course; two of the four thrombi remained despite intensive treatments. The authors have found CDUS to afford rapid and noninvasive detection of tumor thrombus, and it proved useful not only in the detection of tumor thrombus but also in its follow-up in these children who had malignant tumor.

Child, Preschool↗
PubMed1997

Electroclinical study of localization-related epilepsies in early infancy.

To clarify the characteristics of localization-related epilepsies in early infancy, we performed an electroclinical study of 28 epileptic patients whose first seizures occurred before 6 months of age. The patients were retrospectively divided into two groups: the seizure-controlled group (8 patients) and the refractory group (20 patients). The seizure-controlled group included the patients whose seizures were suppressed within 1 year after onset; the refractory group included all other patients. The characteristics of the refractory group were as follows: (1) most patients had serious underlying pathologies; (2) the seizure type in most cases was simple partial seizure or complex partial seizure without secondary generalization; (3) the interictal EEG showed focal abnormalities and severe dysrhythmia on the basic pattern associated with multifocal spikes in most cases; and (4) in some patients, West syndrome developed after localization-related epilepsies and generalized seizures appeared later in some cases.

Age of Onset↗