Search PubMed⌕ Search

Biomedical subjects

M Oda

Publications and source records attributed to M Oda.

At least 127 records · Page 7Linked to original sources

Bone marrow transplantation for the treatment of X-linked adrenoleukodystrophy.

The effects of bone marrow transplantation (BMT) in X-linked childhood adrenoleukodystrophy (ALD) are described in four Japanese patients. Two older patients, 10-year-old boys with IQ 60 and difficulty in school, had favourable results. IQ levels and MRI findings were generally maintained after BMT. One patient showed improvement of gait disturbance. They have both attended ordinary schools after BMT, although a learning disorder persists. On the other hand, two other younger patients with a rapid course and indeterminate IQ at BMT showed deterioration of neurological functions. Indication for BMT seems to be a maintained IQ level, preferably higher than 80, since it seems to be difficult to normalize IQ level after BMT. Younger patients have higher risk of developing a rapidly progressive form of the disease. Identification of presymptomatic boys, and serial and careful follow-up by neuropsychological and neuroradiological studies, are essential prerequisites to successful BMT in X-ALD.

Adrenoleukodystrophy↗

Hepatic sinusoidal endothelial fenestrae express plasma membrane Ca++pump and Ca++Mg++-ATPase.

BACKGROUND/AIM: In general, intracytoplasmic free calcium ions (Ca++) are maintained at a very low concentration in mammalian tissue by extruding Ca++ against a high concentration of extracellular Ca++, mainly through the activity of the plasma membrane Ca++pump-ATPase. The aim of the present study was to demonstrate by electron cytochemical and immunogold methods the ultrastructural localization of two different types of plasma membrane Ca++-ATPase, i.e. Ca++Mg++-ATPase and Ca++pump-ATPase in the hepatic sinusoidal endothelium. METHODS: Liver tissues and the isolated hepatic sinusoidal endothelial cell (SEC)s were subjected to the following procedures. The ultrastructural localizations of Ca++Mg++-ATPase were examined by an electron cytochemical method. The ultrastructural localization of Ca++pump-ATPase was identified by an electron immunogold method. RESULTS: The cytochemical reaction of Ca++Mg++-ATPase was found to be localized on the outer sites of the plasma membrane of sinusoidal endothelial fenestrae (SEF). The immunogold particles indicating the presence of Ca++pump-ATPase were identified on the inner sites (cytoplasmic) of the invaginated plasma membrane of SEF CONCLUSIONS: Both Ca++Mg++-ATPase and Ca++pump-ATPase demonstrated on the SEF plasma membrane may be involved in the regulation of intracytoplasmic Ca++ concentration.

Animals↗

Thermodynamic and kinetic analyses for understanding sequence-specific DNA recognition.

Thermodynamic and kinetic analyses of biomolecular interactions reveal details of the energetic and dynamic features of molecular recognition processes, and complement structural analyses of the free and complexed conformations. The recent improvements in both isothermal titration calorimetry and surface plasmon resonance sensoring provide powerful tools for analysing biomolecular interactions in thermodynamic and kinetic approaches. The thermodynamic and kinetic parameters obtained for binding between protein and DNA indicate the mechanism of specific DNA recognition, in the high-resolution structures of the protein-DNA complexes. The effects of temperature and ionic strength reflect the conformational changes of the protein and DNA molecules upon complex formation, including important contributions of water and solutes. When combined with mutational studies, the interactions can be reduced to several energetic contributions from individual contacts. These studies should be useful to determine general features of protein functions in genetic regulation.

Animals↗

cis-acting regulatory sequences for antitermination in the transcript of the Bacillus subtilis hut operon and histidine-dependent binding of HutP to the transcript containing the regulatory sequences.

The location of the cis-acting regulatory region for histidine-dependent antitermination of the Bacillus subtilis hut operon was determined. A secondary structure, whose sequences partially overlap with the downstream terminator, was found in the regulatory region of the hut transcript. Mutational analysis of the regulatory region showed that the secondary structure was required for histidine-dependent antitermination. An electrophoretic mobility-shift assay demonstrated that, in response to the presence of histidine and Mg2+, purified HutP bound hut RNA bearing putative secondary structure but not RNA lacking the potential to form putative secondary structure. Native gel electrophoresis showed that HutP existed as a hexamer. A filter-binding assay revealed that the concentration of histidine required for half-maximal binding of HutP to RNA was 3.1 mM and that the Kd for binding of HutP to RNA was approximately 0.56 microM in the presence of histidine. These results suggested that putative secondary structure in the regulatory region of hut mRNA could function as an antiterminator to inhibit the formation of the terminator structure and that HutP causes expression of the hut structural genes by binding to the putative antiterminator structure in response to the presence of histidine.

Amino Acid Sequence↗

Hypoxia and heat inhibit inducible nitric oxide synthase gene expression by different mechanisms in rat hepatocytes.

Ischemia/reperfusion contributes to the hepatic injury in resection and transplantation of the liver. However, the precise mechanisms involved in hypoxia stress remain to be clarified. Pro-inflammatory cytokines including interleukin 1beta (IL-1beta) induce a gene expression of inducible nitric oxide synthase (iNOS) and produce nitric oxide, which exerts either a cytoprotective or toxic effect. In this report, we found that hypoxia and heat markedly inhibited the induction of nitric oxide production stimulated by IL-1beta in rat cultured hepatocytes. Both treatments also abolished the induction of iNOS protein and mRNA. However, hypoxia could not prevent either degradation of an inhibitory protein (IkappaBalpha) of nuclear factor-kappaB (NF-kappaB) or translocation of NF-kappaB to the nucleus, whereas heat inhibited both of the IkappaBalpha degradation and NF-kappaB translocation. Transfection experiments with iNOS promoter construct revealed that hypoxia as well as heat significantly inhibited the transactivation of iNOS gene. Further, a hypoxia-response element located in the promoter was not involved in the inhibition of iNOS induction by hypoxia. These results indicate that hypoxia and heat suppress iNOS gene induction at the transcriptional level through different mechanisms. Reduction of nitric oxide production under hypoxic conditions may be implicated in the cellular damage or protection during hepatic ischemia/reperfusion.

Animals↗

Serum midkine levels are increased in patients with various types of carcinomas.

The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many types of human carcinomas. An enzyme-linked immunoassay, which utilizes a combination of rabbit and chicken antibodies revealed that serum MK level in the controls (n = 135) was 0.154 +/- 0.076 (mean +/- SD) ng ml(-1)with an apparent cut-off value as 0.5 ng ml(-1). Serum MK level was significantly elevated in the cancer patients (n = 150) (P< 0.001); 87% of the patients showed levels of more than 0.5 ng ml(-1). All ten types of cancer examined showed a similar profile of serum MK level. There was no or weak correlation between C-reactive protein level, a marker of inflammation, and serum MK level. Furthermore, in case of gastric carcinoma and lung carcinoma, patients with stage I carcinoma already showed elevated serum MK levels. The present results indicated that serum MK could serve as a general tumour marker with a good potential for clinical application.

Adult↗

A stress distribution analysis of a ceramic lunate replacement for Kienbock's disease.

To determine the usefulness of a ceramic lunate replacement for the wrist joint as a possible treatment for Kienböck's disease, stress distribution of five wrist joint models (a normal wrist, one with the lunate bone removed, one with a coiled tendon replacement, one with a coiled tendon replacement with a ceramic core, and one with a ceramic lunate replacement coated with sheets of tendon) were analysed by the finite element method. The results of finite element method analyses were compared with those of pressure distribution analyses on the wrist joint using pressure-sensitive film and measurement of pressure on the radio-lunate joint with a tactile sensor. Both the coiled tendon model and ceramic core model were unable to resist applied force. Stress and pressure were well-distributed in the wrist joint of the ceramic lunate implant model. These results indicate that the ceramic lunate implant could be expected to prevent carpal collapse.

Cadaver↗

Analysis of histidine-dependent antitermination in Bacillus subtilis hut operon.

We have previously shown that a positive regulator, HutP, of Bacillus subtilis hut operon is a RNA binding protein. Here, we report precise binding site of HutP in cis-regulatory region on hut mRNA and the role of HutP in histidine-dependent antitermination of hut expression. Ethylnitrosourea modification interference assay showed that four binding sites of HutP were found in the cis-regulatory sequences and were located at the stem and the internal loop of an antiterminator structure. In vitro transcription assay indicated that HutP suppressed transcription termination in the presence of histidine. These results suggest that HutP function as an antiterminator in response to the presence of histidine.

Bacillus subtilis↗

Increased extra domain-A containing fibronectin and hepatic dysfunction during septic response: an in vivo and in vitro study.

A massive inflammatory reaction resulting from systemic cytokine release is the common pathway underlying sepsis or multiple organ dysfunction. The role of extra domain sequence A-containing fibronectin (EDA+FN) formation during the septic response is not known. The present study investigates the role of EDA+FN during the septic response under in vitro and in vivo conditions. The direct effects of interleukin-1, interleukin-6, and tumor necrosis factor-alpha on EDA+FN production were evaluated in primary cultured human hepatocytes and fibroblasts. Serial plasma EDA+FN levels were measured using an enzyme-linked immunosorbent assay in 24 patients who developed postoperative sepsis following general abdominal surgery of which there were 17 survivors and 7 non-survivors. EDA+FN secretion was significantly increased in cultured hepatocytes but not fibroblasts at 24 and 48 h following exposure to IL-1 compared to controls. In the clinical setting plasma EDA+FN levels in non-survivors were significantly higher than in survivors. Moreover, the EDA+FN levels were correlated closely with liver function tests. EDA+FN levels may represent a specific marker of vascular injury or systemic inflammatory response syndrome that is associated with an adverse clinical outcome.

APACHE↗

Suppressive effects of human herpesvirus-6 on thrombopoietin-inducible megakaryocytic colony formation in vitro.

Two clinical observations, the association of human herpesvirus-6 (HHV-6) with delayed engraftment after stem cell transplantation and thrombocytopenia concomitant with exanthema subitum, prompted us to evaluate the suppressive effects of HHV-6 on thrombopoiesis in vitro. Different culture conditions for thrombopoietin (TPO)-inducible colonies in semi-solid matrices were examined. Using cord blood mononuclear cells as the source of haematopoietic progenitors, two types of colonies, megakaryocyte colony-forming units (CFU-Meg) and non-CFU-Meg colonies, were established. The former colonies were identified by the presence of cells with translucent cytoplasm and highly refractile cell membrane, most of which were positive for the CD41 antigen. Although the plating efficiency of both types was much higher under serum-containing conditions than under serum-free conditions, the proportion of CFU-Meg to non-CFU-Meg colonies was consistently higher under serum-free conditions. The plating efficiency of CFU-Meg colonies was doubled by adding stem cell factor to the serum-free matrix. The effects of two variants of HHV-6 (HHV-6A and 6B) and human herpesvirus-7 (HHV-7) on TPO-inducible colonies were then compared. HHV-6B inhibited both CFU-Meg and non-CFU-Meg colony formation under serum-free and serum-containing conditions. HHV-6A had similar inhibitory effects. In contrast, HHV-7 had no effect on TPO-inducible colony formation. Heat-inactivation and ultra-filtration of the virus sample completely abolished the suppressive effect. After infection of CD34(+) cells with HHV-6, the viral genome was consistently detected by in situ hybridization. These data suggest that the direct effect of HHV-6 on haematopoietic progenitors is one of the major causes of the suppression of thrombopoiesis.

Antigens, CD34↗

Cortical dysplasia with ossification.

We present the first case of cortical dysplasia with extensive intracerebral ossification. An eight-year-old epilepsy patient with a calcified lesion was successfully treated by surgical intervention. Pathological examination revealed a number of bizarre dysplastic cells in the whole lesion, which consisted of an epileptogenic cerebral cortex and a nonepileptogenic hamartomatous lesion with adipose tissue, vascular tissue, calcification, and ossification. The patient was diagnosed as having cortical dysplasia with ossification. Our findings support the notion that cortical dysplasia has a multipotentiality of cellular differentiation, including various hamartomatous tissues. We suggest that cortical dysplasia should be considered as a potential cause for epileptogenicity of a hamartomatous lesion even when magnetic resonance imaging (MRI) fails to disclose cortical dysplasia.

Brain Diseases↗

Surgical indication for refractory childhood epilepsy.

Recent progress in surgical intervention for medically refractory epilepsy has helped to shed light on more complex epileptogenic problems in children and infants. Surgical treatment increasingly is being used in pediatric patients, but the indications for surgery in this age group have not been well defined. The developing child with a seizure disorder has several problems that are different from adults, such as neural plasticity, deleterious effects of seizures on developmental status, and spontaneous resolution of epilepsy. The critical age for irreversible brain dysfunction and the timing of surgery are the main issues for the treatment of children. Thus, earlier surgical intervention is generally recommended to prevent further detrimental seizure effects, but we still do not know the optimal age. Until the establishment of guidelines for pediatric epilepsy surgery, surgical indications should be determined by the prognosis and the presence of a resectable epileptogenic focus, which in turn are based on the localization of the epileptic focus, seizure frequency, severity, and cognitive function of each case, rather than just the patient's age.

Age Factors↗

Role of the DNA sequence downstream of the Bacillus subtilis hut promoter in regulation of the hut operon.

To identify the role of the downstream region of a hut promoter in regulation of the Bacillus subtilis hut operon, three single-base substitutions (+9G-->A, +14C-->T, and +23T-->G) were introduced into the hut operon. Analysis of expression of the hut operon containing each of these three single-base substitutions and the hut-lacZ fusions with the single-base substitutions at position +14 showed that the position at +14 and probably the position at +23 were required for amino acid repression at the hut promoter, while the position at +14 was not required for catabolite repression at the hut promoter. The position at +9 was required for a histidine-dependent increase of activity of the hut promoter. Analysis of expression of the hut-lacZ fusions and the hut operon in the codY mutant indicated that the position at +14 and probably the position at +23 were involved in CodY-mediated amino acid repression at the hut promoter and that CodY was not required for catabolite repression at the hut promoter.

Bacillus subtilis↗

Autocrine motility factor receptor expression associates with tumor progression in thymoma.

We assessed the autocrine motility factor receptor (AMFR/gp78) expression in thymoma. AMFR/gp78 antigen was identified in tumor cells in 16 out of 51 (31.4%) thymomas. The AMFR/gp78 expression was closely associated with the stage (I/II vs. III/IV, p<0.0001), pathological subtypes (epithelial vs. other types, p=0.0214), and enhanced expression of alpha-smooth-muscle actin within stroma (p<0. 0001). The outcome of the patients with AMFR/gp78 expression was significantly worse than for those without it (p<0.01). All initial tumors with recurrence expressed AMFR/gp78. The AMFR/gp78 appears to be involved in tumor progression in thymoma.

Actins↗

A single nucleotide polymorphism of dopamine transporter gene is associated with Parkinson's disease.

We identified two polymorphisms out of all coding regions of the dopamine transporter gene. One existed in exon 9 (1215A/G) and another in exon 15 (1898T/C). The 1215G was significantly less frequent among patients with Parkinson's disease than the controls. Although the polymorphism caused no amino acid substitution, we concluded that it was associated with decreasing the susceptibility to Parkinson's disease through mechanisms other than the protein function of dopamine transporter.

Aged↗

[Recent endoscopic treatment in gastroenterology].

Endoscopic diagnosis and treatment became to be necessary in gastroenterology for last two decades. Indication of endoscopic treatment is amazingly expanding because of developing new techniques and easy-to-use devices. Nowadays, the indication for endoscopic treatment includes the removal of foreign bodies in alimentary tract, the dilatation of stricture lesions by balloon or expandable metallic stent, the resection of polypoid and superficial tumors by polypectomy and EMR (endoscopic mucosal resection) techniques, the injection sclerotherapy and ligation method for gastroesophageal varices, the hemostasis of gastrointestinal hemorrhages by injection method or heat-burn method. In biliary and pancreatic area, there are some endoscopic treatments that are removal and destruction of stones in common bile duct, biliary and pancreatic drainage by tubing method. Our results of endoscopic resection for esophageal and gastric tumors are shown in this papers. In conclusion, complete resection that means histologically tumor negative of lateral and vertical margin of resected specimen is important to prevent recurrence of tumors after resection.

Digestive System Diseases↗

Prognostic factors in childhood acute lymphoblastic leukemia in Japan. Japan Association of Childhood Leukemia Study.

A retrospective analysis of children with acute lymphoblastic leukemia (ALL) was performed to evaluate the current status of diagnosis and treatment of ALL in Japanese children. Clinical records of 670 children with ALL were collected and analyzed; these children had been diagnosed between 1991 and 1995 at the 53 institutions in 4 areas participating in the Japan Association of Childhood Leukemia Study. It was found that T-cell ALL was significantly less frequent in Tokai and Hokkaido than in Kansai and Chu-Shikoku. The overall induction rate was 92.4%. The estimated 7-year overall survival rate and event-free survival (EFS) rate were 76.0% +/- 1.9% and 61.4% +/- 2.1%, respectively. EFS rates were significantly different among the geographic areas. In female patients with B-cell precursor (B-pre) ALL and white blood cell counts at diagnosis (WBCsdiag) below 50.0 x 10(9)/L, favorable outcomes were significant. Favorable outcomes were not significant in B-pre ALL patients with a WBCdiag above 50.0 x 10(9)/L or in T-cell ALL patients. The EFS rate for infants was significantly worse than that for patients over 1 year of age. In B-pre ALL, but not in T-cell ALL, it was found that the higher the WBCdiag, the worse the EFS rate. Multivariate analysis showed that the following factors were significantly unfavorable for EFS: the Philadelphia chromosome, an translocations associated with chromosome 11q23, an acute unclassified leukemia, mixed-lineage leukemia, a WBCdiag above 100.0 x 10(9)/L, and male gender. Hyperdiploidy (> 50 chromosomes) was significantly favorable for EFS. For further tailoring of treatment and to improve the outcome in childhood ALL, a prospective large-scale study should be undertaken in Japan.

Age Factors↗