Biomedical subjects

M Ogata

Publications and source records attributed to M Ogata.

At least 55 records · Page 3Linked to original sources

PubMed2000

Induction of aldose reductase in cultured human microvascular endothelial cells by advanced glycation end products.

Accelerated formation and accumulation of advanced glycation end products, as well as increased flux of glucose through polyol pathway, have been implicated in the pathogenesis of diabetic vascular complications. We investigated effects of advanced glycation end products on the levels of aldose reductase mRNA, protein, and activity in human microvascular endothelial cells. When endothelial cells were cultured with highly glycated bovine serum albumin, aldose reductase mRNA in endothelial cells demonstrated concentration-dependent elevation. The increase in aldose reductase mRNA was accompanied by elevated protein expression and enzyme activity. Significant increase in the enzyme expression was also observed when endothelial cells were cultured with serum obtained from diabetic patients with end-stage renal disease. Pretreatment of the endothelial cells with probucol or vitamin E prevented the advanced glycation end products-induced increases in aldose reductase mRNA and protein. Electrophoretic mobility shift assays using the nuclear extracts of the endothelial cells treated with advanced glycation end products showed enhancement of specific DNA binding activity for AP-1 consensus sequence. These results indicate that accelerated formation of advanced glycation end products in vivo may elicit activation of the polyol pathway, possibly via augmented oxidative stress, and amplify endothelial cell damage leading to diabetic microvascular dysfunction.

Aldehyde Reductase↗

PubMed2000

Temperature-sensitive sodium channelopathy with heat-induced myotonia and cold-induced paralysis.

The authors report a Japanese family with dominantly inherited heat-induced myotonia and cold-induced paralysis with hypokalemia. This phenotype is associated with a novel mutation in the voltage-dependent skeletal muscle sodium channel alpha subunit (SCN4A). This Pro1158Ser mutation is localized between the fourth and fifth transmembrane segments of domain III in SCN4A and may give rise to a new function; that is, thermosensitive permeability changes of the sodium channel.

Adult↗

PubMed2000

Local density of states around a magnetic impurity in high- T(c) superconductors based on the t-J model

The local density of states (LDOS) around a magnetic impurity in high- T(c) superconductors is studied using the two-dimensional t-J model with a realistic band structure. The order parameters are determined in a self-consistent way within the Gutzwiller approximation and the Bogoliubov-de Gennes theory. In sharp contrast with the nonmagnetic impurity case, the LDOS near the magnetic impurity shows two resonance peaks reflecting the presence of spin-dependent resonance states. It is also shown that these resonance states are approximately localized around the impurity. The present results have an immediate connection with the scanning tunneling spectroscopy observation of Bi2Sr2Ca(Cu1-xNi[Zn](x))(2)O(8+delta).

Journal Article↗

PubMed2000

Development of dendritic cells in vitro from murine fetal liver-derived lineage phenotype-negative c-kit(+) hematopoietic progenitor cells.

We describe here that lineage phenotype- negative (Lin)(-)c-kit(+) hematopoietic progenitor cells (HPCs) from day 13 postcoitus (dpc) murine fetal liver (FL) can generate dendritic cell (DC) precursors when cultured in vitro in the presence of PA6 stromal cells plus granulocyte/macrophage colony-stimulating factor (GM-CSF) + stem cell factor (SCF) + Flt3 ligand (Flt3L) for 12 to 14 days, and develop into mature DCs when stimulated with GM-CSF plus mouse tumor necrosis factor alpha (mTNFalpha) for an additional 3 to 5 days. A transwell culture system showed that the generation of DC precursors depended on the support of PA6 cell-secreted soluble factor(s). The mature DCs derived from 13 dpc FL Lin(-)c-kit(+) HPCs showed characteristic morphology and function of DCs and expressed high levels of Ia, CD86, and CD40 molecules, low levels of DEC205, E-cadherin, and F4/80 molecules, but barely detectable CD11c antigen. Once FL-derived HPCs were cultured without GM-CSF, NK1.1(+) cells developed in the presence of PA6 cells + SCF + Flt3L. These NK1.1(+) cells could develop into DC precursors at an earlier stage of differentiation by reculturing with PA6 cells + SCF + Flt3L + GM-CSF, but they would be irreversibly committed to NK cell precursors without GM-CSF after 3 days, suggesting that GM-CSF plays a critical role in controlling the transition of DC and NK cell precursors from 13 dpc FL-derived Lin(-)c-kit(+) HPCs. This study represents the first success in generating mature DCs in vitro from murine FL HPCs. (Blood. 2000;95:138-146)

Animals↗

PubMed2000

Molecular phylogenetic relationships of pond frogs distributed in the Palearctic region inferred from DNA sequences of mitochondrial 12S ribosomal RNA and cytochrome b genes.

The evolutionary relationships of pond frogs distributed in the Far East and Europe were investigated by analyses of nucleotide sequences of mitochondrial 12S ribosomal RNA (12S rRNA) and cytochrome b (cyt b) genes. The nucleotide sequences of a 412-bp segment of the 12S rRNA gene and a 534-bp segment of the cyt b gene were determined by the PCR-direct sequencing method using 19 frogs belonging to six species and one subspecies distributed in the Palearctic region. Phylogenetic trees were constructed by the neighbor-joining and maximum-likelihood methods using Rana catesbeiana or Xenopus laevis as an outgroup. The 412-bp segment of the 12S rRNA gene contained 65 variable sites including gap sites, and the 534-bp segment of the cyt b gene contained 160 variable sites. The nucleotide sequence divergences of the 12S rRNA gene were 0.25-4.83% within the Far Eastern frogs, 0.25-6.22% within the European frogs, and 8.74-11.24% between the Far Eastern and the European frogs, whereas those of the cyt b gene were 3.64-14.73% within the Far Eastern frogs, 0.38-14.42% within the European frogs, and 16.53-23.58% between the Far Eastern and the European frogs. Although most nucleotide substitutions were at the third codon position of the cyt b gene and were silent mutations, 4 amino acid replacements occurred within the Far Eastern frogs, 4 within the European frogs, and 11 between the Far Eastern and the European frogs. The phylogenetic trees constructed from the nucleotide sequence divergences showed slightly different topologies for the 12S rRNA and cyt b genes. R. esculenta from Ukraine was closely related to R. lessonae from Luxembourg in both the 12S rRNA and the cyt b gene sequences.

Animals↗

PubMed2000

No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4gamma gene (HNF4G) in Japanese patients with MODY.

AIMS/HYPOTHESIS: Mutations in the transcription factor hepatocyte nuclear factor (HNF)-4alpha are the cause of one form of maturity-onset diabetes of the young, MODY1. The HNF-4gamma is structurally related to HNF-4alpha and is expressed together with HNF-4alpha in pancreatic islets. We therefore tested the hypothesis that genetic variation in the HNF-4gamma gene (HNF4G) is associated with MODY in Japanese subjects. METHODS: We screened the protein coding region of HNF4G (exons 3-11) for mutations in 57 unrelated Japanese subjects with MODY by amplifying each exon and adjacent intron region using the polymerase chain reaction (PCR) and specific primers and then directly sequencing the PCR products. The frequency of each variant was compared between patients with MODY and a group of non-diabetic subjects. RESULTS: We found ten sequence variants, two of these were located in exons: exon 6, a silent substitution in codon 144, c.432A/G and exon 7, a G-to-A substitution in codon 190 (c.570G/A) resulting in a conservative Met-to-Ile substitution (M/I190) in the putative ligand-binding region of HNF-4gamma protein. The remaining eight variants were located in introns. There was no significant difference in the frequency of these polymorphisms between subjects with MODY and non-diabetic control subjects. CONCLUSION/INTERPRETATION: Genetic variation in the coding region of HNF4G is unlikely to be a major cause of MODY in Japanese people.

Amino Acid Sequence↗

PubMed2000

Decreased substance P concentrations in tears from patients with corneal hypesthesia.

PURPOSE: To determine whether substance P concentrations in tears reflect corneal hypesthesia. METHODS: Sixteen patients with unilateral corneal hypesthesia participated in this study. Unstimulated tears were collected from each eye of all subjects. Substance P concentrations in tears were measured by an enzyme immunoassay system. RESULTS: Substance P concentrations in tears from the affected eye were lower than those in tears from the unaffected eye in all subjects. The mean concentration of substance P in tears from affected eyes was 197.7 +/- 69.5 pg/mL, markedly lower than those from unaffected eyes (333.2 +/- 74.6 pg/mL). CONCLUSION: Substance P concentrations in tears, which are thought to reflect the neuropeptides levels in ocular tissues, can be used as an indicator of corneal denervation.

Adult↗

PubMed2000

Effect of region and dentin perfusion on bond strengths of resin-modified glass ionomer cements.

OBJECTIVES: The purpose of this study was to evaluate the hypothesis that regional differences and pulpal pressure would significantly affect bond strengths of resin-modified glass ionomer cements to dentin. METHODS: Twenty-six extracted caries-free human third molars were ground to expose middle dentin and were randomly divided into two groups for bonding: no pulpal pressure and pulpal pressure of 15cm H(2)O. Fuji II LC, Vitremer, or Photac-Fil Quick were applied to the previously pre-treated surfaces and light-cured as recommended by the manufacturers. After immersion in water at 37 degrees C for 24h, the teeth were sectioned to 0.7mm thick slabs, divided into pulp horn, center, and peripheral regions according to visual criteria, and trimmed along the bonded interface for microtensile bond test to a cross-sectional area of 1mm(2). The slabs were subjected to tensile forces and the data analyzed using ANOVA and Fisher's PLSD at the 95% level of confidence. RESULTS: For Fuji II LC, bond strengths to the pulp horn regions were significantly lower than those to the other regions independent of pulpal pressure (p<0.05). On the other hand, regional bond strengths were not observed for Vitremer and Photac-fil Quick 0.05). CONCLUSIONS: Pulpal pressure had a stronger influence on bond strengths and failure modes of resin-modified glass ionomers than regional differences of the substrate.

Analysis of Variance↗

PubMed2000

Y-chromosomal STR haplotyping in a Japanese population.

The Y-specific STR systems including DYS19, DYS385, DYS389I, DYS390, DYS391 and DYS393, were investigated in 117 Japanese males. Analysis of the 6 loci permitted classification of the samples into 90 haplotypes, and the haplotypic diversity was estimated to be 0.984. Distribution of the haplotypes in the Japanese population studied was different from that in European populations.

Journal Article↗

PubMed2000

Allogeneic bone marrow transplantation-related transmission of human T lymphotropic virus type I (HTLV-I).

We report here the first case report of bone marrow transplantation (BMT)-related transmission of human T lymphotropic virus type-I (HTLV-I). Antibodies against HTLV-I-associated antigens (anti-HTLV-I) were detected in the serum from the BMT recipient 12 days post BMT. IgG against gag core proteins (anti-p19 and anti-p24) appeared earlier than IgM against gag and env proteins (anti-p19, anti-p24 and anti-gp46) during seroconversion. The data presented here differs from blood transfusion-related seroconversion. This phenomenon may be due to the engraftment of anti-HTLV-I producing cells from the donor.

Adolescent↗

PubMed2000

Discrimination of histamine H1 and muscarinic receptor-mediated signalling pathways by phorbol ester in human astrocytoma cells.

1. Histamine H1 receptor-mediated signalling was compared with muscarinic receptor-mediated signalling in 1321N1 human astrocytoma cells. 2. Short-term (2 min) treatment of cells with phorbol 12-myristate 13-acetate (PMA) resulted in a reduction of increases in intracellular Ca2+ ([Ca2+]i) induced by carbachol or histamine. 3. Carbachol-induced increases in [Ca2+]i were 10-fold more sensitive to PMA than the histamine-induced increases. 4. When cells were treated with PMA for 48 or 72 h (long-term treatment), protein kinase C (PKC) was down-regulated and PMA did not inhibit carbachol-induced increases in [Ca2+]i. 5. Histamine-induced increases in [Ca2+]i were significantly reduced by long-term treatment with PMA. 6. These findings suggest that the signalling pathways mediated by histamine H1 and muscarinic receptors can be distinguished by using PKC in 1321N1 human astrocytoma cells.

Astrocytoma↗

PubMed2000

Role of interleukin-10 on hyporesponsiveness of endotoxin during surgery.

OBJECTIVE: To examine whether surgical stress causes blood cells to lose their responsiveness to endotoxin during surgery. DESIGN: Prospective case series. SETTING: A university hospital. PATIENTS: Sixteen volunteers classified as American Society of Anesthesiologists physical status I-II who were scheduled for elective distal partial gastrectomy. INTERVENTIONS: We studied nine patients who underwent elective distal partial gastrectomy. Blood samples for tumor necrosis factor (TNF) and interleukin (IL)-10 assay were obtained before anesthesia, preincision, 2 hrs and 4 hrs postincision, postextubation, and 24 hrs postincision. The rest of each blood sample was diluted with 5 volumes of endotoxin-free saline, incubated for 4 hrs in the presence of lipopolysaccharide (LPS), centrifuged to remove cells, and assayed for TNF. In another seven patients, antihuman IL-10 antibody was added into the diluted whole blood sample before LPS stimulation. MEASUREMENTS AND MAIN RESULTS: TNF activity was not detected in the blood of any patient throughout the study. In contrast, plasma cortisol and IL-10 levels increased rapidly during surgery (p < .01, p < .05, respectively). LPS-induced TNF activity in whole blood decreased significantly during surgery (p < .01) and recovered to control levels by 24 hrs postincision. The peak suppression of LPS-induced TNF and the peak value of plasma IL-10 levels occurred postextubation. Treatment with anti-IL-10 antibody partially restored the ability of LPS to induce TNF activity postextubation (p < .05). CONCLUSIONS: Surgical trauma rapidly induces a transient hyporesponsiveness of blood cells to endotoxin. Plasma IL-10, which increases during surgery, participates in this hyporesponsiveness.

Adult↗

PubMed2000

ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function.

A disintegrin and metalloproteinase (ADAM) represents a protein family possessing both metalloproteinase and disintegrin domains. ADAMTS-1, an ADAM family member cloned from cachexigenic colon adenocarcinoma, is unusual in that it contains thrombospondin type I motifs and anchors to the extracellular matrix. To elucidate the biological role of ADAMTS-1, we developed ADAMTS-1-null mice by gene targeting. Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation. Impaired female fertilization accompanied by histological changes in the uterus and ovaries also resulted. Furthermore, ADAMTS-1(-/-) mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation. ADAMTS-1 thus appears necessary for normal growth, fertility, and organ morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.

ADAM Proteins↗

PubMed2000

Tumor necrosis factor microsatellite polymorphism influences the development of insulin dependency in adult-onset diabetes patients with the DRB11502-DQB10601 allele and anti-glutamic acid decarboxylase antibodies.

Recently, several studies have demonstrated that tumor necrosis factor microsatellite polymorphism (TNFalpha) contributes to the susceptibility of type 1 diabetes. This study investigates the influence of TNFalpha on the predisposition to insulin dependency in adult-onset diabetic patients with type 1 diabetes-protective human leukocyte antigen haplotypes. The TNFalpha of three groups of DRB1*1502DQB1*0601-positive diabetic patients who had initially been nonketotic and noninsulin dependent for more than 1 yr was analyzed. Group A included 11 antibodies to glutamic acid decarboxylase (GADab)-positive patients who developed insulin dependency within 4 yr of diabetes onset. Group B included 11 GADab-positive patients who remained noninsulin dependent for more than 12 yr. Group C included 12 GADab-negative type 2 diabetes, and a control group included 18 nondiabetic subjects. In the group C and control subjects, DRB1*1502-DQB1*0601 was strongly associated with the TNFalpha13 allele. DRB1*1502-DQB1*0601 was strongly associated with the TNFalpha12 allele among the group A patients, but not among the group B patients. Interestingly, sera from all patients with non-TNFalpha12 and non-TNFalpha13 in group B reacted with GAD65 protein by Western blot. These results suggest that TNFalpha is associated with a predisposition to progression to insulin dependency in GADab/DRB1*1502DQB1*0601-positive diabetic patients initially diagnosed with type 2 diabetes and that determination of these patients' TNFalpha genotype may allow for better prediction of their clinical course.

Adult↗

PubMed2000

Antioxidant activity of eugenol and related monomeric and dimeric compounds.

Since the inhibitory effect of eugenol (a), which was isolated as an antioxidative component from plant, Caryopylli flos, on lipid peroxidation was less than that of alpha-tocopherol, we synthesized the eugenol-related compounds dieugenol (b), tetrahydrodieugenol (c), and dihydroeugenol (d), to find new strong antioxidants and assessed them for their inhibitory effect on lipid peroxidation and scavenging ability for superoxide and hydroxyl radicals. The antioxidative activities were in the order: (b)>(c)>(d)>(a) for the thiobarbituric acid reactive substance (TBARS) formation. These results suggest that the dimerized compounds have higher antioxidant activities than that of the monomers. Electron spin resonance (ESR) spin trapping experiments revealed that eugenol and its dimer, having allyl groups in the structure, scavenged superoxide, and that only eugenol trapped hydroxyl radicals under the conditions used. These finding suggest that eugenol and dieugenol have a different mechanism of antioxidation, i.e. eugenol may inhibit lipid peroxidation at the level of initiation, however, the related dimeric compounds may inhibit lipid peroxidation at the level of propagation of free radical chain reaction like alpha-tocopherol.

Antioxidants↗

PubMed2000

Overexpression and localization of heat shock proteins mRNA in pancreatic carcinoma.

In the present study we examined the localization and overexpression of heat shock proteins (hsps), mainly hsp90, in pancreatic carcinoma tissue compared with control tissue (including chronic pancreatitis and normal pancreas tissue), with the aid of immunohistochemical staining, in situ hybridization and reverse transcriptase polymerase chain reaction. Hsp90 alpha mRNA was overexpressed more highly in pancreatic carcinoma than in the control tissue. The proliferating-cell-nuclear-antigen labeling index was also high in pancreatic carcinoma tissue compared with the other tissue. These findings suggest that the overexpression of hsp90 alpha mRNA in carcinomas may be correlated with cell proliferation. However, hsp90 beta was constitutively overexpressed almost equally in all groups of pancreatic tissue including pancreatic carcinoma, chronic pancreatitis and normal pancreas tissue. Immunohistochemical staining demonstrated a differentiation in the expression of hsp90 between histological types of pancreatic carcinoma. These findings suggest that hsp90 alpha is involved in carcinogenesis and that hsp90 beta is correlated to structural conformation. Hsp90 alpha and hsp90 beta seem to perform different functions in tissue containing malignant cells. P53, MDM2 and WAF1, that were cell-cycle-related oncogene product were more strongly expressed in the nuclei of the cancer cells of the cancer tissue. Especially, MDM2 was more strongly expressed in mucinous carcinoma and the mucin secreting tissues surrounding pancreatic carcinoma tissue. The expression of MDM2 protein might also be correlated to secretion systems during structural conformation and be correlated to hsp90 beta.

Adenocarcinoma↗

PubMed2000

beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the gene encoding the basic helix-loop-helix transcription factor neurogenic differentiation 4 (NEUROD4) in Japanese patients with MODY.

The basic helix-loop-helix (bHLH) family of transcription factors plays an important role in the normal development and function of the endocrine pancreas. Heterozygous mutations in the gene encoding one member of this family, NeuroD1/BETA2, are associated with a monogenic form of diabetes that resembles maturity-onset diabetes of the young (MODY) in many respects. This result prompted us to screen the genes encoding related bHLH transcription factors that are also expressed in pancreatic islets for diabetes-associated mutations. We have screened 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in the NeuroD4/Math-3/ATH-3 gene (NEUROD4). This analysis revealed seven frequent polymorphisms that were not associated with MODY, including five in the 5'-untranslated region (UTR) (-477G/A, -436delA, -324delT, -107insTTTT, and -104T/C [cDNA sequences]) and two in the 3'-UTR (1027C/T and 1076C/A). A missense mutation, K68T (203A/C), was found in a heterozygous state in one MODY subject and two nondiabetic subjects. The results of our study suggest that genetic variation in NEUROD4 is not a common cause of MODY in Japanese.

Basic Helix-Loop-Helix Proteins↗

PubMed2000

Beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the hepatocyte nuclear factor-3beta gene (HNF3B) in Japanese patients with maturity-onset diabetes of the young.

Mutations in the transcription factors hepatocyte nuclear factor (HNF)-4alpha and -1alpha, insulin promoter factor-1, and HNF-1beta are the causes of four forms of maturity-onset diabetes of the young (MODY1 and 3-5, respectively). The winged-helix transcription factor HNF-3beta has been implicated in the regulation of expression of each of these MODY genes, suggesting that mutations in the HNF-3beta gene (HNF3B) may also cause MODY. We have tested this hypothesis by screening a panel of 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in HNF3B. This analysis revealed four frequent polymorphisms that were not associated with MODY, including one in the promoter region (-213A/G), two silent mutations in the codons for Ala 97 (291C/T) and Gly 279 (837A/G), and one in the 3'-untranslated region (1424C/T). Two rare substitutions in the 5'-untranslated region, -156C/T and -67A/C, were found in a heterozygous state in two subjects, and two subjects were heterozygous for putative missense mutations, S109N (326G > A) and A328V (983C>T). The two missense mutations were not found in 106 normal chromosomes from nondiabetic subjects. It was not possible to test for co-segregation of these mutations with diabetes and thus, it is unclear whether or not these mutations can cause MODY. The results of our study suggest that mutations in HNF3B are not a common cause of MODY in Japanese subjects.

Adult↗