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Biomedical subjects

M Ogata

Publications and source records attributed to M Ogata.

At least 127 records · Page 7Linked to original sources
PubMed1997

Effect of non-insulin dependent diabetes on cyclosporin A disposition in Goto-Kakizaki (GK) rats.

We previously reported that the pharmacokinetics of cyclosporin A (CyA), particularly absorption, were altered in diabetic rats treated with streptozotocin. In the present study, the effect of diabetes on pharmacokinetics of CyA after intravenous and oral administration of CyA using the blood and lymph and the gastrointestinal transit were examined in Goto-Kakizaki (GK) rats, a genetic model of non-obese non-insulin-dependent diabetes mellitus (NIDDM), and compared to non-diabetic Wistar rats. Although the systemic and lymphatic availability after intravenous administration of CyA to the GK rats was not significantly different from those of the control Wistar rats, those availability after oral administration of CyA to GK rats was markedly reduced in comparison. These results suggest that the pharmacokinetics of CyA, particularly absorption, was altered in GK rats. Studies on the gastrointestinal transit in GK rats showed that the gastric emptying rate was lower than that of Wistar rats, suggesting that a change in gastrointestinal transit in GK rats may influence the absorption of CyA. The gastric emptying rate in GK rats altered not only the systemic availability but also the lymphatic availability, suggesting that the altered systemic availability may cause adverse effects and that altered lymphatic availability may influence the immunosuppressive effects.

Administration, Oral↗
PubMed1997

Determination of the functional domain of a mouse autonomous replicating sequence.

We previously isolated from mouse cells an autonomous replicating sequence (ARS) ARS65 (Ariga, Itani and Iguchi-Ariga, Mol. Cell. Biol. 7, 1-6, 1987). Here we report the nucleotide sequence of ARS65. The sequence from BgIII to EcoRI sites cloned as ARS was 2658 bp long. There exist three interesting domains: a TA repeat, a myc like box (essential sequence for c-myc ARS), and a T rich region. Cloned DNAs containing various segments of pARS65 were transfected to rat 3Y1 cells together with the hygromycinB resistance expression vector, and hygromycinB resistant clones were isolated. Established cell lines transfected with plasmids carrying either a myc-like box or a T rich region harbored the replicated plasmids, indicating that these two elements are necessary for the ARS function of pARS65.

Animals↗
PubMed1997

Evaluation of exposure to mixed solvents by analysis of urinary metabolites and solvents: content ranges.

To evaluate worker's exposure to mixed solvents, equations for the calculation of the biological hazard index, which is defined as biological levels tolerable for exposure to mixture, were developed. When biological levels of exposure indicators were not affected by coexposure, rules similar to those for airborne monitoring could be applied. Namely, when the components had additive effects, the biological hazard index was calculated from the concentration of urinary metabolites or parent solvents, by an equation which was essentially similar to the equation for the calculation of the hazard index. In the present study, the confidence limits of the biological hazard index and predictive limits for individual specimens were calculated. These equations could be used under the condition that the uptake, metabolism and elimination of solvents were practically unaffected by coexposure. When urinary metabolites or solvents of some components of a mixed solvent alone were determined and those of the remaining components were not determined, the concentration of urinary metabolites or solvents of remaining components were estimated from the airborne concentration of the other components.

Environmental Monitoring↗
PubMed1997

Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects with early- and late-onset NIDDM.

Recent studies have shown that mutations in the hepatocyte nuclear factor (HNF)-1alpha gene are the cause of maturity-onset diabetes of the young type 3 (MODY3). We have screened 193 unrelated Japanese subjects with NIDDM for mutations in this gene: 83 with early-onset NIDDM (diagnosis at <30 years of age) and 110 with late-onset NIDDM (diagnosis > or = 30 years of age). All of the members of the latter group also had at least one sibling with NIDDM. The 10 exons, flanking introns, and promoter region were amplified using polymerase chain reaction and were sequenced directly. Mutations were found in 7 of the 83 (8%) unrelated subjects with early-onset NIDDM. The mutations were each different and included four missense mutations (L12H, R131Q, K205Q, and R263C) and three frameshift mutations (P379fsdelCT, T392fsdelA, and L584S585fsinsTC). One of the 110 subjects with late-onset NIDDM was heterozygous for the missense mutation G191D. This subject, who was diagnosed with NIDDM at 64 years of age, also had a brother with NIDDM (age at diagnosis, 54 years) who carried the same mutation, suggesting that this mutation contributed to the development of NIDDM in these two siblings. None of these mutations were present in 50 unrelated subjects with normal glucose tolerance (100 normal chromosomes). Mutations in the HNF-1alpha gene occur in Japanese subjects with NIDDM and appear to be an important cause of early-onset NIDDM in this population. In addition, they are present in about 1% of subjects with late-onset NIDDM.

Age Factors↗
PubMed1997

Organization and partial sequence of the hepatocyte nuclear factor-4 alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY.

Hepatocyte nuclear factor-4 alpha (HNF-4 alpha) is a member of the nuclear receptor superfamily, a class of ligand-activated transcription factors. A nonsense mutation in the gene encoding this transcription factor was recently found in a white family with one form of maturity-onset diabetes of the young, MODY1. Here, we report the exon-intron organization and partial sequence of the human HNF-4 alpha gene. In addition, we have screened the 12 exons, flanking introns and minimal promoter region for mutations in a group of 57 unrelated Japanese subjects with early-onset NIDDM/MODY of unknown cause. Eight nucleotide substitutions were noted, of which one resulted in the mutation of a conserved arginine residue, Arg127 (CGG)-->Trp (TGG) (designated R127W), located in the T-box, a region of the protein that may play a role in HNF-4 alpha dimerization and DNA binding. This mutation was not found in 214 unrelated nondiabetic subjects (53 Japanese, 53 Chinese, 51 white, and 57 African-American). The R127W mutation was only present in three of five diabetic members in this family, indicating that it is not the only cause of diabetes in this family. The remaining seven nucleotide substitutions were located in the proximal promoter region and introns. They are not predicted to affect the transcription of the gene or mRNA processing and represent polymorphisms and rare variants. The results suggest that mutations in the HNF-4 alpha gene may cause early-onset NIDDM/MODY in Japanese but they are less common than mutations in the HNF-1 alpha/MODY3 gene. The information on the sequence of the HNF-4 alpha gene and its promoter region will facilitate the search for mutations in other populations and studies of the role of this gene in determining normal pancreatic beta-cell function.

Alternative Splicing↗
PubMed1997

Size-selective sampling of oil mist in air and subjective symptoms among machine workers.

Oil mists at an automobile factory were measured size-selectively. Furthermore, subjective symptoms were surveyed through the distribution of a questionnaire. The measured levels of respirable-size, 2-10 micrometer oil mists at 3 selected workshops ranged 0.04-0.09 mg/m3 for the lower exposed group (17 men), 0.10-0.18 mg/m3 for the higher exposed group (16 men) to water-insoluble oil, and 0.08-0.29 mg/m3 for the higher exposed group (19 men) to water-soluble oil. The higher the level of exposure to respirable-size particulates, the more workers complained of dissatisfaction with air quality. As to the subjective symptoms, the "yes" rate for "irritated nose" and "sneezing" showed significant differences among the unexposed, lower exposed, and higher exposed groups. Workers using water-soluble oil complained of "uncomfortable smell" more than those who used water-insoluble oil. The results of this study suggested that it is necessary to measure the levels of oil mists size-selectively.

Air Pollutants, Occupational↗
PubMed1997

[Diffuse alveolar hemorrhage associated with idiopathic interstitial pneumonia syndrome after allogeneic bone marrow transplantation].

A 24-year-old male with myelodysplastic syndrome (refractory anemia) was treated with allogeneic bone marrow transplantation (BMT) from HLA-identical brother on September 9, 1994, after conditioning with busulfan and cyclophosphamide. From early in April 1995, the patient complained of cough and fever. Chest X-ray showed interstitial infiltrates involving hilar and lower lung fields. Although pulmonary infiltrates were resolved with methylprednisolone pulse therapy, on May 19, the patient rapidly deteriorated with dyspnea. Diffuse alveolar infiltrates appeared on chest X-ray and he died of respiratory failure. At autopsy, diffuse alveolar hemorrhage accompanied with thickening of the alveolar walls and interstitial infiltration of lymphocytes was demonstrated. There was no evidence of bleeding in other organs. This is a rare case of diffuse alveolar hemorrhage in the late stage of allogeneic BMT. This report should lead to an evaluation of this disease by the collection of similar cases.

Adult↗
PubMed1996

Identification of a novel transmembrane semaphorin expressed on lymphocytes.

Semaphorin (also known as collapsin) members are thought to be involved in axon guidance during neural network formation. Here, we report the isolation of a novel member, mouse semaphorin G (M-sema G), which encodes a semaphorin domain followed by a single putative immunoglobulin-like domain, a transmembrane domain, and a cytoplasmic domain. M-sema G is most closely related to M-sema F, which we previously reported, and semB and semC. These four members appear to constitute a transmembrane type subfamily in mouse semaphorins. In contrast to the predominant expression of M-sema F mRNAs in the nervous tissues, M-sema G mRNAs are strongly expressed in lymphoid tissues, especially in the thymus, as well as in the nervous tissues. The mRNAs are also detected in various cell lines from hematopoietic cells. By generating specific antibodies, we confirmed the strong expression of M-Sema G proteins on the surface of lymphocytes. These results provide the first evidence that semaphorin is expressed on lymphocytes and suggest that semaphorins may play an important role in the immune system, as well as in the nervous system.

Amino Acid Sequence↗
PubMed1996

Absence of the Gly40-ser mutation in the glucagon receptor gene in Japanese subjects with NIDDM.

Recent studies have shown both association and linkage between a Gly40-Ser mutation in the glucagon receptor gene and NIDDM in French patients with familial NIDDM. This mutation was present in heterozygous form in 4.6% of diabetic probands but only 1% of the French population, suggesting that it was an important risk factor in the development of NIDDM. A total of 348 unrelated Japanese subjects (220 with NIDDM, 53 with impaired glucose tolerance (IGT) and 75 normal subjects) were screened for the presence of the Gly40-Ser mutation. Seventy-two percent of the NIDDM patients and 52% of IGT subjects had a positive family history of NIDDM. The Gly40-Ser mutation, which could be readily detected in a positive control subject, was not found in any of the 348 Japanese subjects studied. Thus, the Gly40-Ser mutation does not play an important role in the pathogenesis of NIDDM in Japanese patients.

Adult↗
PubMed1996

Catalytic properties of adenylylsulfate reductase from Desulfovibrio vulgaris Miyazaki.

Adenylylsulfate reductase (EC 1.8.99.2) isolated from Desulfovibrio vulgaris Miyazaki catalyzes electron transfer from dihydroflavin coenzyme (FADH2, FMNH2, or dihydroriboflavin) to adenylyl sulfate (APS), and catalyzes flavin-mediated oxidation of ferrocytochrome c3 with APS. The reaction with FAD as an electron mediator was markedly stimulated in the presence of menadione. Km of the enzyme was about 0.015 mM for riboflavin and FAD in the presence of menadione. Free flavin coenzyme was found to be the normal cellular constituent. These observations suggested that free flavin coenzyme may be a physiological electron carrier for APS reductase, and the enzyme may be called AMP, sulfite:flavin oxidoreductase. Km (APS) of this enzyme is lower than 1 microM. The enzyme is not inhibited by ATP and GTP, but was inhibited by AMP and sulfite. Its extremely low Km (APS) enables this enzyme to reduce any traces of cytosolic APS which is present only at micromolar concentration, and inhibition by sulfite makes this organism utilize an energetically favorable electron acceptor, sulfite, preferentially over APS which is produced from sulfate at the cost of ATP.

Adenosine Triphosphate↗
PubMed1996

A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2.

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.

Chromosomes, Human, Pair 2↗
PubMed1996

Pseudomonas exotoxin exhibits increased sensitivity to furin when sequences at the cleavage site are mutated to resemble the arginine-rich loop of diphtheria toxin.

To be toxic for mammalian cells, Pseudomonas exotoxin (PE) requires proteolytic cleavage between Arg-279 and Gly-280. Cleavage, which is mediated by the cellular protease furin, generates an active C-terminal fragment which translocates to the cytosol and inhibits protein synthesis. In vitro, furin-mediated cleavage is optimal at pH 5.5 with a relatively slow turnover rate. Within cells, only 5-10% of cell-associated PE is cleaved. To investigate the reasons for this inefficient cleavage, the amino acid composition near the cleavage site was altered to resemble more closely the arginine-rich sequence from the functionally similar region of diphtheria toxin (DT). Four PE-DT mutants were generated, whereby 1, 5, 6 or 8 amino acids at the PE-cleavage site were changed to amino acids found at the DT-cleavage site. Mutant proteins were expressed in Escherichia coli, purified and then analysed for their susceptibility to cleavage by furin and trypsin, susceptibility to cell-mediated cleavage, and cytotoxic activity relative to wild-type PE. At pH 5.5, the rate of both furin-mediated cleavage and trypsin-mediated cleavage increased dramatically when amino acids in PE were altered to resemble the DT sequence. This increase did not alter the pH optimum for furin-mediated cleavage of PE toxins, which remained at pH 5.0-5.5. When radioactive versions of selected PE-DT proteins were added to intact cells, an increase in the percentage of molecules that were cleaved relative to wild-type PE was also seen. However, changes that favoured increased proteolysis apparently interfered with other important toxin functions because none of the PE-DT proteins exhibited enhanced toxicity for cells when compared with the activity of wild-type PE.

Animals↗
PubMed1996

Prospective evaluation of abdominal sonography for the diagnosis of bowel obstruction.

OBJECTIVE: The authors determined the utility of sonography compared with plain x-rays in the diagnosis of bowel obstruction. In a contemporaneous group of patients, they compared the cost of operative versus nonoperative management of small bowel obstruction. SUMMARY BACKGROUND DATA: Nonoperative treatment of simple bowel obstruction usually succeeds. However, because of the difficulty in assured diagnosis and the possibility of strangulation or other complication, exploration of suspected bowel obstruction is recommended. Most of these explorations could be avoided if diagnostic accuracy were better, yielding a desirable decrease in the overall cost of managing bowel obstruction. METHODS: Fifty patients whose clinical or plain x-ray findings suggested bowel obstruction underwent prospective evaluation by abdominal sonography and by flat and upright abdominal x-rays. Presence or absence of bowel obstruction was determined at laparotomy and by clinical evolution of the abdominal episode. Direct costs of care were determined from the hospital and physician bills of 54 patients treated contemporaneously with the sonography study. RESULTS: Sonography demonstrated bowel obstruction by showing fluid-filled dilated bowel loops proximal to collapsed bowel in 22 patients with one false-positive and three false-negative examinations. X-rays demonstrated bowel obstruction in 32 patients with nine false-positive and one false-negative examination. Cost data showed that operative treatment of simple bowel obstruction increased costs nearly eightfold. CONCLUSIONS: Sonography is as sensitive but more specific than plain x-rays in the diagnosis of bowel obstruction. Management based on sonographic findings has the potential to reduce costs of surgical care.

Adult↗
PubMed1996

Distribution of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin in regional brain areas of inbred strains of rats and mice with different alcohol preferences.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases, the former two of which are the initial and the rate-limiting enzymes in the biosynthesis of catecholamines and serotonin, respectively. The present study was conducted to determine the levels of 6R-BH4 in the inbred strains of rats BN and F344, and the inbred strains of mice C57BL/6J, C3H/HeJ and DBA/2J, with different genetically determined alcohol preferences. Previous studies have shown that BN and F344 rats exhibit a high and low alcohol preference, respectively; that C57BL/6J and DBA/2J mice show a high and low alcohol preference, respectively, and that C3H/HeJ mice exhibit a moderate alcohol preference. The levels of 6R-BH4 were measured in five regional brain areas of rats and in two regional brain areas of mice. There was about a 3-fold difference in 6R-BH4 levels across the rat brain areas assayed, ranging from a low level in the frontal cortex to a high level in the striatum and midbrain. Midbrain 6R-BH4 levels in F344 rats were higher than those of BN rats (p < 0.05). On the other hand, striatal 6R-BH4 levels in DBA/2J mice were higher than those of the other two strains of mice (p < 0.05). These results indicate that 6R-BH4 is distributed throughout the nigro- and mesostriatal dopaminergic nervous systems, and that brain 6R-BH4 levels may be involved in the genetic differences in alcohol-drinking behavior in animal models.

Alcohol Drinking↗
PubMed1996

Effect of substrate on indirect immunofluorescence test for canine pemphigus foliaceus.

The effect of substrate on indirect immunofluorescence (IIF) tests for the detection of circulating autoantibodies was studied by examining sera from 14 canine pemphigus foliaceus patients, six sera with non-pemphigus dermatoses and ten normal dog sera against five different substrates from three species. These substrates included bovine esophagus, bovine nose, bovine tongue, monkey esophagus, and canine nose skin. Nine out of 14 (64.3%) sera from patients with canine pemphigus foliaceus showed intercellular space staining by indirect immunofluorescence using bovine esophagus as substrate. However, sera from nonpemphigus dermatoses and normal dog did not react with bovine esophagus. In other substrates, only bovine tongue showed 1/8 (12.5%) positive reaction at the intercellular space by sera from canine pemphigus foliaceus. Dog nose skin showed the intercellular space staining against ten of ten (100%) normal dog serum. Monkey esophagus showed the fluorescent deposit at the intercellular space in four of nine (44.4%) of pemphigus foliacues dog sera, however, four of ten (40%) of normal dog sera revealed nonspecificity intercellular staining. These results indicate that the sensitivity and the specifity of IIF test in canine pemphigus foliaceus depend on the substrate. The best substrate for detecting circulating autoantibody in canine pemphigus foliaceus patients among five different substrates was bovine esophagus because of its sensitivity and high specificity. The diagnosis of canine pemphigus foliaceus should be made on the basis of a combination of clinical signs, histopathology, direct immunofluorescence, and the detection of circulating autoantibody.

Animals↗
PubMed1996

Effect of streptozotocin-induced diabetes on cyclosporin A disposition in rats.

We studied the effect of diabetes on the pharmacokinetics of cyclosporin A (CyA) after intravenous and oral administration of CyA using the plasma and lymph of streptozotocin (STZ)-induced diabetic rat. There were no significant differences in the systemic and lymphatic availabilities after intravenous administration of CyA in diabetic rats compared with those of the controls. On the other hand, systemic and lymphatic availabilities after oral administration of CyA were significantly different in diabetic rats compared to those in the controls. These results suggest that the pharmacokinetics of CyA, particularly absorption, were altered in diabetic rats. Gastrointestinal transit in diabetic rats was also studied. The gastric emptying rate in diabetic rats was enhanced compared with that of the controls, but small intestinal transit was reduced in diabetic rats, suggesting that a change in gastrointestinal transit in diabetic rats may influence the absorption of CyA. The increased absorption of CyA from the digestive tract of diabetic rats altered not only the systemic availability but also the lymphatic availability, suggesting that altered systemic availability may cause adverse effects and that altered lymphatic availability may influence the immunosuppressive effects.

Administration, Oral↗
PubMed1996

Lectin affinity electrophoresis of alpha-fetoprotein detected by immunoenzymatic and chemiluminescent amplification followed by direct scanning.

Microdetermination of alpha-fetoprotein (AFP) glycoforms by lectin affinity electrophoresis followed by chemiluminescence reaction using horseradish peroxidase (POD) or alkaline phosphatase (ALP) in antibody-affinity blotting was developed. The intensity of chemiluminescence obtained by ALP was greater than that by POD; however, the coefficient of variation with POD was less than that with ALP. The optimized sensitivity of the chemiluminescence method with POD was two times that of the most sensitive colorimetric method currently available in terms of the chemiluminescence intensity per unit AFP concentration. The lower detection limit by the chemiluminescence method with POD (0.5 ng/ml) was much lower than that by the colorimetric method (3 ng/ml). Both methods gave identical percentages of lentil lectin- and erythroagglutinating phytohemagglutinin-reactive minor bands using a serum with 52 ng/ml AFP. This result indicates that microdetermination of AFP glycoforms by chemiluminescence after lectin-affinity electrophoresis was more sensitive than currently available methods and that it is potentially useful for clinical application.

Electrophoresis↗