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Biomedical subjects

T Orii

Publications and source records attributed to T Orii.

At least 289 records · Page 16Linked to original sources
PubMed1990

Molecular basis of mucopolysaccharidosis type VII: replacement of Ala619 in beta-glucuronidase with Val.

We have identified a mutation causing beta-glucuronidase (beta Gl) deficiency in a 6-year-old girl with mucopolysaccharidosis type VII. Enzyme assay of lysates of a girl's lymphocytes or cultured fibroblasts showed little residual activity and a normal beta Gl-specific mRNA level, as revealed by Northern-blot analysis. Sequencing of the full-length mutated cDNA revealed a C----T transition, an event causing a single Ala619----Val change (we designated this variant beta GGifu). This change is detected by loss of the cleavage site for the enzyme Fnu4HI in the mutated cDNA. On the basis of the loss of Fnu4HI restriction site, the patient was shown to be a homozygote with the beta GGifu mutation and her parents and brother were heterozygotes. This mutation disrupts a functional domain consisting of a region of sequence highly conserved among human, rat and bacterial beta Gls, and it reduces the enzyme activity, as tested by transfection of COS cells with expression vectors harboring the mutated cDNA.

Alanine↗
PubMed1990

Non-existence of a tight association between a 444leucine to proline mutation and phenotypes of Gaucher disease: high frequency of a NciI polymorphism in the non-neuronopathic form.

A 444leucine to proline mutation detected by a NciI polymorphism in the human glucocerebrosidase gene was studied to investigate the correlation of the three clinical phenotypes of Gaucher disease with this mutation in 11 Japanese patients with Gaucher disease (type I, 8 patients; type II, 1 patient; type III, 2 patients) and to determine the feasibility of the use of genomic probe DNA for carrier detection and prenatal diagnosis in 8 Japanese families with Gaucher disease and agreeable to family study (type I, 6 families; type III, 2 families). The homoallelic 444leucine to proline mutation was found only in patients with type I disease. Of the 8 type I patients, 5 had the homoallelic mutation and 2 had one mutant allele. One patient with type II disease did not have this mutant allele. Of the 2 type III patients, one had a single mutant allele whereas the other exhibited no mutation of this kind. These results suggest that the 444leucine to proline mutation is very common in the type I (non-neuronopathic form) disease and is not tightly associated only with neuronopathic types of Gaucher disease in Japanese patients. These findings seem to conflict with others showing that this mutation is partially responsible for the occurrence of neuronopathic Gaucher disease. Thus, the NciI polymorphism will not be useful for the diagnosis of subtypes of Gaucher disease. Carrier detection was feasible in three families with type I disease of the 8 families analyzed by the NciI polymorphism.

Deoxyribonucleases, Type II Site-Specific↗
PubMed1990

Appearance of bisected N-acetylglucosamine residue of biantennary sugar chains and decrease of high molecular weight oligosaccharides of human lymphocytic cell membranes during differentiation.

Asparagine-linked sugar chains obtained from the plasma membranes of human acute lymphocytic leukemic cells, human B cells, Epstein-Barr virus (EBV)-infected B cell lines, and T cells were quantitatively liberated from the polypeptide portions by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. The radioactive oligosaccharides were fractionated by high-voltage paper electrophoresis. Their structures were studied by column chromatography and sequential exoglycosidase digestion. The neutral oligosaccharides were of a high mannose type. The acidic oligosaccharides were bi-, tri-, and tetraantennary complex-type sugar chains with Man alpha----(Man alpha----) Man beta----GlcNAc beta----(+/- Fuc alpha----)GlcNAc as their cores. A comparative study of the oligosaccharides of these cells revealed that the biantennary complex-type sugar chain with bisecting N-acetylglucosamine residues was found only in B cells, B lymphoblasts, and B cell lines. High molecular weight oligosaccharides decreased during the differentiation stage of lymphocytes.

Acetylglucosamine↗
PubMed1990

Lymphocyte responses to food antigens in patients with atopic dermatitis who are sensitive to foods.

The proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin or bovine serum albumin in children with atopic dermatitis (AD) who are sensitive to hen's egg or cow's milk were significantly higher than responses of PBMCs of healthy children and hen's egg- or cow's milk-sensitive children with immediate symptoms. However, the percentages of positive RAST for hen's egg or cow's milk in the patients with AD were lower than percentages in the patients with immediate symptoms. In the patients with AD, there were no significant correlations between the proliferative responses of PBMCs and the RAST values. There were no significant differences of RAST scores among groups of patients having different degrees of severity of AD. The proliferative responses of PBMCs to ovalbumin or bovine serum albumin in patients with severe AD or moderate AD who were sensitive to hen's egg or cow's milk tended to be higher than responses of patients with mild AD, respectively, but there were no significant differences in those results. Taken together, the combination of RAST and the detection of proliferative responses of PBMCs to each food antigen is very useful in the diagnosis of hypersensitivity in children with AD who are sensitive to food allergens.

Animals↗
PubMed1990

Expression of the alpha-chain gene in heterogeneous IgA immunodeficiency.

Five heterogeneous IgA-immunodeficient patients were analysed for expression of the alpha-chain gene. The number of surface IgA-bearing B cells was low in four patients. Southern blot analysis indicated no deletion of immunoglobulin structural genes coding for C alpha or alpha switching-region genes. The number of surface IgM and IgA double-bearing B cells increased in some patients. Addition of recombinant interleukin 4 (rIL-4), rIL-5, and rIL-6 to the normal B cells enhanced IgA production. However, B cells of the patients showed no or one-third lower IgA production in response to these lymphokines, even though there was proliferation. rIL-4, rIL-5, and rIL-6 induced low or no expression of alpha mRNA of the patients' B cells. These results suggested that the patients lacked B cells able to produce transcripts for the IgA heavy chain, and that some patients' B cells might be defective at the switch-recombination process from mu to alpha or from mu and alpha to alpha.

Adolescent↗
PubMed1990

Diabetes mellitus in a young man with Bloom's syndrome.

Bloom's syndrome (BS) is a rare autosomal recessive genetic disorder in which diabetes mellitus unusually frequently develops as a complication. We report on a 21-year-old Japanese male patient with BS who exhibited impaired glucose tolerance (IGT) in the initial oral glucose tolerance test (OGTT) and had developed patterns of diabetes mellitus by the second OGTT at the 2-years-and-2-months follow-up. German and Passarge reported that the onset of diabetes in patients with BS was in late adolescence or early adulthood. Our results support the findings of German and Passarge. Therefore, when a person with BS reaches late adolescence or early adulthood, an OGTT is necessary to ascertain whether the patient has IGT or diabetes mellitus as a complication, regardless of whether or not diabetic signs such as glucosuria are present.

Adult↗
PubMed1990

Molecular cloning and sequence of the complementary DNA encoding human mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant enzymes in cultured fibroblasts from patients with 3-ketothiolase deficiency.

Complementary DNAs encoding the precursor of human hepatic mitochondrial acetoacetyl-CoA thiolase (T2) (EC 2.3.1.9) were cloned and sequenced. The cDNA inserts in these clones were 1,518 bases in length when overlapped, and encoded the 427-amino acid precursor of this enzyme (45,199 mol wt). This amino acid sequence included a 33-residue leader peptide moiety and a 394-amino acid subunit of the mature enzyme (41,385 mol wt). The T2 gene expression in fibroblasts from four patients with 3-ketothiolase deficiency was analyzed by Northern blotting. The T2 mRNA in all four cell lines had the same 1.7 kb as that of the control. However, the amounts of T2 mRNA differed: the content was reduced in two cell lines (cases 1 and 3), whereas it was within a normal range in others (cases 2 and 4). Pulse labeling followed by subcellular fractionation revealed that the T2 proteins in the fibroblasts from these patients are present in the mitochondria. These results suggest that different mechanisms are involved in the enzyme defects in the four patients.

Acetyl-CoA C-Acetyltransferase↗
PubMed1990

Nonspecific lipid transfer protein (sterol carrier protein-2) defective in patients with deficient peroxisomes.

The biosynthesis and intracellular localization of nonspecific lipid transfer protein (nsLTP) in control human subjects and in patients with peroxisome-deficient disorders were investigated. The molecular mass of human nsLTP was indistinguishable from that of rat nsLTP (13 kDa) by immunoblot analysis. Intracellular localization was identical with that of catalase, a marker enzyme of peroxisomal matrix, by a double immunofluorescence study. The nsLTP was deficient in liver tissues or fibroblasts from patients with peroxisome-deficient disorders such as Zellweger syndrome and neonatal adrenoleukodystrophy (ALD). Pulse-chase experiments showed that nsLTP was synthesized as a large precursor in both the control and Zellweger fibroblasts. However, the processing to the 13 kDa mature protein was disturbed and the degradation was rapid in Zellweger fibroblasts. After somatic cell fusion using Zellweger fibroblasts from different genetic groups, the processing was normalized. These results suggest that the biosynthesis and localization of human nsLTP are similar to those of rat nsLTP and that the defect of nsLTP in peroxisome-deficient disorders is a phenomenon secondary to an abnormal transport mechanism of peroxisomal proteins. The defect of nsLTP may play an important role in metabolic disturbances in bile acid synthesis and steroidogenesis in peroxisome-deficient disorders.

Biopsy↗
PubMed1990

Utilization of a computerized system at the pharmacy department of the University of Tokyo Hospital--impact of prescription order entry and computerized dispensing system.

(1) A medication order entry system, (2) a fully automatic tablet counting and packaging machine connected with a medication order entry system, and (3) a check system for one dose package developed and implemented in the University of Tokyo Hospital are described. The principal objectives of these systems are (1) to reduce medication errors and the clerical workload of staff, (2) to make more efficient use of staff, (3) to provide staff with sufficient drug information for patient drug therapy. We compared computerized systems (post-computerization) and traditional multi-dose dispensing systems (pre-computerization) by analyzing inquiry rate and dispensing time in the pharmacy for inpatients. Inquiry rate was 23.0% and 2.6% for pre-computerization and post-computerization, respectively. Total dispensing time per patient was 207 seconds and 147 seconds for pre-computerization and post-computerization, respectively. Implementation of the computerized systems helped significantly in decreasing inquiry rate and time needed to complete the dispensing process when compared with a traditional dispensing system. Implementation of the computerized systems was very useful for physicians, pharmacists, and nurses in conducting drug therapy.

Clinical Pharmacy Information Systems↗