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Biomedical subjects

T Orii

Publications and source records attributed to T Orii.

At least 91 records · Page 5Linked to original sources
PubMed1997

A novel common missense mutation G301C in the N-acetylgalactosamine-6-sulfate sulfatase gene in mucopolysaccharidosis IVA.

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in N-acetylgalactosamine-6-sulfate sulfatase (GALNS). In previous studies, we have found two common mutations in Caucasians and Japanese, respectively. To characterize the mutational spectrum in various ethnic groups, mutations in the GALNS gene in Colombian MPS IVA patients were investigated, and genetic backgrounds were extensively analyzed to identify racial origin, based on mitochondrial DNA (mtDNA) lineages. Three novel missense mutations never identified previously in other populations and found in 16 out of 19 Colombian MPS IVA unrelated alleles account for 84.2% of the alleles in this study. The G301C and S162F mutations account for 68.4% and 10.5% of mutations, respectively, whereas the remaining F69V is limited to a single allele. The skewed prevalence of G301C in only Colombian patients and haplotype analysis by restriction fragment length polymorphisms in the GALNS gene suggest that G301C originated from a common ancestor. Investigation of the genetic background by means of mtDNA lineages indicate that all our patients are probably of native American descent.

Asian People↗
PubMed1997

Liver transplantation for severe hypoxemia caused by patent ductus venosus.

The authors describe the case of a 9-year-old girl who underwent liver transplantation because she suffered from severe hypoxemia caused by patent ductus venosus (PDV). Generally, severe hypoxemia (PaO2 < 50 mm Hg in room air or < 300 mm Hg in pure oxygen) is not an indication for liver transplantation because the hypoxemia may not be improved, and may lead to a fatal outcome. PDV, which is associated with mild liver dysfunction, is not an indication for liver transplantation by itself. But in our patient, most of the mesenteric venous flow directly entered the systemic circulation through the PDV just like the portosystemic shunt, and this caused the pulmonary arteriovenous shunt and hypoxemia. Thus, the authors operated on the patient in an attempt to restore her pulmonary function. Nitric oxide (10 to 20 ppm) was added to the inhaled gas to dilate the functional pulmonary capillaries and to deliver sufficient oxygen after the transplantation. Although the patient suffered various complications after the operation, the final results were excellent.

Angiography, Digital Subtraction↗
PubMed1997

Two different pathological conditions of photoparoxysmal responses in hereditary dentatorubral-pallidoluysian atrophy.

In order to reveal the pathophysiology of photoparoxysmal responses (PPRs) in photosensitive patients with hereditary dentatorubral-pallidoluysian atrophy (DRPLA) who had expansion of the CAG repeat in the DRPLA gene, we studied the characteristics of PPRs using optical filters with specific wavelength transmission. In two patients, the wavelength spectrum around 700 nm (670-720 nm) was apparently the only visible range essential for eliciting PPRs, and flash lights containing the essential wavelength elicited PPRs. In another patient, PPRs were elicited by flash lights above certain quantity of light and independent of the wavelength composition of the lights. These data suggest that two different pathological conditions contribute to PPRs in DRPLA patients; one condition depends on the essential wavelength spectrum around 700 nm, and the other not on the wavelength, but on the quantity of light. The condition contributing to PPRs in all three patients was not determined directly by the level of the CAG repeat expansion in the DRPLA gene.

Adult↗
PubMed1997

Pulmonary hemosiderosis with hypersensitivity to buckwheat.

BACKGROUND: Adverse reactions after ingesting buckwheat are known to be IgE-mediated. Further, hypersensitivity reactions may be involved in some patients with pulmonary hemosiderosis related to cow milk sensitivity. We, however, encountered a patient with pulmonary hemosiderosis related to buckwheat protein without high levels of buckwheat-specific IgE antibodies. OBJECTIVE: The aim of this study was to investigate the mechanisms. METHODS: RAST for anti-buckwheat IgE, skin prick test, skin patch test, and proliferative responses of peripheral blood mononuclear cells to buckwheat were investigated in this patient. RESULTS: RAST values for buckwheat protein were negative, and skin prick test for buckwheat protein also gave negative results. On the other hand, skin patch testing for buckwheat protein elicited positive responses. Further, peripheral blood mononuclear cells of our patient responded to buckwheat protein. CONCLUSIONS: Our patient had pulmonary hemosiderosis related to non-immediate buckwheat protein hypersensitivity.

Cells, Cultured↗
PubMed1997

D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder.

Peroxisomal beta-oxidation proceeds from enoyl-CoA through D-3-hydroxyacyl-CoA to 3-ketoacyl-CoA by the D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxy-acyl-CoA dehydrogenase bifunctional protein (d-bifunctional protein), and the oxidation of bile-acid precursors also has been suggested as being catalyzed by the d-bifunctional protein. Because of the important roles of this protein, we reinvestigated two Japanese patients previously diagnosed as having enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (L-bifunctional protein) deficiency, in complementation studies. We found that both the protein and the enzyme activity of the d-bifunctional protein were hardly detectable in these patients but that the active L-bifunctional protein was present. The mRNA level in patient 1 was very low, and, for patient 2, mRNA was of a smaller size. Sequencing analysis of the cDNA revealed a 52-bp deletion in patient 1 and a 237-bp deletion in patient 2. This seems to be the first report of D-bifunctional protein deficiency. Patients previously diagnosed as cases of L-bifunctional protein deficiency probably should be reexamined for a possible d-bifunctional protein deficiency.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.

Mitochondrial trifunctional protein (TP), an enzyme of beta-oxidation, is a multienzyme complex composed of four molecules of the alpha-subunit (HADHA) containing the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase domains and four molecules of the beta-subunit (HADHB) containing the 3-ketoacyl-CoA thiolase domain. An inborn error of this enzyme complex can cause sudden infant death syndrome, acute hepatic encephalopathy or liver failure, skeletal myopathy, or hypertrophic cardiomyopathy. TP deficiency is classified into two different biochemical phenotypes: one represents the existence of both subunits and the lack of only the 3-hydroxyacyl-CoA dehydrogenase activity and the other represents the absence of both subunits and the lack of all three TP activities, although their clinical features are similar. We have identified two Japanese patients with this disorder. Three enzyme activities of TP were undetectable in fibroblasts from these two patients. We detected two mutations in the HADHB gene from two Japanese patients, an exonic single T insertion which created a new cryptic 5' splice site and a G1331A transition (R411 K). Patient 1 was a compound heterozygote, while patient 2 was a homozygote of a G1331A transition.

Animals↗
PubMed1997

Two novel missense mutations in the ATP-binding domain of the adrenoleukodystrophy gene: immunoblotting and immunocytological study of two patients.

Two novel missense mutations, 1939G to A (R518Q) and 2017A to G (Q544R) were identified in Japanese patients with adrenoleukodystrophy (ALD). They are located in exon 6, which encodes part of the putative adenosine triphosphate binding domain of ALD protein. The ALD protein carrying the R518Q mutation was undetectable in fibroblasts, by immunoblot and immunofluorescence analysis, while the Q544R mutation had no apparent effect on the stability and localization of the ALD protein, but is expected to affect its function.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1997

Epilepsy in peroxisomal diseases.

PURPOSE: To clarify the electroclinical manifestation of epileptic seizures and the evolution of epilepsy in patients with peroxisomal diseases. METHODS: Retrospective review of the medical records and EEGs of 14 patients with peroxisomal diseases: seven with Zellweger syndrome (ZS), two with neonatal adrenoleukodystrophy (NALD), two with acyl-CoA oxidase deficiency (AOXD), two with bifunctional enzyme deficiency (BFED), and one with rhizomelic chondrodysplasia punctata (RCDP). The diagnoses were made by biochemical analysis and pathological examinations in our laboratory. RESULTS: Patients manifested serious neurologic deficits in the neonatal period or in early or late infancy. Patients with ZS or AOXD had partial motor seizures originating in the arms or legs or corners of the mouth. Their seizures did not culminate in generalized tonic-clonic seizures and were easily controlled by antiepileptic drugs (AEDs). Interictal EEGs of the patients with ZS showed infrequent bilateral independent multifocal spikes, predominantly in the frontal motor cortex and its surrounding regions. The EEGs of patients with AOXD showed interictal fast theta activity, predominantly in the frontocentral regions. Patients with BFED also had partial motor seizures in early infancy, but the seizures were intractable, evolving in one case to myoclonic seizures. Interictal EEGs of patients with BFED showed bilateral independent multifocal spikes that evolved to bilateral diffuse high-voltage slow waves in one case and to a hypsarythmic pattern in another case as the disease progressed. Patients with NALD had intractable tonic seizures or epileptic spasms. Interictal EEGs showed high-voltage slow waves and bilateral independent multifocal spikes, evolving in one patient to a flat pattern. The patient with RCDP, whose interictal EEGs showed frequent multifocal independent spikes, did not have epileptic seizures. CONCLUSIONS: The age of epilepsy onset or the duration of survival is related to the types of seizures occurring in patients with peroxisomal diseases. Neonates or young infants usually have partial motor seizures (facial twitching or clonic convulsions of the arms or legs) of various multifocal origins. Older infants may have generalized seizures at the onset of the disease or evolutionally. Seizure intractability is usually less severe in patients with ZS or AOXD than in patients with NALD or BFED. There is no relation between the electroclinical characteristics of epilepsy and the genetic complementation groups in peroxisomal diseases.

Acyl-CoA Oxidase↗
PubMed1997

Enzymes of ketone body utilization in human tissues: protein and messenger RNA levels of succinyl-coenzyme A (CoA):3-ketoacid CoA transferase and mitochondrial and cytosolic acetoacetyl-CoA thiolases.

We describe the distribution in human tissues of three enzymes of ketone body utilization: succinyl-CoA:3-ketoacid CoA transferase (SCOT), mitochondrial acetoacetyl-CoA thiolase (T2), and cytosolic acetoacetyl-CoA thiolase (CT). Hereditary deficiency of each of these enzymes has been associated with ketoacidosis. Physiologically the two mitochondrial enzymes have different roles: SCOT mediates energy production from ketone bodies (ketolysis), whereas T2 functions both in ketogenesis and ketolysis. In contrast, CT is implicated in cytosolic cholesterol synthesis. We investigated the tissue distribution of these enzymes in humans by quantitative immunoblots and by Northern blots. In most tissues, polypeptide and mRNA levels were proportional. CT and T2 proteins were detected in all tissues examined. CT levels were highest in liver, were 4-fold lower in adrenal glands, kidney, brain, and lung, and were lowest in skeletal and heart muscles. T2 was most abundant in liver but substantial amounts were present in kidney, heart, adrenal glands, and skeletal muscle. SCOT was detected in all tissues except liver: myocardium > brain, kidney and adrenal glands. The relative amounts of T2 and SCOT were similar in all tissues except for liver (T2 > > SCOT) and brain (SCOT > T2). The observed distribution of SCOT, T2, and CT is consistent with current views of their physiologic roles.

Acetyl-CoA C-Acetyltransferase↗
PubMed1997

Biochemical and immunocytochemical properties of peroxisomes and mitochondria in bovine chromaffin cells.

The biochemical and immunocytochemical properties of peroxisomal and mitochondrial beta-oxidation enzymes in bovine adrenal chromaffin cells were investigated. Peroxisomes were detectable by immunofluorescence staining using antibodies against acyl-CoA oxidase, peroxisomal 3-ketoacyl-CoA thiolase and catalase. The mitochondria were abundantly stained with antibody against mitochondrial 3-ketoacyl-CoA thiolase. The biosynthesis and intracellular processing of acyl-CoA oxidase and the peroxisomal 3-ketoacyl-CoA thiolase was slower than that in fibroblasts. The peroxisomal beta-oxidation activities shown by [1-14C] lignoceric acid oxidation were slightly lower than those in fibroblasts, whereas the mitochondrial beta-oxidation activities shown by [1-14C] palmitic acid oxidation were almost identical to those in fibroblasts. Adrenal chromaffin cells are useful materials for investigating the peroxisomal and mitochondrial metabolism of autonomic neurons and may contribute to the clarification of neuronal dysfunction in peroxisomal and mitochondrial disorders.

Acetyl-CoA C-Acyltransferase↗
PubMed1996

Peroxisomal disorders: clinical aspects.

Peroxisomal disorders are divided into two groups from a clinical point of view. Diseases in the first group, peroxisome-deficient disorders (PDD), Zellweger-like syndrome, and isolated deficiencies of peroxisomal beta-oxidation enzymes, are characterized by common clinical features including psychomotor retardation, hypotonia, hepatic dysfunction and visual disturbance. The second group includes diseases with a unique manifestation, such as X-linked adrenoleukodystrophy, hyperoxaluria type I and rhizomelic chondrodysplasia punctata. We investigated clinical aspects and the genetic basis of PDD, and the significance of peroxisomes in the development of human brain. Neuroradiological and neurophysiological studies revealed that thick cortex, colpocephaly and multifocal spikes were characteristic findings of PDD patients in the early infantile period. Cytogenetic studies elucidated the presence of eleven complementation groups among PDD, indicating the presence of eleven pathogenic genes for PDD. Molecular studies elucidated two of these genes, PAF-1 and PXR-1. Immunohistochemical studies clarified that the catalase-positive neurons appeared in the basal ganglia, thalamus, and cerebellum at 28 weeks of gestation, and in the cortex at 35 weeks. Immunopositive glial cells appeared from the deep to superficial white matter with increasing gestational age. These results suggest the important role of peroxisomes in neuronal maturation and myelinogenesis.

Brain↗
PubMed1996

Molecular cloning of cDNA encoding rat very long-chain acyl-CoA synthetase.

The cDNA encoding rat very long-chain acyl-CoA synthetase (VLACS) was cloned, using degenerative primers synthesized according to the partial amino acid sequences of the peptide fragments of the purified rat liver enzyme. The longest cDNA insert was 2972 base pairs with a 1860-base pair open reading frame encoding 620 amino acids. The calculated molecular mass of 70,692 daltons was consistent with size of the purified enzyme. In Northern blot analysis, a single band was detected at the position of about 3 kilobases, corresponding to the size of the cloned cDNA. cDNA-directed expression in Escherichia coli resulted in accumulation of expressed protein, as an inclusion body. An antibody was raised using this expressed protein to characterize the cDNA and the enzyme. The subcellular localization of VLACS in peroxisomes and microsomes was demonstrated in Western blot analysis. The specific activity and the substrate specificity of the cDNA expressed enzyme in COS-1 cells were consistent with those of the purified rat enzyme. The predicted amino acid sequence of VLACS had a high sequence similarity to fatty acid transport protein (Schaffer, J. E., and Lodish, H. F. (1994) Cell 79, 427-436), and was considered to have domains for adenylation and thioester formation. The entire structure of VLACS was dissimilar to that of long-chain acyl-CoA synthetase (Suzuki, H., Kawarabayashi, Y., Kondo, Y., Abe, T., Nishikawa, K., Kimura, S., Hashimoto, T., and Yamamoto, T. (1990) J. Biol. Chem. 265, 8681-8685), except for the domains.

Amino Acid Sequence↗