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Biomedical subjects

H Okano

Publications and source records attributed to H Okano.

At least 235 records · Page 13Linked to original sources

Gene organization and transcription of duplicated MBP genes of myelin deficient (shi(mld)) mutant mouse.

A hereditary dysmyelinating mutation, named myelin deficient (shi(mld)), is characterized by reduced expression of myelin basic protein (MBP). In shi(mld), the MBP gene is duplicated and its reduced expression is mainly determined by the level of mRNA. We have characterized the structure and function of the promoter regions of the duplicated MBP genes in shi(mld). Among the lambda clones containing promoter regions of the duplicated MBP genes in shi(mld), one (gene 1) had the same restriction enzyme pattern as that in control mice, but another (gene 2) had a rearrangement on a distal part of the promoter. A 712-bp nucleotide sequence upstream of the first exons of both of the duplicated MBP genes of shi(mld) was completely consistent with that of the control. Promoter activities of 1.3-kb 5'-flanking regions from respective genes of shi(mld) measured by in vitro run-off assay using HeLa whole-cell extracts were indistinguishable from that of the control MPB gene. Chromosomal mapping by in situ hybridization suggested that the duplicated MBP genes were located closely to each other at the distal part of chromosome 18. A recombinational event including the inversion seemed to have occurred within gene 1 and its possible relationship to the reduced expression of MBP is discussed.

Animals↗

Recombination within the upstream gene of duplicated myelin basic protein genes of myelin deficient shimld mouse results in the production of antisense RNA.

The myelin deficient shimld mouse is an autosomal recessive mutant, characterized by hypomyelination in the central nervous system. The expression of the myelin basic protein (MBP) gene is inhibited transcriptionally. The MBP gene is duplicated tandemly in mld, and exons 3 to 7 of the upstream copy is inverted. In the present studies, we determined the approximate position of the 5' boundary and the nucleotide sequence surrounding the 3' boundary of the inversion and found a number of sequences homologous to the switching regions of mouse immunoglobulin heavy chain gene and J regions of human T cell receptor genes. Antisense RNA complementary to exons 3 and 7, which correspond to the inverted segment, was detected by RNase protection studies. This abnormal transcript was also shown to elongate through the inverted segment to reach the transcription initiation site of the downstream gene.

Animals↗

Development of and clinical experience with a new TV monitoring system in electronic endoscopy. Bi-plane TV monitoring system.

We developed a bi-plane TV monitoring system using a TV endoscope (Electronic endoscope manufactured by Toshiba-Machida, Tokyo, Japan) that permits simultaneous display of real-time and prerecorded images. Various findings of the two examinations can be precisely compared using this system, and a detailed evaluation of the progress of peptic ulcers obtained. In addition, the effects of various endoscopic therapies can be accurately evaluated. In endoscopic injection sclerotherapy of esophageal varices, new varices (or recurrent varices) were differentiated. In laser therapy for early gastric cancer, precise delimitation of the lesion for radiation was possible, and the therapeutic effects were more accurately evaluated. These results show the diagnostic as well as therapeutic usefulness of this system. Furthermore, for the examination of the lower digestive tract, X-ray images were incorporated into this system. This is a useful modality for diagnostic and therapeutic procedures in colonic disease.

Electronics, Medical↗

Hemoglobin synthesis of both adult and fetal types in a human CML cell line.

We present evidence for the continuous erythroid differentiation of a cell line, KU-812-F, without the addition of an inducer. Erythroid differentiation of these cells was confirmed according to the following findings: 1) erythroid morphology; 2) existence of glycophorin A and carbonic anhydrase I as a membrane marker protein and an enzyme characteristic of erythroid cells, respectively; 3) synthesis of adult type (HbA and HbA2) and fetal type (HbF) hemoglobins, as detected on isoelectric focusing; and 4) transcription of the alpha-, beta-, and gamma-globin genes, as detected on Northern blot analysis.

Cell Differentiation↗

Swallow syncope after aneurysmectomy of the thoracic aorta.

A case of swallow syncope is presented and 30 previously reported cases from the literature in English are reviewed. A 67-year-old male developed syncope on swallowing 3 months after the resection of an aneurysm of the descending thoracic aorta. Electrocardiographic monitoring during eating demonstrated sinus bradycardia and sinus arrest with loss of consciousness. Neither Valsalva's maneuver nor carotid massage could produce bradycardia or syncope. Intravenous administration of edrophonium produced sinus bradycardia and the drinking of water by the patient after edrophonium administration brought about sinus bradycardia and sinus arrest with loss of consciousness. Sinoatrial node and atrioventricular node functions, evaluated by an atropine test, overdrive suppression test, and His bundle electrocardiogram were normal. No pathological changes were observed following a barium swallow. The patient was treated with a permanent pacemaker.

Aged↗

Immunohistochemical, biochemical and electron microscopic analysis of myelin formation in the central nervous system of myelin deficient (mld) mutant mice.

Myelin deficiency (mld) is an autosomal recessive mutation in mice and is considered to be allelic to the shiverer (shi) mutation. Mld mice are characterized by hypomyelination of the central nervous system (CNS). They show typical symptoms such as tremor, tonic convulsion and ataxic movement. Subcellular fractionation of the CNS revealed that the MBP bands were greatly decreased in the P2A (myelin) fraction and the total content of myelin basic protein (MBP) was much lower than that in the control in all parts of the CNS. Sections from mld mice were examined by immunohistochemical tests with MBP antiserum, and a mosaic expression of MBP was found in the myelin of the mld mice. Since the major dense line is considered to be composed mainly of MBP, we investigated the myelin of mld mice by electron microscopy and found that there were 3 types of myelin: (1) a normal type compact myelin with a major dense line, (2) a shiverer-type myelin with no major dense line, and (3) a mixed-type myelin, in which within a myelin lamella the major dense line abruptly changes to cytoplasm of oligodendrocytes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

The fifth exon of the myelin proteolipid protein-coding gene is not utilized in the brain of jimpy mutant mice.

The jimpy mouse, an X-linked recessive dysmyelinating and demyelinating mutant, has been shown to contain abnormal myelin proteolipid protein (PLP) mRNA. To understand the molecular basis of the mutation, we analyzed the structure of PLP mRNA by an RNase-mapping procedure, using the probes specific to each exon of the mouse PLP gene. We found that the fifth exon of the PLP gene is not utilized in the jimpy.

Animals↗

Inefficient transcription of the myelin basic protein gene possibly causes hypomyelination in myelin-deficient mutant mice.

A hereditary dysmyelination mutation, named myelin deficient (mld), is considered to be allelic to shiverer, a deletion mutation of the myelin basic protein (MBP) gene. The present study showed that MBP expression is greatly reduced in mld, but that it is still detectable. Northern blot analysis revealed that the pronounced decrease in the MBP level in mld resulted from a reduced mRNA level and was not caused by deletion of a large portion of the MBP gene as in shiverer. Southern blot studies with BamHI-digested chromosomal DNA suggested some part of the MBP gene, at least the 5'-portion, was duplicated in mld. These results indicated that the mld and shiverer mutations were different from each other, even though genetic allelism between the two was reconfirmed. We also examined the developmental pattern of the gene expression of MBP and that of another protein, myelin proteolipid protein (PLP), specifically expressed in the oligodendrocyte, in mld by RNA dot blot study. The mRNA level of MBP in mld was greatly reduced during the active myelination stages, gradually increasing and remaining constant in the later stages. The PLP-mRNA content in mld was almost normal (60-80% that of control) at any stage of development. All these findings imply that the primary defect in mld is due to reduced transcriptional activity of the MBP gene.

Alleles↗

Differential induction of adult and fetal globin gene expression in the human erythremia cell line KMOE.

Induction of globin gene expression in KMOE cells derived from a patient with acute erythremia was studied by Northern blot and S1 analysis. KMOE cells exposed to cytosine arabinofuranoside (Ara-C) synthesized beta-globin gene transcripts, however, in the presence of hemin gamma-globin gene transcripts. An increase in alpha-globin gene transcripts was also detectable in KMOE cells treated with both Ara-C and hemin. Upon exposure to hemin after exposure to Ara-C, or exposure to Ara-C after hemin, there was a 5-10-fold increase in gamma-globin gene transcripts compared to that of cells induced by hemin alone. Neither epsilon nor zeta globin transcripts were detected. The KMOE cell line, therefore, exhibits phenotypic properties of adult and fetal erythroid cells.

Cell Line↗