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Biomedical subjects

H Ono

Publications and source records attributed to H Ono.

At least 253 records · Page 14Linked to original sources

Homologous desensitization of thromboxane A2 receptor in 1321N1 human astrocytoma cells.

The desensitization mechanisms that regulate the response to thromboxane A2 (TXA2) were investigated in 1321N1 human astrocytoma cells. Exposure of the cells to 9,11-epithio-11, 12-methanothromboxane A2 (STA2), a stable TXA2 receptor agonist, at a concentration of 1 microM for 30 to 45 min resulted in about a 50% decrease in subsequent STA2-stimulated phosphoinositide hydrolysis and Ca2+ mobilization. However, exposure to STA2 for 0 to 5 hr did not change the binding of [3H]SQ29548, a TXA2 receptor antagonist. Because STA2-induced GTPase activation decreased and the GTP sensitivity in inhibition of [3H]SQ29548 binding by STA2 disappeared after the cells had been exposed to STA2 for 30 min, the TXA2 receptor desensitization during the short-term might result from G-protein-receptor uncoupling. STA2-induced desensitization was specific for the TXA2 receptor and homologous, because SQ29548 suppressed the desensitization and STA2 pretreatment did not affect the response to carbachol, a muscarinic cholinergic receptor agonist. Exposure to STA2 for 24 hr decreased [3H]SQ29548 binding sites to 20 to 30% of control and abolished STA2-stimulated phosphoinositide hydrolysis, indicating that long-term desensitization might induce down-regulation of the TXA2 receptor. However, exposure to STA2 for 1 to 24 hr did not change the level of TXA2 receptor mRNA. These results show that homologous desensitization of the TXA2 receptor in human astrocytoma cells can be divided into two stages; the early stage involves uncoupling of receptors from G-proteins and the late stage involves a loss of receptors in cells. The mRNA levels may not be controlled by stimulation of the TXA2 receptor.

Astrocytoma↗

[An aged case of successful repair for the ruptured distal aortic arch aneurysm associated with aortic regurgitation: a case report].

Ruptured thoracic aortic aneurysm had severely high mortality. A 83-year-old female, who had suddenly complained back pain and been diagnosed as the ruptured distal aortic arch aneurysm with aortic regurgitation by computer tomography and echo cardiogram, was admitted for an emergent surgery. Aortic arch replacement and aortic valve replacement were performed through median sternotomy under deep hypothermic circulatory arrest with the retrograde cerebral perfusion. She was complicated with respiratory ventilation failure due to the massive mediastinal hematoma and her chest was kept open postoperatively. Her chest was closed two days after the first operation and she recovered uneventfully.

Aged↗

[Electron microscopic histochemical studies on the localization of hyaluronic acid in Wharton's jelly of the human umbilical cord].

The mode and distribution of hyaluronic acid in Wharton's jelly of the human umbilical cord was studied by the electron microscopic histochemical technique. By means of ruthenium red (RR) staining, RR-positive material was observed as granules approximately 30nm in diameter in the fibroblast of Wharton's jelly. Around the fibroblast, it was observed as fibril structures on the cell surface or as granules approximately 13nm in diameter in the basement membrane-like structure around the cell. In the extracellular matrix, it was observed as granules or amorphous materials on collagen fibrils. Only the 30nm granules in RR positive structures disappeared due to amylase digestion. The other structures were digested by Streptomyces hyaluronidase. On the basis of the above findings, it was concluded that hyaluronic acid is formed as hydrated gel around the fibroblast and collagen fibrils in Wharton's jelly of the human umbilical cord. These results suggest that its structure is one of the factors in maintaining the elastic aptitude of the umbilical cord, to protect from any pressure, such as fetal movement, etc., in the uterine cavity.

Extracellular Matrix↗

[Five cases of myelodysplastic syndrome treated with cytarabine ocfosfate].

Five cases of myelodysplastic syndrome were treated with cytarabine ocfosfate. Ocfosfate (100-200 mg) was orally administered for 14 days with 14 days' interval. Etoposide was combined in one case, and nartograstim was added in two cases. Two of the five cases achieved remission, one case having complete remission, and another case showing a good response. Their remission durations were 141 and 112 days, respectively. Further improvement of therapy is needed to achieve a higher remission rate and a longer remission duration.

Administration, Oral↗

HLA class II genotyping of sarcoidosis patients in Hokkaido by PCR-RFLP.

To confirm the significant association of sarcoidosis with HLA-DR5, -DR6, and -DR8 associated DRB1 alleles, in sarcoidosis patients from the eastern Japan (Kanto) area found in our previous study, we used HLA class II genotyping of patients in another region-Hokkaido, in northern Japan. The annual incidence of sarcoidosis in Hokkaido is about three times that of eastern Japan, and Hokkaido has one of the world's highest incidences of this disease. For the HLA class II (HLA-DRB1, -DRB3, -DQA1, -DQB1) genotyping, we used the polymerase chain reaction restriction fragment polymorphism (PCR-RFLP) method with 150 subjects: 40 sarcoidosis patients and 110 healthy controls. The frequencies of DRB1*12, DRB1*14, DRB1*08, DQA1*0501, and DQB1*0301 were significantly increased in the patients, compared with the controls. Our finding of a high frequency of DRB1*08 (which lacks the DRB3 gene encoding the DR52 antigen) in patients living in both eastern Japan and in Hokkaido, confirms that it is the HLA-DRB1 locus, rather than that of the HLA-DRB3, -DQA1, or -DQB1, which determines the susceptibility to sarcoidosis.

Adolescent↗

Descending noradrenergic neurones tonically suppress spinal presynaptic inhibition in rats.

We investigated the tonic depressant effect of descending noradrenergic neurones on spinal presynaptic inhibition. Presynaptic inhibition was measured in terms of the decrease in the amplitude of the monosynaptic reflex (MSR) evoked by conditioning stimulation of the adjacent dorsal root. This reduction in the MSR by conditioning stimulation was accompanied by primary afferent depolarization and was inhibited by the GABAA antagonist bicuculline, but not by the glycine antagonist strychnine. This presynaptic inhibition was much greater in spinalized rats than in intact rats, and was potentiated by the depletion of noradrenaline in the spinal cord in intact rats. These results suggest that presynaptic inhibition evoked by stimulation of the adjacent dorsal root seems to be tonically suppressed by descending noradrenergic neurones.

Afferent Pathways↗

Determination of schizandrin in human plasma by gas chromatography-mass spectrometry.

Schizandrin (SZ) is one of the lignan components from Schisandra fruits. A highly sensitive and precise method for the determination of SZ in human plasma was developed involving selected-ion monitoring with gas chromatography-mass spectrometry using a fused-silica capillary column. A 0.1-ml plasma sample was used for solid-phase extraction. A good linear relationship was obtained in the concentration range studied (2.0-500 ng/ml) and the method was sufficiently accurate and precise to support clinical pharmacokinetic studies. After oral administration of SZ at a dose of 15 mg to healthy male subjects, the average value of the maximum plasma concentration of SZ was 96.1 +/- 14.1 ng/ml. The plasma concentration of this substance could be monitored for 8 h after administration.

Cyclooctanes↗

Characterization of T cells immortalized by Tax1 of human T-cell leukemia virus type 1.

Peripheral blood T cells were immortalized in vitro by introduction of the Tax1 gene of human T-cell leukemia virus type 1 (HTLV-1) with a retroviral vector and were characterized for transformation-associated markers. Long-term observation showed that these Tax1-immortalized T cells eventually exhibited very similar features that were characteristic of HTLV-1-immortalized T cells, ie, increased expression of egr-1, c-fos, IL-2R alpha, and Lyn and decreased expression of Lck and cell-surface CD3 antigen. Among these changes, an increase in the expression of Lyn and a decrease in the expression of Lck and cell-surface CD3 antigen were observed only in Tax1-immortalized T cells after long-term culture. The expression level of Tax1 protein did not differ significantly between early and late passage of cells, and the cellular clonality was found to be the same by the analysis of the retroviral vector integration site and the T-cell receptor beta-chain gene rearrangement pattern. These changes in the expression of Lyn, Lck, and cell-surface CD3 antigen probably resulted from indirect effects of Tax1 that appeared after extended culture.

Antigens, Differentiation↗

Sorting of cytochrome b2 to the intermembrane space of mitochondria. Kinetic analysis of intermediates demonstrates passage through the matrix.

Precytochrome b2 is targeted to the mitochondrial intermembrane space by a dual targeting sequence comprising 80 amino acids. A kinetic analysis of intramitochondrial sorting was performed. The intermediate-size form accumulated transiently in the matrix. When import was performed in the presence of metal chelators to prevent the first processing by the matrix processing peptidase, > 40% of the imported precursor was localized in the matrix. A deletion of 13 amino acids in the intermembrane space sorting sequence caused partial inhibition of the first processing, and a transient accumulation of the precursor form in the matrix was also observed. The decrease in this matrix-localized precursor form paralleled an increase in the mature-size form in the intermembrane space. A point mutation in the mitochondrial targeting sequence (N-terminal to the sorting sequence) resulted in missorting to the matrix space. Furthermore, a chimeric protein consisting of the initial 85 residues of cytochrome b2 fused to dihydrofolate reductase was partially targeted to the matrix at 15 degrees C, but not at 25 degrees C. Together, the results presented here indicate that cytochrome b2 passes through the matrix on its sorting pathway to the intermembrane space.

Amino Acid Sequence↗

A novel intermediate on the import pathway of cytochrome b2 into mitochondria: evidence for conservative sorting.

Cytochrome b2 is sorted into the intermembrane space of mitochondria by a bipartite N-terminal targeting and sorting presequence. In an attempt to define the sorting pathway we have identified an as yet unknown import intermediate. Cytochrome b2-dihydrofolate reductase (DHFR) fusion proteins were arrested in the presence of methotrexate (MTX) so that the DHFR domain was at the surface of the outer membrane while the N-terminus reached into the intermembrane space where the sorting signal was removed. This membrane-spanning, mature-sized species was efficiently chased into the mitochondria upon removal of MTX. Thus, an intermediate was generated which was exposed to the intermembrane space but was still associated with the inner membrane. This intermediate was also found upon direct import of cytochrome b2 and derived fusion proteins. These membrane-bound mature-sized cytochrome b2 species loop through the matrix and could be recovered in a complex with mt-Hsp70 and the inner membrane MIM44/ISP45, a component of the inner membrane import apparatus. This novel sorting intermediate can only be explained by a pathway in which cytochrome b2 passes through the matrix. The existence of such an intermediate is inconsistent with a pathway by which entrance of the mature part of cytochrome b2 into the matrix is stopped by the sorting sequence; however, its presence is fully consistent with the conservative sorting pathway.

HSP70 Heat-Shock Proteins↗

Evidence for insertion of a new intron into an Mhc gene of perch-like fish.

The evolution of the major histocompatibility complex (Mhc) has been studied to understand the origin of the immune system, of which it constitutes an essential part. In the present study, the Mhc is used to shed light on questions regarding the origin of introns and the phylogeny of fishes. The organization of the coding (exon) and non-coding (intron) regions of both class I and class II major histocompatibility complex (Mhc) genes is highly conserved in all vertebrate classes; the only variation observed until now is in the number of exons encoding the membrane-anchoring part. Moreover, there is a good correspondence between the exon-intron organization at the DNA level and the division into structurally and functionally defined domains at the protein level. Here we describe the first major exception to this uniformity. The immunoglobulin-like domain of the class II beta-chains in perch-like fishes (Percomorpha) is not encoded in one exon, as it is in all other vertebrates studied thus far, but in two exons. The length of the extra intron varies from gene to gene and from species to species, but is generally less than 200 base pairs (b.p.). Only one of the sequenced introns is about 500 b.p. long. In some of the genes, the intron contains a hexamer repeat. The repeat is present in the transcript at the site at which the intron interrupts exon 3 in the genomic DNA. The intron may therefore have arisen by repeated tandem duplication of this sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased protein tyrosine-phosphorylation in primary T-cells transduced with Tax1 of human T-cell leukemia virus type I.

Protein tyrosine-phosphorylation in primary human T-cells transduced with Tax1 of Human T-cell leukemia virus type I was investigated. In comparison with control T-cells, the level of protein tyrosine-phosphorylation after stimulation with anti-CD3 antibody increased significantly in Tax1-transduced T-cells. This enhancement in tyrosine-phosphorylation possibly accounted for the augmented proliferation response of these cells, which has been reported previously [J. Virol. 67 (1993) 1211-1217].

Cell Line, Transformed↗

Evaluation of vascular compliance and vasoconstrictive reactions in amputated hindlimbs of rats.

The vascular compliance and the contractility of vascular smooth muscle of preserved, amputated hindlimbs of rats were evaluated using a fresh blood extracorporeal circulatory system. Vascular compliance was measured under physiologic circulatory conditions (blood pressure of the amputated limb was maintained at 80-150 mm Hg [10-20 kPa]) and found not to differ significantly from that of freshly amputated limbs after storage at 4 degrees C for 12 hours. However, after more than 24 hours of storage at 4 degrees C, the vascular compliance decreased significantly (p < 0.01). To evaluate the contractility of vascular smooth muscle, the arterial blood pressure in the amputated limbs was transiently increased with injections of norepinephrine. The contractility could be preserved for at least 12 hours at 4 degrees C; however, it decreased markedly after more than 24 hours. The vascular compliance and vasoconstrictive reactions of the amputated limbs were maintained for at least 12 hours at 4 degrees C.

Amputation, Surgical↗