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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 451 records · Page 25Linked to original sources

[Optic neuropathy in systemic lupus erythematosus (SLE)--analysis of 54 cases including our case].

A 46-year old woman with systemic lupus erythematosus (SLE) who had been treated with oral administration of prednisolone (7.5 mg/5 mg on alternate days) at our outpatient clinic suddenly developed a loss of visual acuity, visual field defect, and photophobia on Dec. 15th, 1993. When she was admitted three days later, she was diagnosed as having optic neuropathy, and immediate treatment with methylprednisolone (1 g/day for three days) followed by prednisolone (50 mg/day) resulted in complete disappearance of the above symptoms by Feb. 9th, 1994. As far as we know, fifty-three cases of SLE with optic neuropathy have been reported previously. The result of analysis of the 54 cases including our case indicates that rapid diagnosis and corticosteroid treatment in an early phase of optic neuropathy leads to significant improvement.

Female↗

[Spontaneous regression of cerebral arterio-venous malformation following major artery thrombosis proximal to dominant feeders: a case report].

A rare case of spontaneous regression of cerebral arterio-venous malformation (AVM) is reported. A 76-year-old male was admitted to Juzen General Hospital due to generalized convulsion on August 24, 1987. On admission, results of physical and neurological examinations were normal. Plain CT scans showed an iso-density lesion with a slightly high density spot in the left frontal lobe, and enhanced CT scans showed multiple, irregularly tubular enhancements in the lesion. Left carotid angiogram (CAG) demonstrated an arteriovenous malformation (AVM) in the left frontal lobe, which was fed by the left ACA and MCA and drained by the ascending cerebral vein and superficial Sylvian vein. There was also an anterior communicating artery aneurysm. At the patient's request, he was treated conservatively and was discharged without neurological deficit. Though he continued to take anticonvulsants thereafter, he felt weakness or numbness of the right extremities once a year. Five years after the first admission, he developed sudden onset of right hemiparesis, aphasia and consciousness disturbance. On admission, his platelet aggregation function was elevated. At this time, enhanced CT scans did not show any enhanced area in the left frontal lobe where AVM had been found previously. T2-weighted magnetic resonance image showed a mixed intensity area without any flow void phenomenon suggesting thrombosis of the nidus. Left CAG demonstrated occlusion of the A1-A2 junction of the anterior cerebral artery and disappearance of the AVM. He was treated conservatively again, and was discharged without neurological deficit.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Bispecific antibody-mediated cytotoxicity by CD4+ and CD8(+)-activated T cells generated from leukemia patients after allogeneic bone marrow transplantation.

The F(ab')2 bispecific antibody (BSAb) was prepared from anti-CD3 moAb and anti-CD10 moAb. The BSAb could react with both CD3+ T cells and CD10+ leukemia cells and triggered T cell-mediated cytotoxicity. To apply the BSAb to prevention of leukemic relapse after BMT, we investigated the generation of both CD4+ and CD8+ anti-tumor effector T cells from patient's PBMC 14 days after BMT. Neither CD4+ T cells nor CD8+ T cells, which were activated with immobilized anti-CD3 moAb plus IL-2, could lyse CD10+ leukemia cells by themselves, but they showed augmented cytotoxicity against CD10+ leukemia cells by targeting with anti-CD3 x anti-CD10 BSAb. Moreover, the activated CD4+ T cells were demonstrated to produce IL-2 and IFN-gamma when they were cultured with CD10+ leukemia cells in the presence of the BSAb. The BSAb-mediated cytotoxicity of activated T cells was demonstrated not only against the recipient leukemia cells but also against third party leukemia cells. These results suggested that anti-CD3 x anti-CD10 BSAb might be a good tool to prevent relapse after BMT in combination with activated CD4+ T cells and CD8+ T cells.

Antibodies, Monoclonal↗

[The mu, delta and kappa properties of various opioids].

Recently, the highly selective mu, delta and kappa radiolabeled opioid ligands, such as 3H-DAGO (mu ligand), 3H-DPDPE (delta ligand) and 3H-U69593 (kappa ligand) are available. Using the kappa-homogeneous preparations from human placenta and mu-enriched gerbil cerebellum membrane preparations with these highly selective radiolabeled opioid ligands, clinically used opioids were tested for their mu, delta and kappa properties. The mu agonists such as morphine and fentanyl display a very low affinity for delta and kappa receptor. Among the agonist-antagonist, buprenorphine and butorphanol appeared to be the most highly selective agonists for mu and kappa opioid receptors, respectively. Most ligands identified as specific agonists are in fact only selective and appear to interact at more than one receptor type.

Analgesics, Opioid↗

[Comparison of long-term clinical results of the three models of the Björk-Shiley valve prosthesis and the Omnicarbon valve prosthesis].

A multi-institutional cooperative study, that was a comparison of long-term results of the replacement of the four models of the oblique disc valve prosthesis which had been implanted on aortic and mitral position alone or double from December 1976 to September 1992 in the eight national hospitals in Japan was performed. Seven hundred and thirty-four patients and 765 prostheses that consisted of 582 patients and 610 prostheses of the Björk-Shiley (BS) valve, including 326 patients of the Spherical disc (SP) valve (49 aortic, 259 mitral, and 18 double aortic-mitral), 103 patients of the Convexoconcave disc (CC) valve (45, 51, 7) and 153 patients of the Monostrut (MS) valve (101, 49, 3), and of 152 patients (71, 78, 3) and 155 prostheses of the Omnicarbon (OC) valve were compared with their mortality and morbidity in every valve position respectively according to the approval by STS-guideline. The MS valve and the OC valve showed 0% to 11.3% of operative mortality, 0.3%/py to 1.8%/py of valve related mortality, 85.5% +/- 5.6% to 98.4% +/- 1.6% of actuarial survival rate at 10 years, and 58.5% +/- 6.4% to 82.7% +/- 5.7% of actuarial free rate of all mortality and morbidity at 10 years in every valve position. Structural deteriorations occurred in two patients of the CC valve in the mitral position only, and its rate of all valve positions showed 0.04%/py. Significant differences were seen in actuarial survival rate at 10 years after aortic valve replacement, and in operative mortality rate, improved degree of NYHA class, structural deterioration rate and actuarial free rate of all mortality and morbidity after mitral valve replacement between the group of the MS and OC valve and the group of the SP and CC valve. Therefore the MS valve or the OC valve should be selected to implant rather than the SP valve or the CC valve, and the patient who had been implanted with the CC valve should be treated considering valve position, valve position, valve size, age and activity of the patient and the manufactured date of the prosthesis.

Bioprosthesis↗

[CT findings of primary retroperitoneal cystic tumors: special emphasis on the distinction benignancy from malignancy].

We describe the CT findings of primary retroperitoneal cystic tumors in 20 patients (cystic lymphangioma, 9; cystic teratoma, 3; cystic neurinoma, 4; mucinous cystadenocarcinoma, 3; synovial sarcoma, 1). CT findings were retrospectively reviewed and the findings correlated with the pathological findings to determine malignant or benign cystic tumors. Definite criteria for malignancy were invasion to surrounding organ and the presence of distant metastasis. However, the sensitivity of these criteria was very low (25%). Enhancement of an intracystic solid component was a reliable criterion (p < 0.05) for malignancy (sensitivity 75%, specificity 81%, accuracy 80%). Either unilocular cystic appearance or the presence of a "neck" (between the cystic mass and paraaortic region) strongly suggested the possibility of benignancy (specificity 100%). The "neck" was thought to be morphologically specific for cystic lymphangioma.

Adult↗

[Opioid receptors altered binding nature in guinea-pig brain following the development of morphine dependence].

Morphine is well known to produce tolerance and dependence. The mechanisms for these phenomena are not clearly understood and there are a number of conflicting reports that chronic morphine administration decreases, increases, or leaves unchanged the number of opioid binding sites. We examined the potency of MScontin (oral controlled-release preparation of morphine) to induce morphine dependence and also determined the change of mu, delta and kappa opioid receptor types in brain homogenates obtained from morphine-dependent guinea-pigs. 1. Guinea-pigs were implanted subcutaneously with MScontin (300 mg.kg-1) and naloxone was employed to precipitate jumping behavior of withdrawal symptoms at various times. The highest degree of physical dependence was observed on the 2nd day after implantation. Therefore, this period was chosen to investigate opioid receptor binding assay. 2. Two days after implantation, the binding of 3H-DAGO (mu agonist), 3H-DPDPE (delta agonist) and 3H-U69593 (kappa agonist) to brain membranes prepared from morphine dependent and control guinea-pigs was determined. Scatchard plot of the saturation binding data revealed an increase in Bmax values (maximum specific binding) and no change in the Kd values (equilibrium dissociation constants) of 3H-opioid ligand bindings obtained from morphine-dependent animals as compared to controls. These results indicate that brain mu, delta and kappa opioid receptors are up-regulated in morphine dependent guinea-pigs.

Animals↗

[The internal thoracic artery of poor quality: was cardiac massage a cause of ITA stenosis?].

The case of stenotic left internal thoracic artery (LITA), with a very rare and interesting histological findings is reported. The patient, a 65-year-old man, fell into shock, due to acute myocardial infarction and received cardiopulmonary resuscitation at home immediately. Three months later, patient underwent coronary artery bypass grafting. The LITA was dissected from the chest wall with a tissue pedicle by usual manner. However, it was abandoned to use for grafting, because of extremely poor blood flow even after balloon dilatation was noticed. Histological study revealed a significant granulation of LITA media, led to severe stenosis of LITA lumen on it's portion. On other side, either proximal and distal portion of LITA remained intact. It seems that this unusual histological change of LITA media developed after LITA over stretching due to cardiac massage during cardiopulmonary resuscitation. If patient, scheduled for coronary bypass surgery, has in a personal history the presence of cardiac massage, traffic accident, some contact sport or any other chest trauma, it is recommended to perform LITA angiography preoperatively, if an intention to use the LITA for coronary artery bypass grafting exists.

Cardiopulmonary Resuscitation↗

The STRO-1+ fraction of adult human bone marrow contains the osteogenic precursors.

The monoclonal antibody STRO-1 identifies clonogenic bone marrow stromal cell progenitors (fibroblast colony-forming units [CFU-F]) in adult human bone marrow. These STRO-1+ CFU-F have previously been shown to give rise to cells with the phenotype of fibroblasts, adipocytes, and smooth muscle cells. In this study, the osteogenic potential of CFU-F derived from the STRO-1+ fraction of adult human bone marrow was determined. CFU-F were isolated from normal bone marrow aspirates by fluorescence activated cell sorting, based on their expression of the STRO-1 antigen. Osteogenic differentiation was assessed by the induction of alkaline phosphatase expression, by the formation of a mineralized matrix (hydroxyapatite), and by the production of the bone-specific protein osteocalcin. STRO-1+ cells were cultured in the presence of dexamethasone (DEX; 10(-8) mol/L), ascorbic acid 2-phosphate (ASC-2P; 100 mumol/L), and inorganic phosphate (PO4i; 2.9 mmol/L). After 2 weeks of culture, greater than 90% of the cells in each CFU-F colony stained positive for alkaline phosphatase using a monoclonal antibody specific for bone and liver alkaline phosphatase. Alkaline phosphatase activity was confirmed by histochemistry. A mineralized matrix developed in the CFU-F cultures, after 4 weeks of culture in the presence of DEX, ASC-2P, and PO4i. Mineralization was confirmed by both light and electron microscopy. The mineral was identified as hydroxyapatite by electron dispersive x-ray microanalysis and by x-ray diffraction analysis. In replicate cultures, osteocalcin release was shown after exposure of the cells to 1,25-dihydroxyvitamin D3 (10(-7) mol/L) both by radioimmunoassay and Northern blot analysis. This work provides direct evidence that adult human bone marrow-derived CFU-F are capable of differentiating into functional osteoblasts and that osteoprogenitors are present in the STRO-1+ population.

Adult↗

Selective inhibition of exoplasmic membrane fusion in echinoderm gametes with jaspisin, a novel antihatching substance isolated from a marine sponge.

A specific inhibitor of fertilization of the sea urchin Hemicentrotus pulcherrimus was isolated from the extract of the marine sponge, Jaspis species. Chemical and spectral data of the purified substance, which was designated jaspisin, showed that it is a novel substance with the structure of sodium (E)-5,6-dihydroxystyryl sulfate. Jaspisin at 15 micrograms/ml inhibited exoplasmic fusion of the plasma membrane of acrosome-reacted sperm with the plasma membrane of the egg; it did not affect either the acrosome reaction in sperm or the egg cortical reaction, both of which involve endoplasmic membrane fusion events. When a fertilized egg was cultured in jaspisin, the embryo developed through the mesenchymal blastula stage. However, it was unable to hatch from the fertilization envelope, and spiculogenesis, in which cell-cell fusion of primary mesenchyme cells is involved, was prevented. Jaspisin at 8.6 micrograms/ml inhibited half the activity of hatching enzyme, a kind of Zn(2+)-dependent metalloendoproteinases. Because Zn(2+)-activated metalloendoproteinases are suggested to be involved in both sperm-egg fusion and fusion of primary mesenchyme cells (Lennarz, W.J., and Strittmatter, W.J. (1991) Biochim. Biophys. Acta 1071, 149-158), one of the possible explanations of the jaspisin effects is that the sulfate inhibits these cellular events through blockage of Zn(2+)-activated metalloendoproteinases that are involved in membrane fusion processes.

Animals↗

Gene structure and cell type-specific expression of the human ATP synthase alpha subunit.

The gene structure of the human ATP synthase alpha subunit (hATP1) was determined by cloning and sequencing. This gene is approximately 14 kbp in length and contains 12 exons interrupted by 11 introns. Mapping of the clones of hATP1 and Southern blot analysis of the genomic gene showed that there were a single copy of bona fide hATP1 gene and two pseudogenes. Primer extension and S1 mapping analysis showed the presence of multiple transcription initiation sites of the hATP1 gene. No TATA box or CAAT box was found near the transcription initiation sites. Comparison with the bovine gene showed that the 5'-flanking region of the hATP1 gene has an unconserved guanine-cytosine (GC) rich region, including several binding motifs of transcriptional factors, such as Sp1, AP-2, and GCF. By functional assay of gene expression, the basal promoter activity was located near the GC rich region. Comparison of the 5'-upstream region of the hATP1 gene with those of the genes for bovine ATP synthase alpha, human beta, and human gamma subunits indicated three common sequences, suggesting that putative cis-elements coordinate the expressions of the three subunit genes for the ATP synthase. The enhancer activities derived from the 5'-deletion mutants of a hATP1-CAT chimeric gene were different in cell lines from four different human tissues, suggesting the existence of cell type-specific gene regulation.

Amino Acid Sequence↗

Basic fibroblast growth factor-like immunoreactivity in the rat basilar artery with reference to co-localization with NADPH-diaphorase in the trigeminal ganglion.

The location of basic fibroblast growth factor (bFGF)-like immunoreactivity and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (neuronal nitric oxide synthase) activity in the rat basilar artery and in the trigeminal, sphenopalatine and superior cervical ganglia was investigated. bFGF immunoreactivity was seen mainly in adventitial nerve fibers of the rat basilar artery, but not in the endothelium. Electron microscopy of the tunica media showed a number of immunoreactive nerve endings in the vicinity of local smooth muscle cells. Among the cranial ganglia that innervate the basilar artery, only the trigeminal ganglion had bFGF-immunoreactivity neurons. Nerve cells and fibers with NADPH-diaphorase activity were detected in the basilar artery and in the sphenopalatine and trigeminal ganglia, and the co-localization of bFGF and NADPH-diaphorase was noted only in the trigeminal ganglion. Furthermore, Fluro-gold tracing in combination with bFGF immunohistochemistry demonstrated that bFGF-containing nerve fibers in the wall of the basilar artery arise from the trigeminal ganglion. These findings provide a morphological basis for the nitric oxide-mediated dilatation of cerebral arteries by bFGF.

Animals↗

Isolation, characterization and structural organization of the gene and pseudogene for the dihydrolipoamide succinyltransferase component of the human 2-oxoglutarate dehydrogenase complex.

In the present study, the dihydrolipoamide succinyltransferase gene of the 2-oxoglutarate dehydrogenase complex was isolated from a human genomic DNA library and its entire nucleotide sequence was determined. This gene was approximately 23 kbp in size with 15 exons and 14 introns. All of the donor and acceptor splice sites of this gene conformed to the GT/AG rule. A guanine residue 43 bases upstreams of the ATG initiating translation codon was the transcription initiation site of the human dihydrolipoamide succinyltransferase mRNA. Sequence analysis of the promoter-regulatory region showed the presence of a CAAT-box-like sequence but the presence of a TATA-box-like sequence was not evidenced. Also located in this region were sequences resembling glucocorticoid-responsive and cAMP-responsive elements, and an Sp1 binding site. No nucleotide sequence corresponding to the E3-binding and/or E1-binding domain was found in any region of the gene. Therefore, the exon coding for the E3-binding and/or E1-binding domain may have been lost from the gene during evolution. Moreover, a processed pseudogene of dihydrolipoamide succinyltransferase was isolated and sequenced. The nucleotide sequence of the pseudogene is 93% similar to the sequence of the human dihydrolipoamide succinyltransferase cDNA, but the pseudogene is not functional for base changes, deletions and insertions of the pseudogene. Southern-blot analysis showed the presence of a single copy of this gene and a single copy of a pseudogene in the human genome. In addition, a possible relationship between dihydrolipoamide succinyltransferase and familial Alzheimer's disease is discussed.

Acyltransferases↗

Analysis of urinary and biliary metabolites of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid in rats by liquid chromatography-frit-fast atom bombardment mass spectrometry.

The urinary and biliary metabolites of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid [(+)-MPPB] were examined in rapid-metabolizing (RM) and slow-metabolizing (SM) male Sprague-Dawley rats by means of liquid chromatography-frit-fast atom bombardment mass spectrometry. In the RM-phenotyped rats, unchanged (+)-MPPB could not be detected in urine or bile, but 4-carboxyphenyl-MPPB was detected in bile. In the SM-phenotyped rats, unchanged (+)-MPPB was detected in bile and unchanged (+)-MPPB and beta-oxidized MPPB in urine. Thus, the inter-individual difference in (+)-MPPB metabolism in rats was confirmed in vivo.

Animals↗

Functional and morphological abnormalities of mitochondria in human cells containing mitochondrial DNA with pathogenic point mutations in tRNA genes.

mtDNA with a point mutation in the tRNA(Ile) gene at nucleotide position 4269 found in a patient with fatal cardiomyopathy and mtDNA with a point mutation in the tRNA(Arg) gene at 10410 found in a patient with Alpers disease were transferred cytoplasmically to rho zero HeLa cells (HeLa cells lacking mtDNA) to determine whether these novel mtDNA mutations in the tRNA genes are responsible for the defects in mitochondrial respiration function observed in these diseases. Cybrid clones (clones of rho zero HeLa cells with mtDNA from the patients) were isolated, and respiratory function and morphology of the mitochondria of the cybrid clones containing wild-type mtDNA and mutant mtDNA predominantly were compared. The results showed that accumulation of mutant mtDNA at 4269 alone without defects in the nuclear genome was sufficient to produce a disease phenotype, while mutant mtDNA at 10410 was not related to pathogenesis and reflected one of the rare polymorphic sites of human mtDNA. Moreover, we found that mitochondria in living cells were significantly swollen only when they contained predominantly the pathogenic mutant mtDNA, suggesting that the functional abnormality of mitochondria induced by pathogenic mtDNA mutations in tRNA genes is always associated with their swollen structure.

Cardiomyopathies↗

Transcription of the MRP RNA gene in frog stage I oocytes requires a novel cis-element.

The RNA component of the mitochondrial RNA processing (MRP) enzyme is related to both replication of mitochondrial DNA and processing of 5.8S rRNA, which are accelerated in the frog earliest stage (stage I) of frog oocytes. Microinjection of the deleted genes into the stage I oocytes showed positive cis-elements in the upstream region of the gene. The specific binding of protein(s) to this region was detected in cell extracts from stage I oocytes and liver but not in extracts of stage II-IV oocytes and the concentration of this protein was 40 times higher in the extract of stage I oocytes than that in liver.

Animals↗

Identification of three catalytic triad constituents and Asp-225 essential for function of lysine-specific serine protease, Achromobacter protease I.

Achromobacter protease I is a lysine-specific serine protease that Achromobacter lyticus M497-1 extracellularly secretes. The structural aspects necessary for the protease to function were investigated by means of site-directed mutagenesis to identify the constituents of the catalytic triad and the amino acid residue responsible for lysine specificity. The precursor molecules, which were produced by substitution of His-57, Asp-113, or Ser-194 for alanine, could not be converted to the mature form. In contrast, a precursor of a mutant in which either His-56 or Ser-193 is converted to alanine was perfectly processed autocatalytically and attained full protease activity. Substitution of Glu-190, one of the two candidates for determining lysine specificity, to glutamine, aspartic acid, or leucine had no or little effect on both proteolytic activity and substrate specificity. However, the kinetic parameters were subtly different from one another, depending on the nature of substituents in these mutants. The substitution of the other candidate, Asp-225, for asparagine or leucine resulted in the failure of maturation to the active forms. However, the precursor of the D225E mutant slowly matured and was essentially inactive. The observed reduction of protease activity is largely due to a decrease in the affinity of lysine to the protease. These results suggest that His-57, Asp-113, and Ser-194 are the three constituents of the catalytic triad in Achromobacter protease I and that Asp-225 plays a critical role in restricted substrate specificity as a lysyl endopeptidase.

Alcaligenes↗

Expression cloning of a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase).

A cDNA encoding a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase) was obtained from an expression cDNA library of human melanoma cell line WM266-4 by enrichment of Namalwa KJM-1 cells highly expressing GD3 using an anti-GD3 antibody and a fluorescence-activated cell sorter. Selection of B-cell line Namalwa cells expressing transfected cDNAs in the presence of anti-GD3 monoclonal antibody KM641 gave a cDNA (pAMo-GD3) encoding a protein with a type II transmembrane topology as found for mammalian glycosyltransferases. The following evidence confirms that the cDNA encodes an alpha-2,8-sialyltransferase, which specifically converts GM3 to GD3. (i) Transfection of pAMo-GD3 into Namalwa KJM-1 cells leads to the appearance of GD3 and a GD3 synthase activity. (ii) Northern blot analysis revealed a correlation between the expression of this gene and GD3 in several cell lines. (iii) The putative COOH-terminal active domain of this cloned enzyme fused with protein A has been purified with IgG-Sepharose beads and has been shown to possess GD3-synthesizing activity, excluding the possibility that the cloned cDNA encodes a transacting factor inducing a GD3 synthase. The deduced primary sequence also contains the "sialyl motif" conserved among all the sialyltransferases cloned to date. The polymerase chain reaction analysis reveals that this gene is located on chromosome 12.

Amino Acid Sequence↗