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Biomedical subjects

Y Ono

Publications and source records attributed to Y Ono.

At least 397 records · Page 22Linked to original sources

Human diploid fibroblast cell culture medium contains a factor that increases cytosolic Ca2+ and stimulates prostaglandin synthesis by cultured bovine aortic endothelial cells.

Previously, we demonstrated that conditioned medium (CM) from cultures of human diploid fibroblast cells contains a factor that stimulates the production of prostacyclin (PGI2) by cultured bovine aortic endothelial cells (BAEC). To study the mechanism by which CM stimulates PGI2 production, we measured the effect of removal of extracellular calcium (Ca2+) on the concentration of cytosolic Ca2+ and on the production of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of PGI2. The CM-induced production of 6-keto-PGF1 alpha was dependent on extracellular Ca2+ and did not require nascent protein synthesis. Application of CM to BAEC induced a transient increase in cytosolic Ca2+ concentration that was dependent on extracellular Ca2+. Bradykinin induced the production of 6-keto-PGF1 alpha by BAEC. However, bradykinin induced an increase in cytosolic Ca2+ concentration in the presence or absence of extracellular Ca2+. Voltage dependent Ca2+ channel blocker (verapamil, diltiazem) did not inhibit either the CM-induced increase in cytosolic Ca2+ or the production of 6-keto-PGF1 alpha by BAEC. These data suggest that CM increases the cytosolic Ca2+ concentration and stimulates PGI2 production by BAEC. The increase in cytosolic Ca2+ concentration occurred via the influx of extracellular Ca2+ independent of L-type Ca2+ channels blocked by verapamil or diltiazem.

6-Ketoprostaglandin F1 alpha↗

Effects of lecithinized superoxide dismutase on traumatic brain injury in rats.

Only small amounts of superoxide dismutase (SOD) are present in the extracellular space to scavenge excess amounts of superoxide anions (02-) released after traumatic brain injury (TBI). Experiments were performed in rats with cerebral contusion produced by weight-drop technique. We investigated the effects of exogenous lecithinized SOD (PC-SOD) on accumulation of 02- produced in our model, by measuring the level of SOD activity (using the NBT-reducing method) and the expression of copper, zinc-SOD (Cu, Zn-SOD) mRNA (by Northern blot analysis). As determined by tissue-specific gravity, administration of PC-SOD reduced brain edema in the periphery of the lesion 6 h after contusion. SOD activity increased in the peripheral region at 30 min after contusion, but returned to normal levels at 6 h after TBI. Administration of PC-SOD increased SOD activity up to 6 h after TBI. The expression of Cu, Zn-SOD mRNA increased in the core region, peripheral portion, and contralateral hemisphere up to 6 h after TBI, then was suppressed in all three regions by PC-SOD. Our results confirm the important role of 02- in the development of brain edema after TBI and indicate that PC-SOD diminishes brain edema through a protective effect against 02-.

Animals↗

Deletion of an endosomal/lysosomal targeting signal promotes the secretion of Alzheimer's disease amyloid precursor protein (APP).

Alzheimer's disease amyloid precursor protein (APP) generates a beta-amyloid protein (A beta) that is a main component of the senile plaques found in the brains of Alzheimer's disease patients. APP is thought to undergo proteolysis via two different pathways, the amyloidogenic pathway which produces A beta, and the non-amyloidogenic pathway which releases a large N-terminal fragment into the medium. The proteases that mediate these processes remain unidentified. The physiological function of APP is not clear yet. Therefore, the cytoplasmic region of APP has attracted much interest, because this region is highly conserved among species, and members of the amyloid precursor-like protein (APLP) family. Several potentially functional sequences exist in the region, including signal sequences for protein sorting and a G0-protein binding sequence. We constructed two mutants, 695 deltaNPTY and 695 deltaGYEN. They lack potential endosome/lysosome targeting signals, NPTY and GY, in the cytoplasmic domain of APP695, respectively. The mutant APPs had longer half-lives and were secreted more easily into the medium than the wild type, suggesting that these sequences are important for the secretion and metabolism of APP.

Alzheimer Disease↗

Middle cerebral artery stenosis caused by relatively low-dose irradiation with stereotactic radiosurgery for cerebral arteriovenous malformations: case report.

OBJECTIVE AND IMPORTANCE: There have been occasional reports of stenosis or occlusion of major cerebral arteries occurring several years after stereotactic radiosurgery for cerebral arteriovenous malformations. Nevertheless, little information is available regarding the actual irradiation dose to which the affected artery had been exposed. CLINICAL PRESENTATION: We present a patient with arteriovenous malformations who, although asymptomatic, developed remarkable stenosis of the middle cerebral artery trunk (M1) 3 years after gamma knife radiosurgery. The nidus was covered with a 50% isodose volume. A central dose of 36 Gy was used. A gradual decrease in nidus volume had been suggested by 1- and 2-year postradiosurgical neuroimaging examinations. Three-year postradiosurgical angiography revealed severe segmental stenosis of the M1, as well as remarkable nidus shrinkage. INTERVENTION: The actual irradiation dose delivered to the affected portion of the artery, as retrospectively determined using a highly accurate three-dimensional analysis technique, was estimated to be 5.1 to 9.8 Gy. CONCLUSION: This case suggests that a normal major artery, if located close to the target volume, may be affected by low-dose irradiation (10 Gy or even slightly less) delivered with radiosurgery, although a decrease in blood flow through the M1 because of nidus shrinkage or associated stenosis of the distal middle cerebral artery, as well as other unknown factors, may also contribute to proximal M1 stenosis.

Arterial Occlusive Diseases↗

[A case of primary HIV-1 infection].

A previously healthy 28 year old Japanese man came to us with a genital ulcer which appeared 13 days before admission to our hospital. He had subsequently fever (40 degrees C), arthralgia, a sore throat and oral aphtha 6 days before admission. He had a history of sexual contact with a female commercial sex worker one week before his illness. On the day of admission, he had shallow ulcers on the lip, tongue and penis. Initial laboratory test included leukopenia and thrombocytopenia. His fever abated 3 days after admission. His condition and bicytopenia recovered completely after 12 days of admission. Although, his serum HIV-1 antibody was negative when he was admitted, 3 months later the antibody was seroconverted. And p24 antigen and HIV-1 RNA of stocked serum were positive. Diagnosis of primary HIV-1 infection was made. Recently, HIV-1 infection has been increasing in Japan. Consideration of this disease in differential diagnosis of acute febrile illness is necessary.

Adult↗

Mechanism of the acceleration of CO2 production from pyruvate in liver mitochondria by HCO3-.

To investigate the mechanism by which HCO3- accelerates pyruvate metabolism in guinea pig liver mitochondria, we measured continuously, at pH 7.4 and 37 degrees C, 13C16O2 production from [1-13C]pyruvate by mass spectrometry and NADH concentration by fluorescence and analyzed total malate, citrate, and beta-hydroxybutyrate produced by standard biochemical methods. When [1-13C]pyruvate is added to the mitochondrial suspension, 13C16O2 concentration rises steeply in the first seconds and then slows to a steady lower rate. Carbonic anhydrase (CA) eliminates this initial phase, which shows that decarboxylation of pyruvate produces CO2, not HCO3-, and it does this more rapidly than it can equilibrate without CA. HCO3- (25 mM) increased 13C16O2 production, O2 consumption and total malate and citrate production and decreased NADH concentration and total beta-hydroxybutyrate production. After obtaining the total amount of 13C16O2, malate, citrate, and beta-hydroxybutyrate produced, we calculated that the addition of 25 mM HCO3- to the suspension medium increased the amount of pyruvate decarboxylated by pyruvate dehydrogenase (PDH) 16% and increased the amount carboxylated by pyruvate carboxylase 300%. This supports our initial proposal that HCO3- accelerates the pyruvate carboxylation, which in turn consumes ATP directly and NADH and acetyl CoA secondarily, all of which increase PDH activity. However, we found no acceleration of pyruvate decarboxylation by 0.5 and 1 microM free Ca2+ concentration, unless the mitochondria were uncoupled and ATP was added.

3-Hydroxybutyric Acid↗

beta-Adrenoreceptor antagonistic actions and mutagenicities of R(+)- and S(-)-enantiomers of N-desisopropylpropranolol and its N-acetyl conjugate.

Enantiospecific acetyl conjugation was examined in the rat liver 105000 x g supernatant (cytosol) system using racemic 1-amino-3-(1-naphthyloxy)-2-propanol (NDP), a N-desisopropyl metabolite of propranolol. From the results of chiral separative determination of the samples by HPLC using a Chiralcel OD-R column, more remarkable enantiospecificity was observed in the R(+)-enantiomer on NDP elimination and N-acetyl conjugate (AcNDP) formation. Next, the strength of beta-adrenoceptor antagonistic actions and mutagenicities was compared between R(+)- and S(-)-enantiomers of NDP and AcNDP, respectively. In the case of NDP, both enantiomers possessed weak beta1-adrenoceptor antagonistic effects on isoproterenol-induced positive inotropic and chronotropic actions in the left and right atria isolated from a guinea pig. These actions of R(+)- and S(-)-NDP were 1700-times and 100-times less potent, respectively, than those of propranolol. beta2-Adrenoceptor antagonistic actions of R(+)- and S(-)-NDP in the trachea were 1600-times and 200-times less potent, respectively, than those of propranolol. Enantiospecificity was observed in the beta-adrenoceptor antagonistic action of S(-)-NDP, while R(+)-NDP and both enantiomers of AcNDP appeared to be negligible in this action. On the other hand, the mutagenicities of each enantiomer were examined by the Ames method using 13 kinds of Salmonella typhimurium strains. In the case of AcNDP, the numbers of colonies increased according to the substrate concentration only when rat liver 9000 x g supernatant fraction (S-9 mixture) was added to the plates containing TA100, YG1029, TA104 and YG3003, and then enantiospecificity was observed in the mutagenicity of S(-)-AcNDP. Thus, the ultimate mutagen might be an active metabolite formed mainly from S(-)-AcNDP. Despite of the addition of rat liver S-9 mixture, R(+)-AcNDP and both enantiomers of NDP did not indicate mutagenicity.

Adrenergic beta-Antagonists↗

Synthetic studies of vitamin D analogs. XXIV. Synthesis of active vitamin D3 analogs substituted at the 2 beta-position and their preventive effects on bone mineral loss in ovariectomized rats.

Analogs related to 1 alpha,25-dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D3 (ED-71) (4), oxa-type and carba-type analogs of vitamin D3 bearing substituents at the 2 beta-position of 1 alpha,25-dihydroxyvitamin D3 (1), were synthesized from the alpha-epoxides (6 and 13). Three analogs, ED-71 (4) and two carba-type analogs (16 and 26), showed potent preventive effects on bone mineral loss in pre-osteoporosis model rats. ED-71 (4) was concluded to be an optimized analog and a promising candidate for the treatment of osteoporosis.

Absorptiometry, Photon↗

A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes associated with diabetes mellitus and hypothalamo-pituitary dysfunction.

A 45-year-old woman with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) had muscular atrophy, severe cerebral and cerebellar atrophy, and cardiac hypertrophy. She also had diabetes mellitus treated with insulin, and sensorineural hearing loss. Ragged-red fibers were observed on muscle biopsy and an adenine to guanine transition mutation at position 3243 of her mitochondrial DNA was confirmed. Further investigations revealed that she also had hypothalamo-pituitary dysfunction. It appears that diabetes mellitus, hypothalamo-pituitary dysfunction, and the other abnormalities are all associated with mitochondrial dysfunction in this patient.

Atrophy↗

Effect of sex hormones on the tissue localization of nuclear estrogen receptor positively stained cells in the seminal vesicle of immature castrated rats.

We studied the changes in the tissue localization of nuclear estrogen receptor (ER) positively stained cells in the seminal vesicle of immature castrated rats under various environmental conditions of sex hormones by immunohistochemical methods. In castrated rats of 6 weeks of age, the percentage of nuclear ER positively stained cells showed remarkable increase in the periglandular stroma region, but not in the epithelium and the peripheral stroma region. Estrogen administration to castrated rats dramatically increased the percentage of nuclear ER positively stained cells in both the epithelium and the peripheral stroma region, whereas cessation of estrogen treatment caused a significant percentile decrease. These results suggest that the nuclear ER expression in both the epithelial cells and the peripheral stromal cells seems to respond to estrogen. The concomitant treatment of estradiol-17 beta (E2) with 5 alpha-dihydrotestosterone (DHT) completely inhibited these E2 mediated ER expression in the epithelium and the stroma. This result suggests that ER works only when E2 is given in the absence of DHT in the seminal vesicle of immature castrated rats.

Animals↗

Induction of resistance to etoposide and adriamycin in a human glioma cell line treated with antisense oligodeoxynucleotide complementary to the messenger ribonucleic acid of deoxyribonucleic acid topoisomerase II alpha.

Acquisition of resistance to anticancer agents is a serious problem for cancer chemotherapy. The present study analyzed the relationship between expression of the alpha isoform of deoxyribonucleic acid (DNA) topoisomerase II (topo II alpha) and chemosensitivity to topo II inhibitors by modulating the level of topo II alpha expression. A phosphorothioate analogue of an 18-nucleotide oligomer which is complementary to the translation initiation site of the human topo II alpha messenger ribonucleic acid sequence was used to suppress the expression of topo II alpha in a human glioma cell line (U373MG). The topo II alpha activity of the treated cells was reduced to 1/3 of untreated cells in a decatenation assay using kinetoplast DNA. Antisense oligoDNA-treated cells showed mild resistance to the topo II inhibitors, etoposide and adriamycin, of about 2.0 fold and 1.5 fold, respectively, compared to control cells. Only partial reduction in the activity of topo II alpha in the glioma cell line can cause a measurable resistance to topo II inhibitors, implying that the degree of topo II expression is correlated with chemosensitivity to topo II inhibitors.

Antibiotics, Antineoplastic↗

Single solitary metastasis of the slowly progressive type of renal cell carcinoma to the choroid plexus--case report.

A 68-year-old male developed a solitary metastasis in the choroid plexus of the right lateral ventricle 7 years after left nephrectomy for renal cell carcinoma. The lesion was totally removed and the patient has been free from recurrence for 30 months postoperatively. Pure solitary metastasis to the choroid plexus is very rare, but five of the 15 cases originated from renal cell carcinoma. There may be a link between this type of metastasis and the slowly progressive type of renal cell carcinoma.

Aged↗

Immunohistochemical and biochemical characterization of sulphated proteoglycans in embryonic chick bone.

The type and distribution of sulphated proteoglycans (PGs) in the midshaft subperiosteal bone of 15-18-day embryonic chick femurs were studied immunocytochemically and biochemically, using four monoclonal antibodies (MAb 2B6, 3B3, 1B5, and 5D4). These MAb specifically recognize epitopes in chondroitin 4-sulphate (C4-S) and dermatan sulphate (DS); chondroitin 6-sulphate (C6-S) and unsulphated chondroitin (C0-S); C0-S; and keratan sulphate (KS) respectively. Immunohistochemistry showed that staining of C4-S, DS, and KS, but not of C6-S and C0-S, was limited to osteoid, the cell surface of osteocytes, and to the walls of osteocytic lacunae and bone canaliculi in 15-18-day embryonic specimens. However, no significant difference in the distribution and intensity of immunostaining was observed in these specimens. Bone proteins were extracted from fresh 18-day embryonic specimens with a three extraction procedure, 4 M guanidine HCl (GdnCl, G-1 extract), 0.4 M EDTA (E-extract), followed by GdnCl (G-2 extract), to characterize mineral binding and collagenous matrix associated PGs in E- and G2-extracts respectively. Western blot analysis of E- and G2-extracts demonstrated that chondroitinase ABC-digested PGs with a molecular weight (Mr) approximately of 45,000 containing GAGs predominantly corresponding to C4-S and/or DS, with no detectable C6-S or C0-S present in the mineral and matrix phase, whereas KSPGs having an Mr of approximately 72,000 are only present in the mineral phase. These results indicate that embryonic chick bone contains small PGs having C4-S, DS, and KS chains with preferential localization to osteoid, the cell surface of osteocytes, and to the walls of osteocytic lacunae and bone canaliculi.

Animals↗

Immunohistochemical study of prostacyclin-stimulating factor (PSF) in the diabetic and atherosclerotic human coronary artery.

Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis. We recently found a novel bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis by cultured aortic ECs. Our previous studies demonstrated that PSF is dominantly expressed by arterial smooth muscle cells (SMCs). In the present study, we found PSF to exist in the SMCs of human coronary arteries by means of immunohistochemical methods. Human coronary arteries obtained from autopsies were divided into four subgroups, with or without NIDDM and/or myocardial infarction. Immunostaining for PSF was performed by the avidin-biotin peroxidase complex method using a purified anti-PSF antibody, and the immunostaining for PSF was assessed semiquantitatively. PSF staining was markedly reduced in coronary arterial SMCs from patients with NIDDM and/or myocardial infarction. In addition, the effect of a high glucose culture on PSF mRNA expression and PSF production in bovine aortic SMCs was examined by immunocytochemical staining and both Western and Northern blot analyses. The immunostaining and immunoblot band for PSF also significantly decreased when bovine aortic SMCs were cultured with high concentrations of glucose. Furthermore, as compared with the SMCs cultured with a physiological glucose concentration, the density ratio of PSF mRNA to 28S rRNA expression significantly decreased when the SMCs were cultured with high concentrations of glucose. These results strongly suggest that the decreased PSF production may thus results in a decreased production of PGI2 in the coronary artery, thus leading to the development of both diabetic macroangiopathy and atherosclerosis.

Adult↗

Low back pain among cooks in nursery schools.

A cross-sectional questionnaire study was conducted on cooks working for nursery schools in N city in order to verify epidemiological evidence of the work-relatedness of low back pain among them. After female workers aged 30 or more were selected from a study base of 2,799 workers in social welfare facilities, low back pain prevalence of cooks (n = 240) was compared with nursery school teachers (n = 955). Age-standardized prevalence ratios (PRs) of low back pain were 1.9 (95% CI: 1.5-2.5) in cooks compared with nursery school teachers. Among cooks, relative risks of low back pain increased with the increase in the number of lunches to be prepared and decreased with the increase in the number of cooks making lunches in a logistic regression model controlling age and body length. Low back pain was also found to be associated with self-estimated job stressors/ work load by logistic regression models. Multifactorial effects from ergonomic and psychosocial factors, and individual factors on the low back were suggested. From the viewpoint of epidemiological criteria for work-relatedness, it was concluded that the work-relatedness of low back pain among cooks in nursery schools was partially supported.

Adult↗

Furosemide given by inhalation ameliorates acute exacerbation of asthma.

Previous studies have suggested that inhaled furosemide may have a protective effect against a wide variety of bronchoconstrictor agents, but a therapeutic effect has not been established in acute exacerbation of asthma. The purpose of this study was to investigate whether inhaled furosemide would exhibit any therapeutic benefit in acute asthma. We conducted a double-blind, placebo-controlled, randomized study in 40 patients with acute mild or moderate exacerbation of asthma. All patients received intravenous (i.v.) aminophylline 250 mg for 90 min and i.v. hydrocortisone 100 mg at entry. After randomization, 3 patients were excluded from the final analysis. At 30 min after starting i.v. aminophylline, 20 patients were given inhaled furosemide 20 mg and 17 patients received normal saline as placebo-control. Both inhalations were given by a jet nebulizer. The baseline forced expiratory volume at 1 sec (FEV1), peak expiratory flow rate (PEFR), and serum concentration of theophylline did not differ between the two groups. An increase in FEV1 in the furosemide group by 28.2 +/- 5.9% (mean +/- SE) was noted at 60 min, and this was significantly higher than in the control group. PEFR at 60 min was also significantly higher in the furosemide group than in control group. We conclude that inhaled furosemide has a bronchodilator effect on mild to moderate exacerbation of asthma when it is used with i.v. theophylline. Inhaled furosemide may benefit certain acute asthma patients, especially those suffering complications from the adverse effects of beta 2-agonists.

Acute Disease↗