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Biomedical subjects

S Taira

Publications and source records attributed to S Taira.

At least 37 records · Page 2Linked to original sources

Selective antagonism of endothelin ET(A) or ET(B) receptor in renal hemodynamics and function of deoxycorticosterone acetate-salt-induced hypertensive rats.

Effects of acute and chronic blockade of endothelin ET(A) or ET(B) receptors on renal hemodynamics and function were investigated using deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. At 4 weeks after initiating DOCA-salt treatment, intravenous bolus injection of ABT-627 (1 mg/kg), a selective ET(A) receptor antagonist, produced a sustained and significant hypotension, which was accompanied by potent renal vasodilation. When the selective ET(B) receptor antagonist A-192621 (3 mg/kg) was intravenously administered, there were marked decreases in renal blood flow and glomerular filtration rate, and increases in renal vascular resistance. A slight hypertensive effect was observed after the injection of A-192621. Next, we examined the effects of chronic treatment with ABT-627 (10 mg/kg/d, p.o., b.i.d.) or A-192621 (30 mg/kg/d, p.o., b.i.d.) for 2 weeks on renal function of animals at 2 weeks after initiating DOCA-salt treatment. In the 2-week-treated DOCA-salt animals, the levels of creatinine clearance (Ccr), urinary excretion of protein (Uprotein V) and blood urea nitrogen (BUN) were not significantly different compared with those of sham-operated control animals. These parameters did show statistically significant differences over the 3 to 4 weeks treatment period, between the DOCA-salt and the control animals (decrease in Ccr, and increase in Uprotein V and BUN in DOCA-salt rats), thereby indicating the gradual establishment of renal dysfunction in this hypertensive model. The DOCA-salt-induced changes in renal functional parameters were markedly attenuated by daily administration of ABT-627. In contrast, treatment with A-192621 augmented the above renal dysfunction. Our findings clearly indicate that selective blockade of the ET(B) receptor is detrimental to renal hemodynamics and the function of the hypertensive condition, and support the view that a selective ET(A) receptor antagonist is useful for treatment of subjects with mineralocorticoid-dependent hypertension.

Animals↗

Non-traumatic aneurysms of the cavernous sinus causing massive epistaxis--report of three cases.

Three cases of non-traumatic intracavernous aneurysms that gave rise to massive epistaxis and required operative intervention, are reported. This is a rare but serious cause of epistaxis, because delayed diagnosis and management can lead to repeated bleedings and even to death. It is important, therefore, to diagnose the source of epistaxis and treat it as soon as possible. In our three patients, an emergency angiography enabled us to diagnose an aneurysm in the cavernous sinus. These aneurysms were located in the C3 or C4 portion of the internal carotid artery and were 3-5 mm in diameter. The projections of these aneurysms were infero-medial, antero-inferior, and lateral, respectively. All three patients underwent emergent surgery. Neck clipping of the aneurysm was performed in two patients, and gradual occlusion of the internal carotid artery in the third patient. Emergency surgery successfully prevented further episodes of epistaxis in all three patients.

Aneurysm↗

Intracellular transport of basement membrane-type heparan sulphate proteoglycan in adenoid cystic carcinoma cells of salivary gland origin: an immunoelectron microscopic study.

ACC3, a human adenoid cystic carcinoma cell system of salivary gland origin, is able to synthesize and secrete a large amount of basement membrane molecules in vitro. To define the ultrastructural secreting pathway of these molecules, we immunolocalized heparan sulphate proteoglycan (HSPG) in ACC3 for 7 days of culture. In the early stage of culture, the main compartments immunolabelled were rough endoplasmic reticulum (rER) and small secretory vesicles. From days 3 to 4 after plating, it was noticed that HSPG was localized in partially dilated spaces of the perinuclear, rER and Golgi cisternae and in lysosomes or those fused with multivesicular bodies and endosomes. On and after day 5, almost every Golgi apparatus showed marked dilatation of the cisternae and HSPG was immunolocalized in these dilated spaces. In the later stage of culture, autophagic vacuoles or secondary lysosomes, which were simultaneously labelled for HSPG and cathepsin D, were accumulated in the cytoplasm. HSPG deposition in the intercellular space was clearly demonstrated from day 1 and increased during the culture. The results indicate that ACC3 cells have an enhanced turnover cycle for HSPG: not only its biosynthesis but also degradation of both endogenous or exogenous HSPG. Such intracellular events may be reflected in the characteristic histology and biological behaviour of adenoid cystic carcinomas.

Biological Transport↗

Effects of FR139317 on renal responses to acute nitric oxide blockade in anaesthetized rats.

1. Effects of FR139317, an endothelin ETA receptor antagonist, on renal haemodynamic and excretory responses to acute nitric oxide (NO) blockade were examined using anaesthetized rats. 2. Intrarenal arterial infusion of NG-nitro-L-arginine (NOARG), the NO synthase inhibitor, at a rate of 40 micrograms/kg per min, produced a significant decrease in renal blood flow, with no change in systemic blood pressure. There were significant decreases in urine flow and urinary excretion of sodium during infusion of NOARG. In animals pretreated with FR139317, similar renal responses to the NOARG infusion were observed. 3. These results suggest that an action of endothelin-1 via ETA receptors does not greatly contribute to the renal haemodynamic and excretory responses to acute blockade of renal NO production.

Anesthesia↗

Different contributions of the endothelin ET(A) receptor to hypertension induced by acute or chronic inhibition of nitric oxide synthesis.

The effects of FR139317((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carb onyl] amino-4-methyl-pentanoyl] amino-3-[3-(1-methyl-1H-indoyl)]propionyl]-amino-3-(2-pyridyl)prop ionic acid), an endothelin ET(A) receptor antagonist, on systemic and renal haemodynamic responses and excretory responses to chronic or acute nitric oxide (NO) synthase inhibition with NG-nitro-L-arginine (NOARG) have been examined. An intravenous bolus injection of FR139317 (10 mg kg(-1)) to chronic NO-deficient hypertensive rats (2.74 mM NOARG in drinking water for 4 weeks) elicited only a slight decrease in mean arterial pressure (MAP), to the same extent as seen in normotensive control rats. Injection of this drug induced no alteration of the renal haemodynamics of this chronic hypertensive model. Urine formation in control rats was significantly reduced by administration of FR139317. No significant decrease in urine formation was observed in the chronic NO-deficient rats. Acute intravenous injection of NOARG (5 mg kg(-1)) induced a gradual and significant increase in MAP, with a significant decrease in renal blood flow. A slight but insignificant diuretic effect was observed. In animals pretreated with FR139317 (10 mg kg(-1) i.v.) NOARG induced a significantly less potent increase in MAP, whereas similar renal haemodynamic responses to NOARG were observed. In contrast to the FR139317-untreated group, urine formation tended to decrease after administration of NOARG. These results suggest that endothelin, via the ET(A) receptor, contributes to the systemic pressor response to acute NO synthase inhibition, although renal vasoconstriction and functional changes induced by acute NO synthase inhibition are independent of ET(A) receptor-related effects. These results imply that action of endothelin via the ET(A) receptor is not involved in the maintenance of sustained hypertension induced by chronic NO synthase inhibition.

Animals↗

Comparison of the effects of gemfibrozil and clofibric acid on peroxisomal enzymes and cholesterol synthesis of rat hepatocytes.

We studied whether the peroxisomal proliferation, induction of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and activation of cholesterol synthesis by gemfibrozil shown in whole body (Hashimoto F., Ishikawa T., Hamada S. and Hayashi H., Biochemical. Pharm., 49, 1213-1221 (1995)) is also detected at a culture cell level, and we made a comparative analysis of the effects of clofibric acid. Gemfibrozil at 0.25 mM increased the activity of some peroxisomal enzymes (catalase and the cyanide-insensitive fatty acyl-CoA oxidizing system) after incubation for 72 h. However, contrary to whole body experiments, gemfibrozil decreased the activity of HMG-CoA reductase and cholesterol synthesis from [14C]acetate. At 1 mM, gemfibrozil decreased not only the activity of HMG-CoA reductase and cholesterol synthesis, but also the protein content of the cells and peroxisomal enzyme activity, indicating nonspecific inhibition at this concentration. Clofibric acid (0.25 and 1 mM) increased the activity of peroxisomal enzymes, but decreased the activity of HMG-CoA reductase and cholesterol synthesis. With respect to the direct effect on HMG-CoA reductase in the cell homogenate, gemfibrozil at 0.25 mm did not affect the activity, but it clearly inhibited the activity at 2 mM and above. Clofibric acid at 2 mM hardly affected the activity, but it clearly decreased the activity at 5 mM and over. That is, gemfibrozil directly inhibited the activity more strongly than clofibric acid. The direct inhibition of the enzyme itself required higher concentrations of both agents than did inhibition at the culture cell level. These results suggest that the cytotoxicity of gemfibrozil is greater than that of clofibric acid, and that gemfibrozil, as well as clofibric acid, can induce peroxisomal enzymes in the culture cell level. In contrast to whole body results, gemfibrozil may suppress cholesterol synthesis from [14C]acetate through the inhibition of HMG-CoA reductase at the culture cell level. The decreases in the reductase activity caused by gemfibrozil and clofibric acid at the culture cell level may not be caused by the direct inhibition of the enzyme.

Animals↗

Genomic organization of human and mouse genes for vascular endothelial growth factor C.

We report here the cloning and characterization of human and mouse genes for vascular endothelial growth factor C (VEGF-C), a newly isolated member of the vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) family. Both VEGF-C genes comprise over 40 kilobase pairs of genomic DNA and consist of seven exons, all containing coding sequences. The VEGF homology domain of VEGF-C is encoded by exons 3 and 4. Exons 5 and 7 encode cysteine-rich motifs of the type C6C10CRC, and exon 6 encodes additional C10CXCXC motifs typical of a silk protein. A putative alternatively spliced rare RNA form lacking exon 4 was identified in human fibrosarcoma cells, and a major transcription start site was located in the human VEGF-C gene 523 base pairs upstream of the translation initiation codon. The upstream promoter sequences contain conserved putative binding sites for Sp-1, AP-2, and NF-kappaB transcription factors but no TATA box, and they show promoter activity when transfected into cells. The VEGF-C gene structure is thus assembled from exons encoding propeptides and distinct cysteine-rich domains in addition to the VEGF homology domain, and it shows both similarities and distinct differences in comparison with other members of the VEGF/PDGF gene family.

Alternative Splicing↗

Effect of respiratory acidosis on body movements in the chronically instrumented fetal lamb.

BACKGROUND: In respiratory acidosis, it is reported that the fetal breathing movements as well as the fetal heart rate variability increase. As the increase of these two kinds of fetal activities is occasionally observed in normal conditions, it is difficult to distinguish respiratory acidosis and normal conditions by mere observation of these activities. As the third diagnostic variable, if a different fetal body movement response to respiratory acidosis is observed, it would be helpful for better diagnosis in combination with other activities. We investigated the effect of respiratory acidosis on body movements in the chronically instrumented fetal lamb. METHODS: A total of four experiments were performed on four ewes. Respiratory acidosis was induced in the fetus by maternal administration of a high carbon dioxide gas mixture for 1 hour. Fetal body movements were observed by real-time ultrasonography. The frequency of body movements was expressed as the number of each movement in a 30-minute period. RESULTS: The mean pCO2 increased from 42.9 +/- 4.9 mmHg to 62.9 +/- 14.8 mmHg, and the mean pH decreased from 7.368 +/- 0.04 to 7.209 +/- 0.04 during the experiments. The frequency of fetal body movements significantly decreased. The percentage reduction of these movements of the same fetus during the experiments as compared to the control periods were as follows; the high-frequency movements, 89.2 +/- 9.7%; the rolling movements, 55.6 +/- 13.5%; the simple movements, 78.3 +/- 18.4%. CONCLUSIONS: Normoxemic respiratory acidosis, which is reported to increase fetal breathing movements, caused a marked reduction in fetal body movements. These findings suggest that the ultrasonographic dissociation of fetal behaviors in respiratory acidosis would be potentially helpful in the diagnosis of impending fetal jeopardy.

Acidosis, Respiratory↗

A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin.

Collectins are C-type animal lectins with both collagenous and carbohydrate recognition domains and are involved in the first line host defense against pathogens. We report here a novel Ca(2+)-dependent and GlcNAc-binding lectin consisting of subunits of 35 kDa (P35) with a collagen-like sequence. When P35 is isolated from human serum, it forms a homopolymer by means of intermolecular disulfide bonding, as is the case with collectins. P35 cDNA was cloned from a human liver cDNA library, and the deduced amino acid sequence of 313 residues revealed that the mature form of P35 consists mainly of collagen- and fibrinogen-like domains. The latter contained two potential Ca(2+)-binding sites that may be involved in carbohydrate binding. The overall sequence of P35 was highly homologous to porcine ficolins alpha and beta. Northern blots of various human tissues showed that the major product of the 1.3-kilobase-long P35 transcript is expressed in liver. P35 enhanced phagocytosis of Salmonella typhimurium by neutrophils, suggesting an opsonic effect via the collagen region. P35 was found to bind to GlcNAc-conjugated bovine serum albumin, a neoglycoprotein, as well as to neoglycolipids containing complex-type oligosaccharides derived from glycoproteins, suggesting that P35 recognizes GlcNAc residues such as those found in microbial glycoconjugates and complex-type oligosaccharides. Therefore, P35 represents a new type of GlcNAc-binding lectin with structural and functional similarities to collectins involved in innate immunity.

Acetylglucosamine↗

VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development.

The vascular endothelial growth factor family has recently been expanded by the isolation of two new VEGF-related factors, VEGF-B and VEGF-C. The physiological functions of these factors are largely unknown. Here we report the cloning and characterization of mouse VEGF-C, which is produced as a disulfide-linked dimer of 415 amino acid residue polypeptides, sharing an 85% identity with the human VEGF-C amino acid sequence. The recombinant mouse VEGF-C protein was secreted from transfected cells as VEGFR-3 (Flt4) binding polypeptides of 30-32x10(3) Mr and 22-23x10(3) Mr which preferentially stimulated the autophosphorylation of VEGFR-3 in comparison with VEGFR-2 (KDR). In in situ hybridization, mouse VEGF-C mRNA expression was detected in mesenchymal cells of postimplantation mouse embryos, particularly in the regions where the lymphatic vessels undergo sprouting from embryonic veins, such as the perimetanephric, axillary and jugular regions. In addition, the developing mesenterium, which is rich in lymphatic vessels, showed strong VEGF-C expression. VEGF-C was also highly expressed in adult mouse lung, heart and kidney, where VEGFR-3 was also prominent. The pattern of expression of VEGF-C in relation to its major receptor VEGFR-3 during the sprouting of the lymphatic endothelium in embryos suggests a paracrine mode of action and that one of the functions of VEGF-C may be in the regulation of angiogenesis of the lymphatic vasculature.

Amino Acid Sequence↗

Syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives.

The syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives against plant pathogenic fungi and termites were investigated. Dihydro-5,6-dehydrokawain was isolated by a simple method without chromatography from the leaves of Alpinia speciosa K. SCHUM. The white crystalline compound obtained was identified as dihydro-5,6-dehydrokawain (1) by instrumental analyses. 4-Hydroxy-6-(2-phenylethyl)-2H-pyran-2-one (3) was prepared by hydrolyzing dihydro-5,6-dehydrokawain. Three dihydro-5,6-dehydrokawain derivatives were synthesized by reacting 3 with phosphoric agents. Among the synthesized compounds, dimethyl [6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl]phosphorothionate (4) had the strongest antifungal activity of 91% at 100 ppm against Corticium rolfsii.

Animals↗

Synthesis and antifungal activity of cinnamic acid esters.

Cinnamic, p-coumaric and ferulic acids were isolated from pineapple stems (Ananas comosus var. Cayenne). Twenty-four kinds of esters were prepared from these acids, alcohols and the components of Alpinia. Isopropyl 4-hydroxycinnamate (11) and butyl 4-hydroxycinnamate (12) were found to have almost the same effectiveness in antifungal activity against Pythium sp. at 10 ppm as that of the commercial fungicide iprobenfos (kitazin P).

Anti-Infective Agents↗

[Recent features of parasites detected from clinical specimens].

It is generally considered that we have already been through with problems caused by various kinds of parasites which had once raged throughout the country. On the contrary to our common concept, we occasionally encounter some kinds of parasites in a laboratory as well as in clinical fields, which have become unfamiliar to us in these days. Parasitic diseases are in the first place, proper and limited to certain local regions, but the present situation has been greatly changed. Nowadays, specific parasites are no longer limited to polluted areas, but also they can be detected in any part of the world owing to facilitated transportations and a promoted international exchange of people. A recent gourmet boom is also one of the causes of infection as seen in anisakiasis. This study was conducted on the investigation of parasites detected from clinical specimens in our laboratory during the period from 1989 to 1993. 1) The following parasites were detected : (1) Strongyloides stercoralis, (2) Giardia lamblia, (3) Diphyllobothrium latum, (4) Schistosoma mansoni, (5) Entamoeba histolytica, (6) Necator americanus, (7) Isospora belli. 2) Strongyloides stercoralis was detected at the highest frequency. This result gives an account of high prevalence of the parasite among the inhabitants in Okinawa. In addition, the agar plate medium method which has been newly adopted has definitely led to far-advanced results for detection of this parasite. 3) Schistosoma mansoni and Necator americanus were found from foreigners one of whom was a Tanzanian and the other was a Dominican. 4) Isospora belli was found from those compromised cases such as ATL and AIDS.

Animals↗

Evidence for functional polymorphism of the spvR gene regulating virulence gene expression in Salmonella.

The expression of Salmonella enterica spv virulence genes was studied in serovariants Dublin and Typhimurium using Western blotting (immunoblotting), spv-lacZ operon fusions and Northern blotting. The SpvA protein was detected in immunoblots from stationary phase cultures of Dublin but not from the corresponding cultures of Typhimurium. Transcriptional measurements, using a spvA-lacZ operon fusion, indicated 8-10 times higher spvA transcription in Dublin. In an isogenic Escherichia coli chromosomal background, virulence plasmids from various Dublin strains systematically had a significantly higher induction level of the spvA-lacZ operon fusion than virulence plasmids from Typhimurium strains. The cloned spvR transcriptional activator gene of Dublin strain 2229 was found to activate both spvR-lacZ and spvA-lacZ operon fusions, as well as to raise spv mRNA levels in E. coli TG1. In contrast, the corresponding cloned gene of Typhimurium strain SL2965 possessed a lower induction potential and required higher spvR gene dosage for activation. A comparison of the nucleotide sequences of spvR genes from two Dublin and four Typhimurium strains revealed conserved, serovariant-associated basepair substitutions. Our results indicate that the spv virulence gene cluster possesses different functional alleles of the regulator gene spvR. This finding has important consequences for comparative studies of regulation and virulence in different serovariants of Salmonella.

Base Sequence↗

Pneumocephalus caused by fistulas of the mastoid air cells treated with a temporoparietal fascial flap.

Using a temporoparietal fascial flap and hydroxyapatite ceramics, we treated a patient for complications after a neurosurgical operation for glossopharyngeal neuralgia. These consisted of pneumocephalus and cerebrospinal fluid rhinorrhea resulting from fistulas of mastoid air cells associated with a subcutaneous dead space. By means of the temporoparietal fascial flap, we were able to fill the dead space and reinforce the repaired dural and mastoid lesion as well. Hydroxyapatite ceramics were also useful for closing the mastoid air cell fistulas.

Bone Diseases↗

Mannose-binding protein recognizes glioma cells: in vitro analysis of complement activation on glioma cells via the lectin pathway.

The lectin pathway is a novel pathway for activation of the complement cascade, which is initiated by the binding of mannose-binding protein (MBP) to its carbohydrate ligands. We investigated whether the complement system was activated in vitro by glioma cells through this pathway to the C3 level. MBP was found to bind to all six glioma cell lines tested by using flow cytometric analysis. Binding of a complex of MBP-associated serine protease and MBP was observed in two of the cell lines examined, thereby resulting in C4 consumption. Activation of C3 was hemolytically evaluated in these two lines. C3 consumption was also observed in one. Based on these results, it is likely that recognition by MBP followed by complement activation occurs in certain glioma cell lines.

Carrier Proteins↗

The Escherichia coli G-fimbrial lectin protein participates both in fimbrial biogenesis and in recognition of the receptor N-acetyl-D-glucosamine.

The gafD gene encoding the N-acetyl-D-glucosamine-specific fimbrial lectin (adhesin) protein GafD of uropathogenic Escherichia coli was cloned and subjected to genetic analysis. The corresponding gene product was isolated as a MalE fusion protein. The lectin gene was identified with the aid of deletion mutagenesis; mutations in gafD impaired either receptor binding or both receptor binding and fimbria production, depending on the mutation created. All mutants converted to wild-type expressors when complemented in trans with the cloned intact gafD gene. The predicted 354-amino-acid sequence of GafD, deduced from the nucleotide sequence, is closely related to those of the fimbria-associated F17-G and F17b-G proteins coded for by enterotoxigenic and invasive E. coli strains. Isolated GafD was shown to recognize N-acetyl-D-glucosamine by virtue of specific binding to an immobilized receptor, thus proving directly that GafD is a sugar-binding protein. Our results indicate that GafD as such is sufficient for receptor recognition and that the protein also participates in fimbrial biogenesis.

Acetylglucosamine↗

[Clinical significance of ultrasonographic screening for Down syndrome in the second trimester].

OBJECTIVE: This study was undertaken to evaluate the clinical significance of ultrasonographic screening for the detection of Down syndrome in the second trimester of pregnancy of Japanese women. MATERIALS AND METHODS: BPD (biparietal diameter), FL (femur length), BPD/FL ratio and M/E FL (measured/expected femur length) ratio were measured in 734 normal second-trimester fetuses and 13 consecutive Down syndrome fetuses undergoing genetic amniocentesis mainly for advanced maternal age. RESULTS: Two fetuses with Down syndrome had small BPD, three fetuses had a short femur length, four fetuses had a high BPD/FL ratio and four fetuses had a low M/E FL ratio. A cutoff value of 1.5SD below the mean value for the normal populations for BPD and FL, that of above 1.5SD for BPD/FL ratio, and that of 0.91 or less for M/E FL ratio yielded a sensitivity of 15.4, 23.1, 30.8 and 30.8% and false positive rates of 2.7, 6.0, 5.7 and 11.4%, respectively. CONCLUSION: The ultrasonographic measurements of femur length for the screening of Down syndrome in the Japanese population revealed the low discriminative ability reported in recent studies conducted in Western countries. Further investigation would be necessary to apply it as the routine screening method for Down syndrome in clinical practice.

Adult↗