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Biomedical subjects

S Ueda

Publications and source records attributed to S Ueda.

At least 199 records · Page 11Linked to original sources
PubMed1998

Lacidipine: effects on vascular pressor responses throughout the dosage interval in normotensive subjects.

AIMS: To assess the duration and consistency of the pharmacological activity of the dihydropyridine calcium antagonist drug, lacidipine. METHODS: Eight healthy normotensive young males participated in a double-blind randomised crossover comparison of single and multiple doses (for 2 weeks) of lacidipine and placebo. The calcium antagonist effects were quantified at 2, 6 and 24 h post dose by the extent of the attenuation of the pressor responses to the intravenous administration of the vasoconstrictors angiotensin II and noradrenaline. RESULTS: After 2 weeks of treatment, lacidipine consistently and significantly attenuated the pressor responses to both agents at 2 h post dose. At 6 and 24 h post dose there was a significant and progressive decline in the effectiveness of lacidipine in attenuating the pressor responses and for the response to angiotensin II there was no statistically significant effect at either 6 or 24 h post dose. CONCLUSIONS: These results indicate that there is an obvious 'peak' in the pharmacological activity of lacidipine at about 2 h post dose and that this activity is not fully and consistently maintained throughout 24 h.

Adult↗
PubMed1998

Thyroid hormone-induced apoptosis of larval cells and differentiation of pepsinogen-producing cells in the stomach of Xenopus laevis in vitro.

It is generally known that the anuran stomach begins to express pepsinogens (Pg) during metamorphosis. To clarify the mechanisms of differentiation of Pg-producing cells, we examined immunohistochemically the epithelial transformation from larval to adult form in Xenopus laevis stomach at the cellular level. At the beginning of metamorphic climax, concomitantly with the modification of the basement membrane, apoptotic cells labelled by TUNEL suddenly increased in number in the entire epithelium except for the primordia of adult epithelial cells in the basal region of larval glands. Subsequently, with the development of connective tissue, the adult epithelial cells actively proliferated and replaced the larval cells from the basal to the luminal region. Following the start of morphogenesis of adult glands, Pg-producing cells became differentiated in newly formed adult glands, but not in the adult surface epithelium. We then developed an organ culture system and examined effects of thyroid hormone (TH) on the differentiation of Pg-producing cells in X. laevis stomach in vitro. In the presence of TH, just as in spontaneous metamorphosis, Pg-producing cells differentiated from the adult epithelial primordia after the apoptosis of larval epithelial cells. In contrast, in the absence of TH, neither apoptotic larval cells no Pg-producing cells were detected. Therefore, we conclude that TH triggers organ-autonomously the entire process leading to the differentiation of Pg-producing cells in X. laevis stomach. In addition, the strict localization of Pg-producing cells in the adult glands both in vivo and in vitro suggests the correlation between the differentiation of Pg-producing cells and morphogenesis of the glands surrounded by the developed connective tissue.

Animals↗
PubMed1998

Evaluation of the affinity measurement of anti-HIV-1 p17 monoclonal antibody by BIAcore.

The methods of measuring the affinity constants of anti-HIV-1 p17 monoclonal antibodies (MAbs) using the double antibody methods in the liquid phase and the biomolecular interaction analysis by BIAcore system (Pharmacia Biosensor AB, Uppsala, Sweden) were compared. MAbs, HyHIV1-6, recognizing residues 12-29 (P12-29) of p17 and the naive protein, p17, were used. The kinetic association constants (KAs) obtained using the double antibody method were 2.40 x 10(7) - 1.40 x 10(8)M(-1) for P12-29, and 4.80 x 106 - 1.80 x 10(7) M(-1) for p17. In the BIAcore system where P12-29 or p17 was used as immobilized antigens onto the sensorchip, the KAs were 1.57 x 10(9) - 4.81 x 10(9) M(-1) for P12-29, and 1.52 x 10(9) - 1.21 x 10(10) M(-1) for p17. On the other hand, when MAbs were immobilized onto the sensorchip and P12-29 or rp17 was used as analyte, the KAs for P12-29 and p17 were in the region 3 x10(8) - 3 x 10(9), 1 x 10(8) - 3 x 10(9) M(-1), respectively. These data show that the KAs were higher than those obtained using the double antibody method, however, no significant difference could be observed. Moreover, the KAs obtained for p17 using MAbs as ligand were similar for BIAcore and the double antibody method except for HyHIV2. Therefore, the BIAcore system can be used for the affinity measurement instead of the double antibody method.

Animals↗
PubMed1998

Random expression of human immunodeficiency virus-1 (HIV-1) p17 (epitopes) on the surface of the HIV-1-infected cell.

Twenty monoclonal antibodies (MAbs) were obtained by immunizing Balb/c mice with recombinant p17 (rp17) of HIV-1. Epitope specificity of each MAb was determined using six peptides that cover the entire region of p17. We found that each MAb reacts with only one of the peptides, residues 12-29, 30-52, 53-87, and 87-115 (P12-29, P30-52, P53-87, P87-115) of p17 with the exception of one MAb. Three kinds of MAbs that recognize P30-52, P87-115, and a conformational epitope, suppressed the infectivity of HIV-1 (JMH-1) when they added in the culture of MT-4 cells infected by HIV-1 within 24 h of the infection.

Anti-HIV Agents↗
PubMed1998

Experimental brain injury induces expression of amyloid precursor protein, which may be related to neuronal loss in the hippocampus.

Previous reports have demonstrated that some focal brain injuries increase amyloid precursor protein (APP) immunoreactivity in the region surrounding the injury where it was localized, in damaged axons and in pre-alpha 2 cells of the entorhinal cortex. However, to date, APP expression in the hippocampus remote from the impact site has not been comprehensively studied. Therefore, we have evaluated APP expression not only in the locally injured cerebral cortex but also in the hippocampus remote from the impact site. In the present paper, diffuse axonal injury was induced in rats in midline fluid percussion injury. APP expression was examined post injury using Western blot analysis and immunohistochemistry. Western blot analysis demonstrated that the expression of 100-kd APP was increased in both the cerebral cortex and hippocampus 24 h after injury. It then decreased in the hippocampus, but did not change in the cerebral cortex, 7 days after injury. Immunohistochemical studies showed increased immunoreactivity of APP in the neuronal perikarya and reactive astrocytes near the region of injury in the cerebral cortex 24 h to 7 days after injury. In the hippocampus, APP accumulated in the CA3 neurons 24 h and 3 days after injury, although no hemorrhagic lesions were seen at that site. The APP positive neurons in CA3 showed shrunken cell bodies and pyknotic nuclei 3 days after injury, and some of the neurons in CA3 had disappeared by 7 days postinjury. The results of present study suggest that traumatic brain injury induces overexpression and accumulation of APP in neuronal perikarya and that these events are followed by degeneration of CA3 neurons. Further, the decline in APP expression in the hippocampus is thought to be due to neuronal loss in CA3 subsector.

Amyloid beta-Peptides↗
PubMed1998

Glycolaldehyde-modified low density lipoprotein leads macrophages to foam cells via the macrophage scavenger receptor.

It was shown that proteins modified with advanced glycation end products (AGE) are effectively endocytosed by macrophages or macrophage-derived cells in vitro, and immunohistochemical studies involving anti-AGE antibodies demonstrated the accumulation of AGE-modified proteins (AGE-proteins) in macrophage-derived foam cells in human atherosclerotic lesions in situ, suggesting the involvement of AGE-modified LDL in the atherogenic process in vivo. To examine this suggestion, LDL was modified with glycolaldehyde, a highly reactive intermediate of the Maillard reaction. Physicochemically, glycolaldehyde-modified LDL (GA-LDL) was characterized by increases in negative charge, fluorescence intensity, and reactivity to anti-AGE antibodies, properties highly similar to those of AGE-proteins. The cellular interaction of GA-LDL with mouse peritoneal macrophages showed that GA-LDL was specifically recognized and endocytosed, followed by lysosomal degradation. The endocytic uptake of GA-LDL by these cells was competitively inhibited by acetylated LDL (acetyl-LDL), and the endocytic degradation of acetyl-LDL was also competed for by GA-LDL. Furthermore, incubation of GA-LDL with these macrophages and Chinese hamster ovary cells overexpressing the macrophage scavenger receptor (MSR), but not with peritoneal macrophages from MSR-knockout mice, led to the intracellular accumulation of cholesteryl esters (CE). These results raised the possibility that AGE-modified LDL, if available in situ, is taken up by macrophages mainly via MSR and then contributes to foam cell formation in early atherosclerotic lesions.

Acetaldehyde↗
PubMed1998

Temporary shunt system with a heparin-coated inner surface for interruption of cerebral circulation: experiments in primates.

OBJECTIVE: Temporary interruption of the cerebral circulation is sometimes required during the course of neurosurgical procedures. It would be beneficial to develop some type of vascular shunt system that could be used when temporary interruption of the cerebral circulation is necessary. Recent advances in the production of hemocompatible materials suggested to us that it would be possible to develop a small caliber temporary shunt system. METHODS: We developed and investigated in primates a small caliber, temporary arterial shunt system. The heparin-coated shunt catheter was 30 cm in length and had an internal diameter of 1.2 mm. Five Japanese monkeys were used for these experiments. Flow was maintained for 3 hours through a shunt connecting the radial and carotid arteries. We investigated the following: 1) biocompatibility of the catheter, 2) patency of the system, 3) flow through the system, 4) histology of the inner surface of the catheter, 5) biochemical analysis of blood components adhering to the inner surface of the catheter, and 6) histology of perfused brain. RESULTS: Angiography performed through the shunt showed adequate distal cerebral perfusion. Flow through the catheters was 47+/-1.7 ml per minute. Analysis of the shunt catheter at the conclusion of the perfusion period showed no clot formation in the lumen by gross inspection or electron microscopy. CONCLUSION: This system could prove useful for preventing cerebral ischemia during the course of neurosurgical procedures in which the cerebral circulation must be temporarily interrupted.

Animals↗
PubMed1998

Cis-acting elements in the lytic origin of DNA replication of Marek's disease virus type 1.

The replication origin of Marek's disease virus (MDV) type 1 was analysed by using a transient replication assay with plasmids containing various fragments of MDV strain Md5 genomic DNA. Plasmid pMBH, containing the BamHI-H fragment, showed replication activity in MDV-infected chicken embryonic fibroblasts (CEF). By deletion analysis of pMBH, two regions, the promoter-enhancer region of the MDV pp38 gene and the 132 bp tandem direct repeat, were shown to be required for replication activity. Replication of pMBH was not observed in uninfected CEF, suggesting that a trans-acting factor(s) encoded by the MDV genome was necessary for replication.

Animals↗
PubMed1998

Juvenile hyaline fibromatosis: a report of two unrelated adult sibling cases and a literature review.

Two unrelated adult sibling cases (36- and 32-year-old females) of juvenile hyaline fibromatosis are presented. The parents of one of these patients were non-consanguineous but natives of a small island, and one elder sister among four siblings was affected with the same disease. The parents of the other patient were consanguineous, and one other sibling suffered from the identical disease. Both patients presented with multiple subcutaneous nodules, which they had had since infancy, and had undergone numerous surgical excisions. Light microscopy examination of skin lesions from both patients showed identical histology; an abundance of a homogenous, amorphous, eosinophilic extracellular matrix in which spindle-shaped cells were embedded. Electron microscopically, the spindle-shaped cells had hypertrophic Golgi apparatus and dilated, rough endoplasmic reticulum. Fine fibrillar and granular material-filled structures, the contents of which were occasionally released into the extracellular matrix, were also seen. Immunohistochemically, the spindle-shaped cells were vimentin-positive but negative for alpha-smooth muscle actin and S-100 protein, and the hyaline ground substance was positive for type I and type III collagen but negative for type II and type IV collagen and tenascin. Matrix metalloproteinase-1, -2, and -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2 was positive but TIMP-1 was negative. A review of 39 cases of juvenile hyaline fibromatosis in the literature is also presented. In summary, skin lesions may be the most outstanding symptoms of juvenile hyaline fibromatosis, but joint contracture and gingival hypertrophy precede the skin manifestation.

Adult↗
PubMed1998

Comparative evaluation of sialylated carbohydrate antigens, KL-6, CA19-9 and SLX as serum markers for interstitial pneumonia.

We compared diagnostic values of three serum carbohydrate antigens, KL-6, CA19-9 and SLX to discriminate interstitial pneumonia (IP) from alveolar pneumonia and healthy volunteers. Subjects consisted of 13 patients with idiopathic pulmonary fibrosis and 10 associated with collagen vascular diseases, 12 patients with sarcoidosis and 70 controls (52 healthy volunteers and 18 patients with alveolar pneumonia). Cut-off values were determined at the level at which the diagnostic accuracy became the highest for each marker, 449 U/mL for KL-6, 26 U/mL for CA19-9 and 41 U/mL for SLX. The sensitivity, the specificity and the diagnostic accuracy were 74.3% (26/35), 98.6% (69/70) and 90.5% (95/105) in KL-6, 42.9% (15/35), 94.3% (66/70) and 77.1% (81/105) in CA19-9, and 20.0% (7/35) and 95.7% (67/70) and 70.5% (74/105) in SLX, respectively. Receiver operating characteristic curves revealed that KL-6 was far superior to both CA19-9 and SLX. These results suggest that KL-6 is the best marker for interstitial pneumonia among these carbohydrate antigens.

Adult↗
PubMed1998

Pharmacologic actions of temiverine (p-INN) and its active metabolite, RCC-36, on isolated human urinary bladder muscle.

BACKGROUND: Temiverine (p-INN) is a newly synthesized drug that is expected to have anticholinergic action. We investigated the pharmacologic actions of temiverine and its active metabolite, RCC-36, on isolated human bladder. METHODS: Effects of temiverine and RCC-36 on the detrusor contractions induced by acetylcholine, potassium chloride (KCl), calcium chloride (CaCl2), and electric field stimulation were evaluated using the muscle-bath technique, and compared with the effects of atropine and oxybutynin. RESULTS: Atropine (10(-9) to 10(-6) mol/L), oxybutynin (10(-8) to 10(-5) mol/L), temiverine (10(-8) to 10(-5) mol/L), and RCC-36 (10(-8) to 3 x 10(-6) mol/L) caused a parallel shift to the right of the concentration-response curves to acetylcholine stimulation. The rank order of pA2 value was atropine > oxybutynin = RCC-36 > temiverine. Atropine did not suppress the maximum contractile response to acetylcholine, but the other drugs significantly suppressed this at the higher concentrations. Each drug caused a concentration-dependent inhibition of KCl (80 mmol/L)-, and CaCl2 (5 mmol/L)-induced contractile responses. Rank order of maximum inhibition was RCC-36 = temiverine > oxybutynin > atropine. Each drug caused a concentration-dependent inhibition of electric field-induced contraction with or without 10(-6) mol/L atropine pretreatment. Maximum inhibitions of temiverine and RCC-36 were significantly greater than that of oxybutynin. CONCLUSION: Atropine, oxybutynin, temiverine, and RCC-36 have different efficacies and potencies of anticholinergic and calcium antagonistic activity on isolated human detrusor muscles. Furthermore, temiverine and RCC-36 have significant inhibitory actions toward the atropine-resistant part of contractions, which may be related to the calcium antagonistic actions of these compounds.

Acetylcholine↗
PubMed1998

Prejunctional muscarinic receptors modulating acetylcholine release in rabbit detrusor smooth muscles.

We investigated the presence and subtypes of functionally prejunctional receptors in cholinergic nerve endings of rabbit detrusor smooth muscle strips using high-performance liquid chromatography coupled with a microdialysis procedure. The effects of pretreatment with various drugs on acetylcholine (ACh) release and contractile responses induced by electrical field stimulation were evaluated. Although atropine (a muscarinic nonselective antagonist) and 4-DAMP (a muscarinic M3 antagonist) did not influence the ACh release, they markedly reduced the contractile responses. Pirenzepine (M1 antagonist) decreased ACh release and contractile responses. Methoctramine (M2 antagonist) increased the ACh release, but did not influence to the contractile responses. These results suggest that the muscarinic receptors in the rabbit detrusor smooth muscle are heterogeneous, prejunctional facilitatory (M1 receptors), and inhibitory (M2 receptors) for ACh release and postjunctional M3 receptors mediating contractile responses.

Acetylcholine↗
PubMed1998

The novel insulinotropic mechanism of pimobendan: direct enhancement of the exocytotic process of insulin secretory granules by increased Ca2+ sensitivity in beta-cells.

Pimobendan is a new class of inotropic drug that augments Ca2+ sensitivity and inhibits phosphodiesterase (PDE) activity in cardiomyocytes. To examine the insulinotropic effect of pimobendan in pancreatic beta-cells, which have an intracellular signaling mechanism similar to that of cardiomyocytes, we measured insulin release from rat isolated islets of Langerhans. Pimobendan augmented glucose-induced insulin release in a dose-dependent manner, but did not increase cAMP content in pancreatic islets, indicating that the PDE inhibitory effects may not be important in beta-cells. This agent increased the intracellular Ca2+ concentration ([Ca2+]i) in the presence of 30 mM K+, 16.7 mM glucose, and 200 microM diazoxide, but failed to enhance the 30 mM K+-evoked [Ca2+]i rise in the presence of 3.3 mM glucose. Insulin release evoked by 30 mM K+ in 3.3 mM glucose was augmented. Then, the direct effects of pimobendan on the Ca2+-sensitive exocytotic apparatus were examined using electrically permeabilized islets in which [Ca2+]i can be manipulated. Pimobendan (50 microM) significantly augmented insulin release at 0.32 microM Ca2+, and a lower threshold for Ca2+-induced insulin release was apparent in pimobendan-treated islets. Moreover, 1 microM KN93 (Ca2+/calmodulin-dependent protein kinase II inhibitor) significantly suppressed this augmentation. Pimobendan, therefore, enhances insulin release by directly sensitizing the intracellular Ca2+-sensitive exocytotic mechanism distal to the [Ca2+]i rise. In addition, Ca2+/calmodulin-dependent protein kinase II activation may at least in part be involved in this Ca2+ sensitization for exocytosis of insulin secretory granules.

Androstadienes↗
PubMed1998

The vasodilating effect of insulin is dependent on local glucose uptake: a double blind, placebo-controlled study.

During systemic hyperinsulinemia in man, skeletal muscle vasodilation has consistently been demonstrated. However, most studies that have examined the vascular effect of local hyperinsulinemia have reported either no effect or only weak vasodilation, and all of these have been open in design. The present studies were designed in a double blind, placebo-controlled manner to evaluate the direct (local) vascular effect of insulin alone and in association with physiological concentrations of D-glucose. Forearm blood flow was measured in 17 healthy male volunteers by bilateral venous occlusion forearm plethysmography. Brachial artery infusions of 1 mU/min insulin, 5 mU/min insulin, or vehicle were administered for 90 min on 3 separate study days in random order. The higher dose of insulin was associated with weak (20%) vasodilation compared with placebo (F = 5.75 and P < 0.01, by ANOVA). When this protocol was repeated with intraarterial coinfusion of D-glucose, significant augmentation of the vascular effect was demonstrated (47% vasodilation). No augmentation of insulin-mediated vasodilation was observed with coinfusion of L-glucose, the metabolically inactive stereoisomer. These data suggest that local uptake of D-glucose by insulin-sensitive tissues is an important determinant of insulin-mediated vasodilation.

Adult↗
PubMed1998

A wild-type Japanese measles virus strain inducing predominant early down-regulation of CD46.

Down-regulation of CD46 secondary to stimulation with measles virus (MV) was investigated using CD46-positive cell lines and Japanese wild-type MV strains. The cells used were simian cell lines B95a and Vero in which MV strains have been adapted to be amplified, and Chinese hamster ovary (CHO) cell transfectants expressing human CD46 with (CHO(tail+)) or without (CHO(tail-)) the cytoplasmic tail. Of four Vero-adapted and three B95a-adapted MV strains, one Vero-adapted strain named Khono (KO), down-regulated CD46 within 60 min (early down-regulation) in all cell lines examined except Vero. No strains other than Toyoshima (TY), which induced early down-regulation only in CHO(tail+) cells, induced early down-regulation of CD46 in any combination. On the other hand, conventional down-regulation of CD46 was observed 24 h post-MV inoculation (late down-regulation) when cell lines used were adapted to MV strains. Thus, we concluded that there are two modes of CD46 down-regulation by MV and the unique strain KO markedly induces early down-regulation. Also, the CD46 homologue of B95a, which fails to act as a MV receptor, is down-regulated concomitantly with MV replication (>24 h) in cells principally by competent virus strains.

Amino Acid Sequence↗
PubMed1998

Structure-function relationship of T-2 toxin and its metabolites in inducing thymic apoptosis in vivo in mice.

Recently we found that a single administration of T-2 toxin (T-2), a trichothecene mycotoxin, into mice induced DNA fragmentation, a biochemical hallmark of apoptosis, in the thymus. In this study, we investigated the effective chemical structure(s) of T-2-derived metabolites capable of inducing thymic apoptosis in vivo in mice. Metabolic conversion of T-2 to 3'-hydroxy-T-2 toxin (3'-OH-T-2) did not diminish the apoptosis-inducing activity, since essentially the same level of fragmented DNA was detected in the thymus taken from mice injected with either T-2 or 3'-OH-T-2. In contrast, hydrolysis of T-2 and 3'-OH-T-2 at the carbon-4 (C-4) position to HT-2 toxin (HT-2) and 3'-hydroxy-HT-2 toxin (3'-OH-HT-2), respectively, greatly decreased the level of DNA fragmentation. Similarly, hydrolysis of T-2 at the carbon-8 (C-8) position to neosolaniol strongly diminished its ability to induce DNA fragmentation. T-2 tetraol, having no ester groups, was unable to induce apoptosis. Based on the data presented in this study, we concluded that both the acetyl group at the C-4 position and the isovaleryl or 3'-hydroxyisovaleryl group at the C-8 position of the T-2 molecule are important for inducing cell death through apoptosis in the thymus.

Animals↗
PubMed1998

Development of an enzyme-linked immunosorbent assay using recombinant chicken anemia virus proteins expressed in a baculovirus vector system.

Recombinant baculoviruses were constructed to express the putative proteins VP1, VP2 or VP3 of the chicken anemia virus (CAV). The recombinant VP1, VP2 or VP3 were detected by SDS-PAGE, and their molecular weights were 50, 30/27 and 16 kDa, respectively. The VP2 and VP3 reacted with sera from CAV-infected chickens in Western blot analysis and when used as an enzyme-linked immunosorbent assay (ELISA) antigen, but VP1 did not. Antibodies to CAV were detected, by ELISA using crude insect cell lysates containing VP2 or VP3, from 2 to 20 weeks or 2 to 7 weeks after CAV infection, respectively. These findings indicate that recombinant VP2 and VP3 expressed in the baculovirus vector system can be used as antigens to detect anti-CAV antibodies in ELISA.

Animals↗