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Biomedical subjects

S Ueda

Publications and source records attributed to S Ueda.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1998

Expression and purification of biologically active porcine follicle-stimulating hormone in insect cells bearing a baculovirus vector.

Biologically active recombinant porcine FSH (rec-pFSH) free from the cognate pituitary glycoprotein hormone LH was produced. It was synthesized by a baculovirus vector-insect cell system using two cDNAs encoding the glycoprotein alpha and FSH beta subunits. Its antigenicity was the same as that of pFSH prepared from the pituitary. Glycosylation of rec-pFSH was shown by tunicamycin treatment but the molecular mass of each subunit was lower than that of pituitary-derived FSH, because of the absence of trimming of terminal sugars in insect cells. Rec-pFSH was secreted into the culture medium at about 1 mg/l and purified in six fractions, because of the heterogeneity of the sugar group, by S-Sepharose and concanavalin A-Sepharose column chromatography. The biological activity of rec-pFSH was examined by measuring its effect on progesterone secretion from porcine granulosa cells and germinal vesicle breakdown (GVBD) of porcine oocytes. It showed adequate activity with respect to progesterone secretion, although some fractions rich in the sugar group showed lower activity than that of pituitary-derived FSH. It exhibited higher GVBD activity than that of pituitary-derived FSH at concentrations as low as 1 ng/ml. These results demonstrate that the baculovirus vector-insect cell system can provide biologically active rec-pFSH.

Animals↗
PubMed1998

Hyperperfusion syndrome following carotid endarterectomy: evaluation using diffusion-weighted magnetic resonance imaging--case report.

A 65-year-old female developed hyperperfusion syndrome following carotid endarterectomy for severe stenosis of the left internal carotid artery. Transcranial Doppler monitoring showed a sharp increase in flow velocity in the middle cerebral artery (MCA). Diffusion-weighted magnetic resonance (MR) imaging demonstrated diffuse hyperintensity in the region of the left MCA, which diminished markedly 9 days later. The abnormal hyperintensity decreased as the patient's symptoms improved, suggesting that diffusion-weighted MR imaging can be used for evaluating the course of hyperperfusion syndrome.

Aged↗
PubMed1998

Determination of glycated albumin by enzyme-linked boronate immunoassay (ELBIA).

A new affinity method for quantification of glycated albumin by an enzyme-linked boronate-immunoassay (ELBIA) has been established, based on the interaction between boronic acids and the cis-diols of glycated human serum albumin (HSA) trapped by anti-HSA antibody. To evaluate the ELBIA, we first examined the accuracy of the conventional boronate affinity chromatographic (BAC) method. In the BAC method, 8.1-18.9% of nonglycated albumin calibrator nonspecifically bound to the boronate affinity column, values that were regarded as the column blank. In the modified BAC method, therefore, we substracted the column blank value from the measured glycated albumin value to obtain the true value. Because glycated albumin values measured by ELBIA were exactly the same as reported by the modified BAC method, we suggest that the ELBIA results reflect the real status of albumin glycation. We have also developed a fully automated ELBIA system, allowing multiple, rapid, and precise measurements of glycated albumin.

Boronic Acids↗
PubMed1998

Fluorine-18-labeled fluoroboronophenylalanine PET in patients with glioma.

UNLABELLED: We synthesized fluorine-18-labeled fluoroboronophenylalanine (18F-10B-FBPA), an analog of boronophenylalanine (10B-BPA), and characterized its pharmacokinetics in patients with glioma. We conducted PET studies on three types of gliomas to clarify the relationship between tumor grade and each rate constant [K1 (ml/g/min), k2 (min[-1]) and k3 (min[-1])], and here, we discuss the metabolism of the 10B-BPA analog (18F-10B-FBPA). METHODS: Thirty-three cases of primary gliomas were studied by dynamic PET using DL-18F-10B-FBPA or L-18F-10B-FBPA. Dynamic PET images of 18F-10B-FBPA incorporation into tumors were obtained, and the arterial blood samplings were performed in all cases. RESULTS: When the dynamic PET data were represented as Gjedde-Patlak plots, there was a positive slope, suggesting the involvement of the putative metabolic pool of this tracer. A three-compartment model using rate constants (K1, k2 and k3) was used for the kinetic analysis. The accumulation of 18F-10B-FBPA was found to correlate with the degree of malignancy, and the L form of 18F-10B-FBPA was taken up better than was the DL form. The results of dynamic PET analysis suggested that K1 (measuring amino acid transport process) is a major factor determining the accumulation of 18F-10B-FBPA. A comparison of the rate constants revealed that k3 (metabolic process) did not correlate with the degree of malignancy. The absence of evident differences in k3 between DL and L forms suggests that k3 represents phenomena that are not dependent on the native form of L. CONCLUSION: These PET data will be of practical use for diagnosis of malignancy and direct prediction of the effectiveness of boron neutron capture therapy using 10B-BPA.

Astrocytoma↗
PubMed1998

[Functional deterioration in adults with cerebral palsy].

We studied functional deterioration in adults with cerebral palsy working at community workshops throughout Japan by interviews and direct examinations. The incidence of functional deterioration was 36%, being higher among those with involuntary movements of the head and neck, abnormal movement patterns when moving and those with reported in poor work environment. In more than one-half case, deterioration was associated with inadequate in noise control, lighting, air circulation from the cooling and heating systems, height of the chairs and desks, and height of VDT screens. Though the factors intrinsic to cerebral palsy were often responsible for the functional deterioration, environmental factors were also significant. Studies on the work environment as well as medical evaluations are needed.

Activities of Daily Living↗
PubMed1998

[Increase in pulmonary vascular permeability caused by increased adhesiveness of polymorphonuclear leukocytes and superoxide].

We report that mechanical stimulation of human neutrophils results in their accumulation in isolated rat lungs and in an increase in pulmonary vascular permeability. To determine whether reactive oxygen species were involved in this increase and, if so, whether it is mediate by xanthine oxidase metabolites, we assessed the effect of stimulated and unstimulated neutrophils, and of a superoxide scavenger, superoxide dismutase (SOD), and a xanthine oxidase inhibitor, allopurinol (ALLO) on pulmonary vascular permeability in isolated perfused lungs from Sprague-Dawley rats. Pulmonary vascular permeability in isolated rat lungs was assessed using a filtration coefficient determined by gravimetry. To quantify neutrophil accumulation in the lung, we measured myeloperoxydase (MPO). Neutrophils were stimulated by gentle agitation in a glass container for 10 s and Mac-1 was subsequently upregulated on the surface of the neutrophils. In lungs that received stimulated neutrophils, the pulmonary vascular filtration coefficient was about 5 times higher than in lungs that received unstimulated neutrophils. An increase in filtration coefficient was almost completely blocked by pretreatment with SOD or ALLO. However, the accumulation of stimulated neutrophils was not, or only partly, blocked by SOD or ALLO, respectively. We conclude that the increase in pulmonary vascular permeability caused by mechanically stimulated neutrophils was partly mediated by reactive oxygen species generated via the xanthine oxidase system.

Animals↗
PubMed1998

Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part I.

Determination of tumor boron-10 (10B) levels is required for accurate neutron dosimetry during boron neutron capture therapy. We assessed a new method for quantitative measurement of boronated drug uptake in high-grade gliomas. This method uses positron emission tomography (PET) with fluorine-18-labeled L-fluoroborono-phenylalanine (L-18F-10B-FBPA), which was synthesized as an analogue of L-boronophenylalanine. We studied the accumulation of L-18F-10B-FBPA by PET in patients with high-grade gliomas. Dynamic PET studies of brain tumors revealed that L-18F-10B-FBPA accumulated gradually after bolus injection, and the value of PET activity divided by the integrated plasma activity reached a constant level 42 min after injection, which was defined as the incorporation constant (Ic*). This constant reflected the appropriate L-18F-10B-FBPA accumulation in tumor tissue. Based on the Ic* constant, the methods for estimating tumor 10B concentration were devised. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This method was based solely on PET and can potentially provide data that would assist in the selection of patients for future treatment with boron neutron capture therapy after surgical resection of their brain tumors.

Boron↗
PubMed1998

Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part II.

Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study.

Boron↗
PubMed1998

Evaluation of intraaneurysmal blood velocity by time-density curve analysis and digital subtraction angiography.

PURPOSE: Our purpose was to evaluate intraaneurysmal blood velocity by using time-density curve analysis and digital subtraction angiography. METHODS: In 31 aneurysms, aneurysmal blood velocity was examined with digital subtraction angiography to determine mean transit time (MTF), peak density time (time to peak opacification) (PDT), and time to half-peak opacification (T1/2). Thirty frames per second were acquired, and the time-density curve was calculated. Regions of interest were drawn on the proximal parent artery, on the distal parent artery, and on the aneurysm itself. RESULTS: There was no significant difference in MTT of blood velocity in the proximal site on the parent artery, in the distal site on the parent artery, and in the aneurysm. Similarly, there was no significant difference in PDT in the parent artery, in the distal site on the parent artery, and in the aneurysm; nor was there a significant difference in T1/2 in the parent artery, in the distal site on the parent artery, and in the aneurysm; that is, intraaneurysmal blood velocity was similar to that in the parent artery. PDT and T1/2 of small aneurysms were faster than that of large aneurysms; that is, blood velocity of small aneurysms was faster than that of large aneurysms. CONCLUSION: Intraaneurysmal blood velocity in small aneurysms is similar to that in the parent artery; consequently, the central stream probably reaches the aneurysmal wall. Intraaneurysmal blood velocity in large aneurysms appears to be somewhat slower than that in small aneurysms.

Acute Disease↗