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Biomedical subjects

E Uchida

Publications and source records attributed to E Uchida.

At least 73 records · Page 4Linked to original sources
PubMed1995

Pharmacokinetic study of trimethadione and its metabolite in blood, liver and brain by microdialysis in conscious, unrestrained rats.

A microdialysis method has been developed in the past two decades to determine levels of drug and endogenous compounds in several organs under physiological conditions. In this study, we determined the pharmacokinetics of the model drug, trimethadione (TMO), and its only metabolite, dimethadione (DMO), in liver, blood and brain by the microdialysis method in freely-moving rats. Sampling times were extended up to 24 hours. The construction of a newly developed microdialysis probe for liver and blood is described. The elimination patterns of TMO in liver, blood and brain dialyzates were almost identical and the calculated t1/2 was approximately 3 hr in each sample. However, in brain, tmax was delayed compared with the others while the relative concentration of DMO (AUC0-24h) was lower in brain compared with liver and blood. These studies suggest that this concurrent and successive microdialysis sampling method will not only be a useful tool for pharmacokinetic and drug metabolism studies in the organs of small animals but will also decrease the number of experimental animals needed for a study.

Animals↗
PubMed1995

[Central ocular hypotensive effect of noradrenaline].

We investigated the effects of topical and central administration of noradrenaline (NA) on the intraocular pressure (IOP) in pigmented rabbits. Unilateral instillation of NA (200 micrograms) produced no significant change in IOP. On the other hand, intracerebroventricular (ICV) administration of NA (0.01-1 micrograms) decreased IOP in both eyes in a dose-related fashion. The ocular hypotensive effect of NA was diminished by sympathectomy of the superior cervical sympathetic nerve or by ICV pretreatment with yohimbine hydrochloride 1-10 micrograms). These results suggest that the hypotensive effects of contrally administered NA might be mediated by alpha 2-adrenoceptor stimulation in the central nervous system.

Administration, Topical↗
PubMed1995

[Application of microdialysis for pharmacokinetic study in rabbit anterior chamber].

We evaluated a microdialysis technique for analyzing the pharmacokinetics of instilled or orally administered ofloxacin in the anterior chamber of pigmented rabbits. A microdialysis probe was inserted into the anterior chamber and was perfused (2 microliters/min) with Ringer solution using a microinjection pump. Two hours later, 20 microliters of 0.15 and 0.3% ofloxacin was instilled into an eye, or 20 mg/kg of the drug was administered into the stomach through an intubated catheter. Dialysate was then collected every 15 or 20 min for 6 (instillation) or 8 (oral administration) hours. Ofloxacin concentration in dialysates was determined with a HPLC-spectrofluorometry system. Ofloxacin levels in dialysates increased after the instillation in a dose-related manner, reached a maximum at 30 and 45 min, and then decreased gradually with t1/2 of 136 and 114 min after the 0.15% and 0.3% instillation, respectively. After oral administration, ofloxacin levels in dialysates reached a maximum at 120 min and decreased with t1/2 of 175 min. These data suggest the usefulness of microdialysis for pharmacokinetic studies in the anterior chamber, since continuous and stable data can be obtained from each animal.

Animals↗
PubMed1995

The effects of inhibitors and substrates of different types of cytochrome P450 isozymes on serum dimethadione/trimethadione ratio in rats in vivo.

Trimethadione(TMO) is regarded as a model drug for estimating the hepatic drug oxidative capacity in vivo. However, the P450 isozymes that are responsible for TMO N-demethylation have not been identified clearly yet. This study was designed to determine these P450 isozymes that participate in the TMO N-demethylation in vivo by employing several typical P450 inhibitors and substrates. Male Sprague-Dawley(SD) rats were pretreated with P450 inhibitors or substrates before TMO(100mg/kg, p.o.) treatment. Serum dimethadione(DMO)/TMO ratios were employed for the assessment of metabolic capacity toward TMO. Pretreatment with imidazole and acetone significantly decreased the DMO/TMO ratios in a dose related manner. Weaker inhibitory effects were observed with SKF525A. However, pretreatment with alpha-naphthoflavone, quinine, debrisoquine, triacetyloleandomycin and lauric acid did not affect the ratios. These results suggest that various forms of P450 are involved in TMO metabolism to some extent and that CYP2E1 is attributed to major P450 isozyme for TMO N-demethylation in vivo.

Animals↗
PubMed1994

The enhancement of the extracellular carboxyl-terminal domain of human growth hormone receptor on growth hormone dependent responses of 3T3-F442A cells.

We have expressed the carboxyl-terminal domain (C domain) of the cytokine receptor homologous (CRH) region of human growth hormone receptor (hGHR) as a protein fused with maltose binding protein (MBP) in E. coli. Following proteolytic cleavage by restriction protease factor Xa, the C domain was purified to homogeneity as a monomeric form. The purified C domain appears to be folded properly judged by NMR spectrum and the far-UV circular dichroism (CD) spectrum. The C domain did not exhibit ligand binding activity. However, the C domain enhanced the human growth hormone (hGH) dependent differentiation of preadipose 3T3-F442A cells into adipose cells and the phosphorylation of a 34 kDa membrane protein.

Adipocytes↗
PubMed1994

Characterization of haemolyser-resistant cells increased in the blood of erythropoietin-treated mice.

Recently, we reported a new in vivo assay method for erythropoietin (Epo) by means of counts of the number of haemolyser-resistant cells (HRCs) increased in Epo-injected mice. Here, we attempted to characterize the HRCs. Flow-cytometric studies revealed that HRCs obtained from Epo-injected mice expressed the transferrin receptor on their surface membranes. Furthermore, a fluorophotometric study suggested that the number of transferrin receptor-positive cells increased in a dose-dependent manner in response to treatment with Epo. On the other hand, flowcytometric and fluorophotometric studies of glycophorin A on HRCs using a rabbit antiglycophorin A antibody also showed a high expression of glycophorin A on them as compared with on HRCs from vehicle-treated animals (control). The results indicated that HRCs could be defined by their expression of both transferrin receptors and glycophorin A. We concluded that HRCs might be immature reticulocytes.

Animals↗
PubMed1994

Dexamethasone-induced haptoglobin release by calf liver parenchymal cells.

Parenchymal cells were isolated from the liver of male calves, and monolayer cultures formed were treated with glucocorticoids to examine whether haptoglobin, appearance of which is associated with hepatic lipidosis (fatty liver) in cattle, is induced by steroid hormones. Without addition of dexamethasone, only trace amounts of haptoglobin were detected in culture medium. With addition of dexamethasone (10(-12) to 10(-4) M), considerable amounts of haptoglobin were released into the medium. Maximal release was observed at concentrations of 10(-8) to 10(-6) M dexamethasone. Haptoglobin release was similarly induced by cortisol, although the effect was less potent than that of dexamethasone. Actinomycin D (a known protein synthesis inhibitor) dose-dependently reduced amounts of haptoglobin released in response to 10(-8) M dexamethasone. Dexamethasone also induced annexin I, which is known to be synthesized in response to glucocorticoids. Dexamethasone treatment resulted in reduced protein kinase C activity in the cell cytosol, which has been shown to be an early event in dexamethasone-treated cells. Other than glucocorticoids, estradiol induced haptoglobin release, whereas progesterone was less effective. The association of haptoglobin with hepatic lipidosis can be reasonably explained by the fact that haptoglobin production by the liver is induced by glucocorticoids and estradiol, and these steroid hormones are triggers for development of hepatic lipidosis in cattle.

Animals↗
PubMed1993

Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage.

Acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) are mitogenic polypeptides that may contribute to cancer cell proliferation. In the present study we examined aFGF and bFGF expression in human pancreatic cancer. Northern blot analysis of total RNA isolated from 12 pancreatic cancers revealed elevated aFGF and bFGF mRNA levels in 12 and 10 samples, respectively, by comparison with the normal human pancreas. Immunostaining demonstrated the presence of aFGF and bFGF in many cancer cells and in the atrophic acini and ducts adjacent to the cancer cells, but to a much lesser extent in the surrounding fibroblasts. By in situ hybridization, both mRNA moieties colocalized with their respective proteins and were abundant in many cancer cells. Immunoblotting confirmed that cancer tissues with increased aFGF and bFGF immunoreactivity contained elevated levels of both proteins. To determine the significance of aFGF and bFGF expression in the pancreatic cancer cells, immunohistochemical analysis of 78 human pancreatic carcinomas was performed. aFGF and bFGF immunoreactivity was present in the cancer cells in 47 (60%) and 44 (56%) of the tumors, respectively. There was a significant correlation between the presence of either aFGF or bFGF in the cancer cells and advanced tumor stage, and the presence of bFGF and shorter patient survival. These data suggest that aFGF and bFGF are overexpressed in a significant proportion of human pancreatic carcinoma cells and that this overexpression may contribute to disease progression.

Adult↗
PubMed1993

Radial and median nerve conduction velocities in workers exposed to lead, copper, and zinc: a follow-up study for 2 years.

To evaluate the interactive effects of lead, zinc, and copper on the peripheral nervous system in man, we measured maximal motor and sensory conduction velocities (MCV and SCV) in the distal radial and median nerves in 19 gun metal foundry workers with asymptomatic increased absorption of these metals twice at a 12-month interval. The workers' initial blood lead (BPb) concentrations ranged from 16 to 64 (mean, 42) micrograms/dl. The principal findings in the present study indicated that (1) radial and median nerve conduction velocities were significantly slowed in the gun metal foundry workers; (2) indicators of lead absorption were inversely related to radial nerve conduction velocities, whereas indicators of copper and zinc absorption were positively correlated with the radial and median nerve conduction velocities; and (3) yearly changes in MCV in the radial nerve and in SCV in the median nerve were positively correlated with the changes in indicators of copper and zinc absorption. These findings suggest that zinc and copper antagonize the subclinical neurologic effects of lead. Also, the radial and median nerve conduction velocities provide important indicators of subclinical lead toxicity.

Adolescent↗
PubMed1993

Assessment of central, peripheral, and autonomic nervous system functions in lead workers: neuroelectrophysiological studies.

To assess the effects of lead on central, peripheral, and autonomic nervous systems, the visual-, short-latency somatosensory-, and brainstem auditory-evoked potentials (VEP, SSEP, and BAEP), event-related potential (P300), distribution of nerve conduction velocities (DCV), and electrocardiographic R-R interval variability (CVRR), together with conventional median and radial nerve conduction velocities (NCV), were measured in the lead workers. The lead workers consisted of 22 gun metal foundry workers occupationally exposed to lead, zinc, and copper. In the lead workers with blood lead concentrations below 65 micrograms/dl, the latencies of the VEP (from the retina to the visual cortex), SSEP (from the brachial plexus to the brainstem), and P300 (which reflects cognitive function) were significantly prolonged when compared with the sex- and age-matched controls. All these latencies and the BAEP latencies (from the cochlear nerve to the brainstem) were significantly correlated with the indicators of lead absorption among these workers. The CVRR (especially, a component of parasympathetic activity) was significantly depressed in the lead workers. The slower (V10) velocity of the DCV, the motor, and sensory NCVs were also significantly slowed. These findings suggest that lead affects not only peripheral nerve but also the central and autonomic nervous functions at a subclinical level; zinc may antagonize the neurotoxic effects of lead.

Adult↗
PubMed1993

Are faster or slower large myelinated nerve fibers more sensitive to chronic lead exposure? A study of the distribution of conduction velocities.

To determine which of the faster and slower large myelinated nerve fibers (alpha fiber group) are more sensitive to chronic lead exposure, the distribution of nerve conduction velocities (DCV) as well as conventional sensory nerve conduction velocity (SCV) were measured once a month for 20 and 11 months in two male lead workers with blood lead concentrations of 70 to 121 and of 63 to 85 micrograms/dl, respectively. Differences in the frequency beyond the "normal" ranges between conduction velocities of faster nerve fibers (V80, V90, or SCV) and those of slower fibers (V10 or V20) were analyzed by the McNemar test. In the two lead workers, the values below the lower normal limits for the V80 and V90 velocities were more frequent than those for the V10 and V20 velocities; similarly, lower values for the SCV were more frequent than those for the V10 and V20 velocities (P < 0.05). It was suggested that faster nerve fibers are more sensitive to chronic lead exposure than slower nerve fibers. These findings agree with our published data on the effects of local vibration, thallium, n-hexane, styrene, mixed organic solvents, alcohol dependency, and diabetes mellitus.

Humans↗
PubMed1993

The relationship between the expression of blood group-related antigens and the cell proliferation of pancreatic carcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters.

The relationship between expression of blood group-related antigens (BGRAs) A, B, H, and cell proliferation was investigated during pancreatic carcinogenesis and in transplanted pancreatic carcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters. Immunohistochemical staining was performed using monoclonal antibodies (MoAbs) against BGRAs A, B, H, and bromodeoxyuridine (BrdU). The labeling index (LI) was determined as the ratio of the number of BrdU-labeled cells to the total number of cells counted in each lesion. During carcinogenesis, the LI was observed to increase in line with the increase in the extent of atypism (P < 0.01). The mean LIs of the hyperplasia, atypical hyperplasia, and carcinoma were 0.32, 3.21, and 10.2, respectively. The mean LIs of transplanted carcinomas were higher than those of the original carcinomas (P < 0.01). The reactivity with each of the antibodies was determined using an arbitrary scoring system. Staining with MoAbs A and B (staining intensity; 1+ to 3+) appeared to be more intense than that with MoAb H (1+ to 2+) during carcinogenesis. Regarding the growth rate, which was very high, in the transplanted carcinomas, MoAb A reacted with all the cancer cells (4+), whereas, MoAbs B and H reacted with fewer cells (1+ to 3+). These results indicate that the A antigen in particular is associated with the cell proliferation of pancreas, especially with carcinoma induced in hamsters.

ABO Blood-Group System↗
PubMed1993

Stereoselective pharmacokinetics of oral felodipine and nitrendipine in healthy subjects: correlation with nifedipine pharmacokinetics.

The pharmacokinetics of racemic (rac) felodipine, rac-nitrendipine and nifedipine (all given as an oral dose of 20 mg in solution) have been investigated in a randomised cross-over study in 12 healthy male subjects using stereoselective assays. Both felodipine and nitrendipine exhibited stereoselective pharmacokinetics. On average, the AUCs of the active (S)-enantiomers of felodipine and nitrendipine were 139% and 104% higher than those of their optical antipodes, but the elimination half-lives of the enantiomers of each racemate were not different. The AUCs of nifedipine, rac-felodipine, rac-nitrendipine and of their enantiomers were highly correlated (all r > 0.83), suggesting closely related rate limiting steps in the in vivo first-pass metabolism of these high-clearance drugs. Stereoselectivity was only a minor contributor to inter-individual variability in the oral pharmacokinetics of these compounds in healthy subjects.

Administration, Oral↗
PubMed1993

Site-directed mutagenesis of hGH at the 54-74 loop selectively modifies its lactogenic receptor-mediated biological activity.

Four analogues of human growth hormone (hGH) mutated by site-directed mutagenesis at the 54-74 loop-Met-hGH(P59A), Met-hGH(P61A), Met-hGH(P59A,P61A) and Met-hGH(Des 62-67) were analyzed for: (1) their biological activity mediated through lactogenic receptors using rat lymphoma Nb2-11C cell proliferation and mouse mammary gland HC-11 cell beta-casein synthesis bioassays and (2) their ability to interact with recombinant hGH binding protein (hGHBP). The analogues Met-hGH(P59A), Met-hGH(P61A) and Met-hGH(P59A,P61A) partially lost their activity relative to native hGH in the HC-11, but not in the Nb2-11C cell bioassay. These analogues were nevertheless capable of forming a 1:2 complex with a recombinant hGH binding protein (hGHBP), despite the fact that the affinity of Met-hGH(P61A) and Met-hGH(P59A,P61A) analogues had decreased 8- and 14-fold, respectively. Met-hGH(Des 62-67) failed to form 1:1 or 1:2 complexes with hGHBP and did not compete with [125I]hGH for binding to hGHBP. It lost all biological activity in HC-11 cells, but retained 0.4% of its activity, in the Nb2-11C cell proliferation bioassay. These results confirm the involvement of Pro-61 in the hGH binding and activity mediated through somatogenic receptors, while the activity mediated through two different types of lactogenic receptors was selectively modified. These findings emphasize the fact that lactogen receptors in different species or organs are not identical.

Animals↗
PubMed1993

Socioeconomic factors affecting marriage, divorce and birth rates in a Japanese population.

The effects of low income, urbanisation and young age population on age-adjusted rates of first marriage, divorce and live birth among the Japanese population in 46 prefectures were analysed by stepwise regression for 1970 and for 1975. During this period, Japanese society experienced a drastic change from long-lasting economic growth to serious recession in 1973. In both 1970 and 1975, the first marriage rate for females was inversely related to low income and the divorce rates for both males and females were positively related to low income. The live birth rate was significantly related to low income, urbanisation and young age population only in 1975. The first marriage rate for females and the divorce rates for both sexes increased significantly but the first marriage rate for males and live birth rate significantly decreased between 1970 and 1975. These findings suggest that low income was the essential factor affecting first marriage for females and divorce for males and females.

Adolescent↗
PubMed1993

Saponin and sapogenol. L. On the constituents of the roots of Glycyrrhiza uralensis Fischer from Xinjiang, China. Chemical structures of licorice-saponin L3 and isoliquiritin apioside.

From the air-dried roots of Glycyrrhiza uralensis Fischer collected in Xinjiang province, China ("Shinkyo-Kanzo" in Japanese), a new oleanene-type triterpene oligoglycoside named licorice-saponin L3 and a new chalcone oligoglycoside named isoliquiritin apioside were isolated together with glycyrrhizin, 18 alpha-glycyrrhizin, apioglycyrrhizin, araboglycyrrhizin, licorice-saponins A3, E2, G2, and H2, and six known flavonoid glycosides. On the basis of chemical and physicochemical evidence, the structures of licorice-saponin L3 and isoliquiritin apioside were elucidated as 3 beta-[alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl(1--> 2)-beta-D-glucuronopyranosyloxy]-22 beta-acetoxy-24-hydroxyolean-12-en-30-oic acid (1) and 4-O-[beta-D-apiofuranosyl(1-->2)-beta-D- glucopyranosyl]isoliquiritigenin (6), respectively.

Chalcone↗
PubMed1993

Purification and identification of a serum protein increased by anthelmintic drugs for Dirofilaria immitis in dogs.

Polyacrylamide gel electrophoretic analysis of canine serum protein has revealed that the administration of anthelmintics elicits an increase in a certain serum protein. This protein, named PT60, was partially purified by ammonium sulfate fractionation and preparative electrophoresis. The purified PT60 gave a single band with the molecular size of 53 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions. After reduction with 2-mercaptoethanol, two bands appeared at 35 kDa and 17 kDa, indicating that PT60 consists of two subunits which are linked with each other by disulfide bonds. PT60 had the capacity to bind to hemoglobin. In an immunodiffusion test, an antiserum against PT60 cross-reacted with canine haptoglobin (Hp). N-terminal amino acid sequences of two PT60 subunits were identical to those of alpha and beta subunits of canine Hp, respectively. Thus, PT60 was identified as Hp.

Amino Acid Sequence↗