Search PubMed⌕ Search

Biomedical subjects

E Uchida

Publications and source records attributed to E Uchida.

At least 109 records · Page 6Linked to original sources
PubMed1992

Induction of fatty liver in cows by ethionine administration and concomitant decreases of serum apolipoproteins B-100 and A-I concentrations.

Ethionine, an analogue of methionine, induces fatty liver in rats by inhibiting protein synthesis, including that of apolipoproteins in liver. Ethionine was administered to cows to elucidate the participation in fatty liver development of impaired triglyceride secretion from liver attributable to decreased apolipoprotein synthesis. The administration resulted in a significant increase of liver triglyceride contents. Several apolipoproteins were found to have decreased concentrations. In particular, apolipoprotein B-100 in very low-density (0.95 to 1.006 g/ml) lipoprotein and in low-density (1.006 to 1.063 g/ml) lipoprotein fractions was greatly reduced. The decreases of apolipoprotein B-100 concentrations in the 2 lipoprotein fractions were at least partly correlated to the decreased triglyceride concentrations in the respective fractions. Decreased concentrations of apolipoprotein A-I in high-density (1.063 to 1.210 g/ml) lipoprotein were also observed, although not as distinctly as with apolipoprotein B-100. Total cholesterol and phospholipid concentrations in low- and high-density lipoprotein fractions were decreased. The decrease in cholesterol was attributed to reduced concentrations of cholesteryl esters. It was suggested that the impaired lipid secretion from liver attributable to the decreased apolipoprotein concentrations has a role in ethionine-induced fatty liver of cows.

Animals↗
PubMed1992

[The role of sympathetic cervical ganglion in the effect of clonidine for lowering intraocular pressure].

The contribution of sympathetic cervical ganglion to the mechanism of action of clonidine for lowering intraocular pressure (IOP) was investigated. Pigmented rabbits were used. The animals were divided into 3 groups: normal control group (group 1), animals in which the bilateral cervical sympathetic trunks had been amputated presynaptically (group 2), animals in which the superior cervical ganglion (SCG) had been bilaterally dissected (group 3). Changes in IOP were measured after topical application of clonidine unilaterally. In group 1, IOP was significantly decreased in eye treated by clonidine and contralateral eyes compared to pretreatment values. Decrease of IOP in the contralateral eye was greater than that in the treated eye. In group 2, IOP was decreased in the contralateral eye but increased in the eye treated by clonidine. Pretreatment of yohimbine administered orally antagonized the ocular hypotensive effect of clonidine in a dose-related manner. In group 3, where SCGs were dissected, no changes in IOP were observed in both eyes by unilateral administration of clonidine. These results suggested that the bilateral ocular hypotensive effect of clonidine administered unilaterally is in part due to direct action on the SCG and that the alpha 2 receptor in the SCG plays some role in the regulation of IOP.

Animals↗
PubMed1991

Effect of insulin, glucagon or dexamethasone on the production of apolipoprotein A-IV in cultured rat hepatocytes.

We studied the effects of insulin, glucagon or dexamethasone on the production of apolipoprotein A-IV (apo A-IV) by cultured rat hepatocytes, using specific radioimmunoassay for rat apo A-IV. We also compared the effect of these hormones on the production of apo A-IV with those of albumin and apo A-I, reported previously. In the absence of hormones, apo A-IV and albumin in culture medium increased almost linearly for periods up to 24 h. The rates of accumulation of apo A-IV and albumin in the medium were 15.4 ng/mg cell protein per h and 1.2 micrograms/mg cell protein per h, respectively. The concentration of intracellular apo A-IV remained constant during the incubation. Insulin stimulated the production of albumin, but inhibited the production of apo A-IV dose-dependently. Glucagon inhibited the production of both albumin, and apo A-IV dose-dependently. Dexamethasone showed no significant effects on albumin production, but stimulated apo A-IV production. Thus, apo A-IV production in hepatocytes is regulated by several hormones with different effects on albumin production. The regulatory effects of these hormones on apo A-IV production were almost identical with the effects observed in a course of apo A-I synthesis, suggesting that the production of the two apoproteins are regulated by similar mechanisms.

Albumins↗
PubMed1991

Circadian rhythm of regular spike-wave discharges in childhood absence epilepsy.

Four girls with childhood absence epilepsy with several seizures every day were investigated using an ambulatory cassette EEG. Recordings were started at about 6 pm, and were run continuously for about 22 hours. We studied only the regular and symmetrical 3 Hz spike-wave discharges of at least 5 seconds duration, which are quite similar to or identical with those found in the clinical seizures. Regular spike-wave discharges occurred frequently during wakefulness in 2 cases and during sleep in the other 2 cases: in the latter, they occurred rarely during wakefulness. During wakefulness, we did not find a special time zone in which regular spike-wave discharges were facilitated; during nocturnal sleep, however, they were concentrated in the last third. The rate of regular spike-wave discharges per hour was the highest during stage 1, low during stages 2 and REM, and zero during stage 3 + 4. Average duration of regular spike-wave discharges was the longest during wakefulness in most cases, and shortest during stage 2 in all the cases.

Child↗
PubMed1991

Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans.

The effects of grapefruit juice (150 ml at -15, -10, -1/4, +5, and +10 hours) and cimetidine (200 mg at the same times) on the stereoselective pharmacokinetics and effects of 20 mg oral racemic nitrendipine were investigated in a placebo-controlled crossover study in nine healthy men. In all subjects the AUC of racemic nitrendipine was increased by grapefruit juice (mean increase 106%; 95% confidence interval 64% to 158%) and cimetidine treatment (+154%; 95% confidence interval 77% to 265%). Comparable results were obtained for the peak plasma drug concentration and for both parameters of (S)- and (R)-nitrendipine. There were highly significant differences in the area under the concentration-time curve and peak plasma drug concentration between enantiomers within all treatments. Grapefruit juice had no effect on this stereoselectivity, but cimetidine increased the mean S/R ratio of areas under the curve (2.25) by 20% (95% confidence interval 12% to 29%) compared with placebo treatment (1.89). Half-lives and time to reach peak concentration of the enantiomers were not different within and between treatments. There were no consistent effects on blood pressure with all treatments, but in most subjects there was a small temporary increase in heart rate after intake of nitrendipine. Grapefruit juice and cimetidine did not affect these hemodynamic parameters and did not cause additional adverse effects.

Adult↗
PubMed1991

The effects of diltiazem on hepatic drug metabolizing enzymes in man using antipyrine, trimethadione and debrisoquine as model substrates.

Six healthy male subjects were given single oral doses of antipyrine (7 mg kg-1), trimethadione (4 mg kg-1) and debrisoquine (10 mg) before and during diltiazem treatment (30 mg three times daily orally for 8 days). Antipyrine clearance decreased from 33.7 +/- 9.1 to 22.5 +/- 4.9 ml min-1 (P less than 0.05, mean +/- s.e. mean) after diltiazem treatment without any significant change in apparent volume of distribution (0.59 +/- 0.06 to 0.60 +/- 0.04 1 kg-1), resulting in an increase in antipyrine elimination half-life from 13.4 +/- 4.8 to 19.7 +/- 3.2 h (P less than 0.05). The formation clearance of antipyrine to 4-hydroxyantipyrine was decreased significantly from 10.8 +/- 2.7 to 6.6 +/- 2.7 ml min-1 (P less than 0.05), while that to 3-hydroxymethylantipyrine and norantipyrine was not altered by diltiazem. The metabolic ratio of debrisoquine (urinary excretion of debrisoquine/4-hydroxydebrisoquine) was increased significantly from 0.70 +/- 0.05 to 1.95 +/- 0.20 (P less than 0.05), while that of trimethadione (serum concentration of dimethadione/trimethadione) was not changed significantly (0.48 +/- 0.08 vs 0.41 +/- 0.06) after diltiazem treatment. Diltiazem selectively inhibits cytochrome P-450 isoenzymes.

Adult↗
PubMed1991

The secretion leader of Mucor pusillus rennin which possesses an artificial Lys-Arg sequence directs the secretion of mature human growth hormone by Saccharomyces cerevisiae.

The prepro-peptide of fungal aspartic proteinase, Mucor pusillus rennin, is useful as a secretion leader for efficient secretion of human growth hormone (HGH) from Saccharomyces cerevisiae. For secretion by yeast cells of HGH with the same NH2 terminus as native HGH, an artificial Lys-Arg linker, which is one of the potential KEX2 recognition sequences, was introduced at the junction between the M. pusillus rennin secretion leader and mature HGH. The HGH directed by this construction was the same size as native HGH, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and amino acid sequencing of its NH2 terminus revealed that the secretion leader peptide was removed correctly at the COOH-terminal side of the Lys-Arg linker. On the other hand, when the same plasmid was expressed in a kex2 mutant strain, unprocessed HGH of a higher molecular weight was secreted, indicating that no proteolytic cleavage at the Lys-Arg site occurred. These results clearly showed that the leader peptide with the Lys-Arg linker was recognized and specifically cleaved by the yeast KEX2 protease. The mature HGH purified from yeast culture medium was indistinguishable from native HGH in biological activity, determined by the adipocyte conversion assay, and in secondary structure, determined by circular dichroism spectroscopy.

Amino Acid Sequence↗
PubMed1991

Activity of artificial mutant variants of human growth hormone deficient in a disulfide bond between Cys53 and Cys165.

In order to understand the role of Cys53 and Cys165 of human growth hormone (hGH) in receptor-binding and biological activity, artificial mutant variants of hGH were prepared in Escherichia coli by in vitro mutagenesis. Variants of hGH were constructed by replacement of Cys165 with Ala ([Ala165]hGH) or Ser ([Ser165]hGH), by replacement of Cys53 with Ala ([Ala53]hGH), by replacement of Cys53 and Cys165 with Ala ([Ala53, Ala165]hGH), or by replacement of Cys53 with Ala and Cys165 with Ser ([Ala53,Ser165]hGH). All of the variants constructed as well as reduced hGH exhibited less biological activity than that of intact hGH, and the decreases in biological activity were almost equal, as measured by a sensitive biological assay for growth hormone: adipose conversion assay using 3T3-F442A cells. These variants also showed less receptor-binding activity than that of intact hGH. These results suggest that it is possible neither the residue Cys53 nor Cys165 is directly involved in the receptor binding, and that the disulfide bridge between Cys53 and Cys165 in hGH may not always be crucial for the biological activity, though necessary to express full hGH activity.

Animals↗
PubMed1991

[A case report of esophageal liposarcoma].

We report the first case of esophageal liposarcoma in Japan. A 46-year-old female was admitted to our hospital with chief complaint of protruding tumor out of the mouth. She had two episodes of protruding tumor after nausea in last 6 months. Barium swallow showed a large polypoid lesion of approximately 16cm in length with a stalk. By endoscopic examination, it was the polyp originated from the anterior wall of the cervical esophagus. It was covered with intact squamous epithelia, which had slight redness and erosion in the apex. Under general anesthesia the tumor was cut off at the base through the oral cavity. Specimen was 11 x 4 x 3cm in size and had yellowish cut surface. Histologically, the tumor composed of mature adipocytes and many atypical lipoblasts with spider web shaped cytoplasm. We diagnosed this tumor as well differentiated liposarcoma.

Esophageal Neoplasms↗
PubMed1991

Effect of insulin, glucagon or dexamethasone on the production of insulin-like growth factor I in cultured rat hepatocytes.

We studied the effect of insulin, glucagon or dexamethasone on the production of insulin-like growth factor I (IGF-I) by cultured rat hepatocytes. Hepatocytes were isolated from normal adult rat livers and cultured in MEM, as nearly confluent monolayers. In the absence of such hormones, IGF-I and albumin accumulated in the culture medium almost linearly for periods up to 24 hours with the accumulation rates of 140 mU/mg cell protein per hour and 1.2 micrograms/mg cell protein per hour, respectively. Cycloheximide (5 micrograms/ml) almost completely inhibited the accumulation of IGF-I and albumin in the medium. Insulin at concentrations over 10(-10) M significantly inhibited the production of IGF-I in spite of the increased production of albumin. Conversely, glucagon stimulated the production of IGF-I at concentrations over 10(-8) M, but inhibited the production of albumin at concentrations over 10(-10) M. Dexamethasone stimulated the production of IGF-I at concentrations over 10(-7) M, but had no significant effects on the production of albumin. Thus, IGF-I production of hepatocytes is regulated by several hormones with different manner from albumin production.

Animals↗
PubMed1990

An active site of growth hormone for eliciting the differentiation of preadipose 3T3-F442A cells to adipose cells.

In order to elucidate the active sites of growth hormone for eliciting the differentiation of preadipose 3T3-F442A cells to adipocytes, four artificial mutant variants of human growth hormone (hGH) modified in the loop region of amino acid residues 54-74 were prepared in Escherichia coli by site-directed mutagenesis. Although the P59A (replacement of Pro59 with Ala) variant retained almost the same biological- and receptor binding-activity as hGH, the P61A (replacement of Pro61 with Ala) and the P59A-P61A (replacement of both Pro59 and Pro61 with Ala) both exhibited about half the activity, and the delta (62-67) variant (deletion of the residues 62-67) exhibited only about 0.1% the activity of those of intact hGH. The results suggest that Pro61 may be involved in formation of the active conformation of hGH, but Pro59 may not, and that the amino acid residues around 62-67 may be critical for the specific biological features of hGH.

Adipose Tissue↗
PubMed1990

Archaebacterial ATPases: relationship to other ion-translocating ATPase families examined in terms of immunological cross-reactivity.

Immunological cross-reactivity among three types of H(+)-ATPases, that is, three archaebacterial ATPases, the F1-ATPase from thermophilic bacterium PS3 (TF1) and the vacuolar membrane ATPase from Saccharomyces cerevisiae, was examined by means of immunoblot analyses. The three archaebacterial ATPases were very similar in immunological cross-reactivity, suggesting that they belong to the same family of ATPases. Cross-reaction was also observed between the ATPase from Sulfolobus acidocaldarius, one of the three archaebacteria, and TF1. S. cerevisiae vacuolar ATPase reacted with the antibodies prepared against each of the three archaebacterial ATPases, but did not react with the antibody against TF1. Electron microscopic examination revealed that the oligomeric structure of Sulfolobus ATPase was very similar to that of F1-ATPase. These results, taken together, suggest that the archaebacterial ATPases share close structural similarities with the vacuolar ATPases, and, to a lesser degree, with the F0F1-ATPases.

Adenosine Triphosphatases↗
PubMed1990

Effects of glucocorticoids on deoxyribonucleic acid (DNA) synthesis stimulated by growth factors in cultured rat skin fibroblasts.

The effects of glucocorticoids on deoxyribonucleic acid (DNA) synthesis were studied by using confluent cultured rat skin fibroblasts prepared by enzymatic dispersion and expanded up to passage 3. Dexamethasone caused the inhibition of the DNA synthesis stimulated by 10% fetal calf serum (FCS) in a dose dependent manner. Maximum inhibition (90%-100%) was achieved by the concentration of 10(-7)M. A similar dose dependent inhibition was also obtained in the experiment using epidermal growth factor (EGF) (1 ng/ml) as a stimulant. Dexamethasone (10(-7)M) also inhibited the DNA synthesis stimulated by somatomedin C (100 ng/ml) or platelet derived growth factor (1 half-maximum unit/ml) almost to control levels. Binding studies with 125I-labeled EGF suggested that dexamethasone caused this inhibitory action without modulation of cell surface receptors for EGF. Furthermore, the effects of a variety of glucocorticoids on the DNA synthesis were studied to clarify the structural requirement of glucocorticoids for the inhibition of the DNA synthesis. The results showed that 11 beta-hydroxyl and 21-hydroxyl groups on the steroid nucleus were necessary for the inhibition of the growth factor-stimulated DNA synthesis. Meanwhile, the inhibitory action on the DNA synthesis was markedly diminished by the replacement of a 16 alpha-methyl group by a 16 beta-methyl group in the presence of a bulky group at C-17 (e.g. 17 alpha-valerate). For further elucidation of mechanisms of action of glucocorticoids on the inhibition of the growth factor-stimulated DNA synthesis, the relationships between the structural features of glucocorticoids and their binding ability to the glucocorticoid receptor ([3H]-dexamethasone-binding receptor) were studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Prolactin does not mediate the suppressive effect of the suckling stimulus on luteinizing hormone secretion in ovariectomized lactating rats.

The plasma LH concentration in ovariectomized lactating rats is low for 14 days postpartum, while the prolactin concentration is high during this period. We examined the effect of the inhibition of increased prolactin secretion with bromocriptine (CB-154) on the LH secretion in lactating rats ovariectomized on day 2 (day 0 = day of parturition). Blood samples were collected through an indwelling atrial cannula every day. LH levels were kept low until day 9 in lactating rats injected daily with CB-154 (0.6 mg/day, s.c.). The duration of the period during which LH secretion was suppressed was shorter in lactating rats treated with CB-154 than in saline-injected controls. The replacement with ovine prolactin by means of a mini-osmotic pump (0.3 mg/day, s.c.) in CB-154-treated lactating rats restored the duration of LH suppression. In rats deprived of their pups on day 2, the LH concentration rose immediately after removal of the pups and the LH level was not significantly different between rats treated with CB-154, ovine prolactin and saline, indicating that neither the CB-154 treatment nor the high level of prolactin alone has any effect on LH secretion in rats deprived of their pups. The present results clearly demonstrate that prolactin does not mediate the suppressing effect of the suckling stimulus on LH secretion in early lactation and support our theory that the suckling stimulus controls the LH and prolactin secretion independently at the hypothalamic level.

Animals↗
PubMed1990

[Immunohistochemical study on epidermal growth factor and its receptor in human pancreatic carcinoma].

We investigated immunohistochemical expressions of the epidermal growth factor (EGF) and the epidermal growth factor receptor (EGFR) in 25 cases of pancreatic carcinoma, including 13 cases of metastatic lymph nodes. EGF and EGFR were stained mainly in the cytoplasm and on the surface of some pancreatic carcinoma cells, with positive rates of 18/25 (72%) and 9/25 (36%) respectively. In all cases EGFR was noted only when EGF was also detected. EGF and EGFR were stained frequently in differentiated types. In metastatic lymph nodes, EGF and EGFR were found in 54% and 15% respectively, and they were detected only when they were also noted in the same patient's primary lesions. EGF and EGFR were found more frequently in Stages III and IV than in Stage II. These results emphasize that EGF and EGFR may promote both the proliferation and the differentiation of human pancreatic carcinoma cells, as in other sites.

Adult↗
PubMed1990

[Hepatic functional reserve and tumor size as prognostic factors in patients with primary liver cancer undergoing non-surgical therapy].

A prognostic study on 119 patients with primary liver cancer undergoing nonsurgical therapy was carried out to evaluate the relevance of hepatic functional reserve and tumor size to their cumulative survival rates. All patients were classified into the three groups of Child's classification (A, B and C) according to their hepatic functional reserve and were also divided into the five groups according to their tumor size. The cumulative survival rates of all patients at 1, 2, 3, 4 and 5 years after the diagnosis were 50.9, 28.3, 18.8, 13.5 and 6.7%, respectively. The cumulative survival rates of group V whose tumor occupied more than 40% of the liver area were significantly lower than those of the other tumor-size-groups. The survival rates of Child's group A were significantly higher than those of group B and C. But in those patients who were classified into group V according to their tumor size, there was no significant difference in their survival rates among the three groups of Child's classification. These results suggest that hepatic functional reserve as well as tumor size is an important prognostic factor in patients with primary liver cancer. But if the cancer once develops greater than 40% of the liver area, hepatic functional reserve diminishes in value as a prognostic factor.

Antineoplastic Agents↗