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Biomedical subjects

Y Kiuchi

Publications and source records attributed to Y Kiuchi.

At least 109 records · Page 6Linked to original sources
PubMed1991

A cyclic AMP phosphodiesterase inhibitor, 8'-pivaloyloxymethyl ester (POM-ester) of griseolic acid, lowers rabbit intraocular pressure.

The effects of griseolic acid (GA), a cyclic-AMP phosphodiesterase (PDE) inhibitor, and its 8'-pivaloyloxymethyl (POM) ester on intraocular pressure (IOP) in rabbits were investigated. When 50 microliters of 1 and 2% GA POM ester solutions were topically applied to one eye in normal rabbits, significant IOP decreases were detected at 2 hrs and at 1 to 5 hrs, respectively. Other than ocular hypotension, no other ocular effects were detected locally even after administration of 2% GA POM ester. A more marked reduction in IOP occurred after the intravitreal injection of the GA POM ester. IOP was also reduced when GA was used in an intravitreal injection but not when it was topically applied. The difference in permeability between GA and GA POM ester across the corneal epithelium may explain why GA failed to reduced IOP following topical administration. GA and the GA POM ester inhibited cAMP PDE in rabbit ciliary body at low concentrations, the I50 being 0.075 microM and 2.4 microM, respectively, with 0.25 microM cAMP as substrate. GA and the GA POM ester markedly increased cAMP levels in vitro in iris-ciliary body specimens. Possibly, GA POM ester or its analogues may represent a new mechanistic class of ocular hypotensive agents.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Effects of a cyclic AMP phosphodiesterase inhibitor, 8'-pivaloyloxymethyl ester of griseolic acid, on aqueous humor dynamics in rabbits.

The mechanism by which pivaloyloxymethyl (POM) ester of griseolic acid (GA), a potent cyclic AMP-phosphodiesterase inhibitor, lowers intraocular pressure (IOP) in albino rabbits was studied. The rate of aqueous flow, measured by fluorophotometry, was significantly lower in GA POM ester-treated eyes (2.36 +/- 0.24 microliters/min) than in control eyes (3.02 +/- 0.24 microliters/min). Topically applied GA POM ester did not alter tonographic outflow or uveoscleral outflow. No differences in aqueous humor protein concentrations between GA POM ester-treated and control eyes were observed. It was thought that the GA POM ester lowered the IOP by decreasing the aqueous inflow. Topical application of this compound caused no inflammatory response in the eye or changes in the blood aqueous barrier.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1991

[Effect of topical 8-hydroxy carteolol on intraocular pressure and melanin granules].

It was reported that 8-Hydroxycarteolol (8-OH CA), the major metabolite of carteolol hydroxychloride (CA), has a slightly different pharmacological effect from CA. We studied the reduction of intraocular pressure (IOP) on a single eyedrop application of 8-OH CA in albino and pigmented rabbit eyes. To determine the characteristic of 8-OH CA and CA, we investigated the binding ability of these drugs to synthetic melanin. In the present study, topically applied 2% CA did not significantly decrease IOP in albino and pigmented rabbit eyes. Topically applied 0.01, 0.05, 0.1 and 1.0% 8-OH CA significantly decreased the IOP of albino rabbit as did 0.1 and 1.0% 8-OH to pigmented rabbit eyes. The maximum reduction of IOP was 3.5 +/- 0.33 mmHg (mean +/- SEM) in albino rabbit and 3.0 +/- 0.45 mmHg (mean +/- SEM) in pigmented rabbit. Maximum IOP reduction was obtained after 30 min. from topical application in albino rabbit, but in pigmented rabbit after 1 hour or later. Our binding studies to melanin show that the melanin binding ability is less for 8-OH CA than for CA at any concentrations. These results may indicate that lower concentrations of topically applied 8-OH CA profoundly reduce IOP compared to CA, and 8-OH CA has less effect on melanin than CA.

Administration, Topical↗
PubMed1990

Activation of propylbenzilylcholine mustard-sensitive muscarinic cholinoceptors more effectively utilizes cytosolic Ca2+ for contraction in guinea-pig intestinal smooth muscle.

A 50-min treatment of longitudinal smooth muscle of guinea-pig ileum with propylbenzilylcholine mustard (PrBCM, 3 x 10(-6) M) irreversibly inhibited the responses elicited by carbachol. However, a 90-min treatment with PrBCM had no further significant inhibitory effect on the responses to carbachol, suggesting that there are two subtypes of muscarinic cholinoceptors, PrBCM-sensitive and PrBCM-insensitive receptors. Carbachol caused a rapid increase in cytosolic Ca2+ concentrations ([Ca2+]i), which was followed by a rapid increase in muscle tension in both untreated and PrBCM-treated preparations. There was a positive correlation between [Ca2+]i (R340/380) and tension developed in response to carbachol. A regression line for the two responses was obtained in each preparation. The slope of the line obtained with untreated preparations was steeper than that obtained with PrBCM-treated preparations. These data suggest that, upon activation, PrBCM-sensitive receptors use cytosolic Ca2+ more effectively than PrBCM-insensitive receptors.

Animals↗
PubMed1990

[Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration].

Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration were investigated. We confirmed that reverse tolerance in stereotyped behavior was constructed up to the 28th day after repeated intermittent pretreatment with increasing doses of MAP (2.5, 5, and 7.5 mg/kg x 3 and 10 mg/kg x 2, every other day). During acoustic stimulation, locomotor activity in the saline group was significantly increased, but the activity after the stimulation was completely suppressed. In contrast to the saline group, locomotor activity was not influenced by the acoustic stimulation in the MAP group, suggesting that behavioral hyporesponsiveness to acoustic stimulation was induced by MAP treatment. Two days after the last injection, the contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyphenylacetic acid (5-HIAA) in the cerebral cortex, midbrain + thalamus, hypothalamus and striatum were significantly decreased. These changes were maintained up to the 28th day after the drug withdrawal in the cerebral cortex and the midbrain + thalamus. From these results, the persistence of behavioral hyporesponsiveness to acoustic stimulation might be associated with long-lasting reduction of 5-HT synthesis.

Acoustic Stimulation↗
PubMed1990

Antinucleolar autoantibody induced in mice by mercuric chloride--strain difference in susceptibility.

Eight inbred mouse strains were examined for their reactivity to the induction of antinucleolar autoantibody (AnuA) by mercuric chloride (MC). According to the positive ratio and titer of AnuA induced, the strains were grouped into high-, moderate-, low-, and non-responders. Since the susceptibilities to MC were different among strains having the same H-2 haplotype, involvement of H-2 unlinked gene (s) in AnuA induction by MC was suggested.

Animals↗
PubMed1990

[Changes in ocular hypotensive effect of griseolic acid with isoproterenol, timolol and melanin].

Griseolic acid-ester (GA-ester), one of the strongest cAMP phosphodiesterase inhibitors, was combined with isoproterenol and timolol in this study to evaluate the effect on intraocular pressure (IOP). Furthermore, the ocular hypotensive effect of GA-ester in pigmented and albino rabbits was compared, and the binding ability of GA-ester to synthetic melanin was examined. GA-ester markedly enhanced the hypotensive effect of isoproterenol, and the combination of GA-ester with timolol resulted in an additional fall in IOP. No differences in the hypotensive effect of GA-ester between pigmented and albino rabbits were observed. GA-ester did not bind to synthetic melanin. GA-ester has unique characteristics as an ocular hypotensive agent.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics.

[3H]-Flunitrazepam (FNT) binding was measured in the post-mortem brains of 13 chronic schizophrenics and 10 controls whose mean ages and death-to-freezing intervals were the same in each group. The specific binding of [3H]-FNT to the medial frontal cortex, orbitofrontal cortex, orbital cortex, medial and inferior temporal gyri, superior temporal gyrus, cornu Ammonis 1-3 and putamen was significantly higher in schizophrenics than in controls. Specific binding to the eye movement area (frontal eye field), motor cortex, lateral occipitotemporal gyrus, dentate gyrus of the hippocampus and secondary and tertiary visual cortex did not differ in the two groups. Type 1 benzodiazepine (BZ) binding sites in the superior temporal gyrus of schizophrenics, determined from the displacement of [3H]-FNT binding using a triazolopyridazine, CL 218,872 (200 nM), were significantly higher than in the control group. The increase in type 2 BZ binding sites was not significant. Antipsychotic or benzodiazepine medication did not appear to affect the results. There were significant correlations between specific [3H]-FNT binding and concentration of GABA (positive) and of glutamic acid (negative), specific [3H]-kainic acid binding (positive), activity of tyrosine hydroxylase (positive), and substance P-like immunoreactivity (positive) in many areas of the brain. The Bmax of [3H]-spiperone binding in the putamen was also correlated positively with specific [3H]-FNT binding. These data suggest that dysfunction of BZ receptors may be involved in the pathogenesis and some symptoms of chronic schizophrenia.

Adult↗
PubMed1989

Potential usefulness of a cultured glioma cell line induced by Rous sarcoma virus in B10.A mouse as an immunotherapy model.

A cultured glioma cell line, SR-B10.A, which was derived from a brain tumor induced in an adult female B10.A mouse by Rous sarcoma virus (RSV), has been established. The morphological appearance of the tumor produced by s.c. inoculating SR-B10.A cells was analogous to an astrocytoma of human glioma. Glial fibrillary acidic protein as well as S-100 protein was positive in these SR-B10.A tumor cells. A population doubling time of the cultured cells was 18.5 hours. Chromosomal analysis revealed a defect in one of the sex chromosomes. Integration of RSV genome was proven to be positive in SR-B10.A cells. It was possible to generate cytotoxic effector cells in the syngeneic B10.A mouse against SR-B10.A. The tumor-bearing syngeneic hosts harbored a suppressor activity in the splenocytes. Although recombinant human tumor necrosis factor (rH-TNF) had no growth inhibitory effect on the SR-B10.A cells in vitro, the s.c. implanted and growing tumor regressed when rH-TNF was administered intratumorally several times. In addition, this anti-tumor effect was completely abrogated when the host mice were treated with wholebody x-ray irradiation prior to the tumor cells inoculation. In contrast, neither rH-TNF (i.v.) nor cyclophosphamide (i.p.) induced the regression of SR-B10.A, indicating that efficacy of the locally administered rH-TNF is dependent on the host immune mechanism. These results suggest that SR-B10.A is a potentially useful tumor model in evaluating efficacy of immunomodulators.

Animals↗
PubMed1988

The locus controlling liver GM1(NeuGc) expression is mapped 1 cM centromeric to H-2K.

The polymorphic variation of liver GM1 (NeuGc) ganglioside was found in inbred strains of the mouse. The genetic analysis using C57BL/10 (GM1-negative) and SWR (GM1-positive) mice revealed that a single autosomal gene (Ggm-1) was involved in the expression of liver GM1(NeuGc) and that C57BL/10 mice lacking GM1(NeuGc) expression carried a defective gene on Ggm-1. Since our previous study on H-2 congenic mice indicated that Ggm-1 was linked to the H-2 complex, in this study we measured recombination frequencies among Ggm-1, Glo-1 and H-2K in the backcross progeny between (C57BL/10 X SWR)F1 and C57BL/10. Ggm-1 was mapped 1 cM centromeric to H-2K on chromosome 17.

Animals↗
PubMed1987

Membrane modification during secretory granule formation in rat somatotrophs.

Somatotrophs from male rat anterior pituitary were used to investigate the formation of secretory granules. When enzymatically dispersed cells were incubated with cationized ferritin (CF) for 15 min, CF labeled immature secretory granules, but not mature granules of somatotrophs. Most immature granules labeled by CF transformed to the mature types within 120 min. This indicates that the fusion of endocytic vesicles with the immature granules occurs during the maturation process of secretory granules. The internalized CF was distributed not only in the immature secretory granules, but also in the peripheral region of trans Golgi cisternae or GERL. Enzyme cytochemistry revealed that acid phosphatase-positive cisternae (GERL) were the main site for secretory granule formation, and was devoid of thiamine pyrophosphatase (TPPase) activity. A small number of secretory granules were also present in the peripheral regions of TPPase-positive Golgi cisternae. The granule-forming sites, however, lacked TPPase activity, while the remaining region of the same cisterna showed the positive enzyme activity. This indicates that the granule-forming region at the periphery of Golgi cisterna is different from the remaining part of the same cisterna in terms of cytochemical properties. This probably results from the insertion of endocytic vesicle membrane, since the same granule-forming sites preferentially fused with CF-labeled small vesicles which lacked cytochemical TPPase activity. Taken together. Our results suggest that the membrane of secretory granules is modified during the granule formation, at least partly by the fusion of endocytic small vesicles with Golgi cisternae (or GERL), and with immature secretory granules.

Animals↗
PubMed1986

The effects of amiflamine, a reversible MAO-A inhibitor, on the first pass metabolism of tyramine in dog intestine.

The effects of amiflamine on tyramine deamination were studied using isolated loops of intestine in anesthetized dogs. In the pretreatment experiment, dogs were dosed with amiflamine (3.5 mg/kg/day) once daily for 3 days, with the study being carried out 3 hr after the final dose. [14C] Tyramine (50 mg and 50 microCi) in 10 ml of normal saline was introduced into the isolated loops of gut, and tyramine and p-hydroxyphenylacetic acid in the venous blood were separated by HPLC and measured by scintillation spectrometry. In the untreated dogs, approximately 15% of the tyramine passed through the gut wall unchanged. When tyramine and amiflamine (0.06 to 3.5 mg/kg) were administered simultaneously to the gut loop, about 27 to 65% of the tyramine passed through the gut wall unchanged. On the contrary, after pretreatment with amiflamine for 3 days, percentage of tyramine passing through the gut wall was not increased in comparison with the control. These results suggest that pretreatment with amiflamine does not produce drug concentrations in the lining cells of the gut sufficient to effectively inhibit the deamination of oral tyramine, which is administered at least 3 hr after the final dose of amiflamine.

Animals↗
PubMed1986

Species differences in the angiotensin converting enzyme activity of mammalian serum.

Angiotensin converting enzyme (ACE; EC 3. 4. 15. 1) activities were compared in the serum of various mammals. Cattle, human, monkey, and swine serum showed enzyme levels from 3.7 to 67 mU/ml. Relatively high enzyme activity was observed in rodents, the rat (Wistar) and mouse (BALB/c) showing levels of 93 +/- 7 and 1052 +/- 165 mU/ml, respectively. Among the mammalian sera examined, that of the guinea pig contained the highest ACE level, 2262 +/- 574 mU/ml. No age-related difference in enzyme activity was observed in 10-day-old to 1-year-old guinea pigs.

Adult↗
PubMed1986

Strain difference in mouse natural killer activity augmented by mouse interferon and poly I.C.

The level of natural killer (NK) activity was found to vary considerably among several mouse strains. In vivo and in vitro, interferon (IFN) and IFN inducers have been shown to augment mouse NK activity. C3H/He mice showed high NK activity, DDD/1 and A/J mice low NK activity, and C57BL/6, BALB/c and DBA/2 mice intermediate NK activity after injection with polyinosinic polycytidylic acid (poly I. C.). The same NK activity correlation was observed in nontreated mice, but the NK activities were lower compared with the poly I. C.-injected mice. Moreover, the DDD/1 and A/J mice showed almost no augmentation of NK activity on injection with poly I.C. In vivo, C3H/He, BALB/c and C57BL/6 mice injected with IFN showed augmented NK activity, but DDD/1 mice showed no such reaction. In vitro, C3H/He, BALB/c and C57BL/6 mouse spleen cells treated with IFN also showed augmented NK activity, but DDD/1 mouse spleen cells showed almost none. F1 hybrids between high (C3H/He) and low (DDD/1) NK-activity strains showed high NK activity. Thus, activity is dominant over low activity. The segregation of (DDD/1 X C3H/He) Fl X DDD/1 back-cross mice suggested that the strain differences in NK activity are under polygenic control.

Animals↗
PubMed1985

Enkephalin-degrading dipeptidyl carboxypeptidase in guinea pig serum: its properties and action on bioactive peptides.

A dipeptidyl carboxypeptidase, which cleaved the Gly3-Phe4 bond of enkephalins, was purified from guinea pig serum 420-fold. The optimum pH of the enzyme was in the neutral range (pH 7.25), and the molecular weight was estimated to be approx. 280,000. The enzyme hydrolyzed Met- and Leu-enkephalin with Km values of 0.30 and 0.50 mM, respectively. The enzyme was inhibited by metal chelators and p-chloro-mercuribenzoate. Captopril showed high inhibitory potency, while phosphoramidon and Phe-Ala showed no effect on the enzyme activity. Therefore, the obtained enzyme can be classified as an angiotensin-converting enzyme (EC 3.4.15.1). Among the bioactive peptides examined, bradykinin and angiotensin I were hydrolyzed by the enzyme. Angiotensin III showed a stronger inhibitory effect than that of angiotensin II. Substance P, gastrin I, and secretin were also inhibitory toward the enzyme activity. On high-performance liquid chromatography analysis, Met-enkephalin-Arg6-Phe7 and Leu-enkephalin-Arg6 were cleaved sequentially at the second peptide bond of the C terminus. Thus, the dipeptidyl carboxypeptidase in guinea pig serum may play a role not only in the angiotensin-bradykinin system but also in the metabolism of circulating enkephalins and other bioactive peptides.

Animals↗