Biomedical subjects

Y Kiuchi

Publications and source records attributed to Y Kiuchi.

At least 19 recordsLinked to original sources

PubMed1997

Amended structure of side chains in a cell wall mannan from Candida albicans serotype A strain grown in yeast extract-Sabouraud liquid medium under acidic conditions: detection of the branched side chains corresponding to antigenic factor 4.

In a previous study, we reported the excess production of alpha-1,3-linked mannose residues with the complete disappearance of beta-1,2-linked mannose residues in cell wall mannans of Candida albicans serotype A strain cells, which were grown in yeast extract-Sabouraud liquid medium at pH 2.0. In the present study, we examined the immunochemical reactivity of the same mannan of NIH A-207 with an enzyme-linked immunosorbent assay (ELISA) using several antisera to antigenic factors of the genus Candida (FAbs) and the structure of the mannan by two-dimensional homonuclear Hartmann-Hahn analysis. The ELISA showed that the mannan reacts to FAb 4 but not to FAbs 13b and 34, which are reported to be antibody factors against linear side chains containing an alpha-1,3-linked mannose residue. In the Hartmann-Hahn analysis, we found two branched side chains, Man alpha 1-2Man alpha 1-3[Man alpha 1-6]Man alpha 1-(2Man alpha 1-)(2)2Man and Man alpha 1-3[Man alpha 1-6]Man alpha 1-(2Man alpha 1-)(2)2Man, instead of the previously reported linear side chains. The branched side chains are oversynthesized under acidic conditions.

Antibodies, Fungal↗

PubMed1997

Changes in glutamate receptors, c-fos mRNA expression and activator protein-1 (AP-1) DNA binding activity in the brain of phenobarbital-dependent and -withdrawn rats.

We studied changes in glutamate receptors, expression of immediate early genes, and AP-1 DNA binding activity in the brains of phenobarbital (PB)-dependent and -withdrawn rats to investigate the possible involvement of activation of glutamate receptors in PB withdrawal syndrome. PB-dependent rats were prepared by feeding drug-admixed food for 5 weeks. Autoradiographic analysis showed that binding of [3H(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imin e (MK-801), an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, increased significantly in the cerebral cortices of PB-dependent and 24-h-withdrawn rats. However, [3H]MK-801 binding in the hippocampus and [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and [3H]kainic acid binding in the hippocampus and cerebral cortex were essentially unchanged in both groups. PB withdrawal seizures were followed by increased expression of c-fos mRNA in the hippocampus and cerebral cortex and of c-jun mRNA in the cerebral cortex. The induction of c-fos and c-jun mRNA was suppressed by administration of MK-801. Furthermore, PB withdrawal enhanced AP-1 DNA binding activity in the brain. The present findings suggest functional enhancement of glutamatergic neurotransmission during the development of PB withdrawal syndrome.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Structure of a cell wall mannan from the pathogenic yeast, Candida catenulata: assignment of 1H nuclear magnetic resonance chemical shifts of the inner alpha-1,6-linked mannose residues substituted by a side chain.

We performed an enzyme-linked immunosorbent assay of the cell wall mannan purified from the pathogenic yeast, Candida catenulata, using antisera to factors of the genus Candida. The results suggest that mannan possesses a linear backbone consisting of alpha-1, 6-linked mannose residues and side chains possessing nonreducing terminal alpha-1,2- and alpha-1,3-linked mannose residues. The chemical structure of the mannan was analyzed by two-dimensional homonuclear Hartmann-Hahn and two-dimensional nuclear Overhauser enhancement and exchange spectroscopy. The sequential assignments of the cross-peaks caused by J-coupling and the nuclear Overhauser effect from these terminal mannose residues demonstrate that the H1 signal of an inner alpha-1,6-linked mannose residue substituted by an alpha-oligomannosyl side chain or a single mannose through the C-2 position in an alpha-anomer configuration undergoes a significant downfield shift (delta delta = 0.16 or 0.19 ppm, respectively) compared with that of unsubstituted residues. We therefore propose the exact overall structure of the antigenic mannan obtained from C. catenulata. The assignment data in the present study are useful for the determination of the exact overall structure of various yeast mannans using the two-dimensional nuclear magnetic resonance analysis without the need for harsh procedures.

Antigens, Fungal↗

PubMed1997

Behavioral stimulation without alteration of beta and 5-HT receptors and adenylate cyclase activity in rat brain after chronic sertraline administration.

Effects of chronic treatment with selective 5-HT reuptake inhibitors (SSRIs) on the monoaminergic functions have not been much investigated in compared with tricyclic antidepressants. Therefore, we compared the effects of 3-week treatment with sertraline, a potent SSRI, to those of imipramine (10 mg/kg, IP, twice a day), on monoamine receptors and adenylate cyclase (AC) activity in rat brain. Two-week treatment with both sertraline and imipramine reduced immobility in the water wheel test to the comparable extent. Sertraline treatment did not affect Kd and Bmax of [3H]CGP12177 and [3H]ketanserin bindings or cAMP, accumulation by norepinephrine, isoproternol, 5'-guanylylimidodiphosphate [Gpp(NH)p] and forskolin in the cortical membrane compared with vehicle-treated rats. On the other hand, imipramine treatment decreased Bmax of both bindings and norepinephrine- or isoproternol-stimulated cAMP accumulation. Treatment with either antidepressant induced no apparent changes in [3H]8-OH-DPAT [2-(N, N-dipropylamino)-8-hydroxy-1,2,3,4-tetrahydronaphthalene] binding in the hippocampal membrane. These results suggested that chronic treatment of sertraline induced little effect on monoamine receptors and AC activity in the brain and that the alteration of these functions may not be primarily involved in antidepressive effects of antidepressants, at least of SSRIs.

1-Naphthylamine↗

PubMed1997

Delayed neurite regeneration and its improvement by nerve growth factor (NGF) in dorsal root ganglia from MRL-lpr/lpr mice in vitro.

We studied neurite regeneration in MRL-lpr/lpr mice, a murine model of systemic lupus erythematosus, using a culture system to investigate the influences of immunological abnormalities on neurons. The regeneration of cultured dorsal root ganglion (DRG) neurons from MRL-lpr/lpr mice was delayed compared with control MRL-+/+ mice. This modification of regeneration was age-dependent. MRL-lpr/lpr mice older than 16 weeks of age exhibited less neurite regeneration than controls but those younger than 6 weeks of age showed equal regeneration. Regeneration was improved by adding nerve growth factor (NGF) to culture medium. Following immunocytochemical staining, we counted the low affinity NGF receptor p75-positive DRG neurons in MRL mice. The percentage of p75-positive neurons in MRL-lpr/lpr mice older than 16 weeks of age was higher than that in MRL-+/+ mice. These neuronal abnormalities were thought not to be directly dependent on the genetic defect of Fas antigen, which is related to apoptosis in MRL-lpr/lpr mice, but to be the result of immunological abnormalities. The present study is the first to demonstrate a modification of neurite regeneration by immunological dysfunction in autoimmune mice.

Aging↗

PubMed1997

Circadian intraocular pressure management with latanoprost: diurnal and nocturnal intraocular pressure reduction and increased uveoscleral outflow.

Based on their mechanism of action, the most frequently used ocular hypertensive agents, the beta-blockers, cannot be assumed to reduce IOP during sleep. The need for drugs that reduce IOP around-the-clock is underscored, however, by the fact that inadequate nocturnal ocular perfusion pressure is considered to be one of the likely causes of glaucomatous optic neuropathy especially in some cases of normal tension glaucoma. The studies reviewed here demonstrate that latanoprost, a new ocular hypotensive prostaglandin F2 alpha analogue, applied once a day at a concentration of 0.005%, maintains a statistically highly significant IOP reduction around-the-clock. The magnitude of this IOP reduction was found to be essentially identical during the day and at night, both in patients maintained on timolol and in those not receiving other glaucoma medication. Latanoprost-induced IOP reduction was also found to be associated with increased uveoscleral outflow in normotensive volunteers, both during the day and at night. These circadian studies suggest that this new ocular hypotensive agent can be expected to be particularly useful for the medical management of some forms of glaucoma, such as normal tension glaucoma, when the cause of the glaucomatous damage cannot be linked specifically to diurnal IOP abnormalities.

Administration, Topical↗

PubMed1997

Evidence for a depressive-like state induced by repeated saline injections in Fischer 344 rats.

We investigated the behavioral changes induced by mild stress in animals that may be relatively susceptible to a depressive-like state, the Fischer 344 rat strain. The mild stress of repeated handling and intraperitoneal (i.p.) injections with saline (2 ml/kg, twice a day for 14 days) elicited a moderate suppression of body weight gain, a decrease in open field activity, and a prolonged immobility during the tail suspension test in Fischer 344 rats compared with Sprague-Dawley rats. Chronic treatment of Fischer 344 rats with imipramine (10 mg/kg i.p., twice a day for 14 days) effectively suppressed open field activity and prolonged immobility. These results suggest that repeated saline injections may be a mild stressor in these rats. In the Fischer 344 strain, which may be vulnerable to the effects of mild stressors, repeated saline injections might induce a depressive-like state and could presumably represent an experimental model for depression.

Animals↗

PubMed1997

Protective effect of citalopram against the attenuation of the alpha 1-potentiation of cAMP formation in Fischer 344 strain rats.

We investigated the effects of citalopram, a selective serotonin reuptake inhibitor (SSRI), using an animal model for a depressive state. In Fischer 344 rats, known as emotional animals, repeated stress by twice-daily intraperitoneal (i.p.) saline injections for 14 days elicited a depressive state characterized by a decreased open-field activity and a prolonged immobility during the tail-suspension test. Concomitantly, suppression of norepinephrine (NE)-induced cAMP formation was found in the cerebral cortical slices of the stress-exposed rats without changes in adrenergic alpha 1- or beta-receptors. The difference in cAMP formation between the intact and the stress groups was totally abolished under the blockade of the alpha 1-receptor system or by the stimulation with isoproterenol or forskolin, whereas the suppressed response in the stress group was also observed in combination with isoproterenol and phenylephrine. From these results, we confirmed that the potentiation of the beta-receptor-stimulated cAMP formation by the alpha 1-receptor is attenuated following repeated stress. Chronic i.p. administration of citalopram dissolved in saline improved both the suppressed open-field activity and the prolonged immobility in the tail-suspension test. The animals treated with citalopram exhibited a comparable alpha 1-potentiation effect as observed in the intact rats. However, another SSRI, paroxetine, was less effective on the attenuation of the alpha 1-potentiation in spite of its behavioral improvement in the depressive state. These findings suggest that citalopram has a protective effect against the repeated stress-induced depressive state by mechanisms besides the serotonin reuptake inhibition.

Adrenergic Uptake Inhibitors↗

PubMed1997

Incidence of retinal vein occlusion at the Glaucoma Clinic of Hiroshima University.

We prospectively surveyed the incidence of retinal vein occlusion (RVO) at the glaucoma clinic of Hiroshima University between 1986 and 1991. Among 433 glaucoma patients, 18 (4.2%) subsequently presented with RVO, 9 had central retinal vein occlusion (CRVO) and 9 exhibited branch retinal vein occlusion (BRVO). Seven of 87 (8.1%) patients with primary angle closure glaucoma exhibited RVO, showing the highest incidence among glaucoma types. The incidence of RVO detected by the general outpatient clinic was 0.59% during the same period. The BRVO/CRVO ratio in the glaucoma clinic was 1.0, while it was 4.3 in the general outpatient clinic. Glaucoma is an important risk factor for the development of RVO, especially CRVO.

Adult↗

PubMed1997

Effect of GK-128 [2-[(2-methylimidazol-1-yl)methyl]-benzo[f]thiochromen-1-one monohydrochloride hemihydrate], a selective 5-hydroxytryptamine3 receptor antagonist, on colonic function in rats.

We investigated the effects of various selective 5-hydroxytryptamine (5-HT)3 receptor antagonists, including GK-128 [2-[(2-methylimidazol-1-yl)methyl]benzo[f]thiochromen-1-one monohydrochloride hemihydrate], on colonic function. In conscious rats, 5-HT and a 5-HT3 receptor agonist, 2-methyl-5-HT, dose-dependently increased fecal pellet output, but another 5-HT3 receptor agonist, m-chlorophenylbiguanide, did not affect output. The selective 5-HT3 receptor antagonists GK-128, granisetron, ramosetron, azasetron and ondansetron depressed the increase in fecal pellet output caused by 2-methyl-5-HT and by wrap-restraint stress. However, the rank order of potency of antagonists in the two defecation models was not consistent with that for the von Bezold-Jarisch reflex. Although granisetron and ramosetron dose-dependently reduced the spontaneous excretion of fecal pellets, GK-128 did not affect it. These results suggest that GK-128 may be used for the treatment of stress-induced gastrointestinal dysfunction. Furthermore, the present results suggest that the 5-HT3 receptor involved in colonic motility may be different from the classically defined 5-HT3 receptor and/or that the regulation of colonic motility mediated by 5-HT3 receptors during stress may be different from normal physiological conditions.

Animals↗

PubMed1997

Response and level of beta-adrenergic, vasoactive intestinal peptide, and PACAP receptors during the circadian cycle.

PURPOSE: To determine whether a nocturnal increase of ciliary process beta-adrenergic receptor responsiveness can explain the observation that timolol decreased the aqueous flow rate and intraocular pressure (IOP) during the night but not during the day in rabbits. METHODS: Rabbits were housed in alternating 12-hour periods of light and dark. In vitro stimulation of tissue cyclic adenosine monophosphate (cAMP) levels by isoproterenol (ISO), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), or a soluble derivative of forskolin (sFSK) was measured in ciliary processes harvested at mid-light phase and early and late dark phase. Inhibition of ISO and VIP stimulation of ciliary process cAMP by an alpha 2-adrenergic agonist and maximal binding of [125I]I-pindolol, [125I]I-VIP, and [125I]I-PACAP in ciliary process membranes were measured at the same three times. RESULTS: Although there may have been a nocturnal increase in the sensitivity of ciliary process cAMP levels to stimulation by ISO, this was not observed consistently, VIP, but not PACAP, stimulation increased at night, but there was no change in the response to sFSK. Inhibition by apraclonidine of elevated ciliary process cAMP levels was constant at all three times. Ligand-binding studies showed little change in ciliary process beta-adrenergic, VIP-, or PACAP-receptor levels at the three times. CONCLUSIONS: There is no convincing evidence for a nocturnal increase in beta-adrenergic receptor sensitivity in rabbit ciliary processes that could explain the difference between day and night effects of timolol on aqueous flow and IOP.

Adrenergic alpha-Agonists↗

PubMed1996

Possible involvement of calmodulin-dependent kinases in Ca(2+)-dependent enhancement of [3H]5-hydroxytryptamine uptake in rat cortex.

Effects of Ca2+ on [3H]5-hydroxytryptamine (5-HT) uptake into rat cortical synaptosomes were studied. The uptake was enhanced in the presence of Ca2+ in Krebs-Ringer medium and the uptake at 0.3-5 mM Ca2+ was 2.4-2.7 times greater than that observed in the absence of Ca2+. The maximal increase at the concentration of 1 mM Ca2+ was achieved after 2 min preincubation. Ca(2+)-dependent enhancement of the [3H]5-HT uptake reflected an increase in Vmax of the uptake process. However, Kd and Bmax values for [3H]paroxetine were not significantly changed in the presence of 1 mM Ca2+ compared with Ca(2+)-free condition. On the other hand, uptake was still enhanced after synaptosomes were washed with Ca(2+)-free after preincubation with 1 mM Ca2+. Staurosporine (a protein kinase C inhibitor) and wortmannin (a myosin light chain kinase inhibitor) did not affect Ca(2+)-dependent enhancement of the uptake, whereas 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazin e (KN-62, an inhibitor of Ca2+ /calmodulin-dependent kinase II) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7, a calmodulin antagonist) significantly reduced it. Moreover, L-type, but not P- or N-type, voltage-dependent Ca(2+)-channel blockers suppressed enhancement of the uptake. These results indicate that Ca(2+)-dependent enhancement of [3H]5-HT uptake is mediated by activation of calmodulin-dependent protein kinases, suggesting a possibility of calmodulin-dependent regulation of in vivo 5-HT uptake.

Animals↗

PubMed1996

An attenuated alpha-1 potentiation of beta adrenoceptor-stimulated cyclic AMP formation after repeated saline injections in Fischer 344 strain rats.

We investigated the behavioral and neurochemical features of Fischer 344 strain rats in which a depressive state was induced by repeated handling and saline injections as a mild stressor. The repeated intraperitoneal injections of saline (2 ml/kg, twice a day for 14 days) elicited a moderate suppression of body weight gain, a decrease in their open field activity and a prolonged immobility in the tail suspension test. In the stress-exposed rats, the tissue content of norepinephrine (NE) was increased in the cerebral cortex and hypothalamus, whereas that of dopamine or serotonin was not affected. Although the stress exposure did not affect the binding properties of either the alpha-1 or beta adrenoceptors, it suppressed cAMP formation stimulated by NE, but not by isoproterenol or forskolin, in the cerebral cortical slices. In the presence of prazosin or phorbol ester, the difference in NE-stimulated cAMP formation between the control and the stress groups was totally abolished. Phenylephrine enhanced isoproterenol-stimulated cAMP formation in the control but not in the stress group. From these results, it is postulated that the alpha-1 potentiation of beta adrenoceptor- stimulated cAMP formation was attenuated in the stress group. These findings suggest that the manipulation of mild stressor with repeated handling and saline injections to Fischer 344 rats elicits a depressive state characterized by the behavioral changes and the attenuated alpha-1 potentiation in the cerebral cortex, and that this manipulation might be available for the study of the stress-induced depressive state as a generally acceptable mild stress model.

Animals↗

PubMed1996

Ultrasound biomicroscopic study of ciliary body thickness after topical application of pharmacologic agents.

PURPOSE: To examine the changes in ciliary body thickness after topical application of pilocarpine, cyclopentolate hydrochloride, and PhXA41, a prostaglandin F2alpha analog. METHOD: We used high-frequency Humphrey UBM840 ultrasound biomicroscope to examine 36 healthy young Japanese subjects. RESULTS: The mean ciliary body thickness increased from 0.67 +/- 0.07 mm to 0.073 +/- 0.08 mm (P < .01) after application of 2% pilocarpine; 1% cyclopentolate hydrochloride and 0.005% PhXA41 decreased the mean ciliary body thickness from 0.75 +/- 0.07 mm to 0.69 +/- 0.05 mm (P < .05) and from 0.78 +/- 0.06 mm to 0.75 +/- 0.06 mm (P < .01), respectively. CONCLUSIONS: Our ultrasound study clearly indicates that pilocarpine increased comparative thickness of the ciliary body by 8.3%, whereas PhXA41 decreased comparative thickness by 3.3% in a manner similar to cyclopentolate hydrochloride.

Administration, Topical↗

PubMed1996

Translocation of bacteria from the gastrointestinal tract in immunodeficient mice.

Host defence mechanisms associated with the inhibition of translocation of bacteria from the gastrointestinal (GI) tract were investigated in SCID and beige mice after decontamination with oral antibiotics and colonization with Escherichia coli C25. SCID mice, which have impaired T and B cell function, tended to have a greater incidence of bacterial translocation from the GI tract up to 7 days after inoculation compared with controls. However, after 7 days both SCID and controls cleared the E. coli C25 from the liver, spleen, blood and peritoneal cavity. Beige mice, with impaired NK cell and polymorphonuclear leukocyte function, were not able to clear the inoculated bacteria from their liver by 14 days after inoculation although the controls were cleared by 7 days. Numbers of bacteria in the mesenteric lymph nodes (MLN) of beige mice did not decrease significantly by 14 days after inoculation, whereas numbers in SCID mice decreased markedly within 7 days. These results suggest that defence mechanisms other than T and B cell function are important in the inhibition of systemic infection from the GI tract.

Animals↗

PubMed1996

[Pharmacokinetics of norfloxacin and lomefloxacin in aqueous humour analysed by microdialysis].

The pharmacokinetics of norfloxacin (NFLX) and lomefloxacin (LFLX) in rabbit aqueous humour after instillation of 0.3% solution (20 microliters) and oral administration (20 mg/kg) were investigated by microdialysis. We also measured plasma concentration of fluoroquinolones after oral administration. After instillation, the maximum concentration (Cmax) of NFLX and LFLX in the aqueous humour was 0.80 and 1.20 micrograms/ml, and elimination half time (t1/2) was 130 and 96 min, respectively. After oral administration, the Cmax in plasma of NFLX and LFLX was 2.06 and 1.89 micrograms/ml, and the Cmax in aqueous humour was 0.16 and 0.62 microgram/ml, respectively. t1/2 of NFLX in aqueous humour and plasma was 225 and 295 min, and t1/2 of LFLX was 188 and 175 min, respectively. The ratio of aqueous humour/serum concentration of NFLX and LFLX was 7.8 and 35.3% 4 hrs after oral administration. These results suggest that, after instillation, LFLX penetrated better into the aqueous humour, and was eliminated faster, than NFLX, and that after oral administration, NFLX could not panetrate well into the aqueous humor from the blood.

Animals↗

PubMed1996

[Effects of beta-adrenergic blockers on retinal circulation].

We evaluated the effects of 0.5% betaxolol hydrochloride and 0.5% timolol maleate on retinal blood flow. We measured the diameter of the retinal artery (Da) and vein (Dv), and retinal venous blood flow rate (V) in 8 healthy young volunteers by laser speckle velocimetry before and after the application of betaxolol or timolol topically to both eyes daily for one week. There were no any significant changes. Da before and after the application of betaxolol was 114.2 +/- 6.3 (mean +/- standard deviation) microns and 115.6 +/- 6.7 microns and before and after the application of timolol, 117.5 +/- 12.7 microns and 101.3 +/- 9.5 microns. Dv before and after the application of betaxolol was 149.5 +/- 11.1 microns and 148.4 +/- 13.3 microns, and before and after the application of timolol 148.5 +/- 9.2 microns and 146.2 +/- 10.3 microns. V before and after the application of timolol was 12.3 +/- 2.6 mm/s and 12.6 +/- 2.4 mm/s, and before and after the application of betaxolol, 11.6 +/- 1.5 mm/s and 11.4 +/- 2.1 mm/s. Thus one-week application of the beta-blockers, betaxolol and timolol did not change the retinal arterial or venous blood flow.

Adolescent↗

PubMed1995

The anti-emetic activity of GK-128 in Suncus murinus.

In Suncus murinus, various emetic responses and the anti-emetic activity of a new 5-hydroxytryptamine3 (5-HT3) receptor antagonist, GK-128 (2-[(2-methylimidazol-1-yl) methyl benzo[f]thiochromen-1-one monohydrochloride hemihydrate), were investigated. Cancer chemotherapeutic agents, cisplatin and cyclophosphamide, dose-dependently induced emesis of long-lasting duration. The 5-HT3 receptor agonist, 2-methyl-5-HT, and copper sulfate also induced emesis of short duration. However, another 5-HT3 receptor agonist, m-chlorophenylbiguanide, was not consistently emetic. GK-128 inhibited the emetic responses induced by chemotherapeutic agents and 2-methyl-5-HT with similar potency. The anti-emetic action of GK-128 was more potent than that of ondansetron, Y-25130, granisetron and metoclopramide. The order of potency of these drugs, except granisetron, was consistent with that of their 5-HT3 receptor binding affinity in rat cortex. GK-128 failed to inhibit copper sulfate-induced emesis. These data suggest that GK-128 has a potent inhibitory effect on emesis via the 5-HT3 receptor, and that the 5-HT3 receptor involved in emesis in Suncus murinus may be different from the classically defined 5-HT3 receptor in other animals such as rats, dogs and ferrets.

Animals↗