Biomedical subjects

H Kamei

Publications and source records attributed to H Kamei.

At least 55 records · Page 3Linked to original sources

PubMed1998

Renal effects of the calcium channel blocker aranidipine and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats.

The purpose of this study was to investigate the renal effects of aranidipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats (SHRs). When infused into the renal artery in anesthetized dogs, aranidipine (0.03 microg/kg/min) induced sustained increases in urine volume and urinary excretion of sodium and of potassium. This effect was greater than that elicited by nifedipine (0.1 microg/kg/min). The aranidipine metabolite, M-1 (0.1 microg/kg/min), also caused diuresis and natriuresis almost equal to those of nifedipine. The stop-flow experiment using the anesthetized dog showed that intrarenal infusion of aranidipine (0.03 microg/kg/min), as well as nifedipine (0.1 microg/kg/min), produced natriuresis at the distal tubular site rather than at the proximal site. Aranidipine (0.3, 1, and 3 mg/kg), when administered orally, dose-dependently increased urine volume and urinary excretion of electrolytes in conscious saline-loaded SHRs. M-1 (10 mg/kg, p.o.) also showed diuretic and natriuretic effects comparable to those of nifedipine (10 mg/kg) in SHRs. In addition, after repeated oral administration of aranidipine for 7 days, short-term tolerance was not found for its diuretic and natriuretic effects in SHRs. These results suggest that, apart from antihypertensive efficiency, aranidipine may offer a therapeutic advantage by producing diuresis and natriuresis in hypertensive patients. The metabolite of aranidipine may contribute, in part, to the diuretic, natriuretic, and antihypertensive effects of aranidipine.

Administration, Oral↗

PubMed1998

Pharmacological effects of BAM-1120, a novel ergoline derivative, on central dopaminergic functions in rats.

BAM-1120, an ergoline derivative, has been found to display a relatively high affinity for dopamine D2-like receptor subtypes in a preliminary binding study. This study investigated whether BAM-1120 acts as a dopamine receptor agonist on prolactin-secreting and motor functions. BAM-1120 suppressed hyperprolactinemia induced by pretreatment with reserpine or estradiol in female rats. Furthermore, BAM-1120 was able to shrink a prolactin-secreting pituitary tumor (prolactinoma) in the estradiol-treated female rats. BAM-1120 induced rotations contralateral to the lesion side in rats with unilateral 6-hydroxydopamine-induced lesions of nigrostriatal dopamine pathway at a dose that was at least 30-fold higher than that required for the inhibition of prolactin secretion. These findings suggest that BAM-1120 is characterized as a putative dopamine D2-like receptor agonist that possesses a preference of inhibiting prolactin secretion over activating motor behaviors.

Animals↗

PubMed1998

Effects of sigma receptor ligands on conditioned fear stress.

Mice or rats exhibit a marked suppression of motility when they are replaced in the same environment in which they previously received an electric footshock. To clarify the functional role of sigma receptors in a stressful situation, we investigated the behavioral and neurochemical effects of various sigma receptor ligands on this psychological stress-induced motor suppression, defined as a conditioned fear stress. (+)-SKF-10,047 and dextromethorphan, putative sigma receptor agonists, reversed the conditioned fear stress. However, other sigma receptor ligands, (+)-pentazocine and 1,3-di(2-tolyl)guanidine had no effect. Further, (+)-SKF-10,047, but not (+)-pentazocine, restored the decreased dopamine turnover in the nucleus accumbens in the stressed group to the control level, the effect being consistent with its behavioral effect. We indicated that these controversial results may be due to the presence of multiple types of sigma receptors, and that the activation of phenytoin-sensitive sigma 1 receptors may be involved in the ameliorating effects of sigma receptor agonists on this stress. Our findings suggest that the dysfunction in the mesolimbic dopaminergic neurons is responsible for the development of conditioned fear stress, and that this stress response is restored through phenytoin-sensitive sigma 1 receptors, which are closely connected to the dopaminergic neuronal systems.

Animals↗

PubMed1998

[Significance of pontine high signal intensity lesions on magnetic resonance imaging in patients with cerebral infarction].

We reviewed MRI findings in a series of 211 patients with cerebral infarction. A high signal in the basis pontis bilaterally in T2 weighted images (Central Pontine Hyperintensity, CPH), with almost-normal T1 weighted images, was present in 29 cases (12.9%). CPH findings were present more frequently in elderly patients, and were significantly associated with a previous history of cerebrovascular accident, although not with other arteriosclerotic risk factors. In patients with CPH. periventricular hyperintensity was severe and the number of infarctions of the thalamus was higher. These results suggest that a) CPH may arise from ischemia in subcortical areas or in the territory of the vertebrobasilar system, and that b) chronic brain ischemia, which may be partially due to aging, may play a more important role in cerebral infarction than the usual arteriosclerotic risk factors.

Adult↗

PubMed1998

[Autoantibody to glutamate decarboxylase in a patient with spinocerebellar degeneration and Sjögren syndrome].

We report a 52-year-old woman with Sjögren syndrome from the age of 46, developed cerebellar ataxia, autonomic dysfunction and dysarthria at 50. She had no family history, and all known causes of cerebellar disease were excluded. Serum of the patient contained autoantibodies directed against glutamic acid decarboxylase (GAD) which was an enzyme involved in the biosynthesis of GABA. She also had autoantibodies that were specific with Sjögren syndrome (SS-A, anti-nuclear antibody). Anti-GAD antibody changed into negative after high dose intravenous and oral corticosteroid therapy, but symptoms did not improve. Western blot method revealed abnormal bands to human neuroblastoma cell line (10, 43, 49 kDa), considered relatively specific to nervous tissue. In this case cerebellar ataxia and atrophy were caused by autoimmune pathogenesis including cerebellar GABAergic system and central nerve cells.

Autoantibodies↗

PubMed1998

Involvement of dopaminergic system in phencyclidine-induced place preference in mice pretreated with phencyclidine repeatedly.

In the conditioned place preference test, phencyclidine (PCP) produces place aversion in naive rats, whereas PCP produces place preference in rats treated with PCP repeatedly. Although the PCP-induced place aversion is thought to involve the serotonergic system, the mechanisms of the PCP-induced place preference are unclear. We investigated whether the dopaminergic system is involved in place preference induced by PCP in mice repeatedly treated with PCP, because it is well known that the dopaminergic system plays an important role in the rewarding effect of drugs. PCP (2-8 mg/kg s.c.) induced a dose-dependent place aversion in naive mice, whereas PCP (2-8 mg/kg s.c.) induced a dose-dependent place preference in mice pretreated with PCP (10 mg/kg/day s.c.) for 28 days. The place preference induced by PCP (8 mg/kg s.c.) was attenuated significantly by alpha-methyl-rho-tyrosine (100 mg/kg i.p.), a tyrosine hydroxylase inhibitor, 6-hydroxydopamine (100 micrograms/mouse i.c.v.), a dopaminergic neurotoxin, and R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zepine (0.5 mg/kg s.c.), a dopamine D1 receptor antagonist. These agents themselves produced neither the place preference nor aversion. In contrast to the attenuating effects of these agents, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (30 mg/kg i.p.), a noradrenergic neurotoxin, ritanserin (1 mg/kg i.p.), a serotonin2 receptor antagonist, and (-) sulpiride (50 and 100 mg/kg i.p.), a dopamine D2 receptor antagonist, failed to affect the PCP-induced place preference. In mice pretreated with methamphetamine (1 mg/kg/day s.c.) for 14 days, PCP (8 mg/kg s.c.) induced the place preference, but not aversion. These results demonstrate that the PCP-induced place preference depends on dopaminergic, but not on serotonergic and noradrenergic, neuronal systems and suggest a role for D1 receptors in the mediation of the PCP-induced place preference.

Animals↗

PubMed1998

[A case of HTLV-I associated polyradiculoneuropathy and cerebral white matter lesions with smouldering type adult T cell leukemia].

A 45-year-old female was admitted to our hospital complaining of abnormal sensation in the upper and lower extremities. She was given a diagnosis of smouldering type adult T cell leukemia 9 months before admission. On admission, neurological examination revealed sensory disturbance of polyneuropathy type, and generalized hyporeflexia. Nerve conduction study demonstrated decreased F wave appearance rate. Motor unit potentials in electromyelography had long duration and high amplitude. MR imaging of the brain showed multiple abnormal lesions in the periventricular and subcortical white matter. CSF protein was mildly increased, and anti-HTLV-I antibody was positive. Treatment with corticosteroid was effective, resulting in disappearance of sensory symptoms and normalization of F wave appearance. The present case is different from HAM, and the above clinical features may fit to the disease entity of HTLV-I associated polyradiculoneuropathy and cerebral white matter lesions.

Anemia, Refractory, with Excess of Blasts↗

PubMed1997

Cystine starvation induces reversible large-body formation from nuclear bodies in T24 cells.

Nuclear bodies (PML nuclear bodies; also referred to as PODs or ND10) are small intranuclear structures which contain PML as an essential constituent and from several to 20 or more of them are present per nucleus. When starved of amino acids, nuclear bodies reversibly form one or more doughnut-shaped large bodies in T24 cells. Here, I present evidence that cystine is essential for the maintenance of normal-sized nuclear bodies: Cystine deficiency induces the formation of large bodies, and the addition of cystine or cysteine induces the reappearance of many normal-sized nuclear bodies. Both PML and Sp100 exhibit the same behavior as that of the nuclear body antigen(s) of AP435 MAb with regard to these changes, L-buthionine-[S,R]-sulfoximine, an inhibitor of glutathione synthesis, also induced the formation of large bodies that could be reversed to nuclear bodies by both beta-mercaptoethanol and dithiothreitol as well as cystine. Large bodies have the characteristic electron-dense, spherical, and concentric or reticulated features of nuclear bodies as observed by electron microscopy. The results indicate that environmental cystine controls reversible change between nuclear bodies and large bodies, which are not mere aggregates of nuclear bodies, but rather reconstituted nuclear bodies.

Amino Acids↗

PubMed1997

Role of (+)-SKF-10,047-sensitive sub-population of sigma 1 receptors in amelioration of conditioned fear stress in rats: association with mesolimbic dopaminergic systems.

Rats exhibited a marked suppression of motility when they were re-placed in the same environment as that in which they had previously received an electric footshock. We examined the behavioral and neurochemical effects of (+)-N-allylnormetazocine hydrochloride ((+)-SKF-10,047) and (+)-pentazocine, putative sigma 1 receptor ligands, on this psychological-stress-induced motor suppression, defined as a conditioned fear stress. (+)-SKF-10,047 (3 and 6 mg/kg) dose-dependently attenuated the conditioned fear stress, whereas (+)-pentazocine failed to do so even at a higher dose (32 mg/kg). In rats showing the conditioned fear stress, dopamine turnover (i.e., the ratio of dopamine metabolites/dopamine contents) was decreased in the nucleus accumbens and was increased in the medial prefrontal cortex, but remained unchanged in the striatum. (+)-SKF-10,047 (3 and 6 mg/kg) dose-dependently reversed the decreased dopamine turnover in the nucleus accumbens without changing the increased dopamine turnover in the medial prefrontal cortex. (+)-Pentazocine (32 mg/kg) did not affect the stress-induced changes in dopamine turnover in these brain regions. Thus, the decreased dopamine turnover in the nucleus accumbens appears to be involved in the conditioned fear stress. These results suggest that (+)-SKF-10,047 ameliorates the conditioned fear stress by reversing the psychological stress-induced dysfunction in the mesolimbic dopaminergic systems, and that the (+)-SKF-10,047-sensitive sub-population of sigma 1 receptors may play in important role in this stress response.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Contribution of aranidipine metabolites with slow binding kinetics to the vasodilating activity of aranidipine.

Aranidipine, a novel dihydropyridine derivative, gives rise to two active metabolites, M-1(alpha) and M-1(beta), which exhibit hypotensive activity comparable to that of nifedipine. The aim of this study was to examine the recovery phase of the vasodilating effect of M-1(alpha) and of M-1(beta), to determine their binding characteristics and to compare the results with those for aranidipine and other dihydropyridine derivatives. During intra-arterial infusion into the femoral vascular beds of anesthetized dogs, M-1(alpha), M-1(beta), and nifedipine, produced increases in femoral blood flow at doses three times higher than the dose of aranidipine required to produce a comparable effect. The onset and recovery of the effects of the metabolites on femoral blood flow were significantly slower than the onset and recovery of the effect of nifedipine. The inhibitory activities of M-1(alpha) and M-1(beta) towards stimulated 45Ca uptake in isolated guinea pig aorta were less than that of aranidipine. In binding studies, using porcine heart membrane preparations, [3H]M-1(alpha) and [3H]M-1(beta) had larger Kd values than [3H]aranidipine and [3H]nitrendipine, but the maximal binding number for each of them was almost the same. The association and dissociation rate constants for [3H]M-1(alpha) and [3H]M-1(beta) binding, as well as those for [3H]aranidipine binding, were significantly smaller than those for [3H]nitrendipine, corresponding to the recovery of the in vivo vasodilating effects of the metabolites. The dissociation rate constants of these radiolabeled ligands were highly positively correlated with the elimination rate constants of their in vivo vasodilating effects. From these results, we conclude that M-1(alpha) and M-1(beta), although their binding affinities and Ca2+ antagonistic actions are less potent, possess slower kinetic binding properties than many other dihydropyridines and that the slow kinetic interaction of these metabolites with the dihydropyridine receptor may contribute to the long-lasting in vivo vasodilating effect of aranidipine.

Animals↗

PubMed1997

Influence of flavonoids on cell cycle phase as analyzed by flow-cytometry.

Flavonoids were previously reported to have cytostatic activity in vitro and in vivo. In the present study each phase of the cell cycle was observed by flow-cytometry after HCT-15 cells had been cultured with flavonoids for 2 days. In the control group, two peaks were observed on the histogram, the first peak representing double strands of DNA, and the second, tetra strands. Chalcone, which is known to be a precursor of all flavonoids, seemed to block the passage from S to G2 and M phase. Flavonone, which is freely transformed into chalcone in vivo, showed a similar histogram as chalcone. Among the anthocyanins most effective in suppressing the tumor cell growth, cyanin and pelargonidin made a mild rise between the 1st and 2nd peak suggesting block between G1 and S phase. Delphinidin gave a high percent of cells in G1 phase, suggesting prolongation of G1 phase. When quercetin or kaempherol, both of which are flavonols were added to the culture, the second peak rose significantly, indicating a block between G2 and M phases. Thus, the site of these cytostatic agents seems to differ depending on the kind of flavonoid.

Cell Cycle↗

PubMed1997

Effect of allomelanin on tumor growth suppression in vivo and on the cell cycle phase.

Allomelanins are nitrogen-free macromolecular polymers of simple phenols produced by higher plants and fungi. In an earlier work we found that allomelanins were effective in suppressing the growth of cultured tumor cells. In the present study we examined the effect of these polymers on the survival curve of Balb/C mice inoculated i.p. with Meth/A cells (3 x 10(4) cells/mouse), which originated from a malignant lymphoma. Allomelanins were extracted from black sesame seeds and black soybeans, and given p.o. via the drinking water. The dose of allomelanins was approximately 3 mg/mouse/day. The percent of survivals was significantly higher in the experimental groups than in the control. Also, when HCT-15 cells were cultured for 2 days in medium containing 400 micrograms/ml of protein-free allomelanins, histograms obtained from flow-cytometry data showed a significant increase in the fraction between the diploid and tetraploid peaks, indicating blockage of the S phase of the cell cycle. These results suggest that allomelanins suppressed the tumor cell growth in vitro and in vivo, and that the effect was cytostatic, mostly by blockage of the S phase.

Animals↗

PubMed1997

Antitumor effect of anthocyanin fractions extracted from red soybeans and red beans in vitro and in vivo.

Many bioflavonoids extracted from petals of higher plants and from fruit rinds, as well as purified flavonoids, have been reported to have antitumor effects in vitro and in vivo. Bioflavonoids extracted from red soybeans are mostly cyanin conjugated with glucose and rhamnose, whereas bioflavonoids of red beans are cyanin conjugated with rhamnose as revealed by thin-layer chromatogram. Flavonoids extracted from red soybeans were effective in inhibiting the growth of HCT-15 cells in vitro. On the other hand, flavonoids from red beans were not effective, although their hydrolyzed sugar-free forms were growth inhibitory. Sugar-bonded bioflavonoids extracted from both red soybeans and red beans were effective in prolonging the survival of Balb/C mice bearing syngeneic tumor-Meth/A cells, when they were dissolved in drinking water and given at a dose of approximately 500 micrograms/mouse/day.

Animals↗

PubMed1997

Direct tumor growth suppressive effect of melanoidin extracted from immunomodulator-PSK.

Melanoidin, which belongs to the melanin group of molecules, was extracted from the polysaccharide biological response modifier PSK. Melanoidin was cultured together with HCT-15 cells derived from human colon cancer and with AGS cells derived from human gastric carcinoma. After four days of culture, cell count was compared with that of the control cells. Significant suppression was observed, that is, 50% suppression was shown at concentrations of melanoidin between 200 and 100 micrograms/ml. A histogram generated by flow cytometry showed elevation of the tetraploid peak and of that between diploid and tetraploid peaks, suggesting blockage of S phase and G2 to M phase of the cell cycle. Thus, melanoidins contained in the immunomodulator PSK revealed to have a direct tumor cell growth inhibitory effect.

Adjuvants, Immunologic↗

PubMed1997

Tumor cell growth-inhibiting effect of melanoidins extracted from miso and soy sauce

Melanoidins, a group of plant-produced melanins, were extracted from miso and shoyu (soy sauce), which are products of soybeans and widely consumed as food in oriental countries. The molecular weight of these melanoidins was approximately 5600 as revealed by Sepharose CL-4B column chromatography. The melanoidins were cultured together with HCT-15 cells derived from human colon carcinoma and AGS cells derived from human gastric carcinoma. Significant cell growth suppression was observed by incubating the cells with these melanoidins. The 50% growth suppression dose ranged between 100 micrograms/ml and 25 micrograms/ml, that is, between 2 x 10(-5) mM/ml and 0.5 x 10(-5) mM/ml. Flow cytometric analysis suggested that these melanoidins blocked the S phase and G2 to M phase of the cell cycle.

Journal Article↗

PubMed1997

Suppression of growth of cultured malignant cells by allomelanins, plant-produced melanins.

Allomelanins, which belong to the melanins produced by higher plants and fungi, were studied with respect to their growth suppressive effects on cultured HCT-15 cells derived from human intestinal carcinoma and Meth/A cells derived from a Balb/C mouse lymphoma. Allomelanins were extracted from black soy beans and black sesame seeds with 0.2% NaOH in water. Proteins bonded to the allomelanins were removed by boiling the extracts for 20 hours in 30% NaOH. Although native allomelanins conjugated with protein did not suppress the growth of the cells, protein-free allomelanins did suppress it. That is, 50% suppression of HCT- 15 cell growth was found at a concentration between 100 and 200 micrograms/ml of the melanin prepared from the black soy beans, and between 25 and 100 micrograms/ml of that from the sesame seeds. For Meth/A cells, 50% suppression by allomelanin from the black beans was approximately 100 micrograms/ml; and that by the allomelanin preparation from sesame seeds, between 25 and 100 micrograms/ml. Thus, protein-free allomelanins seemingly suppress cultured mammalian and animal tumor cells.

Animals↗

PubMed1997

Tumor cell growth suppression by chalcone (1,3-diphenyl-2-propen-1-one).

Chalcone or 1,3-diphenyl-2-propen-1-one which is widely distributed in higher plants and is considered to be a precursor of all flavonoids, was studies in terms of its anti-tumor growth activity in vitro and in vivo. Mice given the chalcone, which was suspended in the drinking water, showed a statistically significant rise in percent survival: 66% at the 35th day for the chalcone-treated animals vs. 30% for the control ones. The chalcone also gave significant suppression of growth of HCT-15 and Meth/A cells in vitro. The dose of 50% reduction in growth was between 2.5 micrograms/ml and 0.6 microgram/ml for the HCT-15 cells and less than 10 micrograms/ml for the Meth/A cells. Histograms obtained by flow cytometric examination showed an elevated region between the diploid and the tetra-ploid nucleoidal peaks. A third peak heavier than the tetra-ploid peak was also observed, which peak was not observed in the control. The percentage of cells in the S phase was significantly raised. Microscopically, large nucleated cells were observed following addition of the chalcone. These results suggest that the chalcone induced abnormal DNA synthesis and mitosis in the cultured cells.

Animals↗

PubMed1997

[Magnetic resonance imaging of brainstem lesions in a case of neuro-Behçet disease].

We reported a 28-year-old man with multiple lesions in the brainstem which were clearly identified and followed up with MRI. He had been treated for Behçet uveitis using cyclosporine and colchicine during the past 5 years, and he acutely presented with fever and headache, followed left hemiparesis, dysarthria and dysphagia. MRI on admission revealed multiple lesions in the ventral pontine region which showed mixed-intensity on T1WI, high-intensity on T2WI and enhancement with Gd-DTPA. His clinical symptoms spontaneously and gradually improved, but more rapidly improved due to additional administration of corticosteroid. The lesions in the brainstem became smaller and finally rudimentary during two months after the onset of neurological symptoms.

Adrenal Cortex Hormones↗