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Biomedical subjects

M Sasa

Publications and source records attributed to M Sasa.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effectiveness of mammographic screening for breast cancer in women aged over 50 years in Japan.

The optimal age for effective screening of subjects for breast cancer by mammography in Japan was studied based on the results of two mammographic screening systems (systems I and II) in Tokushima Prefecture. System I consisted of visit screening using a bus equipped with a mammographic apparatus. System II consisted of central screening performed at Tokushima Health Screening Center. The examinees numbered 2,500 and 3,707 in systems I and II, respectively. There was a significant difference between the two screening systems in the age distribution of the examinees. The detection rates of breast cancer were 0.6% and 0.24% in systems I and II, respectively, which are 2-5 times higher than that (0.12%) obtained by conventional screening using physical examination alone. The detection rate increased especially in the sixth and seventh decades of life. The sensitivity of mammography screening was 93.3% in system I and 81.1% in system II. Higher sensitivity (100%) than that (73%) of screening by physical examination was obtained in women aged over 50. The proportion of stage I was 60% in system I and 66.7% in system II, compared with 32-65% in the United States and Europe. The rates of no nodal involvement were high, being 77.8% and 83.3% in systems I and II, respectively, compared with 57-71% in other countries. Breast-conserving therapy was applied to 18 of the 24 patients with breast cancer detected by the two screening systems. In addition, in Wolfe's classification of mammograms, the proportion of DY (mammary dysplasia) pattern was remarkably low, being 3.2% in the sixth decade and 0.8% in the seventh decade, compared with 16.6% in women aged 49 years. These results indicate that mammographic screening is effective in women aged over 50 years in Japan, as has been found in other countries.

Aged↗
PubMed1997

Antiepileptic effects of 20-hydroxyecdysone on convulsive seizures in spontaneously epileptic rats.

We examined the effect of 20-hydroxyecdysone (20-HE), a neurosteroid found in insects that is involved in their developmental process, on both tonic convulsion and absence-like seizure in spontaneously epileptic rat (SER). When 20-HE was given orally to SER at 25-200 mg/kg, significant decreases of the tonic convulsion were observed with 100 and 200 mg/kg. Pretreatment of the animal with bicuculline (1 mg/kg, i.p.) antagonized the inhibitory effects of 20-HE. However, absence-like seizures were not affected by 20-HE. These findings indicate that 20-HE produces antiepileptic effects on tonic convulsion by acting on the modulatory site of GABA(A) receptors.

Administration, Oral↗
PubMed1997

Effects of perospirone, a novel antipsychotic agent, on the dopaminergic neurons in the rat ventral tegmental area.

An electrophysiological study was performed to investigate the effects of cis-N-[4-[4-(1,2-benz-isozole-3-yl)-1-piperazinyl]butyl]cyclohexan e-1,2-dicarboximide hydrochloride (perospirone), a novel antipsychotic agent with high affinities for D2/5-HT2-receptors, on the dopaminergic (DA) neurons in the ventral tegmental area (VTA) using chloral hydrate-anesthetized rats. DA neurons and non-DA neurons in VTA were identified according to the configurations of their action potentials and firing rates. Spontaneous firing of DA neurons was dose-dependently decreased by i.v. injection of methamphetamine (MAP). Most non-DA neurons were unaffected by MAP up to 2 mg/kg, but the firing was increased with MAP in 2 of 7 neurons. Perospirone injected intravenously reversed the MAP-induced decrease in spontaneous firing of DA neurons in a dose-dependent manner. In addition, i.v. injection of perospirone also inhibited the MAP-induced increase in firing of the 2 non-DA neurons. Similarly, inhibition of spontaneous firing in DA neurons by microiontophoretically applied DA was antagonized during iontophoretic application of perospirone. However, the firing of non-DA neurons, which were insensitive to DA, was not affected by iontophoretically applied perospirone. Since the DA neurons are inhibited by DA via D2-receptors, these findings suggest that perospirone acts on the D2-receptors to antagonize the dopaminergic inhibition of DA neurons in VTA.

Animals↗
PubMed1997

[A novel epilepsy animal model (NER)].

A mutant showing convulsive seizures spontaneously in a CJ: Wistar colony was named the Noda epileptic rat (NER). The NER exhibits tonic-clonic convulsion without any external stimuli once every 30 h. However, we succeeded in inducing similar convulsive seizures by applying priming sound stimuli (95 dB, 8 kHz, 30 sec) from 3 weeks of age in all 24 NER examined. When the effects of clinically available antiepileptics were tested on the seizures of such primed NER, the most potent agents were carbamazepine, diazepam, valproate, phenobarbital and trimethadione, while phenytoin and zonisamide showed lower potency. Furthermore, ethosuximide was not effective in inhibiting the seizures. In hippocampal slices of NER with convulsive seizures, repetitive firing accompanied by long-lasting depolarization was observed when a single stimulation was delivered to the mossy fibers in the CA3 pyramidal cell. This depolarization shift was completely blocked with a Ca2+ antagonist (nicardipine 10 nM). The long-lasting hyperpolarization that followed the repetitive firing was also observed with mossy fiber stimulation in the hippocampal CA3 pyramidal cells of the NER. These findings suggest that Ca2+ channel abnormality of the hippocampal CA3 pyramidal cells may be involved in the convulsive seizures.

Animals↗
PubMed1997

[A new approach to innovating selective anxiolytics: pharmacological profile of a novel 5-HT1A agonist (tandospirone)].

Tandospirone (sedil) is a newly developed anxiolytic drug that has a much higher selective affinity for 5-HT1A than dopamine D2 receptors without the binding affinities with noradrenergic, dopaminergic, cholinergic and GABAergic receptors. This agent binds with 5-HT1A receptors located in both 5-HT neurons in the raphe nucleus and other postsynaptic neurons to induce hyperpolarization of the neurons by opening the K+ channels to eventually inhibit the target neuronal activities. With repeated administrations of tandospirone, a decrease in 5-HT2A receptor population was observed. Behavioral studies in experimental animals have demonstrated that tandospirone inhibits conflict in Vogel methods, aggressive behavior and muricide in manners similar to those of diazepam. In addition, tandospirone showed antistress effects in experimental models and antidepressive effects in forced swimming tests. Unlike diazepam, tandospirone does not produce sedative, sleep-inducing, anticonvulsant, nor muscle relaxant effects at doses effective for conflict tests. Drug dependance, one of the serious problems with bezodiazepine, is not observed with repeated treatment of tandospirone in rats and monkeys. Furthermore, tandospirone has been reported to show a significantly more superior or equipotent effect to diazepam in controlling autonomic disturbances, psychiatric cardiovascular and vegetative syndromes as well as neurosis in double blind clinical studies. These effects are probably due to the selective action of tandospirone on 5-HT1A receptors in the limbic system to eventuate anxiolytic and antidepressant effects. A decrease in 5-HT2A receptor population with repeated treatment of tandospirone may have contributed to the antidepressive effect. Furthermore, 5-HT1A receptors relatively, selectively distributed in the limbic system are not involved in sedation, sleep or muscle relaxation. Such unwanted effects of benzodiazepines are thus not observed with tandospirone treatment.

Aggression↗
PubMed1997

D2 receptor activation in distinct striatal neurons in comparison with D3 receptors.

The role of D2/D3 receptors in striatum was electrophysiologically examined in vitro in chloralose-anesthetized rats. In addition, in vitro patch clamp method with rat brain slices was followed. Stimulations of the substantia nigra pars compacta (SN) in vivo elicited spike generation which was inhibited by microiontophoretically applied domperidone, a D2 antagonist. These domperidone-sensitive neurons were activated by microiontophoretic application of D2 agonists such as talipexole, quinpirole and bromocriptine as well as the D2 agonist, 7-OH-DPAT. They were also excited by either intravenous injection of bromocriptine or talipexole in a dose-dependent manner. Furthermore, the SN-induced increases in neuronal firing were blocked during microiontophoretic application of domperidone. In patch clamp whole-cell recording large-sized cells, identified visually under Ramanosky microscope, were depolarized with repetitive firing on bath application of talipexole and 7-OH-DPAT at a current clamp mode. Talipexole-induced depolarization in the large-sized cell was similarly observed in the presence of TTX and high Mg2+ in Ca(2+)-free physiological solution. In contrast, the medium-sized cells were hyperpolarized on bath application of talipexole without being affected by 7-OH-DPAT. These findings suggest that the large-sized cells, which were presumably cholinergic interneurons, are activated by dopamine derived from the SN via D2 and/or D3 receptors, while the medium-sized cells are inhibited by dopamine via D2 receptors.

Animals↗
PubMed1996

Molecular epidemiology of breast cancers in northern and southern Japan: the frequency, clustering, and patterns of p53 gene mutations differ among these two low-risk populations.

Comparison of acquired mutations in the p53 tumor suppressor gene can illuminate factors contributing to carcinogenesis among cancer cohorts. Japan has an ethnically homogeneous population with a low incidence of breast cancer. Previously we reported an unusual frequency, allelic status, and clustering of mutations in breast cancers from the northern part of the main Japanese island. To extend these findings, exons 2-11 and adjacent intronic sequences were analysed in tumors of women from northern (Hokkaido) and southern (Tokushima) Japan. The frequency of breast cancers with p53 gene mutations in the Hokkaido group is the highest reported (81%) while that in Tokushima (28%) is similar to most other populations. Thirteen of the 19 mutations (68.4%) in the Hokkaido cohort were heterozygous, an unusually high frequency for p53 mutations in any tumor type. There were three missense mutations at codon 175, a known hotspot for alterations in the p53 gene, and three missense mutations at codon 179, a rare site for p53 changes. In addition, the patterns of p53 gene mutation differed between the two Japanese cohorts (P=0.04). The multiple differences in acquired p53 mutations suggest unsuspected biological differences among breast cancers in northern and southern Japan. In addition, the high frequency of p53 mutations in breast cancers from Hokkaido predicted a poorer prognosis for this population which was confirmed on examination of mortality data.

Adult↗
PubMed1996

Hypersensitivity of nucleus accumbens neurons to methamphetamine and dopamine following repeated administrations of methamphetamine.

Methamphetamine (MAP) abuse is known to induce reverse tolerance in humans. Electrophysiological studies were performed to elucidate time-related changes in dopamine (DA) receptor sensitivities to DA and MAP after withdrawal following repeated MAP administrations. MAP (5 mg/kg) or physiological saline (1 ml/kg) was injected i.p. to rats once daily for 5 days. Single neuronal activities of nucleus accumbens (Acc) of 5-day MAP-administrated rats were extracellularly recorded with a glass microelectrode attached along a seven-barreled micropipette under chloral hydrate anesthesia. Each barrel was respectively filled with DA, MAP, haloperidol, glutamate and NaCl. Drugs were microiontophoretically applied to the immediate vicinity of Acc neurons receiving inputs from the parafascicular nucleus (Pf) of thalamus. Spikes elicited by Pf stimulation- and glutamate-induced firing were inhibited by iontophoretic application of either DA or MAP at doses of 20-40 nA in the saline-treated rats: EC50 for DA and MAP were 23.8 and 23.2 nA, respectively. At 24-30 hr after the final MAP administration, however, the inhibitory effects of both DA and MAP on Pf stimulation- and glutamate-induced firing of Acc neurons were less pronounced than those in the saline-treated animals. Furthermore, spontaneous firing was enhanced during haloperidol application. On day 5 postadministration, the inhibition of Acc neurons by DA or MAP was significantly more marked than that of saline-treated animals. On day 10 postadministration, the inhibition of Acc neurons by DA or MAP was comparable to that in controls. These results indicate that repeated administrations with MAP induce hyposensitivity and hypersensitivity of Acc neurons to DA and MAP at 24-30 hr and on day 5 postadministration, respectively.

Action Potentials↗
PubMed1996

Inhibition by a putative antipsychotic quinolinone derivative (OPC-14597) of dopaminergic neurons in the ventral tegmental area.

The effects of the newly synthesized quinolinone derivative, OPC-14597 (7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy}-3, 4-dihydro-2(1 H)-quinolinone), on dopaminergic neuronal activity in the ventral tegmental area were examined using both in vivo microiontophoretic methods in chloral hydrate-anesthetized rats and the tight-seal whole-cell patch-clamp technique in thin-slice preparations of the rat brain. Neurons in the ventral tegmental area were classified as type I or type II according to their responses to antidromic stimulation of the nucleus accumbens, probably corresponding to dopaminergic and non-dopaminergic neurons, respectively. Antidromic spikes elicited by nucleus accumbens stimulation were inhibited by microiontophoretic application of dopamine and OPC-14597 in type I, but not in type II neurons. Although the OPC-14597-induced inhibition was antagonized by simultaneous application of domperidone (5-chloro-1-[1-[3-(2,3-dihydro-2-oxo-1 H-benzimidazo-1-yl)-propy]-4-piperidinyl]-1,3-dihydro-2H- benzimidazol-2-one; dopamine D2 receptor antagonist), SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1 H-3-benzazepine hydrochloride; dopamine D1 receptor antagonist) had no such effect. Spontaneous firing of type I neurons was also inhibited by iontophoretically applied OPC-14597 and dopamine, whereas that of type II neurons was unaffected. The inhibitory effect of OPC-14597 on the spontaneous firing of type I neurons was antagonized by domperidone, but not by SCH 23390. In a whole-cell patch-clamp study using a thin-slice preparation of the rat brain, bath application of OPC-14597 induced hyperpolarization accompanied by inhibition of spontaneously occurring action potentials in the large neurons (> 20 microns in diameter) in a concentration-dependent manner. These results suggest that OPC-14597 acts on dopaminergic neurons in the ventral tegmental area as a dopamine D2 receptor agonist to inhibit neuronal activities, probably by increasing membrane potassium conductance.

Animals↗
PubMed1996

Ductal Carcinoma In Situ of the Breast: Is Breast Conserving Treatment Feasible?

Between 1968 and 1993, 43 cases of ductal carcinoma in situ of the breast (DCIS) were treated. We examined the extent of the cancer using multiple sections of surgical specimens and considered whether or not breast conserving treatment (BCT) is feasible for treatment of DCIS. In nine out of 40 patients (23%), extent of the cancer was classified as grade III, defined as extension over a 2.5-cm margin around the tumor. Among those nine cases, 67% (6/9) had extensive microcalcification on mammography. With respect to the correlation between the tumor size and the extent of the cancer, 29%(5/17) of the cases with a small size tumor, ie, 1.0 cm or less, showed grade III or greater. All tumors with a size of 1.1-2.0 cm showed grade II or lower, and 50%(4/8) of cases with a tumor size of 2.1 cm or more showed grade III or greater. Concerning the relationship between the histological subtype and the extent of the cancer, 22%(2/9) of comedo carcinomas and 23%(7/30) of noncomedo carcinomas showed grade III or greater. The histological extent thus showed no difference between comedo carcinoma and noncomedo carcinoma. It follows that, when BCT performed on DCIS consists of lumpectomy alone, BCT is feasible when the tumor size is 1.1-2.0 cm. without extensive microcalcification on mammography. However, BCT for comedo carcinoma should be approached with caution because of its malignant behavior, although there was no difference in histological extent between comedo and noncomedo carcinoma.

Journal Article↗
PubMed1996

A dose-response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients.

Mutations of the p53 tumor suppressor gene are frequent in lung cancers. It is suggested that p53 mutations are associated with smoking-induced lung carcinogenesis. We examined p53 mutations in 53 lung cancers by analyzing reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) to ascertain the association between p53 mutations and smoking. Twenty-five (47%) of 53 lung cancers carried p53 mutations. A discriminant analysis showed that the Brinkman index (0.156) and gender (0.140) significantly influenced p53 mutations. Furthermore, there was a dose-response relationship between the quantity of cigarettes consumed and the frequency of p53 mutations in lung cancer patients (P < 0.001). In patients with adenocarcinoma, the frequency of p53 mutations correlated with the amount of the tobacco smoked (P < 0.05). We suggest that the p53 gene is a target of particular carcinogen in tobacco smoke.

Adenocarcinoma↗
PubMed1996

Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER).

The spontaneously epileptic rat (SER), a double mutant, manifests both tonic and absence-like seizures. The effect of topiramate, a novel antiepileptic drug, on the extracellular levels of excitatory amino acids (EAA) in the hippocampus of SER was investigated using in vivo microdialysis. The basal levels of glutamate and aspartate in dialysates of hippocampus in SER were 2- to 3-fold higher than those in normal Wistar rats. Both the dose-response relationship and the time course of the suppression of tonic seizures by topiramate were similar to the attenuation of glutamate level in SER. Topiramate (40 mg/kg i.p.) significantly (P < 0.05) reduced both glutamate and aspartate levels in SER while showing no effect on normal Wistar rats. These findings suggest that topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of SER. This effect may, at least in part, be related to the anticonvulsant activity of topiramate.

Animals↗
PubMed1996

Effects of a newly developed transdermal clonidine delivery system (M-5041T) on EEG sleep-wake cycle in relation to plasma concentration in rabbits.

1. The effects of a transdermal clonidine delivery system (M-5041T) on EEG sleep pattern with relation to plasma concentrations in unrestrained rabbits were investigated and compared with those of intravenous (i.v.) administration of clonidine. 2. Although M-5041T did not affect the EEG recorded from cortex and hippocampus at doses up to 2.5 mg/kg, slow theta waves in hippocampal EEG accompanied by low-voltage slow waves in cortex were induced at a higher dose of 12.5 mg/kg. On i.v. injection (0.25 mg/kg), EEG tracings with bursts of high-voltage slow waves in cortical EEG and slow theta waves in hippocampus were observed. 3. At doses of 0.5 and 2.5 mg/kg, M-5041T did not cause any alterations of the sleep-wake cycle, and plasma concentrations of 1-2 ng/ml were maintained for an 8-hr observation period. However, this delivery system significantly suppressed the incidence of rapid-eye movement sleep (REMS) from 11.9 to 4.7% and enhanced drowsiness (DW) from 9.0 to 21.0% during the 8-hr recording period at 12.5 mg/kg with a plasma concentration of up to 10 ng/ml. Contrary to transdermal administration, i.v. clonidine (0.25 mg/kg) completely blocked light and deep slow wave sleep as well as REMS with a plasma concentration indicated more than 10 ng/ml at 2 hr post administration. Recovery to a normal sleep-wake cycle was eventually established thereafter. The incidence of REMS and DW were significantly decreased from 11.9 to 6.3% and increased from 9.0 to 25.5%, respectively. 4. Concurrent monitoring of clonidine concentrations in cerebrospinal fluid (CSF) indicated that CSF concentrations after patching M-5041T, as well as i.v. clonidine, were almost equal to plasma levels. 5. These results suggest that alteration of the sleep-wake cycle with clonidine occurs depending upon brain concentrations, which increase to a level similar to that in plasma after administration, and that M-5041T at doses of less than 2.5 mg/kg could establish effective hypertensive therapy without obvious effects on the cycle.

Animals↗
PubMed1996

Long-term antiepileptic effects of chronic intake of CNK-602A, a thyrotropin-releasing hormone analogue, on spontaneously epileptic rats.

Spontaneously epileptic rats (SER), which represent a double mutation (zi/zi, tm/tm), spontaneously exhibit both tonic and absence-like seizures. We examine the long-term effects of a thyrotropin-releasing hormone (TRH) analogue, CNK-602A, acute administration of which was effective inhibiting both types of seizures in SER, to determine if this agent could be used to treat epilepsy for long periods. Food pellets containing 0.001% CNK-602A were given ad libitum to SER from age 7 weeks. CNK-602A significantly inhibited tonic convulsions and prolonged survival. There were no alterations in body weight or plasma levels of triiodotHyronine (T3) and thyroxine (T4). These findings indicate that chronic intake of CNK-602A in a dose that does not affect plasma levels of T3 and T4 inhibits tonic convulsions in SER and suggest that this drug may be an effective treatment for convulsive seizures in patients with epilepsy.

Administration, Oral↗
PubMed1996

Electrophysiological and pharmacological characteristics of ionotropic glutamate receptors in medial vestibular nucleus neurons: a whole cell patch clamp study in acutely dissociated neurons.

A patch clamp study was performed to determine which subtype of ionotropic glutamate receptors is involved in the glutamate-induced excitation of the medial vestibular nucleus (MVN) neurons. Whole cell recording was performed on MVN neurons that were acutely dissociated by enzymatic and mechanical treatments. Application of glutamate at a concentration of 100 microM produced a current with a reversal potential of approximately 0 mV. The glutamate-induced current was completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), a non-N-methyl-D-aspartate (NMDA)-receptor antagonist. Application of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainic acid (KA), non-NMDA-receptor agonists, at concentrations of 30 and 100 microM produced a concentration-dependent depolarization concomitantly with an increase in firing rates during current clamp recording. During voltage clamp recording, glutamate, AMPA and KA elicited a concentration-dependent current with an equilibrium potential of approximately 0 mV. To clarify whether NMDA receptors are present in MVN neurons, the effects of glycine on the glutamate- and NMDA-induced current were examined. Two types of NMDA receptor-mediated current (types 1 and 2) were obtained in terms of the difference in sensitivity to both magnesium ion and MK-801, which act on the NMDA-receptor channel. In the type 1 neurons, the NMDA-induced current was not apparently blocked by magnesium ion or MK-801, although a larger current was obtained in the absence of magnesium ion. In the type 2 neurons, marked blockade of the NMDA-induced current was seen in the presence of magnesium ion and MK-801, as previously reported in other neurons of the central nervous system. These findings indicate the presence of both non-NMDA and NMDA receptors, which are involved in primary afferent transmission, in the MVN neuron, and two distinct types of NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Release and uptake of vitamin B12 by asakusanori (Porphyra tenera) seaweed.

When asakusanori was incubated in artificial seawater, it released a significant amount of vitamin B12. The rate of release was very high at the beginning of incubation and steeply decreased. Four-fifths of the released B12 was a macromolecule-bound form and the rest was free form, of which some were taken up by the asakusanori tissue. Asakusanori took up the free form B12 from the incubation medium by concentration- and temperature-dependent processes. The amount of uptake increased with the time of incubation and did not attain a plateau after 4 h. The capacity was retained even after storage in frozen state for 11 months.

Diffusion↗
PubMed1995

Effect of nicardipine on abnormal excitability of CA3 pyramidal cells in hippocampal slices of spontaneously epileptic rats.

The effects of nicardipine, a Ca2+ channel antagonist, on the abnormal excitability of hippocampal CA3 neurons in spontaneously epileptic rats (SER), a double mutant (zi/zi, tm/tm), were examined to elucidate whether or not the abnormality was due to that of Ca2+ channels. An intracellular recording study was performed using brain slice preparations of SER 12-15 weeks of age, when SER showed both tonic convulsions and absence-like seizures. Bath application of nicardipine (10 nM) completely inhibited the depolarizing shifts lasting for 60-120 ms and accompanying repetitive firings on mossy fiber stimulation in SER. However, this drug did not affect the single action potential induced by the mossy fiber stimulation in CA3 neurons of SER and normal Wistar rats. In the CA3 pyramidal neurons of SER, the Ca2+ spikes induced by the depolarizing pulse applied in the cell in the presence of tetrodotoxin and tetraethylammonium had a different configuration from that in normal Wistar rats. Nicardipine also inhibited the Ca2+ spikes in SER CA3 neurons at a concentration (1 nM) that had no effect on those in normal Wistar rats, while the Ca2+ spikes in Wistar rat CA3 neurons were inhibited by 10 nM nicardipine. These findings suggest that the abnormal excitability of CA3 pyramidal neurons in SER might be attributed to abnormalities of the Ca2+ channels, and that the Ca2+ channel antagonist may be effective as an antiepileptic drug.

Animals↗