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Biomedical subjects

N Koshikawa

Publications and source records attributed to N Koshikawa.

At least 109 records · Page 6Linked to original sources

Prostaglandins and premenstrual syndrome.

We examined plasma PGF2 alpha, PGE, PGE2, TXB2 and 6-keto-PGF1 alpha at intervals throughout 3 menstrual cycles in 20 patients with PMS. Similar measurements throughout 1 menstrual cycle were made in 12 age-matched control women. The plasma concentration of PGF2 alpha in the late luteal phase was significantly lower in patients with PMS compared with that in the control subjects. The plasma concentrations of PGE in the middle follicular phase and middle luteal phase, PGE2 alpha in the middle follicular phase and TXB2 in the middle and late luteal phase were significantly higher in 20 patients compared with the values in the controls. A disturbance of PG metabolism may contribute to the etiology of PMS.

Adolescent↗

Comparison of extracellular matrix-degrading activities between 64-kDa and 90-kDa gelatinases purified in inhibitor-free forms from human schwannoma cells.

Two kinds of gelatinases (or type IV collagenases), 90-kDa and 64-kDa gelatinases, were purified in a tissue inhibitor of metalloproteinases (TIMP)- or TIMP-2-free form from the serum-free conditioned medium of human schwannoma YST-3 cells, and their activities on extracellular matrix proteins were compared. Sequential chromatographies on a gelatin-Sepharose column, an LCA-agarose column, and a gel filtration column in the presence of 5 M urea yielded 600 micrograms of the 64-kDa enzyme and 45 micrograms of the 90-kDa enzyme from 2.8 liters of the conditioned medium. The purified enzymes showed high gelatinolytic activities without activation by p-aminophenyl mercuric acetate (APMA), indicating that 5 M urea used in the final chromatography not only dissociated the inhibitors from the progelatinases but also activated the proenzymes. The inhibitor-free gelatinases showed a much higher activity than the APMA-activated inhibitor-bound enzymes. The specific activity of the 90-kDa enzyme was nearly 25 times higher than that of the 64-kDa enzyme. The 90-kDa gelatinase hydrolyzed type I collagen as well as native and pepsin-treated type IV collagens at 30 degrees C, while at 37 degrees C it potently hydrolyzed types I, III, and IV collagens but not fibronectin or laminin. The 64-kDa gelatinase showed a similar substrate specificity to that of the 90-kDa enzyme, except that it did not hydrolyze type I collagen and native type IV collagen at 30 degrees C.

Collagen↗

[Behavioral assessment of neuroleptics (2)--stereotypy].

This paper describes the definition of stereotypy and the different methods available for measuring both the form and the invariance of stereotyped behavior. With respect to the use of stereotypy for screening antipsychotic drugs, commonly used techniques for observing dopamine agonist-induced oral stereotypy in rats and the relevant points to analyze in the results are discussed. Apart from the ways of visually analyzing stereotyped behavior, some approaches for quantifying the intensity of stereotypy by using automated systems are also discussed.

Animals↗

Cholecystokinin octapeptide and caerulein injection into the dorsomedial nucleus accumbens potentiate apomorphine-induced jaw movements in rats.

The effects of bilateral intra-accumbal and intrastriatal injections of CCK-8 sulphate and its analogue, caerulein, on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. Jaw movements were detected by a photo-transducer attached to the mandible. CCK-8 (5, 10 and 20 ng) and its analogue, caerulein (1 and 5 ng), injected into the dorsomedial nucleus accumbens increased the frequency of apomorphine (0.2 mg/kg i.v.)-induced jaw movements. The potentiation was prevented by administration of a CCK-A receptor antagonist, lorglumide (5 ng), together with CCK-8 (20 ng) or caerulein (5 ng). Injection of lorglumide alone into the dorsomedial nucleus accumbens did not alter apomorphine (0.5 mg/kg i.v.)-induced jaw movements. Injections of CCK-8 (20 ng) and caerulein (5 ng) into adjacent sites (the ventrolateral nucleus accumbens, dorsal striatum and ventral striatum) did not affect the responses elicited by apomorphine (0.2 mg/kg i.v.). These results demonstrate that CCK-8 modulates responses elicited by a dopamine receptor agonist, apomorphine, in a region of the brain where CCK-8 is known to co-exist with dopamine.

Animals↗

Functional interaction between dopamine D1 and D2 receptors in rat jaw movements.

The functional interaction between dopamine D1 and D2 receptors in dopamine-mediated jaw movements was studied in ketamine-anaesthetized rats after C1 spinal transection. Jaw movements were recorded by means of a light-emitting diode attached to the mandible; the method permits a detailed qualitative and quantitative analysis of jaw movements. D1 stimulation with SKF38393 (10 mg/kg i.v.) produced frequent bursts of teeth chattering, which were abolished by pretreatment with SCH23390 (0.25 mg/kg i.v.). D2 stimulation by quinpirole (1-10 mg/kg i.v.) produced infrequent bursts of jaw movements, which were characterized by low frequency jaw opening and closure movements from the rest position of the jaw, and absence of tongue protrusions. An additional stimulation of D1 receptors by giving SKF38393 30 min later produced an almost continuous pattern of jaw openings but less closure movements from the rest position, and the openings were accompanied by frequent tongue protrusions. These results clearly demonstrate that the type of oral behaviour produced by stimulation of D1 and D2 receptors together is qualitatively different from that produced by stimulation of either D1 or D2 receptors alone.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

The effects of tianeptine on wet-dog shakes, fore-paw treading and a flexor reflex in rats are consistent with enhancement of 5-hydroxytryptamine uptake.

Tianeptine is a novel antidepressant which uniquely facilitates 5-hydroxytryptamine (5-HT) uptake. When given in a dose of 10 mg/kg to rats pretreated with either carbidopa or phenelzine, it markedly reduced the frequency of wet-dog shakes, fore-paw treading, tremor and hind-limb abduction evoked by L-5-hydroxytryptophan (L-5-HTP) given 30 or 60 min later. This effect of tianeptine was opposite to that of paroxetine, a selective 5-HT uptake inhibitor, which greatly increased the 5-HTP-induced behavioural syndrome. In contrast, tianeptine did not affect behaviours elicited by the 5-HT receptor agonists, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), which are not substrates for the 5-HT uptake process. In spinal animals, tianeptine attenuated an ipsilateral flexor reflex, an effect opposite to that of citalopram, a selective 5-HT uptake inhibitor. These effects of tianeptine are consistent with its ability to increase 5-HT reuptake.

Amphetamines↗

Effects of dopamine D1 and D2 agonists and antagonists injected into the nucleus accumbens and globus pallidus on jaw movements of rats.

The effects of bilateral injections of selective D1 and D2 agonists and antagonists into the anteromedial part of the nucleus accumbens and the globus pallidus on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. Both SCH 23390 (0.1 and 1 micrograms) and 1-sulpiride (5 and 25 ng) injected into the nucleus accumbens suppressed the display of jaw movements after apomorphine (0.5 mg/kg i.v.). Injection of 1-sulpiride (5 and 25 ng) into the globus pallidus also blocked the effect of apomorphine, whereas SCH 23390 (1 microgram) injected into the same site was ineffective in this respect. Simultaneous application of the selective D1 and D2 agonists, SKF (1 or 5 micrograms) + quinpirole (10 micrograms), into the nucleus accumbens strongly potentiated the effect induced by local administration of each drug alone; a comparable, but smaller, effect was seen after simultaneous injections of these agents into the globus pallidus. These results show that dopaminergic mechanisms within the nucleus accumbens are involved in apomorphine-induced jaw movements, and that the expression of these movements requires concurrent activation of D1 and D2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Central dopaminergic actions of YM-14673, a new TRH analogue, in rodents.

The effects of a new TRH analogue, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate) on spontaneous movement, sniffing, climbing, licking, biting and circling behaviors were compared with those of TRH and methamphetamine, in rodents. YM-14673 in a dose of 1 mg/kg (i.p.) enhanced spontaneous motor activity in rats, and induced sniffing and climbing behaviors in mice. The licking and biting behaviors were not induced by administration of YM-14673 even in a high dose (30-100 mg/kg i.p.) to mice. In addition, ipsilateral circling did not follow the i.p. administration of YM-14673 in rats receiving cis-flupenthixol unilaterally into the striatum. YM-14673 was about 20-30 times more potent than TRH to induce sniffing and climbing behaviors and to increase spontaneous movement. The sniffing and climbing behaviors induced by administration of YM-14673 and TRH were antagonized by treatment with haloperidol and alpha-methyl-para-tyrosine (alpha-MT). Methamphetamine (0.5-10 mg/kg i.p.), unlike YM-14673, showed significant pharmacological effects in all behavioral experiments, so that the pharmacological profile of YM-14673 was different from that of methamphetamine. These results suggest that both YM-14673 and TRH induced behavioral changes, presumably due to facilitatory effects on the central dopaminergic system.

Animals↗

Further evidence for an anomalous regulation of cortical 5-HT2 receptors: studies with 5-HT precursors.

Rats pretreated with either phenelzine (50 mg/kg 18 h and 12 mg/kg 90 min previously) or carbidopa (25 mg/kg 30 min previously) then given tryptophan or 5-hydroxytryptophan (5-HTP), developed wet-dog shakes which were more intense after 5-HTP. Cortical 5-HT2 receptors were significantly reduced within 3 h of tryptophan (150 or 500 mg/kg) given to phenelzine-treated rats. 5-HTP either did not affect (150 mg/kg) or slightly increased (350 mg/kg) 5-HT2 receptor numbers in rats pretreated with carbidopa. The response to 5-HTP (350 mg/kg) was not altered by pretreatment with alpha-methyl-p-tyrosine, haloperidol, propranolol or yohimbine.

5-Hydroxytryptophan↗

Dopamine D-1 but not D-2 receptor stimulation of the dorsal striatum potentiates apomorphine-induced jaw movements in rats.

The effects of bilateral injections of selective D-1 and D-2 agonists and antagonists into the dorsal striata on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. A phototransducer attached to the lower mandible automatically detected jaw movements. YM-09151-2 (0.2 and 0.5 micrograms) and cis(Z)-flupentixol (0.5 and 1 microgram) injected into the dorsal striatum increased the frequency of jaw movements after apomorphine (0.2 mg/kg i.v.). The effects were prevented by administration of SCH23390 (1 microgram) with YM-09151-2 (0.5 microgram) or cis(Z)-flupentixol (1 microgram). Injection of SCH23390 (1 microgram) alone into the dorsal striatum failed to alter the apomorphine (0.5 mg/kg i.v.)-induced jaw movements. Local application of the selective D-1 agonists, SKF38393 (5 micrograms) and SKF75670 (10 micrograms), into the dorsal striatum potentiated the apomorphine (0.2 mg/kg i.v.)-induced jaw movements, while a D-2 agonist, quinpirole (10 micrograms), injected into the same site attenuated these movements. These data are suggestive of an oppositional D-1: D-2 receptor interaction in the dorsal striatum.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Role of dopamine D-1 and D-2 receptors in the ventral striatum in the turning behaviour of rats.

Systemically administered methamphetamine and apomorphine evoked characteristic turning when rats were pretreated with injections of D-1 and D-2 antagonists in the ventral but not in the dorsal striatum. The frequency of turning was greater for rats pretreated with D-2 antagonists (l-sulpiride and YM-09151-2) than for rats pretreated with a D-1 antagonist (SCH 23390). The responses were apparently additive when rats were pretreated with mixed D-1/D-2 antagonists, (cis(Z)-flupentixol and SCH 23390 + l-sulpiride). These results suggest that dopamine D-1 and D-2 receptors in the ventral striatum mediate turning behaviour through separate but cooperative mechanisms.

Animals↗

[Immunohistological demonstration of developmental protein GP68 in human tumor and embryonic tissues].

A developmental protein GP68 is known to appear stage-specifically in the developmental mouse brain. The expression of GP68 in tissues of 265 various human tumors and of 2 human embryos was examined immunohistologically using specific anti-GP68 rabbit antisera. Generally, endodermal, neural, and germ cell tumors were most frequently positive, while mesenchymal tumors were mostly and ectodermal tumors were intermediate. Anti-GP68 also gave positive reactions with some of non-neoplastic cells of cancer patients generally to lesser extents than neoplastic cells. Muscle and bone tissues of a 4-week-old embryo were weakly positive. Some tumors that were negative for CEA and AFP were strongly positive for GP68. The expression of GP68 in human tumor cells may represent an abnormal cellular gene-expression associated with the neoplastic change of the cell.

Carcinoembryonic Antigen↗

[Immunohistological localization of human aldolase A in human neoplastic and non-neoplastic tissues].

The expression of human aldolase A in tissues of cancer patients was examined immunohistologically using 4 monoclonal antibodies (1A2, 3C5, 1D1 and 4C2) to human aldolase A. In frozen sections, but not in paraffin sections, tumor cells of 22 out of 30 patients and non-neoplastic cells of 11 out of 21 patients examined reacted with 1A2 irrespective of cancer types. Positive reactions were seen mostly in the nucleus and some in the cytoplasm. Only tumor cells in a few neoplastic tissues gave positive cytoplasmic reactions with 1D1 or 4C2. No positive reaction was observed with 3C5. Antigens cross-reactive with aldolase A may be expressed more frequently in tumor cells than in non-neoplastic cells of cancer patients.

Antibodies, Monoclonal↗

Rapid development of brain beta-adrenoceptor down-regulation induced by phenelzine: subcellular studies.

The distribution of the specific binding of [3H]dihydroalprenolol in sucrose gradients containing homogenates of rat cerebral cortex centrifuged to equilibrium was examined after acute treatment with phenelzine (50 mg/kg i.p.). There was a time-dependent decrease in the number of beta-adrenoceptors in the plasma membrane fractions (0.8-1.0 M sucrose), without any significant alteration in the light density fractions (0.4-0.5 M sucrose). These results suggest that agonist-induced beta-adrenoceptor down-regulation is promoted by a process other than receptor internalization.

Animals↗

Production of wet-dog shakes in rats and down-regulation of spinal 5-HT2 receptors.

5-HT2 receptors, labelled with [3H]ketanserin, were shown to occur in a low concentration in the spinal cord of rats. The receptor numbers were reduced by 37% within 3 h of giving paroxetine to phenelzine-treated rats and remained low for at least 24 h. Paroxetine also evoked wet-dog shakes. These were of similar frequency in spinal (Cl transection) and intact rats and lessened within 3 h, perhaps because of receptor down-regulation.

Animals↗

Effects of intrastriatal injections of selective dopamine D-1 and D-2 agonists and antagonists on jaw movements of rats.

The effects of bilateral intrastriatal injections of the selective D-1 and D-2 antagonists, SCH23390 and sulpiride on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. A photo-transducer attached to the lower mandible automatically detected jaw movements. Apomorphine (0.2, 0.5 and 1.0 mg/kg i.v.) dose dependently increased jaw movements, an effect prevented by prior administration into the ventral striatum of either SCH23390 (0.1, 0.5 and 1 microgram) or sulpiride (125 ng). To be effective, SCH23390 had to be given less than 30 min before apomorphine whereas sulpiride had to be given earlier. Sulpiride injected into the dorsal striatum potentiated the effects of apomorphine, an action prevented by administering the sulpiride with SCH23390. Local application of the selective D-1 and D-2 agonists, SKF38393 (5 micrograms) and quinpirole (10 micrograms) into sites within the ventral striatum from which repeated jaw movements could be obtained by electrical stimulation, also evoked jaw movements; the effects of combining the two drugs were much greater than the effects of either drug alone.

Animals↗