Search PubMed⌕ Search

Biomedical subjects

K Morikawa

Publications and source records attributed to K Morikawa.

At least 271 records · Page 15Linked to original sources
PubMed1988

Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (first report)--effect on pain threshold and inhibition by naloxone.

It has been claimed that the mechanism of acupuncture analgesia can be explained in part by endogenous opioids. If so, it might be possible to enhance the analgesic effect of acupuncture by the administration of endorphins. If D-phenylalanine (DPA), an inhibitor of the endorphin degrading enzyme, is administered, the analgesic effect of acupuncture should be prolonged due to the increased level of endorphins. From the changes of the pain threshold (PT), we investigated whether or not the pre-administration of DPA can enhance the analgesic effect of acupuncture in humans. In addition, we examined the inhibitory effect of naloxone. 1) In all five subjects whose PT was raised after acupuncture anesthesia (respondents), the rise in PT was significantly prolonged by DPA. 2) Out of 10 subjects whose PT remained almost unchanged after acupuncture anesthesia (non-respondents), the PT was increased by DPA in 5 cases. 3) The rise in PT was most prominent when DPA was administered 30 minutes before the start of acupuncture anesthesia. 4) In all 4 respondents in whom the rise in PT persisted after DPA and acupuncture anesthesia, their raised PT dropped after the intravenous injection of naloxone (10 mg). 5) These findings show that DPA enhances the analgesic effect of acupuncture by the "endorphin mechanism."

Acupuncture Therapy↗
PubMed1988

[Enhancement of antitumor immune responses by bleomycin].

We examined the therapeutic effect of antitumor antibiotic, bleomycin (BLM), using an experimental model of WKA rats and KMT-17 tumor. BLM (5 mg/kg/day) was administered ip for 5 days. The therapeutic effect of BLM was found to be dependent upon the timing of BLM-administration. A remarkable difference in therapeutic effect was observed when BLM was administered from the eighth day after tumor inoculation (late BLM-treatment) rather than when BLM was administered from the day following tumor inoculation (early BLM-treatment) (cured rats/treated rats: 10/21 and 2/16 respectively). By means of a Winn assay, enhancement of tumor neutralizing activity observed in spleen cells from rats given late BLM-treatment but not in spleen from rats given early BLM-treatment. The enhanced tumor neutralizing activity of spleen cells from rats given late BLM-treatment were suppressed by adding spleen cells from untreated tumor bearing rats. The antitumor transplantation resistance in rats immunized with irradiated KMT-17 cells was abrogated by an adoptive transfer of spleen cells from untreated tumor bearing rats or from rats given early BLM-treatment, but not by the spleen cells from rats given late BLM-treatment. These results suggest that BLM-administration during the late stage of tumor bearing eliminates immuno-suppressor cells and results in the enhancement of antitumor immune responses. The enhanced tumor neutralizing activity of spleen cells from rats given late BLM-treatment was mediated by both T-cell fraction and adherent macrophage fraction. The BLM treatment enhanced the in vitro cytolytic activity of splenic and peritoneal macrophages [( 125I] iododeoxyuridine release assay).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Host immune responses to tumor cells augmented by bleomycin and their therapeutic effects on rat fibrosarcoma.

The administration--timing-dependent therapeutic effects of bleomycin (BLM) were observed on a fibrosarcoma implanted SC in WKA rats. Five consecutive IP administrations of BLM (5 mg/kg/d) were found to be more effective when BLM was given from Day 8 than when it was given from Day 1 for tumors implanted on Day 0. The therapeutic effects correlated well with antitumor immune responses, which were examined on Day 13 when the tumor had not yet regressed even in surviving rats. The tumor-neutralizing activity of spleen cells was augmented in rats treated with BLM from Day 8 to Day 12, and the suppressor cell activity detected in the spleen cells of tumor-bearing rats was eliminated by the BLM treatment. The tumoricidal activity of peritoneal exudate cells (PEC) was detected in rats treated from Day 8 but not in rats untreated or treated from Day 1. The in vitro treatment of KMT-17 cells with BLM (20 micrograms/ml) for two hours enhanced the sensitivity of the tumor cells to the activity of tumoricidal PEC. This suggests that the direct action of BLM on tumor cells also plays an immunologic role in BLM treatment. The findings reveal that the therapeutic effect of BLM is elicited by its ability to augment the host immune responses to tumor cells.

Animals↗
PubMed1988

Effects of chronic sulpiride-induced hyperprolactinemia on menstrual cycles of normal women.

We investigated the influence of chronic (27-65 days) sulpiride-induced hyperprolactinemia on the menstrual cycles of four normal women. The hyperprolactinemia (206.4 ng/mL, the average of the mean values of each subject obtained by sulpiride treatment) suppressed the LH surge and the secretion of plasma estradiol-17 beta and progesterone to their basal levels. The results suggest that the endocrine changes in normal women with sulpiride-induced hyperprolactinemia are similar to those in women with spontaneous hyperprolactinemia. Sulpiride-induced hyperprolactinemia may be useful as a model for studying spontaneous hyperprolactinemia.

Adult↗
PubMed1987

Recombinant interferon-alpha, -beta, and -gamma enhance the proliferative response of human B cells.

Recombinant interferons (IFN-alpha, -beta, and -gamma) were examined for their effects on B cell activation. Relatively small IgM+ B cells from human blood samples were isolated by fluorescence-activated cell sorting and were used as target cells. Although the interferons themselves were nonmitogenic, each enhanced the proliferative response induced by a mitogenic anti-mu monoclonal antibody, with IFN-beta usually showing the greatest enhancement and IFN-gamma the least. Pretreatment with the interferons primed resting B cells to undergo enhanced DNA synthesis in response to the anti-mu antibody DA4. Conversely, anti-mu pretreatment, followed by IFN treatment, did not induce B cells to enter the S phase. Time-course analysis revealed that IFN could augment the anti-mu response even when added as late as the final 24 hr of a 3-day culture interval. Combinations of IFN-gamma plus IFN-alpha or -beta were synergistic in the anti-mu response, whereas the IFN-alpha plus IFN-beta combination was not. The data suggest that interferons produced by both lymphocytes (IFN-gamma) and nonlymphoid inflammatory cells (IFN-alpha and -beta) can enhance B cell growth via different mechanisms.

Antibodies, Anti-Idiotypic↗
PubMed1987

Enhancement of therapeutic effects of recombinant interleukin 2 on a transplantable rat fibrosarcoma by the use of a sustained release vehicle, pluronic gel.

We have tested the feasibility of pluronic F-127 gel (PLF-127; a polyoxyethylene-polyoxypropylene surface active block copolymer) as a sustained release vehicle for topical administration of interleukin 2 (IL-2) in order to enhance the therapeutic effects of IL-2 against a rat fibrosarcoma, KMT-17. Injection of human DNA recombinant IL-2 (3 X 10(4) units s.c.) in 30% (w/w) PLF-127 into rats provided detectable serum IL-2 levels for up to 10 h, while injection of IL-2 alone provided detectable IL-2 levels for 3 h. When, following s.c. inoculation with 1 X 10(5) KMT-17 tumor cells into rats, IL-2 (6 X 10(4) units/day) in PLF-127 gels was injected s.c. around the growing tumor inoculum every 2 days for 10 days from Day 1 to Day 19, the survival days of rats were more prolonged [mean survival day, 32.3 +/- 5.4 (SD)] as compared with that of rats treated with saline [20.7 +/- 2.1] than mean survival days of rats treated with IL-2 alone [27.3 +/- 4.5] or PLF-127 alone [22.9 +/- 3.3]. Moreover, the span of mean survival days of rats treated with IL-2 in PLF-127 locally (31.7 +/- 5.9) was much longer than that of rats given IL-2 in PLF-127 systemically (22.8 +/- 3.4). By means of a Winn assay, stronger tumor neutralizing activities were observed in regional lymph node cells obtained from tumor bearing rats treated with IL-2 in PLF-127 than were observed in lymph node cells from rats treated with IL-2 alone or PLF-127 alone (percentage of inhibition, 90.3, 12.2, and -15.5%, respectively). The therapeutic effects of IL-2 were thus found to be consistent with the antitumor activity in regional lymph node cells. These results suggest that the enhanced therapeutic effects of IL-2 in PLF-127 are due to enhancement of antitumor immune responses induced by sustained IL-2 activity at the tumor sites.

Animals↗
PubMed1987

Effects of orientation-selective adaptation on the Zöllner illusion.

The model of inhibitory interaction between orientation detectors was examined by prolonged presentation of grating patterns (which was expected to induce orientation-selective adaptation) before measurement of the Zöllner illusion. Adaptation effects were measured under conditions which excluded intrusion by the tilt aftereffect. In experiment 1, illusion magnitude greatly decreased only when the orientation of the adapting grating was the same as that of the inducing lines, which confirmed the first prediction deduced from the model. There was no effect of adapting grating when it was oriented more than 20 degrees away from the inducing lines. In experiment 2, adaptation effects were selective not only to orientation but also to spatial frequency. In experiment 3 it was shown that illusion reduction was mediated neither by lowered apparent contrast of the inducing lines nor by retinal adaptation. The results are discussed with respect to the nature of adaptation and possible physiological correlates.

Adaptation, Ocular↗
PubMed1987

Characterization of liposomes containing the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and their interaction with mouse macrophages.

The purpose of these studies was to characterize liposomes containing the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and to examine their interaction with mouse peritoneal macrophages. Because of its hydrophobic properties, FMLP can be readily incorporated into both phosphatidylcholine (PC) and PC/phosphatidylserine (PS) (7:3, mol ratio) multilamellar vesicles (MLV). The association of FMLP with the MLVs is stable in medium with or without serum. The size distribution and aqueous trap volume of MLV consisting of PC or PC/PS that contain FMLP at a 10:1 molar ratio do not differ from that of MLV without FMLP. MLV containing equimolar phospholipid-to-FMLP ratios are smaller but have larger aqueous trap volumes. MLV consisting of PC and FMLP (10:1 molar ratio) are phagocytosed more efficiently than PC MLV, and their phagocytosis is mediated via the FMLP receptors on macrophages. In contrast, MLV consisting of PC/PS or PC/PS with FMLP (7:3:1 molar ratios) are phagocytosed to the same extent, and so the FMLP receptors on macrophage surface do not influence this process. The delivery of FMLP in liposomes to macrophages is very efficient: up to 25-fold more FMLP delivered by MLV is internalized into macrophages than when it is in free form. Once associated with the macrophages in either free form or via liposomes, some FMLP is degraded and released into the medium, but the majority of FMLP molecules remain with the macrophages to be degraded at a steady rate. The present findings may explain how liposome-FMLP produces tumoricidal properties in macrophages.

Animals↗
PubMed1987

[Central muscle relaxant activities of 2-methyl-3-aminopropiophenone derivatives].

In this experiment, we synthetized new 2-methyl-3-aminopropiophenone (MP) derivatives, whose structure is known to have central muscle relaxant activities, and quinolizidine and indan . tetralin derivatives derived from MP by cyclization, and we investigated the central muscle relaxant activity. Among the quinolizidine derivatives, there was a very strong central depressant agent, trans (3H, 9aH)-3-(p-chloro) benzoyl-quinolizidine (HSR-740), and among the indan . tetralin derivatives, there was an excitant agents, trans (1H, 2H)-5-methoxy-3, 3-dimethyl-2-piperidinomethyl indan-1-ol (HSR-719). From the results, these derivatives were not considered to be adequate for central muscle relaxant. Among the MP derivatives, (4'-chloro-2'-methoxy-3-piperidino) propiophenone HCl (HSR-733) and (4'-ethyl-2-methyl-3-pyrrolidino) propiophenone HCl (HSR-770) strongly inhibited the cooperative movement in the rotating rod method using mice, and it exerted almost the same depressant activity on the cross extensor reflex using alpha-chloralose anesthetized rats. However, the inhibitory effects of HSR-733 on the anemic decerebrate rigidity and the rigidity induced by intracollicular decerebration in rats were weaker than those of HSR-770 and eperisone. In spinal cats, at a low dose (5 mg/kg, i.v.), HSR-733 depressed monosynaptic and dorsal root reflex potentials as compared with polysynaptic reflex potentials, and inhibitory effects of HSR-733 on these three reflex potentials were more potent than those of eperisone and HSR-770. Although HSR-770 acts on the spinal cord and supraspinal level on which eperisone has been reported to act, HSR-733 may mainly act on the spinal cord. These results indicate that the MP derivative with a 2-methyl group may be suitable as a central muscle relaxant. HSR-770, which has equipotent muscle relaxant activity to eperisone, exerted strong inhibitory effects on oxotremorine-induced tremor and weak inhibitory effects on spontaneous motor activity in the Animex method using mice, as compared with eperisone.

Animals↗
PubMed1987

[Evaluation of tiquizium bromide (HSR-902) as an antiulcer agent].

The effects of HSR-902, an antimuscarinic agent, on development of various gastric and duodenal lesions, gastric secretion, pupil size and salivation in rats were compared with those of pirenzepine.2HC1 (pirenzepine, antiulcer agent) and timepidium bromide (timepidium, antispasmodic). 1) HSR-902 (10-100 mg/kg), given orally, dose-dependently inhibited the developments of gastric lesions induced by water-immersion stress, aspirin, indomethacin, serotonin and reserpine and duodenal lesions induced by cysteamine and mepirizole. The activities of HSR-902 were almost equal or somewhat more potent than those of pirenzepine, and they were more potent than those of timepidium. 2) HSR-902 (30 and 100 mg/kg, p.o.), when examined using pylorus-ligated preparations, dose-dependently inhibited the gastric acid output, pepsin output, and gastric acid and pepsin concentrations, but did not inhibit the gastric volume (HSR-902, in a higher dose, slightly increased the gastric volume.). Pirenzepine (100 mg/kg, p.o.), like atropine sulfate, inhibited the gastric volume, acid output and pepsin output, but did not inhibit the gastric acid and pepsin concentrations. Timepidium (100 mg/kg, p.o.), however, hardly influenced these parameters except for increasing the gastric volume. 3) HSR-902 (100 mg/kg, p.o.) induced the mydoriasis and inhibited the pilocarpine-induced salivation, and its activities were less potent than those of pirenzepine. These results suggest that HSR-902 is a promising agent for the treatment of peptic ulcer.

Animals↗
PubMed1987

[Cytoprotective activity of tiquizium bromide (HSR-902) and its mechanism].

The effects of HSR-902, an antimuscarinic agent, on acute gastric mucosal lesions induced by various necrotizing agents, gastric mucus secretion and gastric HCO3- secretion in rats were compared with those of pirenzepine.2HCl (pirenzepine), an antiulcer agent. 1) HSR-902 (10-100 mg/kg), given orally, dose-dependently prevented the gastric mucosal lesions induced by ethanol-HCl (60% ethanol in 150 mM HCl), aspirin-HCl (150 mg/kg of aspirin in 150 mM HCl), 0.6 N HCl and 0.2 N NaOH; and the cytoprotective effects of HSR-902 were almost equal or somewhat more potent than those of pirenzepine. 2) HSR-902 (30 mg/kg, p.o.), like pirenzepine, increased the alcian blue binding to gastric mucosa and both hexosamine and N-acetylneuramic acid in gastric juice and reversed the decrease of alcian blue binding to gastric mucosa in water-immersion stress. 3) HSR-902 (30 mg/kg, p.o.), unlike pirenzepine and atropine sulfate, increased the gastric HCO3- secretion in the pylorus-ligated preparations. 4) The cytoprotective effect of HSR-902 (30 mg/kg, p.o.), when examined using gastric mucosal lesion induced by aspirin-HCl, was not abolished by the pretreatment with indomethacin (10 mg/kg, s.c.) or N-ethylmaleimide (10 mg/kg, s.c.). 5) HSR-902 (30 mg/kg, p.o.) did not influence the gastric mucosal potential difference. These results suggest that HSR-902 is a promising drug for the treatment of gastritis and peptic ulcers.

Animals↗
PubMed1987

Studies on the affinity and selectivity of tiquizium bromide (HSR-902), a novel spasmolytic agent, for muscarinic receptors.

The affinity and selectivity of a novel spasmolytic agent, tiquizium bromide (HSR-902), for muscarinic receptors were studied by the radioligand binding technique using 3H-quinuclidinyl benzilate. The parameters (Ki, nH) of HSR-902 obtained from competition experiments in cerebral cortex and heart muscarinic receptors showed that HSR-902 was an atropine-type, nonselective muscarinic antagonist. The affinity of HSR-902 toward the stomach and ileal muscarinic receptors was about 3-4 times more potent than atropine.

Animals↗