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Biomedical subjects

T Morikawa

Publications and source records attributed to T Morikawa.

At least 127 records · Page 7Linked to original sources
PubMed1997

Actions of moguisteine on cough and pulmonary rapidly adapting receptor activity in the guinea pig.

With anaesthetized guinea pigs, the actions of moguisteine were tested on the cough reflex, the resting discharge of lung rapidly adapting receptors (RARs), RAR activity induced by aerosols of capsaicin, stimulation of RARs due to i.v. injection of capsaicin, and on the reflex responses to i.v. capsaicin. I.v. moguisteine (20 microg kg(-1)), compared with vehicle, decreased the spontaneous firing of RARs. Intragastric (i.g.) moguisteine (200 mg kg(-1)) had no effect on resting discharge. I.g. moguisteine depressed the cough response due to capsaicin aerosol (0.01(-1) mg ml(-1)) and significantly reduced the increased discharge of the RARs due to the aerosol. I.v. and i.g. moguisteine reduced the proportionate increase in RAR discharge due to i.v. capsaicin (50 microg kg(-1)). It did not appreciably affect the cardiovascular and respiratory responses to i.v. capsaicin, which presumably activated lung C-fibre receptors. We conclude that the antitussive action of moguisteine is mediated at least in part by a decrease in the excitatory response of RARs to tussive stimuli.

Aerosols↗
PubMed1997

Auto power and coherence analysis of delta-theta band EEG during the waking-sleeping transition period.

To evaluate the spatio-temporal variation of delta and theta band EEGs during the waking-sleeping transition period, auto power and coherence analyses of scalp EEGs were carried out on 12 male subjects. The 7 auto power and 21 coherence values obtained from the 7 areas were studied every 20 s from 5 min before stage 1 onset to 24 min after stage 1 onset. The consecutive samples of spectra were computed for two frequency bands (delta: 2.5-3.5 Hz; theta: 4.0-7.5 Hz). Auto power started to increase after stage 1 onset and terminated 8.4 min after stage 2 onset. Topograms of each band power changed with progression towards deep sleep from the flat or relatively low voltage pattern without any focus to the frontopolar-parietal pattern or the fronto-parietal dominant pattern. Principal component analysis of the coherence values revealed generalized and localized components in each band. The generalized component was distributed across scalp areas, while the localized component was distributed in frontopolar-frontal areas. The generalized component decreased to the plateau level of non-rapid eye movement (NREM) sleep 5.4 min after stage 2 onset. The localized component started to increase after stage 1 onset and reached the plateau level of NREM sleep 2.4 min after stage 2 onset. These results indicate that the delta-theta band EEG structures of the waking-sleeping transition period may not be uniform across the scalp areas and the hypnagogic period may start after stage 1 onset and continue for 8.4 min after stage 2 onset.

Adult↗
PubMed1997

Medicinal foodstuffs. VII. On the saponin constituents with glucose and alcohol absorption-inhibitory activity from a food garnish "Tonburi", the fruit of Japanese Kochia scoparia (L.) Schrad.: structures of scoparianosides A, B, and C.

The methanolic extract of a food garnish "Tonburi", the fruit of Japanese kochia scoparia (L.) Schrad. (Chenopodiaceae), was found to inhibit the increase in serum glucose-loaded rats. Through bioassay-guided separation, momordin Ic and its 2'-O-beta-D-glucopyranoside were isolated as the active principles from this medicinal foodstuff together with three new saponins named scoparianosides A, B, and C. The structures of scoparianosides A, B, and C were elucidated on the basis of chemical and physicochemical evidence as 3 beta, 22 alpha-dihydroxyolean-12en-28-oic acid (22 alpha-hydroxyoleanolic acid), 3-O-beta-D-xylopyranosyl (1 --> 3)-beta-D-glucopyranosiduronic acid, 3 beta-hydroxyolean -18-en-28-oic acid (morolic acid), 3-O-beta-D-xylopyranosyl(1 --> 3)-beta-D -glucopyranosiduronic acid, and 3 beta-hydroxyolean-13(18)-en-28-oic acid, 3-O-beta-D-xylopyranoxyl(1 --> 3) -beta-D-glucopyranosiduronic acid. Momordin Ic and its 2'-O-beta-D-glucopyranoside, both of which are the principal saponin constituents of this medicinal foodstuffs, were found to potently inhibit glucose and ethanol absorption in rats.

Animals↗
PubMed1997

Antithrombotic effects of the novel inhibitor of thrombin-induced offtelet aggregation and thrombus formation, 3-[2-[1,1':2',1"]-terphenyl-4'-yl)ethyl]phenoxyacetic acid.

The new compound 3-[2-([1,1':2,1"]-terphenyl-4'yl)ethyl]phenoxyacetic acid (F1070) was synthesized and its effects on platelet aggregation induced by thrombin, thrombin receptor agonist peptide (TRAP), ADP and collagen were evaluated in humans, guinea pigs and rats, and were compared with the effects of he thrombin antagonists argipidine and (D)Phe-Pro-Arg-CH2Cl (FPR). F1070 inhibited the platelet aggregation induced by these agonists and was highly selective in its inhibition of thrombin. F1070 inhibited fibrin formation induced by thrombin, but far less effectively than argipidine. In a guinea pig model of extracorporeal circulation thrombosis, F1070 (10 mg/kg p.o.) significantly inhibited the development of a thrombus. F1070 is thus a key compound that should facilitate the development of new orally active antithrombotic drugs that are specific for thrombin.

Animals↗
PubMed1997

[Palliative intubation of esophageal prosthesis in two patients with lung cancer].

Case one: A 61-year-old man was admitted to the hospital because of coughing. Adenocarcinoma of the lung was diagnosed. The patient was treated with bronchial artery infusion of cisplatin and mitomycin C, followed by irradiation; and there was a partial response. Eighteen months later he was admitted to the hospital because of dysphagia. An esophageal prosthesis was inserted because of esophageal stenosis surrounded by local recurrent tumor. After intubation, the patient was able to eat and was discharged. Although the patient died 5 months later, the tube was patent and functional until that time. Case two: A 63-year-old man was admitted to the hospital because of coughing. Adenocarcinoma of the lung was diagnosed. The patient was treated with 3 cycles of chemotherapy consisting of cisplatin, vindesine, and mifomycin C, which were followed by irradiation; and there was a partial response. Six months later he was admitted to the hospital because of dysphagia. An esophageal prosthesis was inserted because of esophageal stenosis surrounded by mediastinal lymph nodes. Although the patient was able to eat, bilateral pleuritis and mediastinitis developed and he died ten days after intubation. At autopsy the esophagus was found to have been perforated. Palliative intubation of an esophageal prosthesis can be effective in patients with esophageal stenosis due to lung cancer, but care must be taken to prevent fatal complications.

Adenocarcinoma↗
PubMed1997

Anticoagulant activity of the novel thrombin inhibitor 1-butyl-3-(6,7-dimethoxy-2-naphthylsulfonyl) amino-3-(3-guanidinopropyl)-2-pyrrolidinone hydrochloride.

1-Butyl-3-(6,7-dimethoxy-2-naphthylsulfonyl)amino-3-(3-guanidin opropyl)-2-pyrrolidinone hydrochloride (CAS 173440-64-7, SPI-501), which has highly selective thrombin-inhibitory activity, caused a concentration-dependent increase in the time taken for coagulation induced by thrombin in rabbit plasma. The IC50 of SPI-501 was 1.7 mumol/l. Argipidine also prolonged coagulation time and its activity was one order of magnitude greater than that of SPI-501. SPI-501 and argipidine caused dose-dependent increases in the activated partial prothrombin time (APTT) and prothrombin time (PT) of rat plasma. When APTT and PT were measured, IC50 values of SPI-501 were 38.0 and 18.5 mumol/l and those of argipidine, 1.4 and 1.9 mumol/l, respectively. Intravenous administration of SPI-501 (10 and 30 mumol/kg) and argipidine (1 and 3 mumol/kg) prolonged both APTT and PT in rats. While SPI-501 was less potent than argipidine, the durations of the effects of both were the same.

Animals↗
PubMed1997

UFT plus cisplatin in advanced non-small-cell lung cancer: interim analysis of 67 patients.

A single-institution phase II study indicated that combination chemotherapy using UFT (tegafur and uracil) plus cisplatin (Platinol) in patients with non-small-cell lung cancer was active with less host toxicity than other cisplatin-based therapies. To confirm these observations, the Japan JFT Lung Cancer Study Group conducted a multi-institutional phase II trial. The number of patients planned for this trial is 110. Eligibility includes previously untreated stage IIIB or IV non-small-cell lung cancer and a good performance status. UFT 400 mg/m2 in two divided doses is administered orally on days 1 through 14, and cisplatin 80 mg/m2 is injected IV on day 8. This treatment is repeated every 3 or 4 weeks. Between April 1995 and May 1996, 67 patients were enrolled, and all 67 were considered eligible for an interim analysis performed in October 1996. Among 63 patients evaluable for response, there was an overall response rate of 30% (95% confidence interval, 19% to 41%), with one complete response and 18 partial responses. With a median follow-up duration of 44 weeks, the median survival time was 32 weeks and the 1-year survival rate was 25%. Grade 3 leukopenia occurred in only 1 of 67 patients (1.5%), and there was no thrombocytopenia of grade 3 or greater. Vomiting, the most common nonhematologic toxicity observed, reached grade 3 or 4 in only 6 patients (9%). This interim analysis seems to support the observations of the previous single-institution phase II trial.

Aged↗
PubMed1997

Antithrombotic effects of 3-([1:1',2':1"]-3'-terphenyl)propanol in animals.

3-([1:1',2':1"]-3'-Terphenyl)propanol (CAS 186835-06-3, F050) and acetylsalicylic acid (ASA) inhibited platelet aggregation induced by CaCl2, arachidonic acid, collagen, adenosine diphosphate (ADP) and thrombin in guinea pigs, rabbits and rats in vitro. However, F050 had a wider spectrum of actions than ASA. Orally administered F050 inhibited platelet aggregation ex vivo. F050 significantly reduced the thrombus formation in the extracorporeal circulation thrombosis model in guinea pigs. It inhibited erythrocyte hemolysis induced by hypotonic NaCl, while ASA did not. F050, but not ASA, inhibited increases in platelet [CA2+]i caused by thrombin in guinea pigs. F050 is a parent compound that will facilitate the development of an orally active drug for the treatment of thrombotic diseases.

Animals↗
PubMed1996

The robustness of cognitively simple judgment in ecologies of Prisoner's Dilemma games.

Various authors have pointed to the fitness advantage from a capacity to recognize others' intentions in prisoner's dilemma games, yet cognitive mechanisms supporting such perceptiveness might be no more efficient than the simple and presumably inexpensive rule to 'assume that potential partners have the same behavioral intentions as yourself.' Laboratory findings have shown that this projecting heuristic can support the evolution of cooperative behavior absent perceptiveness, but that rule might be vulnerable to invasion by perceptive mutations. This paper shows that perceptive mutants are more likely to destroy an entire ecology of projectors (that would otherwise survive and prosper) than to successfully invade it, while projecting mutants have considerable success invading a population of perceptives. Mutant projectors' success happens when a cooperative ecology is created for them by the initial success of perceptive cooperators; within such an ecology, cooperative projectors have a competitive advantage over cooperative perceptives. Critical parameters are (1) the incidence of cooperativeness in the population and (2) the price of perceptiveness.

Biological Evolution↗
PubMed1996

Power evaluation of various modified Bonferroni procedures by a Monte Carlo study.

Various modified Bonferroni procedures (MBPs) have been proposed in order to improve the power of the classical Bonferroni procedure (CBP). In the present paper, powers of these MBPs are investigated by a Monte Carlo study for pairwise comparisons. It is shown that they can be remarkably more powerful than the CBP and Tukey's procedure with respect to all-pairs power, whereas all these procedures with respect to any-pair power are almost the same. Therefore, we recommend the use of MBPs rather than the CBP or Tukey's procedure. Shaffer's procedure sometimes shows higher power than other MBPs and would be the best choice for pairwise comparisons.

Computer Simulation↗
PubMed1996

Bonding of a mica-based castable ceramic material with a tri-n-butylborane-initiated adhesive resin.

Adhesive bonding of a mica-based castable ceramic material (Olympus Castable Ceramics, OCC) was evaluated in vitro with the use of a silane primer in conjunction with an adhesive luting material. The primer contained a silane coupler and 4-methacryloxyethyl trimellitate anhydride (4-META), while the methyl methacrylate (MMA)-based luting agent was initiated with a tri-n-butylborane derivative (TBB) and contained 4-META (4-META/MMA-TBB resin). Ceramic specimens were sanded with No. 600 silicon carbide paper followed by blasting with alumina and/or etching with ammonium bifluoride. The specimens were bonded with various combinations and shear bond strengths were determined. Both priming and alumina blasting enhanced the bond between 4-META resin and OCC. Although etching with ammonium bifluoride roughened the ceramic surface, this procedure did not improve the bond strength. Electron probe microanalysis of the ceramic surface revealed a decrease in silicon and aluminium elements after etching with ammonium bifluoride.

Acid Etching, Dental↗
PubMed1996

Structure-activity studies on C-terminal hirudin peptides containing sulfated tyrosine residues.

To clarify the role of the negative charge of the C-terminal region of hirudin, we chemically synthesized the C-terminal peptide of hirudin variant-1 (HV-1), HV-1-(54-65), and its analogs, [E61Y,E62Y]HV-1-(54-65) and [E62Y]HV-1-(54-65), and then sulfated the Tyr residue(s) in these peptides by both enzymic and chemical methods. Enzymic O-sulfation of Tyr residues in the peptides by use of sulfotransferase isolated from Eubacterium A-44 allowed us to produce four kinds of the sulfated peptide, whose C-terminal sequences were -PEY(SO3H)YLQ, -PYY(SO3H)YLQ, -PYYY(SO3H)LQ and -PYY(SO3H)Y(SO3H)LQ. On the other hand, all Tyr residues in the peptides were successfully sulfated by chemical reaction with N,N'-dicyclohexylcarbodiimide in the presence of sulfuric acid. Based on the analysis of structure-activity relationships of these sulfated peptides for thrombin inhibition, the Tyr62 and Tyr63 bisulfated peptide GDFEEIPEY(SO3H)Y(SO3H)LQ was found to be the most potent inhibitor of thrombin among the products tested. No increase in potency was observed by further substitution of Glu61 with Tyr(SO3H). The inhibitory activity by substitution with Tyr(SO3H) at position 63 was greater than that obtained by the substitution at position 62.

Amino Acid Sequence↗
PubMed1996

[Assay of specific anti-Chlamydia pneumoniae antibodies by ELISA method. 1. Evaluation of ELISA kit using outer membrane complex].

Studies were conducted with the goal of developing a kit for assaying anti-Chlamydia pneumoniae antibodies in human serum which would enable judging positive cases with high specificity by means of an objective numerical index. Thus, an enzyme-linked immunosorbent assay (ELISA) method employing a C. pneumoniae outer membrane complex protein was established. Elementary bodies (EB) were purified from the YK-41 strain of C. pneumoniae, and subsequent treatment with Sarkosyl, DNase and RNase yielded chlamydial outer membrane complex (COMC). COMC was employed as the antigen and immobilized on 96-well microplates for ELISA method. This ELISA method was used to test 51 serum specimens from patients who had been demonstrated to be positive for C. pneumoniae antigen (throat swab: PCR positive), and the levels of IgG, IgA and IgM antibodies were assayed. For each specimen, comparison was made with the antibody titers determined by the micro immunofluorescence test (Micro-IF method). The results showed good correlation coefficients of 0.950 for IgG, 0.852 for IgA and 0.866 for IgM. In addition, the two assay methods showed the following high agreement rates: 90.2% for IgG, 84.3% for IgA and 82.4% for IgM. Specimens which did not yield the same results with the ELISA method and Micro-IF method were subjected to analysis by Western blot method, and the rates of agreement with the ELISA results were 80% for IgG, 87.5% for IgA and 88.9% for IgM. These data indicate the efficacy of this new ELISA method. Moreover, COMC was reacted with mouse antisera to three Chlamydia species, and the mouse IgG antibody was assayed. Anti-C. pneumoniae antiserum showed the strongest reactivity, whereas weaker reactivity was shown by anti-C. trachomatis antiserum (1/32nd of the reactivity of the anti-C. pneumoniae antiserum) and anti-C. psittaci antiserum (1/4th). In addition, sera from patients infected with C. trachomatis or C. psittaci (Psittacosis) were subjected to the ELISA method using COMC from C. pneumoniae. It was found that the correlation between the ELISA and Micro-IF methods was higher in relation to the anti-C. pneumoniae antibody titer than either the anti-C. trachomatis antibody titer or anti-C. psittaci antibody titer. These findings indicate this new assay kit based on the ELISA method has high specificity for C. pneumoniae.

Animals↗
PubMed1996

Inhibitory effect of erythromycin on interleukin 8 production by 1 alpha,25-dihydroxyvitamin D3-stimulated THP-1 cells.

We have recently reported that long-term administration of erythromycin at a low dose reduced the number of neutrophils and concentrations of interleukin 8 (IL-8) in bronchoalveolar lavage fluid in patients with chronic lower respiratory tract disease. To investigate the mechanism of action of erythromycin, we evaluated its effect on IL-8 production in the 1 alpha,25-dihydroxyvitamin D3-stimulated human monocytic cell line THP-1. Erythromycin at a concentration of 10 micrograms/ml significantly reduced IL-8 production by THP-1 cells stimulated with lipopolysaccharide (10 ng/ml) and 1% normal human serum compared with the amount produced by untreated cells (untreated cells, 2,448 pg/ml; erythromycin-treated cells, 872 pg/ml). Our results suggest that erythromycin may impair IL-8 production by alveolar macrophages, ultimately reducing neutrophil accumulation in the airspace.

Anti-Bacterial Agents↗
PubMed1996

Anticoagulant peptides; synthesis, stability and antithrombin activity of hirudin C-terminal-related peptides and their disulfated analog.

We designed a unique anticoagulant decapeptide, which possesses two O-sulfated tyrosine residues, based on the structure of hirudin's C-terminal functional domain. We first prepared a series of octa-, nona- and decapeptides with no sulfation, Suc-Phe-Glu-Pro-Ile-Pro-Glu-Tyr-Tyr-X-OH [X = bond, Leu or Leu-Gln], by a solution phase method and measured their thrombin times (TT) using human thrombin and rabbit plasma. The shortest octapeptide (3a) showed full antithrombin activity comparable to that of the lead compound hirudin (54-65), and the longest decapeptide (3c) prolonged TT most potently with an IC50 value of 5.8 microM. We consequently converted 3c to a disulfated decapeptide (NF-22) with SO3.pyridine complex and compared its antithrombin activity with that of known hirudin-related peptides: hirugen, MDL28050 and hirulog-1. NF-22 showed potent antithrombin activity with an IC50 value of 0.3 microM, being more potent than hirugen and MDL28050 (IC50 values of 4.0 microM and 1.1 microM, respectively). NF-22 was as potent as hirulog-1. NF-22 showed no change in activity in aqueous solution for 10 d at 60 degrees C, and remained about 90% unchanged in rat plasma on incubation for 24h at 37 degrees C, whereas the corresponding unsulfated peptide (3c) was completely digested under the same condition. NF-22 appears to be one of the most potent and stable peptide anticoagulants among the hirudin analogs.

Amino Acid Sequence↗
PubMed1996

[Two cases of generalized disseminated atypical mycobacterium showing multiple accumulations on bone scintigraphy].

For determining the spread of multiple bone lesions in generalized disseminated atypical mycobacteriosis a rare disease, bone scintigraphy was found useful in our two patients. They were both female, and the pathogenic microbe was M. avium intracellulare complex. The disease appeared to have been induced by defatigation. The depression of cellular immunocompetence was also suspected to be responsible. Bone scintigraphy disclosed multiple abnormal accumulations systematically. The Definitive diagnosis in these cases was established by biopsy. In differential diagnosis of this disease by bone scintigraphy, bone metastasis of a malignant tumor was considered of primary importance. Although antitubercular chemotherapy resulted in improvement of subjective symptoms and inflammation, abnormal accumulation persisted. There was necessity for taking notice that in the decision of the treatment effect of this disease, improvement of abnormal accumulations on bone scintigraphy was delayed that of inflammatory reaction.

Aged↗