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Biomedical subjects

K Morikawa

Publications and source records attributed to K Morikawa.

At least 181 records · Page 10Linked to original sources
PubMed1992

Lateral motion bias associated with reading direction.

We found that when Americans view ambiguous lateral long-range apparent motion, they exhibit a robust bias to experience leftward movement. In successive experiments, right-handers and left-handers, and left-side drivers from Japan equally manifested this leftward bias. However, bilingual viewers whose first language reads from right to left exhibited no lateral bias. Furthermore, the bilingual sample produced a significant correlation between exposure to English and extent of leftward motion bias. The findings provide strong evidence that reading habits can influence directionality in motion perception.

Automobile Driving↗
PubMed1992

Inhibition of proliferation and differentiation of human B-lymphocytes by a biscoclaurine alkaloid.

A biscoclaurine alkaloid, cepharanthine, is known to be a potent inhibitor of snake venom-induced hemolysis by interaction with the lipid bilayer of the membrane. The drug also interferes with the ion channel intracellularly. In this study, we examined the effect of cepharanthine on human B-cell functions. Small dense B-cells from tonsil samples were isolated using a Percoll density gradient from non-rosetted cells and were used as the target cells. Cepharanthine inhibited the proliferation of the lymphocytes and antibody production of human B-lymphocytes. The inhibitory effect of cepharanthine on the proliferation was caused by the arrest of the late G1 to S phase transition in the cell cycle. However, the mechanism of suppression of antibody formation remains unknown. These results suggest that cepharanthine acts on human B-cells as an immunomodulating agent.

Adjuvants, Immunologic↗
PubMed1992

A method for observing cross-sectional views of biomembranes.

Cross-sectional views of intact biomembranes and synthetic lipid bilayer membranes were observed by electron cryomicroscopy using spontaneous orientation of disk-shaped membranes; purple membrane, thylakoid membrane, synthetic phospholipid membrane and a microcrystalline sheet made of Er-binding polypeptide were observed. The membranes were observed fully hydrated, embedded in vitreous ice, and their self-orientation was most probably caused by repulsion between their hydrophobic edges and their hydrophilic environment which forced their edges to be exposed to the air-water interface. The cross-sectional profiles of the native biomembranes were asymmetric and characteristic, whilst those of the synthetic membranes were symmetric and predictable by a simple model. Simple Fourier analysis showed that the cross-sectional images retained structural information up to a medium resolution.

Amino Acid Sequence↗
PubMed1992

Preparation of unsaturated disaccharides by eliminative cleavage of heparin and heparan sulfate with heparitinases.

1. Six kinds of unsaturated disaccharides were prepared by enzymatic digestion of heparin and heparan sulfate with heparitinases I0 and IV, and subsequent column chromatography. They were identified by HPLC showing good separation from each other. 2. The content of each unsaturated disaccharide fraction was determined colorimetrically, and found to range from 130.7 to 722.3 mumol. 3. Molecular extinction coefficient of each unsaturated disaccharide was calculated from absorbance at a wavelength of around 230 nm where a peak appeared on the ultraviolet spectrum of each disaccharide solution at pH 2. The values varied from 6000 to 6600.

Animals↗
PubMed1992

Potent antitumour activity of (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) against advanced L1210 leukaemia in mice.

The time dependency of the antitumour activity of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R) was examined in mice inoculated i.p. with 10(5) mouse L1210 leukaemia cells. The increase in life span was greater in mice treated with 72 mg kg-1 DWA2114R on the 6th day following tumour inoculation than in mice treated at earlier times. Such superior effects against advanced L1210 were also seen with cis-diammine (1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) but not seen with the parent compound, cis-diamminedichloroplatinum(II) (CDDP) or other antitumour agents devoid of platinum. After the injection of DWA2114R on day 6, most of the ascites tumour cells accumulated in the S and G2/M phases of the cell cycle and the total cell number markedly decreased from 10(8) to less than 10(6). On the other hand, only a temporary G1 arrest and a less than 50% reduction of the cell number were induced after a similar treatment on day 3. Interestingly, the superiority of DWA2114R for advanced L1210 was lost in athymic nude mice and mice depleted of T cells by anti-thymocyte antisera. In addition, mice cured of advanced L1210 specifically rejected re-inoculated L1210 cells. These results indicate that the superior antitumour activity against advanced L1210 is unique to DWA2114R among the agents tested (except for CBDCA) and is caused by both an increased drug susceptibility of tumour cells and a drug-induced antitumour effect mediated by T cells of the host mice.

Animals↗
PubMed1992

Inhibitory effects of plant secondary metabolites on cytotoxic activity of polymorphonuclear leucocytes.

The inhibitory effects of 151 natural products, representing most of the frequently occurring types, on the cytotoxicity to MM2 tumor cells of polymorphonuclear leucocytes (PMN) induced by TAK, a polysaccharide immunomodulator, were examined. Forty-two compounds inhibited the TAK-induced activation of PMN. Among them, some naturally occurring quinones and various alkaloids (nicotine, Cinchona alkaloids, isoquinoline alkaloids such as cepharanthine, and indole alkaloids such as ajmaline) exhibited potent inhibitory effects. Using the inhibition assay for monitoring, the extracts of Hydrangea Dulcis folium, Scopoliae rhizoma, Cinchona cortex, Magnoliae cortex, Stephania tuber, and Rauwolfia radix were analysed to characterize the active constituents.

Animals↗
PubMed1992

The suppressive effect of deoxyspergualin on the differentiation of human B lymphocytes maturing into immunoglobulin-producing cells.

Deoxyspergualin, an analog of spergualin, has been known as a novel immunosuppressive agent with strong immunosuppressive activity in in vivo experimental systems. In the present study, we examined the effect of deoxyspergualin (DSG) and methyldeoxyspergualin (MeDSG) on the proliferation and differentiation of human B lymphocytes in vitro. Highly purified B cells from human tonsil samples were isolated by Percoll density gradient from nonrosetted cells and were used as target cells. Both agents had little effect on the proliferative response of resting or activated B lymphocytes. However, they suppressed the immunoglobulin synthesis of B lymphocytes not only in a T cell-dependent, but also in a T cell-independent system. The inhibition of antibody synthesis was manifested in the early stage of B cell differentiation. Both drugs also suppressed Ig secretion, but not proliferation, of an EBV-transformed human B lymphoblastoid cell line. These results indicate that DSG and MeDSG have a selective immunosuppressive effect on the differentiation pathway of B lymphocytes.

Antibody-Producing Cells↗
PubMed1992

The distinct effects of FK506 on the activation, proliferation, and differentiation of human B lymphocytes.

We examined the effect of FK506 on the activation, proliferation and differentiation of human B lymphocytes in vitro. FK506 inhibited the proliferative response of resting B cells induced by Staphylococcus aureus Cowan strain I (SAC) and phorbol myristate acetate (PMA) in a dose-dependent manner. Inhibition of cell proliferation by FK506 was caused by a selective block of G0 to G1 phase transition leading to cell arrest. In addition, the proliferative response of in vivo-activated B cells and lymphokine-driven B cell proliferation were also found to be sensitive to FK506. Interestingly, FK506 did not affect the expression of activation antigens such as CD23, IL-2 receptor (CD25), and transferrin receptor (CD71). Finally, FK506 had little effect on B cell antibody generation in a T cell-independent system. Conversely, FK506 suppressed neither proliferation nor immunoglobulin secretion in a human B lymphoblastoid cell line. These results indicate that FK506 has discrete effects on the different stages of the B cell maturation.

Antibody-Producing Cells↗
PubMed1992

Antitumor activity and cellular accumulation of a new platinum complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platinum( II) monohydrate, in cisplatin-sensitive and -resistant murine P388 leukemia cells.

We have examined the cytotoxicity and accumulation of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R) in parent and cisplatin-resistant mouse P388 leukemia cells (P388 and P388/DDP), in comparison with those of cisplatin (CDDP) and carboplatin (CBDCA). The degrees of resistance to CDDP and CBDCA, expressed as the ratio of IC50 for P388/DDP cells to IC50 for P388 cells, were 75-33 and 100-27, respectively, under the conditions of 2-24 h exposure to each drug at a density of 10(6) cells/ml. The corresponding values (25-7) for DWA2114R were relatively low. Accumulations of CDDP and CBDCA were reduced in P388/DDP cells; however, no reduction in accumulation of DWA2114R was observed at various exposure periods and concentrations of the drugs. The accumulations of CDDP in P388 and P388/DDP cells at drug concentrations corresponding to the IC50 values for drug exposure periods of 2-24 h were 0.41-0.97 and 13.1-33.7 ng Pt/10(7) cells, respectively, suggesting that an intracellular mechanism of resistance against CDDP could be activated in P388/DDP cells. P388/DDP cells also showed relatively low resistance to DWA2114R via this mechanism in comparison with CDDP and CBDCA. From the relationship between structure and activity of several Pt-complexes, these different properties of DWA2114R compared with CDDP and CBDCA could be due not only to the differences in carrier ligand structure but also to the properties of the whole molecule associated with the carrier ligand and leaving group.

Animals↗
PubMed1992

Urinary fibrin and fibrinogen degradation products and the origin of hematuria.

We examined urinary fibrin and fibrinogen degradation product (U-FDP) concentrations in pediatric patients with hematuria using the rapid and highly-sensitive latex particle agglutination test (LPAT), and assessed the value of this test for the localization of the site of hematuria. Patients with hematuria were divided into two groups: 60 with glomerular hematuria and 46 with non-glomerular hematuria. If U-FDP concentrations less than 0.25 microgram/ml are accepted as an indicator of glomerular bleeding, the sensitivity and specificity of localization of glomerular hematuria in the present study were 78% (47/60) and 89% (41/46), respectively. The high U-FDP concentrations observed in patients with non-glomerular hematuria may reflect direct bleeding into the urinary tract. Since all 13 patients with glomerular hematuria and U-FDP concentrations of 0.25 microgram/ml or more had coexistent erythrocyte cylindruria, the U-FDP test seems to be compensated with combined urinalysis for the relatively lower sensitivity. We conclude that a knowledge of U-FDP concentrations by LPAT can be of help in localizing the site of bleeding in hematuria.

Adolescent↗
PubMed1992

Novel phenoxyalkylamine derivatives. VII. Synthesis and pharmacological activities of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives.

To find a novel alpha-blocker with high alpha-blocking selectivity against dopamine D2-receptor affinity, we performed structural modification of the alkylene chains and the substituents on two benzene rings of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives. The modification of the alkylene chain between the amino moiety in the center of the molecule and the benzene ring (ring A) was found to be the most significant. 5-[2-[[2-(5-Fluoro-2-methoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide (II-4), which possesses 1-methylethyl as the alkylene chain, exhibited high alpha-blocking selectivity as well as potent alpha-blocking activity.

Adrenergic alpha-Antagonists↗
PubMed1992

The interactions of (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) and related compounds with deoxyribonucleic acid.

The interactions of a new antitumor platinum (Pt) complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114R, 2) and its related compounds, cis-diamminedichloroplatinum(II) (CDDP, 1), trans-diamminedichloroplatinum(II) (TDDP, 3), (+)-(S)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114S, 4), (R)-2-aminomethylpyrrolidinedichloroplatinum(II) (5) and cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA, 6), with calf-thymus deoxyribonucleic acid (DNA) and DNA nucleosides were investigated by ultraviolet (UV) and circular dichroism (CD) spectrometry. The UV spectra of the DNAs treated with these Pt complexes exhibited both bathochromic shift and hyperchromicity, showing a binding of Pt to the heterocyclic groups of these DNA as well as an alteration in the secondary structure of DNA. The reaction rates of the Pt complexes with DNA, however, differed from one another, and the order was CDDP, TDDP, 5 much greater than DWA2114R, S greater than CBDCA. The CD spectra of the DNAs treated with the Pt complexes, except TDDP, at a low Pt ratio (less than approximately (ca.) 0.1 of Pt bound to DNA/DNA base molar ratio) exhibited an increase of ellipticity at ca. 275 nm. The melting temperature of the DNAs treated with DWA2114R or CDDP were almost the same as the native DNA, while the melting temperature with TDDP was higher by 7-8 degrees C than that of the native DNA. All the Pt complexes reacted with 2'-deoxyguanosine (dG), 2'-deoxyadenosine and 2'-deoxycytidine, but none reacted with thymidine. The CD spectral change of the dG was largest. DWA2114R reacted faster with dG than other nucleosides.

Animals↗
PubMed1992

In vitro pharmacological profile of the novel alpha 1-adrenoceptor antagonist HSR-175.

The pharmacological profile of HSR-175, a new alpha 1-adrenoceptor antagonist, was studied in vitro and compared with those of other alpha 1-antagonists. HSR-175, prazosin, bunazosin and yohimbine competitively antagonized the contractile responses induced by noradrenaline in the dog mesenteric arteries and the rabbit thoracic aorta. The pA2 values for HSR-175 in the dog mesenteric arteries and the rabbit aorta were 10.38 and 9.63, respectively, which were significantly higher than those for prazosin (8.39 and 8.80), bunazosin (8.44 and 8.75) and yohimbine (7.34 and 6.10). HSR-175 also inhibited the sympathetic adrenergic contraction induced by electrical transmural stimulation in the dog mesenteric arteries, and the inhibitory effect of HSR-175 was more potent than those of prazosin and bunazosin. Although HSR-175 also possessed competitive antagonist properties at pre- and postsynaptic alpha 2-adrenoceptors in the rat vas deferens and the dog saphenous veins, those affinities (pA2 = 6.41 and 7.05) were much lower than those at postsynaptic alpha 1-adrenoceptors. Furthermore, HSR-175 at concentration of 10(-6) M showed no inhibition on the contractile responses to 5-HT, histamine, KCl and angiotensin II in the rabbit thoracic aorta. These results indicate that HSR-175 is a very potent and selective alpha 1-adrenoceptor antagonist.

Adrenergic alpha-Antagonists↗
PubMed1992

[Effect of treatment schedule of an antitumor platinum complex, DWA2114R, on the antitumor activity].

Effects of treatment schedule of (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato) platinum (II) monohydrate, DWA2114R, on the antitumor activity against murine colon adenocarcinoma (Colon 26) and Lewis lung carcinoma (3LL) were examined. Colon 26 or 3LL tumors were transplanted s.c. into the flank and subsequently DW A2114R was given i.v. by single or multiple injections. The tumor weight was determined on days 14 or 25 and the antitumor effect was evaluated by GIR%. Although the total dose of DWA2114R was identical in both schedules, single injection was superior to multiple. Effect of treatment schedule of cis-dichlorodiammine-platinum (II), CDDP, and cis-diammine (1, 1-cyclobutanedicarboxylato) platinum (II), CBDCA, on the antitumor activities were the same as in case of DWA 2114R, i.e., single injection was superior to multiple.

Animals↗
PubMed1992

[Combination therapy of a new platinum complex, DWA2114R with various antitumor agents against mouse tumors in vivo].

In vivo antitumor activity of (-)-(R)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) monohydrate (DWA2114R) in combination with various antitumor agents was examined using mouse leukemia P388, Meth-A fibrosarcoma and M5076 reticulum cell sarcoma. The combination treatment of DWA2114R with cyclophosphamide, 5-fluorouracil, adriamycin, etoposide or vindesine showed synergistic effects on the prolongation of survival time of mice bearing P388. Among these combinations, combination of DWA2114R with adriamycin or vindesine showed a good synergism. In the combination treatment with vindesine against Meth-A which is not so sensitive to platinum agent, DWA2114R showed a synergistic or additive effect, but cis-diamminedichloroplatinum (II) (CDDP) showed subadditive. Three-drug combination of DWA2114R or CDDP with cyclophosphamide and adriamycin was examined in mice inoculated i.p. or s.c. with M5076. In both models, the combination of DWA2114R was more active than that of CDDP at the dose less than 1/16-fold of the dose of CDDP which is the ratio of two drugs in clinical trial.

Animals↗
PubMed1991

How does RNase H recognize a DNA.RNA hybrid?

The mechanism of RNase H substrate recognition is proposed from a model of a chemically modified DNA.RNA hybrid Escherichia coli RNase H complex. Site-directed mutagenesis of the enzyme and substrate titration observed by heteronuclear two-dimensional NMR spectra have been carried out. A model complex has been built, based on free structures of the enzyme and the substrate independently determined by x-ray crystallography and NMR distance geometry, respectively. In addition to steric and electrostatic complementarities between the molecular surfaces of the enzyme and the minor groove of the hybrid in the model, putative hydrogen bonds between the polar groups in the enzyme and 2'-oxygens of the RNA strand of the hybrid fix the hybrid close to the active site of the enzyme. The enzymatic activities of the mutant proteins and the changes in NMR spectra during the course of substrate titration are consistent with the present model. Moreover, the specific cleavage of the RNA strand in DNA.RNA hybrids can be explained as well as cleavage modes in modified heteroduplexes. A mechanism of enzymatic action is proposed.

Amino Acid Sequence↗
PubMed1991

The crystal structure of a mutant human lysozyme C77/95A with increased secretion efficiency in yeast.

The three-dimensional structure of a mutant human lysozyme, C77/95A, in which residues Cys77 and Cys95 were replaced by alanine, was determined at 1.8-A resolution by x-ray crystallography. The properties of this mutant protein have been well characterized with respect to its thermal stability and secretion efficiency in a yeast expression system. The overall three-dimensional structure of C77/95A was found to be essentially identical to that of the wild-type human lysozyme, although the coordinates were shifted by more than 0.5 A and the thermal factors of the main-chain atoms were increased in the vicinity of residue 77. The reduction in thermal stability of this mutant has been previously explained by an increase in entropy of the unfolded state. In addition, a packing defect (cavity) produced by the removal of the disulfide bond was detected in the three-dimensional structure of C77/95A. This cavity can also be a reason why the stability of the protein is reduced because the free energy of the folded state could be expected to increase. The increased secretion efficiency cannot be due mainly to the three-dimensional structure, but may possibly be related to some event in the pathway of protein secretion. One of the possibilities might involve molecular flexibilities in the secondary or tertiary structure for lack of one of the disulfide bonds.

Alanine↗