Search PubMed⌕ Search

Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 469 records · Page 26Linked to original sources
PubMed1992

Characterization of [3H]YM617, R-(-)-5-[2-[[2[ethoxyring(n)-3H](o-ethoxyphenoxy)ethyl]amino]- propyl]-2-methoxybenzenesulfonamide HCl, a potent and selective alpha-1 adrenoceptor radioligand.

The binding properties of a new radioligand, R(-)-5-[2-[[2[ethoxyring(n)-3H](o- ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide++ + HCl ([3H]YM617), were studied in membranes of the rat hippocampus and spleen. [3H]YM617 rapidly associated with its binding sites in both membranes and reached steady state by 20 min at 25 degrees C. The specific binding of [3H]YM617 appeared to be saturable, and Scatchard analysis revealed a linear plot, suggesting a single population of binding sites with a dissociation constant of 0.170 +/- 0.016 nM (n = 6) in the hippocampus and 0.195 +/- 0.036 (n = 4) in the spleen. The maximal binding sites in the hippocampus and spleen were 203.0 +/- 43.2 (n = 6) and 72.4 +/- 17.0 (n = 4) fmol/mg protein, respectively. Chlorethylclonidine (10(-5) M for 10 min) treatment reduced the Bmax values of [3H]YM617 and [3H]prazosin to a similar degree in the rat hippocampus (10-15%) and spleen (40-50%). Alpha adrenoceptor agonists and antagonists competed with [3H]YM617 for binding sites in the following order: YM617 > prazosin > WB4101 > bunazosin > 5-methylurapidil > S(+)-isomer of YM617 > phentolamine > yohimbine > norepinephrine = phenylephrine > methoxamine in the hippocampus, and prazosin > YM617 > bunazosin > WB4101 > 5-methylurapidil > phentolamine > S(+)-isomer of YM617 > yohimbine > norepinephrine > phenylephrine > methoxamine in the spleen. In the hippocampus, prazosin and bunazosin produced biphasic displacement of [3H]YM617, but not [3H]prazosin binding. In contrast, only monophasic curves were obtained against either radioligand in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1992

Characterization of YM060, a potent and selective 5-hydroxytryptamine3 receptor antagonist, in rabbit nodose ganglion and N1E-115 neuroblastoma cells.

The 5-hydroxytryptamine (5-HT)3 receptor blocking properties of YM060, [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride], were examined by electrophysiological and radioligand binding studies. Results were compared with those for ondansetron, granisetron and the enantiomer (S-form) of YM060. 5-HT and 2-methyl-5-HT, a selective 5-HT3 receptor agonist, induced dose-dependent depolarizations of rabbit nodose ganglion with ED50 values of 24.0 (19.9-29.1) and 40.1 (30.9-52.1) nmol, respectively (geometric mean, 95% CL). YM060, ondansetron, granisetron and the S-form dose-dependently inhibited 5-HT-induced depolarizations with IC50 values of 3.85 (2.47-5.98), 1.55 (1.26-1.91), 1.45 (1.18-1.79) and 13.5 (11.2-16.2) nM, respectively. Methysergide, a 5-HT1-like and 5-HT2 receptor antagonist, at a concentration of 10(-5) M had no effect on responses to 5-HT. YM060 up to 10(-5) M produced no significant depression of depolarizing responses to 1,1-dimethyl-4-phenylpiperazinium iodide and gamma-aminobutyric acid. YM060, ondansetron, granisetron and the S-form displaced specific binding of [3H]GR65630 to N1E-115 neuroblastoma cell membranes with Ki values of 0.091 (0.086-0.097), 7.03 (5.96-8.01), 2.02 (1.74-2.30) and 10.3 (9.96-10.6) nM, respectively. These results show that YM060, compared with ondansetron and granisetron, has considerably higher affinity for 5-HT3 receptors in N1E-115 cells and slightly less potent 5-HT3 receptor antagonistic activity in rabbit nodose ganglion. Moreover, the isomeric activity ratio (R-form/S-form) was approximately 112 in N1E-115 cells and no greater than 4 in the ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The novel natural product YM-26567-1 [(+)-trans-4-(3-dodecanoyl-2,4,6- trihydroxyphenyl)-7-hydroxy-2-(4-hydroxyphenyl)chroman]: a competitive inhibitor of group II phospholipase A2.

(+)-trans-4-(3-dodecanoyl-2,4,6-trihydroxyphenyl)-7-hydroxy-2-(4- hydroxyphenyl)chroman (YM-26567-1), a novel natural product isolated from the fruit of Horsfieldia amygdaline, dose-dependently inhibited group II phospholipase A2 (PLA2) prepared from rabbit platelet with an IC50 value of 6.7 microM (4.6-9.6 microM, n = 4). In contrast to irreversible PLA2 inhibitors such as manoalide and p-bromophenacyl bromide, the PLA2 inhibition of YM-26567-1 was independent of preincubation time. Lineweaver-Burk analysis revealed that YM-26567-1 behaved as a competitive inhibitor of rabbit platelet PLA2 with a Ki value of 1.6 +/- 0.3 microM (n = 5). Although YM-26567-1 also competitively inhibited group I PLA2 derived from porcine pancreas, the Ki value was approximately 10-fold greater for porcine pancreas than for rabbit platelet PLA2. In vivo, topical application of YM-26567-1 to the mouse ear inhibited 12-O-tetradecanoylphorbol-13-acetate (1 micrograms/ear)-induced mouse ear edema in a dose-dependent manner with a 50% effective dose of 28 micrograms/ear (13-63 micrograms/ear, n = 10/dose), but did not improve arachidonic acid (4 mg/ear)-induced mouse ear edema at 1 mg/ear. These results suggest that YM-26567-1 is a competitive PLA2 inhibitor showing a higher affinity for group II than group I PLA2, and that it may act as a potent anti-inflammatory compound through its direct inhibition of PLA2.

Animals↗
PubMed1992

[Inflammatory cell infiltration around beta 2-microglobulin amyloid deposition: histologic comparison of beta 2-microglobulin amyloidosis with AA or AL amyloidosis].

Thirty-one autopsy cases of beta 2-microglobulin (beta 2M) amyloidosis were pathologically investigated in comparison with 17 autopsy cases of AA or AL amyloidosis. In 20 cases (65%, 20/31) of beta 2M amyloidosis, inflammatory cells, mainly macrophages were seen infiltrating around beta 2M amyloid in intervertebral disks. The more beta 2M amyloidosis advances, the more macrophage infiltration tends to be prominent. In cases of severe beta 2M amyloidosis, the cytoplasm of macrophages around amyloid deposition were swollen with engulfed amyloid substance and were often transforming to foreign body multinucleated giant cells. In addition, granulation tissue was formed with infiltrating macrophages, foreign body multinucleated giant cells, capillary proliferation and fibrosis around beta 2M amyloid deposition. On the other hand, inflammatory cell infiltration around amyloid deposition was scarcely seen in AA or AL amyloidosis. Ultrastructurally, macrophages were abundant in phagocytic vacuoles containing amyloid fibrils. These macrophages were immunohistochemically positive for CD68, IL-1 beta and TNF-alpha. Thus, macrophage infiltration around beta 2M amyloid is thought to be responsible for local pain and tissue destruction of dialysis patients.

Amyloid↗
PubMed1992

[In vitro susceptibilities of Mycobacterium avium and Mycobacterium intracellulare to new macrolides, new quinolones, and antituberculous drugs on Dubos agar medium].

Mycobacterium avium and M. intracellulare were isolated from the sputum of patients infected with atypical mycobacteria using 1% Ogawa medium and identified by the DNA probe test. Then the MICs of various kinds of drugs against these mycobacterial species were determined on Dubos agar medium, and the drug susceptibilities were also determined on 1% Ogawa medium in parallel. The drugs tested were new macrolides, such as clarithromycin (CAM) and roxithromycin (RXM), new quinolones, such as ofloxacin (OFLX) and ciprofloxacin (CPFX), and antituberculous drugs, such as isoniazid (INH), rifampicin (PFP), streptomycin (SM), and ethambutol (EB). The MICs of the drugs tested, especially those of CAM, OFLX, and RFP, when determined on Dubos agar medium, were generally lower against M. intracellulare than against M. avium. The susceptibilities of the mycobacterial isolates tested to RFP and SM determined on Dubos agar medium were markedly different from those determined on 1% Ogawa medium. Such discrepancies may be accounted for by absorption of these drugs to the egg medium and instability of RFP in the egg medium. Overall, our results indicate that the new macrolides and new quinolones are effective against atypical mycobacteria.

4-Quinolones↗
PubMed1992

Role of the serotonin3 receptor in stress-induced defecation.

The possibility that 5-hydroxytryptamine (serotonin; 5-HT) mediates bowel dysfunction caused by stress was evaluated in rats and mice treated with 5-HT or thyrotropin-releasing hormone (TRH) injection and in rats subjected to stress. Restraint stress at room temperature (23 degrees C) significantly increased fecal pellet output without the formation of gastrointestinal mucosal lesions in free-feeding rats, and caused diarrhea in 90 to 100% of animals within 3 hr in food-deprived rats. Oral YM060, ondansetron, granisetron, atropine and diazepam and s.c. tetrodotoxin inhibited these stress-induced changes in bowel function in fed and fasted rats. ED50 values were 1.1 (0.2-6.6) and 2.5 (1.1-5.7) micrograms/kg for YM060, 483 (338-691) and 354 (262-477) micrograms/kg for ondansetron, 208 (111-393) and 142 (48.9-414) micrograms/kg for granisetron, 811 (639-1,030) and 847 (641-1,118) micrograms/kg for atropine, 3,099 (1,499-6,405) and 5,396 (4,768-6,106) micrograms/kg for diazepam and 1.9 (1.7-2.1) and 3.3 (1.6-6.5) micrograms/kg for tetrodotoxin, respectively. Methysergide inhibited stress-induced diarrhea with an ED50 value of 724 (384-1,366) micrograms/kg s.c., whereas it had partial effect on stress-induced increases in fecal pellet output. Exogenous 5-HT increased fecal pellet output in rats and caused diarrhea in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Clinical study of panipenem/betamipron for burn infections in the domain of plastic and reconstructive surgery].

The effectiveness and the safety of panipenem/betamipron, new antibiotics of the carbapenems for burn infections, were studied and the following results were obtained: 1. The preparation, 0.5 g/0.5 g, was administered by intravenous drip infusion twice a day to 11 cases of patients with burn infections. In 10 cases for which clinical effects were evaluable, results were rated as "excellent" in 2 cases, "good" in 2 cases and "fair" in 6 cases, with an efficacy rate of 40%. 2. Penetration to the affected tissue was studied in 2 cases. The tissue level of panipenem was 0.20 micrograms/g immediately after the end of drip infusion and 6.86 micrograms/g 60 minutes thereafter. 3. As for the safety, a slight increase in GOT, GPT and Al-P was noted in 1 case; a slight increase in GPT, NAG and beta 2MG was found in 1 case; and a slight increase in GOT, GPT, Al-P and LAP was noted in 1 case, as abnormal variations in laboratory test results.

Adolescent↗
PubMed1992

Comparison of converting enzyme inhibitor and calcium channel blocker in SHR with nephrotoxic serum nephritis.

In order to compare the protective effects of angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) on the renal function in experimental nephritis, nephrotoxic serum nephritis was induced in male spontaneously hypertensive rats (SHR). The above drugs were then chronically administered to different groups, as follows: the ACEI-treated group (n = 7) received captopril (150 mg/kg/day), and the CCB-treated group (n = 6) was given both nifedipine (40 mg/kg/day) and nisoldipine (20 mg/kg/day). The control group (n = 8) received a placebo. Although the control group developed marked hypertension and proteinuria, the rats treated with either ACEI or CCB demonstrated a significant and equivalent decrease in mean arterial pressure and urinary protein excretion. At 15 weeks after the injection of nephrotoxic serum, all rats were anesthetized with Inactin, and the glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. In the control group, GFR and RPF were markedly attenuated. However, both were preserved at much higher levels in the ACEI-treated group, and GFR was also maintained to a similar degree in the CCB-treated group. Histological studies were carried out after the clearance studies. As a result, it was found that the ACEI treatment significantly limited the development of glomerulosclerosis, whereas CCB modestly ameliorated the glomerular structural lesions. Moreover, ACEI significantly reduced the serum cholesterol, while CCB did not exert such an effect. These results suggest that both ACEI and CCB have a therapeutic effect in experimental glomerulonephritis models which are accompanied by hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

The pH dependence of the action pattern in porcine pancreatic alpha-amylase-catalyzed reaction for maltooligosaccharide substrates.

Porcine pancreatic alpha-amylase (EC 3.2.1.1; abbreviated PPA), which hydrolyzes alpha-D-(1,4) glucosidic bonds in starch and amylose, displays an optimum at pH 6.9 for the majority of substrates. The optimum pH, however, shifted to 5.2 for the hydrolysis of some low molecular substrates (Ishikawa, K., et al., 1990, Biochemistry 29, 7119-7123). Details of the substrate-dependent shift of the optimum pH in PPA were studied by use of a series of maltooligosaccharides with 14C-labeled reducing end glucose as substrates. The optimum pH for maltotriose was 5.2, whereas that for maltopentaose and maltohexaose was unchanged at pH 6.9. The pH profile for the intermediate size substrate maltotetraose showed abnormality; the apparent optimum pH was broadened between 5.5 and 6.5 and the bond cleavage pattern depended on pH, unlike that for the other substrates examined. These results were independent of either buffer systems or substrate concentration. Analyses of the hydrolysates of the maltooligosaccharides revealed that the shift of the optimum pH to the neutral region occurred only when the fifth subsite of PPA in the productive binding modes was occupied by a glucosyl residue of a substrate. The three-catalytic residue model of PPA deduced from the analysis of the hydrolysis of some modified maltooligosaccharides (p-nitrophenyl-alpha-D-maltoside, gamma-cyclodextrin, maltopentaitol, and maltohexaitol) (Ishikawa, K., et al., 1990, Biochemistry 29, 7119-7123) was successfully adapted to the linear maltooligosaccharides used in this work. These results indicate that the different productive binding modes of the linear oligosaccharide substrates affect directly the catalytic power and the optimum pH of PPA.

Animals↗
PubMed1991

An increase in the transglycosylation activity of Saccharomycopsis alpha-amylase altered by site-directed mutagenesis.

The 84th tryptophan residue in Saccharomycopsis alpha-amylase molecule was replaced by a leucine residue and the resulting site-directed mutant, W84L enzyme, showed an increase in transglycosylation activity. At a 40% digestion point of maltoheptaose (G7), for example, maltooligosaccharide products larger than maltodecaose (G10) amounted to approx. 60% of the total product from the mutant enzyme reaction, whereas no such large products were observed in the native enzyme reaction. Analysis of the reaction products from p-nitrophenyl maltooligosaccharides indicated that these large products were formed by addition of the hydrolysis products on the nonreducing end side to the starting intact substrates. These results suggest that the tryptophan residue located at subsite 3 of the enzyme plays an important role not only to hold the substrate, but also to liberate the hydrolysis products from the substrate binding pocket.

Glycosylation↗
PubMed1991

Heat shock proteins in human and mouse embryonic cells after exposure to heat shock or teratogenic agents.

In human chorionic villus tissue at the 10-17th week of a normal pregnancy, heat shock proteins (hsp70, hsp73, hsp85, and hsp105) were induced in vitro by a heat shock or by exposure to sodium arsenite or cadmium chloride. In dispersed cells of the whole mouse embryo on the 11th day of development, heat shock proteins (hsp73 and hsp105) were induced by a heat shock or by exposure to sodium arsenite, but not by exposure to cadmium chloride. After a maternal hyperthermia or an intraperitoneal injection of sodium arsenite or cadmium chloride into a pregnant mouse, heat shock proteins accumulated in the embryo on the 9th day of development, especially in the neuroepithelial tissue. The significance of heat shock proteins in the embryo is discussed.

Animals↗
PubMed1991

Experience with 225 hepatic resections for hepatocellular carcinoma over a 4-year period.

During the past 4 1/2 years, we have performed hepatic resection on 225 patients with hepatocellular carcinoma (HCC). These patients included 171 men and 54 women, whose ages ranged from 29 to 84 years with an average of 60 years. Underlying cirrhosis of the liver was found in 67% of the patients and chronic hepatitis in 27%. Patients undergoing hepatic resection were classified into five groups according to curability as follows: Group A, resection of the tumor-bearing segment and one additional segment; Group B, complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, incomplete resection of the tumor; Group E, surgical approach for advanced HCC with tumor thrombi in the main trunk or the first branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D, and E was 12 (5%), 83 (37%), 58 (26%), 14 (6%) and 58, (26%), respectively. There were 4 deaths (2.4%) among the 167 patients in Groups A to D within 30 days after operation and 12 deaths (20.7%) in Group E. The 3-year survival rate of Groups A, B, C, D, and E was 100%, 74%, 21%, 0%, and 35%, respectively.

Adult↗
PubMed1991

Complexation of thiomalic acid with mercury (II) and lead (II) under physiological conditions.

The complex formation of thiomalic acid (H3L) with Hg(II) and Pb(II) was investigated under physiological conditions of 37 degrees C and 0.15 mol dm-3 NaCl by potentiometric titrations using glass electrodes. From the analysis of the emf data in the two systems by use of computer program MIQUV it was concluded that the species formed in the two systems are [HgH4L2], [HgH3L]-, [HgH2L2]2-, [HgHL2]3-, [HgHL], [HgL]-, [HgL2]4-, [Hg(OH)L]2-, [Hg(OH)L2]5-, [PbH2L2]2-, [PbH2L]+, [PbHL2]3-, [PbHL], [PbL]-, [Pb(OH)L]2-, and [Pb(OH)2L]3-. The hydrolytic reactions of Hg(II), data on which were used in the analysis of the above system, were also studied by separate potentiometric titrations. Measurements of 13C NMR spectra of [HgL2]4- and [PbL]- and [PbHL2]3- in D2O solutions suggested that the ligand coordinates with both the metal ions through the sulfhydryl group and one of the two carboxylate groups in such a way that the five-membered chelate ring is formed within the complexes.

Binding Sites↗
PubMed1991

Subsite structure of Saccharomycopsis alpha-amylase secreted from Saccharomyces cerevisiae.

The kinetic parameters (kcat/Km) and the cleaved-bond distributions for the hydrolysis of linear maltooligosaccharides Gn (3 less than or equal to n less than or equal to 9) by Saccharomycopsis alpha-amylase (Sfamy) secreted from Saccharomyces cerevisiae were determined at pH 5.25 and 25 degrees C. The subsite affinities of Sfamy were also evaluated from these data. The subsite structure of Sfamy is characteristic of the active site of an endo-cleavage type enzyme, consisting of internal repulsive sites with the catalytic residues and external attractive sites. Moreover, the pKa values of the catalytic residues were calculated from the pH dependence plot of the kinetic parameter (kcat/Km). The amino acid residues which contribute to the subsite affinities and the catalytic activity of Sfamy are proposed and compared with those of Taka-amylase A.

Kinetics↗
PubMed1991

Both induction and activation of the branched-chain 2-oxo acid dehydrogenase complex in primary-cultured rat hepatocytes by clofibrate.

Clofibrate administration to rats caused both the activation and induction of the branched-chain 2-oxo acid dehydrogenase complex in the liver; the former phenomenon occurred within the first 6 h after clofibrate administration whereas the latter occurred after 12 h. Essentially the same results were obtained with primary cultures of rat hepatocytes in the presence of 0.5 mM clofibrate, though about three-fourths of the enzyme complex in control cells (without clofibrate addition) was inactivated during a culture for 44 h, with little reduction of the enzyme amount. This was also confirmed by immunotitration analysis with antibodies raised against the purified decarboxylase and transacylase components of the enzyme complex. On the other hand, the activity of dihydrolipoamide dehydrogenase (a constituent of the complex) was little affected by clofibrate administration. The half lives of the decarboxylase and transacylase components in the primary cultures were estimated to be in the range of 22-26 h, and were unchanged in the presence of clofibrate, when determined with the use of cycloheximide and by a pulse-chase experiment. On the contrary, the rates of synthesis of these two enzyme components had increased to about 1.9-fold after 32 h cultivation in the presence of clofibrate. Thus, the increase in the synthesis of both the components resulted in induction of the complex.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗