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Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 415 records · Page 23Linked to original sources
PubMed1994

[Study of 5'-DFUR treatment as postoperative adjuvant chemotherapy for stomach and colorectal cancer. Tokai GATS Group (pilot study)].

In order to study preliminary the safety of 5'-DFUR treatment as postoperative adjuvant therapy, intermittent and continuous treatment regimens were administered to patients undergoing curative resection of carcinomas of the stomach and the colorectum. Two treatment schedules were employed: 5'-DFUR was either given continuously in a daily oral dose of 600 mg/patient (continuous group) or for 2 weeks in a daily oral dose of 1,200 mg/patient followed by 2 weeks of no treatment (intermittent group). Twenty-one stomach cancer patients and 34 colorectal cancer patients were registered in the study. The rates of adverse drug reactions in the patients who completed treatment were 20.0% (2/10) in the continuous group and 50.0% (4/8) in the intermittent group of gastric cancer patients, and 16.6% (2/12) in the continuous group and 17.6% (3/17) in the intermittent group of colorectal cancer patients. The main adverse drug reactions were gastrointestinal symptoms. The incidence of diarrhea, a problematic side effect of 5'-DFUR, was 4.5% (1/22) in the continuous group and 12.0% (3/25) in the intermittent group. There were no statistically significant differences between the continuous group and the intermittent group in regard to the incidence of adverse drug reactions and survival rate. In addition, as there were no serious adverse drug reactions, both treatment regimens were demonstrated to be highly safe when administered as postoperative adjuvant therapy.

Administration, Oral↗
PubMed1993

Substrate recognition at the binding site in mammalian pancreatic alpha-amylases.

Porcine and human pancreatic alpha-amylases (PPA and HPA, respectively) have five binding sites for hexose residues of substrates. As previously reported, when a substrate is too small to occupy subsite 5 of the alpha-amylases, the optimum pH for catalytic activity changes from neutral to acidic [Ishikawa, K., Matsui, I., Honda, K., & Nakatani, H. (1990) Biochemistry 29, 7119-7123]. We studied the mechanism by which the enzyme recognizes the substrate by using the synthetic substrates maltopentaose (G5) and its analogs 4-O-alpha-maltotetraosyl-D-xylose (G4-X), 4-O-alpha-maltotetraosyl-2-deoxy-D-glucose (G4-D), 3-O-alpha-maltotetraosyl-L- sorbose (G4-S), 4-O-beta-maltotetraosyl-D-glucose (G4 beta-G), alpha-maltotetraosyl-beta-D-fructose (G4-F), p-nitrophenyl alpha-maltotetraoside (G4-phi), and maltopentaitol (G4-GOH). The reducing-end residues of these substrates, relevant to subsite 5, are D-xylose (X), 2-deoxy-D-glucose (D), L-sorbose (S), D-glucose (G), alpha-D-fructofuranose (F), p-nitrophenyl (phi), and D-sorbitol (GOH), respectively. The optimum pH for catalytic activity on the substrates G5, G4-X, G4-D, G4-S, G4 beta-G, and G4-phi was neutral, while that for G4-GOH and G4-F was acidic. These results indicate that only six-membered-ring residues and a phenyl group are recognizable by subsite 5. The neutral pH profile for G4-phi suggests that steric compatibility of the substrates at subsite 5 is also important for the enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Molecular characterization of the gene operon of heat shock proteins HSP60 and HSP10 in methicillin-resistant Staphylococcus aureus.

Methicillin-resistance of S.aureus (MRSA) was diminished or depressed at 44 degrees C. In order to investigate whether bacterial heat shock response is correlated with methicillin resistance, we examined the inducibility of the heat shock proteins (HSPs) in MRSA, and cloned and sequenced of their genes. A temperature shift from 37 degrees C to 46 degrees C enhanced the production of at least 8 kinds of cytoplasmic proteins as measured with two-dimensional PAGE. The induced protein profile was almost the same as methicillin sensitive S.aureus, and stress conditions due to ethanol, cadmium or low pH. Two of these proteins were HSP60 and HSP10. Their N-terminal amino acid sequences were 79%, and 83%, homologous with thermobacterium PS3, respectively. A positively hybridized 4.2 kbp DNA fragment encoding both proteins was isolated from the chromosomal DNA of MRSA. The resulting sequence revealed two reading frames and showed high homology to those of hsp60 (groEL) and hsp10 (groES) of bacteria (E.coli) and several other species. The genes of HSP60 and HSP10 in S.aureus comprised an operon as in E.coli. The relationship between those HSPs and PBP2' is currently under investigation.

Amino Acid Sequence↗
PubMed1993

Heat shock promoter of thermophilic chaperonin operon.

The translation of a heat shock protein (HSP), TGroEL, of thermophilic bacterium PS3 increased within 10 minutes when the culture temperature was raised from 60 degrees C to 70 degrees C. In contrast to hyperthermophilic HSPs such as Pyrodictium ATPase, TGroEL is homologous to GroEL of E. coli (Tamada et al. (1991) Biochem. Biophys. Res. Commun. 197, 565-571). The promoter of the thermophilic heat shock gene (tgrE) was sequenced to analyze the heat shock response. The sequences of the promoter were CCTACTTGCA (-35 region) and GTTCATTAATA (-10 region), which are more heat labile than those of the sigma 32 recognition sites of GroEL. The expression of this homologous tgrE in E. coli may be lethal to the cells. The ATPase alpha subunit of this thermophile is also homologous to TGroEL.

Amino Acid Sequence↗
PubMed1993

Extracellular production of human hepatitis B virus preS2 antigen as hybrid proteins with Bacillus subtilis alpha-amylases in high-salt-concentration media.

To produce PreS2 antigen of human hepatitis B virus extra-cellularly in Bacillus subtilis, it was fused with the COOH-termini of B. subtilis alpha-amylases of 522 (Amy+), 467 (Amy+) and 443 (Amy-) amino acids. Among them, alpha-amylase-A467, which has 467 amino acids, was a relatively stable carrier when the cells were cultured in Luria-Bertani (LB) medium. The alpha-amylase-A443-PreS2 hybrid protein (Amy-) was quickly degraded. The alpha-amylase-A522-PreS2 hybrid was most efficiently produced when a B. subtilis transformant of a protease-super-deficient mutant was cultured in the presence of 0.5 M sodium sulphate. The production of A522-PreS2 hybrid protein under such conditions reached 5-10 mg/l and was eight, and 200-500 times higher than those obtained by the transformants of an alkaline/neutral protease-deficient mutant of B. subtilis, and a wild-type strain, in LB medium, respectively.

Bacillus subtilis↗
PubMed1993

Allele frequency distribution of the D1S80 (pMCT118) locus polymorphism in the Japanese population by the polymerase chain reaction.

Population studies among Japanese were carried out at the D1S80 locus by the polymerase chain reaction and subsequent analysis in agarose gel electrophoresis. A total of 58 genotypes and 25 alleles ranging from 16 to 45 repeat units were observed in a population group of 121 unrelated individuals. The alleles with 18, 24 and 30 repeat units were found to be most common. Some large alleles with more than 42 repeat units were first observed in this study. Statistical tests for Hardy-Weinberg equilibrium showed that no significant deviations could be found in this Japanese population sample. The values of the mean exclusion chance and the discriminating power (DP) were calculated to be 0.76 and 0.91, respectively. The observed heterozygosity was 0.91.

Alleles↗
PubMed1993

Short-term changes in lipid and protein metabolism in liver transplants from living-related donors.

The effects of liver transplantation involving living-related donors were investigated in 20 pediatric cases in terms of protein and lipid metabolism using the extent of cholesterol esterification and the levels of total cholesterol, lecithine-cholesterol acyltransferase, apolipoprotein A-I, cholinesterase, and rapid turnover proteins as parameters. Cholesterol esterification increased from preoperative values of 39% +/- 4% to 67% +/- 1% (mean +/- SEM, n = 17) at 3 weeks after liver transplantation in successful cases but decreased from the preoperative value of 45% +/- 10% to 26% +/- 6% (n = 3) at 3 weeks in unsuccessful cases. Cholinesterase, transferrin, and prealbumin levels remained low after 3 weeks even in successful cases. Patients who had partial liver transplantations from living-related donors showed rapid recovery of cholesterol esterification. However, patients with graft livers required an extensive period before normalization of protein metabolism occurred, indicating the necessity for long-term follow-up of recipient development.

Adolescent↗
PubMed1993

Lipid metabolism after liver transplantation from a living related donor.

1. The recovery of lipid metabolism was investigated in paediatric patients treated for terminal liver disease by liver transplantation from living related donors. 2. The cholesterol ester ratio (esterified cholesterol/total cholesterol) and the total cholesterol/phospholipid ratio increased from preoperative values of 0.35 +/- 0.04 and 0.59 +/- 0.03 to 0.65 +/- 0.01 and 0.68 +/- 0.01 at 3 weeks after liver transplantation in successful cases (means +/- SEM, n = 26), respectively, whereas these two parameters decreased in failed cases (n = 4). 3. Biochemical analysis indicated that weekly recoveries in the cholesterol ester ratio and the total cholesterol/phospholipid ratio are characteristic of successful liver transplantation with a graft from a living related donor.

Adolescent↗
PubMed1993

Experience with FK506 in living-related liver transplantation.

The new immunosuppressive agent FK506 was used with steroids to treat 22 pediatric patients who received living-related partial liver transplantation. Seventeen recipients survived and 5 died between one and 16 months after transplantation. Three of the 5 patients who died had required intensive care preoperatively. Autopsy findings showed no evidence of rejection. There was no episode of rejection that required retransplantation in any of the patients. Liver allograft dysfunction, which was suspected to be a rejection response, was encountered in 2 recipients with ABO-nonidentical but compatible grafts. However, their clinical and biochemical findings were ameliorated upon steroid pulse therapy or upon augmented FK506 administration without additional potent immunosuppressive agents. Steroid treatment has been discontinued in all surviving patients at 1-9 months after transplantation. Infectious complications encountered in 9 patients included 2 bacterial, 5 viral, and 2 fungal infections. One recipient died of fungal pneumonia. Abnormal increase of serum creatinine level was confined to the complicated patients. Hypertension was a temporary adverse reaction in the early postoperative period, and only one patient needed an antihypertensive drug at 2 months after transplantation. Acute pancreatitis with hyperamylasemia was observed in one patient who was treated successfully with reduction of FK506 administration. Tremor was observed in 8 patients, itching in 4, insomnia in 2, and vomiting in one. Hirsutism, gingival hypertrophy, and lymphoma were not observed. FK506 was highly effective in living-related partial liver transplantation not only in terms of immunosuppressive potential but also because it produced fewer adverse effects.

Adolescent↗
PubMed1993

Arterial ketone body ratio and glucose administration as an energy substrate in relation to changes in ketone body concentration after living-related liver transplantation in children.

Changes in the arterial ketone body ratio (AKBR [acetoacetate/3-hydroxybutyrate]), which reflect the redox state of the liver mitochondria (NAD+/NADH), as well as those in total ketone body concentration (TKB) and blood glucose level were studied in 30 living-related liver transplantations (LRLT) performed in pediatric patients at Kyoto University Hospital from June 1990 to January 1992. AKBR increased to over 1.0 within 6 hr after reperfusion of the graft in 11 cases (37%), within 12 hr in 7 (23%), on POD 1 in 8 (27%), and on POD 2 in the remaining 4 cases (13%). TKB significantly increased while AKBR remained below 0.7 (266 +/- 40 mumol/L), but it significantly decreased in accordance with the recovery of AKBR above 1.0 (61 +/- 6 mumol/L). This indicates the change in the predominant energy substrate for hepatic mitochondria from fatty acid to glucose during the AKBR recovery process. In 6 cases, the AKBR transiently decreased to below 1.0 after initial recovery concomitant with the fall in blood glucose level and the increase in TKB. However, the AKBR was rapidly restored to over 1.0 again immediately after the glucose administration was increased. This suggests that glucose administration to maintain blood glucose level between 150 and 250 mg/dl is essential for the AKBR recovery above 1.0 that accompanies the normalization of graft metabolic functions, and that, along with the postoperative minimal increase in serum enzymes and favorable outcome of the transplant with no incidence of a primary nonfunctioning graft, the prompt and successful recovery of AKBR reflects the expected high viability of the graft in our LRLT cases.

Adolescent↗
PubMed1993

Suppression of inflammatory responses to 12-O-tetradecanoyl-phorbol-13-acetate and carrageenin by YM-26734, a selective inhibitor of extracellular group II phospholipase A2.

1. YM-26734 [4-(3,5-didodecanoyl-2,4,6-trihydroxyphenyl)-7-hydroxy-2-(4-hydroxyph eny l) chroman] dose-dependently inhibited the activities of extracellular phospholipase A2 (PLA2): rabbit platelet-derived group II and porcine pancreas-derived group I PLA2, with IC50 values of 0.085 (0.056-0.129, n = 5) and 6.8 (5.0-9.6, n = 5) microM, respectively. 2. In contrast, YM-26734 did not reduce the activity of intracellular PLA2 prepared from mouse macrophages, which preferentially hydrolyzed arachidonoyl phospholipids at concentrations up to 50 microM. YM-26734 also showed no effect against either sheep seminal vesicle cyclo-oxygenase or rat leukocyte 5-lipoxygenase. 3. Linewater-Burk analysis showed that YM-26567-1 behaved as a competitive inhibitor of group II PLA2 derived from rabbit platelets, with a Ki value of 48 nM. 4. In mice, YM-26734 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear)-induced ear oedema in a dose-dependent manner, with ED50 values of 45 (30-67) micrograms/ear (n = 5) and 11 (4-32) mg kg-1, i.v. (n = 5), but did not decrease arachidonic acid (4 mg/ear)-induced ear oedema at 1 mg/ear and 30 mg kg-1, i.v. 5. In rats, the accumulation of exudate fluids and leukocytes in the pleural cavity in response to carrageenin injection (2 mg) was significantly less in a group treated with YM-26734 (20 mg kg-1, i.v.) than in the control group (0.43 +/- 0.02 vs 0.59 +/- 0.03 g per cavity and 3.8 +/- 0.2 vs 4.9 +/- 0.3 x 10(7) cells per cavity, respectively; n = 5). 6. These results suggest that YM-26734 is a potent and competitive inhibitor of extracellular PLA2 with selectivity for group II PLA2, and that the inhibition of group II enzymes activity may cause the suppression of inflammatory responses to TPA and carrageenin.

Animals↗
PubMed1993

Cloning and characterization of a Bacillus subtilis gene encoding a homolog of the 54-kilodalton subunit of mammalian signal recognition particle and Escherichia coli Ffh.

By using a DNA fragment of Escherichia coli ffh as a probe, the Bacillus subtilis ffh gene was cloned. The complete nucleotide sequence of the cloned DNA revealed that it contained three open reading frames (ORFs). Their order in the region, given by the gene product, was suggested to be ORF1-Ffh-S16, according to their similarity to the gene products of E. coli, although ORF1 exhibited no significant identity with any other known proteins. The orf1 and ffh genes are organized into an operon. Genetic mapping of the ffh locus showed that the B. subtilis ffh gene is located near the pyr locus on the chromosome. The gene product of B. subtilis ffh shared 53.9 and 32.6% amino acid identity with E. coli Ffh and the canine 54-kDa subunit of signal recognition particle, respectively. Although there was low amino acid identity with the 54-kDa subunit of mammalian signal recognition particle, three GTP-binding motifs in the NH2-terminal half and amphipathic helical cores in the COOH-terminus were conserved. The depletion of ffh in B. subtilis led to growth arrest and drastic morphological changes. Furthermore, the translocation of beta-lactamase and alpha-amylase under the depleted condition was also defective.

Amino Acid Sequence↗
PubMed1993

Immunogenetic analysis of silicosis in Japan.

We previously reported that a gene in linkage disequilibrium with HLA-Bw54, DR4, and DRw53 might control the susceptibility to silicosis (K. Honda et al. 1988. N. Engl. J. Med. 319:1610). To further define the HLA-linked gene and other genetic factors for predisposition of silicosis, we determined for HLA-DQ and DP alleles using the polymerase chain reaction and sequence-specific oligonucleotide probes and made a restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes, immunoglobulin lambda variable chain (IGLV) gene, and T-cell receptor alpha and beta genes in 46 Japanese patients with silicosis. The frequency of DQB1*0401 (relative risk [RR] = 2.2, P < 0.02) was increased and that of DQB1*0601 (RR = 0.36, P < 0.01) was decreased in the patients. RFLP analysis of C4 and IGLV genes showed significant association between silicosis and a specific RFLP pattern of C4A3-C4B5 allotype (RR = 2.3, P < 0.05) and that of IGLV 5.3 kb (RR = 0.33, P < 0.003). No other genetic markers showed significant association. Statistical analyses of the associated genetic markers revealed that the HLA-Bw54 was the allele that showed primary association with silicosis and the frequencies of the C4 and HLA-DQ alleles were suggested to be increased due to their linkage disequilibrium with the HLA-Bw54. We conclude that the major gene for silicosis may be mapped near the HLA-B locus.

Adolescent↗
PubMed1993

The M3-muscarinic cholinoceptor subtype in rat prostate and its down regulation by aging.

Muscarinic cholinoceptor subtypes in the rat prostatic membrane were characterized by using [3H]-methyl-quinuclidinyl benzilate (QNB) in ligand binding studies. [3H]-Methyl-QNB saturation experiments showed the existence of a homogeneous population of binding sites with a high affinity (KD value) of 0.24 +/- 0.04 nM and a maximum binding site number (Bmax) of 219 +/- 65 fmol/mg protein. Inhibition of [3H]-methyl-QNB binding by nonlabelled compounds was in the following order of effectiveness in rat prostate: atropine > 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > hexahydro-sila-difenidol hydrochloride, p-fluoroanalog (p-F-HHSiD) > pirenzepine > methoctramine > [11-((2-((dimethylamino)-methyl)-1-piperidinyl)acetyl)-5,11-dihydro-6H- pyrido(2,3-b)(1,4)benzodiazepine-6-one] (AF-DX 116). This ranking order was similar to that for the salivary gland (M3 subtype), but not for the brain (M1 subtype) or the heart (M2 subtype). These results indicate that the muscarinic cholinoceptors in the rat prostate belong mainly to the M3 subtype. Furthermore, Bmax values for muscarinic cholinoceptors in the aged rat prostate (approximately 1-year-old) were smaller than those in the young rat prostate (6- to 8-week-old) (87 +/- 13 vs. 183 +/- 32 fmol/mg protein). However, KD values for muscarinic cholinoceptors, and Bmax and KD values for beta-adrenoceptors showed no change. These results suggest that the number of prostatic muscarinic cholinoceptors decreases with aging.

Aging↗
PubMed1993

Alpha 1-adrenoceptor subtype in the rat prostate is preferentially the alpha 1A type.

alpha 1-Adrenoceptors in the rat prostate were characterized by a binding assay using the newly synthesized radioligand [3H]-YM617 (5-[2-[[2[ethoxyring(n)-3H](o-ethoxyphenoxy)ethyl]amino]prop yl]-2-methoxybenzenesulfonamide HCl) and an in vitro assay. Specific [3H]-YM617 binding in the rat prostate was saturable and of high affinity (KD = 61.5 +/- 5.9 pM) with 23.2 +/- 6.9 fmol/mg of protein as the maximal number of binding sites (Bmax). alpha-Adrenoceptor agonists and antagonists inhibited the binding of the radioligand with the following order of effectiveness: YM617 > prazosin = bunazosin > WB4101 > 5-methylurapidil = phenoxybenzamine > phentolamine > S(+)-isomer of YM617 > yohimbine > norepinephrine > phenylephrine > methoxamine. alpha 1-Adrenoceptors in the rat prostate preferred the R(-)-isomer of YM617 to the S(+)-isomer. Preincubation with chlorethylclonidine (CEC; 10(-5) M, 10 min) just slightly changed the Bmax value for [3H]-YM617 without changing the KD value in the prostate; however, CEC reduced the Bmax in the aorta. In the isolated tissue, pretreatment with CEC (10(-5) M, 10 and 30 min) time-dependently shifted to the right the dose-response curve for phenylephrine and decreased the maximal contraction of aortas induced by phenylephrine, but did not shift or decrease those of prostates. The present results indicate that the alpha 1-adrenoceptors in the rat prostate are mainly CEC-insensitive (alpha 1A), whereas those in the aorta are CEC-sensitive (alpha 1B).

Adrenergic alpha-Agonists↗