Biomedical subjects

K Hidaka

Publications and source records attributed to K Hidaka.

At least 91 records · Page 5Linked to original sources

PubMed1994

[Hepatic arterial infusion therapy in a patient with multiple hepatic metastases from gastric cancer].

A patient with multiple hepatic metastases (H3) from advanced gastric cancer was treated with pre- and post-operative arterial infusion therapy. A Port-A-Cath was cannulated into the gastroduodenal artery after total gastrectomy. Repeated arterial infusions were performed monthly in the outpatient ward. The volume of hepatic tumors was remarkably decreased to 12% of the pretreatment level. The patient has been alive for 15 months after the operation without any complaint. Arterial infusion chemotherapy through implantable reservoir is useful for the treatment of unresectable hepatic metastasis without decreasing the quality of life.

Chemotherapy, Adjuvant↗

PubMed1994

Skeletal muscle fiber type, resistance training, and strength-related performance.

The research goal was to attempt to clarify the consequences of increased strength on performance at submaximal exercise intensities. Eight subjects (4 males, 4 females) completed a 3-d.wk-1, 16-wk resistance training regimen. After training, upper (bench press, BP) and lower (parallel squat, PS) extremity strength were increased by 23% and 37%, respectively. Performance at the same absolute work rates as before training was increased by 30-159% following training depending on intensity and type of exercise. Performance at the same relative work rates (80%, 60%, 40%) remained unchanged by the training for both exercises. Prior to training, PS repetitions at 40% were correlated (r = 0.69, P < 0.05) with the percentage of slow-twitch (ST) fibers in the vastus lateralis muscle. There were similar relationships at 40% (r = 0.73) and at 60% (r = 0.83) for the PS exercise after training. However, the resistance program did not result in greater relative submaximal performance in individuals with a higher percentage of ST fibers. We conclude that strength improvement of up to 40% does not produce a strength-related performance deficit, when training and testing procedures are identical. Yet, these data do not rule out the potential of a strength-related repetition performance deficit. When subjects were equally divided by strength levels, those tested at the highest absolute resistance had significantly lower bench press repetition performance at 60% and 40% of the 1-RM than the subjects tested at the lowest absolute resistance.

Adult↗

PubMed1994

[Systematic cleaning of the mite antigens in home environment and its effects on atopic dermatitis].

Since mite antigen is an important causative agent of atopic dermatitis (AD), establishment and maintenance of a mite-reduced home environment would be an effective means to mitigate the symptoms. For establishing and maintaining a mite-reduced home environment, the structure of the residence, as well as the life style of the residents are important factors to consider. Based on a hypothesized behavior of the mite antigens a cleaning program was developed. Application of this program for establishing and maintaining a mite-reduced room in a patient's home produced a reduction in both mite population and mite antigen level, as well as a mitigation of the patient's symptoms. An air purifier was shown to have the ability to reduce, to a certain extant, specific mite antigens. The results suggest that an air purifier would be an effective contribution to the maintenance of a mite-reduced home environment.

Adolescent↗

PubMed1993

Comparison of the effects of trimebutine and YM114 (KAE-393), a novel 5-HT3 receptor antagonist, on stress-induced defecation.

YM114 (KAE-393), (R)-5-[(2,3-dihydro-1-indolyl)carbonyl]-4,5,6,7- tetrahydro-1H-benzimidazole hydrochloride, is a derivative of YM060, a potent 5-HT3 receptor antagonist. We investigated the effects of YM114 on 5-HT3 receptors, both in vitro and in vivo, and on bowel dysfunction induced by restraint stress, 5-HT and thyrotropin-releasing hormone (TRH), and compared them with the effect of trimebutine. YM114 dose dependently inhibited the reduction in heart rate induced by 5-HT (30 micrograms/kg i.v.) in rats (ED50 = 0.31 micrograms/kg i.v.), and the potency of YM114 was almost the same as that of the racemate. The S-form of YM114 also inhibited 5-HT-induced bradycardia, but 1350 times less potent than the R-form. YM114 and its S-form inhibited [3H]GR65630 binding to N1E-115 cell membranes in a concentration-dependent manner with Ki values of 0.341 and 616 nM, respectively, showing the isomeric activity ratio (R-/S-form) of YM114 to be much greater (1800). YM114 antagonized 5-HT-induced depolarization of the nodose ganglion (EC50 = 1.39 nM). Trimebutine (1 mg/kg i.v.) failed to inhibit 5-HT-induced bradycardia, implying that it does not possess 5-HT3 receptor antagonistic activity. YM114 significantly and dose dependently prevented restraint stress-, 5-HT- and TRH-induced increases in fecal pellet output, and restraint stress- and 5-HT-induced diarrhea in rats and mice (ED50 = 6.9, 72.5, 154.6, 9.7 and 52.4 micrograms/kg p.o., respectively). Trimebutine significantly prevented stress- and 5-HT-induced diarrhea (ED50 = 29.4 and 87.3 mg/kg p.o., respectively), but only partially affected stress-, 5-HT- and TRH-induced increases in fecal pellet output. Thus, YM114 is a potent and stereoselective 5-HT3 receptor antagonist with much greater protective effects against stress-induced defecation than trimebutine.

Animals↗

PubMed1993

Synthesis and structure-activity studies of a series of spirooxazolidine-2,4-diones: 4-oxa analogues of the muscarinic agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione.

A series of spirooxazolidine-2,4-dione derivatives related to the putative M1 agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (RS86; 1) were synthesized. The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice. Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1. Among these compounds, only 5a exhibited M1-receptor stimulating activity in pithed rats. Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirosuccinimide derivatives including 1. The antiamnesic dose of 3-ethyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter. These results suggest that the 8-azaspiro[4.5]decane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs.

Amnesia↗

PubMed1993

Involvement of protein kinase in environmental stress-induced activation of human multidrug resistance 1 (MDR1) gene promoter.

The human MDR1 gene can be induced in response to various environmental stimuli. To examine whether such stress-induced activation of the MDR1 gene can be modulated by protein kinase, we employed a stable human cancer KB cell line which contained the bacterial chloramphenicol acetyltransferase (CAT) gene directed by the MDR1 gene promoter. H-7, a protein kinase C inhibitor, at more than 40 microM inhibited activation of the MDR1 promoter that was induced by ethylmethane sulfonate, 5-fluorouracil or UV irradiation. DNA binding activity of nuclear factors recognizing the MDR1 promoter was augmented in KB cells treated with UV, but decreased in cells treated concomitantly with H-7. Okadaic acid alone was able to induce the promoter activation, and this induction was dependent on specific promoter sequences. Okadaic acid also enhanced the DNA binding activity of nuclear factors recognizing the MDR1 promoter. The phosphorylation of transacting factors may modulate the MDR1 gene promoter activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

The MEF-3 motif is required for MEF-2-mediated skeletal muscle-specific induction of the rat aldolase A gene.

The rat aldolase A gene contains two alternative promoters and two alternative first exons. The distal promoter M is expressed at a high level only in skeletal muscle. Previous in vitro transfection studies identified the region from -202 to -85 as an enhancer that is responsible for dramatic activation during the differentiation of chicken primary myoblasts. This enhancer contains an A/T-rich sequence resembling the MEF-2 motif, which is an important element of muscle enhancers and promoters. In this study, we demonstrate that the MEF-2 sequence is essential but not sufficient for the activity of the enhancer. Another region required for the activity was recognized by a nuclear factor, tentatively named MAF1. MAF1 was found in both muscle cells and nonmuscle cells, and MAF1 from both cell types was indistinguishable by gel retardation and DNase I footprint experiments. The sequence required for MAF1 binding is very similar to the MEF-3 motif, which is an element of the skeletal muscle-specific enhancer of the cardiac troponin C gene. Because MAF1 and MEF-3 are closely related in both recognition sequence and distribution, MAF1 and MEF-3 probably represent the same nuclear factor which may play an important role in muscle gene transcription. Thus, the muscle-specific induction of the aldolase A gene is governed by muscle-specific MEF-2 and existing MEF-3 (MAF1).

Animals↗

PubMed1993

Protective actions of YM737, a new glutathione analog, against cerebral ischemia in rats.

Effects of YM737[N-(N-r-L-glutamyl-L-cysteinyl)glycine 1-isopropyl ester sulfate monohydrate], a new glutathione (GSH) analog more readily transported into cells than GSH, on cerebral ischemia were compared with those of GSH and some other drugs in rats subjected to occlusion of the bilateral carotid arteries. YM737 significantly reduced lethality, increased brain-water levels as measured by both dry-wet and NMR methods, and increased malondialdehyde (MDA) levels in the cerebral ischemic rats. On the other hand, pharmacological actions of GSH itself was less than those of YM737. In the ischemic rats used in the present study, there was no significant difference in 31P-NMR signals between the normal and the cerebral ischemic rats. These results suggest that YM737 showed anti-cerebral ischemic effects presumably due, in part, to inhibition of lipid peroxidative responses.

Animals↗

PubMed1993

Differentially potentiating effects by dipyridamole on cytotoxicity of 5-fluorouracil against three human maxillary cancer cell lines derived from a single tumor.

Dipyridamole (DPM), an inhibitor of nucleoside transport, is a unique potentiator of 5-fluorouracil (5-FU). We examined the combined effects of DPM and 5-FU on three cell lines (IMC-2, IMC-3, IMC-4) derived from a single tumor of a patient with maxillary cancer. DPM at 1.0-2.0 microM potentiated the cytocidal action of 5-FU > 20-fold against IMC-2 cells, while DPM at 10-20 microM potentiated the action of 5-FU against IMC-3 cells by 2-fold and against IMC-4 cells by approximately 4-fold. We examined why DPM differentially potentiated 5-FU against the three cell lines. The three maxillary cell lines showed heterogeneous sensitivities to the combination of 5-FU and DPM. We compared intracellular metabolism of 5-FU in IMC-2, IMC-3 and IMC-4 cells by HPLC. Determination of 5-FU metabolites demonstrated that cellular contents of 5-fluorodeoxyuridine monophosphate (FdUMP) were 104.66, 15.35 and 61.5 fmol/10(6) cells in IMC-2, IMC-3 and IMC-4 cells, respectively, in the presence of 10 microM DPM when the three cell lines had similar levels (0.21-0.33 fmol/10(6) cells) of FdUMP in the absence of DPM. By contrast, cellular levels of 5-FU and 5-fluorouridine triphosphate (FUTP) were not appreciably changed by DPM in three cell lines. The cellular level of thymidylate synthase mRNA in IMC-2 cells was found to be about one-fifth of that in IMC-3 and IMC-4 cells. The differential effects of DPM on the potentiation of 5-FU cytotoxicity might be closely related to the cellular levels of FdUMP and its target enzyme, thymidylate synthase in three human maxillary cancer cell lines.

Cell Survival↗

PubMed1993

[Clinical study on the effect of continuous transarterial infusion chemotherapy of CDDP for metastatic liver tumors].

Thirteen patients with unresectable liver tumors, including 7 colorectal cancers, 5 gastric cancers, and 1 breast cancer, were treated by intraarterial continuous infusion of CDDP using an implantable reservoir. The catheter was placed by direct insertion at laparotomy (7 cases) or through the inferior epigastric artery (6 cases). The clinical antitumor effects were evaluated by CT-scan or ultrasonography. One CR, 6 PR, and 6 NC were observed among the thirteen patients, respectively. The response rate for all cases was 53.8%, which is evidently higher than that of previously reported "one shot" transarterial MMC and 5-FU infusion chemotherapy. Since this treatment method induces little side effects, it can be maintained in outpatient clinics. Thus, we concluded that this treatment could be useful to improve the quality of life of patients with unresectable liver tumors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Effects of niceritrol on levels of serum lipids, lipoprotein(a), and fibrinogen in patients with primary hypercholesterolemia.

Thirty-three consecutive unselected patients with primary hypercholesterolemia received niceritrol 1.5 g daily for 12 weeks, with the effect of administering divided dose (twice daily (b.i.d.) and three times daily (t.i.d.)) evaluated. The serum concentrations of lipoprotein(a) (Lp(a)), lipids, the major apolipoproteins (apo), cholesteryl ester transfer activity and fibrinogen were determined before and after treatment. The b.i.d. and t.i.d. regimens each significantly reduced the serum levels of total cholesterol and triglyceride. The mean changes in serum lipids and lipoproteins did not differ significantly between the two groups. After 12 weeks of treatment, there was a significant decrease in total plasma cholesterol, triglyceride, low density lipoprotein cholesterol, apo A-II, apo B and fibrinogen and an increase in the high density lipoprotein cholesterol levels. Although the serum level of Lp(a) did not change in every patient, niceritrol significantly reduced the serum Lp(a) level in those with an initially high level of Lp(a) (greater than or equal to 20 mg/dl).

Adult↗

PubMed1992

Pharmacological characterization of a novel muscarinic partial agonist, YM796, in transfected cells expressing the m1 or m2 muscarinic receptor gene.

To investigate the pharmacological effect of a novel compound YM796, we performed radioligand binding experiments and correlative biochemical experiments using the transfected murine fibroblast B82 cells which expressed the m1 and m2 muscarinic receptor genes (cloned cell lines designated as LK3-3 and M2LKB2-2, respectively). [3H](-)methyl-3-quinuclidinyl benzilate [( 3H](-)MQNB) binding in these transfected cell lines was inhibited by different optical isomers of YM796 and other muscarinic drugs, atropine, pirenzepine, AF-DX 116, as well as selected agonists. (-)YM796, (+)YM796 and (+/-)YM796 inhibited [3H](-)MQNB binding in LK3-3 cells with Ki values of 16.4 microM, 30.1 microM and 21.8 microM and in M2LKB2-2 cells with Ki values of 52.0 microM, 108 microM and 77.1 microM, respectively. From functional assays we found the two isomers, (-)YM796 and (+)YM796 had different intrinsic activities for the M1 and M2 muscarinic receptors. (-)YM796 revealed agonistic activity: stimulation of [3H]IP1 accumulation in LK3-3 cells with an EC50 value of 26.5 microM, which was less efficacious (the Emax value was 5.6 times basal) than carbachol, a full agonist (the Emax value was 17.2 times basal). Interestingly, (-)YM796 did not show significant inhibition of cAMP formation in M2LKB2-2 cells except at extremely high concentrations (greater than 1mM). (+)YM796 exhibited no significant efficacy for the M1 and M2 muscarinic receptors. These results suggest that (-)YM796 represents a muscarinic partial agonist with functional selectivity for the M1 muscarinic receptors whereas (+)YM796 shows no efficacy for either M1 or M2 muscarinic receptors in these transfected cells.

Animals↗

PubMed1992

A single MEF-2 site is a major positive regulatory element required for transcription of the muscle-specific subunit of the human phosphoglycerate mutase gene in skeletal and cardiac muscle cells.

In order to analyze the transcriptional regulation of the muscle-specific subunit of the human phosphoglycerate mutase (PGAM-M) gene, chimeric genes composed of the upstream region of the PGAM-M gene and the bacterial chloramphenicol acetyltransferase (CAT) gene were constructed and transfected into C2C12 skeletal myocytes, primary cultured cardiac muscle cells, and C3H10T1/2 fibroblasts. The expression of chimeric reporter genes was restricted in skeletal and cardiac muscle cells. In C2C12 myotubes and primary cultured cardiac muscle cells, the segment between nucleotides -165 and +41 relative to the transcription initiation site was sufficient to confer maximal CAT activity. This region contains two E boxes and one MEF-2 motif. Deletion and substitution mutation analysis showed that a single MEF-2 motif but not the E boxes had a substantial effect on skeletal and cardiac muscle-specific enhancer activity and that the cardiac muscle-specific negative regulatory region was located between nucleotides -505 and -165. When the PGAM-M gene constructs were cotransfected with MyoD into C3H10T1/2, the profile of CAT activity was similar to that observed in C2C12 myotubes. Gel mobility shift analysis revealed that when the nuclear extracts from skeletal and cardiac muscle cells were used, the PGAM-M MEF-2 site generated the specific band that was inhibited by unlabeled PGAM-M MEF-2 and muscle creatine kinase MEF-2 oligomers but not by a mutant PGAM-M MEF-2 oligomer. These observations define the PGAM-M enhancer as the only cardiac- and skeletal-muscle-specific enhancer characterized thus far that is mainly activated through MEF-2.

Animals↗

PubMed1992

Bunazosin enhances receptor-mediated endocytosis of low-density lipoproteins.

The effects of bunazosin, an alpha 1-adrenergic receptor antagonist, on low-density lipoprotein (LDL) receptor activity have been studied in cultured cells. Human skin fibroblasts, swine aortic smooth muscle cells and a human hepatoma cell line (Hep G2) were used for this study. Bunazosinm, at a concentration of 5 x 10(-5) to 10(-4) M, increased 125I-LDL uptake with all of the cell lines and 125I-LDL degradation with human skin fibroblasts and swine aortic smooth muscle cells. However, in human skin fibroblasts pretreated with lipoprotein deficient serum and Hep G2 cells, the degradation of 125I-LDL was decreased by bunazosin. These results suggest that bunazosin increases LDL receptor activity.

Adrenergic alpha-Antagonists↗

PubMed1992

[Intra-arterial chemotherapy with granulocyte colony-stimulating factor for breast cancer before surgical treatment].

Intra-arterial chemotherapy (IAC) for far advanced breast cancer is now performed as a routine adjuvant chemotherapy before surgical treatment. However, the following problems remain unsolved; (1) serious adverse reactions such as myelosuppression, (2) unsuccessful insertion of catheter into the internal thoracic artery, and (3) long waiting-period from IAC to surgical treatment. The present studies were conducted to evaluate the utility of a one-route IAC, in which the subclavian artery alone is used, and the efficacy of granulocyte colony-stimulating factor (G-CSF). There was no significant difference in the antitumor effect between the patients with two-route IAC, in which both internal thoracic artery and subclavian artery are used, and the patients with one-route IAC. Administration of G-CSF in combination with IAC reduced both the frequency and the severity of IAC-induced side effects. G-CSF administration during IAC was more effective than after IAC. G-CSF prevented IAC-induced myelo-suppression and/or accelerated recovery from this complication and thus reduced significantly the waiting-period before surgical treatment.

Breast Neoplasms↗

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

[Identification of two different genetic mutation associated with silent phenotypes for human serum cholinesterase in Japanese].

Two different gene mutations associated with the silent phenotype for human serum cholinesterase were demonstrated. DNA from five individuals with silent gene phenotype of three unrelated Japanese families was amplified by the polymerase chain reaction (PCR) and analyzed by direct sequencing. The first instance demonstrated a G----C transversion at codon 365 from GGA (Gly) to CGA (Arg), which was seen in three individuals of the two families. This mutation was resulted to create a new Taq 1 restriction site (TCGA). The second mutation was shown by a double heterozygous condition with two different silent gene mutations in two members of remaining one family. These mutations were as follows: 1) one type was a frameshift mutation, in which an extra A was inserted in codon 315 (ACC----AACC) to create a new stop codon at position 322 and 2) the other was the same point mutation at codon 365 as seen in the first instance. These results indicated that many silent variants can be distinguished by direct sequence analyses of genomic DNA.

Asian People↗

PubMed1992

Effects of probucol on low-density lipoprotein catabolism in guinea pigs.

We studied the effects of administering probucol on the catabolism of low density lipoprotein (LDL) in guinea pigs. Probucol administration significantly lowered the levels of total and LDL-cholesterol in animals given either normal chow or the high cholesterol (1% W/W) diet. High-density lipoprotein cholesterol was decreased significantly in the animals fed cholesterol, but not normal chow diet. Triglyceride levels were unaffected in both groups. No significant changes were observed in the LDL receptor-dependent and LDL receptor-independent catabolism of native LDL and LDL obtained from a probucol-treated patient. However, when the LDL isolated from a probucol-treated patient was injected, the fractional catabolic rate was significantly lower than that of injected native LDL. This study indicates that probucol lowered the plasma LDL cholesterol level neither by an increased catabolism of LDL via an LDL receptor nor an LDL receptor-independent pathway.

Animals↗