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Biomedical subjects

T Koide

Publications and source records attributed to T Koide.

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

[Clinical phase III study of cimetropium bromide (DA3177) on the pain with upper urinary calculus: a double-blind study in comparison with scopolamine butylbromide. DA3177 Study Group].

A double-blind study was conducted to evaluate the efficacy, safety and usefulness of cimetropium bromide (DA3177) in the patients with pain caused by upper urinary calculus at a daily dose of 75 mg t.i.d. (Group D, 97 patients) in comparison with scopolamine butylbromide at a daily dose of 60 mg t.i.d. (Group B, 101 patients). According to patient's impression, the rate of "moderately improved" or better was significantly higher in Group D (68.7%) than in Group B (53.5%; Wilcoxon 2 sample test: p = 0.0044). For pain, the rate of "moderately improved" or better was 69.1% in Group D and 60.4% in Group B. In global improvement, the rate of "moderately improved" or better was significantly higher in Group D (70.1%) than in Group B (61.4%; Wilcoxon 2 sample test: p = 0.0469). The rate of "no problem in safety" showed no significant difference between Group D (91.5%) and Group B (93.3%). Adverse reactions occurred in 8.5% in Group D and 6.7% in Group B. The major adverse reactions were "dry mouth", "abdominal distension", "constipation" and "nausea". The rate of "useful" or better was 68.7% in Group D, and 60.4% in Group B. In conclusion, DA3177 was confirmed to be a useful drug for patient with pain caused by upper urinary calculus.

Adult↗
PubMed1997

[A randomized study on intravesical pirarubicin (THP) chemoprophylaxis of recurrence after transurethral resection of superficial bladder cancer].

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of tetrahydropyranyladriamycin (THP) following complete transurethral resection (TUR) of superficial bladder cancer. A total of 80 patients were randomized into "THP" or "control" group. In the THP group, 20 mg of THP dissolved in 40 ml saline (or 5% dextrose) was administered intravesically once a week for 10 weeks, starting from about 7 days after TUR. In the control group, 40 ml saline was given with the same schedule. The patients were followed up by cystoscopy and urinary cytology every 3 months. The number of evaluable patients was 36 for the THP group and 37 for the control group. The non-recurrence rates in the THP group and control group were 79.4% versus 63.2% at 1 year and 69.8% versus 47.4% at 3 to 5 years, respectively. These figures were not statistically significant. However, THP instillation significantly reduced tumor recurrence rates for multiple tumors, and also tended to decrease recurrence rates for primary and pT1 tumors. Adverse effects were observed in 53.6% of the patients in the THP group, but they were tolerable. Our results suggest that intravesical THP instillation would not be effective for all patients with superficial bladder cancer. Further study is warranted in a selected group of patients.

Administration, Intravesical↗
PubMed1996

Structural organization and tissue-specific expression of the gene encoding rat cysteine dioxygenase.

Cysteine dioxygenase (CDO) is a key enzyme involved in the metabolism of L-cysteine. Genomic clones containing the 5'-flanking sequence of the rat CDO gene were isolated and characterized. The CDO gene spanned about 15 kb, and comprised 5 exons. All boundaries between the exons and introns matched the GT/AG rule. The major transcription start point (tsp) was A at 213 bp upstream from the ATG codon. The 5'-flanking region contained a TATA-box-like sequence and putative cis-acting regulatory elements. The 3' end of CDO was polyadenylated at several sites. Northern blots of RNA from rat tissues revealed the highest CDO mRNA level in the liver. Significant levels were observed in the kidney, lung and brain, implying tissue-specific differences in CDO promoter function.

Animals↗
PubMed1996

Molecular and cellular basis for type I heparin cofactor II deficiency (heparin cofactor II Awaji).

Heparin cofactor II (HCII) is a serine proteinase inhibitor in human plasma that rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. To understand the molecular mechanism for HCII deficiency in a patient with reduced circulating HCII antigen, we studied a Japanese patient with type I HCII deficiency who suffered from angina pectoris and coronary artery disease. Polymerase chain reaction (PCR)-based sequence analysis showed that the propositus' gene for HCII (HCII Awaji gene) had a thymine insertion after codon (GAT) for Asp88 in exon II, resulting in a frameshift mutation. Consequently, the abnormal HCII Awaji protein was suggested to have an altered amino acid sequence from position 89 and terminate at 107, thus being composed of the NH2-terminal one fifth of normal HCII and dysfunctional for thrombin inhibition. The molecular weight and pI value of HCII Awaji were calculated to be 12,040 and 3.6, respectively, without posttranslational modification. Mutagenic PCR followed by the Tsp509I digestion showed that a half of the PCR products derived from the propositus and his sister was cleaved, suggesting that his sister also has the same mutant allele. Crossed-immunoelectrophoresis and Western blot analyses of plasma and urine from the the propositus and of plasma from his sister did not provide evidence for the existence of the abnormal HCII, suggesting that little truncated HCII was circulating in the patient's blood. However, stable expression assay using human kidney 293 cells transfected with the expression vector containing cDNA encoding wild-type or Awaji-type HCII showed that mutant as well as wild-type HCII was secreted into culture medium normally. These results suggest that the abnormal HCII Awaji protein is secreted normally, but rapidly degraded in the circulating blood.

Amino Acid Sequence↗
PubMed1996

Enzymatic characterization of purified NS3 serine proteinase of hepatitis C virus expressed in Escherichia coli.

Non-structural protein 3 (NS3) of the hepatitis C virus (HCV) has been shown to be a serine proteinase which cleaves the HCV polyprotein thus activating its replicative machinery. To characterize enzymatic activities of NS3 serine proteinase, the proteinase region was expressed in Escherichia coli and purified. The purified proteinase specifically cleaved a purified fusion protein sandwiching the NS5A/5B cleavage sequence. In addition to serine proteinase inhibitors, some chelators also inhibited the cleavage activity. Metal ions were not required for its activity, suggesting that the proteinase may be a novel serine proteinase having a unique binding site for chelators.

ATP-Binding Cassette Transporters↗
PubMed1996

Usefulness and limitation of phylogenetic analysis for hepatitis C virus core region: application to isolates from Egyptian and Yemeni patients.

We report here the nucleotide sequences of the core region of HCV isolates from Egyptian and Yemeni patients and the method for classifying these HCV isolates by phylogenetic analysis. Sequence comparison suggested that the genotypes of these isolates were the same. Preliminary phylogenetic analysis of the HCV core region indicated that the genotypes of both isolates were 1c. However, an additional phylogenetic tree of the HCV core region constructed using a greater number of HCV isolates than that used in the preliminary analysis and on the basis of alignment of nucleotide sequences in an appropriate length indicated that the genotypes of these isolates were 4 and not 1c. For a more detailed analysis, the nucleotide sequences of the HCV E1 region as well as the core region for the same Yemeni patient were determined. A phylogenetic tree of the E1 region confirmed that the genotype of the HCV isolate from the Yemeni patient was 4. These data indicate that even when classifying HCV isolates using phylogenetic analysis, the misclassification would occur if care is not taken regarding the number and sequence lengths of the isolates included in the analysis.

Base Sequence↗
PubMed1996

Molecular analysis of a recombinational hotspot adjacent to Lmp2 gene in the mouse MHC: fine location and chromatin structure.

Meiotic recombinations in the proximal region of the mouse major histocompatibility complex (MHC) are clustered within certain segments of chromosome, known as hotspots. In this study, we found that one of such hotspots, previously mapped between the Pb and Ob genes, is located very close to the 3' end of the Lmp2 gene, which encodes a subunit of a proteolytic proteasome. To analyze the molecular basis of the site specificity of hotspots, we examined the structure of the chromatin around this Lmp2 hotspot and another one located in the MHC class II Eb gene, by monitoring DNase I-hypersensitive sites (DHSSs) of the chromatin. DHSSs were detected at the both hotspots in the somatic cells. In the meiotic cells, DHSS was detected within the Eb hotspot, as previously reported, but not in the Lmp2 hotspot. Thus, open structure of chromatin during meiosis, as monitored by hypersensitivity to DNase I, is not a general feature of mouse recombinational hotspots, contrasting the case of the lower eukaryote, S. cerevisiae, in which hotspots are always associated with DHSSs.

Animals↗
PubMed1996

The effects of 18 alpha,beta-glycyrrhetinic acid on the hormonal induction of tyrosine aminotransferase in rat primary cultured hepatocytes.

The effects of 18 alpha,beta-glycyrrhetinic acid (18 alpha,beta-GA) on the hormonal induction of tyrosine aminotransferase (TAT) in rat primary cultured hepatocytes were investigated. Dexamethassone or glucagon used alone caused an increase in enzyme activity, and in combination their effects were additive. In the 18 beta-GA hepatocytes pretreated for 6 h, the dexamethasone-induced increase in the enzyme activity was slightly reduced in a dose-independent manner, and the glucagon-induced increase and the combined effects of these two inducers were significantly reduced in a dose-dependent manner. On the other hand, 18 alpha-GA, which was the isomer of 18 beta-GA, exerted no influence on the hormonally mediated increase in enzyme activity. Moreover, 18 beta-GA reduced the glucose release induced by glucagon in a dose-dependent manner and 18 alpha-GA did not. These results suggested that 18 beta-GA reduced the glucagon-mediated cell response in rat hepatocytes.

Animals↗
PubMed1996

Flavonoid-mediated tumor growth suppression demonstrated by in vivo study.

Many of flavonoids as well as bioflavonoids extracted from higher plants, which were earlier revealed to have tumor cell growth suppression activity in vitro, were examined for their effect on tumors in vivo. Balb/c mice were inoculated i.p. with syngeneic tumor cells, meth/a, and then provided with flavonoids dissolved in their drinking water during the course of their survival time. Many flavonoids were effective in prolonging the survival period. Furthermore, flavonoids that did not show suppressive activities in the in vitro experiments were effective in the in vivo assay. The data suggested that sugar bonded to the A ring, which suppresses tumor growth inhibition in vitro, plays an important role. Many aglycones that were effective in the in vitro assay on the tumor growth suppression were not effective in the in vivo assay. The reason for this seems to be that most aglycones are unstable and thus break down in vivo. No acute nor chronic toxicity of flavonoids was observed in the mice.

Animals↗
PubMed1996

Influence of OH group and sugar bonded to flavonoids on flavonoid-mediated suppression of tumor growth in vitro.

Many flavonoids extracted from higher plants, synthesized or purified flavonoids, and their aglycones showed anti-tumor activity. Using purified or synthesized flavonoids, we studied the effect of the chemical structure of 2-benzoic flavone on the growth of human tumor cells (HCT-15 in vitro. The type of sugar combined with the A phenol of flavonoids played an important role in the tumor suppression; i.e., glucose attachment at the A phenol caused suppression of tumor cell growth, but other sugars such as rhamnose and lutinoside at that position did not suppress the growth of the cells. OH groups bonded to the B phenol also had a great effect on the growth. Flavonoids with OH groups conjugated to the 3', 4', and 5' of B phenol were stronger in anti-tumor effect than those with the OH groups attached at the 3' and 4' or 4' only, although anthocyanins were generally more effective than the other flavonoids.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Antitumor effect of hydrolyzed anthocyanin from grape rinds and red rice.

When Balb/C mice that were fed with red glutinous rice, white ordinary rice, or commercially available standard food were inoculated with syngeneic Meth/A lymphoma cells i.p., the group fed the red rice survived longer than the other two groups. In order to determine if the anthocyanins contained in red-coloured seeds and fruit rinds were responsible for the tumor suppressive effect, we added anthocyanins extracted from grape rinds and glutinous red rice to petri dishes that had been seeded with HCT-15 cells. After 4 days of culture, cell counts were made. These anthocyanins were not effective in suppressing the tumor growth. However, anthocyanidins, which were generated by keeping anthocyanins in 5 to 6% HC1 methanol for 5 to 6 hours, were effective in the suppression of tumor growth. Flowcytometric histograms were made after 2 days of culture with these bioflavonoids. The histogram of cells treated with crude anthocyanin was similar to that of the control. Hydrolyzed anthocyanidins gave the elevation of S phase, suggesting a block in the step from S-phase to G2-phase. It seemed that the anthocyanidins contained in the grape rinds and red rice were effective on the suppression of cell growth as observed previously for anthocyanins extracted from the petals of higher plants.

Animals↗
PubMed1996

Cellular basis for protein C deficiency caused by a single amino acid substitution at Arg15 in the gamma-carboxyglutamic acid domain.

Protein C is a zymogen of an anticoagulant vitamin K-dependent serine protease. Inherited protein C deficiency is often associated with a high risk for venous thromboembolism. It is characteristic of protein C deficiency that most single amino acid replacements result in type I (secretion defect) deficiency. To determine the molecular and cellular bases of protein C deficiency, we expressed recombinant human protein C mutants in which Arg15 was mutated to either Gly, Trp, Gln, Leu, or Pro by a single base exchange. Arg15 is one of the conservative residues in the gamma-carboxyglutamic acid (Gla) domains of the vitamin K-dependent coagulation factors, and is also one of the high frequency multiple mutation sites in protein C deficiency. In transient expression studies using human kidney 293 cells, the relative amounts of Arg15 mutants secreted into the medium and determined by enzyme-linked immunosorbent assay (ELISA) were as follows: Gly, 42%; Trp, 14%; Gln, 54%; Leu, 22%; and Pro, 13%, the amount of wild-type (Wt) protein C being taken as 100%. Thus, the order of the secreted amounts of the recombinant mutants was determined to be Wt > Gln > Gly > Leu > Trp, Pro. Pulse-chase experiments using both transiently-transfected and a pool of stably-transfected 293 cells, and stably-transfected BHK cells showed the same order of secretion efficiency. Since this order correlated well with that of the hydrophobicity scale of amino acid side chains, a conformational alteration of the Gla domain resulting in impaired secretion may be dependent on the hydrophobicity of the replaced amino acid. In transient cells, the relative radioactivities of pulse-labeled bands of all recombinant protein C were almost equal, suggesting that the same translational efficiency for Wt and all Arg15 mutants. All of the Arg15-mutated protein C precursors were shown to be located in the same organelle as protein disulfide isomerase (PDI), an endoplasmic reticulum-resident protein, and were sensitive to endoglycosidase H digestion. These results suggest that mutations of the highly conserved Arg15 in the Gla domain of protein C caused a secretion defect to variable degrees depending on replaced amino acid residue.

Amino Acid Sequence↗
PubMed1996

Serum prostate-specific antigen values for the prediction of clinical stage and prognosis in patients with prostate cancer: an analysis of 749 cases.

BACKGROUND: The clinical significance of pretreatment serum prostate-specific antigen (PSA) values was studied to determine the ability to predict clinical stage and prognosis using a relatively large number of patients with prostate cancer. METHODS: Serum PSA values at diagnosis were analyzed from 749 patients with newly-diagnosed prostate cancer and registered in the Tokai Urological Cancer Registry. Correlations between the PSA value, the clinical stage and prognosis of the patients were evaluated. RESULTS: Serum PSA values at each stage of diagnosis showed positivity (> or = 3.6 ng/mL) in 23% (stage A1) to 91.2% (stage D2) of patients, and it was possible to obtain statistical differences between the stages, even between A1 and A2. Based on a cumulative study of PSA distribution, stages greater than A2 could be diagnosed using a cut-off of 7.2 ng/mL, with a 99.2% positive predictive value (PPV), and a 16.2% negative predictive value (NPV). At a PSA level of 10.8 ng/mL, stages greater than B2 could be predicted with a PPV of 95.3% but an NPV of 40.3%. Pretreatment PSA values were a significant prognostic indicator in stage D2 patients using 100 to 150 ng/mL as the cut-off values. These differences were primarily found in the poorly differentiated group, which showed a statistical difference using cut-off PSA values from 75 to 150 ng/mL. CONCLUSIONS: Serum PSA levels from a large number of patients can be used to predict the stage and prognosis of prostate cancer patients.

Aged↗
PubMed1996

Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. II. Synthesis and structure-activity relationships of 4,5,6,7-tetrahydro-1H-benzimidazole derivatives.

A novel series of 4,5,6,7-tetrahydro-1H-benzimidazole derivatives 4,5,6 and 7 was prepared and evaluated for activities as 5-hydroxytryptamine (5-HT3) receptor antagonists which may be useful for the treatment of irritable bowel syndrome (IBS) as well as nausea and vomiting associated with cancer chemotherapy. These compounds were designed by modifying the aromatic-carbonyl part of N-(2-methoxyphenyl)-4,5,6,7-tetrahydro-1H-5-benzimidazolylcarboxamide 3, leaving the imidazole moiety unchanged as the amine part. The indole derivatives 7d, g, h and indolizine derivatives 7k, l were found to be highly potent on the von Bezold-Jarisch (B.J.) reflex test with ID50 values of below 0.1 microgram/kg, and the indoline derivative 6c, indole derivatives 7a, d, g, benzofurane derivative 7j and indolizine derivative 7k were observed to be very potent on the colonic contraction with IC50 values of below 0.1 microM. In particular, 7l was the most potent on the B.J. reflex (ID50 = 0.018 microgram/kg), approximately 200 and 50 times more potent than ondansetron 1 and granisetron 2, and 7k was the most potent on the colonic contraction (IC50 = 0.011 microM), approximately 70 and 6 times more potent than 1 and 2, respectively.

Animals↗
PubMed1996

Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. I. Synthesis and structure-activity relationships of conformationally restricted fused imidazole derivatives.

We prepared a novel series of conformationally restricted fused imidazole derivatives 4b, 4c and 4d (possessing 4,5,6,7-tetrahydroimidazo[4,5-c] pyridine and substituted 4,5,6,7-tetrahydro-1H-benzimidazole for 4b, 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine for 4c and 5,6,7,8-tetrahydroimidazo[1,5-a]pyridine for 4d as a basic amine part and (2-methoxyphenyl)aminocarbonyl group as an aromatic-carbonyl part). Their activities were then evaluated as an 5-hydroxytryptamine (5-HT3) receptor antagonist which may be useful for the treatment of irritable bowel syndrome (IBS) as well as for nausea and vomiting associated with cancer chemotherapy. The most potent compound was N-(2-methoxyphenyl)-4,5,6, 7-tetrahydro-1H-benzimidazole-5-carboxamide 14 in this series with an ID50 value of 0.32 microgram/kg on the von Bezold-Jarisch reflex in rats and an IC50 value of 0.43 microM on the isolated colonic contraction in guinea pig, approximately ten and two times more potent than ondansetron 1, respectively. The structure activity relationships (SAR) study suggested that the high potency of 14 may be attributed to the suitable position and direction of the N-C-N centroid in the conformationally restricted imidazole ring against the planar (2-methoxyphenyl)aminocarbonyl part in the binding of 14 to the receptor.

Animals↗
PubMed1996

Evidence for the interaction between (-)-epigallocatechin gallate and human plasma proteins fibronectin, fibrinogen, and histidine-rich glycoprotein.

Human plasma proteins were subjected to affinity chromatography with (-)-epigallocatechin gallate (EGCg)-agarose, and the bound proteins were examined by sodium dodecylsulfate-polyacrylamide gel electrophoresis. A molecular weight evaluation of the protein bands suggested the presence of three proteins, fibronectin, fibrinogen, and a 75-kDa protein. When human serum was used, the 75-kDa protein dominated the bound fraction. The determination of the partial amino acid sequence of a peptide derived by endopeptidase digestion of this fraction suggested the 75-kDa protein to be histidine-rich glycoprotein (HRG). The presence of these proteins in the bound fraction was confirmed by the immunoblotting method. Affinity chromatography of the individual proteins indicated that fibrinogen and HRG had direct affinity for EGCg. Dot binding assays demonstrated the interaction of EGCg with these proteins. The method also showed that only gallate-containing catechins were bound by these proteins. These data suggest that when EGCg is absorbed in the body through the digestive system, it may interact with these proteins in blood plasma.

Antineoplastic Agents↗