Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 613 records · Page 34Linked to original sources

PubMed1994

Enhancement of tumor proliferation by cyclosporine A in early phase of experimental hepatic metastasis.

The effect of cyclosporine A (CsA) on in vivo growth of hepatic metastasis was studied. Murine colon 38 tumor cells (1 x 10(5) were inoculated via the superior mesenteric vein. Mice were grouped depending on CsA dosage and time schedules: Group A: CsA 30 mg/kg body weight on the 7, 8 and 9th post tumor inoculation days by gavage; Group B: CsA 15 mg/kg body weight 30 min before tumor inoculation and 2 times more at 24 h intervals; Group C: CsA 30 mg/kg body weight at the same dose timing as Group B. Measurement of the diameter of the largest tumor serially by weekly laparotomy up to 4 weeks revealed that the tumor growth rates were significantly greater in Groups B and C than those in Group A or the control (without CsA). The mean tumor doubling times in the control, and Groups A, B and C were 2.2 +/- 1.3, 2.0 +/- 0.5, 1.5 +/- 0.4 and 1.3 +/- 0.8 days, respectively. The mean tumor numbers of hepatic metastasis were 13.2 +/- 8.3, 11.3 +/- 7.3, 19.4 +/- 8.7 and 19.6 +/- 6.8, respectively. Values of tumor proliferation index obtained by bromodeoxyuridine immunohistochemistry were 10.0 +/- 6.1%, 14.9 +/- 8.0%, 28.6 +/- 8.2% and 30.1 +/- 12.4%, respectively, with significant differences (Groups B and C vs. A or control, P < 0.05). In vitro MTT assay showed that cell viability rates were greater than 100% in the medium containing CsA concentrations of less than 10(-7) mol/liter. However, a cytostatic effect of CsA was apparent at higher concentrations. In contrast to the previous in vivo finding of a cytostatic effect of CsA on tumor cells, we found a cytoproliferative action when CsA was administered early in the course of metastatic tumor implantation in the liver. The mechanism of cytoproliferative effect of CsA is unknown but may involve multiple factors.

Animals↗

PubMed1994

Effect of topical administration of L-arginine on formalin-induced nociception in the mouse: a dual role of peripherally formed NO in pain modulation.

1. We investigated the effects of intraplantar (i.pl.) administration of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on formalin-induced behavioural nociception in the mouse. 2. L- but not D-arginine, at 0.1-1 microgram per paw, coadministered with i.pl. formalin, enhanced the second-but not the first-phase nociceptive responses, whereas it was without significant effects at 3 micrograms per paw, and conversely, produced antinociception at 10 micrograms per paw, resulting in a bell-shaped dose-response curve. 3. L-NAME at 0.1-1 microgram per paw, when administered i.pl., exhibited antinociceptive activity in the second phase in a dose-dependent manner, although its D-enantiomer produced no effect. 4. An antinociceptive dose (1 microgram per paw) of L-NAME (i.pl.) considerably reduced the increase in second-phase nociception elicited by low doses (1 microgram per paw) of i.pl. L-arginine. The second-phase nociception decrease induced by a large dose (10 micrograms per paw) of i.pl. L-arginine was markedly reversed by i.pl. L-NAME at 0.1 micrograms per paw, raising it to a level above that of the control (formalin only). 5. These results suggest that peripheral NO plays a dual role in nociceptive modulation, depending on the tissue level, inducing either nociceptive or antinociceptive responses.

Administration, Topical↗

PubMed1994

Comparison of antinociception induced by supraspinally administered L-arginine and kyotorphin.

1. Intracerebroventricular (i.c.v.) or intracisternal (i.cist.) administration of kyotorphin (KTP), an endogenous Met-enkephalin releaser, at 5 micrograms per mouse, and L-arginine (L-Arg), a possible KTP precursor, at 30 micrograms per mouse, elicited antinociception in mice to a similar extent, as assessed by the tail-flick test. 2. Intracisternal preadministration of anti-KTP serum abolished the effect of i.cist. KTP and i.c.v. or i.cist. L-Arg, but not of i.c.v. KTP. 3. The antinociceptive effects of i.cist. KTP and of i.c.v. or i.cist. L-Arg disappeared in reserpinized mice, whereas the effect of i.c.v. KTP was unaffected by treatment of mice with reserpine. 4. Intrathecal (i.t.) phentolamine markedly reduced the antinociception induced by i.cist. KTP and by i.c.v. or i.cist. L-Arg, but not by i.c.v. KTP. 5. Intrathecal methysergide attenuated the antinociceptive effects of i.cist. KTP, but not of i.c.v. KTP and i.c.v. or i.cist. L-Arg. 6. These results suggest that the antinociception produced by i.cist. KTP, but not by i.c.v. KTP, is mediated by the brainstem-spinal noradrenergic and 5-hydroxytryptaminergic systems, and that L-Arg given i.c.v. or i.cist. increases KTP formation in the lower brain, possibly the brainstem, resulting in antinociception mediated by the descending noradrenergic system. Therefore, the regional distribution of KTP receptors and KTP synthetase in the brain does not appear to be common.

Analgesics↗

PubMed1994

The noradrenaline precursor L-threo-3,4-dihydroxyphenylserine exhibits antinociceptive activity via central alpha-adrenoceptors in the mouse.

1. Systemic (s.c. or p.o.) administration of L-threo-3,4-dihydroxyphenylserine (droxidopa, L-threo-DOPS; L-DOPS), a noradrenaline precursor, at a dose-range of 100-800 mg kg-1, produced naloxone-resistant antinociception in a dose-dependent manner in the mouse, as assessed by the tail flick test, kaolin-induced writhing test and formalin-induced nociception test. 2. Antinociception elicited by L-DOPS (400 mg kg-1, s.c.) was not affected by s.c. injection of benserazide, a peripherally preferential L-aromatic amino acid decarboxylase inhibitor, but was suppressed by its intracerebroventricular (i.c.v.) injection. 3. I.c.v. or intrathecal (i.t.) administration of the non-selective alpha-blocker, phentolamine, significantly reduced L-DOPS-induced antinociception. 4. I.c.v. administration of the alpha 1-blocker, prazosin, but not the alpha 2-blocker, yohimbine, abolished the antinociceptive effects of L-DOPS. In contrast, both blockers, when administered i.t., exhibited significant inhibitory effects. 5. These results suggest that systemic L-DOPS produces opioid-independent antinociception, mediated by supraspinal alpha 1-adrenoceptors and by spinal alpha 1- and alpha 2-adrenoceptors and may predict additional therapeutic applications of L-DOPS as an analgesic.

Administration, Oral↗

PubMed1994

Portal venous invasion by pancreatobiliary carcinoma: diagnosis with intraportal endovascular US.

PURPOSE: To evaluate use of intraportal endovascular ultrasonography (IPEUS) in diagnosing portal venous invasion by pancreatobiliary carcinoma. MATERIALS AND METHODS: IPEUS was performed in 26 consecutive patients with pancreatobiliary carcinoma. All patients underwent surgery. IPEUS was performed intraoperatively in 20 cases and preoperatively in six. The sonographic criterion for detection of portal venous invasion was obliteration of the echogenic band of the portal vein. The IPEUS results were compared with those of computed tomography (CT) and arterial portography. RESULTS: Vascular invasion was confirmed with use of resected specimens in seven patients and operative findings in five patients. For diagnosis of portal venous invasion, the sensitivity, specificity, and overall accuracy of IPEUS were all 100%; respective values were 92%, 64%, and 77% for angiography and 50%, 79%, and 65% for CT. CONCLUSION: IPEUS allows detection or exclusion of early invasion of the portal venous wall by pancreatobiliary carcinoma.

Aged↗

PubMed1994

Potentiated 1,25(OH)2D3-induced 24-hydroxylase gene expression in uremic rat intestine.

24-Hydroxylase has been considered a major enzyme regulating metabolism of circulating 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]. To understand the metabolism of 1,25(OH)2D3 in chronic renal failure, we examined 1,25(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) gene expression in the intestine of uremic rats. Northern blot and dot blot analyses showed that the induction of duodenal 24-hydroxylase gene expression was 2.0- to 3.8-fold greater in uremic rats than in sham-operated rats (P < 0.05, Student's t-test) at 6 h after 1,25(OH)2D3 administration. Gene induction of calbindin D9k by 1,25(OH)2D3 was not augmented in uremic group. In situ hybridization analysis revealed that the induction of 24-hydroxylase mRNA by 1,25(OH)2D3 was observed exclusively in the columnar epithelium of the crypt and the lower part of the villi, suggesting that the stage of epithelial cell differentiation is a major determinant of 1,25(OH)2D3-induced 24-hydroxylase gene expression. In uremia, 1,25(OH)2D3-induced 24-hydroxylase gene expression was accelerated selectively, possibly because of poorly differentiated epithelial cells.

Animals↗

PubMed1994

Hepatic hemodynamics and oxygen metabolism during hepatic artery occlusion and reperfusion: effects of dobutamine and inhalation of 100% oxygen.

Hepatic hemodynamics, oxygen metabolism, and lactate metabolism during hepatic artery occlusion and reperfusion with and without supplemental oxygen and dobutamine (DOB) were studied in dogs. After a 60-min occlusion, hepatic arterial blood flow recovered about 80% of the preocclusion values after 10 min of reperfusion. However, portal vein blood flow gradually decreased during both occlusion and reperfusion. The partial pressure of oxygen in the portal vein blood (PPVO2) did not change significantly during the experiment. Accordingly, hepatic oxygen (HO2) delivery and consumption (HVO2) decreased markedly during occlusion and did not recover completely after 60 min of reperfusion. Although inhalation of 100% oxygen did not affect hepatic hemodynamics, it markedly increased PPVO2. DOB did not effectively increase PPVO2 though it increased portal vein flow (PVF). Both inhalation of 100% oxygen and DOB infusion enhanced HO2 delivery and HVO2 during hepatic artery occlusion and reperfusion. The hepatic lactate uptake was limited in the control group, however, it was improved by 100% oxygen and, especially, DOB both during occlusion and reperfusion. These data support the conclusion that inhalation of 100% oxygen and DOB administration effectively support hepatic function during hepatic artery occlusion.

Animals↗

PubMed1994

Quantitative assay of (1-3)-beta-D-glucan in culture media of Candida albicans using the G-test.

The diagnosis of invasive candidiasis is often difficult. The limulus test, which has been used for the assay of endotoxin in blood, was also found to react with (1-3)-beta-D-glucan, a component of the fungal cell wall. The factor in the limulus test that is activated by glucan, but not by endotoxin, is called factor G. The G-test utilizes the activation pathway starting with factor G, and sensitivity reacts with trace amounts of glucan. In this study, we investigated in vitro proliferation of Candida albicans and changes in the glucan concentration of RPMI-1640 media in the presence and absence of neutrophils and antifungal agents, as a pilot evaluation to possible clinical applications of the G-test. The proliferation of C. albicans and the glucan level measured in the culture media showed parallel changes. The glucan level in the culture media also increased when C. albicans was phagocytosed and digested by neutrophils, but not with administration of amphotericin B. The G-test closely reflected quantitative changes of C. albicans in vitro, and should be considered for future clinical studies in the diagnosis and evaluation of therapeutics in invasive candidiasis.

Amphotericin B↗

PubMed1994

Expression of neural cell adhesion molecule in normal gastric mucosa and in gastric carcinoid tumors.

Expression of neural cell adhesion molecule (NCAM) in the digestive system was studied with NE-150 monoclonal antibody, together with those against Lewis blood group antigens. NE-150 did not react with any of 32 cell lines tested derived from digestive tract cancers. In gastric adenocarcinomas NCAM was not expressed regardless of its differentiation status, while in gastric carcinoids and in other carcinoid tumors of different organs, it was present in all the specimens tested. Among normal tissues, it reacted with the deep gastric gland and the islets of Langerhans. These results suggest that NCAM is one of the most specific markers for gastric carcinoid tumors. It was also suggested that the gastric carcinoid tumor might be derived from NCAM-positive cells in the deep gastric gland. These findings should be exploitable in subgrouping gastric tumors in terms of antigen expression.

Adenocarcinoma↗

PubMed1994

Selective inhibition of a step of myotube formation with wheat germ agglutinin in a murine myoblast cell line, C2C12.

Myoblast cells, C2C12, which is an established cell line from satellite cells of skeletal muscle of C3H mouse, start to fuse and form multinucleated cells (myotubes) and begin to express creatine phosphokinase and myosin, when culture medium is changed from the growth medium to the differentiation medium. Among the 12 lectins that we tested, wheat germ agglutinin apparently suppressed the myotube development judged by phase-contrast microscopy, but did not affect the induction of creatine phosphokinase activity. The addition of N-acetylglucosamine or N,N',N"-triacetylchitotriose, which is a specific ligand for wheat germ agglutinin, to the differentiation medium, recovered this apparently suppressive effect of wheat germ agglutinin on the myotube development. Tachypleus tridentatus (Japanese horseshoe crab) lectin that specifically recognizes N-acetylneuraminic acid, one of the sialic acids, showed no effect on the myotube development. It was suggested that wheat germ agglutinin suppressed the process through recognizing N-acetylglucosamine containing sugar. Surprisingly, even in the presence of wheat germ agglutinin, the ratio of mononucleated cell numbers to the genomic DNA content, which represents the fusion level, decreased after incubation in the differentiation medium, indicating that even when wheat germ agglutinin was present in the medium, cell fusion, which is the initial step of the myotube formation, occurred. Immunostaining with anti-skeletal muscle myosin antiserum confirmed that the myosin expressing cells actually fused and formed multinucleated cells. Their shape, however, was thin compared to that in the absence of wheat germ agglutinin. We propose that the membrane fusion step to form myotubes is composed of two distinct steps in C2C12; one fusion step is to form long and thin myotubes from mononucleated cells and the other one is to develop fat myotubes. Wheat germ agglutinin specifically inhibits the latter fusion step.

Agglutinins↗

PubMed1994

Characterization of an acidic polysaccharide with immunological activities from the tuber of Pinellia ternata.

An acidic polysaccharide, called pinellian PA, was isolated from the tuber of Pinellia ternata Breit. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was estimated to be 11.8 x 10(4). Pinellian PA is composed of L-arabinose: D-galactose: L-rhamnose: D-galacturonic acid: D-glucuronic acid in the molar ratio of 5:15:1:3:3, in addition to small amounts of O-acetyl groups and peptide moieties. Reduction of carboxyl groups, methylation analysis and nuclear magnetic resonance studies show that the core structural features include a backbone chain composed of beta-1,3-linked D-galactose units. Some of the galactose units in the backbone carry beta-1,6-linked D-galactosyl side-chains at position 6. Pinellian PA produces significant potentiation of the reticuloendothelial system, as shown by a carbon clearance test, and also exhibits potent anti-complementary activity.

Animals↗

PubMed1994

Pyridonecarboxylic acids as antibacterial agents. VI. Synthesis and structure-activity relationship of 7-(alkyl, cycloalkyl, and vinyl)-1-cyclopropyl-6-fluoro-4-quinolone-3-carboxylic acids.

The title compounds (1a-i) have been synthesized starting with ethyl 1-cyclopropyl-6,7-difluoro-4-quinolone-3-carboxylate (2). The 7-cyclopropyl and 7-vinyl derivative (1e and 1i) exhibited potent in vitro antibacterial activities against both gram-positive and gram-negative bacteria, being equipotent with ciprofloxacin (CPFX) except for the activity against Pseudomonas aeruginosa. The two compounds were significantly less toxic than CPFX in terms of convulsion-induction as determined by intracerebral administration to mice, but showed lower urinary recoveries on intravenous administration.

4-Quinolones↗

PubMed1994

Pyridonecarboxylic acids as antibacterial agents. IX. Synthesis and structure-activity relationship of 3-substituted 10-(1-aminocyclopropyl)-9-fluoro-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]- 1,4-benzoxazine-6-carboxylic acids and their 1-thio and 1-aza analogues.

A series of the title compounds listed in Chart 1 have been synthesized to study the effects of 3-alkyl substituents on the antibacterial potency and in vivo efficacy of 10-(1-aminocyclopropyl)-9-fluoro-7-oxo-2,3-dihydro-7H-pyrido[1,2,3 -de]-1,4-benzoxazine-6-carboxylic acid and its 1-thio and 1-aza variants. Compound (S)-1, which proved most active in vitro against five representative gram-positive and gram-negative organisms, was assayed in vivo using Staphylococcus aureus and Pseudomonas aeruginosa mouse infection models. It exhibited an excellent in vivo efficacy, being superior to ofloxacin and ciprofloxacin, and was then assayed for convulsion-inducing activity, mammalian cell cytotoxicity, and topoisomerase II inhibition. The biological results showed that (S)-1 displayed antibacterial and toxicological advantages over ofloxacin and ciprofloxacin. Compound (S)-1 and its methanesulfonate showed high serum concentrations after oral and intravenous administrations to mice.

Animals↗

PubMed1994

Molecular cloning of the gene for microbial transglutaminase from Streptoverticillium and its expression in Streptomyces lividans.

The microbial transglutaminase (TGase)-producing strains S-8112 [Agric. Biol. Chem., 53, 2613-2617 (1989)] was identified as a variant of Streptoverticillium mobaraense. We amplified a partial gene fragment by polymerase chain reaction (PCR) using oligonucleotides synthesized from the amino acid sequence of TGase, and cloned the gene for TGase using the PCR amplified fragment as a probe. The gene encoded a precursor of TGase consisting of 406 amino acid residues, which comprised the prepro region of 75 amino acid residues and the mature region of 331 amino acid residues. We expressed the TGase gene in Streptomyces lividans under a tyrosinase promoter, and found an active and mature recombinant enzyme, indicating the processing of the gene product.

Amino Acid Sequence↗

PubMed1994

Chemical synthesis of the gene for microbial transglutaminase from Streptoverticillium and its expression in Escherichia coli.

The gene coding for microbial transglutaminase (TGase) from Streptoverticillium, which consists of 331 amino acids, was chemically synthesized. The codons have been substituted for those mainly favored in yeast. Our strategy involved the construction of the TGase gene in five sections (54 oligomers) that contained unique restriction enzyme sites at both ends, which could readily be ligated to form the full-length product. The chemically synthesized gene was inserted downstream from the ompA signal peptide of the E. coli expression vector, pIN-III-ompA, which carries lpp and lac promotors. The resultant plasmid directed the expression of TGase, with the activity being secreted mainly into the periplasmic space of E. coli. The induced gene product was identical with native TGase in size and in immunological properties, though the enzyme activity was low.

Amino Acid Sequence↗

PubMed1994

Effect of maternal paraquat administration on the fetal ductus arteriosus in the rat.

The ductus arteriosus (DA) in the fetal rat was calibrated using a whole-body freezing method, 3 hr after maternal treatment with paraquat at a dose of 25 mg/kg of body weight on days 19-21 of gestation. On days 20 and 21, the DA was significantly constricted. The DA was also significantly constricted on day 19 2/3 but not on day 19 1/2. It is concluded that paraquat has a constrictive effect on the DA and that the onset of this effect occurs in the first half of day 19 of gestation.

Animals↗

PubMed1994

Constrictive effects of paraquat on the ductus arteriosus in fetal rats.

Rats on day 21 of pregnancy received a subcutaneous injection of paraquat (2, 7 or 25 mg/kg). The inner diameter of the ductus arteriosus (DA) of their fetuses was measured using the whole-body freezing method 1, 3, 6 and 24 hours after injection. The 7 mg/kg dose group showed a significant constriction of the DA 3 hours after paraquat treatment. The 25 mg/kg dose group showed a significant constriction 3 and 6 hours after treatment. The constrictive effect was dose-dependent, that is, the magnitude of constriction observed 3 hours after paraquat injection was greater in the 25 mg/kg dose group than in the 7 mg/kg dose group. The 2 mg/kg dose group showed no significant change in the inner diameter of the DA at any point of measurement (1, 3, 6 and 24 hours after injection), compared to the saline treated controls. These results indicate that paraquat induces constriction of the fetal rat DA in a dose-dependent manner when administered in late stages of gestation, and that this effect of paraquat is not seen at a dose level of 2 mg/kg.

Animals↗

PubMed1994

Cerebral bacterial aneurysm and indications for cerebral angiography in infective endocarditis.

Six infective endocarditis patients who developed cerebral bacterial aneurysm were reviewed to clarify the indications and timing for cerebral angiography to achieve early detection of unruptured aneurysms. All cerebral bacterial aneurysms were confirmed either angiographically or at autopsy. All patients were treated conservatively. Four patients died due to ruptured aneurysm. Four of the six patients showed the signs and symptoms of cerebral and/or systemic embolism, followed by rupture or detection of cerebral bacterial aneurysm. Prodromal signs and symptoms of embolism in patients with infective endocarditis should be considered as indicators for cerebral angiography to detect cerebral bacterial aneurysms before rupture.

Adolescent↗