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Biomedical subjects

M Takami

Publications and source records attributed to M Takami.

At least 19 recordsLinked to original sources
PubMed2000

A new assay for lipiodol in a tumor using a combination of m-chloroperbenzoic acid-mediated oxidation and the iodo-starch reaction.

Lipiodol, an iodine adduct lipid, has been used as a targeting carrier of anticancer drugs in experimental animals and humans. In most studies, the concentrations of the anticancer drugs in tissues and organs have been monitored, but not of the carrier because a simple method for measuring lipiodol in biological organs did not exist. Here we present an analytical method for the quantitative determination of lipiodol in tissue. This method is based on the measurement of iodine released from lipiodol by an oxidative reaction. The released iodine was measured spectrophotometrically by monitoring the iodo-starch reaction. Using this method, we were able to demonstrate the tumor specificity of lipiodol using rabbits bearing VX2 tumors in the liver. The present method is also expected to be applicable to human cancers, such as hepatic and colon cancer.

Animals↗
PubMed2000

Microwave coagulation therapy for multiple hepatic metastases from colorectal carcinoma.

BACKGROUND: Compared with other treatments, microwave coagulation is a relatively less invasive treatment for various kinds of solid tumors. Although its effectiveness in primary hepatocellular carcinoma has been shown, its effectiveness in the treatment of hepatic metastases from colorectal carcinoma has been unclear. The aim of this study was to evaluate its effectiveness in the treatment of multiple hepatic metastases from colorectal carcinoma by comparing this technique with that of hepatic resection. METHODS: Thirty patients with multiple metastatic colorectal tumors in the liver who were potentially amenable to hepatic resection were randomly assigned to treatment with microwave coagulation (14 patients) or hepatectomy (16 patients). Tumors in the microwave group were coagulated after laparotomy at an output of 60-100 W for 2-20 minutes under the guide of ultrasonography, whereas tumors in the hepatectomy group were treated with lobectomy, segmentectomy, subsegmentectomy, and/or wedge resection. RESULTS: One-, 2-, and 3-year survival rates and mean survival times were 71%, 57%, 14%, and 27 months, respectively, in the microwave group, whereas they were 69%, 56%, 23%, and 25 months, respectively, in the hepatectomy group. The difference between these two groups was statistically not significant (P = 0.83). On the other hand, the amount of intraoperative blood loss in the microwave group (360 +/- 230 mL) was smaller than that in the hepatectomy group (910 +/- 490 mL, P < 0.05). Blood transfusion was necessary for 6 patients in the hepatectomy group, but it was not necessary in the microwave group. CONCLUSIONS: Microwave coagulation therapy is suggested to be equally effective as hepatic resection in the treatment of multiple (two to nine) hepatic metastases from colorectal carcinoma, whereas its surgical invasiveness is less than that of hepatic resection.

Adult↗
PubMed2000

Combined assessment of T-wave alternans and late potentials used to predict arrhythmic events after myocardial infarction. A prospective study.

OBJECTIVES: The aim of the present study was to determine whether the combination of two markers that reflect depolarization and repolarization abnormalities can predict future arrhythmic events after acute myocardial infarction (MI). BACKGROUND: Although various noninvasive markers have been used to predict arrhythmic events after MI, the positive predictive value of the markers remains low. METHODS: We prospectively assessed T-wave alternans (TWA) and late potentials (LP) by signal-averaged electrocardiogram (ECG) and ejection fraction (EF) in 102 patients with successful determination results after acute MI. The TWA was analyzed using the power-spectral method during supine bicycle exercise testing. No antiarrhythmic drugs were used during the follow-up period. The study end point was the documentation of ventricular arrhythmias. RESULTS: The TWA was present in 50 patients (49%), LP present in 21 patients (21%), and an EF <40% in 28 patients (27%). During a follow-up period of 13 +/- 6 months, symptomatic, sustained ventricular tachycardia or ventricular fibrillation occurred in 15 patients (15%). The event rates were significantly higher in patients with TWA, LP, or an abnormal EF. The sensitivity and the negative predictive value of TWA in predicting arrhythmic events were very high (93% and 98%, respectively), whereas its positive predictive value (28%) was lower than those for LP and EF. The highest positive predictive value (50%) was obtained when TWA and LP were combined. CONCLUSIONS: The combined assessment of TWA and LP was associated with a high positive predictive value for an arrhythmic event after acute MI. Therefore, it could be a useful index to identify patients at high risk of arrhythmic events.

Arrhythmias, Cardiac↗
PubMed2000

Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction.

Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the differentiation of osteoclast progenitors of the monocyte/macrophage lineage into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF, also called CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF-dependent bone marrow macrophages (M-BMM phi) appeared within 3 d. Tartrate-resistant acid phosphatase-positive osteoclasts were also formed when M-BMM phi were further cultured for 3 d with mouse tumor necrosis factor alpha (TNF-alpha) in the presence of M-CSF. Osteoclast formation induced by TNF-alpha was inhibited by the addition of respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not by osteoclastogenesis inhibitory factor (OCIF, also called OPG, a decoy receptor of ODF/RANKL), nor the Fab fragment of anti-RANK (ODF/RANKL receptor) antibody. Experiments using M-BMM phi prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-alpha. Osteoclasts induced by TNF-alpha formed resorption pits on dentine slices only in the presence of IL-1alpha. These results demonstrate that TNF-alpha stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL-RANK system. TNF-alpha together with IL-1alpha may play an important role in bone resorption of inflammatory bone diseases.

Acid Phosphatase↗
PubMed2000

Lack of an association between T-wave alternans and ST-segment depression during exercise-induced ambulatory ischemia.

It is known that T-wave alternans (TWA), which identify patients at risk for arrhythmic events, often occur during acute coronary occlusion in association with ST-segment elevation. To test the hypothesis that TWA is associated with a certain state/severity of myocardial infarction/ischemia, we assessed the association between TWA and ST-segment depression during exercise-induced ambulatory ischemia. Of 351 consecutive patients with coronary artery disease who underwent assessment of microvolt TWA by exercise, 23 patients with effort angina without a history of infarction with ST depression (> or =0.11 mV) during TWA test were selected. These patients were compared with 222 postinfarction patients consisting of 38 patients with, and 184 patients, without the ST depression, and 18 normal individuals. The incidence (9%) of determinate TWA in the patients with angina was significantly (P < .0001) lower than that (52%) in the postinfarction patients. There was no significant difference between the angina patients and the controls (6%). There was also no difference between the patients with (58%) and without the ST depression (51%) in the postinfarction patients. Moreover, no correlation existed between the TWA voltage and the ST-depression magnitude in both angina and postinfarction patients. We concluded that there is no association between TWA and ambulatory ischemia with ST depression.

Coronary Disease↗
PubMed2000

Eicosatetraynoic and eicosatriynoic acids, lipoxygenase inhibitors, block meiosis via antioxidant action.

We previously showed that nordihydroguaiaretic acid (NDGA) and other antioxidants inhibit the resumption of meiosis in oocyte-cumulus complexes (OCC) and denuded oocytes (DO). Because NDGA is well known to be an inhibitor of lipoxygenases (LOX), we assessed whether other LOX inhibitors influence spontaneous germinal vesicle breakdown (GVBD) in OCC and DO. Spontaneous GVBD in rat OCC obtained from preovulatory follicles was significantly and reversibly inhibited by the minimum effective doses of 80 and 100 microM 5,8,11, 14-eicosatetraynoic acid (ETYA) and 5,8,11-eicosatriynoic acid (ETI), respectively. In DO, GVBD was significantly inhibited by 100 microM ETYA or ETI. The minimum effective concentrations of ETYA and ETI for inhibition of GVBD in either OCC or DO are approximately 30- to 50-fold higher than the concentrations necessary to inhibit LOX activity by 50% in intact cells. Because we previously showed that NDGA and other antioxidants inhibit the spontaneous resumption of meiosis, we assessed whether ETYA and ETI may act similarly as scavengers of reactive oxygen species (ROS). Luminol-amplified chemiluminescence showed that 50 microM of either ETYA or ETI markedly and significantly reduced ROS generated with 10 mM 2, 2'-azobis(2-amidinopropane)dihydrochloride (AAPH). Moreover, incubation of DO with 30 mM AAPH reversed the inhibition of GVBD produced by 100 microM ETYA or ETI. These findings support the conclusion that ETYA and ETI inhibit oocyte maturation by acting as antioxidants rather than by inhibiting LOX.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed2000

Importance of membrane- or matrix-associated forms of M-CSF and RANKL/ODF in osteoclastogenesis supported by SaOS-4/3 cells expressing recombinant PTH/PTHrP receptors.

SaOS-4/3, a subclone of the human osteosarcoma cell line SaOS-2, established by transfecting the human parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor complementary DNA (cDNA), supported osteoclast formation in response to PTH in coculture with mouse bone marrow cells. Osteoclast formation supported by SaOS-4/3 cells was completely inhibited by adding either osteoprotegerin (OPG) or antibodies against human macrophage colony-stimulating factor (M-CSF). Expression of messenger RNAs (mRNAs) for receptor activator of NF-kappaB ligand/osteoclast differentiation factor (RANKL/ODF) and both membrane-associated and secreted forms of M-CSF by SaOS-4/3 cells was up-regulated in response to PTH. SaOS-4/3 cells constitutively expressed OPG mRNA, expression of which was down-regulated by PTH. To elucidate the mechanism of PTH-induced osteoclastogenesis, SaOS-4/3 cells were spot-cultured for 2 h in the center of a culture well and then mouse bone marrow cells were uniformly plated over the well. When the spot coculture was treated for 6 days with both PTH and M-CSF, osteoclasts were induced exclusively inside the colony of SaOS-4/3 cells. Osteoclasts were formed both inside and outside the colony of SaOS-4/3 cells in coculture treated with a soluble form of RANKL/ODF (sRANKL/sODF) in the presence of M-CSF. When the spot coculture was treated with sRANKL/sODF, osteoclasts were formed only inside the colony of SaOS-4/3 cells. Adding M-CSF alone failed to support osteoclast formation in the spot coculture. PTH-induced osteoclast formation occurring inside the colony of SaOS-4/3 cells was not affected by the concentration of M-CSF in the culture medium. Mouse primary osteoblasts supported osteoclast formation in a similar fashion to SaOS-4/3 cells. These findings suggest that the up-regulation of RANKL/ODF expression is an essential step for PTH-induced osteoclastogenesis, and membrane- or matrix-associated forms of both M-CSF and RANKL/ ODF are essentially involved in osteoclast formation supported by osteoblasts/stromal cells.

Animals↗
PubMed1999

Cytotoxic effects of NSL-1406, a new thienopyrimidine derivative, on leukocytes and osteoclasts.

We synthesized a series of thienopyrimidine derivatives and examined their cytotoxic effects on several cell lines. One of the derivatives, NSL-1406, was shown to exert potent cytotoxic effects on leukemia cell line including P388 cells and J774 cells. It was also inhibitory on mouse osteoclasts and suppressed the in vitro bone resorption by osteoclasts at nanomolar concentrations.

Animals↗
PubMed1999

Effect of DP-1904, a thromboxane synthetase inhibitor, on antigen- and spasmogen-induced bronchoconstriction in rodents.

The effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8-tetra-hydronaphthalene-2-car boxylic acid hydrochloride], a selective thromboxane synthetase inhibitor, was examined on antigen- and spasmogen-induced bronchoconstriction in rodents. Oral administration of DP-1904 (1, 3, 10 mg/kg) as well as OKY-046 (sodium (E)-3[4-(1-imidazolylmethyl)-phenyl]-2-propanoate, 100 mg/kg), significantly inhibited immunoglobulin G-mediated bronchoconstriction in actively sensitized guinea pigs. Immunoglobulin E-mediated bronchoconstriction in actively sensitized rats was also inhibited by both DP-1904 (1, 10 mg/kg) and OKY-046 (100 mg/kg). DP-1904 (3-30 mg/kg) and OKY-046 (30 mg/kg) suppressed leukotriene D4-induced bronchoconstriction in guinea pigs. In these models, the endogenous levels of thromboxanes significantly increased following the stimulus (antigen and leukotriene D4). DP-1904 (10 mg/kg) inhibited the increase in thromboxane level in both plasma and bronchial alveolar lavage fluid. These actions of DP-1904 persisted for more than 12 h, indicating a long-lasting effect of DP-1904 on bronchoconstriction. The results showed that the biological activity of DP-1904 in our rodents models is more potent than that of OKY-046 (Ozagrel), which is available as an anti-asthma agent in Japan.

Acetylcholine↗
PubMed1999

Pharmacokinetics of 9alpha-fluoromedroxyprogesterone acetate in rats: comparison with medroxyprogesterone acetate.

Medroxyprogesterone acetate (MPA) is widely used in endocrine therapy for breast cancer and other diseases. Recently, it has been demonstrated that 9alpha-fluoromedroxyprogesterone acetate (FMPA) also has anti-tumour activity in chemical-induced rat mammary tumour and its activity is greater than that of MPA. In the present study, the physico-chemical properties of FMPA and MPA and their pharmacokinetics in female rats were investigated. Partition coefficients (log P) of FMPA and MPA were 3.1 and 3.8, respectively, while the solubilities of FMPA and MPA in phosphate buffer saline were 3.8 and 1.1 microg/mL, respectively. When the two agents were intravenously or orally administered into female rats, there was no significant difference between their plasma concentrations. However, unmetabolized drug excreted into urine accounted for 4.7 and 0.7% of the intravenous dose of FMPA and MPA, respectively. The free fraction of FMPA in rat plasma was approximately four times that of MPA. Assuming the well-stirred model, hepatic intrinsic clearances of FMPA and MPA were estimated to be 64 and 293 L/h per kg, respectively. In addition, the free fraction of FMPA in blood is estimated to be higher than that of MPA, which may explain the higher anti-tumour activity.

Administration, Oral↗
PubMed1999

Localization of a locus responsible for the bovine chondrodysplastic dwarfism (bcd) on chromosome 6.

A hereditary chondrodysplastic dwarfism caused by an autosomal recessive gene has been reported in a population of Japanese Brown cattle. Affected calves show an insufficiency of endochondral ossification at the long bones of the limbs. In the present study, we mapped the locus responsible for the disease (bcd) by linkage analysis, using microsatellite markers and a single paternal half-sib pedigree obtained from commercial herds. Linkage analysis revealed a significant linkage between the bcd locus and marker loci on the distal region of bovine Chromosome (Chr) 6. The bcd locus was mapped in the interval between microsatellite markers BM9257 and BP7 or BMS511 with a recombination fraction of 0.05 and 0.06, and a lod score of 8.6 and 10.1, respectively. A comparison of genetic maps between bovine Chr 6 and human Chr 4 or mouse Chr 5 indicates possible candidate genes including FGFR3 and BMP3 genes, which are responsible for human chondrodysplasias and associated with bone morphogenesis, respectively.

Animals↗
PubMed1999

Cloning of bovine LYST gene and identification of a missense mutation associated with Chediak-Higashi syndrome of cattle.

An inheritable bleeding disorder with light coat color caused by an autosomal recessive gene has been reported in a population of Japanese black cattle. The disease has been diagnosed as Chediak-Higashi Syndrome (CHS) of cattle which correspond to a human inheritable disorder caused by mutation in LYST gene. To characterize the molecular lesion causing CHS in cattle, cDNAs encoding bovine LYST were isolated from a bovine brain cDNA library. The nucleotide and deduced amino acid sequences of bovine LYST had 89.6 and 90.2% identity with those of the human LYST gene, respectively. In order to identify the mutation within the LYST gene causing CHS in cattle, cDNA fragments of the LYST gene were amplified from an affected animal by RT-PCR and their nucleotide sequences were completely determined. Notably, a nucleotide substitution of A to G transition, resulting in an amino acid substitution of histidine to arginine (H2015R) was identified in the affected animal. The presence of the substitution was completely corresponding with the occurrence of the CHS phenotype among 105 members of pedigrees of the Japanese black cattle and no cattle of other populations had this substitution. These findings strongly suggested that H2015R is the causative mutation in CHS of Japanese black cattle.

Amino Acid Sequence↗
PubMed1999

Osteoblastic cells induce fusion and activation of osteoclasts through a mechanism independent of macrophage-colony-stimulating factor production.

Fusion and activation of osteoclasts are the final two events in osteoclastic bone resorption. To investigate the regulatory mechanism of these events, mononuclear osteoclasts (preosteoclasts, pOCs) were isolated from co-cultures of mouse osteoblastic cells and bone marrow cells. Most of the pOCs cultured without any additives died within 12 h. Survival of pOCs was supported by addition of either osteoblastic cells or macrophage-colony-stimulating factor (M-CSF). pOCs began to fuse with each other after culture for 12 h in the presence of osteoblastic cells or M-CSF. However, the properties of multinucleated osteoclast-like cells (OCLs) induced by osteoblastic cells were considerably different from those induced by M-CSF. Fusion of pOCs induced by osteoblastic cells was retarded after culture for 24 h. In contrast, M-CSF-induced fusion of pOCs continued throughout the 48-h culture period, which was not inhibited by addition of calcitonin. When pOCs together with osteoblastic cells were cultured for 48 h on dentine slices, many resorption pits were formed on the slices. Calcitonin completely inhibited the fusion and pit-forming activity of pOCs treated with osteoblastic cells. Resorption pits were hardly detected on dentine slices in pOC cultures treated with M-CSF. Osteoblastic cells prepared from osteopetrotic (op/op) mice, which cannot produce functional M-CSF, stimulated the fusion and pit-forming activity of pOCs. Recombinant RANKL (receptor activator of NF-kappaB ligand), a cytokine which is produced by osteoblastic cells and is responsible for osteoclast differentiation, induced the fusion and pit-forming activity of pOCs. These results suggested that osteoblastic cells are involved in fusion and activation of osteoclasts through a mechanism independent of M-CSF production. RANKL appears to be responsible for fusion and activation of osteoclasts induced by osteoblastic cells.

Animals↗
PubMed1999

A possible involvement of thromboxane A2 and peptide leukotrienes in hyperresponsiveness of Sephadex-treated rat lung parenchyma.

An augmented contraction and elevated thromboxane (TX) B2 release were observed, when the isolated parenchyma from Sephadex-treated rats was stimulated by 5-hydroxytryptamine (5-HT). Release of peptide leukotrienes (pLTs) was also increased by the stimuli. In the Sephadex-induced hyperresponsiveness model, DP-1904, a novel TX synthetase inhibitor, at the concentrations of 3 x 10(-7) to approximately 3 x 10(-6) M, reduced the augmented contraction. Also, indomethacin (3 x 10(-6) M), a histamine H1 antagonist and AA-2414 (10(-6) M, a TXA2 antagonist, significantly attenuated the hyperresponsiveness to 5-HT. ICI-198,615 (10(-7) M), a leukotriene receptor antagonist, partially but significantly reduced the augmented contraction. In an ex vivo study, oral DP-1904 significantly inhibited both the augmented contraction and elevated TXB2 release from Sephadex-treated rat parenchyma, but did not affect the blood eosinophilia induced by Sephadex-treatment. These results suggested that the ability to synthesize newly generated lipid mediators such as TXA2 and pLTs to exogenous 5-HT was altered upward by Sephadex injection, and so could lead to augmented contraction of established hyperresponsiveness in rats.

Animals↗
PubMed1999

Antioxidants reversibly inhibit the spontaneous resumption of meiosis.

We previously showed that the cell-permeant antioxidant 2(3)-tert-butyl-4-hydroxyanisole (BHA) inhibited germinal vesicle breakdown (GVBD) in oocyte-cumulus complexes (OCC) of the rat. The objective of the present studies was to assess other antioxidants and whether such inhibition was reversible. Spontaneous GVBD in OCC incubated for 2 h was significantly inhibited (P < 0.005) by nordihydroguaiaretic acid (NDGA; GVBD = 19.4%), BHA (GVBD = 25.7%), octyl gallate (OG; GVBD = 52.2%), ethoxyquin (EQ; GVBD = 58.8%), 2, 6-di-tert-butyl-hydroxymethyl phenol (TBHMP; GVBD = 59%), butylated hydroxytoluene (BHT; GVBD = 59.5%), and tert-butyl hydroperoxide (TBHP; GVBD = 60.0%). Other antioxidants that produced lower but significant (P < 0.05) inhibition of oocyte maturation included propyl gallate (PG; GVBD = 70.3%), 2,4,5-trihydroxybutrophenone (THBP; GVBD = 71.4%), and lauryl gallate (LG; GVBD = 71.4%). Antioxidants that had no effect on oocyte maturation at the same concentration (100 microM) included ascorbic acid, vitamin E, and Trolox. Inhibition of GVBD was evident for up to 8 h of incubation of OCC and denuded oocytes (DO) with BHA or NDGA and was reversed by washing. NDGA was less potent than BHA for inhibition of GVBD in DO, unlike that seen with OCC. Oocyte maturation was induced by incubation of follicles for 3 h with human chorionic gonadotropin (hCG), and this response was inhibited by BHA or NDGA. These findings support the conclusion that cell-permeant antioxidants inhibit spontaneous resumption of meiosis, which may implicate a role of oxygen radicals in oocyte maturation.

Animals↗
PubMed1999

A simple technique for anatomical slow pathway ablation in atrioventricular nodal reentrant tachycardia.

The slow pathway potential or the slow potential serves as a useful marker in catheter ablation of the slow pathway. However, an anatomical approach without recording of these potentials is also an effective way to cure atrioventricular nodal reentrant tachycardia (AVNRT). Moreover, the origin of these potentials is a matter of controversy. We compared 2 approaches to ascertain whether or not recording of these potentials is necessary in eliminating the slow pathway and to estimate the usefulness of the simple anatomical approach. The study population consisted of 24 patients with a conventional approach (Group P) and 19 patients with an anatomical approach (Group A). In group A, the ablation site was determined by fluoroscopy, which was the lowest one-third of the area between the His bundle electrogram recorded position and the coronary sinus orifice at the right anterior oblique view, and just in front of and above the coronary sinus orifice also posterior to the His catheter at the left anterior oblique view where the His catheter was seen tangentially. The slow pathway was successfully ablated in all patients without any complications, including more than first-degree AV block. Although there were no significant differences in total energy or number of applications between the 2 groups, the procedure time was significantly shorter in group A (p < 0.01). In conclusion, recording of the slow pathway potential or the slow potential is not always necessary for slow pathway ablation in the treatment of AVNRT. Because our anatomical approach was performed simply, effectively and safely, it is recommended for the slow pathway ablation of AVNRT.

Adolescent↗
PubMed1999

Percutaneous microwave hepatic tumor coagulation with segmental hepatic blood flow occlusion in seven patients.

OBJECTIVE: We assess the usefulness of microwave hepatic tumor coagulation therapy with balloon occlusion of segmental hepatic blood flow for eight recurrent metastatic hepatic tumors in seven patients. CONCLUSION: Limited early experience with microwave hepatic tumor coagulation therapy and segmental hepatic blood flow occlusion has been positive, suggesting that further clinical evaluation is warranted.

Catheterization↗