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Biomedical subjects

M Tagawa

Publications and source records attributed to M Tagawa.

At least 109 records · Page 6Linked to original sources
PubMed1998

Comparison of electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, in patients with ventricular tachyarrhythmias.

Electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, were evaluated in 5 and 6 patient with ventricular tachyarrhythmia, respectively. Six patients had sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation (VF). Electrophysiologic study was performed before and after administration of E-4031 and MS-551 [E-4031; loading infusion 9 micrograms/kg for 5 min + 0.15 microgram/kg/min, MS-551; loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min]. The QT intervals were significantly prolonged after administration of E-4031 and MS-551 from 409 +/- 37 to 455 +/- 49 msec (11%), and from 359 +/- 52 to 411 +/- 63 msec (14%), respectively. The QTc intervals were significantly prolonged from 457 +/- 17 to 494 +/- 24 msec (8%), and from 410 +/- 36 to 452 +/- 47 (10%), respectively. There were no significant differences in the QT and QTc intervals between these two agents. The right ventricular effective refractory period (VERP) with E-4031 was prolonged at 600 (from 244 +/- 27 to 270 +/- 31 msec, 11 +/- 2%), 400 (from 222 +/- 23 to 242 +/- 24 msec, 9 +/- 3%), and 300 msec (from 206 +/- 19 to 218 +/- 25 msec, 6 +/- 4%), and those with MS-551 were prolonged at 600 (from 240 +/- 23 to 268 +/- 23 msec, 12 +/- 2%), 400 (from 225 +/- 22 to 250 +/- 24 msec, 11 +/- 4%), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, 7 +/- 4%). Both E-4031 and MS-551 prolonged VERP in a "reverse" use-dependent manner without changing the conduction velocity. E-4031 prevented the induction of VT in one patient. MS-551 prevented the induction of VT and VF in one patient each. Further evaluation of these selective class III agents may be needed to determine if higher doses are required to achieve the pharmacological effects in patients with ventricular tachyarrhythmias.

Adult↗
PubMed1998

A comparison of electrophysiologic properties between responders and non-responders to DL-sotalol among patients with ventricular tachyarrhythmia. Importance of the lack of a reverse use-dependent effect on ventricular refractoriness to responders.

This study was undertaken to determine whether dl-sotalol can prevent ventricular tachyarrhythmia inducibility that can be predicted from electrophysiologic parameters. The effects of dl-sotalol in 16 patients (ventricular tachycardia (VT) in 11 and fibrillation (VF) in 5) were determined in electrophysiologic studies before and after dl-sotalol (320 mg/day). In 9 of 16 patients (56%) after dl-sotalol, ventricular tachyarrhythmia could not be induced by the entire stimulation protocol (responders). There were significant differences in QT interval (462 +/- 52 vs. 415 +/- 34 msec; p < 0.05) and ventricular effective refractory period (VERP) at 600, 400 and 300 msec (302 +/- 28 vs. 262 +/- 20 msec; p < 0.001, 280 +/- 23 vs. 240 +/- 21 msec; p < 0.001, 256 +/- 24 vs. 222 +/- 12 msec; p < 0.005, respectively) between responders and non-responders. The percentile increases in VERP (% VERP) at 600, 400, and 300 msec in responders were 25%, 26%, and 27%, whereas those in non-responders was 9%, 7%, and 7%, respectively. Isoproterenol administered to responders did not fully reverse the dl-sotalol-induced prolongation of VERP (delta VERP) at 600, 400, and 300 msec, which remained significantly prolonged compared to the baseline (281 +/- 18 vs. 241 +/- 16 msec; p < 0.01, 258 +/- 20 vs. 223 +/- 21 msec; p < 0.01, 247 +/- 22 vs. 202 +/- 16 msec; p < 0.01, respectively). % VERP did not exhibit significant differences at 600 (16%), 400 (15%), and 300 (20%) msec, indicating the lack of a reverse use-dependency. The results suggest that delta VERP in responders did not show reverse use-dependency, and that the phenomenon may account for the efficacy of dl-sotalol.

Action Potentials↗
PubMed1998

Induction of antitumor effect on human esophageal carcinoma cells by the retroviral expression of granulocyte macrophage-colony stimulating factor gene.

We have examined antitumor effect of human esophageal carcinoma cells (T.Tn) which were retrovirally transduced to express mouse granulocyte macrophage-colony stimulating factor (mGM-CSF) gene. Nude mice inoculated with T.Tn cells secreting mGM-CSF developed small tumors but the tumors regressed spontaneously, although the proliferation in vitro of transduced cells was not different from that of wild-type cells. In contrast, the tumor of T.Tn cells transduced with human GM-CSF grew as that of wild-type cells, since murine GM-CSF receptors do not bind to human GM-CSF. Histological examination of the regressing tumor of mGM-CSF-producing T.Tn cells revealed predominant infiltration of inflammatory cells including macrophages. In addition, local injection of mGM-CSF-producing T.Tn cells into the established wild-type tumors significantly induced the retardation of subsequent wild-type tumor growth, suggesting that T-cell independent local response plays a crucial role in destroying tumor cells.

Animals↗
PubMed1998

Impaired tumorigenicity of IL-4-producing murine neuroblastoma cells in immunodeficient nude mice.

We have examined antitumor effect of murine neuroblastoma cells (C1300) retrovirally transduced with interleukin-4 (IL-4) gene in syngeneic A/J and nude mice. Although in vitro proliferation of IL-4-secreting C1300 cells (C1300/IL-4) was not different from that of wild-type cells, the in vivo tumor growth of C1300/IL-4 cells subcutaneously inoculated into immunocompetent A/J mice was retarded compared with that of wild-type cells and consequently, the survival of the A/J mice which received C1300/IL-4 cells was prolonged. In immunodeficient nude mice we observed accelerated growth rate of wild-type tumors in comparison with the tumors developed in A/J mice. In contrast, the tumor growth of C1300/IL-4 cells in nude mice was significantly suppressed and the growth was much slower than that of C1300/IL-4 cells inoculated in A/J mice. Thus, the secretion of IL-4 from tumor cells produced antitumor effect more efficiently in mature T cell-defective hosts than in immunocompetent mice. Our results suggest a possible clinical application of IL-4 expression in tumor cells via genetic manipulations especially in immunocompromised cancer patients.

Animals↗
PubMed1998

Antitumor vaccine effect of irradiated murine neuroblastoma cells producing interleukin-2 or granulocyte macrophage-colony stimulating factor.

We have examined vaccination effects of cytokine-producing murine neuroblastoma cells (C1300). C1300 cells retrovirally transduced with interleukin-2 (IL-2) or granulocyte macrophage-colony stimulation factor (GM-CSF) gene were established. Their in vitro proliferation rates and the class I expression of major histocompatibility complex were not different from those of wild-type cells. Five-Gy irradiation of the respective cytokine producers slightly reduced the in vitro cell growth but treatment with 15 Gy significantly impaired the proliferation. In contrast, the secretion of both cytokines from the respective transduced cells was retained compared with the cell growth. We immunized syngeneic mice with irradiated wild-type cells as a control or cytokine-producing cells and challenged the mice with unirradiated wild-type cells. The control mice developed tumors of the challenged wild-type cells, on the contrary, the mice which had received irradiated IL-2 or GM-CSF producers did not. Thus, IL-2- or GM-CSF-expressing syngeneic tumor cells can be potentially used as a tumor vaccine by inducing protective immunity against low immunogenic neuroblastomas in the inoculated hosts.

Animals↗
PubMed1998

Antitumor response of genetically engineered IL-2 expression to human esophageal carcinoma cells in mature T cell-defective condition.

We examined whether antitumor effect could be produced by retrovirally expressed human interleukin-2 (hIL-2) gene in human esophageal cancer cells (T.Tn) using immunocompromised nude mice. Loss of tumorigenicity of hIL-2-producing T.Tn (T.Tn/hIL-2) cells inoculated subcutaneously was observed in contrast to continuous tumor growth of wild-type cells, although in vitro proliferation of T.Tn/hIL-2 cells remained the same as that of wild-type cells. The antitumor effect was also evidenced by the injection of T.Tn/hIL-2 cells into established tumors of wild-type cells. The injection significantly retarded the subsequent growth of wild-type tumors. Histological examination of regressing T.Tn/hIL-2 cells revealed necrotic areas and infiltration of several types of inflammatory cells. Treatment of nude mice with anti-asialoGM1 antibody did not influence the IL-2-mediated tumor rejection. Vaccination of nude mice with irradiated T.Tn/hIL-2 cells whose secretion of hIL-2 in amount was comparable to that of unirradiated cells did not develop protective immunity. Taken together, the antitumor effect achieved in nude mice by the inoculation of T.Tn/hIL-2 cells is mediated by non-T non-natural killer cells.

Animals↗
PubMed1998

Immunolocalization of androgen receptor in canine prostatic hyperplasia--effect of antiandrogen.

The effect of a synthetic steroidal anti-androgen, chlormadinone acetate (CMA), on spontaneous benign prostatic hyperplasia (BPH) in the dog was investigated. Old male beagle dogs (5 to 8 years old) were divided into the following experimental groups: group 1 consisting of BPH controls, and group 2 which received CMA of 0.3 mg/kg/day orally for 6 months. In group 1, glandular hyperplasia of the prostate was clearly observed. The glandular epithelial cells showed uniformly intense nuclear immunostaining for androgen receptor (AR). In contrast, CMA produced marked atrophy of the glandular epithelium. The interacinar fibromuscular stroma was prominent. Furthermore, nuclear immunostaining for AR in both epithelial and stroma cells was remarkably decreased. These results indicate that the uptake of testosterone and/or its androgenic effect on the prostate may be suppressed by CMA. The decreased AR-immunostaining may be explained by the decrease in the number of AR and/or antibody binding sites for AR.

Androgen Antagonists↗
PubMed1998

Ultrastructural study in canine prostatic hyperplasia--effect of antiandrogen.

Ultrastructural changes in canine prostates after treatment with chlormadinone acetate (CMA) were investigated. Old male beagle dogs (5-8 years old ) were divided into two experimental groups; group 1 consisted of benign prostatic hyperplasia (BPH) controls, and group 2 received 0.3 mg/kg/day CMA orally for 6 months. In group 1 animals, the most striking ultrastructural changes were detected in the rough endoplasmic reticulum (rER) and Golgi complexes. The secretory granules were lined up along the apical plasma membrane, and exocytosis was frequently seen. In group 2 animals, the cytoplasm was electron-lucent and contained relatively few, poorly developed organelles. The rER was sparse and consisted of a few scattered, short profiles studded with ribosomes. The Golgi complexes were inconspicuous. The secretory granules were markedly decreased in both number and size. Furthermore, mitochondrial degeneration such as swollen or disappeared mitochondrial cristae or decreased electron density of the matrix were frequently seen in the smooth muscle cells. Based on our data, atrophy after treatment with CMA may be due to shrinkage of both glandular and stromal compartments in the prostate tissue.

Animals↗
PubMed1998

Correlation of the mutation of p53 gene and the polymorphism at codon 72 in smoking-related non-small cell lung cancer patients.

The polymorphism of p53 gene at codon 72 consisting of either arginine (Arg)- or proline (Pro)-encoded allele is suggested to be associated with the susceptibility of tobacco-related lung cancer. In this study we examined the polymorphism of 224 non-small cell lung cancer (NSCLC) patients and that of 303 control persons with a polymerase chain reaction method and found that Pro-allele carriers were significantly more frequent in those patients who smoked and were affected at a younger age (<65) (P<0.05). We also investigated whether the mutational alterations of this gene could be influenced by the genotype. The overall mutation rate of 114 NSCLC patients examined with a single-strand conformation polymorphism method was 31%, which agreed with previous reports. However, the mutation rate was significantly increased in those patients who smoked and were affected at a younger age (<65) (P<0.05). Although the Pro-allele carriers among the smoker patients showed higher mutation rate than the Arg/Arg homozygotes, the difference between the genotypes had marginal significance (0.1<P<0.05) and was statistically insignificant, if the study was confined to younger patients. Thus, the present data cannot confirm a possible association of the p53 polymorphism with its mutation rate regarding smoking-related lung cancer.

Adenocarcinoma↗
PubMed1997

Identification of a receptor-type protein tyrosine phosphatase expressed in postmitotic maturing neurons: its structure and expression in the central nervous system.

We have isolated a rat cDNA encoding a receptor-type protein-tyrosine-phosphatase (RTP) expressed in brain and kidney (RPTP-BK) and characterized its expression in the developing central nervous system. RPTP-BK has seven fibronectin type III-like repeats in the extracellular region and a unique catalytic phosphatase domain in the cytoplasmic region. Bacterial expression of its phosphatase domain showed that the dephosphorylation of phosphotyrosine residues was mediated by the cytoplasmic catalytic domain. Sequence comparison revealed that RPTP-BK is homologous with GLEPP1, a rabbit PTP expressed in renal glomerular epithelia, and has the same phosphatase domain as murine PTPphi expressed in macrophages. RPTP-BK has also significant homology with Drosophila DPTP10D in the phosphatase domain, whose expression is localized exclusively in growth cones of the embryonal brains. The gene for RPTP-BK is well conserved among other species, and the expression in the brain but not in the kidney is developmentally regulated during the neonatal stage. Hybridization in situ showed that RPTP-BK is highly expressed in the postmitotic maturing neurons of the olfactory bulb, developing neocortex, hippocampus and thalamus. Because the expression of RPTP-BK in the developing neocortex is correlated with the stage of axonogenesis in cortical neurons, RPTP-BK might be crucial in neural cell development of the mammalian central nervous system.

Amino Acid Sequence↗
PubMed1997

Partial cloning of the hormone-binding domain of the cortisol receptor in tilapia, Oreochromis mossambicus, and changes in the mRNA level during embryonic development.

Cortisol is one of the central hormones in osmoregulation in fish, especially in seawater adaptation. A cDNA of 453 bp was cloned from liver mRNA of freshwater-reared tilapia (Oreochromis mossambicus), by reverse transcription polymerase chain reaction (RT-PCR) with primers designed for the hormone-binding domain of glucocorticoid receptors (GRs) in mammals and rainbow trout. The sequence of PCR product has 83% homology to the trout GR at the nucleotide level and 92% at the amino acid level. The PCR product of tilapia showed highest homology (74% at the amino acid level) to GR among human steroid hormone receptors, including mineralocorticoid receptor. The length of the receptor mRNA of tilapia was about 6.5 kb as determined by Northern blot hybridization. The mRNA concentration in the gills was relatively higher among various organs, the highest concentration being observed in blood cells. Signal intensity of the receptor message in the gills was stronger in fish reared in freshwater than in those reared in seawater or in concentrated (160%) seawater. During early development of tilapia, the highest concentration of receptor mRNA in the total RNA extracted from the whole egg was found just after fertilization, and its concentration decreased steadily toward hatching. The absolute amount of receptor mRNA per egg increased gradually before the initiation of cortisol production by the embryo. When embryos were transferred from fresh water to seawater 2 days before hatching, no difference was observed in the signal intensity of the receptor mRNA among embryos after 1, 2 (the day of hatching), 4, and 7 days.

Animals↗
PubMed1997

Bone morphogenetic protein-2 stimulates differentiation of cultured spinal ligament cells from patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by heterotopic bone formation occurring in spinal ligament, causing severe compression myelopathy. In order to investigate the mechanism of OPLL development, we isolated spinal ligament cells from OPLL patients as well as non-OPLL patients, and established 10 OPLL cell lines and 7 non-OPLL cell lines, respectively. We analyzed the effects of bone morphogenetic protein-2 (BMP-2) on these cells with respect to alkaline phosphatase (AP) activity, DNA synthesis, and collagen production. BMP-2 caused a significant increase of AP activity in 4 OPLL cell lines, whereas the activity did not change in any non-OPLL cells. Among OPLL cells, BMP-2 stimulated DNA synthesis in four cell lines and procollagen type I carboxyl-terminal peptide (PICP) synthesis in five cell lines. Some non-OPLL cells also responded to BMP-2, as there was an increase of DNA synthesis in three cell lines and PICP synthesis in one cell line. These data collectively indicate that BMP-2 preferentially induces osteogenic differentiation in OPLL cells rather than in non-OPLL cells. OPLL cells, therefore, exhibit a different response to BMP-2 than non-OPLL cells, suggesting that the expression of BMP receptor(s) and/or the signal transduction initiated by BMP-2 in the spinal ligament cells of OPLL patients somewhat deviate from those in normal spinal ligament cells. Such abnormal characteristics of OPLL cells as described here provide some clues to the clarification of the pathogenesis of OPLL.

Alkaline Phosphatase↗
PubMed1997

GB virus-C RNA in Japanese patients with hepatocellular carcinoma and cirrhosis.

BACKGROUND/AIMS: The involvement of non-B, non-C virus in the incidence of hepatocellular carcinoma (HCC) is not yet known. We have therefore examined the occurrence of GBV-C RNA in such patients. METHODS: One hundred and eleven patients diagnosed as having HCC and 67 patients with cirrhosis without HCC were examined for the prevalence of GBV-C RNA by nested reverse transcription polymerase chain reaction with primers located at the helicase region. Sera were obtained and kept at -20 degrees C until analysis. RESULTS: GBV-C RNA was positive in 11/111 (9.9%) cases with HCC, in 10/74 (13.5%) anti-HCV positive cases, in 1/25 (4%) HBsAg positive cases, and in 0/8 (0%) anti-HCV and HBsAg negative cases. GBV-C RNA was also positive in 7/67 (10.4%) cases with cirrhosis, in only 1/18 (5.6%) anti-HCV and HBsAg negative cases, in 4/33 (12.1%) anti-HCV positive, and in 2/14 (14.3%) HBsAg positive cases. The clinical background of patients with anti-HCV positive HCC who were also positive for GBV-C RNA did not differ from the background of those negative for GBV-C RNA. CONCLUSIONS: GBV-C is unlikely to be a major etiologic agent of non-B, non-C chronic liver diseases and HCC in Japan.

Adult↗
PubMed1997

Prediction of drug cytotoxicity in 9L rat brain tumor by using flow cytometry with a deoxyribonucleic acid-binding dye.

OBJECTIVE: Flow cytometry (FCM) with a deoxyribonucleic acid (DNA)-binding dye, propidium iodide, provides a rapid and quantitative method to detect apoptotic cell death. This technique was used to examine the sensitivity of tumor cells to anticancer agents, as a novel test of chemosensitivity in vitro. METHODS: The in vitro chemosensitivity of 9L gliosarcoma cells to a panel of anticancer agents (cisplatin, nimustine, adriamycin, cyclophosphamide, vincristine, 5-fluorouracil, and methotrexate) was investigated by both FCM, yielding DNA histograms, and a microtiter tetrazolium test, measuring cellular metabolism. Clinically achievable concentrations of the agents were used for the analysis of DNA histograms and proliferation of 9L cells in vitro. Rats intracranially inoculated with 9L cells were treated with the agents, and tumor masses were visually monitored by using magnetic resonance imaging with gadolinium-diethylenetriaminepentaacetic acid enhancement. RESULTS: The cytotoxic effect of anticancer agents examined by the microtiter tetrazolium test correlated with a decreased G0/G1 peak in the DNA histograms. Serial FCM analysis showed that the decrease in the G0/G1 peak was subsequently accompanied by increased hypodiploid areas, suggesting DNA fragmentation induced by the agents. The in vitro chemosensitivity test and cell proliferation examination showed that all agents except cisplatin were effective. Growth retardation of inoculated brain tumors and prolonged survival of inoculated rats were observed with treatment with the anticancer agents, except cisplatin. CONCLUSION: The present study shows that FCM analysis with a DNA-binding dye can detect DNA damage induced by anticancer agents, and it suggests that this technique is a novel method to test chemosensitivity in vitro.

Animals↗
PubMed1997

Dirofilaria immitis: experimental infection of rabbits with immature fifth-stage worms.

To establish an animal model for human pulmonary dirofilariasis, we experimentally infected nine rabbits with immature fifth-stage worms of Dirofilaria immitis. The rabbits were infected by subcutaneous transplantation with various numbers of immature worms collected from 110- and 120-day-old infections of dogs. Four of seven rabbits infected with up to four larvae possessed encapsulated worms in the lungs at 196 or 308 days post-transplantation. Two rabbits transplanted with eight worms died of pulmonary hemorrhagic infarction 18 and 28 days post-transplantation. Marked histopathologic changes were observed in the lungs at the site of degenerating worms, which were encapsulated by a fibrous wall. Severe to mild infiltrations with eosinophils, heterophils, lymphocytes, plasma cells, and histiocytes were found in granulomas and their surrounding areas. The findings in these rabbits resemble those reported for human cases of pulmonary dirofilariasis.

Animals↗
PubMed1997

[The old and new problems of the antibiotics treatment in hemorrhagic enterocolitis and hemolytic uremic syndrome, according to Japanese epidemiological studies].

The treatment for hemorrhagic enterocolitis due to O157 E. coli infection has been discussed to prevent its aggravation to HUS, especially in terms of the effect of antibiotics. In June, 1996, massive outbreak of the infection occurred in Sakai city, Osaka, Japan. For the purpose of the prevention against secondary infection, antibiotics therapy was employed routinely in Sakai. The epidemiological results were as follows. A total of 25996 school children probably faced infection. Among them 4671 (admission 995) children became symptomatic and 102 developed HUS, leading the ratio of HUS versus symptomatic children to 2.18% which is significantly less than the average occurrence ratio of 4.0% at the same age group nationwide. We studied the possibility of lowering the incidence of HUS by the early diagnosis and the use of antibiotics. According to our survey(86-95), we examined 193 diarrhea associated HUS cases on the effect of antibiotics. There is no meaningful change despite treatment of antibiotics during enterocolitis stage in reducing the complication of HUS, but antibiotics therapy after the onset of HUS brought the prolongation of disease course. These two results were controversial, but the main factor might be the age difference between the two study groups. As previously reported, we could'nt propose the administration of antibiotics to the infants with hemorrhagic enterocolitis due to E. coli O157.

Adolescent↗
PubMed1997

Expression of glutathione-peroxidase (GSH-PO) in the rat ventral prostate--effect of castration and administration of testosterone.

Immunolocalization of glutathione-peroxidase (GSH-PO), apoptosis and bcl-2 protein in the rat ventral prostate was investigated in the presence or absence of androgen. Male Sprague-Dawley rats were divided into four experimental groups. Group 1 consisted of intact controls. In group 2, rats were sacrificed two days after castration. In groups 3 and 4, rats were administered subcutaneously 1 mg/animal of testosterone-propionate daily for three or seven days at two days after castration. The intensity of GSH-PO staining in the glandular epithelial cells of the ventral prostate was remarkably decreased after castration (Group 2), and it clearly recovered when testosterone was administered (Groups 3 and 4) to the castrated rats. The prostatic GSH-PO mRNA levels were diminished in the castrated rat ventral prostate but greatly increased by testosterone (Groups 3 and 4). Furthermore, castration (Group 2) induced apoptosis in the prostatic glandular epithelial calls and the apoptosis was reduced by testosterone-administration (Groups 3 and 4) to the castrated rats. In groups 3 and 4, expression of bcl-2 protein was clearly detected in the glandular epithelial cells of the ventral prostate. These findings strongly suggested that expression of GSH-PO and bcl-2 protein in the glandular epithelial cells of the rat ventral prostate is testosterone-dependent.

Animals↗