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Biomedical subjects

O Ueda

Publications and source records attributed to O Ueda.

At least 37 records · Page 2Linked to original sources
PubMed1997

A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.

Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.

Animals↗
PubMed1997

Cytomedical therapy for IgG1 plasmacytosis in human interleukin-6 transgenic mice using hybridoma cells microencapsulated in alginate-poly(L)lysine-alginate membrane.

Cytomedical therapy for human interleukin-6 transgenic mice (hIL-6 Tgm) was implemented by the intraperitoneal injection of alginate-poly(L)lysine-alginate (APA) membranes microencapsulating SK2 hybridoma cells (APA-SK2 cells) which secrete anti-hIL-6 monoclonal antibodies (SK2 mAb). IgG1 plasmacytosis in the hIL-6 Tgm was suppressed by a single injection of APA-SK2 cells, and the survival time of these mice was remarkably prolonged. The viable cell number and the SK2 mAb-secretion of APA-SK2 cells increased for at least one month both under culture conditions and in allogeneic recipients (in vivo). Moreover, SK2 mAb which were secreted from APA-SK2 cells injected into allogeneic recipients was detected in serum at high concentrations; 3-5 mg/ml from day 14 to day 50 post-injection. In contrast, the injection of free SK2 cells had no therapeutic effect on hIL-6 Tgm. These results strongly suggest that APA membranes microencapsulating cells which were modified to secrete molecules useful for the treatment of a disorder were effective as an in vivo long-term delivery system of bioactive molecules, as 'cytomedicine'.

Alginates↗
PubMed1997

Positive effect of partial zona-pellucida dissection on the in vitro fertilizing capacity of cryopreserved C57BL/6J transgenic mouse spermatozoa of low motility.

Although cryopreservation of mouse spermatozoa has recently become available for use, as yet there are considerable differences in fertilization efficiency of cryopreserved spermatozoa among various mouse strains. In this study, oocytes subjected to partial dissection of the zona pellucida (PZD) were inseminated with frozen-thawed C57BL/6J mouse spermatozoa. At 30, 60, 120, and 240 min after insemination, the oocytes were washed in human tubal fluid medium and cultured for 3-6 h. The fertilization rates of the PZD oocytes in each group at 6-7 h after insemination were significantly higher than that of the zona-intact control (73-88% vs 12%, respectively) (p < 0.01); but the incidence of polyspermy was nevertheless quite low (1.3-2.4%). The development rates of the monospermic oocytes to the morula and early blastocyst stages were in the 87-92% range, with 31-40% of those developing into offspring after embryo transfer. When the cryopreserved spermatozoa of C57BL/6J transgenic mice were used to fertilize PZD oocytes, the fertilization rates were as high as (73-76%) those of the PZD oocytes inseminated with the cryopreserved C57BL/6J spermatozoa, with 30-31% of the morulae and early blastocysts derived from the monospermatic oocytes developing into offspring. These results indicate that PZD of oocytes may provide an alternative when the fertilizing capacity of mouse spermatozoa has been compromised by cryopreservation.

Animals↗
PubMed1997

Therapeutic effect of cytomedicine on mesangio-proliferative glomerulonephritis in human interleukin-6 transgenic mice.

We previously demonstrated that IgG1 plasmacytosis in human interleukin-6 transgenic mice (hIL-6 Tgm) was suppressed by the implantation of SK2 hybridoma cells (SK2 cells, which secrete anti-hIL-6 monoclonal antibodies) microencapsulated in a semipermeable and biocompatible device. In this study, we demonstrated that the mesangio-proliferative glomerulonephritis in hIL-6 Tgm was also improved by the same treatment. These results strongly support the concept of cytomedicine, which is a novel drug delivery system (DDS) using living cells. However, an electron microscopy study showed that cytomedicine has a limited duration of effectiveness because of the disappearance of space for cell proliferation in the microcapsule. Thus, the control of cell proliferation in a device must be developed to prolong the function and effectiveness of cytomedicine.

Animals↗
PubMed1997

Germ-line contribution of embryonic stem cells in chimeric mice: influence of karyotype and in vitro differentiation ability.

The effect of the karyotype and the ability to differentiate in vitro upon germ-line transmission by A3-1 embryonic stem (ES) cells in chimeric mice were examined. Germ-line transmission was confirmed in ES cells exhibiting 38% and more of the normal karyotype, but no chimeric mice and/or germ-line transmitters were observed regardless of the karyotype when the cystic embryoid body (CEB) was formed on day 8 and later in the suspension culture. Germ-line transmission of the ES cells was not significantly influenced by formation of the simple embryoid body (SEB). Germ-line transmitters were preferentially observed in chimeras when the ES cell contribution to coat color was markedly increased, but this contribution to coat color varied regardless of the karyotype or in vitro differentiation ability. These results suggest that A3-1 ES cells which exhibit CEB at 7 days after suspension culture and approximately 40% of normal karyotype are capable of germ-line transmission in chimeric mice.

Animals↗
PubMed1996

A new transgenic mouse mutagenesis test system using Spi- and 6-thioguanine selections.

A new transgenic mouse mutagenesis test system has been developed for the efficient detection of point mutations and deletion mutations in vivo. The mice carry lambda EG10 DNA as a transgene. When the rescued phages are infected into Escherichia coli YG6020-expressing Cre recombinase, the phage DNA is converted into plasmid pYG142 carrying the chloramphenicol-resistance gene and the gpt gene of E. coli. The gpt mutants can be positively detected as colonies arising on plates containing chloramphenicol and 6-thioguanine. The EG10 DNA carries a chi site along with the red and gam genes so that the wild-type phages display Spi- (sensitive to P2 interference) phenotype. Mutant phages lacking both red and gam genes can be positively detected as plaques that grow in P2 lysogens of E. coli. These mutant phages are called lambda Spi-. The spontaneous gpt mutation frequencies of five independent transgenic lines were 1.7 to 3.3 x 10(-5) in bone marrow. When the mice were treated with ethylnitrosourea (single i.p. treatments with 150 mg/kg body weight; killed 7 days after the treatments), mutation frequencies were increased four- to sevenfold over the background in bone marrow. The average rescue efficiencies were more than 200,000 chloramphenicol-resistant colonies per 7.5 micrograms bone marrow DNA per packaging reaction. In contrast to gpt mutation frequencies, spontaneous Spi- mutation frequencies were 1.4 x 10(-6) and 1.1 x 10(-6) in bone marrow and sperm, respectively. No spontaneous Spi- mutants have been detected so far in spleen, although 930,000 phages rescued from untreated mice were screened. In gamma-ray-treated animals, however, induction of Spi- mutations was clearly observed in spleen, at frequencies of 1.4 x 10(-5) (5 Gy), 1.2 x 10(-5) (10 Gy), and 2.0 x 10(-5) (5O Gy). These results suggest that the new transgenic mouse "gpt delta" could be useful for the efficient detection of point mutations and deletion mutations in vivo.

Animals↗
PubMed1996

Further metabolism of 2-formylaminofluorene, a metabolite of 2-aminofluorene, in rats.

The further in vivo metabolism of 2-formylaminofluorene (FAF), which is a metabolite of 2-aminofluorene, was examined in rats. The 48 h urine collected following oral administration of FAF to rats was treated with beta-glucuronidase/arylsulfatase and extracted with benzene. When the benzene extract was subjected to HPLC, ten peaks due to FAF and its metabolites were detected. Among these metabolites, major metabolites 1, 2, 4 and 5 were isolated and identified unequivocally as 7-hydroxy-2-formylaminofluorene, 7-hydroxy-2-acetylaminofluorene, 5-hydroxy-2-formylaminofluorene and 5-hydroxy-2-acetylaminofluorene, respectively, by comparing their MS and UV spectra, and HPLC and TLC behavior with that of authentic specimens. Minor metabolites, 7-hydroxy-2-aminofluorene, 5-hydroxy-2-aminofluorene, 2-acetylaminofluorene and 2-aminofluorene together with the parent compound were detected by HPLC. These metabolites of FAF were also detected in the feces of rats given FAF.

Animals↗
PubMed1995

Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose.

Mice carrying a null mutation in the glucokinase (GK) gene in pancreatic beta-cells, but not in the liver, were generated by disrupting the beta-cell-specific exon. Heterozygous mutant mice showed early-onset mild diabetes due to impaired insulin-secretory response to glucose. Homozygotes showed severe diabetes shortly after birth and died within a week. GK-deficient islets isolated from homozygotes showed defective insulin secretion in response to glucose, while they responded to other secretagogues: almost normally to arginine and to some extent to sulfonylureas. These data provide the first direct proof that GK serves as a glucose sensor molecule for insulin secretion and plays a pivotal role in glucose homeostasis. GK-deficient mice serve as an animal model of the insulin-secretory defect in human non-insulin-dependent diabetes mellitus.

Alternative Splicing↗
PubMed1995

N-acetylation and N-formylation of carcinogenic arylamines and related compounds in dogs.

When sulfanilamide, p-aminobenzoic acid, 4-amino-biphenyl, 2-aminofluorene or 1-aminopyrene was given orally to dogs, the corresponding N-acetyl and N-formyl derivates were isolated from urine or feces. These metabolites were identified unequivocally by comparison with an authentic sample by UV and mass spectrometry and their behaviour in TLC and HPLC. Dog intestinal flora and several bacterial strains exhibited both N-acetylating and N-formylating activities, in varying degrees, toward all of the arylamines tested. The metabolites formed by the intestinal bacteria were also isolated and identified unequivocally. The results suggest that the intestinal microflora plays an important role in the formation of N-acyl derivatives from arylamines in dogs.

Acetylation↗
PubMed1995

Production of mice entirely derived from embryonic stem (ES) cell with many passages by coculture of ES cells with cytochalasin B induced tetraploid embryos.

Mice entirely derived from ES cells were obtained from aggregates of TT2 ES cells and cytochalasin B induced tetraploid embryos. Tetraploid embryos were cocultured with ES cells in a well on the Multiplate-Terasaki. After embryo transfer of the aggregates, the male newborns were recovered normally after Cesarean section and reached adulthood. The male mice exhibited complete pigmentation of the eye and coat, suggesting ES cell contributions alone. Alkaline phosphatase-1 analysis yielded no evidence of tetraploid cells in the kidney or liver. The TT2-derived males were fertile, produced normal offspring, and exclusively transmitted the TT2 genotype to their progeny. This result clearly shows that ES cells are able to support complete fetal development.

Animals↗
PubMed1995

[Fate of two different stages of embryos transferred to an identical recipient in mice].

To define the developmental fate of two different stages of embryos existing together in the mouse reproductive tract, different stages of fresh and frozen-thawed embryos were transferred separately into the oviducts of identical recipients. ICR and FvB embryos were flushed from the oviducts and/or uterus of superovulated females on Day 1 (2-4-cell stage) and Day 2 (8-cell-morula stage) of pregnancy. Day 1 embryos were transferred separately to the right or left oviduct of recipients, while the other oviduct received Day 2 embryos. There were no significant differences between Day 1 and Day 2 embryos with respect to the number of implantation sites and live fetuses in either the fresh or frozen-thawed embryos. These results concerning to the embryonic stage were similar to those of control experiments, in which Day 1 or Day 2 embryos were transferred to both right and left oviducts of recipients. Furthermore, no strain differences were observed in this study. No developmental retardation or anomalies were observed in fetuses derived from either Day 1 or Day 2 embryos. The embryo transfer in this study revealed that differences in developmental stage at preimplantation were synchronized by the maternal uterine environment.

Animals↗
PubMed1993

[An application of in vitro fertilization--embryo culture--embryo transfer system on the drug safety evaluation: fertility test of male mice administered with the anticancer drug].

We examined an application of in vitro fertilization--embryo culture--embryo transfer system for reproductive and developmental study on the drug safety evaluation in mice. The male mice at 10 weeks of age were administered intravenously with a single dose of 75 mg/kg of the anticancer platinum complex (DWA 2114R) which inhibits DNA synthesis. Four to six weeks after administration, the males were mated with the superovulated females. Fertilization rates were significantly lower than the controls at each weeks after the administration. Furthermore, delayed formation of pronucleus was observed as compared with the control. Four weeks after administration, the preimplantation development to blastocyst stage of those embryos in vitro and the survival rates on the day 17 of gestation after embryo transfer suggested that a DNA synthesis in germ cells during maturation was inhibited and/or prevented by DWA 2114R. The results of in vitro fertilization reflected its sperm concentration rather than the administration of DWA 2114R. Thus, an analysis of the delayed formation of pronucleus observed fertilization in vivo could not done in detail. To use for the drug safety evaluation, there exist plenty of room for improvement in this system. These results have showed that the embryo culture and the embryo transfer are useful techniques as the reproductive and developmental study on the drug safety evaluation. These techniques bring additional informations on the pre- and post-implantation development in vivo.

Animals↗
PubMed1992

[Lymphoid infiltration of colon cancer and clinical significance of the skin test].

It was reported that lymphoid infiltration (LI) of colon cancer tended to be found more commonly in patients with colonic cancer in an early stage than in an advanced stage. This time, the correlation among LI of colon cancer, cell-mediated immunity and the cumulative 5-year survival rate was studied in 124 patients with resected colon cancer. The results were as follows: 1) The cumulative 5-year survival rate in patients with positive LI was higher than that in the patients with negative LI. 2) There was correlation between the degree of LI of the cancer and Su-PS skin reaction. 3) Postoperative cell-mediated immunity was reduced in the cases of poor prognosis. Therefore we insist on paying attention to immunochemotherapy for 24 months after surgery.

Colonic Neoplasms↗
PubMed1991

[Cardiopulmonary support in PTCA for severe coronary artery disease: its efficacy].

Percutaneous transluminal coronary angioplasty (PTCA) assisted by cardiopulmonary femorofemoral bypass was performed in 4 patients who were considered to be candidates for this technique because of their severe coronary artery diseases, including 2 with left main trunk disease, one with cardiogenic shock, and one with severe 3-vessel disease. Here we report the efficacy of cardiopulmonary support in PTCA. Case 1: An 85-year-old man with persistent unstable angina despite maximal doses of medications. Stenosis of the left anterior descending coronary artery (90%) was resolved by PTCA with cardiopulmonary bypass and intraaortic balloon pumping (IABP). Case 2: An 83-year-old man with unstable angina had high grade stenoses in the distal left main, left anterior descending and right coronary arteries. Although IABP was instituted for sustained chest discomfort and ST depression, the patient developed congestive heart failure. PTCA of the left main coronary artery with cardiopulmonary bypass was successfully performed. Case 3: A 64-year-old man with acute myocardial infarction. PTCA of the occluded left anterior descending coronary artery resulted in shock despite IABP, which was resolved by cardiopulmonary bypass with percutaneous insertion of cannulae, the technique we developed. Case 4: A 74-year-old man with unstable angina. He had a severe 3-vessel disease and a thrombus in the right coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Intracoronary administration of ergonovine maleate for detecting vasospastic angina; one dose method].

Coronary spasm is an important etiologic mechanism in the pathogenesis of myocardial ischemia. Provocative test of coronary spasm during coronary arteriography is clinically useful. The ergonovine test has gained widespread use, and we have examined the efficacy and safety of intracoronary ergonovine application with a fixed dose of 16 micrograms. We studied 119 patients undergoing coronary arteriography. Coronary spasm was induced in 34 cases by intracoronary administration of 16 micrograms of ergonovine maleate. Coronary spasm was readily resolved by intracoronary administration of isosorbide dinitrate. None of the cases negative to the intracoronary ergonovine applications could be induced by additional systemic administration of 0.4 mg of ergonovine. Side effects of ergonovine such as elevation of blood pressure, headache and chest symptoms were infrequent in the intracoronary ergonovine test. We conclude that our method of intracoronary ergonovine application is sensitive and safe for the diagnosis of coronary spasm.

Aorta↗
PubMed1990

Percutaneous transluminal coronary angioplasty with cardiopulmonary bypass for stenosis of the most proximal part of the left anterior descending coronary artery.

An 85 year old man with unstable angina pectoris was treated successfully with percutaneous transluminal coronary angioplasty supported by cardiopulmonary bypass and intra-aortic balloon pumping. Coronary angiography had shown stenoses in both the left main stem and left anterior descending coronary arteries. Drug treatment had been ineffective and he was too old for coronary arterial bypass grafting.

Aged↗