Biomedical subjects

Yuji Oshima

Publications and source records attributed to Yuji Oshima.

34 records · Page 2Linked to original sources

PubMed2004

Fertilization success and sexual behavior in male medaka, Oryzias latipes, exposed to tributyltin.

We evaluated the effects of tributyltin (TBT), polychlorinated biphenyls (PCBs), and a mixture of TBT and PCBs on reproduction, gonadal histology, and sexual behavior in Japanese medaka (Oryzias latipes). We administered TBT (1 microg g(-1) body weight [b.w.] daily), PCBs (1 microg g(-1) b.w. daily), or both to medaka for 3 weeks. We assessed reproductive success during week 3 and the sexual behavior of male medaka after the exposure period. Fertilization success was significantly decreased in groups that received TBT. The profiles of fertility developed a bimodal distribution in the TBT and TBT+PCBs groups, and the numbers of males that performed "following" and "dancing" were significantly decreased in the TBT+PCBs group. The frequency of "dancing" also decreased after treatment with TBT, whereas fish that received PCBs only showed no difference in sexual behavior. Testes that had oocytes showed normal spermatogenesis, even though two of the five males treated with TBT+PCBs had some indication of testis-ova, which did not occur in any other group. Our results indicate that TBT, but not PCBs, affects sexual behavior and reproduction in medaka.

Animals↗

PubMed2004

Effect of maternal exposure to tributyltin on reproduction of the pearl oyster (Pinctada fucata martensii).

We examined the effect of tributyltin (TBT) on reproduction of the pearl oyster (Pinctada fucata martensii). In a maternal exposure test, five female pearl oysters were exposed to TBT at measured concentrations of 0 (control), 0.092, or 0.191 microg/L at 25 degreesC for one week, and the embryo developmental success (the ratio of normal D-larvae to all larvae) was measured. The embryo developmental success was significantly decreased in the 0.191-microg/L treatment group (65.5%) compared to that in the control group (82.5%; p = 0.031). Concentrations of TBT in the ovary reached 0.088 microg/g in the 0.191-microg/L treatment group. In a waterborne exposure test, inseminated eggs were exposed to TBT at measured concentrations of 0 (control), 0.020, 0.045, 0.091, 0.192, or 0.374 microg/L for 24 h. The embryo developmental success also was significantly decreased in the 0.192-microg/L treatment group (78.3%; p = 0.020) and no development at all was observed in the 0.374-microg/L treatment group compared with that in the control group (95.4%). These results clearly demonstrate that TBT accumulating in the bodies of bivalves has the potential to inhibit reproduction.

Animals↗

PubMed2004

Distribution of tributyltin, dibutyltin and monobutyltin in the liver, brain and fat of rats: two-generation toxicity study of tributyltin chloride.

The distribution of tributyltin (TBT) and its metabolites, dibutyltin (DBT) and monobutyltin (MBT), was examined in the liver, brain and fat tissues in a two-generation reproductive toxicity study of tributyltin chloride (TBTCl) in rats using dietary supplementation at concentrations of 5, 25 and 125 ppm. In the liver, irrespective of TBTCl dietary concentration, gender or generation, the highest concentration of metabolite was consistently MBT, followed by DBT, and then TBT. In contrast, TBT was consistently present at the highest concentration in the brain, nearly always followed by DBT and MBT. In fat tissues, the concentrations of the three butyltin compounds showed similar relationships to those observed in the brain, although the concentrations were much lower. In the liver, the concentration of TBT was higher in females, and those of DBT and MBT were higher in males. Factorial ANOVA also suggested the effect of gender on the concentrations of the three butyltin compounds in the liver. The results of this study suggest tissue-dependent distribution of TBT, DBT and MBT and gender-dependent distribution of the three metabolites in the liver of rats.

Adipose Tissue↗

PubMed2003

Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1.

Understanding molecular mechanisms regulating angiogenesis may lead to novel therapies for ischemic disorders. Hypoxia-inducible factor 1 (HIF-1) activates vascular endothelial growth factor (VEGF) gene expression in hypoxic/ischemic tissue. In this study we demonstrate that exposure of primary cultures of cardiac and vascular cells to hypoxia or AdCA5, an adenovirus encoding a constitutively active form of HIF-1alpha, modulates the expression of genes encoding the angiogenic factors angiopoietin-1 (ANGPT1), ANGPT2, placental growth factor, and platelet-derived growth factor-B. Loss-of-function effects were also observed in HIF-1alpha-null embryonic stem cells. Depending on the cell type, expression of ANGPT1 and ANGPT2 was either activated or repressed in response to hypoxia or AdCA5. In all cases, there was complete concordance between the effects of hypoxia and AdCA5. Injection of AdCA5 into mouse eyes induced neovascularization in multiple capillary beds, including those not responsive to VEGF alone. Analysis of gene expression revealed increased expression of ANGPT1, ANGPT2, platelet-derived growth factor-B, placental growth factor, and VEGF mRNA in AdCA5-injected eyes. These results indicate that HIF-1 functions as a master regulator of angiogenesis by controlling the expression of multiple angiogenic growth factors and that adenovirus-mediated expression of a constitutively active form of HIF-1alpha is sufficient to induce angiogenesis in nonischemic tissue of an adult animal.

Adenoviridae↗

PubMed2003

Intraocular expression of endostatin reduces VEGF-induced retinal vascular permeability, neovascularization, and retinal detachment.

Endostatin, a proteolytic fragment of collagen XVIII, is an endogenous inhibitor of tumor angiogenesis that also inhibits choroidal neovascularization. In this study, we assessed the effects of increased intraocular expression of endostatin on vascular endothelial growth factor (VEGF)-induced changes in the retina. After subretinal injection of a pair of gutless adenoviral vectors (AGV) designed to provide tamoxifen-inducible expression of endostatin, diffuse endostatin immunoreactivity was induced thoroughout the retina by administration of tamoxifen. Induction of endostatin in double transgenic mice with doxycycline-induced expression of VEGF in the retina resulted in significant suppression of leakage of intravascular [3H]mannitol into the retina. The ability of endostatin to reduce VEGF-induced retinal vascular permeability was confirmed by using [3H]mannitol leakage and two other parameters, fluorescein leakage and retinal thickness, after subretinal injection of a bovine immunodeficiency lentiviral vector coding for endostatin (BIV-vectored endostatin, or BIVendostatin). Subretinal injection of BIVendostatin resulted in more discrete, less intense staining for endostatin in the retina than that seen with the inducible AGV system, which suggested lower levels and allowed visualization of sites where endostatin was concentrated. Endostatin staining outlined retinal blood vessels, which suggested endostatin binding to a component of vessel walls. More prolonged or higher level expression of VEGF in the retina resulted in neovascularization and retinal detachment, both of which were also significantly reduced by BIVendostatin. These data suggest that endostatin may be an endogenous inhibitor of vasopermeability as well as neovascularization. In patients with diabetic retinopathy, endostatin gene transfer may provide a way to decrease the risk of three causes of visual loss: macular edema, neovascularization, and retinal detachment.

Animals↗

PubMed2003

Suppression of sexual behavior in male Japanese medaka (Oryzias latipes) exposed to 17beta-estradiol.

Mating pairs of Japanese medaka (Oryzias latipes) received 17beta-estradiol (E2; dose, 3 and 30 microg/g body weight daily) in their diet and E2-free diet (control) for two weeks. The effect on reproductive success was assessed in the mating pairs, and sexual and nonsexual behaviors in the male were quantified. The fecundities of the E2-treated groups were reduced significantly (p < 0.05) compared with those of control, and the sexual behaviors (following, dancing, floating, and crossing) of male fish in response to prostaglandin F2alpha (PG)-injected E2-unexposed females were suppressed dramatically. While the fertility of spawned eggs and the frequencies of the nonsexual behaviors of resting and swimming in a straight line performed by male were unchanged in E2-exposed groups. Therefore, sexual behavior in male may be linked with reproductive success in mating pair of madaka exposed to E2. This assay for sexual behavior using PG may provide a useful tool for assessing the effect of endocrine-disrupting chemicals.

Animals↗

PubMed2003

Topical nepafenac inhibits ocular neovascularization.

PURPOSE: Topical nepafenac readily penetrates the cornea and is metabolized to amfenac, a potent cyclooxygenase (COX)-1 and COX-2 inhibitor. In this study, we tested the effect of topical nepafenac in three murine models of ocular neovascularization (NV). METHODS: A masked trial was performed to compare the topical effects of vehicle with one of several concentrations of nepafenac (0.01%, 0.03%, 0.1%, or 0.5%), 0.1% diclofenac, or 0.5% ketorolac tromethamine in mice with oxygen-induced ischemic retinopathy, mice with choroidal NV (CNV) due to laser-induced rupture of Bruch's membrane, or transgenic mice with increased expression of vascular endothelial growth factor (VEGF) in photoreceptors (rho/VEGF transgenic mice). RESULTS: Mice treated with 0.1% or 0.5% nepafenac had significantly less CNV and significant less ischemia-induced retinal NV than did vehicle-treated mice. Nepafenac also blunted the increase in VEGF mRNA in the retina induced by ischemia. In rho/VEGF transgenic mice, nepafenac failed to inhibit neovascularization. In additional studies, compared with vehicle-treated mice, mice treated with 0.1% or 0.03% nepafenac had significantly less CNV, whereas eyes treated with 0.1% diclofenac showed no significant difference. Mice treated with 0.5% ketorolac tromethamine for 14 days had high mortality, but when evaluated after 7 days of treatment showed no difference from mice treated with vehicle for 7 days. CONCLUSIONS: Topical nepafenac inhibits CNV and ischemia-induced retinal neovascularization by decreasing production of VEGF. The absence of effect in rho/VEGF transgenic mice is consistent with this mechanism. Topical nepafenac may provide an effective new treatment for ocular neovascularization. The excellent corneal penetration of nepafenac certainly plays an important role in this effect. It is possible that other antiangiogenic agents are also amenable to topical application after formulations are identified that maximize their corneal penetration. Because of the many advantages of the topical route of delivery, this is a possible topic for exploration.

Administration, Topical↗

PubMed2003

Effects of 4-nonylphenol on reproduction of Japanese medaka, Oryzias latipes.

We exposed mature Japanese medaka (Oryzias latipes) to 4-nonylphenol (4-NP) to elucidate its reproductive effects and estrogenic responses. For each treatment, eight breeding pairs were exposed for 3 weeks at measured 4-NP concentrations of 24.8, 50.9, 101, and 184 micrograms/L. Egg production of the pairs during the third week of exposure (15-21 d) was significantly decreased in the > or = 101-microgram/L treatment group, and fertility was significantly decreased in the 184-microgram/L group. Induction of testis-ova was observed in male fish at all 4-NP concentrations, whereas abnormality of spermatogenesis was found only in those receiving the 184-microgram/L treatment. The gonadosomatic index of the males in the 184-microgram/L group was also remarkably reduced. Hepatic vitellogenin (VTG) levels were significantly increased in both sexes receiving 4-NP treatments of > or = 50.9 micrograms/L. Overall, the lowest-observed effective concentrations (LOECs) of 4-NP for decreasing reproductive capacity (fecundity and fertility) and eliciting estrogenic responses (induction of testis-ova and VTG) were 101 and < or = 24.8 micrograms/L, respectively. The LOEC for reduced reproduction in medaka was at least four-fold greater than that required to elicit estogenic responses in male fish. Thus, we suggest that the estrogenic responses expressed in male fish are not responsible for the reduction in reproductive capacity.

Animals↗

PubMed2003

Effect of acute L-tryptophan exposure on the brain serotonergic system and behavior in the male medaka.

The aim of this study was to investigate the effect of exposure to L-tryptophan (TRP) on the metabolism of 5-hydroxytryptamine (5HT) and behavior of medaka. In the first experiment, the fish were exposed to a 0, 1, 2 or 4 g/l of TRP solution for 24 hr. Although no significant difference in the brain 5HT content was detected, 5-hydroxyindoleacetic acid (5HIAA), a major 5HT metabolite, increased in a dose-dependent fashion. In the second experiment, the fish were maintained in a 0 or 4 g/l of TRP solution for 28 hr, and then their behaviors were monitored. The fish reared in under TRP solution were divided into two groups and transferred to either fresh water or a TRP solution. The locomotion of the TRP-treated group significantly increased compared to the control group irrespective of water conditions. It was suggested that TRP exposure activated the brain 5HTnergic systems and stimulated behavior of medaka.

Animals↗

PubMed2003

Tributyltin causes masculinization in fish.

We examined the effect of tributyltin (TBT) on the sex differentiation process in genetically female Japanese flounder (Paralichthys olivaceus). The fish were fed an artificial diet containing tributyltin oxide (TBTO) at concentrations of 0.1 and 1.0 microg/g diet from 35 to 100 d after hatching, which includes the sex differentiation period. The ratio of sex-reversed males significantly increased to 25.7% of the flounder fed the 0.1 microg/g diet and to 31.1% of those fed the 1.0 microg/g diet compared with the control (2.2%). From morphological and histological examination of the fish in the TBT-treated groups, normal females had typical ovaries and sex-reversed males had typical testes. These results clearly demonstrated the masculinization of flounder exposed to TBTO. This is the first report of TBT inducing sex reversal in vertebrates.

Animals↗

PubMed2002

Targeted gene transfer to corneal stroma in vivo by electric pulses.

This study was conducted to develop a method of targeted gene transfer by electric pulses to a selected area of corneal stroma in vivo. Plasmid DNA with a green fluorescent protein (GFP) gene under a cytomegalovirus promoter was injected through the corneal pocket into the corneal stroma of the adult Brown Norway rat, and various intensities of electric pulses ranging from 10 to 30 V were delivered to the corneal epithelial side with an electric probe. Direct stereomicroscopy of the fluorescent using real-time imaging was used to determine in vivo gene expression on days 1, 2, 4, 6, 8, 10, 15, and 20 after gene transfer. Transgene expression was detected in the corneal stroma as early as day 1 and until day 15. The most intense expression was noted on days 4 and 6. Gene transfer was most effective using eight electric pulses of 20 V for 50 msec. Histologic study disclosed GFP expression in keratocytes within the targeted area. There was no apparent cell damage in the gene transferred cells. No apparent inflammation was found in the anterior chamber or trabecular cells when electric pulses less than 30 V were used. In summary, the present technique transferred the gene of interest to a highly selected area of corneal stroma with no apparent damage. This method will likely be useful not only for developing gene therapy for corneal diseases but also for corneal research in general.

Animals↗

PubMed2002

Effect of 17beta-estradiol on the reproduction of Japanese medaka (Oryzias latipes).

Estrogenic compounds such as 17beta-estradiol (E2) and its analogs are present in the aquatic environment and can adversely affect the reproductive systems of aquatic organisms. Although E2 has been detected at a maximum concentration of 64 ng/l in effluents of sewage treatment works (STWs), few reports address the associated effects on reproduction in fish. Therefore, we exposed adult medaka (Oryzias latipes) to mean measured E2 concentrations of 29.3, 55.7, 116, 227, and 463 ng/l for 21 d and assessed the effects on the egg number and fertility of paired medaka during the exposure period. In addition, we determined the hepatic vitellogenin (Vtg) concentration and histologically assessed the gonads of these fish. The number of egg produced and fertility of the paired medaka exposed to 463 ng/l E2 were significantly less compared with those of the control fish. Males in all treatment groups had developed testis-ova. Males treated with E2 concentrations = 55.7 ng/l contained relating great concentrations of hepatic Vtg. Therefore, although only the greatest E2 concentration tested in our study affected fecundity and fertility, effects of E2 were observed on induction of Vtg and testis-ova in male medaka exposed to environmentally relevant concentrations of E2.

Animals↗

PubMed2002

Critical role of photoreceptor apoptosis in functional damage after retinal detachment.

PURPOSE: Although apoptosis is assumed to play a pivotal role in retinal function loss, its mechanism and real influence on retinal function are still unclear. To investigate the relation between retinal function and apoptosis, we studied photoreceptor apoptosis in experimental retinal detachment (RD). METHODS: We induced RD by subretinal injection of sodium hyaluronate in Brown Norway rats. Apoptotic photoreceptors were detected by TdT-dUTP Terminal Nick-End Labeling (TUNEL). To evaluate the function of the detached retina, electroretinograms (ERGs) were taken on day 1, 3 with corneal electrodes and full-field stimulation. RESULTS: Apoptotic DNA fragmentation appeared 12 hours after RD, was most prominent on day 3, and decreased thereafter. The ERGs showed that the amplitudes of dark-adapted a-waves and light adapted 2 Hz b-waves decreased immediately after RD and continued to decrease over time. The administration of Fas/Fc chimera recombinant protein or a caspase inhibitor, Z-VAD.fmk, failed to prevent either photoreceptor apoptosis or retinal functional damage. In contrast, brain derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) significantly impeded both apoptosis and dysfunction. The ERGs recognized the functional changes sensitively, and these ERG changes correlated well to the amount of photoreceptor apoptosis. Immunohistochemical study showed that apoptosis-inducing factor (AIF), a novel caspase-independent apoptotic factor, was relocalized from mitochondria to the nucleus in this process. CONCLUSIONS: The present results showed that apoptosis was a key phenomenon in the retinal dysfunction in RD and that this process was transmitted mainly by mitochondria-dependent pathways rather than Fas/Fas-L or downstream caspase dependent pathways.

Animals↗

PubMed2002

Purification and identification of a tributyltin-binding protein from serum of Japanese flounder, Paralichthys olivaceus.

Tributyltin (TBT) is an industrial chemical used as an antifoulant in marine environments. Previously, we reported that TBT accumulates in the serum or plasma of some fishes and is bound to a high molecular weight compound in the serum of the Japanese flounder, Paralichthys olivaceus. In this study, we succeeded in purifying the TBT-binding protein (TBT-bp) from the serum of Japanese flounder by using gel filtration chromatography, anion exchange chromatography, and polyacrylamide gel electrophoresis, with a 2.6% yield and a 77-fold purification. The molecular mass of TBT-bp was approximately 46.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its isoelectric point was approximately 3.0 on isoelectric focusing-polyacrylamide gel electrophoresis. The TBT-bp contained 42% N-glycan. The cDNA nucleotide sequence of TBT-bp was determined by reverse transcription-polymerase chain reaction of Japanese flounder liver, and we deduced a sequence of 191 amino acids of mature TBT-bp. No sequence identical to the TBT-bp amino acid sequence was found within the SWISS-PROT (http://www.nig. ac.jp/) protein database; however, a lipocalin-like sequence pattern was observed. We concluded that the TBT-bp was a novel protein that has not yet been reported, although some DNA sequences from expressed sequence tags (ESTs) of Japanese flounder liver had a high identity. A high expression level of TBT-bp gene was found in the liver, but the gene was slightly detectable in the kidney and brain.

Amino Acid Sequence↗

PubMed2002

Effects of bisphenol a on the reproduction of Japanese medaka (Oryzias latipes).

We elucidated the effects of bisphenol A (BPA) on the reproductive capacity (fecundity and fertility) and estrogenic response of adult Japanese medaka (Oryzias latipes) and studied the transgenerational effects (F, generation growth and sex) of this agent on the F1 offspring. Eight mating pairs of medaka were exposed to BPA for three weeks at a measured concentration of 837, 1,720, or 3,120 microg/L. Throughout the exposure period, we observed no reduction of fecundity and fertility in any treatment group and no reduction in survival and growth or any imbalance of the sex ratio of the offspring. However, histologic examination revealed testis-ova in 13% of the males in the 837-microg/L treatment group, 86% of those in the 1,720-microg/L group, and 50% of those that received 3,120 microg BPA/L. In addition, concentrations of hepatic vitellogenin were increased significantly in males treated with BPA at 3,120 microg/L (p = 0.0148). These results suggest that BPA is a weakly estrogenic compound that has the potential to alter sexual development and induce vitellogenin in male medaka but that has no adverse effect on reproductive success.

Animals↗

PubMedDate not supplied

Progress in sigmoidectomy for cancer during the last 24 years in our department.

BACKGROUND/AIMS: In the treatment for colon cancer, changes may have taken place in areas such as surgical devices, concepts for basic strategies, composition of the medical team, postoperative management and adjuvant chemotherapy. No one knows the net effect of these alterations in treatment on sigmoid colon cancer patients. METHODOLOGY: A total of 147 patients were divided into 2 groups based upon the time of the surgery. Comparisons were made based upon the several parameters, including survival. In addition, to determine the effect of the degree of lymph node dissection on survival, patients were divided into 3 groups based upon the ligated portion of artery. RESULTS: Blood loss significantly decreased. Other factors were almost the same except for survival. In Dukes' A and B, 5-year survival rates were the same (90%). But in Dukes' C, the 5-year survival rate was better in the later period (90%) than in the earlier period (70%). In Dukes' C, the extent of lymph node dissection significantly influenced the survival. CONCLUSIONS: The parameters have not changed very much in these 24 years except for the 5-year survival rates in Dukes' C. The extent of lymph node dissection is probably sufficient just below the root of left colic artery.

Chemotherapy, Adjuvant↗