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Biomedical subjects

Minoru Tanaka

Publications and source records attributed to Minoru Tanaka.

At least 19 recordsLinked to original sources
PubMed2003

Targeted disruption of oncostatin M receptor results in altered hematopoiesis.

Oncostatin M (OSM) is a multifunctional cytokine that belongs to the interleukin 6 (IL-6) family. As OSM is expressed in adult as well as embryonic hematopoietic tissues, OSM has been considered to play a role in hematopoiesis. To uncover roles of OSM, we have generated mutant mice deficient in the OSM-specific receptor beta subunit (OSMR). While OSMR-/- mice were healthy and fertile, hematologic analysis of OSMR-/- mice demonstrated that the numbers of peripheral erythrocytes and platelets were reduced compared with wild-type mice. Consistent with this, progenitors of erythroid and megakaryocyte lineages were reduced in OSMR-/- bone marrow (BM), suggesting that OSM is required for the maintenance of erythroid and megakaryocyte progenitor pools in BM. To investigate whether OSM acts on the hematopoietic progenitors directly or indirectly, we performed BM transplantation experiments. The OSMR-/- mice, engrafted with wild-type BM cells, failed to produce erythrocytic and megakaryocytic progenitors to the levels in wild-type mice, indicating that OSM affects hematopoietic microenvironments. On the other hand, erythrocytic and megakaryocytic progenitors were reduced in the wild-type mice reconstituted with OSMR-/- BM cells. Thus, OSM regulates hematopoiesis in vivo by stimulating stromal cells as well as hematopoietic progenitors, in particular megakaryocytic and erythrocytic progenitors.

Animals↗
PubMed2003

Determination of 4-alkylphenols by novel derivatization and gas chromatography-mass spectrometry.

A simple and sensitive method for the determination of alkylphenols in water samples has been developed using gas chromatography-mass spectrometry. Alkylphenols were determined after the extractive derivatization with pentafluoropyridine. The derivatization of alkylphenols efficiently proceeded to give the corresponding 4-tetrafluoropyridyl derivatives under the biphasic reaction system. The derivatization conditions including the phase-transfer catalyst, the amount of pentafluoropyridine, the reaction time, the concentration of NaOH and organic solvent were optimized. On the mass spectra of these derivatives, intense specific ion peaks were observed: m/z 256 for 4-n-alkylphenols and m/z 284 for 4-tert.-alkylphenols. Calibration curves were linear in the range of 20-1000 ng/l (200-10,000 ng/l for nonylphenol), and the detection limits varied between 6.93 and 15.7 ng/l (85.2 ng/l for nonylphenol). The average recoveries of the alkylphenols in a fortified river water sample (100 ng/l except for nonylphenol: 1000 ng/l) ranged from 91.1 to 112%. The relative standard deviations were found to be between 5.6 and 16%. This method was successfully applied to the determination of alkylphenols in river water.

Calibration↗
PubMed2003

Oxidative DNA damage induced by toluene is involved in its male reproductive toxicity.

Toluene is widely used as an organic solvent in various industries and commercial products. Recent investigations have shown that toluene may induce male reproductive dysfunctions and carcinogenicity. To clarify whether the toxicity results from the interference of endocrine systems or direct damage to reproductive organs, we examined the effects of toluene on the male reproductive system in rats, comparing to those of diethylstilbestrol (DES), a potent synthetic estrogen. Toluene (50, 500 mg/kg) or DES (2 mg/kg) injected subcutaneously to male Sprague-Dawley rats once a day for 10 days decreased the epididymal sperm counts and the serum concentrations of testosterone. The mRNA level for gonadotropin-releasing hormone receptor in the pituitary was decreased by DES, but not by toluene. On the contrary, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in testes, the biological marker for oxidative DNA damage, was increased by toluene but not by DES. These results suggest that toluene induces reproductive toxicity via direct oxidative damage of spermatozoa, whereas DES affects endocrine systems via the hypothalamo-pituitary-gonadal axis. Morphological findings supported the idea. To determine the mechanism of 8-oxodG formation in vivo, we examined DNA damage induced by toluene metabolic products in vitro. Minor toluene metabolites, methylhydroquinone and methylcatechols, induced oxidative DNA damage, and the methylcatechols induced NADH-mediated 8-oxodG formation more efficiently than methylhydroquinone did. We propose that oxidative DNA damage in the testis plays a role in reproductive toxicity induced by toluene.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Penetrating keratoplasty surgery combined with vitrectomy after failing previous corneal surgery.

PURPOSE: The preoperative and postoperative factors influencing visual outcome were analyzed in 15 eyes of 15 patients with graft opacity after keratoplasty associated with vitreoretinal disease who underwent combined surgery of fresh corneal retransplantation and vitrectomy. MATERIALS AND METHODS: The data obtained consisted of diagnosis, preoperative visual acuity, corneal and vitreoretinal findings at the time of surgery, interval between the first visit and surgery, intraocular pressure before surgery, gonioscopic findings, results of bacterial culture of surgical specimens, surgical procedure for vitrectomy, corneal and vitreous findings after surgery, visual acuity 6 months after surgery, intraocular pressure after surgery, and additional surgical techniques. RESULTS: The cause of corneal opacity was graft rejection in all patients, who had been treated with high-dose administrations of steroids and cyclosporin. The preoperative diagnosis was proliferative vitreoretinopathy (PVR) in eight eyes and fungal endophthalmitis in seven eyes. Corneal transparency was achieved in 7 eyes (46.6%) 6 months after surgery. Vitreoretinal findings improved in 9 eyes (60%) and PVR recurred in 6 eyes (40%). Visual acuity improved in 7 eyes (46.6%), did not change in 2 eyes (13.3%), and deteriorated in 6 eyes (40%). The six eyes with decreased visual acuity developed phthisis bulbi. Preoperative intraocular pressure was 2.1 mmHg on average in the phthisis bulbi group, significantly lower than in the group with superior prognosis. Goniosynechia was noted before surgery and did not improve after surgery in all six eyes. CONCLUSIONS: The outcome was poor in eyes with goniosynechia and ocular hypotony, and combined surgery is not indicated for either anatomic or visual preservation in such cases. Care should be taken not to overlook intraocular infection in patients undergoing immunosuppressive therapy against graft rejection. The early detection of retinal detachment is also important in eyes exhibiting hypotony after surgery.

Adult↗
PubMed2002

Molecular cloning and characterization of DMRT genes from the medaka Oryzias latipes and the platyfish Xiphophorus maculatus.

The DMRT genes constitute a family of genes, which possess a common motif called the DM domain. DMRT1 is considered to be involved in sex determination and/or sex differentiation, but not much information exists about the function of the other gene family members. We cloned DMRT genes of two important model fish species, the medaka, Oryzias latipes, and the platyfish, Xiphophorus maculatus. Based on sequence similarity and genomic structure with known DMRT genes, the gene from the medaka was identified as OlaDMRT4, and those from the platyfish as XmaDMRT2 and XmaDMRT4. OlaDMRT4 was assigned to the linkage group 18 (LG18) of the medaka by linkage analysis and fluorescence in situ hybridization. The earlier cloned medaka DMRT1, 2 and 3 genes form a cluster on LG9. Therefore, OlaDMRT4 does not belong to the DMRT gene cluster. In adult medaka fish, OlaDMRT4 is expressed in the brain, eyes, gill, kidney, as well as testis and ovary. During development, OlaDMRT4 exists as maternal transcripts, and is expressed until early larval stages. This pattern of expression differs from the other known medaka DMRT genes. Surprisingly it is also not the same as its putative tilapia ortholog (DMO). These differences in expression suggest that DMRT4 might fulfill divergent functions in different species.

Animals↗
PubMed2002

IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions.

Atopic dermatitis (AD) is a pruritic inflammatory skin disease. Because IL-18 directly stimulates T cells and mast cells to release AD-associated molecules, Th2 cytokines, and histamine, we investigated the capacity of IL-18 to induce AD-like inflammatory skin disease by analyzing KIL-18Tg and KCASP1Tg, which skin-specifically overexpress IL-18 and caspase-1, respectively. They spontaneously developed relapsing dermatitis with mastocytosis and Th2 cytokine accumulation accompanied by systemic elevation of IgE and histamine. Stat6-deficient KCASP1Tg displayed undetectable levels of IgE but manifested the same degree of cutaneous changes, whereas IL-18-deficient KCASP1Tg evaded the dermatitis, suggesting that IL-18 causes the skin changes in the absence of IgE/stat6. KIL-18Tg and IL-1-deficient KCASP1Tg took longer to display the lesion than KCASP1Tg. Thus, AD-like inflammation is initiated by overrelease of IL-18 and accelerated by IL-1. Our present study might provide insight into understanding the pathogenesis of and establishing therapeutics for chronic inflammatory skin diseases including AD.

Animals↗
PubMed2002

Analysis of organotin compounds by grignard derivatization and gas chromatography-ion trap tandem mass spectrometry.

The determination of organotin compounds in water using gas chromatography-tandem mass spectrometry (GC-MS-MS) is described. Several organotin derivatives were synthesized by the reaction of organotin chlorides with Grignard reagents such as methyl-, propyl- and pentylmagnesium halides. After the optimization of the GC-MS-MS conditions, several derivatizations with the Grignard reagents were compared by evaluating the molar responses and volatilities of the derivatives and derivatization yields. As a result, the derivatizing reagent of choice is pentylmagnesium bromide. Calibration curves for the mono-, di- and tributyltins and mono-, di- and triphenyltins with pentylmagnesium bromide were linear in the range of 0.5-100 pg of Sn. The instrumental detection limits of six organotins ranged from 0.20 to 0.35 pg of Sn. The recovery tests from water samples (500 ml) were performed by using sodium diethyldithiocarbamate (DDTC) as a complexing reagent. Except for monophenyltin, the absolute recoveries of organotins from pure water at 200 ng of Sn/l were satisfactory. The recoveries calibrated by surrogate compounds (perdeuterated organotin chlorides) ranged from 71 to 109%. The method detection limits ranged from 0.26 to 0.84 pg of Sn (500-ml sample). This method was applied to the recovery of organotins from river water and seawater. The calibrated recoveries were between 90 and 122%.

Calibration↗
PubMed2002

Structural characterization of GnRH loci in the medaka genome.

To help clarify the origin of a third gonadotropin-releasing hormone (GnRH) paralog found only in the teleost lineage, we have characterized GnRH loci in a teleost species, the medaka Oryzias latipes, and compared corresponding regions of the medaka and human genomes. Three GnRHs for medaka-type GnRH (mdGnRH), chicken-II-type GnRH (cGnRH-II), and salmon-type GnRH (sGnRH) exist as single-copy genes and reside on separate chromosomes in the medaka genome. Both medaka mdGnRH and human mGnRH are closely linked to FLJ20038 encoding a hypothetical protein, and both cGnRH-IIs in the medaka and humans are adjacent to PTP(alpha) for protein tyrosine phosphatase alpha. These conserved syntenies demonstrate that mdGnRH and cGnRH-II in teleosts are orthologous to mGnRH and cGnRH-II in tetrapods, respectively. On the other hand, the third paralogous GnRH in the medaka, sGnRH, is adjacent to PTP(epsilon), a paralog of PTP(alpha). Although humans possess PTP(epsilon) on 10q26, no sGnRH-like sequence was found in the human genome databases. Therefore a gene duplication that gave rise to the third paralogous GnRH likely occurred before the divergence of teleosts and tetrapods, and it has been lost only in the tetrapod lineage. Additionally, together with the prior observations that like GnRH, PTP(alpha)/PTP(epsilon) are strongly expressed in neural and tumor cells and that GnRH can increase PTP activity, the current data suggests that the physically linked cGnRH-II/sGnRH and PTP(alpha)/PTP(epsilon) are also functionally linked.

Amino Acid Sequence↗
PubMed2002

Conserved physical linkage of GnRH-R and RBM8 in the medaka and human genomes.

Candidate genes for human type II gonadotropin-releasing hormone receptor (GnRH-RII) reside on two separate loci, 1q12-q21 and 14q21-23, yet neither locus generates functional GnRH-RII. Instead, their opposite DNA strands encode functional RNA-binding motif protein 8 (RBM8s), which is also encoded by another locus, 5q13-q14. To elucidate the mechanism through which such multiple human GnRH-RII/RBM8 loci arose, here we have defined an RBM8 locus in a comparative model species, the medaka Oryzias latipes. The medaka RBM8, which exists as a single copy gene, is linked to, but does not overlap with, GnRH-R2 on linkage group (LG) 16, demonstrating the ancient origin of the physical linkage between GnRH-R and RBM8. The medaka LG 16 contains orthologous segments to the human chromosome 1 and therefore the 1q12-q21 locus would be an originating human GnRH-RII/RBM8 segment. Furthermore, like the human RBM8s on 1q12-q21 and 5q13-q14 but not that on 14q21-q23, the medaka RBM8 is a multiexon gene, indicating that the 14q21-q23 and 5q13-q14 loci were generated by retrotransposition and segmental genomic duplication, respectively, of the originating 1q12-q21 locus.

Amino Acid Sequence↗
PubMed2002

Sox9 in a teleost fish, medaka (Oryzias latipes): evidence for diversified function of Sox9 in gonad differentiation.

Sox9 is a transcription factor containing the Sry-related high-mobility-group (HMG) box. Mutations in human SOX9 gene cause skeletal defects and male-to-female sex reversal, indicating its essential roles in chondrogenesis and testis development. Comparative studies have shown that Sox9 is expressed in chondrogenic tissues and testis in other vertebrates. Therefore, it was suggested that roles of Sox9 in cartilage and male gonad development are conserved among vertebrates. To investigate the evolutional significance of Sox9 in the gonad and cartilage development of teleost fish, we isolated medaka sox9 and analyzed its expression. Two kinds of transcripts (sox9 and sox9lf) were isolated by cDNA library screening. The sox9 encoded 487 amino acids and showed approximately 70% amino acid identity with known vertebrate SOX9 proteins. The sox9lf was a longer form of the sox9, which was transcribed from an additional exon in the 5' upstream region. Interestingly, the expression of medaka sox9 was predominantly observed in the adult ovary by northern blot and in situ hybridization analyses, whereas in the testis, its expression was detectable only by RT-PCR. During medaka embryogenesis, its expression was observed in the cranial cartilage and pectoral fin endoskeleton. These observations suggest that the function of Sox9 in the cartilage is conserved among vertebrates, while that in the gonad is quite different in medaka.

Amino Acid Sequence↗
PubMed2002

Developmental expression pattern of oncostatin M receptor beta in mice.

Oncostatin M (OSM), which is predominantly expressed in bone marrow, is a member of the interleukin-6 family of cytokines, and appears to play important roles in hematopoiesis and the development of the liver. Recently, specific beta subunit of OSM receptor (OSMRbeta) was isolated from LO cells originated from aorta-gonad-mesonephros (AGM) region. In this study, we performed in situ hybridization to explore the expression pattern of OSMRbeta during murine embryogenesis, postnatal development, and in adult tissues. At 11.5 days postcoitum (dpc), the expression of OSMRbeta was first detected in aortic endothelial cells of the AGM region. At 14.5dpc, its gene expression was clearly observed in the primordia of some organs, including liver, thymus, choroid plexus, and limb, and persisted into postnatal mice. After birth, its gene expression became detectable in the other organs, such as lymph node, bone, heart, kidney, small intestine, nasal cavity, and lung.

Animals↗
PubMed2002

Teleost ovarian carbonyl reductase-like 20beta-hydroxysteroid dehydrogenase: potential role in the production of maturation-inducing hormone during final oocyte maturation.

17alpha,20beta-Dihydroxy-4-pregnen-3-one is the major oocyte maturation-inducing hormone of several teleost species. Gonadotropin-induced increase in ovarian 20beta-hydroxysteroid dehydrogenase activity is essential for the synthesis of maturation-inducing hormone. Cloning and expression studies suggest that ayu (Plecoglossus altivelis) ovarian carbonyl reductase can function as 20beta-hydroxysteroid dehydrogenase. The amino acid sequence deduced from the isolated cDNA had 276 amino acid residues and shared approximately 60% homology with mammalian and teleostean carbonyl reductases. The sequence data search showed that the ayu cDNA clone belongs to the short-chain dehydrogenase/reductase family. The clear lysate prepared from Escherichia coli harboring the cDNA catalyzed the production of maturation-inducing hormone. Its identification was confirmed by two-dimensional, thin-layer chromatography followed by recrystallization. Purification of the E. coli-expressed cDNA product revealed that it possessed both carbonyl reductase and steroid dehydrogenase activities, and 17alpha-hydroxyprogesterone, the endogenous immediate precursor of maturation-inducing hormone, was one of the preferred substrates. Furthermore, Northern blot analysis denoted that the transcripts are present both in fully grown, immature ovarian follicles and at higher levels in mature ovarian follicles. These results demonstrate that the carbonyl reductase of ayu ovary is involved in the production of maturation-inducing hormone, and they provide evidence for a novel physiological role of this enzyme in the final maturation of oocytes. Based on its functional properties, the enzyme can be referred to as carbonyl reductase-like 20beta-hydroxysteroid dehydrogenase.

Alcohol Oxidoreductases↗
PubMed2002

Identification of a novel first exon of prolactin receptor gene expressed in the rat brain.

A novel first exon, E1(4), whose sequence was distinct from those of the three known first exons, E1(1), E1(2), and E1(3), of the rat PRL receptor (PRL-R) gene was identified by cDNA cloning for the 5'-end region of PRL-R mRNA expressed in the rat brain. Sequence analysis revealed the presence of two different length E1(4) cDNAs. The longer cDNA contained the 243-bp E1(4) sequence, and the shorter cDNA lacked the 139-bp sequence at the 5'-end of the longer one. Neither E1(4) cDNA has a second exon sequence, indicating that the E1(4) first exon is extensively spliced to the third exon. E1(4)-containing PRL-R mRNAs were detected only in the brain by RT-PCR and ribonuclease protection assay. The longer E1(4) mRNA was expressed as the major PRL-R mRNA species in the brain and was greatly increased in pregnant (d 18) and lactating (d 5) rats. A genomic clone containing the E1(4) first exon together with its 5'- and 3'-flanking regions was isolated from a rat kidney genomic library. Ribonuclease protection assay revealed that the position corresponding to the 5'-end of the shorter E1(4) cDNA is the major transcription start point for the E1(4) exon. The 5'-flanking region of E1(4) contained a TATA box-like element 23 bp upstream of the major transcription start point. Other putative transcription factor-binding sites, such as CCAAT, Sp1, and glucocorticoid-responsive elements, were observed at further upstream regions. These results suggest that PRL-R gene expression in rat brain is controlled by the promoter for the E1(4) first exon.

Animals↗
PubMed2002

Exercise training increases the activity of pyruvate dehydrogenase complex in skeletal muscle of diabetic rats.

The effects of diabetes and exercise training on the activity of pyruvate dehydrogenase (PDH) complex in skeletal muscle were examined in rats. Male Sprague-Dawley rats were divided into four groups as follows: non-diabetic sedentary, non-diabetic trained, diabetic sedentary, and diabetic trained groups. Diabetic rats were prepared by a bolus injection of intravenous streptozotocin (50 mg/kg body weight). Exercise training was performed by having rats run on a treadmill at a speed of 25 m/min for 45 min/day, 6 days/wk for 4 wks. Exercise training decreased serum concentrations of glucose and non-esterified fatty acid in diabetic rats. GLUT4 content in skeletal muscle in sedentary rats was significantly decreased by diabetes; however, exercise training significantly increased the GLUT4 content in diabetic rats. The total and actual activities and the proportion of actual activity of the PDH complex were decreased in diabetic sedentary rats. Exercise training did not affect the total activity of the PDH complex in non-diabetic rats, whereas it increased the total activity in diabetic rats to the same level as that in non-diabetic rats. In diabetic rats, exercise training tended to increase the proportion of actual activity of the PDH complex from 2.7 +/- 0.4% to 4.7 +/- 0.8%, although the proportion of actual activity in non-diabetic rats was decreased by exercise training. The present study suggests that exercise training may improve glucose metabolism in the skeletal muscle of streptozotocin-induced diabetic rats probably through the mechanisms of increasing both GLUT4 content and the activity of the PDH complex.

Animals↗
PubMed2002

A graft-versus-tumor effect in a patient with ependymoma who received an allogenic bone marrow transplant for therapy-related leukemia. Case report.

Graft-versus-leukemia effect is an immune-mediated antitumor phenomenon associated with allogenic bone marrow transplants (BMTs) for hematological malignancies, and recent findings have indicated that a similar effect could occur in some solid tumors such as breast cancers. The authors report on a 42-year-old man with a recurrent ependymoma who received an allogenic BMT for therapy-related leukemia. After transplantation, the patient developed chronic graft-versus-host disease, which was controlled with steroid agents. Interestingly, the recurrent ependymoma regressed steadily over the next 21 months posttransplant, until the tumor became almost undetectable on magnetic resonance images. This case indicates that the graft-versus-tumor effect, mediated by cytotoxic T cells, may be able to target intraparenchymal neuroepithelial tumors, despite the brain's generally recognized status as an immunoprivileged organ.

Adult↗
PubMedDate not supplied

Multifunction vitreous forceps (maculorrhexis forceps).

We developed novel multifunction vitreous forceps to decrease the frequency of forceps insertion and enable the removal of the internal limiting membrane and other intravitreal membranes for better surgical results. The basic forceps were conventional continuous curvelinear capsulorrhexis (CCC) forceps. The size of the shaft is 23G and its pointed end measures 500 microm in diameter. Additionally, there is a platform in its tip. The pointed end with platform helps to hold the membrane because the outer sheath can be moved while the tip of the forceps is fixed in position, and its pen hold type grip helps to reduce hand movement. The most advantageous thing is that the sharp point enables us to make an initial flap easily and the desired area of internal limiting membrane can be peeled off by firmly holding the platform.

Capsulorhexis↗
PubMedDate not supplied

Efficacy of daunorubicin encapsulated in liposome for the treatment of proliferative vitreoretinopathy.

BACKGROUND AND OBJECTIVE: To investigate the efficacy of daunorubicin encapsulated in liposome as a drug delivery system to treat proliferative vitreoretinopathy (PVR). MATERIALS AND METHODS: An experimental PVR model was made in pigmented rabbits by injecting a suspension of conjunctival fibroblasts and platelet-rich plasma into the vitreous cavity. Daunorubicin was encapsulated in newly developed empty liposome by mixing the empty liposome with the drug solution. Studies were performed 24 hours, 1 week, and 1 month after injection of daunorubicin encapsulated in empty liposome in an experimental PVR model. RESULTS: Compared with the control PVR model, daunorubicin prevented the formation of PVR. Although pathologic changes were observed in the eyes injected with daunorubicin alone, there were no adverse effects observed in the eyes injected with daunorubicin encapsulated in empty liposome. CONCLUSIONS: Daunorubicin encapsulated in empty liposome seems to be effective in preventing PVR without causing any adverse effects to the retina.

Animals↗