Genital tract development in peripubertal female CD IGS rats.
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Aging↗
Biomedical subjects
K Shinoda
Publications and source records attributed to K Shinoda.
Clinical characteristics of 14 japanese patients with X-linked juvenile retinoschisis associated with XLRS1 mutation.
To characterize the clinical features associated with XLRS1 gene mutations in Japanese patients with X-linked juvenile retinoschisis (xlRS), we evaluated the following data on 14 Japanese males from 13 unrelated families with XLRS1 mutations: age and symptoms at first visit to an ophthalmologist and ophthalmologic findings including visual acuity, refractive errors, fundoscopic appearance, and results of electroretinography (ERG) and electro-oculography (EOG). Each clinical finding was reviewed when the patients were between six and eight years of age. The best-corrected visual acuity in 12 patients (24 eyes) between the ages 6 and 8 years ranged from 1.0 to no light perception. Macular abnormalities were present in all cases. Peripheral retinoschisis was present in 14 of 26 eyes (53.8%). In the 21 eyes for which a single-flash ERG had been recorded, b-wave amplitude was reduced in 17 eyes. The EOG showed a low Arden ratio in three of the 13 eyes in the seven patients evaluated. No clear relationship was observed between the clinical features and the existing mutations. Three of four patients with a visual acuity less than 0.1 had retinal detachment or severe macular lesion that had occurred before the age of four years. Two patients harbored deletions of exon 1 or of the boundary region between exon 3 and intron 3, and one patient harbored R182C in exon 6. The present study shows a heterogeneity of mutations in the XLRS1 gene and phenotypic variations in 14 Japanese patients with xlRS.
Adolescent↗
Clinical factors related to the aqueous levels of vascular endothelial growth factor and hepatocyte growth factor in proliferative diabetic retinopathy.
PURPOSE: To investigate clinical factors related to the aqueous humor levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in patients with proliferative diabetic retinopathy (PDR). METHODS: Undiluted aqueous humor was obtained during ocular surgery from 46 eyes of 46 patients and the levels of growth factors were measured using enzyme-linked immunosorbent assays. VEGF and HGF levels were compared with the number of photocoagulation. VEGF and HGF levels in patient groups stratified according to the existence of vitreous hemorrhage, retinal detachment, and fibrovascular membrane were analyzed. And clinical parameters associated with the growth factors were determined by multiple regression analysis. RESULTS: The levels of VEGF decreased significantly as the extent of photocoagulation increased and showed significant positive correlation with the existence of vitreous hemorrhage. There was no significant correlation between VEGF levels and the existence of fibrovascular membrane and traction retinal detachment. The levels of HGF also decreased significantly as the extent of photocoagulation increased, but increased significantly when fibrovascular membrane existed. There were no significant correlations between HGF levels and the existence of vitreous hemorrhage and traction retinal detachment. Concerning systemic conditions, each growth factor has no significant correlation with duration and type of diabetes mellitus, the treatment regimen, the control of hemoglobin A1C, and the existence of hypertension or renal dysfunction. CONCLUSION: The therapeutic effect of panretinal photocoagulation on PDR might be partly exerted by reduction of the levels of VEGF and HGF in ocular fluid. Since the clinical parameters associated with VEGF were different from those associated with HGF, these growth factors might influence the progression of retinopathy in different ways.
Adult↗
Octa- and nonaprenylhydroquinone sulfates, inhibitors of alpha1,3-fucosyltransferase VII, from an Australian marine sponge Sarcotragus sp.
Alpha1,3-fucosyltransferase (Fuc TVII) is a key enzyme in the biosynthesis of selectin ligands. We have isolated two inhibitors of Fuc TVII from a marine sponge Sarcotragus sp. They were characterized as octa- and nonaprenylhydroquinone sulfates on the basis of spectral data. These compounds inhibited Fuc-TVII with IC50 values of 3.9 and 2.4 microg/mL, respectively.
Animals↗
Effect of TPA on aquaporin 4 mRNA expression in cultured rat astrocytes.
Aquaporin 4 (AQP4) is a predominant water channel protein in mammalian brains, localized in the astrocyte plasma membrane. The regulation of AQP4 is believed to be important for the homeostasis of water in the brain, but the AQP4 regulatory mechanisms are not yet known. In this study, we investigated the effect of a protein kinase C (PKC) activator on the expression of AQP4 mRNA in cultured rat astrocytes. Cultured rat astrocytes constitutively expressed AQP4 mRNA. Treatment of the cells with 0.1 microM of phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of PKC, caused a rapid decrease in AQP4 mRNA. This effect was time- and dose-dependent. The TPA-induced decrease in AQP4 mRNA was inhibited by a relatively specific PKC inhibitor, 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H7) in a dose-dependent manner. Moreover, prolonged treatment of the cells with TPA eliminated the subsequent decrease in AQP4 mRNA by TPA. These results strongly suggest that the TPA-induced decrease in AQP4 mRNA is mediated by PKC activation. To test whether the effect of TPA requires protein synthesis, astrocytes were pretreated with cycloheximide, an inhibitor of protein synthesis. Pretreatment of the cells with cycloheximide did not inhibit the decrease in AQP4 mRNA induced by TPA. To test whether the TPA-induced decrease in AQP4 was due to a decrease in the mRNA stability, we examined the effect of actinomycin D, an inhibitor of transcription, on TPA-treated cells. The stability of AQP4 mRNA was not decreased by the pretreatment of the cells with actinomycin D. The results suggest that AQP4 mRNA is inhibited by TPA via PKC activation without de novo protein synthesis, and that the inhibition of AQP4 mRNA could be at the transcriptional level.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Distribution and developmental changes of adenylate kinase isozymes in the rat brain: localization of adenylate kinase 1 in the olfactory bulb.
Changes in the levels of three adenylate kinase isozymes (AK1, AK2, and AK3) in the rat brain during development were investigated by immunoblot analysis. The levels of AK1 and AK3 of the whole brain increased after birth, while AK2 was detected only in the early embryonic period. In the adult rat brain, high levels of AK1 were present in the olfactory bulb. Immunohistochemical analysis showed that AK1 was found predominantly in the olfactory nerve layer and the glomerular layer. In the olfactory bulb, AK1 gene expression was enhanced in the early postnatal days, whereas it remained low in the cerebellum during the first 10 postnatal days. These results suggest that the AK isozymes are involved in neuronal maturation and regeneration. The understanding of the physiological actions of adenosine and ATP as neurotransmitters/neuromodulaters in the central nervous system has improved. ATP and adenosine receptors have been found to be widely distributed over the whole brain, although the intra- and extracellular metabolism of these compounds has not been well elucidated.
Adenylate Kinase↗
Identification of four novel mutations of the XLRS1 gene in Japanese patients with X-linked juvenile retinoschisis. Mutation in brief no. 234. Online.
The XLRS1 gene (HUGO-approved symbol, RS1) has been found to cause X-linked recessive retinoschisis (RS) which is characterized by splitting of the superficial layer of the retina. Recent mutation analysis of this gene revealed 82 different mutations in 214 patients with RS. We have now identified 10 mutations of the XLRS1 gene in 11 unrelated Japanese males with RS. Mutations found in these patients were; 1) a 20-kb deletion in exon 1 region; 2) mutations in the initiation sequence (M1V); 3) mutations in the splice donor site (IVS1 + 1 g-->a); 4) two nonsense mutations (Q88X, W163X); and 5) five missense mutations (E72K, Y89C, R182C, G109E, P203L). Four (M1V, Q88X, G109E, and W163X) of the 10 mutations were novel. The R182C mutation was identified in 2 unrelated patients. The 3 mutations found between exons 1 and 3 cause premature translation termination in the XLRS1 protein. The rest of the 7 mutations were clustered between exons 4 and 6. This region of the protein is homologous to the proteins implicated in cell-cell adhesion.
Cell Adhesion↗
Development of a compact computed tomographic apparatus for dental use.
OBJECTIVE: To describe a compact computed tomographic apparatus (Ortho-CT) for use in dental practice. METHODS: Ortho-CT is a cone-beam-type of CT apparatus consisting of a multifunctional maxillofacial imaging machine (Scanora, Soredex, Helsinki, Finland) in which the film is replaced with an X-ray imaging intensifier (Hamamatsu Photonics, Hamamatsu, Japan). The region of image reconstruction is a cylinder 32 mm in height and 38 mm in diameter and the voxel is a 0.136-mm cube. Scanning is at 85 kV and 10 mA with a 1 mm Cu filter. The scan time is 17 s comparable with that required for rotational panoramic radiography. A single scan collects 512 sets of projection data through 360 degrees and the image is reconstructed by a personal computer. The time required for image reconstruction is about 10 min. RESULTS: The resolution limit was about 2.0 lp mm-1 and the skin entrance dose 0.62 mGy. Excellent image quality was obtained with a tissue-equivalent skull phantom: roots, periodontal ligament space, lamina dura, and cancellous bone were clearly visualized. CONCLUSION: Ortho-CT provides three-dimensional images of excellent quality for dental use at a low entrance dose.
Humans↗
Severe juvenile retinoschisis associated with a 33-bps deletion in XLRS1 gene.
X-linked juvenile retinoschisis is a form of vitreoretinal dystrophy that is characterized by foveal and peripheral splitting of the retinal nerve fiber layer. Pathognomonic of this disorder is a microcystic radiate appearance in the fovea. We encountered a 10 year-old, mildly retarded, Japanese boy, who exhibited a widely extended macular retinoschisis bilaterally. A break in the inner layer of the left eye mimicked a lamellar macular hole, which is a rare manifestation of the disease. Peripheral retinoschisis was absent. Only a few reports have described marked bilateral macular retinoschisis that involved entire posterior pole, while various other macular findings have been reported. This patient with a severe form of retinoschisis was found to harbor the deletion of 33 base pairs, including the boundary region of exon 3 and intron 3 in the XLRS1 gene.
Child↗
Comparison of the levels of hepatocyte growth factor and vascular endothelial growth factor in aqueous fluid and serum with grades of retinopathy in patients with diabetes mellitus.
AIMS: To determine the relation between the stages of diabetic retinopathy (DR) and the levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in aqueous fluid and serum. METHODS: Levels of HGF and VEGF in serum and aqueous humour obtained during ocular surgery were measured by enzyme linked immunosorbent assay in 58 diabetic patients with 32 non-diabetic patients (NDM) as controls. The patients with diabetes were classified into three groups according to the stage of DR: no DR (NDR; 15 cases), non-proliferative DR (NPDR; six cases), and proliferative DR (PDR; 37 cases). RESULTS: No significant differences were found between any of the groups in serum concentrations of HGF or VEGF. The aqueous HGF levels increased with the stage of DR: NDM, median 397 pg/ml, range 133-930 pg/ml; NDR, 371 pg/ml, 142-1536 pg/ml; NPDR, 455 pg/ml, 162-1007 pg/ml; and PDR, 638 pg/ml, 187-2222 pg/ml. The aqueous VEGF levels in PDR (median 212 pg/ml, range 14-1216 pg/ml) were significantly higher than in NDM (105 pg/ml, 9-203 pg/ml), but aqueous HGF concentrations were unrelated to those of VEGF. CONCLUSION: The results of the present study suggest that both HGF and VEGF present in the ocular tissues may play important roles in the progression of DR.
Adult↗
Development of X-ray TV M-mode and reconstructed ultrasound M-mode methods for investigating tongue movement during swallowing in humans.
There were two purposes of this study. The first purpose was to introduce the "X-ray TV M-mode waveform" which is reconstructed from sequential X-ray TV images and the "reconstructed ultrasound M-mode waveform" which is delivered from ultrasound B-mode images. The second purpose was to evaluate the usefulness of these two types of waveforms in the investigation of tongue movement during swallowing. The instrument system employed in this study consisted of ultrasound and X-ray TV synchronized by a time marker. After the X-ray images and ultrasound B-mode images were recorded on an optical disk, X-ray TV M-mode waveform and ultrasound M-mode waveform were reconstructed using an MC 68030/OS-9 computer. No significant differences in quality of images were observed between the X-ray TV M-mode waveform and the reconstructed ultrasound M-mode waveform. Therefore, both waveforms of the X-ray TV M-mode and the reconstructed ultrasound M-mode are equally useful in measuring tongue movement.
Adult↗
[A new method for quantification of metamorphopsia in patients with epiretinal membrane].
PURPOSE: We have developed a new method for quantification of metamorphopsia and applied it to study distorted vision resulting from epiretinal membrane (ERM). PATIENTS AND METHODS: We prepared a modified Amsler chart, which was a square grid formed by black lines on a white background with 12 cm on a side and divided into 2 cm quadrants. The patients were asked to trace any straight lines on the chart which appeared irregular or curved. The length of all lines traced by the patients was measured except for the outer frame. The total length of the chart itself was 1,200 mm, but it would appear longer in patients with metamorphopsia. In addition, the severity of metamorphopsia was scored subjectively as follows: 1, absent; 2, slight; 3, mild; 4, moderate; and 5, severe. The relationship of the length to the score and to the visual acuity were analysed. Sixty-three patients with unilateral ERM were examined. RESULT: The length of the line ranged from 1,200 to 1,259 mm (mean 1,223.3 mm) and was correlated significantly to the score. CONCLUSION: This method might be applied usefully in evaluating the severity of metamorphopsia and the surgical outcome of eyes with ERM.
Adolescent↗
Involvement of apoptosis in the rat germ cell degeneration induced by nitrobenzene.
Nitrobenezene (NB) produces germ cell degeneration, especially of spermatocytes in rats. To examine the possible involvement of apoptosis in this process, the extent and nature of nuclear DNA fragmentation after NB dosing were assessed using both terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and DNA gel electrophoresis, in addition to conventional histological and electron microscopic procedures. Adult Sprague Dawley rats were treated with a single oral dose of NB (250 mg/kg) and euthanized subsequently at 6, 12, and 24 h and 2, 3, 5, and 7 days. The earliest morphological signs of germ cell degeneration in testes were found in pachytene spermatocytes 24 h after dosing. Electron micrographs of degenerating spermatocytes showed marked nuclear chromatin condensation at the nuclear periphery and crowding of cytoplasmic constituents, which are characteristic of apoptosis. Coincident with the appearance of such morphological changes, degenerating spermatocytes contained fragmented DNA as revealed by TUNEL. The presence of DNA laddering, a hallmark of apoptosis on gel electrophoresis, was first apparent and most prominent at 24 h, gradually becoming less detectable. No such changes were observed up to 12 h after dosing or in control animals. These results demonstrated unequivocal involvement of apoptosis in the induction of germ cell degeneration caused by NB.
Animals↗
Novel antiallergic and antiinflammatory agents. Part I: Synthesis and pharmacology of glycolic amide derivatives.
A series of mono-glycoloylamino derivatives was synthesized by treatment of the corresponding aromatic monoamine derivatives with glycoloyl chloride derivatives in pyridine or dichloromethane, in the presence of a base such as triethylamine or pyridine. Hydrolysis of acetoxy compounds in aqueous ammonia and methanol solution produced hydroxy derivatives with ease. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Thiazole and thiadiazole derivatives showed moderate inhibition in this assay. In contrast, benzothiazole and benzonitrile derivatives exhibited marked inhibition. In particular, compound 5t also showed marked inhibition of eosinophil adhesion to TNF (tumor necrosis factor) -alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M.
Administration, Oral↗
Novel antiallergic and antiinflammatory agents. Part II: Synthesis and pharmacology of TYB-2285 and its related compounds.
A series of m-bis(glycoloylamino)benzene derivatives was synthesized by treatment of the corresponding m-diaminobenzene derivatives with glycoloyl chloride derivatives in pyridine. Hydrolysis of acetyl compounds gave hydroxy derivatives, from which other acyl derivatives could be synthesized. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Benzonitrile derivatives (4c, 5c, 6c, 4h, 5h) exhibited notable inhibition in this assay. Compounds 5c and 6c also showed remarkable inhibition of eosinophil adhesion to TNF- (tumor necrosis factor) alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M. Compound 5c is now under investigation in Japan as TYB-2285 (Figure 1) for asthma and atopic dermatitis in phase II clinical studies.
Administration, Oral↗
Detailed acceptor specificities of human alpha1,3-fucosyltransferases, Fuc-TVII and Fuc-TVI.
To clarify the acceptor specificity of Fuc-TVII, its activity toward various analogs of a 2-(trimethylsilyl)ethyl alpha2,3-sialyl lacto-N-neotetraose, an acceptor for both Fuc-TVII and Fuc-TVI, was examined in comparison with that of Fuc-TVI. Fuc-TVII required three portions of alpha2,3-sialylated type-2 oligosaccharide structures (i.e., the hydroxyl group at C-4 of Gal, the hydroxyl group at C-3 of GlcNAc, and the carbonylamino group at C-2 of GlcNAc) for its acceptor recognition. Fuc-TVI required the carbonylamino group at C-2 of GlcNAc for its acceptor recognition. Fuc-TVII showed higher affinity toward two analogs, in which the hydroxyl group at C-6 of GlcNAc has been deoxygenated and the acetamide group of N-acetylneuraminic acid has been replaced with a glycolylamino group, respectively, than that toward the original compound. On the other hand, Fuc-TVI showed higher affinity toward an analog, in which the acetamide group of GlcNAc has been modified with a lauroylamino group, than that toward the original compound. Analysis involving mass spectrometry confirmed that both Fuc-TVII and Fuc-TVI could fucosylate these three analogs to yield sialyl Lewis x derivatives.
Binding, Competitive↗
Panosialins, inhibitors of an alpha1,3-fucosyltransferase Fuc-TVII, suppress the expression of selectin ligands on U937 cells.
Panosialins A and B were isolated as inhibitors of an alpha1,3-fucosyltransferase, Fuc-TVII, which is a key enzyme in the biosynthesis of selectin ligands, from culture broth of Streptomyces sp. Panosialins A and B inhibited the Fuc-TVII activity with IC50 values of 4.8 and 5.3 microg/ml, respectively. Panosialin A suppressed expression of selectin ligands on U937 cells, and inhibited the cell adhesion to immobilized E-selectin-immunoglobulin. Panosialins are the first reported Fuc-TVII inhibitors which can suppress the biosynthesis of selectin ligands and then inhibit selectin-mediated cell adhesion.
Benzene Derivatives↗
Five cases of thrombocytopenia induced by primary human herpesvirus 6 infection.
Five patients suffering from exanthem subitum with thrombocytopenia were confirmed as primary human herpesvirus 6 (HHV-6) infection by serological test. All cases had thrombocytopenia during the acute phase of exanthem subitum. The clinical features of these cases were benign, and all recovered without any specific treatment. Moreover, 4 of the 5 cases showed a mild elevation of hepatic transaminase during the same period, and other viral infections including cytomegalovirus, Epstein-Barr virus, and human herpesvirus 7 were ruled out in these patients. It was speculated that direct inhibition of platelet production by the virus or cytokine induced by the virus-infected cells was the mechanism of the thrombocytopenia induced by primary HHV-6 infection.
Acute Disease↗