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Biomedical subjects

N Ohba

Publications and source records attributed to N Ohba.

At least 73 records · Page 4Linked to original sources

Lectin-histochemical study of O-linked glycoconjugates in dysplastic retina of Norrie disease.

The carbohydrate chains of O-linked glycoconjugates in dysplastic retina from a Japanese female infant with Norrie disease were examined by lectin histochemistry. The avidin-biotinylated peroxidase method was used. The retina was highly dysplastic and composed of undifferentiated embryonic tissues containing a number of rosettes of varying sizes. The lumina of the rosettes were stained by peanut agglutinin, which recognizes the Gal beta 1,3GalNAc sequence of O-linked glycans. However, the lumina were not labeled by wheat germ agglutinin, which reacts with sialic acid and/or N-acetylglucosamine. These observations suggest that the O-linked glycoconjugates in the lumina of rosettes were not sialylated in the present case. Their lack of terminal sialic acids may be related to the rosette formation.

Acetylglucosamine↗

Novel mutation at the initiation codon in the Norrie disease gene in two Japanese families.

We have identified a new mutation of Norrie disease (ND) gene in two Japanese males from unrelated families; they showed typical ocular features of ND but no mental retardation or hearing impairment. A mutation was found in both patients at the initiation codon of exon 2 of the ND gene (ATG to GTG), with otherwise normal nucleotide sequences. Their mothers had the normal and mutant types of the gene, which was expected for heterozygotes of the disease. The mutation of the initiation codon would cause the failure of ND gene expression or a defect in translation thereby truncating the amino terminus of ND protein. In view of the rarity and marked heterogeneity of mutations in the ND gene, the present apparently unrelated Japanese families who have lived in the same area for over two centuries presumably share the origin of the mutation.

Base Sequence↗

Cloning, expression and sequence analysis of cDNA for the luciferases from the Japanese fireflies, Pyrocoelia miyako and Hotaria parvula.

Cloning and sequence analysis of cDNA for the luciferases of Pyrocoelia miyako and Hotaria parvula were carried out (GenBank accession numbers L39928 and L39929, respectively). The amino acid sequence, deduced from the nucleotide sequence, showed P. miyako luciferase to consist of 548 amino acid residues with a molecular weight of 60,955, while the luciferase of H. parvula consisted of 548 amino acid residues with a molecular weight of 60,364. Pyrocoelia miyako luciferase showed 82.1% homology with the luciferase of Photinus pyralis and less than 70% homology with other firefly luciferases, whereas H. parvula luciferase showed 98%, 82.5% and 81.2% homology with the luciferases of Luciola mingrelica, Luciola lateralis and Luciola, cruciata respectively. Two regions in the enzymes were found to be highly conserved. The amino acid sequences were used to construct a phylogenetic tree, which showed that the fireflies could be divided into two groups.

Amino Acid Sequence↗

Expression of distribution of alpha 2,3-sialyltransferase mRNA in rat cornea.

The glycocalyx, present on the surface of the corneal epithelium, contains sialoglycoconjugates. The developmental change in the sialylated residues may be evaluated by examining the expression of the sialyltransferase mRNA. We examined the distribution of Gal beta 1,3GalNAc alpha 2,3-sialyltransferase mRNA in rat corneas during development using in situ hybridization histochemistry to detect the starting point of the synthesis of O-linked sialoglycoconjugates. Eyelid opening occurred between postnatal days 14 (P14) and 16 (P16). In the corneal epithelium, little hybridization signal was observed until P12, whereas distinct hybridization signals were identified at P14 and thereafter. The expression of alpha 2,3-sialyltransferase mRNA is developmentally regulated, based on the programmed time-course of the gene expression, and the corneal epithelium may start to synthesize O-linked sialoglycoconjugates prior to the critical eyelid opening stage.

Animals↗

Functional Rescue of photoreceptors from the damaging effects of constant light by survival-promoting factors in the rat.

PURPOSE: To investigate whether and how survival-promoting agents rescue photoreceptor cell function and morphology from constant light damage, the authors recorded electroretinographic (ERG) responses and examined light micrographs of retinas in those rats given intravitreal injection of midkine (MK) and basic fibroblast growth factor (bFGF) before constant exposure. METHODS: Albino Sprague-Dawley rats were injected with MK, bFGF, or phosphate-buffered saline (PBS) 2 days before the onset of 1 week of constant light. ERG responses were recorded using white flash stimuli with the intensity range of 4 log units, followed by histologic examinations of retinas, including quantitative assessment of the outer nuclear layer thickness as an index of photoreceptor cell loss. RESULTS: ERG responses were barely detectable in uninjected eyes after 1 week of constant light. On the other hand, distinct responses were recordable in eyes injected intravitreally with MK and bFGF, and the degree of ERG rescue in terms of the amplitude of b-wave was approximately 40% to 60% compared with normal eyes. Intravitreally injected PBS showed slight, but noticeable, preservation of ERG responses as well. Histologic examination revealed that MK and bFGF protected photoreceptors from light damage. A good correlation was found between anatomic rescue of photoreceptors as assessed by outer nuclear layer thickness and the functional rescue as defined by the magnitude of ERG responses. CONCLUSIONS: Functional and anatomic rescue of photoreceptors in albino rats from constant light damage is achieved by prior intravitreal injection of MK and bFGF.

Animals↗

[HTLV-I associated retinochoroidal degeneration].

A review of 100 patients with HTLV-I (human T-cell lymphotropic virus type I) associated myelopathy revealed 9 cases (9.0%) of retinochoroidal degeneration. Most of the cases developed the ocular disease at age 50 or older, either preceded or followed by neurologic disease. Ophthalmoscopic abnormalities included classic retinitis pigmentosa and localized degenerative changes of the retina and choroid, with visual disturbance corresponding to the severity of retinal changes. None of the cases showed any contributory family history. In reference to the prevalence of retinitis pigmentosa, these cases were thought to indicate a meaningful rather than coincident association between HTLV-I associated myelopathy and retinochoroidal degeneration. Hence, HTLV-I may involve the underlying etiology of a newly defined disease called HTLV-I associated retinochoroidal degeneration. On the other hand, since HTLV-I seroprevalence in patients with isolated retinitis pigmentosa was comparable with that in the general population, it appears unlikely that the retrovirus may also involve an isolated form of retinochoroidal degenerative disease.

Aged↗

[Binding of amaranthin in human retina].

The binding of amaranthin, specific for Gal beta 1,3 GalNAc and sialic acid Gal beta 1,3 GalNAc sequences, to the human retina was investigated with avidin biotinylated peroxidase. Amaranthin bound to the cone and rod photoreceptors, inner plexiform layer, ganglion cells, and nerve fibers. Since peanut agglutinin, specific for Gal beta 1,3 GalNAc, selectively binds to cones, we conclude that O-glycoside-linked glycoconjugates are present on the surfaces of both cones and rods: Gal beta 1,3 GalNAc and sialic acid Gal beta 1,3 GalNAc are terminal sugars of the glycoconjugates around cones and rods, respectively.

Glycoconjugates↗

[Distribution of alpha 2,3-sialyltransferase mRNA in rat iris and ciliary body].

The distribution of alpha 2,3-sialyltransferase (alpha 2,3-ST) mRNA in the rat iris and ciliary body was investigated with in situ hybridization histochemistry. Strong expression of alpha 2,3-ST mRNA was detected in the inner epithelial layer of the ciliary body and weak expression in the iris epithelium. Since the synthesis of sialoglycoconjugates is completed by terminal sialylation by the action of sialyltransferase (ST), the ST-expressed portions are considered to produce sialoglycoconjugates. Hence, the source of the sialoglycoconjugates found in the inner epithelial layer of the ciliary body in previous histochemical studies is the same epithelial cell.

Animals↗

Binding of amaranthin in photoreceptors of monkey retina.

The binding of amaranthin, specific for the Gal beta 1,3 GalNAc and NeuAc alpha 2,3 Gal beta 1,3 GalNAc sequences, to the photoreceptors of the monkey retina was investigated using the avidin-biotinylated peroxidase method. Amaranthin bound to the surfaces of both cone and rod photoreceptors. This and previous lectin histochemical studies show that O-glycoside-linked glycoconjugates are present on the surfaces of both cones and rods: Gal beta 1,3 GalNAc and NeuAc alpha 2,3 Gal beta 1,3 GalNAc are the terminal sugars of the glycoconjugates around cones and rods, respectively.

Animals↗

Maackia amurensis lectin binding in developing rat retina.

The developmental changes in the binding of Maackia amurensis lectin, specific for sialic acid alpha 2,3 galactose sequence, to the rat retina was investigated using the avidin-biotinylated peroxidase method. The lectin bound to the surfaces of photoreceptor outer segments from postnatal day 16 (P16), whereas it had bound to the other retinal layers from P14. The intense labelings of the outer segments were interspersed with unstained portions, which may correspond to cone photoreceptors. These results confirm that the sialic acid residues on the terminus of carbohydrate chains increase at P16 and mask the beta-galactose residues around rod outer segments.

Animals↗

[Light-dependent changes of ribosome distribution in photoreceptor inner segments of the mouse retina].

We studied the distribution pattern of free ribosomes in the photoreceptor inner segments of adult mice with reference to environmental light. Eyeballs were obtained from animals at the light or dark phase of the ordinary cyclic light, and photoreceptor inner segments were examined by electron microscopy. In the light phase, free ribosomes were distributed in a random fashion, although meticulous observations revealed that they appeared to be arranged either in a spiral or linear form, or in isolation. In the dark phase, several free ribosomes were arranged in a clustered fashion. When animals were kept in continuous darkness as long as 27 hours, most of the inner segment free ribosomes showed a clustered pattern similar to that in the dark phase of the cyclic light. We discussed the light-dependent configurational changes of ribosomes with respect to their activity or inactivity in protein synthesis.

Animals↗

HTLV-I associated uveitis and hyperthyroidism.

The records of 76 consecutive patients with etiology-undefined uveitis examined during the 3-year period between 1990 and 1992 were reviewed and 6 patients were found who had concomitant hyperthyroidism. These 6 patients had presented with uveitis symptoms and signs when hyperthyroidism was relieved with thiamazole therapy. The uveal disease was characterized by acute, granulomatous or nongranulomatous anterior uveal involvement and granular or membranous vitreous opacities with or without retinal vascular change. These manifestations resolved in a few weeks in response to topical and/or systemic corticosteroids. Three patients had recurrence of uveitis after remission for months to years. All of the patients had serum antibodies to HTLV-I. The uveal disease resembled HTLV-I associated uveitis that may develop in patients with HTLV-I associated myelopathy or HTLV-I carriers; 2 cases had chronic myelopathy or arthropathy that was considered associated with the retrovirus. The present observations suggest that the association between uveitis and hyperthyroidism is not accidental but shares a common underlying etiologic factor, HTLV-I, although the pathomechanism remains to be defined.

Adult↗

Rescue of photoreceptors from the damaging effects of constant light by midkine, a retinoic acid-responsive gene product.

PURPOSE: To evaluate the protective effects of midkine (MK), the product of a retinoic acid-responsive gene, on constant light-induced retinal degeneration in albino Sprague-Dawley rats. METHODS: Midkine, basic fibroblast growth factor (bFGF), MK plus heparin, or buffer controls were injected intravitreally 2 days before constant light exposure. After 7 days of continuous light exposure, the eyes were perfused with fixative, bisected along the vertical meridian, embedded in paraffin, and sectioned. The degree of retinal light damage was assessed for paraffin-embedded sections by cytologic analysis, by measuring the thickness of the outer nuclear layer (ONL), and by counting the number of macrophages. RESULTS: After 1 week of constant light exposure, uninjected controls and those injected with phosphate-buffered saline (PBS) lost most of the photoreceptor inner and outer segments, and the thickness of the ONL was decreased. Eyes that were injected with MK or bFGF demonstrated a significant rescue in the photoreceptor layer with a two- to threefold increase in the ONL thickness. The number of macrophages in eyes injected with MK was significantly suppressed compared with controls. Those injected with bFGF had a 1.5-fold increase in number compared with controls. CONCLUSIONS: Midkine has shown strong survival-promoting activity in constant light-induced retinal degeneration, and thus has a high degree of neurotrophic activity in vivo.

Animals↗

A multicenter case-control study of HTLV-I associated uveitis. Study Group for HTLV-I Associated Ocular Diseases.

To elucidate the epidemiology of human T-lymphotropic virus type I (HTLV-I) associated uveitis (HAU), a multicenter case-control study was carried out by the collaboration of university hospitals throughout Kyushu and Okinawa in southwestern Japan where HTLV-I is endemic; two institutions in the non-endemic metropolitan areas of Tokyo and Yokohama also participated. A total of 426 cases of endogenous uveitis were registered during the five-month period between September 1992 and January 1993; the etiology and clinical entity of about half of the cases were definable, and for the remaining half were unknown. Assessment of antibodies to HTLV-I revealed that the group of entity-undefined uveitis cases showed a significantly high seroprevalence when compared with age- and sex-matched controls. Estimate of the risk of HTLV-I provided supportive evidence for its etiologic contribution to a considerable proportion of hitherto undefined isolated uveitis cases. The prevalence of HAU thus defined was found to correspond to the seroprevalence in the relevant areas. Occasional cases were found among residents in the nonendemic metropolitan areas who had moved from the endemic areas.

Adolescent↗

Clinical features of HTLV-I associated uveitis determined in multicenter collaborative study. Study Group for HTLV-I Associated Ocular Diseases.

The elucidation of the clinical features of human T-lymphotropic virus type I (HTLV-I) associated uveitis (HAU) was advanced by the results of a multicenter study performed by the collaboration of university hospitals throughout Kyushu and Okinawa and two institutions in the Tokyo-Yokohama metropolitan areas of Japan. A total of 426 cases of endogenous uveitis were registered during the five-month study period between September 1992 and January 1993. The etiology and clinical entity remained unknown for about half of these cases. A series of 50 cases of HTLV-I seropositive, entity-undefined uveitis were suspected to be HAU, and analyses of these cases provided the following clinical features of this recently defined uveitis entity. 1) middle-aged adult of either sex develops acute, inflammatory uveal disease and presents with visual haze or floaters, or both; 2) active disease consists of granulomatous or nongranulomatous reactions accompanied by vitreous opacities and retinal vasculitis with rare retinochoroidal exudative changes; 3) the disease resolves with response to corticosteroids, although leaving sequelae in occasional cases; 4) the disease affects one or both eyes, and up to half of cases show recurrent disease within years; 5) the visual outcome is usually favorable; 6) the disease occurs as an isolated disorder, but may sometimes be complicated by HTLV-I associated myelopathy. Hyperthyroidism is also associated in occasional cases; 7) the titer of serum HTLV-I antibodies is significantly high compared with that of HTLV-I carriers, suggesting an immune mechanism as the pathogenesis of HAU.

Adolescent↗

[A multicenter clinico-epidemiological study of HTLV-I associated uveitis].

To elucidate the clinical and epidemiologic features of HTLV-I associated uveitis (HAU), a multicenter case-control study was performed by collaboration of university hospitals throughout Kyushu and Okinawa and two university hospitals in the central metropolitan area. A total of 426 cases of endogenous uveitis were collected and studied between September 1992 and January 1993; about half of the cases were definable for etiology or clinical entity, and the remaining cases were unknown. Assessment of the serum antibodies to HTLV-I revealed that the group of entity-undefined uveitis had a significantly high prevalence of HTLV-I as compared with the age- and sex-matched control subjects, giving supportive evidence for HAU. The titer of serum HTLV-I antibodies was significantly higher in entity-undefined uveitis than in HTLV-carriers. Assuming that a collection of 50 cases of HTLV-I seropositive, etiology-undefined uveitis represents HAU, its clinical features consisted were: (1) middle-aged, otherwise healthy adults developed acute inflammatory uveal disease and presented with visual haze and/or floaters; (2) the disease showed granulomatous or nongranulomatous anterior uveal reactions accompanied by vitreous opacities and retinal vasculitis; (3) the lesions resolved in response to topical or systemic corticosteroids; (4) the visual outcome was usually favorable; (5) nearly half of the cases had recurrent disease; (6) the cases remained systemically unremarkable, except for two cases of HTLV-I associated myelopathy and eight cases of hyper thyroid disease.

Adolescent↗

[Antibodies to human T-cell lymphotropic virus type 1 in the aqueous humor of HTLV-I associated uveitis].

To elucidate the pathomechanism of human T-cell lymphotropic virus type 1 (HTLV-I) associated uveitis (HAU), we assessed antibodies to HTLV-I and IgG for paired samples of serum and aqueous humor. Seven of 10 samples from HAU patients showed antibodies to HTLV-I in the aqueous humor with antibody titer ranging from 16 to 128, and five of these samples showed significantly high antibody quotients as calculated by reference to the IgG levels in the serum and aqueous humor, hence suggesting local production of antibodies rather than their transfer from the serum. On the other hand, eight of 45 control samples from HTLV-I carriers with senile cataract but without uveitis had antibodies to HTLV-I in the aqueous humor with antibody titer ranging from 8 to 128, but none of these samples showed high antibody quotient. We conclude that, although antibodies to HTLV-I in aqueous humor were detected in those HAU and control cases which showed high antibody titer in the serum, intraocular synthesis of antibodies to HTLV-I may sometimes occur in HAU.

Adult↗