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N Ohba

Publications and source records attributed to N Ohba.

At least 37 records · Page 2Linked to original sources
PubMed2000

Diagnostic potential of mitochondrial DNA assessment in patients with optic neuropathy.

OBJECTIVE: To study the primary mutations of mitochondrial DNA (mtDNA) associated with Leber's hereditary optic neuropathy (LHON) in patients with optic neuropathy. METHODS: Seventy-nine patients with a variety of bilateral optic neuropathies were examined. Mutations at np3460, np11,778 and np14,484 of mtDNA were tested by PCR-restriction detection in peripheral blood DNA from 16 cases of clinically probable LHON, 44 cases of possible LHON, 2 cases of alcohol amblyopia, 4 cases of multiple sclerosis, 5 cases of autosomal dominant optic atrophy, 4 cases of primary open-angle glaucoma, 3 cases of spinocerebellar degeneration, and 1 case of ethambutol-induced optic neuropathy. RESULTS: The mutation at np11778 was identified in 31 cases (39.2%) to establish LHON, which consisted of: all 16 of clinically probable LHON cases, 13 cases (29.5%) of possible LHON, and 2 cases of alcohol amblyopia. The remaining 48 cases were negative for mtDNA mutations at np3460, np11 778, and np14,484. CONCLUSION: Assessment of mtDNA provides a useful diagnostic aid in the definition and exclusion of LHON, in particular family history-negative, otherwise undefined bilateral optic nerve inflammatory disease.

Adolescent↗
PubMed1999

REP-1 gene mutations in Japanese patients with choroideremia.

BACKGROUND: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. METHODS: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1-15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. RESULTS: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. CONCLUSIONS: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Hepatocyte growth factor stimulates cell growth and enhances the expression of transforming growth factor alpha mRNA in AsPC-1 human pancreatic cancer cells.

We investigated the effects of hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF alpha) on cell growth in four human pancreatic cancer cell lines. Changes in the expression of mRNAs of HGF, c-met, TGF alpha, and epidermal growth factor receptor (EGFR) by treatment with HGF and TGF alpha were observed. Cell growth with growth factors was assessed with the MTT assay and compared with basal growth without growth factors. Although HGF stimulated cell growth in AsPC-1, COLO-357, and T3M4 cells, Panc-1 cells showed no response to HGF. TGF alpha stimulated the growth of all the above cells. The expression of c-met mRNA under nonstimulated conditions was detected with Northern blotting in all cells. Treatment with HGF slightly enhanced the expression of c-met mRNA only in COLO-357 cells. The intensity of EGFR expression was consistent, and HGF mRNA was not detected during induction experiments in any cell type. Concomitant treatment with HGF and TGF alpha exerted an effect that was additive or less on the growth of all cells. Expression of TGF alpha was enhanced by HGF treatment only in AsPC-1 cells. These results suggested that HGF and TGF alpha stimulated cell growth through a final common pathway of signal transduction.

Blotting, Northern↗
PubMed1999

A novel truncating mutation of cytochrome P4501B1 (CYP1B1) gene in primary infantile glaucoma.

PURPOSE: To report a novel mutation of the CYP1B1 gene in a Japanese patient with primary infantile glaucoma. METHODS: DNA was extracted from leukocytes of six unrelated patients with primary infantile glaucoma. The coding regions of the CYP1B1 gene were amplified by polymerase chain reaction, examined by agarose gel separation and heteroduplex methods, and directly sequenced. RESULTS: One of the patients with primary infantile glaucoma had a mutation of the CYP1B1 gene, with an abnormal shift in agarose gel separation and heteroduplex analysis. Direct sequencing disclosed a homozygous insertion of guanine at nucleotide 1620 of exon 3, which produced a frameshift leading to premature termination of amino acid translation. The patient was male and had sporadic, classic primary infantile glaucoma. None of the other five patients with infantile glaucoma, the 30 patients with primary adult-onset glaucoma, or the 70 healthy control subjects showed any abnormalities in the CYP1B1 gene. CONCLUSIONS: This is the first report of CYP1B1 gene mutation in primary infantile glaucoma from the Eastern world. CYP1B1 gene mutation for primary infantile glaucoma spreads worldwide, but its prevalence may have ethnic or geographic differences.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

A longitudinal study of cycloplegic refraction in a cohort of 350 Japanese schoolchildren. Anisometropia.

The intereye difference of cycloplegic refraction was determined in a cohort of 350 rural Japanese schoolchildren aged 6 to 11 years. The intereye spherical difference remained statistically unchanged throughout 5 years, with mean value ranging from 0.21 to 0.28 D, median from 0.15 to 0.20 D, and the 95th percentile from 0.58 to 0.85 D. The prevalence of 1.0 D or greater spherical anisometropia was up to 3.1%. Linear regression analyses of the longitudinal data from individual children revealed that 295 (84.3%) children and remained unchanged while 55 (15.7%) showed significant increase or decrease in the amount of anisometropia with increasing age. The intereye astigmatic difference was also statistically unchangeable, with mean value ranging from 0.28 to 0.36 D, median from 0.20 to 0.39 D, and the 95th percentile from 0.70 to 0.90 D. The prevalence of 1.0 D or greater astigmatic anisometropia was up to 4.3%. There was a significant correlation between the spherical and astigmatic anisometropia. The results show the current state of intereye refractive difference in Japanese schoolchildren, demonstrating that it remains unchanged and significant anisometropia is rare during school age.

Anisometropia↗
PubMed1999

A longitudinal study of cycloplegic refraction in a cohort of 350 Japanese schoolchildren. Cycloplegic refraction.

We performed a 5 year longitudinal study of cycloplegic refraction in a cohort of 350 Japanese schoolchildren from 6 to 11 years of age in a rural area of southwestern Japan. The spherical refraction was measured under cycloplegia with an infrared autorefractometer. The grouped data from 350 right eyes showed leptokurtic frequency distributions, and the median was +0.91 D at age 6 yrs, shifted towards emmetropia with increasing age and reached +0.34 D at age 11 years. The prevalence of myopia of -1.0 D or more was 0.3%, 0.6%, 2.0%, 2.6%, 2.9%, and 4.9% from age 6 to 11 years, and the prevalence of myopia of more than -2.0 D was less than 1% at age 6-9 years and thereafter increased up to 6.0% at age 11 years. Linear regression analysis for the longitudinal refractive data revealed that 247 (70.6%) of the 350 eyes exhibited first-order linear decrease in hyperopia or increase in myopia with an average annual change of -0.15 D/year, 14 (4%) showed second-order curvilinear change, and 89 (25.4%) remained unchanged. In the eyes with linear change, there was a significant relationship between the refraction at age 6 years and the rate of subsequent change such that the less hyperopic or emmetropic at age 6 years, the larger the change. The refraction at birth was estimated by extrapolation of the linear regression analysis results, implying that 88% of newborns have hyperopia of +1.0 D or greater and myopia is rare. These results indicate the current state of refraction in Japanese schoolchildren of a rural area.

Child↗
PubMed1999

[Sorsby's fundus dystrophy: a literature review].

BACKGROUND: Sorsby's fundus dystrophy (SFD) is an autosomal dominant macular dystrophy first described in a 1949 study of five British families, and it has received attention because of its clinical similarity to age-related macular degeneration and recent identification of the pathogenic gene. CLINICAL FEATURES: To date, about twenty families with SFD have been reported from Europe, North America, South Africa, Australia, and Japan. A review of the literature found that the age of onset is usually during the fourth or fifth decade of life, the prominent ophthalmoscopic finding is hemorrhagic or atrophic lesion in the macula, and functional prognosis is usually unfavorable due to additional peripheral chorioretinal dystrophy, ultimately leading to poor ambulatory vision in the late decades of life. MOLECULAR GENETICS: Recent molecular studies have identified mutations in the tissue inhibitor of metalloproteinases-3 (TIMP 3) gene as the pathogenic gene defect. CONCLUSIONS: TIMP 3 gene examinations not only allow accurate diagnosis but also lay the groundwork for future studies of potential therapeutic protocols.

Corneal Dystrophies, Hereditary↗
PubMed1999

[Clinical and genetic features of choroideremia].

BACKGROUND: Choroideremia is an X-linked hereditary eye disease that causes progressive degeneration of the choroid and retina and frequently leads to legal blindness in later life. Recent molecular genetic studies have revealed mutations involving the Rab escort protein (REP-1) gene localized at Xq 21. CLINICAL FEATURES: The clinical picture and rate of progression may vary among affected individuals in different families and within the same family. Usually, hemizygous males develop night blindness in their teenage years, followed by progressive peripheral visual field constriction and visual disability in late age. Heterozygous female carriers are mostly asymptomatic, but their fundi show characteristic pigment changes in the midperiphery closely resembling the fine mottling observed in the initial stage of the disease in males. MOLECULAR GENETICS: Assessment of the REP-1 gene in European and Japanese choroideremia patients has revealed a wide variety of mutations, including gross deletions and point mutations such as nonsense, frameshift, and splice-site mutations. All these mutations are thought to fail in intact REP-1 protein synthesis. CONCLUSIONS: The recent molecular studies may open a new chapter in the research on choroideremia and provide the groundwork for therapeutic potential as well as diagnosis and genetic counseling.

Adaptor Proteins, Signal Transducing↗
PubMed1999

[Introduction to genetics in ophthalmology. Value of family studies].

This paper reviews the author's personal experience with genetic eye diseases and discusses the significance of family studies in providing key information for the advancement of molecular research. CHOROIDEREMIA: This disease has long been known as an X-linked progressive tapetoretinal degeneration, but it was first described in Japan in 1974 after finding asymptomatic fundus changes in heterozygous female carriers that are compatible with X chromosomal inactivation. Mutations in the disease-causing gene (REP-1) provide a clue to the diagnosis and pathophysiology of the disease. LEBER'S HEREDITARY OPTIC NEUROPATHY: The clinical expression is so variable among affected individuals and families that mild optic nerve disease of insidious onset should be differentiated from autosomal dominant optic atrophy. Molecular assessment of mitochondrial DNA leads to a definite diagnosis of the disease, but mitochondrial DNA mutations do not fully account for the clinical manifestation and phenotypic variability of the disease. NORRIE DISEASE: This rare X-linked vitreoretinal dysplasia, characterized by congenital bilateral blindness, was documented in Japan some twenty years ago and the disease has been identified in four unrelated Japanese families. The disease, once diagnosed on the basis of elaborate clinical and familial studies, can now be defined by molecular assessment of the Norrie disease gene. CONGENITAL NYSTAGMUS: A four-generation family was described which presented with autosomal dominantly inherited congenital nystagmus, peripheral corneal opacity, and foveal hypoplasia without any iris tissue malformation. The diagnosis of this family was established by detection of a missense mutation in the paired domain of the PAX 6 gene, hence conforming to a forme fruste of congenital aniridia. SORSBY'S FUNDUS DYSTROPHY: Two Japanese families with Sorsby's fundus dystrophy showed late-onset retinal dystrophy characterized by submacular hemorrhage and atrophy. Our patients presented with visual loss as late as 50 years of age or older due to macula-confined degenerative changes that were similar in all respects to exudative age-related macular degeneration and showed a novel mutation in the tissue inhibitor of the metalloproteinases-3 gene. AGE-RELATED MACULAR DEGENERATION (ARMD): We have studied whether there is any association of candidate polymorphic genes involving xenobiotic or antioxidant metabolism with susceptibility to ARMD. Preliminary results suggest that the genetic polymorphism of microsomal epoxide hydrolase is related to potential risk of ARMD.

Aged↗
PubMed1998

A novel splice site mutation in the tissue inhibitor of the metalloproteinases-3 gene in Sorsby's fundus dystrophy with unusual clinical features.

Sorsby's fundus dystrophy (SFD) is an autosomal dominant macular dystrophy which is developed usually in the third or fourth decade of life, and is characterized by central visual loss and nyctalopia due to fundus changes of exudative or atrophic macular lesions. Its functional prognosis is usually poor because of disciform macular scars and peripheral chorioretinal atrophies. To date, five different mutations in the tissue inhibitor of the metalloproteinases-3 (TIMP3) gene have been identified in families of a wide geographic origin, all of which are missense mutations that cause replacement by cysteine of conserved amino acids in the C-terminus of exon 5 of TIMP3. We have studied two Japanese families with SFD, the first report from the Eastern world, and identified a novel 3' splice site mutation in the TIMP3 gene, namely a single base insertion at the intron 4/exon 5 junction which converts the consensus sequence CAG to CAAG in the splice acceptor site. In addition, our patients displayed a distinctive clinical expression in that they developed macular dystrophies at an approximately 30-year later age of onset and preserved functional vision until later life with essentially uninvolved peripheral retina. The present findings may provide some insight into the genotype-phenotype relationship in SFD.

Aged↗
PubMed1998

Ultracytochemical demonstration of glycogen in cone, but not in rod, photoreceptor cells in the rat retina.

The presence of native glycogen in photoreceptor cells of the rat retina has not been identified in the literature. We have studied this ultracytochemically. After perfusion with glutaraldehyde fixative, the eyes were enucleated, and the retinal tissues, postfixed with OsO4, were embedded in epoxy resin. Some tissues were treated with saliva before postfixation. Ultrathin sections, stained by the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method or with uranyl acetate and lead citrate, were examined by electron microscopy. On routinely stained sections, glycogen particles seemed to be absent in the cytoplasmic matrix of the photoreceptor cells because they were indistinguishable from the numerous ribosomes. This was due to a similarity in size and electron density. After PA-TCH-SP staining, fine electron-dense reaction products appeared on small cytoplasmic particles (but not on ribosomes) in the inner segments, perikarya and synaptic terminals of a subpopulation of photoreceptor cells. These particles, 15-25 nm in diameter, were identified as beta-particles of glycogen because of their susceptibility to enzyme digestion. The glycogen-rich photoreceptor cells were thought to be cone cells by reasons of their morphological features, such as synaptic terminals, nuclei and outer segments. These results suggest that the cone, but not the rod, photoreceptor cells in the rat contain abundant glycogen.

Animals↗
PubMed1998

Retinal manifestations in mitochondrial diseases associated with mitochondrial DNA mutation.

PURPOSE: To scrutinize retinal involvement associated with distinct mitochondrial DNA (mtDNA) defects, we reviewed the records of a consecutive series of patients with various mitochondrial diseases. METHODS: Clinical, laboratory and mtDNA studies were performed in: five patients with Kearns-Sayre syndrome (KSS); six patients with chronic progressive external ophthalmoplegia (CPEO); three patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS); three patients with myoclonic epilepsy and ragged-red fibers (MERRF); 20 patients with Leber's hereditary optic neuropathy (LHON); 30 patients with simple diabetes mellitus. RESULTS: All KSS patients with neurologic and cardiac symptoms associated with a deletion of mtDNA in muscle biopsy specimens showed widespread retinal pigmentary changes characterized by salt- and pepper-like appearance of the fundus. Three of six patients with CPEO, a mild variant of KSS, showed subtle defects at the level of retinal pigment epithelium of the posterior pole, although mtDNA deletion was similar to that in KSS. Of three patients with MELAS syndrome, one patient showed juvenile cataract and mild retinal pigmentary defect in the posterior pole. Of three patients with MERRF syndrome associated with a mtDNA mutation at nucleotide position (np) 8344, one patient showed mild pigment disorder in the posterior pole in addition to optic neuropathy. Two of 20 patients with LHON associated with a mtDNA mutation at np 11778 showed mild pigmentary defect in the macula together with typical optic neuropathy. In addition, two of 30 patients with isolated diabetes mellitus showed a mtDNA mutation at np 3243 (MELAS mutation), but they did not present with any other neurologic or multisystem disorder. CONCLUSION: The retina, in particular the retinal pigment epithelium, is highly vulnerable to be involved by mtDNA defect, and the retinopathy is phenotypically variable and frequently subclinical, depending to some extent on the type or site of mtDNA defect.

Adolescent↗
PubMed1997

Genotypes of aldehyde dehydrogenase and alcohol dehydrogenase polymorphisms in patients with Leber's hereditary optic neuropathy.

To define whether alcohol drinking provides a risk for Leber's hereditary optic neuropathy (LHON), the genotypes of low K(m) aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase type 2 (ADH2), major enzymes involving the alcohol metabolism, were examined in 29 unrelated Japanese patients with LHON associated with mitochondrial DNA 11778 mutation, 24 unrelated asymptomatic carriers with the mutation and 57 normal controls without the mutation. PCR-restriction detection revealed three genotypes of ALDH2 and ADH2. The allele frequencies of either enzyme in LHON patients, asymptomatic carriers, or both, did not differ from those in normal controls. There is no association between LHON and genotypes of alcohol-metabolizing enzymes. However, six of the LHON patients had frequent alcohol consumption, while none of the asymptomatic carriers claimed frequent drinking habit. Thus, we could not make a denial of drinking effects on optic nerve damage in LHON.

Adolescent↗
PubMed1997

[Lectin histochemistry of the glycoconjugates in conjunctival goblet cells].

The distribution of O- and N-linked glycoconjugates in human conjunctival goblet cells was examined histochemically using biotinylated and fluorescence-labeled lectins simultaneously. Both peanut agglutinin and Erythrina cristagalli agglutinin, specific for O- and N-linked sugar chains, respectively, bound to the same goblet cell, which demonstrated that a conjunctival goblet cell produces and contains both types of glycoconjugates. Maackia amurensis lectin II, specific for sialic acid alpha 2, 3 galactose, bound to the goblet cells, while Sambueus nigra agglutinin, specific for sialic acid alpha 2, 6 galactose, did not. This observation suggested that the terminal galactosyl residue of the glycoconjugates is alpha 2, 3-sialylated in the human conjunctival goblet cells.

Conjunctiva↗
PubMed1997

[Lectin-histochemical analysis of pleomorphic adenoma of the lacrimal gland].

The sugar structures of the glycoconjugates in pleomorphic adenoma of the lacrimal gland were analyzed by examining the binding sites of 5 biotinylated lectins on tissue sections with or without sialidase digestion. Both galactose (Gal) beta 1,3 N-acetylgalactosamine and Gal beta 1,4 N-acetylglucosamine were present on the surfaces of ductal basal cells and stromal cells. The galactsyl residues in the glycoconjugates of ductal basal cells were either sialylated or exposed, whereas those of stromal cells were all sialylated. Since the synthesis of sugar chains of glycoconjugates is terminated by sialylation, their structure may mature as they progress from ductal basal cells to stromal cells.

Acetylgalactosamine↗
PubMed1997

[Glycohistochemical analysis of rat eyelid epithelium].

The glycoconjugates in eyelids of adult rats were examined by lectin histochemistry and in situ hybridization histochemistry. Since Maackia amurensis lectin II and jacalin bound to the cell membranes of basal and apical epithelial cells, sialic acid alpha 2,3 galactose (Gal) beta 1,3 N-acetylgalactosamine (GalNAc) sequence is present in the glycoconjugates of their cell membranes. Peanut agglutinin bound to the cell membranes of spinous cells in the middle of the epithelium, suggesting that Gal beta 1, 3 GalNAc sequence is present in their glycoconjugates. The mRNA of Gal beta 1,3 GalNAc alpha 2,3-sialyltransferase was detected in the cytoplasm of the epithelial cells other than the basal cells. This observation suggests that sialoglycoconjugates may be newly synthesized in the spinous and apical cells, while the glycoconjugates in the cell membranes of basal cells may be produced at an early stage of development and are stable without turnover.

Animals↗