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Biomedical subjects

Y Mashima

Publications and source records attributed to Y Mashima.

At least 73 records · Page 4Linked to original sources
PubMed1998

Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy.

PURPOSE: To investigate the incidence and clinical significance of primary or proposed secondary mitochondrial DNA (mtDNA) mutations in Japanese patients with Leber's hereditary optic neuropathy (LHON). METHODS: Blood samples from the 80 unrelated Japanese patients with bilateral optic atrophy were screened for primary LHON mutations. Patients found to have a primary LHON mutation were then tested for 9 proposed secondary LHON mutations. We investigated the association between these mutations and clinical characteristics. RESULTS: Primary mtDNA mutations were identified in 68 patients: at np 3460 in 3 (4%) of 68 patients, at np 11,778 in 59 patients (87%), and at np 14,484 in 6 patients (9%). We identified 5 secondary mtDNA mutations (at np 3394, 4216, 7444, 9438 or 13,708) in 10 (15%) of 68 LHON patients and 3 mutations (at np 3394, 4216 or 3708) in 6 (7%) of 90 healthy Japanese individuals. No patient was positive for more than one secondary mutation. The frequency of secondary mutations was similar in the 68 LHON patients and 90 controls. The clinical features of the Japanese patients with any of the 3 primary LHON mutations were similar to those of Caucasian patients, despite different mtDNA backgrounds in these populations. The percentage of patients with familial LHON harboring the 3460 or 14,484 mutations was lower in the Japanese population. CONCLUSIONS: Japanese patients with LHON exhibited a very high incidence (87%) of the 11,778 primary mutation. Most of the proposed secondary LHON mutations were rare in the Japanese population and they, except the 7444 mutation, may not influence the clinical features of LHON.

Adolescent↗
PubMed1998

Severe form of juvenile corneal stromal dystrophy with homozygous R124H mutation in the keratoepithelin gene in five Japanese patients.

AIM: To confirm the mutation of the keratoepithelin gene in patients with a severe form of superficial juvenile granular corneal dystrophy (GCD). METHODS: Five Japanese probands in whom GCD was diagnosed after histopathological examination and who developed severe manifestations of GCD in their first decade of life were investigated. Other affected family members of two probands were also examined. All probands were the offspring of consanguineous parents. DNA was extracted from their peripheral blood leucocytes and mutational analysis of the gene was performed by the polymerase chain reaction and direct sequencing. RESULTS: Four of the five probands underwent their first keratectomy or keratoplasty in their teens and subsequently underwent a second or third keratoplasty. Each proband had a homozygous G-->A transition at codon 124, replacing Arg-->His, of the keratoepithelin gene. Their moderately affected family members were heterozygous for the mutation. CONCLUSIONS: This finding suggests that the severity of the corneal phenotype depends on the dose effect of the mutant gene.

Adult↗
PubMed1998

Quantitative analysis of lipid deposits from Schnyder's corneal dystrophy.

AIM: To report the quantitation of the lipid composition of a corneal button from a Japanese woman in her 60s with clinically and histopathologically proved Schnyder's corneal dystrophy. METHODS: Total lipids extracted from the corneal button of the patient were analysed by the method of thin layer chromatography flame ionisation detection. Two different solvent systems were used for neutral lipid analysis and phospholipid analysis. Results were compared with three age matched corneal buttons obtained from cadaveric eyes. RESULTS: The lipids that accumulated in the cornea in Schnyder's dystrophy consisted mainly of unesterified cholesterol and phospholipids. The analysis of phospholipids showed sphingomyelin to be the predominant phospholipid in the patient's cornea. CONCLUSION: Findings suggest that this disorder involves a disturbance of the metabolism of cholesterol and/or sphingomyelin metabolism that is limited to the cornea.

Cholesterol↗
PubMed1998

Orbital high resolution magnetic resonance imaging with fast spin echo in the acute stage of Leber's hereditary optic neuropathy.

Some evidence suggests that the primary locus of the lesion in Leber's hereditary optic neuropathy (LHON) may be intraocular rather than retrobulbar. To clarify this issue, the condition of the retrobulbar portion of the optic nerve was evaluated in patients with the acute stage of LHON. High resolution MRI with fast spin echo sequences of the optic nerve complex in the orbit was carried out. Five patients with acute stage LHON were compared with seven patients with acute stage optic neuritis. On T2 weighted fast spin echo MRI, signal changes did not appear in the retrobulbar optic nerve complex in acute stage LHON. By comparison, patients with optic neuritis showed pronounced high signals in the optic nerve. Subsequent orbital MRI in the atrophic stages of the same patients with LHON showed an increase in signal intensity in the optic nerve toward the orbital apex in both eyes. The present results support the hypothesis that a primary lesion in LHON may be intraocular.

Acute Disease↗
PubMed1998

Transforming growth factor-beta 1 promotes contraction of collagen gel by bovine corneal fibroblasts through differentiation of myofibroblasts.

PURPOSE: To determine whether the ability of transforming growth factor-beta (TGF-beta) to influence the contractile activity of corneal fibroblasts depends on their differentiation into myofibroblasts. METHODS: Bovine corneal fibroblasts were cultured on collagen gel in MED 5 medium (F-12 nutrient mixture supplemented with 5% fetal bovine serum) with or without TGF-beta 1 (0.01-10 ng/ml). To evaluate the corneal fibroblast-derived contraction of collagen gel, the thickness of the gel was measured daily for 6 days. The total number of cells on the gel was counted with a Coulter counter. The detection of alpha-smooth muscle actin (alpha-SMA); a marker for myofibroblasts, on these cells was performed immunocytochemically by using a mouse monoclonal antibody against alpha-SMA. The number of myofibroblasts (alpha-SMA-positive cells) was determined. RESULTS: The control gels containing bovine corneal fibroblasts that were cultured with the MED 5 medium alone significantly contracted to 72.3 +/- 1.2% of their original thickness after 6 days. TGF-beta 1 increased the contraction of collagen gel mediated by bovine corneal fibroblasts in a dose-dependent manner. Approximately 0.2% of the cells on the control gels cultured with MED 5 medium alone were alpha-SMA positive. TGF-beta 1 significantly increased the expression of alpha-SMA in a dose-dependent manner. There was no significant correlation between the thickness of the collagen gel and the total number of cells. However, there was a significant negative correlation between the thickness of collagen gel and the number of myofibroblasts. CONCLUSIONS: TGF-beta 1 increased the contractile activity of bovine corneal fibroblasts and their ability to differentiate into myofibroblasts. Because contractile activity was correlated with differentiation, the influence of TGF-beta 1 on corneal fibroblast-induced collagen gel contraction may depend on the promotion of myofibroblast differentiation.

Actins↗
PubMed1998

A family with Leber's hereditary optic neuropathy with mitochondrial DNA heteroplasmy related to disease expression.

A Japanese family has members with Leber's hereditary optic neuropathy resulting from the heteroplasmic 11778 mutation and the homoplasmic 4216 mutation. Quantitative determination of heteroplasmy was performed by a combination of polymerase chain reaction and single-strand conformation polymorphism analysis. The association between heteroplasmy and clinical features was determined. Eleven people from the maternal side of the family, including four affected and seven unaffected members, showed heteroplasmy of the mtDNA mutation ranging from 5% to more than 95%. Four possibly affected patients had more than 90% of the mutant mtDNA. Seven unaffected people had mutant mtDNA ranging from 5% to 77%. A recovery episode of visual acuity was noted in the history of three of the four patients. Heteroplasmy is likely to be a factor in the expression of disease in this family.

Adult↗
PubMed1998

Patient with Kearns-Sayre syndrome exhibiting abnormal magnetic resonance image of the brain.

A 33-year-old Japanese man had Kearns-Sayre syndrome (KSS), which consists of the triad of external ophthalmoplegia, heart block, and "salt-and-pepper" retinopathy. The other systemic manifestations included sensorineural hearing loss, slight generalized muscle weakness, cerebellar ataxia, and elevated levels of cerebrospinal fluid protein. He exhibited a heteroplasmic mitochondrial DNA deletion of approximately 9 kb between the cytochrome c oxidase subunit 1 and cytochrome b genes. In the authors' experience, this deletion is one of the longest to be observed in such patients. His fundi were characterized bilaterally by white flecks in the inner layers of retina at the midperiphery. Visual evoked potentials showed delayed latency in the P100 component. The tibial somatosensory evoked potential revealed a marked prolongation of interpeak latency between the N20 and P40 components. Brain magnetic resonance images revealed high-intensity foci in several regions on T2-weighted images. Electrophysiological and magnetic resonance imaging findings suggested an involvement of the white matter of the central nervous system in this patient that was not reflected in the clinical findings.

Adult↗
PubMed1997

Cloning of the cDNA for a new member of the immunoglobulin superfamily (ISLR) containing leucine-rich repeat (LRR).

We isolated cDNAs for a novel protein with a calculated molecular mass of 46 kDa, containing a leucine-rich repeat (LRR) with conserved flanking sequences and a C2-type immunoglobulin (Ig)-like domain. This novel protein was considered to be a new member of the Ig superfamily and was named ISLR (immunoglobulin superfamily containing LRR). These domains are known to be important for protein-protein interaction or cell adhesion, and therefore it is possible that the novel protein ISLR may also interact with other proteins or cells. Northern blot analysis showed the presence of a 2.4-kb transcript in various human tissues including retina, heart, skeletal muscle, prostate, ovary, small intestine, thyroid, adrenal cortex, testis, stomach, and spinal cord as well as fetal lung and fetal kidney. The ISLR gene was mapped on human chromosome 15q23-q24 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1997

A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping.

We have isolated a human cDNA clone encoding a novel acidic protein of MW 55,000 that we designated "myocilin" since it has homology to myosin and is localized preferentially in the ciliary rootlet and basal body of the connecting cilium of photoreceptor cells. The deduced amino acid sequence of human myocilin showed significant homologies with nonmuscle myosin of Dictyostelium discoideum in the N-terminal region and also with olfactomedin of bullfrog in the C-terminal region. Myocilin contained a leucine zipper-like motif similar to that seen in kinectin and other cytoskeletal proteins. These findings suggest that myocilin is a novel cytoskeletal protein involved in the morphogenesis of ciliated neuroepithelium such as photoreceptor cells. The myocilin gene (MYOC) was mapped to human chromosome 1q23-q24 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1997

Human retina-specific amine oxidase (RAO): cDNA cloning, tissue expression, and chromosomal mapping.

In search of candidate genes for hereditary retinal disease, we have employed a subtractive and differential cDNA cloning strategy and isolated a novel retina-specific cDNA. Nucleotide sequence analysis revealed an open reading frame of 2187 bp, which encodes a 729-amino-acid protein with a calculated molecular mass of 80,644 Da. The putative protein contained a conserved domain of copper amine oxidase, which is found in various species from bacteria to mammals. It showed the highest homology to bovine serum amine oxidase, which is believed to control the level of serum biogenic amines. Northern blot analysis of human adult and fetal tissues revealed that the protein is expressed abundantly and specifically in retina as a 2.7-kb transcript. Thus, we considered this protein a human retina-specific amine oxidase (RAO). The RAO gene (AOC2) was mapped by fluorescence in situ hybridization to human chromosome 17q21. We propose that AOC2 may be a candidate gene for hereditary ocular diseases.

Adult↗
PubMed1997

Preventing symblepharon formation with a gelatin sponge in the eye of a patient with an alkali burn.

PURPOSE: To report a patient with symblepharon caused by an alkali injury whom we treated by using a gelatin sponge. METHODS: Four days after the burn, a gelatin sponge was inserted into the upper conjunctival sac to separate the raw conjunctival surfaces. RESULTS: The gelatin sponge adhered to the tarsal side of the upper fornix and was kept there for 11 days until no epithelial defect was visible in the bulbar conjunctiva. No symblepharon formation was observed 6 months after the injury. CONCLUSION: Application of a gelatin sponge proved to be a simple and effective way of preventing symblepharon formation after an alkali burn.

Alkalies↗
PubMed1997

Dissociation of damage to spatial and luminance channels in early Leber's hereditary optic neuropathy manifested by the visual evoked potential.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder characterised by the acute or subacute loss of central vision, leading to severe optic atrophy. The occurrence of a demyelinating disease such as multiple sclerosis (MS) has been reported mainly in females with the mitochondrial DNA 11778 mutation. They had a poor visual outcome. To investigate the damage to the optic nerve in an early stage of LHON as compared with optic neuritis (ON), including MS, we examined patients by testing their pattern visual evoked potential (PVEP) and flash VEP (FVEP). The mean amplitude and latency in the PVEP were reduced and delayed, respectively, in patients with LHON or ON. The mean amplitude in the FVEP was reduced in patients with LHON or ON, but the mean latency was not delayed in patients with LHON as compared with normal subjects or patients with ON. Luminance-related fibres may be less affected than are the spatial-vision-related fibres in patients with early LHON.

Adolescent↗
PubMed1997

Fluorophotometric measurement of pH of human tears in vivo.

PURPOSE: To measure the pH in the precorneal tear film of humans in vivo using a pH-sensitive fluorescent dye, bis-carboxyethyl-carboxyfluorescein (BCECF). METHODS: The measurement was initiated by instilling 1 microliter of 2 mM BCECF solution into the subject's eye. The pH was calculated by measuring the ratio of fluorescent intensities at two excitation wavelengths (490/430 ratio), which was dependent on pH, but independent of the dye concentration and other variables. The tears of the same subject were then collected and loaded on to a micro pH-meter to ensure the accuracy of the measurement. RESULTS: The mean pH values of 40 eyes from 20 healthy volunteers was 7.50 (SD +/- 0.23), which corresponded well with those measured by the micro pH-meter. CONCLUSIONS: The method described was useful in measuring the pH of the precorneal tear film of humans with minimal invasion.

Calibration↗
PubMed1997

Detection of human papillomavirus infection in squamous tumours of the conjunctiva and lacrimal sac by immunohistochemistry, in situ hybridisation, and polymerase chain reaction.

BACKGROUND: Squamous tumours of the ocular surface, including the lacrimal pathway, range from benign lesions to invasive carcinomas. Some of these tumours are associated with human papillomavirus (HPV) infection, with the types of HPV differing among papillomas and dysplastic or malignant lesions. METHODS: The relation between squamous tumours of the conjunctiva and lacrimal sac and HPV infection was investigated in 17 individuals with such tumours. Nine of the 17 tumours were benign, four were dysplastic lesions, and four were carcinomas. RESULTS: Eight specimens showed positive immunohistochemical staining with antibodies to HPV; four of these eight were papillomas, three were dysplastic lesions, and one was a carcinoma. Koilocytosis was detected in seven of these eight tumours. Five of the eight specimens positive for immunohistochemical staining were also positive for HPV DNA by in situ hybridisation, and all eight were positive for HPV DNA by the polymerase chain reaction (PCR) method. CONCLUSION: Approximately 50% of squamous tumours of the ocular surface and lacrimal sac were associated with HPV infection. This is the first report, to our knowledge, of the detection of HPV in the field of ophthalmology by a combination of immunohistochemistry, in situ hybridisation, and PCR.

Adult↗
PubMed1997

High incidence of visual recovery among four Japanese patients with Leber's hereditary optic neuropathy with the 14484 mutation.

The 14484 mutation in the ND6 gene of mitochondrial DNA (mtDNA) is a genetic mutation associated with Leber's hereditary optic neuropathy (LHON) in Caucasian patients who show a high incidence of visual recovery. We evaluated four Japanese patients with LHON associated with the 14484 mutation who were negative for eight proposed secondary mutations. There was no family history of optic atrophy in three of the four patients. All four patients were initially diagnosed as having optic neuritis, either anterior (Cases 1 and 3) or retrobulbar (Cases 2 and 4), based upon their fundus findings and clinical history. Molecular genetic testing of mtDNA confirmed the diagnosis of LHON in all four patients. The three patients who experienced recovery had their vision return to 20/50 or better in both eyes. The patient who did not was a heavy consumer of alcohol and tobacco. These findings indicate that Japanese patients with the 14484 mutation have a visual prognosis similar to that of Caucasians with this mutation.

Adolescent↗
PubMed1997

[Inhibition of corneal neovascularization by a new analog of fungal product].

The anti-angiogenic activity if FR 118487, a new synthetic analogue of Scolecobasidium arenarium products, was examined in corneas of Japanese white rabbits. We studied locally administered FR 118487 with hydron pellets in two models; corneal neovascularization after implantation of a CuCl2 pellet (CuCl2-induced model) and a Wistar rat's cornea (keratoplasty model) into a rabbit cornea. In the CuCl2-induced model, maximum length of neovascularization was 0.08 +/- 0.10 (mean +/- standard deviation) mm with FR 118487 (control 2.84 +/- 0.13 mm) at 1 week after the implantation. In the keratoplasty model, maximum length of neovascularization was 0.05 +/- 0.05 mm with FR 118487 (control 3.33 +/- 0.18 mm) at 2 weeks after the implantation. In both models, FR 118487 had a significant (p < 0.01) effect on inhibition of corneal neovascularization.

Animals↗