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Biomedical subjects

Y Oguchi

Publications and source records attributed to Y Oguchi.

At least 73 records · Page 4Linked to original sources
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

RANTES production in a conjunctival epithelial cell line.

PURPOSE: Although corneal tissue damage in allergic ocular diseases is thought to be induced by inflammatory cells that infiltrate from conjunctival tissue, the mechanisms of recruiting these cells remain unclear. The objective of this study was to demonstrate whether conjunctival epithelial cells have the ability to produce "regulated on activation, normal T-cell expressed and secreted" (RANTES). To test this hypothesis, we investigated RANTES expression in the conjunctival tissue and also RANTES production by cytokine stimulation in a human conjunctival epithelial cell line. METHODS: We investigated the expression of the chemokine RANTES in conjunctival epithelium from two patients with atopic keratoconjunctivitis (AKC) and one patient with vernal keratoconjunctivitis (VKC) by using immunohistochemistry. We also investigated the production and suppression of RANTES from a human conjunctival epithelial cell line, Wong-Kilbourne-derived human conjunctiva (WK-hC) by using enzyme-linked immunosorbent assay (ELISA). RESULTS: Conjunctival epithelium from a patient with AKC stained positively for RANTES. We found that tumor necrosis factor-alpha (TNF-alpha) induced de novo production of RANTES, and interferon-gamma (IFN-gamma) synergistically increased the TNF-alpha-dependent production of RANTES from WK-hC cells. Dexamethasone suppressed the RANTES production from the cell line. CONCLUSION: Taken together, human conjunctival epithelial cells were capable of producing RANTES in response to inflammatory stimuli such as TNF-alpha and may play a role in recruiting inflammatory cells such as eosinophils and T lymphocytes toward the ocular surface.

Adolescent↗
PubMed1997

Suppression of nuclear factor kappa B and CD18-mediated leukocyte adhesion to the corneal endothelium by dexamethasone.

PURPOSE: To demonstrate that leukocyte adhesion to cultured corneal endothelial cells is mediated by the CD18 antigen, and to determine whether dexamethasone directly suppresses adhesion by inhibiting activation of nuclear factor kappa B (NFkappaB). METHODS: Cultured bovine corneal endothelium was stimulated for 6 hours by 40 micron/ml tumor necrosis factor alpha (TNFalpha). Dexamethasone was added 1 hour before TNFalpha stimulation in the dexamethasone group. After stimulation, neutrophils separated from a healthy human volunteer were added with or without anti-CD18 antibody. The culture plate was settled for 15 minutes at 37 degrees C, and then neutrophils were activated by N-formyl-methionyl-leucyl-phenylalanine for 5 minutes. Nonadherent neutrophils were removed by sealing and inverting the culture well. The intracellular localization of NFkappaB after TNFalpha simulation was determined by confocal immunocytochemistry using an anti-p65 antibody. RESULTS: Neutrophil adhesion to cultured corneal endothelial cells increased significantly on exposure to TNFalpha (451.4+/-45.4 cells/mm2, n = 16) compared to control (156.7+/-27.3 cells/mm2, n = 16, P < 0.01). This increased adhesion was suppressed by the addition of anti-CD18 antibody (157.6+/-25.1 cells/mm2, n = 8, P < 0.01) and by pretreatment with 10(-7) M dexamethasone (207.9+/-31.5 cells/mm2, n = 10, P < 0.01). Immunocytochemistry 60 minutes after stimulation revealed that NFkappaB was located in the cytoplasm in unstimulated cells; however, the addition of TNFalpha caused NFkappaB to translocate into the nucleus. Pretreatment with dexamethasone tapered NFkappaB translocation into the nucleus. CONCLUSIONS: Leukocyte adhesion to the corneal endothelium was shown to be mediated by CD18 expressed on activated leukocytes. Pretreatment of the endothelium with dexamethasone inhibited leukocyte adhesion; this may be due in part to the suppression of NFkappaB entry into the nucleus.

Animals↗
PubMed1996

High-resolution magnetic resonance imaging of the intraorbital optic nerve and subarachnoid space in patients with papilledema and optic atrophy.

OBJECTIVE: To evaluate the orbital portion of the optic nerve and the subarachnoid space using fast spin-echo magnetic resonance imaging in normal subjects and in patients with papilledema or optic atrophy. DESIGN: Measurements of the optic nerve complex on coronal images were made using high-resolution magnetic resonance imaging with fast spin-echo sequences. PATIENTS: Twenty-one patients, including 5 patients with papilledema due to congenital hydrocephalus, intracranial tumors, or meningitis, as well as 16 patients with optic atrophy, were studied. Sixteen healthy volunteers served as controls. MAIN OUTCOME MEASURES: The longitudinal diameter of the optic nerve, the longitudinal outer diameter of the subarachnoid space, the diameter ratio, and the area of the subarachnoid space were determined. RESULTS: In normal subjects, the ring-shaped area of high signal intensity that represented the subarachnoid space was widest behind the globe, then narrowed toward the orbital apex. In patients with papilledema, the area of the subarachnoid space was markedly dilated, the optic nerve was compressed, and the nerve sheath was widened, resulting in a small diameter ratio compared with that of controls. Patients with pallor of the temporal aspect of the optic disc appeared to exhibit dilation of the subarachnoid space; the size of the optic nerve was decreased more than that of the nerve sheath, resulting in a small diameter ratio compared with controls. Patients with complete pallor of the disc, however, exhibited hyperintense optic nerve complexes without a ring-shaped appearance toward the orbital apex. CONCLUSION: Fast spin-echo magnetic resonance imaging appears useful for objectively evaluating the optic nerve and surrounding subarachnoid space in patients with papilledema and optic atrophy.

Adolescent↗
PubMed1996

Subthreshold UV radiation-induced peroxide formation in cultured corneal epithelial cells: the protective effects of lactoferrin.

Acute exposure to suprathreshold ultraviolet B radiation (UV-B) is known to cause photokeratitis resulting from the necrosis and shedding of corneal epithelial cells. however, the corneal effects of low dose UV-B in the environmental range is less clear. In this study, subthreshold UV-B was demonstrated to cause non-necrotic peroxide formation in cultured corneal epithelial cells, which was attenuated by the major tear protein lactoferrin. Intracellular oxidative insults and cell viability of rabbit corneal epithelial cells (RCEC) were assessed by dual-color digital microfluorography using carboxydichlorofluorescin (CDCFH) diacetate bis (acetoxymethyl) ester, a hydroperoxide-sensitive fluoroprobe, and propidium iodide (PI), respectively. The magnitude of UV-induced oxidative insults was calibrated by concentrations of exogenously applied H2O2 which evoke compatible levels of CDCFH oxidation. Exposure of RCEC to low-dose UV-B (2.0 mJ cm-2 at 313 nm, 10.0 mJ cm-2 total UV-B) caused intracellular oxidative changes which were equivalent to those elicited by 240 microM hydrogen peroxide under the conditions of the study. The changes were dose dependent, non-necrotic, and were partially inhibited by lactoferrin (1 mg ml-1) but not by iron-saturated lactoferrin. Pretreatment with deferoxamine (2 mM) or catalase (100 U ml-1) also attenuated the UV-induced oxidative stress. The results indicate that UV-B comparable to solar irradiation levels causes significant intracellular peroxide formation in corneal epithelial cells, and that lactoferrin in tears may have a physiological role in protecting the corneal epithelium from solar UV irradiation.

Animals↗
PubMed1996

High incidence of pre-excitation syndrome in Japanese families with Leber's hereditary optic neuropathy.

Cardiac conduction abnormalities have been reported in families with Leber's hereditary optic neuropathy (LHON). The pre-excitation syndrome Wolff-Parkinson-White syndrome or Lown-Ganong-Levine syndrome, is reportedly common in Finns with LHON, being seen in 14 (9%) of the 163 individuals with mitochondrial DNA (mtDNA) mutations. While this syndrome is thought to be rare in other ethnic groups with LHON, the present study of 35 Japanese LHON families confirmed that it is also relatively common among Japanese families, being seen in 5 (8%) of the 63 individuals with mtDNA mutations. It remains to be determined whether the high incidence of the pre-excitation syndrome in Finnish and Japanese LHON families is due to a particular genetic composition of ethnic groups such as in Finland and in Japan, or only to a reporting bias.

Comorbidity↗
PubMed1996

The use of epoxy patch grafts for the repair of experimentally-created diaphragmatic defects in dogs.

Canine pericardium which had been treated with polyepoxy compounds (Denacol EX-313) was used as a patch graft for the correction of experimentally-created diaphragmatic defects in five dogs belonging to the same litter. Clinical, macroscopic and histological examinations were conducted every month up to five months after suturing of the patch graft. Clinical examination of the patch graft showed no apparent abnormalities. Macroscopic examination conducted during autopsy showed that the patch graft maintained adequate elasticity for five months after suturing, the surface of the patch graft was covered with a thin membrane and neovascularization was observed. Histological examination showed that the surface of the patch graft was covered with a thin membrane. Inflammatory tissue reactions were observed at one month, but gradually decreased from the second month onwards. In addition, the patch graft had excellent tissue affinity.

Animals↗
PubMed1996

Antimetastatic effect of PSK, a protein-bound polysaccharide, against the B16-BL6 mouse melanoma.

We examined the effect of PSK, a protein-bound polysaccharide, upon in vivo metastasis and in vitro invasion of the B16-BL6 mouse melanoma cells. (1) PSK suppressed in vivo artificial and spontaneous lung metastases of B16-BL6 in C57BL/6 mice. (2) PSK in a dose-dependent fashion suppressed in vitro invasion and chemotaxis of the tumor cells using filters coated with a reconstituted basement membrane. (3) PSK had little effect on DNA synthesis in tumor cells in vitro, but suppressed tumor cell adhesion to, degradation of, and haptotaxis to components of the basement membrane. (4) PSK suppressed the binding of tumor cells to components of the basement membrane. These findings suggest that PSK may suppress metastasis through inhibition of tumor cell invasion and that this effect is the result of interactions between PSK and components of the basement membrane.

Animals↗
PubMed1995

The involvement of transforming growth factor beta in the impaired antitumor T-cell response at the gut-associated lymphoid tissue (GALT).

We studied the antitumor immune response in gut-associated lymphoid tissue (GALT), which is the tolerance-inducing site for numerous dietary antigens. The mice inoculated with colon 26 carcinoma (C-26) into the subserosal space of the cecum (i.c.) showed a more rapid tumor growth than did the mice inoculated s.c. with C-26 into the flank. In addition, the serum of the i.c. C-26-inoculated mice showed a more potent suppressive activity, and their plasma contained a higher level of transforming growth factor than the s.c. C-26-inoculated mice. We also evaluated the tumor-specific T-cell response in the GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The rejection of i.c. inoculated B7/P815 was delayed compared to that of the s.c. inoculated B7/P815. The draining axillary lymph node (LN) cells of the s.c. B7/P815-inoculated mice exhibited a CD4+ T-cell-dependent proliferative response to in vitro restimulation, whereas the draining mesenteric LN cells of the i.c. B7/P815-inoculated mice exhibited no apparent response even with the addition of interleukin 2. However, such draining mesenteric LN cells did produce higher levels of interleukin 2 and transforming growth factor beta than the draining axillary LN without any stimulation, and their production of such cytokines depend on the CD4+ and CD8+ cells, respectively. Collectively, our results suggest the possibility that the impaired antitumor T-cell response in the GALT may be attributed to "bystander suppression" by TGF-beta-producing CD8+ T cells.

Animals↗
PubMed1995

Risk of false-positive molecular genetic diagnosis of Leber's hereditary optic neuropathy.

PURPOSE/METHODS: The most common pathogenic mitochondrial mutation at nucleotide 11778 in Leber's hereditary optic neuropathy is usually detected by the loss of an SfaNI restriction site. To evaluate a false-positive diagnostic error in this molecular genetic assay, we investigated SfaNI polymorphism in 120 patients with bilateral optic atrophy. RESULTS/CONCLUSIONS: The ratio of false-positive to true-positive results was 1:36. Mitochondrial DNA polymorphism at nucleotide 11779 reflects a false-positive genetic error.

DNA↗
PubMed1995

A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese.

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness with all other visual functions, including visual acuity, visual field, and colour vision being usually normal. A typical clinical feature of the disorder is a golden or gray-white discolouration of the fundus which disappears in the dark-adapted state and reappears shortly after the onset of light ('Mizuo phenomenon'; Fig. 1). The course of dark adaptation of rod photoreceptors is extremely retarded in Oguchi disease while that of cones appears to proceed normally. The locus for Oguchi disease was recently mapped between D2S172 and D2S345 on distal chromosome 2q by linkage analysis. Interestingly, the gene for arrestin, an intrinsic rod photoreceptor protein implicated in the recovery phase of light transduction, also maps to this region of chromosome 2q (refs 6, 7). Here we report that in five out of six unrelated Japanese patients with Oguchi disease, we have identified a homozygous deletion of nucleotide 1147 (1147delA) in codon 309 of the arrestin gene, predicting a shift in the reading frame and a premature termination of translation which may result in 'functional null alleles.'

Adolescent↗
PubMed1995

Lack of differences among mitochondrial DNA in family members with Leber's hereditary optic neuropathy and differing visual outcomes.

Investigation of a maternal family of three generations of Leber's hereditary optic neuropathy (LHON) showed four affected and three unaffected individuals. Two of the four patients had recovered near-normal vision, one spontaneously, and one following treatment with idebenone, a quinol compound. One patient whose visual impairment persisted was a heavy consumer of alcohol and tobacco. Molecular genetic analysis of 12 known primary or secondary mutations in mitochondrial DNA (mtDNA) associated with LHON revealed only the 11778 mutation in a homoplasmic fashion with no secondary mutations. The variations in clinical outcome thus could not be explained by synergistically interacting secondary mutations in mtDNA. Environmental factors may play an etiologic role in the development of optic atrophy.

Adult↗
PubMed1995

Quantitative determination of heteroplasmy in Leber's hereditary optic neuropathy by single-strand conformation polymorphism.

PURPOSE: The maternal inheritance of Leber's hereditary optic neuropathy (LHON) is caused by defects in the genes of mitochondrial DNA (mtDNA). The most prevalent mtDNA mutation, present in 40% to 90% of families with this disease, is a G to A substitution at nucleotide position 11778. The rapid and accurate quantification of heteroplasmy of this mutation will help determine the relative risk for disease expression. METHODS: The authors conducted screening tests for heteroplasmy in 44 visually affected patients with the 11778 mutation and 34 unaffected members of 36 Japanese families with LHON using the single-strand conformation polymorphism analysis. This method can detect even a single base difference between the sequences of wild type and mutant DNA strands. The percentage of mutant mtDNA was calculated using an image analyzer. RESULTS: Single-strand conformation polymorphism analysis allowed the detection of heteroplasmy ranging from 5% to 95%. Five (14%) of the 36 families showed heteroplasmy, and 14 (18%) of the 78 persons tested had heteroplasmy ranging from 10% to 94%. Seven patients with heteroplasmy with visual loss had mutant mtDNA ranging from 62% to 94%. CONCLUSIONS: Single-strand conformation polymorphism analysis is rapid, efficient, and accurate for detecting point mutations and quantifying heteroplasmy in mtDNA. Individuals with heteroplasmy with less than 60% of mutant mtDNA in circulating leukocytes are probably at lesser risk for developing optic atrophy.

Adult↗
PubMed1995

[Molecular genetic analysis of Leber's hereditary optic neuropathy with the 3460 mutation in Japanese pedigrees].

We have identified a point mutation at nucleotide position 3460 in the ND1 gene of complex I in a Japanese pedigree with Leber's hereditary optic neuropathy by sequencing the ND genes in mitochondrial DNA. None of the 60 healthy Japanese had the 3460 mutation. The proband and his mother also had the 7444 mutation in the COI gene of complex IV and became nearly blind at age 19 with visual acuities of 0.02 OD and 0.04 OS We screened 30 patients with bilateral optic atrophy for the 3460 mutation, and identified one male patient who had the 3460 mutation in heteroplasmic fashion without carrying the 7444 mutation. He lost his sight at age 14 but it recovered to 1.2 OD and 0.7 OS about two years and half after the onset. The difference in final visual acuity between these two patients may reflect the degree of reduction in mitochondrial energy production.

Adolescent↗
PubMed1995

Clinical features of Japanese Leber's hereditary optic neuropathy with 11778 mutation of mitochondrial DNA.

The G to A transition of nucleotide position (nt) 11778 of mitochondrial DNA (mtDNA) has been frequently observed in Japanese Leber's hereditary optic neuropathy (LHON) cases. Therefore, we performed a multi-institutional study in Japan of LHON cases with this 11778 mutation of the mtDNA. Genetic and clinical data on 108 cases (90 affected and 18 carriers) in 79 unrelated families were obtained from 64 Japanese institutions. Detection of the nt11778 mutation was performed using restriction enzymes (74 cases) or dot blot with allele specific oligonucleotide (34 cases). Heteroplasmy was observed in 13 of the 90 affected cases and in 8 of the 18 carrier cases. Forty-five families had family history of LHON (44 maternal inheritance, 1 undetermined), and in 28 families (35.9%) there were isolated cases. The male-to-female ratio in the affected was 82:7 (92.1% male). The age at onset of visual loss ranged from 7 to 59 years (average: 23.4 years). All cases had bilateral involvement except one case with a blind eye resulting from ocular infection during childhood. Onset interval between the two eyes ranged from simultaneous to 17 months (average: 2.5 months), in 91.3% of cases being under 6 months. Visual acuity was 0.1 or worse in 152 (85.9%) of 177 eyes, only 6 eyes showing over 0.5. Progression of visual loss ranged from 0 to 48 months (average: 6.2 months). Central visual field abnormality was observed in 162 eyes (96.4%) of 168 eyes. Nonsuspect fundus in the ophthalmoscopic examination constituted 22.8% of eyes. Systemic corticosteroid was given to 45 (52.9%) of 85 cases and visual acuity was improved in only 2 cases (4.4%). Arrhythmia, neurological and muscular abnormality were observed as rare general complications. The present survey indicates that the male-to-female ratio is higher than the previous Japanese LHON statistics and that the visual outcome is better than in American LHON cases with the 11778 mutation.

Adolescent↗