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Biomedical subjects

Y Oguchi

Publications and source records attributed to Y Oguchi.

At least 19 recordsLinked to original sources

Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice.

We investigated both the effect and the mechanism of oral (p.o.) administration of PSK, a protein-bound polysaccharide derived from Basidiomycetes, on the anti-tumor T-cell response in gut-associated lymphoid tissue (GALT). The p.o. administration of PSK significantly suppressed the growth of colon 26 carcinoma (C-26) inoculated into the subserosal space of the cecum (i.c.), and augmented the tumor-neutralizing activity of the draining mesenteric lymph node (LN) cells. PSK treatment also significantly decreased the levels of immunosuppressive factors such as plasma transforming growth factor (TGF)-beta in the i.c. C-26-inoculated mice. We also evaluated the improving effect of PSK on the anti-tumor T-cell response in GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The PSK treatment promoted the rejection of i.c.-inoculated B7/P815 and restored the CD4+ T-cell-dependent proliferative response of the draining mesenteric LN cells against in vitro restimulation. Furthermore, the treatment also decreased the TGF-beta production but increased the IFN-gamma production of these cells. The p.o. administration of PSK, however, showed no effect in the CD8+ T-cell-dependent cytolytic activity of the draining mesenteric LN cells after in vitro restimulation. Overall, these results indicate that the p.o. administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in GALT, mainly through a suppression of TGF-beta production and a restoration of IFN-gamma production.

Administration, Oral

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

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

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

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

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

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

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

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

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

[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

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

[A statistical study of ocular complications of herpes zoster ophthalmicus and its prolongation factors].

A statistical study was carried out on 218 patients (107 male and 111 female) with herpes zoster ophthalmicus (HZO) who visited our clinic from April 1985 to March 1992. The incidence of ocular complications (OCs) and the rate of prolonged OCs (over 6 months) were also studied with the factors that were considered to have affected them. There were 114 patients who showed OCs out of 218 HZO patients (52.3%). The incidence of OCs was higher among the patients with nose eruption than among those without (p < 0.001), and lower among the patients with acyclovir treatment in advance than among those without (p < 0.001). The rate of prolonged OCs was higher among the patients over 50 years old than among those under 50 years old (p < 0.05), higher among the patients with nose eruption than among those without (p < 0.05), and lower among the patients with acyclovir treatment in advance than among those without (p < 0.01). Those with nose eruption had a high rate of prolonged iritis. Severe visual acuity loss remained in 3 cases (2.6%): 2 cases of corneal opacity in the center and 1 case of neurouveitis. Two patients suffered from high intraocular pressure complicated with prolonged iritis.

Adolescent

Histamine and tryptase levels in allergic conjunctivitis and vernal keratoconjunctivitis.

Tryptase is useful as a specific and accurate indicator of mast cell activation, whereas histamine, a mast cell's major mediator, also exists in basophils. The aim of this study is to investigate histamine and tryptase levels in allergic conjunctiva. We measured histamine and tryptase levels in conjunctival epithelial cell suspension of children with allergic conjunctivitis (AC) and vernal kerato-conjunctivitis (VKC), and controls, and we evaluated correlations with clinical observations. Both the histamine and tryptase levels in VKC were significantly higher than controls (p < 0.05, p < 0.01), and histamine levels in VKC was also greater than AC (p < 0.05). The histamine/tryptase (H/T) ratios were 0.03 +/- 0.04 in AC, 0.08 +/- 0.09 in VKC and 0.006 +/- 0.006 in controls. The H/T ratios in VKC were significantly higher than controls (p < 0.05) and AC (p < 0.05), and were also found to correlate with the superficial punctate keratopathy (SPK) score (r2 = 0.89). Analyzing the histamine and tryptase levels in conjunctival epithelium may be useful in evaluating the allergic ocular surface, especially in the cases with SPK, where the increase in the histamine levels is not accompanied by an increase in tryptase levels. This suggests an important role for inflammatory cells such as basophils infiltrating into the conjunctival epithelium in allergic reactions.

Child

Rhinogenous optic neuritis with drastic diurnal variation of visual function.

We report a case of rhinogenous optic neuritis in a 50-year-old man demonstrating drastic diurnal variation in visual function. His left vision was 20/15 in the morning, which gradually decreased to counting fingers at night. Pupillary reaction and visual field showed the same fluctuation as vision. Complete remission of visual symptoms was achieved after endonasal ethmoid sinusotomy.

Circadian Rhythm

Autosomal dominant retinitis pigmentosa. A mutation in codon 181 (Glu-->Lys) of the rhodopsin gene in a Japanese family.

The PCR/restriction endonuclease digestion (RE) assay and PCR/SSCP analysis of the rhodopsin gene in 13 Japanese families with autosomal dominant retinitis pigmentosa (ad RP) revealed a G-A substitution of the first nucleotide of codon 181, replacing Glu (GAG) with Lys (AAG), in one family. The proband showed an early onset of symptoms in childhood with a diffuse loss of rod and cone function and a relatively good preservation of cone function, corresponding to the type with relatively rapid progression to blindness (type I category of ad RP).

Adult