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Biomedical subjects

Y Oguchi

Publications and source records attributed to Y Oguchi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Generation of plasma cells from peripheral blood memory B cells: synergistic effect of interleukin-10 and CD27/CD70 interaction.

B cells can differentiate into the antibody-secreting cells, plasma cells, whereas the crucial signals that positively control the entry into the pathway to plasma cells have been unclear. Triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). Differentiation into plasma cells by a combination of IL-10 and CD70 transfectants occurred in CD27+ B cells but not in CD27- B cells. Moreover, addition of IL-2 to the IL-10 and CD70-transfect activation system greatly induced differentiation into plasma cells. In the presence of only IL-2, IL-4, or IL-6, CD70 transfectants did not promote differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B-cell pool from peripheral blood B cells primarily activated by IL-2, IL-10, and anti-CD40 monoclonal antibody (MoAb). Finally, CD27 signaling also rescued B cells from IL-10-mediated apoptosis. These data demonstrate that CD27 ligand (CD70) is a key molecule to prevent the IL-10-mediated promotion of apoptosis and to direct the differentiation of CD27+ memory B cells toward plasma cells in cooperation with IL-10.

Adult↗
PubMed1998

A novel homozygous Ile535Asn mutation in the rod cGMP phosphodiesterase beta-subunit gene in two brothers of a Japanese family with autosomal recessive retinitis pigmentosa.

PURPOSE: Recently, mutations in several genes have been identified as being responsible for the pathogenesis of autosomal recessive retinitis pigmentosa (arRP). These genes include rhodopsin, beta-subunit of rod cGMP phosphodiesterase (PDEB), alpha-subunit of rod cGMP phosphodiesterase (PDEA), and alpha-subunit of rod cGMP-gated channel. We here attempted to identify a novel mutation in the PDEB gene in Japanese arRP patients. METHODS: Using the PCR-SSCP method, sequencing analysis, and restriction endonuclease digestion assay, we analyzed the PDEB gene in 17 Japanese families with non-dominant retinitis pigmentosa. RESULTS: A novel Ile535Asn mutation was identified in two patients in a single family and the mutation cosegregated with RP in this family. Among 90 unrelated healthy individuals, no one was identified as homozygous for this mutation, except for one individual who was found to be heterozygous. CONCLUSIONS: Isoleucine at codon 535 in the PDEB gene is conserved among various mammals. Missense mutations of the PDEB gene causing arRP have been reported in a limited region (codon 527-codon 699) in which codon 535 is located. Thus, the Ile535Asn mutation is an additional missense mutation which is responsible for the pathogenesis of arRP.

3',5'-Cyclic-GMP Phosphodiesterases↗
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

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

Visual function in retinitis pigmentosa related to a codon 15 rhodopsin gene mutation.

To determine the phenotype of a Japanese family in which retinitis pigmentosa cosegregates with a rhodopsin gene mutation, i.e. an asparagine-to-serine change at codon 15 (Asn-15-Ser), 5 affected and 5 unaffected members of one pedigree underwent several ophthalmic examinations as well as Ganzfeld electroretinography (ERG) and multifocal ERG. Genomic DNA samples were analyzed by PCR amplification, sequencing and restriction enzyme digestion. A codon 15 rhodopsin gene mutation (Asn-15-Ser) was found in all affected members. The region of pigmentary degeneration was localized in the lower hemiretina, and visual field defects corresponded to the retinal pigmentary changes. Scotopic ERG amplitudes, rather than photopic ERG amplitudes, were reduced. Multifocal ERG revealed a low magnitude of response density, even for the upper hemiretina, which showed no bony corpuscle pigmentation. Visual function in sectorial retinitis pigmentosa associated with rhodopsin gene codon 15 mutation is on the basis of the rod-cone dystrophy, regardless of differences in phenotypic expression.

Adult↗
PubMed1998

Progression of visual field loss in patients with retinitis pigmentosa of sporadic and autosomal recessive types.

PURPOSE: We examined the natural course of patients with retinitis pigmentosa of the eight sporadic and five autosomal recessive forms over 5 years. METHODS: We measured the areas of the visual fields by Goldmann perimetry using a digitizer and a computer software. RESULTS: The visual field of V-4 isopters in 4 sporadic cases was approximately 200 cm2 during 30 years after the initial examination, but decreased down to 40 cm2 in the next 10 years. The visual field was reduced to half the normal field in 3 autosomal recessive cases early below the age of 25 years. In 4 sporadic and 2 autosomal recessive cases, the inferior temporal visual field was the widest at the onset of the disease, but exhibited the most severe loss. The superior nasal area was the narrowest initially, and showed the mildest progression. CONCLUSIONS: The visual field in retinitis pigmentosa is constricted age-dependently with severe loss of the inferior temporal visual area and mild damage to the superior nasal area.

Adolescent↗
PubMed1998

Visual function and gene analysis in a family with Oguchi's disease.

A family with 1 case of retinitis pigmentosa (III-1) and 2 cases of Oguchi's disease (III-2, 3) was examined in terms of electrophysiology as well as molecular biology. The proband (III-3), a 42-year-old female, and 2 older brothers (III-1, 2, aged 52 and 45 years) and 2 unaffected members in the same family participated in this study. Corrected visual acuities of the individuals with Oguchi's disease (III-2, 3) were 1.2. On funduscopy, blood vessels stood out in relief against a metallic-appearing background and a Mizuo-Nakamura phenomenon was evident. Full-field electroretinograms (ERGs) recorded from the proband were indicative of rod dystrophy, but results of other electrophysiological examinations (multifocal ERG, pattern ERG and visual-evoked cortical potential recordings) were within normal limits. Patient III-1 had corrected visual acuities of RE 20 cm/m.m. and LE 30 cm/n.d., severe chorioretinal atrophy in both fundi, and full-field ERG revealed rod-cone dystrophy. Mutation of the arrestin gene (1147de1A) was detected in all 3 patients. Visual function in each patient coincides with that of retinitis pigmentosa or Oguchi's disease, respectively.

Adult↗
PubMed1998

[Visual information processing and the mechanism of vision. Clinical application].

Psychogenic disturbance of vision includes various abnormalities such as low vision, abnormal visual field, abnormal color sense and disturbance of binocular function, although there are no abnormalities either in the eyeball or optic nerve, and no organic changes in brain computed tomography (CT) or magnetic resonance imaging (MRI). To clarify these abnormalities, it is necessary first to study the mechanism of visual information processing. In this report, the mechanism of visual information processing such as visual acuity, visual field, vision and attention and binocular function was studied by standard electrophysiological methods as well as by new techniques including electroencephalography (EEG) topography, visual evoked response imaging system (VERIS), and magnetoencephalogram (MEG). The following four items and the possibilities for clinical application were studied and discussed. The subjects were normal adults and child volunteers, patients with disturbance of vision of psychogenic origin, and patients with abnormal visual fields caused by organic changes in the visual pathway. 1. Visual acuity (form vision). 1) Visually evoked potemtial (VEP), early receptor potential (ERP), and MEG examination were carried out for normal subjects and patients with psychogenic disturbance of vision. 2) The P 100 of pattern reversal VEP of the patients showed a significantly higher response. 3) In normal subjects, the P 300 was observed widely around the Pz in the ERPs during Landolt's ring stimulation. 4) In normal children, the P 300 was observed slightly temporal to the Pz. 5) In some patients maximum amplitude of P 300 was observed in the occipital or temporal region, but in other patients there was no P 300 response in any derivation. 6) MEG in patients with the conversion type of psychogenic disturbance of vision showed only 2 small dipolar patterns around 117 ms during flash stimulation. It was quite different from that of normal subjects. 2. Visual field. 1) Multifocal VEP using VERIS could detect experimental artificial hemianopia caused by conclusion of the half visual field in normal subjects. 2) Multifocal VEP could detect hemianopia or quadratanopia. 3) In multifocal VEP in normal subject, off-latency time was about 36 ms longer than on-latency time both in the center and at the periphery of the retina. The ratio of on/off response decreased from the center to the periphery. 4) In MEG using flash stimulation, hemianopia could be detected even in patients with fixation difficulties. 5) As the subjective visual field was not always in accord with the objective field, objective visual field evaluation is important. 3. Vision and attention. 1) To confirm the influence of attention on visual information processings in patients with disturbance of vision of psychogenic origin, a hypothetical 'island of attention' was postulated. 2) The 'spiral visual field' and the 'Inazuma-type visual field' could be explained by application of this hypothesis for patients with disturbance of vision. 3) Three kinds of waves in VEF, W 1, W 2, and W 3, were detected by MEG after the stimulation of line motion illusion. There was a tendency for the latency time on the attention side to be shorter than on the non-attention side in waves W 2 and W 3. 4) There was a tendency for the amplitude of the attention side to be higher than that of the non-attention side in wave W 3. 5) Attention may influence vision. 4. Binocular vision. 1) A stimulus target was devised which did not elicit N 75, P 100, or N 140 waves. When this target was used for stereoptic stimulation, a negative wave was elicited with a latency of 170 to 280 ms. 2) When the same stimulus target without parallax was used, this negative wave was elicited but the amplitude was small. 3) When evoked potentials were measured under the same conditions, an electric dipole was elicited from the occipital to the temporal region by the electric current source. (ABSTRACT TRUNCATED)

Adolescent↗
PubMed1998

[The clinical features of 9 cases of intraocular malignant lymphoma of oculocerebral origin].

We reviewed a series of 13 eyes in 9 cases of intraocular lymphoma with or without intracranial involvement during the past 15 years. The cases were characterized by moderate or no inflammation in the anterior ocular segment and by the presence of vitreous opacity and fundus lesions. Contrary to the accepted view that this disease simulates uveitis with various manifestations, the fundus lesions in the present series showed disseminated or tumorous subretinal lesions suggestive of proliferation of tumor cells. Only a few cases showed retinal vasculitis or retinal exudates. Electrooculograms showed findings suggestive of widespread impairment of the retinal pigment epithelium. Because of poor prognosis and sensitivity to radiation, we advocate early diagnosis and treatment for this disease.

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

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↗
PubMed1997

Use of high-speed, high-resolution thermography to evaluate the tear film layer.

PURPOSE: To evaluate the tear film layer in patients with dry eye and in normal subjects by measuring the corneal temperature with infrared radiation thermography. METHODS: One eye of each of 13 patients with dry eye and one eye of each of seven normal subjects were evaluated randomly. The corneal temperature was measured continuously with a recently improved infrared radiation thermography technique. We calculated the k value, which reflected the steepness of the corneal temperature change. The bigger the k value was, the more rapid was the decrease in corneal temperature, and this was directly related to increased evaporation. RESULTS: With normal blinking, the mean k value for patients with dry eye (5.6 +/- 2.9 per second) was significantly less than that in the control subjects (9.3 +/- 5.0 per second; P < .05). Keeping the eyes open after closing the eyes significantly decreased the k values compared with normal blinking in both groups (P < .05). CONCLUSIONS: Our findings demonstrate the usefulness of this method of measuring corneal temperature to evaluate the tear film layer. High-speed, high-resolution thermography detected subtle changes in corneal temperature with enhanced sensitivity and spatial and temporal resolution. We found that the mean k value, and therefore the rate of decline in corneal temperature in patients with dry eye, was significantly less than that in normal subjects. The k value may therefore reflect tear film layer stability. The measurement of the changes in the corneal temperature can thus give us valuable information on the tear film layer.

Adult↗
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↗