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Biomedical subjects

S Kotake

Publications and source records attributed to S Kotake.

At least 73 records · Page 4Linked to original sources

Posterior sub-Tenon injections of repository corticosteroids in uveitis patients with cystoid macular edema.

Repository corticosteroid was injected into the posterior sub-Tenon space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. There were 12 cases of Behçet's disease, 7 cases of sarcoidosis, one case of tuberculous uveitis, and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated 2 to 7 times at intervals of more than 2 weeks. Twenty-two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Fifteen of the 22 eyes had maintained improved visual acuity over 6 months. Eleven eyes showed no improvement in vision. Most of them already had poor visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon space is of value in the treatment of CME secondary to uveitis. However, we have to beware of the complications of treatment.

Adolescent↗

[MHC and non-MHC gene effects on the development of experimental autoimmune uveoretinitis].

Experimental autoimmune uveoretinitis (EAU) can be induced in rats by interphotoreceptor retinoid-binding protein (IRBP), and served as a model for human uveitis. Using IRBP-derived peptide R16, we investigated the MHC and non-MHC genes' effect on the regulation and susceptibility to EAU. EAU-high susceptible LEW (RT1l), EAU-low susceptible WKAH (RT1k), and WKAH.1L rats which carry RT1l and WKAH background were immunized with 2 nmol of R16. One hundred percent of LEW rats developed EAU and 92.9% of WKAH. 1L rats. Only, 18.8% of WKAH rats developed EAU. Among these strains tested, the severity of EAU was 2.06 in LEW, 1.23 in WKAH.1L, and 0.38 in WKAH. R16 evoked substantial proliferative responses in all these strains. The present data suggest that both MHC and non-MHC genes play distinct roles in development of EAU.

Animals↗

Participation of non-major histocompatibility antigen complex gene in experimental autoimmune uveitis.

It is known that the susceptibility to experimental autoimmune uveitis (EAU) is controlled by both major histocompatibility antigen complex (MHC) and non-MHC genes. In this report, we studied the role of non-MHC genes in the induction of EAU. LEW, WKAH, (LEW x WKAH)F1, and (LEW x WKAH)F2 rats were examined to determine the incidence and severity of EAU induced by immunization with bovine S-antigen (S-Ag). We found that all the LEW rats developed severe EAU within 2 weeks after immunization, but no WKAH rats did. Most of the F1 rats developed mild inflammation in 3-4 weeks after immunization. A quarter of the F2 rats developed EAU within 2 weeks, half of them, in 3-6 weeks after immunization, and the others did not. These findings suggest that only one non-MHC gene controls the susceptibility to S-Ag-induced EAU in rats.

Animals↗

Interphotoreceptor retinoid-binding protein derived peptide can induce experimental autoimmune uveoretinitis in various rat strains.

Experimental autoimmune uveoretinitis (EAU) is an intraocular inflammatory disease model induced by retinal specific antigens such as S-antigen and interphotoreceptor retinoid-binding protein (IRBP). The present study was aimed at testing the uveitogenicity of IRBP and an IRBP-derived peptide in various strains of rats with different RT1 (major histocompatibility complex in rats) haplotypes. Immunization with IRBP induced distinct EAU in LEW (RT1l), WKAH (RT1k) W/M (RT1k), LEJ (RT1j), and BUF (RT1b) rats. IRBP also induced a low grade of EAU in SDJ (RT1u), but no disease was detected in TO rats, another strain of the RT1u haplotype. IRBP-derived peptide R16 (aa 1177-1191) induced severe EAU in LEW rats and moderate disease in the WKAH and W/M strains. Immunization with R16 also induced low levels of inflammation in eyes of 75% and 20% of LEJ and BUF rats, respectively, but this peptide did not cause any disease in SDJ and TO rats. Injection of Bordetella pertussis had minimum or no effect on the induction of EAU by peptide R16 in this study. These data thus indicate that peptide R16 can bind to various RT1 molecules in addition to RT1l. Further, our observations support the notion that certain epitopes of IRBP could be uveitogenic in humans with different HLA haplotypes.

Amino Acid Sequence↗

[Familial occurrence of Behçet's disease].

Familial occurrence of Behçet's disease was studied in the Uveitis Survey Clinic of Hokkaido University Hospital. Eighteen patients in the nine families had familial occurrence of this disease. Male to female ratio was 0.28 in the familial cases, which was significantly higher than in the sporadic cases. Familial occurrence was most frequently seen among siblings. Most patients, including all of the females, belonged to the complete type. They had typical ocular lesions and exhibited bilateral uveoretinitis with poor visual prognosis, particularly in the females. The frequency of HLA-B5 was 92% in the familial patients, which was significantly higher than in the normal controls and the sporadic cases. It is probable that patients with familial occurrence of this disease have poorer prognosis with stronger immunogenetic backgrounds.

Adult↗

[New approaches to the regulation of autoimmune disease].

Recent advancement in immunology has revealed that autoimmune diseases occur when T lymphocytes become activated on recognizing a self-antigen linked to the autologous class II molecule of the major histocompatibility complex (MHC). The resulting complex of antigen, MHC, and T cell receptor could be a target for treatment of autoimmune disease. This approach is now being studied in animal models. Experimental autoimmune uveoretinitis is a T cell mediated autoimmune disease directed against retinal proteins and has been studied as a model for human uveitis. In Lewis rats, uveitogenic peptides and uveitogenic T cell receptor families have been detected. It is a first step toward developing specific immunotherapy. This paper describes a general outline of the steps of T cell activation and ways of suppression of autoimmune diseases by the modulation of these steps, especially in experimental autoimmune uveoretinitis.

Amino Acid Sequence↗

[Posterior sub-Tenon's injections of repository corticosteroids in uveitis patients with cystoid macular edema].

Repository corticosteroid was injected into the posterior sub-Tenon's space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. They included 12 cases of Behçet's disease, 7 cases of Sarcoidosis, one case of tuberculous uveitis and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated twice to seven times at intervals of more than 2 weeks. Twenty two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Eleven eyes showed no improvement in vision. Most of them had already had bad visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon's space was effective in the treatment of CME secondary to uveitis. However, we have to beware of the complications of this treatment.

Adolescent↗

[Participation of non-major histocompatibility complex gene in experimental autoimmune uveitis].

It is known that the susceptibility of experimental autoimmune uveitis (EAU) is controlled by both major histocompatibility antigen complex (MHC) and non-MHC genes. In this report, we studied the role of non-MHC gene in the induction of EAU. LEW, WKAH, (LEW x WKAH) F1 and (LEW x WKAH) F2 rats were examined for their incidence and severity to develop EAU by immunization with bovine S-antigen (S-Ag). We found that all LEW rats developed severe EAU within 2 weeks after immunization, but no WKAH rat did. Most F1 rats developed mild inflammation in 3-4 weeks after immunization. A quarter of F2 rats developed EAU within 2 weeks, half of them developed it in 3-6 weeks after immunization, and the others did not. These findings suggest that only one non-MHC gene controls the susceptibility to S-Ag induced EAU in rats.

Animals↗

Control of experimental autoimmune uveoretinitis by low dose T cell vaccination.

Autoimmune T lymphocytes can be used under appropriate conditions to induce resistance to the specific autoimmune disease that they usually produce. This practice, termed T cell vaccination, was found to be effective with the injection of a low (subpathogenic) number of autoaggressive T line lymphocytes. We report here that T cell vaccination produced marked resistance to the expression of experimental autoimmune uveoretinitis (EAU) in Lewis rats. In addition, vaccination led to the appearance of lymphoid cells in the vaccinated rats that demonstrated proliferative responses against idiotypic and ergotypic specificities of the injected T cells. This is the first report demonstrating the effector T lymphocytes specific for ocular antigens may be used as agents to modulate immunopathogenic responses responsible for EAU.

Amino Acid Sequence↗

The existence of two completely distinct antigenic sites within a decapeptide.

A decapeptide (1182-1191) derived from the bovine interphotoreceptor retinoid-binding protein (IRBP) was found to contain two completely distinct antigenic sites when tested in Lewis rats. One site, localized in sequence 1182-1191, is the core of the immunodominant and highly uveitogenic determinant of IRBP. The second site localizes within sequence 1183-1191 and becomes detectable only when tryptophan at position 1182 is deleted. Lymphocytes sensitized against the first, larger site recognized all longer peptides within sequence 1169-1191, as well as whole IRBP. In contrast, lymphocytes sensitized against the second, short epitope recognized only two peptides, 1184-1191 and (to a lesser degree) 1183-1191. The responses to both sites were restricted by the same major histocompatibility complex (MHC) product (I-A), as shown by monoclonal antibody blocking and by the finding that the lymphocyte response to 1184-1191 was competitively inhibited by peptide 1181-1191. The unique finding of two completely distinct antigenic sites within a decapeptide could be explained by the hypothesis that peptides of the two sites combine with the MHC molecule on antigen-presenting cells by different configurations, thus forming two distinct antigenicities.

Amino Acid Sequence↗

Purification of cytochrome c oxidase by lysine-affinity chromatography.

A method for the purification of cytochrome c oxidase that is based on the affinity of this enzyme for polycations such as poly-L-lysine is described. When detergent extracts of bovine cardiac mitochondria were applied to either a poly-L-lysine-agarose or a lysine-Sepharose column at low ionic strength, cytochrome c oxidase was found to adhere tightly, whereas the bulk of the proteins were eluted by washing with the same buffer. The cytochrome c oxidase was eluted by application of a linear potassium chloride gradient to the columns. The resulting enzyme was identical to that obtained by more traditional purification methods in terms of its subunit composition, optical and resonance Raman spectra, and cytochrome c oxidizing activity. When detergent extracts of spheroplasts from Paracoccus denitrificans were applied to these columns, the cytochrome c oxidase from this organism was also found to adhere tightly. Thus this purification method appears applicable to both prokaryotic and eukaryotic forms of the enzyme. The advantages of this new purification method are that it is less labor intensive than the traditional procedure and less expensive than methods based on cytochrome c-affinity chromatography.

Animals↗

Antibody response to oral streptococci in Behçet's disease.

The serum antibody titers against oral streptococci were studied by enzyme-linked immunosorbent assay (ELISA) both in patients with Behçet's disease (BD) and control groups. The patients with BD showed significantly higher antibody titers to S. sanguis strains 113-20, 114-23, and 118-1 which were isolated from patients with BD, in comparison with control groups. Also, the reactions of high-titered sera to the crude cell wall and soluble (or membrane) fractions of the 113-20 strain were observed by western blot test. The sera of the patients with BD demonstrated strong bands of approximately 36 kDa, 82 kDa, and 87 kDa in the crude cell wall fractions, and many bands of 80 kDa to 150 kDa in the membrane fractions, indicating that these proteins are the ones leading the high antibody titers to this bacterium in the sera of patients with BD.

Antibodies, Bacterial↗

[Unique immunological properties of short forms of the interphotoreceptor retinoid-binding protein derived uveitogenic peptide].

Interphotoreceptor retinoid-binding protein (IRBP) induces experimental autoimmune uveoretinitis in a variety of animals. We have previously shown that sequence 1169-1191 of bovine IRBP has strong uveitogenicity and immunogenicity in Lewis rats. In this study, two completely distinct antigenic sites were detected within a short form of this peptide. One site is localized in sequence 1182-1191. The second site localizes within sequence 1183-1191 and becomes detectable only when tryptophan at 1182 is deleted. Lymphocytes sensitized against the first determinant recognized a longer peptide as well as whole IRBP. Lymphocytes sensitized against the second determinant recognized only two peptides 1184-1191 and 1183-1191. No cross reactivity was detected between these two determinants. Amino acid substitution of tryptophan with alanine or glutamic acid at 1182 in peptide 1182-1191 caused complete loss of uveitogenicity and immunogenicity, while substitution with phenylalanine did not change any immunological activities of the original peptide. The unique immunological properties of IRBP-derived peptides were discussed.

Amino Acid Sequence↗

[Eosinophilia-myalgia syndrome].

Eosinophilia-myalgia syndrome (EMS) is a newly recognized disease, characterized by peripheral eosinophilia with scleroderma-like features. By July 1991, 1543 cases of EMS, including 31 fatal cases, have been reported. Although epidemiologic studies strongly suggest the association of EMS with ingestion of L-tryptophan (LT) containing a contaminant from a single manufacture, the pathogenesis of this disease is not well understood. The insight obtained from the study of EMS may be applicable to scleroderma or eosinophilic fasciitis. Recent advances in the understanding of clinical and pathologic features of EMS are reviewed.

Adolescent↗

[Low dose cyclosporin treatment for ocular lesions of Behçet's disease].

Cyclosporin is an immunosuppressant that has recently been used for the treatment of Behçet's disease. We evaluated the clinical effect of low doses of cyclosporin (5 mg/kg/day) on 20 patients of Behçet's disease with refractory ocular involvement. The therapeutic effect of cyclosporin was judged by the frequency of ocular inflammatory attacks. It was effective in more than 70% of the patients. On the other hand, it had some adverse side effects such as renal dysfunction, indigestion, and neurological disorders. Most side effects were mild with low dose treatment, but neurological side effects were similar in frequency and severity to those seen with 10 mg/kg/day usage. These findings indicate that low dose cyclosporin (5 mg/kg/day) administration may be acceptable as a standard plan for treatment of Behçet's disease, but that we have to use cyclosporin with great attention to its side effects, especially neurological symptoms.

Adult↗

Detection of myeloid precursors (granulocyte/macrophage colony forming units) in the bone marrow adjacent to rheumatoid arthritis joints.

Various cytokines were recently found to be involved in the pathogenesis of rheumatoid arthritis (RA) and particularly, cytokines with hematopoietic activity have been detected in synovial tissues. We counted the number of myeloid precursors in terms of granulocyte/macrophage colony forming units (CFU-GM) and the number of stromal cell progenitors in terms of fibroblast colony forming units (CFU-F) in the tibial bone marrow adjacent to the joints affected by RA (n = 21), osteoarthritis (OA) (n = 10), and trauma (n = 2) using the colony formation unit assay. We also quantitated the amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony stimulating factor (GM-CSF) in the culture supernatant of synovial tissue explants of these patients by enzyme linked immunosorbent assay (ELISA). The mean number (+/- SEM) of CFU-GM in patients with RA (7.4 +/- 4.9) was greater than that in patients with OA (0.5 +/- 0.2), while CFU-GM was not detected in trauma patients. The number of CFU-GM in the tibial bone marrow of patients with RA correlated well with the amount of IL-1 beta (r = 0.64, p < 0.01), but not with GM-CSF or with IL-6 from synovial tissues. These findings suggest that active bone marrow is present adjacent to the affected joints in patients with RA and that hematopoietic activity is influenced by IL-1 beta produced in nearby synovial tissues.

Aged↗

[The diagnosis of sarcoidosis based on ocular manifestations].

A total of 131 patients with typical ocular manifestations of sarcoidosis were studied. From systemic examinations, 56 cases were confirmed histologically as sarcoidosis, 59 cases were clinically diagnosed as sarcoidosis and 16 cases were not diagnosed as sarcoidosis. There were no differences among the three groups in terms of laterality of eye involvement, sex distribution, ocular findings and prognosis. The only difference was that the age of patients not diagnosed as sarcoidosis was lower than the other two groups. In systemic examinations, patients diagnosed as sarcoidosis histologically or clinically had higher ratios of positive findings of bilateral hilar lymphadenopathy, 67Ga scanning, bronchoalveolar lavage fluid and serum angiotensin converting enzyme than patients who were not diagnosed as sarcoidosis. Some cases of the third group may be diagnosed as sarcoidosis in the future by repeated systemic examinations. The difficulty of diagnosis of sarcoidosis from ocular findings alone was discussed.

Adolescent↗