Search PubMed⌕ Search

Biomedical subjects

S Kotake

Publications and source records attributed to S Kotake.

At least 91 records · Page 5Linked to original sources
PubMed1991

Detection of antibodies against Borrelia burgdorferi in patients with uveitis.

We determined the antibody response against Borrelia burgdorferi strains isolated from Japanese Ixodes ovatus and Ixodes persulcatus ticks by enzyme-linked immunosorbent assay and indirect immunofluorescence assay of serum specimens from 127 patients with uveitis. We examined samples of serum from Japanese patients with unclassified uveitis, iridocyclitis caused by herpes zoster virus, Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, or other conditions (sympathetic ophthalmia, Posner-Schlossman syndrome and acute anterior uveitis with ankylosing spondylitis). Serum from healthy individuals and patients with Lyme disease served as negative and positive control samples, respectively. Significantly higher antibody titers were demonstrated in patients with uveitis than in control subjects. Of 29 patients with unclassified uveitis, nine (31) had significantly increased antibody titers against B. burgdorferi strain H014 by ELISA testing. Five patients also showed higher IgG and IgM responses than in three control subjects with Lyme disease. All positive controls showed joint problems characteristic of rheumatoid arthritis. One of three patients had uveitis. The patients were diagnosed as having Lyme disease on the basis of their history and serologic tests. A positive antibody response was recognized in several patients with Behçet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, and other conditions (acute anterior uveitis with ankylosing spondylitis), but not in control subjects.

Antibodies, Bacterial↗
PubMed1991

Resolution of the electronic transitions of cytochrome c oxidase: evidence for two conformational states of ferrous cytochrome alpha.

Second-derivative absorption spectra are reported for a variety of oxidation and ligation states of bovine cytochrome c oxidase (ferrocytochrome-c:oxygen oxidoreductase, EC 1.9.3.1). The high resolving power of the second-derivative method allows us to assign the individual electronic transitions of cytochrome alpha and cytochrome alpha 3 in many of these states. In the fully reduced enzyme, one observes a single electronic transition at 444 nm, corresponding to the Soret transition for both ferrous cytochrome alpha and ferrous cytochrome alpha 3. When the cytochrome alpha 3 site is occupied by an exogenous ligand (CN or CO), one observes two absorption bands assignable to the ferrous cytochrome alpha chromophore, one at ca, 443 nm and the other at ca, 450 nm. The appearance of the 450-nm band is dependent only on ligand occupancy at the cytochrome alpha 3 site and not on the oxidation state of the cytochrome alpha 3 iron. These results can be interpreted either in terms of a heterogeneous mixture of two ferrous cytochrome alpha conformers in the cytochrome alpha 3-ligated enzyme or in terms of a reduction in the effective molecular symmetry of the ferrous cytochrome alpha site that results in a lifting of the degeneracy of the lowest unoccupied molecular orbital associated with the Soret pi,pi* transition of cytochrome alpha. In either case, the present data indicate that ferrous cytochrome alpha can adopt two distinct conformations. One possible structural difference between these two states could be related to differences in the strength of hydrogen bonding between the ferrous cytochrome alpha formyl oxygen and a proton donor from an unidentified amino acid side chain of the enzyme. The implications of such modulation of hydrogen-bond strength are discussed in terms of possible mechanisms of proton translocation and electron transfer in the enzyme.

Animals↗
PubMed1991

Analysis of the pivotal residues of the immunodominant and highly uveitogenic determinant of interphotoreceptor retinoid-binding protein.

Interphotoreceptor retinoid-binding protein (IRBP), a retinal-specific Ag, induces experimental autoimmune uveitis in a variety of animals. We have previously shown that sequence 1169-1191 of bovine IRBP is the immunodominant epitope of this protein in Lewis rats and is highly immunogenic and uveitogenic in these rats. The active site of peptide 1169-1191 was determined by testing its truncated forms. The shortest peptide to be immunologically active was found to be 1182-1190 (WEGVGVVPD). To determine the role of individual residues of this sequence, we have tested the immunologic activities of nine analogs of peptide 1181-1191, in which each of residues 1182-1190 was substituted with alanine (A). The tested activities included the capacity to induce experimental autoimmune uveitis and cellular responses in immunized rats, as well as the capability to stimulate lymphocytes sensitized against IRBP or the parent peptide 1181-1191. Analogs that did not stimulate these lymphocytes were also tested for their capacity to competitively inhibit the proliferative response to 1181-1191. Analogs A(1184), A(1186), and A(1187) resembled 1181-1191 in their activities, whereas the other analogs exhibited remarkably reduced activities, with several patterns being noticed. Analog A(1182) was inactive in all tests. Analog A(1190) was very weakly uveitogenic and non-immunogenic, but it stimulated lymphocytes sensitized against IRBP or 1181-1191 when added at exceedingly high concentrations. Analogs A(1183) and A(1185) resembled A(1190) in being weakly uveitogenic and A(1185) was also found to be poorly immunogenic. In addition, relatively high concentrations of A(1183) and A(1185) were needed to stimulate lymphocytes sensitized against IRBP or 1181-1191. However, a different pattern of activities was exhibited by analogs A(1188) and A(1189). These peptides were uveitogenic and immunogenic, but failed to stimulate lymphocytes sensitized to IRBP or 1181-1191. Furthermore, A(1188) and A(1189), but not A(1182), also inhibited the response to 1181-1191 of a cell line specific toward this parent peptide. The data are interpreted to show that residues 1188 and 1189 are involved in the interaction of the peptide with the TCR, whereas residues 1182 and 1190 and, perhaps, 1183 and 1185, are pivotal for the binding of peptide 1181-1190 to the MHC molecules on APC.

Amino Acid Sequence↗
PubMed1991

Physicochemical characterization of bovine retinal arrestin.

The native conformation of bovine retinal arrestin has been characterized by a variety of spectroscopic methods. The purified protein gives rise to a near uv absorption band centered at 279 nm which results from the absorbance of its 14 tyrosine and one tryptophan residue. The extinction coefficient for this absorption band was determined to be 38.64 mM-1, cm-1 using the tyrosinate-tyrosine difference spectrum method; this extinction coefficient is ca. 17% lower than the previously reported value, and provides estimates of protein concentration which are in good agreement with estimates from the Bradford colorimetric assay. When native arrestin is purified to homogeneity, it displays a fluorescence spectrum which is dominated by tyrosine emission with no discernible contribution from tryptophan. Observation of the tyrosine-like fluorescence is dependent on the purity and structural integrity of the protein. Denaturation of arrestin by guanidine hydrochloride results in a diminution of tyrosine fluorescence and the concomitant appearance of a second fluorescence maximum at ca. 340 nm, presumably due to the single tryptophan residue. Thermal denaturation of arrestin leads to a conformation characterized by a broad fluorescence band centered at ca. 325 nm. Study of the arrestin fluorescence spectrum as a function of temperature indicates that the thermal denaturation is well modeled as a two-state transition with a transition midpoint of 60 degrees C. Temperature-dependent far uv circular dichroism studies indicate that changes in secondary structure occur coincident with the change in fluorescence. Studies of the temperature dependence of arrestin binding to light-adapted phosphorylated rhodopsin shows a strong correlation between the fluorescence spectral features of arrestin and its ability to bind rhodopsin. These data suggest that the relative intensities of tyrosine and tryptophan fluorescence are sensitive to the structural integrity of the native (i.e., rhodopsin binding) state of arrestin, and can thus serve as useful markers of conformational transitions of this protein. The lack of tryptophan fluorescence for native arrestin suggests an unusual environment for this residue. Possible mechanisms for this tryptophan fluorescence quenching are discussed.

Amino Acid Sequence↗
PubMed1991

Platelet aggregation induced by uncommon serotypes of Streptococcus sanguis isolated from patients with Behçet's disease.

Uncommon serotypes were tested for their ability to induce aggregation in platelet-rich plasma. Both uncommon and common serotypes induced platelet aggregation in rabbit platelet-rich plasma, but serotonin release was higher with the uncommon serotypes. Aggregation at ATP release varied between uncommon and common serotypes. With human platelet-rich plasma, only uncommon serotypes showed aggregation. Differences in serotype selectivity and the rate of aggregation were noted among platelet donors. About half of the patients with Behçet's disease and 30% of health controls showed platelet aggregation. Plasma from non-responder patients with Behçet's disease inhibited aggregation of healthy responder platelets within 20 min. Thus selective binding of uncommon serotypes of Strep. sanguis to platelets might cause the vasculitis in Behçet's disease.

Adenosine Triphosphate↗
PubMed1991

FK506 treatment of S-antigen induced uveitis in primates.

FK506 is a new immunosuppressive agent which has been found more potent than cyclosporine based on the dosage. FK506 was examined here for its effect on the development of uveitis in primates immunized with S-antigen. FK506 successfully inhibited uveitis in monkeys, even when administered three weeks after the first immunization, at the time when the immunopathogenic mechanism of uveitis is assumed to be developed. All four monkeys injected with 0.5 mg/kg/day of FK506 did not develop uveitis, 2 out of 4 treated with the 0.25 mg and 3 out of 4 of those receiving the 0.125 mg also did not develop disease. FK506 suppressed to some extent the cellular and humoral immune responses to S-antigen. The main side effect of FK506 was weight loss. We consider that this drug may be considered as a new potential therapeutic agent for immune-mediated ocular disease in humans.

Animals↗
PubMed1991

Trials of vaccination against experimental autoimmune uveoretinitis with a T-cell receptor peptide.

T lymphocytes which mediate several experimental autoimmune diseases, including encephalomyelitis (EAE) and uveoretinitis (EAU) in Lewis rats, preferentially utilize V beta 8 gene product in their receptor. Vaccination against a V beta 8.2-derived peptide was reported to inhibit EAE induction and we report here on the effect of vaccination with this peptide on the development of EAU. Experimental rats were pretreated with the V beta 8.2 peptide, emulsified in adjuvant (CFA), whereas control animals were untreated or injected with saline in CFA. Rats of all groups were immunized 30 or 40 days later with the immunopathogenic antigen, emulsified in Mycobacterium-enriched CFA. Vaccination with CFA emulsions containing either the V beta 8.2 peptide or saline, remarkably inhibited the development of the tested diseases, as compared to the untreated controls. Vaccination with the V beta 8.2 peptide had variable effects in this study on disease development: it inhibited the S-antigen-induced EAU more than did treatment with CFA in four out of six experiments, had a similar effect to that of CFA in one experiment and enhanced the disease in another experiment. Conversely, vaccination with the V beta 8.2 peptide slightly enhanced the EAU induced by the interphotoreceptor retinoid-binding protein (IRBP), or its dominant determinant, in three of four experiments and had no apparent effect in the fourth experiment. In addition, we could not reproduce the reported protective effect of vaccination with the V beta 8.2 peptide against induction of EAE. Vaccination with the V beta 8.2 peptide also had no clear effect on the development of humoral or cellular immune responses against S-antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Close association of Streptococcus sanguis and Behçet's disease].

The oral flora of patients with Behçet's disease was investigated and compared to that of controls. The proportion of Streptococcus (S.) sanguis in the flora of patients with this disease was always higher than that of healthy controls. It is noteworthy that serotypes of S. sanguis in the oral flora of patients were different from controls. Immune responses against S. sanguis were also examined in the patients. Antibody titers against S. sanguis were higher in patients than in controls. Furthermore, the patients showed significantly increased skin reactivity to S. sanguis. These results suggest that uncommon serotypes of S. sanguis play an important role in the pathogenesis of Behçet's disease.

Adolescent↗
PubMed1991

Unusual immunologic properties of the uveitogenic interphotoreceptor retinoid-binding protein-derived peptide R23.

Peptide R23, consisting of residues 1091-1115 of bovine interphotoreceptor retinoid-binding protein (IRBP), had some unusual immunologic properties in Lewis rats. The peptide induced experimental autoimmune uveoretinitis and pinealitis in these rats, but only at high doses. The minimal immunopathogenic dose was found to be 100 nmol/rat. On the other hand, R23 was highly immunogenic in Lewis rats, producing cellular immunity, as measured by the lymphocyte proliferation assay, with a minimal dose of 1 nmol/rat. This unusual dissociation between the uveitogenic and immunogenic activities of R23 was attributed to different sites on the peptide, stimulating either the lymphocytes which induce disease or those which vigorously proliferate in culture. The potent immunogenicity of R23 was consistent with the peptide being immunodominant, as demonstrated by its capacity to be recognized by lymphocytes sensitized against whole IRBP and to stimulate these cells in culture to proliferate and acquire uveitogenic capacity. Likewise, lymphocytes sensitized against R23 are stimulated in culture by whole IRBP. Unexpectedly, peptide R23 was inferior to whole IRBP in its capacity to stimulate uveitogenicity in R23-sensitized lymphocytes. This finding also was attributed to the preferential stimulation by R23 of the lymphocytes specific for the putative "nonuveitogenic" site on the peptide. Peptide R23 also differs from the other tested bovine IRBP-derived peptides in the specificity of its antibodies. Unlike antibodies to the other peptides, those to R23 showed a strong cross reactivity toward whole IRBP.

Amino Acid Sequence↗
PubMed1990

Stimulation in vitro of lymphocytes for induction of uveoretinitis without any significant proliferation.

Experimental autoimmune uveoretinitis can be adoptively transferred into naive recipients by lymphocytes from rats immunized with uveitogenic Ag, provided these cells are activated in vitro before being injected. The activation of sensitized lymphocytes, by the immunizing Ag, or by cross-reacting Ag, is usually accompanied by vigorous proliferation. We report, however, on a complete dissociation between the capacity of a peptide to generate uveitogenicity and to stimulate proliferation in cultured lymphocytes. This peptide, which occupies sequence 579-591 of the bovine interphotoreceptor retinoid-binding protein (IRBP), is one of the three "repeats" that exhibit partial sequence homologies with the immunodominant and highly immunogenic peptide, 1179-1191. Peptide 579-591 is nonimmunogenic and nonuveitogenic in Lewis rats and does not stimulate any significant proliferation in lymphocytes sensitized against whole IRBP, peptide 1179-1191, or another "repeat" peptide, 271-283, which is immunogenic and uveitogenic. In contrast, peptide 579-591 effectively generates uveitogenicity in the lymphocytes sensitized against these three Ag. Unlike 579-591, peptides 271-283 and 1179-1191 stimulated both proliferation and uveitogenicity in these sensitized lymphocytes. A different pattern of activities was observed with the other "repeat" peptide, 880-892. This peptide did not have any effect on the lymphocytes sensitized against IRBP, 271-283 or 1179-1191, but did stimulate both proliferation and uveitogenicity in lymphocytes sensitized against itself. The data suggest that 579-591 selectively stimulates a lymphocyte subset that is uveitogenic, but is incapable of mounting proliferative responses.

Animals↗
PubMed1990

Repeated determinants within the retinal interphotoreceptor retinoid-binding protein (IRBP): immunological properties of the repeats of an immunodominant determinant.

Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein which localizes in the retina and pineal gland, induces inflammatory changes in these organs (EAU and EAP, respectively) when injected into various mammals. We have previously identified a determinant (residues 1169-1191) in bovine IRBP which is immunodominant and highly immunogenic and immunopathogenic in Lewis rats. IRBP exhibits a fourfold repeat structure and we report here on the comparison between the active sequence 1179-1191 and its three repeat peptides. Only one of the repeats, 271-283, cross-reacted with 1179-1191 and exhibited immunodominance, albeit of a low level. Peptide 271-283 was also immunogenic and immunopathogenic in Lewis rats, but with a minimal dose approximately 100 times higher than that of 1179-1191. Peptide 880-892, a nondominant determinant, resembled 271-283 in its immunogenicity, but was markedly less immunopathogenic. No immunological activity was detected in the fourth repeat peptide, 579-591. Peptide 1179-1191 was superior to the other repeats also in its antigenicity, i.e., the capacity to stimulate presensitized lymphocytes in culture: the minimal stimulatory concentrations of 1179-1191 was greater than 1000 times lower than those of 271-283 or 880-892. Furthermore, 1179-1191 was stimulatory at concentrations lower than those of 271-283 even when tested with lymphocytes sensitized against 271-283. A correlation was also found between the immunological activities of the repeat peptides and their amphipathicity. This study thus identifies two new immunopathogenic determinants of IRBP and provides additional data to show the association between immunodominance of peptides and their various immunological activities.

Amino Acid Sequence↗
PubMed1990

Chemiluminescence of neutrophils from patients with Behçet's disease and its correlation with an increased proportion of uncommon serotypes of Streptococcus sanguis in the oral flora.

Zymosan-induced chemiluminescence was investigated in whole blood and in neutrophils: in both, the peak count was frequently elevated in Behçet's disease, and was significantly higher than in healthy controls; similarly the peak time was shorter. There were more uncommon serotypes of Streptococcus sanguis in the oral flora of patients with Behçet's disease. Common serotypes were present in the flora of healthy controls, but not in patients with the disease. The percentage of Strep. sanguis in the oral flora was significantly correlated with the level of chemiluminescence response. Thus infection with uncommon serotypes of Strep. sanguis may play a role in the aetiology of Behçet's disease.

Behcet Syndrome↗
PubMed1990

Uveitis and immune responses in primates immunized with IRBP-derived synthetic peptides.

Monkeys immunized with bovine IRBP-derived synthetic peptides R4 (sequence 1158-1180) or R14 (1169-1191) developed EAU which was detected by both clinical and histological examinations. The inflammation localized mainly in the choroid, with only minor changes being noticed in the adjacent retinal tissue. EAU developed in only one of the two monkeys immunized with each of the peptides and the animals with disease also showed higher levels of cellular immunity toward the immunizing peptide than did the monkeys with no disease. The cellular immune responses, measured by the lymphocyte proliferation assay, were specific toward the immunizing peptides, with no cross responsiveness to whole IRBP. This finding suggests that the two uveitogenic peptides were non-immunodominant in the tested monkeys. In contrast, peptide R14 is highly immunodominant in the Lewis rat. Also, the fine specificity of the monkey response to R14 differed from that of the Lewis rat. The possible genetic control of the monkey susceptibility to EAU induction by the peptides is discussed and the unique finding of an autoimmune disease induction by a non-immunodominant peptide is underscored.

Amino Acid Sequence↗
PubMed1989

Synthesis of an immunopathogenic fusion protein derived from a bovine interphotoreceptor retinoid-binding protein cDNA clone.

We have extended the cDNA sequence of bovine interphotoreceptor retinoid-binding protein (IRBP) and subcloned one of the sequenced cDNA fragments into an expression vector. The nucleotide (nt) sequences of four bovine IRBP cDNA clones have been determined. These sequences when assembled cover the 3' proximal 3629 nt of the IRBP mRNA and encode the C-terminal 551 amino acids (aa) of IRBP. This cDNA sequence validates the intron: exon boundaries predicted from the gene. A 2-kb EcoRI insert from lambda IRBP2, one of the clones sequenced, encoding the C-terminal 136 aa of IRBP was subcloned into the expression vector pWR590-1. Escherichia coli carrying this plasmid construction, pXS590-IRBP, produced a fusion protein containing 583 N-terminal aa of beta-galactosidase, three linker aa residues, 136 C-terminal aa of IRBP and possibly a number of additional C-terminal residues due to suppressed termination. This 86-kDa fusion protein, purified by detergent/chaotrope extraction followed by reverse-phase high-performance liquid chromatography, cross-reacted with anti-bovine IRBP on Western blots. This protein induced an experimental autoimmune uveo-retinitis and experimental autoimmune pinealitis in Lewis rats indistinguishable from that induced by authentic bovine IRBP. Thus, it is evident that biological activity of this region of IRBP, as manifested by immuno-pathogenicity, is retained by the fusion protein.

Amino Acid Sequence↗
PubMed1989

Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP).

Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein specific for the retina and pineal gland, induces inflammatory changes in these two organs in immunized animals. We report here on the identification of an immunodominant determinant of bovine IRBP that is highly immunogenic and immunopathogenic in the Lewis rat. The peptide, which comprises the sequence 1169-1191 of bovine IRBP, was shown to be immunodominant by its capacity to stimulate lymphocytes sensitized against whole IRBP. A comparison was made between peptide 1169-1191 and another peptide, 1158-1180, which is nondominant but is immunogenic and immunopathogenic in the Lewis rat. Peptide 1169-1191 was found to be superior in its immunological capacities; the minimal dose of 1169-1191 needed to induce cellular immune response or disease in Lewis rats (0.02-0.1 nmol/rat) is congruent to 1,000 times smaller than that of 1158-1180. In addition, unlike the ocular disease induced by 1158-1180, the disease produced by 1169-1191 resembled that induced by whole IRBP in its kinetics and histopathological features. The immunological activity of 1169-1191 in the Lewis rat was localized to the 10 residues at the COOH terminus; no such activity was exhibited by the truncated peptide 1169-1188, which comprises the 20 residues at the NH2 terminus of the full peptide. The usefulness of this unique experimental system in analyzing the role of immunodominance in peptide immunogenicity and immunopathogenicity is underscored.

Amino Acid Sequence↗
PubMed1989

An 18-mer peptide derived from the retinal S antigen induces uveitis and pinealitis in primates.

S-antigen, a photoreceptor cell protein, induces a predominantly T-cell mediated autoimmune uveitis in many vertebrate animals, including primates. Because of this activity and the finding of immune responses to S antigen in patients with uveitis, this protein has been implicated in the pathogenesis of uveitis in humans. Peptide M, an 18-amino acid component of S antigen, has previously been shown to be highly uveitopathogenic in rats and guinea pigs. We report here that peptide M is immunopathogenic in some monkeys, producing inflammatory changes in eyes and pineal glands similar to those induced by native S antigen. Monkeys with disease also developed intense immune responses to peptide M, measured by the lymphocyte proliferation assay. In addition, lymphocytes from these monkeys reacted against whole S antigen. Furthermore, lymphocytes from certain monkeys immunized with whole S antigen responded well against peptide M, thus indicating that this peptide is an immunodominant epitope in these animals. Two of the four monkeys immunized with peptide M did not develop disease. Lymphocytes from these two animals did not respond in culture against the peptide. Following immunization with the whole protein, these monkeys were capable, however, of developing cellular immunity against S antigen and one of them developed disease. The possible involvement of peptide M in the pathogenesis of uveitis in humans is discussed.

Animals↗
PubMed1988

[Investigations of interferon and oligo-2',5'-adenylate systems in endogenous uveitis].

The interferon (IFN) and oligo-2',5'-adenylate (2-5A) systems were investigated in endogenous uveitis. It was shown that oligo-2',5'-adenylate synthetase (2-5AS) activities of peripheral blood lymphocytes (PBL) were significantly increased in Behcet's disease (P less than 0.01), Vogt-Koyanagi-Harada's disease (VKH disease, P less than 0.01), and sarcoidosis (P less than 0.01) compared with those in controls. In order to investigate the effect of cyclosporin A (Cy A) on IFN systems in Behcet's disease, 2-5AS activities of PBL from 2 patients under Cy A therapy (10 mg/kg/day) were examined. The enzyme activities were high before treatment in both patients, but the activities were suppressed after treatment. The effect of Cy A on the production of IFN by PBL in vitro was also examined. IFN synthesis was markedly suppressed by Cy A in patients and controls. The effect of corticosteroids on IFN and 2-5A systems in VKH disease was studied. Two patients were given 200 mg of prednisolone with gradual tapering. Activities of 2-5AS of PBL from patients were high before treatment, and they were markedly suppressed after prednisolone treatment. The serum IFN, 2-5AS activities of PBL and the synthesis of IFN in vitro were examined in one patient who was given pulse methylprednisolone therapy. The serum IFN and 2-5AS activity of PBL were suppressed by this therapy. The production of IFN-alpha induced by herpes simplex virus and IFN-gamma induced by staphylococcal enterotoxin A and OK-432 were greatly suppressed. These results suggest that the IFN and 2-5A systems in endogenous uveitis play some significant role in the immunopathophysiology of these diseases.

2',5'-Oligoadenylate Synthetase↗