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Biomedical subjects

S Sakuragi

Publications and source records attributed to S Sakuragi.

At least 19 recordsLinked to original sources
PubMed2001

Uveitopathogenic sites in recoverin.

PURPOSE: This study was carried out in order to determine the most potent and novel uveitopathogenic sites of recoverin using synthetic peptides. METHODS: Several synthetic peptides containing the recoverin sequence plus adjuvants were injected into Lewis rats, and the uveitopathogenic sequence was defined, clinically, histologically, and immunologically. RESULTS: Peptides containing of amino acids 57-85 and 136-167 induced severe EAU, and the lowest doses to induce EAU were 20 microg and 10 microg, respectively. Lymphocyte proliferative reactions were also positive for peptides 57-85 and 136-167. The core sequences within the uveitopathogenic site were 65-79 and 153-164. Peptides of amino acids 65-79 within 57-85 and 149-167 within 136-167 were the smallest in the recoverin sequence, respectively, that could induce severe EAU. CONCLUSION: We found recoverin has some novel potent uveitopathogenic sites, 149-167. These findings of the uveitopathogenic sites in recoverin may lead to improved understanding of the pathogenesis of uveitis and the means to design specific treatment.

Animals↗
PubMed2001

Identification of the hexon region of an adenovirus involved in a new outbreak of keratoconjunctivitis.

We tested 15 adenovirus (Ad)-positive patients involved in a case of nosocomial spread of keratoconjunctivitis. A neutralization test, PCR-restriction fragment length polymorphism analysis, and sequencing of the hypervariable regions of the hexons were performed in order to identify the type of Ad involved. The serotype of the Ad was not identical to any published Ad sequence by either method.

Adenovirus Infections, Human↗
PubMed2001

Hypervascular liver metastasis from hypovascular ductal cell carcinoma of the pancreas.

In a case of hypervascular metastatic liver tumor, the vascularity of primary focus, pancreatic carcinoma was hypovascular. Based on the imaging findings, we thought before the operation that the two lesions were double cancers. Histological examination showed that the stromal volume of metastatic tumorous tissue was richer than that of the primary focus. It was suggested that the difference in the stromal volume was related to the difference of the vascularity. Some foctors originating in stromal cells might be involved in angiogenesis.

Carcinoma, Pancreatic Ductal↗
PubMed2000

Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease (and sympathetic ophthalmia) is an ocular inflammatory disease that is considered to be a cell-mediated autoimmune disease against melanocytes. The purpose of this study was to determine the Ags specific to VKH disease and to develop an animal model of VKH disease. We found that exposure of lymphocytes from patients with VKH disease to peptides (30-mer) derived from the tyrosinase family proteins led to significant proliferation of the lymphocytes. Immunization of these peptides into pigmented rats induced ocular and extraocular changes that highly resembled human VKH disease, and we suggest that an experimental VKH disease was induced in these rats. We conclude that VKH disease is an autoimmune disease against the tyrosinase family proteins.

Adult↗
PubMed2000

Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rats.

Vogt-Koyanagi-Harada (VKH) disease is an ocular inflammatory disease and is considered to be a cell-mediated, autoimmune disease against melanocytes. To learn more about the mechanisms involved in VKH disease, the identification of the antigens specific to the disease and the development of an animal model are critically important. We have expressed and purified the melanocyte specific proteins, tyrosinase-related protein 1 (TRP1) and 2 (TRP2). Lewis rats developed an ocular and extraocular inflammatory disease 12 days after immunization with TRP1 or TRP2 that was characterized clinically by the infiltration of inflammatory cells and accumulation of massive fibrin in the anterior and posterior chambers of the eye. Histologically, inflammatory cells were found in the anterior and posterior chambers, iris, ciliary body, the choroid, subretinal space and vitreous body. In severe cases, a serous detachment of the retina was observed. In mild cases, focal inflammatory lesions surrounded by normal chorioretinal architecture were observed and the inflammation persisted for more than 42 days after the injection. Some eyes showed accumulation of epithelioid cells in the choroid or the retinal pigment epithelium which were similar to the Dalen-Fuchs nodules found in patients with VKH disease. The alterations of the photoreceptor outer segment and the outer nuclear layer were less severe than in experimental autoimmune uveitis induced by retinal antigens. Extraocular manifestations such as skin lesions and meningitis were also observed. The clinical course and histological findings in these rats resembled the changes in patients with VKH disease.

Animals↗
PubMed1999

Interaction between the nucleotide exchange factor Mge1 and the mitochondrial Hsp70 Ssc1.

Function of Hsp70s such as DnaK of the Escherichia coli cytoplasm and Ssc1 of the mitochondrial matrix of Saccharomyces cerevisiae requires the nucleotide release factors, GrpE and Mge1, respectively. A loop, which protrudes from domain IA of the DnaK ATPase domain, is one of six sites of interaction revealed in the GrpE:DnaK co-crystal structure and has been implicated as a functionally important site in both DnaK and Ssc1. Alanine substitutions for the amino acids (Lys-108 and Arg-213 of Mge1) predicted to interact with the Hsp70 loop were analyzed. Mge1 having both substitutions was able to support growth in the absence of the essential wild-type protein. K108A/R213A Mge1 was able to stimulate nucleotide release from Ssc1 and function in refolding of denatured luciferase, albeit higher concentrations of mutant protein than wild-type protein were required. In vitro and in vivo assays using K108A/R213A Mge1 and Ssc1 indicated that the disruption of contact at this site destabilized the interaction between the two proteins. We propose that the direct interaction between the loop of Ssc1 and Mge1 is not required to effect nucleotide release but plays a role in stabilization of the Mge1-Ssc1 interaction. The robust growth of the K108A/R213A MGE1 mutant suggests that the interaction between Mge1 and Ssc1 is tighter than required for function in vivo.

Arginine↗
PubMed1999

Decreased tear lactoferrin concentration in patients with chronic hepatitis C.

BACKGROUND/AIMS: Decreased tear volume in patients with chronic hepatitis C has been reported in the literature. Lactoferrin is abundantly present in human tears, the main source of which is the acini of the lacrimal glands. In this study tear lactoferrin levels were measured to investigate the dry eye condition of patients with chronic hepatitis C. METHODS: Lactoferrin in tears/fluid was measured by a radial immunodiffusion assay in 42 patients with chronic hepatitis C. The rate of lacrimal secretion was determined by the cotton thread test. Rose bengal staining of the ocular surface was also performed. RESULTS: Only three patients out of 42 complained of dry eye sensation and, in 31 patients, six showed positive results on the rose bengal staining test of the ocular surface. The lactoferrin concentration of tear fluid in the chronic hepatitis C group (1.42 (SD 0.56) mg/ml) was significantly lower than in the control group (1.90 (0.62) mg/ml; p <0.00048). The cotton thread test results in the chronic hepatitis C group (12.9 (5. 5) mm) were significantly lower than in the control group (17.9 (5. 3) mm; p<0.00048). Also, in the chronic hepatitis C group, tear lactoferrin concentration correlated with the results of the cotton thread test (r = 0.35, p<0.05). CONCLUSION: Chronic hepatitis C patients showed both decreased tear volume, and decreased tear lactoferrin concentration. These findings suggest that there may be dysfunction of the lacrimal glands in patients with chronic hepatitis C, which may account for the mild dry eye.

Adult↗
PubMed1999

Investigation of luminal surface structures of rod photoreceptor outer segments by lectin cytochemistry combined with freeze-etching.

The luminal surface of the rod photoreceptor disk membrane was exposed by means of osmotic shock and labeled with ferritin- conjugated concanavalin A. The structural changes of the luminal surface were examined by a freeze-etching procedure with cryoprotectant (methanol). On replicas from freeze-etched membranes with concanavalin A labeling, 6- to 10-nm particles were codistributed with ferritin particles on the luminal surface of the disk membrane. By contrast, there were few ferritin particles or less numerous 6- to 10-nm particles on the corresponding surface without concanavalin A labeling. If 6- to 10-nm particles corresponded to the carbohydrate moiety of rhodopsin, concanavalin A binding might tend to preserve this carbohydrate moiety. These results suggest that the two-dimensional analysis of lectin-induced structural changes of the membrane surface glycoconjugates may become available by lectin cytochemistry combined with freeze-etching.

Animals↗
PubMed1998

A case of effusive-constructive pericarditis: an efficacy of GD-DTPA enhanced magnetic resonance imaging to detect a pericardial thickening.

A 38-year-old man underwent pericardiectomy because of effusive-constrictive pericarditis. The gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging showed pericardial thickening separate from the effusion, which could not be shown by unenhanced computed tomography. Gd-DTPA enhanced magnetic resonance imaging could be useful for the early detection of effusive-constrictive pericarditis.

Adult↗
PubMed1998

Recurrent varicella-zoster virus retinitis in a patient treated with systemic corticosteroids.

A case of recurrent unilateral varicella-zoster virus (VZV) retinitis is reported. The retinitis was characterized by arteriolitis and retinal necrosis with secondary chorioretinal atrophy localized in the periphery of the supratemporal quadrant of the retina. Polymerase chain reaction analysis of aqueous humor demonstrated VZV DNA in both the initial and recurrent episode. The Goldmann-Witmer coefficient for VZV IgG was elevated. The initial VZV retinitis was successfully treated with acyclovir and corticosteroids. Three years later, high-dose corticosteroids alone were used to treat idiopathic facial nerve palsy. One month after concluding corticosteroids therapy, the VZV retinitis recurred in the same eye, suggesting that administration of the high-dose corticosteroids caused VZV reactivation and induced recurrence of VZV retinitis.

Acyclovir↗
PubMed1998

Sialoglycoconjugates in primary and recurrent mixed tumors of lacrimal glands.

We examined the activity of Griffonia simplicifolia II agglutinin (GS2) before and after neuraminidase treatment in 2 cases of primary benign mixed tumor (BMT) and a case of recurrent mixed tumor (MT). Histologically, each type of MT is comprised of epithelial and mesenchymal components. GS2, which showed no binding to either structural component in the primary BMT, was specifically bound to the mesenchymal component in the recurrent MT. After neuraminidase treatment, there was a marked increase in GS2-binding levels in the epithelial component of the primary BMT and in both components of the recurrent MT. These results might reveal a prominent sialylation in the recurrent MT.

Adult↗
PubMed1998

Intraocular pressure during pneumatic retinopexy.

BACKGROUND AND OBJECTIVE: A simplified method of monitoring intraocular pressure (IOP) during pneumatic retinopexy was devised and used clinically to decrease the risk of complications associated with unnecessary IOP elevation. PATIENTS AND METHODS: Intraoperative IOP and IOP immediately after sulfur hexafluoride (SF6) injection were monitored during pneumatic retinopexy in 22 eyes with rhegmatogenous retinal detachment. Intraoperative IOP was measured with a sphygmomanometer connected to the side of a gas-filled syringe. RESULTS: Intraoperative IOP and IOP immediately after gas injection were 97.2 +/- 28.5 (mean +/- SD) and 46.5 +/- 19.6 mm Hg, respectively. Two eyes temporarily lost light perception immediately after the gas injection. The intraoperative IOP and the IOP immediately after the gas injection were 130 and 80 mm Hg, respectively, in one eye, and 180 and 90 mm Hg, respectively, in the other. CONCLUSIONS: In general, to ensure effective and safe results of pneumatic retinopexy, the authors recommend that the gas be injected either to approximately 90 mm Hg of intraoperative IOP or to the maximum acceptable volume (2.0 to 2.5 ml of 100% SF6).

Aged↗
PubMed1998

Analysis of uveitogenic sites in phosducin molecule.

PURPOSE: Phosducin, a retinal photoreceptor protein, induces experimental autoimmune uveitis (EAU). In this study, we attempted to determine the numbers of uveitogenic sites in phosducin using synthetic peptides. METHODS: Antigen peptides were synthesized according to the amino acid sequence of the rat-derived phosducin with a peptide-synthesizer and purified by reversed-phase HPLC. First, 13 peptides covering the entire sequence of phosducin were synthesized, and each was injected into the hind footpad of Lewis rats for immunization, and induction of EAU was examined clinically and histologically. Next, peptides that appeared to contain sequences of a uveitogenic site were newly synthesized and examined clinically and immunologically. RESULTS: Of the 13 peptides used in the first immunization, 7 induced inflammation. Similar to other EAU antigens, clinical changes began with fibrin deposition in the anterior segment and posterior synechia, followed by posterior chamber hypopyon. Histologically, inflammation was observed mainly in the outer segment of photoreceptor cells and outer nuclear layer, and serous retinal detachment was found in cases of severe inflammation. Infiltration of inflammatory cells in the pineal gland was also observed. In experiments designed to further specify the uveitogenic sites, the presence of inflammation-inducing sequences was inferred for amino acid sequences 1-20, 23-37, 79-91, 127-142 and 198-212. The rats immunized with these peptides also exhibited high value on lymphocyte proliferation assay. CONCLUSION: Phosducin has 5 uveitogenic sites. Among others, one of them has potent and others weak uveitogenicity.

Amino Acid Sequence↗
PubMed1997

Characterization of a potent uveitopathogenic site derived from rat phosducin.

Phosducin is a retinal and pineal phosphoprotein assumed to play an important role in visual phototransduction. Phosducin is also a uveitopathogenic retinal antigen, but its potency has been reported to be mild. During the course of studies aimed at identifying uveitopathogenic sites in phosducin, we found that rat phosducin possessed a potent uveitopathogenic site. In this study, we characterize the potent uveitopathogenic site by using synthetic peptides. Several synthetic peptides from this region plus adjuvants were injected into Lewis rats, and the uveitopathogenic core sequence was defined. We also determined the pivotal amino acid residues by using synthetic peptides with single residue substitution. Immunization with PDC(R)65-96 (amino acid residues 65 through 96 derived from rat phosducin) at doses of 0.83 nmol or more induced severe experimental autoimmune uveitis (EAU) in all rats within 12 days. Experimental autoimmune pinealitis (EAP) was also observed in all rats after immunization with 0.83 nmol or higher doses of the peptide. The lowest dose of the peptide to induce EAU and EAP was 0.24 nmol. The smallest peptide that induced EAU as severe as PDC(R)65-96 was PDC(R)77-87, which consisted of 11 amino acid residues (YELIHQDKEDE). The core sequence within the uveitopathogenic site was a pentapeptide (LIHQD), amino acid residues from 79 to 83. To determine the role of individual residues within PDC(R)77-87, we tested the uveitopathogenicity of analogues of PDC(R)75-85 and PDC(R)77-89, respectively, in which each of the residues from 77 to 87 was replaced by alanine (A). Analogous peptides bearing a single residue substitution at 80 (I-->A) and 82 (Q-->A), respectively, were not uveitopathogenic. Our findings demonstrated the presence of a potent uveitopathogenic site in PDC(R)65-96 whose potency in Lewis rats was comparable to that of S-antigen. The pivotal amino acid residues for uveitopathogenicity were the residues at 80 (I) and 82 (Q). The clinical and histological features of this EAU closely resembled those of the EAU induced by S-antigen and recoverin.

Adoptive Transfer↗
PubMed1997

Preference of peanut agglutinin labeling for long-wavelength-sensitive cone photoreceptors in the dace retina.

Peanut agglutinin (PNA) was known for its selective binding to cone cells. In the present study, we investigated whether there was any difference in PNA binding among various subtypes of cone photoreceptor cells in the dace retina. The outer segments of the long-double- and long-single-cone cells were preferentially labeled with PNA. Ultrastructural pre-embedding labeling revealed that the binding sites of PNA were confined to the calycal processes of these cells. By contrast, only slight labeling was discerned on the corresponding regions of other types of cone cells. The results indicate that PNA can distinguish the long-wavelength-sensitive cone from the short-to-middle-wavelength-sensitive cone cells.

Animals↗
PubMed1997

Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of beta-dystroglycan in the outer plexiform layer of the retina.

Dp260 is a C-terminal isoform of dystrophin and is expressed specifically in the retina. Abnormal electroretinograms (ERG) in some Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients are likely linked to a disruption of Dp260. To clarify the importance of Dp260 in the retina, we examined dystrophin exon 52 knock-out mice, whose expression of Dp260 is impaired. We also confirmed the localization of Dp260 in the outer plexiform layer (OPL) of the retina. Disruption of Dp260 causes a change in the localization of beta-dystroglycan, which is normally found in the OPL of the retina. This suggests a requirement for Dp260 for normal formation of the dystrophin-dystroglycan complex in the retina. Dp71, also expressed in the retina, was, however, not detected in the OPL. The difference in localization of Dp260 and Dp71 implies that the two isoforms have different functions. The dystrophin exon 52 knock-out mice had a prolonged implicit time of the b-wave in ERG, although no significant change was observed in amplitude. These ERG findings differed from those of DMD and BMD patients, especially with regard to amplitude of the b-wave, but make it clear that Dp260 is required for normal electrophysiology.

Animals↗
PubMed1997

Mechanism of vestibular adaptation of fish under microgravity.

In a space experiment, the adaptation of goldfish behavior during flight and readaptation after landing were investigated. Six goldfish (1 normal, 1 with otoliths removed on both sides, 4 with otoliths removed on one side) were flown in a fish package (F/P) of Aquatic Animal Experiment Unit (AAEU). The dorsal light responses (DLRs) of fish with otoliths removed were recorded after operation until launch and after landing. The behaviors of the fish were recorded with a video camera on Mission Elapsed Time (MET) Day-00, 02, 05, 08, 12. On MET Day-00, two fish with otoliths removed on one side showed flexion of body toward the operated side. These fish also showed rolling behavior toward the operated side. However, the body flexion disappeared on MET Day-05 or MET Day-08. No rolling behaviors were observed after that time. Five fish showed backward looping behaviors during the mission. Although the frequency of looping episodes decreased after MET Day-08, five fish still showed looping behavior on MET Day-12, that was the last day of video recording on orbit. In microgravity, visual system of fish did not seem to provide sufficient cues to prevent them from looping or rolling. After landing, no looping and rolling behavior was observed. However, the tilt angle of the DLR increased in the fish with otolith removed 5 month before launch but not in normal fish and those with otoliths removed 2 weeks before launch. These results suggest that the behavioral dysfunction and the adaptational process in space are dependent on vestibular inputs.

Adaptation, Physiological↗