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Biomedical subjects

Shigeaki Ohno

Publications and source records attributed to Shigeaki Ohno.

At least 73 records · Page 4Linked to original sources
PubMed2004

Anti-inflammatory effects of alpha-melanocyte-stimulating hormone against rat endotoxin-induced uveitis and the time course of inflammatory agents in aqueous humor.

PURPOSE: We examined the effects of the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) on rat endotoxin-induced uveitis, and to measure the expression of inflammatory cytokines and chemokines with and without the alpha-MSH treatment over the course of the disease. METHODS: We injected Lewis rats once with Salmonella typhimurium lipopolysaccharide (LPS) to induce uveitis. The rats were given intravenous injections of 250, 500 or 1000 microg of alpha-MSH. The eyes were examined over the next 24 h for inflammation. Aqueous humor was collected 6, 12 and 24 h after endotoxin injections and the number of infiltrating cells were counted in anterior chamber. In addition, we assayed the concentration of protein, nitric oxide, TNF-alpha, IL-6, MCP-1 and MIP-2. RESULTS: Rats injected with alpha-MSH showed a significant decrease in the number of infiltrating cells in anterior chamber. Moreover, alpha-MSH-treated rats with endotoxin-induced uveitis (EIU) showed significantly lower concentrations of protein, nitric oxide, proinflammatory cytokines and chemokines in their aqueous humor. Even the early stages of EIU were suppressed by the injection of alpha-MSH. CONCLUSIONS: Our results demonstrate that the immunosuppressive neuropeptide alpha-MSH inhibits the early induction events of endotoxin-induced inflammation in the eye; therefore, suppresses the subsequent infiltration of cells and intraocular production of inflammatory cytokines and chemokines in eyes. alpha-MSH has a possibility of being a therapeutic strategy for anterior uveitis.

Animals↗
PubMed2004

Molecular diagnosis of human adenoviruses d and e by a phylogeny-based classification method using a partial hexon sequence.

Human adenoviruses (HAdVs) are the major causes of a variety of acute illnesses. Virus isolation and neutralization tests are usually done to identify the causative virus, but these tests are labor-intensive and time-consuming, and standardized antisera are in limited supply. This study investigated a rapid and reliable method of virus identification based on PCR and phylogenetic analysis. The phylogenetic tree constructed by neighbor joining on the basis of the newly determined partial hexon sequences from 33 prototypes of HAdV-D and -E, along with 11 available prototypes of HAdV-A to -C and -F from GenBank, allowed HAdVs to be grouped into six distinct clusters. These clusters correspond closely to the six newly designated species, HAdV-A to -F. The partial hexon sequences of 57 isolates from patients with acute conjunctivitis obtained over 20 years plus those of 44 prototype strains were analyzed. Each isolate formed a monophyletic cluster along with its respective prototype strain, allowing serotype identification. Partial-hexon-based classification appears to be an effective tool for studying the molecular epidemiology of HAdVs.

Adenovirus Infections, Human↗
PubMed2004

New genome type of adenovirus serotype 4 caused nosocomial infections associated with epidemic conjunctivitis in Japan.

Human adenovirus type 4 is one of the major serotypes isolated from patients with adenoviral conjunctivitis. In 2001 we encountered nosocomial infections with epidemic conjunctivitis in the ophthalmology ward of one hospital in Sapporo, which is in the northern part of Japan. Adenoviruses were isolated from the patients with this nosocomial infection and identified as adenovirus type 4 (AdV-4) by a neutralization test with serotype-specific antiserum. When the cleavage patterns of the isolates were compared with the full viral genome with BamHI and SmaI, the cleavage patterns of the isolates were shown to be different from those of AdV-4p and other previously known AdV-4 variants. The nucleotide sequences of the fiber gene of the isolates showed the highest homologies (94.3%) with AdV-4 among the nucleotide sequences available from GenBank and formed a monophyletic cluster along with the prototype strain of AdV-4. The isolates, however, were located in a different lineage from those of AdV-4p and the AdV-4 variant from the sporadic infections. We conclude that the nosocomial infection that appeared in 2001 was caused by a new genome type of AdV-4, which was designated AdV-4c.

Adenoviridae↗
PubMed2004

Inhibition of endotoxin-induced uveitis and potentiation of cyclooxygenase-2 protein expression by alpha-melanocyte-stimulating hormone.

PURPOSE: The efficacy of alpha-melanocyte-stimulating hormone (alpha-MSH) on endotoxin-induced uveitis (EIU) was investigated in rats. Several studies have demonstrated that there are various inflammatory reactions mediated by an alpha-MSH receptor in macrophages. In addition, as it is known that cyclooxygenase (COX)-2 is induced by a variety of stimuli and plays an important role in inflammation, COX-2 expression was also investigated in macrophage cells treated with alpha-MSH in vitro to clarify its anti-inflammatory effect. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). The number of infiltrating cells and protein concentration in the aqueous humor collected 24 hours after the LPS treatment was determined. The levels of prostaglandin (PG)-E2, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 production were determined. RAW 264.7 cells were pretreated with various concentrations of alpha-MSH for 24 hours and subsequently incubated with 10 microg/mL LPS for 24 hours. COX-2 protein expression was analyzed by Western blot analysis. RESULTS: alpha-MSH suppressed the development of EIU in a dose-dependent fashion. The treatment with alpha-MSH reduced the PGE2, TNF-alpha, IL-6, and MCP-1 concentrations in aqueous humor. The COX-2 protein expression in the alpha-MSH group decreased. CONCLUSIONS: This study suggests that alpha-MSH has an antiocular inflammatory effect, by suppression of PGE2, TNF-alpha, IL-6, and MCP-1 production and blocking of COX-2 expression.

Animals↗
PubMed2004

Involvement of p27KIP1 in the proliferation of the developing corneal endothelium.

PURPOSE: To examine the involvement of p27(KIP1) in the regulation of the proliferation of the developing corneal endothelium. METHODS: Central and peripheral corneas in C57Bl6 mice at postnatal day (P)1, P11, and 12 weeks after birth were analyzed by immunocytochemistry with anti-p27(KIP1), -p57(KIP2), and -proliferating cell nuclear antigen (PCNA) antibodies. Nuclear staining was performed with 4',6'-diamino-2-phenylindole (DAPI) in wholemounts of corneal endothelium of the center and peripheral cornea in wild-type and p27(KIP1) knockout (-/-) mice at 12 weeks of age. p27(KIP1-/-) and control mice were injected with bromodeoxyuridine (BrdU) once on P7, twice per day on P8 and P9, and once on P10 and then were analyzed by a BrdU cell-proliferation assay on P11. RESULTS: On P1, p27(KIP1) immunoreactivity was detected in a small number of corneal endothelial cells, and many endothelial cells expressed PCNA. At P11 and 12 weeks after birth, p27(KIP1) immunoreactivity was detected in many corneal endothelial cells. PCNA-positive cells in the endothelium were rare on P11 and completely absent at 12 weeks after birth. p57(KIP2) was not detected in either corneal epithelium or endothelium at P1, P11, or 12 weeks after birth. In wholemounts of corneal endothelium at 12 weeks of age, the number of endothelial nuclei in the p27(KIP1-/-) mice was significantly higher than that in wild-type mice in both the center and peripheral regions of the cornea. In the BrdU assay, positive cells were abundant in the corneal endothelium of p27(KIP1-/-) mice, whereas there were few positive cells in control mice. PCNA immunoreactivity in the endothelium of the p27(KIP1-/-) mice was completely absent at 12 weeks after birth. CONCLUSIONS: These results suggest that p27(KIP1) is involved in the regulation of proliferation in the endothelium of the developing cornea.

Animals↗
PubMed2004

Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet's disease with refractory uveoretinitis.

OBJECTIVE: Behçet's disease (BD) with uveoretinitis is a chronic refractory disease accompanied by ocular attacks. As the decrease in visual acuity due to ocular attack is seriously life-threatening, development of a new drug is anticipated. Since tumor necrosis factor-a (TNF-a) is involved in the symptoms of BD, particularly the activity of ocular symptoms, suppression of TNF-a might be effective in treating BD with uveoretinitis. We conducted a clinical trial of infliximab, an anti-TNF-a chimeric monoclonal antibody, in patients with BD. METHODS: In this open label trial, the efficacy, safety, and pharmacokinetics of repeated administration of infliximab were evaluated in 13 patients with BD accompanied by refractory uveoretinitis. Infliximab was administered 4 times at Weeks 0, 2, 6, and 10 at doses of either 5 or 10 mg/kg by intravenous drip infusion. Frequency of ocular attacks was used as the primary index for evaluation of efficacy, with visual acuity and extraocular symptoms as secondary indices. RESULTS: The mean numbers of ocular attacks, converted to frequency per 14 weeks, were 3.96 times for the 5 mg/kg group and 3.79 times for the 10 mg/kg group during the observation period. Following treatment with infliximab, they decreased to 0.98 times and 0.16 times, respectively. A serious adverse event, tuberculosis, was observed in one case in the 10 mg/kg group. Serum infliximab concentration increased with dosage. CONCLUSION: Administration of infliximab in patients with BD with refractory uveoretinitis suppressed the frequency of ocular attacks, and multiple administration was well tolerated, suggesting that infliximab is effective for this condition.

Adolescent↗
PubMed2003

Cytokine production profile in patients with Behcet's disease treated with infliximab.

Although the etiology of Behcet's disease (BD) still remains uncertain, various immune abnormalities have been implicated in BD. We studied cytokine production in patients with active and inactive BD, and evaluated the effect of treatment with infliximab (anti-TNF-alpha antibody) on disease activity and cytokine production by the ELISPOT assay. The numbers of cells spontaneously secreting IFN-gamma, IL-12, and TNF-alpha were significantly increased in patients with active BD. Mitogen-stimulated IL-4 secretion was elevated in active patients, though the ratio of IFN-gamma:IL-4 secreting cells was significantly increased in active BD. Next, we monitored cytokine production and expression of IL-12 receptor beta1 chain (IL-12Rbeta1) during short- and long-term infliximab treatment. A single infusion of infliximab significantly reduced the number of PBMC secreting TNF-alpha within 24 h. A rise in TNF-alpha production was associated with clinical deterioration. Infliximab treatment induced a significant increase in the number of cells secreting IFN-gamma and expressing IL-12Rbeta1. A favorable clinical response to infliximab was associated with a persistent reduction in TNF-alpha secretion, but did not correlate with IFN-gamma production. Our findings indicate that TNF-alpha plays a pivotal role in BD, and that anti-TNF-alpha therapy both reduces TNF-alpha production and modulates the functional activity of type 1 cells.

Anti-Inflammatory Agents↗
PubMed2003

Increase of KL-6 in sera of uveitis patients with sarcoidosis.

BACKGROUND: KL-6 is a human glycoprotein secreted by type II alveolar cells in lung, and its serum levels increase in pneumonia of various causes. KL-6 is a member of the MUC-1 family, which is expressed in lung, cornea, and conjunctiva. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for diagnosing sarcoidosis in patients with uveitis. METHODS: Sera were obtained from 24 uveitis patients diagnosed with sarcoidosis, 37 uveitis patients with other etiologies, and 138 healthy control subjects. Serum concentration of KL-6 was determined by a human KL-6 electrochemiluminescence immunoassay. RESULTS: The average level of KL-6 in the sera of uveitis patients with sarcoidosis was 387 U/ml. This was significantly higher than in healthy subjects and uveitis patients with other etiologies. The KL-6 measurements identified 45.8% of sarcoidosis-positive patients. When the KL-6 results were combined with serum angiotensin-converting enzyme (ACE) concentrations, 87.5% of sarcoidosis patients were identified, compared to 66.7% using ACE results alone. The combined measurement identified 10.8% of the non-sarcoid patients and 0.72% of healthy subjects as positive (false positive). CONCLUSION: Combined measurements of serum KL-6 and ACE may be useful as a screening for sarcoidosis in uveitis patients.

Antigens↗
PubMed2003

Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo.

PURPOSE: Astaxanthin (AST) is a carotenoid that is found in marine animals and vegetables. Several previous studies have demonstrated that AST exhibits a wide variety of biological activities including antioxidant, antitumor, and anti-Helicobacter pylori effects. In this study, attention was focused on the antioxidant effect of AST. The object of the present study was to investigate the efficacy of AST in endotoxin-induced uveitis (EIU) in rats. In addition, the effect of AST on endotoxin-induced nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF)-alpha production in a mouse macrophage cell line (RAW 264.7) was studied in vitro. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). AST or prednisolone was administered intravenously at 30 minutes before, at the same time as, or at 30 minutes after LPS treatment. The number of infiltrating cells and protein concentration in the aqueous humor collected at 24 hours after LPS treatment was determined. RAW 264.7 cells were pretreated with various concentrations of AST for 24 hours and subsequently stimulated with 10 microg/mL of LPS for 24 hours. The levels of PGE2, TNF-alpha, and NO production were determined in vivo and in vitro. RESULTS: AST suppressed the development of EIU in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg AST was as strong as that of 10 mg/kg prednisolone. AST also decreased production of NO, activity of inducible nitric oxide synthase (NOS), and production of PGE2 and TNF-alpha in RAW264.7 cells in vitro in a dose-dependent manner. CONCLUSIONS: This study suggests that AST has a dose-dependent ocular anti-inflammatory effect, by the suppression of NO, PGE2, and TNF-alpha production, through directly blocking NOS enzyme activity.

Animals↗
PubMed2003

Effect of human cationic antimicrobial protein 18 Peptide on endotoxin-induced uveitis in rats.

PURPOSE: Human cationic antimicrobial protein 18 (hCAP18, 18 kDa) was originally identified in leukocytes on the basis of its antimicrobial activity. The peptide composed of the 27 C-terminal amino acids of hCAP18 (hCAP18(109-135)) binds lipopolysaccharide (LPS). The purpose of the present study was to investigate the effects of hCAP18 peptide on endotoxin-induced uveitis (EIU) in rats. METHODS: EIU was induced by footpad injection of LPS. Each rat was injected intravenously with 1, 10, or 100 micro g hCAP18 peptide in 0.1 mL of PBS immediately after LPS injection in male Lewis rats. At 24 hours after LPS injection, enzyme-linked immunosorbent assay was performed to evaluate concentrations of protein, nitric oxide (NO), tumor necrosis factor (TNF)-alpha, prostaglandin (PG)-E2, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 in aqueous humor. Also, EIU was evaluated by counting inflammatory cells in aqueous humor. RESULTS: hCAP18 peptide at 10 and 100 micro g significantly suppressed an LPS-induced increase in the number of inflammatory cells and the levels of protein, NO, TNF-alpha, PGE2, MCP-1, and MIP-2. The anti-inflammatory effect of 10 micro g hCAP18 peptide was as strong as that of 100 micro g hCAP18 peptide. Treatment with 1 micro g hCAP18 peptide did not suppress EIU, compared with the LPS group. CONCLUSIONS: The present results indicate that hCAP18 peptide suppresses development of EIU. A possible mechanism for the ocular anti-inflammatory effect of hCAP18 peptide is that it suppresses onset of LPS-triggered inflammatory reactions by binding directly to LPS.

Animals↗
PubMed2003

Efficacy of rebamipide as adjunctive therapy in the treatment of recurrent oral aphthous ulcers in patients with Behçet's disease: a randomised, double-blind, placebo-controlled study.

BACKGROUND: Behçet's disease (BD) is a recurrent inflammatory disease involving chronic recurrent oral aphthous ulcers (aphthae), uveitis, skin lesions and genital ulcers. We prospectively investigated the efficacy of rebamipide, a gastroprotective drug, against oral aphthous ulcers in BD patients. METHODS: In a multicentre, double-blind, placebo-controlled study, 35 patients with BD, having as the main symptom oral aphthosis, were randomised to receive rebamipide 300 mg/day or placebo for 12 to 24 weeks between August 1994 and December 1996. Oral aphthosis must have occurred within 4 weeks prior to enrolment and must have been visible for at least 7 days during that time. Oral aphthae count and pain scores were recorded daily in a diary by the patients themselves. Monthly aphthae count and pain scores were defined as the sum of aphthae count and pain scores for a month, respectively. Investigators rated the global improvement in aphthae count and pain using a 6-point scale. The rate of change in monthly aphthae count and pain scores in the first 3 and last 3 months of treatment were assessed in patients with more severe symptoms whose aphthae count and pain score were >28 at baseline (trial entry). RESULTS: The rate of moderate or marked improvement in aphthae count and pain was 36% (5 of 14 subjects) in the placebo group and 65% (11 of 17 subjects) in the rebamipide group. During months 2 to 6 of treatment, aphthae count tended to increase and reached a peak at month 4 in the placebo group but decreased in the rebamipide group. Pain score decreased to the same extent in both groups for the first 3 months of treatment; however, in the fourth to sixth months of treatment, the pain score tended to increase in the placebo group but decreased in the rebamipide group. In patients with a monthly aphthae pain score >28 at baseline, pain and count scores decreased throughout the 6 months of rebamipide treatment but increased during the last 3 months of treatment in the placebo group (p < 0.01 for the between-group comparisons). CONCLUSIONS: Rebamipide is well tolerated and improves the aphthae count and pain score in BD patients. It may therefore be useful in the treatment and prevention of frequently recurrent oral aphthous ulcers (not restricted to BD). Administration of rebamipide is not cumbersome, and it does not cause any discomfort, which corticosteroid ointments for example may do; furthermore, there are no specific adverse drug reactions. Rebamipide is therefore recommended as a long-term treatment for recurrent oral aphthous ulcers.

Adult↗
PubMed2003

[Antiviral effect of sulfated sialyl lipid against a clinical strain of adenovirus].

PURPOSE: Currently, there is no antiviral drug for adenovirus(AdV). We have reported that sulfated sialyl lipid(NMSO) 3, a NMSO, has an antiviral effect against AdV prototype strains. We evaluated the antiviral inhibitory effect and the mechanism of NMSO 3 against AdV strains from patients with conjunctivitis in vitro. METHODS: Viruses used for the experiment were clinically isolated AdV type 3(AdV 3), AdV type 4(AdV 4), type 8(ADV 8), AdV type 19(AdV 19), and type 37(AdV 37). We examined three antiviral agents, i.e., NMSO 3, cidofovir(HPMPC), and zalcitabine(ddC). 50% effective concentration(EC50), 50% cytotoxic concentration(CC50), and selectivity index(SI) of compounds were determined for AdV infection in HEp-2 cells using 3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods. We also evaluated the anti-AdV activity of NMSO 3 when it was added during the stage of virus adsorption. RESULTS: NMSO 3, HPMPC, and ddC showed an inhibitory effect against all five AdV clinical strains. The EC50 values of NMSO3 were lower than those of HPMPC and ddC. NMSO 3 exhibited minimal cytotoxicity. NMSO 3 inhibited AdV infection only when it was added during the stage of virus adsorption. CONCLUSIONS: NMSO 3 inhibited the replication of all clinical AdV serotypes tested. NMSO 3 was the most potent and selective anti-AdV compound. The mechanism of anti-AdV activity by NMSO 3 was inhibition of viral adsorption to cells.

Adenoviridae↗