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Biomedical subjects

Nobuyuki Abe

Publications and source records attributed to Nobuyuki Abe.

6 recordsLinked to original sources
PubMed2006

Safety and efficacy of nasal application of CpG oligodeoxynucleotide as a mucosal adjuvant.

OBJECTIVES: Nasal vaccination is an effective regimen to prevent upper respiratory infections. An appropriate adjuvant is required for the development of a nasal vaccine. The safety and efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined. METHODS: Mice were nasally administered various doses of CpG ODN weekly, a total of three times. Histologic changes in the spleen and the nasal mucosa were examined, and the alterations in cell subpopulations were analyzed by flow cytometry. In addition, the mice were nasally immunized with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) and CpG ODN, and P6-specific immune responses were examined. RESULTS: No inflammation or tissue damage was observed locally or systemically after nasal administration, even with a high dose of CpG ODN. A high dose of CpG ODN induced an increase in CD8+ T cells in the nasal mucosa and B cells in the spleen. When CpG ODN was coadministered with P6, P6-specific mucosal and systemic immune responses were effectively induced, since high levels of the specific IgA and IgG were detected in the nasal wash and serum, respectively. CONCLUSIONS: These findings suggest that CpG ODN is a safe and effective mucosal adjuvant. Further, nasal vaccination with P6 and CpG ODN might be an effective regimen to prevent upper respiratory infections.

Adjuvants, Immunologic↗
PubMed2006

Nasal vaccination with CpG oligodeoxynucleotide induces protective immunity against non-typeable Haemophilus influenzae in the nasopharynx.

OBJECTIVES: Nasal vaccination is an effective therapeutic regimen for preventing otitis media. Since cholera toxin (CT) is toxic, an alternative adjuvant is required for the development of a nasal vaccine. The efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined. METHODS: Mice were immunized intranasally with P6 protein of non-typeable Haemophilus influenzae (NTHi) and adjuvant, CT, or CpG ODN, and P6-specific antibody responses were examined. The expression of P6-specific cytokine mRNA in splenic CD4 T cells was also determined. In addition, NTHi challenges were performed and the NTHi was quantified in nasal washes. RESULTS: P6-specific IgA in nasal wash and serum IgG titers were elevated significantly after nasal immunization. The IgG1/IgG2a ratio in serum from P6+CpG-immunized mice was less than that of P6+CT-immunized mice. Although IL-6 was expression similarly in both groups, IFN-gamma expression was greater in P6+CpG-immunized mice than in P6+CT-immunized mice. Enhanced clearance of NTHi from the nasopharynx was also shown equally in both groups. CONCLUSION: These results indicate that CpG ODN might be an effective mucosal adjuvant, acting by mechanisms that are different from CT. These findings suggest that nasal vaccination with P6 and CpG ODN might be an effective regimen for the induction of NTHi-specific protective immunity.

Adjuvants, Immunologic↗
PubMed2005

Eustachian tube possesses immunological characteristics as a mucosal effector site and responds to P6 outer membrane protein of nontypeable Haemophilus influenzae.

The eustachian tube (ET) plays an important role in the pathogenesis of otitis media (OM). To better understand its biology and to develop a nasal vaccine for preventing OM, mucosal lymphocytes in the ET were analyzed, and the ET's immunological function was investigated. Mononuclear cells were isolated from murine ET, and lymphocyte subsets were analyzed by flow cytometry. Antibody-producing cells were determined by enzyme-linked immunospot assay. The expression of cytokine mRNA in ET CD4(+) T cells was determined by RT-PCR. Results in naive mice showed that the ET contained many immunocompetent cells, including a relative large number of IgA-producing cells and Th2 cytokine-expressing T cells. Next, we investigated antigen-specific immune responses in the ET. Mice were immunized intranasally with the P6 outer membrane of nontypeable Haemophilus influenzae (NTHi) and cholera toxin (CT), and P6-specific immune responses in the ET were examined. P6-specific IgA producing cells markedly increased in the ET. Moreover, in vitro stimulation with P6 of purified CD4(+) T cells from immunized mice resulted in the proliferation of CD4(+) T cells that expressed Th2 cytokine mRNA. These results indicate that the ET might be characterized as a mucosal effector site and that antigen-specific IgA and Th2 immune responses could be induced in the ET by intranasal immunization. These findings suggest that the ET might be a key immunological organ in the pathogenesis of OM, and in the development of a nasal vaccine.

Animals↗
PubMed2004

Clinical and genetic characteristics of GAD-antibody positive patients initially diagnosed as having type 2 diabetes.

The present study was conducted to clarify the clinical and genetic characteristics of the diabetic patients who have antibodies to glutamic acid decarboxylase (GADab) but are diagnosed initially as type 2 diabetes because of the slow progression. Fifty-five GADab+ patients and 137 GADab- patients were recruited. The GADab+ patients were divided into two subgroups according to their antibody titers. The high-titer subgroup (Ab > or = 20 U/ml) had lower urinary C-peptide concentrations, and was assigned insulin therapy more often than the GADab- patients. In contrast to the high-titer subgroup, clinical parameters in the low-titer subgroup were similar to the GADab- diabetic patients. The urinary C-peptide levels correlated negatively with the GADab titer in the GADab+ patients. Analysis of type 1 diabetes-susceptible HLA alleles revealed high frequencies of the B54 and DRB1*0405 allele, but not the B61 and DRB1*0901 alleles, in the high-titer subgroup, whereas the frequency of the protective DRB1*1502 allele was decreased. The GADab+ patients with the B54 allele had higher GADab titers and lower urinary C-peptide excretion than patients without this allele. These data indicated that patients with a high-GADab titer share the autoimmune background characteristic of type 1 diabetes.

Adult↗
PubMedDate not supplied

High serum TNF-alpha level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells.

A high dose of tumor necrosis factor (TNF)-alpha induces endothelial dysfunction and enhances apoptosis in vitro. The present study was conducted to examine whether incubating human umbilical vein endothelial cells (HUVECs) with serum from Type 2 diabetic patients complicated with retinopathy and/or microalbuminemia demonstrate endothelial dysfunction. Serum levels of TNF-alpha and vascular endothelial growth factor (VEGF) were elevated in diabetic patients. Plasma levels of TNF-alpha, two soluble TNF-alpha receptors (sTNFR), and VEGF were assessed in diabetic patients (CD, n=21) complicated with retinopathy and/or nephropathy, uncomplicated diabetic patients (UD, n=18), and in healthy normal participants (NS, n=16). In HUVECs incubated with patient's serum, endothelial constitutive nitric oxide synthase (eNOS) protein expressions were measured by Western blot analysis. Apoptosis in HUVECs was determined by optical microscopy, DNA fragmentation, and CPP32-like protease activity. Serum TNF-alpha, sTNFR-I, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS, in CD were significantly higher than in UD or NS. While, serum sTNFR-I and VEGF levels were significantly increased in the both diabetic patients, compared with those of NS, no difference was observed in the serum TNF-alpha, sTNFR-II, and ADMA levels between UD and NS. eNOS down-regulation and apoptosis were seen in HUVECs incubated with serum from CD for 24 h, but those observations were completely counteracted in the incubation by the addition of the antihuman TNF-alpha antibody. These results imply that eNOS down-regulation in CD is associated with high serum TNF-alpha levels despite of high serum of VEGF levels. Therefore, endothelial dysfunction in diabetic patients complicated with microangiopathy may, in part, be attributed to high serum TNF-alpha levels.

Adult↗