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Biomedical subjects

Hideo Hara

Publications and source records attributed to Hideo Hara.

10 recordsLinked to original sources
PubMed2005

Mechanism of natural killer (NK) cell regulatory role in experimental autoimmune encephalomyelitis.

The mechanism of natural killer (NK) cell regulatory role in experimental autoimmune encephalomyelitis (EAE) was studied in SJL/J mice. In vivo experiments showed that NK cell depletion by anti-NK1.1 monoclonal antibody treatment enhanced EAE in mice. To investigate the mechanism, we cultured proteolipid protein (PLP)136-150 peptide-specific, encephalitogenic T cell lines, which were used as the NK cell target. Our results show that NK cells exert a direct cytotoxic effect on autoantigen-specific, encephalitogenic T cells. Furthermore, cytotoxicity to PLP-specific, encephalitogenic T line cells was enhanced by using enriched NK cells as effector cells. However, the cytotoxic effect of NK cells to ovalbumin-specific T line cells and ConA-stimulated T cells could also be detected with a lesser efficiency. Our studies indicate that NK cells play a regulatory role in EAE through killing of syngeneic T cells which include myelin antigen-specific, encephalitogenic T cells, and thus ameliorate EAE.

Amino Acid Sequence↗
PubMed2005

[Abeta vaccine therapy for Alzheimer's disease].

In 1999, Schenk et al reported that vaccination of PDAPP-transgenic mice with synthetic Abeta42 in complete Freund's adjuvant showed markedly decrease of the amyloid burden in the brain. The second trial of vaccine, AN1792, for Alzheimer's patients was halted because of meningoencephalitis found in 6% of patients and one autopsy case was reported. Here, we comment the methods and the immunological mechanisms of Abeta vaccine therapy and discuss the pathological changes in the brain and side effects after AN1792 treatment. Furthermore, we present an oral Abeta vaccine therapy for Alzheimer's disease with the recombinant adeno-associated virus (AAV) vector that we developed.

Alzheimer Disease↗
PubMed2004

Development of a safe oral Abeta vaccine using recombinant adeno-associated virus vector for Alzheimer's disease.

A new oral vaccine for Alzheimer's disease was developed using recombinant adeno-associated virus vector carrying Abeta cDNA (AAV/Abeta). Oral administration of the vaccine without adjuvant induced the expression and secretion of Abeta1-43 or Abeta1-21 in the epithelial cell layer of the intestine in amyloid precursor protein transgenic mice. Serum antibody levels were elevated for more than six months, while T cell proliferative responses to Abeta was not detected. Brain Abeta burden was significantly decreased compared to the control without inflammatory changes. This oral AAV/Abeta vaccine seems to be promising for prevention and treatment of Alzheimer's disease.

Administration, Oral↗
PubMed2004

[Treatment of Alzheimer disease: A beta vaccine].

Alzheimer disease (AD) is regarded as an amyloidosis of the brain, and, therefore, the prevention/deletion of beta amyloid deposition is one of the most promising target of the treatment. Particularly, immune-mediated strategy is now known as A beta vaccination, which is thought to be a highly feasible way being applicable to AD patients. The A beta vaccination was originated by Schenk et al. in 1999. Since active and passive immunization of amyloid precursor protein (APP) gene- transgenic mice showed significant reduction of beta amyloid deposits in the brain and the immunized mice showed improvement in cognitive functions, clinical trials were performed in US and Europe. However, the trial was suspended, because about 6% of patients who received the vaccine developed meningoencephalitis probably mediated by T cells reactive to A beta. Although the trial was halted, an autopsy case who had had the meningoencephalitis suggested the disappearance of senile plaques (Nicoll et al., 2003). Moreover, patients who developed antibodies that recognize senile plaques by immunohistochemistry showed significantly milder decline of cognitive functions than those who did not (Hock et al., 2003). Here, we report a safe and effective oral vaccine using adeno-associated virus vector carrying A beta cDNA tested in tg2576 mice.

Alzheimer Disease↗
PubMed2002

Elevated levels of anti-CD9 antibodies in the cerebrospinal fluid of patients with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive and highly lethal disease of the central nervous system. Although the primary cause of SSPE is believed to be persistent infection of neuron and glial cells by a measles virus, the precise mechanism of the progression of this disease has not yet been elucidated. CD9, a member of the tetraspanin family, is expressed in myelin and other nervous tissues. This study detected significant amounts of anti-CD9 antibodies in the cerebrospinal fluid (CSF) of all patients with SSPE included in the study. Anti-CD9 antibodies were also detected in the CSF of some patients with other neurologic disorders, but those patients had lower levels of anti-CD9 antibodies than did the patients with SSPE. The level of anti-CD9 antibodies was elevated and reached a peak that coincided with the appearance of brain atrophy. These findings shed light on a new aspect of the causes and progression of SSPE.

Adolescent↗
PubMed2002

Accelerated production of nucleosome in cultured human mononuclear cells in untreated Graves' disease.

The apoptosis of lymphocytes, which occurs in autoimmune diseases, is usually induced by the Fas/Fas ligand system. As the assay of nucleosomes produced by apoptotic cells can be used to quantitate apoptosis, we evaluated nucleosome and soluble Fas ligand (sFasL) levels of cultured mononuclear cells to clarify the apoptosis of mononuclear cells in patients with autoimmune thyroid diseases by enzyme-linked immunosorbent assay. Nucleosome levels of cultured mononuclear cells in patients with untreated Graves' disease were significantly higher (3.27+/-2.90 U/ml) than those of control subjects (1.39+/-0.24 U/ml) and euthyroid patients with treated Graves' disease (1.53+/-0.33 U/ml). Nucleosome levels of cultured mononuclear cells were positively correlated with sFasL levels (r=0.544, p<0.01). It is therefore likely that increased sFasL levels elicit apoptosis of these cells in untreated Graves' disease.

Adult↗
PubMed2002

Circulating nuclear matrix protein in Graves' disease.

The Fas/Fas ligand system induces apoptosis, while soluble Fas (sFas) blocks the system and soluble Fas ligand (sFasL) functions to induce apoptosis. The assay of nuclear matrix protein (NMP) released from dead or dying cells can be used to quantitate cell death. Therefore, we evaluated the relationship among serum levels of NMP, sFas, and sFasL in patients with Graves' disease. We measured serum levels of sFas, sFasL, NMP, thyroid hormones and TSH receptor antibody in 20 normal control subjects (5 men, 15 women; mean age, 44.3 years), 32 patients with untreated Graves' disease (4 men, 28 women; mean age, 44.1 years), and 10 patients with Graves' disease treated by methimazole (3 men, 7 women; mean age 39.2 years). Serum NMP was significantly lower (10.4 +/- 4.3 IU/ml, p < 0.02) in patients with untreated Graves' disease than in patients with treated Graves' disease (16.4 +/- 7.3 IU/ml) and control subjects (15.3 +/- 8.9 IU/ml). Serum sFas and sFasL were significantly higher in patients with untreated Graves' disease than in patients with treated Graves' disease and in control subjects. In the patient groups with Graves' disease, serum NMP was negatively correlated with sFas (r = -0.612, p < 0.001) and serum sFas was positively correlated with FT4 (r = 0.360, p < 0.05) and TRAb (r = 0.384, p < 0.05). Serum NMP was correlated with sFas. These results suggest that serum NMP is decreased in patients with untreated Graves' disease, and that cell death or apoptosis in patients with Graves' disease is affected by soluble Fas under the influence of thyroid function.

Adult↗