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Biomedical subjects

Akiko Okamoto

Publications and source records attributed to Akiko Okamoto.

11 recordsLinked to original sources
PubMed2006

Gene therapy of arthritis with TCR isolated from the inflamed paw.

In recent years, the treatment of autoimmune diseases has been significantly advanced by the use of biological agents. However, some biologics are accompanied with severe side effects, including tuberculosis and other types of infection. There is thus a critical need for nonsystemic and lesion-specific methods of delivering these therapeutic agents. We attempted to treat a mouse model of arthritis by using T cells that expressed a regulatory molecule and were specifically directed to the inflamed paw. To this end, we first identified the TCR alphabeta genes accumulating in the inflamed paw of mice with collagen-induced arthritis (CIA) by a combination of single-strand chain polymorphism analysis of TCR and single-cell sorting. We identified an expanded clone B47 which is autoreactive but is not specific to type II collagen. In vivo, TCR genes from B47-transduced T cells accumulated in the inflamed paw. Injection of cells cotransduced with the B47 and soluble TNFRIg genes resulted in a significant suppression of CIA. The suppression was correlated with the amount of TNFRIg transcripts in the hind paw, not with the serum concentrations of TNFRIg. Moreover, T cells cotransduced with the B47 and intracellular Foxp3 genes significantly suppressed CIA with reductions in TNF-alpha, IL-17A, and IL-1beta expression and bone destruction. T cells cotransduced with B47 and Foxp3 genes also suppressed the progression of established CIA. Therefore, immunosuppressive therapy with autoreactive TCR is a promising therapeutic strategy for arthritis whether the TCRs are used to deliver either soluble or intracellular suppressive molecules.

Adoptive Transfer↗
PubMed2006

Regional cerebral blood flow changes associated with interoceptive awareness in the recovery process of anorexia nervosa.

BACKGROUND: An abnormality in regional cerebral blood flow (rCBF) in anorexia nervosa (AN) patients has been reported. There are very few studies that have investigated the rCBF changes in the recovery process of AN. METHODS: For eight female AN patients, we performed (123)I-IMP single photon emission computed tomography (SPECT) and four psychological assessments (Eating Disorder Inventory (EDI), Eating Attitude Test (EAT), Self-Rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI)) both before and after inpatient-behavioral therapy. SPECT images were analyzed using statistical parametric mapping software. We also performed correlational analysis between rCBF and clinical variables. RESULTS: Following treatment, the patients showed significant body weight recovery. They showed significant improvement in EAT, SDS, STAI and a subscale of EDI - interoceptive awareness (IA) - but not in total EDI or other EDI subscales. Significant rCBF increases were observed in the precuneus, posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC) by the treatment. Significant correlation was observed between rCBF of right DLPFC and IA score before treatment. CONCLUSIONS: Changes of rCBF in right DLPFC, ACC, MPFC, PCC and precuneus were related to the AN recovery process and might be associated with improvement of IA following treatment.

Adolescent↗
PubMed2006

Interactions between IL-32 and tumor necrosis factor alpha contribute to the exacerbation of immune-inflammatory diseases.

IL-32 is a newly described cytokine in the human found to be an in vitro inducer of tumor necrosis factor alpha (TNFalpha). We examined the in vivo relationship between IL-32 and TNFalpha, and the pathologic role of IL-32 in the TNFalpha-related diseases - arthritis and colitis. We demonstrated by quantitative PCR assay that IL-32 mRNA was expressed in the lymphoid tissues, and in stimulated peripheral T cells, monocytes, and B cells. Activated T cells were important for IL-32 mRNA expression in monocytes and B cells. Interestingly, TNFalpha reciprocally induced IL-32 mRNA expression in T cells, monocyte-derived dendritic cells, and synovial fibroblasts. Moreover, IL-32 mRNA expression was prominent in the synovial tissues of rheumatoid arthritis patients, especially in synovial-infiltrated lymphocytes by in situ hybridization. To examine the in vivo relationship of IL-32 and TNFalpha, we prepared an overexpression model mouse of human IL-32beta (BM-hIL-32) by bone marrow transplantation. Splenocytes of BM-hIL-32 mice showed increased expression and secretion of TNFalpha, IL-1beta, and IL-6 especially in response to lipopolysaccharide stimulation. Moreover, serum TNFalpha concentration showed a clear increase in BM-hIL-32 mice. Cell-sorting analysis of splenocytes showed that the expression of TNFalpha was increased in resting F4/80+ macrophages, and the expression of TNFalpha, IL-1beta and IL-6 was increased in lipopolysaccharide-stimulated F4/80+ macrophages and CD11c+ dendritic cells. In fact, BM-hIL-32 mice showed exacerbation of collagen-antibody-induced arthritis and trinitrobenzen sulfonic acid-induced colitis. In addition, the transfer of hIL-32beta-producing CD4+ T cells significantly exacerbated collagen-induced arthritis, and a TNFalpha blockade cancelled the exacerbating effects of hIL-32beta. We therefore conclude that IL-32 is closely associated with TNFalpha, and contributes to the exacerbation of TNFalpha-related inflammatory arthritis and colitis.

Adoptive Transfer↗
PubMed2004

Nucleosome-specific regulatory T cells engineered by triple gene transfer suppress a systemic autoimmune disease.

The mechanisms of systemic autoimmune disease are poorly understood and available therapies often lead to immunosuppressive conditions. We describe here a new model of autoantigen-specific immunotherapy based on the sites of autoantigen presentation in systemic autoimmune disease. Nucleosomes are one of the well-characterized autoantigens. We found relative splenic localization of the stimulative capacity for nucleosome-specific T cells in (NZB x NZW)F(1) (NZB/W F(1)) lupus-prone mice. Splenic dendritic cells (DCs) from NZB/W F(1) mice spontaneously stimulate nucleosome-specific T cells to a much greater degree than both DCs from normal mice and DCs from the lymph nodes of NZB/W F(1) mice. This leads to a strategy for the local delivery of therapeutic molecules using autoantigen-specific T cells. Nucleosome-specific regulatory T cells engineered by triple gene transfer (TCR-alpha, TCR-beta, and CTLA4Ig) accumulated in the spleen and suppressed the related pathogenic autoantibody production. Nephritis was drastically suppressed without impairing the T cell-dependent humoral immune responses. Thus, autoantigen-specific regulatory T cells engineered by multiple gene transfer is a promising strategy for treating autoimmune diseases.

Abatacept↗
PubMed2003

Japanese version of the Body Attitude Test: its reliability and validity.

The Body Attitude Test (BAT) was developed by Probst et al. (1995) for female patients with eating disorders (ED). This test measures the subjective body experience and attitudes toward one's body. The present authors have developed the Japanese version of the BAT and the purpose of the present paper was to investigate its reliability and validity in control (CON, n = 599) and ED patients (n = 46). The ED patients consisted of 21 anorexia nervosa, restricting type (AN-R) patients and 25 bulimia nervosa (BN) patients. Internal consistency was determined with Cronbach's alpha coefficient in CON. Factor analysis was conducted on BAT ratings given by CON. Factor analysis indicated that BAT was composed of two factors. These were body dissatisfaction (factor 1) and lack of familiarity with one's body (factor 2). A comparison was made among AN-R, BN, and CON. Bulimia nervosa had a significantly higher score than the other two groups. The BAT scores of ED patients correlated significantly with the Self -rating Depression Scale, and State-Trait Anxiety Inventory. These results show that ED patients have negative feelings toward their own body, similar to the findings in the original report. On factor analysis, however, it was not possible to distinguish between negative appreciation of body size and general body dissatisfaction as described in the original report. The authors also examine influences on this difference from a cross-cultural view point.

Adolescent↗
PubMed2002

A behavior therapy program combined with liquid nutrition designed for anorexia nervosa.

We have introduced behavior therapy as standard in-patient treatment for anorexia nervosa and have modified the treatment program. At first, we used Fukamachi's activity restriction therapy (FT), followed by Token economy therapy (TET), which combined token economy with FT. Finally, we have developed Kyoto Prefectural University of Medicine Behavior Therapy (KPT). According to KPT, only liquid formula is given in the early stages of hospitalization and a target weight is not set at admission. We examined the effect of these three programs with respect to bodyweight gain. Thirty-five anorexic patients participated in these three programs in our hospital: seven completed FT, seven completed TET and 21 completed KPT. We compared the effects of these three programs on body mass index (BMI). Furthermore, the effects of these three programs on BMI were compared at admission, 1 month after admission and at discharge, 6 months after discharge. In addition, the rate of increase of BMI for the following three periods was investigated: 1 month after admission, total hospitalization (from admission to discharge) and from admission to 6 months after discharge. The result is that KPT was the most effective of the three programs with regard to both the amount and the rate of increase of BMI at all points and there is a significant difference between KPT and FT. This effectiveness may be attributable to the use of an oral liquid formula, the setting of target weight at a later stage of hospitalization and the release of activity restriction based on weight gain.

Activities of Daily Living↗
PubMed2002

Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety.

OBJECTIVE: The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania. METHOD: This 3-week randomized, double-blind, placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer (lithium or divalproex) and placebo, risperidone, or haloperidol. The primary efficacy measure was the Young Mania Rating Scale. Other assessments used the Brief Psychiatric Rating Scale, the Clinical Global Impression scale, and safety measures. RESULTS: The trial was discontinued by 25 (49%) of the 51 placebo group patients, 18 (35%) of the 52 risperidone group patients, and 28 (53%) of the 53 haloperidol group patients. Mean modal doses were 3.8 mg/day (SD=1.8) of risperidone and 6.2 mg/day (SD=2.9) of haloperidol. Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group, compared with the placebo group. Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without psychotic features at baseline. Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients. Antiparkinsonian medications were received by 8%, 17%, and 38% of patients in the placebo, risperidone, and haloperidol groups, respectively. CONCLUSIONS: Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone, and as efficacious as haloperidol plus a mood stabilizer, for the rapid control of manic symptoms and was well tolerated.

Acute Disease↗