Katsuhiko Takabayashi

Increased interleukin-17 production in patients with systemic sclerosis.

OBJECTIVE To determine the role of a novel T cell-derived cytokine, interleukin-17 (IL-17), which activates fibroblasts and endothelial cells, in the pathogenesis of systemic sclerosis (SSc). METHODS We examined IL-17 production by lymphocytes from the peripheral blood (PBL) and from fibrotic lesions of the skin and lungs of SSc patients by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. We also studied the effect of IL-17 on the proliferation of fibroblasts and on the production of cytokines and the expression of adhesion molecules on endothelial cells in vitro. RESULTS IL-17 messenger RNA was expressed in unstimulated PBL and lymphocytes from the skin and lungs of SSc patients, but not in similar samples from patients with systemic lupus erythematosus (SLE) or polymyositis/dermatomyositis or from healthy donors. IL-17 levels were also increased in the serum of SSc patients, but not in that of SLE patients or healthy donors. IL-17 overproduction was significantly related to the early stage of SSc, but not to other clinical features of SSc. Moreover, IL-17 enhanced the proliferation of fibroblasts and induced the expression of adhesion molecules and IL-1 production in endothelial cells in vitro. CONCLUSION IL-17 is overproduced by T cells from the peripheral blood and fibrotic lesions of the skin and lungs in SSc patients. These results suggest that IL-17 overproduction plays an important role in the pathogenesis of SSc, especially in the early stages of the disease, by inducing the proliferation of fibroblasts and the production of IL-1 and the expression of adhesion molecules on endothelial cells.

Preventive Effect of Monoclonal Anti-L3T4 Antibody on Development of Diabetes in NOD Mice

We analyzed the surface phenotypes of infiltrated cells in pancreases of nonobese diabetic (NOD) mice with monoclonal antibodies to mouse lymphocytes. Most of the infiltrated cells were Thy1+ and Ly1+ T-lymphocytes, and most of them were L3T4+ helper T-lymphocyte subsets. To elucidate the role of L3T4+ T-lymphocytes in the development of insulitis and diabetes in NOD mice, we treated the animals with injections of monoclonal anti-L3T4 antibody. Administration of this antibody prevented the insulitis and diabetes in NOD mice. These results lead to conclusions that the L3T4+ helper T-lymphocytes may play an essential role in the pathogenesis of type I diabetes and that the manipulation of the OKT4+ (Leu3+) T-lymphocyte subset, the human homology of L3T4, with monoclonal antibodies may provide effective therapy for human type I diabetes.

Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment

OBJECTIVES To investigate the actual time of onset of osteonecrosis (ON) after high dose corticosteroid treatment in systemic lupus erythematosus (SLE). METHODS 72 patients with active SLE, who received high dose corticosteroid for the first time, for the development of ON at hips and knees were monitored by magnetic resonance imaging for at least 12 months. RESULTS ON lesions were detected in 32/72 patients (44%) between one and five months (3.1 months on average) after starting high dose corticosteroid treatment. No osteonecrotic lesion was newly detected from the sixth month of treatment until the end of the follow up period. CONCLUSION The findings suggested that the actual time of onset of ON in SLE is within the first month of high dose corticosteroid treatment.

Effect of FK-506, a novel immunosuppressive drug on murine systemic lupus erythematosus

A novel immunosuppressive compound extracted from the fermentation broth of Streptomyces tsukubaensis belongs to the macrolide family. We gave this drug (FK-506) to MRL/lpr and NZB X NZW F1 (B/W F1) mice, an animal model of human systemic lupus erythematosus (SLE), to investigate its effect on the course of the disease. This drug showed potential to prolong the lifespan, to reduce proteinuria, and to prevent the progression of nephropathy. Appreciable differences in the levels of anti-dsDNA antibodies between treated and control animals were nil.

Protein losing enteropathy associated with collagen diseases.

Four patients with collagen diseases are described, who developed protein losing enteropathy in the course of their disease. Their protein losing enteropathies subsided after treatment with 60 mg/day oral prednisolone. Immunohistological studies of the small intestine showed deposits of C3 in the capillary walls of villi in two patients. Increased capillary permeability due to autoimmune phenomena may have a role in the pathogenesis of protein losing enteropathy associated with collagen diseases.

Data analysis and data mining: current issues in biomedical informatics.

BACKGROUND Medicine and biomedical sciences have become data-intensive fields, which, at the same time, enable the application of data-driven approaches and require sophisticated data analysis and data mining methods. Biomedical informatics provides a proper interdisciplinary context to integrate data and knowledge when processing available information, with the aim of giving effective decision-making support in clinics and translational research. OBJECTIVES To reflect on different perspectives related to the role of data analysis and data mining in biomedical informatics. METHODS On the occasion of the 50th year of Methods of Information in Medicine a symposium was organized, which reflected on opportunities, challenges and priorities of organizing, representing and analysing data, information and knowledge in biomedicine and health care. The contributions of experts with a variety of backgrounds in the area of biomedical data analysis have been collected as one outcome of this symposium, in order to provide a broad, though coherent, overview of some of the most interesting aspects of the field. RESULTS The paper presents sections on data accumulation and data-driven approaches in medical informatics, data and knowledge integration, statistical issues for the evaluation of data mining models, translational bioinformatics and bioinformatics aspects of genetic epidemiology. CONCLUSIONS Biomedical informatics represents a natural framework to properly and effectively apply data analysis and data mining methods in a decision-making context. In the future, it will be necessary to preserve the inclusive nature of the field and to foster an increasing sharing of data and methods between researchers.

Mining hepatitis data with temporal abstraction

The hepatitis temporal database collected at Chiba university hospital between 1982--2001 was recently given to challenge the KDD research. The database is large where each patient corresponds to 983 tests represented as sequences of irregular timestamp points with different lengths. This paper presents a temporal abstraction approach to mining knowledge from this hepatitis database. Exploiting hepatitis background knowledge and data analysis, we introduce new notions and methods for abstracting short-term changed and long-term changed tests. The abstracted data allow us to apply different machine learning methods for finding knowledge part of which is considered as new and interesting by medical doctors.

Decreased Regional Cerebral Metabolic Rate for Glucose in Systemic Lupus erythematosus Patients with Psychiatric Symptoms

To determine brain functional abnormality in systemic lupus erythematosus (SLE) patients with psychiatric symptoms, we evaluated 12 active SLE patients with or without psychiatric symptoms by means of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (PET), magnetic resonance imaging and neuropsychological testing. Patients with psychiatric symptoms showed significantly poorer performance in tests which subserved attentional function. The PET study revealed that the psychiatric patients had significantly decreased regional cerebral metabolic rates for glucose in the prefrontal, inferior parietal and anterior cingulate regions. Prefrontal, inferior parietal and anterior cingulate dysfunction may be related to attentional deficits that are involved in various psychiatric symptoms in SLE. PET is an invaluable tool to reveal such brain functional abnormality seen in SLE patients with psychiatric symptoms.

Automatic DPC code selection from electronic medical records: text mining trial of discharge summary.

OBJECTIVES We extracted index terms related to diseases recorded in hospital discharge summaries and examined the capability of the vector space model to select a suitable diagnosis with these terms. METHODS By morphological analysis, we extracted index terms and constructed an original dictionary for the discharge summary analysis. We chose 125 different DPC (Japanese DRG system) codes for the diseases, each of which had more than 20 cases. We divided them into two groups. One group consisted of 5927 cases from 2004 fiscal year and was used to generate the document vector space according to the DPC. The other group of 3187 cases was collected to verify the automatic DPC selection by using data from 2005 fiscal year. The top 200 extracted index terms for each disease were used to calculate the weight of each disease. RESULTS The DPC code obtained by the calculated similarity was compared with the original codes of patients for 125 DPCs of 3187 cases. Eighty percent of the cases matched the diagnosis of the DPC (first six digits) and 56% of the cases completely matched all 14 digits of the DPC. CONCLUSIONS We demonstrated that we could extract suitable terms for each disease and obtain characteristics, such as the diagnosis, from the calculated vectors. This technique can be used to measure the qualification of discharge summaries and to integrate discharge summaries among different facilities. By the text mining technique, we can characterize the contents of electronic discharge summaries and deduce diagnoses with the data.

Detecting interesting exceptions from medical test data with visual summarization

We propose a method which visualizes irregular multidimensional time-series data as a sequence of probabilistic prototypes for detecting exceptions from medical test data. Conventional visualization methods often require iterative analysis and considerable skill thus are not totally supported by a wide range of medical experts. Our PrototypeLines displays summarized information based on a probabilistic mixture model by using hue only thus is considered to exhibit novelty. The effectiveness of the summarization is pursued mainly through use of a novel information criterion. We report our endeavor with chronic hepatitis data, especially discoveries of interesting exceptions by a nonexpert and an untrained expert.