Biomedical subjects

Hiroyuki Honda

Publications and source records attributed to Hiroyuki Honda.

At least 55 records · Page 3Linked to original sources

PubMed2004

Industrial application of fuzzy control in bioprocesses.

In a bioprocess, for example a fermentation process, many biological reactions are always working in intracellular space and the control of such a process is very complicated. Bioprocesses have therefore been controlled by the judgment of the experts who are the skilled operators and have much experience in the control of such processes. Such experience is normally described in terms of linguistic IF-THEN rules. Fuzzy inference is a powerful tool for incorporating linguistic rules into computer control of such processes. Fuzzy control is divided into two types--direct fuzzy control of process variables, for example sugar feed rate and fermentation temperature, and indirect control via phase recognition. In bioprocess control the experts decide the value of controllable process variables such as sugar feed rate or temperature as output data from several state variables as input data. Fuzzy control is regarded as a computational algorithm in which the causal relationship between input and output data are incorporated. In Japan fuzzy control has already been applied to practical industrial processes such as production of pravastatin precursor and vitamin B2 and to the Japanese sake mashing process; these examples are reviewed. In addition, an advanced control tool developed from a study on fuzzy control, fuzzy neural networks (FNN), are introduced. FNN can involve complicated causality between input and output data in a network model. FNN have been proven to be applicable to a research in biomedicine, for example modeling of the complicated causality between electroencephalogram or gene expression profiling data and prognostic prediction. Successful results on this research will be also explained.

Algorithms↗

PubMed2004

Application of knowledge information processing methods to biochemical engineering, biomedical and bioinformatics fields.

In biochemical and biomedical engineering fields there are a variety of phenomena with many complex chemical reactions, in which many genes and proteins affect transcription or enzyme activity of others. It is difficult to analyze and estimate many of these phenomena using conventional mathematical models. Recently some knowledge information processing methods, such as the artificial neural network (ANN), fuzzy reasoning, fuzzy neural network (FNN), fuzzy adaptive resonance theory (fuzzy ART) and the genetics algorithm (GA), were developed in the computer science field and have been applied to analysis in a variety of research fields. In this chapter, these methods will be briefly reviewed. Next, the application of these methods in the biochemical field will be introduced, instancing two examples in actual industrial processes. In addition, the application in the biomedical and bioinformatics field as another attractive field will be reviewed. Two examples are our research such as the prediction of prognosis for cancer patients from DNA microarray data using FNN and gene clustering for DNA microarray data using fuzzy ART.

Artificial Intelligence↗

PubMed2004

Large-scale micropropagation system of plant cells.

Plant micropropagation is an efficient method of propagating disease-free, genetically uniform and massive amounts of plants in vitro. The scale-up of the whole process for plant micropropagation should be established by an economically feasible technology for large-scale production of them in appropriate bioreactors. It is necessary to design suitable bioreactor configuration which can provide adequate mixing and mass transfer while minimizing the intensity of shear stress and hydrodynamic pressure. Automatic selection of embryogenic calli and regenerated plantlets using image analysis system should be associated with the system. The aim of this chapter is to identify the problems related to large-scale plant micropropagation via somatic embryogenesis, and to summarize the micropropagation technology and computer-aided image analysis. Viscous additive supplemented culture, which is including the successful results obtained by us for callus regeneration, is also introduced.

Alginates↗

PubMed2004

Prognostic predictor with multiple fuzzy neural models using expression profiles from DNA microarray for metastases of breast cancer.

Gene expression profiling data from DNA microarray were analyzed using the fuzzy neural network (FNN) modeling method for predicting the distant metastases of breast cancer. The best model consisting of five genes was able to predict metastases of breast cancer with 94% accuracy. Furthermore, 100% accuracy was achieved by majoritarian decision using only 25 genes from five noninferior models which were constructed independently. From the constructed model, gene expression rules, which may cause distant metastases, were explicitly extracted and 60% of the metastases cases could be explained by this rule. The FNN modeling method described in this paper enables precise extraction of significant biological markers affecting prognosis without prior knowledge.

Journal Article↗

PubMed2004

A preprocessing method for inferring genetic interaction from gene expression data using Boolean algorithm.

Unknown genetic regulation mechanisms are expected to be discovered by information technology using large amount of biological data especially for gene expression data. In this study, we propose a novel inferring method for genetic interactions that combines our original preprocessing method and the Boolean algorithm. First, the performance of our method was evaluated using artificial data. The results showed that our method was able to infer genetic interactions with high specificity (specificity=0.629). Then, using our method, the genetic interaction was inferred from the experimental time course data collected using microarray on 69 genes of cell cycle for Saccharomyces cerevisiae. Our method estimated about 80% of all genetic interactions in Kyoto Encyclopedia Genes and Genomes (KEGG) for these genes. Furthermore, our method was able to infer several other genetic interactions that are not included in KEGG but whose existence is supported by other biological reports.

Journal Article↗

PubMed2003

Antitumor effects of combined therapy of recombinant heat shock protein 70 and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma.

Heat shock proteins (HSPs) are recognized as significant participants in cancer immunity. We previously reported that HSP70 expression following hyperthermia using magnetic nanoparticles induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by administration of recombinant HSP70 protein into the tumor in situ. Hyperthermia was conducted using our original magnetite cationic liposomes (MCLs), which have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs and recombinant mouse HSP70 (rmHSP70) were injected into melanoma nodules in C57BL/6 mice, which were subjected to AMF for 30 min. Temperature within the tumor reached 43 degrees C and was maintained by controlling the magnetic field intensity. The combined treatment strongly inhibited tumor growth over a 30-day period and complete regression of tumors was observed in 20% (2/10) of mice. It was also found that systemic antitumor immunity was induced in the cured mice. This study suggests that novel combined therapy using exogenous HSP70 and hyperthermia has great potential in cancer treatment.

Animals↗

PubMed2003

Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles.

In this study we demonstrated that heat shock protein (HSP) 70 expression by hyperthermia induced antitumor immunity in the T-9 rat glioma. Our hyperthermic system using magnetic nanoparticles induced necrotic cell death that correlated with HSP70 expression. We purified the HSP70-peptide complexes from the tumor after hyperthermia to investigate whether HSP70 was involved in the antitumor immunity, and we found that in the F344 rats immunized with T-9-derived HSP70 the tumor growth of T-9 was significantly suppressed. Tumor rejection assay after hyperthermic treatment of implanted T-9 cells with incorporated magnetite cationic liposomes (MCL) was performed to investigate whether antitumor immunity was induced by release of HSP70 from the necrotic cells in the F344 rat. Tumor growth was strongly suppressed in the rats subjected to hyperthermia of implanted T-9 cells, and 50% of rats were protected from challenge with T-9 cells. Immunogenicity was enhanced when the HSP70-overexpressing T-9 cells were killed via necrosis in rats by hyperthermia, after which all rats were completely protected from challenge with T-9 cells. Our hyperthermic system produces vaccination with HSP70-peptide via necrotic tumor cell death in vivo, resulting in antitumor immunity. This phenomenon, which may be termed in situ vaccination, has important implications for the development of novel antitumor therapies.

Animals↗

PubMed2003

Analysis of organic solvent tolerance in Escherichia coli using gene expression profiles from DNA microarrays.

To investigate the biological mechanism of organic solvent tolerance (OST), DNA microarrays were used to collect and compare the gene expression profiles of normal and organic solvent-tolerant Escherichia coli strains. First, we compared the tolerant-strain OST3410 to its sensitive parent strain JA300 in the absence of organic solvents. Numerous genes showed higher expression levels in OST3410, and Northern analysis was used to confirm the higher expression level of some genes. Next, the gene expression profiles of JA300 and OST3410 exposed to hexane as an organic solvent were investigated and compared with JA300 before exposure to organic solvent. In OST3410 and JA300, 115 and 47 hexane-induced genes were found, respectively. As candidates for genes related to OST, we focused on six genes: cysD, marA, mg1B, tnaA, tnaB and yihM, which were upregulated by hexane in both strains. When these genes were over-expressed on plasmids, only the marA plasmid increased OST activity. It should be noted that we succeeded in finding a gene related to OST activity using only DNA microarray data, without any biochemical or biological knowledge.

Journal Article↗

PubMed2003

Proliferation and stratification of keratinocyte on cultured amniotic epithelial cells for tissue engineering.

Human amniotic epithelial cells (HAECs) are formed from amnioblasts, separated from the epiblast at about the 8th day after fertilization. Recent studies suggest that HAECs can produce various biologically active substances. In this study, the effects of cultured HAECs on keratinocytes were investigated. First of all, the effect of the medium conditioned by cultured HAECs on the proliferation of keratinocytes was examined. The conditioned medium significantly enhanced the proliferation (P<0.05). Next, the effect of co-culture with HAECs was also examined. The keratinocytes formed a stratified epithelium on day 7 after the start of co-culture. The cultured epithelium formed by the co-culture was five to six layers thick, could be detached by dispase treatment, and had sufficient strength as a sheet. These results suggest that HAECs will be a novel supplemental material for the tissue engineering of skin.

Journal Article↗

PubMed2003

Selection of causal gene sets for lymphoma prognostication from expression profiling and construction of prognostic fuzzy neural network models.

To assess the response of lymphomas to chemotherapy, gene expression profiling data from DNA microarrays were analyzed using the fuzzy neural network (FNN) modeling method. We used the FNN modeling method to produce 10 noninferior models. Using these models, we were able to predict diffuse large B-cell lymphoma (DLBCL) patient outcome with 93% accuracy. Of the 37 genes in the 10 models, 13 genes were repeatedly selected, indicating that these genes are important for prognostication. On Kaplan-Meier plots of overall survival, patients predicted by the FNN model to be cured survived significantly longer than those predicted to be refractory (P<0.0001), indicating that the FNN could successfully identify patients with a relatively poor prognosis among low-clinical-risk patients. The FNN modeling method presented here is able to precisely extract significant biological markers affecting prognosis.

Journal Article↗

PubMed2003

Simple and rapid cell growth assay using tetrazolium violet coloring method for screening of organic solvent tolerant bacteria.

Tolerance to organic solvents is an important characteristic for selecting bacteria that are useful for producing commodity chemicals. An assay method for tolerance should be easy to perform and differences in tolerance should be reproducible. We propose a cell growth assay using tetrazolium violet and image analysis for assessing tolerance. When five microorganisms including Escherichia coli were tested, the organic solvent tolerance (OST) of microorganisms used was rapidly and qualitatively assessed and the degrees of OST coincided with those from the conventional method using solvent overlaid-solid medium. Moreover, the proposed method was applicable to the estimation of OST for cyclohexane resistant E. coli OST3410 using various organic solvent mixtures.

Journal Article↗

PubMed2003

Complete regression of mouse mammary carcinoma with a size greater than 15 mm by frequent repeated hyperthermia using magnetite nanoparticles.

Magnetite cationic liposomes (MCLs) have a positive surface charge and are used as a heating mediator for hyperthermia, because they generate heat in an alternating magnetic field (AMF) due to hysteresis loss. In our previous paper, hyperthermia using MCLs was applied to animals having several types of tumors in mice, rats, hamsters, and rabbits, and a strong anticancer effect was observed. For mice, complete tumor regression was observed when the tumor size was smaller than 5 mm. However, a protocol for large tumors is necessary for the clinical application. In the present paper, a protocol for tumors with a size greater than 15 mm in mice was investigated. MCLs were injected into an MM46 tumor (size, 15 mm) in C3H/HeN mice, which were subjected to AMF for 30 min. The temperature at the surface of the tumor reached 45 degrees C and was maintained by controlling the magnetic field intensity. Hyperthermia treatment was repeated twice with 24-h intervals (repeated hyperthermia; RH), and RH was carried out until complete tumor regression was observed. Complete tumor regression was achieved in all mice treated once, twice or six times with RH, and mice acquired antitumor immunity. This protocol, which is termed frequent RH, is a potent approach for cancer therapy.

Journal Article↗

PubMed2003

Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles.

Heat shock proteins (HSPs) are recognized as significant participants in immune reactions. We previously reported that expression of HSP70 in response to hyperthermia, produced using our original magnetite cationic liposomes (MCLs), induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by hsp70 gene transfer. A human hsp70 gene mediated by cationic liposomes was injected into a B16 melanoma nodule in C57BL/6 mice in situ. At 24 hours after the injection of the hsp70 gene, MCLs were injected into melanoma nodules in C57BL/6 mice, which were subjected to an alternating magnetic field for 30 minutes. The temperature at the tumor reached 43 degrees C and was maintained by controlling the magnetic field intensity. The combined treatment strongly arrested tumor growth over a 30-day period, and complete regression of tumors was observed in 30% (3/10) of mice. Systemic antitumor immunity was induced in the cured mice. This study demonstrates that this novel therapeutic strategy combining the use of hsp70 gene therapy and hyperthermia using MCLs may be applicable to patients with advanced malignancies.

Animals↗

PubMed2003

Anticancer effect and immune induction by hyperthermia of malignant melanoma using magnetite cationic liposomes.

The hyperthermic effect of magnetic particles was examined in an in vivo study of mouse B16 melanoma. Magnetite cationic liposomes (MCLs) have a positive surface charge and generate heat under an alternating magnetic field (AMF) by hysteresis loss. MCLs were injected into melanoma nodules, which were then subjected to an AMF. The mice were divided into four groups: group I (control), group II (hyperthermia at 43 degrees C for 30 min, once), group III (hyperthermia at 46 degrees C for 30 min, once) and group IV (hyperthermia at 46 degrees C for 30 min, twice). Complete tumour regression was observed in 90% of the mice in group IV, while no mice in groups I and II and only 40% in group III showed regression. To examine whether hyperthermia caused immune induction in B16 melanoma, in vitro cytotoxicity assays and rechallenge experiments were performed. Cytotoxic activity was observed in the spleen cells of the cured mice in group IV. In the rechallenge experiment, 66% of the cured mice rejected melanoma cells. These results suggest that hyperthermia using MCLs is an effective therapy for melanoma, since this treatment can kill the tumour cells not only by heat but also by inducing an immune response.

Animals↗

PubMed2003

Multiple fuzzy neural network system for outcome prediction and classification of 220 lymphoma patients on the basis of molecular profiling.

A fuzzy neural network (FNN) using gene expression profile data can select combinations of genes from thousands of genes, and is applicable to predict outcome for cancer patients after chemotherapy. However, wide clinical heterogeneity reduces the accuracy of prediction. To overcome this problem, we have proposed an FNN system based on majoritarian decision using multiple noninferior models. We used transcriptional profiling data, which were obtained from "Lymphochip" DNA microarrays (http://llmpp.nih.gov/DLBCL), reported by Rosenwald (N Engl J Med 2002; 346: 1937-47). When the data were analyzed by our FNN system, accuracy (73.4%) of outcome prediction using only 1 FNN model with 4 genes was higher than that (68.5%) of the Cox model using 17 genes. Higher accuracy (91%) was obtained when an FNN system with 9 noninferior models, consisting of 35 independent genes, was used. The genes selected by the system included genes that are informative in the prognosis of Diffuse large B-cell lymphoma (DLBCL), such as genes showing an expression pattern similar to that of CD10 and BCL-6 or similar to that of IRF-4 and BCL-4. We classified 220 DLBCL patients into 5 groups using the prediction results of 9 FNN models. These groups may correspond to DLBCL subtypes. In group A containing half of the 220 patients, patients with poor outcome were found to satisfy 2 rules, i.e., high expression of MAX dimerization with high expression of unknown A (LC_26146), or high expression of MAX dimerization with low expression of unknown B (LC_33144). The present paper is the first to describe the multiple noninferior FNN modeling system. This system is a powerful tool for predicting outcome and classifying patients, and is applicable to other heterogeneous diseases.

Cluster Analysis↗

PubMed2003

Tumor regression by combined immunotherapy and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma.

Immunotherapy (IT) has become an accepted therapeutic modality. We previously reported that intracellular hyperthermia (IH) using magnetic nanoparticles induces antitumor immunity. We undertook these studies in order to study the combined effects of IT and IH on melanoma. Magnetite cationic liposomes (MCLs) have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs were injected into a B16 melanoma nodule in C57BL/6 mice, which were subjected to AMF for 30 min. The temperature at the tumor reached 43 degrees C and was maintained by controlling the magnetic field intensity. At 24 h after IH, interleukin-2 (IL-2) or granulocyte macrophage-colony stimulating factor (GM-CSF) was injected directly into the melanoma. Mice were divided into six groups: group I (control), group II (IH), group III (IL-2), group IV (GM-CSF), group V (IH + IL-2), and group VI (IH + GM-CSF). Complete regression of tumors was observed in mice of groups V and VI (75% (6/8) and 40% (4/10) of the mice, respectively), while no tumor regression was observed in mice of the other groups. This study supports the combined use of IT and IH using MCLs in patients with advanced malignancies.

Animals↗

PubMed2003

Prognostic models in patients with non-small-cell lung cancer using artificial neural networks in comparison with logistic regression.

It is difficult to precisely predict the outcome of each individual patient with non-small-cell lung cancer (NSCLC) by using conventional statistical methods and ordinary clinico-pathological variables. We applied artificial neural networks (ANN) for this purpose. We constructed a prognostic model for 125 NSCLC patients with 17 potential input variables, including 12 clinico-pathological variables (age, sex, smoking index, tumor size, p factor, pT, pN, stage, histology) and 5 immunohistochemical variables (p27 percentage, p27 intensity, p53, cyclin D1, retinoblastoma (RB)), by using the parameter-increasing method (PIM). Using the resultant ANN model, prediction was possible in 104 of 125 patients (83%, judgment ratio (JR)) and accuracy for prediction of survival at 5 years was 87%. On the other hand, JR and survival prediction accuracy in the logistic regression (LR) model were 37% and 78%, respectively. In addition, ANN outperformed LR for prediction of survival at 1 or 3 years. In these cases, PIM selected p27 intensity and cyclin D1 for the 3-year survival model and p53 for the 1-year survival model in addition to clinico-pathological variables. Finally, even in an independent validation data set of 48 patients, who underwent surgery 10 years later, the present ANN model could predict outcome of patients at 5 years with the JR and accuracy of 81% and 77%, respectively. This study demonstrates that ANN is a potentially more useful tool than conventional statistical methods for predicting survival of patients with NSCLC and that inclusion of relevant molecular markers as input variables enhances its predictive ability.

Adenocarcinoma↗

PubMed2003

Screening of stress enhancer based on analysis of gene expression profiles: enhancement of hyperthermia-induced tumor necrosis by an MMP-3 inhibitor.

To improve the therapeutic benefit of hyperthermia, we examined changes of global gene expression after heat shock using DNA microarrays consisting of 12 814 clones. HeLa cells were treated for 1 h at 44 degrees C and RNA was extracted from the cells 0, 3, 6, and 12 h after heat shock. The 664 genes that were up or down-regulated after heat shock were classified into 7 clusters using fuzzy adaptive resonance theory (fuzzy ART). There were 41 genes in two clusters that were induced in the early phase after heat shock. In addition to shock response genes, such as hsp70 and hsp40, the stress response genes c-jun, c-fos and egr-1 were expressed in the early phase after heat shock. We also found that expression of matrix metalloproteinase 3 (MMP-3) was enhanced during the early response. We therefore investigated the role of MMP-3 in the heat shock response by examining HeLa cell survival after heat treatment in the presence and absence of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)glycylhydroxamic acid (NNGH) or N-hydroxy-2(R)-[[4- methoxysulfonyl](3-picolyl)amino]-3-methylbutaneamide hydrochloride (MMI270). The number of surviving cells 3 days after heat treatment significantly decreased, reaching 3.5% for NNGH and 0.2% for MMI270. These results indicate that the MMP-3 inhibitors enhanced heat shock-induced cell death and behaved as stress enhancers in cancer cells. This valuable conclusion was reached as a direct result of the gene expression profiling that was performed in these studies.

Cell Survival↗