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Biomedical subjects

S Imoto

Publications and source records attributed to S Imoto.

At least 19 recordsLinked to original sources

Primary tumour-vessel tumour-nodal tumour classification for patients with invasive ductal carcinoma of the breast.

There are many studies that show biological differences between invasive ductal carcinoma (IDC) with and without nodal metastasis, but no prognostic classification taking into consideration any biological differences between them is currently available. We previously investigated the histological characteristics that play an important role in tumour progression of IDCs according to their nodal status, and a new prognostic histological classification, the primary tumour-vessel tumour-nodal tumour (PVN) classification, was devised based on the histological characteristics of IDCs with and without nodal metastasis. Multivariate analyses using the Cox proportional hazard regression models were used to compare the ability of the PVN classification to predict tumour recurrence and death in 393 IDC patients based on the following histological classifications: (1) the pTNM classification, (2) the Nottingham Prognostic Index, (3) the modified Nottingham Prognostic Index, and (4) the histologic grade. In IDCs without nodal metastasis, only the PVN classification significantly increased the hazard rates (HRs) of tumour recurrence and death (P<0.05), independent of the hormone receptor status. Similarly, in IDCs with nodal metastases, only the PVN classification significantly increased the HRs of tumour recurrence and death (P<0.05), independent of the hormone receptor status. We conclude that the PVN prognostic histological classification is the best classification available for IDC of the breast.

Breast Neoplasms↗

Predicting gene regulation by sigma factors in Bacillus subtilis from genome-wide data.

MOTIVATION: Sigma factors regulate the expression of genes in Bacillus subtilis at the transcriptional level. We assess the accuracy of a fold-change analysis, Bayesian networks, dynamic models and supervised learning based on coregulation in predicting gene regulation by sigma factors from gene expression data. To improve the prediction accuracy, we combine sequence information with expression data by adding their log-likelihood scores and by using a logistic regression model. We use the resulting score function to discover currently unknown gene regulations by sigma factors. RESULTS: The coregulation-based supervised learning method gave the most accurate prediction of sigma factors from expression data. We found that the logistic regression model effectively combines expression data with sequence information. In a genome-wide search, highly significant logistic regression scores were found for several genes whose transcriptional regulation is currently unknown. We provide the corresponding RNA polymerase binding sites to enable a straightforward experimental verification of these predictions.

Algorithms↗

Open source clustering software.

SUMMARY: We have implemented k-means clustering, hierarchical clustering and self-organizing maps in a single multipurpose open-source library of C routines, callable from other C and C++ programs. Using this library, we have created an improved version of Michael Eisen's well-known Cluster program for Windows, Mac OS X and Linux/Unix. In addition, we generated a Python and a Perl interface to the C Clustering Library, thereby combining the flexibility of a scripting language with the speed of C. AVAILABILITY: The C Clustering Library and the corresponding Python C extension module Pycluster were released under the Python License, while the Perl module Algorithm::Cluster was released under the Artistic License. The GUI code Cluster 3.0 for Windows, Macintosh and Linux/Unix, as well as the corresponding command-line program, were released under the same license as the original Cluster code. The complete source code is available at http://bonsai.ims.u-tokyo.ac.jp/mdehoon/software/cluster. Alternatively, Algorithm::Cluster can be downloaded from CPAN, while Pycluster is also available as part of the Biopython distribution.

Algorithms↗

Predicting the operon structure of Bacillus subtilis using operon length, intergene distance, and gene expression information.

We predict the operon structure of the Bacillus subtilis genome using the average operon length, the distance between genes in base pairs, and the similarity in gene expression measured in time course and gene disruptant experiments. By expressing the operon prediction for each method as a Bayesian probability, we are able to combine the four prediction methods into a Bayesian classifier in a statistically rigorous manner. The discriminant value for the Bayesian classifier can be chosen by considering the associated cost of misclassifying an operon or a non-operon gene pair. For equal costs, an overall accuracy of 88.7% was found in a leave-one-out analysis for the joint Bayesian classifier, whereas the individual information sources yielded accuracies of 58.1%, 83.1%, 77.3%, and 71.8% respectively. The predicted operon structure based on the joint Bayesian classifier is available from the DBTBS database (http://dbtbs.hgc.jp).

Bacillus subtilis↗

Using protein-protein interactions for refining gene networks estimated from microarray data by Bayesian networks.

We propose a statistical method to estimate gene networks from DNA microarray data and protein-protein interactions. Because physical interactions between proteins or multiprotein complexes are likely to regulate biological processes, using only mRNA expression data is not sufficient for estimating a gene network accurately. Our method adds knowledge about protein-protein interactions to the estimation method of gene networks under a Bayesian statistical framework. In the estimated gene network, a protein complex is modeled as a virtual node based on principal component analysis. We show the effectiveness of the proposed method through the analysis of Saccharomyces cerevisiae cell cycle data. The proposed method improves the accuracy of the estimated gene networks, and successfully identifies some biological facts.

Algorithms↗

Finding optimal models for small gene networks.

Finding gene networks from microarray data has been one focus of research in recent years. Given search spaces of super-exponential size, researchers have been applying heuristic approaches like greedy algorithms or simulated annealing to infer such networks. However, the accuracy of heuristics is uncertain, which--in combination with the high measurement noise of microarrays--makes it very difficult to draw conclusions from networks estimated by heuristics. We present a method that finds optimal Bayesian networks of considerable size and show first results of the application to yeast data. Having removed the uncertainty due to the heuristic methods, it becomes possible to evaluate the power of different statistical models to find biologically accurate networks.

Algorithms↗

Sentinel node biopsy for breast cancer patients in Japan.

Sentinel node biopsy may become a standard procedure to detect lymph node metastases in early breast cancer. Numerous studies have confirmed and demonstrated the reliability of the hypothesis of sentinel node biopsy, with a high identification rate and overall accuracy connected with dye-guided and radio-guided sentinel node biopsy. To assess the benefit of sentinel node biopsy, randomized clinical trials are underway in Western countries comparing sentinel node biopsy with conventional axillary lymph node dissection. In Japan, feasibility studies on sentinel node biopsy started in the mid-1990s. The dye and radiopharmaceuticals associated with sentinel node biopsy commonly used in Western countries are not available in Japan. Japanese investigators have attempted to perform sentinel node biopsy using other dyes and radiopharmaceuticals. The results from feasibility studies have been similar to those reported previously. In conclusion, sentinel node biopsy for breast cancer patients is successful in Japan. The current status and the problems are discussed.

Breast Neoplasms↗

Usefulness of automatic detection of fragmented red cells using a hematology analyzer for diagnosis of thrombotic microangiopathy.

We previously reported an automatic method for quantitative analysis of schistocytes or fragmented red cells using an automatic hematology analyzer, XE-2100. In the study reported here, we evaluated the accuracy of this detection method in patients with thrombotic microangiopathy (TMA). A follow-up study was performed on 14 patients with two types of TMA, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. Schistocyte percent was evaluated both with an automatic counter and by means of microscopic observation. Total activity and isoenzyme pattern of lactate dehydrogenase (LD) were also determined. In these patients, schistocyte percent determined by automatic counting correlated highly with that determined by manual counting under microscopic observation (r = 0.852, P < 0.0001). Schistocyte percent was shown to correlate significantly with isoenzyme fractions 1 and 2 of LD (r = 0.732, P < 0.02), reflecting hemolysis. Nine of 11 patients tested had high concentrations of LD isoenzyme five without distinct liver damage, and schistocyte percent did not relate to fraction 5 of LD. Automatic detection of schistocyte percent using a hematology analyzer was useful for an accurate diagnosis and follow-up of thrombotic microangiopathy. The origin of LD fraction 5 remains to be determined.

Adult↗

Statistical analysis of a small set of time-ordered gene expression data using linear splines.

MOTIVATION: Recently, the temporal response of genes to changes in their environment has been investigated using cDNA microarray technology by measuring the gene expression levels at a small number of time points. Conventional techniques for time series analysis are not suitable for such a short series of time-ordered data. The analysis of gene expression data has therefore usually been limited to a fold-change analysis, instead of a systematic statistical approach. METHODS: We use the maximum likelihood method together with Akaike's Information Criterion to fit linear splines to a small set of time-ordered gene expression data in order to infer statistically meaningful information from the measurements. The significance of measured gene expression data is assessed using Student's t-test. RESULTS: Previous gene expression measurements of the cyanobacterium Synechocystis sp. PCC6803 were reanalyzed using linear splines. The temporal response was identified of many genes that had been missed by a fold-change analysis. Based on our statistical analysis, we found that about four gene expression measurements or more are needed at each time point.

Algorithms↗

T-cell receptor gammadelta T-cell leukemia with the morphology of T-cell prolymphocytic leukemia and a postthymic immunophenotype.

T-cell prolymphocytic leukemia (T-PLL) is a postthymic T-cell neoplasm with a characteristic morphology and heterogeneous immunophenotype. Most cases of T-PLL express membrane T-cell receptors (TCRs) of the alphabeta phenotype. We experienced a 30-year-old man suffering from TCRgammadelta T-cell leukemia with morphology compatible to T-PLL with a postthymic phenotype. He was admitted with skin eruption and pancytopenia. Peripheral blood and bone marrow were occupied with medium-sized lymphocytes, which had moderately condensed chromatin with a single nucleolus and sparse, nongranular basophilic cytoplasm. The immunophenotype was CD1a-, CD2-, CD3+, CD4-, CD5+, CD7+, CD8-, and terminal deoxynucleotidyl transferase negative. Hepatosplenomegaly was absent. He was diagnosed as having T-PLL and was treated with combination chemotherapy. Six months later the leukemic cell became chemoresistant. Although the patient showed transient improvement in response to pentostatin, he died 13 months after the diagnosis. To our knowledge, this is the first case of T-PLL with a TCRgammadelta phenotype.

Adult↗

Reactivation of latently infected hepatitis B virus in a leukemia patient with antibodies to hepatitis B core antigen.

A 66-year-old man with chronic B-cell leukemia who had antibody to hepatitis B core antigen (anti-HBc) but not hepatitis B surface antigen (HBsAg) suffered from lethal hepatitis caused by hepatitis B virus (HBV) reactivation. He initially lacked circulating viral genomes in his sera and did not have a past history of liver dysfunction. In this patient, the immunosuppressive condition introduced by disease progression of leukemia induced reactivation of dormant HBV, and the withdrawal of chemotherapy resulted in fatal liver failure. Mutation-specific assay based on competitive polymerase chain reaction (PCR) and sequencing analyses revealed the predominant reactivation of an HBV strain with missence mutation (point mutation G-to-A at nucleotide 1896) in the precore regions, as well as point mutations in the core promoter regions. Therefore, it is important to note the risk of HBV reactivation, with resulting lethal hepatic failure, in anti-HBc-positive healthy individuals, even when they lack HBsAg. who receive immunomodulating therapy.

Aged↗

A case of disseminated extrahepatic hepatocellular carcinoma after US-guided biopsy and percutaneous ethanol injection therapy.

A case of disseminated extrahepatic hepatocellular carcinoma (HCC) occurring after ultrasound (US)-guided biopsy and percutaneous ethanol injection therapy is presented. A 72-year-old man with hepatitis-C-virus-related cirrhosis underwent percutanous ethanol injection therapy (PEIT) two times with complete remission: the first for moderately-differentiated HCC in segment six (S6), and the second for well-differentiated HCC in another part of S6. Imaging studies including carbon dioxide (CO(2))-US angiography, incremental computed tomography, and dynamic magnet resonance imaging showed that both HCCs were hypovascular. Twenty-one months after the first PEIT and 7 months after the second, a 5.5x4.5 cm extrahepatic mass interfaced with S6 of the liver was detected by imaging studies. The patient underwent surgery for extrahepatic HCC. Grossly, the main tumor was 5.5x4.5 cm with capsule and septum; the disseminated tumors were detected on the surface of the liver, including the right diaphragm and the falx ligamentosa. Histologically, it was moderately- to poorly-differentiated HCC, which, although not attributed to direct track seeding, was suspected of being induced by the percutaneous US-guided biopsy procedure or by PEIT, irrespective of a hypovascular tumor. Further studies may provide insight into the risk factor engendered by these procedures.

Journal Article↗

Biomedical and psychosocial determinants of psychiatric morbidity among postoperative ambulatory breast cancer patients.

There has been much interest in the psychosocial issues faced by breast cancer patients because of the high prevalence of the disease and the severe psychological impact of the cancer itself, as well as its treatment. The objective of our study was to investigate the determinants of psychiatric morbidity among postoperative ambulatory breast cancer patients. The variables examined included the patients' biomedical characteristics, demographic characteristics, current concerns, coping responses and social support factors. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the Mental Adjustment to Cancer scale (MAC scale), and information pertaining to demographic variables, current concerns and social support factors was obtained by a specially designed questionnaire. Available data were obtained from 148 randomly selected postoperative ambulatory breast cancer patients. The prevalence of psychiatric morbidity (including clinical anxiety and depression) evaluated by using the HADS cut-off point was 23%. The results of univariate analyses indicated that pain, dyspnea, having children with health problems, various other concerns (about children, other family members, the patients' own health and future treatment) and poor coping responses (low fighting spirit, high anxious preoccupation, high fatalism and high helplessness/hopelessness) were significant determinants of the patients' psychiatric morbidity. Additionally, in the logistic regression analysis, having children with health problems and having a low fighting spirit and a high helplessness/hopelessness were final significant determinants. Postoperative ambulatory breast cancer patients with these problems should be given careful attention, and psychosocial intervention may be beneficial for them.

Adaptation, Psychological↗

Highly proliferative fibroblasts forming fibrotic focus govern metastasis of invasive ductal carcinoma of the breast.

We have already reported that invasive ductal carcinomas (IDCs) with fibrotic focus (FF) have more aggressive characteristics than those without FF. FF is composed of a mixture of fibroblasts and various amounts of collagen fibers, suggesting that highly proliferative fibroblasts forming FF increase the malignant potential of IDCs with FF. The purpose of this study was to examine whether there is a difference of proliferative activity of fibroblasts forming and not forming FF, which plays an important role in the tumor progression of IDCS: Two hundred three consecutive cases of IDC of the breast surgically treated at the National Cancer Center Hospital East formed the basis for this study. The proliferative activity of the fibroblasts forming the FF was immunohistochemically evaluated by using mouse MIB-1 monoclonal antibody against Ki-67 antigen. The MIB-1 labeling index (LI) is the percentage of fibroblasts forming FF that have positively stained nuclei, and 300 fibroblasts were counted in each FF. The significance of the proliferative activity of fibroblasts forming FF with regard to lymph node metastasis (LNM) or distant-organ metastasis (DOM) was compared with well-known prognostic parameters. Multivariate analysis demonstrated that high MIB-1 LI of fibroblasts forming FF significantly increased the relative risk of LNM and the hazard rate of DOM (P < .001 and P = .009). The present study indicated that the metastatic ability of IDCs with FF is highly dependent on the proliferative activity of the fibroblasts forming FF.

Adult↗

Kinetic analysis of cytokine gene expression in patients with GVHD after donor lymphocyte infusion.

Patients who receive a donor lymphocyte infusion (DLI) for the treatment of relapsed leukemia after allogeneic BMT (alloBMT) often developed GVHD. To determine whether cytokines might have a role in GVHD, an intensive kinetic analysis of in vivo cytokine gene expression was performed on PBMC from three such patients. Expression of IL-1beta, IL-2, IFN-gamma, IL-4, IL-5, IL-8, IL-10, IL-12, TNF-alpha, and IL-2Ralpha was examined using a sensitive semi-quantitative reverse transcription (RT)-PCR assay system. Six normal controls were also analyzed for comparison. Expression of type 1 T helper (Th1) cytokines, IL-2 and IFN-gamma was greatly increased in all three patients. In particular, the changes in IL-2 gene expression correlated well with disease progression, suggesting that IL-2 has a critical role in the development of GVHD. Although the pattern of type 2 T helper (Th2) cytokine gene expression differed in each patient, the expression of IL-4 was inversely related to expression of Th1 cytokines. These results suggest that Th1 dominates in the development of human clinical GVHD.

Adult↗

Effects of bisphosphonate on the remodeling of rat sagittal suture after rapid expansion.

The purpose of this study was to investigate the effects of bisphosphonate (BP), an inhibitor of bone resorption, on the remodeling of the rat sagittal suture after rapid expansion. Wistar strain male rats were divided into 4 groups and subjected to rapid mechanical expansion with an initial force of 60 g for 3 days. Immediately after the sutural expansion, the appliance was removed in 2 of the groups. In the S group, half of the animals were injected with saline solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. In the B group, half of the animals were injected with bisphosphonate daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. The remaining 2 groups underwent 7 days of mechanical retention before the appliance was removed. In the SR group, half of the animals were injected with saline solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. In the BR group, half of the animals were injected with bisphosphonate solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. The calvariae were fixed in 4% neutral formalin, decalcified, and embedded in paraffin. The amount of relapse and the relevant bone remodeling were evaluated in terms of a relapse ratio and the number of osteoclasts. The relapse ratio was 54.11% in the S group and 32.53% in the B group 7 days after the injection. This ratio was 25.13% in the SR group and 9.60% in the BR group. The number of osteoclasts 3 days after injection was 15.47 in the S group, which was significantly greater than the 5.26 present in the B group. This number was 7.08 in the SR group, which was significantly greater than the 1.83 in the BR group. These results demonstrate that the injection of BP after rapid expansion, if combined with mechanical retention, may produce more secure retention by inhibiting bone resorption, indicating a possibility of employing a pharmaceutical aid to decrease the skeletal relapse after mechanotherapy in clinical orthodontics.

Acid Phosphatase↗

Quantification of red blood cell fragmentation by automated haematology analyser XE-2100.

The extent of red blood cell fragmentation in peripheral blood is useful for diagnosis and follow-up in many diseases, e.g. haemolytic uremic syndrome, transplantation-associated thrombotic microangiopathy (BMT-TMA). However, this quantification still relies on manual counting of fragmented red cells on blood smears. We have developed a quantification system by gating a fixed area of fragmented red blood cells (Gate 1) on an automated haematology analyser (XE-2100, Sysmex Co., Kobe, Japan). The fragmented red cell percentage (FRC%) calculated with this system, from 100 samples, was highly correlated with the manual count (r=0.902, P < 0.0001). Because microcytic anaemia specimens usually occupy a lower position on the XE-2100 scattergram, with microcytic cells overlapping Gate 1 and causing a spuriously high FRC% calculation, a supplementary gate (Gate 2) was added. Using the particle number in this gate as well as in Gate 1, a revised method for such samples was developed and its validity confirmed (revised FRC% correlated with a manual count for 10 subjects (P < 0.001). Because this gating system can be programmed on any XE-2100, it is likely to prove useful for accurate quantification of red blood cell fragmentation and for the monitoring of the development of BMT-TMA.

Anemia, Iron-Deficiency↗