Biomedical subjects

Osamu Maruyama

Publications and source records attributed to Osamu Maruyama.

13 recordsLinked to original sources

PubMed2025

CDACHIE: chromatin domain annotation by integrating chromatin interaction and epigenomic data with contrastive learning.

MOTIVATION: Chromatin domain annotation identifies functional genomic regions, such as active and inactive zones, based on epigenomic features like histone modifications, DNA methylation, and chromatin accessibility. While recent methods have utilized both chromatin interaction data (e.g. Hi-C) and epigenomic data, they often overlook the direct relationship between these data types. RESULTS: In this study, we introduce Chromatin Domain Annotation using Contrastive Learning for Hi-C and Epigenomic Data (CDACHIE), a method for identifying chromatin domains from Hi-C and epigenomic data. Our approach leverages contrastive learning to generate aligned representative vectors for both data types at each genomic bin. The concatenated vectors are then clustered using K-means to classify distinct chromatin domain types. CDACHIE achieves superior performance in Variance Explained, evaluated across gene expression, replication timing, and ChIA-PET data. This highlights its robust ability to integrate semantic associations between Hi-C and epigenomic features within the embedding space. AVAILABILITY AND IMPLEMENTATION: The source code is available at GitHub: https://github.com/maruyama-lab-design/CDACHIE. An archival snapshot of the code used in this study is available on Zenodo: https://doi.org/10.5281/zenodo.15751780.

Chromatin↗

PubMed2006

Naftopidil monotherapy vs naftopidil and an anticholinergic agent combined therapy for storage symptoms associated with benign prostatic hyperplasia: A prospective randomized controlled study.

AIM: The aim of this study was to compare the efficacy and safety of alpha1-adrenoceptor (alpha1-AR) antagonist monotherapy with combination therapy using alpha1-AR antagonist and anticholinergic agent for benign prostatic hyperplasia (BPH) with storage symptoms as the chief complaint. METHODS: In this prospective comparative study, either 25-75 mg/day of naftopidil monotherapy (monotherapy group) or combination therapy using 25-75 mg/day of naftopidil and an anticholinergic agent (10-20 mg/day of propiverine hydrochloride or 2-6 mg/day of oxybutynin hydrochloride; cotherapy group) were administered for 12 weeks to 101 BPH patients with storage symptoms. RESULTS: International prostate symptom score (IPSS) and quality of life (QOL) index improved significantly in both groups, with no marked differences between groups. Maximum flow rate (Qmax) and residual urine volume (RUV) tended to improve in both groups, again with no marked differences between groups. However, median post-therapeutic RUV was significantly worse for the cotherapy group (45.0 mL) than for the monotherapy group (13.5 mL; P = 0.0210). Ratio of patients with increased RUV was also significantly worse for cotherapy (22.9%) than for monotherapy (5.0%; P = 0.038). CONCLUSIONS: Although the anticholinergic dosage was low, the present results suggest that naftopidil monotherapy was as useful as combination therapy of naftopidil and an anticholinergic agent. Therefore, naftopidil is a useful agent as the first choice in BPH patients with storage symptoms.

Adrenergic alpha-Antagonists↗

PubMed2006

The pivot wash in two impeller modes for the Baylor/Miwatec centrifugal blood pump.

A centrifugal blood pump with a double pivot impeller and an eccentric inlet port is being developed as an implantable artificial heart by the Baylor College of Medicine and Miwatec Co. Ltd. Flow visualization measurements were conducted to compare the flow around the pivot for two impeller operational modes: the top and the bottom contact modes. In the top contact mode, one-way flow in the pivot gap due to the eccentric vortex was observed, and sufficient wall shear rate to prevent thrombus formation was attained around the bottom pivot for over 1,400 rpm. Computational fluid dynamic analyses confirmed that the causes of the eccentric vortex were the inlet eccentricity and the pressure imbalance in the volute.

Assisted Circulation↗

PubMed2006

Hemolysis resulting from surface roughness under shear flow conditions using a rotational shear stressor.

The degree of hemolysis as a function of surface roughness value and roughened area under shear flow conditions was investigated using a rotational shear stressor. The shearing portion of the stressor is cone shaped in its upper and lower positions, with a cylindrical central section. Surface roughness was applied to the cylindrical section. Bovine blood was sheared for 30 min over a set of roughened surfaces of between arithmetic mean roughness (Ra) 0.1 and 0.8 mm covering 10% of the surface area of the cylindrical section (equivalent to 1.8% of the whole blood contact area) at a shear rate of 3750/s. The threshold value thus obtained for rapid increase in hemolysis was between Ra 0.6 and 0.8 mm. When sheared with a roughened surface of Ra 0.8 mm applied to the cylindrical surface at areas between 0 and 100% (equivalent to between 0 and 18% of the whole blood-contacting area), the hemolysis level did not increase from 10 to 100%, but a significant difference was obtained between 0 and 10%. This suggests that red blood cells were destroyed not by fatigue failure caused by rolling on the roughened surface, but due to the high shear stress generated by surface roughness. Moreover, it appears that the shear stress was generated over the entire cylindrical section, regardless of the area of surface roughness.

Animals↗

PubMed2005

Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells.

BACKGROUND: Transforming growth factor beta (TGF-beta) facilitates metastasis during the advanced stages of cancer. Smad6, Smad7, and c-Ski block signaling by the TGF-beta superfamily proteins through different modes of action. We used adenovirus-mediated gene transfer of these natural inhibitors in a mouse model of breast cancer to examine the roles of TGF-beta superfamily signaling in tumor growth and metastasis. METHODS: We systemically administered, by intravenous injection, adenoviruses (AdCMV) containing the mouse cDNAs for Smad7, Smad6, c-Ski, the c-Ski mutant c-Ski (ARPG), or LacZ (control) to nude mice (>19 mice/group) bearing tumors derived from mouse mammary carcinoma JygMC(A) cells, which spontaneously metastasize to lung and liver, and examined their effects on survival and metastasis. High-throughput western blotting analysis was used to examine the expression levels for 47 signal transduction proteins in JygMC(A) cells and primary tumors. We also investigated the proliferation, migration, and invasion of JygMC(A) cells that stably overexpressed Smad6 or Smad7. Nonparametric comparisons were done by Kruskal-Wallis H statistic and Wilcoxon's rank sum tests. Parametric comparisons were done by one-way analysis of variance or two-sided unpaired Student's t tests. All statistical tests were two-sided. RESULTS: Control mice bearing tumors derived from JygMC(A) cells showed many metastases to the lung and liver; all animals died by 50 days after cell inoculation. By contrast, mice treated with AdCMV-Smad7 or AdCMV-c-Ski demonstrated a dramatic decrease in metastasis and statistically significantly longer survival than control mice (Smad7 versus LacZ: medium survival = 55 days versus 41 days, difference = 14 days [95% confidence interval {CI} = 6 days to 22 days], P < .001), whereas mice treated with AdCMV-Smad6 or AdCMV-c-Ski (ARPG) did not. Expression of Smad7 in JygMC(A) cells was associated with increased expression of major components of adherens and tight junctions, including E-cadherin, decreased expression of N-cadherin, and decreases in the migratory and invasive abilities of the JygMC(A) cells. CONCLUSION: Smad7 inhibits metastasis, possibly by regulating cell-cell adhesion. Systemic expression of Smad7 may be a novel strategy for the prevention of metastasis of advanced cancers.

Adenoviridae↗

PubMed2005

Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marker for renal cell carcinoma and potential target for molecular therapy.

To identify molecules to serve as diagnostic markers for renal cell carcinoma (RCC) and as targets for novel therapeutic drugs, we investigated genome-wide expression profiles of RCCs using a cDNA microarray. We subsequently confirmed that hypoxia-inducible protein-2 (HIG2) was expressed exclusively in RCCs and fetal kidney. Induction of HIG2 cDNA into COS7 cells led to secretion of the gene product into culture medium and resulted in enhancement of cell growth. Small interfering RNA effectively inhibited expression of HIG2 in human RCC cells that endogenously expressed high levels of the protein and significantly suppressed cell growth. Moreover, addition of polyclonal anti-HIG2 antibody into culture medium induced apoptosis in RCC-derived cell lines. By binding to an extracellular domain of frizzled homologue 10 (FZD10), HIG2 protein enhanced oncogenic Wnt signaling and its own transcription, suggesting that this product is likely to function as an autocrine growth factor. ELISA analysis of clinical samples identified secretion of HIG2 protein into the plasma of RCC patients even at an early stage of tumor development, whereas it was detected at significantly lower levels in healthy volunteers or patients with chronic glomerulonephritis. The combined evidence suggests that this molecule represents a promising candidate for development of molecular-targeting therapy and could serve as a prominent diagnostic tumor marker for patients with renal carcinomas.

Animals↗

PubMed2005

Hemolysis caused by surface roughness under shear flow.

In this study, the relationship between the degree of roughness of blood contact surfaces under laminar shear flow conditions and the level of hemolysis resulting from this roughness was investigated using a rotational shear stressor. Unlike previous in vitro experiments that used a pumped circuit, the level of hemolysis was directly evaluated under a constant shear flow. In total, 1.8% of the blood contact area was roughened to an arithmetic mean roughness (Ra) value of between 0.4 and 9.2 microm by machine processing and a shear load was applied for 30 min at a shear flow rate of 3750 s(-1). As a result, the threshold Ra value for the induction of hemolysis was found to be between 0.4 and 0.8 microm. In addition, the results of this experiment suggested that the high shear stress resulting from surface roughness plays a major role in determining the level of hemolysis caused by surface roughness.

Animals↗

PubMed2005

Four pregnancies in nonmosaic Klinefelter's syndrome using cryopreserved-thawed testicular spermatozoa.

OBJECTIVE: To investigate feasibility of using cryopreserved-thawed testicular spermatozoa from patients with nonmosaic Klinefelter's syndrome for intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: University-based hospital and IVF clinic. PATIENT(S): Six patients with nonmosaic Klinefelter's syndrome who underwent testicular sperm extraction for ICSI. INTERVENTION(S): Microdissection testicular sperm extraction (TESE) and ICSI. MAIN OUTCOME MEASURE(S): We compared results of ICSI using cryopreserved testicular spermatozoa with those previously reported in Klinefelter's syndrome and those in nonobstructive azoospermia patients using cryopreserved testicular spermatozoa at our institution with respect to embryo cleavage rate, implantation rate, and pregnancy outcome. RESULT(S): Four of six patient couples with successful microdissection TESE achieved pregnancy using cryopreserved-thawed testicular spermatozoa. One pregnancy resulted in early-pregnancy abortion, two in delivery of healthy singleton girls, and one delivery of a healthy singleton boy. CONCLUSION(S): Cryopreserved-thawed testicular spermatozoa can be used successfully for ICSI in patients with nonmosaic Klinefelter's syndrome.

Adult↗

PubMed2005

The hemolytic characteristics of monopivot magnetic suspension blood pumps with washout holes.

The hemolytic characteristics of monopivot magnetic suspension blood pumps as a function of impeller washout hole configuration and female pivot shape are observed. The pump impellers are designed with three washout hole configurations for blood circulation, and four female pivot shapes to reduce blood stagnation and to enhance antithrombogenicity. The hemolytic characteristics of the monopivot pumps were observed to be better than those of a currently available commercial centrifugal blood pump, BP-80, and changed to be nearly equal when the female pivot shape was changed. This indicates that hemolysis in monopivot pumps is mainly caused by shear stress between the male and female pivots.

Animals↗

PubMed2004

The most profitable use of flow visualization in the elimination of thrombus from a monopivot magnetic suspension blood pump.

The purpose of this study was to eliminate fluid dynamic causes of thrombus formation for the monopivot magnetic suspension centrifugal pump under development with the aid of flow visualization as an indirect measurement tool for animal experiments. The formation of thrombus observed in early animal experiments was successfully overcome by combining the multiple washout holes at the center into a single hole, optimizing the hole diameter, and eliminating the pivot gap. Flow visualization was used to optimize the washout hole diameter influencing the flow around the pivot. In animal experiments flow visualization showed that the contours of thrombus corresponded to shear rates of 300 s(-1) or 1300-1700 s(-1). It was found that flow visualization is a useful technique to predict locations where low shear thrombi form and to optimize the pump design in the development stage.

Animals↗

PubMed2003

Finding optimal degenerate patterns in DNA sequences.

MOTIVATION: The problem of finding transcription factor binding sites in the upstream regions of given genes is algorithmically an interesting and challenging problem in computational biology. A degenerate pattern over a finite alphabet Sigma is a sequence of subsets of Sigma. A string over IUPAC nucleic acid codes is also a degenerate pattern over Sigma = {A, C, G, T}, and is used as one of the major patterns modeling transcription factor binding sites in the upstream regions of genes. However, it is known that the problem of finding a degenerate pattern consistent with both positive and negative string sets is in general NP-complete. Our aim is to devise a heuristic algorithm to find a degenerate pattern which is optimal for positive and negative string sets w.r.t. a given score function. RESULTS: We have proposed an enumerative algorithm called SUPERPOSITION for finding optimal degenerate patterns with a pruning technique, which works with most all reasonable score functions. The performance score of the algorithm has been compared with those of other popular motif-finding algorithms YMF, MEME and AlignACE on various sets of co-regulated genes of yeast. In the computational experiment, SUPERPOSITION has outperformed the others on several gene sets. AVAILABILITY: The python script SUPERPOSITION is available at http://www.math.kyushu-u.ac.jp/~om/softwares.html

Algorithms↗

PubMed2002

Extensive feature detection of N-terminal protein sorting signals.

MOTIVATION: The prediction of localization sites of various proteins is an important and challenging problem in the field of molecular biology. TargetP, by Emanuelsson et al. (J. Mol. Biol., 300, 1005-1016, 2000) is a neural network based system which is currently the best predictor in the literature for N-terminal sorting signals. One drawback of neural networks, however, is that it is generally difficult to understand and interpret how and why they make such predictions. In this paper, we aim to generate simple and interpretable rules as predictors, and still achieve a practical prediction accuracy. We adopt an approach which consists of an extensive search for simple rules and various attributes which is partially guided by human intuition. RESULTS: We have succeeded in finding rules whose prediction accuracies come close to that of TargetP, while still retaining a very simple and interpretable form. We also discuss and interpret the discovered rules.

Amino Acid Sequence↗

PubMedDate not supplied

Fractural characteristic evaluation of a microcapsule suspension using a rotational shear stressor.

We are developing microcapsule suspensions to evaluate the absolute hemolytic properties of centrifugal blood pumps. Four types of microcapsule suspensions, with maximum diameters of 100 microm or 10 microm, and membranes of polyurethane or melamine resin, were exposed to fluid dynamic shear up to 15,000 s(-1) with a rotating shear stressor developed in our laboratory. As a result, destruction was observed of only the 100 microm microcapsules. The microcapsules with polyurethane membranes broke at a high shear velocity range over 11,250 s(-1), a tendency similar to that observed using bovine blood. The microcapsules with melamine resin ruptured at approximately 7,500 s(-1). These observations could lead to determination of absolute hemolysis from shear stress occurring in centrifugal blood pumps.

Biomechanical Phenomena↗