Biomedical subjects

Hiroyuki Abe

Publications and source records attributed to Hiroyuki Abe.

At least 19 recordsLinked to original sources

PubMed2007

Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system.

Since the prognosis of human osteosarcoma in advanced stage remains poor, the development of new and effective therapies including immunotherapy is required. To identify tumor-associated antigens of osteosarcoma applicable to the immunotherapy of this malignancy, we employed the serological analysis of recombinant cDNA expression library (SEREX) technique that defines tumor antigens recognized by the humoral immune system. Screening a cDNA library derived from an osteosarcoma cell line MG63 with sera from osteosarcoma patients identified 43 positive clones, representing 14 distinct antigens. Among them, CLUAP1 (clusterin-associated protein 1) was highly expressed in osteosarcoma tissue samples and cell lines. Overexpression of CLUAP1 was observed in other malignancies including ovarian, colon, and lung cancers. Our results suggest that CLUAP1 may be useful as a prognostic/diagnostic marker and/or for a target of immunotherapy of osteosarcoma.

Adolescent↗

PubMed2006

Role of the hyaluronan receptor CD44 during porcine oocyte maturation.

Previous our studies have shown that CD44, the principal receptor for hyaluronan, is present on cumulus cells during oocyte maturation. Although hyaluronan-CD44 interaction has been implicated in cumulus expansion and/or oocyte maturation, the full significance of CD44 remains unknown. The objective of the present study was to further investigate the role of CD44 in cumulus expansion and oocyte maturation in pigs. We demonstrate here in that CD44 has a key role in oocyte maturation but not in cumulus expansion. Previous studies have reported the physiological significance of cumulus expansion in oocyte maturation. However, our results suggest that cumulus expansion is a necessary condition for oocyte maturation, but that it is not sufficient on its own. Furthermore, western blot analysis demonstrated that the CD44 of the in vitro-matured cumulus-oocyte complexes (COCs) had a larger molecular weight and more terminal sialic acid, which has been proven to inhibit the hyaluronan-binding ability of the receptor, than the CD44 of the in vivo-matured COCs, indicating that the hyaluronan-CD44 interactions during in vitro maturation might be insufficient compared with those in vivo. The insufficient interactions of hyaluronan-CD44 during in vitro maturation may cause the inferior capacity of fertilization and development of oocytes matured in vitro.

Animals↗

PubMed2006

TccP2 of O157:H7 and non-O157 enterohemorrhagic Escherichia coli (EHEC): challenging the dogma of EHEC-induced actin polymerization.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 and enteropathogenic E. coli (EPEC) trigger actin polymerization at the site of bacterial adhesion by inducing different signaling pathways. Actin assembly by EPEC requires tyrosine phosphorylation of Tir, which subsequently binds the host adaptor protein Nck. In contrast, Tir(EHEC O157) is not tyrosine phosphorylated and instead of Nck utilizes the bacterially encoded Tir-cytoskeleton coupling protein (TccP)/EspF(U), which mimics the function of Nck. tccP is carried on prophage CP-933U/Sp14 (TccP). Typical isolates of EHEC O157:H7 harbor a pseudo-tccP gene that is carried on prophage CP-933 M/Sp4 (tccP2). Here we report that atypical, beta-glucuronidase-positive and sorbitol-fermenting, strains of EHEC O157 harbor intact tccP and tccP2 genes, both of which are secreted by the LEE-encoded type III secretion system. Non-O157 EHEC strains, including O26, O103, O111, and O145, are typically tccP negative and translocate a Tir protein that encompasses an Nck binding site. Unexpectedly, we found that most clinical non-O157 EHEC isolates carry a functional tccP2 gene that encodes a secreted protein that can complement an EHEC O157:H7 DeltatccP mutant. Using discriminatory, allele-specific PCR, we have demonstrated that over 90% of tccP2-positive non-O157 EHEC strains contain a Tir protein that can be tyrosine phosphorylated. These results suggest that the TccP pathway can be used by both O157 and non-O157 EHEC and that non-O157 EHEC can also trigger actin polymerization via the Nck pathway.

Actins↗

PubMed2006

Effects of fasting and refeeding on expression of atrogin-1 and Akt/FOXO signaling pathway in skeletal muscle of chicks.

This experiment was conducted to study the effects of fasting and refeeding on expression of the atrogin-1 and Akt/FOXO signaling pathway in skeletal muscle of chicks. Chicks were fasted for 24 h and refed for 2 h. Atrogin-1 mRNA expression was increased by fasting, and their increment was reduced by refeeding. Phosphorylations of Akt and FOXO1 were not decreased by fasting, but, they were increased by refeeding. These results indicate that refeeding stimulates phosphorylation of Akt/FOXO, resulting in a decrease in atrogin-1 expression in skeletal muscle of chicks.

Animal Feed↗

PubMed2006

Role of natural killer cells in hormone-independent rapid tumor formation and spontaneous metastasis of breast cancer cells in vivo.

Natural killer (NK) cells play a central role in host defense against tumor and virus-infected cells. Direct role of NK cells in tumor growth and metastasis remains to be elucidated. We here demonstrated that NOD/SCID/gammac(null) (NOG) mice lacking T, B and NK cells inoculated with breast cancer cells were efficient in the formation of a large tumor and spontaneous organ-metastasis. In contrast, breast cancer cells produced a small tumor at inoculated site in T and B cell knock-out NOD/SCID mice with NK cells while completely failed to metastasize into various organs. Immunosupression of NOD/SCID by treatment with an anti-murine TM-beta1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhancing tumor formation and organ-metastasis in comparison with non-treated NOD/SCID mice. Activated NK cells inhibited tumor growth in vivo. The rapid and efficient engraftment of the breast cancer cells in NOG mice suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of tumor cell growth and metastasis. Our results suggest that NK cells play an important role in cancer growth and metastasis and could be a promising immunotherapeutic strategy against cancer either alone or in combination with conventional therapy.

Animals↗

PubMed2006

An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination.

Several pathogenic strains of Escherichia coli exploit type III secretion to inject "effector proteins" into human cells, which then subvert eukaryotic cell biology to the bacterium's advantage. We have exploited bioinformatics and experimental approaches to establish that the effector repertoire in the Sakai strain of enterohemorrhagic E. coli (EHEC) O157:H7 is much larger than previously thought. Homology searches led to the identification of >60 putative effector genes. Thirteen of these were judged to be likely pseudogenes, whereas 49 were judged to be potentially functional. In total, 39 proteins were confirmed experimentally as effectors: 31 through proteomics and 28 through translocation assays. At the protein level, the EHEC effector sequences fall into >20 families. The largest family, the NleG family, contains 14 members in the Sakai strain alone. EHEC also harbors functional homologs of effectors from plant pathogens (HopPtoH, HopW, AvrA) and from Shigella (OspD, OspE, OspG), and two additional members of the Map/IpgB family. Genes encoding proven or predicted effectors occur in >20 exchangeable effector loci scattered throughout the chromosome. Crucially, the majority of functional effector genes are encoded by nine exchangeable effector loci that lie within lambdoid prophages. Thus, type III secretion in E. coli is linked to a vast phage "metagenome," acting as a crucible for the evolution of pathogenicity.

Bacteriophage lambda↗

PubMed2006

Potential role of natural killer cells in controlling growth and infiltration of AIDS-associated primary effusion lymphoma cells.

Natural killer (NK) cells are an important component of the innate immune response against microbial infections and tumors. Direct involvement of NK cells in tumor growth and infiltration has not yet been demonstrated clearly. Primary effusion lymphoma (PEL) cells were able to produce tumors and ascites very efficiently with infiltration of cells in various organs of T-, B- and NK-cell knock-out NOD/SCID/gammac(null) (NOG) mice within 3 weeks. In contrast, PEL cells formed small tumors at inoculated sites in T- and B-cell knock-out NOD/SCID mice with NK-cells while completely failing to infiltrate into various organs. Immunosupression of NOD/SCID by treatment with an antimurine TM-beta1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhanced tumorigenicity and organ infiltration in comparison with non-treated NOD/SCID mice. Activated human NK cells inhibited tumor growth and infiltration in NOG mice. Our results suggest that NK cells play an important role in growth and infiltration of PEL cells, and activated NK cells could be a promising immunotherapeutic tool against tumor or virus-infected cells either alone or in combination with conventional therapy. The rapid and efficient engraftment of PEL cells in NOG mice also suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of pathogenesis and malignant cell growth.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Oxygen consumption of cell suspension in a poly(dimethylsiloxane) (PDMS) microchannel estimated by scanning electrochemical microscopy.

A quantitative analysis of the oxygen concentration profile near a poly(dimethylsiloxane) (PDMS) microfluidic device was performed using scanning electrochemical microscopy (SECM). A microchannel filled with sodium sulfite (Na(2)SO(3)) aqueous solution was imaged by SECM, showing that the oxygen diffusion layer of the PDMS microchannel was observed to be hemicylindrical. Based on a theoretical analysis of the hemicylindrical diffusion layer of the microchannel, the total oxygen mass transfer rates of oxygen to the PDMS microchannel filled with the Na(2)SO(3) solution was calculated to be (4.01 +/- 0.30) x 10(-12) mol s(-1). This is the maximum value of the oxygen transfer rate for this PDMS microchannel device. The oxygen consumption rate increased almost linearly with the logarithm of the concentration of E. coli cells (10(6) approximately 10(8) cells). The respiratory activity for a single E. coli cell was estimated to be approximately 4.31 x 10(-20) mol s(-1) cell(-1).

Cells↗

PubMed2006

Antitumor activity of chimeric immunoreceptor gene-modified Tc1 and Th1 cells against autologous carcinoembryonic antigen-expressing colon cancer cells.

To generate tumor-specific and interferon (IFN)-gamma-producing Tc1 and Th1 cells applicable for many cancer patients, we previously developed a protocol for generating carcinoembryonic antigen (CEA)-specific Tc1 and Th1 cells from healthy human T cells by transduction with a lentivirus containing a chimeric immunoglobulin T-cell receptor (cIgTCR) gene composed of single-chain variable fragments from an anti-CEA-specific monoclonal antibody fused to an intracellular signaling domain of CD28 and CD3zeta. These cells, designated Tc1-T and Th1-T bodies, respectively, showed strong antitumor activity against CEA-expressing tumor cells in RAG2-/- mice when both of them were transferred. However, it remains unclear whether it is possible to generate Tc1-T and Th1-T bodies from cancer patients with defective T-cell function because of significant immunosuppression. Here, we prepared Tc1-T and Th1-T bodies from T cells of a colon cancer patient, and asked whether these T bodies can exert effective T-cell function against autologous tumor cells. These T bodies showed high cytotoxicity and produced IFN-gamma in response to CEA-expressing autologous tumor cells, even in the presence of soluble CEA. It was also demonstrated that Th1-T bodies supported the survival of Tc1-T bodies through cell-to-cell interactions. Furthermore, our protocol utilized retrovirus for cIgTCR transduction to achieve better induction efficiency compared to lentivirus-mediated transduction. Taken together, our findings here indicate that retrovirally transduced Tc1-T and Th1-T bodies will become a promising strategy for adoptive immunotherapy of human cancer.

Carcinoembryonic Antigen↗

PubMed2006

Prenatal developmental changes in glucose transporters, intermediary metabolism and hormonal receptors related to the IGF/insulin-glucose axis in the heart and adipose tissue of bovines.

Glucose transporter ontogenesis is likely to play a key role in glucose uptake by foetal tissues in order to satisfy their energy requirements. We thus investigated developmental changes in the bovine heart and perirenal adipose tissue in two glucose transporter isoforms, namely GLUT1 and GLUT4, the latter being responsible for the regulation of glucose uptake by insulin. Other key players of the glucose/insulin axis were also assessed. Plasma glucose concentration in the foetus was lower at 8 and 8.5 months of age than previously. In the heart, GLUT1 protein level markedly decreased between 3 and 4 months of age, whereas the number of insulin and IGF-I binding sites continually decreased, especially between 7 and 8 or 8.5 months of age. On the contrary, the GLUT4 level increased until 8 months of age and remained high until 2 weeks after birth. The activities of enzymes of glucose metabolism (namely phosphofructokinase [PFK] and lactate dehydrogenase [LDH]) increased throughout gestation and reached a plateau at 6 and 8.5 months of age for PFK and LDH, respectively. The activities of enzymes involved in fatty acid metabolism increased especially at birth. In perirenal adipose tissue, high mitochondrial activity was detected before birth which is a characteristic of brown adipose tissue. Furthermore, lipoprotein lipase activity and GLUT4 protein level markedly increased to reach a maximum at 6-7 and 8 months of age, and sharply decreased thereafter, whereas GLUT1 protein level increased between 6 and 7 months of age. In conclusion, considerable changes in the regulation of the insulin/glucose axis were observed from 6 months onwards of foetal development in both the heart and adipose tissue of cattle, which probably alters the potential of these tissues to use glucose or fat as energy sources.

Adipose Tissue↗

PubMed2006

BopC is a novel type III effector secreted by Bordetella bronchiseptica and has a critical role in type III-dependent necrotic cell death.

In Bordetella bronchiseptica, the functional type III secretion system (TTSS) is required for the induction of necrotic cell death in infected mammalian cells. To identify the factor(s) involved in necrotic cell death, type III-secreted proteins from B. bronchiseptica were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization tandem mass spectrometry. We identified a 69-kDa secreted protein designated BopC. The gene encoding BopC is located outside of the TTSS locus and is also highly conserved in both Bordetella parapertussis and Bordetella pertussis. The results of a lactate dehydrogenase release assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay demonstrated that BopC is required for necrotic cell death. It has been reported that tyrosine-phosphorylated proteins (PY) of host cells are dephosphorylated during B. bronchiseptica infection in a TTSS-dependent manner. We found that BopC is also involved in PY dephosphorylation in infected host cells. It appears that the necrotic cell death triggered by BopC occurs prior to the PY reduction in host cells, because Bordetella-induced cell death was not affected even in the presence of a dephosphorylation inhibitor. Furthermore, a translocation assay showed that the signal sequence for both secretion into culture supernatant and translocation into the host cell is located in 48 amino acid residues of the BopC N terminus. This report reveals for the first time that a novel type III effector, BopC, is required for the induction of necrotic cell death during Bordetella infection.

Animals↗

PubMed2006

Fat suppression with spectrally selective inversion vs. high spectral and spatial resolution MRI of breast lesions: qualitative and quantitative comparisons.

PURPOSE: To compare conventional fat-suppressed MR images of the breast to images derived from high spectral and spatial resolution MR data. Image quality and the level of fat suppression are compared qualitatively and quantitatively. MATERIALS AND METHODS: Women with suspicious breast lesions found on X-ray mammography were imaged on 1.5 Tesla GE SIGNA scanners. High spectral and spatial resolution (HiSS) data were acquired using echo-planar spectroscopic imaging. Images with intensity proportional to the water signal peak height in each voxel were synthesized. Conventional fat-suppressed images were acquired using a frequency selective inversion method. The experimental (HiSS) and conventional images were compared by experienced radiologists to evaluate the quality of fat suppression. In addition, fat suppression and image quality were evaluated quantitatively. RESULTS: Fat suppression, tumor edge delineation, lesion conspicuity, and image texture were improved in the peak height images derived from HiSS data. CONCLUSION: The results demonstrate that the water peak height images obtained from HiSS data potentially could improve the quality of fat suppression, detection and diagnosis of breast cancer. HiSS allowed detection of lesions and evaluation of lesion morphology prior to contrast media injection. J. Magn. Reson. Imaging 2006. (c) 2006 Wiley-Liss, Inc.

Adipose Tissue↗

PubMed2006

Computer-aided diagnosis for the detection and classification of lung cancers on chest radiographs ROC analysis of radiologists' performance.

RATIONALE AND OBJECTIVES: The aim of the study is to investigate the effect of a computer-aided diagnostic (CAD) scheme on radiologist performance in the detection of lung cancers on chest radiographs. MATERIALS AND METHODS: We combined two independent CAD schemes for the detection and classification of lung nodules into one new CAD scheme by use of a database of 150 chest images, including 108 cases with solitary pulmonary nodules and 42 cases without nodules. For the observer study, we selected 48 chest images, including 24 lung cancers, 12 benign nodules, and 12 cases without nodules, from the database to investigate radiologist performance in the detection of lung cancers. Nine radiologists participated in a receiver operating characteristic (ROC) study in which cases were interpreted first without and then with computer output, which indicated locations of possible lung nodules, together with a five-color scale illustrating the computer-estimated likelihood of malignancy of the detected nodules. RESULTS: Performance of the CAD scheme indicated that sensitivity in detecting lung nodules was 80.6%, with 1.2 false-positive results per image, and sensitivity and specificity for classification of nodules by use of the same database for training and testing the CAD scheme were 87.7% and 66.7%, respectively. Average area under the ROC curve value for detection of lung cancers improved significantly (P = .008) from without (0.724) to with CAD (0.778). CONCLUSION: This type of CAD scheme, which includes two functions, namely detection and classification, can improve radiologist accuracy in the diagnosis of lung cancer.

Clinical Competence↗

PubMed2006

Image-processing technique for suppressing ribs in chest radiographs by means of massive training artificial neural network (MTANN).

When lung nodules overlap with ribs or clavicles in chest radiographs, it can be difficult for radiologists as well as computer-aided diagnostic (CAD) schemes to detect these nodules. In this paper, we developed an image-processing technique for suppressing the contrast of ribs and clavicles in chest radiographs by means of a multiresolution massive training artificial neural network (MTANN). An MTANN is a highly nonlinear filter that can be trained by use of input chest radiographs and the corresponding "teaching" images. We employed "bone" images obtained by use of a dual-energy subtraction technique as the teaching images. For effective suppression of ribs having various spatial frequencies, we developed a multiresolution MTANN consisting of multiresolution decomposition/composition techniques and three MTANNs for three different-resolution images. After training with input chest radiographs and the corresponding dual-energy bone images, the multiresolution MTANN was able to provide "bone-image-like" images which were similar to the teaching bone images. By subtracting the bone-image-like images from the corresponding chest radiographs, we were able to produce "soft-tissue-image-like" images where ribs and clavicles were substantially suppressed. We used a validation test database consisting of 118 chest radiographs with pulmonary nodules and an independent test database consisting of 136 digitized screen-film chest radiographs with 136 solitary pulmonary nodules collected from 14 medical institutions in this study. When our technique was applied to nontraining chest radiographs, ribs and clavicles in the chest radiographs were suppressed substantially, while the visibility of nodules and lung vessels was maintained. Thus, our image-processing technique for rib suppression by means of a multiresolution MTANN would be potentially useful for radiologists as well as for CAD schemes in detection of lung nodules on chest radiographs.

Algorithms↗

PubMed2006

A case of sclerodermatous graft-versus-host disease following autologous peripheral blood stem cell transplantation.

We report a 65-year-old woman with chronic graft-versus-host disease (GVHD) who developed severely sclerotic skin on the fingers, hand and trunk following autologous peripheral blood stem cell transplantation (APBSCT). The patient had suffered from breast cancer and been treated with surgery and chemotherapy. She showed pancytopenia and was treated with APBCST. Four years after APBSCT, she developed the severe sclerotic changes on the fingers, hands, extremities and trunk. The skin biopsy showed a flattened epidermis and a proliferation of collagen bundles in the dermis. No anti-nucleolar DNA titers were detected in the serum. She was diagnosed with chronic GVHD. Despite treatment with oral prednisolone, the skin sclerotic change developed and the breast cancer recurred. She died due to pericarditis. This is a rare case of sclerodermatous GVHD following APBSCT. The serum interleukin (IL)-12 levels were examined during the treatment.

Aged↗

PubMed2006

ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes.

For a new pathogen to emerge, it must acquire both virulence genes and a system for responding to changes in environmental conditions. Starvation of nutrients or growth arrest induces the stringent response in Escherichia coli, via increased ppGpp. We found the adherence capacity of enterohaemorrhagic E. coli (EHEC) and gene expression in the locus of enterocyte effacement (LEE) were enhanced by a downshift in nutrients or by entry into the stationary growth phase, both of which increase the ppGpp concentration. The activation was dependent on relA and spoT, which encode enzymes for the synthesis and degradation of ppGpp, and on dksA, which encodes an RNA polymerase accessory protein required for the stringent response. Upon induction of RelA expression, LEE gene transcription was activated within 20 min, even without starvation. The expression of two LEE transcriptional regulators, Ler and Pch, was activated by ppGpp and essential for the enhancement of LEE gene expression. In addition, the ler and pch promoters were directly activated by ppGpp in an in vitro transcription system. These findings suggest that the regulation of virulence genes in EHEC is integrated with E. coli's stringent response system, through the regulation of virulence regulatory genes.

Adhesins, Bacterial↗

PubMed2006

The slaty mutation affects the morphology and maturation of melanosomes in the mouse melanocytes.

The slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome tautomerase in melanocytes and to reduce the melanin content in skin, hairs and eyes. Although the melanosomes in slaty melanocytes are reported to be eumelanosome-like, detailed melanosome biogenesis is not well studied. To address this point, melanosomes in neonatal epidermal melanocytes from wild-type (Dct+/Dct+) mice at the slaty locus as well as its congenic mouse mutant (Dct(slt)/Dct(slt)) in serum-free primary culture were observed under the electron microscope. Wild-type melanocytes possessed exclusively elliptical melanosomes with internal longitudinal structures, whereas in mutant melanocytes, numerous spherical melanosomes with globular depositions of pigment and elliptical melanosomes as well as mixed type of the two melanosomes were observed. Mature stage IV melanosomes were greatly decreased in mutant melanocytes, whereas immature stage III melanosomes were more numerous than in wild-type melanocytes. These results suggest that the slaty mutation affects the morphology and maturation of melanosomes in mouse melanocytes.

Animals↗

PubMed2006

Effects of orally administrated amino acids on myofibrillar proteolysis in chicks.

We examined the effects of orally administrated amino acids on myfibrillar proteolysis in food-deprived chicks. Plasma N(tau)-methylhistidine concentration, as an index of myofibrillar proteolysis, was decreased by the administration of Glu, Gly, Ala, Leu, Ile, Ser, Thr, Met, Trp, Asn, Gln, Pro, Lys and Arg but not by Asp, Val, Phe, Tyr or His to chicks. Orally administrated Cys was fatal to chicks. These results indicate that oral Glu, Gly, Ala, Leu, Ile, Ser, Thr, Met, Trp, Asn, Gln, Pro, Lys and Arg administration suppressed myofibrillar proteolysis in chicks.

Administration, Oral↗