Biomedical subjects

Akira Ishikawa

Publications and source records attributed to Akira Ishikawa.

At least 19 recordsLinked to original sources

PubMed2006

Expression of IP-10/CXCL10 is upregulated by double-stranded RNA in BEAS-2B bronchial epithelial cells.

BACKGROUND: Interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10/CXCL10) is a potent chemoattractant for activated T and NK cells, and elevated levels of IP-10 are identified in bronchoalveolar lavage fluids from patients with pulmonary disorders related to Th-1-type immunity, which is a prerequisite for elimination of viral pathogens. Bronchial epithelial cells play an important role in respiratory infections as the initiator of airway inflammation by releasing chemokines and expressing cell surface membrane molecules involved in leukocyte adhesion. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA) and induces antiviral reactions in cells. OBJECTIVES: We investigated the regulation of IP-10 in BEAS-2B bronchial epithelial cells in response to poly IC, and also addressed the possible role of retinoic-acid-inducible gene-I (RIG-I) and IFN-regulatory factor 3 (IRF-3), two genes involved in the signaling induced by viral infection. METHODS: The expressions of IP-10 mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The overexpression of RIG-I or IRF-3 was performed by transfection of BEAS-2B cells with each cDNA. RESULTS: Poly IC enhanced the expression of IP-10 mRNA and protein in concentration- and time-dependent manners. Overexpression of RIG-I or IRF-3 potentiated the poly-IC-induced upregulation of IP-10. CONCLUSIONS: IP-10 may contribute to antiviral activity through the activation of Th-1-type immunity, and RIG-I and IRF-3 may be involved in this reaction.

Bronchi↗

PubMed2006

Recurrent paralytic ileus associated with strongyloidiasis in a patient with systemic lupus erythematosus.

We present an interesting case of recurrent paralytic ileus due to strongyloidiasis in a woman who was being treated with corticosteroids and immunosuppressants for systemic lupus erythematosus (SLE). She was also a carrier of human T-cell leukemia virus type I. She had a history of strongyloidiasis 8 years earlier. Recurrent episodes of paralytic ileus due to strongyloidiasis occurred during treatment of her SLE with corticosteroids. Ivermectin was given and improved the symptoms. This case shows that symptomatic strongyloidiasis can be induced in immunocompromised hosts by immunosuppressive therapy. It is important to rule out strongyloidiasis prior to starting immunosuppressive therapy in patients from endemic areas.

Animals↗

PubMed2006

Local balance of transforming growth factor-beta1 secreted from cholangiocarcinoma cells and stromal-derived factor-1 secreted from stromal fibroblasts is a factor involved in invasion of cholangiocarcinoma.

Tumor-stromal interactions are important for the progression of malignant tumors. The purpose of the present study was to examine interactions of cholangiocarcinoma (CC) cells and stromal fibroblasts with respect to stromal-derived factor-1 (SDF-1) and transforming growth factor (TGF)-beta1. Two cell lines of CC (HuCCT-1 and CCKS-1) and WI-38 fibroblast cell line were used for cell culture, and 12 CC tissue specimens for immunohistochemical studies. Invasion of CC cells was increased significantly by the supernatant from fibroblast cultures, but not by the supernatant from fibroblasts cocultured with CC cells. Expression of SDF-1 in cultured fibroblasts was downregulated by TGF-beta1 treatment, and coculture with CC cells and anti-TGF-beta1 neutralizing antibody restored the decreased SDF-1 expression, suggesting that TGF-beta1 secreted from CC cells might have reduced the expression of SDF-1 by fibroblasts and might have reduced the increased invasion of CC cells induced by the supernatant from fibroblasts. Immunohistochemical expression of TGF-beta1 in CC cells was focal or negative and that of SDF-1 was evident in stromal fibroblasts at the invasive front of CC. In conclusion, local mutual influence of TGF-beta1 secreted from carcinoma cells and SDF-1 expressed by stromal fibroblasts may be involved in invasion of CC cells.

Aged↗

PubMed2006

Detection of quantitative trait loci causing abnormal spermatogenesis and reduced testis weight in the small testis (Smt) mutant mouse.

The small testis (Smt) mutant mouse is characterized by a small testis of one third to one half the size of a normal testis, and its spermatogenesis is mostly arrested at early stages of meiosis, although a small number of spermatocytes at the late prophase of meiosis and a few spermatids can sometimes be seen. We performed quantitative trait locus (QTL) analysis of these spermatogenic traits and testis weight using 221 F2 males obtained from a cross between Smt and MOM (Mus musculus molossinus) mice. At the genome-wide 5% level, we detected two QTLs affecting meiosis on chromosomes 4 and 13, and two QTLs for paired testis weight as a percentage of body weight on chromosomes 4 and X. In addition, we found several QTLs for degenerated germ cells and multinuclear giant cells on chromosomes 4, 7 and 13. Interestingly, for cell degeneration, the QTL on chromosome 13 interacted epistatically with the QTL on chromosome 4. These results reveal polygenic participation in the abnormal spermatogenesis and small testis size in the Smt mutant.

Animals↗

PubMed2006

Possible regulation of migration of intrahepatic cholangiocarcinoma cells by interaction of CXCR4 expressed in carcinoma cells with tumor necrosis factor-alpha and stromal-derived factor-1 released in stroma.

Intrahepatic cholangiocarcinoma (ICC) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. We examined roles of CXCR4 and its ligand, stromal cell-derived factor (SDF)-1, in migration of ICC with respect to tumor-stromal interaction by using two ICC cell lines, a fibroblast cell line (WI-38), and 28 human ICC tissues. The two ICC cell lines expressed CXCR4 mRNA and protein, and WI-38 fibroblasts expressed SDF-1 mRNA and protein. Migration of cultured ICC cells in Matrigel was induced by co-culture with WI-38 fibroblasts and by incubation with SDF-1. Anti-SDF-1 antibody suppressed migration, demonstrating that SDF-1 released from WI-38 fibroblasts was responsible for this migration. Tumor necrosis factor (TNF)-alpha pretreatment of ICC cells up-regulated CXCR4 mRNA and protein expression in a concentration-dependent manner. Administration of SDF-1 and TNF-alpha increased synergistically ICC cell migration, which was suppressed by the CXCR4 antagonist AMD3100. In ICC tissue, TNF-alpha was mainly expressed in infiltrated macrophages, CXCR4 in ICC cells, and SDF-1 in stromal fibroblasts. In conclusion, the interaction of SDF-1 released from fibroblasts and CXCR4 expressed on ICC cells may be actively involved in ICC migration, and TNF-alpha may enhance ICC cell migration by increasing CXCR4 expression. CXCR4 could be a therapeutic target to prevent ICC invasion.

Aged↗

PubMed2006

[Correlaton of mortality for lower urinary tract cancer and medical resource factor].

PURPOSE: To compare mortality among different populations, the standardized mortality ratio (SMR) is usually used. This study is investigated the relationships between health care resources and mortality for lower urinary tract cancer. MATERIALS AND METHODS: Data for medical resource factors were obtained from annual reports published by the Ministry of Health, Labor and Welfare, Japan. A Bayesian regression model was used to examine the relationships between SMR and these factors. The SMRs for prostate cancer and bladder cancer were calculated for the period from 2000 to 2002 and for 1990. RESULTS: When the number of urological hospitals increased to 1 per 100,000 person in a region, the influence of the SMR for prostate cancer was - 3.0 - 0.5%, the male bladder cancer SMR was - 0.2 - 1.8% and the female bladder cancer SMR was - 2.6 - 0.8%. These findings were not significant. CONCLUSION: The study shows that an appropriate distribution of urology resources is one of the factors contributing to a reduction in the mortality for urological cancer in a region. However, further increase of urological hospitals in a region exerts a limited beneficial influence on reducing the mortality.

Bayes Theorem↗

PubMed2006

[Prostate cancer].

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Androgen Antagonists↗

PubMed2005

Effect of peroxisome proliferator-activated receptor-gamma ligands on the expression of retinoic acid-inducible gene-I in endothelial cells stimulated with lipopolysaccharide.

Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH box protein family and designated as a putative RNA helicase. RIG-I is implicated in host defense and inflammatory reactions by regulating the expression of various genes. RIG-I is expressed in endothelial cells and upregulated with lipopolysaccharide (LPS). Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor and regulates gene expressions in response to its specific ligands. In the present study, we examined the effect of PPAR-gamma ligands on the LPS-induced RIG-I expression in cultured human umbilical vein endothelial cells (HUVEC). 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), a metabolite of PGD2, is a natural ligand for PPAR-gamma and known to modulate inflammatory reactions by regulating the expression of various genes in PPAR-gamma-dependent and -independent manners. LPS-induced RIG-I expression in HUVEC was inhibited by pretreatment of the cells with 15d-PGJ2 in time-and concentration-dependent manners. However, ciglitazone and bisphenol A diglycide ether, authentic and specific ligands for PPAR-gamma, did not affect the RIG-I expression. These results suggest that 15d-PGJ2 inhibits LPS-induced RIG-I expression through a mechanism independent on PPAR-gamma. 15d-PGJ2 may regulate inflammatory reactions, at least in part, by inhibiting the expression of RIG-I.

Base Sequence↗

PubMed2005

Methylation status of EXT1 and EXT2 promoters and two mutations of EXT2 in chondrosarcoma.

Germline mutation and functional loss of EXT1 or EXT2 are commonly found in multiple osteochondromas and predispose to the development of chondrosarcoma. Mutations of EXT1 and EXT2 have rarely been detected in sporadic secondary chondrosarcomas from osteochondroma; these frequently display loss of heterozygosity at the EXT1 and EXT2 loci, but primary chondrosarcomas typically do not. To evaluate promoter methylation (which is an epigenetic gene silencing mechanism) of EXT1 and EXT2, we performed methylation-specific polymerase chain reaction (PCR) for 20 chondrosarcoma cases (12 primary, 3 secondary to osteochondroma, 2 secondary to enchondromatosis, 2 extraskeletal ordinary, and 1 clear cell) and in five cell lines. In addition, mutation analysis of the EXT1 and EXT2 coding regions was performed using PCR-single-strand conformation polymorphism and sequencing analysis for 12 of the 20 chondrosarcoma cases (8 primary, 1 secondary to enchondromatosis, 1 secondary to osteochondroma, and 2 extraskeletal ordinary) and five cell lines. Promoter methylation of EXT1 and EXT2 was not detected in any of the cases, and both EXT1 and EXT2 were expressed in all cell lines. Two missense mutations in EXT2 (D227E and R299H) were detected among the chondrosarcoma cases. When considering tumor development in primary chondrosarcoma, we should include mutations in EXT2, along with the status of other members of the EXT gene family.

5' Untranslated Regions↗

PubMed2005

Platelet-activating factor enhances the expression of nerve growth factor in normal human astrocytes under hypoxia.

Nerve growth factor (NGF) is required for the survival of neurons. We have addressed the effect of platelet-activating factor (PAF), one of the mediators of ischemic injury of the brain, on NGF expression in astrocytes. Normal human astrocytes in culture were stimulated with PAF, and levels of NGF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). PAF increased the expressions of NGF mRNA and protein in astrocytes in time- and concentration-dependent manners. After 48-h stimulation, 10 nmol/L PAF increased the levels of NGF protein in astrocyte-conditioned medium by 1.4-fold. The PAF-induced stimulation of NGF expression was further enhanced (2.1-fold of the control) in the cells under hypoxic culture condition. BN52021 (Ginkgolide B), an antagonist for PAF binding sites, suppressed the effect of PAF. We conclude that PAF enhances NGF gene expression in human astrocytes, and the PAF-induced increase in the expression of NGF under hypoxia may benefit the protection of the nervous tissue by promoting neuronal survival.

Astrocytes↗

PubMed2005

A new mouse model for infantile neuroaxonal dystrophy, inad mouse, maps to mouse chromosome 1.

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive hereditary neurodegenerative disease of humans. So far, no responsible gene has been cloned or mapped to any chromosome. For chromosome mapping and positional cloning of the responsible gene, establishment of an animal model would be useful. Here we describe a new mouse model for INAD, named inad mouse. In this mouse, the phenotype is inherited in an autosomal recessive manner, symptoms occur in the infantile period, and the mouse dies before sexual maturity. Axonal dystrophic change appearing as spheroid bodies in central and peripheral nervous system was observed. These features more closely resembled human INAD than did those of the gad mouse, the traditional mouse model for INAD. Linkage analysis linked the inad gene to mouse Chromosome 1, with the highest LOD score (=128.6) at the D1Mit45 marker, and haplotype study localized the inad gene to a 7.5-Mb region between D1Mit84 and D1Mit25. In this linkage area some 60 genes exist: Mutation of one of these 60 genes is likely responsible for the inad mouse phenotype. Our preliminary mutation analysis in 15 genes examining the nucleotide sequence of exons of these genes did not find any sequence difference between inad mouse and C57BL/6 mouse.

Animals↗

PubMed2005

Quantitative trait loci for proteinuria in the focal glomerulosclerosis mouse model.

The FGS/Kist strain of mice, a new animal model for focal glomerulosclerosis (FGS) in humans, was previously established by recurrent selection for high proteinuria, which is a principal marker of FGS, from descendants of CBA/Nga and RFM/Nga strains. We performed a genome-wide scan for quantitative trait loci (QTLs) affecting proteinuria in a population of 356 backcross progeny derived from a cross between FGS/Kist and the standard normal strain, C57BL/6J. Five proteinuria QTLs (Ptnu1-5) were detected at the genome-wide 5% or less level. Ptnu1 and Ptnu2, located on Chromosomes (Chrs) 8 and 17, respectively, had main effects on proteinuria and also interacted epistatically with each other. However, Ptnu3 on Chr 9 and Ptnu4 and Ptnu5 both on Chr 15 had epistatic interaction effects only. Except for the epistatic interaction effect of Ptnu4 and Ptnu5, all alleles derived from FGS/Kist were responsible for the high proteinuria. These results indicated that the genetic control of proteinuria is complex and the identified QTLs may provide new insights into the pathogenesis of FGS in mice as well as in humans.

Analysis of Variance↗

PubMed2005

Polyinosinic-polycytidylic acid induces the expression of GRO-alpha in BEAS-2B cells.

Growth-related oncogene protein-alpha (GRO-alpha)/CXCLl is a chemokine that activates neutrophils and plays an important role in inflammatory reactions. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA), which is a ligand for Toll-like receptor-3. Poly IC mimics viral infection when applied to cells and induces inflammatory and immune responses. In the present study, we found the induction of GRO-alpha in BEAS-2B bronchial epithelial cells treated with poly IC. Pretreatment of cells with 2-aminopurine, an inhibitor for dsRNA-dependent protein kinase (PKR), inhibited the expression of GRO-alpha-induced by poly IC. Overexpression of interferon-regulatory factor-3 (IRF-3) or retinoic-acid inducible gene-I (RIG-I) enhanced the induction of GRO-alpha by poly IC. PKR, IRF-3, and RIG-I may be involved in the poly IC-induced expression of GRO-alpha in BEAS-2B cells. Airway viral infection may elicit GRO-alpha expression in the bronchial epithelium, which may be implicated in inflammatory and immune reactions.

Bronchi↗

PubMed2005

Further mapping of quantitative trait loci for postnatal growth in an inter-sub-specific backcross of wild Mus musculus castaneus and C57BL/6J mice.

We performed a quantitative trait locus (QTL) analysis of eight body weights recorded weekly from 3 weeks to 10 weeks after birth and two weight gains recorded between 3 weeks and 6 weeks, and between 6 weeks and 10 weeks in an inter-sub-specific backcross population of wild Mus musculus castaneus mice captured in the Philippines and the common inbred strain C57BL/6J ( M. musculus domesticus ), to elucidate the complex genetic architecture of body weight and growth. Interval mapping identified 17 significant QTLs with main effects on 11 chromosomes. In particular, the main effect of the most potent QTL on proximal chromosome 2 increased linearly with age, whereas other QTLs exerted effects on either the early or late growth period. Surprisingly, although wild mice displayed 60% of the body size of their C57BL/6J counterparts, the wild-derived allele enhanced growth at two QTLs. Interestingly, five of the 17 main-effect QTLs identified had significant epistatic interaction effects. Five new epistatic QTLs with no main effects were identified on different chromosomes or regions. For one pair of epistatic QTLs, mice that were heterozygous for the wild-derived allele at one QTL and homozygous for that allele at another QTL exhibited the most rapid growth in all four possible genotypic combinations. Out of the identified QTLs, several showed significant sex-specific effects.

Animals↗

PubMed2005

Double-stranded RNA stimulates the expression of monocyte chemoattractant protein-1 in BEAS-2B bronchial epithelial cells.

BEAS-2B bronchial epithelial cells were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic double-stranded RNA (dsRNA) analog, and the expressions of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein were analyzed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Poly IC enhanced the expression of MCP-1 and release of mononuclear cell chemotactic activity, which were inhibited by dexamethasone pre-treatment. The poly IC-induced up-regulation of MCP-1 was blocked by 2-aminopurine, a specific inhibitor of dsRNA-dependent protein kinase, but not by nuclear factor (NF)-kappaB inhibitor SN50.

Base Sequence↗

PubMed2005

Development and characterization of CATS markers for genetic linkage mapping in the house musk shrew, Suncus murinus.

To serve as an initial step in developing an ideal genetic marker map for the house musk shrew, Suncus murinus, 318 comparative anchor tagged sequence (CATS) primer pairs were assessed for polymorphism ascertainment and linkage mapping. Of the 112 (35.2%) CATS primer pairs that were successfully amplified by PCR in the shrew, 18 (16.1%) showed polymorphism between two mutant strains, BAN-kc, oeb and WZ. Linkage analysis of the polymorphic CATS markers and three visible mutant genes, kc, oeb and wz, genotyped in a 77 F2 mapping panel from a cross of the two mutant strains, assigned wz and five CATS markers into three linkage groups. Sequence analysis revealed that two (ADA and TXN) out of nine CATS amplified sequences had a total of six deletions of varying sizes and 17 single nucleotide polymorphisms (SNPs). BLAST search identified three CATS (ADA, CYP1A2, and TXN) products matching the genes from which they were originally designed, while the remaining six markers could not be identified. Together with the use of the detected SNPs as genetic markers, the five CATS markers linkage mapped in this species will serve as anchors in establishing the first framework map for locating loci affecting all heritable qualitative and quantitative traits in the musk shrew.

Animals↗

PubMed2005

Quantitative trait Loci for glomerulosclerosis, kidney weight and body weight in the focal glomerulosclerosis mouse model.

In 183 male progeny derived from a backcross between the FGS/Kist strain, a new mouse model for focal glomerulosclerosis (FGS) in humans, and the standard normal strain, C57BL/6J, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting the glomerulosclerosis index (GSI) based on histological observation as well as kidney and body weights. Two QTLs for GSI (Gsi1-2) located on chromosomes (Chrs) 8 and 10, a kidney weight QTL (Kdw1) on Chr 19, and a body weight QTL (Bdw1) on Chr 13 were detected at the genome-wide 5% or less level. The allele derived from FGS/Kist increased GSI at Gsi1, but decreased it at Gsi2. The mice homozygous for the FGS/Kist allele decreased body and kidney weights. The identified QTLs accounted for 5-8% of the phenotypic variance.

Animals↗

PubMed2005

Arrest of spermatogenesis at the early meiotic stage in the small testis mutant (Smt) mice.

A spontaneous mutant having small testes was found in a laboratory mouse strain of mixed origins. The testis size was 1/3-1/2 of normal size, but no significant difference was seen in body mass and weight of organs such as kidney and seminal vesicle, which are influenced by androgen. Small testis males were found to be infertile by the mating test, although formation of a vaginal plug was normally observed in their female partners. Histological and air-dried specimens revealed degeneration of zygotene or early pachytene spermatocytes and very few numbers of pachytene and diplotene spermatocytes, round and elongate spermatids and mature spermatozoa in the mutant testis. Therefore, it was concluded that spermatogenesis is disrupted at the zygotene to early pachytene stages of meiosis in the mutant males. Segregation ratios of normal and mutant males were in accord with the assumption that the small testis character is caused by an autosomal recessive mutation. This mutant may be useful for research that would contribute to the elucidation of genetic mechanisms controlling the process of spermatogenesis and as a model animal for male infertility in humans.

Animals↗