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Biomedical subjects

Yuichi Ishikawa

Publications and source records attributed to Yuichi Ishikawa.

At least 37 records · Page 2Linked to original sources
PubMed2005

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.

Aldehyde Reductase↗
PubMed2005

Chylomicron remnants regulate early growth response factor-1 in vascular smooth muscle cells.

Early growth response factor-1 (Egr-1) is a zinc-finger transcription factor that induces genes that promote atherosclerosis. The goal of the present study was to determine whether Egr-1 expression is modulated by atherogenic, triglyceride rich lipoproteins known as chylomicron remnants. Chylomicron remnants induced Egr-1 mRNA and protein expression in rat cultured vascular smooth muscle cells (VSMCs) and activated extracellular signal-regulated kinase (ERK) 1/2 in VSMCs. Further, chylomicron remnant-induced Egr-1 expression was inhibited by PD98059, a selective inhibitor of MAPK kinase (MEK), suggesting that the action of chylomicron remnants on Egr-1 was dependent on the ERK/MEK pathway. Chylomicron remnants also induced mRNA expression of the pro-inflammatory cytokines, IL-2 and IFN-gamma in VSMCs. We conclude that chylomicron remnants act as atherogenic lipoproteins via induction of Egr-1 expression and via cytokine-mediated inflammation.

Animals↗
PubMed2005

EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22)(p21;q12).

POU5F1(OCT3/4) is a sequence-specific transcription factor that is essential for keeping germ cells and embryonic stem cells in an immature and pluripotent status. In this article, we report that POU5F1 was fused to EWSR1 in a case of undifferentiated sarcoma derived from pelvic bone with chromosomal translocation t(6;22)(p21;q12). The EWSR1-POU5F1 chimera consists of exons 1-6 of EWSR1 and exons 2-5 and a part of exon 1 of POU5F1. The predicted amino acid sequence indicates that the chimera is composed of the N-terminal QSY domain of EWS that functions as a transcriptional activation domain and the C-terminal POU DNA-binding domains derived from POU5F1. The t(6;22) tumor does not belong to any known categories of bone and soft-tissue tumors (BSTs). It is suggested that EWS-POU5F1 may act as an oncogenic transcription factor and that its expression may contribute to undifferentiated and immature phenotypes of BST.

Artificial Gene Fusion↗
PubMed2005

Meningioma arising in Werner syndrome confirmed by mutation analysis.

OBJECTIVE AND IMPORTANCE: Meningioma arising in Werner syndrome has been described previously, but never in association with a mutation analysis. We present the first reported case of meningioma in a patient with Werner syndrome and a confirmed major mutation. In addition, we review 27 previously reported patients with meningioma associated with Werner syndrome. CLINICAL PRESENTATION: We report a 56-year-old Japanese woman with Werner syndrome and a meningioma. She presented with pain and redness of the right eye and a headache. Cranial CT revealed a tumor the in right frontal and temporal lobes. Pathological examination after surgical removal confirmed meningioma. She displayed typical features of Werner syndrome including juvenile cataract, short stature and low weight, a bird-like face, a hoarse voice, and dry, atrophic, pigmented skin. INVESTIGATION: To confirm the clinical diagnosis, a mutation analysis based on the mutant allele-specific amplification (MASA) method was performed. CONCLUSION: Mutation analysis of peripheral blood leukocyte DNA showed amplification of the mutation 4/4. There were 22 patients with Werner syndrome and meningioma reported from Japan and 5 from outside Japan. There was only one malignant meningioma. Meningiomas in Werner syndrome have a higher frequency in males and occur at a younger age than those of the general population.

Adult↗
PubMed2005

Can one eat collaboration? Menus as metaphors of interprofessional collaboration.

The turn of the century has seen a sudden upsurge in publications and initiatives around the development of interprofessional collaboration in Japan. In Japanese, the term 'team-treatment' is generally used to mean interprofessional collaboration, but hitherto there have been no generally accepted definitions and conceptualizations of the term, nor are there guidelines as to how it may be implemented in practice. In order to facilitate understanding of the different modes of interprofessional collaboration and issues in practice, we introduced the use of menus as metaphors for interprofessional collaboration in a class of first year students of nursing. There were two 90-minute classes available for exploring this topic. Through the use of a metaphor the students demonstrated they were able to conceptualize interprofessional collaboration, identify the value of nurses working together with other professionals and issues involved in making team-treatment work. The purpose of this paper is to share the experience of using metaphors as a teaching/learning strategy, including reflection on the successes and some limitations of what, for us, was an interesting educational innovation.

Cooperative Behavior↗
PubMed2005

Pulmonary adenocarcinomas with enteric differentiation: histologic and immunohistochemical characteristics compared with metastatic colorectal cancers and usual pulmonary adenocarcinomas.

Primary pulmonary adenocarcinomas with enteric differentiation (PAED) are mainly composed of tall-columnar cells that show similarity to intestinal epithelia and colorectal carcinomas. In this study, we analyzed the immunostaining profiles of 7 PAEDs in comparison with 14 metastatic colorectal carcinomas (MCRs) and 30 usual pulmonary adenocarcinomas (PACs), using antibodies against CDX-2, cytokeratin 7 (CK7), cytokeratin 20 (CK20), TTF-1, surfactant apoprotein-A (SP-A), Napsin A, and MUC2. The positive rates for CDX-2, CK7, CK20, TTF-1, SP-A, Napsin A, and MUC2 were 71%, 100%, 43%, 43%, 14%, 0%, and 43%, respectively, in the PAEDs; 100%, 0%, 86%, 0%, 0%, 0%, and 57% in the MCRs; 3%, 100%, 0%, 93%, 73%, 90%, and 0% in PACs. As expected, immunoreactivity of CDX-2, CK20, and MUC2 was detected in PAEDs. The observed decrease or loss of immunoreactivity for TTF-1, SP-A, and Napsin A indicates that these lesions demonstrate a shift away from their pulmonary phenotype, although CK7 expression was retained. The results indicate that CK7 and CK20 may be useful markers for distinction of PAEDs from MCRs.

Adenocarcinoma↗
PubMed2005

Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern.

Micropapillary differentiation in adenocarcinomas has recently been associated with poor prognosis because these tumors are more likely to metastasize. However, no clear explanation exists as to why the presence of a micropapillary pattern is associated with metastasis. A case of primary lung adenocarcinoma with a prominent micropapillary pattern is presented here, with special reference to the immunohistochemical expression of the E-cadherin-mediated system and IQGAP1. Histologically, the tumor was diagnosed as a moderately differentiated papillary adenocarcinoma, showing an extensive micropapillary pattern, with intrapulmonary metastases, pulmonary disseminations, lymphovascular invasions, and lymph node metastases. Immunohistochemically, positive staining for the adhesion molecules E-cadherin, alpha-catenin, and beta-catenin was detected in both the micropapillary and non-micropapillary areas, whereas IQGAP1 was detected in the micropapillary, but not in the non-micropapillary, area. The adhesive function of E-cadherin depends on the integrity of the entire cadherin-catenin-actin network, and thus the expression of IQGAP1 may lead to adherens junction disassembly, and consequently, the release of carcinoma cells organizing in a micropapillary pattern. This is the first report to suggest correlation between adenocarcinoma with a micropapillary pattern and the presence of adhesion molecules, and offers an intriguing first glimpse on the role of the micropapillary pattern in the process of metastasis.

Adenocarcinoma↗
PubMed2005

Exercise- or dipyridamole-loaded QGS is useful to evaluate myocardial ischemia and viability in the patients with a history of Kawasaki disease.

BACKGROUND: Evaluation of myocardial ischemia and viability is very important for the management of patients with a history of Kawasaki disease (KD). (99m)Tc-tetrofosmin myocardial perfusion scintigraphy combined with quantitative gated single photon computed emission tomography (QGS) gives us information, not only about perfusion, but also the percentage change in left ventricular wall thickness (%WT) and relative changes in left ventricular wall motion (LVM). METHODS: The subjects were 27 patients with a history of KD followed as outpatients at the National Cardiovascular Center, Osaka, Japan. Exercise-loaded QGS was performed on 21 patients, and dipyridamole- loaded QGS was performed in six patients younger than 7 years old. RESULTS: Perfusion defects (PD) were observed in 12 patients. Of the 12 patients, four with old myocardial infarction (OMI) had decreased %WT. All patients with OMI showed a decrease in %WT in the areas where PD was seen on the image. The other eight patients without OMI showed no decrease in %WT. In non-infarcted cases, the %WT was normal in the PD-positive area. CONCLUSIONS: It is possible to evaluate myocardial ischemia and viability in KD patients by comparing PD on the image with %WT determined by QGS using exercise or drug-loaded myocardial scintigraphy alone.

Adolescent↗
PubMed2005

Successful treatment of chemo-refractory pulmonary metastases of renal pelvic cancer by second-line chemotherapy including gemcitabine followed by salvage surgery.

A 51-year-old woman developed multiple pulmonary metastases after receiving nephroureterectomy and two cycles of adjuvant chemotherapy for the treatment of renal pelvic transitional cell carcinoma. All metastases disappeared after four cycles of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by radiotherapy; however, 8 months later two pulmonary metastases recurred. The patient was entered into a phase I study of combination chemotherapy with gemcitabine, etoposide and cisplatin, designed for chemorefractory urothelial cancer. The lung masses showed significant reduction after two cycles of this chemotherapy; following salvage surgery, the patient has been well with no evidence of recurrence for more than 3 years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Prenatal diagnosis and management for a large fetal cardiac tumor complicated with hydrops fetalis.

Fetal cardiac tumor is a rare disease, and its prognosis varies in relation to the complications such as arrhythmia and out-flow obstruction. Hydrops fetalis is one of severe complications that result in an unfavorable outcome. A case is presented herein of a large fetal cardiac tumor diagnosed at 28 weeks gestation. At 30 weeks gestation, the fetus complicated with hydrops fetalis because of impaired cardiac function. Increased peak systolic velocity in the ascending aorta and marked reversed flow in the ductus venosus were observed. Oral digoxin therapy was administered to the mother as a cardiotonic agent and the hydropic condition was immediately diminished. After normal delivery, the cardiac tumor gradually decreased in size and the infant developed normally, but required an antiarrhythmic drug. The case indicates that the in utero digoxin therapy could be a choice for hydrops fetalis caused by cardiac tumor.

Adult↗
PubMed2005

Polymorphisms in four genes related to triglyceride and HDL-cholesterol levels in the general Japanese population in 2000.

We studied the association of six common polymorphisms of four genes related to lipid metabolism with serum lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the genes for cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (LIPC), and apolipoprotein CIII (APOC3), and studied 2267 individuals randomly selected from the participants of Serum Lipid Survey 2000. There was a significant association of CETP polymorphism (D442G, Int14 +1 G --> A, and TaqIB), LPL polymorphism (S447X), and LIPC polymorphism (-514 --> CT) with HDL-cholesterol levels. We also found a significant association of LPL polymorphism (S447X) and APOC3 polymorphism (SstI) with triglyceride levels. This is the largest database showing the association of common genetic variants in lipid metabolism with serum lipid levels in the general Japanese population. Further study is necessary to elucidate the role of these gene polymorphisms in cardiovascular events.

Apolipoprotein C-III↗
PubMed2005

Serum lipid survey and its recent trend in the general Japanese population in 2000.

To determine the recent serum lipid levels and other serum variables in the general Japanese population and trends in their changes over the past 40 years, a nationwide survey of serum lipid levels was conducted in 36 institutes from various districts around Japan in 2000. The total number of subjects was 12,839, aged 4 through 99 years. The mean total cholesterol level was 201 mg/dl; 202 mg/dl in men and 200 mg/dl in women. The mean HDL-cholesterol level was 59 mg/dl; 55 mg/dl in men and 65 mg/dl in women. The mean LDL-cholesterol level was 118 mg/dl; 121 mg/dl in men and 115 mg/dl in women. The mean triglyceride level was 118 mg/dl; 136 mg/dl in men and 92 mg/dl in women. The total cholesterol level slightly increased by 5 mg/dl in 10 years. Although the triglyceride level in women did not change, the triglyceride level in men increased over 10 years, especially in the 30s through 70s age bracket, indicating a possible increase in metabolic syndromes in the future. The present results will become the standard serum lipid level data for the Japanese people, and succeeding 10-year surveys will clarify the trends of lipid levels in this country.

Adolescent↗
PubMed2004

Cancer and aging: symposium of the 27th annual meeting of the Japanese society for biomedical gerontology, Tokyo.

Although many hypotheses have been proposed to explain the strong link between aging and cancer, the exact mechanisms responsible for the increased frequency of occurrence of cancer with advancing age have not been fully defined. Recent evidence indicates that malregulation of the apoptotic process may be involved in some aging process as well as in the development of cancer. Although it is still under debate how apoptosis is expressed during aging in vivo, this phenomenon is an important factor in unwinding the complicated mechanisms that link cancer and aging. In this review, we report on the discussion at the symposium of the 27th annual meeting of the Japanese society for biomedical gerontology, regarding recent findings from aging and carcinogenesis studies using animal models, the characteristics of cancer in patients with Werner's syndrome, the epigenetic changes in human cancers and aging, and the characteristics of human cancers in the elderly. It was concluded that apoptosis plays a role in the aging process and carcinogenesis in vivo, likely as an inherent protective mechanism against various kinds of damages to genes/chromosomes.

Aging↗
PubMed2004

Micropapillary clusters in early-stage lung adenocarcinomas: a distinct cytologic sign of significantly poor prognosis.

BACKGROUND: It is known that patients who have pulmonary adenocarcinomas with a pathologic micropapillary pattern (pMPP) featuring small papillary tufts that lack a central fibrovascular core have a poor prognosis. Although the pMPP initially was identified in surgical material, preoperative detection is desirable from the standpoint of making treatment decisions. Therefore, the authors focused on cytologic features resembling the pMPP in lung adenocarcinomas, with particular reference to the survival of patients with pathologic Stage I disease. METHODS: The authors reviewed clinical course data, preoperative cytologic specimens, and histologic materials from 110 patients with Stage I adenocarcinoma of the lung who presented between 1986 and 1995. Cytology of micropapillary clusters (MPCs) was characterized by round, 3-dimensional, cohesive clusters of neoplastic cells (consisting of > 3 cells and < 20 cells) with a pseudopapillary configuration. Total counts of cohesive clusters that consisted of more than three neoplastic cells on slides and frequencies of MPCs were investigated. RESULTS: All patients (54 females and 56 males) had a preoperative diagnosis of malignancy and underwent complete surgical resection. The patients with Stage I disease were subclassified into an MPC-positive group (n = 41) and an MPC-negative group (n = 69). The 5-year survival rate was 91.3% for patients in the MPC-negative group and 75.6% for patients in the MPC-positive group; this difference was statistically significant. CONCLUSIONS: MPC cytology is a distinct prognostic marker for early-stage lung adenocarcinoma with poor prognosis. The presence of this component, therefore, should alert the clinician to the need for close follow-up.

Adenocarcinoma↗
PubMed2004

Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles.

BACKGROUND: Classification of high-grade neuroendocrine tumours (HGNT) of the lung currently recognises large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC) as distinct groups. However, a similarity in histology for these two carcinomas and uncertain clinical course have led to suggestions that a single HGNT classification would be more appropriate. Gene expression profiling, which can reproduce histopathological classification, and often defines new subclasses with prognostic significance, can be used to resolve HGNT classification. METHODS: We used cDNA microarrays with 40?386 elements to analyse the gene expression profiles of 38 surgically resected samples of lung neuroendocrine tumours and 11 SCLC cell lines. Samples of large-cell carcinoma, adenocarcinoma, and normal lung were also included to give a total of 105 samples analysed. The data were subjected to filtering to yield informative genes before unsupervised hierarchical clustering that identified relatedness of tumour samples. FINDINGS: Distinct groups for carcinoids, large-cell carcinoma, adenocarcinoma, and normal lung were readily identified. However, we were unable to distinguish LCNEC from SCLC by gene expression profiling. Three independent rounds of unsupervised hierarchical clustering consistently divided SCLC samples into two main groups with LCNEC samples largely integrated with these groups. Furthermore, patients in one of the groups identified by clustering had a significantly better clinical outcome than the other (83% vs 12% survived for 5 years; p=0.0094. None of the highly proliferative SCLC cell lines subsequently analysed clustered with this good-prognosis group. INTERPRETATION: Our findings show that HGNT of the lung can be classified into two groups independent of SCLC and LCNEC. To this end, we have identified many genes, some of which encode well-characterised markers of cancer that distinguish the HGNT groups. These results have implications for the diagnosis, classification, and treatment of lung neuroendocrine tumours, and provide important insights into their underlying biology.

Biomarkers, Tumor↗
PubMed2004

Two GLOBOSA-like genes are expressed in second and third whorls of homochlamydeous flowers in Asparagus officinalis L.

Garden asparagus (Asparagus officinalis L.) has homochlamydeous flowers. Like Liliaceae plants such as lily and tulip, the perianths of asparagus have two whorls of almost identical petaloid organs, called tepals. Floral structures of these homochlamydeous flowers could be explained by a modified ABC model, in which the expression of the class B genes has expanded to whorl 1, so that the organs of whorls 1 and 2 have the same petaloid structure. In this study, we isolated and characterized two GLOBOSA-like genes (AOGLOA and AOGLOB), one of class B gene, from asparagus. Southern blot showed that AOGLOA and AOGLOB genes are single copy genes. Northern blot analysis indicated that these genes were specifically expressed in male and female flowers. In situ hybridization showed that the expression of AOGLOA and AOGLOB genes is confined to whorls 2 and 3 (inner tepal and stamen) and not detected in whorl 1 (outer tepal). The other asparagus class B gene, AODEF, was also not expressed in outer tepal [Park et al. (2003) Plant Mol Biol. 51: 867]. These results indicate that the class B genes are not involved in the outer tepal development in asparagus, not supporting the modified ABC model in asparagus.

Amino Acid Sequence↗