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Biomedical subjects

N Matsuura

Publications and source records attributed to N Matsuura.

At least 19 recordsLinked to original sources
PubMed2006

Expression of PPARdelta in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology.

Whether peroxisome proliferator-activated receptor (PPAR) delta is a good target for the chemoprevention and/or treatment of colorectal cancer (CRC) remains controversial. Our goal was to examine PPARdelta expression in multistage carcinogenesis of the colorectum and to assess the relevance of PPARdelta in CRC. Immunohistochemical analysis indicated that PPARdelta expression increased from normal mucosa to adenomatous polyps to CRC. In cancer tissues, the PPARdelta protein was accumulated only in those cancer cells with highly malignant morphology, as represented by a large-sized nucleus, round-shaped nucleus, and presence of clear nucleoli. Interestingly, the cancer tissue often contained both PPARdelta-positive and -negative areas, each retaining their respective specific morphological features. Moreover, this pattern persisted even when PPARdelta-positive and -negative cells were aligned next to each other within a single cancer nest or gland and was present in the majority of CRC cases. Immunohistochemistry for Ki-67 proliferation marker showed no significant correlation between Ki-67 and PPARdelta in CRC samples. Based on Western blot analysis and quantitative RT-PCR, high PPARdelta protein expression correlated with high PPARdelta mRNA levels. Peroxisome proliferator-activated receptor delta may have a supporting role in tumorigenesis, and the close association between PPARdelta expression and malignant morphology of CRC cells suggests a pivotal role in cancer tissue.

Adenocarcinoma↗
PubMed2006

Type 1 diabetes in Japan.

Type 1 diabetes is a multifactorial disease which results from a T-cell-mediated autoimmune destruction of the pancreatic beta cells in genetically predisposed individuals. The risk for individuals of developing type 1 diabetes varies remarkably according to country of residence and race. Japan has one of the lowest incidence rates of type 1 diabetes in the world, and recognises at least three subtypes of the condition: acute-onset ('classical'), slow-onset, and fulminant type 1 diabetes. The incidence rate of type 1 diabetes in children aged 0-14 years in Japan increased over the period from 1973-1992, but remained constant over the last decade, averaging 2.37 cases per 100,000 persons per year; the incidence does not appear to have increased in older age groups. Although there are few reports regarding the incidence and prevalence of type 1 diabetes in adult-onset patients, it appears that the prevalence of type 1 diabetes in adults is more than twice that in childhood-onset patients and that two-thirds of them have a slow-onset form of type 1 diabetes. Differences and similarities in the association of MHC and non-MHC genes with type 1 diabetes are observed in Japan and in countries with Caucasoid populations. Highly susceptible class II HLA haplotypes identified in patients of Caucasoid origin are rarely seen in Japanese patients, whereas protective haplotypes are universal. Non-MHC genes associated with susceptibility to type 1 diabetes in both Japanese and Caucasoid patients include polymorphisms in the insulin gene, the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, the interleukin-18 (IL18) gene and the major histocompatibility complex class I chain-related gene A (MICA) gene. Fulminant type 1 diabetes is a unique subtype of type 1 diabetes that accounts for about 20% of acute-onset type 1 diabetes, and is seen mainly in adults. The challenge for the future is to investigate the underlying pathogenesis of beta cell destruction, including the genetic or environmental factors that may modify the form of onset for each subtype of Japanese type 1 diabetes.

Adolescent↗
PubMed2006

Preoperative portal vein embolization with a mixture of gelatin sponge and iodized oil: efficacy and safety.

PURPOSE: To evaluate whether portal vein embolization (PVE) using a mixture of gelatin sponge (GS) pieces and iodized oil is safe and effective in inducing hypertrophy of the future liver remnants (FLR). MATERIAL AND METHODS: PVE was performed in 14 patients (eight male and six female, mean age 65 years, range 35-81 years) diagnosed with malignant liver tumor before surgery, whose FLR volumes were judged too small to allow for safe resection. Liver volume change, biochemical data change, complications related to PVE, and postoperative complications were retrospectively evaluated. RESULTS: PVE was successful in all patients, and there were no procedural complications. Absolute FLR volume and FLR/total liver volume (TLV) ratio increased by 102 cm3 and 8% (mean values), respectively. Planned hepatectomies were cancelled in three patients due to extrahepatic metastasis or bile duct infection. Five of the 11 patients (45%) who underwent hepatectomies had major postoperative complications. However, complications due to hepatic failure were not seen. In 10 patients, except one whose outcome was fatal outcome, the mean hospitalization days with and without major complications were 73 and 33 days, respectively. CONCLUSION: PVE using a mixture of GS and iodized oil seems to be effective and safe in inducing hypertrophy of the FLR.

Adult↗
PubMed2006

Association study of polymorphisms in SOCS family genes with type 1 diabetes mellitus.

Suppressors of cytokine signalling (SOCS) proteins play important roles in the negative regulation of cytokine signal. We first searched for polymorphisms in SOCS-1, SOCS-3 and SOCS-5 genes, and examined the association of the polymorphisms with type 1 diabetes (T1D). As a result, we did not find any significant associations between SOCS genes and T1D.

Case-Control Studies↗
PubMed2006

[Extensive educational program for high performance medical technologists].

The education system for medical technologists has recently been revolutionized, their educational periods vary from 2 to 9 years, and some already have doctoral degrees. In such a new situation, our faculty thinks that the most important point for new medical technologists is the ability to have a broad view of the clinical fields, especially the view of patients. Special training in bed-side education and a stint in several divisions, such as the surgical operation room, rehabilitation. radiological examination room, pharmacy, central storage room of medical records, and medical informatics, and so on, of the hospital is a powerful tool to obtain a broad view of the various clinical fields and can be essential for developing high performance medical technologists. As nine years have passed since starting this education, we evaluated this practice through systematic personal communication. As a result, it was found to be extremely effective for many reasons such as having a continuous image of the patient when they examine the blood sample in the hospital laboratory, showing advanced laboratory performance, and having no mental barrier to visiting the wards and so on. The abilities of our alumni are praised highly by many large scale hospitals around the country and 50% of them are working in the clinical laboratory division of these hospitals. About 40% are working in the division of research and development in various companies. We express sincere thanks to the director and all cooperative individuals for this course in the Osaka University Hospital.

Curriculum↗
PubMed2004

Polo-like kinase 1 overexpression is an early event in the progression of papillary carcinoma.

Polo-like kinase 1 (PLK1) is one of the serine threonine kinases that contributes to cell mitosis and is regarded as a marker of cellular proliferation. However, its protein expression in human carcinoma has not been studied in depth. We investigated PLK1 expression in various thyroid neoplasms in order to elucidate its physiological significance in thyroid carcinoma. Normal follicular cells only occasionally expressed PLK1. In follicular tumours and anaplastic carcinoma, PLK1 overexpression was not a common event and only 5.9% of follicular adenoma, 7.1% of follicular carcinoma, and 11.8% of anaplastic carcinoma overexpressed this protein. However, 43.7% of papillary carcinoma overexpressed PLK1. Polo-like kinase 1 overexpression was more frequently observed in smaller papillary carcinoma lesions, and 62.5% of microcarcinoma (ranging from 4 mm to 1.0 cm) and even 66.7% of incidental carcinoma (less than 4 mm) overexpressed it, whereas this phenomenon could only be seen in 20.0% of lesions larger than 4.0 cm. Furthermore, PLK1 overexpression was not related to cell-proliferating activity evaluated by Ki-67 labelling index, but it was inversely linked to UICC stage, extrathyroidal invasion, and the presence of poorly differentiated lesion as proposed by Sakamoto et al. These findings strongly suggest that, unlike other carcinomas previously studied, PLK1 does not act as a cell cycle regulator but plays a constitutive role in papillary carcinoma especially in the early phase, and may contribute to the malignant transformation of this carcinoma.

Blotting, Western↗
PubMed2004

Effects of a novel antihyperlipidemic agent, S-2E, on the blood lipid abnormalities in homozygous WHHL rabbits.

To improve mixed hyperlipidemia in the low-density lipoprotein (LDL) receptor-deficient state, suppression of very-low-density lipoprotein (VLDL) particle production may be an important approach. We previously reported that S-2E, (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl] methoxybenzoic acid, suppressed VLDL particle production by inhibiting the biosynthesis of both sterol and fatty acids in the liver. We therefore examined whether S-2E lowered the blood cholesterol and triglyceride (TG) levels simultaneously in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, which correspond to human familial hypercholesterolemia. S-2E given orally at doses of 30 to 300 mg/kg significantly lowered serum total cholesterol (TC) levels at 1 week as well as TG at 2 weeks, and the lowering of TC and TG levels by S-2E reached a maximum at 3 to 4 weeks. In contrast, oral administration of pravastatin at doses of 10 to 100 mg/kg resulted in a significant suppression of TC levels (100 mg/kg) but not TG levels. Further analysis of the TC content in fractionated serum of control and S-2E-treated animals showed that suppression of TC level by S-2E is attributable to a decrease in the proportions of VLDL, intermediate-density lipoprotein (IDL), and LDL. It is, therefore, reasonable to assume that S-2E may be useful to improve the blood lipid abnormalities in the LDL receptor-deficient state.

Animals↗
PubMed2004

Helicobacter bilis infection in biliary tract cancer.

BACKGROUND: Biliary tract cancer is a highly fatal disease with poor prognosis, but the aetiology is poorly understood. AIM: We aimed to identify Helicobacter bilis infection in the gallbladder in patients with biliary tract disease. METHODS: Archival gallbladder specimens from 34 patients (14 males and 20 females) with an average age of 61.4 +/- 12.2 years (mean +/- SE) were retrieved, consisting of 11 cases of gallbladder cancer, three of bile duct cancer, 16 of cholecystolithiasis and four of pancreatic cancer. DNA was extracted and nested PCR using primers specific for 16S rRNA of H. bilis was performed. RESULTS: Amplification was observed in 3 of 11 gallbladder cancer cases (27.2%) and one of three cases with biliary duct cancer (33.3%). In total, four of 14 cases with biliary tract cancer were positive for H. bilis (28.6%). In addition, the presence of H. bilis was shown in two of 16 cases (12.5%) with cholecystolithiasis. Notably, although the number of cases examined was small, none of the four cases with pancreatic cancer showed the presence of H. bilis infection in the gallbladder without apparent abnormalities. CONCLUSION: H. bilis infection may play a role in biliary tract disease, particularly in biliary tract cancer.

Biliary Tract Neoplasms↗
PubMed2004

Promoter polymorphism of SLC11A1 (formerly NRAMP1) confers susceptibility to autoimmune type 1 diabetes mellitus in Japanese.

Defective function of antigen-presenting cells has been postulated to be one of the non-HLA-linked susceptibility factors for type 1 diabetes mellitus, though the underlying genetic factors remain unclear. SLC11A1 (formerly NRAMP1), a divalent cation transporter, plays a crucial role in macrophage activation. We performed a case-control study in 224 healthy and 95 type 1 diabetic Japanese subjects, examining the length polymorphisms in the promoter region (-377 to -222) of SLC11A1, which may influence transcriptional activity. Alleles designated 2, 3, and 7 have been identified in Japanese subjects. The frequency of allele 7 was significantly higher in subjects with type 1 diabetes (9.47%) than in the healthy controls (4.46%). The difference is more marked in the subpopulation of Japanese subjects with type 1 diabetes; diabetic subjects with at least one protective HLA class II allele and those without any susceptibility HLA class II haplotypes, DR4-DQ4 or DR9-DQ9, had a much higher allele 7 frequency than controls. These findings suggest that the novel promoter polymorphism of SLC11A1 influences the susceptibility to type 1 diabetes in Japanese subjects.

Adolescent↗
PubMed2003

Expression level of integrin alpha 5 on tumour cells affects the rate of metastasis to the kidney.

Tumour metastasis is known clinically to have organ specificity. We hypothesised that integrins might be involved in determining the organ specificity of tumour metastasis. Here, we report the results of spontaneous metastasis tested in nude mice that were inoculated with Chinese hamster ovary (CHO) cells expressing integrin alpha 5 beta 1 at various levels. The growth of the primary tumour inversely correlated with the alpha 5 expression level on CHO cells, which is consistent with a previous report (Schreiner et al, 1991). The rates of pulmonary, lymph node, and adrenal metastases that developed in nude mice were not related to changes of the alpha 5 expression level on CHO cells. Kidney metastasis developed in 40% of nude mice inoculated with alpha 5B2 cells (CHO cells overexpressing alpha 5) and in 20% of mice with CHO-K1 cells (CHO cells expressing native alpha 5), whereas inoculation with CHO-B2 cells (alpha 5-defective mutants) and alpha 5CHO cells with the highest expression of alpha 5 did not lead to development of kidney metastasis. Furthermore, alpha 5CHO, which shows the slowest growth of these cell types, did not lead to primary tumours in nude mice. These findings suggest that there is an appropriate level of alpha 5 expression on tumour cells that leads to metastasis. Microscopic observations revealed that micrometastasis in the kidney was formed in glomeruli. An adhesion assay using frozen sections of the kidney demonstrated that alpha 5B2 cells, but not CHO-B2 cells, effectively adhered to glomeruli. Kidney metastasis in vivo and the adhesion of alpha 5B2 to glomeruli shown ex vivo were significantly suppressed by the administration of GRGDS peptide. Finally, we conclude that the interaction of alpha 5 beta 1 on tumour cells with fibronectin in kidney glomeruli is involved in kidney metastasis and that the tumour has appropriate levels of integrins crucial for metastasis.

Adrenal Gland Neoplasms↗
PubMed2003

Cyclooxygenase-2 expression in thyroid neoplasms.

AIMS: Previous studies have demonstrated that cyclooxygenase-2 (COX-2) plays a role in carcinogenesis and carcinoma development. In this study, we investigated its expression in thyroid neoplasms in order to elucidate its role. METHODS AND RESULTS: COX-2 expression was studied immunohistochemically in 20 anaplastic (undifferentiated) carcinomas, 49 papillary carcinomas, 22 follicular carcinomas and 15 follicular adenomas. Positive staining was only occasionally seen in normal follicles or stromal cells. COX-2 over-expression was found in only 20.0% of follicular adenomas and 40.9% of follicular carcinomas. In papillary carcinomas, the incidence (81.3%) was significantly higher (P < 0.0001) than in follicular carcinomas, although COX-2 expression was reduced in cases with old age (P = 0.0190), large size (P = 0.0028), advanced stage (P = 0.0225), satellite tumours (P = 0.0363), and the presence of solid, scirrhous or trabecular growth patterns (P = 0.0018). Undifferentiated carcinomas less frequently over-expressed COX-2 (P = 0.0004), with an incidence of 40.0%. CONCLUSIONS: These results indicate that the up-regulation of COX-2 may contribute predominantly in the early phase of papillary carcinoma progression, whereas it plays a more adjuvant role in follicular carcinoma progression.

Carcinoma↗
PubMed2003

Syndecan-1 expression in thyroid carcinoma: stromal expression followed by epithelial expression is significantly correlated with dedifferentiation.

AIM: To investigate the expression of syndecan-1 in thyroid neoplasia. Syndecan-1 is a proteoglycan regulating cell adhesion. Previous studies have demonstrated that decreased expression of syndecan-1 is linked to malignant progression. METHODS AND RESULTS: Syndecan-1 expression in thyroid neoplasia was studied immunohistochemically. Syndecan-1 was expressed in stromal cells as well as neoplastic epithelial cells. Stromal syndecan-1 expression was observed more frequently in papillary carcinomas larger than 10 mm in size than in microcarcinomas and in widely invasive than in minimally invasive follicular carcinomas. Furthermore, poorly differentiated carcinomas showed this phenomenon more than well-differentiated carcinomas, but the expression in undifferentiated carcinomas was similar to that of poorly differentiated carcinomas. Epithelial syndecan-1 expression was more frequently observed in anaplastic (undifferentiated) carcinomas than in papillary and follicular carcinomas. No significant difference in epithelial expression was found between well and poorly differentiated carcinomas, but undifferentiated carcinomas expressed epithelial syndecan-1 more frequently than did poorly differentiated carcinomas. CONCLUSIONS: These results are in contrast to those previously reported for carcinomas at other sites. It is suggested that the role of syndecan-1 in thyroid carcinomas might be unique. Stromal syndecan-1 expression followed by its epithelial expression is significantly related to progression, including dedifferentiation of thyroid carcinoma.

Adenocarcinoma↗
PubMed2002

Expression of cdc25A and cdc25B proteins in thyroid neoplasms.

Cdc25B and cdc25A phosphates are prominent stimulators of cell cycle progression and recent studies have also suggested their oncogenic roles. To elucidate the role of these proteins in thyroid neoplasms, we immunohistochemically investigated their expression, and neither protein was expressed in normal follicular cells. Cdc25B was frequently overexpressed in follicular adenoma and minimally invasive follicular carcinoma, but the incidence was significantly lower in widely invasive follicular carcinoma. Furthermore, the cdc25B expression level significantly decreased with the dedifferentiation of thyroid carcinoma. Cdc25A overexpression was observed in high incidences in all types of thyroid neoplasms. These results suggest that cdc25B and cdc25A play oncogenic roles in thyroid follicules and that cdc25B works predominantly in the early phase of the progression of thyroid carcinoma, whereas cdc25A plays a fundamental role in the development of thyroid neoplasms.

Adenoma↗
PubMed2002

Caveolin-1 overexpression is an early event in the progression of papillary carcinoma of the thyroid.

Caveolin-1 is a major structural component of caveolae, which are plasma membrane microdomains implicated in the regulation of intracellular signalling pathways. Previous in vitro and in vivo studies on the function of caveolin-1 in carcinoma showed controversial results, indicating that the physiological role of caveolin-1 varies according to the origin of carcinoma. In this study, we investigated caveolin-1 expression in thyroid neoplasms by means of immunohistochemistry using a rabbit polyclonal antibody against caveolin-1. Normal follicular cells did not express caveolin-1. In papillary carcinoma, caveolin-1 expression was observed in high incidence, and especially in microcancer (less than 1.0 cm in diameter), caveolin-1 was positive in all cases except one. In undifferentiated (anaplastic) carcinoma, its incidence was significantly reduced. On the other hand, all cases of follicular carcinoma and adenoma were classified as negative for caveolin-1. These results suggest that caveolin-1 may play a role predominantly in the early phase of papillary carcinoma, whereas it has little influence on follicular tumours.

Adenoma↗
PubMed2002

Synthesis of functionally graded MgCO3 apatite accelerating osteoblast adhesion.

As a means of improving the biological properties of materials for use as bone substitutes, functionally graded carbonate apatite containing Mg, FGMgCO3Ap, was synthesized at 60 degrees C and pH 7.4 using a gradient magnesium supply system. X-ray diffraction analysis of FGMgCO3Ap showed a poorly crystallized apatitic pattern, similar to that of human bone. ESCA analysis clearly showed the negative gradient distribution in Mg1s intensity (atomic concentration) of magnesium from the crystal surface toward the inner core. When the FGMgCO3Ap crystals were mixed with collagen, the resulting FGMgCO3Ap-collagen composite, irradiated with UV light for 4 h, retained their features in the saline solution. After washing away the nonadhesive cells, a cell adhesion assay showed that the optical density of the FGMgCO3Ap-collagen composite was higher than that of the CO3Ap-collagen composite. SEM observation showed that the osteoblast-like cells adhered well to the surface of the FGMgCO3Ap-collagen composite. Staining with hematoxylin-eosin and alizarin red confirmed the existence of a great many more cells and a thicker extracellular matrix layer on the FGMgCO3Ap-collagen composite than on the CO3Ap-collagen composite. This result demonstrated the acceleration effect of magnesium ions on osteoblast adhesion on the FGMgCO3Ap-collagen composite.

Animals↗
PubMed2002

Association study between CD30 and CD30 ligand genes and type 1 diabetes in the Japanese population.

CD30-CD30 ligand (CD30L) signal transduction appears to protect against autoimmune diabetes by preventing expansion of autoreactive T cells and suppressing Th1-cytokine response. The purpose of this study was to determine whether CD30 or CD30L genes serve as a novel susceptibility gene for type 1 diabetes in humans. We screened CD30 and CD30L genes for polymorphisms in Japanese patients with type 1 diabetes and control subjects. Then, association studies were performed between each of the identified polymorphisms and type 1 diabetes. Direct-sequencing analysis of the CD30 and CD30L genes revealed four polymorphisms: one in the CD30 gene (-201G/A from the transcription start site), and three in the CD30L gene [CA repeat in the promoter, 276G/A in the exon 3, -73T/C in the intron 3 (IVS3 -73T/C)]. Association studies revealed no association between the CD30 and CD30L genes and type 1 diabetes in the whole population. In the female and male subpopulations, however, the frequency of (CA)(9) allele of the CD30L gene promoter or T allele of IVS3 -73T/C polymorphism in the CD30L gene was slightly higher in female patients with type 1 diabetes than that in control females. In conclusion, we could not find significant association between CD30 or CD30L genes and type 1 diabetes, but (CA)(9) allele in the promotor or T allele of -73T/C in intron 3 in CD30L gene might play a minor role in the pathogenesis of type 1 diabetes, only in the Japanese female population.

Adolescent↗
PubMed2002

Induction of peripheral mononuclear cell apoptosis in asthmatic patients in remission.

Apoptosis regulates inflammatory cell survival in allergic inflammation, and decreased apoptosis contributes to the chronicity of inflammation. To investigate the mechanisms of onset and remission of mite-sensitive childhood asthma, we evaluated peripheral blood mononuclear cell apoptosis in patients with asthma and in remission. There was a similar percentage of hypodiploid cells in unstimulated mononuclear cell cultures from patients with active asthma (29.5+/-5.0%) and normal individuals (25.9+/-4.9%). In contrast, the percentage increased in patients in remission (44.5+/-3.2%). In Dermatophagoides farinae (Df) antigen-stimulated mononuclear cell, the stimulation index was lower in patients with active asthma (0.95+/-0.06%) than in normal individuals (1.31+/-0.16%). In contrast to active patients, the proportion of hypodiploid cells stimulated with Df in patients with remission was equivalent to that of normal controls. After phytohemaglutinin (PHA) stimulation, the percentage of hypodiploid cells in patients with active asthma (35.1+/-3.2%) was also lower than in normal individuals (48.5+/-4.3%) or patients in remission (49.5+/-5.7%). Apoptosis occurred predominantly in CD8+, but not CD4+, cells in patients in remission. Interleukin IL-2 inhibited apoptosis in Df-activated cells in normal individuals, whereas IL-2 did not inhibit apoptosis in cells from patients in remission as well as with active asthma. The expression of Fas receptors on resting mononuclear cells was similar in the three groups. However, Fas receptor expression in Df-stimulated mononuclear cells was greater in patients with active asthma than in healthy individuals. In patients with remission that was equivalent to healthy controls. The PHA increased Fas expression to a similar degree in the three groups. With regard to Fas ligand, the expression was lower in unstimulated cultured mononuclear cells from patients than in normal individuals. In patients in remission that was comparable to normal individuals. The Df stimulation upregulated the Fas ligand in patients with active asthma, and downregulated it in patients in remission. In conclusion, apoptosis in Df-stimulated mononuclear cells is impaired in patients with active asthma, while spontaneous apoptosis of CD8+ cells in vivo is augmented in patients in remission, and may be involved in the onset and remission of mite-sensitive asthma.

Adolescent↗