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Biomedical subjects

A Shimizu

Publications and source records attributed to A Shimizu.

At least 19 recordsLinked to original sources
PubMed2006

Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes.

AIMS/HYPOTHESIS: Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown. MATERIALS AND METHODS: We analysed expression of genes involved in OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with NGT using serial analysis of gene expression (SAGE) and DNA chip analysis. We evaluated the correlation between expression levels of genes involved in OXPHOS and the clinical parameters of individuals with type 2 diabetes and NGT. RESULTS: Both gene analyses showed that genes involved in OXPHOS were significantly upregulated in the type 2 diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that expression of genes involved in OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-alpha or peroxisome proliferator-activated receptor-gamma, was a predictor of fasting plasma glucose levels, independently of age, BMI, insulin resistance and fasting insulin levels (p = 0.04). Surprisingly, genes involved in OXPHOS did not correlate with peroxisome proliferator-activated receptor-gamma coactivator-1alpha or nuclear respiratory factor 1. CONCLUSIONS/INTERPRETATION: Our results indicate that upregulation of genes involved in OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, is associated with fasting hyperglycaemia in patients with type 2 diabetes.

Aged↗
PubMed2006

Differential cross section and photon-beam asymmetry for the gamma n --> K+ Sigma- reaction at E gamma = 1.5-2.4 GeV.

Differential cross sections and photon-beam asymmetries have been measured for the gamma n --> K+ Sigma- and gamma p --> K+Sigma0 reactions separately using liquid deuterium and hydrogen targets with incident linearly polarized photon beams of E gamma = 1.5-2.4 GeV at 0.6 < cos ThetacmK< 1. The cross section ratio of sigma K+ Sigma-/sigma K+ Sigma0, expected to be 2 on the basis of the isospin 1/2 exchange, is found to be close to 1. For the K+ Sigma- reaction, large positive asymmetries are observed, indicating the dominance of K* exchange. The large difference between the asymmetries for the K+ Sigma- and K+ Sigma0 reactions cannot be explained by simple theoretical considerations based on Regge model calculations.

Journal Article↗
PubMed2006

Simultaneous colorectal and liver resections for synchronous colorectal metastases.

BACKGROUND: The surgical strategy for the treatment of colorectal cancer and synchronous hepatic metastases remains controversial. Many surgeons fear anastomotic leakage and intraperitoneal abscesses when performing a one-step procedure. They prefer a two-step procedure with a liver resection 2 to 3 months after resection of the colorectal primary lesion. SUBJECTS AND METHODS: We analysed medical records from April 1994 to April 2002 for a total of 42 patients with colorectal cancer and synchronous liver metastases who underwent simultaneous liver and colorectal resections with a primary anastomosis. Special attention was paid to data on surgical procedures, postoperative morbidity, and mortality. RESULTS: Forty-two patients, 24 men and 18 women, were studied. Median operating time was 6.50 hours (3.75-11.0 hours), and median blood loss was 1522 ml (range 288 to 5650 ml). Postoperative complications included pleural effusion in 4 patients, ileus in 3, anastomotic leakage in 2, intraperitoneal pelvic abscesses in 1, pneumonia in 1, bile leakage in 1, atelectasis in 1, and wound infection in 1. There was no perioperative mortality. CONCLUSION: Simultaneous colorectal resection with a primary anastomosis and hepatectomy for synchronous liver metastases is considered a safe procedure.

Adult↗
PubMed2006

Plasma ghrelin levels in healthy elderly volunteers: the levels of acylated ghrelin in elderly females correlate positively with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure.

Aging is associated with a decrease in growth hormone (GH) secretion, appetite and energy intake. As ghrelin stimulates both GH secretion and appetite, reductions in ghrelin levels may be involved in the reductions in GH secretion and appetite observed in the elderly. However, only preliminary studies have been performed on the role of ghrelin in elderly subjects. In this study, we sought to clarify the physiologic implications of the age-related alterations in ghrelin secretion by determining plasma ghrelin levels and other clinical parameters in healthy elderly subjects. Subjects were > or = 65 years old, corresponding to the SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and had not been treated with hormones. One hundred and five volunteers (49 men and 56 women) were admitted to this study (73.4 +/- 6.3 years old). Plasma levels of acylated ghrelin in elderly female subjects positively correlated with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. In elderly men, desacyl ghrelin levels correlated only weakly with bowel movement frequency. These findings suggest that the plasma levels of the acylated form of ghrelin may influence the age-related alterations in GH/IGF-I regulation, blood pressure and bowel motility. These observational associations warrant further experimental studies to clarify the physiologic significance of these effects.

Acylation↗
PubMed2005

Rapid disease progression correlates with instability of mutant SOD1 in familial ALS.

Studies on the clinical course of familial ALS suggest that the duration of illness is relatively consistent for each mutation but variable among the different mutations. The authors analyzed the relative amount of mutant compared with normal SOD1 protein in the erythrocytes from 29 patients with ALS with 22 different mutations. Turnover of mutant SOD1 correlated with a shorter disease survival time.

Adult↗
PubMed2005

Loss of peritubular capillaries in the development of chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) remains the most important cause of late renal graft loss. In this study, we examined the role of peritubular capillary (PTC) injury in the development of CAN. METHODS: We studied renal biopsies (n = 79) obtained from grafts with CAN. PTC injury was examined morphologically by immunohistochemistry for CD34. These findings were correlated with interstitial fibrosis and graft dysfunction. Humoral immunity involved in CAN was studied by C4d staining. RESULTS: The CAN cases in the present study included chronic rejection (CR) (n = 14, 17.8%) and C4d-positive chronic humoral rejection (CHR; n = 6, 42.9% in CR cases). Irrespective of CR, CHR, or other CAN, the development of CAN was characterized by injury to and loss of identifiable PTCs, accompanied with the development of interstitial fibrosis. In CR and CHR cases, the loss of PTCs was prominent and seemed to progress within a relatively short period after transplantation. A decrease in the number of PTCs significantly correlated with the development of interstitial fibrosis (r = -0.75, P < .001) and impairment of graft function (r = -0.69, P < .001). CONCLUSIONS: Irrespective of whether CR, CHR, or other factors contribute to CAN, the processes involved in its development appear similar and are characterized by progressive injury and loss of PTCs, with the development of renal scarring. Immunohistochemistry for CD34 in human renal biopsies is a useful method for the detection of microvascular injury.

Antibody Formation↗
PubMed2005

Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference.

Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.

Adenoviridae↗
PubMed2005

Clinicopathological features of cutaneous lesions of adult T-cell leukaemia/ lymphoma.

BACKGROUND: Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). ATLL frequently involves the skin. OBJECTIVES: To correlate the clinicopathological features and prognosis in patients with ATLL and cutaneous lesions. METHODS: We examined the HTLV-I proviral state and the clinicopathological features of the cutaneous lesions in 80 patients with serum anti-ATL antibody, to clarify the correlation between macroscopic/histopathological findings and prognosis. Southern blot analysis was performed in all cases to detect monoclonal HTLV-I proviral DNA integration. RESULTS: The cutaneous lesions of 46 patients were positive for proviral DNA integration. The median survival time of patients with monoclonal proviral DNA integration in cutaneous lesions was 14 months, which was markedly shorter than that of patients negative for proviral DNA integration (72 months). Of the 46 patients with proviral DNA, 21 had solitary or multiple red nodules (including three with subcutaneous induration), eight had multiple red papules and 17 had erythema. Patients with papules and nodules had poorer prognosis than those with erythema. Histopathologically, the prognosis was poorer in patients with nodular or diffuse infiltration of medium-sized to large lymphoma cells, compared with those with perivascular infiltration of small to medium-sized lymphoma cells. CONCLUSIONS: Our results show a close correlation between clinicopathological features of HTLV-I-associated cutaneous lesions and prognosis.

Adult↗
PubMed2005

Prenatal exclusion of harlequin ichthyosis; potential pitfalls in the timing of the fetal skin biopsy.

BACKGROUND: Harlequin ichthyosis (HI) is a severe and usually fatal congenital skin disorder with autosomal recessive inheritance. Several cases of HI prenatal diagnosis have been performed using fetal skin biopsy, mainly at around 23 weeks estimated gestational age (EGA), and reported in the literature. However, prenatal testing must be done earlier than 21 weeks EGA in several countries including Japan where the present HI families live, because termination is legally allowed only until 22 weeks EGA. OBJECTIVES: We report the successful prenatal exclusion of HI in two fetuses from two independent families and discuss the technical difficulties and potential pitfalls in the prenatal exclusion of HI at early gestation stages. METHODS: Fetal skin biopsy specimens and amniotic fluid samples at 19 and 20 weeks EGA from two fetuses at risk of HI were examined by light and electron microscopy. RESULTS: For the prenatal diagnosis in case 1, the fetal skin biopsy samples were obtained at 20 weeks EGA and showed normal keratinization in the hair canals; no abnormalities were observed in the keratinized cells. In case 2, the interfollicular epidermis and the hair follicles in the samples obtained at 19 weeks EGA had not differentiated enough to show proper keratinization. However, lamellar granules were normally formed in the inner root sheath cells of the late bulbous hair pegs. From these ultrastructural findings, the case 1 fetus was diagnosed as unaffected with HI, and the case 2 fetus was diagnosed as unlikely to be affected. Subsequently, both were born as healthy, unaffected babies. CONCLUSIONS: The timing of biopsies at 19 weeks EGA is not ideal for fetal skin biopsy because the samples are not always sufficiently differentiated for the prenatal diagnosis of HI. However, morphological observations of lamellar granules gives us important additional information useful for HI prenatal diagnosis.

Amniotic Fluid↗
PubMed2005

Polymorphisms in PTCH1 affect the risk of ameloblastoma.

Ameloblastoma is the most common odontogenic tumor, but the genetic nature of the changes in the tumor cells has been unclear. Mutations of CTNNB1 or PTCH1 are observed in many human tumors. Both CTNNB1 and PTCH1 are important in tooth development and are expressed in ameloblastoma. The aim of this study was to investigate whether genetic alterations of CTNNB1 and PTCH1 are present in ameloblastoma. We investigated 14 cases of ameloblastoma. The polymorphisms found in the ameloblastoma patients were further examined in a subsequent case-control study. We found a CTNNB1 mutation in one case of plexiform-type ameloblastoma. CGG triplet repeat-number polymorphism (CGG7/CGG8) in the 5'-untranslated region of PTCH1 was observed. The proportion of CGG8 alleles was significantly higher in the ameloblastoma group. The results of this study indicate a possible relationship between the CGG8 allele in PTCH1 and the risk for ameloblastoma.

Adult↗
PubMed2004

Identification of zonal flows in a toroidal plasma.

This Letter presents experimental confirmation of the presence of zonal flows in magnetically confined toroidal plasma using an advanced diagnostic system--dual heavy ion beam probes. The simultaneous observation of an electric field at two distant toroidal locations (approximately 1.5 m apart) in the high temperature (approximately 1 keV) plasma provides a fluctuation spectrum of electric field (or flow), a spatiotemporal structure of the zonal flows (characteristic radial length of approximately 1.5 cm and lifetime of approximately 1.5 ms), their long-range correlation with toroidal symmetry (n=0), and the difference in the zonal flow amplitude with and without a transport barrier. These constitute essential elements of turbulence-zonal flow systems, and illustrate one of the fundamental processes of structure formation in nature.

Journal Article↗
PubMed2004

Effect of mutated transporters associated with antigen-processing 2 on characteristic major histocompatibility complex binding peptides: analysis using electrospray ionization tandem mass spectrometry.

A novel allele of transporters associated with the antigen-processing (TAP) 2 gene, TAP2*Bky2 (Val(577)), is significantly increased in Japanese patients with Sjögren's syndrome (SS), and has a strong association with SS-A/Ro autoantibody production in SS and autoantibody including anti-SS-A/Ro and anti-U1 RNP antibody in systemic lupus erythematosus (SLE). To determine the influence of this natural mutated TAP on peptides loaded onto MHC class I, we analyzed the repertoire of peptides loaded onto MHC class I on transfectants with TAP1 and TAP2 or mutated TAP2 by electrospray ionization tandem mass spectrometry (ESI-MS/MS). After comparison of the peptide profiles we identified three peptides from only mutated TAP transfectants. Moreover, one of these peptides is derived from snRNP A, which is a target for anti-U1 RNP antibody. To our knowledge this is the first report to show that the natural mutation of TAP2 changes the peptide profile loaded onto MHC class I molecules.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Utilization of sludge in building material.

Several thermal solidification processes have been developed mainly in Japan. They are lightweight aggregates, brick, interlocking tile, char, and slag. A full-scale plant of them has been successfully operated for more than 10 years. The quality of the end products is better than the traditional ones. They are all substitutive to existing ones. The Japanese experience proves that all the processes are technically feasible, but not economically. Their manufacturing cost is always higher than market price. In addition, they consume large amounts of energy. However, if they are identified for a process of sludge disposal, all of them are worth considering for a big city where there is no place for the sludge to go. The end products can be reused inside the city. A new alternative is "Portland cement". A Portland cement manufacturer accepts sewage sludge, if being paid some amount of money. An average payment is US$100 each 1,000 kg of ash or sludge cake. The Portland cement manufacturer accepts either cake or ash at the same price. It is about 50 to 30% of the energy cost of thermal solidification. The question is which is the better, dewatered cake or incinerated ash, for the Portland cement application. The answer is "it depends on the distance between the sewage plant and the Portland cement plant."

Calcium Compounds↗
PubMed2003

First case of a single heterozygote of an abnormal hemoglobin, Hb Stanmore, [beta111(G13)Val-->Ala].

We describe a hemoglobin beta-chain mutant detected incidentally in an unusual profile of glycated hemoglobin (HbA1c) measured by ion-exchange HPLC. Analysis of intact globin by electrospray ionization mass spectrometry (ESI-MS) and peptide analysis by on-line HPLC-ESI-MS-MS revealed the substitution, [beta111(G13)Val-->Ala], which was confirmed by DNA analysis. This was the second case of Hb Stanmore. As the first case combined beta(0)-thalassemia, and the family study in that case showed no case of Hb Stanmore without combined thalassemia, the case presented here is the first case of single heterozygote, and the first Japanese case. Hb Stanmore is isoelectrophoretically silent with only mild clinical symptoms, although stability by isopropanol test was positive.

Adult↗