Biomedical subjects

N Sato

Publications and source records attributed to N Sato.

At least 37 records · Page 2Linked to original sources

PubMed2005

Allelic loss analysis of early-stage flat-type colorectal tumors.

BACKGROUND: Flat-type colorectal tumors are rare, but are known for their unusual flat morphology and aggressive clinical behavior despite their small size. To identify distinct genetic alterations, loss of heterozygosity (LOH) analysis was performed on microdissected tissues. MATERIALS AND METHODS: DNA was extracted from multiple microdissected foci in 43 cases of early-stage flat-type colorectal tumors and LOH analysis was performed on 2q, 4q, 5q, 12q, 14q, 15q, 17p, 18q, 18p and 22q. RESULTS: LOH patterns were detected in one of two forms: (i) homogeneous LOH throughout the microdissected foci, which indicated the early acquisition of LOH; and (ii) heterogeneous LOH, which were detected in a part of analyzed foci. Homogeneous and heterogeneous LOH were most frequently detected on 17p (92%) followed by 18q (81%), 18p (81%), 5q (61%), 22q (51%), 14q (44%), 15q (41%), 2q (39%), 12q (36%) and 4q (32%). Homogeneous LOH was detected most frequently on 17p (68%) followed by 18p (53%), 18q (53%), 22q (34%) and 12q (27%). The average fractional allelic loss (FAL) for heterogeneous and homogeneous LOH was 0.57 and the average FAL for homogeneous LOH was 0.37. CONCLUSIONS: Early flat-type colorectal tumors frequently shows the early occurrence of multiple LOH including 17p, 18p, 18q and 22q, which is coupled with additional LOH of other loci either simultaneously or in the early clonal progression phase. The extent and sequences of LOH may be the mechanisms responsible for the aggressive clinical behaviors of these tumors.

Adult↗

PubMed2005

Quantitative evaluation of anterior tibial translation during isokinetic motion in knees with anterior cruciate ligament reconstruction using either patellar or hamstring tendon grafts.

We studied 79 patients with unilateral injury to the anterior cruciate ligament (ACL). The patients were randomly allocated to reconstruction with autologous patellar bone-tendon-bone (BTB) grafts (49 knees) or hamstring tendon (ST) grafts (30 knees). We measured anterior tibial translation (ATT) during isokinetic concentric contraction exercise 18-20 months after surgery using a computerized electrogoniometer. In both groups the highest ATT during exercise was observed at a knee flexion of about 20 degrees and was 13.5+/-3.0 mm in the BTB group and 13.9+/-3.4 mm in the ST group. There was no difference in the ATT between the reconstructed and healthy knees. For a range of knee flexion between 30 and 50 degrees the ATT in the ST group was significantly higher on the reconstructed side than on the healthy side. In the BTB group, the mean ATT in the reconstructed group was similar to that on the healthy side at a knee flexion angle between 0 and 90 degrees .

Adolescent↗

PubMed2005

Metastases-related genes in the classification of liver and peritoneal metastasis in human gastric cancer.

INTRODUCTION: With the aim of identifying metastases-related genes in gastric cancer, we performed a broad analysis of differential gene expression between low-metastatic parental cell lines and established highly metastatic sublines. MATERIALS AND METHODS: We established novel cell lines, AZ-H5c, NUGC-3H5, and TMK-1H7, with a high potential of liver metastasis, and AZ-P7a, NUGC-3P4T, and TMK-1P4a, with a high potential of peritoneal metastasis. These cell lines were derived from low-metastatic parental AZ-521, NUGC-3, and TMK-1 cell lines, respectively. Furthermore, to investigate different levels of gene expression implicated in metastatic potentials in gastric cancer, we investigated approximately 2000 expressed genes in each cell line using a DNA microarray. RESULTS: Varieties of genes were up-regulated or down-regulated in highly metastatic liver and peritoneal cell lines. Fifty-eight genes, including the transferrin receptor, ras-related rho, and osteopontin, and 22 genes, including apolipoprotein E and inhibin A-submit, were up-regulated and down-regulated in two or three liver metastatic sublines. On the other hand, 19 genes, the transferrin receptor, c-fos, and RANTES, and 26 genes, including MAC25, PISSLRE, and RNA polymerase, were up-regulated and down-regulated in two or three peritoneal metastatic sublines. CONCLUSION: How gene expression is implicated in gastric cancer metastasis has never been thoroughly explained, and further studies are necessary to understand the involvement of genes in cancer metastasis more thoroughly. We hope that our highly metastatic liver and peritoneal experimental models are helpful for further study and gene therapy of human gastric cancer.

Cell Line, Tumor↗

PubMed2005

Aberrant methylation of the Human Hedgehog interacting protein (HHIP) gene in pancreatic neoplasms.

Hedgehog pathway overactivity has been implicated in the development of a variety of human cancers. The Human Hedgehog interacting protein (HHIP), a negative regulator of hedgehog signaling, has been shown to be underexpressed in pancreatic cancers. In this study we determined if the HHIP gene is a target for genetic and epigenetic alterations. While no mutations of HHIP were identified, we found complete methylation of the HHIP promoter CpG island in three pancreatic cancer cell lines, and partial hypermethylation in 13/17 (80%) pancreatic cancer cell lines, 35/75 (46%) primary pancreatic cancers and 14/18 (78%) pancreatic cancer xenografts, but no methylation in 13 normal pancreata. In pancreatic cancer cell lines, complete methylation was associated with absent or reduced HHIP expression by real-time RT-PCR. HHIP expression could be restored in methylated cell lines using epigenetic modifier drugs. Restoring the expression of HHIP in pancreatic cancer cells by 5-aza-2'-deoxycytidine led to a decrease in Gli reporter activity, consistent with downregulation of Hedgehog signaling. These results indicate in some pancreatic adenocarcinomas that HHIP is epigenetically inactivated by promoter methylation, and its silencing could contribute to the increased Hedgehog signaling observed in pancreatic neoplasms.

Adenocarcinoma↗

PubMed2005

Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis.

BACKGROUND: The polymorphic enzyme cytochrome P450 2C19 affects omeprazole metabolism. This influence on metabolism might affect serum gastrin levels, and safety, during long-term treatment of reflux oesophagitis. AIM: To examine the relationship between cytochrome P450 2C19 genotype and the safety profile of long-term omeprazole treatment. METHODS: A total of 119 Japanese patients with recurrent reflux oesophagitis underwent cytochrome P450 2C19 genotyping prior to receiving daily omeprazole 10 mg or 20 mg for 6-12 months, during which adverse event frequency, serum gastrin levels and endoscopic findings were monitored. RESULTS: The incidences of adverse events, serious adverse events and adverse events leading to withdrawal did not differ between homozygous extensive metabolizer (n = 46), heterozygous extensive metabolizer (n = 53) or poor metabolizer (n = 20) groups. In all genotype groups, serum gastrin increased during the first 3 months of dosing but stabilized thereafter. No significant differences were seen either in the rate of reflux oesophagitis healing or symptom improvement among genotype groups. CONCLUSIONS: Long-term treatment with omeprazole was well-tolerated in Japanese patients, irrespective of their cytochrome P450 2C19 metabolic genotype, indicating that dose adjustment depending on metabolic genotype is not required during treatment with omeprazole.

Adult↗

PubMed2005

Wave-like appearance of diffuse pachymeningeal enhancement associated with intracranial hypotension.

Diffuse pachymeningeal enhancement on magnetic resonance (MR) imaging is important in identifying spontaneous and secondary intracranial hypotension (IH) [cerebrospinal fluid (CSF) hypovolemia] in patients with postural headache, because CSF pressure at lumbar puncture is variable. We examined the pachymeningeal enhancement pattern in patients with IH. MR imaging findings of pachymeningeal enhancement were examined before and after treatment in seven consecutive patients with spontaneous IH and one patient with IH after lumbar puncture. Diffuse non-nodular dural enhancement was observed in all patients. Characteristic thick, uninterrupted, enhancement was observed, mainly in the dura of the frontal, temporal, and retroclival regions, and the tentorium. Thin and uninterrupted, or partially interrupted, enhancement was observed, mainly in the parieto-occipital region and cerebellar convexity. Curved linear enhancement was observed along the calvarium of all patients. A wave-like appearance, a clear pattern of dural unevenness parallel to the brain, was detected in the frontal and temporal regions, near the base, in all patients. A wave-like appearance, especially in the frontal and temporal base, may be a characteristic MR imaging indicator of IH.

Adult↗

PubMed2005

Mucosa-associated bacteria in ulcerative colitis before and after antibiotic combination therapy.

BACKGROUND: We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis. AIM: To examine the efficacy of antibiotic combination therapy against F. varium and to investigate the mucosa-associated bacteria before and after the therapy using a new molecular approach. METHODS: Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline and metronidazole for 2 weeks) and no-antibiotics group. Clinical assessment, colonoscopic and histological evaluations were performed at 0 and 3-5 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism with the restriction enzyme HhaI and MspI, and quantified the change in the number of bacteria by real-time polymerase chain reaction. Immunohistochemical detection of F. varium in biopsy specimens was also performed. RESULTS: After the treatment, the clinical assessment, colonoscopic and histological scores improved in the antibiotic group compared with the control group. Three peaks of terminal restriction fragment length polymorphism decreased after treatment only in the antibiotic group. Eubacterium rectale, Dorea formicigenerans, Clostridium clostridioforme and F. varium were included in these peaks. Based on the real-time polymerase chain reaction study, only F. varium was significantly reduced after treatment. In the immunostaining, post-treatment scores in treatment group were significantly lower than that in control group. CONCLUSIONS: Antibiotics combination therapy was effective for ulcerative colitis. The number of mucosa-associated F. varium significantly decreased after the treatment.

Amoxicillin↗

PubMed2005

Netherton syndrome in two Japanese siblings with a novel mutation in the SPINK5 gene: immunohistochemical studies of LEKTI and other epidermal molecules.

BACKGROUND: Netherton syndrome (NS) is a severe autosomal recessive disorder characterized by ichthyosiform erythroderma, bamboo hair and atopy. The disease is caused by mutations in the SPINK5 gene, which encodes a putative serine protease inhibitor, LEKTI (lymphoepithelial Kazal-type-related inhibitor). Previous studies have clearly shown a crucial role for LEKTI in skin barrier formation. OBJECTIVES: To identify pathogenic mutations in two Japanese siblings with NS, and further to investigate the consequences of the mutations at the protein level. METHODS: To screen for mutations in the SPINK5 gene, all of its exons and splice junctions were amplified by polymerase chain reaction and directly sequenced. In addition, immunohistochemical staining of LEKTI, desmoglein (Dsg) 1 and elafin was performed with their specific antibodies. RESULTS: Mutation analysis resulted in the identification of compound heterozygous mutations, Q713X and R790X, in the SPINK5 gene of both patients. The former one is a novel mutation. Immunohistochemical studies in one patient demonstrated a complete absence of LEKTI and a strong expression of elafin in the patient's skin. Dsg1 was normally expressed in our patient. CONCLUSIONS: In this report, we describe compound heterozygous mutations in the SPINK5 gene in two Japanese siblings with NS. The result of immunohistochemistry shows LEKTI deficiency and upregulation of elafin in the skin of one patient. Furthermore, our data indicate that degradation of Dsg1 does not always occur in NS.

Carrier Proteins↗

PubMed2005

Acute inflammatory sensorimotor polyradiculoneuropathy associated with immune thrombocytopenic purpura.

Although acute inflammatory polyneuropathy (AIP) and immune thrombocytopenic purpura (ITP) are both believed to be immune-mediated disorders, only a few cases have been reported in which these two diseases co-existed. We describe a case of a 67-year-old patient who developed quadriparesis, ophthalmoplegia and severe sensory impairment along with thrombocytopenia. Detailed examinations, including the measurement of anti-ganglioside antibodies and anti-glycoprotein-IIb-IIIa-IgG-producing B-cells, revealed that he developed AIP and ITP. By reviewing past similar reports, we noticed that AIP associated with ITP tends to manifest severe sensory impairment and is often preceded by upper respiratory tract infection, but not by gastrointestinal infection.

Acute Disease↗

PubMed2005

HLA class II DPB1, DQA1, DQB1, and DRB1 genotypic associations with occupational allergic cough to Bunashimeji mushroom.

We previously reported that two-third of workers in a Bunashimeji mushroom (Hypsizigus marmoreus) farm complained of respiratory allergic symptoms, but one-third workers did not suffer from such symptoms even when working for a long period. CD4+ T-helper (Th) cells increased, and Th2/Th1 ratio increased in the allergic workers. To address these immunological backgrounds, we have investigated whether there is any relationship between mushroom allergy and human leukocyte antigen (HLA) class II alleles of DPB1, DQA1, DQB1, and DRB1 by using the polymerase chain reaction-restriction fragment length polymorphism (RFLP) and sequencing-based typing methods. We observed that the allele frequencies of DQA1*0103, DQB1*0601, and DRB1*0803 were significantly higher in the workers having no allergic symptoms than allergic workers (DQA1*0103: 57 vs 25%, DQB1*0601: 49 vs 14%, and DRB1*0803: 29 vs 0%). However, this phenomenon was not seen in workers producing another kind of mushroom, Honshimeji (Lyophyllum aggregatum). The HLA-DRB1*0803 allele alone, the DRB1*0803, DQA1*0103, DQB1*0601 haplotype, or both were negatively associated with allergy to Bunashimeji, and these alleles might be involved in the prevention of Bunashimeji mushroom-specific respiratory allergy.

Adult↗

PubMed2005

Effective in vivo purging with rituximab and autologous peripheral blood stem cell transplantation in a woman with CD5 positive primary cutaneous diffuse large B-cell lymphoma.

Generalized subcutaneous tumors developed without any other sites of the disease in a Japanese woman. Skin biopsy revealed CD5(+) and CD20(+) atypical diffuse large cells infiltrating subcutaneous tissues. The diagnosis was CD5(+) primary cutaneous diffuse large B-cell lymphoma. Tumor-specific PCR showed the existence of malignant cells in the peripheral blood and bone marrow. After three cycles of chemotherapy, she was remained in partial remission. Peripheral blood stem cells (PBSC) were harvested after the fourth cycles of chemotherapy combined with rituximab for in vivo purging. The contamination of tumor cells in PBSC was negative with PCR. She then underwent autologous peripheral blood stem cell transplantation using purged PBSC and has remained in complete remission for the past 24 month.

Antibodies, Monoclonal↗

PubMed2005

Frequent overexpression of epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation.

AIMS: To evaluate the expression of common biological markers and the epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation (DCMDs). MATERIALS/METHODS: Thirty DCMDs were clinicopathologically and immunohistochemically analysed and compared with 36 control cases of high grade conventional invasive ductal carcinoma (IDC). RESULTS: EGFR, HER2/neu, oestrogen receptor, progesterone receptor, and p53 expression was seen in 21, one, three, four, and 20 of the 30 DCMDs, compared with eight, nine, 18, 17, and five of the 36 conventional IDCs (p<0.05), respectively. In 16 of the 30 DCMDs, metastases were found in the brain, lung, bone, and liver, within a maximum of 47 months (mean, 13.9) after initial surgery, whereas only four of the 36 conventional IDCs metastasised to the lung and bone within a maximum of 27 months (mean, 18.0) after initial surgery (p=0.0001). There was a significant difference in disease free survival between DCMD and conventional IDC (p=0.001). EGFR was frequently overexpressed in DCMD compared with conventional IDC, whereas the expression of HER2/neu and hormone receptors was lower in DCMD. Fluorescent in situ hybridisation revealed that the mean EGFR to chromosome 7 centromere (CEP7) ratio of the 24 DCMD cases available for evaluation was 1.03, and EGFR gene amplification was not detected in the 21 DCMD cases with EGFR overexpression. CONCLUSION: Immunohistochemistry for myoepithelial markers and EGFR is useful for the accurate diagnosis and molecular target treatment of high grade DCMD.

Adult↗

PubMed2005

Statin attenuates high glucose-induced and angiotensin II-induced MAP kinase activity through inhibition of NAD(P)H oxidase activity in cultured mesangial cells.

An increased oxidative stress may contribute to the development of diabetic nephropathy. We have recently reported that high glucose level stimulated superoxide production through protein kinase C (PKC)-dependent activation of NAD(P)H oxidase in cultured vascular cells. Here we show that 3-hydroxy-3-methylglutaryl CoA reductase inhibitor (statin) attenuates both high glucose level-induced and angiotensin II (Ang II)-induced activation of p42/44 mitogen-activated kinase (MAP kinase) in cultured human mesangial cells through inhibition of NAD(P)H oxidase activity. The intracellular oxidative stress in cultured mesangial cells was evaluated by electron spin resonance (ESR) measurement. MAP kinase activity was evaluated by western blot analysis using anti phospho-specific MAP kinase antibody and anti-ERK-1 antibody. Exposure of the cells to high glucose level (450 mg/dl) for 72 hrs significantly increased MAP kinase activity as compared to normal glucose level (100 mg/dl). This increase was completely blocked by the treatment of pitavastatin (5x10(-7) M) as well as a NAD(P)H oxidase inhibitor (diphenylene iodonium, 10(-5) M) in parallel with the attenuation of oxidative stress. Ang II-induced activation of MAP kinase was also completely blocked by pitavastatin as well as a diphenylene iodonium in parallel with the attenuation of oxidative stress. In conclusion, pitavastatin attenuated high glucose-induced and Ang II- induced MAP kinase activity in mesangial cells through inhibition of NAD(P)H oxidase. Thus, statins may have a potential as a therapeutic tool for early diabetic nephropathy.

Angiotensin II↗

PubMed2005

[Carney triad; report of a case].

We report a case of Carney triad which is very rare disease composed of gastrointestinal stromal tumor (GIST), pulmonary chondroma and paraganglioma. A 15-year-old girl was reffered for treatment with multiple tumors in the left lung. At the age of 13, she underwent total gastrestomy for GIST. At that time multiple pulmonary tumors have already developed and made a diagnosis of chondroma. Progressive enlargement of their size and persistent bloody sputum made her received operation. Finally she underwent left pneumonectomy. In general all 3 tumors have manifested for a long time. Gastric tumors and paragangliomas are often lethal. This shows the necessity of intensive and long-term follow-up.

Adolescent↗

PubMed2005

[Pulmonary pleomorphic carcinoma; report of a case].

We report a case of a 64-year-old man with pleomorphic carcinoma of the lung and thymic cyst. He was admitted to our hospital because of an abnormal shadow observed on chest X-ray. Computed tomography (CT) showed a mass lesion located in the right upper lobe and a non-invasive anterior mediastinal tumor adjacent to the left brachiocepharic vein. On enhanced CT, the lung mass showed central low-attenuation areas with a substantial enhancement in the periphery. Preoperative transbronchial blushing cytology of the mass revealed adenocarcinoma. With a diagnosis of primary lung cancer (cT3N0M0) and mediastinal tumor, an operation was performed through a median sternotomy. The mediastinal tumor was excised and a right upper lobectomy and were also accomplished, because the lung tumor did not show adhesion or pleural invasion. Histopathologic examination of the resected specimen revealed that the lung tumor composed of a mixture of spindle and giant cell features and contained a component of adenocarcinoma and squamous cell carcinoma. This finding yielded a pathological diagnosis of pleomorphic carcinoma (pT2N0M0). The mediastinal tumor was diagnosed as thymic cyst. The postoperative course was uneventful, and he is currently well 6 months after surgery.

Adenocarcinoma↗

PubMed2004

Mini-laparoscopic appendectomy using a needle loop retractor offers optimal cosmetic results.

BACKGROUND: Do conventional laparoscopic appendectomy (LA) techniques provide truly satisfying results for patients and surgeons? We have devised a more advanced technique that improves cosmesis. METHODS: A 2-mm scope is inserted at the umbilicus, and a 12-mm working trocar is inserted through a suprapubic incision placed below the line of pubic hair. A needle loop retractor (NLR) is inserted to hold the appendix in the lower right abdomen. In this NLR, a stainless steel wire is placed within a needle having a diameter of 2 mm. From the suprapubic trocar, a bipolar coagulator is inserted to transect the appendiceal mesentery. A series of 30 patients underwent this procedure. RESULTS: There were no conversions to laparotomy and no intra- or postoperative complications. CONCLUSIONS: Laparoscopic appendectomy using a 2-mm scope, suprapubic trocar, and an NLR yields optimal cosmetic results. For surgeons, the NLR allows the appendix to be held more firmly than then a 5- or 2-mm grasping forceps is used.

Adult↗

PubMed2004

Search for the lepton-flavor-violating decay tau- -->micro-eta at Belle.

We have searched for the lepton flavor violating decay tau(-)-->micro(-)eta using a data sample of 84.3 fb(-1) accumulated with the Belle detector at KEK. The eta meson was detected through the decay modes: eta-->gammagamma and pi(+)pi(-)pi(0). No signal candidates are found, and we obtain an upper limit for the branching fraction B(tau(-)-->micro(-)eta)<3.4 x 10(-7) at the 90% confidence level.

Journal Article↗

PubMed2004

Effects of tirofiban on haemostatic activation in vitro.

BACKGROUND: Thrombin plays a critical role in normal haemostasis and pathological thrombosis. Heparin has long been a mainstay choice of antithrombotic regimen in cardiac patients, but persistent thrombin generation seems to occur during heparin therapy. Because platelets are integral to primary haemostasis and clot formation, we evaluated the use of tirofiban (Aggrastat),a platelet inhibitor, as a therapy to improve heparin sensitivity and delay thrombin formation. METHODS: Blood samples were obtained from healthy subjects (n=8) and cardiac surgical patients (n=34). Thrombin formation was measured in platelet-rich plasma with a Thrombogram-Ascent fluorescent plate reader system. Platelet inhibition by tirofiban was evaluated with Plateletworks, and the interaction of tirofiban and heparin (>1.5 U ml(-1)) on clot formation was evaluated with Sonoclot Analyzer or kaolin activated clotting times (ACTs). RESULTS: Addition of tirofiban (70-280 ng ml(-1)) progressively delayed onset of thrombin generation triggered by adenosine diphosphate (ADP). Plateletworks showed platelet inhibition with tirofiban (>35 ng ml(-1)), whereas heparin per se failed to produce platelet inhibition at 7 U ml(-1). Heparin (1.5 U ml(-1)) slowed the onset and rate of fibrin formation on Sonoclot analyses, and this was further slowed after addition of tirofiban (70 ng ml(-1)) to heparin-containing blood samples. Significant increases in ACT at all heparin concentrations were observed with the addition of tirofiban (70 ng ml(-1)). The addition of antithrombin (0.2 units/ml) to heparinized blood samples further prolonged ACTs, but the difference was not statistically significant when compared with heparin alone. CONCLUSION: Tirofiban delays platelet activation-mediated thrombin generation and prolongs ACT in heparinized blood.

Adenosine Diphosphate↗