Biomedical subjects

N Nakamura

Publications and source records attributed to N Nakamura.

At least 19 recordsLinked to original sources

PubMed2006

Identification of tumor markers and differentiation markers for molecular diagnosis of lung adenocarcinoma.

To identify tumor markers and differentiation markers for lung adenocarcinoma (AdC), we analysed expression profiles of 14,500 genes against three cases of type II alveolar epithelial cells, bronchiolar epithelial cells, and bronchial epithelial cells, respectively, and 10 cases of AdC cells isolated by laser capture microdissection. Hierarchical clustering analysis indicated that AdC cells and noncancerous lung epithelial cells are significantly different in their expression profiles, and that different sets of differentiation markers are expressed among alveolar, bronchiolar and bronchial epithelial cells. Nine genes were identified as being highly expressed in AdC cells, but not expressed in noncancerous lung epithelial cells. Sixteen genes were identified as differentiation markers for lung epithelial cells. Real-time RT-PCR analysis of 45 lung AdC cases further revealed that expression of four tumor markers in AdC cells was significantly higher than that in noncancerous lung cells and that expression of ten differentiation markers was retained in a considerable fraction of lung AdC cases. Five tumor markers and seven differentiation markers were not expressed in peripheral blood cells. Similarities and differences in expression profiles between normal epithelial cells from different lung respiratory compartments and AdC cells demonstrated in this study will be informative for the molecular diagnosis of lung AdC.

Adenocarcinoma↗

PubMed2006

Anti-p97/VCP antibodies: an autoantibody marker for a subset of primary biliary cirrhosis patients with milder disease?

We previously reported that 12.5% of primary biliary cirrhosis (PBC) sera reacted with a 95 kDa cytosol protein (p95c) that was subsequently identified as a p97/valosin-containing protein (VCP). The clinical features and course of the six anti-p97/VCP-positive PBC patients with Scheuer's stage 1 and 2 liver biopsies were monitored for an average of 15 years. This group was compared with 50 PBC patients that did not have detectable anti-VCP. Autoantibodies to a full-length recombinant p97/VCP were assayed by immunoprecipitation. All six PBC patients with anti-VCP had antibodies to the mitochondrial pyruvate dehydrogenase complex-E2 antigen as measured by an addressable laser bead immunoassay. The first was a male with no evidence of liver failure that died of cerebral infarction at the age of 85. The second was a 73-year-old female with Hashimoto's thyroiditis who has remained clinically stable without ursodeoxycolic acid (UDCA) treatment. Although the third had no HCV antibodies, he developed hepatocellular carcinoma at the age of 76 and died of renal failure at 78. The fourth was a 50-year-old female who remained clinically stable during follow-up and the fifth with Hashimoto's thyroiditis and stable liver function following UCDA treatment. The sixth was a male patient presenting a mild clinical course. The clinical course of these patients was in contrast to the 50 comparison group PBC patients who did not have anti-p97/VCP. As the six PBC patients with anti-p97/VCP antibodies had slowly progressive liver disease and no mortality related to autoimmune liver disease, our observations suggest that this autoantibody might be an indicator of a favourable prognosis.

Adenosine Triphosphatases↗

PubMed2006

Radiation therapy combined with cis-diammine-glycolatoplatinum (nedaplatin) and 5-fluorouracil for Japanese stage II-IV esophageal cancer compared with cisplatin plus 5-fluorouracil regimen: a retrospective study.

To evaluate the treatment outcome of radiotherapy combined with cis-diammine-glycolatoplatinum (nedaplatin) plus 5-fluorouracil (5-FU) for esophageal cancer. From January 2000 to December 2004, a total of 12 esophageal cancer patients with locally advanced and metastatic esophageal cancer (stages II-IVB) were treated with radiation therapy (50.4 Gy) combined with nedaplatin (80 mg/m(2), bolus infusion) and 5-FU (800 mg/m(2)/24 h, continuous infusion for 4 days) (NDP group). We compared the data with those of patients during the same period receiving a different chemotherapy regimen consisting of cisplatin (75 mg/m(2), bolus infusion) and 5-FU (1000 mg/m(2)/24 h, continuous infusion for 4 days) (n = 29, CDDP group) combined with the same radiation therapy. The median survival period was 11.5 months in the NDP group and 13.1 months in the CDDP group. The overall survival rates at 1-, 2-, and 3-years were 40%, 13%, and 13% in the NDP group and 56%, 42%, and 8% in the CDDP group (P = 0.2472), respectively. Grade III and IV leukocytopenia was observed in six (50%) and none of the patients in the NDP group and 14 (48%) and seven (24%) in the CDDP group, respectively. Grade III thrombocytopenia was observed in three (25%) in the NDP group and four (14%) in the CDDP group. Radiation combined with nedaplatin and 5-FU is a safe and effective method for treating esophageal cancer. We recommend that NDP should be used rather than dose-reduction of CDDP combined with 5-FU in patients with impaired renal function as indicated by low creatinine clearance value (40-60 mL/min).

Adenocarcinoma↗

PubMed2006

Characterization of Bacillus subtilis strains in Thua nao, a traditional fermented soybean food in northern Thailand.

AIMS: To clarify the diversity of Bacillus subtilis strains in Thua nao that produce high concentrations of products useful in food manufacturing and in health-promoting compounds. METHOD AND RESULTS: Production of amylase, protease, subtilisin NAT (nattokinase), and gamma-polyglutamic acid (PGA) by the Bacillus subtilis strains in Thua nao was measured. Productivity of protease NAT by these strains tended to be higher than by Japanese commercial natto-producing strains. Molecular diversity of isolated strains was analysed via randomly amplified polymorphic DNA-PCR fingerprinting. The strains were divided into 19 types, including a type with the same pattern as a Japanese natto-producing strain. CONCLUSION: B. subtilis strains that could be a resource for effective production of protease, amylase, subtilisin NAT, or PGA were evident in Thua nao produced in various regions in northern Thailand. SIGNIFICANCE AND IMPACT OF THE STUDY: This study clearly demonstrated the value of Thua nao as a potential resource of food-processing enzymes and health-promoting compounds.

Amylases↗

PubMed2006

Refractory ascites after liver transplantation: an analysis of 1058 liver transplant patients at a single center.

A retrospective study of 1058 liver transplant recipients was performed to determine: (i) the incidence, etiology, timing, clinical features and treatment of refractory ascites (RA), (ii) risk factors for RA development, (iii) predictors of RA disappearance, (iv) predictors of survival following RA and (v) the impact of RA on patient survival. Sixty-two patients (5.9%) developed RA and its disappearance occurred in 27/62 cases. Patients having hepatitis C virus (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No other baseline characteristic was associated with RA. Cox stepwise regression analysis of the hazard rate of RA disappearance found two significant factors: HCV recurrence as the reason for developing RA implied a poorer outcome (p = 0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In addition, survival following RA was significantly poorer among patients having bacterial peritonitis or HCV recurrence. Finally, the mortality rate was significantly (nearly 8.6 times) higher in patients following RA development while it was ongoing (p < 0.00001); however, if the RA disappeared, then the additional risk of death also disappeared. This study illustrates the importance of developing an optimal treatment strategy to (i) effectively treat RA if it develops and (ii) prevent hepatitis C recurrence.

Adolescent↗

PubMed2006

Pleomorphic adenoma presenting low T2 signal-intensity on magnetic resonance imaging.

We report an unusual case of pleomorphic adenoma of the submandibular gland in a 48-year-old female. The present case appeared as a relatively homogeneous, low to intermediate signal-intensity on the T(2) weighted magnetic resonance (MR) images. To our knowledge, the MR feature of low T(2) signal-intensity of pleomorphic adenoma has not been reported in the literature.

Adenoma, Pleomorphic↗

PubMed2006

A method to differentiate between the levels of ESR signals induced by sunlight and by ionizing radiation in teeth from atomic bomb survivors.

Electron spin resonance (ESR, or electron paramagnetic resonance, EPR) analysis of tooth enamel is an effective method for the retrospective estimation of individual radiation doses. One problem with this technique is that the observed ESR signal may include a contribution from ultraviolet (UV) light exposure from sunlight, especially in front teeth. Thus there has been a need to find ways to estimate the UV-light effect in the total signal so that the net ESR dose from ionizing radiation can be determined. To examine this issue, we measured 96 teeth of various types, but with buccal and lingual parts measured separately, from a control group of atomic bomb survivors (estimated dose <5 mGy). We found that, except for molars, the mean ESR-estimated dose for the buccal halves was, on average, nearly twice that from the lingual side, which indicates that the UV-light-induced lingual dose equals the difference between the two halves. Using these corrections for UV-light exposure to front teeth that had been exposed to both ionizing radiation and UV light, it was found that the estimated radiation doses closely approximated the previously estimated ESR dose to molars from the same donors or the estimated dose arrived at with cytogenetic methods. We concluded that, when using ESR to estimate radiation dose, measuring molars is the first choice, but if only front teeth are available, separate measurements to the buccal and lingual parts can provide an estimation of the mean UV-light contribution to the ESR-determined dose.

Dose-Response Relationship, Radiation↗

PubMed2006

New nanotechnology for the guided tissue regeneration of skin--potential of lyotropic liquid crystals.

Tissue in body must quickly recognize injury to response to the rapid pace of epidermal growth. In skin, the epidermal cells must also react to danger signals from the surrounding extracellular lipid of the stratum corneum spaces and immediately participate by initiating the wound repair process. The topical administration of the lyotropic liquid crystal nanocube to stratum corneum rapidly broke down the lipid lamella structure which would be recognized as a wound without organ-change. This can activate a variety of biological processes. This study set out to determine whether the phase transition of the lipid to a neighbouring different physicochemical structure can stimulate keratinocyte cells and what mechanism is responsible for this response. Using small angle x-ray scattering (SAXS) analysis, a response to the transient structural change of lipid was detected which might result from the diffusion of oil and/or water from nanocube liquid crystal towards the lipid lamella phase. Simultaneously, a significant increase in growth factors and inflammatory cytokines was detected after administration of nanocube. Not only the excess expression of cytokines but also the extent of TEWL as a barrier marker of skin increased. These observations suggest that a structural change in lipid can stimulate and trigger recognition of a slight injury in the wound defence and a repair response as homeostasis. This method actually succeeded in improving photo-induced hyperpigmentation on a human face.

Animals↗

PubMed2006

Enhanced skin regeneration by nanoegg formulation of all-trans retinoic acid.

All-trans retinoic acid (atRA) which could smooth wrinkles and produce less pigmented skin after a few months of treatment has been studied in research into topical treatments for a potent inhibitor of new melanin production. However, the clinical responses of commercial atRA cream predominantly comprise severe inflammation. We report a novel nanotechnology "nanoegg" system giving improved effects of atRA self-assembly which were coated by CaCO3. Dorsal areas of hairless mouse and porcine skin were employed for administration of nanoegg ointment and commercial products. The mRNA for heparin-binding epidermal growth factor-like growth factor (HB-EGF) from tissues was measured by a real-time PCR method. All tissues were stained for detection of hyaluronate and the thickness of the epidermis. A clinical trial in humans was carried out at St. Marianna University in Japan. As a result, the irritation and inflammation associated with atRA molecules were substantially reduced. The physicochemical instability of atRA was also dramatically improved. Furthermore, nanoegg enhanced marked expression of mRNA for HB-EGF from keratinocytes, which is known as one of the markers of keratinocyte turnover. Also, production of hyaluronate was surprisingly in the intercellular spaces of the basal and spinous cell layers 2 days after treatment. Even at the low concentration of atRA in the nanoegg system, the proliferation and differentiation of keratinocyte was somewhat enhanced. A nanoegg may thus not only prevent adverse effects, but also markedly enhance the main effect.

Administration, Topical↗

PubMed2005

Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity.

The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7+/-2.6 vs. 15.0+/-1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: beta=0.159, p=0.035; HDL: beta=-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.

Adiponectin↗

PubMed2005

Daily profile of plasma %CoQ10 level, a biomarker of oxidative stress, in patients with diabetes manifesting postprandial hyperglycaemia.

The purpose of this study was to investigate the effect of regular meals on the daily profile of blood oxidative stress markers in type 2 diabetic patients with postprandial hyperglycaemia. %CoQ10, calculated as the ratio of ubiquinone-10 (oxidised form of coenzyme Q10) to ubiquinol-10 (reduced form), was used as a sensitive marker of oxidative stress. Blood samples were collected from patients before and 2 h after breakfast, lunch and supper, and at 10 p.m. Patients were selected for the study if their blood glucose levels were <7 mmol/l before breakfast and > or =11.1 mmol/l on at least one occasion after breakfast. %CoQ10 levels after breakfast and throughout the day were significantly higher than those before breakfast (p=0.006-0.04). In contrast to the wave-like changes in plasma glucose levels, %CoQ10 levels increased after breakfast and remained at high levels throughout the day. These results indicated that diabetic patients with postprandial hyperglycaemia were exposed to meal-induced periods of oxidative stress during the day. Postprandial hyperglycaemia therefore has the potential to increase the risk of atherosclerotic cardiovascular disease through induction of oxidative stress.

Ascorbic Acid↗

PubMed2005

Effects of cilostazol on lipid and fatty acid metabolism.

Cilostazol is a selective inhibitor of phosphodiesterase III with anti-platelet-aggregatory and vasodilating properties. Randomised, double-blind, placebo-controlled trials in 2702 patients with intermittent claudication demonstrated that cilostazol significantly increased walking distances compared with placebo. Furthermore, the agent has beneficial effects on the serum lipid profile and fatty acid composition in plasma. Consequently, cilostazol may be useful to prevent atherosclerosis from progressing by ameliorating lipid and fatty acid metabolism.

Aged↗

PubMed2005

Prognosis of HTLV-I-positive renal transplant recipients.

HTLV-I is the pathogen that causes adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). The rate of disease development is low and the latency time is a few decades. However, the possible influence of immunosuppression on this disease development is unclear. The purpose of this study was to investigate the risk of development of ATL and HAM among the large number of HTLV-I-positive renal transplant recipients in western Japan. In principle immunosuppressive drugs have the possibilities to accelerate ATL development but are thought to suppress HAM development. Of 120 renal transplant recipients, 10 HTLV-I-positive recipients were reviewed, none of whom developed ATL or HAM. There are 11,896 dialysis patients in Japan and 300 dialysis patients in Okinawa who are registered with the JOTN for cadaveric renal transplant. The numbers of HTLV-I-positive patients in these groups were 97 (0.82%) and 26 (8.67%), respectively. These numbers are thought to be sufficient for an HTLV-I-positive recipient pool for HTLV-I-positive donors. Ten cases of ATL development and two of HAM development have been previously reported. Because of low number of ATL development, renal transplantation does not appear to be a contraindication for HTLV-I-positive chronic renal failure patients. In other words, kidneys from HTLV-I carriers, which include cadaveric donors, could be used for HTLV-I-positive recipients.

Adult↗

PubMed2005

PGE1 inhibits the expression of PAI-1 mRNA induced by TNF-alpha in human mesangial cells.

We examined the effect of PGE1 on the expression of plasminogen activator inhibitor-1 (PAI-1) mRNA induced by tumor necrosis factor-alpha (TNF-alpha) in human mesangial cells, because PAI-1 is one of major factors for the progression of glomerulosclerosis. The expression of PAI-1 mRNA was increased after stimulation with TNF-alpha, and it was diminished by pre-incubation with PGE1. Next, we examined the effect of PGE1 on the phosphorylation of mitogen activated protein kinase (MAPK) family and Akt. TNF-alpha activated the phosphorylation of p44/42 MAPK, p38 MAPK, SAPK/JNK and Akt in mesangial cells. PGE1 inhibited the TNF-alpha induced phosphorylation of SAPK/JNK and Akt, but not p44/42 MAPK and p38 MAPK. The TNF-alpha induced expression of PAI-1 mRNA was not affected by PD98059, an inhibitor of MEK, SB203580, an inhibitor of p38 MAPK, nor LY294002, an inhibitor of PI3 K. However, DMAP, an inhibitor of SAPK/JNK, inhibited the expression of PAI-1 mRNA, suggesting that the TNF-alpha induced expression of PAI-1 mRNA is regulated by the SAPK/JNK dependent pathway in human mesangial cells. By the incubation with H8, an inhibitor of PKA, the inhibitory effect of PGE1 on the expression of PAI-1 mRNA was abolished, suggesting that PGE1 inhibited the PAI-1 mRNA expression via the PKA pathway. Our results suggest that the inhibition of PAI-1 synthesis by PGE1 in human mesangial cells may have therapeutic implications for glomerulosclerosis such as occurs in diabetic nephropathy.

Alprostadil↗

PubMed2005

Lymphomatous polyposis of the gastrointestinal tract, including mantle cell lymphoma, follicular lymphoma and mucosa-associated lymphoid tissue lymphoma.

AIMS: Lymphomatous polyposis (LP) is considered to represent mantle cell lymphoma (MCL) of the gastrointestinal (GI) tract. However, a few reports have suggested that some are follicular lymphoma (FL) or mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we analysed 35 patients and clarified the clinicopathological features of LP. METHODS AND RESULTS: Paraffin-embedded tissue samples were stained immunohistochemically and analysed by tissue-fluorescence in situ hybridization (T-FISH) for IGH/CCND1 (cyclin D1) and IGH/BCL2. The average age of the patients was 58.3 years. Over half of the cases showed gastric, duodenal, small intestinal, ileocaecal and sigmoid colonic lesions (15, 19, 15, 16 and 16 cases, respectively). Phenotypically, cases were classified into three types of MCL (cyclin D1+ CD5+ CD10-) (n=12), FL (cyclin D1- CD5- CD10+) (n=14) and MALT (cyclin D1- CD5- CD10-) (n=9). T-FISH identified 11 of the 11 examined cases with MCLs to have IGH/CCND1, while seven of 10 cases with FL had IGH/BCL2, and none of the MALT cases were positive for IGH/CCND1 or IGH/BCL2. At the study endpoint, five of 12 patients with MCL were dead, two of 14 with FL and one of nine with MALT were dead of other disease. Event-free survival analysis showed significantly poorest outcome in MCL, followed by FL, while MALT was associated with a favourable outcome (P=0.0040). CONCLUSIONS: Our study emphasizes the importance of differentiating MCL, FL and MALT of LP in evaluating prognosis and hence the most suitable therapeutic regimen.

Aged↗

PubMed2005

Salvage radiotherapy for postoperative loco-regional recurrence of esophageal cancer.

The aim of this paper is to evaluate the treatment outcome of radiation therapy (RT) for 16 loco-regionally recurrent esophageal cancer patients. Between 1995 and 2004, patients with loco-regional recurrence of esophageal cancer after curative surgery received RT with or without chemotherapy (CTx) at an average total dose of 56.6 Gy (n = 16, REC group). The site of recurrence was the supraclavicular region in three patients, the mediastinal region in nine patients, and both the supraclavicular and mediastinal regions in four patients. We compared the data with those of patients receiving palliative RT with or without CTx for mediastinal relapse, distant metastasis or malignant pleural effusion (n = 39, META group) and with those of patients receiving postoperative RT with or without CTx in a planned fashion 4-6 weeks after esophagectomy (n = 27, PORT group). The median survival period was 13.8 months in the REC group, 3.5 months in the META group, and 19.1 months in the PORT group. The survival rates at 1 and 2 years were 56% and 19% in the REC group, 6% and 3% in the META group (P = 0.0003), and 70% and 43% in the PORT group (P = 0.1917), respectively. According to univariate analysis, the factor of worse prognosis was not found in the REC group. Complete or partial responses were observed in four (25%) and nine (56%) of the REC group patients, respectively. In the REC group, changes in clinical symptoms, such as dysphagia and recurrent nerve paralysis, could be evaluated in eight patients, and improvement in symptoms was obtained in five (63%) patients. The prognosis of patients who received RT for postoperative loco-regional recurrence of esophageal cancer was significantly better than that of the META group patients and compatible with that of the PORT group patients. Additionally, there is symptomatic relief in a substantial proportion of such patients, and long-term survival is possible in some patients.

Adult↗

PubMed2005

Association between alcohol consumption and serum dehydroepiandrosterone sulphate concentration in men with Type 2 diabetes: a link to decreased cardiovascular risk.

AIMS: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with Type 2 diabetes. Both light-to-moderate alcohol consumption and higher serum concentrations of dehydroepiandrosterone (DHEA) are associated with reduced CVD mortality, raising the possibility of DHEA as a causal intermediate in CVD and alcohol consumption. METHODS: Relationships between alcohol consumption and serum DHEA sulphate (DHEA-S) concentration, carotid atherosclerosis as evaluated by carotid ultrasonography and major cardiovascular risk factors were investigated in 404 consecutive men with Type 2 diabetes. Patients were divided into three groups according to mean ethanol consumption per week: non-drinkers, light-to-moderate drinkers (< 210 g per week) or heavy drinkers (> or = 210 g per week). RESULTS: Plasma HDL-cholesterol was positively associated with the degree of alcohol consumption. Intima-media thickness (0.92 +/- 0.21 vs. 1.09 +/- 0.35 mm, P < 0.0001) and plaque score (3.0 +/- 3.3 vs. 5.2 +/- 4.9, P = 0.008) were lower in light-to-moderate drinkers than in non-drinkers. Serum DHEA-S concentrations were higher in light-to-moderate drinkers (1264.2 +/- 592.2 ng/ml, P < 0.0001) and heavy drinkers (1176.2 +/- 607.6 ng/ml, P = 0.0100) than in non-drinkers (956.8 +/- 538.6 ng/ml). In a subgroup aged 60-75-year-old patients (n = 277), serum DHEA-S concentrations were higher in light-to-moderate drinkers (1126.8 +/- 502.5 ng/ml, P = 0.0121) than in non-drinkers (937.9 +/- 505.1 ng/ml). Also, in a subgroup without CVD (n = 339), serum DHEA-S concentrations were higher in light-to-moderate drinkers (1328.5 +/- 593.7 ng/ml, P < 0.0001) than in non-drinkers (970.1 +/- 540.7 ng/ml). CONCLUSIONS: Higher serum DHEA-S concentrations in light-to-moderate drinkers may represent part of the link between light-to-moderate alcohol consumption and lower CVD mortality.

Aged↗

PubMed2005

Differentiation of mouse hepatitis virus genotypes by restriction fragment length polymorphism analysis.

Reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of the nucleocapsid (N) gene of mouse hepatitis virus (MHV) successfully detected 36 strains from the faeces of mice that had been housed in animal facilities in Japan from 2000 to 2003. Subsequent restriction fragment length polymorphism (RFLP) analysis, using the enzymes Acc I, Alu I, EcoR I and Mbo I, demonstrated that these strains could be divided into five distinct subgroups and that the same MHV strains were detected from closely related mouse facilities. Furthermore, strains from the same facility showed the same RFLP pattern, irrespective of the year of detection, but this pattern varied between different locations. This study shows that RFLP analyses are a rapid and useful method for differentiation of MHV strains.

Animals↗