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Biomedical subjects

N Uchida

Publications and source records attributed to N Uchida.

At least 19 recordsLinked to original sources

A prospective, double-blind, randomized trial of caudal block using ropivacaine 0.2% with or without fentanyl 1 microg kg-1 in children.

BACKGROUND: It has been reported that ropivacaine produces vasoconstriction in contrast to vasodilation produced by bupivacaine. It is possible that additives to ropivacaine can provide further analgesic advantages compared with bupivacaine. We thus evaluated whether the addition of fentanyl to ropivacaine prolonged the duration of analgesia after a single shot caudal block. METHODS: A total of 36 children undergoing surgical procedures below the umbilicus were randomly allocated to one of two groups: Group F received ropivacaine 0.2%, 1 ml kg(-1) with fentanyl 1 microg kg(-1) and Group S received ropivacaine 0.2%, 1 ml kg(-1) with saline. The analgesic effect of the caudal block was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and sedation was assessed using the Steward score at 30 min after extubation and at 1, 2, 4, 6, 12 and 24 h. The first analgesic requirement time and side-effects in a 24 h period were also recorded. RESULTS: There were no differences in characteristics between the groups. The end-tidal concentration of sevoflurane at extubation in Group F was significantly lower than in Group S. However, there was no significant difference in time from discontinuation of the volatile anaesthetics to tracheal extubation. No statistical differences were found in the CHEOPS and Steward score, and the time to first analgesia. The incidence of postoperative vomiting was not significantly different. CONCLUSION: We found that the addition of fentanyl 1 mug kg(-1) to ropivacaine 0.2% for caudal analgesia provides no further analgesic advantages over ropivacaine 0.2% alone.

Amides↗

Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex.

We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances ( approximately 1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker beta-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.

Animals↗

Repeated adenoviral administration into the biliary tract can induce repeated expression of the original gene construct in rat livers without immunosuppressive strategies.

BACKGROUND: Systemic adenoviral readministration appears to be limited by immunogenicity. AIMS: We examined the feasibility of repeated adenovirus mediated gene transfer into the liver via the biliary tract. METHODS: Recombinant adenoviruses carrying a reporter lacZ gene were infused retrogradely into the common bile duct of rats. Transduction efficiency of the lacZ gene was estimated histochemically and quantitatively. RESULTS: Retrograde administration of recombinant adenoviruses into the common bile duct of rats resulted in efficient transgene expression in the liver, specifically in hepatocytes, but not in biliary epithelia. Transduction efficiency induced by intrabiliary adenoviral administration was not substantially different from that induced by intraportal adenoviral infusion. Transgene expression in the liver was however transient, and development of neutralising antibodies against adenovirus was observed in serum but not in bile. When adenoviruses were readministered into the common bile duct, successful re-expression of the transgene in the liver was achieved despite the existence of neutralising antibodies in serum. Interestingly, although proliferation of adenovirus specific T cells in response to adenoviral readministration was suppressed significantly by immunosuppressive FK506 treatment, levels of transgene expression in the liver achieved by intrabiliary adenoviral readministration were not significantly different between animals treated with and without FK506. Furthermore, third adenoviral administration into the common bile duct also induced successful transgene expression in the liver. CONCLUSIONS: These results suggest that adenovirus mediated gene transfer into the liver may be repeatable without immunosuppressive strategies in clinical settings by means of endoscopic retrograde cholangiography.

Adenoviridae↗

No association found between the type 1 sigma receptor gene polymorphisms and methamphetamine abuse in the Japanese population: a collaborative study by the Japanese Genetics Initiative for Drug Abuse.

It has been suggested that individual genetic factors are involved in susceptibility to drug dependence and the manifestation of drug-induced psychosis. The aim of this study was to examine the relation between methamphetamine abusers/psychosis and the type 1 sigma receptor gene polymorphisms. Subjects comprised 143 MAP abusers and 181 healthy controls. Two polymorphisms in the type 1 sigma receptor gene, GC-241-240TT and A61C (Gln2Pro), were examined in the present study. No significant differences were observed in either polymorphism between healthy controls and MAP abusers/psychosis. In the subgroup analyses, the rate of CC genotype of A61C tended to be higher in MAP patients who had experienced spontaneous relapse without MAP use than in those who had not (P = .06, OR = 3.02 95%CI = 0.92-9.92). However, the level of this significant trend did not remain after the Bonferroni's multiple correction. This study suggests that type 1 sigma receptor gene is unlikely to play a major role in substance abuse liability and/or the development of MAP psychosis.

Adult↗

Pharmacokinetic differences between Caucasian and Japanese subjects after single and multiple doses of a potential combined oral contraceptive (Org 30659 and EE).

OBJECTIVES: To compare the pharmacokinetic parameters and safety of the progestagen, Org 30659, (17alpha)-17-hydroxy-11-methylene-19-norpregna-4,15-dien-20-yn-3-one), and ethinyl estradiol (EE) in Caucasian and Japanese women after single and multiple doses. METHODS: This was an open-label parallel design of a single dose followed by a multiple dose period in healthy young Japanese and Caucasian subjects. RESULTS: The area under the curve (AUC) of Org 30659 after single dosing was increased by a factor of 1.75 [90% confidence interval (CI): 1.48-2.08] in Japanese women compared to Caucasian women. At steady state, this difference increased to a factor of 1.90 (90% CI: 1.60-2.25). The AUC of EE after single dosing was similar in Caucasian and Japanese women, but at steady state it was increased by a factor 1.38 (90% CI: 1.15-1.64) in the Japanese group. Weight normalization reduced, but did not remove, all the observed differences. Sex hormone binding globulin played no significant role in the differences between Caucasian and Japanese subjects. Both the single- and multiple-dose treatments with Org 30659/EE were generally well tolerated by all subjects. The Japanese population reported more and different treatment-related adverse events than the Caucasian population. CONCLUSIONS: The peak concentration and extent of exposure of Org 30659, and to a lesser extent of EE, in Japanese women are higher than in Caucasian women. Furthermore, the peak concentration and extent of exposure at steady state of Org 30659, and to a lesser extent of EE, are higher than would be predicted assuming linear pharmacokinetics over time. No major safety issues were observed.

Adult↗

pp60c-src activation in lung adenocarcinoma.

Nine src family members are known including c-Src, c-Yes, c-Lck, c-Fyn, c-Hck, c-Lyn, c-Blk, c-Fgr and c-Yrk. They encode proteins with molecular weights of 55-62 kilodaltons (kDa), which are either cytoplasmic or membrane-associated protein tyrosine kinases. A close correlation exists between an elevated pp60c-src tyrosine kinase activity and cell transformation. However, the level of activation of pp60c-src in non-small cell lung cancers (NSCLC) remains obscure. The aim of this study was to examine the level of activity of pp60c-src in NSCLC. pp60c-src expression and in vitro protein tyrosine kinase activity in lung cancer tissue samples were measured by western blotting and in vitro kinase assays and compared with those in the surrounding non-tumour lung tissue from the same patient. pp60c-src phosphorylation was assessed by two-dimensional tryptic phosphopeptide mapping. The kinase activity of pp60c-src was significantly activated in NSCLC, especially in adenocarcinomas. In addition, the pp60c-src kinase activity increased with the size of the adenocarcinoma. Two-dimensional tryptic phosphopeptide mapping showed dephosphorylation of pp60c-src at Tyr 530 in adenocarcinomas. The proto-oncogene product, pp60c-src, was activated in NSCLC, especially in adenocarcinomas, in part through the dephosphorylation of Tyr 530. Our results suggest that activation of pp60c-src might play an important role in the progression of lung adenocarcinomas.

Adenocarcinoma↗

A case of gallbladder carcinoma diagnosed preoperatively by the detection of human telomerase reverse transcriptase mRNA in endoscopically obtained gallbladder bile.

It is difficult to accurately diagnose the nature of polypoid lesions in the gallbladder. To increase diagnostic accuracy, we have developed an endoscopic technique for obtaining gallbladder bile, termed endoscopic transpapillary catheterization into the gallbladder (ETCG). We describe here a case of gallbladder carcinoma diagnosed preoperatively by the detection of human telomerase reverse transcriptase (hTERT) mRNA, a catalytic subunit of telomerase, in gallbladder bile obtained using the ETCG technique. A patient with a polypoid lesion 15 mm in diameter in the gallbladder was admitted to our hospital for further examinations. Gallbladder bile collected by the ETCG technique was evaluated cytologically and also analyzed for telomerase activity and hTERT mRNA. Although the results for cytology and telomerase activity were negative, that for hTERT mRNA was positive. Open surgery was carried out and it was confirmed that the lesion was an adenocarcinoma invading the subserosa. The molecular biological analysis of gallbladder bile collected using the ETCG technique was shown to be effective for diagnosing the nature of the polypoid lesion in the gallbladder.

Adenocarcinoma↗

Threshold values of visceral fat measures and their anthropometric alternatives for metabolic derangement in Japanese obese boys.

OBJECTIVE: To determine whether the direct measure of visceral adipose tissue (VAT) by computed tomography (CT) is a superior diagnostic criterion to the anthropometric surrogates and more classical criteria of obesity. DESIGN: Cross-sectional, clinical study. Obese boys were classified according to the occurrence of abnormal values in either serum triglyceride, alanine aminotransferase or insulin level. A threshold value of each criterion for such metabolic derangement was calculated, using the analysis of receiver operating characteristic (ROC) curve. SUBJECTS: Seventy-five consecutive outpatient Japanese obese boys, ranging in age from 6 to 14 y, were studied. MEASUREMENTS: Anthropometric indices measured were height, body weight, waist girth, hip girth, triceps and subscapular skinfold thicknesses. Classical criteria for obesity used were percentage overweight (POW), body mass index (BMI) and percentage body fat. Waist girth, sagittal diameter by CT and waist-hip ratio (WHR) were evaluated as anthropometric surrogates for VAT. The areas of total abdominal fat (TAF), VAT and subcutaneous adipose tissue (SAT) were measured by CT at the level of the umbilicus. Clinical blood biochemistry was analyzed in fasting blood samples of obese boys. RESULTS: Thirty-three boys were classified into a no-complication group, and 42 into a complication group. TAF, VAT and SAT areas were closely associated with age, body size and degree of overweight and adiposity, while VAT/SAT was not. VAT area, sagittal diameter, TAF area and waist girth were closely correlated with alanine aminotransferase, insulin, TG and HDL-C. VAT/SAT, BMI, SAT area, WHR, percentage body fat and POW were less closely associated with these biochemical indices. The descending order of the values of area under the curve for the ROC curves were as follows: VAT>sagittal diameter>TAF>VAT/SAT>waist girth>BMI>WHR>percentage body fat>POW. Both VAT area and VAT/SAT gave >80% of sensitivity and specificity. Among the anthropometric indices studied, the sagittal diameter was the best surrogate of visceral fat measure. The sensitivity and specificity for the rest of the anthropometric indices were in an unsatisfactory range. The threshold values for VAT area, VAT/SAT and sagittal diameter were 58.0 cm(2), 0.276 and 19.2 cm, respectively. CONCLUSION: The threshold values for VAT area, VAT/SAT and sagittal diameter for detecting biochemical complication in Japanese obese boys were lower than the respective values reported in adults. These values can be used for classifying the obese boys into two types: those with medical problem and those without.

Abdomen↗

Casimir effect in fluids above the isotropic-lamellar transition.

We study fluctuation-induced interaction in confined fluids above the isotropic-lamellar transition. At an ideally continuous transition, the disjoining pressure has the asymptotic form Pi(d-->infinity) approximately -Ck(B)Tq(2)(0)/d, where d is the interwall distance, q(0) is the wave number of the scattering peak, and C = 1/4pi in the strong anchoring limit. The long-rangedness is enhanced due to continuous distribution of soft modes in the q space. An unconventionally strong Casimir force with a range of several lamella thicknesses is realistic above the transition. We also find an oscillatory force profile near a surface-induced transition.

Journal Article↗

Sequence-dependent antitumor efficacy of combination chemotherapy with nedaplatin, a newly developed platinum, and paclitaxel.

We evaluated the sequence dependency of antitumor efficacy and toxicity in combination therapy of nedaplatin (NDP) with paclitaxel (TXL) against Lewis lung carcinoma. The sequential administration of NDP prior to TXL (NT therapy) resulted in severe body weight loss followed by frequent toxic death of mice. In contrast, the sequential dosing of TXL prior to NDP (TN therapy) resulted in synergistically enhanced inhibition of tumor growth with less toxicity compared with the NT therapy. Comparing the antitumor activity of NDP plus TXL with that of cisplatin (CDDP) plus TXL or carboplatin (CBDCA) plus TXL, the combination effect of NDP plus TXL was significantly higher than that of CDDP plus TXL or CBDCA plus TXL. These results indicate that the TN therapy may have significant potential in clinical use.

Animals↗

Mismatch repair and microsatellite instability in esophageal cancer cells.

Using in vitro mismatch repair (MMR) assay, we have identified 3 of 22 esophageal cancer cell lines exhibiting reduced MMR activity. By means of gel-shift assay, decreased binding ability to GT mismatch and CA loop was observed in these 3 cell lines. However, we could not find any mutations in the hMSH2, hMSH3 and hMSH6 genes, the protein products of which exhibit mismatch binding activity in human cells. In addition, when using antibodies against 5 MMR-related proteins (hMSH2, hMSH3, hMSH6, hPMS2 and hMLH1), no aberrant expression was detected in any of them. When we examined 9 microsatellite loci in endogenous genomic DNA, these 3 esophageal cancer cell lines, deficient in MMR, did not exhibit microsatellite instability. However, when we examined the repetitious sequence on exogenous plasmid DNA which was introduced into these 3 esophageal cancer cells, the results suggested that MMR deficiency in esophageal cancer cells could result in moderate instability of the exogenous sequence.

Adaptor Proteins, Signal Transducing↗

Histopathologic comparison of anti-mitochondrial antibody-positive primary biliary cirrhosis and autoimmune cholangiopathy.

The present study aimed to investigate whether antimitochondrial antibody (AMA)-positive primary biliary cirrhosis (PBC) and AMA-negative PBC with autoantibodies differ histologically, especially with respect to infiltrating cells in portal tracts involved by chronic non-suppurative destructive cholangitis. Liver specimens were stained from 15 primary biliary cirrhosis with AMA (group 1), nine patients consistently negative for AMA but positive for antinuclear antibodies (ANA) (group 2). Group 2 showed overlapping features of PBC and autoimmune hepatitis type 1, in a pattern recently termed autoimmune cholangiopathy (AIC). We analyzed the cell population, including lymphocytes, plasma cells, large histiocytes, eosinophils and neutrophils, which had infiltrated portal tracts involved by destructive lesions. Although serum immunoglobulin M levels were higher in group 1 compared to those in group 2 (P=0.0282), patients of both groups were broadly comparable with respect to clinical features and laboratory data. Histologically, the number of plasma cell and its percentage among inflammatory infiltrating cells in the portal tract were higher in group 2 than in group 1 (P=0.0015, P=0.0070, respectively). The percentage of lymphocyte infiltration among inflammatory infiltrating cells in the portal tract were higher in group 1 than in group 2 (P=0.0052). The percentage of plasma cell infiltration among inflammatory infiltrating cells in the portal tract was correlated to immunoglobulin G levels in group 2 (r=0.949, P=0.0016). In conclusion, AMA-positive PBC and AIC showed differences in inflammatory cell population in involved portal tracts in this preliminary study.

Journal Article↗

Immunosuppressive therapy for patients with refractory anemia.

Trials of immunosuppressive therapy have been reported in some case reports of hypoplastic myelodysplastic syndrome (MDS). In this study, we gave immunosuppressive therapies to eight patients with normo- or hyperplastic MDS of refractory anemia subtype without karyotypic abnormalities and analyzed the HLA-DRB1 type or the presence of paroxysmal nocturnal hemoglobinuria (PNH) neutrophils in these patients. Cyclosporin A (CyA) therapy was effective for improving cytopenia in four of the eight MDS patients. While the side effects of CyA were mostly mild and transient, one patient demonstrated karyotypic abnormality following CyA therapy and accelerated to refractory anemia with an excess of blasts. Additional antithymocyte globulin (ATG) therapy was effective in one of three nonresponders to CyA therapy. One patient died due to leukemic transformation after ATG therapy. When we analyzed the correlation between the response to CyA therapy and the HLA-DRB1 type, there were more responders with DRB1*1501 (three of four patients) than without (one of four patients), but a statistically significant difference was not evident between the two groups. In addition, the presence of PNH neutrophils was not correlated with the response to CyA and/or ATG therapy. These results indicate the usefulness of immunosuppressive therapies even for normo- or hyperplastic MDS patients. Further trials using more patients with a long follow-up period would be worthwhile in order to clarify the possibility of disease progression and in order to predict the response of patients.

Adult↗