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Biomedical subjects

N Ikeda

Publications and source records attributed to N Ikeda.

At least 73 records · Page 4Linked to original sources
PubMed2000

Quantitative analysis of estrogen receptor-beta mRNA and its variants in human breast cancers.

We have carried out a quantitative analysis of ER-alpha and ER-beta mRNA expression in normal (n = 11) and breast cancer (n = 112) tissues using a real-time (Taq-Man) PCR assay. Expression of ER-beta mRNA variants has also been studied by triple-primer PCR assay. ER-alpha mRNA levels in normal breast tissues were significantly (p < 0.01) lower than those in ER-positive breast cancers but not significantly different from those in ER-negative breast cancers. However, ER-beta mRNA levels in normal breast tissues were significantly (p < 0.01) higher than those in ER-positive and ER-negative breast cancers. Proportions of ER-beta1 and ER-beta2 mRNA expression among total ER-beta mRNA expression were significantly higher and those of ER-beta5 and ER-beta5; mRNA were significantly lower in normal breast tissues than in ER-positive and ER-negative breast cancers. ER-beta mRNA levels and proportions of ER-beta mRNA variants did not show any significant correlation with age, tumor size, lymph node status and histological grade. Our results demonstrate that ER-alpha mRNA is up-regulated and ER-beta mRNA is down-regulated during carcinogenesis of breast cancers. Changes in proportions of ER-beta mRNA variants are also implicated in this process.

Adult↗
PubMed2000

Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in breast carcinoma by real-time polymerase chain reaction.

BACKGROUND: Estrogen action is mediated not only through a classic estrogen receptor (ER) (ER-alpha) but also through a second ER (ER-beta) that has a structure and function similar to ER-alpha. A correlation between ER-beta mRNA expression with ER and progesterone receptor (PR) protein levels as well as prognostic factors remains to be established in breast carcinoma. METHODS: The authors conducted a quantitative analysis of ER-alpha and ER-beta mRNA expression in 116 breast tumors using real-time polymerase chain reaction (PCR), and investigated a possible correlation between ER-alpha and ER-beta mRNA expression and ER and PR status as determined by enzyme immunoassay as well as with various prognostic factors. RESULTS: ER-alpha mRNA levels were significantly (P < 0.01) higher in ER positive compared with ER negative tumors. Conversely, ER-beta mRNA levels were significantly (P < 0.01) lower in ER positive compared with ER negative tumors. Accordingly, the ratio of ER-beta to ER-alpha was significantly (P < 0.01) higher in ER negative compared with ER positive tumors. A subset analysis based on ER and PR status showed that ER-beta mRNA levels as well as the ratios of ER-beta to ER-alpha mRNA level were highest in ER negative and PR negative tumors (P < 0.05). ER-alpha mRNA levels were significantly (P < 0.05) higher in postmenopausal compared with premenopausal tumors. Histologic Grade 3 tumors showed a significant decrease in ER-alpha mRNA levels compared with Grade 1 and 2 tumors (P < 0.01 and P < 0.05, respectively). No significant correlation between ER-alpha and ER-beta mRNA levels and histologic type, tumor size, or lymph node status was observed. CONCLUSIONS: An absolute and relative increase in ER-beta mRNA levels in ER negative and PR negative breast tumors, which rarely respond to endocrine therapy, suggests the possible involvement of up-regulation of ER-beta mRNA in the development of estrogen-independent tumors.

Adult↗
PubMed2000

Breast cancer risk associated with polymorphism in CYP19 in Japanese women.

Screening of the entire coding and major promoter regions of the CYP19 gene identified two novel polymorphisms at codon 39 (Trp to Arg) and codon 408 (silent) in addition to those reported previously at codon 264 (Arg to Cys) and intron 4 [tetranucleotide (TTTA) simple tandem repeat]. A case-control study was conducted in order to see whether or not these polymorphisms were associated with breast cancer risk in Japanese women. Homozygous and heterozygous carriers of the variant allele Arg at codon 39 showed a significantly decreased risk of breast cancer (OR=0.39, 95%C.I.=0. 17-0.89). On the other hand, homozygous carriers of the allele with 10 or more TTTA repeats at intron 4 showed a trend toward an increase (OR=1.80, 95%C.I.=0.97-3.36) in breast cancer risk. Other polymorphisms were found not to be associated with breast cancer risk. These results suggest that the CYP19 polymorphisms at exon 39 and intron 4 would be useful for selecting Japanese women at a high risk of breast cancer.

Adult↗
PubMed2000

Determination of nitrate in blood by gas chromatography and gas chromatography-mass spectrometry.

We devised a sensitive and simple method for determining nitrate in whole blood, using an extractive alkylation technique. Nitrate in whole blood was reduced to nitrite by hydrazine sulfate in the presence of Cu2+ and Zn2+ as catalysts, and alkylated with pentafluorobenzyl bromide using tetradecyldimethylbenzylammonium chloride as the phase-transfer catalyst. The obtained derivative was analyzed qualitatively by gas chromatography-mass spectrometry and quantitatively by gas chromatography with electron-capture detection. The detection limit of nitrate in whole blood was 0.01 mM. The calibration curve was linear over the concentration range from 0.02 to 1.0 mM for nitrate in whole blood. The accuracy and precision of the method were evaluated and the relative standard deviations were found to be within 10%. Using this method, the blood nitrate levels of two victims who committed suicide by inhaling automobile exhaust gas were determined.

Alkylation↗
PubMed2000

Genetic polymorphism in CYP17 and breast cancer risk in Japanese women.

A case-control study was conducted to investigate the association of two genetic polymorphisms (1931T/C and 1951G/A) in the promoter region of the CYP17 gene with breast cancer risk in Japanese women. No significant association was observed between CYP17 polymorphism(1951G/A) and breast cancer risk (odds ratio (OR) = 1.71, 95% confidence interval (CI): 0.28-1.84). In contrast, a significant increase in breast cancer risk (OR= 1.82. 95% CI: 1.07-3.12) was observed in CYP17(1931C/C) homozygotes compared with CYP17(1931T/C) heterozygotes and CYP17(1931T/T) homozygotes when women aged > or = 55 years were considered, but such a significant increase was not observed when women aged < or = 54 years were considered (OR = 0.96, 95% CI: 0.56-1.63). These results suggest that CYP17 polymorphism(1931T/C) would be useful in the selection of Japanese women at a high risk for developing breast cancer at the age of > or = 55 years.

Adult↗
PubMed2000

Sudden death of an infant with bronchopulmonary dysplasia and bilateral cervical lymphadenopathy--a vagal death?

A sudden unexpected death is reported in a 15-month old boy, born with an extremely low birth weight and then had suffered prolonged respiratory complications arising from infantile respiratory distress syndrome. The autopsy revealed severe bronchopulmonary dysplasia (BPD) in his lungs with secondary pulmonary heart disease; a tracheotomy was carried out to enable his survival. The cause of death was established as being acute cardiac and pulmonary failure due to severe BPD, rather than mechanical asphyxia. The perilaryngeal lymph nodes were also significantly enlarged and closely surrounded the vagus bilaterally. Such cervical lymphadenopathy could have resulted in the mechanical compression of the vagus upon movement of the neck. For this reason, anatomical examination of the cervical portion of the vagus and its path may be of great significance when analyzing the cause of death in the cases of sudden infant death.

Journal Article↗
PubMed2000

Sudden unexpected death with dysplastic change in the atrioventricular node artery.

We report an autopsy case of a 19-year-old male who died suddenly. Death happened while he was sleeping after drinking alcoholic beverages. His heart revealed concentric hypertrophy of the left ventricle without asymmetric septal hypertrophy or mitral regurgitation. Upon microscopic examination, the epicardial atrioventricular (AV) node artery revealed stenosis with intimal thickening before it entered the ventricular septum and acute ischemic change was observed beneath the conduction system in the upper ventricular septum. This finding suggests that death occurred after some preceding localized ischemic event within the ventricular septum. We therefore consider that the cause of death was fatal arrhythmia due to dysplastic change to the AV node artery.

Journal Article↗
PubMed2000

Outcome following a population screening programme for oral cancer and precancer in Japan.

The purpose of this study was to evaluate the validity and outcome of an oral mucosal screening programme conducted in Japan. All adults over the age of 40 years resident in Tokoname city were invited by letter to attend a free general health screen and oral examinations annually. Twenty- to 39-year-old females were also encouraged to participate. During the years 1996-98, a total of 19056 subjects (5885 male, 13171 female: mean age 60.7+/-11.3 years) were examined by three types of screeners: postgraduate dental residents (n=17), hospital dentists (n=5) and general dental practitioners (n=15). In the cohorts examined screening dentists recorded oral mucosal lesions in 783 (4.1%) subjects. Of those detected with mucosal lesions, 200 (25.5%) were referred and 137 (68. 5%) attended for follow up examination in hospital departments by specialists with full diagnostic back up facilities. Thirty-nine subjects were confirmed as having oral cancer or precancer (two squamous cell carcinomas, 37 leukoplakias) and 40 with lichen planus. Five false positives (3.6%) were found. Among the cases referred under other diagnostic labels no cancers were detected. Among those who attended for confirmation of oral cancer or precancer by a specialist, sensitivity, specificity and positive predictive value were 0.92, 0.64 and 0.78, respectively. In males with oral cancer/leukoplakia, the prevalence of smoking, drinking and combined habits was higher than those with lichen planus or among negative subjects. The sensitivity and specificity determined from this research suggests that the performance of the Japanese dentists employed in screening was satisfactory. An attendance of 68% for re-examination by specialists compares well with other reported studies measuring patient compliance.

Adult↗
PubMed2000

Serum antioxidant micronutrients and the risk of oral leukoplakia among Japanese.

A population-based case-control study was designed for the investigation of any association between serum micronutrient levels and oral leukoplakia. Out of a total of 9536 subjects over the age of 40 years who participated in the oral mucosal screening programme in Tokoname city, 48 cases detected with oral leukoplakia (38 male:10 female) were recruited. For each case, four controls matched by age and sex were selected from the same cohort. We examined the fasting serum levels of retinol, alpha-tocopherol, zeaxanthin and lutein, cryptoxanthin, lycopene and carotenoids (alpha-carotene and beta-carotene) by high-performance liquid chromatography. Among males with leukoplakia mean serum lycopene and beta-carotene levels (0.175+/-0.202, 0.357+/-0.295 micromol/l) were significantly lower than those of controls (0.257+/-0.252, 0.555+/-0.408 micromol/l) (P<0.05, P<0.005). Logistic regression analysis with leukoplakia as the dependent variable showed that high serum levels of beta-carotene were related to low risk of oral leukoplakia (odds ratio 0.160, 95% C.I.: 0.029-0.866, P<0.05). There were no significant differences in any of the serum nutrients estimated in female subjects. Our results suggest for the first time that high serum levels of beta-carotene may provide protection against oral precancer for the Japanese male.

Adult↗
PubMed2000

Antioxidative and prooxidative action of stilbene derivatives.

The effects of stilbene derivatives, including resveratrol, diethylstilboestrol and stilbene, as antioxidants or prooxidants were examined. Resveratrol and diethylstilboestrol, but not stilbene, strongly inhibited NADPH- and adenosine 5'-diphosphate (ADP)-Fe3+-dependent lipid peroxidation at the initial and propagation stages. In addition, phenolic stilbenes also inhibited ultraviolet light-induced lipid peroxidation. Resveratrol and diethylstilboestrol efficiently scavenged 2,2'-azobis-(2-amidinopropane)-dihydrochloride peroxyl radicals. However, 2,2'-diphenyl-p-picrylhydrazyl radicals were trapped only by resveratrol, but not by diethylstilboestrol. These results suggest that the inhibitory effect of phenolic stilbenes on lipid peroxidation was due to their scavenging ability of lipid peroxyl and/or carbon-cantered radicals. Resveratrol efficiently reduced ADP-Fe3+, but not EDTA-Fe3+. Stilbenes and diethylstilboestrol did not reduce either ADP-Fe3+ or EDTA-Fe3+. The strand breaks of DNA were stimulated during the interaction of resveratrol with ADP-Fe3+ in the presence of H2O2. These results suggest that phenolic stilbenes act as antioxidants of membrane lipids and that resveratrol has a prooxidative effect DNA damage during interaction with ADP-Fe3+ in the presence of H2O2.

Animals↗
PubMed2000

Effect of amino acid substitution at the P(3) and P(4) subsites of fusion proteins on kex2 protease activity.

The effect of amino acid substitution at the P(3) and P(4) subsites on the cleavage activity of a recombinant secretory-type Kex2 protease (Kex2-660) was investigated using recombinant fusion proteins. They were constructed from a truncated Escherichia coli beta-galactosidase (beta G-117S) followed by human parathyroid hormone amino acids 1-34 [hPTH(1-34)] with a junction designed to allow cleavage with Kex2-660. Kex2-660 preferentially cleaved the fusion protein with Arg-His at the P(3)-P(4) subsite, whereas it poorly cleaved the fusion proteins with Val-Asp, Gly-His, Cys-His and Leu-His compared with the original sequence, Val-Lys. As for Asp and Glu at P(4), they precluded the cleavage almost completely. Some of the substitutions were investigated kinetically using the fusion proteins and peptide-substrate mimics corresponding to the 15 amino acids contained in the junction. The substitution Val-Lys to Arg-His resulted in a 2-fold increase in k(cat) and the introduction of Asp at P(4) of the peptide substrate resulted in a large increase in K(m) and a change in the optimum pH. The ordered cleavage of the fusion protein was attained by introducing the two dibasic sites, Arg-His and Asp-His, at P(4)-P(3). The fusion protein was cleaved with Kex2 only at the former site in 3.0 M urea at pH 8.0 and the liberated peptides containing the latter site could be cleaved further with Kex2 at pH 6.5 once purified in urea-free solution. Thus Kex2 exhibited extended substrate specificity beyond P(2)-P(1) in the cleavage of the fusion proteins, although it depended on the reaction conditions.

Amino Acid Sequence↗
PubMed2000

Parameters for the preoperative evaluation of arteriosclerosis for free-flap transfers in head and neck surgery.

The microsurgical transfer of free tissue has become essential for reconstructive surgery in the head and neck, and arteriosclerosis is one of the risk factors for microvascular anastomosis. In order to detect severe arteriosclerosis and to determine the parameters useful for evaluating arteriosclerosis preoperatively, the grade of arteriosclerosis was investigated with respect to age, PWV (Aortic Pulse Wave Velocity), ocular fundus findings, and histopathological findings of the recipient arteries in 40 patients with malignant tumours. Severe arteriosclerosis was detected in 2/40 patients by the PWV, in the same 2/40 patients by the ocular fundus findings and in the same 2/40 patients by histopathological findings. The current observations indicate that the PWV and ocular fundus findings are useful parameters for the preoperative evaluation of the grade of arteriosclerosis.

Adult↗
PubMed2000

Hypoglycaemic brain lesions in a dog with insulinoma.

A 5-year-old female Collie dog showed excessive salivation, vomiting and neurological signs, including hind-limb weakness, mental dullness and subsequent recumbency with paddling movements of the limbs. Blood glucose and insulin concentrations were 35 mg/dl and 70.0 microU/ml, respectively. At necropsy, two masses, one at the caudal edge of the pancreas and the other in the omentum, were found and diagnosed as insulinoma. Histological examination of the brain showed early signs of acute neuronal necrosis exclusively in the superficial layers of the cerebral cortex, in addition to spongy changes in the dentate gyrus of the hippocampus. The light microscopical findings were identical in character and distribution with those of naturally occurring hypoglycaemia in humans and experimentally induced hypoglycaemia in animals.

Animals↗
PubMed2000

The impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma.

Interferon gamma (IFN-gamma) plays an important role in host defense mechanism and participates in the progression of chronic liver disease. IFN-gamma exerts its pleiotrophic effects by transcriptional regulation of expression of numerous genes, such as major histocompatibility complex (MHC) class I and Fas, through interaction with IFN-gamma receptor (IFN-gamma-R). Although hepatocytes in normal liver express weak or no IFN-gamma-R, those in acute and chronic liver disease up-regulate its expression. A study using IFN-gamma-R alpha-chain knock-out mice revealed the actions of IFN-gamma on tumor cells as an extrinsic tumor-suppressor mechanism. However, it is unclear whether or how hepatocellular carcinoma (HCC) blocks the signal transduction of IFN-gamma to evade host immune surveillance. We examined the expression of IFN-gamma-R and IFN-gamma-inducible genes in 44 cases with HCC using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In noncancerous liver tissues (n = 38), IFN-gamma-R expression on the cell surface was up-regulated in 27 cases. In IFN-gamma-R-negative cases (n = 15), tumor size was larger (P =.032), serum alpha-fetoprotein (AFP) level was higher (P =.001), intrahepatic and extrahepatic metastasis was more common (P =.044 and.013, respectively), and Ki-67 labeling index (LI) was higher (P =.041), compared with IFN-gamma-R-positive cases. Accordingly, the evasion mechanism may play an important role in progression, especially metastasis, in HCC. The significant correlation between the status of IFN-gamma-R and the expression of Fas and MHC implies that the loss of IFN-gamma-R might contribute to the mechanism of escape from host immune rejection in HCC.

Aged↗
PubMed2000

Survival factors in digital replantation: significance of postoperative anaemia.

Two hundred and fifty-two consecutive digital replantations and revascularizations in 201 patients were retrospectively reviewed to determine factors influencing survival. Children under 9 years of age, women, complete amputations, blood transfusions and secondary thrombectomy were poor prognostic factors. In addition, low haemoglobin and haematocrit levels during the postoperative period were associated with a higher failure rate. Inappropriate use of anticoagulants and excessive postoperative anaemia should be avoided following replantation.

Adult↗
PubMed2000

Sensitive and selective determination of tetracaine and its metabolite in human samples by gas chromatography-mass spectrometry.

A sensitive and reliable method was developed for the determination of tetracaine and its metabolite, p-butylaminobenzoic acid, in human samples. Tetracaine and the metabolite, effectively extracted using a liquid-liquid extraction procedure from 0.5 g of sample, were analyzed by gas chromatography-mass spectrometry. Tetracaine was analyzed without derivatization, and the metabolite was analyzed after tert-butylolimethylsilyl derivatization. Dibucaine and p-dimethylaminobenzoic acid were used as internal standards for tetracaine and the metabolite, respectively. The calibration curve for each compound was linear in the concentration range from 10 to 1,000 ng/0.5 g, and the lower limits of detection were 10 ng/g for tetracaine and 0.6 ng/g for the metabolite in whole blood and tissues. The accuracy and precision of the method were evaluated in whole blood and brain at the concentrations of 50 ng/0.5 g and 500 ng/0.5 g for tetracaine and 10 ng/0.5 g and 100 ng/0.5 g for the metabolite. The coefficients of variation ranged from 0.8 to 3.0% for tetracaine and 2.4 to 9.8% for the metabolite. We used this method to determine tetracaine and its metabolite in human whole blood and tissues of an autopsied patient who died during spinal anesthesia induced by tetracaine.

4-Aminobenzoic Acid↗