Search PubMed⌕ Search

Biomedical subjects

Y Kondo

Publications and source records attributed to Y Kondo.

At least 55 records · Page 3Linked to original sources

Effect of intravenous infusion of NIK-716 in anesthetized pediatric patients.

NIK-716 is a maintenance fluid based on the new concept of containing acetate as a base source and 5% glucose as an energy source. It was administered to pediatric patients under general anesthesia for less invasive surgical operations, and its efficacy was investigated by performing blood chemistry examination and urinalysis before and after administration. For efficacy assessment, the three items selected as efficacy parameters, i) the replacement and maintenance of water (assessment of hydration and urine output); ii) the maintenance of serum electrolytes (Na and K); and iii) the utilization of glucose (blood glucose and urinary glucose), were evaluated based on the results of laboratory examination (hematology, blood chemistry and urinalysis), and overall improvement was rated on the basis of total scores of these assessment items. No adverse events or abnormal laboratory values attributable to the maintenance fluid were observed in any of the 25 children administered NIK-716. In an overall improvement rating, NIK-716 proved markedly effective or effective in 79.2% of the 24 children evaluated. The overall safety rating was judged as 'no problem' in all 25 children. These findings suggest that NIK-716 is a useful and safe maintenance fluid that can be administered to pediatric patients during the course of surgery.

Adolescent↗

High-sensitivity instrument for measuring atmospheric NO2.

We report on the development of a high-sensitivity detection system for measuring atmospheric NO2 using a laser-induced fluorescence (LIF) technique around 440 nm. A tunable broad-band optical parametric oscillator laser pumped by the third harmonic of a Nd:YAG laser is used as a fluorescence excitation source. The laser wavelength is tuned at peak and bottom wavelengths around 440 nm alternatively, and the difference signal at the two wavelengths is used to extract the NO2 concentration. This procedure can give a good selectivity for NO2 and avoid interferences of fluorescent or particulate species other than NO2 in the sample air. The NO2 instrument developed has a sensitivity of 30 pptv in 10 s and S/N = 2. The practical performance of the detection system is tested in the suburban area for 24 h. The intercomparisons between the LIF instrument and a photofragmentation chemiluminescence (PF-CL) instrument have been performed under laboratory conditions. The correlation between the two instruments is measured up to 1000 pptv. A good linear relationship between the LIF measurements and the PF-CL measurements is obtained.

Air Pollution↗

Observation of a (6)(LambdaLambda)He double hypernucleus.

A double-hyperfragment event has been found in a hybrid-emulsion experiment. It is identified uniquely as the sequential decay of ( 6)(LambdaLambda)He emitted from a Xi(-) hyperon nuclear capture at rest. The mass of ( 6)(LambdaLambda)He and the Lambda-Lambda interaction energy DeltaB(LambdaLambda) have been measured for the first time devoid of the ambiguities due to the possibilities of excited states. The value of DeltaB(LambdaLambda) is 1.01+/-0.20(+0.18)(-0.11) MeV. This demonstrates that the Lambda-Lambda interaction is weakly attractive.

Journal Article↗

Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha.

Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that regulate a number of adaptive responses to low oxygen tension. They are composed of alpha- and beta-subunits that belong to the basic helix-loop-helix-PAS superfamily. Here we examined the expression of HIF-alpha subunit proteins in the human kidney and found that, in addition to HIF-1alpha and -2alpha, HIF-3alpha was also expressed. The sequence analysis revealed that, like mouse HIF-3alpha, human HIF-3alpha has high similarity with HIF-1alpha and -2alpha in the bHLH and PAS domains, but lacks structures for transactivation found in the C-terminus of HIF-1alpha and -2alpha. Furthermore, we performed reporter gene analysis and showed that HIF-3alpha suppresses hypoxia-inducible HIF-mediated gene expression. HIF-3alpha might be a negative regulator of hypoxia-inducible gene expression in the human kidney.

Amino Acid Sequence↗

STM images apparently corresponding to a stable structure: considerable fluctuation of a phase boundary of the Si(111)-(square root of (3) x square root of (3))-Ag surface.

We study scanning tunneling microscopy (STM) images near a phase boundary of the Si(111)- (square root of (3) x square root of (3))-Ag surface by using Monte Carlo simulations based on results of first-principles calculations. The boundary is found to fluctuate from snapshot to snapshot, and the feature of the simulated STM images differs distinctly from the observed one with a straightly extending honeycomb pattern of bright spots. Remarkably, statistical averages of the simulated images reproduce the observed feature. This study gives a warning of our tendency to relate STM images revealing clear arrangement of bright spots with some stable structure.

Journal Article↗

Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (human telomerase reverse transcriptase) gene promoter.

Because the apoptotic pathway is often disrupted in tumor cells, its genetic restoration is a very attractive approach for the treatment of tumors. To treat malignant gliomas with this approach, it would be preferred to restrict induction of apoptosis to tumor cells by establishing a tumor-specific expression system. Telomerase is an attractive target because the vast majority of malignant gliomas have telomerase activity whereas normal brain cells do not. Activation of telomerase is tightly regulated at the transcriptional level of the telomerase catalytic subunit [human telomerase reverse transcriptase, (hTERT)]. Therefore, we hypothesized that using a hTERT promoter-driven vector system, an apoptosis-inducible gene may be preferentially restricted to telomerase- or hTERT-positive tumor cells. In this study, we constructed an expression vector consisting of the constitutively active caspase-6 (rev-caspase-6) under the hTERT promoter (hTERT/rev-caspase-6) and then investigated its antitumor effect on malignant glioma cells. The rationale for using the rev-caspase-6 gene is because it induces apoptosis independent of the initiator caspases. We demonstrated that the hTERT/rev-caspase-6 construct induced apoptosis in hTERT-positive malignant glioma cells, but not in hTERT-negative astrocytes, fibroblasts, and alternative lengthening of telomeres cells. In addition, the growth of s.c. tumors in nude mice was significantly suppressed by the treatment with hTERT/rev-caspase-6 construct. The present results strongly suggest that the telomerase-specific transfer of the rev-caspase-6 gene under the hTERT promoter is a novel targeting approach for the treatment of malignant gliomas.

Animals↗

Expression of thyroid hormone receptor betaA gene assayed by transgenic Xenopus laevis carrying its promoter sequences.

The responsiveness of thyroid hormone responsive element (TRE)-containing promoter sequence to thyroid hormone (TH) was studied utilizing Xenopus laevis carrying a transgene containing 5'-upstream region of TRbetaA1 gene and green fluorescent protein (EGFP) gene. EGFP-expression was seen first in neurulae, which continued to stage 45, then became weak, and again started to increase at the prometamorphic stage, culminating at the metamorphic climax stage. Immunohistochemistry identified eyes, viscera, and muscles as the EGFP-expressing larval tissues. The treatment of premetamorphic tadpoles with TH induced the precocious EGFP-expression. We also showed that the transgenic Xenopus adults were responsive to exogenous TH, a high responsiveness being seen in brain, small intestine, kidney, and bone. TRbeta-expression in the embryo, larva, and adult was verified by Western blotting. Thus, TH not only regulates the metamorphosis, but also might play some biological role(s) in embryos and adults.

Animals↗

Impaired retention of technetium-99m tetrofosmin in hypertrophic cardiomyopathy.

The purpose of this study was to determine whether myocardial imaging using technetium-99m tetrofosmin can noninvasively identify myocardial damage in hypertrophic cardiomyopathy (HC). The study consisted of 10 patients with apical HC, 10 with asymmetric septal HC (ASH) group, 5 with dilated cardiomyopathy (DC)-like group, and 20 healthy subjects. With use of a bull's-eye map of single-photon emission computed tomographic imaging, the total defect score of tetrofosmin and the washout rate were assessed in 5 segments (septum, and anterior, lateral, and inferior walls, and apex) of the left ventricle. A localized increase in defect score and washout rate was observed in the hypertrophied region in the group with apical HC. An increased washout rate was observed in the ASH group regardless of hypertrophy, suggesting that tetrofosmin retention by the mitochondria was impaired in the entire left ventricular wall. The washout rate was further increased at all segments in the DC-like group versus the ASH group. Tetrofosmin retention by mitochondria was impaired in the entire left ventricular wall in the ASH group and was increased further in the DC-like group. The dysfunction of myocardial cells was limited to the hypertrophied region in the apical HC group.

Cardiomyopathy, Dilated↗

DNA methyltransferase expression and DNA methylation of CPG islands and peri-centromeric satellite regions in human colorectal and stomach cancers.

We evaluated the significance of aberrant DNA methyltransferase expression in human carcinogenesis by examining 32 colorectal and 34 stomach cancers. Levels of mRNAs encoding DNA methyltransferases were measured by reverse transcription, followed by real-time quantitative detection of PCR products. The DNA methylation state of CpG islands and peri-centromeric satellite regions was examined by bisulfite modification and Southern blotting, respectively. The average level of mRNA for DNMT1 and DNMT3b in colorectal and stomach cancers was significantly higher than in corresponding non-cancerous mucosae, whereas the average level of mRNA for DNMT2 was significantly lower in colorectal and stomach cancers than in non-cancerous tissue. Over-expression of DNMT3b in stomach cancer was significantly higher in cases with lymph node metastasis than in cases without. DNA hypermethylation on the p16, human Mut L homologue-1 and thrombospondin-1 genes and the methylated in tumor (MINT) 1, 2, 12, 25 and 31 clones was found in 23%, 27%, 9%, 23%, 20%, 23%, 20% and 10% of the colon cancers and in 9%, 19%, 30%, 25%, 34%, 19%, 81% and 3% of the stomach cancers, respectively. Criteria for identification of the CpG island methylator phenotype (CIMP) were met in 23% of colorectal cancers and 31% of stomach cancers. DNA hypomethylation on satellites 2 and 3 was detected in 0% and 8% of colorectal and stomach cancers, respectively. Over-expression of DNMT1 mRNA was significantly associated with CIMP, whereas the level of DNMT3b mRNA was not associated with CIMP or DNA hypomethylation of peri-centromeric satellite regions. These data suggest that both over-expression of the maintenance DNA methyltransferase DNMT1 and over-expression of a newly identified de novo DNA methyltransferase, DNMT3b, are involved in human carcinogenesis, probably at different stages and through different mechanisms.

Adult↗

Mesityllithium as a reagent for chemoselective halogen-lithium exchange reaction.

[figure: see text] Mesityllithium was found to be an excellent selective lithiating agent to prepare aryllithium compounds having alkoxycarbonyl groups. To extend our studies on chemoselective lithiation, an important precursor for the synthesis of camptothecin was prepared using a halogen-lithium exchange reaction followed by an intramolecular 1,2-addition.

Camptothecin↗

Characterization of low dose streptozotocin-induced progressive diabetes in mice.

Our previous study indicated that a single i.p. injection of 100 mg/kg streptozotocin (STZ) is able to induce slowly progressive diabetes mellitus in adult ICR mice. In the present study, the non-fasting serum insulin levels of the mice administered 100 mg/kg STZ were normal throughout the 24-week-observation after STZ injection. In the STZ-administered mice, the area of islets and the number of insulin-immunoreactive cells (beta-cells) were normal at 1 week and then continued to decrease gradually as the time went on. In contrast, there was a relative increase in the number of glucagon-immunoreactive cells (alpha-cells) in these mice. In addition, in the STZ-administered mice, the degree of glucose tolerance continued to reduce from 2 weeks till 12 weeks when the experiment terminated. The rise in serum insulin levels stimulated by glucose in the STZ-administered mice began to subside from about 2 weeks and had completely ceased by 12 weeks. These results indicate that 100 mg/kg STZ-induced diabetic mouse model is non-insulin-dependent diabetes, which is characterized by impaired insulin response to glucose stimulation.

Journal Article↗

Establishment of embryonic stem cell lines from cynomolgus monkey blastocysts produced by IVF or ICSI.

Human embryonic stem (ES) cells are predicted to be a valuable source for producing ES-derived therapeutic spare tissues to treat diseases by controlling their growth and differentiation. To understand the regulative mechanisms of their differentiation in vivo and in vitro, ES cells derived from nonhuman primates could be a powerful tool. We established four ES cell lines from cynomolgus monkey (Macaca fascicularis) blastocysts produced by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The ES cells were characterized by the expression of specific markers such as alkaline phosphatase and stage-specific embryonic antigen-4. They were successfully maintained in an undifferentiated state and with a normal karyotype even after more than 6 months of culture. Pluripotential competence was confirmed by the formation of teratomas containing ectoderm-, mesoderm-, and endoderm- derivatives after subcutaneous injection into SCID mice. Differentiation to a variety of tissues was identified by immunohistochemical analyses using tissue-specific antibodies. Therefore, we established pluripotent ES cell lines derived from monkeys that are widely used as experimental animals. These lines could be a useful resource for preclinical stem cell research, including allogenic transplantation into monkey models of disease.

Animals↗

Evaluation of the rodent micronucleus assay by a 28-day treatment protocol: Summary of the 13th Collaborative Study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Environmental Mutagen Society of Japan (JEMS)-Mammalian Mutagenicity Study Group (MMS).

To examine whether micronucleus tests can be incorporated into general toxicology assays, we performed micronucleus tests applying the treatment protocols typically used in such assays. In this 13th Collaborative Study of the CSGMT, both rats and mice were tested, although rats were used in the majority of the studies. Fifteen mutagens were tested in rats, mainly by oral (p.o.) administration. Micronucleus induction was evaluated 2, 3, and 4 days, and 1, 2, 3, and 28 days after the beginning of the treatment in the peripheral blood, and at 28 days in the bone marrow. Of the 15 chemicals that induced micronuclei in rats in short-term assays, two chemicals (1,2-dimethylhydrazine.2HCl and mitomycin C) were negative in all our experiments, possibly because of insufficient dose levels. The remaining 13 were positive within the estimated dose range of a general toxicology assay, suggesting the possibility of integrating the micronucleus assay into general toxicology assays. Three patterns were observed in micronucleus induction during the period of repeated treatment: (1) gradual increases in micronucleus frequency with sequential doses, (2) a peak at 3-5 days followed by gradual decreases in micronucleus frequency with sequential doses, and (3) a rapid increase in micronucleus frequency followed by a plateau. We evaluated factors that might have been involved in those patterns, such as the spleen function, target organ exposure, extramedullary hematopoiesis, hypothermia, and hypoxia. Another factor we considered was dosage. Because the dosages employed in a general toxicity assay are usually lower than those used in short-term micronucleus assays, this discrepancy was considered the greatest potential problem for integrating the micronucleus assay into general toxicology assays. Our results indicate that the integration of the micronucleus assay into a 28-day toxicological assay is feasible. To serve this purpose, blood samples collected 4 days after the beginning of treatment and blood and bone marrow samples collected at autopsy should be examined. Furthermore, although it is recognized that mice may be suitable for performing independent micronucleus assays, we propose that rats can provide biologically important and relevant information regarding potential chemical mutagens that can be evaluated under conditions used in the conduct of general toxicology studies.

Animals↗

Effects of sedentary work on physical fitness and serum cholesterol profile in middle-aged male workers.

OBJECTIVES: To evaluate independent and interactive health effects of physical activity at work (PAW) and physical activity at habitual exercise (PAHE). METHODS: A cross-sectional study on 1,117 male workers aged 29 to 46 years with a mean of 37.0 years. Using a self-administered questionnaire, the subjects were classified into 'High'/'Low' (n = 338/779) on PAW, and into 'Yes'/'No' (n = 353/764) on PAHE. As outcome indices, physical fitness expressed as maximal oxygen uptake (VO2max) was estimated, and serum total cholesterol (TC), HDL-cholesterol (HDLC) and TC/HDLC ratio were determined. Age, body mass index (kg/m2), alcohol-drinking and smoking were used as confounding factors. RESULTS: The 'High' PAW group had a significantly higher level of VO2max than the 'Low' PAW group (+ 1.0 ml/kg min; 34.4 vs. 33.4 ml/ kg min in adjusted means). The 'High' PAW group also had a better profile of serum cholesterol than the 'Low' PAW group, but it was not significant. The 'Yes' PAHE group had significantly higher levels of VO2max (+ 2.0 ml/kg min; 34.9 vs. 32.9 ml/kg min) and serum HDLC (+0.09 mmol/l; 1.48 vs. 1.39 mmol/l), and a significantly lower TC/HDLC ratio (-0.29; 3.90 vs. 4.19) than the 'No' PAHE group. Among PAW PAHE subgroups, the 'High-Yes' group (n = 110), most physically active, had the best profile of VO2max and serum cholesterol, and the 'Low-No' group (n = 536), least physically active, had the worst one. Interactive effects of PAW and PAHE were not found either on VO2max or on serum cholesterol profile. All the results were not influenced by statistical adjustments for the four confounding factors used here. CONCLUSIONS: Both sedentary work and lack of habitual exercise are very common in Japanese workers. Sedentary work, independently from lack of habitual exercise, may increase the risk of diseases related to physical inactivity by affecting physical fitness and serum cholesterol profile.

Adult↗

A clinicopathologic study of mucinous adenocarcinoma of the stomach.

BACKGROUND: Mucinous adenocarcinoma of the stomach is a rare histologic type of gastric adenocarcinoma and its features are still controversial. We attempted to clarify the clinicopathologic characteristics of this histologic type. METHODS: We reviewed the records of 112 patients with mucinous adenocarcinoma of the stomach (MUC) and 4160 patients with nonmucinous gastric adenocarcinoma (NMUC) for factors including age; sex; tumor location, size, and depth; lymph node metastasis; lymphatic or venous permeation; peritoneal dissemination; liver metastasis; and survival rate. We also investigated the relationship between cancer depth and lymph node metastasis. Statistical analysis included chi 2 and Student's t-tests. Survival rates were calculated by the Kaplan-Meier method and analyzed by the log rank test. RESULTS: MUC was found mostly in younger patients, in the lower part of the stomach and was of larger size, invading to or beyond the muscularis propria, positive for lymph node involvement, and associated with peritoneal dissemination. The overall 5-year survival rate in patients with MUC was lower than that in NMUC patients, because the MUC patients more frequently had advanced stage disease; however, the survival rates in the two groups did not differ significantly. As for the relationship between cancer depth and lymph node involvement, the frequency of lymph node metastasis increased when invasion reached the submucosa in patients with MUC compared with those with NMUC while the frequency of lymph node metastasis increased in the muscularis propria in patients with NMUC compared with those with NMUC. CONCLUSION: MUC was characteristically found in younger patients, at lower sites, at an advanced stage, and with peritoneal dissemination; MUC had a poor prognosis. Lymph node metastasis should be suspected when MUC invades to the submucosa or deeper.

Adenocarcinoma, Mucinous↗

A new approach to mRNA in proximal tubule cells of patients with CLCN5 channelopathy.

ClC-5 is a chloride channel whose gene mutations have been reported to be associated with X-linked nephrolithiasis (XRN), X-linked recessive hypophosphatemic rickets (XLRH), Dent disease, and idiopathic low-molecular-weight proteinuria (ILMWP) in Japanese children. To establish more efficient screening for CLCN5 abnormalities, we developed a new diagnostic method using reverse transcription and polymerase chain reaction (RT-PCR) of cultured renal tubular cells from the urine of patients. Using this new method, we successfully detected microdeletion of ClC-5 mRNA in a patient and splicing abnormality of the CLCN5 Cl channel.

Cells, Cultured↗

Measurement of circulating biliary glycoprotein (CD66a) in liver diseases.

PURPOSE: Biliary glycoprotein (BGP), a member of the carcinoembryonic antigen (CEA) gene family, is produced by hepatocytes, and is suggested to function as a cell adhesion molecule, mouse hepatitis virus receptor, and tumor suppressor. Our aim was to establish an enzyme immunoassay for circulating BGP and to study its significance in liver diseases. METHODS: For enzyme immunoassay, a monoclonal antibody (mAb), TS135, which recognizes BGP was used as a catcher, and biotin-labeled polyclonal anti-CEA antibodies were used as a tracer. Seventy-six serum specimens obtained from patients with various liver diseases were submitted to the assay. RESULTS: The incidence of positivity for antigen TS135 in the serum samples of the 76 patients was 57.9%. The most significant correlation among conventional liver function tests was found between antigen TS135 and gamma-glutamyl transpeptidase (gamma-GTP). However, among the 56 patients whose serum antigen TS135 and gamma-GTP levels could be measured simultaneously, 5 were antigen TS135-positive and gamma-GTP-negative (8.9%) and 6 were antigen TS135-negative and gamma-GTP-positive (10.7%). The increased serum level of antigen TS135 in 6 cholangiocellular carcinoma (CCC) patients led us to the immunohistochemical study of CCC, in which 8 of the 8 tissue specimens tested were positive for mAb TS135, indicating the production of the antigen from CCCs. CONCLUSIONS: This preliminary study suggests that the circulating antigen TS135 level correlates with gamma-GTP in liver diseases, but that TS135 may also have a unique significance, different from that of gamma-GTP, as a liver function test.

Adult↗