Search PubMed⌕ Search

Biomedical subjects

S Ueno

Publications and source records attributed to S Ueno.

At least 91 records · Page 5Linked to original sources

The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants.

The serotonin transporter (5-HTT) gene is a promising candidate for introducing the heritability of interindividual variation in personality and the genetic susceptibility for various psychiatric diseases. Transcription of the gene is modulated by a common polymorphism in its upstream regulatory region (5-HTT gene-linked polymorphic region: 5-HTTLPR). The 5-HTTLPR consists of variation of the repetitive sequence containing GC-rich, 20-23-bp-long repeat elements. A deletion/insertion in the 5-HTTLPR was first reported to create a short (S) allele and a long (L) allele (14- and 16-repeats, respectively). Three other kinds of alleles (18-, 19- and 20-repeats) in addition to the S and L alleles in 5-HTTLPR have been reported. In the present study, we examined the 5-HTTLPR polymorphism in detail and identified ten novel sequence variants, concluding that the alleles reported as S and L are divided into four and six kinds of allelic variant, respectively. Subsequently, we developed a method for genotyping. The total number of alleles (14-A, 14-B, 14-C, 14-D, 15, 16-A, 16-B, 16-C, 16-D, 16-E, 16-F, 19, 20 and 22) in the 5-HTTLPR was 14 in our populations (Japanese: n = 131; Caucasian: n = 74) in the present study. In addition, a significant ethnic difference between Japanese and Caucasian populations was observed for distributions of alleles and genotypes (P < 0.0001 and P < 0.0001, respectively). Our results suggest that the analyses of the 5-HTTLPR should be revised by genotyping with a more complete subdivision of alleles. Molecular Psychiatry (2000) 5, 32-38.

Alleles↗

Genetic structure of Camellia japonica L. in an old-growth evergreen forest, Tsushima, Japan.

The spatial genetic structure of Camellia japonica was investigated, using microsatellite markers, in a 4-ha permanent plot within an old-growth forest. Spatial distribution of individuals was also assessed to obtain an insight into spatial relationships between individuals and alleles. Morisita's index of dispersion showed that 518 C. japonica individuals in the plot were clumped, and Moran's I spatial autocorrelation coefficient revealed weak genetic structure, indicating a low level of allele clustering. Average I correlograms showed that there was stronger genetic structure over short-distance classes. The clumped distribution of individuals and the positive autocorrelation over short-distance classes may result from the limited seed dispersal and microsite heterogeneity of the stand, while the genetic structure may be weakened by overlapping seed shadow and extensive pollen flow, mediated by animal vectors, and the high outcrossing rate found in C. japonica.

Ericales↗

Regulation of alpha3 nicotinic acetylcholine receptor subunit mRNA levels by nerve growth factor and cyclic AMP in PC12 cells.

To investigate the effects of nerve growth factor (NGF) and cyclic AMP (cAMP) on the level of the nicotinic acetylcholine receptor subunit alpha3 mRNA, we used PC12h cells, PC12 cells expressing dominant-negative Ras protein, and the parental PC12 cells. PC12h cells have NGF-responsive tyrosine hydroxylase activity. Expression of dominant-negative Ras protein prevents the signaling through the Ras-mitogen-activated protein kinase cascade. The morphological changes of the parental PC12 cells in response to NGF and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPTcAMP), a cell-penetrating cAMP analogue, were similar to those of PC12h cells. NGF up-regulated the alpha3 mRNA level in PC12h cells and down-regulated the alpha3 mRNA level in the parental PC12 cells. Expression of dominant-negative Ras protein and an inhibitor of mitogen-activated protein kinase kinase inhibited the effects of NGF on alpha3 mRNA level. CPTcAMP down-regulated the alpha3 mRNA level in all three PC12 cell lines. An inhibitor of protein kinase A inhibited the CPTcAMP-induced down-regulation of alpha3 mRNA. The alpha3 mRNA down-regulation required prolonged treatment with CPTcAMP even after cAMP response element binding protein phosphorylation was decreased. Membrane depolarization with high K+ had no effect on the alpha3 mRNA level in PC12h cells. Based on these results, we propose that at least two unknown effectors regulate alpha3 mRNA levels in PC12 cells.

Animals↗

The influence of antioxidants on cigarette smoke-induced DNA single-strand breaks in mouse organs: a preliminary study with the alkaline single cell gel electrophoresis assay.

According to published information, the lung is the only clear target organ for tumors when mice are exposed to cigarette smoke. Liver, skin, and upper digestive tract are target organs when orally or dermally exposed to cigarette smoke condensate, but not kidney, brain, or bone marrow. We tested the genotoxicity of cigarette smoke in the known target organ (lung), possible target organs (stomach and liver), and non-target organs (kidney, brain, and bone marrow) of the mouse using the alkaline single-cell gel electrophoresis (SCG, or comet) assay, as modified by us. We also tested the effect of free radical scavengers on the genotoxicity of the smoke. Male ICR mice were exposed to cigarette smoke. DNA single-strand breaks (SSB) were measured by the SCG assay 15, 30, 60, 120, and 240 min after the exposure. Fifteen min after the animals were exposed for 1 min to a 6-fold dilution of smoke, SSB appeared in the lungs, stomach, and liver; the damage in the lungs and liver returned to almost control levels by 60 min, and that of the stomach by 120 min. Kidney, brain, and bone marrow DNA were not damaged. Exposure to more dilute smoke (12- or 24-fold dilution) did not cause DNA damage. Single oral pretreatment (100 mg/kg) of either ascorbic acid (VC) or alpha-tocopherol acetate (VE) 1 h before smoke inhalation prevented SSB in the stomach and liver, while VE but not VC significantly reduced SSB in the lung. Five consecutive days of either VC or VE (100 mg/kg/day) pretreatment completely prevented SSB in the lung, stomach, and liver. Thus, the SCG assay detected DNA SSB, induced by cigarette smoke, in the known target organ, two possible target organs, and none of the non-target organs. Antioxidants could prevent those effects, suggesting that free radicals may have been a source of the damage. Our results suggest the importance of the SCG assay as a tool in the study of genotoxicity and carcinogenicity.

Animals↗

Amlodipine inhibits expression of matrix metalloproteinase-1 and its inhibitor in human vascular endothelial cells.

Matrix metalloproteinase-1 (MMP-1) may play an important role in the pathogenesis of atherosclerosis and atherosclerotic plaque rupture. We investigated the effect of the calcium channel blockers amlodipine and nifedipine on the expression of MMP-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in endothelial cells (ECs). MMP-1 and TIMP-1 levels in conditioned media of human vascular ECs were measured by enzyme-linked immunosorbent assay. Collagenolytic activity was determined by fluorescence-labeled collagen digestion. The addition of interleukin-1beta (IL-1beta) increased MMP-1 levels in the culture media of ECs. Amlodipine, but not nifedipine, significantly decreased MMP-1 levels in IL-1beta-stimulated ECs. TIMP-1 levels also were significantly increased by IL-1beta, and its expression was slightly decreased by amlodipine, not by nifedipine. Amlodipine significantly inhibited collagenolytic activity in the culture media of IL-1beta-stimulated ECs, whereas nifedipine showed no significant effect on the activity. Our findings revealed that amlodipine, but not nifedipine, inhibits IL-1beta-induced MMP-1 expression in human ECs.

Amlodipine↗

Endogenously generated nitric oxide by nitric-oxide synthase gene transfer inhibits cellular proliferation.

We investigated whether endothelial nitrite oxide synthase (NOS) gene transfer inhibited cellular proliferation. Endothelial NOS and endothelin type A receptor genes were transferred into 293 cells, a human embryonic kidney cell line, by calcium-phosphate coprecipitation. The cytosolic free Ca(2+) levels ([Ca(2+)](i)) of transfected cells were estimated with fura-2 fluorescence. Thymidine incorporation was increased by endothelin-1 in type A receptor-transfected cells. The endothelial NOS gene transfer did not affect endothelin-1-induced increase in [Ca(2+)](i) of type A receptor-transfected cells, but markedly inhibited mitogen-activated protein kinase and c-fos promoter activities. The endothelial NOS gene transfer also inhibited thymidine incorporation into type A receptor-transfected cells in response to endothelin-1, which was abolished in the presence of the NOS inhibitor N(G)-monomethyl-L-arginine acetate. The endothelin-1-induced increase in cell number was significantly suppressed by endothelial NOS gene transfer as well as by the mitogen-activated protein kinase inhibitor PD98059. These results indicate that endothelial NOS gene transfer inhibits cellular proliferation via inhibition of the mitogen-activated protein kinase cascade.

Calcium↗

Biological and morphological effects on the brain after exposure of rats to a 1439 MHz TDMA field.

We investigated the effects of exposure to a 1439 MHz TDMA (Time Division Multiple Access) field, as used in cellular phones, on the permeability of the blood-brain barrier (BBB), on the morphological changes of the brain, and on body-mass fluctuations. Male Sprague-Dawley (SD) rats were divided into three groups of eight rats each. The rats in the EM(+) group, which had their heads arrayed in a circle near the central antenna of an exposure system, were exposed to a 1439 MHz field for one hour a day. The rats in EM(-) group were also in the exposure system, however, without high-frequency electromagnetic wave (HF-EMW) exposure. The animals in the control group were neither placed in the system nor exposed to HF-EMWs. The exposure period was two or four weeks. The energy dose rate peaked at 2 W/kg in the brain; the average over the whole body was 0.25 W/kg. The changes in the permeability of BBB were investigated by Evans blue injection method and by immunostaining of serum albumin. HF-EMWs had no effect on the permeability of BBB. The morphological changes in the cerebellum were investigated by assessing the degeneration of Purkinje cells and the cell concentration in the granular layer. No significant changes were observed in the groups of rats exposed to HF-EMWs for two or four weeks. Averaged body masses were not affected by HF-EMWs exposure. In conclusion, a 1439 MHz TDMA field did not induce observable changes in the permeability of the BBB, morphological changes in the cerebellums, or body mass changes in rats, as evaluated by the conventional methods.

Animals↗

Magnetic stimulation of the sacral roots for the treatment of stress incontinence: an investigational study and placebo controlled trial.

PURPOSE: We designed an investigational study and placebo controlled trial to evaluate the potential efficacy of magnetic stimulation of the sacral roots for the treatment of stress incontinence. MATERIALS AND METHODS: A total of 75 patients with stress incontinence were studied. A 15 Hz. repetitive magnetic stimulation of the sacral roots with 50% intensity output and duration of 5 seconds per minute was applied for 30 minutes. Urodynamic investigations under magnetic stimulation were performed in 13 patients to evaluate acute effects to lower urinary tract function. There were 62 women (mean age 58 years) enrolled in a placebo controlled study to investigate the short-term efficacy of magnetic stimulation. The number of leaks for 3 days, amount of urine loss on a pad test and quality of life score were evaluated before and 1 week after stimulation. RESULTS: The urodynamic investigations revealed an apparent elevation of urethral closure pressure induced by stimulation (mean 8.2 +/- 3.0 cm H2O, p = 0.0000004) and a significant increase in bladder capacity after stimulation (mean 40.0 +/- 51.0 ml., p = 0.0152). In the placebo controlled study the number of leaks and amount of urine loss on a pad test significantly decreased more in the active than in the sham stimulation group (p = 0.0023 and 0.0377, respectively). The quality of life score significantly improved in the active stimulation group (p = 0.0006) in contrast to no significant improvement in the sham stimulation group. The improvement rate in the active stimulation group was 74%, which was significantly higher than the 32% in the sham stimulation group (p = 0.0009). No adverse effects were noted in any patients. CONCLUSIONS: These results suggest that magnetic stimulation of the sacral roots may be useful for the treatment of stress incontinence. Further studies are needed to evaluate the long-term efficacy of this potential treatment.

Adult↗

[Effects of nilvadipine on retinal microcirculation and systemic circulation].

PURPOSE: The effects of nilvadipine on retinal blood flow and systemic circulation were studied by the hydrogen clearance method. MATERIALS AND METHODS: The subjects were 10 male beagles. Under general anesthesia, nilvadipine (32 micrograms/ml/kg), dissolved in polyethylene glycols was injected into the stomach of 5 beagles, and only polyethylene glycols was injected into the stomach of the other 5 beagles as controls. Retinal tissue blood flow, heart rate, arterial blood pressure, pulmonary arterial pressure, central vein pressure, cardiac output, and systemic vessel resistance were measured over time and compared between the two groups. RESULTS: Retinal tissue blood flow showed significant increase only in the Nilvadipine group (max 29.2%). No marked changes were observed in the systemic circulation in either group. The time to maximum blood concentration of Nilvadipine was 120 min, and the maximum blood concentration was 1.27 ng/ml. CONCLUSION: Nilvadipine may directly and selectively increase retinal tissue blood flow, while having only minimal effect on systemic circulation including arterial blood pressure.

Animals↗

[Day surgery for pediatric inguinal hernia repair].

Pediatric patients with inguinal hernia can be good candidates for day surgery. Since 1986, 1273 such patients have been treated under our day surgery system. Although 8 patients (0.6%) were unable to go home after surgery due to perioperative complications and 21 (1.6%) visited earlier than scheduled after discharge, no major complications were noted and postoperative complications did not differ from those seen in the inpatient setting. Our questionnaire survey demonstrated that 96% of the families were satisfied with the system. Based on our own experience and a literature review of day surgery for inguinal hernia repair in children, the problems surrounding the day care system are discussed. Patient selection, preoperative assessment, general anesthesia, postoperative care including oral intake and analgesia, and postoperative follow-up are considered the most important issues in the day care system. A team approach including pediatric surgeons, anesthesiologists, and pediatric nurses is considered indispensable for the safe and satisfactory day surgery treatment.

Ambulatory Surgical Procedures↗

Global and fine information coded by single neurons in the temporal visual cortex.

When we see a person's face, we can easily recognize their species, individual identity and emotional state. How does the brain represent such complex information? A substantial number of neurons in the macaque temporal cortex respond to faces. However, the neuronal mechanisms underlying the processing of complex information are not yet clear. Here we recorded the activity of single neurons in the temporal cortex of macaque monkeys while presenting visual stimuli consisting of geometric shapes, and monkey and human faces with various expressions. Information theory was used to investigate how well the neuronal responses could categorize the stimuli. We found that single neurons conveyed two different scales of facial information in their firing patterns, starting at different latencies. Global information, categorizing stimuli as monkey faces, human faces or shapes, was conveyed in the earliest part of the responses. Fine information about identity or expression was conveyed later, beginning on average 51 ms after global information. We speculate that global information could be used as a 'header' to prepare destination areas for receiving more detailed information.

Animals↗

Effects of exposure to repetitive pulsed magnetic stimulation on cell proliferation and expression of heat shock protein 70 in normal and malignant cells.

This study focused on the effects of repetitive pulsed magnetic stimulation (RPMS) on normal and malignant cells of humans. We used three human cell lines, HBL-100 (human normal breast epithelium), MCF-7 (human breast cancer), and HeLa (human cervical cancer). Cell proliferation at 37 degrees C and 40 degrees C and the expression of heat shock protein (HSP) 70 at 37 degrees C, 40 degrees C, and 42 degrees C, before and after the exposure to RPMS, was investigated. Cell proliferation showed no effects of exposure to RPMS in both normal and malignant cells; however, HSP70 expression was increased by RPMS exposure under thermal stress at 40 degrees C and 42 degrees C in HBL-100 and HeLa. We concluded that RPMS exposure potentiates the effect of thermal stress on both normal and malignant cells, and malignant cells derived from different organs respond differently to RPMS exposure.

Breast↗

Chimeric domain analysis of the compatibility between H(+), K(+)-ATPase and Na(+),K(+)-ATPase beta-subunits for the functional expression of gastric H(+),K(+)-ATPase.

Gastric H(+),K(+)-ATPase consists of alpha-subunit with 10 transmembrane domains and beta-subunit with a single transmembrane domain. We constructed cDNAs encoding chimeric beta-subunits between the gastric H(+),K(+)-ATPase and Na(+),K(+)-ATPase beta-subunits and co-transfected them with the H(+),K(+)-ATPase alpha-subunit cDNA in HEK-293 cells. A chimeric beta-subunit that consists of the cytoplasmic plus transmembrane domains of Na(+),K(+)-ATPase beta-subunit and the ectodomain of H(+),K(+)-ATPase beta-subunit assembled with the H(+),K(+)-ATPase alpha-subunit and expressed the K(+)-ATPase activity. Therefore, the whole cytoplasmic and transmembrane domains of H(+),K(+)-ATPase beta-subunit were replaced by those of Na(+),K(+)-ATPase beta-subunit without losing the enzyme activity. However, most parts of the ectodomain of H(+),K(+)-ATPase beta-subunit were not replaced by the corresponding domains of Na(+), K(+)-ATPase beta-subunit. Interestingly, the extracellular segment between Cys(152) and Cys(178), which contains the second disulfide bond, was exchangeable between H(+),K(+)-ATPase and Na(+), K(+)-ATPase, preserving the K(+)-ATPase activity intact. Furthermore, the K(+)-ATPase activity was preserved when the N-terminal first 4 amino acids ((67)DPYT(70)) in the ectodomain of H(+),K(+)-ATPase beta-subunit were replaced by the corresponding amino acids ((63)SDFE(66)) of Na(+),K(+)-ATPase beta-subunit. The ATPase activity was abolished, however, when 4 amino acids ((76)QLKS(79)) in the ectodomain of H(+),K(+)-ATPase beta-subunit were replaced by the counterpart ((72)RVAP(75)) of Na(+),K(+)-ATPase beta-subunit, indicating that this region is the most N-terminal one that discriminates the H(+),K(+)-ATPase beta-subunit from that of Na(+), K(+)-ATPase.

Amino Acid Sequence↗

Postoperative prediction of and strategy for metastatic recurrent hepatocellular carcinoma according to histologic activity of hepatitis.

BACKGROUND: The hepatitis activity index (HAI) score describes the histologic status of accompanying chronic hepatitis and was established by pathologists. The aim of this study was twofold: 1) to investigate the correlation between intrahepatic metastatic recurrence (IM) and the HAI score of the noncancerous region of the liver and 2) to estimate the usefulness of postoperative preventive chemotherapy in patients with hepatocellular carcinoma (HCC). METHODS: The study included 158 consecutive patients who underwent curative resection for HCC and had been observed for > 1 year. Based on the HAI scores of the noncancerous region the patients were classified into 3 groups: those with mild hepatitis (n = 33) (i.e., with HAI scores of 0-5), those with moderate hepatitis (n = 77) (with HAI scores of 6-9), and those with severe hepatitis (n = 48) (those with HAI scores of > or = 10). In addition, a prospective randomized trial of postoperative adjuvant chemotherapy was performed for 21 patients with moderate hepatitis. RESULTS: The patients in the moderate hepatitis group were found to be at higher risk for IM recurrence within 2 years after HCC resection compared with those patients in the mild (P = 0.05) and severe (P < 0.01) hepatitis groups. The incidences of more than two tumors and portal vein involvement in patients with moderate hepatitis were much higher than in those patients with mild or severe hepatitis. Multivariate analysis showed that intraoperative bleeding volume, the number of nodules, portal vein involvement, and moderate hepatitis were independent predictive factors for IM recurrence free survival. Ten patients with moderate hepatitis had received postoperative intrahepatic arterial chemotherapy (2-3 courses with a maximum dose of 80 mg of cisplatin and 10 mg of mitomycin C at 1-month intervals) for the last 3 years. Although the number of patients was small, the therapy improved the disease free survival rate significantly compared with 11 patients who received no therapy. CONCLUSIONS: The patients with moderate hepatitis (HAI score of 6-9) had the highest rate of IM recurrence among the three HAI groups. Postoperative hepatic arterial chemotherapy may be useful in improving the rate of disease free survival after surgery among these patients.

Aged↗

Dynamic cortical activation in mental image processing revealed by biomagnetic measurement.

The mental rotation task has been reported to activate the human parietal and extra-striate areas, based on the results of fMRI and PET analysis. In the present study, we investigated the dynamic properties of the distributed cortical activity related to mental rotation processes at high temporal resolution by means of brain magnetic field measurements and a linear inversion algorithm. Distributed neural activities during the mental rotation and control tasks were estimated for six subjects, and the differences in the activity distribution were analyzed. Statistically significant differences in the parietal and lateral posterior temporal region were detected 200-300 ms after the visual stimulus, indicating that the dorsal and ventral pathway were included in the mental image processing.

Adult↗