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Biomedical subjects

M Shono

Publications and source records attributed to M Shono.

At least 19 recordsLinked to original sources
PubMed2001

Effect of serum depletion on centrosome overduplication and death of human pancreatic cancer cells after exposure to radiation.

The tumor microenvironment is one of the key factors affecting the cellular response to radiation; however, the influence of serum concentration on tumor radiosensitivity remains poorly understood. We recently discovered that gamma-irradiation of tumor cells causes centrosome overduplication, which may lead to lethal nuclear fragmentation through the establishment of multipolar mitotic spindles. In the present study, we investigated the effect of serum depletion on radiation-induced cell death in relation to the centrosome dynamics in human pancreatic cancer cells. Exposure of Capan-1 cells to gamma-irradiation resulted in a time-dependent increase in cells containing multiple centrosomes in association with the appearance of mitotic cell death. Treatment of irradiated cells with serum depletion drastically accelerated centrosome overduplication and the formation of multipolar spindles, resulting in increased nuclear fragmentation and cell death. Cell cycle analysis of irradiated cultures revealed that the reduced serum level increased the population of cells arrested in the G2/M phase, which might be responsible for the abnormal centrosome accumulation. These findings suggest that serum concentration can influence radiation-induced cell killing through modulating cell cycle progression and possibly centrosome overduplication.

Cell Death↗
PubMed2001

Hepatic stellate cells contain the functional estrogen receptor beta but not the estrogen receptor alpha in male and female rats.

In an earlier study, we showed that estradiol (E2) inhibits proliferation and transformation in cultured rat hepatic stellate cells (HSCs) and that the actions of E2 are mediated through estrogen receptors (ERs). This study reports on an investigation of the cellular localization of ER subtypes ERalpha and ERbeta using immunohistochemistry in experimental fibrotic liver rats and of each ER subtype expression in cultured rat HSCs by evaluating the produced mRNA and protein. The results indicate that high levels of ERbeta expression and low or no levels of ERalpha expression were observed in normal and fibrotic livers and in quiescent and activated HSCs from both males and females. The specificity of E2-mediated antiapoptotic induction through the ERbeta was shown by dose-dependent inhibition by the pure ER antagonist ICI 182,780 in HSCs which were undergoing early apoptosis. These findings demonstrate for the first time that rat HSCs possess functional Erbeta, but not Eralpha, to respond directly to E2 exposure.

Animals↗
PubMed2001

Molecular cloning of Na(+)-ATPase cDNA from a marine alga, Heterosigma akashiwo.

We cloned novel Na(+)-ATPase (HANA) cDNA from marine alga Heterosigma akashiwo. The full-length HANA cDNA was 4467 bp long and coded for a 1330 amino acid protein with a molecular weight of 146,306. The deduced product exhibited around 40% identity in amino acids with Na(+)/K(+)-ATPase alpha-subunits. A hydrophilic sequence of 285 amino acid residues that showed no homology with any sequence listed in databases existed in the M7--M8 junction of HANA. This is the first report on the primary structure of putative Na(+)-transporting ATPase from plant cells.

Adenosine Triphosphatases↗
PubMed2001

Instability of chromosome 8 as an indicator of aggressive tumor phenotype in pancreatic cancer.

BACKGROUND AND OBJECTIVES: Chromosomal instability is a common feature of pancreatic carcinoma, but its biological significance remains unclear. In this study, we investigated the association between chromosomal instability and biological aggressiveness in human pancreatic cancer cells. METHODS: Fluorescence in situ hybridization was performed to examine changes in chromosomal numbers in a total of 13 pancreatic cancer cell lines. We also assessed the potential for tumor aggressiveness within cancer cells by in vitro migration and invasion assay and by subcutaneous implantation into nude mice. RESULTS: Chromosomal instability, characterized by numerical variations in copy numbers of chromosome 8, was observed in most cell lines, and the magnitude of instability was correlated well with both motility (P < 0.001) and invasion rate (P < 0.001) of these cells. Furthermore, a significant positive correlation existed between chromosome instability and tumor growth in vivo (P < 0.01). CONCLUSIONS: These results suggest that the increased level of chromosomal instability may play a critical role in the development of aggressive tumor phenotype during pancreatic cancer progression. J. Surg. Oncol. 2001;76:181-187.

Animals↗
PubMed2001

Most apoptotic cells in mdx diaphragm muscle contain accumulated lipofuscin.

An age-related pigment, lipofuscin (LF), which accumulates in postmitotic, long-lived cells, is formed by the oxidative degradation of cellular macromolecules by oxygen-derived free radicals. In the present study we show that LF is accumulated in some myofibres, myosatellite cells and interstitial cells in the diaphragm muscles of the X chromosome-linked muscular dystrophic (mdx) mice at the age of 10 weeks when repetitive cycles of de- and regeneration of myofibres occur. In contrast, LF is virtually absent in diaphragm muscles of age-matched C57BL/10 (C57) normal control mice. Therefore, mdx muscle is more susceptible to oxidative stress than normal muscle. We hypothesise that gene-regulated cell death (apoptosis) occurs in dystrophic muscle cells that accumulate LF as a consequence of either oxidative stress or injury. We found that 74-79% of apoptotic myosatellite cells, interstitial cells and myofibres in mdx diaphragm contain accumulated or dotted LF granules, but only 12-20% of non-apoptotic cells contain LF. Apoptotic cells are very rare in the diaphragm of age-matched C57 control mice. This suggests that the regeneration of mdx diaphragm muscle initiated from myosatellite cells is impaired by their apoptosis as the result of either oxidative stress or a product of oxidative injury.

Animals↗
PubMed2001

Isolation and characterization of a Na+/H+ antiporter gene from the halophyte Atriplex gmelini.

With a homologous gene region we successfully isolated a Na+/H+ antiporter gene from a halophytic plant, Atriplex gmelini, and named it AgNHX1. The isolated cDNA is 2607 bp in length and contains one open reading frame, which comprises 555 amino acid residues with a predicted molecular mass of 61.9 kDa. The amino acid sequence of the AgNHX1 gene showed more than 75% identity with those of the previously isolated NHX1 genes from glycophytes, Arabidopsis thaliana and Oryza sativa. The migration pattern of AgNHX1 was shown to correlate with H+-pyrophosphatase and not with P-type H+-ATPase, suggesting the localization of AgNHX1 in a vacuolar membrane. Induction of the AgNHX1 gene was observed by salt stress at both mRNA and protein levels. The expression of the AgNHX1 gene in the yeast mutant, which lacks the vacuolar-type Na+/H+ antiporter gene (NHX1) and has poor viability under the high-salt conditions, showed partial complementation of the NHX1 functions. These results suggest the important role of the AgNHX1 products for salt tolerance.

Amino Acid Sequence↗
PubMed2001

Stepwise progression of centrosome defects associated with local tumor growth and metastatic process of human pancreatic carcinoma cells transplanted orthotopically into nude mice.

Recent evidence indicates that loss of centrosome integrity may be a major cause of genetic instability underlying various human cancers. The aim of this study was to define the role of centrosome defects during the in vivo tumor progression of pancreatic carcinoma using an orthotopic implantation model. Injection of Suit-2 human pancreatic cancer cells into the pancreata of nude mice reproduced the pattern of local tumor growth and distant metastasis observed in humans. Pancreatic xenografts, peritoneal disseminations, and hepatic metastases were harvested, and tumor cells were examined for centrosomes by immunofluorescence microscopy. Centrosome abnormalities, characterized by increased numbers of centrosomes, were detected in only a small fraction of parental Suit-2 cells in culture, whereas the frequency was markedly increased in cells isolated from the pancreatic xenografts. Abnormal centrosome numbers were found at higher frequencies in metastatic foci than in pancreatic xenografts. A significant positive correlation existed between the fraction of cells with multiple centrosomes and that with multipolar mitotic spindles, suggesting a functional involvement of aberrant centrosomes in spindle disorganization and chromosome missegregation. In addition, the increased frequency of abnormal centrosomes was associated with an enhanced degree of chromosomal instability. These findings suggest a novel model of pancreatic tumor progression whereby a stepwise increase in the magnitude of centrosomal abnormalities confers an increased chance for aberrant mitotic events, thus accelerating genetic instability and causing the tumor to progress to a more advanced stage.

Animals↗
PubMed2001

A new method to analyze basic rest-activity cycle.

A new method was proposed to analyze a basic rest-activity cycle (BRAC), termed BRAC-A. This method calculates a significant cycle length by chi-squared method and the starting points of a resting phase and an active one by analysis of the array consisting of the segmented time series in the same length. Using 20 3-day computer-simulated time series of standard deviation in fetal heart rate fluctuation with known periodicity of the BRAC, we demonstrated that the BRAC-A was a useful tool to reveal the characteristics of the BRAC.

Activity Cycles↗
PubMed2001

Changes in fractal structure of heart rate variability during a nap in one case.

The objective of the present study was to analyze fractal structures of adult heart rate (HR) variability during a nap. Fractal analysis was carried out in one case over consecutive 10-min time series of HR, which were simultaneously recorded with electroencephalogram. Scaling relationships showed cross-over patterns characterized by alphas and alphal (i.e. slopes above and below a cross-over point). The alphas and alphal were black and white noise at Stage 4 of NREM sleep, and black and 1/f noise in REM sleep. Cross-over points changed from the first to second sleep cycle. We demonstrate the multifractal structures of HR variability during a nap in the present case.

Adult↗
PubMed2001

A longitudinal study of diurnal variation in baseline fetal heart rate in one dichorionic-diamniotic twin pregnancy.

A longitudinal study to analyse the diurnal variations in baseline fetal heart rate (FHR) and sustained fetal tachycardia (SFT) in twin pregnancy was performed on one dichorionic twin. Twenty-four hour FHR recordings on twins were made at 32, 34 and 36 weeks of gestation simultaneously. Significant diurnal variations were found in both twins in all gestational weeks. The diurnal variations in baseline FHR of twins were highly correlated with no phase-lag. No coincidence was recognized in the appearance of SFT between twins. These results suggest the maternal influence equally affects FHR in each fetus of dichorionic twin since 32 weeks of gestation, while the appearance of SFT might be independent from maternal influence.

Adult↗
PubMed2001

Functional analysis of salt-inducible proline transporter of barley roots.

We cloned a cDNA encoding Hordeum vulgare Proline Transporter (HvProT) from salt-stressed barley roots by differential display. HvProT was 2,161 bp long and had an open reading frame encoding 450 amino acids. The deduced amino acid sequence of HvProT was similar to those of proline transporter proteins of rice (65.7%), Arabidopsis (57.7%) and tomato (42.0%). Northern blot analysis showed that the transcript level of HvProT was induced in roots at 30 min after 200 mM NaCl treatment and its peak was observed at 3 h. However, the transcript level was very low in leaves and did not increase by salt stress. The expression level of Delta(1)-pyrroline-5-carboxylate synthetase (P5CS), encoding a key enzyme of proline synthesis, was induced later than HvProT by salt stress. A transport assay using a yeast with mutation in proline uptake revealed that HvProT was a transporter with high affinity for L-proline (K(m) = 25 microM). HvProT was found to be a unique transporter with high affinity for L-proline. Since its transport activity was dependent on the pH gradient, HvProT was suggested to be a H(+)/amino acid symporter. In situ hybridization analysis showed that the HvProT mRNA was strongly expressed in root cap cells under salt stress. HvProT might play an important role in the transport of proline to root tip region urgently upon salt stress.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed2001

Analysis of heart rate variability of an anencephalic fetus using a new method to determine a fractal dimension of non-stationary time-serial data.

Human fetal heart rate (HR) variabilities were analyzed using the QIS-A, which we devised to determine a fractal dimension of non-stationary time series. Fifteen 10-min HR data of an anencephalic fetus at 23 weeks and 3 days of gestation and those of 10 normal fetuses at the same weeks of gestation were obtained by ultrasonic cardiography. The anencephalus preserved the spinal cord, medulla and partial anterior hypothalamus. The fractal scaling exponent alpha of the anencephalus was compared with that of each normal fetus by Student's t-test. In results, the scaling relationship in each case had a crossover pattern characterized by alpha(s) and alpha(l), which were slopes above and below a crossover point, respectively. Differences in mean alpha(s) and mean alpha(l) between the anencephalus and each normal fetus were significant (P < 0.01): mean alpha(s), 1.0 +/- 0.1 (+/-SD) (1/f fluctuation) and 1.6 +/- 0.2 (+/-SEM); mean alpha(l), 1.6 +/- 0.2 (+/-SD) and 1.4 +/- 0.1 (+/-SEM). There were six significant differences in mean crossover point between the anencephalus and each normal fetus: 13.8 +/- 5.7 s (+/-SD) and 15.3 +/- 5.6 s (+/-SEM). These results reveal the relationship between fractal structure of fetal HR variability and the developing central nervous system (CNS). In particular, the 1/f fluctuation of HR variability in an anencephalic fetus from the 1.25 to 13.8 s time scale might have a strong relation to the defect of the CNS.

Algorithms↗
PubMed2001

[Clinical study on mortality of rheumatoid arthritis compared with malignant rheumatoid arthritis].

OBJECTIVE: To determine how the mortality of patients with rheumatoid arthritis (RA) behave in comparison with that of patients with malignant rheumatoid arthritis (MRA). METHODS: The mortality of RA patients selected at randam identified in 1991-2000 (n = 104) was compared with that of 18 MRA patients. Hazard ratios of death were calculated with a multivariate survival analysis. A clinical study of patients with both RA and MRA was performed in mortality. RESULTS: Excess mortality was seen in MRA patients in Kaplan-Meier survival curves (p = 0.02 by log-rank test). MRA patients were treated more often with cytostatic and immunosuppressive drugs. Infection was the main cause of death in both RA and MRA patients. Vasculitis was not reported as the cause of death in MRA patients. Secondary amyloidosis played an important role in RA death rather than MRA. CONCLUSION: There remained an excess mortality in MRA patients compared with RA, and infection was attributable to the key cause of death in both RA and MRA suggesting therapeutic side effects.

Aged↗
PubMed2000

Induction of inducible nitric oxide synthase by ginsenosides in cultured porcine endothelial cells.

Mechanism of Nitric oxide (NO) production by ginsenosides was investigated in cultured porcine endothelial cells. Beta-nicotinamide adenine dinucleotide phosphate (beta-NADPH) staining showed that the NO production was significantly enhanced by the presence of 40 microg/ml ginsenosides with 10 microM L-arginine after 12 h incubation. NO production was suppressed by addition of 0.5 microM Nomega-Nitro-L-arginine (L-NNA), an inhibitor of NO synthases (NOSs), to the incubation medium. In addition, the immunoreactive signals of inducible NOS (iNOS) were appeared in endothelial cells after 12-h incubation of ginsenosides, whereas the signals were not observed in non-treated cells. Our findings suggest that ginsenosides can enhance NO production by induction of iNOS in addition to its direct effect on endothelial cells by increasing intracellular Ca2+ concentration.

Animals↗