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Biomedical subjects

N Ishida

Publications and source records attributed to N Ishida.

At least 199 records · Page 11Linked to original sources
PubMed1994

Interferon-beta endogenously produced by intratumoral injection of cationic liposome-encapsulated gene: cytocidal effect on glioma transplanted into nude mouse brain.

The cytocidal effect of endogenously produced human interferon-beta was tested on glioma transplanted into the brain of nude mice by intracranial injection of a cell suspension of human glioma cell line U251-SP. When plasmid pSV2IFN-beta, bearing the human interferon-beta gene, was encapsulated into cationic multilamellar liposomes composed of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, dilauroyl phosphatidylcholine, and dioleoyl phosphatidylethanolamine in a molar ratio of 1:2:2 and injected intratumorally, human interferon-beta was produced in the tumor. The tumor completely disappeared if the injection was done shortly after the transplantation. Even when the tumor did not disappear, survival of the tumor-bearing nude mice was markedly prolonged. In control experiments made with normal brain having no glioma, interferon-beta was not detected.

Animals↗
PubMed1994

Alcohol ingestion enhances hepatocarcinogenesis induced by synthetic estrogen and progestin in the rat.

We examined the effect of alcohol ingestion on rat hepatocarcinogenesis induced by oral administration of synthetic female hormones, 0.075 mg of ethynylestradiol (EE) and 6.0 mg of norethindrone acetate (NA), everyday for 12 months to Wistar rats. Concomitant administration of 10% ethanol in drinking water resulted in the development of hepatocellular carcinoma (HCC) in 40.8% in female rats and 11.8% in male rats at 12 months, although the incidences of HCC following hormones administration alone were 8.0% in female rats and 0% in male rats. The incidence and the number of hyperplastic nodules in rats with concomitant alcohol treatment were significantly higher than that in rats with hormone treatment alone. The additional alcohol administration significantly increased the values of nuclear and cytosol estrogen receptors at 4 months. Synthetic female hormones and/or alcohol treatment also significantly increased the value of cytosol progesterone receptor at 4 months. 32P-postlabeling analysis of liver DNA revealed that alcohol enhanced the DNA adduct formation induced by hormones. Consequently, alcohol may affect rat hepatocarcinogenesis caused by synthetic female hormones in enhancing cell-proliferating activity via estrogen and progesterone receptors, and DNA adduct formation induced by synthetic female hormones.

Alcohol Drinking↗
PubMed1994

[Case of death by fire with kerosene--analysis of contents of trachea and stomach].

UNLABELLED: In death caused by fuel oil burning, it's difficult to examine the vital reaction in the burning skin surface. In these cases, in stead of skin examination, we've been determining the fuel oil in blood. In this case, besides this method, we tried to examine the contents of the trachea of a person who died of kerosene oil burns. CASE: A 49-year-old female was found dead in a cabin. Burns on her body ranged from first to fourth-degree, and 91% of the body was charred. Carbon particles were detected within the trachea and the bronchus, and were slightly detected in the gastric contents and the esophagus. Carboxyhemoglobin concentration was found to be 21% in the right heart blood and 22% in the left heart blood. The level of cyanide detected was 4.3 microM in the right heart blood and 1.7 microM in the left heart blood. Ethanol was not detected in either sample. Kerosene components were detected in each sample (blood, trachea content, gastric content and body surface). According to the formulation of kerosene components, results of contents of the trachea were most likely from a kerosene on the market. In the blood, many volatile paraffin hydrocarbons were found, and, on the body surface, many high boiling-point paraffin hydrocarbons were detected. The means that values of detected kerosene formulation from the blood and trachea contents were similar to types of kerosene on the market. From these results, we concluded that the victim inhaled kerosene vapor.(ABSTRACT TRUNCATED AT 250 WORDS)

Burns↗
PubMed1993

An immunohistochemical analysis for cancer of the esophagus using monoclonal antibodies specific for modified nucleosides.

BACKGROUND: Modified nucleosides such as 1-methyl-adenosine and pseudouridine exist as minute components of transfer ribonucleic acid (tRNA) and are excreted in the urine in large amounts in the presence of malignancy. Although use of these modified nucleosides as tumor markers has long been studied and many reports have detailed their relationship with malignant tumors and the urinary excretion of various modified nucleosides, there have been no reports on modified nucleosides in esophageal carcinoma. METHODS: Monoclonal antibody patterns against 1-methyladenosine and pseudouridine were studied in esophageal carcinoma, freshly resected esophageal carcinoma tissue specimens fixed in 10% neutral formaldehyde solution, embedded in paraffin, and sectioned for immunohistochemical study. Inhibition enzyme-linked immunosorbent assay (ELISA) was used to examine urinary excretion of these modified nucleosides in patients with esophageal carcinoma. RESULTS: Although rare in normal esophageal epithelium, these modified nucleosides were strongly stained in esophageal carcinoma cells. Most carcinoma cells exhibited a cytoplasmic pattern, although some cells at the infiltrating edge displayed a nuclear pattern. These modified nucleosides were intensely imaged in 11 of 12 cultured esophageal cell lines, the exception being one line that had a much longer doubling time. Using ELISA, urinary excretion of these modified nucleosides was found to be significantly higher in patients with esophageal carcinoma than in healthy subjects; such excretion correlated with carcinoma size and stage and tended to decrease after treatment. CONCLUSIONS: These findings indicate that the modified nucleosides 1-methyladenosine and pseudouridine may be useful as tumor markers for esophageal carcinoma.

Adenosine↗
PubMed1993

Circadian regulation of per repeat mRNA in the suprachiasmatic nucleus of rat brain.

We have recently reported fluctuations in the expression of the period repeat sequence (pp2.5) during light-dark cycles in the suprachiasmatic nucleus (SCN) of rat [Neurosci. Lett., 122 (1991) 113-116]. Presently, we performed in situ hybridization which shows that the fluctuation of pp2.5 expression continues during constant darkness conditions in the SCN of rat. The light exposure during subjective night but not subjective day triggered its elevated expression in a time-dependent manner which is parallel to that of c-fos expression. The results suggest the involvement of pp2.5 in the entrainment pathway of the circadian rhythm in rodent SCN.

Animals↗
PubMed1993

Mos is degraded by the 26S proteasome in a ubiquitin-dependent fashion.

Mos, the c-mos proto-oncogene product, is a key regulator of cell cycle progression. Recently, rapid turnover of Mos in an early stage of meiotic maturation of Xenopus oocytes was found to be mediated by the ubiquitin pathway, but the protease responsible for its breakdown was not identified. In the present study, we found that 35S-labeled Mos synthesized in an in vitro transcription/translation system was degraded ATP- and time-dependently by the 26S proteasome, but not by the 20S proteasome, in the presence of a ubiquitin-ligation system. The 26S proteasome did not degrade a mutant Mos in which Ser3 was replaced by Asp3 that is metabolically stable in oocytes, indicating a similarity in the proteolytic events in vivo to those observed in vitro in the present work. This is the first demonstration that the proteasome catalyzes the ATP-dependent degradation of a naturally occurring, short-lived oncoprotein by the ubiquitin pathway. This finding suggests that the proteasome may regulate the intracellular stability of various oncoproteins.

Adenosine Triphosphate↗
PubMed1993

Arachidonic acid-selective cytosolic phospholipase A2 is crucial in the cytotoxic action of tumor necrosis factor.

The role of phospholipase A2 (PLA2) in the cytotoxic action of tumor necrosis factor (TNF) was examined. Recently, we described the characterization of TNF-resistant sublines isolated from TNF-sensitive cell line L929 (Hayakawa, M., Oku, N., Takagi, T., Hori, T., Shibamoto, S., Yamanaka, Y., Takeuchi, K., Tsujimoto, M., and Ito, F. (1991) Cell Struct. Funct. 16, 333-340). The most remarkable features of these TNF-resistant sublines were the defects in TNF-stimulated arachidonate metabolism. In this study, we characterized the PLA2 activities of these sublines and found a significant decrease in the activity in one of the TNF-resistant sublines, C12 cells. The enzymological features, such as Ca2+ requirement and substrate specificity, suggested that the high molecular weight arachidonoyl-selective cytosolic PLA2 (cPLA2) was involved in the TNF action. Northern hybridization analysis demonstrated the reduced expression of high molecular weight cPLA2 in C12 cells. Furthermore, expression of a cloned cPLA2 cDNA in C12 cells increased the sensitivity of cells to the TNF cytotoxicity. These results indicate the crucial role of the high molecular weight cPLA2 in the TNF-induced cytolysis.

Animals↗
PubMed1993

Epileptic seizure of El mouse initiates at the parietal cortex: depth EEG observation in freely moving condition using buffer amplifier.

The initiation site of seizure discharges and the relationship between behavioral manifestations and electroencephalography were investigated in the El mouse, a hereditary epilepsy model. The chronic depth electrodes were implanted stereotaxically into the frontal cortex, parietal cortex, temporal cortex, hippocampus, striatum, amygdaloid complex, non-specific nuclei of thalamus and substantia nigra. Electrical activities were recorded in freely moving condition with use of the buffer amplifier devised in the laboratory and behaviors were monitored simultaneously. Seizure spike discharges started in the parietal cortex and spread out into other brain areas. When the hippocampus was involved, the tonic convulsion occurred behaviorally. The paper describes the first direct evidence of the initiation and propagation of seizure discharges in the brain of El mouse.

Amplifiers, Electronic↗
PubMed1993

Cloning of inducible nitric oxide synthase in rat vascular smooth muscle cells.

We previously showed that interferon(IFN)-gamma inhibited the proliferation of rat vascular smooth muscle cells(VSMC) by generation of nitric oxide(NO) through the induction of an NO synthase(NOS). To identify the NOS in the VSMC at molecular level, we analyzed messenger RNA(mRNA) levels and primary structure of the novel NOS by cDNA cloning with application of polymerase chain reaction(PCR). mRNA of the NOS was induced and the level of induction was significantly increased by IFN-gamma in VSMC within a few hours. The amino acid sequence deduced from the cloned NOS cDNA was distinct from that of the previously reported constitutive types of NOSs, while highly similar to that of macrophage NOS. Cofactor binding regions were highly conserved among these NOSs. These findings show that the NOS is inducible and could regulate the proliferation of VSMC. Besides, this is the first report of cloning of the NOS in VSMC.

Amino Acid Oxidoreductases↗
PubMed1993

Tumor necrosis factor stimulates the synthesis and secretion of biologically active nerve growth factor in non-neuronal cells.

Tumor necrosis factor-alpha (TNF) markedly stimulates the synthesis and secretion of immunoreactive nerve growth factor (NGF) in quiescent mouse fibroblasts, which is a result of increase in the NGF mRNA level. NGF produced by TNF-treated fibroblasts has a molecular mass of 13 kDa on SDS-polyacrylamide gel electrophoresis, which is consistent in size with the subunit of mouse beta-NGF, and induces neurite outgrowth in paravertebral sympathetic neurons. Several peptide growth factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor also stimulate NGF production in the cells, but not platelet-derived growth factor. The dose responses of TNF and bFGF to stimulate NGF production in the cells are, respectively, similar to those to induce cell proliferation. However, no correlation is observed between the ability of these growth factors to stimulate NGF production and that to induce cell proliferation. Thus, the stimulation of NGF production in the cells seems to be a specific activity of TNF and some other growth factors. TNF stimulates the synthesis and secretion of NGF also in other cells such as human glioblastoma cells. These findings suggest that TNF plays a role in regulating neuronal cell function through an indirect mechanism by which it stimulates NGF production in glial cells and fibroblasts.

3T3 Cells↗
PubMed1993

Generation of hydroxyl radical from lipid hydroperoxides contained in oxidatively modified low-density lipoprotein.

When low-density lipoprotein (LDL) was oxidatively modified and incubated with an epinephrine-FeCl3 mixture, an electron spin resonance spectrum characteristic of the spin adduct of 5,5-dimethyl-1-pyrroline-N-oxide and hydroxyl radical (DMPO-OH) was obtained. The amount of DMPO-OH formed increased with an increase in the concentration of lipid hydroperoxides contained in the oxidatively modified LDL. These results indicate that oxidatively modified LDL would generate hydroxyl radicals in vivo if an appropriate iron chelate were present and that the cytotoxicity of oxidatively modified LDL is ascribable, at least in part, to its capability to generate such radicals.

Animals↗
PubMed1993

Induction of antitumor L3T4-positive T cells by OK-432 at tumor sites in mice.

We have previously reported the development of antitumor effector cells by day 12 after tumor implantation using a murine malignant ascites model with BAMC-1 tumor, which could be cured completely by five consecutive i.p. injections of OK-432 starting on day 2. In contrast, the OK-432 treatment with the same protocol failed to cure the tumor-bearing athymic mice, though it could suppress tumor growth temporarily. The results suggest that T cells may play a critical role in achieving a therapeutic effect. The present study was designed to clarify the nature of the antitumor effector cells induced by OK-432 in euthymic mice. The number of tumor cells in the peritoneal cavity of OK-432-treated euthymic mice increased gradually up to day 12 and dropped suddenly on day 14, while in the athymic mice the tumor cells transiently decreased in the first 7 days then started to expand drastically on day 8. The timing of the appearance of the effector cells was examined by adoptive-transfer experiments. The peritoneal exudate cells (PEC) obtained from BAMC-1 bearing euthymic mice on various days during the treatments with OK-432 were passively transferred intraperitoneally on the respective days (synchronous transfer) or on day 7 (convergent transfer) to BAMC-1-bearing athymic mice, which were treated similarly with OK-432. More than 85% of the recipient athymic mice survived when an adoptive transfer was made on and after day 7. These results indicated that the effector cells developed before day 8 in euthymic mice. The effector cells detectable on day 7 in the PEC represent plastic- or nylon-wool-column-nonadherent cells, which could cure the tumor-bearing athymic mice. Furthermore, the effector cells were destroyed when the nylon-wool-column-nonadherent cells were treated with an anti-L3T4 antibody and complement whereas the same treatment with anti-Lyt2 antibody had no effect. These L3T4+ cells did not possess asialo-GM1 antigen. Although the exact mechanism of action of the effector cells is yet to be clarified, the induction of human equivalents of this type of effector cell would be a good parameter indicative of clinical effects induced by OK-432 or other biological response modifiers in an individual cancer patient.

Animals↗
PubMed1993

Assessment of obesity of children with spina bifida.

Percentage body fat of 35 children with spina bifida and 129 age-matched normal children was measured by underwater weighing and skinfold thickness to assess obesity. Percentage body fat of patients below five years was similar to that of controls; however, 58 per cent of patients above six years had an increased percentage of body fat. The neurological level and ambulatory ability were associated with percentage body fat. A significant correlation between percentage body fat and hydrocephalus suggests that the metabolic and nutritional maladaptation is caused not only by these patients' physical inactivity but also by the condition itself. Appropriate nutritional and mobility programmes should be started early to prevent the development of obesity.

Adipose Tissue↗
PubMed1993

Cytotoxic effect of hinokitiol and tropolone on the growth of mammalian cells and on blastogenesis of mouse splenic T cells.

Hinokitiol (I) and tropolone (II) showed characteristic cytotoxic effects in vitro on five kinds of human and murine cell lines and blastic lymphocytes from mouse splenocytes. The cytotoxic effect of I on the growth of murine and human tumor cell lines, including RL male-1, MH134, HL60, K562 and KATO-III was definite when examined by thymidine incorporation into DNA and its 50% inhibitory concentration (IC50) on all cells was 0.3-0.6 microgram/ml. Compound II also showed comparable cytotoxic effects on these cell lines, indicating a little lower activity when compared to I. Furthermore, I and II also completely suppressed the [3H]thymidine ([3H]TdR) incorporation of mitogen-induced blastic lymphocytes. The suppressive activity on mouse lymphocyte proliferative response to concanavaline-A was also found with both compounds at a low concentration of 0.32 microgram/ml. As compound I is known to be of fairly low toxicity (LD50: 453 + 24 mg/kg in mice), the antitumor and immuno-suppressive effect of hinokitiol (I) should be further investigated.

Animals↗
PubMed1993

[Clinical study on judgement of brain death by the nasopharyngeal lead with the aid of an automatic EEG analysis system].

We investigated the relationship between scalp electroencephalogram (EEG) and nasopharyngeal EEG using Automatic EEG Analysis System in 10 patients with the age between 17 and 66 who were clinically presumed brain death because of flat line EEG and loss of auditory brainstem response (ABR). Among 10 patients, nasopharyngeal lead EEG showed low voltage and slow waves of 10-20 microV in 4 cases and flat line EEG in 6 cases. However, Automatic EEG Analysis system-assisted analysis of EEGs recorded on a magnetic tape revealed that equivalent electric potentials in the scalp EEG from these patients were smaller than those of healthy volunteers, but those in the nasopharyngeal EEG from all patients showed low voltage within the range of distribution in normal volunteers (delta:6, theta 1:6, theta 2:2, alpha 1:1, alpha 3:10, beta 1:6 in 10 cases). The present results show that in addition to the routine scalp EEG, it is clinically useful to employ simple and easy nasopharyngeal lead EEG method and to analyze data using Automatic EEG Analysis System for the judgement of brain death.

Adolescent↗
PubMed1993

[Determination of benzodiazepines by thermospray liquid chromatograph-mass spectrometer. Part 1. Nitrazepam, estazolam, bromazepam, flunitrazepam].

Thermospray liquid chromatography mass spectrometric method is described for the determination of the benzodiazepines (Nitrazepam, Estazolam, Bromazepam, Flunitrazepam). Reversed-phase liquid chromatography was performed using a 15 cm Shim-pack CLC-ODS (Shimadzu) column, with acetonitrile-water (40:60) + 0.1 M ammonium acetate as mobile phase, at a flow rate of 1.0 ml/min. The temperature of the vaporizer, block and TH of the source block were 166, 270 and 275 degrees C, respectively. Positive ion thermospray mass spectra by thermospray ionization (TSP ionization) mode or thermospray on filament ionization (filament-on ionization) mode were obtained. Formation of the MH+ ion was observed as a base peak under TSP ionization and filament-on ionization conditions and fragment ions were very few. On both ionization mode, peaks representing nitrazepam as MH+ at m/z 282 at a retention time (R.T.) of 6.4 min, from estazolam as MH+ at m/z 295 at an R.T. of 6.4 min, from bromazepam as MH+ at m/z 316 at an R.T. of 4.5 min and from flunitrazepam as MH+ at m/z 314 at an R.T. of 8.8 min. The detection limit for all the benzodiazepines under investigation was less than 0.5 ng (S/N = 9.4 +/- 4.6) using selected ion monitoring.

Benzodiazepines↗