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Biomedical subjects

S Ishida

Publications and source records attributed to S Ishida.

At least 235 records · Page 13Linked to original sources

[Effects of chronic volume loading on atrial natriuretic peptide release in human].

In the present study, we investigated whether release of hANP increases during mild and long-term volume loading. Eight lung cancer patients in good performance state (five men and three women, 35 to 68 years), who needed to have pre-hydration for cancer chemotherapy with cisplatin, were infused with about seven liters of isotonic saline over 48 hours through Swan-Ganz catheter placed in the pulmonary artery. The mean infusion rate was 0.042 ml/min.kg body weight. During the infusion, change in plasma volume (delta PV) increased by 5.8 + 3.3 (mean +/- SE) %. Right atrial pressure (RAP) did not change significantly, and pulmonary artery wedge pressure (PAWP) increased from 4.3 +/- 1.0 to 5.8 +/- 0.7 mmHg. Plasma hANP was significantly elevated from 50.6 +/- 0.7 to 105.1 +/- 19.3 pg/ml by the second day of the infusion with a suppression of plasma renin activity (PRA) and aldosterone, though plasma ADH did not change. The infusion rate at 20:00 on the first day was the same as that on the second day. Further increase in plasma hANP was shown at 20:00 on the second day compared with the level at the same time on the first day, though RAP, PAWP and delta PV did not change. These results indicate that mild and chronic volume loading increases plasma hANP, and suggest that the prolongation of volume expansion plays an important role in the releasing of hANP in humans.

Adult↗

[Combination effect of caffeine and cisplatin on a cisplatin resistant human lung cancer cell line].

The development of resistance to anti-cancer drugs is a major factor in limiting the response rate of cancer chemotherapy. Several mechanisms of such resistance are reported. Recently, expression of MDR gene and synthesis of p-glycoprotein by the MDR gene was reported as a mode of multi-drug resistance, but the mechanism of the resistance to cisplatinum (CDDP) remains unclear. Detoxification of CDDP, increase of the efflux of the drug and increase of DNA repair are considered to be the mode of CDDP resistance. It is widely documented that caffeine enhances the cytocidal effect of certain anti-cancer agents. The inhibition of DNA repair by caffeine has been considered to be one mechanism which enhances the cytocidal effect of such agents. We conducted the present study to evaluate the combination effect of caffeine and CDDP on the human lung adenocarcinoma cell line PC9/P and its CDDP resistant cell line PC9/R. Cell growth inhibition was measured by clonogenic assay and cell cycle analysis was performed with propidium iodide (PI) stain using flow cytometer (FCM). Caffeine enhanced the effect of CDDP on PC9/P synergistically. However, the combination effect of the two drugs was not apparent on PC9/R. Caffeine decreased G2M accumulation due to CDDP exposure in both cell lines. The data indicate that caffeine does not overcome the resistance of PC9/R, whereas caffeine enters PC9/R. It is suggested that increase of DNA repair might not be a mode of the CDDP resistance of PC9/R.

Adenocarcinoma↗

Flow cytometric analysis of the kinetic effects of cisplatin on lung cancer cells.

The effects of cisplatin on the cell cycle and DNA synthesis of human lung adenocarcinoma cell line PC-9 were examined by flow cytometry. The cellular DNA content and the bromodeoxyuridine (BrdUrd) incorporation rate were measured simultaneously using a monoclonal anti-BrdUrd antibody. Following exposure to cisplatin (1.0 micrograms/ml) for 1 and 24 hr, the bivariate DNA/BrdUrd distributions revealed a delayed S-phase transit and an accumulation of cells in the G2M phase. The BrdUrd-linked green fluorescence intensity continued to decrease with the lapse of time. However, early- and mid-S-phase cells soon recovered DNA synthesis activity, and the former showed higher activity than the control cells. These findings suggested the vigorous DNA synthesis of cells in early S phase. However, for quantitative analysis of chemotherapeutic effects, some problems remained to be resolved regarding the condition for DNA denaturation and its alteration by the agents.

Adenocarcinoma↗

Modes of genotoxicity of a macromolecular antibiotic, SN-07, a novel type of interstrand DNA cross-linker.

The modes of genotoxicity of a novel macromolecular antitumor antibiotic (SN-07) were examined using both prokaryotic and eukaryotic cells in vitro. The antibiotic induced a frameshift-type reverse mutation in Ames Salmonella typhimurium TA98 at 1.6-400 ng/plate with and without S9 mix. SN-07 also induced chromosomal aberrations and a forward mutation (6-TGr) in Chinese hamster V79 cells after 1 h treatment at 12.5-100 ng/ml without metabolic activation. The alkaline elution technique revealed that SN-07 induced interstrand DNA cross-linking dose-dependently after treatment with 2.5-10 micrograms/ml for 1 h followed by elution at pH 12.1, but it did not induce the dose-dependent cross-linking after the same treatment followed by elution at pH 12.6. It was also found that SN-07 induced single-strand DNA breaks (pH 12.1) and alkali-labile (pH 12.6) sites after treatment with 0.1-10 micrograms/ml for 1 h followed by 24-h post-incubation.

Animals↗

The pyrogenicity of pertussis vaccine in mice and the factors in the vaccine responsible for this effect.

The injection of whole cell pertussis vaccine into mice produced a biphasic fever reaction with two peaks appearing after about one and four hours, respectively. A method for the quantitative determination of each peak fever activity was developed and the factor responsible for each activity was investigated. The first and the second peak fever activities did not parallel each other in individual vaccines. The earlier fever activity appeared to correlate with endotoxin activity in individual vaccines while the later appeared to correlate with histamine-sensitizing factor (HSF) activity. The later peak fever activity was greatly reduced by heating the vaccine at 100 degrees C for 30 min while the first was little affected by such treatment. It was concluded that the fever activity of pertussis vaccine in mice may be ascribed to the combined actions of endotoxin and a heat-labile substance, possibly HSF.

Animals↗

Binding of glycyrrhizin to human serum and human serum albumin.

The binding of glycyrrhizin (GLZ) to human serum and human serum albumin (HSA) was examined by an ultrafiltration technique. Specific and nonspecific bindings were observed in both human serum and HSA. The association constants (K) for the specific bindings were very similar: 1.31 x 10(5) M-1 in human serum and 3.87 x 10(5) M-1 in HSA. The number of binding sites (n) and the linear binding coefficient (phi) in HSA were 1.95 and 3.09 x 10(3) M-1, respectively. When the human serum protein concentration was assumed to be 4.2% (equal to the measured serum albumin concentration), n in human serum was 3.09, which is similar to the n value in HSA, and phi in human serum was 0.71 x 10(3) M-1, which is reasonably close to that for HSA. The binding pattern of GLZ with human serum protein on Sephadex G-200 column chromatography showed that GLZ binds to only the albumin fraction. It was concluded that the GLZ-binding sites in human serum exist mainly on albumin and GLZ binds to specific and nonspecific binding sites at lower and higher concentrations than approximately 2 mM, respectively.

Glycyrrhetinic Acid↗

Pharmacokinetics of glycyrrhetic acid, a major metabolite of glycyrrhizin, in rats.

The pharmacokinetics of glycyrrhetic acid (GLA) was examined in rats after bolus i.v. injection at a dose of 2, 5, or 12 mg/kg. The decline in plasma concentration was generally biexponential at each dose, but the terminal disposition became much slower with increase of dose. A greater than proportional increase in plasma GLA concentration was observed with increase of dose, suggesting a dose-dependency of GLA disposition. Apparent total body clearance decreased significantly with increase of dose. On the other hand, the apparent steady-state distribution volume after i.v. administration was unaffected by dose. The plasma disposition at each dose fitted well to a two-compartment pharmacokinetic model with Michaelis-Menten elimination. It was concluded that the pharmacokinetics of GLA in the rat is dose-dependent owing to a saturable elimination rate. The plasma level of GLA after glycyrrhizin (GLZ) i.v. dosing (100 mg/kg) in the control rats (without biliary fistulization) sustained the concentration range of 1.5-3 micrograms/ml during 1-48 h, but that in the rats with biliary fistulization declined with time. It was suggested that the sustained plasma level of GLA is accounted for by the intestinal reabsorption of GLA produced from GLZ and GLA-conjugates during the enterohepatic recycling of both.

Animals↗

Effect of dietary sodium bicarbonate and magnesium oxide on cows with milk fat depression in several dairy herds.

Buffer mainly consisting of 100 g of sodium bicarbonate and 30 g of magnesium oxide was added to the feed per head per day and given for 8 months to groups of 92 cows of milk fat depression. Milk fat increased from 3.06% (pre-treatment) to 3.68% at 4 months and 3.71% at 8 months post-treatment. Solids-not-fat was slightly increased by the buffers. Milk production was not affected. The number of rumen protozoa increased from 2.85 X 10(5)/ml (pre-treatment) to 9.61 X 10(5)/ml at 8 months post-treatment and the kinds of protozoa diversified. An increase of acetate and decrease of propionate were observed together with increased milk fat at 8 months post-treatment. An increase of hematocrit, lactate dehydrogenase, sodium and potassium, and a decrease of cholesterol and gamma-glutamyl transpeptidase in blood were recognized after the treatment. The incidence of disease was reduced. There was a significant correlation between increased milk fat percentage and increase in the number and the kinds of protozoa.

Animals↗

[Study on surface treatment of silica filler. Hydrolytic deterioration of the silane coupling layer].

The mechanism of the hydrolytic deterioration of the silane coupling agent layer on silica filler of composite resin was examined. As a result of the desorption of the absorbed silane molecules, the contact angle between water drop and the silica plate treated with the silane coupling agent decreased when the plate was soaked in hot water and the rate of the decrease in the contact angle leveled off with an increase in the concentration of the silane coupling agent solution. With an increase in the soaking time in hot water, the strength of adhesion of poly (BIS-GMA) to the silica treated with the silane coupling agent decreased and the position of the fracture shifted from the matrix resin (adherend failure) to the silane coupling layer (adhesion failure). The time when the adhesion failure took place depended on the concentration of the silane coupling agent solution and there was the optimum concentration for water-resistant adhesion.

Composite Resins↗

Oligo-2',5'-adenylate synthetase activity in K562 cell lines persistently infected with measles or mumps virus.

Fluctuation of oligo-2',5'-adenylate synthetase (2-5AS) activity was examined in K562 cells infected with vaccine strains of measles virus (strains AIK-C and CAM-70) and mumps virus (strains Torii and Miyahara). Persistent infection was easily established in the mumps virus-infected cells without significant cytolysis or cell killing. In contrast, most of the cells infected with measles virus were killed by extensive cytolysis within 3 to 4 days. The small number of cells that did survive became persistently infected. That these persistently infected cells carried a virus antigen was confirmed by fluorescein isothiocyanate-labelled anti-measles virus rabbit antiserum and anti-mumps virus rabbit antiserum. The cells produced infectious progeny virus as well as interferon (IFN). Little induction of 2-5AS activity by IFN was demonstrated during the early stages of infection by these viruses. Similar results were observed in some of the persistently infected cells but not, however, K-CMP cells (K562 cells persistently infected with CAM-70) or K-MMP cells (K562 cells persistently infected with Miyahara). Failure to induce 2-5AS activity was unchanged in cells cultured for more than 6 months. The decrease of 2-5AS activity observed in K-MTP cells (K562 cells persistently infected with Torii) was the result of suppression of transcription of 2-5AS mRNA. On the other hand, a normal level of mRNA was found in K-AKP cells (K562 cells persistently infected with AIK-C). Therefore, it is suggested that the decrease of 2-5AS activity in K-AKP cells may be due to a failure to translate 2-5AS mRNA.

2',5'-Oligoadenylate Synthetase↗