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Biomedical subjects

A Yoshimura

Publications and source records attributed to A Yoshimura.

At least 73 records · Page 4Linked to original sources
PubMed1989

Autoregulation of renal blood flow in streptozocin-induced diabetic rats.

Autoregulation of renal blood flow (RBF) was studied in male Wistar rats. We studied 11 control rats, 11 rats with severe streptozocin (STZ)-induced hyperglycemia (diabetic group), and 10 moderately hyperglycemic rats made diabetic by injection of STZ but given 2-8 U s.c. insulin daily (insulin-treated group). RBF was measured by an electromagnetic flowmeter during stepwise reduction of renal perfusion pressure 4-8 wk after injection of STZ (older group). RBF autoregulation of the diabetic group was impaired compared with the control group. In the insulin-treated group, autoregulatory capability was less attenuated than in the diabetic group. The average autoregulatory index (ARI) of the diabetic group (0.61 +/- 0.05) was greater than that of the control (0.24 +/- 0.02, P less than .01) and the insulin-treated (0.33 +/- 0.07, P less than .05) groups. To study the relationship between autoregulation and the duration of diabetes, an autoregulatory study was also made in a group of 22 rats (11 diabetic and 11 control) that were tested 2-3 wk after injection of STZ (younger group). The ARI in the younger diabetic group was smaller than that in the older diabetic group (P less than .05). The results suggest that in uncontrolled diabetes RBF fluctuates with blood pressure change, and protection against hypertensive injury of glomerular capillaries may be diminished. Autoregulatory disability develops with time, and insulin treatment diminishes impairment of autoregulation. These findings may also explain the adverse consequences of hypertension on the progression of diabetic nephropathy in poorly controlled diabetes.

Animals↗
PubMed1989

[A molecular basis for multidrug resistance and reversal of the resistance].

Multidrug-resistance is frequently characterized by enhanced drug efflux resulting from a membrane glycoprotein of 170,000 daltons (P-glycoprotein). Analysis of cloned cDNAs for the human MDR 1 gene, whose product is the P-glycoprotein, indicates that P-glycoprotein is an energy-dependent drug-efflux system for cytotoxic hydrophobic anticancer drugs. We have demonstrated that a photoanalog of a reversing agent, SDB-ethylenediamine, specifically binds to P-glycoprotein. The binding site on P-glycoprotein seems to be identical with that of anticancer agents and other reversing agents. On the other hand, the radioactive photoactive dihydropyridine calcium channel blocker, [3H] azidopine, photolabels P-glycoprotein in membrane vesicles from multidrug-resistant cells. This photolabeling is almost completely inhibited by excess dihydropyridine analogs that reverse or lower drug-resistance. In contrast, the labeling is not significantly inhibited by analogs that do not reverse resistance. These results suggest that it may be possible to quickly screen for dihydropyridine analogs that reverse multidrug resistance by measuring the inhibition of [3H] azidopine labeling of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Synthetic isoprenoid photoaffinity labeling of P-glycoprotein specific to multidrug-resistant cells.

The synthetic isoprenoid N-solanesyl-N,N'-bis(3,4-dimethoxy-benzyl)ethylenediamine (SDB) is known to reverse drug resistance in human multidrug-resistant KB cells. SDB inhibits the photolabeling of P-glycoprotein with the vinblastine analog N-(pazido-(3-(125)l)salicyl)-N'-beta-aminoethylvindesine. We synthesized photoactive radioactive SDB and used it to photoaffinity label membrane vesicles from human KB cells and their multidrug-resistant subline KB-C2 cells. A 150 to 170 kDa protein in membrane vesicles from KB-C2 cells was specifically labeled by the photoanalog of SDB. The labeled band was not detectable in parenteral drug-sensitive cells. The photolabeled 150 to 170 kDa protein was immunoprecipitated with a monoclonal antibody (C219) specific to P-glycoprotein. P-glycoprotein labeling was inhibited by anticancer agents, vinblastine, vincristine, actinomycin D, and daunomycin, with half-maximal inhibition at 2.0, 2.3, 18, and 23 microM, respectively. Only 33 and 18% of the labeling was inhibited by 100 microM Adriamycin and colchicine, respectively. The labeling was also inhibited by agents that reverse multidrug resistance, such as verapamil, reserpine, cepharanthine, and SDB. The existence of other molecules that specifically bind to 125l-SDB-photoanalog was suggested in both KB and KB-C2 membrane vesicles. The fact that we could identify the synthetic isoprenoid acceptor in membrane vesicles from multidrug-resistant cells confirms that P-glycoprotein plays a role in the multidrug resistance phenotype and provides an explanation for the fact that SDB circumvents multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Organ distribution of 3H-endotoxin in rats with liver fibrosis and rats with liver cirrhosis.

The organ distribution of 3H-endotoxin was investigated in rats with CCl4-induced liver injury. Wistar male rats were given water containing phenobarbital (Controls), or were treated with water containing phenobarbital and CCl4 inhalation. Rats inhaling CCl4 for 6 weeks developed liver fibrosis (Group LF), while those inhaling it for 10 weeks developed liver cirrhosis (Group LC). Animals were killed and examined 24 hours after an intravenous injection of 3H-endotoxin (12,000 CPM/l g body weight). Compared with the control rats, the measured amount of 3H-endotoxin per unit weight of spleen, lungs, and blood increased, while that of the liver significantly decreased in the rats of groups LF and LC. These results suggest that endotoxemia may be enhanced by a diminished uptake of endotoxin by the liver in liver fibrosis and liver cirrhosis.

Animals↗
PubMed1988

Novel feature of metabolism of low density lipoprotein receptor in a mouse macrophage-like cell line, J774.1.

Biosynthesis, processing, and degradation of low density lipoprotein (LDL) receptors were studied in a mouse macrophage-like cell line, J774.1, by immunoprecipitation and immunoblotting with an antibody directed against the COOH-terminal 14 amino acids of the LDL receptor. The molecular weight of the mature LDL receptor of J774.1 cells maintained in RPMI medium was 140,000 under nonreducing condition and 160,000 under reducing condition in sodium dodecyl sulfate-polyacrylamide gels. These sizes are 10,000-15,000 daltons larger than those of the receptor in other mouse fibroblastic cells or P388 leucocyte. However, when J774.1 cells were cultured in Dulbecco's modified Eagle's medium, the molecular weight of the mouse cell lines, 123,000 under nonreducing condition and 153,000 under reducing condition. The larger LDL receptor molecules produced by J774.1 cells cultured in RPMI were insensitive to the treatment with end-alpha-N-acetylgalactosaminidase (O-glycanase), suggesting that aberrant serine/threonine-linked (O-linked) glycosylation might account for the apparent large size. Pulse-chase experiments revealed that the rate of processing of the LDL receptor from precursor to mature form in J774.1 was similar to that in other mouse cell lines, but the rate of degradation was much faster: half-life of the LDL receptor of J774.1 was about 2 h. No significant difference in biological function or lifetime was observed between the normal and the larger LDL receptor. This novel character of molecular size and lifetime of the LDL receptor in J774.1 is discussed in relation to altered maturation and/or modification during receptor biosynthesis.

Animals↗
PubMed1988

Estrogen inhibits the growth of MCF-7 cell variants resistant to transforming growth factor-beta.

Human breast cancer MCF-7 cells containing estrogen receptor are killed by transforming growth factor-beta (TGF-beta). We isolated variants of MCF-7 highly resistant to TGF-beta. Variants ES-1 and ES-4 were cloned, and the growth of ES-1 and ES-4 was found to be inhibited by estradiol, whereas estradiol stimulated the growth of the parental MCF-7 cells. ES-1 cells contained about 2-fold higher level of estradiol receptor than MCF-7 cells. Addition of estradiol to the culture medium for MCF-7 and the variant changed the expression of several secreted proteins. The repertoire of secreted proteins was markedly altered in the variant. Polypeptides of molecular weight 52,000 (52 K), 65 K and 160 K were increased about 10- to 50-fold in both estradiol-treated MCF-7 and ES-1 cells. Polypeptide of 130 K was decreased in estradiol-treated ES-1 cells while this polypeptide was increased about 4-fold in estradiol-treated MCF-7, as compared with untreated MCF-7. Polypeptide of 100 K was specifically secreted in ES-1 whether or not estradiol was present, but there appeared to be no significant amount of the 100 K protein in MCF-7. The estradiol-hypersensitive phenotype is discussed in relation to its aberrant expression of secreting proteins.

Breast Neoplasms↗
PubMed1988

Cardiotonic activity of 5-methyl-6-(4-pyridyl)-2H-1,4-thiazin-3(4H)-one hydrochloride (ZSY-27).

Cardiotonic activity of a new, non-catecholamine and non-glycoside positive inotropic agent, 5-methyl-6-(4-pyridyl)-2H-1,4-thiazin-3(4H)-one hydrochloride (ZSY-27), was investigated in isolated guinea pig left atria, cat right ventricular papillary muscle and cross-circulated excised dog papillary muscle preparations, and in anesthetized open-chest dogs. In electrically driven guinea pig left atria and cat papillary muscle preparations, ZSY-27 (3 x 10(-6)-10(-4) M) increased the developed tension in a concentration-related manner. The positive inotropic effect of ZSY-27 was not blocked by propranolol (3 x 10(-8) M) in the guinea pig atria, but was significantly inhibited by carbachol (5 x 10(-6) M) in cat papillary muscle preparations. The positive inotropic effect of ZSY-27 was comparable to that of milrinone in guinea pig atria. ZSY-27 (0.01-3 mg) increased dose-dependently the developed tension in cross-circulated excised dog papillary muscle preparations as well. In anesthetized dogs, ZSY-27 (0.03-1 mg/kg, i.v.) produced a dose-dependent increase in left ventricular contractile force and a decrease in blood pressure, while the increase in heart rate was relatively small. The pharmacological profile of ZSY-27 in anesthetized dogs was similar to that of milrinone. These results suggest that ZSY-27 is potent cardiotonic agent with vasodilator activity and its effect may be partially due to an increase in the intracellular adenosine 3',5'-cyclic monophosphate level.

Animals↗
PubMed1988

[X-ray dosimetry using a charge injection type condenser].

An X-ray dosimeter has been investigated with the use of a charge injection type condenser. The detector is small size and is housed in an epoxy resin approximately 4.5 X 2.5 X 1.5 mm. The X-ray dose can be determined by decreasing the amount of electron injected into floating gate through X-ray irradiation. The X-ray irradiation dose can be measured by decreasing of the capacitance. This dosimeter shows good linearity but the X-ray energy response for low energy region is higher than high energy region.

Radiometry↗
PubMed1988

[X-ray dosimetry using SAMOS type read-only memory].

An X-ray dosimeter has been investigated with the use of a PROM of a SAMOS (stacked gate avalanche injection type MOS) structure. The SAMOS is employed as a memory IC. The SAMOS is different from a FAMOS (floating gate avalanche injection type MOS) in the presence of a control gate, with the use of this electrode, the analog amount of electrical charge accumulated in the floating gate can be measured. The X-ray dose can be determined by decreasing the amount of electron injected into floating gate by avalanche effect through X-ray irradiation. This dosimeter shows good linearity and flat energy response. The dosimeter has no effect on fading.

Radiometry↗
PubMed1988

[Improved performance of a waste water radiation monitor].

Gamma ray waste water radiation monitor has been improved by using multichannel analyzer. Maximum permissible concentrations of 125I are one thousandth lower than 51Cr. This condition, the radioactive waste water cannot be pumped out occasionally. Gamma ray energy spectrum is measured by microcomputer based multichannel analyzer by which 125I photo-peak counts is separated from other radionuclide counts. Also detecting vessel is washed with pressured fresh water to prevent contamination.

Environmental Monitoring↗