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Biomedical subjects

S Sawada

Publications and source records attributed to S Sawada.

At least 487 records · Page 27Linked to original sources
PubMed1985

Pharmacological comparison of captopril and MK-422 by a new method for measuring activity of angiotensin converting enzyme (ACE).

The authors recently reported the development of a new method for measuring angiotensin converting enzyme (ACE) by means of a highly sensitive angiotensin II RIA technique. We have carried out a comparative study of the pharmacological properties of captopril and MK-422, two ACE inhibitors recently developed as new antihypertensive agents. In this study, in vivo and in vitro animal experiments were performed using the Göttingen Mini-pig (Mini-pig G) animal model of the human disease. In the in vivo experimental system, each drug was administered by intravenous injection at a dose of 1 mg/kg, and a slight difference was found in the time-course of the per cent inhibition of ACE in the blood. In the in vitro system (cultured aortic endothelial cells), the ACE inhibitory activities of the two drugs were compared in terms of the 50%-inhibition point on the dose response curve, and it was found that MK-422 was about 100 times more potent than captopril. These results indicate that our newly-developed experimental system can be useful in the establishment of the clinical dose of vasoactive drugs that act on the renin-angiotensin system.

Animals↗
PubMed1985

An improved method for measuring angiotensin I converting enzyme activity using a highly sensitive angiotensin II radioimmunoassay.

A highly sensitive assay for angiotensin I converting enzyme has been developed by using angiotensin I as a substrate. Angiotensin II generated in the reaction mixture was measured by a newly developed specific radioimmunoassay. To protect against angiotensin II destruction, bestatin, an inhibitor of renin, was also used to inhibit plasma renin activity. The reaction was stopped by adding EDTA and MK-521, inhibitors of angiotensin I converting enzyme. The specificity of the antiserum used for the angiotensin II radioimmunoassay was very high. The cross reactivity with angiotensin I was less than 0.5% and none of the proteolytic enzyme inhibitors crossreacted in the assay. The inhibitory effect of pepstatin on plasma renin activity was very high (more than 80%) under the standard assay conditions employed. Serum angiotensinase activity was completely inhibited by the addition of bestatin. An excellent correlation was obtained between this new method and the spectrophotometric method using a synthetic substrate, Hip-His-Leu. The generation of as little as 12 pM of Angiotensin II can be detected. Such low concentration have not been measurable with the usual spectrophotometric method. This new method will facilitate clinical and experimental studies on this unique enzyme, since very low levels of activity can be determined by this highly sensitive radioimmunoassay for angiotensin II.

Angiotensin I↗
PubMed1984

Fast and slow depolarizing potentials induced by short pulses of kainic acid in hippocampal neurons.

Responses of hippocampal neurons to short pulses of alpha-kainic acid (KA) were studied intracellularly in thin brain slices of the guinea pig. A KA pulse induced a slow depolarizing potential either with or without a preceding much faster depolarization. Large fast responses were induced only at the center of glutamate-sensitive spots, where short pulses of L-glutamate (Glu) induced large depolarizations in the impaled neuron. The fast responses resembled Glu-induced depolarizations in time-course, in sensitivity to movement of the tips of amino acid-pipettes, in sensitivity to Glu-antagonists and in reversal potential. The slow response was much more resistant to movement of the amino acid-pipettes and to Glu-antagonists. Mn2+ was without effect on the fast as well as the slow responses. Glu-induced depolarizations super-imposed on the slow response were simply depressed. These results indicate that two different types of receptors are activated by administration of KA, and suggest that the slow response results from a direct action of KA and the fast response is produced as a consequence of either the direct action of KA on the Glu receptors or a calcium-independent release of Glu by KA.

Acetates↗
PubMed1984

Gamma-D-glutamylglycine and cis-2,3-piperidine dicarboxylate as antagonists of excitatory amino acids in the hippocampus.

The actions of gamma-D-glutamylglycine (DGG) and cis-2,3-piperidine dicarboxylate (PDA) were studied in thin hippocampal sections of the guinea pig by intracellular recording. DGG and PDA suppressed depolarizations induced in CA3 neurons by short pulses of L-aspartate (Asp), D-homocysteate (DH) or L-glutamate (Glu). Asp- and DH-responses were more susceptible to the antagonists than were Glu-responses. The sensitivity difference between Glu-responses and Asp- or DH-responses was not so pronounced that these antagonists could be used to differentiate between Glu-mediated and Asp-mediated synapses. Glu and Asp pulses induced long hyperpolarizing deflections in some neurons. In about half of these neurons, PDA and DGG were without effect on the hyperpolarizing responses. The depolarizing action of gamma-amino butyric acid was unaffected by DGG and PDA. These antagonists blocked excitatory postsynaptic potentials induced by fimbrial stimulation. These results suggest that DGG and PDA are relatively specific antagonists of excitatory amino acids in the hippocampus, and that Glu (or Asp) is the neurotransmitter released from axons of CA3 neurons.

Amino Acids↗
PubMed1984

Repair of lethal, mutagenic and transforming damage induced by X-rays in golden hamster embryo cells.

We compared the frequencies of mutation and morphological transformation in relation to the repair of potentially lethal damage (PLD) and sublethal damage (SLD) in X-irradiated golden hamster embryo (GHE) cells. The repair of PLD induced in GHE cells by X-rays was shown to be an error-free process which reduced the frequency of mutation and morphological transformation. However, if cells were irradiated with doses divided into two halves separated by various time intervals to study repair of SLD, the frequency of mutants and morphological transformants depended upon the length of the interval between the doses. If the interval was 2 h, the frequency of mutants and transformants was lower than if the total dose were delivered in a single exposure. If the interval was 4 h, these frequencies were higher than the latter. The transformation frequencies remained high even if this interval was increased to 12 h, but the frequency of mutants decreased again. Thus, enhancement of mutant or transformant frequency by a second exposure to X-rays, 4 h after the first irradiation, correlated with recovery of DNA synthesis in the X-irradiated cell populations. Studies with synchronized cells also showed that induction of mutants and transformants was highest in cells irradiated at the DNA synthesis (S) phase. These results suggest that DNA synthesis plays a critical role in the process of X-ray-induced morphological transformation and mutagenesis.

Animals↗
PubMed1984

Protection against infection with Pseudomonas aeruginosa by passive transfer of monoclonal antibodies to lipopolysaccharides and outer membrane proteins.

Experimental infection with Pseudomonas aeruginosa was treated with eight different monoclonal antibodies (MCAs) produced by hybridoma cells obtained through cell fusion of mouse plasmacytoma cells and spleen cells from mice immunized with a virulent strain of P. aeruginosa (Homma serotype 7). Five MCAs bound to lipopolysaccharides (LPSs) specific to serotype 7 or serotypes 2, 7, and 13, whereas the other three MCAs bound with broad specificities to outer membrane protein (OMP) fractions. The MCAs to LPS were highly protective against infection, with 50% protective doses of 0.05-2.5 micrograms of immunoglobulin per mouse. In contrast, the MCAs to OMP were much less protective, with a 50% protective dose range of 10 to greater than 100 micrograms of immunoglobulin per mouse. Most of the MCAs to LPS agglutinated P. aeruginosa cells, but all the MCAs to OMP produced so far have not, although all the MCAs bound well to the cells. Agglutinating MCAs provided better protection than did nonagglutinating MCAs.

Agglutination Tests↗