Biomedical subjects
Publications and source records attributed to K Yamafuji.
The enzyme which could produce kinin-like peptides from rat plasma at acidic condition and at coexistence of thiol compound was separated from acid extract of rat spleen. The isolation procedure of this enzyme was established. Substrate specificity was examined against fluologenic substrates and two types of collagen. The purified enzyme was proved to have kinin-forming activity and also collagenlytic activity.
Electrical characteristics in a membrane constructed from a porous filter adsorbed with a lipid analogue, dioleoyl phosphate (DOPH), were investigated in a situation interposed between 100 mM NaCl + 3 mM CaCl2 and 100 mM KCl. Calcium ions affected significantly the membrane characteristics. The membrane potential was negative on the KCl side, which implies the higher permeability to K+ than Na+; this tendency was increased by a tiny amount of Ca2+. While the membrane showed a low electrical resistance of several k omega . cm2 under K+/Na+ gradient, it showed several M omega . cm2 by Ca2+. The surface structure of the membrane exhibited many voids in the low-resistance state, but the surface was covered by oil droplets in the high-resistance state. Oscillations of the membrane potential appeared spontaneously with application of the electrical current from the KCl side to the NaCl + CaCl2 side. The frequency was increased with the electrical current. All these results were explained comprehensively using an electrochemical kinetic model taking account of the Ca2+ binding effect, where DOPH assemblies make a phase transition between oil droplets due to Ca2+ and multi-bilayers with excess K+. The oscillation arises from coupling of the phase transition to accumulation and release of K+ or Ca2+. This membrane can be used as an excitable element regulated by Ca2+ in neuro-computer devices.
The susceptibility to cancer in the vagotomized stomach which was assigned either to selective vagotomy (SV) or selective proximal vagotomy (SPV) was studied by gastric carcinoma model of male Wistar rat on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) administration. Predilection for cancer of the remnant stomach was also studied. Four groups of the rats submitted to either one of the SV, SPV, antrectomy (Billroth-I reconstruction) or control (simple laparotomy) group, were prepared. The techniques of SV and SPV in rat was originally developed. MNNG in drinking water was given as carcinogen. Gastric acid output, gastric stasis, serum gastrin levels together with the number and the invasiveness of the atypical glands those were recognized in the glandular stomach of rats were examined. The results were as follows: (1) the reduction rate of gastric acid output was the most conspicuous at antrectomy group followed by SV and SPV groups, (2) gastric stasis was observed in almost the same degree in SV and SPV groups, (3) serum gastrin level was the highest in SV group followed by SPV, control and antrectomy groups in this order and (4) the susceptibility to malignancy was significantly high at SV group but not high at SPV and antrectomy group as compared with control group.
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The electric membrane potential as functions of position and time of Characean internode has been studied using a modified water-film electrode technique. Between the low-conductance hyperpolarized region (called the H-region or acidic region) and the high-conductance depolarized region (D-region), there is a difference in the direction of responses to light-off and -on stimulations. In darkness the membrane potential becomes hyperpolarized in the D-region, whereas it is depolarized in the H-region at the steady state. The potential difference between D- and H-regions, delta Vm, is increased by exposure to pure O2, N2, or CO2-free air. When the amount of water surrounding the internode is limited, the formation of an electric pattern occurs rapidly. In contrast, the recovery is delayed. The membrane potential of the D-region is sometimes hyperpolarized significantly with lowering of the extracellular pH to 7.5, while the potential of the H-region is slightly depolarized. This seems to be an all-or-none type response. However, the electric profile is always homogenized with the pH of 6.8. Thus, the pH around 7.5 may be a threshold level to open/close putative OH- (or H+) channels of the D-region.
A model membrane constructed from a Millipore filter, whose pores were impregnated with dioleyl phosphate, exhibited an electric self-oscillation under nonequilibrium conditions. The membrane interposed between two solutions with the same KCl concentrations showed no temporal change in membrane potential. However, the potential became oscillatory on application of an electric current to the membrane. The frequency was proportional to the magnitude of the electric current. When both KCl solutions were replaced by NaCl solutions, a similar trend was observed, although the oscillation was not as regular as in the case of KCl. A membrane placed between equimolar solutions of KCl and NaCl, on the other hand, gave rise to an oscillation even without current application. When a membrane was placed between 5 mM KCl and 100 mM KCl, it was found that NaCl added to the 5 mM KCl side had a pronounced effect on the membrane with respect to the frequency response of the oscillation. These results indicate that the dioleyl phosphate membrane discriminates Na+ from K+.
With the aim of clarifying the nature of the synergistic action of LNT with endocrine therapy for mammary tumor, the effect of LNT post-treatment was investigated in rats with DMBA-induced mammary tumors and also in patients with recurrent breast cancer. LNT injection following surgical therapy (Ax + Ox) resulted in a much greater regression of tumor growth than that obtained by surgery alone, but not after medical therapy (Tamoxifen). Image analysis using an immunohistochemical technique revealed that LNT-surgical therapy resulted in marked atrophy of tumors and as well as intense infiltration of T cells, B cells and macrophages into the stroma around the tumor. Blood prolactin level was greatly reduced by LNT injection. A clinical randomized controlled study demonstrated the efficacy and safety of LNT post-treatment with surgical therapy in 33 patients with recurrent breast cancer. The mode of the synergistic action of LNT in combination with endocrine therapy on hormone-dependent tumors was discussed.
Intracellular distributions of acid kininogenases were investigated following the subcellular fractionation of bovine and rat spleens. Acid kininogenases as well as other acid hydrolases were observed to be distributed in several fractions. Relatively high kinin forming activity was found in two fractions which were considered to contain lysosomes from reticulum cells and from lymphocytes respectively. The latter fraction had shown the higher sensitivity to thiol compound for its activation. These findings led us to the separation of the free cells existing in spleen each other. We adopted the techniques such as Ficoll-Isopaque centrifugation, plastic dish treatment and iron carbonyl treatment for this purpose. Lymphocyte from rat thymus was also examined and proved to have acid kininogenase activity as well.
A model membrane constructed from a Millipore filter, whose pores are filled with dioleyl phosphate molecules, exhibits a self-oscillation of the electric potential with a period of about a few seconds in the presence of a salt-concentration difference, pressure difference and/or electric current across the filter. In this paper, the effects of chemicals such as KCl, CaCl2, pH and sucrose on the self-oscillation are investigated experimentally. These chemical substances are shown to alter the characteristic properties as the frequency of oscillation. Theoretical consideration of electrochemical interaction between these substances and DOPH molecules gives a fairly good explanation of the observed results.
Two kinin forming enzymes were extracted from bovine spleen and separated from cathepsin B1 and B2 by DEAE-Cellulose chromatography. Since these catheptic kininogenases were found to release kinins from kininogens at acidic pH's, these were named acid kininogenase I and II. The presence of SH compounds was not necessary for I to have a kinin forming activity, while it was necessary for II. These have only minor difference for electrophoretic behaviors as can be seen, e.g., from a small difference in pI values, but could be separated by polyacrylamide gel electrophoresis. Their production of kinins from bovine crude bradykininogen was highly reproducible. Kininogenase I was proved to react on bovine HMW kininogen and also to release some kinin from LMW kininogen and leukokininogen. From the study of several substrates, these enzymes were revealed to have very low tryptic and little esterolytic activities and to have affinity to some hydrophobic amino acids.
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