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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 1,135 records · Page 63Linked to original sources

Desensitization of gonadotropin-releasing response following vaginal consecutive administration of leuprolide in rats.

The vaginal absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide), and the gonadotropins (luteinizing hormone and follicule-stimulating hormone)-releasing response after continuous vaginal and subcutaneous administration of the analog to rats were determined by the radioimmunoassay. A marked suppressive effect on the gonadotropin-releasing response along with long-lasting serum levels of leuprolide were paradoxically observed after consecutive 3-d vaginal administration of the analog at doses of 1 microgram/kg or greater. Pituitary function recovered progressively with cessation of the treatment but was not complete 4 d after cessation. Continuous vaginal and subcutaneous infusion resulted in an almost complete inhibition of both gonadotropins response. It is suggested that effective desensitization of the pituitary gonadotropin response is elicited by continuous administration of leuprolide and, therefore, the vaginal administration resulting in prolonged serum levels of the analog could be preferable as a self-administration method for medical treatments such as anti-tumor therapy and birth control.

Absorption↗

Activation of the alternative complement pathway by natural antibody to glycolipids in guinea-pig serum.

Liposomes containing paragloboside (PG) on their membrane were readily lysed by C4-deficient guinea-pig serum (C4D-GPS) through activation of the alternative complement pathway (ACP). Therefore we examined the reactivity of several types of guinea-pig serum (GPS) on PG-liposomes and determined that all GPS except that from specific pathogen-free (SPF) Hartley guinea-pigs had lytic capacity in Mg-EGTA-GVB (gelatin veronal-buffered saline containing Mg++ and ethyleneglycol-bis(beta-aminoethyl ether)N,N'-tetraacetate). This lytic capacity of GPS corresponded with the amount of natural antibody to PG in those sera. Although GPS of SPF guinea-pigs (SPF-GPS) could not lyse PG-liposomes in Mg-EGTA-GVB, it could lyse the liposomes when heated C4D-GPS or Hartley GPS was added. Natural antibody to PG in the heated sera was regarded to have sensitized PG-liposomes to lysis by SPF-GPS via ACP activation. Since the antibody to PG-liposomes was removed by lacto-N-nor-hexaosylceramide which has the same chemical structure in the terminal oligosaccharide, the antibody to PG in GPS was suggested to have a specificity to the terminal structure of oligosaccharide shared by lacto-N-nor-hexaosylceramide. Furthermore, the IgM fraction, which had been prepared by gel filtration of heated C4D-GPS on a Sephadex G200 column, could also sensitize PG-liposomes to lytic reaction of SPF-GPS in Mg-EGTA-GVB. This sensitizing capacity of heated C4D-GPS was suppressed by absorption of the serum or its IgM fraction with anti-guinea-pig mu-chain antibody coupled to Sepharose. Therefore, it was concluded that the lysis of PG-liposomes by GPS in Mg-EGTA-GVB was a result of ACP activation mediated by natural antibodies to PG of the IgM type which are present in usual GPS. This conclusion indicated that natural antibodies of the IgM type might play a role with ACP in host defence, especially in C4-deficient guinea-pigs where the classical complement pathway is impaired.

Animals↗

A cleavage product of mouse C3 adsorbable to (1----3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140.

By using affinity chromatography of TAK, a gel-forming antitumor (1----3)-beta-D-glucan produced by Alcaligenes faecalis var. myxogenes IFO 13140 also known as an activator of the alternative complement pathway (ACP), we obtained from mouse serum a cleavage product of C3 (tentatively designated as C3X). Binding between C3X and TAK seemed to be noncovalent. In contrast to C3, C3X had an intact beta chain (70,000 daltons) and instead of an alpha chain, two peptide chains (40,000 and 30,000 daltons) linked by disulfide bonds. C3X retained a portion of C3 antigenicity. By trypsinolysis C3 yielded a fragment similar to C3X on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results suggest that C3X is C3c. Since C3X was obtained by elution with a high salt solution from TAK incubated with ethylenediaminetetraacetate (EDTA)-serum (serum containing EDTA) but not from TAK incubated with EDTA-plasma, C3X could already be present in the serum before the activation of ACP by TAK.

Adsorption↗

Cytolysis of Sendai virus-infected guinea-pig cells by homologous complement.

Guinea-pig line 10 tumor (GPL10) cells, which were transplantable in strain 2 guinea-pigs, gained the capacity to activate the homologous alternative complement pathway (ACP) following infection with ultraviolet-irradiated Sendai virus (UV-SV). The ACP activation of homologous serum on the UV-SV-infected GPL10 cells (UV-SV-GPL10 cells) resulted in cytolysis of the tumor cells. This indicates that UV-SV infection induced not only the capacity to activate complement on the GPL10 cells, but also made them sensitive to complement attack, because GPL10 cells have been demonstrated to be resistant to the reaction of homologous complement via the classical pathway in the presence of rabbit antibody. Furthermore, UV-SV-GPL10 cells prepared with as little as 0.1 plaque-forming unit equivalent of UV-SV per cell showed suppressed growth in syngeneic strain 2 guinea-pigs. The essential role of complement in the elimination of UV-SV-GPL10 cells in vivo was confirmed by demonstrating that UV-SV-GPL10 could grow in guinea-pigs whose complement had been depleted by administration of cobra venom factor.

Animals↗

Isolation and identification of the third component of complement of Japanese quails.

The identification of the third component of complement (C3) of Japanese quails was attempted by using rabbit antiserum prepared against quail serum-treated zymosan (ZX) as an initial reagent. This antiserum (anti-ZX) had agglutinating activity on rabbit erythrocytes reacted with quail antibody and quail complement (EACq) but not on EAq, and developed two precipitin lines against quail serum at beta- and gamma-regions in crossed immunoelectrophoresis. Subsequently, monospecific antisera to each of these precipitin lines were prepared in rabbits, and quail serum proteins reactive with these antisera were purified by salt precipitation followed by Sephadex gel filtration and DEAE cellulose column chromatography. One protein with a m.w. of 184,000 (184K) resembled mammalian C3 in that: 1) monospecific antiserum (anti-184K protein serum) agglutinated EACq but not EAq; 2) treatment of fresh quail serum with either inulin or zymosan resulted in the conversion of the precipitin line developed against 184K protein from gamma to beta in crossed immunoelectrophoresis; 3) the 184K protein was shown to consist of two polypeptide chains of 110K and 73K linked by disulfide bonds. Furthermore, the 184K protein in serum was cleaved through the incubation with inulin to 174K and 140K proteins that might correspond to C3b and C3c of human complement; 4) the 184K protein bound to zymosan was eluted with hydrazine or methylamine but not with Nonidet P-40, indicating that 184K protein binds to zymosan by a covalent bond but not by a hydrophobic one; and 5) by treatment of fresh quail serum with methylamine, complement reactivity was reduced, although its activity was restored by the addition of purified 184K protein. These results suggest the 184K protein is the quail's equivalent to mammalian C3. When quail serum was reacted with cells that had complement-activating capacity, quail C3 deposited on their membrane as in mammalians; however, no conversion of quail C3 was noted by the reaction with CVF. Antibody to quail C3 failed to cross-react with that in mammals.

Animals↗

Regression of rat mammary tumors by a potent luteinizing hormone-releasing hormone analogue (leuprolide) administered vaginally.

Potent luteinizing hormone-releasing hormone analogues are known to cause regression of hormone-dependent mammary tumors. We have observed that high and long-lasting serum levels of a potent luteinizing hormone-releasing hormone analogue [desglycyl10-(D-leucyl6) luteinizing hormone-releasing hormone ethylamide, leuprolide] resulted from vaginal administration which effectively caused down regulation in the pituitary by chronic treatment. Regression of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in Sprague-Dawley rats by consecutive daily vaginal administration of leuprolide was investigated. In untreated rats, 71% of tumors were growing at 8 weeks, whereas after i.p. injection of leuprolide (500 micrograms/kg) all tumors were regressing 2 weeks after commencement of treatment and 86.7% of tumors disappeared by 8 weeks. Vaginal administration of 100 micrograms/kg for 8 weeks produced regression in 80% of tumors and disappearance in 35%. The vaginal administration of a higher dose (500 to 5000 micrograms/kg) produced highly significant antitumor effects [regression in 82.2 +/- 4.0% (S.E.) and disappearance in 52.9 +/- 2.1%]. These results are consistent with the effects produced by ovariectomy. Whereas 13 and 7 new tumors appeared in untreated rats and those treated vaginally with leuprolide (100 micrograms/kg), respectively, only one or two tumors appeared in i.p. and vaginally (above 500 micrograms/kg) treated rats during treatment. Histological classification of the mammary tumors after treatment indicated therapeutic effects similar to those shown by tumor size determination. Thus, it was concluded that vaginal application of leuprolide at doses above 500 micrograms/kg might be a potentially useful method for antitumor therapy.

Animals↗

[Evaluation of cefotetan in obstetrics and gynecology].

Fundamental and clinical studies on gynecological use of cefotetan (CTT), a new cephamycin antibiotic, were performed with following results. Following the intravenous administration of 2.0 g of CTT, T 1/2 beta in serum was 3.1 hours and longer than the previous cephamycin antibiotics. The yields of CTT from serum to various uterine tissues and discharge from retroperitoneum were about 30 approximately 50%. In clinical use, 14 patients with gynecological infections were administrated CTT, and it showed excellent or good efficacy in all patients. No side effects were noted except 1 transient disturbance in liver function.

Adult↗

[Fundamental and clinical studies on T-1982 (cefbuperazone) in the field of obstetrics and gynecology].

Fundamental and clinical studies were carried out on T-1982 (cefbuperazone) a new cephamycin antibiotic, with the following result. Following a single intravenous administration of 1.0 g of T-1982, the transfer of T-1982 to the internal genital organs was found to be good. The transfer of T-1982 to retroperitoneal fluid was also good. In clinical trial, T-1982 was administered to 10 patients with obstetrical and gynecological infection. Efficacy was excellent in 4 cases and good in 6 cases. No side effects were observed. In laboratory findings, a transient elevation of alkaline phosphatase was noted in 1 case.

Adult↗

[Experimental and clinical studies on latamoxef during the perinatal period].

Fundamental and clinical studies on the perinatal use of latamoxef (LMOX) were performed, with the following results. Concentration of LMOX was examined in maternal serum, umbilical cord serum and amniotic fluid after intravenous administration of 2 g dose. Data were analyzed by the simulation curves using the two-compartment model. The peak level of LMOX in maternal serum was 218.4 micrograms/ml and half-life of the beta-phase was 1.9 hours. The peak levels of LMOX in umbilical cord serum and amniotic fluid were 37.4 micrograms/ml (1.4 hours) and 27.5 micrograms/ml (8.9 hours) after administration. The concentration of LMOX in amniotic fluid decreased in amount after the peak, but it still remained 21.9 micrograms/ml (16 hours) after administration. Above these results, it was concluded that the transfer of LMOX to umbilical cord serum and to amniotic fluid was sufficient. In clinical use, LMOX was administered to 30 pregnant patients with premature rupture of membrane. It showed excellent efficacy in preventing perinatal infection. Seven patients with perinatal infections were treated with LMOX and all of them had excellent efficacy. No side effects were observed in any of the cases studied.

Adult↗

Nuclear translocation of progesterone receptor--progestogen complex in vitro.

The nuclear translocation of receptor-progestogen complex was investigated in the estrogen-primed rabbit uterus. To avoid the influence of the in vivo steroid metabolism, the incubation of cytosol with progestogens, and that of the nuclear suspension with steroid-cytosol complex were performed in the in vitro systems. The quantity of the steroid receptor translocated by progestogens to the nucleus was measured using the [3H]-progesterone exchange assay. [3H]-progesterone-receptor complex in the cytosol was exchanged for cytosolic receptor sites by progesterone, dydrogesterone or norethindrone effectively. When the steroid receptors translocated to the nucleus by such steroids in the in vitro system were determined using exchange assay, progesterone translocated the receptor to the nucleus much more than did dydrogesterone or norethindrone. It was suggested that progesterone was potent in the ability of the nuclear translocation of its own receptor. The highly potent biological activities of norethindrone and dydrogesterone in vivo must be explained in the other way.

Animals↗

[Meningioma with extracranial multiple metastases--a case report].

A case of meningioma with extracranial multiple metastases is reported in this paper. The patient was a 21 years old woman. The removal of the convexity meningioma and the surrounding intracerebral hematoma in the left occipital region was performed. The histological diagnosis of the tumor was malignant fibroblastic meningioma. The patient was given radiotherapy, 6000 rads in the whole brain. Two years later, the recurrence occurred. The metastasis appeared to the lung and six months later to the liver. There occurred an intraperitoneal bleeding from multiple liver metastases and the patient died in November, 1980. The mode and site of the metastases have been discussed with a review of the literature.

Adult↗