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H Okada

Publications and source records attributed to H Okada.

At least 1,153 records · Page 64Linked to original sources

Membrane sialoglycolipids regulate the activation of alternative complement pathway by liposomes containing trinitrophenylaminocaproyldipalmitoylphosphatidylethaolamine.

We found that liposomes associated with trinitrophenylaminocaproyldipalmitoylphosphatidylethanolamine (TNP-Cap-DDPE) activate the alternative complement pathway (ACP) of guinea-pig. The complement-activating capacity (CAC) of liposomes with TNP-Cap-DPPE (TNP-Cap-liposomes) was found to be inhibited by the insertion of sialoglycolipids such as GM3 onto the membrane. However, neutral glycolipids tested had no inhibitory effect on the CAC of the TNP-Cap-liposomes. The minimum amount of sialoglycolipids required for the inhibition of the ACP-activating capacity of TNP-Cap-liposomes was 0.01 or less in molar ratio to dimyristoylphosphatidylcholine in the liposomes. Since the insertion of charged amphiphiles did not affect the status of TNP-Cap-liposomes containing glycolipids with respect to their ACP-activating capacity, the surface potential caused by sialoglycolipids was disregarded as being the factor responsible for restriction of the complement-activating effect. For the inhibitory effect to be manifested, it was demonstrated that the presence of GM3 was required on the same liposome membrane as where the TNP-Cap-triggered ACP activation is taking place. Therefore, sialoglycolipids may inhibit ACP activation by reacting directly on certain nascently activated complement proteins. However, insertion of GM3 could not inhibit liposome lysis via the classical complement pathway. Furthermore, the presence of antibody reaction significantly reduced the inhibitory capacity of GM3 indicating that natural antibody may be responsible for discriminating between self and heterologous surfaces, thus cancelling the glycolipid-mediated restriction of ACP activation in the case of heterologous cell surface, bringing about lysis by the cancellation of the glycolipid-mediated restriction of ACP activation on heterologous cell surfaces.

Animals↗

Vaginal absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) in rats I: absorption by various routes and absorption enhancement.

The absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) through different routes was evaluated by determining the ovulation-inducing activity in diestrous rats. Vaginal administration showed the greatest potency among nonparenteral routes and was followed successively by rectal, nasal, and oral administration. Mixed micellar solution with monoolein-bile acids improved the intestinal absorption of leuprolide, and nasal absorption was enhanced by adding sodium glycocholate, surfactin, or polyoxyethylene 9 lauryl ether, but these bioavailabilities were still insufficient. The vaginal absorption was enhanced by organic acids: citric, succinic, tartaric, and glycocholic; the absolute bioavailability increased to approximately 20%. The vaginal absorption from jellies, as practical dosage forms, yielded sufficient activity of leuprolide, but absorption was slightly reduced with highly polar polymers or with higher concentrations of polymers. It was concluded that vaginal administration of leuprolide can be a rational dosage method for a long-term antitumor therapy.

Absorption↗

Immunological activities of Capnocytophaga cellular components.

Whole cells of a clinical isolate (strain S-3) of the genus Capnocytophaga were divided into cell envelope (CE) and cytoplasm (CP) fractions by mechanical disintegration followed by differential centrifugation, and a part of the CE fraction was further fractionated by sodium dodecyl sulfate (SDS) treatment into the peptidoglycan and SDS-supernatant fractions. The other part of the CE was extracted with butanol-water or hot phenol-water to isolate butanol-lipopolysaccharide and phenol-lipopolysaccharide, respectively. All of the test fractions except CP exhibited multifold immunomodulating activities, namely, the adjuvant activities to cellular as well as humoral immune responses against ovalbumin in guinea pigs, the mitogenicity on splenocytes of guinea pigs and BALB/c mice (but not on their thymocytes), the stimulation of guinea pig peritoneal macrophages (in terms of increased glucosamine uptake), and the activation of the human complement system through alternative as well as classical pathways. In addition, the test fractions other than the CP evoked dermatoxic reactions on rabbit skin with characteristic variations among them. The immunomodulating activities of SDS-supernatant were noteworthy in view of the fact that this fraction was essentially free of muramic acid and diaminopimelic acid and did not cause the gelation of horseshoe crab amoebocyte lysate except when it was used at the very high dose, suggesting that there was practically no contamination by peptidoglycans and lipopolysaccharides in the SDS-supernatant.

Adolescent↗

Detection of rotavirus antibody by inhibition of reverse passive hemagglutination.

A reverse passive hemagglutination inhibition (RPHI) test was developed for detecting rotavirus antibody in patients' sera. Sheep erythrocytes coated with guinea pig antibody against Nebraska calf diarrhea virus (NCDV) were readily hemagglutinated by NCDV in a reaction called reverse passive hemagglutination (RPHA). Inhibition of this RPHA reaction was used to detect the presence of rotavirus antibody in patients' sera which cross-reacted with NCDV. The sensitivity of RPHI was consistently at least 10 times greater than that of the complement fixation test for detection of rotavirus antibody in patients' sera. Since immunoglobulin M (IgM) antibody activity detected by RPHI was destroyed by pretreatment of serum with dithiothreitol (DDT), whereas DTT-resistant antibodies such as IgG remained unchanged, the titer of IgM antibody could be distinguished from that of DTT-resistant antibody by comparing the results of two RPHI tests performed with and without DTT pretreatment. From the IgM antibody response pattern, primary and secondary rotavirus infections could be distinguished.

Adolescent↗

Activation of the alternative complement pathway of guinea-gip by liposomes incorporated with trinitrophenylated phosphatidylethanolamine.

By incorporation of trinitrophenylamino-caproyldipalmitoylphosphatidylethanolamine (TNP-Cap-DPPE) into liposomes composed of an equimolecular mixture of dimyristoylphosphatidylcholine (DMPC) and cholesterol (TNP-Cap-liposomes), liposomes became readily lysed by guinea-pig serum (GPS) in Mg++-EGTA-GVB (gelatin veronal buffered saline containing 2 mM MgCl2 and 10 mM ethyleneglycol-bis (beta-amino-ethyl ether)N-N'-tetraacetate) as well as in GVB++ (gelatin veronal buffered saline containing 0.15 mM CaCl2 and 0.5 mM MgCl2). Since the classical complement pathway (CCP) does not work in Mg++-EGTA-GVB, TNP-Cap-liposome lysis by GPS in Mg++-EGTA-GVB was thought to be mediated by the activation of the alternative complement pathway (ACP). This conclusion was supported by observations that heating of GPS at 50 degrees impaired its lytic activity while C4-deficient GPS was capable of lytic activity, no lysis occurred in EDTA, and there was noted consumption of complement in GPS treated with TNP-Cap-liposomes at 30 degrees. For TNP-Cap-liposome lysis by GPS in Mg++-EGTA-GVB, the epitope density of the TNP hapten was required to be 5% or more of the DMPC. Changing the acyl group of the phosphatidylcholine (PC) significantly influenced the ACP activating capacity of TNP-Cap-liposome. Dipalmitoyl-PC, DMPC and distearoyl-PC facilitated the ACP activating capacity of the TNP-Cap-liposome, while dilauroyl-PC, egg-PC and dioleoyl-PC did not. Furthermore, the length of spacer between TNP and dipalmitoylphosphatidylethanolamine (DPPE) also influenced the ACP activating capacity and maximum activation was noted when the spacer was aminocaproyl. These physicochemical characteristics which increase the ACP activating capacity coincided with those reported to increase the immunogenicity of hapten-sensitized liposomes.

Animals↗

[Fundamental and clinical studies on piperacillin in the field of obstetrics and gynecology].

We conducted a study on the utility in the obstetric and gynecological field of piperacillin (PIPC) which is a broad spectrum penicillin developed here in Japan. After administration of PIPC by intravenous one shot injection or intravenous dripping infusion the yield of PIPC to the various uterine tissues was a favorable 30 approximately 40% in comparison with the serum concentration and the discharge from retroperitoneum was about 100% to 300% in 4 hours. Thus it is thought to be useful in the treatment of infections of the retroperitoneum. During a clinical trial PIPC was administered to 16 patients with obstetrical and gynecological infections and it proved to be excellent in 4 patients, good in 10 patients and ineffective in 2 patients. Thus an overall efficacy rate of 87.5% was obtained. The only side effects observed was a slight transitory abnormality of liver function in 2 patients. Thus in the overall evaluation, this drug was considered to be useful in the treatment of infections in the obstetric and gynecological field.

Adult↗

[Experimental and clinical studies of cefmenoxime in the field of obstetrics and gynecology].

The study group was organized to evaluate the usefulness of cefmenoxime (CMX) injection, a new synthetic cephalosporin, for the treatment of infections in the field of obstetrics and gynecology. Fundamental and clinical studies were made by the society and the following results were obtained. 1. The peak distribution of CMX's MIC for E. coli, Klebsiella sp., Enterobacter sp., Bacteroides sp. and Peptococcus sp. isolated from obstetrical and gynecological infections with relatively high frequencies area 0.1, less than or equal to 0.05, 0.2, 3.13, 1.56 micrograms/ml, respectively, with an inoculation of 10(6) cells/ml. 2. When 1 g of CMX is administered by intravenous drip infusion for 1 hour, the maximum concentrations in various tissues of female genital organs were as follows: 14.2 and 13.2 micrograms/g in ovary and oviduct, respectively, at 1.20 hours after the start of administration, and 16.9 and 26.3 micrograms/g in corpus uteri and cervix uteri, respectively, after 1 hour. As for the transfer to the exudate in the pelvic dead cavity, the peak concentration was 15.6 micrograms/ml after 2.13 hours. 3. In the clinical studies, CMX was given to 258 cases with female genital organ infections and others. As for the clinical effects, with exclusion of 3 cases in which other antibiotics are concomitantly used, responses were excellent in 76 cases, good in 162 cases and poor in 17 cases, among 255 cases in total. The efficacy rate was 93.3%. The efficacy rates by diseases were 97.1% (68/70) for intrauterine infections, 88.8% (79/89) for intrapelvic infections, 98.4% (62/63) for adnexitis, and 100% (23/23) for infections of external genital organs. As for the clinical effects on causative bacteria, the efficacy rates were 100% (19/19) for single infections due to Gram-positive bacteria, 94.8% (55/58) for single infections due to Gram-negative bacteria, and 88.2% (15/17) for single infections due to anaerobic bacteria. And its efficacy rates were 89.6% (69/77) for mixed infection cases. Side effects were observed in 2 cases (0.8%); 1 case with eruption, and 1 case with diarrhea and vomiting. As for abnormal laboratory findings, lower white blood cell count was observed in 2 cases and elevation of the values regarding hepatic functions in 9 cases. All cases were returned to the normal after the completion of the administration. Cefmenoxime showed a satisfactory clinical efficacy and a potent bacteriological effect in treatment of the infections in the field of obstetrics and gynecology, and it has been concluded that cefmenoxime will be useful addition to the antibiotics for the therapy of these infections.

Adolescent↗

[Fundamental and clinical studies on cefotaxime in the perinatal period].

Fundamental and clinical studies on the perinatal use of cefotaxime (CTX, HR-756), a new cephalosporin antibiotic, were done, with the following results. 1. Following intravenous administration of 2 g of CTX, transport of CTX from maternal serum to umbilical cord serum and to amniotic fluid was found to be good. CTX was not transferred into mother's milk. 2. In clinical use, CTX was given to 16 pregnant patients with premature rupture of the membrane. It showed excellent efficacy in preventing perinatal infection. Five patients with perinatal infections were administered CTX, and in 4 patients CTX had good efficacy. No side effects were noted in any cases.

Amniotic Fluid↗

[Effect of prostacyclin on cerebral vasospasm--an experimental study].

Prostacyclin(PGI2), a strong vasodilator of cerebral vessels and a potent inhibitor of platelet aggregation, was infused intravenously in 7 cats after induction of prolonged vasospasm by hourly application of oxyhemoglobin solution into the subarachnoid space around the basilar artery. PGI2, at a concentration of 50 ng/kg/min, was effective in releasing the vasospasm in the 7 cats. On the other hand, PGI2 did not produce significant hypotension. This report will discuss our results and the probable mechanism of action of PGI2 in cerebral vasospasm.

Animals↗