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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 811 records · Page 45Linked to original sources
PubMed1990

Estrone sulfatase activity in human uterine leiomyoma.

Human uterine leiomyoma is a benign tumor and its development is closely related to estrogen. In this study, estrone sulfatase (E1SF) activity and concentrations of estrone (E1) and estrone sulfate (E1S) were measured in endometrial, leiomyoma, and myometrial tissues of the same human uterus (n = 11) with a leiomyoma. E1SF activity in endometrial tissue overlying a leiomyoma was 2.62 +/- 0.29 nmole/hr/mg protein (mean +/- SD), this activity being significantly higher (P less than 0.01) compared with that in normal endometrial tissue (2.0 +/- 0.24 nmole/hr/mg protein). E1SF activity in normal endometrial tissue was significantly higher (P less than 0.001) compared with that in leiomyoma tissue (0.49 +/- 0.82 nmole/hr/mg protein) or myometrial tissue (0.76 +/- 0.10 nmole/hr/mg protein). We also found a significant difference (P less than 0.05) in E1SF activity between leiomyoma tissue and myometrial tissue. On the other hand, the E1 concentration in endometrial tissue overlying a leiomyoma (10.9 +/- 8.9 pg/mg protein) proved to be higher than that in endometrial tissue overlying normal myometrium (1.23 +/- 1.97 pg/mg protein). E1S concentrations in these tissues, however, were 631 +/- 339 and 902 +/- 482 pg/mg protein, respectively, these values showing a trend opposite that of the E1 concentration data. Thus, these results suggest that high E1SF activity and high E1 concentration in the endometrium overlying a leiomyoma may be related to estrogen supply to a uterine leiomyoma node.

Endometrium↗
PubMed1990

Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency.

A series of 5,7-disubstituted 1-cyclopropyl-6,8-difluoro-4(1H)-oxoquinoline-3-carboxylic acids (10-36) were prepared; the C-5 substituent in these compounds comprised halo, hydroxy, mercapto, and amino groups and the C-7 functional group included variously substituted piperazines. In vitro antibacterial screening results indicated that the amino group was optimal among the C-5 substituents. A combination of the C-5 amino group and the C-7 3,5-dimethylpiperazinyl appendage in this series conferred the best overall antibacterial property with lack of adverse drug interactions. Compound 36k [named sparfloxacin, originally AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-7-(cis-3,5-dimethyl-1-piperazinyl)- 4(1H)-oxoquinoline-3-carboxylic acid] was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent.

4-Quinolones↗
PubMed1990

Characterization of homologous restriction factor (HRF20) in human skin and leucocytes.

Homologous restriction factor with a molecular weight of 20 kD (HRF20) is a membrane protein that inhibits assembly of the membrane attack complex of homologous complement. Distribution of HRF20 in normal human skin was studied. The plasma membrane of keratinocytes was stained, and the intensity of the staining pattern was higher in the basal cell layer than in the granular layer. Endothelial cells of blood vessels in the dermis were also stained. The molecular weight of HRF20 on erythrocytes and epidermis is 16 kD, determined by Western blot analysis. Those of polymorphonuclear cells and lymphocytes appeared as two bands, a major band of 20 kD and a minor band of 16 kD. Susceptibility of HRF20 to phosphatidylinositol-specific phospholipase C (PIPLC) was examined. After PIPLC treatment of the sections, HRF20 was not detected on the epidermis and was very slightly expressed on the blood vessels. These results indicate that HRF20 attaches to keratinocytes and blood vessels via phosphatidylinositol, regulating the formation of membrane attack complexes of homologous complement on the cell membrane.

Blood Proteins↗
PubMed1990

Erythrocytes of patients with paroxysmal nocturnal haemoglobinuria acquire resistance to complement attack by purified 20-kD homologous restriction factor.

A 20-kD homologous restriction factor (HRF20) which is a membrane inhibitor of the terminal stage of human complement action can be detected by the monoclonal antibody 1F5, and is deficient on abnormal erythrocytes as well as leucocytes from patients with paroxysmal nocturnal haemoglobinuria (PNH). The erythrocytes of PNH patients significantly improved their resistance to homologous complement after adsorption of purified HRF20.

CD59 Antigens↗
PubMed1990

Effect of infection with Eikenella corrodens on the progression of ligature-induced periodontitis in rats.

The periodontopathic ability of Eikenella corrodens 1073-R (EcR) on ligature-induced periodontal defects in immunosuppressed and non-immunosuppressed rats was studied bacteriologically and histologically. Silk ligatures were placed around the maxillary second molars of rats, and the rats were divided into eight groups. Four groups received cyclophosphamide (CY), an immunosuppressive agent, the day after ligature placement. On days 3 and 4, the oral cavities of the rats in all four groups were inoculated with 8 x 10(8) cells of live EcR. Rats were sacrificed on d 1, 3, 5, 8, 11 and 18. Alveolar bone resorption of ligated rats was enhanced by the implantation of EcR, although the number of total cultivable bacterial cells from ligated sites was not changed by the implantation of EcR. CY suppressed the number of white blood cells, inflammatory cellular infiltrates in gingival tissue, and repair of periodontal tissue, and enhanced bone destruction. The implantation of EcR in the ligature- and CY-treated rats also enhanced osteoclastic bone resorption. Without ligatures, high doses of CY or EcR inoculum did not result in periodontal destruction. These results indicate that it is possible to establish EcR in conventional rat flora with a ligature and that EcR causes osteoclastic bone resorption in this model.

Alveolar Bone Loss↗
PubMed1990

Local ofloxacin delivery using a controlled-release insert (PT-01) in the human periodontal pocket.

PT-01, a controlled-release insert, was developed for topical chemotherapy in periodontal disease. It is a soluble insert that consists of fast-release and sustained-release parts containing ofloxacin (OFLX) as an antibacterial agent. In this study, the release profile of OFLX from PT-01 was investigated in vitro. Twelve adult volunteers were administered OFLX as PT-01 or as an aqueous solution into their periodontal pockets, OFLX concentrations in gingival crevicular fluid (GCF) were evaluated from the viewpoint of pharmacokinetics. The in vitro release profile of OFLX from PT-01 showed a biphasic pattern. The release rate of OFLX was relatively rapid in the early phase and slow thereafter. When OFLX aqueous solution was administered into periodontal pockets, the OFLX level in GCF rapidly decreased to be about 1/100 after 30 minutes. When PT-01 was inserted into the pockets, the OFLX level in GCF immediately reached a peak (about 12 mg/ml), and gradually decreased until the 3rd day, and maintained a constant level above 2 micrograms/ml, the effective minimum antibacterial concentration for periodontopathic microorganisms, from the 3rd to 7th day after insertion. No side-effects were observed in the volunteers who received the PT-01 insert. The above results suggest that PT-01 is a suitable pharmaceutical preparation for periodontal chemotherapy.

Adult↗
PubMed1990

Medroxyprogesterone acetate binding sites in human endometrium and endometrial cancer.

Medroxyprogesterone acetate (MPA) binding sites in both human normal endometrium and endometrial carcinoma were identified and characterized by sucrose gradient centrifugation. These binding components were divided into two classes by saturation analysis, one with high affinity and low capacity and the other with low affinity and high capacity. The concentrations of low-affinity binding sites for MPA in endometrial carcinoma were higher than those in normal endometrium (p less than 0.01). By sucrose gradient centrifugation, 4S and 8S components were observed in both high- and low-affinity binding sites of normal endometrium. These components were moved to 4S by the addition of salt. However, in endometrial carcinoma, low-affinity binding sites were displayed at about 4S under either low- or high-salt conditions. High-affinity binding sites in endometrial carcinoma had the same sedimentation patterns as in normal endometrium. An obvious difference between normal endometrium and endometrial cancer was observed in low-affinity binding sites. Our results on the binding sites for MPA suggest that low-affinity binding sites may be related to the response of endometrial cancer to high-dose MPA treatment.

Binding Sites↗
PubMed1990

Synthesis of 7-thio-substituted 4-oxoquinoline-3-carboxylic acids with antibacterial activity.

A series of C-7 thio-substituted 1-cyclopropyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared and tested for their antibacterial activity. Structure-activity relationships associated with the C-5 and C-7 substituents were discussed. Among the C-7 substituents including alkylthio, arylthio, heteroarylthio, and cyclic aminothio groups, a 2-aminoethylthio group was the best for enhancing in vitro antibacterial activity. The C-5 variants increased activity in the order OH less than F less than H less than NH2. Of compounds prepared in this work, 5-amino-7-(2-aminoethyl)thio-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4 -oxo-quinoline-3-carboxylic acid (18) was the most active.

4-Quinolones↗
PubMed1990

An improved chemiluminescence-based liposome immunoassay involving apoenzyme.

An improved liposome immunoassay system (LIS) combining the chemiluminescence-based LIS with an apoenzyme reactivation immunoassay system (ARIS) was developed. A low-molecular-weight co-factor, FAD (flavin adenine dinucleotide), was incorporated into liposomes instead of the high-molecular-weight enzyme GOD (glucose oxidase). FAD released from liposomes by cytolysin-hapten conjugates bound to Apo-GOD and regenerated GOD. The system allowed detection of 10 pM digoxin, the model analyte and was linear over 10 pM to 13 nM digoxin. This sensitivity was about 300 times higher than that of the homogeneous system using GOD-containing liposomes and 30 times higher than that of the heterogeneous system which we reported previously. The time required for incubation during the detection of digoxin was reduced from 20 to 3 h.

Apoenzymes↗
PubMed1990

Selective aromatase inhibition by pyridoglutethimide, an analogue of aminoglutethimide.

The inhibitory effects of pyridoglutethimide (3-ethyl-3-(4-pyridyl)piperidine-2,6-dione), an analogue of aminoglutethimide, on aromatase and other cytochrome P-450-dependent steroid-metabolizing enzymes were studied in vitro. Pyridoglutethimide and aminoglutethimide showed competitive inhibition of human placental aromatase activity with apparent Ki values of 1.7 and 0.7 mumol/l, respectively. Both pyridoglutethimide and aminoglutethimide inhibited the aromatase activity of uterine leiomyoma and cultured choriocarcinoma Enami cells as well as immunopurified human placental aromatase cytochrome P-450 by more than 90%, with IC50 values of 10-19 and 5-7 mumol/l, respectively. These results might suggest that the inhibitors interacted directly with the aromatase cytochrome P-450 of these tissues. Aminoglutethimide inhibited bovine adrenal cholesterol side-chain cleavage activity with an IC50 value of 40 mumol/l and inhibited 21-hydroxylase activity slightly, but did not inhibit 17 alpha-, 11 beta- and 18-hydroxylase at concentrations up to 100 mumol/l. On the other hand, pyridoglutethimide had no inhibitory effect on any of these enzymes at concentrations up to 50 mumol/l, although it inhibited 11 beta- and 18-hydroxylase slightly at 100 mumol/l. These results indicated that pyridoglutethimide was an aromatase inhibitor of a comparable potency to aminoglutethimide, but that it did not inhibit other steroid hydroxylases.

Aminoglutethimide↗
PubMed1990

Granular cell tumor of the tongue: an electron microscopical and immunohistochemical study.

Granular cell tumor of the tongue in a 29-year-old woman is reported including details of studies using electron microscopy and immunohistochemistry. Immunohistochemically, the tumor cells showed moderate positivity for S-100 protein. Electron microscopically, basal lamina, angulate bodies, myelin-like figures and axon-like structures were observed in the tumor. These findings may indicate that this tumor is a lesion of Schwann cell origin. The Japanese literature on oral granular cell tumor is also reviewed and discussed.

Adult↗
PubMed1990

[Clinical experience with three cases of haemorrhagic tendency--bladder carcinoma with hemophilia A, a bladder carcinoma with von Willebrand disease and a benign prostatic hypertrophy with idiopathic thrombocytopenic purpura (ITP)].

Recent understanding of the pathogenicity of haemorrhagic tendency as well as advance of management of patients with this disease makes its surgical treatment possible. Since 1979 we have experienced three male patients with haemorrhagic tendency. The first case was a bladder carcinoma with hemophilia A. He had been given 2500 unit of Conco-eight (coagulation factor VIII) before transurethral resection of bladder tumor (TUR-Bt) and was given 1000 unit of Conco-eight every eight to twelve hours for seven days postoperatively. The second case was a bladder carcinoma with von Willebrand disease. This case was also pretreated by Conco-eight before operation and we had difficulty in controlling his coagulopathy for one month postoperatively. The third case was a benign prostatic hypertrophy with idiopathic thrombocytopenic purpura (ITP). He had been given a huge dose of gamma globulin for six days before operation and on the operation day his platelet count was normalized. Since his prostate was estimated to weight over 70 g, suprapubic prostatectomy was selected. All these three cases were operated uneventfully. From this experience we believe that with proper preoperative and postoperative management, patients with haemorrhagic tendency can be operated safely.

Adult↗
PubMed1990

Expression of HRF20, a regulatory molecule of complement activation, on peripheral blood mononuclear cells.

HRF20 is a homologous restriction factor of 20,000 MW that prevents cells from membrane attack by homologous complement. HRF20 has been identified by a monoclonal antibody (mAb), 1F5, and is one of the phosphatidylinositol(PI)-anchored cell-surface glycoproteins. We analysed the distribution of HRF20 expressed on subsets of peripheral blood lymphocytes using 1F5. HRF20 is expressed in relatively large amounts on T cells. In contrast, adherent cells possess smaller amounts of HRF20 while having large quantities of decay-accelerating factor (DAF). Although DAF was shown to be deficient or present at rather low levels on NK cells, HRF20 was detected in 95% of large granular lymphocytes (LGL), as described by FACS analysis. We also determined the effect of 1F5 on both mononuclear leucocytes and T cells in terms of their growth response. The results show that 1F5 induces T-cell proliferation when cells are stimulated with interleukin-2 (IL-2). In addition, induction of proliferation is facilitated by cross-linking 1F5 with a second antibody. These results suggest that HRF20 expressed on T cells not only protects them from cytotoxic attack by homologous complement, but also may initiate intracellular signals leading to cell activation when they happen to be cross-linked.

Antibodies, Monoclonal↗
PubMed1990

Tissue distribution of HRF20, a novel factor preventing the membrane attack of homologous complement, and its predominant expression on endothelial cells in vivo.

A 20,000 molecular weight (MW) homologous restriction factor (HRF20), detected by 1F5 monoclonal antibody (mAb), is present on blood cell surfaces and inhibits the terminal stage of the formation of membrane attack complexes by homologous complement activation. The tissue distribution of HRF20 was studied by immunohistochemical analysis using 1F5. HRF20 was predominantly expressed on endothelial cells of systemic arteries, veins and capillaries, as well as on the surface of cultured human umbilical vein endothelial cells. HRF20 was also detected, to a lesser extent, on the Schwann sheath of peripheral nerve fibres, ependymal cells and certain epithelial cells such as acinar cells of the salivary gland, bronchial epithelium, renal tubules and squamous epithelium. The distribution pattern of HRF20 differed somewhat from that of decay-accelerating factor (DAF), which is another membrane inhibitor of homologous complement activation.

Antibodies, Monoclonal↗
PubMed1990

Expression of decay-accelerating factor on hematopoietic progenitors and their progeny cells grown in cultures with fractionated bone marrow cells from normal individuals and patients with paroxysmal nocturnal hemoglobinuria.

Decay-accelerating factor (DAF), a complement-regulating glycoprotein, has been shown to be expressed on hematopoietic progenitors and their progeny cells in normal individuals but not on abnormal cells in patients with paroxysmal nocturnal hemoglobinuria (PNH). Fluorescence histograms of bone marrow cells showed the heterogeneity of DAF expression on their cell membranes, suggesting mixed hematopoietic cell populations in PNH. We have previously shown that DAF is a maturational protein expressed on normal hematopoietic cells. In order to elucidate the relationship between DAF expression and cell maturity in PNH, we fractionated bone marrow cells according to amount of DAF and cultured these cells in methylcellulose for clonal assay of erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM), followed by reanalysis of DAF expression on their progeny. The matured cells from the bursts/colonies in cultures with DAF-negative PNH marrow cells had no or little DAF, but those grown from DAF-positive PNH progenitors showed nearly as much of this factor as those grown from normal progenitors. These results clearly indicate that there are at least two distinct populations of hematopoietic progenitors with respect to the membrane expression of DAF and that abnormalities occur at the level of the stem cell in PNH.

Bone Marrow↗
PubMed1990

[Optimal calcium concentration for the proliferation of oral mucosal epithelial cells from adult rabbit in vitro].

We studied a primary culture of oral epithelial cells from adult rabbit and reported about dose-dependent growth by Ca increase. Therefore, in the present study we examined the relationship between total Ca, or Ca ion concentration and the proliferation of oral epithelial cells. The results were as followings. 1. The optimal Ca concentration for the growth in primary culture of oral epithelial cells was affected by the serum concentration in the medium. But Ca ion concentration for the best growth was in 10-30 micrograms/ml (0.25-0.74 mM) regardless of the serum concentration. 2. The optimal Ca ion concentration was shifted to 3-20 micrograms/ml (0.075-0.5 mM) in the medium containing chelated serum. This fact, suggests that the chelated serum may play different action from whole serum. 3. The optimal Ca ion concentration in the present study was higher density region than Hennings's view (0.04-0.1 mM) and it was lower than that of Tong (1.4-2.8 mM). Our data coincided with that of Wille (0.18-0.36 mM) who used MCDB 153 medium.

Animals↗