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Biomedical subjects

Y Osada

Publications and source records attributed to Y Osada.

At least 127 records · Page 7Linked to original sources
PubMed1990

Synthesis and antitumor activity of lipid A analogs having a phosphonooxyethyl group with alpha- or beta-configuration at position 1.

Three novel lipid A analogs, which have an alpha- or beta-glycosidically bound phosphonooxyethyl group instead of the alpha-glycosyl phosphate group of natural lipid A, were synthesized. The first analog (2) had an alpha-phosphonooxyethyl group on the identical acylated disaccharide 4'-phosphate structure found in natural lipid A (from Escherichia coli) and hence differed from the latter only in the nature of the acidic group at position 1. The second one (3) had tetradecanoyl groups in place of the two (R)-3-hydroxytetradecanoyl groups bound to the 2- and 3-hydroxyl function of 2, retaining the alpha-phosphonooxyethyl group. The structure of the third analog (4) was the same as that of 3 except that the phosphonooxyethyl group of the former was beta-oriented. Compounds 2 and 3 exhibited potent activity against Meth A at the same level as natural lipid A, whereas 4 showed less activity. This fact revealed that the glycosidic phosphate is not a prerequisite for the antitumor activity of lipopolysaccharide. It can be replaced with a phosphonooxyethyl group without any loss of activity provided that the alpha-anomeric configuration at C-1 is retained. The replacement of the hydroxytetradecanoyl groups with tetradecanoyl groups does not change the activity either.

Animals↗
PubMed1990

Stimulation of macrophages by muroctasin to produce colony-stimulating factors.

Murocatasin (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18], a muramyl dipeptide derivative, has been reported to increase the number of peripheral granulocytes and monocytes after subcutaneous administration to animals and humans. When macrophage cell lines such as P388D1 and J774.1 cells were incubated with muroctasin in vitro, the production of colony-stimulating factor (CSF) from these cells was increased significantly. By Northern blot analysis, expression of the M-CSF gene, but not the G-CSF gene, in these macrophage cell lines was found to be enhanced by treatment with muroctasin. However, expression of the G-CSF gene in NFSA cells, a fibrosarcoma cell line established as a G-CSF producer, was actually enhanced by incubation with the conditioned medium from P388D1 cells stimulated with muroctasin. Thus, the hematopoietic activity of muroctasin was suggested to be attributable primarily to the enhanced production of M-CSF from macrophages. The enhanced G-CSF production from NFSA cells may be due at least to interleukin-1 released from muroctasin-stimulated macrophages.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Inhibitory effects of DN-9693 on platelet-enhanced tumor cell attachment to cultured endothelium.

The effects of DN-9693, a platelet aggregation inhibitor, on tumor cell attachment to endothelium were investigated to clarify its inhibitory action on metastasis. The role of platelets in the attachment of murine metastasizing tumor cells to endothelium was first examined in vitro. Morphological studies and quantitative isotope measurements revealed that tumor-cell-activated platelets significantly enhanced tumor cell attachment to the endothelium. This amplification is considered to depend on morphological and functional changes of endothelial cells: activated platelets may accelerate endothelial retraction, exposing more reactive subendothelium, and may increase the adhesiveness of endothelial cells. The platelet-enhanced tumor cell attachment to the endothelium was inhibited in the presence of DN-9693. The pretreatment of endothelial cells with the compound was also effective in inhibiting cell attachment. These data suggest that the inhibitory effects of DN-9693 on metastasis are in part mediated by the prevention of tumor cell attachment to the vascular endothelium.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Elevation by muroctasin of the serum level of the complement subcomponent C1q in mice and of its biosynthesis by cultured mouse peritoneal macrophages.

Augmentative effects of muroctasin (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, (MDP-Lys(L18] on the production of a subcomponent of the first complement component, C1q, in mice were examined. The serum level of C1q in mice treated subcutaneously with muroctasin was found to be elevated significantly at 24 h (p less than 0.1) and 48 h (p less than 0.01). At 24 h, samples of peritoneal macrophages were derived from mice, and incubated with Dulbecco's Modified Eagle Medium (MEM) at 37 degrees C for 24 h. At 19 h of incubation, the C1q concentration in the supernatant of the culture also increased significantly (p less than 0.05). Moreover, when the peritoneal macrophages from non-treated mice were cultured in MEM containing muroctasin (0.001 microgram/ml), the amount of C1q in the culture supernatants also increased significantly 3 h (p less than 0.01) after cultivation. These results indicate that muroctasin activated C1q generation by macrophages in mice through direct and/or indirect mechanisms.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Antitumor effects of an antiangiogenic polysaccharide from an Arthrobacter species with or without a steroid.

A sulfated polysaccharide-peptidoglycan complex, DS-4152, isolated from the culture supernatant of an Arthrobacter species inhibited angiogenesis and tumor growth and enhanced the antiangiogenic activity of 11 steroid hormones by 2 to 100 times. In the presence of cortisone acetate or tetrahydro S, DS-4152 suppressed chick chorioallantoic membrane angiogenesis and murine tumor M5076 cell-induced s.c. angiogenesis. The antitumor effects of DS-4152 administered in combination with a steroid whose dose level did not affect tumor growth were examined. DS-4152 significantly inhibited the growth of s.c.-implanted B16 melanoma in combination with cortisone acetate. DS-4152 plus tetrahydro S inhibited the growth of s.c. solid tumors and prolonged the survival time of mice bearing highly metastasizing M5076. The body weight increase was not affected by any administration. On the other hand, the survival of mice with ascitic M5076 tumors was not affected by the combination of DS-4152 plus tetrahydro S. The antiangiogenic activity of DS-4152 was more potent than that of heparin. Furthermore, DS-4152 is an angiogenesis inhibitor by itself, without steroid hormones. Successive s.c. treatment with heparin caused hemorrhagic death, but with DS-4152, suppressed tumor growth without reducing body weight.

Animals↗
PubMed1989

Detection of glycoproteins as tumor-associated Hanganutziu-Deicher antigen in human gastric cancer cell line, NUGC4.

NUGC4 cells derived from a human gastric cancer gave 6% Hanganutziu-Deicher (HD) antigen-positive cells by flow cytometric analysis using an affinity-purified chicken antibody to N-glycolyneuraminyl-lactosyl-ceramide (HD3 ganglioside). The cells showed no HD antigenic ganglioside by thin-layer chromatography enzyme-immunostaining; however, they were revealed to contain HD antigenic proteins with molecular masses of 150, 100, 90, 70, 65, 60, 47, and 40 kDa, by both immunoblotting after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoprecipitation of [35S]-methionine-labeled proteins, followed by SDS-PAGE and autoradiography. Neuraminidase treatment destroyed the antigenicity of all proteins, indicating that these molecules are glycoproteins and have N-glycolyneuraminic acid at the non-reducing terminal of carbohydrate chains as an HD antigenic epitope.

Antigens, Heterophile↗
PubMed1989

Striated muscle in the biopsy specimen of the prostate.

We had a chance to see striated muscle fibers in the biopsy specimen of the prostate. We examined the prostate specimens of autopsied cases and biopsy specimens. The distribution of striated muscle fibers was studied with an immunohistochemical method for myoglobin to obtain their anatomical distribution in detail. We showed that the striated external sphincter muscle fibers were present in the peripheral zone of the prostatic gland (9.1%). Therefore, if striated muscle fibers are found in biopsy specimens of prostatic cancer, pathologists and urologists should not diagnose simply that the cancer invades beyond the prostatic capsule.

Adenocarcinoma↗
PubMed1989

Effect of combined intrapleural administration of Lactobacillus casei (LC9018) and adriamycin on experimental malignant pleurisy in mice.

The combined effect of Lactobacillus casei YIT9018 (LC9018) and adriamycin (ADR) on malignant pleurisy was investigated using an experimental model in BALB/c mice in which Meth A fibrosarcoma cells were intrapleurally implanted. The control mice died from dyspnea due to pleural effusion, before significant growth of tumor nodules could be achieved in the thoracic cavity. Intrapleural (ipl) administration of LC9018 (20-200 micrograms/head) on days 1 and 5 reduced the effusion volume and induced pleural adhesions in a dose-related manner. A statistically significant and reproducible prolongation of survival was observed at a dose of LC9018 200 micrograms/head: increase of lifespan (ILS) values of 15-39% were obtained. An ipl administration of ADR (2-4 mg/kg) on day 1 was also effective in prolonging survival without severe toxicity (ILS values of 100-122%). The combined use of ADR and LC9018 induced a high incidence of pleural adhesions, a delay in effusion accumulation, and an additive prolongation of lifespan (ILS values of 133-178%), compared with ADR monotherapy. In the combination therapy group, a marked and continuous ipl exudation of neutrophils, macrophages, and lymphocytes was observed with a significant decrease in pleural tumor cells. These findings suggest that ipl administration of LC9018 enhances the effect of ADR, probably through both host-mediated tumoricidal activity and sclerosing effects on the pleura.

Animals↗
PubMed1989

Structure-epileptogenicity relationship of quinolones with special reference to their interaction with gamma-aminobutyric acid receptor sites.

The relationship between the chemical structure and epileptogenic activity of quinolones was investigated. When the quinolones were administered intravenously to mice concomitantly with oral biphenylacetic acid, a major metabolite of the nonsteroidal antiinflammatory drug fenbufen, enoxacin, norfloxacin, ciprofloxacin, and pipemidic acid, which have an unsubstituted piperazine moiety at the 7 position of their parent nuclei, provoked clonic convulsions and subsequent death at doses of 6.25 mg/kg or more in a dose-dependent manner. AM-1091 and T-3262, which have an unsubstituted aminopyrrolidine moiety at their 7 positions, were less epileptogenic than the compounds listed above were. In contrast, ofloxacin, AT-4140, and nalidixic acid, which have piperazine substituted with methyl group(s) or no piperazine moiety at their 7 positions, never induced convulsions, even at doses of 100 mg/kg. Lomefloxacin, which has a 3-methyl piperazine, however, provoked convulsions at doses of 6.25 mg/kg or more. In the presence of biphenylacetic acid, all the test quinolones except nalidixic acid competitively inhibited [3H]muscimol binding to receptor sites for gamma-aminobutyric acid (GABA) in vitro. Nalidixic acid did not inhibit the binding at all, even at the highest concentration tested, i.e., 10(-4) M. The 50% inhibition doses for [3H]muscimol binding varied within 4 orders of magnitude or more, between 10(-8) to more than 10(-4) M for various compounds, and there was a close correlation between the epileptogenic activities of quinolones and their inhibitory potencies for [3H]muscimol binding to GABA receptor sites. These results indicate that the epileptogenic activity of quinolones possibly relates to the GABA-like structures of substituents at their 7 positions, which act as antagonists of GABA receptors.

4-Quinolones↗
PubMed1989

Inhibitory effects of quinolones on DNA gyrase of Escherichia coli and topoisomerase II of fetal calf thymus.

The in vitro inhibitory effects of quinolones on the bacterial DNA gyrase of Escherichia coli KL-16 and topoisomerase II of fetal calf thymus were compared. All the quinolones tested required higher concentrations to inhibit the topoisomerase II than to inhibit the DNA gyrase, and no correlation existed among their inhibitory activities against both enzymes. However, there was a large difference among the quinolones in their selectivities between the bacterial enzyme and its eucaryotic counterpart. The selectivity of ofloxacin was highest, and the selectivities of CI-934 and nalidixic acid were lowest.

4-Quinolones↗
PubMed1989

Sub-inhibitory and post-antibiotic effects of an optically active isomer of ofloxacin.

The sub-inhibitory and post-antibiotic suppressive effects of DR-3355, an optically active isomer (S-(-) form) of (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7- oxo-7H- pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (ofloxacin) were compared with those of ofloxacin, ciprofloxacin and ceftazidime by observing changes in bacterial multiplication and morphology in vitro. DR-3355 affected the proliferation of Staphylococcus aureus E46, Escherichia coli E77156 and Pseudomonas aeruginosa PI-III at 1/4 to 1/2 times the minimal inhibitory concentration (MIC) for each strain. The compound also affected the morphology of these strains at 1/32 times the MICs. Upon MIC basis, these sub-inhibitory effects of DR-3355 were almost identical to those of the reference compounds. On the other hand, exposure of E. coli to 1 and 4 times the MIC of DR-3355 for 3 h produced post-antibiotic effects of 0.7 and 1.9 h, respectively, and the effects of the compound were almost equal to those of ofloxacin and ciprofloxacin and much greater than that of ceftazidime.

Bacteria↗
PubMed1989

Chemotherapeutic efficacy of ofloxacin against experimental pneumonia with Pseudomonas aeruginosa in guinea pigs.

The chemotherapeutic efficacy of ofloxacin against experimental pneumonia was investigated with special reference to its treatment regimen. A pneumonia model was successfully produced by inhalation of a virulent strain of Pseudomonas aeruginosa in guinea pigs immunosuppressed with cortisone acetate. One or 4 days after infection, the animals were treated orally with the fixed daily doses of ofloxacin either once a day or thrice a day for 3 consecutive days. Ofloxacin given thrice a day eliminated the organisms from the lung more efficiently than the equivalent total doses injected once a day in both series of treatment, starting 1 or 4 days after infection. The superiority of the triple dosing in chemotherapeutic efficacy of ofloxacin was found to be attributable at least to the longer retention of its pulmonary levels exceeding the antibiotic concentrations.

Animals↗
PubMed1988

Binding site of the rat liver specific monoclonal antibody.

A rat liver-specific antigen (RLSA) lost its binding ability to the corresponding monoclonal antibody after treatment with N-glycanase or sialidase, which suggested that the specific binding site might be in a portion of the sugar chain containing sialic acid. The specific antigen reacted with wheat germ agglutinin, lentil lectin, erythroagglutinating phytohemagglutinin and Ricinus communis agglutinin, but not with concanavalin A or peanut agglutinin. These results suggest that the specific antigen has asparagine-linked complex-type sugar chains which might be the binding sites of the monoclonal antibody.

Animals↗
PubMed1988

In vitro activity of DR-3355, an optically active ofloxacin.

DR-3355, the S-(-)-isomer of ofloxacin, was generally twice as potent as ofloxacin against a variety of gram-positive and gram-negative pathogens, and its action was bactericidal. The compound was characterized by having the highest level of activity against staphylococci, Bacteroides fragilis, and Peptococcus spp. of the fluorinated quinolones tested, including ofloxacin, ciprofloxacin, fleroxacin, and NY-198. The activity of DR-3355 was not affected by different media, inoculum size, or human serum, but decreased under acidic conditions at pH 5.0 or in human urine.

Gram-Negative Bacteria↗
PubMed1988

Cytoprotective action of cetraxate against HCl.ethanol-induced gastric lesion in rats.

The protective effect of cetraxate, an antiulcer and antigastritis agent, on HCl.ethanol-induced gastric lesions was investigated in rats. Oral administration of 1 ml of HCl.ethanol (60% ethanol in 150 mM HCl) induced within 1 hr linear hemorrhagic necrosis in the gastric mucosa. Either oral or intraperitoneal treatment with cetraxate (30-300 mg/kg) significantly inhibited such macroscopic gastric lesions in a dose-related manner, and the inhibition at the oral highest dose (300 mg/kg) was practically complete. Histological analysis also confirmed that cetraxate effectively prevented deep mucosal necrosis, but showed that it was without protective effect on the surface epithelial disruption and submucosal edema in response to HCl.ethanol. The antilesion activity of cetraxate was of statistically significance for at least 3 hr after a single injection, and it was hardly affected by the removal of the gastric contents just prior to application of the necrotizing agent. However, subcutaneous treatment of rats with indomethacin (5 mg/kg) resulted in a partial but significant attenuation in the protection afforded by cetraxate, suggesting that dual mechanisms related and unrelated to endogenous prostaglandins may be involved in its protective activity. The results demonstrate that cetraxate is a potent cytoprotective agent effectively preventing the formation of gastric mucosal necrosis induced by HCl.ethanol.

Animals↗