Search PubMed⌕ Search

Biomedical subjects

Y Shibata

Publications and source records attributed to Y Shibata.

At least 667 records · Page 37Linked to original sources

[Fundamental and clinical studies of a sustained release preparation of cefaclor in the surgical field].

Fundamental and clinical studies of S6472 (sustained release preparation of cefaclor (CCL] were conducted in the surgical field and it was confirmed that the preparation is a useful drug. The following is the summary of the results from the fundamental and clinical studies: In vitro antibacterial activity. CCL showed MICs of 0.78 to 6.25 micrograms/ml against almost strains of S. aureus, E. coli and Klebsiella isolated from surgical wound regions, and the antibacterial activities were stronger than those of cephalexin (CEX). Clinical efficacy. S6472 was orally administered to 33 patients with skin and soft tissue infections in 2 divided doses. As a result, excellent clinical response was observed in 13 patients, good response observed in 14 patients, fair in 4 and poor in 1. The clinical efficacy in 1 of the 33 patients was unknown. Overall clinical effective rate was 84.4%. Adverse reaction. In 2 patients, mild gastrointestinal symptoms were observed.

Abscess↗

[Clinical evaluation of S6472 (prolonged action preparation of cefaclor) in the treatment of skin and soft tissue infections. A double blind comparison of S6472 and cefaclor].

A double-blind comparative study of S6472 and cefaclor (CCL) was conducted to evaluate the therapeutic efficacy, safety and usefulness in the treatment of skin and soft tissue infections. Either 750 mg b.i.d. of S6472 or 750 mg t.i.d. of CCL was administered orally to patients for a period of 7 consecutive days. Of the 250 cases (123 cases of S6472 group and 127 cases of CCL group) recruited in this trial, 228 cases (114 cases of S6472 and 114 cases of CCL) were adopted by the committee members for the evaluation of therapeutic efficacy, 238 cases (118 cases of S6472 group and 120 cases of CCL group) for usefulness, and 245 cases (121 cases of S6472 group and 124 cases of CCL group) were adopted for the evaluation of side effects. The backgrounds of both patients group were almost similar. The results obtained were as follows: Overall clinical effectiveness Of the 114 patients treated with S6472, excellent clinical responses were obtained in 11 patients, good in 79, fair in 19, poor in 5 (efficacy rate 78.9%), and of the 114 patients treated with CCL, excellent were in 16, good in 78, fair in 13, poor in 7 (efficacy rate 82.5%). There was no statistically significant difference between the 2 groups. Clinical effectiveness classified by initial severity and bacteriological efficacy There was no significant difference between the 2 groups in the clinical effectiveness classified by initial severity and in the bacteriological efficacy. Side effects were noticed in 5 patients of 121 treated with S6472 (4.1%) and in 2 patients of 124 treated with CCL (1.6%), and other 13 patients developed some abnormal laboratory findings. But these undesirable reactions were mild, and developed no significant difference between the 2 groups in the incidence of side effects. There was no significant difference between the 2 groups in the usefulness of the drugs. Conclusively, 750 mg b.i.d. of S6472 is anticipative of the same clinical efficacy, safety and usefulness as compared with that of 750 mg t.i.d. of CCL in the treatment of skin and soft tissue infections.

Administration, Oral↗

A monoclonal anti-human platelet antibody: a new platelet aggregating substance.

A monoclonal anti-human platelet antibody, TP82, is described, which caused irreversible aggregation of platelets in association with the release of adenosine triphosphate or [14C] serotonin, and which inhibited ristocetin-induced agglutination. Immunofluorescence assay showed that the antibody binds to platelets, megakaryocytes, and common acute lymphoblastic leukemia cells. The antibody (IgG1) immunoprecipitated a polypeptide of 23,000 daltons with an isoelectric point of about 7.0. The aggregation induced by the purified antibody and/or F(ab')2 fragments occurred in platelet-rich plasma and with washed platelets, but not with formalin-fixed washed platelets. TP82-induced aggregation was completely inhibited by disodium ethylendiaminotetraacetate, diltiazem, W-7, PGE1, and several metabolic inhibitors. At a concentration of apyrase or CP/CPK, which inhibited adenosine 5-diphosphate-induced aggregation. TP82-induced aggregation was only partially affected. Thrombin was not required for the antibody-mediated effects, since two thrombin inhibitors failed to block the reaction. The antibody, at least at a high concentration, induced platelet aggregation by a mechanism almost independent of thromboxane A2 formation, since cyclooxygenase inhibitors had little inhibitory effect on aggregation. TP82 monoclonal antibody is a new platelet-aggregating substance that interacts with a low-molecular-weight binding site on the platelet membrane.

Adenosine Triphosphate↗

The effect of hemopoietic microenvironment on splenic suppressor macrophages in congenitally anemic mice of genotype Sl/Sld.

Mechanisms underlying mononuclear phagocyte specialization are being probed by studying suppressor macrophages (M phi) as a reference population in mouse models with impaired blood monocyte formation. Splenic suppressor M phi, defined by PGE-mediated inhibition of Con A-induced T lymphocyte proliferation are induced by the i.p. administration of Corynebacterium parvum (CP). Mice severely depleted of bone marrow and blood monocytes by treatment with 89Sr fail to show this suppressor M phi response to CP, although M phi-forming stem cells, assessed as splenic M-CFC in vitro, are increased 20-fold. These observations suggest that radiosensitive bone marrow stem cells are necessary for the generation of both suppressor M phi and monocytes and that one such stem cell may be common to both types of mononuclear phagocytes. This notion was explored further by employing congenitally anemic mice of the genotype S1/S1d in which the hemopoietic microenvironment is genetically defective and thus unable to support the proliferation, differentiation, and function of stem cells. The congenital defect was found to be additionally expressed in the S1/S1d mouse by a monocytopenia of less than 10% of the values in normal congenic littermate controls and by the failure of splenic M-CFC to increase in response to CP. PGE-producing suppressor M phi expressing Fc gamma 2b receptors, however, were induced by CP in S1/S1d mice with no significant diminution of suppressor activity. These data establish the fact that significant impairment of the formation of monocytes is part of the overall hemopoietic defect in S1/S1d mice. PGE-producing suppressor M phi, however, were inducible at normal functional levels in the presence of a profound monocytopenia, and therefore appear to be independent of the mechanisms that regulate blood monocyte formation. Ablation of the bone marrow with 89Sr resulted in failure of CP to induce suppressor M phi in the spleens of the S1/S1d mice as in the littermate controls. Other observations in the present study, when taken with data from the 89Sr model, show the additional independence of these suppressor M phi from splenic M-CFC. In aggregate, these findings delineate three functionally definable populations of mononuclear phagocytes that appear to be independently regulated.

Anemia, Hemolytic, Congenital↗

Kynurenine metabolism in vitamin-B-6-deficient rat liver after tryptophan injection.

Tryptophan contents of liver, serum and kidney were determined in normal and vitamin-B-6-deficient rats after tryptophan injection. Tryptophan contents of normal and B-6-deficient liver were different, but not those in serum and kidney. Both kynurenine and 3-hydroxykynurenine accumulated in B-6-deficient liver more than in the normal. The 3-hydroxykynurenine contents after tryptophan injection (30 mg/100 g body wt.) increased to 1380 nmol/g of liver at 1-1.5 h, a value sufficient to produce xanthurenate, in view of the Km value of kynurenine aminotransferase. The enzymes metabolizing kynurenine were assayed at various times after tryptophan injection. The activity of kynureninase holoenzyme in B-6-deficient liver was much decreased, but the activity of total enzyme was not changed. It appeared that a high dose of tryptophan in B-6-deficient rats could cause a greater deficiency of pyridoxal 5-phosphate. Tryptophan metabolism in B-6-deficient rat liver after tryptophan administration is discussed.

Animals↗

Relationships between suppressor macrophages and macrophage precursors in the spleens from tumor-bearing mice.

Suppressor macrophages (M phi) which can inhibit mitogen-induced lymphocyte proliferation appeared in the spleens of mice bearing transplanted MC-A fibrosarcoma cells. An analysis of the ontogeny of such M phi revealed additional suppressor activity directed against macrophage stem cells. Treatment of spleen cell suspensions with carbonyl iron followed by centrifugation removed suppressor M phi but did not deplete M phi-colony forming cells (M-CFC) which could be demonstrated in soft agar culture in L-cell conditioned medium (LCM). Untreated spleen cells had normal numbers of M-CFC; phagocyte-depleted mononuclear cells showed a threefold increase in M-CFC 14 days after subcutaneous inoculation of 10(6) MC-A cells per mouse. Further increases in M-CFC were also evident in similar preparations on Days 21 and 28 when the M-CFC concentration reached a maximum of eight times the normal level. The M phi which developed from the M-CFC grown in the presence of LCM were later shown to have indomethacin-sensitive suppressor activity suggesting the mediation of this phenomenon by prostaglandins. These observations suggest that locally produced phagocytic suppressor M phi from the spleens of tumor-bearing mice play important roles not only as inhibitors of lymphocyte proliferation as reported earlier, but also as regulators of monocyte-M phi production.

Animals↗

Photochemically induced dynamic nuclear polarization study on microsomal NADPH-cytochrome P-450 reductase.

Sedimentation equilibrium experiments with NADPH-cytochrome P-450 reductase showed that increasing 1-O-n-octyl-beta-D-glucopyranoside levels promoted disaggregation of the flavoprotein. The reductase was monomeric at a molar ratio of detergent to protein above 10(3). Addition of N3-carboxymethyllumiflavin to the flavoprotein in the presence of 1-O-n-octyl-beta-D-glucopyranoside results in photochemically induced dynamic nuclear polarization (CIDNP) signals in the aromatic region. The CIDNP spectrum of the holoprotein shows sharp resonances due to histidine residues. On removal of FMN from the protein, CIDNP signals originating from a tyrosine residue appeared, suggesting that the tyrosine residue is exposed to solvent after the depletion of FMN. However, this tyrosine residue appears to become inaccessible to the external dye after full incubation of FMN-depleted reductase with FMN. This suggests that the tyrosine residue could be located in the vicinity of the FMN-binding domain which constitutes the active center of the reductase.

Animals↗

Clinical application of prostaglandin E1 (PGE1) upon orthodontic tooth movement.

Chemically produced prostaglandin E1 (PGE1) was administered in clinical cases of orthodontic tooth movement. In the first phase, lingual arch springs were applied on both sides of the maxilla to upper first premolars which were scheduled for extraction. One side received submucosal injections of PGE1 and the other received vehicle injections. The rate of tooth movement in the buccal direction approximately doubled on the side of several PGE1 injections as compared to the control side. In the second phase, the PGE1 injections were applied in canine-retraction cases for up to 3 weeks in first-premolar-extraction cases. The rate of distal canine movement was almost double on the side receiving PGE1 injections as compared to the vehicle-injected side. In the third phase, the PGE1 injections were applied on routine canine retraction in first-premolar-extraction cases. The rate of distal canine movement was almost 1.6-fold on the side of PGE1 injections as compared to the vehicle-injected side. Throughout this study, no side effects were observed macroscopically in the gingiva and roentgenographically in the alveolar bone, except for a slight pain reaction consistent with orthodontic tooth movement.

Alprostadil↗

A deep-etching study of the guinea pig tracheal cilium with special reference to the ciliary transitional region.

The fine structure of the cilium was examined by freeze-fracture-etch studies. In the interior of the transitional region, three types of plate structures were clearly observed. While the terminal plate contained fine fibrillar linkers suspending the central core plates from its peripheral doublet microtubules, two other types of plates had no suspending linkers. At the upper level of transitional region, one of the central microtubules elongated deeper than the other in the space surrounded by ring structure. Axosome-like structure was not observed in our replicas. Central vesicle of the basal body was also suspended by fine fibrillar linkers from peripheral triplets. Though membrane particles of ciliary necklace were recognized on protoplasmic and external fracture faces, and the external surface, particle arrays were not observed on protoplasmic surface. Instead, Y-shaped, cross bridges, one end of which attached to the doublet microtubules, merged in the circular ridge structure at opposite ends. This circular ridge structure at the necklace region may play a role as an anchoring site of both membrane particles of the necklace and cross bridges from peripheral doublet microtubules.

Animals↗

Oxygen metabolism of human colostral macrophages: comparison with monocytes and polymorphonuclear leukocytes.

Human colostral macrophages stimulated by opsonized zymosan or phorbol myristate acetate (PMA) released superoxide anions (O2-) and hydrogen peroxide (H2O2) with activities comparable to those of monocytes and about one-fourth of those of polymorphonuclear leukocytes (PMNL) of blood. The O2- -forming oxidase in the macrophages stimulated by PMA was dependent on NADPH as an electron donor with an apparent Km value for NADPH of 27.6 +/- 4.0 microM, which is comparable to those obtained for the stimulated monocytes and PMNL of blood. The Vmax was 1.86 +/- 0.33 nmol O2/min/10(6) cells, which is essentially the same as that of monocytes and about half of that of PMNL. p-Chloromercuribenzoate or cetyltrimethylammonium bromide completely inhibited oxidases of all three types of phagocytes. A b-type cytochrome was identified in the macrophages but the concentrations in the macrophages and monocytes were less than half of that in PMNL. These results suggest that the differences in the O2- -forming activities of the three types of phagocytes are quantitative rather than qualitative. The macrophages and monocytes showed very low activities of myeloperoxidase [EC 1.11.1.7] in contrast to PMNL. The activity of beta-glucuronidase [EC 3.2.1.31] in the macrophages was much higher than those of the monocytes and PMNL, but little difference was observed in the activities of lysozyme [EC 3.2.1.17], catalase [EC 1.11.1.6] and superoxide dismutase [EC 1.15.1.1] among the three types of phagocytes examined. Electron micrographs of the macrophages showed little increase of vacuoles upon exposure to PMA, in contrast to the cases of monocytes and PMNL.

Catalase↗

Cultured human monocytes, granulocytes and a monoblastoid cell line (THP-1) synthesize and secrete immunosuppressive acidic protein (a type of alpha 1-acid glycoprotein).

Immunosuppressive acidic protein (IAP, pI 3.0) is a type of alpha 1-acid glycoprotein (alpha 1-AG). The secretion of IAP into the culture fluids of different subpopulations of human peripheral blood leukocytes was examined by a newly devised passive hemagglutination (PHA)-inhibition test. Human peripheral monocytes, an established monoblastoid cell line (THP-1) and peripheral granulocytes produced IAP. However, neither T nor B lymphocytes, nor lymphoblastoid cell lines induced by TCGF or EB virus respectively, produced IAP. The IAP concentration reached a maximum (215 ng/ml) in the culture fluids of peripheral monocytes (1 X 10(6)/ml) when monocytes were stimulated by the addition of either immune complex, carrageenan or endotoxin. The synthesis de novo and shedding of IAP by THP-1 were demonstrated by the immunoprecipitation of radioactive IAP in the culture fluids of [3H]leucine-labeled cells. SDS-polyacrylamide gel electrophoresis of the immunoprecipitates showed two peaks of radioactivity, one comigrated with authentic IAP at 50,000 daltons, and the other at 38,000 daltons, suggesting that two different forms of IAP (and/or alpha 1-AG) are produced from human monocytes.

Animals↗

Double-axis rotary replication for deep-etching.

We have developed a simple new method of rotary shadowing, double-axis rotary replication, for observing three-dimensional structures in deep-etched, rapid-frozen tissues. The technical details of this method are described and compared with the conventional fixed-angle rotary shadowing procedure.

Animals↗

Mixed passive hemagglutination with soluble platelet antigens.

Mixed passive hemagglutination (MPHA) test was established using platelet-supernatant and indicator cells coated with purified antihuman IgG antibodies. The supernatant was shown to contain HLA A and B antigens, platelet alloantigens and blood group A, B and H antigens released spontaneously from the platelets. Unlike the MPHA with platelet monolayer, the in vitro-formed immune complex (IC) or IC containing pathologic sera did not give positive reactions in the MPHA with platelet supernatants presumably due to relatively low Fc receptor activities of the supernatants. By means of this test, HLA A or B antibodies were demonstrated in sera of 32 (44%) of 72 patients with multiple platelet transfusions including 'cytotoxicity negative absorption positive' sera. This test would provide a sensitive procedure for cross-match of sera of recipients of platelet transfusion and screening of HLA A and B typing sera.

ABO Blood-Group System↗