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Biomedical subjects

Y Endo

Publications and source records attributed to Y Endo.

At least 541 records · Page 30Linked to original sources

[The effect of protease inhibitors in shock].

UNLABELLED: Protease inhibitors, such as ulinastatin and gabexate mesilate, are widely used for the patients in shock state. The purpose of this study was to evaluate the effects of these protease inhibitors on renal protection and coagulofibrinolytic disorders. The obtained results were as follows: 1. Ulinastatin studies. 1) Beta 2-microglobulin (BMG) excretion and N-acetyl-beta-D-glucosaminidase (NAG) activity in urine were increased in cases of emergency operation (10 patients) compared with elective operation (38 patients). 2) In canine experimental model of renal ischemia, ulinastatin significantly improved urine volume and urine NAG levels. 3) Administration of ulinastatin suppressed urine NAG level in 12 patients, but BMG level did not significantly change. 2. Gabexate mesilate (FOY) studies. 1) All patients in shock state showed coagulofibrinolytic disorders. Especially remarkable hypercoagulability was observed in 21 patients. 2) FOY suppressed platelet aggregation and the release of beta-thromboglobulin and platelet factor 4. 3) In 24 patients, administration of FOY markedly increased the antithrombin III levels in early postoperative period. 4) Fibrinolytic system was not affected any significant changes with administration of FOY. CONCLUSION: Our results suggested that protease inhibitors are useful for management of the patients in shock state.

Animals↗

Relationship between the pharmacological effects of benzodiazepines and their in vivo binding sites in the brain of rats.

To compare the in vitro pharmacological effect and in the brain distribution of benzodiazepines and phenobarbital, three group of sixty anesthetized rats (470-480 g) were administered 5 microCi of 3H-diazepam, 3H-flunitrazepam or 3H-phenobarbital. The rats were decapitated 3, 10, or 40 minutes after the intravenous injection of these drugs. Radioactivity of the tissue was measured and calculated as d.p.m./g. tissue. 3H-diazepam radioactivity in the brain-stem and hypothalamus was significantly higher than in the brain cortex 3 and 10 minutes after the injection. 3H-flunitrazepam radioactivity in the brain cortex was higher than in other regions. There was no significant decrease in 3H-phenobarbital brain concentration, even 40 minutes after injection. The distribution of benzodiazepine is closely related with its pharmacological effect, and this suggests that in vitro benzodiazepine binding sites are not responsible for the pharmacological action in vivo.

Animals↗

[Methicillin-resistant staphylococcal enterocolitis developed after induction chemotherapy in a case of acute promyelocytic leukemia].

A case of methicillin-resistant staphylococcal (MRSA) enterocolitis following combination chemotherapy for acute promyelocytic leukemia is presented. MRSA enterocolitis has characteristic clinical features of high fever, frequent vomiting and watery diarrhea, and its mortality rate is very high without a proper antibiotic therapy. When the patient with hematological malignancy has the above-mentioned clinical manifestations during antineoplastic chemotherapy, appropriate antibiotics for MRSA should be promptly begun before a bacteriological diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗

[Recovery of marrow myeloid progenitors (CFU-GM) after bone marrow transplantation, especially associated with chronic graft-versus-host disease (GVHD)].

Six patients underwent allogeneic bone marrow transplantation (BMT) for treatment of acute non-lymphocytic leukemia. Hemopoietic reconstitution after BMT was monitored by peripheral blood counts, counts of bone marrow cellularity, bone marrow pictures, and clonal assays for myeloid progenitors (CFU-GM). Although bone marrow samples were markedly hypocellular on day 7 posttransplant, myeloid and erythroid elements were seen in 5 of 6 patients. Peripheral blood recovery of these 5 patients was achieved by third weeks posttransplant. The values of (CFU-GM) per 1 X 10(5) marrow mononuclear cells reached normal values on day 7 in two patients and significantly increased by day 28 in a patient. After day 84 the values of (CFU-GM) were remained almost normal and they had no relation to the occurrence of chronic graft-versus-host disease (GVHD). But in patients with chronic GVHD, marrow (CFU-GM) values were significantly increased on day 7 and day 14. These results suggest that marrow (CFU-GM) values by day 28 may predict the occurrence of chronic GVHD.

Bone Marrow Transplantation↗

[The present status in prophylaxis and treatment of HIV infected patients with hemophilia in Japan].

Thirty six hemophiliacs with HIV infection were treated with high-dose glycyrrhizin, Stronger Neo-Minophagen C (SNMC). The dose was 100-200 ml of SNMC in eighteen patients and 400-800 ml in the other 18. The patients were divided into an asymptomatic carrier (AC) group and AIDS related complex (ARC)/AIDS group. SNMC was administered intravenously daily for the first 3 weeks, every second day for the following 8 weeks to 36 HIV positive hemophilia patients in accordance with the protocol proposed by the Japanese National Research Committee. The CD 4/CD 8 ratio and CD 4 positive lymphocyte counts did not change during the treatment period. However, significant improvement was noted in some cases. A slight increase in mitogenic responsiveness to phytohemagglutinin, Concanavalin A and pokeweed mitogen was noted in most patients of both groups, especially in the AC group administered over 400 ml of SNMC. Furthermore, complete improvement was noted in liver dysfunction, which has been thought to be a major problem in hemophiliacs treated with blood products. Thus prophylactic administration of high-dose SNMC to HIV positive hemophiliacs having impaired immunological ability and liver dysfunction was considered to be effective to prevent the development from AC/ARC to AIDS.

AIDS-Related Complex↗

[Response to antitumoral agents of a human medulloblastoma implanted into the chorioallantoic membrane of a chick embryo].

In a previous study the authors have reported on a correlation between the effects of drugs on gliomas grown in the eggs and in the nude mice, and in this study, they have observed the antineoplastic effects of ACNU or combined chemotherapy (CAP-cyclophosphamide, adriamycin, cisplatin) against a medulloblastoma applied onto the chorioallantoic membrane (CAM) of a chick embryo. In this model, ACNU was thought to be ineffective because of an intracerebral dissemination that occurred in spite of the administration of ACNU. ACNU also proved ineffective against the medulloblastoma that grew on the CAM. There seemed to be correlation between the results of this test and the clinical course of this model. Thus this sensitivity test is thought to be useful in the screening of drugs against gliomas.

Adolescent↗

A new tumor promoter from the seed oil of Jatropha curcas L., an intramolecular diester of 12-deoxy-16-hydroxyphorbol.

A new type of phorbol ester, which has a macrocyclic dicarboxylic acid diester structure, was isolated from the seed oil of Jatropha curcas L. (Euphorbiaceae). Based on the results of spectroscopic analyses of the compound and its chemical degradation products, its structure is proposed to be an intramolecular 13,16-diester of 12-deoxy-16-hydroxyphorbol, 12-deoxy-16-hydroxyphorbol-4'-[12',14'-butadienyl]-6'-[16',18',20' - nonatrienyl]-bicyclo[3.1.0]hexane-(13-O)-2'-[carboxylate]-(16-O)-3 '- [8'-butenoic-10']ate (DHPB). DHPB showed slightly weaker biological and biochemical activities than 12-O-tetradecanoylphorbol-13-acetate (TPA). DHPB induced ornithine decarboxylase in mouse skin (2.8 nmol CO2/30 min/mg protein/34 nmol application), inhibited the specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to phorbol ester receptors (50% effective dose, 17.0 nM), and activated protein kinase C in vitro (50% effective dose, 36.0 nM). Also, a weak tumor-promoting activity of DHPB was found in a two-stage carcinogenesis experiment on mouse skin. One week after initiation of mice with 100 micrograms of 7,12-dimethyl-benz(a)anthracene, topical application, twice a week, of 2 micrograms of DHPB until week 17, followed by application of 5 microgram of DHPB until week 30 at the same rate, resulted in 46.7% incidence of tumors by week 30. The groups treated with 7,12-dimethylbenz(a)anthracene alone or DHPB alone did not produce significant numbers of tumors. These results indicate that the new phorbol ester, DHPB, is a tumor promoter with weaker activity than 12-O-tetradecanoylphorbol-13-acetate.

Animals↗

Role of ornithine decarboxylase in the regulation of cell growth by IL-1 and tumor necrosis factor.

Ornithine decarboxylase (ODC) is a rate-limiting enzyme in polyamine synthesis, and polyamines are required for cell growth. As an approach to clarifying the mechanism of action IL-1, the effects of IL-1 on ODC activity were examined in various cell lines whose proliferation was either suppressed or enhanced by IL-1. The proliferation of all cell types used in these experiments was markedly suppressed by a specific ODC inhibitor, alpha-difluoromethyl ornithine (DFMO), substantiating the crucial role of ODC activity for cell proliferation. ODC activity also was considerably suppressed by IL-1 in those cells on which IL-1 exerts an antiproliferative effect, such as a human melanoma cell line (A375) and malignant human mammary cell lines (MCF-7 and T-47D). On the other hand, ODC activity was stimulated in cells that are stimulated to proliferate in response to IL-1, such as a mouse helper T cell line (D10.G4.1), a NK cell-like cell line (YT), and a human glioblastoma cell line (U373 MG). The effect of IL-1 on ODC activity preceded and directly correlated in a dose-dependent manner with its effect on DNA synthesis. Furthermore, putrescine, a product of the ODC reaction and a precursor of polyamines, was able to overcome most, but not all, the antiproliferative action of IL-1 in A375 melanoma cells, which were the most sensitive to suppression by IL-1. However, putrescine did not reverse the cytostatic effect of IL-1 on MCF-7 and T-47D cell lines. In contrast, putrescine, like IL-1, exhibited some co-mitogenic activity on D10.G4.1 cells. Because the biological activities of TNF and IL-1 show considerable overlap, the effect of TNF on ODC activity also was examined. TNF had an antiproliferative effect on A375 cells and stimulated the proliferation of U373 MG cells. The ODC activity in A375 cells was suppressed by TNF, and the ODC activity in U373 MG cells was stimulated by TNF. Putrescine also partially overcame the inhibitory effect of TNF. These results suggest that the regulation of ODC activity may be a key component in the antiproliferative and proliferative action of IL-1 and TNF in some tumor cell types.

Animals↗

Immunohistochemical demonstration of S-100 protein in the brain neurosecretory cells of invertebrates (insects and earthworms).

This immunohistochemical study demonstrated the presence of S-100 protein (-like substance) in the nervous systems of some invertebrate animals. The immunoreactivity of S-100 protein was detected in some neurosecretory cells, but not in glial cells in the brains (cerebral ganglia) of silkworms, cockroaches and earthworms. The immunoreactive nerve fibers extended to the neurohemal organs. These results suggested the possibility that S-100 protein (-like substance) may act as a neurohormone or carrier protein in invertebrate animals.

Animals↗

The RNA N-glycosidase activity of ricin A-chain. The characteristics of the enzymatic activity of ricin A-chain with ribosomes and with rRNA.

Ricin A-chain cleaves the N-glycosidic bond at A-4324 in 28 S rRNA when intact rat ribosomes are the substrate. Cleavage occurs at a concentration of the toxin of 1 X 10(-10) M, and specificity for this single residue is retained when the concentration is as high as 3 X 10(-7) M. The apparent Michaelis constant (Km) for the reaction is 2.6 microM, and the turnover number (Kcat) is 1777 min-1. The same N-glycosidic bond is cleaved by ricin A-chain in naked 28 S rRNA, but at a greatly reduced rate. The Km value for this reaction is 5.8 microM. The results suggest that the A-chain has a similar affinity for 28 S rRNA in ribosomes and in the absence of ribosomal proteins. Ricin A-chain has no effect on 23 S rRNA in Escherichia coli ribosomes, however, the N-glycosidic bond at A-2600 in naked 23 S rRNA is cleaved by the toxin; this corresponds to the ricin site in eukaryotic 28 S rRNA. Since the Km value (3.3 microM) for the reaction with E. coli 23 S rRNA approximates that obtained with rat liver ribosomes, it is possible that E. coli ribosomal protein(s) protect this site against ricin attack in intact ribosomes. Ricin A-chain also acted on naked 16 S rRNA cleaving the N-glycosidic bond of adenine at position 1014. The results suggest that ricin A-chain recognizes a specific structure in rRNA, perhaps a loop and stem having the sequence GAGA in the loop.

Animals↗

Ricin and alpha-sarcin alter the conformation of 60S ribosomal subunits at neighboring but different sites.

The effects of ricin and alpha-sarcin separately or in combination on the conformation of rat liver ribosomes were investigated by measuring the relative accessibility of individual ribosomal proteins to N-ethylmaleimide after 80S ribosomes were treated with these toxins. By using a double-labelling technique in which ribosomes were incubated with the toxins and then treated with 3H-labelled or 14C-labelled N-ethylmaleimide, it was found that labelling of protein L14 was specifically reduced by treatment with ricin, and that of proteins L3 and L4 by treatment with alpha-sarcin, suggesting that the toxins alter the conformation of ribosomes in the vicinity of these proteins. When ribosomes were treated with both ricin and alpha-sarcin, the extent of labelling of protein L3 was reduced compared to that observed after treatment with alpha-sarcin alone. These results are discussed in relation to previous observations showing that these three proteins are neighbours in the 60S ribosomal subunit and probably play important roles in protein biosynthesis, and in the actions of ricin and alpha-sarcin on 28S rRNA.

Animals↗