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S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 1,225 records · Page 68Linked to original sources
PubMed1984

Acute and subacute toxicity studies of AC-1370 sodium in mice and rats.

The i.v. LD50 of the cephalosporin antibiotic 7-beta-D(-)-alpha-[4(5)-carboxyimidazole-5(4) carboxamido]phenylacetamido-3-(4-beta-sulfoethylpyridinium) methyl-3-cephem-4 carboxylic acid sodium (AC-1370 sodium) for the rat was found to be 4.2 and 3.5 g/kg body weight for males and females, respectively; corresponding values for the mouse were 2.7 (male) and 2.9 (female). Daily i.v. administration to rats for 35 days caused decreased food intake and increased water consumption and body weight gain, relative increase of kidney weight, elevated blood urea nitrogen (BUN) and proteinuria, renal tubular degeneration and/or necrosis and ballooning of the caecum at 1500 mg/kg/day, and less marked changes at 500 mg/kg/day. There were so significant adverse effects at 40 or 150 mg/kg/day. The approximate LD50 values (g/kg) by other routes were: s.c. mouse, 7-8; s.c. rat, 11-12; i.m. mouse and rat, greater than 1.2; per os mouse and rat, greater than 15.

Animals↗
PubMed1984

Transcriptional activation of the rat liver tyrosine aminotransferase gene by cAMP.

The enzyme tyrosine aminotransferase (Tyr-ATase; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5), which is synthesized in rat liver, is induced by glucocorticoids, insulin, and glucagon or its intracellular mediator cAMP. We have used cloned TyrATase genomic and cDNA sequences to study the mechanism of induction by cAMP. RNA blot analysis shows that cAMP causes a rapid 5-fold increase in TyrATase mRNA concentration in rat liver. Transcription in isolated rat liver nuclei was studied to determine the relative rate of transcription of the TyrATase gene after cAMP administration. We show that the accumulation of TyrATase mRNA after cAMP stimulation is a consequence of transcriptional activation of the TyrATase gene. Combined dexamethasone and cAMP treatment leads to higher TyrATase mRNA concentrations than each inducer alone, which implies that dexamethasone and cAMP act by distinct mechanisms.

Animals↗
PubMed1984

Mechanism of inhibition of activated protein C by protein C inhibitor.

Protein C inhibitor isolated from human plasma inhibited thrombin, factor Xa, trypsin and chymotrypsin as well as activated protein C, but had very little effect on urokinase and plasmin. The inhibition constants (K1) of protein C inhibitor for activated protein C, thrombin and factor Xa were 5.6 X 10(-8) M, 6.7 X 10(-8) M and 3.1 X 10(-7) M, respectively. The second-order rate constant for inhibition of activated protein C by the inhibitor increased about 30-fold in the presence of an optimal heparin concentration (5-10 units/ml). The inhibition of activated protein C by plasma protein C inhibitor was also accelerated by heparin. When activated protein C (Mr = 62,000) was incubated with protein C inhibitor (Mr = 57,000), enzyme-inhibitor complexes with apparent Mr = 102,000 and 88,000 were observed in the nonreduced and the reduced samples, respectively, on SDS-polyacrylamide gel electrophoresis. In addition to these complexes, a band of unbound enzyme and a band with Mr = 54,000 were detected. When 125I-labeled protein C inhibitor was exposed to activated protein C, the inhibitor band was converted to bands with apparent Mr = 102,000 and 54,000 in the nonreduced samples, as determined by autoradiography after gel electrophoresis in SDS. The band with Mr = 54,000 also appeared when the inhibitor reacted with other serine proteases. The activated protein C was released from the inactive complex by treatment with 1 M ammonia or hydroxylamine. This phenomenon was found by SDS-polyacrylamide gel electrophoresis to represent the dissociation of the enzyme-inhibitor complex by ammonia or hydroxylamine into the free enzyme and the proteolytically modified inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗
PubMed1984

Protein S is essential for the activated protein C-catalyzed inactivation of platelet-associated factor Va.

The prothrombin-converting activity of Factor Xa was enhanced by thrombin-stimulated Factor V-deficient platelets and supplementary extraneous Factor Va, and also by thrombin-stimulated normal human platelets. Both extraneous Factor Va and intra-platelet Factor Va were equally inactivated by a gamma-carboxyglutamic acid-containing plasma protease, activated protein C. However, a relatively larger amount of activated protein C was required for efficient inactivation of platelet-associated Factor Va as compared with the amount of activated protein C needed for inactivation of phospholipid vesicle-associated Factor Va. Protein S, another gamma-carboxyglutamic acid-containing plasma protein, increased the rate of the inactivation of platelet-associated Factor Va about 25-fold. This stimulating effect was observed only slightly with the thrombin-modified protein S. Thus, it was concluded that protein S is essential for the process of inactivation of platelet-associated Factor Va by activated protein C.

Blood Platelets↗
PubMed1984

Oxygen radical production by peritoneal macrophages and Kupffer cells elicited with Lactobacillus casei.

BALB/c mice were injected intraperitoneally (i.p.) or intravenously (i.v.) with Lactobacillus casei YIT9018 (LC 9018). The i.p. injected LC 9018 augmented oxygen radical (OR) production by peritoneal macrophages (PM) and suppressed the production of prostaglandin E2 by PM. The growth of i.p. inoculated Meth A fibrosarcoma was also inhibited by an i.p. injection of LC 9018. i.v. injection of LC 9018 stimulated OR production by fixed macrophages and inhibited the growth of Listeria monocytogenes in the liver. Furthermore, glucose-6-phosphate dehydrogenase activity in the liver was significantly increased (10 to 20 times) by LC 9018 i.v. injection. A significant correlation was observed between the augmentation of OR production by PM or fixed macrophages in the liver and inhibition of growth of Meth A or L. monocytogenes. The augmentation of OR production by LC 9018 was more marked and was maintained for a longer period of time than that by other bacterial immunostimulants.

Animals↗
PubMed1984

Expression of the E4 gene is required for establishment of soft-agar colony-forming rat cell lines transformed by the adenovirus 12 E1 gene.

Rat 3Y1 cells were transfected with recombinant gARC ( pSV2gpt carrying the adenovirus 12 early region 1 [E1] gene), and focus formation was observed in monolayer cultures after culture of cells in gpt-selective medium (Eagle medium containing 10% fetal calf serum, xanthine, thymidine, aminopterin, and mycophenolic acid) for 10 days, followed by focus formation. Transformed E1Y cell lines were then established from these foci. The E1Y cells were transformed morphologically similarly to cells transformed with intact adenovirus 12 DNA but formed no colonies in soft-agar culture and induced tumors in transplanted rats only after a long incubation period. For the establishment of completely transformed cells, 3Y1 cells were transformed with combinations of gARC , pE3 (pBR322 carrying the adenovirus 12 E3 gene), and gE4 ( pSV2gpt carrying the adenovirus 12 E4 gene) DNA. E1- 3Y cells (3Y1 cells transformed with gARC and pE3 DNA), E1- 4Y cells (3Y1 cells transformed with gARC and gE4 DNA), and E1-3- 4Y cells (3Y1 cells transformed with gARC , pE3 , and gE4 DNA) were established. These transformed cell lines were compared for growth in Eagle medium with 2 or 10% fetal calf serum, colony formation in soft-agar culture, and tumor growth in rats transplanted with the transformed cells. Several transformed cell lines of E1- 4Y and E1-3- 4Y cells showed colony formation in soft-agar culture and abundant expression of the E1B gene. T antigen f was seen by immunofluorescence as flecks in these cells, in which the E4 gene was transcribed, but was not seen in E1Y cells, suggesting that T antigen f was encoded by the E4 gene. The suggestion was confirmed by the observation that T antigen f was detected in COS-1 cells transfected singly with gE4 DNA by immunofluorescence with polyclonal and monoclonal antibodies. Transcription of the E4 gene was confirmed in gE4 -transfected COS-1 cells. T antigen f, one of the E4 gene products, was identified as a polypeptide of molecular weight 11,000 (E4- 11K ) by immunoprecipitation with monoclonal antibodies. The above results also suggest that expression of the E4 gene gives cells the advantage of forming colonies in soft-agar culture. A tendency was noticed for E1B gene expression to be enhanced by E4 gene expression. The relationship between enhancement of colony formation in soft-agar culture and enhancement of E1B gene expression is discussed.

Adenoviruses, Human↗
PubMed1984

Potentiation of tumoricidal properties of murine macrophages by Nocardia rubra cell wall skeleton (N-CWS).

Intraperitoneal injection of squalene-treated cell wall skeleton of Nocardia rubra (N-CWS) caused increase in number of peritoneal exudate cells (PEC). Adherent macrophages obtained from N-CWS-treated PEC suppressed growth of methylcholanthrene-induced fibrosarcoma (Meth-A), when injected intradermally with the tumor cells into BALB/c mice. The macrophages showed strong cytotoxicity against Meth-A cells in vitro. When treated with 10 micrograms/ml of N-CWS in vitro, proteose peptone-induced macrophages acquired tumoricidal property but resident macrophages showed no cytotoxicity after the treatment. In the supernatant of spleen cells cultured for 72 hours in the presence of N-CWS (10 micrograms/ml), the presence of (a) factor(s) with macrophage activating effect was observed. This factor, shown to be identical to macrophage activating factor (MAF) in molecular weight, showed synergy with N-CWS in potentiating macrophage cytotoxicity against tumor cells.

Adjuvants, Immunologic↗
PubMed1984

[Effect of various types of analgesic drugs on an experimental model of chronic inflammatory pain in mice].

We attempted to develop an experimental model of chronic inflammatory pain in mice. The mice were injected intradermally at the base of the tail with various kinds of irritants (yeast, carrageenin, mustard and adjuvant). The pain threshold was measured by the pressure method every 60 min for 5 hr and once a day at the same time throughout the experimental period. The group of 10% yeast-injected mice exhibited the most intensive hyperalgesia. The analgesic effect of various types of analgesic drugs were studied, comparing the effects in normal mice and various kinds of irritants-induced hyperalgesia mice. It was demonstrated by observing ED50 values that nonsteroidal antiinflammatory drugs (NSAIDs), narcotic analgesic drugs and agonist/antagonist type of analgesic drugs were effective, but CNS-acting drugs were ineffective in yeast hyperalgesia mice. In comparison with yeast hyperalgesia mice, larger doses of analgesic drugs were required in normal mice and other irritants-treated mice. Especially, acidic NSAIDs were more effective in yeast hyperalgesia mice than normal mice. It was suggested that acidic NSAIDs specifically inhibit inflammatory pain. Moreover, yeast hyperalgesia mice are useful for the quantitative measurement of analgesic drugs.

Analgesics↗
PubMed1984

Host-mediated antitumor effect of DMG, a degraded D-manno-D-glucan from Microellobosporia grisea culture fluid.

DMG, a new polysaccharide with a well-characterized structure, isolated from the culture filtrate of an actinomycetes and then degraded by acid treatment, was tested for antitumor activity on allogeneic and syngeneic tumors in mice. In the allogeneic Ehrlich solid tumor system, DMG showed antitumor activity over a wide dose range, its optimal dose being 10-100 mg/kg. The optimal time of DMG administration was 1-2 weeks after tumor inoculation, but DMG was also effective when given before tumor inoculation. DMG was effective when given ip, sc, it (intratumorally) or iv. DMG also had antitumor effects on syngeneic tumors. It rapidly inhibited the growth of MM46 mammary carcinoma, MH134 hepatoma, and Meth A fibrosarcoma, and also inhibited spontaneous pulmonary metastases of B16-BL6 melanoma. However, it had no direct cytocidal action on tumor cells in vitro. Its antitumor activity was much less in athymic nude mice and in mice immunosuppressed by whole-body X-irradiation than in normal hosts.Thus, DMG was shown to exert antitumor activity via host-mediated mechanisms. Its antitumor activity is discussed in comparison with those of other antitumor polysaccharides.

Animals↗