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Biomedical subjects

K Furuno

Publications and source records attributed to K Furuno.

At least 127 records · Page 7Linked to original sources
PubMed1989

Effect of acute treatment of mice with L-histidine on the brain levels of amino acids.

The brain histidine level in mice dose-dependently increased 1 and 2 hr after an i.p. injection of 0.5-1.5 g/kg of L-histidine. The treatment with 1.0 and 1.5 g/kg but not 0.5 g/kg of L-histidine significantly decreased the brain levels of tyrosine, phenylalanine and some other amino acids 1 hr later. A complete recovery or a rebound rise of amino acid levels was observed 2 hr after treatment. These results indicate that there is a change in the transport of amino acids into the brain after treatment with large doses of L-histidine.

Amino Acids↗
PubMed1989

Influence of electric foot shock on pharmacokinetics of isosorbide dinitrate orally administered to rats.

The influence of emotional stress on the pharmacokinetics of isosorbide dinitrate (ISDN) was studied in rats. Plasma levels of orally administered ISDN and metabolites (5-isosorbide mononitrate and 2-isosorbide mononitrate) were lower in rats emotionally stressed by foot shock than in non-stressed control rats. The decrease in the ISDN levels may be mainly due to the delay of drug absorption from the gastrointestinal tract.

Administration, Oral↗
PubMed1989

Influence of electric foot shock on pharmacokinetics of isosorbide dinitrate subcutaneously administered to rats.

The influence of emotional stress on the pharmacokinetics of isosorbide dinitrate (ISDN) administered s.c. to rats was studied. The plasma level of ISDN in emotionally stressed (ES) rats was the same as that in non-stressed control rats. However, the levels of its metabolites, 5-isosorbide mononitrate (5-ISMN) and 2-isosorbide mononitrate (2-ISMN), were markedly lower in ES rats than in the control rats. On the other hand, urine ISDN and 2-ISMN excretion rates were lower in ES rats than in the control rats. These observations suggest that the pharmacokinetics of ISDN administered s.c. is influenced by emotional stress such as foot shock.

Animals↗
PubMed1989

Bilateral slowly progressive big blind spot syndrome.

A 33-year-old woman was found with bilateral enlargement of the blind spot without optic disc edema. Her bilateral peripapillary retinas appeared slightly decolored and elevated with obscure margins and fluorescein angiography indicating only slight hyperfluorescence in the late venous phase. Four years after her initial visit, both of her blind spots became enlarged further and dark adaptation was remarkably difficult. Peripapillary retinal lesions appearing as retinal pigmentary degeneration were evident with very definitive margins. The lesions showed strong hyperfluorescence in the arteriovenous phase owing to window defects. From these findings, it appears that bilateral big blind spots without optic disc edema may possibly result from peripapillary retinal degeneration, which may become evident at a much later date.

Adult↗
PubMed1988

Biosynthesis and processing of lysosomal cathepsin L in primary cultures of rat hepatocytes.

The biosynthesis and proteolytic processing of lysosomal cathepsin L was studied using in vitro translation system and in vivo pulse-chase analysis with [35S]methionine and [32P]phosphate in primary cultures of rat hepatocytes. Messenger RNA prepared from membrane-bound but not free polysomes directed the synthesis of a primary translation product of an immunoprecipitable 37.5-kDa cathepsin L in vitro. The 37.5-kDa form was converted to the 39-kDa form when translated in the presence of dog pancreas microsomes. During pulse-chase experiments with [35S]methionine in cultured rat hepatocytes, cathepsin L was first synthesized as a 39-kDa protein, presumably the proform, after a short time of labeling, and was subsequently processed into the mature forms of 30 and 25 kDa in the cell. On the other hand, considerable amounts of the proenzyme were found to be secreted into the culture medium without further proteolytic processing during the chase. The precursor and mature enzymes were N-glycosylated with high-mannose-type oligosaccharides, and the proenzyme molecule contained phosphorylated oligosaccharides. The effects of tunicamycin and chloroquine were also investigated. In the presence of tunicamycin, a 36-kDa unglycosylated polypeptide appeared in the cell and this protein was exclusively secreted from the cells without undergoing proteolytic processing. These results suggest that cathepsin L is initially synthesized on membrane-bound polysomes as a 37.5-kDa prepropeptide and that the cotranslational cleavage of the 1.5-kDa signal peptide and the core glycosylation convert the precursor to the 39-kDa proform, which is subsequently processed to the mature form during biosynthesis. Thus, the biosynthesis and secretion of lysosomal cathepsin L in rat hepatocytes seem to be analogous to those of the major excreted protein of transformed mouse fibroblasts [S. Gal, M. C. Willingham, and M. M. Gottesman (1985) J. Cell Biol. 100, 535-544] and the mouse cysteine proteinase of activated macrophages [D.A. Portnoy, A. H. Erickson, J. Kochan, J. V. Ravetch, and J. C. Unkeless (1986) J. Biol. Chem. 261, 14697-14703].

Animals↗
PubMed1988

Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin 1 or other known monokines.

During sepsis or after injection of endotoxin into rats, there is a large increase in muscle protein breakdown and prostaglandin E2 (PEG2) production. Prior studies showed that partially purified interleukin 1 (IL-1) from human monocytes can stimulate these processes when added to isolated rat muscles. The availability of pure recombinant IL-1 and other monokines has allowed us to investigate the identity of the active agent in this process. Incubation of muscles with recombinant human or murine IL-1 alpha or IL-1 beta or with IL-1 plus a phorbol ester did not stimulate muscle proteolysis or PGE2 production. Homogeneous natural porcine IL-1 ("catabolin") and mouse or human IL-1 beta were also not effective in vitro. In addition, a variety of other human cytokines, including tumor necrosis factor ("cachectin"), epidermal thymocyte-activating factor, eosinophil cytotoxicity-enhancing factor, interferon-alpha, beta, and gamma, platelet-derived growth factor, and transforming growth factor (TGF) beta, which are all released by activated macrophages, TGF-alpha, or mixtures of these polypeptides, also failed to activate proteolysis or PGE2 production. By contrast, a large increase in net protein breakdown could be induced in the rat soleus by polypeptides released from porcine monocytes or by the serum from febrile cattle which had been injected with Pasteurella haemolytica or bovine rhinotracheitis virus. Therefore, a still-unidentified product of activated monocytes appears to be responsible for the negative nitrogen balance that accompanies infectious illness.

Animals↗
PubMed1986

The activation of protein degradation in muscle by Ca2+ or muscle injury does not involve a lysosomal mechanism.

By use of different inhibitors, we distinguished three proteolytic processes in rat skeletal muscle. When soleus muscles maintained under tension were exposed to the calcium ionophore A23187 or were incubated under no tension in the presence of Ca2+, net protein breakdown increased by 50-80%. Although leupeptin and E-64 inhibit this acceleration of protein breakdown almost completely, other agents that prevent lysosomal function, such as methylamine or leucine methyl ester, did not inhibit this effect. A similar increase in net proteolysis occurred in muscle fibres injured by cutting, and this response was also inhibited by leupeptin, but not by methylamine. In contrast, all these inhibitors markedly decreased the 2-fold increase in protein breakdown induced by incubating muscles without insulin and leucine, isoleucine and valine. In addition, the low rate of proteolysis seen in muscles under passive tension in complete medium was not affected by any of these inhibitors. Thus the basal degradative process in muscle does not involve lysosomes or thiol proteinases, and muscle can enhance protein breakdown by two mechanisms: lack of insulin and nutrients enhances a lysosomal process in muscle, as in other cells, whereas Ca2+ and muscle injury activate a distinct pathway involving cytosolic thiol proteinase(s).

Animals↗
PubMed1986

Biosynthesis and intracellular transport of rat liver 5'-nucleotidase.

To investigate biosynthesis and intracellular transport of 5'-nucleotidase, we purified this enzyme from rat liver and prepared antibodies. In immunoblot analysis, 5'-nucleotidase from the plasmalemmal, Golgi, and tritosomal fractions migrated as a single band of 72 kDa. The immunoreactive 68-kDa band was detected in the rough microsomal fraction and only the 72-kDa polypeptide contained sialic acids. The single polypeptide of 61 kDa immunoprecipitated from the translation products with the membrane-bound polysomal RNAs by the cell-free system converted to the 68-kDa form associated with membranes, when translated in the presence of microsomal vesicles. 5'-Nucleotidase from cultured primary hepatocytes pulse-labeled with [35S]methionine for 20 min migrated as a 68-kDa polypeptide. Within 45 min of chase, the 68-kDa form was converted to the 72-kDa form. Upon treatment with tunicamycin, a new immunoreactive polypeptide of 59 kDa was obtained. These results suggest that 5'-nucleotidase is translated on the membrane-bound polysomes as a 61-kDa precursor and that the cleavage of the 2-kDa signal peptide and the core glycosylation co-translationally convert the precursor to the 68-kDa form, which is subsequently processed in the Golgi complex to the 72-kDa form.

5'-Nucleotidase↗
PubMed1986

Lack of evidence for the involvement of catecholaminergic mechanisms in the behavioral anti-methamphetamine effect of L-histidine in the mouse.

The effects of L-histidine (HIS) on the hypermotility and the changes in brain monoamine dynamics induced by methamphetamine (MAMP) were examined in mice. HIS (1000 mg/kg) completely inhibited the hypermotility induced by MAMP (1 mg/kg). MAMP (1 mg/kg) significantly increased the dopamine level and decreased the 3,4-dihydroxyphenylacetic acid level. MAMP (5 and 10 mg/kg) also produced changes in the levels of noradrenaline, serotonin and their metabolites. HIS administered alone caused no significant changes in the levels of these amines and metabolites, nor did it affect MAMP-induced alterations in monoamine dynamics. These results suggest that catecholaminergic mechanisms are not involved in the behavioral anti-MAMP action of HIS.

Animals↗
PubMed1985

Accumulation of autolysosomes after receptor-mediated introduction of Ep459-asialofetuin conjugate into lysosomes in rat hepatocytes.

Administration of Ep459-asialofetuin conjugate (Ep459-AF) and pepstatin-asialofetuin conjugate (Ps-AF) to rats effectively inhibited lysosomal BANA hydrolase and cathepsin D in the liver, respectively, at a very low dose. Ep459-AF treatment also led to an accumulation of autolysosomes in rat liver. There was a close correlation between the accumulation of autolysosomes and the inhibition of BANA hydrolase activity. However, as opposed to the inhibition of thiol proteases, the inhibition of cathespin D did not cause accumulation of autolysosomes in the rat liver. These results suggest that autophagy in rat hepatocytes is a common occurrence under normal physiological conditions and that thiol proteases are digestive enzymes essential for the autolysomes.

Aminopeptidases↗
PubMed1985

Determination of the onset of beta-methyl-digoxin action by potentiation of the adenosine response in guinea pigs.

The onset of beta-methyl-digoxin action was investigated by the potentiation of the adenosine response in guinea pigs and rats, and compared with that of digoxin and dipyridamole. A number of i.v. infusions of adenosine were given to determine the mean control adenosine response and its 95% confidence limits. After oral administration of the drugs, successive infusions of adenosine were continued until a drug-induced potentiation of the adenosine response was observed. The time of appearance of the potentiated adenosine response was marked as the onset of action of the drugs. The onset of action in guinea pigs was 9 to 12 min for 0.2 to 0.4 mg/kg of beta-methyl-digoxin, 90 to 100 min for 0.2 mg/kg of digoxin and 25 min for 5 mg/kg of dipyridamole. The maximal potentiation was 48.8 to 53.8% at 18 to 21 min for beta-methyl-digoxin, 74.5% at 130 min for digoxin and 74.8% at 80 min for dipyridamole. Adenosine infused i.v. into rats produced heart block, as in guinea pigs. However, in rats, the adenosine response was not potentiated by beta-methyl-digoxin and digoxin. Dipyridamole at a dose as high as 200 mg/kg produced 25.8% potentiation at 36 min after oral administration to rats.

Adenosine↗
PubMed1985

[Studies on CA 125, CA 19-9, TPA and IAP as tumor markers in patients with ovarian cancer].

CA 125, CA 19-9, TPA and IAP were useful for diagnosis of ovarian cancer. CA 125 was localized immunohistochemically in the surface and cytoplasma of cancer cells of serous cystadenocarcinomas, clear cell carcinomas, endometrioid carcinomas and undifferentiated carcinomas and CA 19-9 localized in mucinous cystadenocarcinomas and endometrioid carcinomas. When the cut off value of CA 125 was set by 35 U/ml in the control group, the patients with serous cystadenocarcinoma showed positive in 81%, resulting by 1,766.5 U/ml as an average value. As for CA 19-9 having set by 37 U/ml as the cut off value, patients suffering from mucinous cystadenocarcinoma who revealed positive by 60%, were 194 U/ml in an average value. It is considered that measuring values of CA 125 and CA 19-9 are valuable not only to diagnose as ovarian cancers but also to evaluate their prognosis.

Adenocarcinoma, Mucinous↗
PubMed1984

Characterization of subfractions of autolysosomes isolated from rat liver after leupeptin treatment.

Autolysosomes were isolated from leupeptin-treated rat liver (Furuno, K., Ishikawa, T., & Kato, K. (1982) J. Biochem. 91, 1943-1950). They were disrupted by hypotonic treatment and subfractionated by centrifugation in a discontinuous sucrose gradient into three distinct parts: the membranes, the soluble contents, and the insoluble remnants. The content fraction contained the bulk of the activities of lysosomal enzymes with a protein yield of about 36%. The membrane fraction, representing about 5% of protein of the autolysosomes, had a high specific activity of acid phosphatase. In SDS-polyacrylamide gel electrophoretic analysis, the autolysosomal membranes showed protein profiles similar to those of normal lysosomal membranes. The aggregates of partially digested cellular components, including organelles, in the autolysosomes were recovered as granular materials with a very high density (designated as the remnant fraction). This fraction accounted for more than half of protein of the autolysosomes but contained little of the activities of lysosomal enzymes. Lipid analyses revealed that the autolysosomes were poor in lipids because the lipid content of the insoluble remnants was very low. Measurements of the rate of protein degradation in vitro in the crude lysosomal fraction and the isolated autolysosomes from leupeptin-treated rat liver showed that proteolysis was suppressed within the autolysosomes. It was suggested that lipids of sequestered cellular components were preferentially digested within the autolysosomes due to the inhibition of proteolytic activity by leupeptin, and the resulting massive accumulation of proteins was responsible for the enhanced autolysosomal density.

Animals↗
PubMed1984

[A study on tumor marker of tissue-polypeptide-antigen (TPA) in gynecologic malignancies].

Tissue polypeptide-antigen (TPA), a tumor-associated antigen reported by Bjorklund et al., is a single chain polypeptide of approximately 22,000-45,000 molecular weight, which is being studied in various fields as a tumor marker. We determined the serum TPA level and tissue distribution of TPA in patients with gynecologic malignancies and healthy women. In healthy women, the serum TPA level was under 110 mu/l, without any relation to age or sex. In benign tumors, the mean serum TPA was 123.9 mu/l and it is comparable with that in healthy women. In cervical cancers, it was 212 mu/l and significantly higher than those in healthy women and in patients with benign tumors (p less than 0.01). In ovarian cancers, it was 414.7 mu/l, which showed significantly higher levels of serum TPA in ovarian cancers than those in healthy women and in patients with benign tumor, and it was also significantly higher than that in cervical cancers (p less than 0.001). As for the values after treatment, the serum TPA level clearly tended to fall in patients exhibiting good response, and tended to rise in those showing poor response. TPA was markedly localized in the cancer cells, but was almost entirely absent from the normal tissues of the cervix and endometrium.

Adenocarcinoma, Mucinous↗