Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 883 records · Page 49Linked to original sources

PubMed1990

Prolonged and ubiquitous inhibition by interferon gamma of bone resorption induced by parathyroid hormone-related protein, 1,25-dihydroxyvitamin D3, and interleukin 1 in fetal mouse forearm bones.

To investigate the mechanism of the inhibitory effects of interferon-gamma (IFN-gamma) on bone resorption, the effects of murine IFN-gamma on 45Ca release from prelabeled fetal mouse forearm bones were investigated. Murine IFN-gamma usually did not affect basal 45Ca release but almost completely and equipotently inhibited bone resorption induced by PTH(1-34), PTH-rP(1-34), 1,25(OH)2D3, and interleukin 1 (IL-1). The half-maximal concentration for inhibition of bone resorption induced by IL-1 alpha was 25.8 +/- 14.6 U/ml (mean +/- SD for 13 experiments), which is not different from those for PTH, PTH-rP, and 1,25(OH)2D3. There was no correlation between prostaglandin E2 concentration in the conditioned medium and 45Ca release from the IFN-gamma-treated forearm bones. The inhibitory effect of IFN-gamma on bone resorption induced by PTH-rP (1-34) or IL-1 alpha continued during 6 days of culture, whereas that of calcitonin disappeared after 2 days of culture. These findings suggest that IFN-gamma non-preferentially inhibits bone resorption induced by various bone-resorbing factors in fetal mouse forearm bones via a PGE2-independent mechanism. As no escape phenomenon developed in IFN-gamma-treated bones, the cytokine may be potentially useful for treatment of certain patients with malignancy-associated hypercalcemia.

Animals↗

PubMed1990

The cardiovascular effects of atracurium and it's metabolite.

The administration of atracurium to humans has been reported to produce little cardiovascular effects in clinical doses. The cardiovascular effect, histamine-releasing and catecholamine releasing effects of intravenous injection of atracurium 0.6 and 1.2 mg.kg(-1) were studied in man, and also the cardiovascular and catecholamine releasing effects of laudanosine which is a metabolite of atracurium by Hofmann degeneration, were studied in dogs. The increase in human plasma concentration of histamine, hypotension and tachycardia were found with the dose of atracurium 1.2 mg.kg(-1). The intravenous administration of laudanosine 10 micro g.kg(-1) to dogs produced minimal epinephrine, norepinephrine releases and cardiovascular changes.

Journal Article↗

PubMed1990

The purification and properties of aldose reductase from rat ovary.

Aldose reductase has been highly purified from rat ovary to apparent homogeneity, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme proved to be a monomeric protein with a molecular weight of about 39,900. The enzyme catalyzed the NADPH-dependent reduction of a number of aromatic and aliphatic aldehydes as well as aldo-sugars. The enzyme was potently inhibited by p-chloro-mercuribenzoate and a commercially developed aldose reductase inhibitor, M79175. The result of an immunoinhibition study, using antibody against the purified enzyme, indicated that the enzyme was responsible for more than 50% of the overall catalytic activity of D-glucose reduction in rat ovarian cytosol. Western blotting analysis revealed that immunoreactive proteins to anti-ovarian aldose reductase antibody were present in adrenal gland, various reproductive tissues, brain, lung, and heart of rats. Furthermore, ovarian tissues of various species contained immunoreactive proteins, though in small amounts. The enzyme was primarily localized in the granulosa cells and oocytes of all stages of follicular development during the estrous cycle, though it was also found in the corpora lutea cells in the pregnant rats.

Aldehyde Reductase↗

PubMed1990

Characterization of molecular species of liver microsomal carboxylesterases of several animal species and humans.

Seven carboxylesterase isozymes were purified to electrophoretic homogeneity from liver microsomes of mouse, hamster, guinea pig, rabbit, and monkey by the same procedure used previously to obtain three isozymes from the rat, and their physical, enzymological, and immunological properties were compared with those of the rat isozymes. The substrate specificity and immunological reactivity of liver microsomal carboxylesterases from pig, cow, beagle dog, and human were also examined for comparison, though these enzymes were not purified. The ten purified preparations have similar subunit weight (57,000-64,000), but their isoelectric points differ widely (4.7-6.5). The purification procedure of all isozymes included concanavalin A-Sepharose column chromatography. The isozymes were not eluted from the column with a high concentration of sodium chloride, but were efficiently eluted with alpha-methylmannoside. This observation suggested that the carboxylesterases studied are glycoproteins. All the isozymes except rat RL1 and RL2 possess a high hydrolytic activity toward all the substrates examined. Long-chain monoglyceride was hydrolyzed by the purified carboxylesterase isozymes. Anti-rat RH1 immunoglobulin G was found to possess high cross-reactivity with all isozymes tested, except monkey MK2, by immunoblotting analysis. The amino acid compositions of carboxylesterase isozymes showed considerable similarities, except for monkey MK2. The amino-terminal amino acid sequences showed a striking homology, except for monkey MK2, though the amino-terminal amino acid itself was different in every isozyme. Hepatic microsomal carboxylesterases in mammals play an important role in drug and lipid metabolism in the endoplasmic reticulum, and it is noteworthy that the isozymes from various species examined here showed considerable similarities in physical, enzymatic, and immunochemical properties.

Amino Acid Sequence↗

PubMed1990

Ultraviolet-induced suppressor T cells and factor(s) in murine contact photosensitivity. III. Mode of action of T-cell-suppressor factor(s) and interaction with cytokines.

The mode of action of T-cell-suppressor factor (TsF) induced by ultraviolet B (UVB) preirradiation in terms of interaction with several cytokines was studied. Suppression of murine contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) by preirradiation of the sensitizing site to low doses of UVB was caused by antigen-specific suppressor T cells (Ts) and was not associated with the generation of efferent limb-acting suppressor cells. TsF released by Ts inhibited the proliferation of immune lymph node (LN) cells in vitro and reduced interleukin (IL)-2 production of these cells in an antigen-specific fashion without affecting the IL-2 receptor (IL-2R) expression. Both rIL-2 and rGM-CSF have the ability to restore CPS responses in the UVB-preirradiated mice when administered after but not before photosensitization. However, rIL-2 but not rGM-CSF counteracted the in vivo inhibitory effect of TsF. rGM-CSF did not affect the density of I-A+ epidermal Langerhans cells (LCs). It was suggested that TsF inhibited IL-2-mediated immune T-cell proliferation, while rGM-CSF reconstituted the CPS by enhancing the function of photodamaged LCs. These results indicate multiple steps of the UVB-induced immunosuppression circuit, each of which seems to be controlled by different immunomodulators.

Animals↗

PubMed1990

Inhibitory effect of glucocorticoid and stimulatory effect of human chorionic gonadotropin on ovarian carbonyl reductase in rats.

Effects of three glucocorticoids on ovulation, and on content and activity of ovarian carbonyl reductase in rats were investigated. Glucocorticoid treatment caused both significant decrease in ovarian and uterine weights, blockade of ovulation and marked decrease in content and activity of ovarian carbonyl reductase. Furthermore, the weak immunoreactivity to antibody against ovarian carbonyl reductase was shown in the theca cells and the interstitial gland cells in the glucocorticoid-treated ovary. The treatment with hCG (LH activity specific) restored the ovarian weight, and both the content and activity of ovarian carbonyl reductase, which were inhibited by glucocorticoids, to control level as well as ovulation. These results indicate that the ovarian carbonyl reductase may be closely involved in ovarian function, especially ovulation, and may be an LH-dependent enzyme, because it is well known that glucocorticoids inhibit both LH surge and ovulation in rats.

Alcohol Oxidoreductases↗

PubMed1990

An epoxysuccinic acid derivative(loxistatin)-induced hepatic injury in rats and hamsters.

Loxistatin is a possible therapeutic agent of muscular dystrophy. A single oral administration of loxistatin to male rats caused focal necrosis of the liver with inflammatory cell infiltration. The severity of the lesions was dose-dependent up to 200 mg/kg and also manifest by an increase in serum alanine aminotransferase and aspartate aminotransferase activities. Hepatic glutathione (GSH) levels decreased with a maximum 20% depletion within 5 hr after the oral administration of loxistatin. Pretreatment with diethyl maleate did not potentiate the loxistatin-induced hepatic injury. On the other hand, the hepatoprotective effect of cysteamine was observed when cysteamine was administered 24 hr before loxistatin dosing, but the effect was not observed when the antidote was administered concomitantly with loxistatin. Pretreatment of rats with phenobarbital or trans-stilbene oxide provided partial protection against the hepatotoxic effect of loxistatin. Pretreatment with SKF-525A resulted in increased hepatic injury, while pretreatment with piperonyl butoxide, cimetidine, or 3-methylcholanthrene had no effect on hepatic damage by loxistatin. Five hours after [14C]loxistatin administration to rats, the covalent binding of the radioactivity to proteins was greatest in the liver, followed by the kidney, then muscle and blood to a lesser extent. [14C]Loxistatin acid, the pharmacologically active form of loxistatin, irreversibly bound to rat liver microsomal proteins; more binding occurred when the NADPH-generating system was omitted and when the microsomes were boiled first. GSH did not alter the extent of irreversible binding, whereas N-ethylmaleimide decreased the binding of [14C]loxistatin acid to rat liver microsomal proteins by 75%. Unlike the rat, administration of loxistatin to hamsters caused neither hepatic injury nor hepatic GSH depletion even at a high dose (500 mg/kg). Both the distribution and covalent binding of radioactivity in the hamster liver were one-third of those in rats following [14C]loxistatin dosing. These results suggest that loxistatin causes species-specific hepatotoxicity and that, at least in part, some of the toxic effects of loxistatin are mediated by the nonenzymatic covalent binding of loxistatin acid to thiol residues on cellular macromolecules.

Alanine Transaminase↗

PubMed1990

Stimulation by a TRH precursor, TRH-Gly, of TSH and PRL secretion in rats: effect of starvation.

The hypophysial activities of a possible direct precursor of thyrotropin (TSH)-releasing hormone (TRH), TRH-Gly, were evaluated in estrogen, progesterone-primed rats under urethane anesthesia. Intravenous administration of TRH-Gly in doses of 2-200 micrograms caused a significant and dose-dependent increase in blood TSH and prolactin (PRL). The stimulatory activity of TRH-Gly was 170 to 400-times less potent than that of TRH. The lower potency was confirmed by the action of TRH-Gly on the anterior pituitary cells in vitro. In starved rats, TRH-Gly apparently stimulated TSH and PRL secretion in a dose-dependent manner, and the stimulatory activity increased in starved rats as compared to normal controls. TRH-Gly did not affect [3H-MeHis]TRH binding in pituitary plasma membranes. These data imply that large amounts of TRH-Gly may have significant biological activities and these are potentiated in the starved condition.

Animals↗

PubMed1990

Platelet-derived growth factor stimulates formation of active p21ras.GTP complex in Swiss mouse 3T3 cells.

The ras gene product (p21) is a GTP-binding protein and is thought to play an important role in signal transduction of growth and differentiation in many types of mammalian cells. The p21.GTP complex is an active conformation, as described previously for polypeptide chain elongation factors (EF-Tu and EF-G) and heterotrimeric GTP-binding proteins (G proteins). In the study reported here, we measured the amounts of p21-bound guanine nucleotides under various conditions in the G54 cell line, a derivative of Swiss 3T3 cells that overexpresses normal c-Ha-ras. More p21.GTP complexes were present in growing cells than in quiescent cells. When quiescent cells were stimulated with fetal bovine serum to promote DNA synthesis, p21.GTP increased approximately 2-fold. Among a number of purified growth factors, platelet-derived growth factor enhanced the formation of p21.GTP, whereas the combination of bombesin and insulin, which also induces DNA synthesis, did not. These results strongly suggest that p21 is a transducer of the growth signal from the platelet-derived growth factor receptor in Swiss 3T3 cells and that the signal is transmitted through a p21.GTP complex.

Animals↗

PubMed1990

Accumulation of p21ras.GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity.

The ras gene product (p21) is a GTP-binding protein and has been thought to transduce signals regulating proliferation or differentiation of cells. Like other GTP-binding proteins, p21.GTP is an active conformation, which can transduce the signals downstream, whereas p21.GDP is an inactive one. Recently, we have shown that p21.GTP levels increased in cells treated with fetal bovine serum or platelet-derived growth factor to initiate DNA synthesis. In this paper, we report that epidermal growth factor can also increase the amounts of p21.GTP in the cells. Effects of epidermal growth factor and platelet-derived growth factor are not additive. In contrast, mutant [Val12]p21, which has transforming activity, responded neither to platelet-derived growth factor nor to epidermal growth factor. We also found that the ratio of p21.GTP to p21.GDP increased 3- to 4-fold in transformants carrying activated erbB-2/neu or v-src oncogenes. These results strongly suggest an important role of p21 in transduction of signals for both normal proliferation and malignant transformation through growth factor receptors with tyrosine kinase activity or related oncogene products.

Animals↗

PubMed1990

The inositol 1,4,5,-trisphosphate receptor in cerebellar Purkinje cells: quantitative immunogold labeling reveals concentration in an ER subcompartment.

The Ca2+ mobilization effect of inositol 1,4,5-trisphosphate, the second messenger generated via receptor-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate, is mediated by binding to intracellular receptors, which are expressed in high concentration in cerebellar Purkinje cells. Partially conflicting previous reports localized the receptor to various subcellular structures: elements of ER, both rough and smooth-surfaced, the nuclear envelope, and even the plasma membrane. We have now reinvestigated the problem quantitatively by using cryosections of rat cerebellar tissue immunolabeled with polyclonal monospecific antibodies against the inositol 1,4,5-trisphosphate receptor. By immunofluorescence the receptor was detected only in Purkinje cells, whereas the other cells of the cerebellar cortex remained negative. In immunogold-decorated ultrathin cryosections of the Purkinje cell body, the receptor was concentrated in cisternal stacks (piles of up to 12 parallel cisternae separated by regularly spaced bridges, located both in the deep cytoplasm and beneath the plasma membrane; average density, greater than 5 particles/micron of membrane profile); in cisternal singlets and doublets adjacent to the plasma membrane (average density, approximately 2.5 particles/micron); and in other apparently smooth-surfaced vesicular and tubular profiles. Additional smooth-surfaced elements were unlabeled. Perinuclear and rough-surfaced ER cisternae were labeled much less by themselves (approximately 0.5 particles/micron, two- to threefold the background), but were often in direct membrane continuity with heavily labeled, smooth-surfaced tubules and cisternal stacks. Finally, mitochondria, Golgi cisternae, multivesicular bodies, and the plasma membrane were unlabeled. In dendrites, approximately half of the nonmitochondrial, membrane-bound structures (cisternae, tubules, and vesicles), as well as small cisternal stacks, were labeled. Dendritic spines always contained immunolabeled cisternae and vesicles. The dendritic plasma membrane, of both shaft and spines, was consistently unlabeled. These results identify a large, smooth-surfaced ER subcompartment that appears equipped to play a key role in the control of Ca2+ homeostasis: in particular, in the generation of [Ca2+]i transients triggered by activation of specific receptors, such as the quisqualate-preferring trans(+/-)-1-amino-1,3-cyclopentamedicarboxylic acid glutamatergic receptors, which are largely expressed by Purkinje cells.

Animals↗

PubMed1990

Intracoronary endothelin-1 increases coronary retrograde pressure by constricting arterioles.

STUDY OBJECTIVE: The aim was to determine the site of coronary vasoconstriction induced by endothelin, by investigating the response in terms of retrograde pressure and reactive hyperaemia. EXPERIMENTAL MATERIAL: Twelve anaesthetised mongrel dogs, 12-14 kg, were used for the studies. DESIGN: The left anterior descending coronary artery was cannulated and perfused with blood through an extracorporeal bypass. The effects of intracoronary endothelin-1 (1-500 pmol) on coronary blood flow, coronary flow reserve (the peak reactive flow and the repayment after 15 s coronary occlusion), and retrograde coronary pressure during coronary occlusion were studied (n = 7). The retrograde coronary flow was collected from the bypass at each dose (n = 5). MEASUREMENTS AND MAIN RESULTS: At doses of greater than 20 pmol the coronary flow decreased dose dependently and reached almost zero flow at 500 pmol. The coronary flow reserve also decreased; however, the retrograde pressure was raised dose dependently at doses of greater than 10 pmol. At a dose of 500 pmol, the retrograde pressure was increased to 61 mm Hg [82(SEM 12)% of the coronary perfusion pressure]. Retrograde flow remained unchanged throughout the experiment. CONCLUSIONS: The endothelin-1 induced rise in retrograde pressure is in accordance with a dose dependent reduction in coronary flow reserve, and collateral flow was not augmented by endothelin. It is concluded that the effect of endothelin-1 on coronary circulation in situ was mainly due to the constriction of small resistant vessels.

Animals↗

PubMed1990

Calcium-dependent control of caldesmon-actin interaction by S100 protein.

Caldesmon from chicken gizzard muscle has been examined for ability to interact with S100 protein using sedimentation, low-shear viscosity, and affinity chromatography. Ca2+/S100 protein, like Ca2+/calmodulin, inhibited the binding of caldesmon to F-actin in a concentration-dependent manner and the inhibition was not observed in the absence of Ca2+. Caldesmon was bound to S100 protein-Sepharose in the presence of Ca2+ and released with EGTA, indicating that there is a direct interaction between caldesmon and S100 protein. The binding of S100 protein to caldesmon also relieved actomyosin Mg2(+)-ATPase inhibition by caldesmon. The molar ratio of S100 protein to caldesmon required for half-maximal restoration was about 0.3, a value less than that in the case of calmodulin. S100 protein, however, was less effective in terms of the maximal extent of the restoration. With respect to Ca2(+)-sensitivity, the restoration profiles were monophasic with a midpoint at 3 x 10(-5) M for S100 protein and 8 x 10(-6) M for calmodulin. The restoration by S100 protein was almost wholly inhibited by TFP, but not by W-7. Taken together, our results suggest that a Ca2(+)-binding protein other than calmodulin may regulate caldesmon-dependent cellular functions.

Actins↗

PubMed1990

Immunological and enzymological localization of carbonyl reductase in ovary and liver of various species.

The tissue distribution of carbonyl reductase in ovary and liver of various animal species was investigated by measuring the reduction of 13,14-dihydro-15-keto-prostaglandin F2a, a specific substrate for rat ovarian carbonyl reductases, and by means of Western blotting analysis using anti-rat ovarian carbonyl reductase antibody. The highest ovarian carbonyl reductase activity towards 13,14-dihydro-15-keto-PGF2a was found in rat among ten animal species tested, followed by hamster and monkey. The immunoreactive protein was detected in hamster and monkey ovaries. Although carbonyl reductase activity towards 13,14-dihydro-15-keto-PGF2a was not detectable in non-pregnant rabbit ovary, pregnant rabbit ovary showed not only moderate activity but also immunoreactivity with anti-rat ovarian carbonyl reductase antibody. On the other hand, carbonyl reductase activity towards 13,14-dihydro-15-keto-PGF2a was detected in hepatic tissue of all the species tested, except for rat and left-eye flounder. Immunoreactive proteins were present in hepatic tissue of various species that exhibited measurable carbonyl reductase activity towards 13,14-dihydro-15-keto-PGF2a.

Alcohol Dehydrogenase↗

PubMed1990

Changes in rat ovarian carbonyl reductase activity and content during the estrous cycle, and localization.

Carbonyl reductase activity and content in the rat ovary were measured at various stages of the estrous cycle, and the enzyme protein in the ovary was localized by immunohistochemistry. The enzyme activity increased after the preovulatory surge of luteinizing hormone (LH) on proestrus, and the enzyme content began to increase prior to the LH surge. Although the enzyme content reached the highest level at 2000 h and remained at a plateau for 8 h, the enzyme activity increased linearly until it reached the highest level at 0800 h on the morning of estrus. At their maximum, enzyme activity and content were approximately 1.5-fold and 2-fold greater, respectively, then basal diestrus values. The enzyme protein amounted to 1-4% of the ovarian cytosolic protein. An immunohistochemical study revealed that the enzyme was primarily localized in interstitial gland cells and theca interna cells of secondary and Graafian follicles as well as atretic follicles.

Alcohol Oxidoreductases↗

PubMed1990

Changes and localization of ovarian carbonyl reductase during pseudopregnancy and pregnancy in rats.

The present study investigates changes in the activity and enzyme content of ovarian carbonyl reductase (CR), which catalyzes the reduction of 9-keto and 15-ketoprostaglandins in rats during pseudopregnancy and pregnancy. The activity of ovarian CR decreased from the onset of pseudopregnancy and pregnancy, reaching 20-30% of the Day 1 value by Day 12 of pseudopregnancy and 50-60% of the Day 1 value by Day 14 of pregnancy. In the case of pregnant rats, the enzyme activity maintained a minimal level between Day 14 of pregnancy and Day 22 of parturition. An acute increase of the enzyme activity was found on the morning after parturition. The CR content in the ovary maintained a constant level from Day 1 to Day 12 of pseudopregnancy and to Day 18 of pregnancy. In pregnant rats, there was a gradual decrease after 18 days and then a surge during parturition. CR was primarily localized in interstitial gland cells and in theca interna cells but was not found in corpora lutea cells in the ovary during the estrous cycle. Additional immunostaining was also observed in corpora lutea cells during pseudopregnancy and pregnancy. The changes in ovarian CR activity, i.e. the rapid decrease with progressing pseudopregnancy and pregnancy, correlated with the increase in progesterone and the decrease in LH. These results indicate that rat ovarian CR may be regulated via the hypothalamo-pituitary-ovarian axis and may also be involved in luteal function.

Alcohol Oxidoreductases↗

PubMed1990

Genetic control of contact photosensitivity to tetrachlorosalicylanilide. I. Preferential activation of suppressor T cells in low responder H-2k mice.

The genetic control of contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) was studied in H-2- and IgH-congenic mice. The H-2 complex was found to play a major role in determining the pattern of responsiveness, whereas the effect of the Igh locus on the response was not apparent. The H-2k haplotype was closely associated with low responders, whereas mice with the H-2b,d alleles were high responders. The responsiveness of the H-2k strains was converted from low to high levels by treatment with cyclophosphamide (CY) before photosensitization. Transfer of spleen cells from photosensitized H-2k mice showed a suppressive effect on the development of the CPS reaction of syngeneic recipients pretreated with CY. These spleen cells contained antigen-specific CD4+, CD8- suppressor T cells (Ts) that functioned in the induction phase of CPS. The in vitro proliferation of immune lymph node T cells pulsed with photohapten-coupled cells plus peritoneal adherent cells was suppressed by the addition of anti-I-A monoclonal antibody in both H-2d and H-2k strains, suggesting that the I-A molecule are responsible for inducing the positive immune response. On the other hand, such proliferation was significantly enhanced by the addition of anti-I-E alpha antibody in H-2k, but not H-2d, mice. This implies that the low responsiveness of CPS in the H-2k strain is due to the preferential activation of Ts via I-Ek molecules. The present observation further supports the important role of the I-E molecule in the suppressor circuit of CPS to TCSA.

Animals↗

PubMed1990

Histological diagnostic criteria for accessory tragi.

The histological features of accessory tragi from 13 patients were analyzed. All the lesions showed numerous tiny mature hair follicles in various phases, while the presence of cartilage was not essential. Of importance was the prominent connective tissue framework in the subcutaneous fat that seemed to be one of the diagnostic criteria for accessory tragi.

Adolescent↗