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Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 415 records · Page 23Linked to original sources
PubMed1989

Differential inhibition by staurosporine, a potent protein kinase C inhibitor, of 12-O-tetradecanoylphorbol-13-acetate-caused skin tumor promotion, epidermal ornithine decarboxylase induction, hyperplasia and inflammation.

The effect of staurosporine on 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin papilloma formation was examined in CD-1 mice. A topical application of staurosporine 15 min prior to each TPA treatment resulted in a dose-related inhibition of tumor formation. Staurosporine by itself had no tumor producing activity in DMBA-initiated mice. Staurosporine failed to prevent TPA-induced edema formation, whereas quercetin markedly suppressed it. Staurosporine by itself did not induce a significant edema. Histological studies revealed that staurosporine failed to inhibit TPA-induced inflammation but rather augmented TPA-induced polymorphonuclear leukocyte (PMN) infiltration. Staurosporine by itself induced a slight PMN infiltration 1 h after the drug application, but the effect was only transient. Although staurosporine failed to inhibit the TPA-induced epidermal hyperplasia and DNA synthesis significantly, nuclear atypism of the superficial layer of the epidermis appeared to be less remarkable in staurosporine-pretreated mice. TPA-caused epidermal ornithine decarboxylase (ODC) induction was not inhibited by staurosporine but rather augmented by this agent. TPA enhanced the phosphorylation of 34 kd protein in intact epidermal cells in a concentration-dependent manner. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) suppressed the TPA-stimulated phosphorylation of 34 kd protein, but palmitoylcarnitine failed to suppress it. In addition, TPA-stimulated superoxide generation of rabbit peritoneal PMN was potently inhibited by staurosporine. It is possible that TPA induces inflammation, ODC activity, epidermal hyperplasia and tumor promotion through the activation of different type(s) of protein kinase C and staurosporine inhibits only certain type(s) of protein kinase C. Another possible explanation is that the protein kinase C inhibition by staurosporine depends on the nature of the substrate proteins or the intracellular localization of the enzyme.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Enzymatic acetylation and sulfation of N-hydroxyarylamines in bacteria and rat livers.

In mammalian hepatic cytosol both acetyltransferase and sulfotransferase are involved in the activation of N-hydroxy derivatives of arylamines and arylamides. The role of acetyltransferase is also shown in Salmonella, whereas no rigid evidence is provided on the role of sulfotransferase in Salmonella. In Ames mutagenesis test without S9-mix, the number of revertants of Salmonella typhimurium TA98 induced was 10-fold higher with 2-hydroxyamino-3-methylimidazo[4,5-f] quinoline (N-hydroxy-IQ) than with 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1). The extents of the binding to calf thymus DNA of N-hydroxy-Glu-P-1 were, however, 3.9 to 8.6-fold higher than that of N-hydroxy-IQ in both acetyl CoA- and PAPS-fortified rat hepatic cytosol systems. To understand the mechanism causing the apparent discrepancy between the results of the mutation and DNA binding, the activating capacities of cytosols of S. typhimurium TA98 and TA98/1,8-DNP6 strains on the binding of N-hydroxy-Glu-P-1 and N-hydroxy-IQ have been examined in comparison with those of rat livers. Although both N-hydroxyarylamines were activated by hepatic cytosols in the presence of PAPS, no significant DNA binding of these N-hydroxyarylamines was detected in the presence of PAPS and either one of the two strains of bacterial cytosols. In addition, both cytosols of TA98 and TA98/1,8-DNP6 strains showed no measurable activity on the sulfation of p-nitrophenol, suggesting no capacity for sulfotransferase-mediated activation of N-hydroxyarylamines in Salmonella. On the contrary, the extents of the acetyl CoA-dependent binding of N-hydroxy-IQ in cytosols of TA98, but not of TA98/1,8-DNP6, were respectively 6- and 9-fold higher than those in hepatic cytosols of male and female rats, although the extents of the binding of N-hydroxy-Glu-P-1 were rather higher in hepatic than in bacterial cytosols. In addition, the covalent binding of N-hydroxy-2-acetylaminofluorene to DNA was detected in hepatic, but not in bacterial cytosols, although the binding of N-hydroxy-2-aminofluorene was detectable in both hepatic and bacterial cytosols in the presence of acetyl CoA. These results indicate that the metabolic activating capacities of Salmonella and rat liver cytosols differ qualitatively, and the difference in the substrate specificity of acetyltransferase between Salmonella and rat livers may be involved, in part, in the difference of their DNA damage in bacteria and mammals.

Acetyltransferases↗
PubMed1989

Role of growth hormone in modulating the constitutive and phenobarbital-induced levels of two P-450(6)beta (testosterone 6 beta-hydroxylase) mRNAs in rat livers.

The role of growth hormone in the expression of two forms of hepatic cytochrome P-450(P-450), P-450(6)beta-1(6 beta-3), and P-450(6)beta-4, was investigated using RNA blots. The level of P-450(6)beta-1(6 beta-3) mRNA was twenty times higher than that of P-450(6) beta-4 mRNAs in untreated male rat livers. The levels of P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs were increased two fold and three fold, respectively, by hypophysectomy of adult male rats. By intermittent injection of human growth hormone (hGH) into hypophysectomized male rats, both mRNAs were decreased to the level of normal rats, and almost disappeared after continuous infusion of hGH. In female rats, these two mRNAs were not detected, but were increased remarkably by hypophysectomy. The increases in these mRNAs were almost abolished after continuous infusion of hGH in hypophysectomized female rats. The effect of hGH on PB-mediated induction of P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs was also examined. The PB-mediated increases in P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs were higher in hypophysectomized male rats (2.5-fold and 10.9-fold, respectively) than in normal male rats (1.5-fold and 5.2-fold, respectively). Thus, the levels of P-450(6)beta-1(6-beta-3) and P-450(6)beta-4 mRNAs were 4.1-fold and 7.3-fold, respectively, higher in PB-induced hypophysectomized rats than in normal male rats. Concerning the postnatal developmental profiles, P-450(6)beta-1(6 beta-3) mRNA was detectable at neonate and reached a maximal level at around 17 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Induction of peroxidase and thyroglobulin by TSH in cultured thyroid cells from patients with Basedow's disease and its inhibition by actinomycin D.

The effects of TSH on peroxidase activity (PO) and thyroglobulin (TG) production were investigated using primary cultures of thyroid cells obtained from patients with Basedow's disease (Basedow's cells). PO activity of cultured cells and TG concentration in the culture medium were measured by biochemical and sandwich enzyme immunoassays, respectively. The addition of TSH (10 mU/ml/day) to the medium did not increase the cell number but did increase the PO activity and TG concentration. It took more than 3 days for the PO activity of cells cultured with TSH (stimulated group) to reach a level twice that of cells cultured without TSH (control group), whereas 2 days of incubation with TSH was sufficient for increasing the TG concentration. When actinomycin D (AD) was added to the medium on the first day of 3-day incubation with TSH, the stimulatory effect of TSH on PO was completely blocked and the TG concentration was reduced to half that of the control group. AD given to the stimulated group on the last day of induction produced no inhibitory effect on the induction of PO activity by TSH, but reduced the TG concentration to almost half that in the stimulated group. An electron microscopic study of Basedow's cells cultured with AD and TSH failed to reveal any cytopathic change. The findings of the present study suggested that in cultured Basedow's cells TSH induces PO activity and TG production through the synthesis of new messenger RNA.

Cell Count↗
PubMed1989

Stimulation by ATP of inositol trisphosphate accumulation and calcium mobilization in cultured adrenal chromaffin cells.

Effects of ATP on accumulation of inositol phosphates and Ca2+ mobilization were investigated in cultured bovine adrenal chromaffin cells. When the cells were stimulated with 30 microM ATP, a rapid and transient rise in intracellular Ca2+ concentration was observed. At the same time, ATP rapidly increased accumulation of inositol phosphates. The concentration-response curve for the ATP-induced Ca2+ mobilization was similar to that for inositol trisphosphate (IP3) accumulation. ATP exerted its maximal effects at 30 microM for either IP3 accumulation or Ca2+ mobilization. The order of the efficacy of the agonists for IP3 accumulation and Ca2+ mobilization at 100 microM was ATP greater than ADP greater than AMP approximately adenosine, AMP (100 microM) and adenosine (300 microM) failed to induce IP3 accumulation and Ca2+ mobilization. Although 100 microM GTP and 100 microM UTP also induced IP3 accumulation and Ca2+ mobilization, their efficacy was less than that of ATP. CTP (100 microM) induced a slight IP3 accumulation, but it did not induce Ca2+ mobilization. Nifedipine (10 microM), a Ca2+ channel antagonist, and theophylline (100 microM), a P1-purinergic receptor antagonist, failed to inhibit the ATP-induced IP3 accumulation and Ca2+ mobilization. The above two cellular responses induced by ATP were also observed in the Ca2+-depleted medium. ATP induced a rapid and transient accumulation of 1,4,5-IP3 (5s), followed by a slower accumulation of 1,3,4-IP3. These results suggest that ATP induces the formation of 1,4,5-IP3 through the P2-purinergic receptor and consequently promotes Ca2+ mobilization from intracellular storage sites in cultured adrenal chromaffin cells.

Adenosine Diphosphate↗
PubMed1989

Usefulness of rate responsive atrial pacing in patients with sick sinus syndrome.

We studied heart rate response and blood lactate changes during treadmill exercise testing in 10 patients with sick sinus syndrome (SSS) and normal atrioventricular (AV) conduction in whom an activity detecting multi-programmable rate responsive pacemaker was implanted for atrial pacing (AAI pacing). Treadmill exercise testing was performed twice in each patient under the two different AAI pacing modes: rate responsive function off (fixed rate 60 pulses per minute [ppm]; RR-off) and rate responsive function on (rate response 10, activity threshold medium, basic rate 60 ppm, and maximum rate 150 ppm; RR-on). Chronotropic response and blood lactate change during exercise were compared among patients under each pacing mode and eight healthy volunteers of ages matching those of the patients. In patients under the RR-off pacing mode (RR-off patients), chronotropic response was lower (P less than 0.01) and blood lactate level was higher (P less than 0.05) than those in patients under the RR-on pacing mode (RR-on patients) and volunteers during exercise. In RR-on patients, however, both chronotropic response and lactate level changes during exercise were comparatively improved, with no significant differences between RR-on patients and volunteers. These data suggested that improvement of chronotropic response by rate responsive pacing, in comparison with nonrate responsive pacing, increased the blood supply to the working muscles and resulted in less lactate production during exercise. It was concluded that rate responsive AAI pacing which could maintain AV synchrony and normal intraventricular conduction was an optimal physiological pacing mode for SSS patients with normal AV conduction.

Adult↗
PubMed1989

Developmental changes in the effects of carbachol and morphine on cGMP contents of plasma, heart, and lung of mice.

It is considered that carbachol increases plasma cGMP levels by acting on muscarinic receptors and morphine increases these levels by acting on opioid receptors, followed by stimulation of muscarinic receptors. We investigated the ability of carbachol and morphine to increase cGMP contents of plasma, heart, and lung and the guanylate cyclase activity of heart and lung homogenate in 1-, 2-, 3-, and 7-week-old mice. The increase in plasma cGMP levels induced by carbachol showed a peak at 2 and 3 weeks of age. The basal cGMP contents in heart and lung and their rise induced by carbachol, as well as the guanylate cyclase activity of these organs, were decreased in 7-week-old mice. The effects of morphine on the cGMP contents showed a similar developmental change, except for no effect in 1-week-old mice. These changes in the effects of carbachol and morphine may be the result of developmental changes of the muscarinic receptor--guanylate cyclase system and opioid receptors.

Aging↗
PubMed1989

[Signal transduction and calcium homeostasis in stimulus-secretion coupling].

Cultured adrenal chromaffin cells are regarded as a suitable system for studying the regulatory mechanism of "stimulus-secretion coupling". Indeed, the term "stimulus-secretion coupling" was originally coined by Douglas and Rubin for the chromaffin cells. Although it has been suggested that calcium plays a central role in this coupling process, there still remain many important and unresolved issues on the molecular mechanisms of "stimulus-secretion coupling" such as (1) the regulatory mechanisms of the calcium uptake, (2) the mechanism by which calcium entry into the cell induces membrane fusion and exocytosis, and (3) the roles of phospholipase C and C-kinase in mediating intracellular calcium homeostasis and catecholamine secretion. In this review, roles of intracellular calcium and inositol phosphate formation in "stimulus-secretion coupling" in cultured bovine adrenal chromaffin cells are discussed, mainly on the basis of the biochemical and pharmacological differences between agonist- and potassium depolarization-induced cellular responses.

Acetylcholine↗
PubMed1989

Induction of cytochrome P-450c and P-450d by metyrapone in the primary culture of rat hepatocytes.

The effects of metyrapone on qualitative changes in cytochrome P-450-dependent drug metabolizing activities in primary cultures of rat hepatocytes were investigated. Metyrapone apparently increased benzo(a)pyrene hydroxylation and maintained both ethoxycoumarin-O-deethylation and propoxycoumarin-O-depropylation, whereas it had little effect on methoxycoumarin-O-demethylation. Furthermore, P-450d (high spin type of P-448) as well as P-450c (low spin type of P-448) were induced by metyrapone, while P-450b and P-450e were not. In conclusion, metyrapone act as a 3-methylcholanthrene-like inducer in the primary cultures of rat hepatocytes.

Animals↗
PubMed1989

Hepatic level of mRNA in relation to polymorphism and strain difference in expression of cytochrome P-450g.

Hepatic level of mRNA for P-450g was determined in male and female rats of Sprague-Dawley, ACI and Fischer strains using a specific oligonucleotide probe. The mRNA level in female Sprague-Dawley and Fischer rats was undetectable in accordance with a very low or undetectable level of P-450g protein. The mRNA was detected in all male ACI rats, in which high levels of P-450g protein were detected. In Fischer male rats, mRNA for P-450g was clearly detected in the liver, but P-450g protein was not detected. Moreover, the mRNA was detected in the liver of all male Sprague-Dawley rats, irrespective of the expressed level or absence of P-450g protein. As a most plausible explanation of the observed discordance in the levels of P-450g mRNA and protein, translation of unstable protein for microheterogeneous P-450g is discussed.

Animals↗
PubMed1989

[Tracheobronchial reconstruction of malignant tumors].

To August, 1988, we performed tracheobronchial reconstruction for 159 patients with malignant tumors. Operative methods in these patients and the operative results studied in the end of March, 1989, was reported. As for adenoid cystic carcinoma, we stressed, by illustrating cases, that postoperative radiation therapy was useful and that it should be given for all patients with this disease. About one half of patients with thyroid carcinoma infiltrating the trachea died of symptoms related with tracheal stenosis. However, tracheobronchial reconstruction improved 10 year survival rate in patients with advanced thyroid carcinoma remarkably, which became close to that in patients with non-infiltrating thyroid carcinoma. As for lung cancer, tracheobronchial reconstruction had good indication for squamous cell carcinoma.

Adult↗
PubMed1989

Suppression of hepatic levels of an ethanol-inducible P-450DM/j by growth hormone: relationship between the increased level of P-450DM/j and depletion of growth hormone in diabetes.

The mechanism of the suppression of an ethanol-inducible cytochrome P-450 (P-450DM/j) by pituitary hormone has been studied in rats. The hepatic content of P-450DM/j protein quantitated by Western blots was low but was 2-fold higher in male than female untreated rats (75 and 34 pmol/mg of protein, respectively). The content was increased 2.6-fold (male) and 5.6-fold (female) by hypophysectomy and the sex-related difference was abolished. Treatment of hypophysectomized rats with human growth hormone (hGH), but not with prolactin, reversed the increased amounts of P-450DM/j protein. The hGH-induced suppression was more effective with the continuous infusion than intermittent injection. The hepatic level of P-450DM/j mRNA, determined by the use of a 23-mer oligonucleotide probe, was also changed by hypophysectomy and/or hGH-treatment, largely in parallel with the changes in the content of P-450DM/j protein and microsomal p-nitrophenol and aniline hydroxylations. These results suggest that growth hormone exerts the suppressive effect on P-450DM/j through a somatogenic receptor-mediated process. In another growth hormone-depleted condition, diabetes, the hepatic level of P-450DM/j mRNA was also increased to a level similar to that in hypophysectomized rats, but the protein content was 2- to 3-fold higher in diabetic than hypophysectomized rats. These results indicate, in addition to the reduction of serum growth hormone level, the presence of another stimulatory factor, which acts translationally or posttranslationally in livers of diabetic rats. On the other hand, coordinate changes in the level of P-450DM/j protein and the mRNA in hypophysectomized rats indicate that growth hormone acts rather directly and suppresses the level of P-450DM/j mainly at a pretranslational step in rat livers.

Animals↗
PubMed1989

H-7, a protein kinase C inhibitor, inhibits phorbol ester-caused ornithine decarboxylase induction but fails to inhibit phorbol ester-caused suppression of epidermal growth factor binding in primary cultured mouse epidermal cells.

12-O-tetradecanoylphorbol-13-acetate (TPA) induced ornithine decarboxylase (ODC) and suppressed 125I-epidermal growth factor (EGF) binding in primary cultured mouse epidermal cells. TPA (30 nM)-caused ODC induction was almost completely blocked by 30 microM H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], a well known protein kinase C inhibitor, but the same concentration of H-7 failed to restore the 125I-EGF binding suppressed by TPA (10 nM). On the other hand, sphingosine, another protein kinase C inhibitor, blocked not only TPA-caused ODC induction but also TPA-caused suppression of 125I-EGF binding. Concentration-response curves of sphingosine for these two TPA-caused cellular responses were almost identical. 1,2-Diacylglycerols such as 1,2-dioctanoylglycerol (30-300 microM) and 1-oleoyl-2-acetylglycerol (OAG) (30-300 microM) mimicked TPA actions. Similar to the case of TPA, suppression of 125I-EGF binding by OAG was barely inhibited by H-7, whereas sphingosine was more effective in inhibiting the OAG-caused suppression of 125I-EGF binding than was H-7. In TPA (50 nM)-pretreated epidermal cells, TPA (10 nM) failed to suppress 125I-EGF binding. H-7 (30 microM) did not affect TPA (30 nM)-caused translocation of protein kinase C. These results clearly demonstrate the differential inhibition by H-7 of the TPA-caused cellular responses and indicate that TPA-caused suppression of 125I-EGF binding to epidermal cells is mediated through protein kinase C function, which is barely inhibited by H-7.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

[Endoscopic Nd-YAG laser treatment in lung cancer].

Authors have treated a total of 199 cases consisting of 92 lung cancer cases, 14 primary tracheal cancer, 50 metastatic airway lesions and 43 benign airway lesions. In 167 of which effective results were obtained. Out of 92 effective results were obtained in 73, 79% in lung cancer cases. Out of 30 emergency cases in which the procedure was performed to widen the airway, effective results were obtained in 29. It was also effective in 35 of 48 cases in which the procedure was performed for staged (palliative) widening of airway. In 9 of 13 cases in which the procedure was performed for curative vaporization of cancer invasion and 1 of 2 cases in which procedure was performed for hemostasis, successful results were obtained.

Airway Obstruction↗
PubMed1989

[New classification and analysis of lung sounds].

Recently, classification and nomenclature of lung sounds has been changed from assessment based on subjective interpretation to assessment based on objective, measureable criteria related to mechanisms of sound generation. The adventitious sounds was classified to four kinds of principal terms, continuous adventitious sounds (wheezes, rhonchi) and discontinuous adventitious sounds (coarse crackles, fine crackle) at the 1985 International Symposium on Lung Auscultation. Lung sounds in the surgical patients were digitized for the analysis of both the time domain and the frequency domain which had been recorded by tape recorder. Rhonchi, fine crackle and tracheal stenotic sounds were characterized by the analysis of the frequency domain. Lung sound analysis is promising because it is safe, non invasive and may be used for clinical studies in the surgical patients.

Humans↗