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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 685 records · Page 38Linked to original sources
PubMed1985

New antitumor antibiotics, FR-900405 and FR-900406. II. Production, isolation, characterization and antitumor activity.

The new antitumor antibiotics, FR-900405 and FR-900406, were isolated from the culture broth of Actinomadura pulveracea sp. nov. No. 6049. These compounds which contain sulfur in the molecule, represent a novel class of antitumor agents. FR-900405 and FR-900406 are highly active in mice against experimental tumors and exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi.

Actinomycetales↗
PubMed1985

Cell-free system studies on the phosphorylation of the 17,000-20,000 dalton protein induced by phorbol ester in human leukemic cells and evidence for a similar event in virally transformed murine fibroblasts.

We have shown previously that a prominent early signal in the phorbol-12-myristate-13-acetate (PMA) effect on leukemic cells as well as on other malignant cells is a rapid and dramatic increase in the turnover of phosphate in a Mr 17,000 to 20,000 cytosolic protein and a moderate increase in turnover of phosphate in a Mr 27,000 protein, as detected in the intact cells by 2-dimensional gel electrophoresis. To further elucidate the mechanism of this phosphorylation event, we have examined the protein kinases which can reconstitute this event in a cell-free system. Activation of the endogenous Ca2+-activated phospholipid-dependent protein kinase (Ca-PL-PK) as well as addition of purified Ca-PL-PK to the cytosol of HL-60 leukemic cells resulted in enhanced phosphorylation of phosphoprotein Mr 27,000 (PP27) but did not affect the phosphorylation of phosphoprotein Mr 17,000 to 20,000 (PP17-20). In contrast, PP17-20 was heavily phosphorylated under cell-free conditions by the catalytic subunit of cAMP-dependent protein kinase (cAMP-PK). Exposure of intact cells to dibutyryl-cAMP resulted in increased phosphorylation of PP17-20. These conditions also enhanced the phosphorylation of PP27, showing that PP27 can act as a substrate for both Ca-PL-PK and cAMP-PK under cell-free conditions. Tryptic digest analysis of PP17-20 showed that one of four phosphopeptides is preferentially phosphorylated in PMA-induced PP17-20. An additional phosphopeptide was phosphorylated in cAMP-PK-catalyzed PP17-20. Thus, cAMP-PK alone mimics the effect of PMA on phosphorylation of PP17-20, but it introduces additional modifications. The precise role of this kinase in PMA-induced phosphorylation of PP17-20 remains to be clarified. We found further that enhanced phosphorylation of PP17-20 is also associated with malignant transformation of NIH/3T3 cells transformed by V-rasKi oncogene of Kirsten sarcoma virus. The tryptic phosphopeptide map of PP17-20 (phosphorylated in vivo) in the transformed cells was similar to that of PP17-20 in PMA-treated HL-60 cells but not to that induced by cAMP-PK, suggesting that the process activated by PMA which leads to phosphorylation of PP17-20 resembles an intrinsic cellular process which is enhanced in certain malignant cells.

Animals↗
PubMed1985

[Calmodulin].

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Blood Platelets↗
PubMed1984

Abnormalities in plasma catecholamine response and tissue catecholamine accumulation in streptozotocin diabetic rats: a possible role for diabetic autonomic neuropathy.

Plasma catecholamine levels, determined by high performance liquid chromatography, were elevated in response to blood withdrawal in normal rats. Such a response was also observed in streptozotocin diabetic rats 2 and 6 weeks after disease onset, but was no longer seen at 13 weeks. Tissue (adrenal, heart, skin, kidney) catecholamine levels in diabetic rats were increased at 6 weeks as well as at 13 weeks. These abnormalities were corrected by insulin treatment in at least a part of diabetic rats. The present data suggest that there might be a catecholamine accumulation, which is later accompanied with an impairment of catecholamine secretion, in diabetic rats, and they gave a basis for an inference that similar changes might play some role in the pathogenesis of diabetic autonomic neuropathy in man.

Adrenal Glands↗
PubMed1984

Protein kinase C modulates in vitro phosphorylation of the smooth muscle heavy meromyosin by myosin light chain kinase.

Protein kinase C phosphorylates different sites on the 20,000-Da light chain of smooth muscle heavy meromyosin (HMM) than did myosin light chain kinase (Nishikawa, M., Hidaka, H., and Adelstein, R. S. (1983) J. Biol. Chem. 258, 14069-14072). Although protein kinase C incorporates 1 mol of phosphate into 1 mol of 20,000-Da light chain when either HMM or the whole myosin molecule is used as a substrate, it catalyzes the incorporation of up to 3 mol of phosphate/mol of 20,000-Da light chain when the isolated light chains are used as a substrate. Threonine is the major phosphoamino acid resulting from phosphorylation of HMM by protein kinase C. Prephosphorylation of HMM by protein kinase C decreases the rate of phosphorylation of HMM by myosin light chain kinase due to a 9-fold increase of the Km for prephosphorylated HMM compared to that of unphosphorylated HMM. Prephosphorylation of HMM by myosin light chain kinase also results in a decrease of the rate of phosphorylation by protein kinase C due to a 2-fold increase of the Km for HMM. Both prephosphorylations have little or no effect on the maximum rate of phosphorylation. The sequential phosphorylation of HMM by myosin light chain kinase and protein kinase C results in a decrease in actin-activated MgATPase activity due to a 7-fold increase of the Km for actin over that observed with phosphorylated HMM by myosin light chain kinase but has little effect on the maximum rate of the actin-activated MgATPase activity. The decrease of the actin-activated MgATPase activity correlates well with the extent of the additional phosphorylation of HMM by protein kinase C following initial phosphorylation by myosin light chain kinase.

Animals↗
PubMed1984

Phosphorylation of phospholamban by calcium-activated, phospholipid-dependent protein kinase. Stimulation of cardiac sarcoplasmic reticulum calcium uptake.

Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) is able to catalyze the phosphorylation of phospholamban in a canine cardiac sarcoplasmic reticulum preparation. This phosphorylation is associated with a 2-fold stimulation of Ca2+ uptake by cardiac sarcoplasmic reticulum similar to that seen following phosphorylation of phospholamban by an endogenous calmodulin-dependent protein kinase or by the catalytic subunit of cAMP-dependent protein kinase. Two-dimensional peptide maps of the tryptic fragments of phospholamban indicate that the three protein kinases differ in their selectivity for sites of phosphorylation. However, one common peptide appears to be phosphorylated by all three protein kinases. These findings suggest that protein kinase C may play a role similar to those played by cAMP- and calmodulin-dependent protein kinases in the regulation of Ca2+ uptake by cardiac sarcoplasmic reticulum, and raise the possibility that the effects of all three protein kinases are mediated through phosphorylation of a common peptide in phospholamban.

Animals↗
PubMed1984

Phosphorylation of mammalian myosin light chain kinases by the catalytic subunit of cyclic AMP-dependent protein kinase and by cyclic GMP-dependent protein kinase.

The phosphorylation of the calmodulin-dependent enzyme myosin light chain kinase, purified from bovine tracheal smooth muscle and human blood platelets, by the catalytic subunit of cAMP-dependent protein kinase and by cGMP-dependent protein kinase was investigated. When myosin light chain kinase which has calmodulin bound is phosphorylated by the catalytic subunit of cAMP-dependent protein kinase, 1 mol of phosphate is incorporated per mol of tracheal myosin light chain kinase or platelet myosin light chain kinase, with no effect on the catalytic activity. Phosphorylation when calmodulin is not bound results in the incorporation of 2 mol of phosphate and significantly decreases the activity. The decrease in myosin light chain kinase activity is due to a 5 to 7-fold increase in the amount of calmodulin required for half-maximal activation of both tracheal and platelet myosin light chain kinase. In contrast to the results with the catalytic subunit of cAMP-dependent protein kinase, cGMP-dependent protein kinase cannot phosphorylate tracheal myosin light chain kinase in the presence of bound calmodulin. When calmodulin is not bound to tracheal myosin light chain kinase, cGMP-dependent protein kinase phosphorylates only one site, and this phosphorylation has no effect on myosin light chain kinase activity. On the other hand, cGMP-dependent protein kinase incorporates phosphate into two sites in platelet myosin light chain kinase when calmodulin is not bound. The sites phosphorylated by the two cyclic nucleotide-dependent protein kinases were compared by two-dimensional peptide mapping following extensive tryptic digestion of the phosphorylated myosin light chain kinases. With respect to the tracheal myosin light chain kinase, the single site phosphorylated by cGMP-dependent protein kinase when calmodulin is not bound appears to be the same site phosphorylated in the tracheal enzyme by the catalytic subunit of cAMP-dependent protein kinase when calmodulin is bound. With respect to the platelet myosin light chain kinase, the additional site that was phosphorylated by cGMP-dependent protein kinase when calmodulin was not bound was different from that phosphorylated by the catalytic subunit of cAMP-dependent protein kinase.

Blood Platelets↗
PubMed1984

Chromatographic separation and chemical analysis of polymers formed by penicillin G.

To elucidate the chemical structures of penicillin polymers that may elicit an allergic reaction, a 25% aqueous solution of penicillin G potassium was kept standing in the dark at room temperature for 14 days and was then separated by gel filtration chromatography on Sephadex G-25. The fractions of Kav 0.0-0.3, 0.3-0.55 and 0.55-0.75 were designated fractions A, B and C, respectively. Chemical and spectral data indicated that fractions A and B had almost similar chemical structures, but differed in molecular weight. They consisted of equimolar phenylacetyl and thiazolidine moieties and showed a C:N:S ratio almost equal to that of penicillin G. Their degrees of polymerization were 10 for A and 3.2 for B. Comparison of 1H NMR and IR spectra and thin-layer chromatographic RF values with those of authentic standards showed that the main components of fraction C were N- formylpenicillamine , benzylpenilloic acid, benzylpenicilloic acid and benzylpenillic acid.

Allergens↗
PubMed1984

Increased phosphorylation of myosin light chain kinase after an increase in cyclic AMP in intact smooth muscle.

The role of cyclic adenosine monophosphate-mediated phosphorylation of myosin light chain kinase in relaxing smooth muscle was examined. The kinase was immunoprecipitated from tissue extracts and the phosphate content was determined. The addition of forskolin to resting or methacholine-contracted muscles resulted in an increase in myosin light chain kinase phosphorylation of myosin light chain kinase is one of the reactions in the process by which cyclic adenosine monophosphate causes relaxation of smooth muscle.

Animals↗
PubMed1984

Effect of high doses of synthetic estrogen on lipid metabolism in castrated male rats.

The mechanism by which high doses of estrogen influences lipid metabolism was studied with a microtubular blocking agent. Castrated male rats received oral injection daily for 14 days of 3 mg hexestrol in olive oil, or oil alone as controls. About half of the animals in each group were injected intraperitoneally with 4 mg/100 g body weight colchicine 3 hr before they were killed. Hexestrol treatment caused an accumulation of esterified cholesterol in the liver while it decreased those in serum. Triglyceride concentrations slightly decreased in the liver but were unaffected in serum. On polyacrylamide-gel disc electrophoresis, the peaks of high density lipoproteins (HDL) and low density lipoproteins (LDL) were decreased remarkably. Electron microscopic examination of hepatocytes revealed electron-lucent lipid droplets in the cytoplasm. After a colchicine treatment of the control animals, concentrations of esterified cholesterol and triglycerides markedly increased in the liver, while those in serum decreased. Electron microscopic examination of hepatocytes revealed numerous secretory vesicles filled with nascent VLDL. In hexestrol-treated animals, the colchicine treatment was associated with marked decreases in serum-esterified cholesterol and triglyceride as seen in the controls. However, there were no further increases of esterified cholesterol in the liver, and the increase of triglycerides was slight. Electron microscopic examination showed less secretory droplets than in the controls. These data suggest that very low density lipoproteins (VLDL) synthesis in the liver of hexestrol treated rats was inhibited. An accumulation of esterified cholesterol with a marked decrease in serum could not be accounted for by the inhibition of lipoproteins secretion, but rather by their enhanced entry into the liver.

Animals↗
PubMed1984

Eliciting IgE-mediated passive cutaneous anaphylactic reaction by synthetic D-benzylpenilloic acid analogs.

The ability of various D-benzylpenilloic acid analogs to evoke the passive cutaneous anaphylactic (PCA) reaction was tested in rats sensitized with mouse IgE antibodies to a benzylpenicillin preparation. D-benzylpenilloic acid synthesized chemically from materials that had no potency to evoke the PCA reaction showed almost the same antigenicity in eliciting the reaction as that prepared from benzylpenicillin. Changes in the chemical structures of the side-chain and thiazolidine ring of D-benzylpenilloic acid resulted in a reduction in the activity, but the removal of either alpha- or beta-methyl did not greatly affect it. From these results, it was concluded that benzyl and amidomethyl at C-2, the D-configuration at C-4, and dimethyl at C-5 on the thiazolidine ring have a significant effect on the PCA reaction.

Animals↗
PubMed1984

Effect of cadmium-feeding on tissue concentrations of elements in germ-free silkworm (Bombyx mori) larvae and distribution of cadmium in the alimentary canal.

Silkworm (Bombyx mori) larvae were reared on an artificial diet containing cadmium (Cd) at concentrations of 5 and 80 micrograms/g wet diet from hatching to the fourth instar and then for 5 days at the fifth instar, respectively. Concentrations of Cd and other elements in the alimentary canal, Malpighian tubes, silk gland, fat body and other organs were determined simultaneously by inductively coupled argon plasma-atomic emission spectrometry. Cd was accumulated in the alimentary canal and Malpighian tubes at concentrations of 1100 and 470 micrograms/g dry wt, respectively. The distribution of Cd in the supernatants of the two highly accumulated organs were determined on an SW column by high performance liquid chromatography-atomic absorption spectrophotometry. Cd was primarily bound to inducible high molecular weight Cd-binding proteins.

Animals↗
PubMed1984

Interaction of digitonin and its analogs with membrane cholesterol.

The interaction of digitonin with membrane cholesterol was studied by using various digitonin analogs, and radioactive desglucodigitonin. The following results were obtained concerning the effect of digitonin on erythrocytes, granulocytes and liposomes. Digitonin and its analogs showed activity to induce hemolysis, granulocyte activation and liposomal membrane damage. The activity was affected by change of the carbohydrate residue of the molecule; the order of hemolytic activity was digitonin greater than or equal to desglucodigitonin much greater than glucosyl-galactosyl-digitogenin greater than galactosyl-digitogenin, digitogenin. The relative activities of these compounds to induce granulocyte activation and liposomal membrane damage were similar to those observed in the hemolysis. [3H]Desglucodigitonin could bind to cholesterol in liposomes. The binding was stoichiometric and the ratio of desglucodigitonin bound to liposomes/cholesterol in liposomes was close to 1, irrespective of the cholesterol content in liposome. Damage to liposomes was, however, induced by desglucodigitonin only when they contained more than 0.2 molar ratio of cholesterol to phospholipid. Addition of digitonin as well as desglucodigitonin to preformed liposomes deprived of cholesterol affected the anisotropic molecular motion of spin-labeled phosphatidylcholine incorporated into the liposomes, suggesting that the molecules could be inserted into the lipid bilayer free of cholesterol. Molecules of desglucodigitonin in the lipid phase may, however, be equilibrated with those in the aqueous phase, unless they form a complex with cholesterol, since no appreciable amount of [3H]desglucodigitonin could be detected in the liposome fraction after separation by column chromatography. Digitonin decreased the order parameter of spin-labeled phosphatidylcholine when liposomes contained equimolar cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Plasma adrenocorticotropin and cortisol responses to ovine corticotropin-releasing factor in patients with adrenocortical insufficiency due to hypothalamic and pituitary disorders.

Plasma ACTH and cortisol responses to intravenous injection of 100 micrograms synthetic ovine corticotropin-releasing factor (CRF) were studied in 4 patients with hypothalamic hypopituitarism, 2 patients with Sheehan's syndrome, 2 patients with isolated ACTH deficiency and 10 normal subjects. All 4 patients with hypothalamic hypopituitarism had exaggerated plasma ACTH responses to CRF compared to normal subjects and gradual but definite increases in plasma cortisol from low basal levels. Of 2 patients with Sheehan's syndrome, one had slight ACTH and cortisol increases after CRF injection, whereas the other had no increase in either. In 2 patients with isolated ACTH deficiency, plasma ACTH and cortisol remained undetectable (ACTH less than 10 pg/ml, cortisol less than 0.6 microgram/dl) after CRF injection. These results suggest that the CRF test is a useful tool in evaluating patients with secondary adrenocortical deficiency.

Adolescent↗
PubMed1984

[Chronic toxicity test of garlic extract in rats].

The influence of garlic extract on the chronic toxicity test were examined orally in Wistar rats for 6 months. There were no toxic symptoms due to garlic extract even at dose level of 2000 mg/kg for 5 times a week during 6 months. High dose of garlic extract did not inhibit the body weight gain, while the food consumption decreased slightly for the nutritional effects of it in both male and female rats. There were no significant differences in urinary, hematological and serological examinations compared each groups. In the histopathological findings, no toxic signs were observed on any of the tissues and organs examined.

Animals↗
PubMed1984

[A case of Marfan's syndrome with a ruptured distal middle cerebral aneurysm].

A case of ruptured distal middle cerebral aneurysm is reported, A 20-year-old man with Marfan's syndrome suffered from sudden loss of consciousness. A CT scan and cerebral angiogram revealed a distal middle cerebral aneurysm with a large intracerebral hematoma. The aneurysm was clipped and the hematoma was evacuated successfully. This case is presented and the literature related to the aneurysm associated with Marfan's syndrome is reviewed.

Adult↗