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Biomedical subjects

M Kusaka

Publications and source records attributed to M Kusaka.

At least 109 records · Page 6Linked to original sources
PubMed1988

Possible induction of fatty acid cyclooxygenase in mouse osteoblastic cells (MC3T3-E1) by cAMP.

Prostaglandin E2 (PGE2), a bone-resorption factor, was essentially the sole arachidonate metabolite in an osteoblastic cell line cloned from mouse calvaria (MC3T3-E1). When the cells were cultured in the presence of 2% newborn bovine serum, 1 microM epinephrine markedly stimulated PGE2 synthesis from endogenous arachidonic acid. The PGE2 synthesis commenced after a lag phase of 1-2 h, and reached a maximum at about 3 h after the addition of epinephrine. The effect of epinephrine was inhibited by propranolol, and epinephrine could be replaced by isoproterenol, suggesting beta-adrenergic stimulation of PGE2 production. A rapid increase in intracellular cAMP was observed upon the addition of epinephrine. When the intracellular cAMP level was raised using cholera toxin or forskolin, the PGE2 synthesis was also stimulated. The enhanced PGE2 synthesis was attributed to an increased level of cyclooxygenase, which was shown by immunoprecipitation of the enzyme using anti-cyclooxygenase antibody. Inhibitors of transcription and translation suppressed the epinephrine-dependent increase in cyclooxygenase activity. These findings suggest induction of cyclooxygenase involving cAMP via an as yet unclarified mechanism.

Animals↗
PubMed1988

Effect of interleukin 1 beta on osteoblastic clone MC3T3-E1 cells.

The effect of recombinant interleukin 1 Beta (IL-1(beta)) was investigated on osteoblastic cell line MC3T3-E1 cloned from mouse calvaria. IL-1(beta) stimulated cell proliferation which increased cell number and caused dose-related stimulation of DNA synthesis, with a maximal effect at a concentration of 12.5 U/ml; suppressed alkaline phosphatase activity and collagen synthesis maximally at 0.5 and 62.5 U/ml, respectively; and increased the amount of free [3H] hydroxyproline in the cultures, but the amount was quite low. Prostaglandin E2 synthesis was also stimulated dose dependently by the presence of IL-1(beta), with a maximal increase at 2.5 U/ml, at which concentration the prostaglandin E2 level in the medium was 1.61 +/- 0.10 ng/ml. The increased prostaglandin E2 synthesis did not affect either the IL-1(beta)-mediated change in DNA or collagen synthesis or alkaline phosphatase activity. These results extend the possibility that IL-1(beta) is to act as a regulator of bone formation.

Animals↗
PubMed1988

The effect of atrial natriuretic peptide on acid-base balance in rats with chronic renal failure.

We explored the effects of 12-hour infusion of atrial natriuretic peptide (alpha-rANP:rat, 1-28) on arterial acid-base balance, using 5/6 nephrectomized rats with chronic renal failure. Before the infusion, nephrectomized rats had a higher mean arterial blood pressure, greater urine volume, and lower creatinine clearance than the normal controls, but they did not show a significant difference in arterial hydrogen ion concentration (pH), plasma bicarbonate concentration (HCO3-), partial pressure of carbon dioxide (PCO2), plasma base excess (BE), or plasma ANP concentration. alpha-rANP infusion produced a continuous blood pressure reduction in both nephrectomized and control rats. Urine volume and urinary sodium and potassium excretion tended to increase at 2-hour infusion, but not at 12-hour infusion. In the controls alpha-rANP significantly increased pH from 7.47 to 7.50, and decreased PCO2 by 14%. In contrast, in nephrectomized rats alpha-rANP significantly decreased pH from 7.48 to 7.44, HCO3- by 13%, and BE from -0.07 to -3.22 meq/l. Rats with chronic renal failure had greater reduction in HCO3- than the controls (p less than 0.05). There was no difference in plasma ANP level between the two groups. Thus, it is indicated that the long-term infusion of alpha-rANP reduces pH in rats with chronic renal failure, thereby adversely affecting the acid-base balance.

Acid-Base Equilibrium↗
PubMed1988

Environmental risk assessment of surfactants: fate and environmental effects in Lake Biwa basin.

Environmental risk incurred with the use of synthetic surfactants is dealt with in this paper. The background and necessity of risk management related to surfactant usage in the Lake Biwa basin are introduced, as well as a research scheme that acknowledges risks in three sub-processes--consumption and discharge, fate in aquatic environment, and ecotoxicological response of linear alkylbenzene sulfonate (LAS). The ayu (Plecoglossus altivelis) has been selected as the significant biological target in the basin. Results of a field survey of the behavior of LAS along streams flowing down to the lake are presented. Included are the estimation and verification of an original unit of surfactant consumption per capita per day based on LAS and MBAS concentrations observed in diurnal monitoring. A simulation model representing the flowdown process of LAS dynamically is formulated, with which longitudinal dispersion, settling, and modified biodegradation of LAS are evaluated in the field survey. On the basis of the research scheme described above, ecotoxicological laboratory tests on ayu have been carried out. The special significance of acute and subchronic effects on ayu in various life stages exposed to low concentrations of LAS can be recognized. It has been concluded that the LC50 of young ayu is not greater than 0.1 ppm under the disadvantageous condition of high temperature or extreme hardness even in normal ranges of environmental indicators. An advanced plan of risk management for surfactant usage is proposed based on methods of elevated risk, comparative risk, risk--benefit, and balanced risk. The occurrence and magnitude of risk phenomena in each subdivided basin adjacent to the lake are identified, taking into consideration features such as (1) the spawning place of ayu and aquafarms, (2) COD and MBAS concentrations and their tolerable levels in current regulation of stream pollution, (3) socioeconomic perspectives including recreational activities and voluntary actions to improve the neighborhood environment, and (4) future preparation of measures for resolving technological risk including sewerage construction. Because LAS concentrations in several rivers exceed the tolerable level of the most delicate life stage of ayu, latent environmental effects can be suggested. It is concluded therefore that it is necessary to establish a water quality goal related to surfactants that takes patterns of water use and conservation of the ecosystem in the local environment into consideration. These judgments are followed by formulation of the "requirement" for environmental management practice for the Lake Biwa administration.

Animals↗
PubMed1988

Simultaneous determination of metoprolol and alpha-hydroxymetoprolol in human plasma and urine by liquid chromatography with a preliminary observation on metoprolol oxidation in Japanese subjects.

A simple, sensitive, and highly reliable liquid chromatographic method using fluorescence detection is described for the simultaneous determination of metoprolol and alpha-hydroxymetoprolol in plasma and urine. This method involves a single extraction of the compounds with the internal standard pindolol from alkalinized plasma or urine into dichloromethane. A reconstituted aliquot with a mobile phase is injected onto a reversed-phase, Zorbax ODS column, and the detection is achieved by the excitation and emission wavelengths at 230 and 300 nm, respectively. The assay is reproducible and precise for metoprolol and alpha-hydroxymetoprolol in both plasma and urine samples, as judged by a coefficient of variation of less than 9.2% at all concentrations examined. The standard curves for metoprolol and alpha-hydroxymetoprolol are linear over 10-200 ng/ml in plasma and over 0.5-10 micrograms/ml in urine. The lower detection limit is 2 ng/ml for each of the compounds in plasma using a 0.5-ml sample. Preliminary data on the oxidation polymorphism of metoprolol in Japanese subjects are reported using the current assay method. In 183 Japanese subjects no poor metabolizer of metoprolol has been identified so far.

Chromatography, Liquid↗
PubMed1987

Does so-called streptozocin hypertension exist in rats?

Although the existence of so-called streptozocin hypertension seems well established, some reports have indicated that no rise in blood pressure (BP) occurred after streptozocin treatments. To ascertain the streptozocin-induced BP response, normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated with streptozocin, 40 to 45 and 35 mg/kg i.v., respectively, and BP was determined directly and indirectly every week for 3 to 4 weeks. Direct mean BP was determined without anesthesia or restraint through a cannula inserted into the rat's abdominal aorta. Indirect BP was determined at the tail without anesthesia after prewarming the rat in a holder. Compared with control values, indirect BP increased significantly in diabetic WKY 2 weeks after streptozocin treatment. In contrast, direct BP of these rats decreased, compared with control values. Indirect BP of diabetic SHR was as high as that of the controls, whereas direct BP of diabetic SHR decreased significantly 1 week after the treatment and thereafter, compared with control values. These discrepancies between the direct and indirect BP values may be caused by severe emaciation of diabetic rats. Extra pressure in the cuff may be necessary to occlude the bloodstream. These results indicate that under these conditions the value of BP obtained by the direct measurement is more reliable than that by the indirect one; therefore, we concluded that so-called streptozocin hypertension does not exist.

Animals↗
PubMed1986

Stimulation of prostaglandin E2 synthesis in cloned osteoblastic cells of mouse (MC3T3-E1) by epidermal growth factor.

Prostaglandin (PG) E2, known as a bone-resorption factor, was released as a predominant arachidonate metabolite in the culture medium of an osteoblastic cell line cloned from mouse calvaria (MC3T3-E1). Epidermal growth factor (EGF) (10 ng/ml) prominently enhanced endogenous PGE2 synthesis, requiring the simultaneous presence of unidentified factor(s) contained in bovine serum. PGE2 synthesis increased after a lag phase for 1-2 h and reached a maximum level at about 3 h after EGF addition. EGF-stimulated PGE2 synthesis was almost completely blocked by 10 microM cycloheximide or 1 microM actinomycin D. Furthermore, when the cells were pretreated with EGF, the microsomes exhibited an increased activity of fatty acid cyclooxygenase (arachidonic acid----PGH2), whereas the activity of PGE synthase (PGH2----PGE2) remained unchanged. These results suggested an EGF-mediated induction of cyclooxygenase. Following increased PGE2 synthesis, DNA synthesis increased and alkaline phosphatase activity decreased in a slower response to EGF. PGE2 (above 0.1 microM) added to the cells could replace EGF. However, such effects of EGF on the osteoblasts could not be attributed totally to an autocrine function of PGE2 produced by stimulation with EGF because these effects of EGF were not abolished by indomethacin, which blocked the PGE2 synthesis.

Alkaline Phosphatase↗
PubMed1984

12- and 15-lipoxygenases in rat pineal gland.

A whole organ or a homogenate of rat pineal gland was incubated with arachidonic Acid. Two predominant metabolites were identified by mass spectrometry to be 12-hydroxy-5,8,10,14-eicosatetraenoic acid and 10-hydroxy-11,12-epoxy-5,8,14-eicosatrienoic acid. 15-Hydroxy-5,8,11,13-eicosatetraenoic acid was also formed in a smaller amount. In addition, peroxy acids appeared rapidly only at the initial stage of reaction. In various parts of rat brain the 12-lipoxygenase activity was by far the highest in pineal gland, and less than 5% of the activity was found in pituitary gland and hypothalamus.

Animals↗
PubMed1980

Interaction of triazolam with desipramine. Effects of single and repeated treatment on certain pharmacologic responses and brain catecholamine levels.

The present study was undertaken to evaluate the effects of single and repeated doses of triazolam (1 mg/kg IP) and desipramine (DMI) (10 mg/kg IP) alone and in combination on certain pharmacologic responses and brain catecholamine levels in rats. The significant findings were: (1) triazolam and DMI given alone and in combination were synergistic with pentobarbital (PB) hypnosis; (2) repeated treatment with DMI alone repressed body weight gain; triazolam potentiated this anorectic effect; (3) triazolam induced muscle relaxation acutely, but was not affected by concomitant DMI treatment; and (4) triazolam and DMI given in combination produced hypothermia although the drugs given separately did not. Development of tolerance to hypothermia and to anorectic effects produced by triazolam and DMI significantly decreased norepinephrine (NE) levels in the hypothalamus as compared to the repeated treatment with triazolam, and significantly increased NE and dopamine (DA) levels in the striatum and DA levels in the cortex, as compared to the single treatments.

Animals↗
PubMed1979

Simple method for the determination of choline and acetylcholine by prolysis gas chromatography.

An improved purification procedure is described for the simultaneous assay of endogenous choline and acetylcholine by pyrolysis gas chromatography, particularly for providing a simple and effective method for propionylation of choline in the presence of acetylcholine. The reaction was carried out in acetonitrile solution prepared by dissolving the evaporated residue of the supernatant of brain homogenate. Thus samples for propionylation were prepared without the use of ion-exchange chromatography.

Acetylcholine↗
PubMed1977

Tracer kinetic analysis of Cori cycle activity in the rat: effect of feeding.

Turnover rates of blood glucose and lactate, along with the rates of their interconversion, were calculated from changes of their specific activities in rats infused with [U-14C] glucose and [U-14C] lactate based on a simple flux model of the Cori cycle. In the fasted state, most (75%) of the glucose metabolized was converted to lactate, whereas only a small fraction (35%) of the lactate metabolized was converted to glucose. Of the glucose metabolized, 27% returned from the lactate pool to the glucose pool. Feeding stimulated the outflow of glucose carbon from the Cori cycle via the action of secreted insulin. Insulin-induced stimulation of blood glucose removal was associated with increased glucose production, whereas anti-insulin serum-induced stimulation of glucose production was associated with increased glucose removal. It is argued that a "compensatory" mechanism independent of insulin and epinephrine might be in operation to minimize the glycemic changes that would otherwise occur in response to drastic metabolic changes.

Animals↗
PubMed1977

Activation of the Cori cycle by epinephrine.

The effect of epinephrine on Cori cycle activity has been studied by a tracer kinetic technique. The subcutaneous injection of epinephrine into fasted adrenodemedullated rats activated gluconeogenesis and increased glucose utilization. Most of the glucose utilized in epinephrine-treated rats was converted to lactate, and the conversion to the metabolites other than lactate was markedly suppressed by epinephrine. As a result, not only hyperglycemia and hyperlactacidemia developed, but also the contribution of the Cori cycle to glucose metabolism increased after epinephrine. The glucose-alanine cycle, which is roughly one-third as active as the Cori cycle, was only slightly activated by epinephrine. No evidence was obtained, in vivo and in vitro, for the increased formation of lactate from muscle glycogen which decomposed in response to epinephrine. It is suggested that, in epinephrine-treated rats, blood glucose was converted to blood lactate predominantly while muscle glycogen selectively yielded the metabolites other than blood lactate. This suggests compartmentalization of glycolytic pathway in the peripheral tissues of epinephrine-treated rats.

Adrenal Medulla↗
PubMed1977

Massive intramedullary globules in IgA monoclonal gammopathy associated with gastric carcinoma.

The bone marrow of a patient with IgA monoclonal gammopathy associated with gastric carcinoma was massively infiltrated with extracellular globules of varying sizes from 2 to 110 micron. These exposed globules were not found in the metastatic lesions heavily infiltrated with plasma cells, but were exclusively confined to the bone marrow. They were indistinguishable from Russell bodies and composed of monoclonal immunoglobulin (IgA, lambda). Of interest is the fact that, despite a small number of plasma cells, there was an intramedullary extensive infiltration of exposed globules. The following conditions may be related to these changes. (1) The globules were not removed rapidly by effectual phagocytosis. (2) The environment of the bone marrow may be favorable for their remaining. In our case, however, the possibility that the plasma cells around the tumor were not of the same clonal origin as the marrow plasma cells cannot be ruled out. (3) The marrow plasma cells may produce immunoglobulin more vigorously, whereas their survival time be shorter than usual. As a result, these exposed globules released on the death of the cells accumulated massively in the bone marrow.

Adenocarcinoma, Papillary↗