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Biomedical subjects

S Umeki

Publications and source records attributed to S Umeki.

At least 145 records · Page 8Linked to original sources

A possible cyclic AMP-mediated regulation of microsomal fatty acyl-CoA desaturation system in Tetrahymena microsomes.

Profound alterations in the microsomal fatty acyl-CoA desaturase activities and cyclic AMP production of a unicellular eukaryote, Tetrahymena pyriformis NT-1, originally grown in the glucose-deficient medium, were observed, following the administration of glucose or beta-adrenergic agonists such as epinephrine and isoproterenol. There was a great increase of stearoyl-CoA (delta 8) desaturase activity coincident with a 2-fold decrease of oleoyl-CoA (delta 12) desaturase activity over the first 2 h after administration of these compounds. During this period of time, it was found that the production in vivo of labeled oleic acid from [14C]acetic or [3H]palmitic acid increases 2-fold and the formation in vivo of each labeled linoleic and gamma-linolenic acids drastically decreases. Glucose or beta-adrenergic agonists caused an increase of stearoyl-CoA-stimulated reoxidation rate of NADH-reduced cytochrome b5 but depressed oleoyl-CoA-stimulated reoxidation rate of b5, indicating that both desaturase activities are controlled by the respective terminal components of the desaturase system. A significant and reproducible increase of adenylate cyclase activity and a slight decrease of cyclic AMP phosphodiesterase activity were observed to occur within the first 2 h after the addition of these compounds, when cyclic AMP content in Tetrahymena cell rose by 3-4-fold. Propranolol, a beta-adrenergic blocker, abolished the effects of glucose or beta-adrenergic agonists on the activities of fatty acyl-CoA desaturases and the terminal components as well as cyclic AMP production of cells. These results suggest that glucose and beta-adrenergic agonists may modulate the microsomal fatty acyl-CoA desaturase system in Tetrahymena by acting through the increase of intracellular cyclic AMP content.

3',5'-Cyclic-AMP Phosphodiesterases↗

Suppression by dexamethasone of isoproterenol-mediated changes in fatty acyl-CoA desaturase activity of Tetrahymena microsomes.

Preincubation of Tetrahymena pyriformis cells with dexamethasone inhibited the microsomal fatty acyl-CoA desaturase activities of isoproterenol-induced modulation; that is, an increase in delta 9-desaturase activity accompanied by a decrease in delta 12-desaturase activity. Although isoproterenol caused an increase in delta 9-terminal component activity with decreased delta 12-terminal component activity, dexamethasone reduced these isoproterenol-mediated activity changes. In cells treated with dexamethasone prior to isoproterenol administration, stimulation of cyclic AMP accumulation by isoproterenol was inhibited. These results suggest that dexamethasone may repress isoproterenol modulation of the activity of terminal components (cyanide-sensitive factor) in the fatty acyl-CoA desaturase system by reducing the cyclic AMP level.

Animals↗

Alterations in serum pancreatic elastase 1 content in acute and chronic pancreatitis: comparison with alpha-amylase activity.

Serum pancreatic elastase 1 content in 45.9% of 203 samples from 32 patients with acute pancreatitis was found to be greatly elevated to greater than 1000 ng/dl, much higher than the control values (90 to 270 ng/dl), whereas serum alpha-amylase activity, in 62.3% of the same samples, was within the control range (100 to 460 IU/L). The increased pancreatic elastase 1 content persisted for several days after serum alpha-amylase activity returned to normal, suggesting that, compared with serum alpha-amylase activity, pancreatic elastase 1 content truly reflects the clinical course of acute pancreatitis. The measurement of pancreatic elastase 1 content appears to be more valuable in the diagnosis and prognosis of acute pancreatitis than that of serum alpha-amylase activity. In 41 patients with chronic pancreatitis, on the other hand, pancreatic elastase 1 content and serum alpha-amylase activity were within the normal range in 38.3% and 56.2% respectively, of 336 samples.

Acute Disease↗

Repression by dexamethasone of epinephrine-induced modulation of the fatty acyl-CoA desaturase system in Tetrahymena microsomes.

Epinephrine modulation of the fatty acyl-CoA desaturase activities in Tetrahymena microsomes, namely the stimulation of delta 9 desaturase activity with a decreased activity of delta 12 desaturase, was markedly inhibited by dexamethasone administered 30 min prior to epinephrine addition. This effect by dexamethasone was dose-dependent. With epinephrine or dexamethasone prior to epinephrine administration, the activities of delta 9-terminal and delta 12-terminal components were found to change in parallel with those of delta 9 and delta 12 desaturase activities respectively. Furthermore, addition of dexamethasone as early as 30 min before epinephrine repressed the epinephrine-mediated stimulation of cyclic AMP production and of adenylate cyclase activity. Therefore, it is suggested that dexamethasone may inhibit the modulation by epinephrine of the terminal component activity, which plays a crucial role in microsomal fatty acyl-CoA desaturase system, through the reduction of cyclic AMP accumulation by decreased responsiveness to epinephrine of Tetrahymena cells.

Adenylyl Cyclases↗

Chronic ethanol administration decreases fatty acyl-CoA desaturase activities in rat liver microsomes.

The delta 9-desaturase system in liver microsome from rats treated chronically with ethanol was studied. Stearoyl-CoA desaturase activity decreased by 80% and palmitoyl-CoA desaturase activity was not detectable in microsomes from ethanol-fed rats, while activities of electron transport components such as NADH-cytochrome c and NADH-ferricyanide reductases remained unchanged. However, chronic ethanol administration resulted in an adaptive induction of the activity of NADPH-cytochrome c reductase and the contents of cytochrome b5 and P-450. The activity of the terminal component (cyanide-sensitive factor; CSF) of the desaturase system was greatly depressed by ethanol treatment. The NADH/NAD ratio in microsomes of ethanol-fed rats increased over 2-fold. These results suggest that, during chronic ethanol ingestion, decreased activities of delta 9-desaturases are due mainly to a decreased content of the terminal component of the desaturase system.

Animals↗

Thermoadaptive regulation of microsomal desaturase and electron-transport enzyme activities in lipid-manipulated Tetrahymena cells. Extent of unsaturated fatty acid production is dependent on membrane fluidity before temperature down-shift.

Exposure of Tetrahymena pyriformis NT-1 to chimyl alcohol (1-O-hexadecyl glycerol) produced a reproducible enhancement in unsaturated fatty acids and a great decrease in order parameter (S), which result from the 2-fold increases of stearoyl-CoA and oleoyl-CoA desaturase activities in microsomes. When the chimyl alcohol-fed cells were shifted from 34 to 15 degrees C (down-shift), unlike the drastic increases in palmitoyl-CoA, stearoyl-CoA and oleoyl-CoA desaturase activities in the native cells, there was only a slight increase in palmitoyl-CoA desaturase activity with a parallel rise in the activity of the terminal component (cyanide-sensitive factor; CSF) of the desaturase system. During cold acclimation, the decrease of order parameter in chimyl alcohol-fed cells was smaller than that in native cells, since the order parameter had already been decreased by the addition of chimyl alcohol before the shift. These results suggest that chimyl alcohol-fed cells are easily able to accomplish temperature acclimation without requiring great modification of fatty acid composition and membrane fluidity, while the non-fed control cells have difficulty doing so.

Acclimatization↗

Modulation by dexamethasone of the fatty acyl-CoA desaturase system in Tetrahymena microsomes.

Dexamethasone produced an increased activity of stearoyl-CoA desaturase through the enhancement of delta 9-terminal component activity, and a corresponding decrease of oleoyl-CoA desaturase activity via the reduced activity of delta 12-terminal component in Tetrahymena microsomes. However, the content of cytochrome b5 as well as the activities of NAD(P)H-cytochrome c and NADH-ferricyanide reductases showed no significant changes by dexamethasone. Additionally, dexamethasone evoked a 3.5-fold increase of intracellular cyclic AMP content 2 hr after administration. These results suggest that dexamethasone may modulate microsomal fatty acyl-CoA desaturase system in Tetrahymena by increasing intracellular cyclic AMP content.

Animals↗

Effects of sterol manipulation on microsomal desaturase activities in Tetrahymena: with regard to thermal acclimation.

There was a great increase in microsomal palmitoyl-CoA desaturase activity of ergosterol-replaced Tetrahymena (ergosterol-cells), which exhibited a pronounced elevation of palmitoleate (16:1 delta 9) in fatty acid composition. At 2 hr after the growth temperature-shift from 34 to 15 degrees C (shift-down), palmitoyl-CoA desaturase activity in ergosterol-cells increased 6-fold compared to that in native cells containing tetrahymanol before the shift-down. These results suggest that, unlike drastic increases of palmitoyl-CoA, stearoyl-CoA and oleoyl-CoA desaturase activities by the shift-down in native cells, ergosterol-cells accomplish an adaptive modification of fatty acid composition by a preferential increase in palmitoyl-CoA desaturase activity, being which is principally due to the increased content of the terminal component (cyanide sensitive factor; CSF) of the desaturase system.

Animals↗

Modification of microsomal lipid composition and electron transport enzyme activities in isovalerate-supplemented cells of novel Tetrahymena ISO.

Tetrahymena ISO cells, which have an unusually high level of iso odd-numbered fatty acids, were grown medium supplemented with various concentrations of isovalerate. There was a marked increase in the total proportion of iso odd-numbered fatty acids in supplemented whole cells (28.9 leads to 70.3%) and microsomes (37.7 leads to 84%), with a corresponding decrease in normal fatty acids, although no significant alteration of phospholipid composition was observed during 11 hr isovalerate-supplementation. Microsomal palmitoyl-CoA and stearoyl-CoA desaturase activities in isovalerate-supplemented cells decreased by 45.7% and 30.6% during 11 hr, respectively. NADH-cytochrome c reductase and NADH-ferricyanide reductase activities as well as the content of cytochrome b560ms, which is similar to mammalian microsomal cytochrome b5, were reduced in microsomes from 11 hr-supplemented cells, whereas NADPH-cytochrome c reductase activity was constant. It is suggested that the alteration of the cross-sectional area of lipid molecules in the bilayer, which results from the replacement of normal fatty acids with iso- 15:0 and iso- 17:1, would result in the decline of palmitoyl- and stearoyl-CoA desaturation in the isovalerate-supplemented cells, in order to maintain membrane fluidity at a functional level.

Animals↗

The purification and identification of calmodulin from human placenta.

A protein which showed similarity to bovine brain calmodulin in electrophoretic mobilities on polyacrylamide gels in the presence of 40% glycerol (pH 8.6) and 0.1% sodium dodecyl sulfate (pH 7.2) was isolated from human placenta. Its final yield was approx. 4 mg per kg human placenta. The placenta protein was similar to bovine brain calmodulin in stimulating bovine brain calmodulin-deficient cyclic nucleotide phosphodiesterase in the presence of calcium. However, its stimulating activity was eliminated by ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) or trifluoperazine. In addition, there is a close resemblance in amino acid composition between the placental protein and bovine brain calmodulin. These results indicate that calmodulin is present in human placenta.

3',5'-Cyclic-AMP Phosphodiesterases↗

Ca2+-dependent modulator proteins from Tetrahymena pyriformis, sea anemone, and scallop and guanylate cyclase activation.

Previously, the guanylate cyclase activity of Tetrahymena pyriformis was shown to be activated by an endogenous modulator (calmodulin)-like protein (Na-gao, S., Suzuki, Y., Watanabe, Y., and Nozawa, Y. (1979) Biochem. Biophys. Res. Commun. 90, 261-268). This protein has now been identified as the modulator protein. The identification was based on the capability of this protein to activate the brain modulator-deficient phosphodiesterase and the mobility of this protein upon polyacrylamide gel electrophoresis. The activation of guanylate cyclase was specifically attributable to the Tetrahymena modulator protein since other modulator proteins examined (bovine brain, sea anemone, and scallop) were ineffective. Under the conditions where the activation of Tetrahymena guanylate cyclase occurred, guanylate cyclase activities from other sources, that include rat brain, rat lung, and human platelet, were not affected. In the phosphodiesterase activation, the potencies of scallop and Tetrahymena modulator proteins, which are represented by reciprocals of the quantities of proteins required for half-maximal activation of enzyme, were 66% and 55%, respectively, of that of the brain protein. The same decreasing order was seen for the affinity of these proteins for Ca2+ in enzyme activation. The results suggest a directional change of the modulator protein during the molecular evolution toward an increase in the capability in Ca2+-dependent enzyme activation.

Animals↗

Regional difference in susceptibility to damage of vestibulo-semicircular canals in experimental labyrinthine lesion.

In the study on regional difference in susceptibility to damage of vestibulo-semicircular canals upon causing labyrinthine lesion by four different procedures, namely, by intracranial approach, through the middle ear, through the facial nerve and by means of experimental endolymphatic hydrops, the following results were obtained. 1. The crista of posterior semicircular canal among the semicircular canals and the macula of the saccule within the vestibule were most susceptible to impairment. In other words, the most susceptible region was the so-called pars inferior. In regard to the impairment of the cupulas, the posterior semicircular canal was the most susceptible region. 2. Recovery from markedly reduced caloric nystagmus within a short period so as to see provocation of caloric nystagmus may result from the reconstruction of the cupulas and the normalization of vacuole-like findings of the sensory epithelium.

Animals↗

Age-related changes in the manifestations of tuberculosis. Implications for drug therapy.

Although the overall number of tuberculosis cases reported in developed countries has decreased markedly since about the middle of the twentieth century, at present active tuberculosis in the geriatric population is highly prevalent even in developed countries. With an increase in the aged population and striking progress in medicine during the past two decades, the development of tuberculosis infections and the active disease has been gradually changed; namely, the number of older people at risk of infection has been increasing. In the elderly, postprimary pulmonary tuberculosis and miliary tuberculosis are particularly difficult to diagnose. A high index of suspicion, a tuberculin skin test, and appropriate laboratory studies are essential for early diagnosis. In choosing the proper therapy for tuberculosis in the elderly, efficacy, patient compliance, and toxicity must be considered. During this decade, more so than ever before, much time and work will be required to more completely understand the factors that place a patient at risk for infection and to accomplish eradication of tuberculosis.

Adult↗