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Biomedical subjects

K Suda

Publications and source records attributed to K Suda.

At least 235 records · Page 13Linked to original sources

Behenoyl cytosine arabinoside, aclacinomycin A, 6-mercaptopurine, and prednisolone combination therapy for acute non-lymphocytic leukaemia in adults.

38 consecutive, previously untreated adult patients with acute non-lymphocytic leukaemia (ANLL) were treated with BHAC-AMP (N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine, aclacinomycin A, 6-mercaptopurine, and prednisolone) therapy between March 1980 and February 1985. 25 patients (65.8%) achieved complete remission (CR). Median CR duration and median survival of patients who achieved CR were 14, and 24 months, respectively. The Kaplan-Meier analysis revealed a probability for remaining in CR of 18.0% at 5 years. Analysis of failure cases revealed that most of them were due to resistant disease. Major toxicities were infection, diarrhoea, liver dysfunction, nausea and vomiting but these were acceptable. The results indicate that BHAC-AMP therapy is comparable to the regimen with daunorubicin and cytosine arabinoside and a further clinical trial is necessary for previously untreated adult patients with ANNL.

Aclarubicin↗

Beta-adrenergic receptor adaptation after an acute exercise in rat myocardium.

An acute dynamic exercise provokes the translocation of beta-adrenergic receptors (beta-AR) from light vesicle fractions to sarcolemmal membranes in rat myocardium. However, 15 min after an acute exercise the density of beta-AR in both fractions returned to the pre-exercise level. The mean maximal activity of adenylate cyclase in response to isoproterenol roughly paralleled the redistribution of beta-AR. The dose-response curves, however, were substantially shifted to the right with increase in EC50 for isoproterenol stimulation of adenylate cyclase. Thus, the sensitivity of sarcolemmal beta-AR was found to be blunted 15 min afterwards.

Adenylyl Cyclases↗

Effects of adenosine and pertussis toxin on lipolysis in adipocytes from exercise-trained male rats.

The sensitivity and responsiveness of adipocyte lipolysis to adenosine and pertussis toxin were studied in exercise-trained male rats. Exercise training (9 weeks of treadmill running) significantly increased lipolytic response of adipocytes to noradrenaline (NA). Addition of adenosine deaminase (ADA) to reaction mixture effectively enhanced NA-stimulated lipolysis in adipocytes from both conditioned rats. However, under these conditions, the difference due to exercise training was still evident, although the difference was less pronounced. The inhibition curves of the R-site adenosine analogue N6-phenylisopropyladenosine (PIA) against "basal" (lipolysis in the presence of ADA) and NA-stimulated lipolysis were almost comparable between two groups. Only a small (approx. 2-fold) increase in IC50 of adipocyte lipolysis was observed in each inhibition curve in exercise-trained rats. Within 120 min of addition of pertussis toxin to adipocytes from control rats, "basal" lipolysis was significantly increased as compared to "basal" lipolysis in the absence of toxin at the same point. Similarly, pertussis toxin significantly increased "basal" lipolysis in exercise-trained adipocytes. However these were relatively sensitive to pertussis toxin, since significant effect of toxin was seen within 60 min. An addition of NA (0.1 uM) to the medium in the presence of ADA and toxin significantly increased adipocyte lipolysis in both conditioned rats. Again, under these conditions, we observed that the maximal rate of lipolysis of adipocytes from exercise-trained rats was increased as compared to control rats. These results suggest that the decreased input through the inhibitory pathway in lipolytic cascade may be not rate limiting for the amplified lipolytic responsiveness of adipocytes to hormonal stimuli in exercise-trained rats.

Adenosine↗

[The modes of spread of pancreas head cancer based on difference of the pancreatic anlagen].

Embryologically the pancreas head consists of a dorsal and a ventral portion and these were able to be differentiated by the shape of the islets and the density of pancreatic polypeptide (pp) cells. We examined histologically the modes of spread of carcinoma of the head of the pancreas. The material were 15 cases with T1 and T2 cancer resected (T1;8;T2;7) and included 8 tumors arising from a ventral pancreas and 7 dorsal. We conclude that most of pancreas head cancers arising from a ventral pancreas involved the retropancreatic soft tissue at the early stage, and those arising from a dorsal pancreas showed an apparent tendency of a spread to the epithelial linings of the main pancreatic duct.

Adult↗

Mutations restoring import of a yeast mitochondrial protein with a nonfunctional presequence.

An internal deletion in the presequence of the precursor to yeast cytochrome oxidase subunit IV blocks import of the protein into mitochondria. We have identified two mechanisms by which yeast cells can suppress the defect of the plasmid-borne defective gene. One mechanism creates a new functional presequence by point mutations, or local DNA rearrangements, within the open reading frame or its 5'-untranslated region. The second mechanism compensates for the defective presequence by recessive mutations in single nuclear genes. The plasmid-linked mutations may mimic the mechanism(s) by which mitochondrial presequences arose during evolution whereas the chromosomal mutations may help to identify components of the mitochondrial import machinery.

Amino Acid Sequence↗

Possible mechanism of regulating adenylate cyclase activity in adipocyte membranes from exercise-trained male rats.

(-)-Isoproterenol-stimulated adenylate cyclase activities were significantly greater in membranes from exercise-trained male rats than in sedentary male rats. GTP-inhibition of forskolin (10 microM)-stimulated cyclase activities were observed in sedentary membranes, whereas the inhibitory actions of GTP were significantly reduced in membranes from trained rat adipocytes. Treatment of membranes with islet-activating protein, a pertusis toxin, completely abolished the differences in GTP-inhibition of forskolin-stimulated cyclase activities between the two groups. The amounts of the inhibitory regulatory protein (41kDa/40kDa polypeptides) were about 40% less in membranes from trained rats than in sedentary membranes, whereas that of the stimulatory regulatory protein (a 45kDa polypeptide) was equivalent. It is concluded that the enhanced cyclase activities of adipocyte membranes from trained male rats appear to result from, in part, an attenuation of the inhibitory pathway due to a specific decrease in the amount of the inhibitory regulatory proteins.

1-Methyl-3-isobutylxanthine↗

Sugar permeases of the bacterial phosphoenolpyruvate-dependent phosphotransferase system: sequence comparisons.

The amino acyl sequences of eight permeases (enzymes II and enzyme II-III pairs) of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) have been analyzed. All systems show similar sizes, and six of these systems exhibit the same molecular weight +/- 2%. Several exhibit sequence homology. Characteristic NH2-terminal and COOH-terminal sequences were found. The NH2-terminal leader sequences are believed to function in targeting of the permeases to the membrane, whereas the characteristic COOH-terminal sequences are postulated to mediate interaction with the energy-coupling protein phospho HPr. One of the systems, the one specific for mannose, exhibits distinctive characteristics. A pair of probable phosphorylation sites was detected in each of the five most similar systems, those specific for beta-glucosides, sucrose, glucose, N-acetylglucosamine, and mannitol. One of the two equivalent phosphorylation sites (proposed phosphorylation site 1) was located approximately 80 residues from the COOH terminus of each system. The other site (proposed phosphorylation site 2) was located approximately 440 residues from the COOH termini of the glucose and N-acetylglucosamine systems, approximately 320 residues from the COOH termini of the beta-glucoside and sucrose systems, and 381 residues from the COOH terminus of the mannitol system. Intragenic rearrangement during evolutionary history may account for the different positions of phosphorylation sites 2 in the different PTS permeases. More extensive intragenic rearrangements may have given rise to entirely different positions of phosphorylation in the glucitol, mannose, and lactose systems. A single, internal amphipathic alpha-helix with characteristic features was found in each of seven of the eight enzymes II. The lactose-specific enzyme III of Staphylococcus aureus was unique in possessing a COOH-terminal amphipathic alpha-helix rich in basic amino acyl residues. Possible functions for these amphipathic segments are discussed.

Amino Acid Sequence↗

Bacterial proteins with N-terminal leader sequences resembling mitochondrial targeting sequences of eukaryotes.

Amphipathic, alpha-helical, leader sequences, analogous to those that direct nuclear-encoded eukaryotic proteins into mitochondria, have been found in one and only one class of bacterial integral membrane proteins. These bacterial proteins are the sugar permeases of the phosphoenolpyruvate-dependent phosphotransferase system. The amphipathic leader sequence in each of these proteins is terminated by a helix breaker, either a prolyl residue or 2 adjacent glycyl residues. Preliminary evidence suggests that these leader sequences function to target the proteins to the envelope fraction of the prokaryotic cell during their biosynthesis.

Amino Acid Sequence↗

The diagnostic value and clinical significance of light exercise 201T1 ECT in coronary artery disease.

To examine the clinical significance of scintigraphic transient perfusion defects preceding the occurrence of anginal pain and ischemic ST depression, we performed both maximal and light exercise thallium-201 emission computed tomography in 13 patients with effort angina pectoris. The target heart rate in the light test was set at 80% of the peak heart rate in the maximal test. The scintigraphic transient perfusion defect was observed in all cases in both tests, while the incidence of anginal pain and/or ischemic ST depression was lower in the light test (5/13 cases) comparing to the maximal test (13/13 cases). However, the number of defect segments in the light test was smaller than that in the maximal test (13 vs 19 segments). In the former 13 segments, the initial relative activity in the maximal test was not significantly different from that in the light test (69.4 +/- 9.3 vs 70.1 +/- 10.0%). These results suggest that the light test can precipitate a transient perfusion defect preceding anginal pain and/or ischemic ST depression, therefore the light test is useful to detect coronary artery disease in patients who cannot perform the maximal test.

Aged↗

Effects of cyclic nucleotide derivatives on the Na+ pump activity and the release of sialic acid in dog submandibular glands.

The effects of dibutyryl cyclic AMP (DBcAMP) and cyclic GMP (DBcGMP) on the Na+,K+-ATPase activity and the release of sialic acid were investigated in dog submandibular gland pieces. The Na+,K+-ATPase activity and the release of sialic acid were significantly stimulated in the presence of 100 microM DBcAMP or in the combination of 3 mM NaF and 50 microM 1-methyl-3-isobutylxanthin but were not by DBcGMP. When the pieces were incubated in the Ca2+-free medium, the DBcAMP-induced Na+,K+-ATPase activity slightly decreased but the sialic acid release was unaffected. The corresponding results were also observed in the Ca2+-free medium supplemented with 2 mM EGTA. These results suggest that the cytosolic cyclic AMP modifies the Na+ pump activity.

Animals↗

Some characteristics of the beta-adrenergic system in rat adipocyte membranes after the chronic administrations of isoproterenol.

The effects of chronic administrations of isoproterenol (IPR) on adipocyte beta-adrenergic system were investigated. A 21-days in vivo administration of IPR (2.5 mg/kg BW/day) reduced (-)-IPR- and 5'-guanylylimidodiphosphate-stimulated adenylate cyclase activities. Moreover, the number of beta-adrenergic receptors (beta-AR) and (-)-IPR-stimulated [3H]GDP release from adipocyte membranes were significantly depressed in the treated rats compared to controls. These results suggest that the desensitized response of adenylate cyclase to beta-agonists, induced by chronic in vivo administrations of IPR, may result from impaired coupling efficiency between beta-AR and adenylate cyclase with the significant loss of the number of beta-AR and possible change(s) of guanine nucleotide regulatory proteins.

Adenylyl Cyclases↗

Two types of hormone-responsive adenylate cyclase in the rat liver.

We have demonstrated the existence of two types of hormone-responsive adenylate cyclase in the isolated perfused rat liver. One, less abundant, is linked to glycogenolysis and the other is not. Glucagon stimulates mainly the glycogenolysis-linked fraction and, to a lesser extent, the fraction which is not linked to glycogenolysis. The suppressive effect of insulin is specific for the glucagon-responsive adenylate cyclase and is inhibited by 3-isobutyl-1-methylxanthine (IBMX). However, this mechanism can explain only partly the ability of insulin to suppress glycogenolysis, and is not observed when cAMP is increased sufficiently by glucagon. Secretin-responsive adenylate cyclase is not linked to glycogenolysis and is suppressed specifically by oxymetazoline. The capacity of this suppressive effect is large and not inhibited by IBMX. These results suggest that there is a functional compartmentalization of cAMP within the hepatocyte or among hepatocytes.

1-Methyl-3-isobutylxanthine↗