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Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 1,009 records · Page 56Linked to original sources

[Studies on the efficient application by STKS and 8200].

We examined the usefulness of differential leukocyte counts provided by the automated STKS (Coulter) using the VCS method, the cell analyzer 8200 (Hitachi) using the image analysing as compared with that of the traditional manual method. In the STKS, about 8000 leukocytes can be counted within one minute and 5 part differential counts (neutrophils, eosinophils, monocytes, lymphocytes) are provided. The STKS may provided adequate identification of patients who have significant leukocyte abnormalities that require further study. Potential deficiencies of this system included an inability to detect abnormal lymphocytes such as ATL cells. In addition, low numbers of erythroblasts were missed, although these cells could be warned by a flagging system. In the cell analyzer 8200, the differential leukocyte count is done by the microscopic examination of stained blood films which is prepared by automatic device. Results from counts performed with this system correlated well with those obtained by the manual method. This system also missed low numbers of erythroblasts and ATL cells. Another potential deficiencies of the system is that number of cells observed within one minute were limited to about 100. When a prescribed set of cut-off limits, carefully chosen qualitatively, is introduced into these systems, automated leukocyte differential counts, with combination of STKS, 8200 and the manual method, clearly improve turn around time for laboratory blood assessments and this help to reduce unnecessary differential leukocyte counts by the manual method.

Evaluation Studies as Topic↗

[Effect of cefclidin and E1077, new cephalosporins, on the alcohol-metabolizing system in rats].

Administration of latamoxef and cefoperazone, reported to act like disulfiram in humans, caused a depression of mitochondrial low Km aldehyde dehydrogenase (low Km ALDH) activity in rats. In addition, a marked increase of blood acetaldehyde concentration was observed when rats were given alcohol orally at 18 hours after administration of these cephalosporins. However, mitochondrial low Km ALDH activity and blood acetaldehyde level were not altered by repeated administration of 300 mg and 1,000 mg of cefclidin (CFCL, E1040) or E1077 per kg. From these results, it was concluded that neither CFCLn or E1077 affected the alcohol metabolizing-system.

Acetaldehyde↗

[Coexistence of myeloma and primary myelodysplastic syndrome (MDS)].

Coexistence of myeloma and MDS was noted in a patient without history of exposure to cytotoxic drugs. A 73-year-old man was admitted because of fever and dyspnea on exertion. A complete blood count revealed macrocytic anemia with hemoglobin 7.1 g/dl, RBC 191 x 10(4)/microliters and MCV 111.2 fl. WBC was 6,000/microliters, with normal differentials. Bone marrow showed erythroid hyperplasia with M/E ratio of 1.36. There were marked tri-lineage cellular abnormalities, which included megaloblastic changes, multinucleated erythroblasts, hypersegmentation of neutrophils, giant neutrophils, and giant platelets. Ringed-sideroblasts were demonstrated in 20% of the erythroblasts. These findings were compatible with MDS. Although plasma cells accounted for only 9.7% of the nucleated marrow cells, there were many immature plasma cells with inclusion bodies, and the patient showed lambda-light chain type monoclonal gammopathy with corresponding Bence Jones protein. Immuno-histochemical staining of the bone marrow biopsy specimen revealed monoclonal growth of lambda-positive plasma cells. A punched-out lesion of the skull eventually developed. These findings suggest existence of myeloma. There have been some reports of coexistence of MDS and myeloma; supporting the idea of pluripotent stem cell origin of the disease. This is the first documentation of such a case in Japan.

Aged↗

Japanese experience in the treatment of myelodysplastic syndromes.

In spite of the numerous therapeutic attempts cited, the overall results have been unsatisfactory, because responses are usually modest, short in duration, and often associated with considerable toxicity. No treatment has proven superior to conventional supportive care. A marked heterogeneity exists in the clinical manifestations and outcome of MDS on the whole, and even within single subtypes of MDS. The heterogeneity should be taken into account in the selection of therapeutic options. Leukemic transformation and nonleukemic death, notably infections and bleeding, are the two major determinants of prognosis. The risk factors for the two clinical settings are, at least in part, separable. In addition, some patients can survive for more than 5 years. Analysis of the clinical conditions of these long-term survivors suggests that, in a small number of patients, the chance of long-term survival is more likely to be a part of the natural history rather than the result of treatment. Thus, careful evaluation of the initial data is essential in designing treatment for MDS patients so that risks and benefits can be weighed against the possibility of long-term survival. Recombinant hematopoietic growth factors may provide some hope. These biologic factors have considerable advantages over many pharmaceuticals in that they are natural, short-lived, less toxic, and highly effective. In fact, the overall efficacy of CSFs has been outstanding for disorders hitherto viewed as otherwise refractory. Maintenance treatment utilizing these factors in a carefully designed prospective study is urgently needed to determine whether such a treatment modality may lead to alteration of the natural history and prolongation of survival. Finally, combined use of these growth factors is another area warranting further investigations to achieve sustained improvement in either two- or three-cell lineages.

Cell Differentiation↗

Cytoprotection by 16,16-dimethylprostaglandin E2. Role of gastric juice and mucus gel layer.

A mechanism of cytoprotection by 16,16-dimethylprostaglandin E2 (16,16-dimethyl-PGE2) was investigated in rats with respect to possible roles of the gastric juice and the mucus gel layer. 16,16-Dimethyl-PGE2 significantly increased the volume of gastric juice and mucus thickness. In a gastric juice-emptied stomach, 16,16-dimethyl-PGE2 protected the gastric mucosa against 30% ethanol, but not against 40% ethanol. Moreover, this agent did not show any cytoprotective action even against 30% ethanol when both gastric juice and mucus gel were removed. In this situation there was no histological change in the depth of injury, whether 16,16-dimethyl-PGE2 was given as pretreatment or not. These results suggest that there are two mechanisms that may play major roles in the cytoprotection of the gastric mucosa by 16,16-dimethyl-PGE2: (a) dilution of necrotizing agents by increased gastric juice and (b) thickening of the mucus gel layer.

Animals↗

Avidin protein-conjugated column for direct injection analysis of drug enantiomers in plasma by high-performance liquid chromatography.

A new concept in high-performance liquid chromatography supports is proposed for the direct injection analysis of drug enantiomers in plasma. The new supports are designed with disuccinimidyl suberate as a hydrophobic internal region, and avidin protein as a hydrophilic and bulky surface region. Plasma proteins are excluded by the avidin phase and are eluted immediately from the column, whereas low-molecular-mass analytes can penetrate the surface region and interact with disuccinimidyl suberate. Enantiomers interact differentially with avidin, and are thereby separated. This column was used in reversed-phase high-performance liquid chromatographic analysis to determine ketoprofen enantiomers in plasma by direct injection. The recovery of racemic drug from plasma was almost 100%.

Acetonitriles↗

Striatal N-methyl-D-aspartate receptors in haloperidol-induced catalepsy.

Bilateral ablation of the frontal cortex of rats markedly reduced the catalepsy induced by haloperidol (1 mg/kg i.p.). Similarly, the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, D(-)-2-amino-5-phosphonopentanoic acid (10 micrograms/side), injected bilaterally into the rostral part of the caudate-putamen (CP) reduced haloperidol-induced catalepsy whereas its injection into the intermediate part of the CP was ineffective. The quisqualate receptor antagonist, L-glutamic acid diethyl ester (100 micrograms/side), did not affect haloperidol-induced catalepsy when injected into the rostral part of the CP. On the other hand, NMDA (1 micrograms/side) injected bilaterally into the rostral part of the CP was able to restore haloperidol-induced catalepsy in frontally decorticated rats without any notable cataleptic effect of its own. These findings suggest that a certain degree of tonic stimulatory effect of corticostriatal glutamatergic pathways on NMDA receptors within the rostral part of the CP is a prerequisite for the expression of the cataleptogenic action of haloperidol.

Animals↗

Cyclic GMP-dependent protein kinase stimulates the plasma membrane Ca2+ pump ATPase of vascular smooth muscle via phosphorylation of a 240-kDa protein.

The plasma membrane Ca2+ pump ATPase from porcine aorta was isolated by the calmodulin affinity chromatographic method of Kosk-Kosicka et al. (Kosk-Kosicka, D., Scaillet, S., and Inesi, G. (1986) J. Biol. Chem. 261, 3333-3338). Its activity was restored by adding either phosphatidylcholine or phosphatidylserine. Cyclic GMP-dependent protein kinase (G-kinase) stimulated the enzyme in a concentration-dependent manner. However, phosphatidylinositol kinase (PI-kinase) activity was not detected in the enzyme preparation, and the presence of phosphatidylinositol was not necessary for stimulation by G-kinase. Furthermore, adenosine, a potent PI-kinase inhibitor, did not affect the stimulation. The enzyme preparation contained three major proteins, with molecular masses of 240, 145, and 135 kDa, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 240- and 135-kDa proteins were phosphorylated in association with the stimulation by G-kinase, but only the phosphorylation of the 240-kDa protein was dependent on the G-kinase concentration. A purified enzyme without the 240-kDa protein, prepared by our previous method (Imai, S., Yoshida, Y., and Sun, H.-T. (1990) J. Biochem. (Tokyo) 107, 755-761), was not activated by G-kinase. Immunoblotting with an antibody against the human erythrocyte Ca2+ pump revealed that the 135-kDa protein corresponded to one of the isoforms of the plasma membrane Ca2+ pump. These results suggest that the phosphorylation of the 240-kDa protein is responsible for stimulation of the plasma membrane Ca2+ pump ATPase by G-kinase.

Adenosine↗

A novel prenyltransferase for a small GTP-binding protein having a C-terminal Cys-Ala-Cys structure.

smg p25A/rab3A p25 is a member of the small GTP-binding protein superfamily which is implicated in intracellular vesicle transport. smg p25A has a cDNA-predicted C-terminal structure of Cys-Ala-Cys. The protein purified from bovine brain membranes is geranylgeranylated at both the two cysteine residues and carboxyl-methylated at the C-terminal cysteine residue. Two types of prenyltransferase for small GTP-binding proteins have thus far been reported: ras p21 farnesyltransferase (ras p21 FT) and rhoA p21 geranylgeranyltransferase (rhoA p21 GGT). Neither of them geranylgeranylated smg p25A having a C-terminal Cys-Ala-Cys structure. In this paper, a smg p25A GGT was partially purified from bovine brain cytosol and separated from the ras p21 FT and rhoA p21 GGT by column chromatographies. smg p25A GGT transferred the geranylgeranyl moiety from geranylgeranyl pyrophosphate to both the two cysteine residues in the C-terminal Cys-Ala-Cys structure of smg p25A. smg p25A GGT did not use farnesyl pyrophosphate as a substrate and was also inactive on c-Ha-ras p21 and rhoA p21 with either farnesyl pyrophosphate or geranylgeranyl pyrophosphate as a substrate. These results indicate that there are at least three types of prenyltransferase for small GTP-binding proteins in mammalian tissues.

Amino Acid Sequence↗

Effect of dietary alpha-linolenate on platelet-activating factor production in rat peritoneal polymorphonuclear leukocytes.

The effects of dietary alpha-linolenate (18:3, n-3) and linoleate (18:2, n-6) on platelet-activating factor (PAF) production were examined. Rats were fed an alpha-linolenic acid-rich (perilla oil) diet or a linoleic acid-rich (safflower oil) diet for 6 wk, and polymorphonuclear leukocytes (PMN) were elicited by peritoneal injection of casein. The overall phospholipid content and composition as well as the subclass distribution of choline and ethanolamine glycerophospholipids in PMN were not altered by these diets. However, with the perilla oil diet their content of a putative precursor of PAF, 1-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine was approximately 50% of that with safflower oil diet. On exposure to various concentrations of FMLP, PAF formation by PMN in the perilla oil group was less than 50% of that by PMN in the safflower oil group. A larger difference in PAF productions by PMN in the two dietary groups was observed on their stimulation with calcium ionophore A23187. These results demonstrate that PAF production is modulated in some as yet unknown way by changing the alpha-linolenate/linoleate balance of the diet.

Animals↗

Different substrate specificities of lanosterol 14a-demethylase (P-45014DM) of Saccharomyces cerevisiae and rat liver for 24-methylene-24,25-dihydrolanosterol and 24,25-dihydrolanosterol.

The purified lanosterol 14a-demethylase (P-45014DM) of S. cerevisiae catalyzed the 14a-demethylation of 24-methylene-24,25-dihydrolanosterol (24-methylenelanost-8-en-3 beta-ol, 24-methylene-DHL), the natural substrate of the demethylase of filamentous fungi, as well as its natural substrate, lanosterol. Lanosterol 14a-demethylase of rat liver microsomes also catalyzed the 14a-demethylation of 24-methylene-DHL, but the activity was considerably lower than that for lanosterol. The activity of the rat liver enzyme for 24-methylene-DHL was also lower than that for 24,25-dihydrolanosterol (DHL), while the activity of yeast P-45014DM for 24-methylene-DHL was considerably higher than that for DHL. Since 24-substituted sterols are not found in mammals and DHL is not an intermediate of ergosterol biosynthesis by yeast, above-mentioned different substrate specificities between the yeast and the mammalian 14a-demethylases may reflect certain evolutional alteration in their active sites in relation to the difference in their sterol biosynthetic pathways.

Animals↗

C terminus of the small GTP-binding protein smg p25A contains two geranylgeranylated cysteine residues and a methyl ester.

smg p25A, also known as the rab3A protein, is a small GTP-binding protein that has been implicated in intracellular vesicle transport and the secretion of neurotransmitters. It has been shown to bind reversibly to membranes, though its cDNA-predicted sequence contains no obvious membrane-binding domains. However, smg p25A does contain a cDNA-predicted C-terminal Cys-Ala-Cys sequence at positions 218 through 220, which suggests that it may be posttranslationally modified. In the present study we used two different approaches to investigate this possibility. First, we incubated pheochromocytoma cells with [3H]mevalonolactone, examined the proteins that became labeled by two-dimensional gel electrophoresis, and demonstrated that two of these proteins exactly corresponded to smg p25A. Second, we purified smg p25A from bovine brain membranes and analyzed both the full-length protein and a proteolytically derived C-terminal peptide by a combination of high performance liquid chromatography and mass spectrometry. This approach revealed that the protein's C-terminal region is methyl-esterified and contains two geranylgeranyl groups linked via thioether bonds to Cys-218 and Cys-220. Since smg p25A is one of several small GTP-binding proteins that share a C-terminal Cys-Xaa-Cys consensus sequence (where Xaa is an unspecified amino acid), our results suggest that these proteins may be similarly geranylgeranylated and methyl-esterified.

Adrenal Gland Neoplasms↗