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Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 919 records · Page 51Linked to original sources
PubMed1993

Relationship between Helicobacter pylori colonization and acute inflammation of the duodenal mucosa.

A relationship between Helicobacter pylori colonization and acute inflammation of the duodenal mucosa was studied in 75 patients with duodenal ulcer and nine with endoscopically normal duodenal mucosa. A biopsy of the duodenal bulb in each patient was used for both detection of H. pylori and histological assessment of acute inflammation [polymorphonuclear leukocyte (PMN) infiltration and regenerative changes of the duodenal epithelial cells]. Biopsies with regenerative changes showed a marked PMN infiltration, regardless of the duodenal H. pylori status. In biopsies without regenerative changes, H. pylori colonization was closely associated with PMN infiltration. Acute inflammation in the duodenal mucosa surrounding ulcers is caused mainly by acid, but our data suggest that H. pylori is another important factor in the development of PMN infiltration in the duodenal mucosa.

Biopsy↗
PubMed1993

Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan.

It is well known that cytogenetic analysis in patients with myelodysplastic syndrome (MDS) provides information useful in determining their prognosis. Based on the chromosomal results obtained from 401 MDS patients by a multicentric study in Japan, we studied correlations between chromosomal findings and prognosis or leukemic transformation in MDS patients. Patients with complex aberrations (cytogenetic abnormalities at more than three chromosomes), of any subtype, had a poor prognosis; for example, > 60% of patients with refractory anemia (RA) showing complex aberrations died within one year, but only 11% of them developed leukemia. In patients with RA with ringed sideroblasts (RARS), > 70% of those with complex aberrations evolved into the leukemic phase and survived for less than one year, suggesting a biologic heterogeneity in RARS patients. By contrast, about 5% of patients with RA or RARS exhibiting chromosomal findings other than -7/7q-, +8, two aberrations, and complex aberrations, developed leukemia and had a favorable prognosis. Therefore, the presence of chromosome abnormalities alone in patients with RA or RARS is not a factor in predicting leukemic transformation or poor prognosis. In patients with refractory anemia with an excess of blasts (RAEB), the presence of chromosome aberrations at MDS diagnosis affected the occurrence of leukemic transformation (24% versus 43%), however, no particular difference was noted in patients with RAEB in transformation with regard to whether they had chromosome changes or not, and about 60% of them evolved into leukemia. The poor prognosis related to complex aberrations was consistently noted in all MDS subtypes or age-matched groups, indicating that this cytogenetic anomaly is an independent risk factor for a poor prognosis in MDS patients. The duration between MDS diagnosis and development of the leukemic phase and that between the latter and death were significantly shorter in patients with complex aberrations than those without this change. Although the clinical significance of certain chromosomal abnormalities differs among subtypes of MDS, a new scoring system for predicting prognosis by cytogenetic changes, in combination with hematologic parameters, was proposed.

Adolescent↗
PubMed1993

Re-analysis of prognosis in refractory anemia alone, with ring sideroblasts, and with excess of blasts.

Based on 473 primary cases of refractory anemia (RA), RA with ring sideroblasts (RARS), or with an excess of blasts (RAEB), new staging systems for overall survival, leukemic transformation, and nonleukemic death were developed. The reproducibility of these new staging systems, our former staging systems for leukemic transformation and nonleukemic death, and that for overall survival provided by Sanz et al. (Blood 1989;74:395-408), were estimated using a total of 132 patients with RA, RARS, or RAEB (test sample). The correlation of risk ratios of the test sample from our system and that of Sanz et al. was poor (tau = 0.24; Kendall rank correlation). Our risk ratio was a significant (p = 0.0012) continuous covariate of the Cox model life-table analysis in the test sample but that of Sanz et al. was not. The new and previous staging systems for leukemic transformation were highly similar (tau = 0.7) and risk ratios of both systems were significant in the test sample (p = 0.00046 and 0.0017, respectively). Based upon the new system, patients at high risk for leukemic transformation RA or RARS were identified as males, with bone marrow myeloblasts higher than 2.5%, abnormal granules in the granulocytes, and circulating erythroblasts. Their cumulative leukemic transformation rate exceeded 50% within 2 years from presentation. The new and previous systems for nonleukemic death were moderately correlated (tau = 0.47). The risk ratios of both systems were significant in the test sample (p = 0.00012 and 0.000024, respectively) but failed to stratify test sample patients into three distinct risk groups. In conclusion, our new staging systems for overall survival and leukemic transformation were reproducible in RA, RARS, or RAEB patients and will be useful especially in identifying high-risk patients with RA or RARS, who are considered to be at lower risk by the FAB classification.

Adolescent↗
PubMed1993

[Ferrokinetics and bone marrow scanning in patients with myelodysplastic syndrome, hypoplastic myelodysplastic syndrome and aplastic anemia].

Ferrokinetic measurement were performed in a total of 48 patients with myelodysplastic syndrome (MDS), 13 with hypoplastic MDS and 25 with aplastic anemia (AA). Forty seven % of patients with hypoplastic MDS progressed to acute leukemia, however none of the patients with AA progressed to acute leukemia. Sixty-nine% of the patients with MDS showed increased erythron transferrin uptake (ETU) caused by ineffective erythropoiesis. On the other hand, 85% of the patients with hypoplastic MDS and all patients with AA showed decreased ETU caused by reduced erythropoiesis. Positive correlation was observed between ETU and the erythroid precursor cells in the bone marrow. Bone marrow scintigraphy utilizing 99mTc-sulphur colloid showed peripheral expansion of active marrow in MDS patients and islands-like distribution in hypoplastic MDS and AA patients. Ferrokinetics and bone marrow scintigraphy demonstrated the difference between typical MDS and hypoplastic MDS. Hypoplastic MDS appears to be a distinct clinicopathologic entity.

Anemia, Aplastic↗
PubMed1993

Myelodysplastic syndromes: from morphology to molecular biology. Part I. Classification, natural history and cell biology of myelodysplasia.

The myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic disorders predominantly affecting the elderly. Patients frequently develop acute leukemia, but the majority suffer from the consequences of bone marrow failure. The underlying acquired genetic abnormality is the inadequate production of dysplastic and poorly functional cells resulting from defective differentiation and premature cell death of the abnormal hematopoietic clone. Although the pathogenesis is unknown, recent evidence suggests that a sequence of DNA lesions leads to alteration of the cellular function, emergence and consequent evolution of the premalignant clone.

Humans↗
PubMed1993

Myelodysplastic syndromes: from morphology to molecular biology. Part II. The molecular genetics of myelodysplasia.

Most studies of the clonal origin of the underlying lesion(s) and all investigations using X-inactivation, have concluded that the myelodysplastic syndromes arise from a multipotent stem cell. Non-random chromosomal abnormalities, particularly deletions of 5q and 7q, are common, most notably in therapy related MDS. Progression to AML is also frequently accompanied by increased genomic instability as evidenced by the emergence of multiple karyotypic abnormalities. While some evidence hints at the presence of tumour suppressor genes on chromosomes 5, 7, 20 and 12, no such genes have yet been identified. The search for point mutations in known oncogenes has concentrated on two oncogenes RAS and c-FMS. Point mutation frequency generating active forms of RAS oncogenes is approximately 40% in MDS overall, up to 80% in studies of CMML. 60% of all MDS RAS mutation involves a G to A transition, producing a substitution of aspartate for glycine at a frequency of 50% (of total ras mutants). RAS mutation is associated with progression to AML, although the presence of a RAS point mutation alone is neither necessary nor sufficient for leukaemic transformation. Mutation of c-FMS is also more common in CMML in comparison to other MDS subtypes and, as yet, point mutation potentiating the response of the receptor to CSF-1 (codon 969) has been found more frequently than point mutation resulting in permanently activated receptor (codon 301). However, recent work has identified additional mutations which produce transforming proteins, and mutation rates at these sites may be relevant in MDS.

Humans↗
PubMed1993

A randomized study of alfacalcidol in the refractory myelodysplastic anaemias. A Japanese cooperative study.

A multi-institutional randomized trial of alfacalcidol (1 alpha hydroxyvitamin D3) was performed to determine the therapeutic effect of alfacalcidol in patients with refractory myelodysplastic anaemias. Twenty-three evaluable patients were randomized to receive either a single daily oral dose of 6 micrograms of alfacalcidol or only supportive care as a control. Treatment was continued, whenever possible, for a period of 6 months. Response was assessed by weekly blood counts, clinical course and repeated marrow examinations. No significant difference was noted between the alfacalcidol and control groups. Three of the 13 patients in the alfacalcidol group, and two of the 10 patients in the control group, suffered a progression of their disease. One patient with refractory anaemia showed a good response to alfacalcidol in all three haematopoietic cell lineages; the response, however, could not be maintained, because discontinuation of the drug resulted in a worsening of pancytopenia which was refractory to a second course of alfacalcidol therapy. Hypercalcaemia was the major toxic side-effect of alfacalcidol therapy. The results indicate that alfacalcidol therapy, when used alone, does not induce a beneficial effect in patients with refractory myelodysplastic anaemias.

Adolescent↗
PubMed1993

[Determination of the standard level of serum erythropoietin in relation to hemoglobin concentration].

Serum erythropoietin (EP) concentration was measured by the recombinant EP-based radioimmunoassay and was examined to standardize the hemoglobin (Hb) related level of 144 normal control and 56 patients with iron deficiency anemia and hemolytic anemia excluding paroxysmal nocturnal hemoglobinuria. The standardization was achieved by logarithmic regression of the EP titier on Hb either by the two-phase linear form or by the third degree sigmoid form at a 95% confidence limit for each regression. The third degree regression was found to be preferable from the view point of both statistics and the negative feedback mechanism. The average and scattering of the deviation from the standard level thus determined of the disease groups indicated that the EP level is: (1) 12 fold higher than the standard level in 42 aplastic anemias (the most in excess and a few in standard). (2) three fold higher than that in 27 myelodysplastic syndromes (relatively higher dispersed state). (3) 29% of the standard level in 33 anemias associated with chronic renal failure (deficient state). (4) 105% of the extrapolated standard level in 22 polycythemia veras (standard state). The standardization of Hb-related Ep titer may provide new pathophysiological approaches in a variety of hematopoietic disorders.

Anemia, Hemolytic↗
PubMed1992

Inhibition by a novel azole antifungal agent with a geranyl group on lanosterol 14 alpha-demethylase of yeast.

AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7-dimethylocta-2,6- dienyloxy)ethyl]-1H-imidazole) is a new imidazole derivative characterized by a geranyl substituent showing strong antifungal activity. Azole antifungal agents are known to be potent inhibitors of lanosterol 14 alpha-demethylase (P450(14)DM) of fungi. The role of the geranyl group of AFK-108 on interaction of AFK-108 with the target was studied by using Saccharomyces cerevisiae P450(14)DM as the model enzyme. AFK-108 and some of its derivatives bound to oxidized P450(14)DM with one-to-one stoichiometry and inhibited the demethylase activity. AFK-108 derivatives having the longer farnesyl or the shorter prenyl group showed lower affinity than AFK-108 for the enzyme. AFK-108 caused 100% inhibition at the equivalent concentration to P450(14)DM in the reaction mixture (0.07 microM), while the farnesyl derivative inhibited the activity by 60% at the same concentration. AFK-108 interfered with the binding of CO to the ferrous P450(14)DM. However, the interfering effect of the prenyl derivative was lower than that of AFK-108. Another AFK-108 derivative having the saturated 3,7-dimethyloctyl group was also a weaker inhibitor than AFK-108. These experiments suggest that the geranyl group of AFK-108 interacts with the substrate binding site of P450(14)DM that recognises the side chain of the substrate. AFK-108 is the first example of an azole derivative interacting with the side chain recognising region of the substrate binding site of P450(14)DM.

Antifungal Agents↗
PubMed1992

Structural analysis of the interaction between the side-chain of substrates and the active site of lanosterol 14 alpha-demethylase (P-450(14)DM) of yeast.

The role of the side-chain of lanosterol in the enzyme-substrate interaction of yeast P-450(14)DM (lanosterol 14 alpha-demethylase) was analyzed with lanosterol derivatives having functional groups on the side-chain. Purified P-450(14)DM from Saccharomyces cerevisiae catalyzed 14 alpha-demethylation of 26-hydroxylanosterol and 25-hydroxy-24,25-dihydrolanosterol with a lower activity than lanosterol and 24,25-dihydrolanosterol. This enzyme demethylated the (Z)-24-ethylidene-24,25-dihydrolanosterol with a low rate, but did not metabolize the E-isomer. The apparent Km of 26-hydroxylanosterol was 10.8 microM, which was higher than that of lanosterol, but lower than that of 24,25-dihydrolanosterol. On the other hand, competition experiments suggested that the affinity of 25-hydroxy-24,25-dihydrolanosterol and (Z)-24-ethylidene-24,25-dihydrolanosterol for P-450(14)DM was significantly lower than that of 24,25-dihydrolanosterol. Integration of the present results with the preceding ones (Aoyama, Y., Yoshida, Y., Sonoda, Y. and Sato, Y. (1991) Biochim. Biophys. Acta, 1081, 262-266 and Aoyama, Y. and Yoshida, Y. (1991) Biochem. Biophys. Res. Commun., 178, 1064-1071) suggests that yeast P-450(14)DM recognizes two parts of the side-chain, the structure around C-24 and the terminal fork consisting of C-25, C-26 and C-27.

Binding Sites↗
PubMed1992

Action of ebselen as an antioxidant against lipid peroxidation.

The action of ebselen (2-phenyl-1,2-benzoisoselenazol-3(2H)-one) as an antioxidant was studied under various conditions to clarify how it prevents oxidative damage. It did not react with diphenylpicrylhydrazyl nor did it suppress the oxidation of methyl linoleate in acetonitrile solution or in aqueous dispersions induced by free radical initiator, suggesting that ebselen does not act as a potent radical scavenging antioxidant. On the other hand, it suppressed the oxidation of methyl linoleate emulsions in aqueous dispersions induced by iron. It also suppressed the spontaneous oxidation of rat brain and liver homogenates, but it did not suppress the oxidation of these homogenates induced by a free radical initiator. It was also found that ebselen reduced the fatty acid hydroperoxides to their corresponding alcohols and this reaction was enhanced by the presence of glutathione. These results suggest that ebselen acts as an antioxidant by reducing hydroperoxides, but that it does not act as a radical-scavenging antioxidant.

Animals↗
PubMed1992

Active site topology of Saccharomyces cerevisiae lanosterol 14 alpha-demethylase (CYP51) and its G310D mutant (cytochrome P-450SG1).

Incubation of phenyldiazene (PhN = NH) with lanosterol 14 alpha-demethylase, a cytochrome P-450 enzyme (CYP51) that oxidatively removes the 14 alpha-methyl group of lanosterol, results in the appearance of a 478-nm band indicative of phenyl-iron complex formation. In situ oxidation of the phenyl-iron complex by ferricyanide yields exclusively the N-phenylprotoporphyrin IX regioisomer with the phenyl group on the nitrogen of pyrrole ring C (NC). The biphenyl-iron complex formed in the analogous reaction of the enzyme with biphenyldiazene similarly rearranges on treatment with ferricyanide to the NC regioisomer of N-biphenylprotoporphyrin IX. The active site cavity must therefore be at least 10 A high directly above the iron atom and pyrrole ring C of the heme group, and lanosterol binds to the enzyme in the region above pyrrole ring C. Phenyl-iron complex formation is not detected spectroscopically with cytochrome P-450SG1, a catalytically inactive G310D mutant of lanosterol 14 alpha-demethylase in which the sixth iron coordination site is thought to be occupied by an imidazole ligand. Nevertheless, oxidation of the phenyldiazene-treated enzyme with ferricyanide provides the NA and NC regioisomers of N-phenylprotoporphyrin IX in a 40:60 ratio. The single amino acid substitution in cytochrome P-450SG1 thus causes a conformational change that retracts the amino acid residues that cover pyrrole ring A and moves an imidazole ligand into the active site.

Binding Sites↗
PubMed1992

Conalbumin-conjugated silica gel, a new chiral stationary phase for high-performance liquid chromatography.

A new chiral stationary phase using conalbumin (from chicken egg white) was developed for high-performance liquid chromatography. Chiral resolution of racemic azelastine, an antiallergic drug, was achieved on a conalbumin-conjugated silica gel column. The effects of the pH, the concentration of organic solvents and salts in the mobile phase, and the temperature on the capacity factor and resolution of racemic azelastine were examined. This column shows good stability and can separate optical isomers with an aqueous mobile phase. It should be very useful in studies on pharmacokinetics and in clinical chemistry.

Chromatography, High Pressure Liquid↗
PubMed1992

Oxidation of methyl linoleate in aqueous dispersions induced by copper and iron.

The oxidations of methyl linoleate micelles in aqueous dispersions induced by copper and iron have been studied, aiming specifically at elucidating the action of the copper ion in the chain initiation. Sodium dodecyl sulfate (SDS) and tetradecyltrimethylammonium bromide (TTAB) were used as anionic and cationic surfactants, respectively, in order to see the effect of the electric charge of the micelle surface. Both copper and iron induced the oxidations of methyl linoleate micelles by decomposing lipid hydroperoxide contained initially in methyl linoleate, tert-butyl hydroperoxide, or hydrogen peroxide added to the aqueous phase. The rate of oxidation induced by cupric ions was proportional to the first power of methyl linoleate concentration and to the half power of both cupric ion and hydroperoxide concentrations, suggesting that the oxidation was initiated by the peroxyl and alkoxyl radicals formed in the decomposition of hydroperoxide by copper. The formation of alkoxyl radicals was confirmed by its trapping with a spin trap. The rate of oxidation was dependent on the type of surfactant. Methyl linoleate containing a very small amount of hydroperoxide was oxidized by copper in the SDS system, but the rate of its oxidation was negligible when TTAB was used. However, the addition of tert-butyl hydroperoxide induced the oxidation even in the TTAB system. Hydroperoxyl and hydroxyl radicals formed in the SDS system induced the oxidation, but those formed in the TTAB system did not. It was shown that the effect of radicals on the initiation of lipid peroxidation depends on the type of radicals and site of radical formation.

Copper↗