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Biomedical subjects

T Okuda

Publications and source records attributed to T Okuda.

At least 307 records · Page 17Linked to original sources

Reciprocal t(14;19)(q32.3;q13.1) in a patient with B-cell lymphoma.

A patient with B-cell lymphoma with a chromosome rearrangement of t(14;19)(q32.3;q13.1) is reported. This patient had leukemic features and an aggressive clinical course. The histopathologic diagnosis was malignant lymphoma, small noncleaved cell. Chromosome analysis of the cells from a cervical lymph node and peripheral blood showed a reciprocal translocation between chromosome 14 with a break at band q32.3 and chromosome 19 with a break at band q13.1, to which the bcl-3 gene has been mapped. Monoclonal rearrangement of the JH gene was detected by Southern blot analysis. However, we could not detect rearrangement of the bcl-3 gene. This case also had a t(2;8)(q13;q24.1), but the c-myc gene remained in its germline. This is the first case with the reciprocal t(14;19) and 8q24 chromosomal breakpoint in a B-cell lymphoid malignancy.

Chromosomes, Human, Pair 14↗

Actions of human interleukin-4/B-cell stimulatory factor-1 on proliferation and differentiation of enriched hematopoietic progenitor cells in culture.

We studied the effects of recombinant human interleukin-4 (IL-4) on colony formation by enriched hematopoietic progenitors. IL-4 alone did not support colony formation at all. When IL-4 was combined with granulocyte colony-stimulating factor (G-CSF), the number of pure neutrophil colonies increased three times over that supported by G-CSF alone. IL-4 added 5 days after the addition of G-CSF failed to exert this synergistic effect, indicating that IL-4 acts on the early stage of proliferation. The mapping experiments (sequential observation of colony formation) have clearly shown that IL-4 did not initiate progenitor cell proliferation. Based on these data, IL-4 may possess a direct action on progenitor cells; however, it can only act as a costimulant with G-CSF. In contrast, IL-4 had possible inhibitory effects on macrophage colony formation supported by interleukin-3 (IL-3) and macrophage colony-stimulating factor (M-CSF). In other words, IL-4 may induce progenitor cells to become sensitive to G-CSF and thereby induce neutrophil differentiation. Delayed addition experiments demonstrated that human IL-4, unlike murine IL-4, could support neither proliferation nor survival of erythroid burst or mixed colony forming cells. Neutrophil colony forming cells only survived and recovered after addition of G-CSF and erythropoietin on day 5 of incubation. On the other hand, IL-3 supported neutrophil, erythroid burst, and mixed colony forming cells as reported previously (Sonoda et al, Proc Natl Acad Sci USA, 85:4360, 1988). These results led us to propose that IL-4 possibly acts with more mature progenitor cells than those of IL-3 or granulocyte-macrophage (GM)-CSF.

Bone Marrow↗

The unbalanced 1;7 translocation in de novo myelodysplastic syndrome and its clinical implication.

In our chromosome study of 97 patients with myelodysplastic syndrome (MDS), six showed an unbalanced translocation between chromosomes 1 and 7 [-7, +der(1)t(1;7)(p11;p11)]. All of them had morphologic myelodysplasia in trilineage of bone marrow cells, and cytopenia was the major finding in the peripheral blood. All six patients had symptoms of infection at the time of diagnosis, and five showed immunologic abnormalities (polyclonal hypergammaglobulinemia in four and increased marrow plasma cells in three). None of the patients survived more than 11 months after the diagnosis; the median survival time was 4 months. Both of the two patients whose karyotypes were reexamined in the course of their disease showed karyotypic evolution accompanying the coincidental leukemic transformation. Six patients with MDS who had the same chromosome abnormality [t(1;7)] are described and their characteristic clinical features are presented.

Adolescent↗

Effect of second-messenger modulators in K-562 cell differentiation: dual action of calcium/phospholipid-dependent protein kinase in the process of differentiation.

We investigated the roles of second messengers in K-562 cell differentiation induced by either commitment-inducing agents (Ara-C, thymidine), or a noncommitment-inducing agent (hemin). Cell differentiation induced by both types of agents was inhibited by dbc-AMP, staurosporine, and H-7. In contrast, OAG enhanced hemin-induced cell differentiation, but it inhibited that due to Ara-C or thymidine. When K-562 cells were incubated with 4 x 10(-6)M hemin or 2 x 10(-7)M Ara-C for 2 days, an increase of epsilon-mRNA occurred. The addition of cycloheximide (1 microgram/ml) completely blocked this change, suggesting that de novo protein synthesis was necessary for the increase of epsilon-mRNA. Simultaneous treatment with Ara-C and cycloheximide for 2 days did not block either the increase of epsilon-mRNA or that of benzidine-positive cells, which were measured after 5 days of further incubation without additives. This suggested that the process of Ara-C-induced K-562 cell differentiation could be divided into two steps, i.e., a commitment step and a phenotypic expression step, and that the commitment step was at least partly resistant to cycloheximide. We investigated the roles of second messengers in each step. Our results suggested that PKC may act as a negative regulator of commitment step and as a positive regulator of the phenotypic expression. This may explain the differing effects of OAG on hemin- and Ara-C-induced K-562 cell differentiation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

New antitumor promoters: (-)-epigallocatechin gallate and sarcophytols A and B.

EGCG, the main constituent of green tea, and sarcophytols A and B, isolated from a soft coral, inhibited tumor promotion by teleocidin in a two-stage carcinogenesis experiment on mouse skin. EGCG and sarcophytols showed inhibition of tumor development by chemical carcinogenesis. A possibility of developing these compounds as cancer chemopreventives for human beings is discussed.

9,10-Dimethyl-1,2-benzanthracene↗

An infected congenital commissural lip fistula. Report of a case.

A case of infected congenital commissural lip fistula is presented. It appeared as a cheek swelling associated with inflammation due to infection. This case was treated with antibiotics and surgical drainage through the fistula. Our experience suggests that the possibility of infection of the fistula should be considered particularly in cases involved with angular stomatitis and/or scratching injury close to the commissure of the lips.

Adult↗

Chromosome abnormalities of gastric cancer detected in cancerous effusions.

The chromosomes were examined in cancerous effusions obtained from 7 patients with gastric cancer. In 1 patient, the modal chromosome number was 46 with a normal chromosome complement in the majority of the cells examined. The other 6 patients revealed numerical and structural aberrations. Among the structural rearrangements detected, chromosome 3 was involved in the short arm and in the long arm, each in three patients; bands p25, q21, q23, and q27 were recurrently involved and a band q23 was lost in 3 patients. Rearrangements of chromosome 5 in the long arm and of chromosome 17 at or near the centromere were also observed in three patients each. Gains of chromosome 7 was seen in 5 patients and of chromosome 13 in 4. Some of these alterations may be specific for gastric cancer.

Adult↗

Affinities of SM-7338 for penicillin-binding proteins and its release from these proteins in Staphylococcus aureus.

SM-7338, a carbapenem antibiotic, had high affinities for penicillin-binding proteins (PBPs) 1, 2, and 4 of Staphylococcus aureus but not for PBP 3 when a competition assay with [14C]benzylpenicillin was used. However, binding of [14C]SM-7338 was saturated for PBP 3 at a concentration of 1 microgram/ml. These results were due to the rapid release of SM-7338 from PBP 3-SM-7338 complexes with a half-life of 2 min.

Bacterial Proteins↗

In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent.

SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.

Administration, Cutaneous↗

Direct effects of endothelin in the rat kidney.

In the present study, we tested the direct effects of endothelin (ET) on rat kidney in vivo. ET was infused into the left renal artery of anesthetized rats at a rate of 0.5, 5, 20, or 40 pmol/h. ET reduced ipsilateral urine volume (V), clearance of inulin (CIN), and clearance of p-aminohippuric acid (CPAH) in a dose-dependent manner. Thus ET at 20 pmol/h did not change V but decreased renal plasma flow (RPF) and glomerular filtration rate (GFR) by 27.6 +/- 14.3 and 30.8 +/- 10.4%, respectively, in the ipsilateral kidney. ET at 0.5 pmol/h was without effect and at 5 pmol/h had only minor effects on CIN and CPAH of ipsilateral kidney. At 40 pmol/h, ET reduced ipsilateral V, GFR, and RPF by 52.3 +/- 21.4, 58.4 +/- 14.5, and 72.5 +/- 10.6%, respectively. Filtration fraction and fractional excretion of Na remained unchanged during ET infusion. ET, 40 pmol/h, infused into the renal artery together with atrial natriuretic peptide (ANP) at a rate of 12 pmol/h reduced the ipsilateral V, GFR, and RPF by 33.2 +/- 6.3, 26.1 +/- 6.0, and 27.2 +/- 7.1%, respectively, decrements less than those with ET alone. When a calcium-channel blocker nicardipine was infused at a rate of 2.5 micrograms/h into the renal artery together with ET, 20 pmol/h, there was little change in the ipsilateral V, RPF, and GFR; ET, 40 pmol/h, with nicardipine did not change V and decreased GFR and RPF by 25.9 +/- 5.6 and 23.1 +/- 10.8%, respectively, decrements less than those without nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Woodfordin C, a macro-ring hydrolyzable tannin dimer with antitumor activity, and accompanying dimers from Woodfordia fruticosa flowers.

Three new dimeric hydrolyzable tannins, woodfordins A, B and C, along with seven known hydrolyzable tannins, including oenothein B, a dimer exhibiting marked host-mediated antitumor activity, were isolated from an Indonesian crude drug, Sidowayah [dried flowers of Woodfordia fruticosa (L.) Kurz (Lythraceae)]. The structures of the new tannins were elucidated based on chemical and spectral evidence. Woodfordin C, having a macro-ring structure, was also found to exhibit a significant antitumor activity.

Animals↗

Effects of interaction of tannins with co-existing substances. VII. Inhibitory effects of tannins and related polyphenols on xanthine oxidase.

The inhibitory effects of hydrolyzable tannins, condensed tannins and related polyphenols on the activity of xanthine oxidase (XOD), catalyzing uric acid formation from xanthine, were investigated. Marked differences in the strength of the inhibition were observed. Some of the differences among the monomeric hydrolyzable tannins were due to their molecular weights, reflecting the number of phenolic hydroxyl groups in the molecule. However, the inhibitory activity of several oligomeric hydrolyzable tannins seemed particularly low in spite of their large molecular size. It was also observed that differences in location of acyl groups on the carbohydrate cores caused differences in the inhibitory activity among monomeric and oligomeric hydrolyzable tannins. A caffeic acid derivative (caffeetannin), 3,5-di-O-caffeoylquinic acid (24), also inhibited this enzyme. Galloylation and the degree of polymerization in proanthocyanidins were also shown to affect remarkably the strength of the inhibition. Among the compounds tested in the present study, valoneic acid dilactone (29), isolated from Mallotus japonicus, inhibited the enzyme most effectively. A kinetic study showed that this dilactone inhibited XOD non-competitively. Comparison of the inhibitory effect on XOD, with the binding activity to hemoglobin, for each tannin, suggests that their inhibition of XOD is not based on non-specific binding to the protein. Similar comparison of the inhibitory effect on XOD with the inhibitory effect on the generation of superoxide anion radical (O2-.) from the hypoxanthine-XOD system revealed that the inhibition of O2-. generation by tannins is due to their radical-scavenging activity, and not due to their inhibitory activity upon the enzyme.

Flavonoids↗

[Electromyographic study on motor skill in chewing movement. A new concept on relating electromyographic analysis to chewing movements].

This article was aimed to propose a new concept on evaluating electromyographic activities of masticatory muscles during chewing movements viewed from the standpoint of motor skill. Correlation coefficients between the ratio of lateral distance to ten vertical level set at 0.5 mm to 5.0 mm with 0.5 mm step from the end of closing phase and activities of bilateral masseter, anterior and posterior temporalis in each chewing stroke were evaluated using raisin, peanut, soft and hard testing gum in five subjects. Habitual chewing side always demonstrated less numbers of subjects who showed high correlation coefficients especially in the case of soft testing gum.

Chewing Gum↗

Comparison of two carbapenems, SM-7338 and imipenem: affinities for penicillin-binding proteins and morphological changes.

We investigated the binding affinities of SM-7338 for penicillin-binding proteins (PBPs) and the morphological changes induced by it compared with those of imipenem. Both SM-7338 and imipenem had the highest binding affinities for PBP-2 of Escherichia coli, which were in good agreement with the primary morphological response of spherical cell formation. SM-7338 also showed high affinities for PBP-1A, -1Bs, and -3, and imipenem showed high affinities for PBP-1A and -1Bs but not for PBP-3. At 4-fold MIC, SM-7338 induced a indeterminate form, whereas imipenem did not. This may be due to the higher affinity of SM-7338 for PBP-3 compared to that of imipenem. Against Pseudomonas aeruginosa, SM-7338 had very high affinities for PBP-2 and -3, and imipenem had higher affinities for PBP-2 and -1A. SM-7338 induced this organism to filamentous cells at a concentration lower than its MIC, bulge cells at 2-fold MIC, and spherical cells at 4-fold MIC, while imipenem principally induced round cell formation at each concentration. These morphological differences in P. aeruginosa may be due to the differences in binding profiles to PBPs. We also studied the affinities for PBPs using radioactive SM-7338. The data obtained supported these results.

Bacterial Proteins↗