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Biomedical subjects

N Kawamura

Publications and source records attributed to N Kawamura.

At least 199 records · Page 11Linked to original sources
PubMed1995

4-oxo retinoic acid for refractory acute promyelocytic leukemia in children with all-trans retinoic acid therapy.

Therapy with all-trans retinoic acid (ATRA) achieves complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), but the efficacy is reported to relate to plasma ATRA level after oral administration. The pharmacokinetics of ATRA and 4-oxo all-trans retinoic acid (4-oxo ATRA), a metabolite of ATRA, were studied in four children with APL at the time of initial oral administration. After administration of ATRA at a dose of 30 mg/m2, the peak plasma ATRA level was 20-741 ng/ml and was reached at 60-120 min. The patient with the lowest peak plasma level did not achieve complete remission and had a very high 4-oxo ATRA level compared to the patients with complete remission. These findings suggest that accelerated metabolism of ATRA plays a role in the failure of this agent in the patients without remission.

Administration, Oral↗
PubMed1995

Synthesis and biological activities of TAN-1511 analogues.

TAN-1511 analogues were synthesized and their effects on the proliferation of bone marrow cells were examined. To exert potent activity the following conditions are necessary: the configuration of the 2-amino-6,7-dihydroxy-4-thiaheptanoic acid moiety must be (2R,6R), long chain acyl groups (C14 to C18) must be bound to both hydroxyl groups, the amino group must be free or acylated with the long chain fatty acid (ca. C14) and the peptide moiety must have glutamic acid as a component. Among the synthesized compounds, trisodium (2R,6R)-2-amino-6,7-bis (hexadecanoyloxy)-4-thiaheptanoyl glycyl glutamyl glutamate, which has improved solubility, was effective in experimental leukocytopenia in mice.

Amino Acid Sequence↗
PubMed1995

[Clinical evaluation of enzyme immuno assay systems for HCV antibody--synthetic peptide antigen and recombinant antigen].

To evaluate the frequency of the false positive results, we examined 168 patients for the presence of HCV using two HCV antibody assay systems, Synpep HCV-EIA (Synpep) and Abbott EIA II (Abbott). The results obtained by the two methods were significantly different in 22 patients. Cases in 17 of these patients, the results were positive with Abbott but negative with Synpep, and there were no clinical signs or delectable virus RNA. However, in 2 cases, the results were markedly positive with Abbott and weakly positive with Synpep. The presence of virus RNA and the increase of transaminase were observed in one case but both were noted in the other case. The serum of these two patients reacted with the C33C and C22-3 regions in RIBA II. We observed another 2 cases in which the elevation of the cut-off index with Synpep preceded that with Abbott at the early stage of acute hepatitis C. We also compared the cut-off index with the histology activity index (HAI) score determined by liver biopsy. The average cut-off index with Synpep was proportional to the HAI score in the range between 0 and 13. Based on the cut-off index/HAI score relationship, we suggest that patients with inactive chronic hepatitis show a Synpep cut-off index less than 11.

Antigens, Viral↗
PubMed1995

[Production of HTLV-II env protein and its suppressive effect on infection].

HTLV-II env protein, which cross-reacts with HTLV-I env, has been known to induce antibodies in infected individuals. In an attempt to suppress HTLV-II infection, we first generated HTLV-II env precursor glycoprotein (gp63) using baculovirus vector and the Sf-9 cell system. The production of antibodies to the cleaved env glycoprotein gp46 was verified by analysis of immunized rabbit sera as well as HTLV-II infected human sera using Western blotting. Moreover, the rabbit antibody was shown to suppress syncytial formation of the cells (Vines) infected with human T-cell leukemia virus type II (HTLV-II: HTLV-II-Vines). HTLV-II infection in rabbits was produced by intravenous injection of HTLV-II-Vines into female rabbits (New Zealand White). Antibody against HTLV-II could be detected by the 2nd week after inoculation, and its titer reached the maximum at the 10th week. Specific antibodies against env gp46 and gag p24 were detected in 2 of 2 rabbits and in 1 of 2 by Western blotting methods, respectively. Proviral DNA was detected by nested PCR, which was verified by Southern hybridization, at all times checked after inoculation, suggesting the persistence of infection, albeit at low levels. In the studies to determine if vaccination could protect against HTLV-II infection, rabbits were first immunized with the env protein, then were challenged by inoculation with HTLV-II-Vines as described above. Employing nested PCR, the provirus could not be detected at any time after challenge. The observation that active immunization could effectively protect rabbits from infection would seem to have important implications for equivalent vaccination of humans against both HTLV-I and HTLV-II.

Animals↗
PubMed1995

[Induction and maintenance therapy in all-trans retinoic acid with relapsed acute promyelocytic leukemia].

We reported a 17-year-old girl with relapsed acute promyelocytic leukemia (APL) who achieved complete remission and has been received maintenance therapy with all-trans retinoic acid (ATRA). The patient was diagnosed as APL in 1986. The ANLL 861 protocol of the Children's Cancer and Leukemia Study Group induced complete remission, and the chemotherapy was discontinued in 1989. However, she suffered a relapse with APL in 1991 and begun receiving ATRA (30 mg/m2/day) therapy because of disseminated intravascular coagulation. Bleeding tendency was discontinued by day 5. During the treatment, the white blood cell count increased markedly to 35,510 per microliters on 15th day, however she achieved complete remission morphologically on day 18. After informed consent was obtained from the family, she has been given ATRA orally for more than three years at the time of this report. The pharmacokinetics examination (ATRA 20 mg/m2 single per os) was performed 12 and 22 months after the induction therapy. The each peak plasma level of ATRA was 89 and 149 ng/ml. The concentration of ATRA has yet reached a level despite the continuous ATRA therapy. We considered that it may be useful to monitor plasma levels of ATRA during the treatment.

Adolescent↗
PubMed1994

Identification of unlawful food dyes by thin-layer chromatography-fast atom bombardment mass spectrometry.

A thin-layer chromatographic-fast atom bombardment mass spectrometric (TLC-FAB-MS) method incorporating an analyte condensation technique was established for the identification of the 27 food dyes consisting the twelve dyes permitted for use in foods and the fifteen unlawful dyes in Japan. The use of magic bullet [1,4-dithiothreitol-1,4-dithioerythritol (3:1)] as a matrix allowed the measurement of the FAB mass spectra of the food dyes except for Food Blue No. 2 (Indigo Carmine). The separation was performed on a C18-modified silica gel TLC plate using the following two solvent systems: methanol-acetonitrile-5% aqueous sodium sulphate solution (3:3:10) and methyl ethyl ketone-methanol-5% aqueous sodium sulphate solution (1:1:1). The condensation technique for concentration of a diffuse sample spot on the TLC plate improved the detection limit 4-20-fold with good reproducibility. The method was successfully applied to the identification of unlawful dyes in imported foods.

Chromatography, Thin Layer↗
PubMed1994

Novel acyl-CoA:cholesterol acyltransferase inhibitors. Synthesis and biological activity of 3-quinolylurea derivatives.

A series of 3-quinolylurea derivatives (1) was synthesized and evaluated for acyl-CoA:cholesterol acyltransferase (ACAT) inhibitory activity. For in vitro studies, the most potent inhibitory activity was found in derivatives having substituents at the 6,7- or 6,8-positions and an ortho-substituted phenyl group at the 4-position of quinoline ring. The 2,4-difluorophenyl group appeared to be the optimum N'-substituent of the urea moiety. The IC50 values of compounds 52-54 and 59 were in the nanomolar order. Plasma cholesterol-lowering activity of compounds 50, 52, and 54 was observed at less than 1 mg/kg/day in cholesterol-fed rats. Compound 52 was also hypocholesterolemic in hamsters fed a diet without loading cholesterol.

Animals↗
PubMed1994

Rate of calcium entry determines the rapid changes in protein kinase C activity in angiotensin II-stimulated adrenal glomerulosa cells.

The present study was conducted to monitor precisely the activity of protein kinase C (PKC) in adrenal glomerulosa cells stimulated by angiotensin II (ANG II). PKC activity in cells was monitored by measuring phosphorylation of a synthetic KRTLRR peptide, a specific substrate for PKC, immediately after the permeabilization of the cells with digitonin [Heasley and Johnson J. Biol. Chem. (1989) 264, 8646-8652]. Addition of 1 nM ANG II induced a gradual increase in KRTLRR peptide phosphorylation, which reached a peak at 30 min, and phosphorylation was sustained thereafter. When the action of ANG II was terminated by adding [Sar1,Ala8]ANG II, a competitive antagonist, both Ca2+ entry and KRTLRR phosphorylation ceased rapidly, whereas diacylglyercol (DAG) content was not changed significantly within 10 min. Similarly, when blockade of Ca2+ entry was achieved by decreasing extracellular Ca2+ to 1 microM or by adding 1 microM nitrendipine, KRTLRR peptide phosphorylation was decreased within 5 min. In addition, restoration of Ca2+ entry was accompanied by an immediate increase in KRTLRR peptide phosphorylation. Under the same condition, DAG content did not change significantly. We then examined the role of the PKC pathway in ANG II-induced aldosterone production. Ro 31-8220 inhibited ANG II-induced KRTLRR phosphorylation without affecting the activity of calmodulin-dependent protein kinase II. In the presence of Ro 31-8220, ANG II-mediated aldosterone production was decreased to approx. 50%. Likewise, intracellular administration of PKC19-36, a sequence corresponding to residues 19-36 of the regulatory domain of PKC known to inhibit PKC activity, attenuated ANG II-mediated activation of PKC and aldosterone output. These results indicate a critical role of Ca2+ entry in the regulation of PKC activity by ANG II.

Aldosterone↗
PubMed1994

Enhancement by tocoretinate of epidermal growth factor-induced DNA synthesis in human intestinal epithelial cells.

Tocoretinate (TR) is a hybrid compound composed of alpha-tocopherol esterified with retinoic acid. The present study was conducted to clarify whether or not TR affects DNA synthesis in a human intestinal cell line, FHs 74 Int. In these cells, addition of 10% serum resulted in an approximately 10-fold increase in DNA synthesis as assessed by [3H]thymidine incorporation. Epidermal growth factor (EGF) augmented DNA synthesis three- to fourfold. When EGF was added together with insulin-like growth factor-I (IGF-I), which had only a small effect by itself, a combination of these growth factors reproduced the effect of serum. In quiescent FHs 74 Int cells, TR had no effect on DNA synthesis by itself. However, when quiescent cells were pretreated with TR for 24 hr, DNA synthesis induced by EGF was markedly enhanced. Thus, in TR-pretreated cells, EGF stimulated DNA synthesis to the same extent as 10% serum. The effect of TR was dose-dependent and the maximal effect was obtained by 10(-7) M TR. Pretreatment with TR enhanced the effect of EGF on DNA synthesis but did not change the dose-response relationship for EGF-mediated DNA synthesis. All-trans-retinoic acid had similar stimulatory effect on EGF-induced DNA synthesis. When the medium was changed during the treatment with TR, the effect of TR on DNA synthesis was reduced. In addition, pretreatment with TR resulted in release of immunoreactive IGF-I into medium. Finally, the effect of TR was attenuated by an addition of antibody against IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗
PubMed1994

Cloning of the macrolide antibiotic biosynthesis gene acyA, which encodes 3-O-acyltransferase, from Streptomyces thermotolerans and its use for direct fermentative production of a hybrid macrolide antibiotic.

A gene encoding the macrolide modification enzyme 3-O-acyltransferase (acyA) was cloned by chromosome walking onto the carbomycin biosynthetic region in Streptomyces thermotolerans TH475, with the 3' region of the gene encoding the macrolide modification enzyme 4"-O-acyltransferase (acyB1) as a probe. A shortened fragment (1.8 kb) containing acyA was subcloned with pIJ350. A high-level tylosin producer, Streptomyces fradiae MBBF, transformed with the plasmid could produce a hybrid macrolide, 3-O-acetyltylosin, most efficiently.

Acyltransferases↗
PubMed1994

Mechanism of an early lysis by fatty acids from axenic Phormidium tenue (musty odor-producing cyanobacterium) and its growth prolongation by bacteria.

We have previously demonstrated that bacteria-containing Phormidium tenue, a cyanobacterium which produces musty odor 2-methylisoborneol, grew beyond 8 weeks, whereas axenic alga perished suddenly between the 3rd week and the 4th week while being cultured in the laboratory. This mechanism was investigated. It is assumed that when algal cells grow beyond a certain level, the supply of CO2 becomes inadequate and results in the rapid lysis of axenic alga. At that time, inhibitory substances liberated from algal cells kill the surviving alga. Since the process occurs continuously, this alga is finally annihilated. On the other hand, since inhibitory substances are metabolized or degraded by bacteria coexistent with alga, bacteria-containing P. tenue maintains growth for a long time. The growth-inhibitory substance was found to be unsaturated free fatty acids.

Bacteria↗
PubMed1994

A method for detecting visceral malformations in gelatin-embedded rat fetuses using an automatic slicing apparatus.

A method for observing whole rat fetal viscera embedded in gelatin using an automatic slicing apparatus is described. Fetuses were immersed in Bouin's solution. Part of the thoracic and abdominal skin of each fetus was removed, and fetuses were immersed consecutively in sodium bicarbonate 30% in 70% ethanol, gelatin 15% in water, gelatin 30% in water, then embedded in fresh 30% gelatin. The gelatin blocks containing the fetuses were immersed in 10% formalin. After fixation, the block was sliced into 200 microns serial transverse sections using a rotor-slicer at a rotation speed of 120 rpm and a cutting speed of 25 mm/sec. Complete slicing of a single fetus required about 20 min. The advantages of the method presented here include: complete fetal serial sections are produced, thin and uniform sections are obtained easily, viscera can be identified easily, and observation can be carried out at any time after slicing. The method presented can be used to detect whole fetal visceral malformations in developmental toxicity tests.

Animals↗
PubMed1994

Homocysteine induces iron-catalyzed lipid peroxidation of low-density lipoprotein that is prevented by alpha-tocopherol.

Homocystinuria is an inborn error of methionine metabolism that is characterized by the premature development of arteriosclerosis. As one of the major factors in the pathogenesis of arteriosclerosis, modification of low-density lipoprotein (LDL) has received widespread attention by many investigators. In this study, to elucidate the relationship between elevated homocysteine levels and premature arteriosclerosis, we investigated the role of homocysteine in the iron-catalyzed oxidative modification of LDL. When LDL isolated from a healthy subject was incubated with homocysteine and ferric ion, a gradual decrease of polyunsaturated fatty acids (PUFA), formation of thiobarbituric acid-reactive substances (TBARS) and fluorescent substances, and the fragmentation of apoprotein B (apoB) were observed. The extent of oxidative modification was dependent on the concentration of homocysteine. Modification of LDL was suppressed until the remaining alpha-tocopherol concentration reached a critical level. When the alpha-tocopherol content of LDL was increased by 2.6-fold, both the formation of TBARS and the fragmentation of apoB were suppressed. These results suggest that homocysteine might promote iron-catalyzed oxidation of LDL and imply its role for the development of premature arteriosclerosis.

Adult↗
PubMed1994

[Clinical evaluation of whole blood histamine release test simultaneously testing multiple allergens--correlated with bronchial provocation test].

We compared the efficacy of the novel histamine release test (HRT), which allows the determination of many allergens at the same time using a small amount of whole blood, with other conventional allergen diagnostic tests. HRT and RAST were both performed along with bronchial provocation tests (BPT) on 44 bronchial asthma patients in whom the etiologic allergen could not be determined by either intracutaneous tests (ICT) or ophthalmic response tests (ORT). The HRT uses a microtiterplate on which glass fibers have 10 kinds of allergens affixed. The histamine release ability at 6 different concentrations of each kind of allergen was examined. The concordance of HRT with respect to BPT was the highest at 82% in comparison with RAST at 66%, ICT at 55% and ORT at 60%. With each of the allergens, HRT had the highest concordance with BPT. On the other hand, RAST, ICT and ORT showed different results depending on the allergens. The positive predictive value of HRT was the highest at 76% compared with RAST at 59%, ICT at 51% and ORT at 64%. From these results, we concluded that HRT is a more useful diagnostic method for the confirmation of a clinical allergy than other conventional diagnostic methods.

Adolescent↗
PubMed1994

[Regulation of the complement C3 gene expression: regulatory elements required for cytokine-induced expression].

I isolated murine and human genomic cosmid clones of complement C3 gene and sequenced 5'-flanking region of their transcriptional initiation sites to determine cis-elements that participate in regulation of C3 gene expression. The murine and human 5'-flanking regions are 51% identical overall, with positions -36 to -1 and -146 to -68 showing 80% identity. Four TATA boxes were identified upstream of the murine transcriptional initiation site, but only the TATA element at position -30 is essential for expression of murine C3 in hepatocytes. Deletion and transfection analysis indicated that sequences -395 to -111 are essential for constitutive expression of C3 gene and suggested that sequences between -1457 and -800 contain regulatory elements that are involved in suppressing basal expression. Mutation analyses showed that sequences between -88 and -83 are essential for IL-6 responsiveness and both sequences between -88 and -83 and -77 to -72 are necessary for enhancer activity and responsiveness to IL-1. These sequences are highly homologous to binding sites of DNA binding proteins, C/EBP and NF-kappa B, respectively. Collectively, these results localize cis-acting elements involved in constitutive and IL-1/IL-6-regulated murine C3 gene expression, and provide implication for specific trans-acting factors.

Animals↗