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H Sato

Publications and source records attributed to H Sato.

At least 19 recordsLinked to original sources
PubMed1992

Neutralizing activity of human antibodies against the structural protein of human T-cell lymphotropic virus type I.

We have identified and mapped the regions responsible for neutralization in the human T-cell leukemia virus type I (HTLV-I) structural proteins by using region-specific human antibodies derived from seropositive blood donors. We have obtained 18 kinds of region-specific antibody (2 in the p19 gag, 10 in the gp46 env and 6 in the gp21 env proteins) from seropositive human plasma by means of an affinity column coupled with the synthetic peptides corresponding to the antigenic regions of the HTLV-I structural proteins. These antibodies were highly specific in ELISA using synthetic peptides as an antigen. Subsequently, we examined the neutralizing activity expressed by the inhibition of virion-induced syncytium formation by region specific antibodies. Twelve of 16 antibodies derived from the env protein were able to inhibit syncytium formation induced by co-cultivation of 8C cells with HTLV-I antigen-positive T cells. The antibodies derived from the p19 gag protein and the seronegative plasma used as the control showed no significant activity. The sequences recognized by the 10 neutralizing antibodies were sites corresponding to amino acids 20 to 49, 89 to 115, 136 to 160, 175 to 199, 213 to 236, 235 to 254, 277 to 292, 332 to 352, 350 to 386, 382 to 403, 426 to 448 and 458 to 488 from the amino terminal of the env protein. These observations suggest that the neutralizing epitopes were widely distributed in the env proteins of HTLV-I.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Inhibition of active oxygen generation by dipyridamole in human polymorphonuclear leukocytes.

The effect of dipyridamole on active oxygen generation by human polymorphonuclear leukocytes (PMN) was investigated. Dipyridamole inhibited the production of oxidative metabolites from human PMN stimulated by opsonized zymosan and formyl-methionyl-leucyl-phenylalanine dose and time dependently. To determine whether dipyridamole directly inhibits the production of oxygen metabolites by human PMN, human PMN were preincubated with dipyridamole washed prior to stimulation. Dipyridamole was found to directly inhibit human PMN from generated active oxygen metabolites at therapeutic concentrations. Dipyridamole may possibly be a potential scavenger of active oxygen metabolites since it inhibited active oxygen metabolite production from human PMN very rapidly. Dipyridamole was also found to directly affect the scavenging of active oxygen metabolites generated by opsonized zymosan-stimulated human PMN at therapeutic concentrations. This action of dipyridamole was also noted to be exerted against hydroxyl radicals and superoxide anions produced biochemically by an electron spin resonance spectrometer. It thus follows that dipyridamole may inhibit human PMN active oxygen metabolite generation and affect directly the scavenging of active oxygen metabolites at therapeutic concentrations.

Dipyridamole↗
PubMed1992

Determination of creatinine and ultraviolet-absorbing amino acids and organic acids in urine by reversed-phase high-performance liquid chromatography.

A simple and reliable method for the determination of urinary creatinine, amino acids and organic acids was developed. A urine sample was preliminarily separated into an organic acid fraction (including neutral species) and an amino acid fraction by cation-exchange chromatography. Both fractions were analysed by reversed-phase high-performance liquid chromatography, with a phosphoric acid-methanol gradient elution system and ultraviolet detection at 210 nm. Relationships between concentrations and peak heights were linear from 2 to 500 microM for the analytes. Overall recoveries were ca. 100%. The concentrations of creatinine for 37 urine samples, from 20 healthy newborns and from 17 patients with several inherited metabolic disorders, were 2.35 +/- 2.29 mM (ranging between 0.27 and 10.15 mM). The method was applied to the determination of several diagnostically useful metabolites in urine. The concentrations of phenylalanine and phenylacetic acid for five urine samples from patients with phenylketonuria were 347 +/- 177 and 282 +/- 224 microM/mM creatinine, respectively. The concentrations of tyrosine and 4-hydroxyphenyllactic acid in the urine of a patient with tyrosinemia were 112 and 1871 microM/mM creatinine, respectively.

Acidosis↗
PubMed1992

Existence of two pathways for the endocytosis of epidermal growth factor by rat liver: phenylarsine oxide-sensitive and -insensitive pathways.

The effect of phenylarsine oxide (PAO) on the internalization rate of epidermal growth factor (EGF) was investigated using perfused rat liver and isolated rat hepatocytes. In perfused liver, a tracer concentration of 125I-EGF alone or with excess unlabeled EGF (20 nM) was perfused and the internalization rate constants (kint) were measured. In the absence of PAO, kint values did not differ significantly for either dose condition. However, with the addition of PAO to the perfusate, the kint value dropped to 4% of that of the control at the low concentration of EGF, while dropping to only 40% of that of the control at the high concentration of EGF. These results suggest the existence of a PAO-insensitive internalization pathway having a kint value comparable with that of the other pathway. Similar EGF concentration-dependent inhibition of 125I-EGF internalization caused by PAO was ascertained using isolated rat hepatocytes. PAO also decreased the cellular ATP content in isolated hepatocytes. However, when we lowered the cellular ATP content with rotenone, the cell-surface binding and internalization of EGF were comparable with the control levels. We concluded that there exist dual pathways for the internalization of EGF and that excess doses of EGF lead to EGF internalization not only through a PAO-sensitive pathway but also through a PAO-insensitive pathway, whereas at a tracer dose of EGF, the internalization occurs mainly via the PAO-sensitive pathway.

Adenosine Triphosphate↗
PubMed1992

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 1.

A series of 11-[[2-[(arylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acids and related derivatives were synthesized. The compounds were tested for their antagonizing effects on guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationships are discussed. (+/-)-11-[[2-[(Styrylsulfonyl)amino]ethyl]-thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acid (41) and (+/-)-11-[[2-[(phenylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]thiepin-2-carboxylic acid (4af) were the most promising compounds with K(i) values of 6.5 +/- 0.29 and 3.7 +/- 0.31 nM, respectively, for the TXA2/PGH2 receptor. These compounds also significantly inhibited U-46619-induced guinea pig platelet aggregation ex vivo (10 mg/kg po). Compound 41 was resolved into its optically active form. The (-)-isomer was 60-fold more potent than the (+)-isomer in the TXA2/PGH2 receptor binding assay. Some compounds tested in this study showed both TXA2/PGH2 receptor antagonizing and TXA2 synthase inhibitory effects.

Animals↗
PubMed1992

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 2.

A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Synthesis and antiallergic activity of 11-(aminoalkylidene)-6,11-dihydrodibenz[b,e]oxepin derivatives.

A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin-2-carboxylic acid derivatives was synthesized and demonstrated to be orally active antiallergic agents. These compounds are structurally related to 1 (KW-4994), which we had reported previously to be a new antiallergic agent. Most compounds synthesized exhibited potent inhibitory effects on 48-h homologous passive cutaneous anaphylaxis (PCA) in rats and on IgG1-mediated bronchoconstriction in guinea pigs. Additionally, compounds possessing a terminal carboxyl group at the 2-position of the dibenz[b,e]oxepin ring system exhibited inhibitory effects on specific [3H]pyrilamine binding to guinea pig cerebellum histamine H1 receptors, whereas these demonstrated negligible effects on specific [3H]QNB binding to rat striatum muscarinic acetylcholine M1 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced antiallergic activities: (1) a 3-(dimethylamino)propylidene group as the side chain at the 11-position, (2) a terminal carboxyl moiety at the 2-position, and (3) a dibenzoxepin ring system. Among the compounds synthesized, (Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid hydrochloride (16) was selected for further evaluation. It had an ED50 value of 0.049 mg/kg po in the PCA test in rats and an ID50 value of 0.030 mg/kg po in inhibiting anaphylactic bronchoconstriction in guinea pigs. Furthermore, it had a Ki value of 16 +/- 0.35 nM for the histamine H1 receptor, while it exhibited negligible CNS side effects up to a dose of 600 mg/kg po. Compound 16 is now under clinical evaluation as KW-4679.

Animals↗
PubMed1992

Synthesis and anti-HIV activity of 9-[c-4,t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine.

The synthesis and in vitro anti-HIV activity of two new racemic nucleoside analogues are described; namely, 9-[c-4,t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine (12) and its guanine analogue 18. While the latter (18) showed no activity, the therapeutic index of the former (12) was 200 and comparable to that (400) of carbovir. One enantiomer of 12 may be viewed as an analogue of carbocyclic oxetanocin and the other as an analogue of carbovir. Hence, these results indicate that one or both of the individual enantiomers of 12 could serve as candidates or lead compounds for the development of anti-AIDS agents.

Adenine↗
PubMed1992

Resolution of 9-(c-4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine and selective inhibition of human immunodeficiency virus by the (-) enantiomer.

Two enantiomers of 9-(c-4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H- adenine (BCA) which showed a potent and selective anti-HIV effects have been synthesized and evaluated against human immunodeficiency virus type 1. The result demonstrated that the potent-HIV activity of racemic BCA is expressed solely by the (-) isomer.

Adenine↗
PubMed1992

Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy.

The polymerase chain reaction (PCR) method was used to determine the presence and amount of human T lymphotropic virus type I (HTLV-I) proviral DNA in central nervous system (CNS) tissue obtained at autopsy from 6 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 1 patient with adult T-cell leukemia (ATL) and CNS infiltration of leukemic cells, and 9 control subjects with other neurological disorders. HTLV-I pX and env but not pol DNA were detected in CNS tissue from 5 of 6 patients with HAM/TSP. The ATL samples were positive for pX, env, and pol DNA by PCR. None of the control samples was consistently positive for HTLV-I by PCR, but all showed positive bands on beta-globin PCR. Quantitative PCR combined with histological studies showed no correlation between HTLV-I proviral DNA amounts and extent of perivascular mononuclear cell infiltration in the HAM/TSP CNS. Also, the amounts of pX and probably env DNA were greater in the HAM/TSP samples than in the ATL sample, although the extent of mononuclear cell infiltration was far less in the HAM/TSP samples than in the ATL sample. Therefore, in addition to infiltrating mononuclear cells, constituent cells of the CNS may harbor the HTLV-I genome, at least in the pX and env regions, in patients with HAM/TSP.

Base Sequence↗
PubMed1992

An immunoenzymometric assay for a CA125-like antigen, CA602.

An immunoenzymometric assay (IEMA) for a new CA125-like antigen, CA602, was developed. Five monoclonal antibodies raised against a human ovarian carcinoma cell line could detect their respective antigens in the sera of ovarian carcinoma patients. The antigen levels detected in serum by the various antibodies correlated significantly to each other, and to CA125 levels. The results of epitope analyses and combined IEMAs suggested that the epitopes recognized by these antibodies are not same, but exist on the same antigen which bears the CA125 epitope. A sensitive IEMA was developed with 602-1 and 602-6 antibodies which showed high reactivity to the CA125-like antigen. The antigen defined by these two antibodies was designated as CA602, and serum CA602 levels correlated well with CA125 levels. The CA602 antigen is a CA125-like antigen. Furthermore, the serum CA602 levels did not correlate to CA54/61 levels. The combined assays of CA602 and CA54/61 may increase the detection of ovarian carcinoma.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Specificity of a tumor marker (CA54/61) and its individual epitopes recognized by monoclonal antibodies, MA54 and MA61, in human tumor patients.

The specificity of a tumor marker (CA54/61) and its individual epitopes (CA54 and CA61) recognized by monoclonal antibodies (MA54 and MA61) and expressed by the same tumor marker were studied. Serum levels of CA54 and CA61 were compared with that of CA54/61. In lung adenocarcinoma and ovarian carcinoma, the positive rates of CA61 (42% and 68%) were higher than those of CA54 (32% and 32%) and similar to those of CA54/61 (45% and 74%). The serum levels of CA54 and CA61 showed a significant correlation (r = 0.78), but 22% of tested sera were positive for CA54 and negative for CA61 or negative for CA54 and positive for CA61. It was demonstrated that the tumor specificity between CA54 and CA61 was not same and that the tumor specificity of CA54/61 was similar to that of CA61 rather than CA54. Moreover, the difference in the tumor specificity between CA54 and CA61 was considered to be reflected in the difference in their epitope structure.

Antibodies, Monoclonal↗
PubMed1992

Effect of lipopolysaccharide on transport and metabolism of arginine in mouse peritoneal macrophages.

The transport activity of arginine in mouse peritoneal macrophages was strongly induced when they were cultured with 1 ng/ml bacterial lipopolysaccharide (LPS) for 12 h. Arginine in the medium decreased whereas ornithine in the medium increased during the culture. This time-dependent change of arginine to ornithine was accelerated by LPS. However, the activity of arginase in the macrophages did not change during the culture with or without LPS and release of arginase from the cells to the medium was not detected. It is suggested that the transport of arginine and ornithine was a rate-limiting step in arginine-to-ornithine conversion in the macrophage culture medium. A possible role of the induction of arginine transport activity in the macrophage cytocidal activity due to arginine depletion and nitric oxide production is discussed.

Animals↗