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Biomedical subjects

S Konishi

Publications and source records attributed to S Konishi.

At least 109 records · Page 6Linked to original sources

Comparison of feline parvovirus subspecific strains using monoclonal antibodies against a feline panleukopenia virus.

Four monoclonal antibodies (mAb) against a feline panleukopenia virus (FPLV) TU 1 strain, one of the host range variants of feline parvovirus (FPV), were produced and applied for antigenic analysis of FPLV, canine parvovirus (CPV) and mink enteritis virus (MEV). All mAbs were considered to be directed at epitopes on the virus capsid surface because they neutralized the infectivity and inhibited the hemagglutination (HA) of the homologous virus as well as other FPV strains. They were of the mouse IgG1 type. High antigenic homogeneity among FPLV strains was confirmed by HA-inhibition (HI) test with the mAbs and polyclonal immune sera against FPLV or CPV. But the TU 11 strain of FPLV was antigenically distinguished from the remaining 14 FPLV strains by both the HI test and the micro-neutralization test with one of the mAbs produced. MEV Abashiri strain was found to be antigenically indistinguishable from FPLV. Most of the CPV strains isolated after 1981 were considered to be antigenically different from earlier CPV isolates when some mAbs were applied in the serological tests, confirming the replacement of CPV by an antigenic variant in Japan. However, antigenically different CPVs were detected at the end of 1984 from unrelated epizootics occurred a month apart in the same area.

Animals↗

Long-term prognosis and residual abnormalities of idiopathic acquired aplastic anemia in children.

We evaluated the long-term prognosis and quality of cure of idiopathic acquired aplastic anemia in children. Of the 244 patients registered from 1965 to 1985, those registered in 1965-1975 and 1976-1985 had a survival rate of 50.1% and 62.0%. The percentage of cure, undertreatment and death was 30, 30 and 40%, respectively. About 40% of the patients with moderate cases, died dead or required frequent blood transfusions. In the case of pediatric patients, as the success rate of bone marrow transplantation was high. This modality should be considered for patients with moderate severity who require blood transfusion 3 months after the diagnosis and an HLA identical donor is available. Physical development was almost normal but 35% of the patients showed residual abnormalities such as bleeding tendency, and hepatic disorders due to treatment. Thrombocytopenia and ineffective hematopoiesis were observed in one-third of the patients and all of the patients showed abnormal committed stem cell assay. The CD 4/8 ratio was reduced in 50% of the patients and 15% exhibited psychological problems. These residual abnormalities last for years, and sometimes a lifetime.

Anemia, Aplastic↗

Inositol trisphosphate-linked calcium mobilization couples substance P receptors to conductance increase in a rat pancreatic acinar cell line.

The action of substance P (SP) on a rat pancreatic acinar cell line, AR4-2J, was examined using the whole-cell voltage-clamp technique. Pressure application of SP evoked inward currents accompanying increased membrane conductance. The SP-induced response was suppressed in Ca2+-free or low-Na+ solution. Treatment of cells with caffeine or A23187 produced a transient inward current and depressed the response to SP. Intracellular application of inositol 1,4,5-trisphosphate or guanosine 5'-O-(3-thiotriphosphate) elicited sustained inward currents and suppressed the SP-induced response. The results suggest that activation of SP receptors stimulates the formation of inositol phosphates via a guanine nucleotide-binding protein and leads to the rise in intracellular Ca2+, thereby activating a cation conductance in AR4-2J cells.

Animals↗

Cytogenetic findings and clinical features in acute leukemia and transient myeloproliferative disorder in Down's syndrome.

Cytogenetic, immunologic, and electron microscopic studies were performed on the blast cells of 28 pediatric patients with Down's syndrome, 13 with acute leukemia (DS-AL) and 15 with transient myeloproliferative disorders (DS-TMD). Clonal chromosome abnormalities were found in the cells of all patients with DS-AL but not those with DS-TMD. The younger ages and higher hemoglobin concentrations, platelet counts, and WBC counts of DS-TMD patients provided a clinical contrast with the frankly leukemic cases. Myelodysplastic syndrome, characterized by a small percentage of leukemic blast cells, was observed in 11 of the 13 patients with DS-AL compared with none in the DS-TMD group. Electron microscopy disclosed a positive platelet peroxidase reaction in each of the 11 DS-TMD patients and in nine of the 13 DS-AL patients. Immunologic studies revealed antiplatelet-megakaryocyte antigens on the blast cells of the majority of patients in both study groups. Our findings suggest that the blast cells in cases of DS-AL and DS-TMD arise from cells of the megakaryocytic lineage or from a myeloid progenitor with the capacity for megakaryocytic differentiation. The high risk of the development of AL in patients with DS who are less than 3 years old may be related to increased megakaryocyte proliferation in this age group.

Acute Disease↗

Mouse strain differences in the induction of micronuclei by polycyclic aromatic hydrocarbons.

The frequency of micronucleated erythrocytes (MNE) in 3 inbred mouse strains and 2 of their hybrids (C57BL/6, BALB/c, DBA/2, BDF1 and CDF1) were examined after polycyclic aromatic hydrocarbons (PAHs; 7,12-dimethylbenz[a]anthracene (DMBA), 3-methylcholanthrene (3-MC), benzo[a]pyrene (BaP), benzo[e]pyrene (BeP) and anthracene (ANT] were injected i.p. PAHs are thought to form active metabolites after being administered to mammals. In mouse strains with inducible PAH activating enzymes, such as C57BL/6 or BALB/c, MNE were significantly induced, as compared to control mice, 48 h after DMBA, BaP, or 3-MC was injected. No increase in the frequency of MNE occurred in the DBA/2 strain which cannot induce the activating enzymes. BeP and ANT did not increase the frequency of MNE in any mouse used. The levels of MNE induction in BDF1 or CDF1 hybrids were similar to those in C57BL/6 or BALB/c. These results support the view that the genetic capacity to metabolize PAHs is strongly associated with micronucleus induction as in the case of PAH carcinogenesis.

Animals↗

Heterogeneity of acute undifferentiated leukemia at the immunoglobulin and T-cell receptor genes level.

Phenotypic markers of leukemic cells from 76 children with acute leukemia were examined. Of these cases, 7 were diagnosed as acute undifferentiated leukemia (AUL) whose leukemic cells were negative for myeloperoxidase and did not react with lineage-specific or lineage-associated monoclonal antibodies. Then, we analyzed the configuration of both immunoglobulin (Ig) and T-cell receptor beta-chain (T beta) gene in these 7 AUL cases. Three cases had no rearrangement of Ig or T beta genes which was suggestive of non-lymphoid origin of these cases. In contrast, 4 cases showed rearrangements of Ig and/or T beta genes. One of these 4 cases demonstrated T beta gene rearrangement with retention of the germline configuration of Ig genes. Two cases with both Ig and T beta gene rearrangements also showed kappa-chain gene rearrangements. These findings indicate the heterogeneity of AUL at the DNA level, and may cast new light on the early differentiation of hematopoietic progenitor cells.

Acute Disease↗

Glycyrrhetic acid inhibits tumor-promoting activity of teleocidin and 12-O-tetradecanoylphorbol-13-acetate in two-stage mouse skin carcinogenesis.

Glycyrrhetic acid suppressed tumor promoter-induced effects in vitro, such as stimulation of 32Pi-incorporation into phospholipids of cultured cells and down-regulation of the epidermal growth factor receptor. Glycyrrhetic acid inhibited the promoting activity of both 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA). The percentage of tumor-bearing mice in the group treated with DMBA plus teleocidin was 88% at week 18, whereas that in the group treated with DMBA plus teleocidin and glycyrrhetic acid (10 mumol/painting) was 6%. Similarly, the percentage of tumor-bearing mice of the group treated with DMBA plus TPA was 97% at week 20, whereas that of the group treated with DMBA plus TPA and glycyrrhetic acid was 40%. Therefore, glycyrrhetic acid was proved to inhibit the activity of two different tumor promoters, teleocidin and TPA, in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗

Mouse skin melanoma induced in two stage chemical carcinogenesis with 7,12-dimethylbenz[a]anthracene and croton oil.

Mouse skin melanomas were induced in two stage skin carcinogenesis with 7,12-dimethylbenz[a]anthracene as initiator and croton oil as promoter. After approximately 25 weeks of promotion, small black macules of the skin were observed in C57BL, CDF1 and BDF1 mice, and progressively grew with time. Macules less than 2 mm in diameter were localized mostly in the lower portion of the dermis and, histologically, these lesions were consistent with the diagnosis of melanocytoma and were composed of polygonal to round cells loaded with large numbers of melanin granules. The cells were closely packed forming well-demarcated cell-nests with occasional columnar arrangement. In the macules over 2 mm in diameter, the cells were closely packed to form irregularly bordered cell-nests, showing invasive growth into the surrounding tissues. The lesions were diagnosed as malignant melanomas. The incidence of benign and/or malignant melanoma differed among strains: 80% in BDF1, 70% in CDF1, 30% in C57BL/6 and 0% in DBA/2 mice. One example of tumor induced in a CDF1 mouse was transplantable to homologous CDF1 mice.

9,10-Dimethyl-1,2-benzanthracene↗

Identification of cembratriene-4,6-diol as antitumor-promoting agent from cigarette smoke condensate.

Cigarette smoke condensate (CSC) was separated into several fractions and each was tested for an inhibitory effect on the early antigen (EA) of Epstein-Barr virus (EBV) which can be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Two diastereoisomers of 2,7,11-cembratriene-4,6-diol (alpha- and beta-CBT) were isolated from the neutral fractions of CSC and these showed potent inhibitory effects on the induction of EBV-EA by TPA. The doses of alpha- and beta-CBT required for 50% inhibition of EBV-EA induction by TPA were 7.7 and 6.7 micrograms/ml, respectively, which are comparable with those of retinoic acid, a potent inhibitor of induction of epidermal ornithine decarboxylase (ODC) activity and tumor promotion by TPA in mice. Application of alpha- and beta-CBT to mouse skin prior to treatment with TPA inhibited TPA-induced ODC activity. The degree of inhibition was dependent on the dose and application of 16.5 mumol/mouse of alpha- and beta-CBT resulted in a 50 and 40% reduction, respectively, of the maximum of the ODC activity induced as a result of treatment with TPA. In initiation-promotion experiments, alpha-CBT markedly inhibited the promoting effect of TPA on skin tumor formation in mice which were initiated with 7,12-dimethylbenz[a]anthracene, but beta-CBT was found to be less effective. Application of 3.3 mumol of alpha-CBT 40 min prior to treatment with TPA (1 microgram) resulted in a 53% reduction in the number of papillomas per mouse. Our present data suggest that EBV-EA inhibition assay using Raji cells is effective for the first screening of inhibitors of tumor promotion, and provide evidence that CSC contains antitumor-promoting agents in addition to carcinogenic and tumor-promoting agents already reported.

Animals↗

The role of substance P as a neurotransmitter in the reflexes of slow time courses in the neonatal rat spinal cord.

In order to reveal the spinal reflexes involving the transmitter action of substance P (SP), the effects of capsaicin and an SP antagonist on the isolated spinal cord of the neonatal rat studied. When a single shock stimulus was given to a dorsal root (L3-L5) or a sciatic nerve, depolarizing responses of various time courses were recorded extracellularly from both ipsi- and contra-lateral ventral roots of the corresponding segments. The reflex response recorded from the contralateral ventral root consisted of fast and slow components, which will be referred to as contralateral fast and slow ventral root potentials (v.r.ps). The latter contralateral slow v.r.p. had a time-to-peak of 2-5 s and lasted 10-30 s. The threshold for the contralateral slow v.r.p. was about two times higher than that for the monosynaptic reflex, and it coincided with the threshold for activating the slow-conducting afferent fibres. The contralateral slow v.r.p. was abolished after the spinal cord was treated with capsaicin (1 microM for 30 min) in vitro. The contralateral slow v.r.p. was absent in the spinal cord derived from 4-day-old rats that had received capsaicin (50 mg kg-1, s.c.) on the 2nd day of life. The contralateral fast v.r.p. and other reflexes of fast time courses remained unaltered after treatment with capsaicin in vitro or in vivo. Administration of an SP antagonist, [D-Arg1, D-Pro2, D-Trp7,9 Leu11]-SP in concentrations of 5-16 microM depressed the contralateral slow v.r.p., but did not affect the monosynaptic reflex, the dorsal root potential and the contralateral fast v.r.p. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP (5 microM) markedly depressed the SP-induced depolarizing response recorded from the ventral root whereas the responses to noradrenaline, 5-hydroxytryptamine, neurotensin and thyrotrophin releasing hormone (TRH) were unaffected by the SP antagonist. The response of the ventral root to acetylcholine was slightly depressed by the antagonist. The SP antagonist at 5-10 microM did not exert any agonist action on the motoneurones. The present results in conjunction with those of previous studies support the hypothesis that SP released from certain primary afferent fibres acts as a neurotransmitter, producing in dorsal horn neurones slow excitatory postsynaptic potentials which lead to the generation of the contralateral slow v.r.p.

Animals↗

Blockade of slow excitatory post-synaptic potential by substance P antagonists in guinea-pig sympathetic ganglia.

The effects of three substance P (SP) antagonists on the inferior mesenteric ganglion of the guinea-pig were studied using intracellular recording techniques, and the possible role of SP as a transmitter for the non-cholinergic slow excitatory post-synaptic potential (e.p.s.p.) was examined. The SP antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP, exerted a depolarizing action on the ganglion cells when applied by perfusion at a concentration of 3-16 microM or by pressure ejection from a micropipette. This depolarizing action is probably due to a release of endogenous histamine because it was abolished by treatment with a histamine antagonist, mepyramine (1-3 microM), or by a repeated application of the antagonist. When applied by pressure ejection, SP at 0.5-1 microM depolarized the ganglion cells. In the presence of mepyramine, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP suppressed the SP-induced depolarization by 41% at a concentration of 8 microM and by 75% at 16 microM. By contrast the SP antagonist did not affect the depolarizing action of angiotensin II on the ganglion cells. The non-cholinergic slow e.p.s.p. evoked in the ganglion cells by repetitive stimulation of the lumbar splanchnic nerves was suppressed by [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP at 8 or 16 microM. The degrees of suppression of both the non-cholinergic slow e.p.s.p. and the SP-induced depolarization by the SP antagonist were approximately equal. The cholinergic fast e.p.s.p. evoked by preganglionic nerve stimulation was not affected by the SP antagonist. [D-Pro2, D-Trp7,9]SP exhibited the properties of an SP antagonist similar to, but slightly weaker than [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP. [D-Pro2, D-Phe7, D-Trp9] at a concentration of 16 microM had a depolarizing action on the ganglion cells, which was not blocked by mepyramine. The peptide exerted hardly any antagonistic action against the SP-induced depolarization of the ganglion cells. Stimulation of the other preganglionic (intermesenteric) nerves and the post-ganglionic (colonic and hypogastric) nerves produced a non-cholinergic slow e.p.s.p. in the inferior mesenteric ganglion cells. The non-cholinergic slow e.p.s.p. evoked by both pre- and post-ganglionic nerve stimulation were depressed by [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP to similar extents. The present results show that [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP and [D-Pro2, D-Trp7,9]SP can serve as specific SP antagonists in the inferior mesenteric ganglion of the guinea-pig.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗