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S Ichikawa

Publications and source records attributed to S Ichikawa.

At least 181 records · Page 10Linked to original sources
PubMed1993

Nerve terminals associated with the central lacteal lymphatics in the duodenal and ileal villi of the monkey.

An intimate association of nerve fibers with the central lacteal endothelium was demonstrated in the duodenum and ileum of the monkey by immunohistochemistry and transmission electron microscopy. In the basal portion of the central lacteal, nerve fibers containing large cored vesicles and small clear vesicles were located closely beneath the lacteal endothelium. Identification of nerves was performed by immunohistochemistry using antisera against substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide, gastrin-releasing peptide and neuropeptide Y. These nerves contained immunoreactivities for SP and CGRP only. Some of the nerves, either singly or in a dense bundle, indented the endothelial cells to form a conspicuous cushion protruding into the lumen. The attenuated endothelium covering the cushion occasionally was failing, and the nerves were exposed to the lumen. Tight of occasionally subendothelial nerve terminals bundles formed a synapse-like association between themselves: a swollen axonal profile was invaginated by a finger-like projection of another axon, the latter being filled with synaptic vesicles. These results suggest that the central lacteal lymphatics might be afferently monitored, presumably with regard to the luminal pressure, and, at the same time, efferently modulated by these nerves.

Animals↗
PubMed1993

Pharmacological properties of KF18259, a novel 5-HT3-receptor antagonist, in rats: inhibition of the distal colonic function.

We investigated the effects of KF18259 (endo-(8-methyl-8-aza- bicyclo[3.2.1]oct-3-yl)-1-isobutyl-2-oxo-1,2-dihydro-4-quinolinecarboxyl ate hydrochloride), a novel 5-HT3-receptor antagonist, in a variety of rat models, which are assumed to be mediated via 5-HT3 receptors, in comparison with those of YM060 ((R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride), granisetron and ondansetron. KF18259 inhibited wrap-restraint stress-induced defecation. The doses of KF18259 to inhibit wrap-restraint stress-induced defecation were lower than those to inhibit the 5-HT-induced von Bezold-Jarisch reflex and the cisplatin-induced slowing of gastric emptying. In contrast, the doses of YM060, granisetron and ondansetron to inhibit these three responses were similar. Moreover, KF18259 inhibited the wrap-restraint stress-induced propulsive motility of the proximal and distal colon. The effect of KF18259 on the distal colon was as potent as that on defecation and was more potent than that on the proximal colon. These results indicate that KF18259 potently inhibits the distal colonic function. KF18259 may be a useful tool for the discrimination of the 5-HT3-receptors located on the distal colon and other tissues.

Animals↗
PubMed1993

T-cell non-Hodgkin's lymphoma of the lung.

We report a case of primary T-cell non-Hodgkin's lymphoma of the lung. A definite diagnosis was made histologically at open lung biopsy. Atypical cells in the biopsy specimen reacted with monoclonal T-cell markers. Transbronchial lung biopsy and bronchoalveolar lavage fluid were useful in the diagnosis. Primary T-cell lymphoma of the lung is rare and is reviewed in this report.

Adult↗
PubMed1993

[Prediction of future trends of HIV infection and AIDS in Japan].

Current status and future trends of HIV infection and AIDS in Japan were estimated based on AIDS surveillance data up until 1992, excluding HIV infection from blood products and blood-borne transmission. The coverage rate of reports of HIV infection was estimated as the proportion of the reported AIDS cases who are also included in reports of HIV infection. Current numbers of HIV infected persons were then estimated to be the reported numbers divided by the coverage rate. Future numbers of HIV infected persons were predicted by extrapolation. Future numbers of AIDS cases were predicted based on the predicted numbers of HIV infected persons and the incubation distribution. The results were as follows: 1) The coverage rate of the reports of HIV infection was estimated to be 11.5%. 2) The numbers of HIV infected persons were estimated to be 2,900 in Japanese and 4,500 in foreigners by the end of 1992, and are predicted to be 7,700 in Japanese and 15,500 in foreigners by the end of 1997. 3) The numbers of AIDS cases were reported to be 125 in Japanese and 52 in foreigners by the end of 1992, and are predicted to be 1,100 in Japanese and 1,600 in foreigners (including AIDS cases developed after return to home country) by the end of 1997.

Acquired Immunodeficiency Syndrome↗
PubMed1992

New bronchodilators. 3. Imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones.

In order to develop new oral bronchodilators, a series of novel imidazol[4,5-c][1,8]naphthyridin-4(5H)-ones 5 were designed and synthesized. Some of these new heterocycles exhibited more potent bronchodilator activity in vitro and in vivo than theophylline. With respect to modification at the 5-position, both phenyl and n-butyl substitution produced potent activity. Though bulk tolerance at N-3 is observed with short and small lipophilic groups, any substitution at the other positions and transformations of the parent skeleton eliminated activity. Thus 5-phenyl-1H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (23) (KF17625), which satisfied these conditions, was selected for further studies (antigen inhalation-induced bronchospasm model; minimum effective dose (MED) = 1 mg/kg, po; antigen-induced contraction of trachea (the Schultz-Dale reaction), IC50 = 2.2 microM). Compound 23 inhibited carbachol-, histamine-, or leukotriene D4-induced contraction and relaxed spontaneous tone in guinea pig isolated tracheal preparations with, 4- to 16-fold greater potency than aminophylline. Thus it appeared to relax directly the airway smooth muscle. 23 did not have any influence on adenosine binding at 10 microM, but inhibited canine tracheal phosphodiesterase (PDE) IV (IC50 = 12 microM) and concanavalin-A-induced histamine release from rat mast cells (44% inhibition at 10 microM). Although the detailed mechanisms of these compounds remain to be elucidated, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

Animals↗
PubMed1992

5-HT3 receptor antagonists. 1. New quinoline derivatives.

A series of esters and amides of 1-alkyl-2-oxo-1,2-dihydroquinoline-4- carboxylic acid or 2-alkoxy-quinoline-4-carboxylic acid containing a basic azabicycloalkyl moiety has been synthesized and evaluated for affinity for the [3H]quipazine-labeled 5-HT3 receptors. Most of the esters exhibited 10-fold more potent activity than that of ondansetron (1; Ki = 7.6 nM). Lipophilic substituents at the 1- or 2-position of the quinoline ring enhanced affinity for the receptors. Compounds 21 and 37 showed the highest affinity (Ki = 0.32 and 0.31 nM, respectively) among them. On the other hand, most of the amides showed 100-fold lower affinity than that of the esters. Molecular modeling studies indicated that the carbonyl moiety in 19 (ester) or 31 (amide) was not coplanar to the plane of an aromatic ring (over 20 degrees deviation). Although some of the selected compounds exhibited potent activity in the Bezold-Jarisch (B-J) reflex test, good correlation was not observed between the affinity for the 5-HT3 receptors and the activity in the B-J reflex test (in vivo). From these data, it was suggested that our quinoline derivatives might interact with the 5-HT3 receptors in a different way from that of the reported 5-HT3 receptor antagonists presumably due to the presence of the heterogeneity of the 5-HT3 receptors between brain and heart.

Animals↗
PubMed1992

Tradescantia stamen-hair system as an excellent botanical tester of mutagenicity: its responses to ionizing radiations and chemical mutagens, and some synergistic effects found.

The stamen-hair system of Tradescantia heterozygous for flower color (blue/pink, the pink color being recessive) is an excellent botanical tester of mutagenicity. It is especially useful for detection of the genetic effects of both ionizing radiations and chemical mutagens at the low levels of exposure to which the human population may actually be exposed. This system exhibits a high accuracy in laboratory experiments, and is also applicable for in situ monitoring in the environment. The use of the Tradescantia stamen-hair system is inexpensive and requires only a short training time. Simplified scoring methods which endorse a high statistical accuracy have newly been developed to score larger samples of pink somatic mutations. In the present paper, the most widely used clones, methods for their cultivation, and use in a variety of experiments with radiations and chemical mutagens are also reviewed.

Chromatids↗
PubMed1992

New bronchodilators. 1. 1,5-Substituted 1H-imidazo[4,5-c]quinolin-4(5H)-ones.

A series of novel xanthine-based tricyclic heterocycles in 1H-imidazo[4,5-c]quinolin-4(5H)-ones was designed, synthesized, and tested as potential active bronchodilators. Inhibition of the Schulz-Dale (SD) reaction-induced contraction in trachea and inhibition of antigen inhalation-induced bronchospasm in passively sensitized guinea pigs served as primary in vitro and in vivo assays, respectively. Simultaneous measurement of acute lethal toxicity (minimum lethal dose; MLD, po) in mice allowed determination of a safety margin. The bronchodilatory activity of these heterocycles was considerably varied with the nature of substituents at the 5-position. The most active substituents at the 2- and 5-positions and on the aromatic ring were found to be hydrogen, n-butyl, and hydrogen, respectively. There was a bulk tolerance for lipophilic substituents at the 1-position. 5-Butyl-substituted compounds appeared to be less toxic than theophylline on the basis of MLD data. Thus 5-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-4(5H)-one (10) (IC50 value of the SD assay = 0.25 microM, MLD > 300 mg/kg) was selected for further studies. Compound 10 (KF15570) reduced bronchoconstriction produced by antigen (Konzett-Rössler preparation in anesthetized guinea pigs, ED50 = 0.42 mg/kg, iv) more effectively than aminophylline (ethylenediamine salt of theophylline, ED50 = 7.8 mg/kg, iv) but had fewer side effects on the heart and CNS than theophylline. Compound 10 and its derivatives showed weak adenosine antagonism and phosphodiesterase (PDE) inhibition which could not account for their potent bronchodilation. Although their precise mechanism of action remains unclear, this series of novel tricyclic heterocycles represents a new class of bronchodilator.

Airway Resistance↗
PubMed1992

New antiinflammatory agents. 2. 5-Phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-ones: a new class of nonsteroidal antiinflammatory agents with potent activity like glucocorticoids.

We previously described new antiinflammatory agents, 4-hydroxy-2-oxo-1-phenyl-1H-1,8-naphthyridine-3-carboxamides 1. Further modification of the compounds bearing 1-phenyl-1,8-naphthyridin-2-one as a mother skeleton led to 5-phenylimidazo[4,5-c][1,8]naphthyridin-4(5H)-one derivatives 2 and 3. Regioselective synthesis of these compounds bearing a substituent at the 1- or 3-position was conducted according to the method shown in Schemes I and II. In this series of compounds, antiinflammatory activities were greatly influenced by the position and nature of substituents on imidazole. 3-Alkyl or 3-benzyl substitution result in the potent activity, but 1-substitution did not. Minor modification of the benzyl group reduced or eliminated the activity. Detailed examination of structure-activity relationships led to 3-benzyl-5-phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (22), which exhibited potent oral antiinflammatory activities in carrageenan-, zymosan-, and reversed passive Arthus reaction-induced rat paw edemas (ED40 = 5.3, 0.37 mg/kg, ED50 = 0.47 mg/kg, respectively). This broad activity of 22 was like that of glucocorticoids. Compound 22 did not affect activities of CO and 5-LO enzymes and receptor binding of various ligands. As one of the mechanisms of action, induction of release of glucocorticoids was postulated. These results suggest that 22 represents a novel class of antiinflammatory agents.

Animals↗
PubMed1992

Cloning and disruption of the cefG gene encoding acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase from Acremonium chrysogenum.

Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C (CPC) in Acremonium chrysogenum. The gene encoding DCPC-ATF, cefG, has been isolated from an A. chrysogenum genomic library using a DCPC-ATF cDNA probe. Nucleotide sequence analysis revealed that cefG contains two short introns of 79bp and 65bp. The gene was found to be closely linked to the cefEF gene encoding deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase, which catalyses the preceding two steps in the pathway. The two genes are separated by a 1114 bp segment from which they are divergently transcribed. Introduction of the cloned cefG gene to A.chrysogenum resulted in an increased level of DCPC-ATF activity. A plasmid carrying a cefG gene interrupted in the coding region by a selectable marker for resistance to hygromycin B was constructed and used to disrupt the cefG locus in A.chrysogenum. The cefG-disrupted strains were found to lack the ability to produce CPC, and accumulated its precursor, deacetylcephalosporin C in the culture broth. Southern hybridization analysis confirmed that the disruption resulted from a gene replacement event at the cefG locus.

Acetyltransferases↗
PubMed1992

Stable isotope aided nuclear magnetic resonance study to investigate the receptor-binding site of human interleukin 1 beta.

Resonance assignments for interleukin 1 beta at neutral pH were made by using three-dimensional NMR in combination with specific labeling and double-labeling methods with stable isotopes. On the basis of the present assignments, 15N single-quantum coherence spectra of N-terminal truncated and fusion mutants were compared with that of the wild-type. Although these mutants have reduced biological activity, they showed 15N-SQC spectra similar to that of the wild-type. However, small but significant chemical shift changes were observed for amino acid residues within a loop 86-99, in spite of the modification at the N-terminus, supporting the idea that this loop forms a biologically active part of interleukin 1 beta. Receptor-binding activity was studied for mutants (Asp-93)-, (Leu-93)- and des-(Arg-98)interleukin 1 beta's. The results show significant loss of the receptor-binding activity. The N-terminus, the C-terminus, and the loop 86-99 form a part of the open end of a beta-barrel [Finzel, B. C., Clancy, L. L., Holland, D. R., Muchmore, S. W., Watenpaugh, K. D., & Einspahr, H. M. (1989) J. Mol. Biol. 209, 779-791; Clore, G. M., Wingfield, P. T., & Gronenborn, A. M. (1991) Biochemistry 30, 2315-2323], which forms the receptor-binding site of IL-1 beta.

Amides↗
PubMed1992

Molecular cloning of acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase cDNA from Acremonium chrysogenum: sequence and expression of catalytic activity in yeast.

Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C, the conversion of deacetylcephalosporin C to cephalosporin C. A cDNA encoding DCPC-ATF has been isolated from a cDNA library of a cephalosporin C producing fungus Acremonium chrysogenum using oligonucleotide probes based on N-terminal amino acid sequences of the enzyme. The cDNA contains a single large open reading frame for a putative precursor consisting of 12 amino acid(AA) leader peptide of unknown function, 274 AA large subunit and 126 AA small subunit at the carboxyl end. The cDNA was expressed in yeast exhibiting a functional DCPC-ATF activity. It was also indicated that the leader peptide was not essential for expression of the enzyme activity. The primary structure of DCPC-ATF shows significant homology with those of acetyl CoA: homoserine o-acetyltransferase in Saccharomyces cerevisiae and Ascobolas immersus.

Acetyltransferases↗