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Biomedical subjects

H Iinuma

Publications and source records attributed to H Iinuma.

At least 91 records · Page 5Linked to original sources
PubMed1990

Screening of antibiotics preferentially active against ras oncogene-expressed cells.

During the course of in vitro screening of agents which are preferentially active against ras oncogene-expressed cells, a new anthracycline (identified as 2-demethylsteffimycin D) and a heptaene (possibly a new member of partricins) were isolated from microbial fermentation broths. Among known compounds tested, 5-fluorouracil, 5-fluorodeoxyuridine and oxanosine showed high selectivity towards ras oncogene-expressed cells.

Animals↗
PubMed1990

Biological activities of cyclophellitol.

Cyclophellitol [1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4,1,0] heptane-2,3,4-triol) was tested against 9 glycosidases and found to be a specific inhibitor of almond beta-glucosidase. Cyclophellitol inhibited almond beta-glucosidase activity by 50% at 0.8 micrograms/ml and was a competitive inhibitor of almond beta-glucosidase as revealed by Lineweaver-Burk plot. Cyclophellitol was inactive against yeast alpha-glucosidase, beta-galactosidase, beta-glucuronidase, alpha-L-fucosidase, end-beta-N-acetyl glucosaminidase, alpha-mannosidase, and cellulase. It was weakly active toward fungal beta-xylosidase. Cyclophellitol-treated almond beta-glucosidase was equally suppressed after dialysis; thus cyclophellitol is likely to bind to almond beta-glucosidase irreversibly. The inhibitor was found by fluorimetric assay to be active against beta-glucosidase but inactive toward alpha-glucosidase in Molt-4 microsomal fraction. It also inhibited Molt-4 beta-glucocerebrosidase completely at 2 micrograms/ml when the enzyme was assayed with a synthetic labeled substrate, and the inhibitory activity was more than one hundred times higher than that of nojirimycin, castanospermine, or of deoxynojirimycin. Mice administered 1 mg of cyclophellitol daily for 5 days began to exhibit severe abnormalities of nervous system similar to those found in Gaucher's mouse.

1-Deoxynojirimycin↗
PubMed1990

Production, isolation and structure determination of a novel beta-glucosidase inhibitor, cyclophellitol, from Phellinus sp.

In the course of our screening of beta-glucosidase inhibitor, a culture filtrate of a mushroom, Phellinus sp. strongly inhibited the enzyme activity. The active substance was isolated through charcoal separation, column chromatography and crystallization. Spectroscopic and crystallographic analysis revealed that it had a novel cyclitol structure, (1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4,1,0]heptane-2,3,4-tri ol, and we named it cyclophellitol. It inhibited almond-derived beta-glucosidase with an IC50 of 0.8 micrograms/ml.

Basidiomycota↗
PubMed1989

Prevention of pneumococcal bacteremia by immunization with type 6 pneumococcal capsular polysaccharide vaccine in splenectomized rats.

Postsplenectomy sepsis is well recognized and prophylactic vaccination with pneumococcal polysaccharide is recommended. However, the efficacy of vaccination with the polysaccharide in splenectomized individuals is not clear. The effect of type 6 pneumococcal polysaccharide vaccine on the clearance of pneumococci from the bloodstream and lung was studied in splenectomized rats as was survival after intravenous challenge with Streptococcus pneumoniae, serum opsonic activity, and specific antibody titer by ELISA. Rats immunized with type 6 pneumococcal polysaccharide vaccine had significantly increased survival (P less than .05) and clearance of pneumococci from the bloodstream and lung (P less than .05) after intravenous challenge with S. pneumoniae, significantly higher serum opsonic activity (P less than .02), and increased specific IgG and IgM antibody titer to the type 6 polysaccharide compared with controls treated with saline. There was close correlation between IgG antibody titer to type 6 polysaccharide and opsonic activity (r = .95). These results suggest that pneumococcal polysaccharide vaccine is effective for preventing pneumococcal bacteremia in splenectomized hosts.

Animals↗
PubMed1989

The response of digitalized canine ventricle to programmed stimulation: a study on triggered activity arrhythmias in the whole heart.

Triggered activity (TA) has recently received increased attention as a mechanism responsible for cardiac arrhythmias. However, few studies have shown TA in the intact heart. In an ouabain-treated dog's heart we have shown: (a) overdrive acceleration, (b) a concordant relationship between the postpacing interval (PI) and pacing cycle length (CL), and (c) a discordant relationship between the PI and number of paced beats necessary to induce TA. These findings appear to agree with the distinctive characteristics of TA arrhythmias elucidated in previous in vitro studies and suggest TA rather than a reentrant tachycardia. In addition, it is possible that this heart preparation could be considered as a suitable model for the study of TA arrhythmias. These results were obtained using a programmed stimulation protocol in this dog model: (1) Following single programmed ventricular stimulation during sinus rhythm, a repetitive ventricular response (RVR) of more than 3 beats occurred in only 20% of hearts. The relationship between PI and the coupling interval (CI) of the extrastimulus was concordant in 80% (12/15) and discordant in 13% (2/15) of all experiments. The PI-CI relationship was influenced by the mutual relationship between the stimulating, recording, and originating sites of TA. (2) RVR of more than 3 beats was induced by consecutive overdrive ventricular stimulation during sinus rhythm (78%). In addition, the PI-pacing CL relationship was concordant (100%). (3) The transient termination of sustained VT that occurred spontaneously after administration of a large dose of ouabain was seen in only 15% of the cases after a single programmed premature ventricular stimulation. The return cycle-CI relationship was biphasic in 75% (15/20) experiments and discordant in 25% (5/20) of the experiments. (4) The termination of spontaneous sustained VT by overdrive ventricular stimulation occurred in only 8% of the cases. Transient overdrive acceleration of VT occurred after overdrive pacing (53%). In contrast, overdrive suppression occurred in only 13%. Thus, the characteristics of TA arrhythmias observed in the whole heart preparations differed, in some respects, from those obtained by in vitro studies. These quantitative observations could suggest a differentiation, based on probability, between TA and the reentrant mechanism that would respond to programmed stimulation in a similar manner. The differentiation between reentrant and triggered ventricular tachycardia can be made with reasonable assurance using these programmed stimulation techniques.

Animals↗
PubMed1989

Suppression of the activities of T-lymphocyte-related enzymes in spleen by administration of an immunosuppressant, 15-deoxyspergualin.

We investigated the effects of both (-) and (+)-enantiomers of 15-deoxyspergualin (DSG), an immunosuppressant, on enzyme networks in spleens of ICR mice. Of the 14 hydrolytic enzymes tested, the activity of dipeptidyl aminopeptidase IV (DAP-IV) was found to be significantly suppressed by the administration of (-)-DSG but not by that of (+)-DSG. In contrast, the activity of N-acetyl-beta-D-glucosaminidase (GlcNAc-ase) was suppressed by the administration of both enantiomers of DSG. Judging from the previous reports of ours and others which suggested specific relations of these enzymes to T-lymphocytes, the above findings may warrant further studies of these enzymes in relation to immunologic functions of the body.

Acetylglucosaminidase↗
PubMed1988

Purification of a low molecular weight factor that induces differentiation and inhibits growth in myeloid leukemia cells.

A procedure is described for purifying a low molecular weight peptide that induces differentiation in mouse myeloid leukemia M1 cells. The factor comes from the conditioned medium of macrophage-like cells differentiated from mouse myeloid leukemia M1 cells. The procedure for purification includes gel filtration on Sephadex G-15, anionic exchange chromatography, thin-layer chromatography, reverse-phase high-performance liquid chromatography on a C18 hydrophobic support, and high-performance liquid chromatography gel filtration. The molecular weight of the factor estimated from the amino acid composition was approximately 1280, which agrees well with that obtained by high-performance liquid chromatography gel filtration. The half-maximal concentration of the purified factor for inducing differentiation of M1 cells was approximately 3.2 x 10(-7) M as judged by nitroblue tetrazolium staining ability. The purified factor also inhibits the growth of human leukemia HL-60 cells.

Animals↗
PubMed1988

Synthesis of histargin and related compounds and their inhibition of enzymes.

A novel method for the synthesis of histargin and its analogs is described. It includes two kinds of N-alkylation reactions that prevent the formation of side products. The inhibition of enzymes by these compounds was also measured. Some of the compounds strongly inhibited carboxypeptidase B, carboxypeptidase A, carboxypeptidase N (kininase I), and angiotensin converting enzyme.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Feedback analysis of the behavior of the renin-angiotensin system under inhibition of angiotensin-converting enzyme.

It was previously shown that autoregressive modeling can be used for feedback analysis in the body. We used this method to investigate the dynamic changes in and around the renin-angiotensin system in vivo induced by angiotensin-converting enzyme (ACE) inhibition. Long-term studies were performed on rabbits, which were given a daily injection of one of the following ACE inhibitors: captopril, foroxymithine, or histargin. For comparison, other rabbits received injections of saline or the renin inhibitor pepstatin. Autoregressive coefficients were computed from the raw data thus observed and were used to simulate the impulse-response function proper to each animal. The response of each animal estimated in this way exposed the effects of ACE inhibitors in vivo which were obscured by the feedback regulation of the renin-angiotensin system. Also, it was suggested that histargin has a peculiar action, blocking the negative feedback that would be elicited by the usual ACE inhibition. Feedback analysis seems to be essential to elucidate the in vivo effects of enzyme inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

[Follow-up study on women suffered from severe toxemia of pregnancy].

We started a special follow-up system for women who had a history of severe toxemic pregnancy in our department since 1975. All medical records from 1956 to 1975 were reviewed and 468 deliveries with such disease were registered at that time. One hundred and ninety five deliveries (186 women) also were added from the prospective point of view until 1985. Among 654 patients, 374 women were available to address. I. The latter 186 women were divided into 7 groups: A1, A2, A3, A4, B1; and B2. The definitions of each group were as follows. A1: primipara with severe toxemia; A2: multipara that had a severe toxemia at the first time and then normal pregnancy (ies); A3: multipara that had a severe toxemia in the first pregnancy and then mild one(s); A4: multipara that repeated severe diseases; A5: multipara that had a severe toxemia and then unclassified type(s) of the disease; B1: multipara that had a normal pregnancy at the first time and then severe toxemia(s); B2: multipara that had a mild toxemia in the first pregnancy and then severe one(s). The percent of each group was 25, 24, 13, 15, 4, 6, and 12% respectively. Those women who had severe toxemia(s) were found to have hypertension, high levels of blood urea nitrogen, hyperhematocritemia, and hyperlipemia from the results of clinical and laboratory data. Consequently, they are a high risk group of atherosclerosis, because hypertension and hyperlipemia are main risk factors of that disease. II. Eighty percent of 374 women who had a history of severe toxemia from 1956 to 1985 was able to be followed up by us until 1987. Those women also were divided into the same groups as described above except A5, and checked up as to hypertension, hyperlipemia, body weight, and so on. The characteristic features were that the group A2 is in a well condition, and that many of group A4 are suffering from various diseases with regard to the remote prognosis. In conclusions, it was suggested that there may be four etiologic causes as to toxemia of pregnancy. The first is a disadaptation during pregnancy, and this seems to consist mainly of pregnancy induced hypertension. The second has various underlying diseases, such as chronic hypertension or renal disease, etc.. The third has a hypertensive trait which is manifested as the pregnancy advances. The fourth is considered to be related to biologic ageing.

Adult↗
PubMed1987

New antibiotic napyradiomycins A2 and B4 and stereochemistry of napyradiomycins.

Napyradiomycins A2 and B4, new members of the napyradiomycins, have been isolated from the culture broth of Chainia rubra MG802-AF1. The structure of napyradiomycin A2 was elucidated as 16-hydroxy-17-methylenenapyradiomycin A1 by NMR studies. The absolute structure of napyradiomycin B4 was determined as 13-hydroxy-13-methylnapyradiomycin B1 by X-ray crystallography and therefore the configuration of C(4a) in other napyradiomycins is assumed as the R configuration. The geometrical isomerism of napyradiomycin C1 was estimated as 12E and 16E by nuclear Overhauser effect experiments.

Anti-Bacterial Agents↗
PubMed1987

Synthesis and antitumor activity of spergualin analogues. II. Chemical modification of the spermidine moiety.

Chemical modifications of the spermidine moiety of an antitumor antibiotic, spergualin (Ia), and the structure-activity relationship are described. Replacement of spermidine with other polyamines decreased the antitumor activity against mouse leukemia L1210. Analogues containing an oxidized spermidine moiety that probably formed during oxidation with amine oxidase were inactive. Spermidine is indispensable for the antitumor activity. A facile method for the synthesis of glyoxyloyl polyamine, a key intermediate of spergualin-related compounds, is also reported.

Animals↗