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Biomedical subjects

H Sakurai

Publications and source records attributed to H Sakurai.

At least 451 records · Page 25Linked to original sources
PubMed1991

In vitro and in vivo studies of the growth inhibitory effect of a newly synthesized peptide, obiopeptide-1, on mice-bearing methylcholanthrene-induced murine tumours.

Novel synthetic Obiopeptide (Obi-1), Glycil-penta-Glutamate, as an immunoregulator, injected intramuscularly to methylcholanthrene (MC) induced tumour bearing mice at 30-100 micrograms per mouse weekly, significantly inhibited tumour growth, compared to that of the untreated control. Numbers of mononuclear cells (MNC) in the spleen obtained from Obi-1 treated and untreated mice were reduced to 64% and 10% of the normal levels, respectively. In histopathological findings, variations of MNC in the spleen was observed in colonies of large MNC and lymphocytes in Obi-1 treated red marrow, while untreated one showed only scattered number of small lymphocytes. A significant O2- production was noted in monolayers of normal macrophages incubated with 0.5 mg Obi-1/ml for 48 hr. Cytotoxicity of spleen MNC cultured with Obi-1 against MC-tumour, Meth A, P-815 and YAC-1 target cells showed less than 10% cytotoxic activity in almost all experiments.

Animals↗
PubMed1991

Metabolism and excretion of a new 5-lipoxygenase inhibitor in rats, guinea-pigs, beagles and rhesus monkeys.

1. The 5-lipoxygenase inhibitor (I), a substituted benzothiazole is metabolized mainly by glucuronide and/or sulphate conjugation in rat, guinea-pig, beagle and rhesus monkey. Glucuronidation is the major pathway, and sulphation is more extensive in rat and beagle than in guinea-pig and rhesus monkey. 2. After a single oral dosing of 14C-I (10 mg/kg), more than 96% of the dose was excreted in 7 days in all four species, however there is species difference in urinary excretion, which was 2.8 +/- 0.3% in rat, 46.9 +/- 1.6% in guinea-pig, 2.6% in beagle and 68.2% in rhesus monkey. 3. After a single i.v. dose of 14C-I to bile duct-cannulated rats and guinea pigs, bile was a major route of elimination, and in rats the ratio of glucuronide to sulphate in excreta increased from 0.71 +/- 0.01 to 0.93 +/- 0.05 as the dose was increased from 0.2 to 20 mg/kg.

Animals↗
PubMed1991

Evaluation of superoxide scavenging activity of OPC-14117 by electron spin resonance technique.

OPC-14117 is a potent drug which has both brain function activating effect and protective effect against cerebral ischemia. Occurrences of these effects might be expected due to superoxide dismutase-like activity of OPC-14117. The present study has been conducted to evaluate the active oxygen scavenging activity of OPC-14117 and to explain the mechanisms of its pharmacological activities. The reaction of OPC-14117 and superoxide anion, generated in potassium superoxide, was examined by electron spin resonance technique at both liquid nitrogen (77 K) and room (22 degrees C) temperatures. OPC-14117 showed a higher superoxide scavenging activity than that of alpha-tocopherol in an aprotic solvent system. The active moiety of OPC-14117 to provide the scavenging effect was found due to the phenolic hydroxyl group of its indan skeleton.

Electron Spin Resonance Spectroscopy↗
PubMed1991

Metal- and photo-induced cleavage of DNA by podophyllotoxin, etoposide, and their related compounds.

Podophyllotoxin (PD) and its derivative etoposide (VP-16), a clinically useful anticancer drug, exhibit different mechanisms of action. PD binds specifically to tubulin to prevent its polymerization, whereas VP-16 lacks this action. The DNA strand breakage caused by VP-16 is thought to be due to its interaction with topoisomerase II or to free radical formation by oxidation of its 4'-phenolic hydroxyl group to a semiquinone free radical. We have demonstrated that PD, VP-16, 4'-demethylepipodophyllotoxin (DEPD), and syringic acid (SA) exhibit no DNA-cleaving activity but, in the presence of metal ions such as Cu2+ and Fe3+, DEPD and SA form metal complexes, which in turn show high activity for DNA strand scission at pH 7.8 under air. Furthermore, it was found that DNA cleavage was greatly promoted by irradiation with UV light. The PD-Fe3+ system at pH 7.8 showed very low DNA-cleaving activity, but irradiation with UV light in the system induced almost complete DNA breakage. DNA cleavages were significantly inhibited in the presence of hydroxyl radical scavengers, such as sodium benzoate and dimethylurea, in the Cu(2+)-SA and Fe(3+)-PD systems, with or without UV irradiation. These reactions were investigated by optical and ESR spectra, coupled with ESR spin-trapping techniques, by which the formation of hydroxy radicals was clearly detected in all systems. These findings have led us to a new proposal of the metal- and photo-induced mechanism for understanding the antitumor action of PD, VP-16, and their related compounds.

DNA↗
PubMed1991

[Residual stenosis after intracoronary thrombolysis: its clinical significance].

The effects of residual stenosis after intracoronary thrombolysis (ICT) on the hospital course and on left ventricular function were investigated in 94 patients with acute myocardial infarction. The in-patient hospital events including death, post-infarction angina, and re-infarction occurred in 6 of 24 (25%) patients with 100-99% residual stenosis (Group I), 18 of 55 (32.7%) patients with 95-90% stenosis (Group II) and one of 15 (7%) patients with 75% or less stenosis (Group III), suggesting that the presence of severe residual stenosis could be associated with the occurrence of in-patient hospital events. However, re-infarction occurred in only 3.6% of Group II patients. In an analysis of left ventricular function, global and regional wall motion was significantly improved in this group of patients, compared with patients who had no reperfusion (Group I). What is more, the degree of the improvement in wall motion in Group II, despite the severe stenosis, was the same as that in Group III with 75% or less stenosis. It was concluded that further intervention following thrombolysis may not be necessarily required for patients who underwent reperfusion without filling delay, even if the residual stenosis is greater than 90%.

Aged↗
PubMed1991

Changes in mouse brain monoamine oxidase activity in the first, second and fourth generations after manganese administration.

The present study was conducted to explore whether or not manganese effect on brain monoamine oxidase (EC 1.4.3.4) is subject to hereditary genetic amplification. Mice of both sexes were given manganese through four generations, and the enzyme activity was measured in the cerebral cortex, cerebellum, hypothalamus and hippocampus of each of the generations except for the third, whose activity we were not in a position to measure. Intrinsic enzyme activity was highest in the cerebellum, and was followed by those in the cerebral cortex and hypothalamus. The activity in the hippocampus was the lowest. Manganese administration greatly stimulated the activity in the cerebellum. However, as generation succeeded, the level of susceptibility to manganese gradually declined. Manganese concentration in pooled suborgan fractions proved to be, in every case, higher in the cerebral cortex, cerebellum and hippocampus and lower in the hypothalamus. No indication was found that the manganese effect is genetically inherited.

Activation Analysis↗
PubMed1991

[Clinical studies on lung disease due to atypical mycobacteria in our hospital during the past 13 years].

Among the patients with pulmonary diseases admitted to our hospital during a 13-year period from 1977 to 1989, clinical examinations and laboratory data on admission and the following clinical courses of 102 cases where atypical mycobacteria had been identified three times or more in sputum cultures at the time of hospitalization were investigated. 1. The ratio of the number of cases positive for atypical mycobacteria to those positive for acidfast bacilli in sputum cultures tested on admission was fairly constant, 6.0 to 7.8% every year since 1981. In the cases associated with positive sputum cultures for atypical mycobacteria, M. avium complex was observed in 84% of the cases: M. kansasii, M. fortuitum and M. chelonae were found in 13, 2 and 1 cases, respectively, since 1984. 2. A total of 102 cases studied consisted of 66 male and 36 female patients; the mean age was 61.9 years. 3. Sputa became negative on culture in 19 (86.4%) out of 22 cases of primary infection. In all primary infection cases, roentgenographic findings did not worsen and prognosis was extremely good. In secondary infection cases, sputum cultures became negative in 25 (83.3%) out of 30 cases expectorating a small quantity of mycobacteria on admission, where x-ray findings worsened in only one case. In contrast, in 47 cases expectorating a large quantity of the bacilli at the time of admission, negative sputum cultures were attained in only 14 cases (29.8%) and x-ray findings worsened in 10 cases, and their prognosis were poor. 4. In general, sputum cultures turned negative within 3 months after admission. If sputum cultures remained positive thereafter, it was found very difficult to stop expectoration of the bacilli in these patients, and hence their prognosis are supposed to be greatly affected by the bacteriologic findings in early stages of the disease.

Adult↗
PubMed1991

[A study of exercise programs and instructors for a fitness program in a corporate setting].

The objective of the study was to evaluate the importance of diversity in exercise programs and athletic instructors in a corporate physical fitness program. Subjects were 717 Japanese chemical factory employees (male 524, female 193) in Japan who were surveyed using a questionnaire, with a resultant response rate of 84%. Many employees who participated in regular physical activities on a voluntary basis were motivated to exercise for reasons other than health, with a variety of motivating factors suggested. The total number of sports programs in which male and female employees participated voluntarily were 31 and 15, respectively. For employees not yet participating in physical activities but expressing interest in joining a company sponsored sports class, the total number of programs in which interest was shown was 40 for males and 22 for females. Professional athletic instructors from outside fitness clubs appeared to have far more appeal to employees than athletic instructors who were recruited from company employees and given a short athletic instructor course to become health care leaders at the same factory in addition to their regular job. In order to enhance participation in and adherence to a corporate fitness program, it was suggested that the number of exercise programs be increased and that outside professional athletic instructors be employed.

Adult↗
PubMed1990

In vitro transcription of the plasma protein genes of Bombyx mori.

An efficient cell-free transcription system was developed from the extract of BmN cells established from an ovarian tissue of the silkworm, Bombyx mori. The cloned genes coding for major plasma proteins of B. mori including SP 1, SP 2 and 30K protein, were faithfully and efficiently transcribed in the extract prepared from BmN cells. The S1 nuclease mapping and primer extension analyses demonstrated that the transcription initiation site recognized in vitro is identical to that which functions in vivo. The transcription assay reconstituted from the fractionated BmN cell extract revealed that at least four protein factors are required for accurate transcription of the SP 1 and adenovirus major late genes. The results of in vitro transcription experiments employing a series of the 5' deleted mutant templates of the SP 1 gene indicated that partial deletion of the TATA box results in considerable loss of faithful transcript, while complete removal of the TATA-sequence totally abolishes the transcript. These observations suggest that the promoter element essential for transcription in cell-free systems is located in a region between nucleotide positions -44 and +16 of the SP 1 gene.

Animals↗
PubMed1990

ESR analysis with long-chain alkyl spin labels in bovine blood platelets. Relationship between the increase in membrane fluidity by alcohols and phenolic compounds and their inhibitory effects on aggregation.

Four spin-labeled probes (5-doxylstearic acid (5-NS), its methyl ester (5-NMS), 16-doxylmethylstearate (16-NMS) and 4-(N,N-dimethyl-N-pentadecyl)ammonium-2,2,6,6-tetramethylpiperidine-1-ox yl (CAT-15)) were used to monitor membrane fluidity change in bovine platelets induced by three alkyl alcohols, benzyl alcohol and two phenolic compounds. The relationship between the increase in membrane fluidity induced by these compounds and their inhibitory effects on platelet aggregation was observed. Experiments with the four probes showed that n-hexyl alcohol induced decreases in the order parameter of 5-NS and apparent rotational correlation times of the other probes at the same minimal alcohol concentration. The decreases were observed in the concentration range that inhibited aggregation. n-Amyl alcohol and n-butyl alcohol decreased the values of the parameters of the above mentioned only at higher concentrations that were dependent on their hydrophobicities. Like alkyl alcohols, benzyl alcohol and phenolic compounds decreased the values of the parameters in the concentration ranges in which these compounds inhibited platelet aggregation. The concentration of these compounds causing 50% inhibition of platelet aggregation, the IC50 values, and data on 5-NS-labeled platelets indicated that they inhibited aggregation and decreased the value of the order parameter at lower concentrations relative to their Poct values in comparison to the effective concentrations of alcohols. Phenolic compounds also decreased the values of the apparent rotational correlation times of 5-NMS and 16-NMS. These results indicate that the inhibition of platelet aggregation by alcohols and phenolic compounds is due to membrane perturbation in wide range in depths within the lipid bilayer.

Alcohols↗
PubMed1990

Unusual hyperporphyrin spectrum by bis(glutathione dimethyl ester)-hemin complex, a model of cytochrome P-450-thiolate complexes.

A bis(thiolato) complex of iron-porphyrin exhibiting a "split Soret band" with peaks at 374 and 466 nm, classified as a "hyperporphyrin (HP) spectrum", was prepared with Fe(III)protoporphyrin dimethyl ester (FePPIXDME), glutathione dimethyl ester (GSHDME) and tetrabutylammonium hydroxide in acetone solvent. The structure of the complex was characterized by comparing their electronic absorption and electron spin resonance (ESR) spectra with those of thiolate adducts of cytochrome P-450 and their chemical model complexes. Under the same conditions as those for the formation of the HP spectrum, the generation of the free superoxide anions was detectable by ESR spectrometry at 77K. On the basis of the results, the possible reaction mechanism generating the superoxide anions by the bis(GSHDME)-FePPIXDME complex was proposed.

Animals↗
PubMed1990

[Serodiagnosis of scrub typhus by dot-blot method].

Microimmunofluorescence (IF) and immunoperoxidase tests are generally used for the serodiagnosis of scrub typhus. While these tests give satisfactory results in the hands of experienced personnel, they can be troublesome for inexperienced technicians. To develop a simpler diagnostic method, dot-blot assay was examined in this study. Six antigenically distinctive strains of Gilliam, Karp, Kato, Shimokoshi, Kawasaki and Kuroki of Rickettsia tsutsugamushi and a strain of Rickettsia sibirica were dotted on a nitrocellulose sheet by a dot-blot instrument. The sheets were treated with patient sera, followed by peroxidase-conjugated anti-human immunoglobulin-antibody and then with the substrate of the enzyme, and the color development on the dots was compared by naked eye observation. By this procedure, anti-rickettsial antibody-positive patient sera showed clear color development on at least one, usually several dots, while the very faint color was observed by the treatment with antibody-negative sera. On the other hand, it was ascertained that the antigens on nitrocellulose sheets were stable for at least 4 months at room temperature. Therefore the diagnostic kits were prepared, and the practical application of this procedure for diagnosis of scrub typhus were tested in Shizuoka and Miyazaki Prefectural Pabulic Health Laboratories. The results indicated a very good comparability between the dot-blot assay and IF-tests, and this dot-blot method was ascertained as a simple and useful method for the scrub typhus serodiagnosis.

Adolescent↗
PubMed1990

Characterization of a new antigenic type, Kuroki, of Rickettsia tsutsugamushi isolated from a patient in Japan.

The Kuroki strain of Rickettsia tsutsugamushi, isolated from a patient in Kyushu, Japan, has a major, type-specific antigenic polypeptide which is distinct from the prototype strains in size (58 kilodaltons), in antigenicity, and in its cleavage pattern with N-chlorosuccinimide. These results indicate that Kuroki is another antigenic type of R. tsutsugamushi.

Antigens, Bacterial↗
PubMed1990

Health risk assessed by temporal course of weight gain.

Health risks induced by the temporal course of weight gain were studied. Of 1,627 male company employees, 437 subjects were selected as follows. The criteria for eligibility were: 1) A subject must have undergone more than 20 health checkups. 2) The subject's weight gain since adolescence must have exceeded 7 kilograms. Four hundred and thirty-seven subjects were selected using these criteria. The average subject's age was 46.2 +/- 5.1 (Mean +/- S.D.) years. Subjects were classified into 3 groups according to the rate of weight gain. As a result, 167 were classified as the rapid weight-gain group (defined as a weight gain of more than 5 kilograms per 5 years), 212 were designated as the moderate weight-gain group (less than 5 kilograms per 5 years) and 58 were assigned to a miscellaneous group (temporal weight loss during the observation period). This miscellaneous group was excluded from further analysis. Comparison between the rapid and moderate weight-gain groups indicate that the prevalence of abnormal fasting blood glucose levels was significantly higher in the rapid weight-gain group than in the moderate group (p less than 0.01). The Mantel-Haenszel overall odds ratio adjusted for the current relative body weight for the abnormal fasting blood glucose level was 2.86 (95% C.I.: 1.35-6.06). To determine the factors related to the occurrence of abnormal fasting blood glucose levels, stepwise logistic regression was performed by selecting the rate of weight gain, age, weight gain amount and current relative body weight as independent variables. Age and rate of weight gain were shown to be significant variables in abnormal fasting blood glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Biological activity of obiopeptide-1, a synthetic peptide derived from the native immune-regulator obioactin.

Tachyzoites of Toxoplasma gondii were killed in mouse macrophage and human somatic cell monolayers by a novel synthetic peptide (Obiopeptide-1) which is a Glycil-penta-Glutaminate (GpG) derivative of native Obioactin. In view of the worldwide prevalence of this protozoan disease and the lack of effective treatments, Obiopeptide-1 may be a new and unique antimicrobial active substance of non-antibiotic chemotherapeutic agents for intracellular parasites, T. gondii and associated nonspecific hypoimmune responses that occur in infected hosts.

Adjuvants, Immunologic↗