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Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 397 records · Page 22Linked to original sources

Analgesic component of Notopterygium incisum Ting.

Notopterol was identified as the analgesic component of Notopterygium incisum TING by using the acetic acid-induced writhing method. Notopterol also indicated an anti-inflammatory activity by its inhibitory effect in the vascular permeability test. The intensive prolongation of pentobarbital-induced hypnosis was possibly caused by its inhibitory effect on the drug metabolism in liver. Pharmacological differences between the analgesic components of N. incisum, Aralia cordata and Angelica pubescens were also discussed.

Animals↗

Effect of rebamipide on lipid peroxidation and gastric mucosal injury induced by indometacin in rats.

The protective effect of rebamipide (CAS 11911-87-6), a novel anti-ulcer agent, was investigated in rats with hemorrhagic erosions on the glandular stomach induced by intragastric administration of 25 mg/kg of indometacin. Pretreatment with 100 mg/kg of rebamipide significantly inhibited the increase in total area of erosions in the stomach and the increase in lipid peroxides in the gastric mucosa. Rebamipide also inhibited the in vitro increase of lipid peroxides in the gastric mucosal homogenates induced by free radical initiators. These results indicate that rebamipide's protective effect against indometacin-induced gastric mucosal injury may result, in part, from its antioxidant effect, which inhibits lipid peroxidation.

Alanine↗

[Pharmacokinetic, bacteriological and clinical studies on S-1108 in children].

Pharmacokinetic, bacteriological and clinical studies on S-1108 were performed in children. The results were as follows: 1. A total of 11 patients were treated with S-1108. Each dose was 3 mg/kg, orally administered 3 times daily for 4-14 days. The clinical efficacies of S-1108 in 10 patients with bacterial infections (1 with bacteremia, 4 with pneumonia, 1 with acute maxillary sinusitis, 1 with scarlet fever and 2 with streptococcal pharyngitis) were evaluated as excellent in 8 patients and as good in 2 patients with an efficacy rate of 100%. Only one patient with staphylococcal scalded skin syndrome due to methicillin resistant Staphylococcus aureus (MRSA) who received gamma-globulin was not evaluated. Fourteen causative strains of 5 species were found in 10 patients. Three strains of Streptococcus pneumoniae out of 5, 2 of 3 Branhamella catarrhalis strains, none of Staphylococcus aureus and all 3 strains of Streptococcus pyogenes were eradicated. No adverse reaction was observed in any of the 11 patients. 2. MICs of S-1108 against 5 clinically isolated S. pneumoniae from cases of infections were examined. All of them were relatively highly resistant to penicillins. S-1108 was compared with cefteram pivoxil, cefpodoxime proxetil, cefaclor and cefixime, and it showed better antibacterial activity or than other cephems. 3. Double peaks were obtained in plasma levels of S-1108 orally administered at a dose of 3 mg/kg at 30 minutes after meal and were 1.03 microgram/ml and 0.74 microgram/ml at 1 and 4 hours after administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

[Anesthesia for pneumonectomy in a patient with an amphetamine psychosis].

We report a 50 year old male patient with an amphetamine psychosis who had anesthesia for a pneumonectomy. The patient had been intoxicated with methylamphetamine since 1976. After drug abuse for 2 years, he suffered from hallucination and delusion. He was diagnosed to have amphetamine psychosis by psychiatrists and treated with major tranquilizers. During the treatment for the psychosis, a squamous cell carcinoma in the lung was found. Pneumonectomy was scheduled. Anesthesia was induced with thiopental 300 mg and maintained with isoflurane, nitrous oxide, oxygen and epidural lidocaine. In the recovery room, he was injected with a major tranquilizer. Epidural buprenorphine was used to lighten the pain stress. Psychotic state did not appear after the surgery. We also discuss amphetamine psychosis in Japan.

Amphetamine↗

[Pharmacokinetic, bacteriological and clinical studies on cefditoren pivoxil in children].

Pharmacokinetic, bacteriological and clinical studies on cefditoren pivoxil (CDTR-PI, ME 1207) were performed in children. The results were as follows: 1. A total of 18 patients (19 infections) were treated with CDTR-PI. The doses ranged 2.1-3.2 mg/kg, and it was orally administered 3 times daily, for 4-10 days. Clinical efficacies of CDTR-PI in 18 patients with 19 bacterial infections (3 with tonsillitis, 1 with bronchitis, 7 with pneumonia, 1 with acute maxillary sinusitis, 4 with otitis media, 1 with urinary tract infection, 2 with skin and soft tissue infection) were evaluated as excellent in 13 infections and as good in 6 infections with an efficacy rate of 100%. Twelve causative strains of 5 species were found in 11 patients. Streptococcus pneumoniae in 2 cases out of 3, Haemophilus influenzae in 4/4, Staphylococcus aureus in 2/2, Haemophilus parainfluenzae in 2/2 and Escherichia coli in 1/1 were eradicated. Two patients had mild diarrhea but did not need specific treatment. Severe adverse reaction was not observed in any of the 18 patients. 2. MICs of CDTR were examined against 4 clinically isolated S. pneumoniae strains. Two strains of S. pneumoniae were relatively resistant to penicillins. 3. Pharmacokinetic studies Peak serum CDTR concentrations in 3 patients were 2.38 micrograms/ml, 0.72 micrograms/ml and 2.25 micrograms/ml at a dose of CDTR-PI 3 mg/kg orally administered at 30-minute after meal.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Modulation of epidermal growth factor receptor activity and related responses by the 7-deazaguanine derivative, queuine.

Epidermal growth factor (EGF) induces autophosphorylation of its cognate receptor at tyrosine residues. Here we show that queuine (q), a widely distributed modified guanine analogue occurring free or as a tRNA wobble base, modulates this EGF receptor activity in vitro and in intact cells. Autophosphorylation of the immunopurified receptor from human A431 epidermoid carcinoma cells was enhanced three to fourfold in the presence of physiological concentrations of q. Using a membrane fraction of A431 cells, a twofold increase in autophosphorylation activity in the presence of q was observed, however, only when the receptor was activated by the ligand. In intact A431 cells, q enhanced the initial ligand-induced autophosphorylation of the EGF receptor three to fourfold. However, upon longer treatment of the cells with EGF in the presence of q, significantly less autophosphorylated receptor was detectable compared with stimulation of cells in the absence of q. A similar q-dependent modulation of EGF receptor autophosphorylation was observed also in human cervical carcinoma cells HeLa-S3. Treatment of q-deficient HeLa cells with EGF induced the c-fos gene expression, transiently increased the activity of the anoxic stress protein LDH k, and stimulated proliferation. Treatment of HeLa cells with EGF in the presence of q resulted in a delayed c-fos gene expression and an accelerated increase and decrease of LDH k activity. The stimulatory effect of low doses of EGF on HeLa cell proliferation was completely antagonized in the presence of q. The results suggest that the mitogenic signalling initiated by the EGF receptor is modulated by q.

Cell Line↗

Amplification of c-MYC oncogene and point mutation of N-RAS oncogene point mutation in acute myelocytic leukemias with double minute chromosomes.

Two patients with acute myelocytic leukemia (AML) showing double minute (dmin) chromosomes were analysed to identify oncogene activation. Cytogenetic analysis showed 1-53 dmin chromosomes with the normal karyotype in the first patient and 1-84 dmin chromosomes with complex chromosome aberrations. Analysis of DNA from two patients revealed five- to tenfold amplification of c-MYC oncogene in the leukemic cells. The other sixteen oncogenes studied showed no increase in the gene content. Furthermore, a transforming gene, N-RAS was detected in the first patient by nude mouse tumorigenicity assay (in vivo selection assay). These results suggest that the amplification of c-MYC gene is common in dmin-positive AML patients and co-ordination of c-MYC and N-RAS oncogene might also play a significant role in the pathogenesis of some AML patients.

Aged↗

A nickel-binding serpin, pNiXa, induces maturation of Xenopus oocytes and shows synergism with oncogenic ras-p21 protein.

A nickel-binding serine proteinase inhibitor, pNiXa (43 kDa), was isolated from Xenopus ovary and assayed for effects on oocyte maturation. Microinjection of pNiXa (0.12 pmol/50 nl) induced maturation in 60% of Xenopus oocytes, beginning at 4 hours and reaching completion by 9 hours. Microinjection of oncogenic ras-p21 protein (0.12 pmol/50 nl) induced maturation in 79% of oocytes, beginning at 6 hours and reaching completion by 12 hours. Microinjection of pNiXa in combination with ras-p21 protein had a synergistic effect on maturation, which occurred in 92% of oocytes, beginning at 4 hours and reaching completion by 9 hours. Oocyte maturation did not occur in control oocytes, which received a microinjection of bovine serum albumin. In oocytes exposed to a combination of pNiXa (0.12 pmol/50 nl, by microinjection) and progesterone (10 micrograms/ml, in the medium), maturation was intermediate (68% at 9 hours) between that induced by pNiXa (60%) or progesterone (85%) alone. This study shows (a) that pNiXa is a potent inducer of oocyte maturation, (b) that pNiXa's effect is synergistic with that of oncogenic ras-p21 protein, and (c) that pNiXa partially antagonizes progesterone induction of oocyte maturation.

Animals↗

[Relationship of in- and outpatient medical expenditure for the elderly to socioeconomics, medical services, and health and welfare projects].

In order to clarify what factors are associated with per capita medical care expenditure for those aged 65 years and over, for inpatients and outpatients respectively, correlation analyses were performed using several indices of medical services, socioeconomics, medical supply, health and welfare projects for fiscal 1989 among 99 administrative areas in Gifu Prefecture. The expense for inpatients was correlated with the service-acceptance rate, while on the other hand the expense for outpatients was correlated with average cost of medical receipts. Two major factors were number of physicians per person aged 65 years and over and per capita income. For outpatients, population density and per capita amount of subsidy for "elderly welfare projects" were significantly correlated with medical expenditure, with the latter showing a negative correlation. Multiple regression analyses indicated that these factors were independently correlated with the expenses. These findings indicate that expenses for inpatients and outpatients have different construction, with each being associated with different factors.

Aged↗

Modulation of C2 and C3 gene expression of human peripheral blood monocytes by interleukin 1 beta, interferon gamma, tumor necrosis factor alpha and lipopolysaccharide.

The effect of interleukin 1 beta (IL-1 beta), interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF alpha) and lipopolysaccharide (LPS) on the expression of the C2 and C3 genes in human adherent monocytes was studied. Stimulation of monocytes with IFN-gamma increased both C2 and C3 mRNA. IL-1 beta also increased C2 mRNA level, whereas C3 gene expression was not enhanced. TNF alpha failed to increase either C2 or C3 mRNA. LPS increased C2 mRNA, but suppressed C3 gene expression. These results suggest that C2 and C3 production by monocytes is regulated by IL-1 beta and IFN-gamma in the local tissues.

Complement C2↗

Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II.

The central region of the N-myc protein has a characteristic amino acid sequence EDTLSDSDDEDD, which is very similar to those of particular domains of adenovirus E1A, human papilloma virus E7, Simian virus 40 large T, c-myc and L-myc proteins. Domains of these three viral oncoproteins have recently been shown to be specific binding sites for the tumor-suppressor gene retinoblastoma protein. We have noted that the sequence of serine followed by a cluster of acidic amino acids is exactly the same as that of a typical substrate of casein kinase II (CKII). Therefore, we investigated whether these nuclear oncoproteins are phosphorylated by CKII. For this purpose, we fused the beta-galactosidase and N-myc genes including this domain and expressed it in Escherichia coli cells. Several mutant N-myc genes, containing single amino acid substitutions in this domain, were also used to produce fused proteins. Strong phosphorylation by CKII was detected with the fused protein of wild-type N-myc. However, no phosphorylation of beta-galactosidase itself was observed and the phosphorylations of fused mutant proteins were low. Another fused N-myc protein containing most of the C-terminal region downstream of this acidic region was not phosphorylated by CKII. Analysis of phosphorylation sites in synthetic peptides of this acidic region identified the major sites phosphorylated by CKII as Ser261 and Ser263. On two-dimensional tryptic mapping of phosphorylated N-myc proteins, major spots of in vitro-labeled and in-vivo-labeled N-myc proteins were detected in the same positions. These results suggest that two serine residues of the acidic central region of the N-myc protein are phosphorylated by CKII in vivo as well as in vitro. The functional significance of this acidic domain is discussed.

Amino Acid Sequence↗

DNA strand cleavage at 8-hydroxyguanine residues by hot piperidine treatment.

The two findings indicate that 8-hydroxyguanine(8-OH-Gua) is a hot piperidine-sensitive lesion in DNA. These are cleavages of DNA containing 8-OH-Gua at the site of this residue and decomposition of 8-hydroxydeoxyguanosine when the DNA and nucleoside were treated in 1 M piperidine for 30 min at 90 degrees C. However, no cleavage was observed in DNA containing 8-hydroxyadenine or O6-methylguanine. 8-OH-Gua was found to be different from apurinic sites that are also alkali-labile lesions since the former was more resistant to alkali treatment. This property of 8-OH-Gua can be used as a check for the incorporation of this base into DNA after the synthesis of DNA containing 8-OH-Gua at a specific position or possibly can be one of the markers for the identification of 8-OH-Gua formed in DNA exposed to reactive oxygen species.

Base Sequence↗

Deficiency of 8-hydroxyguanine DNA endonuclease activity and accumulation of the 8-hydroxyguanine in mutator mutant (mutM) of Escherichia coli.

In this report, we have characterized mutM mutant with respect to its ability to repair 8-hydroxyguanine (oh8Gua) in DNA. The oh8Gua DNA endonuclease activity in mutM strain was minimal as compared with that in the wild-type cells. The presence of oh8Gua in DNA of mutM was 6-fold that of the wild-type strain corresponding to a characteristically higher frequency of G.C-->T.A transversions in this mutant strain. These results suggest that mutator phenotype of mutM is at least partially due to a spontaneous accumulation of oh8Gua resulting from a greatly reduced oh8Gua DNA endonuclease activity.

Base Sequence↗

Photosensitized formation of 8-hydroxydeoxyguanosine in cellular DNA by riboflavin.

Photosensitized formation of 8-hydroxydeoxyguanosine (oh8dG) in DNA by riboflavin has recently been shown in vitro. The present study describes the formation of oh8dG in cellular DNA by photo-irradiation of cultured mammalian cells in the presence of riboflavin. Formation of oh8dG was dependent on the concentration of riboflavin as well as the duration of photoirradiation. These results suggest that photosensitized formation of oh8dG in DNA by riboflavin may be involved in photocarcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

Cyclic AMP-dependent phosphorylation and regulation of the cardiac dihydropyridine-sensitive Ca channel.

A polyclonal antibody, CR2, prepared using the C-terminal peptide of the alpha 1 subunit of the rabbit cardiac DHP-sensitive Ca channel, specifically immunoprecipitated the [3H]PN200-110-labeled Ca channel solubilized from cardiac microsomes. The antibody recognized 250 and 200-kDa cardiac microsomal proteins as determined by immunoblotting, and cAMP-dependent protein kinase phosphorylated the 250-kDa, but not the 200-kDa protein in vitro. CHO cells, transfected with the cardiac alpha 1 subunit cDNA carried by an expression vector, synthesized a 250-kDa protein which was recognized by CR2. Adding db-cAMP or forskolin to the transformed CHO cells induced phosphorylation of the 250-kDa protein and stimulated the DHP-sensitive Ba current under patch-clamp conditions. These results suggested that the cardiac DHP-sensitive Ca channel was regulated by cAMP-dependent phosphorylation of the alpha 1 subunit.

Animals↗