Search PubMed⌕ Search

Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 667 records · Page 37Linked to original sources

Induction of methamphetamine-specific antibody using biodegradable carboxymethyl-chitin.

Induction of a specific antibody for methamphetamine, an antihypnotic drug, has been studied using carboxymethyl-chitin (CM-chitin) as a hapten carrier. The hapten-specific antiserum was induced by only a couple of hypodermal injections every 2 weeks. Inhibition of antigen-antibody complex formation was linearly related to methamphetamine concentration in the range 0.5 to 50 ng/50 microliter when an enzyme-linked immunosorbent assay was performed using an avidin-biotin-peroxidase complex. Little antibody directed against CM-chitin and CM-chitin oligomer was detected. Thus it seems to be advantageous in the hapten-bovine serum albumin system. The specificity of the antibody was high as shown by the use of various methamphetamine analogs.

Animals↗

Mutagenic metabolites in urine and feces of rats fed with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, a carcinogenic mutagen present in cooked meat.

To study the in vivo fate of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a carcinogenic mutagen present in cooked meat, rats were fed MeIQx in the diet and their urine and feces were analyzed for the metabolites. The isolation procedure included specific adsorption of MeIQx derivatives to blue cotton and subsequent fractionations by thin layer chromatography on silica gel and by high pressure liquid chromatography. Attention was focused on mutagenically active metabolites. Three metabolites were isolated from the urine, and their structures were elucidated on the basis of 1H nuclear magnetic resonance, ultraviolet, and mass spectra. The first metabolite characterized was 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxaline (Compound I), the second was 2-acetylamino-3,8-dimethylimidazo[4,5-f]quinoxaline (Compound II), and the third was 2-amino-8-methylimidazo[4,5-f]quinoxaline (Compound III). Compound I was isolated also from the feces. Compounds I-III were mutagenic to Salmonella typhimurium TA98 with metabolic activation. The mutagenic potency of Compounds I and II was as high as that of MeIQx, and that of Compound III was much lower than that of MeIQx.

Animals↗

Elevation of plasma levels of fluorinated pyrimidines by guanosine 5'-monophosphate.

The plasma concentration of 5-fluorouracil (FUra) following the i.v. administration of FUra and guanosine 5'-monophosphate (GMP) or guanosine 5'-triphosphate (GTP) was markedly elevated. These values were more than 5-fold higher than those obtained with FUra alone over 60 min after administration. The elevation of plasma levels corresponded to the dose of GMP. Higher levels of FUra were maintained in the plasma after injection of inosine or inosine 5'-monophosphate in combination with FUra than after FUra alone, but they were lower than those induced by GMP or GTP. Moreover, plasma levels of two other fluorinated pyrimidines, 5'-deoxy-5-fluorouridine (DFUR) and 5-fluoro-2'-deoxycytidine (FdCyd), were also elevated by GMP. The combination of DFUR and GMP resulted in higher plasma levels of DFUR itself and FUra (12- and 10-fold, respectively, 30 min after treatment). After administration of FdCyd plus GMP, the plasma levels of FdCyd, 5-fluoro-2'-deoxyuridine, which is converted from FdCyd by cytidine deaminase, and FUra were 2-, 6-, and 7-fold higher, respectively, than those after FdCyd alone 30 min after treatment. Thus, GMP is the most effective compound for the maintenance of high plasma levels of fluorinated pyrimidines.

Animals↗

Insulin Wakayama: familial mutant insulin syndrome in Japan.

We describe a family from Japan displaying the mutant insulin syndrome with hyperinsulinaemia and an increased insulin: C-peptide molar ratio. Serum insulin isolated from several family members showed reduced in vitro biological activity, and analysis by high performance liquid chromatography revealed a peak co-eluting with human insulin and a second species of increased hydrophobicity co-migrating with the previously reported Insulin Wakayama. The insulin genes from the propositus were cloned and sequenced, revealing one normal allele; the second allele, encoding a leucine for valine amino acid substitution at position 3 of the insulin A chain, was similar to that previously described for Insulin Wakayama. Synthesized [LeuA3] insulin showed 0.14% of receptor binding activity on rat adipocytes and a 10-fold prolonged half-life in a somatostatin-infused dog compared with human insulin. The finding of the same mutant gene in two unrelated Japanese families suggests that Insulin Wakayama may be discovered in additional Japanese families with hyperinsulinaemia and/or diabetes.

Adult↗

Magnetic resonance imaging: lumbosacral lipoma.

To evaluate the clinical efficacy of magnetic resonance imaging (MRI) of lumbosacral lipomas, the magnetic resonance images of nine patients were reviewed. T1- and T2-weighted spin echo sequences were used with a 0.5-T magnetic resonance system. The tethered or low-positioned conus medullaris, the lipoma itself, the lipoma--cord interface, the subarachnoid space, and hydromyelia were clearly disclosed. The nerve rootlets were not as clear. These results indicate the possible discontinuance of myelography and metrizamide computed tomography (CT) cisternography for such imaging. The diagnostic modalities of choice for lumbosacral lipoma imaging are plain spine films, plain CT scan, and MRI.

Adolescent↗

An ab initio molecular orbital study on the characteristics of 8-hydroxyguanine.

To investigate the mechanism by which the 8-hydroxyguanine residue in DNA affects the fidelity of DNA replication, the intrinsic properties of this modified base were investigated using an ab initio molecular orbital method. The most stable 8-hydroxyguanine form was revealed to be 6,8-diketo. The addition of an oxygen atom to the 8 position of a guanine base was shown to change the electrostatic potential of the molecule entirely and to give it a negative character. This effect may influence the local structure of 8-hydroxyguanine-containing DNA and the interaction with DNA polymerase, thereby resulting in infidelity of DNA replication.

Base Composition↗

Effect of multiporous microspheres derived from chitin and partially deacetylated chitin on the activation of mouse peritoneal macrophages.

Multiporous microspheres were prepared from 80% deacetylated chitin (DAC-80) and chitin, and their effects on the activation of murine peritoneal macrophages in vivo and on the production of monokines such as colony-stimulating factor (CSF) and interleukin 1 (IL-1) were examined. Multiporous DAC-80 microspheres of mean diameter 2.5 microns [MS-DAC-80(2.5)] enhanced the cytolytic activity of peritoneal macrophages and the production of CSF in vitro by macrophages, spleen cells and bone marrow cells, and in vivo. MS-DAC-80(2.5) also stimulated the production of IL-1 by both resident and thioglycolate-induced peritoneal macrophages. Multiporous chitin microspheres [MS-chitin(2.5)] showed no effect on the activation of peritoneal macrophages in vivo and on the production of IL-1 in vitro, but slightly enhanced the production of CSF in serum in vivo.

Acetylation↗

Mechanism of potentiation of antitumor activity of 5-fluorouracil by guanine ribonucleotides against adenocarcinoma 755.

The effect of various guanine ribonucleotides on the antitumor activity of 5-fluorouracil (FUra) was investigated by its action on adenocarcinoma 755. 5'-GDP and 5'-GMP were both equally effective in potentiating the antitumor activity of FUra without increasing toxicity. 5'-GTP and 5'-IMP also potentiated the activity but not as much as 5'-GMP. 2'-GMP and 3'-GMP did not enhance the antitumor activity. In contrast, cGMP antagonized the effects of FUra. The incorporation of 3H-labeled FUra into RNA or DNA showed there was no obvious association between the incorporation and antitumor activity after any treatment with guanine ribonucleotides. The combination of FUra and 5'-GMP produced the greatest inhibition of RNA synthesis. The combination of FUra and 2'-GMP had no effect on RNA synthesis. The inhibition of RNA synthesis may be the result of decreased pyrimidine pool size and increased incorporation of FUra into RNA. Potentiation of the antitumor activity of FUra by 5'-GMP was reversed by the injection of cytidine. Moreover, the combination of 5-fluorocytidine (FCyd) and 5'-GMP showed greater antitumor activity than FCyd alone. These results indicate that a decreased CTP pool potentiates the antitumor activity of FUra. Thus, 5'-GMP or 5'-GDP strongly enhanced the antitumor activity of FUra, and the potentiation resulted from the inhibition of RNA synthesis caused by reduction of the CTP and UTP pool sizes and increased incorporation of FUra into RNA.

Adenocarcinoma↗

Natural UAG suppressor glutamine tRNA is elevated in mouse cells infected with Moloney murine leukemia virus.

Two species of glutamine tRNA were isolated from mouse liver and their nucleotide sequences were determined. The minor glutamine tRNA(tRNA(UmUGGln)) that possesses UmUG (where Um stands for 2'-O-methyluridine) as the anticodon sequence was found to have suppressor activity for the UAG termination codon of tobacco mosaic virus RNA in a rabbit reticulocyte in vitro translation system. The amount of this suppressor glutamine tRNA in mouse liver was 1-2% of the amount of the major glutamine tRNA(tRNA(CUGGln)) that has the CUG anticodon sequence, but it was markedly increased in NIH 3T3 cells infected with Moloney murine leukemia virus and in Ehrlich ascites cells. These results support the hypothesis that tRNA(UmUGGln) actually functions in vivo as a suppressor tRNA that recognizes the UAG termination codon located at the gag-pol gene junction of Moloney murine leukemia virus and results in the synthesis of the virus-encoded protease.

Animals↗

Oral administration of the renal carcinogen, potassium bromate, specifically produces 8-hydroxydeoxyguanosine in rat target organ DNA.

Following oral administration of a renal carcinogen, potassium bromate (KBrO3), to the rat, a significant increase of 8-hydroxydeoxyguanosine (8-OH-dG) in kidney DNA was observed. In the liver, a non-target tissue, the increase in 8-OH-dG was not significant. The non carcinogenic oxidants, NaCIO and NaCIO2, had no effect on 8-OH-dG formation in kidney DNA. These results suggest that formation of 8-OH-dG in tissue DNA is closely related to KBrO3 carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

The Escherichia coli dnaJ mutation affects biosynthesis of specific proteins, including those of the lac operon.

Temperature-sensitive dnaJ mutants of Escherichia coli showed a thermosensitive defect in the synthesis of beta-galactosidase. Synthesis of the lac mRNA was greatly reduced at the restrictive temperature. The mutants were also conditionally defective in the synthesis of a subset of membrane proteins such as succinate dehydrogenase, whereas the synthesis of anthranilate synthetase, encoded by trpED, as well as that of most cellular proteins, was unaffected at the restrictive temperature. The defect was specific for the dnaJ mutants among several dna mutants which are known to be involved in the initiation of DNA synthesis: dnaK, dnaA, and dnaB mutants synthesized each of these proteins normally even at the restrictive temperature. At the restrictive temperature, growth of the dnaJ mutants was arrested at a specific stage of the cell cycle.

Anthranilate Synthase↗

Prognostic significance of the electrically elicited blink reflex in neonates.

The electrically elicited blink reflex was examined in ten normal neonates, 11 postasphyxial neonates, and 3 congenital hydrocephalus cases. The blink reflex was elicited in all cases. In normal neonates, the latencies and amplitudes were 10.9 +/- 0.7 msec and 159 +/- 62 microV at R1, 34.3 +/- 1.4 msec and 123 +/- 30 microV at R2, and 40.7 +/- 2.3 msec and 84 +/- 25 microV at R'2 respectively. Ischemic-hypoxic brain damage during the neonatal period mainly influenced the late components of the blink reflex. The blink reflex of the postasphyxial neonates showed significantly prolonged latencies of R2 and R'2. The amplitudes were increased in cases with a fair prognosis and decreased in cases with a poor prognosis. A case of congenital hydrocephalus with mental retardation also showed the prolonged latencies of R2 and R'2 in neonatal period. The blink reflex in neonates appears to be useful in predicting the outcome in cases of neonatal asphyxia and congenital hydrocephalus.

Asphyxia Neonatorum↗

[Effect of platonin on bone wound healing in rat calvaria--with special reference to the interaction of platonin and steroid hormones].

Interaction of Platonin (PI) and dexamethasone (DM) or testosterone propionate (TP) on bone wound healing was studied by measuring the areas of wound holes which were made in the rat parietal bone. The result was compared with that of the growth of the femur. 1) No significant difference was observed between the control group and pl groups (1, 10 and 100 micrograms/kg, s.c., for 4 weeks) on the wound hole area or the length, weight, calcium content (Ca) or hydroxyproline content (HP) in the femur. 2) The bone wound healing was delayed by DM (2 mg/kg, s.c., for the first 2 weeks). The inhibition of growth was also observed in the femur length and weight, but no significant effect of DM was observed in the Ca and HP of the femur. The combination of Pl and DM promoted the recovery from delayed bone wound healing and femur weight gain caused by DM. 3) No significant effects of TP (4 mg/kg, s.c., for the first 2 weeks) were observed on the wound healing and the femur growth, but an increase of the femur weight and Ca was observed by the combination of Pl and TP. These results indicate that Pl promotes the recovery from delayed bone wound healing and femur weight gain by DM, although no significant effects were observed in bone growth and bone wound healing by the administration of Pl alone. It is also suggested that a combination of Pl and TP promotes bone growth and mineralization.

Animals↗