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Biomedical subjects

H Uchida

Publications and source records attributed to H Uchida.

At least 541 records · Page 30Linked to original sources
PubMed1986

High-performance liquid chromatographic determination of 6,8-difluoro-1-(2-fluoroethyl)-1,4- dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid and its metabolites in laboratory animals.

A simple, sensitive and specific high-performance liquid chromatographic method for a new quinolone antimicrobial agent, 6,8-difluoro-1-(2-fluoroethyl)-1,4- dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid (AM-833, I), and its metabolites in serum and urine has been developed for their simultaneous determination. This method is based on ion-pair extraction and separation by ion-pair reversed-phase chromatography with ultraviolet or fluorescence detection. The major metabolites in the serum and urine of mice, rats, dogs and monkeys were N-desmethyl I (compound II) and I N-oxide (compound III). Rabbit serum and urine contained N-desmethyl-3-oxo I (compound IV), 3-oxo I (compound V) and N-desmethyl-4-formyl I (compound VI) in addition to compounds I, II and III. Unchanged drug accounted for 80-90% of total serum concentrations in mice and more than 90% in rats, dogs and monkeys up to 6 h after dosing, whereas the fraction of compound I in rabbits was 34-67%. Unchanged drug was the most predominant in the urine of mice, rats, dogs and monkeys, whereas compound II was the most abundant in rabbit urine. Although rabbits and monkeys excreted 70-80% of dose in three-day urine, the total urinary excretion of mice, rats and dogs was relatively low, 40-50% of oral dose. The fraction of compound I in total urinary excretion was 63, 73, 27, 55 and 78% in mice, rats, rabbits, dogs and monkeys, respectively. These results suggest that there is a species difference in the metabolism and excretion pathway of compound I.

Animals↗
PubMed1986

Nucleotide sequence of the Escherichia coli dnaJ gene and purification of the gene product.

The dnaJ and dnaK genes are essential for replication of Escherichia coli DNA, and they constitute an operon, dnaJ being downstream from dnaK. The amount of the dnaJ protein in E. coli is substantially less than that of the dnaK protein, which is produced abundantly. In order to construct a system that over-produces the dnaJ protein, we started our study by determining the DNA sequence of the entire dnaJ gene, and an operon fusion was constructed by inserting the gene downstream of the lambda PL promoter of an expression vector plasmid, pPL-lambda. Cells containing the recombinant plasmid produced dnaJ protein amounting to 2% of the total cellular protein when cells were induced. The overproduced protein was purified, and Edman degradation of the protein indicated that the NH2-terminal methionine was found to be processed. From the DNA sequence of the dnaJ gene, the processed gene product is composed of 375 amino acid residues, and its molecular weight is calculated to be 40,975.

Amino Acid Sequence↗
PubMed1986

Action of thyrotropin-releasing hormone (TRH) on the occurrence of fibrillation potentials and miniature end-plate potentials (MEPPs). An experimental study.

The effect of TRH on fibrillation potentials and MEPPs were studied to determine the sites of action of TRH on muscle weakness. Intravenous administration of 10(-4) U thyroid-stimulating hormone (TSH) did not change the fibrillation-frequency of the denervated muscles of rats, but subsequent intravenous administration of 1 mg TRH did. Drip application of 0.6 mg TRH directly onto the denuded denervated muscles of rats did not cause an increase in fibrillation. Application of 1 mg TRH to the rat diaphragm increased the frequency of MEPPs. Both the increase in frequency of fibrillation potentials and the increase in frequency of MEPPs by application of TRH suggest that TRH influences nerve terminals, and that TRH seems suitable for treatment of muscle weakness in patients with ALS.

Animals↗
PubMed1986

Macrophage-mediated acute-phase transport protein production induced by lentinan.

A new bioactive factor capable of stimulating the production of acute-phase transport proteins, haptoglobin, hemopexin and ceruloplasmin, was found in mouse serum soon after the administration of lentinan, an immunomodulatory polysaccharide. This factor (APPIF) was produced by macrophages, and may regulate the production of acute-phase transport proteins in hepatocytes. The mice given the serum obtained from donor mice 2-6 h after an injection of 10 mg/kg of lentinan showed a marked increase of the acute-phase transport proteins in their serum 4 days after the serum injection. Pretreatment with the antimacrophage agents, carrageenan and mouse Ia antiserum, before the lentinan treatment to donor mice inhibited the production of acute-phase transport proteins in the recipient mice. Thymus or T-cells had no role in the production of APPIF. As the activity of APPIF disappeared after pronase treatment of the serum, APPIF seems to be a peptide compound. Appearance of APPIF is considered to be one of the earliest manifestations of the mode of action of lentinan in addition to its augmented production of vascular dilatation and hemorrhage inducing factor and interleukin-1. The correlation between these inflammatory and immune responses in earlier stages of the host defence mechanisms is also discussed.

Acute-Phase Proteins↗
PubMed1986

Vascular changes associated with growth of primary and transplantable pancreatic adenocarcinomas induced in Syrian golden hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP).

Microangiographic and histological methods were used to characterize vascular structure of primary and transplantable pancreatic adenocarcinomas induced by propylnitrosamines in Syrian golden hamsters. Originally of well-differentiated tubular morphology, serial transplantation subcutaneously to the back region was not associated with change in histopathological pattern or increase in invasive or metastatic potential. In contrast, pancreatic subserosal grafts displayed prominent invasion of surrounding tissues. Whereas primary tumors induced by N-nitrosobis(2-oxopropyl)amine (BOP) and those transplanted subserosally were characterized by hypovascularity, subcutaneous transplantation resulted in hypervascular tumors. Encasement, which is defined as invasion of normal arteries by the tumor, showing uneven caliber, irregular outline, appeared on earlier microangiographic findings rather than luminal irregularity, which is change of tumor vessels in neovascularization and occurs in tumor blood vessels subsequent to transplantation. The vascular component of subcutaneously transplanted tumors had a total vessel length ranging from 9.2 +/- 0.7 mm to 18.1 +/- 1.1 mm, a total vessel surface from 2.5 +/- 0.4 mm2 to 9.3 +/- 0.6 mm2 and a total vessel volume from 0.07 +/- 0.02 mm3 to 0.49 +/- 0.04 mm3, indicating that the vessels were of relatively large diameter and short length.

Adenocarcinoma↗
PubMed1986

Pharmacokinetics of a new quinolone, AM-833, in mice, rats, rabbits, dogs, and monkeys.

The pharmacokinetics of AM-833 [6,8-difluoro-1-(2-fluoroethyl)-1, 4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid] were studied in mice, rats, rabbits, dogs, and monkeys by reversed-phase high-performance liquid chromatography. AM-833 was rapidly and completely absorbed from the digestive tracts of mice, rats, and dogs. About half of AM-833 bound to rat and dog serum proteins. Drug levels in lung, spleen, liver, and kidney tissues of rats and dogs were greater than the respective levels in serum but lower in brain tissue. Drug levels in tissues declined with the decrease in levels in serum. AM-833 penetrated rapidly and well into inflammatory exudate of rats. Elimination half-lives in serum were species dependent, ranging from 1.57 h in rabbits to 9.42 h in dogs. Profiles of drug levels in serum were dose related over a single dose range from 2 to 40 mg/kg and not modified significantly during multiple dosing in dogs. Unchanged AM-833 was excreted in urine and bile in both rats and dogs. The metabolism of AM-833 was suggested by evidence that 24-h total recovery of unchanged AM-833 in urine and bile accounted for about half of the intravenous dose in rats.

Animals↗
PubMed1986

RNase H and replication of ColE1 DNA in Escherichia coli.

Amber mutations within the rnh (RNase H) gene of Escherichia coli K-12 were isolated by selecting for bacteria capable of replicating in a sup+ background replication-defective cer-6 mutant of the ColE1 replicon. The cer-6 mutation is an alteration of one base pair located 160 nucleotides upstream of the unique replication origin of this plasmid. Subsequently, we determined the DNA alterations present within these mutants. ColE1 DNA replicated in rnh(Am) recA cells, indicating that (i) RNase H, which has been shown to be absolutely required for in vitro initiation of ColE1 DNA replication, is dispensable in vivo, and (ii) ColE1 replication in the absence of RNase H is not dependent on "stable DNA replication," which has been reported to be an alternative mode of chromosomal DNA replication. Another class of bacterial mutations was also isolated. These mutations, named herB, suppressed cer-6 replication in rnh+ bacteria. herB mutations mapped close to the polA gene on the E. coli chromosome and increased the activity of DNA polymerase I. These findings suggest that when the DNA polymerase I has an opportunity to initiate DNA synthesis before RNase H acts, the replication-defective cer-6 mutant or the wild-type ColE1 replicates in E. coli.

DNA Polymerase I↗
PubMed1986

Pulmonary asbestosis: CT study of subpleural curvilinear shadow. Work in progress.

High-resolution computed tomographic scans of 19 patients with pulmonary asbestosis revealed a subpleural curvilinear shadow (SCLS) parallel to the inner chest wall in the lungs of 15 (78.9%) patients. Most (46.7%) SCLS measured greater than 5 cm but less than 10 cm in length and occurred less than 1 cm from the inner chest wall in all cases. SCLS was distributed mainly in the lower lobe in patients with mild pulmonary fibrosis and in segments where fibrosis was mild in patients with honeycomb shadows. This may reflect initiation of pulmonary fibrosis leading to the formation of a honeycomb shadow. Radiologic-pathologic correlation, achieved in one postmortem specimen, seemed to indicate that SCLS was associated with the initial change of fibrosing bronchioloalveolitis, which is characteristic of pulmonary asbestosis.

Asbestosis↗
PubMed1986

Spontaneous hepatocellular carcinomas in lungfish.

Liver tumors were observed in 2 South American lungfish (Lepidosiren paradoxa) and in 1 African lungfish (Protopterus amphibius) kept in 3 different aquariums in Japan for 2-5 years. In the first case a single, large nodule (70 X 60 X 55 mm) in the liver had been noted externally as a swelling 1 year prior to death. In the second case 2 rounded nodules (25 X 15 X 15 mm and 15 X 10 X 10 mm) were incidentally found at autopsy. In the third case, which also demonstrated abdominal swelling for 1 year preceding death, 2 green nodules (50 X 50 X 40 mm and 17 X 17 X 17 mm) were found in the liver together with multiple metastatic lesions. Histologically, variation was evident from tumor to tumor, even within the same animal. The most common histologic type was typical trabecular hepatomas. Admixtures of glandular or papillary structures were noted in some tumors. A region of poorly differentiated hepatocellular carcinoma with spindle-shaped cells in a sheetlike arrangement was noted in one case. The cause of these tumors is unknown. Since liver tumors were discovered at relatively high incidence (3/14 autopsied cases, including 6 species), lungfish seem to be predisposed to the development of liver tumors.

Animals↗