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T Nishigaki

Publications and source records attributed to T Nishigaki.

At least 73 records · Page 4Linked to original sources
PubMed1990

Localization of the anti-allergic agent tranilast in the urinary bladder of rats as demonstrated by light microscopic radioautography.

Tranilast (N-(3,4-dimethoxycinnamoyl)anthranilic acid), an anti-allergic drug, has been developed and used for the treatment of anaphylactic hypersensitivity such as bronchial asthma in Japan. Recently, many cases with eosinophilic cystitis associated with administration of this drug have been reported. In a series of studies to elucidate the pathoetiology of this unusual cystitis, the distribution of tranilast in urinary bladder of rats was investigated. Light microscopic radioautography using tritiated tranilast showed that this drug was localized specifically in the transitional epithelial cells of the mucosa and the endothelial cells of venous vessels for a fairly long time after an oral administration. These results should be taken into consideration in further studies of this drug-associated cystitis.

Animals↗
PubMed1989

Species differences in the effects of bezafibrate, a hypolipidemic agent, on hepatic peroxisome-associated enzymes.

The effects of bezafibrate on hepatic peroxisome-associated enzymes of rats, mice, guinea pigs, hamsters, rabbits, dogs and monkeys were examined. Dogs and monkeys were given bezafibrate orally at 30 mg/kg body wt daily for 2 weeks and at 125 mg/kg body wt daily for 13 weeks, respectively, and other species at 100 mg/kg daily for 2 weeks. In male rats, marked changes were observed in the activities of catalase (1.73-fold), D-amino acid oxidase (DAAO; 0.56-fold), fatty acyl-CoA oxidizing system (FAOS; 12.9-fold) and carnitine acetyltransferase (CAT; 35.8-fold); in female rats, the changes were less than in the males. In mice, there were no apparent sex differences in the responses of hepatic peroxisomal enzymes to bezafibrate and the increases in the activities of catalase, FAOS and CAT were 1.76-, 3.75- and 7.94-fold respectively. In guinea pigs, only slight increases in the activities of FAOS (3.00-fold) and CAT (2.83-fold) were observed. In hamsters, the increases in catalase, FAOS and CAT activities, were 1.23-, 2.19- and 2.77-fold respectively. Although rabbits and dogs showed slight increases in CAT activity, no significant response to the drug was observed in monkeys. Hepatomegaly and the increase of hepatic content of peroxisome proliferation-associated polypeptide (PPA-80), which has been recognized as a peroxisomal bifunctional protein in the fatty acid beta-oxidation pathway, were observed only in rats and mice. These results show that there were marked species differences in the effects of bezafibrate on hepatic peroxisomes, and that bezafibrate induced hepatic peroxisome proliferation in rodents, especially rats and mice.

Animals↗
PubMed1989

Intravenous flunitrazepam for status epilepticus.

Flunitrazepam (FZP) was administered intravenously, with success, to two patients with status epilepticus. Case 1 was a patient with a tonic-clonic status epilepticus. Intravenous phenytoin had no effect. Case 2 had minor status epilepticus. With the intravenous administration of FZP, diluted 1:10 with distilled water at a dose of 0.03 mg/kg at a slow rate, both patients were relieved of the status epilepticus. Unlike diazepam, FZP neither looks cloudy when diluted with distilled water nor causes angialgia. No disturbances in circulation or respiration occurred. Considering that FZP has a strong anticonvulsant action on status epilepticus, it can be expected to be a useful therapeutic agent for status epilepticus in infants and children.

Child↗
PubMed1988

Tumor markers in pleural effusion diagnosis.

In order to discriminate between malignant and benign effusions, the values of carcinoembryonic antigen (CEA), ferritin, beta2-microglobulin (BMG), acid-soluble glycoprotein (ASP), tissue polypeptide antigen (TPA), adenosine deaminase (ADA), and immunosuppressive acidic protein (IAP) were measured in the pleural fluid of 54 patients with lung cancer, 20 with malignancies other than lung cancer, 18 with tuberculous pleurisy, and 22 with benign diseases other than tuberculosis. CEA levels in malignant effusions were significantly higher than those in benign effusions. At a cutoff level of 5 ng/ml, 68% of the patients with lung cancer and 44% of the patients with other malignancies showed elevated pleural fluid CEA levels. In 13 lung cancer cases with negative pleural fluid cytology, nine cases had elevated pleural fluid CEA levels. The mean pleural fluid BMG level of patients with benign diseases was significantly higher than that of patients with malignant diseases, but there was a marked overlap between those with malignant and benign diseases. No significant differences were found in the pleural fluid ferritin, ASP, TPA, and IAP levels between malignant and benign conditions. ASP and IAP pleural fluid levels showed significant correlations with the pleural fluid C-reactive protein (CRP) concentrations suggesting that they also reflect inflammatory activity. The mean ADA activity in tuberculous effusion was significantly higher than that resulting from other causes of pleural effusion.

Adult↗
PubMed1988

Mast cell degranulation and its inhibition by an anti-allergic agent tranilast. An electron microscopic study.

Degranulation of IgE-sensitized rat mast cells by antigen was studied quantitatively in vitro and in vivo by electron microscopy. The inhibition of this degranulation by an anti-allergic drug, N-(3,4-dimethoxycinnamoyl)anthranilic acid (Tranilast), was also examined both in vitro and in vivo. In the in vitro study using peritoneal mast cells, alteration of the granules, cavity formation by fusion of the perigranular membrane and granule discharge due to fusion of the cavity membrane with the cell membrane were observed and were accompanied by histamine release. Scanning electron microscopy disclosed the extrusion of smooth, round bodies from pores formed on the cell surface. In the in vivo study of passive cutaneous anaphylaxis (PCA), the characteristic features of mast cell degranulation were obvious 5 min after the injection of antigen; leakage of dye increased progressively from 5 to 30 min but was not found at 6 h. From quantitative analysis of the substructure of mast cells, it was demonstrated that degranulation of IgE-sensitized mast cell induced by antigen was achieved by sequential exocytosis both in vitro and in vivo. Tranilast inhibited these changes to a remarkable extent and it was concluded that the inhibition of mast cell degranulation by this drug might play an important role in anti-allergic treatment.

Animals↗
PubMed1988

A specific domain of the adenovirus EIV promoter is necessary to maintain susceptibility of the integrated promoter to EIA transactivation.

We constructed a series of mutations that delete sequences in the promoter region of the early-region IV (EIV) promoter of adenovirus type 5. We fused these promoter mutations to the coding sequences of either the chloramphenicol acetyltransferase or the dihydrofolate reductase (DHFR) gene and tested the ability of a cotransfected EIa gene to stimulate EIV expression. All of the mutations tested were stimulated in these assays, implying that no specific sequence is required for stimulation. Two mutant promoters, deleted for either the TATA box or the region residing between -39 and -177 upstream from the cap site of EIV mRNA, did show a reduced level of stimulation by the EIa products. To assess the effects of the EIA gene products on expression from an EIV promoter integrated into the chromosome, we isolated CHO cell lines containing EIV-DHFR chimeric genes. After introduction of the EIa gene with a second selectable marker, expression from all mutant EIV-DHFR genes was increased. Surprisingly, one mutant promoter, deleted for sequences between -39 and -177, lost the ability to respond to the EIa region on passage of cells, although deletions in any part of the region still retained this ability. These results demonstrate that multiple elements residing between -39 and -177 in the EIV promoter are necessary to maintain susceptibility of the integrated promoter to regulation.

Acetyltransferases↗
PubMed1987

Regulation of in vitro and in vivo transcription of early-region IV of adenovirus type 5 by multiple cis-acting elements.

A series of deletion mutants spanning the promoter of the adenovirus early-region IV (EIV) gene were tested for transcriptional activity, using both in vitro and in vivo assays. Four distinct domains had additive effects on efficient transcription from the EIV promoter in HeLa whole-cell extracts. The first resided 20 to 27 bases upstream of the initiation site and included the TATA box. Deletion of the TATA box drastically reduced the transcriptional activity in vitro but had a lesser effect in vivo. The second region extended from -32 to -177 and contained two 17-base-pair inverted repeats, centered around -40 and -162. Sequences lying between -140 and -173 were important for efficient transcription since deletion of this region reduced the activity fourfold. Deletion of either one of the two inverted repeats or insertion of DNA fragments between them resulted in the synthesis of extra transcripts that initiated at sites upstream from the EIV site. The third region was located between -198 and -250 and contains three guanosine-plus-cytosine-rich sequences, present around -212 (GGGCGG), -233 (GGGCGG), and -251 (CGCGGG). The fourth, most upstream region was located between -260 and -307. Deletion of this region, which contains the NF-1 factor-binding site, slightly reduced transcriptional activity both in vivo and in vitro. The data indicate that multiple cis-acting elements are required for efficient transcription from the EIV promoter in both in vitro and in vivo systems.

Adenoviridae↗
PubMed1986

No evidence for linkage between the loci for coagulation factor XIII-A and HLA.

The linkage analysis between the locus for coagulation factor XIII-A (F13A) and HLA region genes (HLA-A, -C, -B) was performed. In males, the maximum of lod scores between F13A and HLA was 0.33 at 0 = 0.30, and in females lod scores were negative at all values of 0. The results provided no evidence for close linkage between F13A and HLA genes.

Chromosome Mapping↗
PubMed1985

Interaction of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitroso urea hydrochloride with nucleic acids and proteins.

The binding of the 14C-labelled-ethylene and -pyrimidine moieties of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) to the biological macromolecules was studied with the AH-130 hepatoma-bearing rats, suspension of AH-130 cells, and isolated nucleic acids and proteins. In all systems examined, a significant level of the binding of the [14C]ethylene of ACNU to nucleic acids, probably due to alkylation, was observed. In contrast, the extent of the binding of the [14C]-pyrimidine was negligible. When a compound lacking the 4-amino group of ACNU (deamino-ACNU) was used for the binding study, relatively higher binding of this compound than that of ACNU to [14C]lysine was observed. It was revealed, therefore, that the low binding of ACNU to proteins could be due to instantaneous depletion of an isocyanate-intermediate, according to the formation of an intramolecularly carbamoylated product with the amino-group on the pyrimidine ring of ACNU molecule during incubation. This could be the molecular basis for the low carbamoylating activity of ACNU in vivo and in vitro, and the antitumor action of ACNU would be dependent on its alkylating activity only.

Animals↗
PubMed1985

Identification of major urinary metabolites of ACNU, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitroso urea hydrochloride in rats.

Metabolites of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1- nitrosourea hydrochloride (ACNU) in rat urine were investigated. After intravenous administration of 14C-ACNU into rats, four major radioactive metabolites and two minor ones were detected in the urine by two-dimensional thin-layer chromatographic analysis. The main metabolite was identified to be an imidazolidinone compound, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-5-hydroxy-2-imidazolidinone (M-D). One of the other major metabolites was identified to be a nitrosated compound of the main metabolite i.e., 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]- 5-hydroxy-3-nitroso-2-imidazolidinone (M-C). These were new types of metabolites which have not been reported in the metabolic study of other chloroethylnitrosourea derivatives. Compared with authentic compounds, two metabolites were identified to be a denitrosated derivative of ACNU i.e., 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)urea (M-B), and a cyclized pyrimidopyrimidine compound which lacks the ethylene moiety of ACNU, i.e., 3,4-dihydro-7-methylpyrimido[4,5-d]pyrimidin-2-(1H)-one (M-A). The two minor metabolites were supposed to be compounds derived from M-A. Discussions were made on mechanism of formation of these metabolites in vivo.

Animals↗
PubMed1985

In vitro metabolism of ACNU, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitroso urea hydrochloride, a water-soluble antitumor nitrosourea.

In vitro decomposition of ACNU, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros ourea hydrochloride, in various conditions was studied with the use of the 14C-labeled compound. Metabolite A, 3,4-dihydro-7-methylpyrimido[4,5-d]pyrimidin-2(1H)-one (an intramolecular cyclized product), was formed spontaneously in the phosphate buffer (pH 7.4) with simultaneous liberation of the alkylating moiety. With rat liver enzyme preparations, formation of three metabolites was observed. Those were metabolite B, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)urea (a denitrosated product), metabolite C, 1-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-5-hydroxy-3-nitroso-2-imidazolidinone (a product via oxidative dechlorination), and metabolite D, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-5-hydroxy-2-imidazolidinone (a denitrosated product of metabolite C). Formation of metabolite B was catalyzed with both cytosolic and microsomal enzymes, not inhibited with SKF-525A, and partly dependent on nicotinamide adenine dinucleotide phosphate (NADPH). These results suggest that at least two enzymatic steps would be involved in the formation of this product. Metabolites C and D were produced by the microsomal preparation, being dependent on O2 and NADPH, inhibited by CO and SKF-525A, and enhanced by phenobarbital pretreatment. When metabolite C was incubated with cytosolic and microsomal preparations, more efficient formation of metabolite D with the former than the latter was observed. From these results, it was assumed that oxidative dechlorination of ACNU to metabolite C would be catalyzed with the microsomal mixed function oxidase, and metabolite D would be produced via denitrosation process of metabolite C.

Animals↗
PubMed1985

The susceptibility of experimental glomerulonephritis in six different strains of mice.

An experimental glomerulonephritis was produced in mice by an injection with a sub-nephrotoxic dose of nephrotoxic serum after immunization with rabbit IgG. In order to examine the susceptibility of disease, we tested the onset of nephritis in 6 different strains (ICR,C57BL/6,C3H,DBA/2, nu/nu and DDY) of mice. Strain C57BL/6 mice indicated the highest susceptibility to the disease with a high degree of reproducibility. The excretion of protein in urine, the elevation of serum cholesterol and blood urea nitrogen level and the decrease of serum albumin were observed in nephritic mice. Typical histopathological changes in the kidney were crescent formation in glomeruli, thickening of glomerular basement membrane and cast of urinary tubuli. Cyclophosphamide, at doses of 5 and 10 mg/kg, inhibited the development of nephritis in C57BL/6 mice. These results suggest that the experimental glomerulonephritis model in C57BL/6 mice is useful for immunopharmacological studies of nephritis.

Animals↗
PubMed1984

[The clinical significance of an oscillating flap in the acute stage of dissecting aneurysm: report of three cases].

The important two-dimensional echocardiographic finding of dissecting aneurysm in the acute stage is characterized by the presence of an oscillating intimal flap which is thought to be of highly diagnostic value. This report describes about three cases with dissecting aneurysm in which an oscillating flap was transiently observed. In Case 1 (62-year-old female), an oscillating flap observed in the aortic arch seven hours after the onset was not detected three days later. A flap in Case 2 (65-year-old male) which had been present in the descending aorta three hours after the onset of illness disappeared two days later. In Case 3 (55-year-old male), only an intimal flap without fine oscillation was demonstrated in the abdominal aorta by echocardiography performed three days after the onset of illness. In the acute phase of dissection, the echocardiographic detection of an oscillating flap seems to depend on the time of the study after the attack.

Aged↗
PubMed1983

[Calcification of the tricuspid annulus in association with pulmonary stenosis: report of a case].

A 51-year-old woman was admitted to our hospital because of palpitation, dyspnea and anterior chest discomfort. She had had a heart murmur since childhood. On physical examination, a rough grade 6/6 ejection systolic murmur was maximally audible at the second left intercostal space with a systolic thrill. The chest X-ray film showed the cardiothoracic ratio of 54% and the electrocardiogram demonstrated right ventricular hypertrophy. Calcification of the tricuspid annulus was recognized by chest X-ray films (anteroposterior and lateral views), M-mode and cross-sectional echocardiograms and the computed tomogram (CT) of the chest. Cardiac catheterization revealed the presence of valvular pulmonary stenosis and atrial septal defect. These findings were confirmed by surgical operation. Since the first description of Paktovskii in 1960, nine cases of calcification of the tricuspid annulus were reported, but no case has been described in the Japanese literature. Contrary to the mitral annulus, the echocardiographic and computed tomographic features of the calcification of the tricuspid annulus has not been reported previously. In this paper, we reported a middle aged patient with circumferential calcification of the tricuspid annulus in association with severe pulmonary stenosis and atrial septal defect, and the features of the echocardiogram and CT images were illustrated.

Calcinosis↗