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Biomedical subjects

S Manabe

Publications and source records attributed to S Manabe.

At least 127 records · Page 7Linked to original sources
PubMed1988

Spinal cord compression by epidural metastases. Fibrosarcoma experiments in rats.

Morphologic changes were studied in 43 rats that were paralyzed by an epidural fibrosarcoma inoculated through the spinous process. By this technique, of 29 rats examined radiographically, the tumor destroyed vertebral bone in 22. Changes of the cord in the early stage of paralysis were specially analyzed by Marchi's stain and microangiograms. In compromised cord segments in the early stage, extravasation of contrast medium was observed in the gray matter and the dorsal funiculus; and in the dorsal funiculus just proximal or distal to the compressed portion, hemorrhagic areas were present. Ascending degenerated fibers in the dorsal funiculus, which were derived from the degenerated posterior nerve root or the degeneration of the dorsal funiculus in the compressed segments, were characteristically detected in rats in the early stages. In the advanced stages a transverse cord lesion was observed at the involved level. Based on the present analyses, to prevent more advanced damage to the spinal cord, the tumor should be removed at an early stage that clinically coincides with the period when radicular signs appear.

Animals↗
PubMed1988

Metabolic activation of a protein pyrolysate promutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline by rat liver microsomes and purified cytochrome P-450.

The enzymatic activation of a promutagenic pyrolysate, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), was studied using the Ames mutagenesis test system. The enzyme catalyzing the mutagenic activation of MeIQx is mainly localized in the microsomal fraction. A large number of revertants was observed in the presence of hepatic microsomes obtained from 3-methylcholanthrene (3-MC)- or polychlorinated biphenyl (PCB)-treated rats but only a minimal number with the hepatic microsomes from untreated or phenobarbital (PB)-treated rats. In addition, the microsomal activation was reduced efficiently by known inhibitors of cytochrome P-450-mediated reactions such as 7,8-benzoflavone, ellipticine and flavone. Among five forms of purified rat cytochrome P-450, the highest sp. act. (no. of revertants induced/nmol cytochrome P-450) for the activation of MeIQx was observed with a high-spin form of cytochrome P-450, P-448-H, followed by the low-spin form, P-448-L, and to a lesser extent by PB-inducible forms, P-450b and P-450e. P-450-male, which is a main constitutive form of cytochrome P-450 in male rat livers, showed considerable catalysis for the mutagenic activation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and MeIQx. These results indicate that the metabolic activation of MeIQx is catalyzed mainly by two forms of cytochrome P-450, P-448-H and P-488-L, in the livers of PCB- or 3-MC-treated rats, but also that P-450-male may play an important role in the activation in livers of intact male rats.

Animals↗
PubMed1988

In vitro and in vivo N-acetylation of carcinogenic glutamic acid pyrolysis products in humans.

The carcinogenic glutamic acid pyrolysis products, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), and their N-acetyl derivatives have been demonstrated to be present in human urine, bile, liver and kidney. In vitro experiments have revealed that Glu-P-1 and Glu-P-2 are N-acetylated to form N-acetyl derivatives by the cytosolic fraction from a human autopsy liver specimen. From these results our data strongly suggest that Glu-P-1 and Glu-P-2 derived from everyday foods are partially N-acetylated in human organs and that they are excreted in bile and urine with their N-acetyl derivatives. Our data also provide the first reliable evidence that humans can metabolize the carcinogenic heterocyclic amines.

Acetylation↗
PubMed1988

Presence of carcinogenic glutamic-acid pyrolysis products in human cataractous lens.

The carcinogenic glutamic-acid pyrolysis products, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), were found to be present in human cataractous lenses, but not in normal bovine lenses. Contents of Glu-P-1 and Glu-P-2 in 35 human cataractous lenses were 832 and 20 ng, respectively. These results indicate that the human cataractous lens is exposed to the fluorescent compounds, carcinogenic glutamic pyrolysis products.

Aged↗
PubMed1988

Carcinogenic tryptophan pyrolysis products potent inhibitors of type A monoamine oxidase and the platelet response to 5-hydroxytryptamine.

The effects of carcinogenic heterocyclic amines and beta-carbolines on 5-hydroxytryptamine-induced human platelet aggregation, on the uptake of 5-hydroxytryptamine by platelets, and on human monoamine oxidase activity were investigated. Of the dietary carcinogens and beta-carbolines studied, carcinogenic tryptophan pyrolysis products had greater pharmacological activities than other heterocyclic amines. The carcinogenic tryptophan pyrolysis products, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole, which have been identified in the dialysis fluid of uraemic patients, were the most potent inhibitors of the aggregation response to 5-hydroxytryptamine, with IC50 (the concentrations causing 50% inhibition) values of 10 mumol/l and 50 mumol/l, respectively. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole by themselves did not induce platelet aggregation, although these dietary carcinogens structurally resemble 5-hydroxytryptamine. Kinetic analyses showed that 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole were potent competitive inhibitors of 5-hydroxytryptamine uptake by platelets with Ki 18 mumol/l and 42 mumol/l, respectively. Furthermore, carcinogenic tryptophan pyrolysates as well as beta-carbolines were found to be competitive selective inhibitors of monoamine oxidase 'type A'.

Blood Platelets↗
PubMed1988

Incidence and ultrastructure of rudimentary cilia in benign and malignant peripheral nerve tumors.

The incidence and ultrastructure of cilia were examined in 26 peripheral nerve tumors. The cilia had the common features of elongated shafts and basal structures consisting of two basal bodies. The basal body contained two basal feet and some long striated rootlets. The cilia lacked central tubules and two dynein arms of subfiber A, suggesting that they were nonmotile and rudimentary. The quantitative results showed that the incidence of cilia was low in Schwann cells and fibroblasts of the 20 benign tumors and slightly higher in perineurial cells of the 12 neurofibromas. Conversely, the incidence was high in most of the 6 malignant tumors. Only one perineurial cell from normal mature nerve examined carried a cilium, although no cilia were seen in the other perineurial cells, Schwann cells, and fibroblasts observed. The results showed that ciliary formation was more marked in the more actively proliferating tissues such as malignant tumors, and less so in the less actively proliferating tissues such as benign tumors. Ciliary formation may be one of the ultrastructural features commonly observed in proliferative tissues.

Cilia↗
PubMed1988

Alkaline bismuth solution as an en bloc stain for formaldehyde-glutaraldehyde potassium permanganate fixed fungal spores.

An alkaline solution of bismuth subnitrate reacted well with the cell membranes and cell walls of formaldehyde-glutaraldehyde potassium permanganate fixed Alternaria spores, demonstrating them with greater contrast than in sections stained with uranyl acetate and lead citrate. Optimal fine structure of fungal spores was obtained by en bloc staining with alkaline bismuth solution after aldehyde and permanganate fixation. The contrast of the cell organelles and cell walls was high enough in sections cut after the alkaline bismuth en bloc stain for direct ultrastructural observation. Our results indicate that the alkaline bismuth stain is useful either as an en bloc or section stain for aldehyde and permanganate fixed fungal spores.

Alternaria↗
PubMed1988

Anterolateral uncoforaminotomy for cervical spondylotic myeloradiculopathy.

Thirty-five patients with cervical spondylotic radiculopathy and myeloradiculopathy had anterolateral uncoforaminotomy. Spondylotic spurs associated with radiculopathy were continuous from the uncovertebral joint to the posterior ridge of the vertebral body in 33 patients and to the posteriorly bulging disc with posterolateral bony spurs in 2 patients. Anterolateral uncoforaminotomy was found safe to remove the continuous type of spur, resulting in decompression of the cord-root complex, which shifted anteriorly after surgery. The outcome was satisfactory in 19 of 20 radiculopathy patients, and in all 15 myeloradiculopathy patients. Decompression of the cord-root complex is the most important factor in relieving neurologic manifestations of cervical spondylosis.

Adult↗
PubMed1988

Carcinogenic glutamic acid pyrolysis product in the dialysate of uremic patients treated by continuous ambulatory peritoneal dialysis.

By using a high-performance liquid chromatography (HPLC) method, we determined the contents of 2-amino-6-methyldipyrido[1,2-a:3', 2'-d] imidazole (Glu-P-1) and 2-aminodipyrido[1,2-a:3', 2'-d]imidazole (Glu-P-2) in the dialysate of patients with uremia. The total dialysate (approximately 6 liters) per day of the patients who had received continuous ambulatory peritoneal dialysis (CAPD) was examined. The amounts of Glu-P-1 and Glu-P-2 in the total dialysate per day were 552.2 +/- 266.9 pmole and 386.3 +/- 146.0 pmole (mean +/- SD, n = 10), respectively. The recoveries of Glu-P-1 and Glu-P-2 in the dialysate on our assay method were 68.2% and 54.3%, respectively. Based on the recoveries, the average amounts of Glu-P-1 and Glu-P-2 in the dialysate of uremic patients were assumed to be 809.7 pmole and 711.4 pmole, respectively.

Adult↗
PubMed1987

Accumulation of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole and 2-aminodipyrido[1,2-a:3',2'-d]imidazole, carcinogenic glutamic acid pyrolysis products, in plasma of patients with uremia.

In order to investigate the exposure of humans to 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole [(Glu-P-1) Chemical Abstracts Service:67730-11-4] and 2-aminodipyrido[1,2-a:3',2'-d]imidazole [(Glu-P-2) Chemical Abstracts Service:67730-10-3], carcinogenic heterocyclic amines, we developed a high-performance liquid chromatography method to detect Glu-P-1 and Glu-P-2 in biological samples, and compared the plasma levels of the carcinogens in normal subjects with those in uremic patients in which higher incidence of malignancy has been reported. Glu-P-1 and Glu-P-2 levels in plasma of uremic patients before induction of hemodialysis treatment were 12.62 +/- 3.65 (SD) pmol/ml (n = 5) and 14.81 +/- 5.17 pmol/ml (n = 5), respectively, whereas Glu-P-1 and/or Glu-P-2 could be detected in only two of seven normal subjects and the levels were lower than 3.1 pmol/ml. Approximately 10% of these carcinogens in plasma of uremic patients could be removed by the first hemodialysis treatment, and reasonable amounts of these carcinogens could be detected in the dialysate of uremic patients. However, significant amounts of Glu-P-1 and Glu-P-2 were still detected in plasma of all uremic patients even after 1 month-hemodialysis treatments. These results suggest that one of the excretory pathways of these carcinogens is via kidney.

Adult↗
PubMed1987

Detection of Trp-P-1 and Trp-P-2, carcinogenic tryptophan pyrolysis products, in dialysis fluid of patients with uremia.

In order to estimate the exposure levels of mutagenic and carcinogenic heterocyclic amines in humans, we developed a high-performance liquid chromatography method to detect 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in dialysis fluid of patients with uremia. Using this methods, dialysis fluid of 12 patients who had received hemodialysis treatment or continuous ambulatory peritoneal dialysis was examined. Trp-P-1 was detected in dialysate of all uremic patients (727 +/- 282 pmoles, n = 12). In patients who had been treated with continuous ambulatory peritoneal dialysis, the average amount of Trp-P-1 found in whole dialysate (6 l) per day was 710 +/- 203 pmoles (mean +/- S.D., n = 8). Moreover, Trp-P-2 could be detected in 5 out of 12 patients (206 +/- 85 pmoles, n = 5). These results indicate that patients with uremia are actually exposed to carcinogenic tryptophan pyrolysis products. The average exposure level of Trp-P-1 in uremic patients apparently exceeded 710 pmoles (150 ng) per day.

Carbolines↗
PubMed1987

Inhibitory effects of tryptophan pyrolysis products on human platelet aggregation through inhibition of prostaglandin endoperoxide synthetase.

To determine the effects of the carcinogenic heterocyclic amines on the stimulus-reaction system in cells, the effects of several such amines, including 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), on human platelet aggregation and of Trp-P-1 and Trp-P-2 on human polymorphonuclear leucocyte aggregation were investigated. Of the carcinogens studied, only Trp-P-1 and Trp-P-2 had potent inhibitory effects on human platelet aggregation induced by sodium arachidonate. The concentrations of Trp-P-1 and Trp-P-2 causing 50% inhibition of human platelet aggregation induced by sodium arachidonate were 15 and 25 microM, respectively. The heterocyclic amines examined had no significant effects on human polymorphonuclear leucocyte aggregation. Moreover, radiochemical studies of arachidonate metabolism showed that Trp-P-1 and Trp-P-2 inhibited, in a dose-dependent manner, the formation of cyclooxygenase products in platelets induced by sodium arachidonate. These results indicate that Trp-P-1 and Trp-P-2 have potent inhibitory effects on prostaglandin endoperoxide synthetase in the stimulus-reaction system of human platelets.

Adult↗
PubMed1987

Studies in the development of Japanese encephalitis vaccine: expression of virus envelope glycoprotein V3 (E) gene in yeast.

A safe, effective and economical vaccine is required for the prevention of Japanese encephalitis (JE), a disease with high mortality and grave sequelae, which is prevalent in Japan and other countries in east, south-east and southern Asia. As the initial step to produce a second-generation vaccine, recombinant DNA technology was utilized to express the JE virus envelope glycoprotein V3 (E) gene in yeast cells.This report describes the construction of a yeast expression vector in which a cDNA clone covering the V3 gene was connected to the acid-phosphatase promoter of a yeast vector plasmid. Successful expression of the V3 gene was detected by ELISA and Western blotting using monoclonal antibodies against JE V3. Immunization of mice with the V3 antigen expressed in yeast produced limited but definite levels of anti-JE antibodies which could neutralize JE virus. The results are an encouraging step in the development of a practical second-generation JE vaccine.

DNA, Recombinant↗
PubMed1987

Regulation of hepatic sulfotransferase catalyzing the activation of N-hydroxyarylamide and N-hydroxyarylamine by growth hormone.

The regulatory mechanism of hepatic sulfation of N-hydroxyarylamine and N-hydroxyarylamide by endocrine factors has been studied in rats. The cytosolic sulfations of N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) and 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1), which were determined by the reductive formations of 2-acetylaminofluorene and Glu-P-1, were seven to nine times and three times higher, respectively, in male than female rats. Hypophysectomy of male rats decreased their activities to 23% and 41% of the levels of the untreated animals, respectively. Intermittent treatment of hypophysectomized male and female rats with human growth hormone (hGH) significantly increased their sulfating activities of both compounds. Infusion of hGH also enhanced the sulfating activity of N-hydroxy-AAF but not of N-hydroxy-Glu-P-1. The sulfating activity of N-hydroxy-AAF was also decreased by castration at neonate and was increased by the administration of testosterone propionate to gonadectomized male and female rats. Testosterone propionate and estradiol benzoate had no effect on hypophysectomized rats, but estradiol benzoate repressed the sulfating activities of N-hydroxy-AAF and N-hydroxy-Glu-P-1 in hGH-treated hypophysectomized male rats. These results indicate that sex steroids elicit their effects on the sulfations of N-hydroxyl-aryl compounds through modulating the action of growth hormone at hypothalamus-pituitary and hepatic levels in rat livers.

2-Acetylaminofluorene↗