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Biomedical subjects

N Koga

Publications and source records attributed to N Koga.

At least 109 records · Page 6Linked to original sources

[Percutaneous transluminal angioplasty in patients with prior coronary artery bypass grafting].

Seventeen patients with stenosis of bypass grafts or native coronary arteries (NCA) following coronary artery bypass underwent percutaneous transluminal angioplasty (PTCA). Stenoses were located in the saphenous vein graft (SVG) in 11 cases (involving 16 lesions), in the internal mammary artery graft (IMAG) in 2 cases (2 lesions), and in the NCA in 9 cases (13 lesions). All patients had disabling angina pectoris or a post-operative stenosis of more than 50%. PTCA was successful in 75% of all the SVG stenotic lesions, 50% of the IMAG lesions and in 67% of the NCA lesions. There were no complications associated with PTCA. After successful PTCA, restenosis developed in 23% of the SVG cases, 0% of the IMAG cases and in 38% of the NCA cases. Though relief of chest pain was found in 10 patients (59%), PTCA of the NCA was not so effective as PTCA of the bypass grafts.

Angioplasty, Balloon↗

[Tissue distribution, inductive effect on liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran in Golden Syrian hamsters].

The hamsters have been known to be the least sensitive mammalian species to the acute toxicity of highly toxic polyhalogenated hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. In the present study, the tissue distribution, inductive effect of liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) in male Golden Syrian hamsters were examined. The highest content (about 48% of dose) of PenCDF was found in the liver 5 days after a single i.p. dose of 1.0 mg/kg. The amount ranging about 5 to 10% of dose was also distributed to mesentery, skin and muscle. In liver, the distribution of PenCDF was just parallel to that of cytochrome P-450 (P-450), marker enzymes of liver endoplasmic reticulum, suggesting that PenCDF binds to P-450. The mode of inductive effects of PenCDF in hamsters was 3-methylcholanthrene-type as reported previously in rats. However, the typical enzymes such as benzo(a)pyrene 3-hydroxylase and DT-diaphorase were induced to a relatively less extent than did in rats. In hamsters pretreated with PenCDF at a dose of 0.5 mg/kg, the potent atrophy of thymus and the 3-fold increase of liver lipid peroxide were observed, whereas the body weight gain was not suppressed at all. These results suggest that the induction of liver enzymes and the atrophy of thymus might not be the direct cause of PenCDF-induced lethality in hamsters.

Animals↗

[Studies on distribution, excretion and subacute toxicity of squalane in dogs].

In the previous papers, we demonstrated, by using rats, that squalane (2,6,10,15,19,23-hexamethyltetracosane) could stimulate the fecal excretion of 2,3,4,7,8-pentachlorodibenzofuran, which was regarded as the most important etiologic agent of yusho among PCB and PCDF congeners found in the causal rice oil. We also reported that, in rats, squalane was not essentially absorbed from the gastrointestinal tract, and did not show any appreciable side effects during the 3-month treatment. In the present paper, we have investigated the distribution, excretion and subacute toxicity of squalane in beagle dogs. The fecal excretion of squalane accounted for about 83% of dose during the initial 2 days after administration at a single oral dose of 1,200 mg/kg to male dogs. On day 3, absorbed squalane was mostly distributed to the hair and the skin, and the concentrations in these tissues were decreased on day 6. These results suggested that most of squalane administered orally was not absorbed from the gastrointestinal tract, but a part was absorbed and excreted through the hair. In addition, squalane distributed into the liver was found to be eliminated rather slowly. A long-term (13-week) treatments with squalane orally at doses of 400 mg/kg/day or 1,200 mg/kg/day in male and female dogs, resulted also in accumulation of squalane in the liver at a level of about 3% (400 mg/kg) or about 6% (1,200 mg/kg) of the daily dose. This accumulation of squalane in the liver was highest among all the tissues. Nevertheless, no appreciable toxic signs were observed in the serum biochemical tests and the hepatic functional test for squalane groups. Therefore, squalane accumulating in the liver, did not seem to disturb the hepatic physiological functions. It was suggested also in a long-term treatment that the skin and the hair played the most important role in the elimination of squalane. In conclusion, the present studies on subacute toxicity tests suggested that squalane did not give any significant toxic effects on dogs as well as rats.

Animals↗

[Mycotic abdominal aneurysm requiring emergency operation due to sudden thrombotic obstruction: a case report].

A 59-year-old man was admitted with history of low grade fever, general malaise and low back pain. Physical examination showed a pulsatile mass in the mid-abdomen. There were slight leucocytosis, elevated BSR and CRP. Abdominal ultrasonography, CT and MRI revealed an abdominal aneurysm within which there was an intimal flap and thrombus. Though blood culture was not positive, antibiotic therapy was initiated on the presumption of a mycotic abdominal aneurysm. Six days after admission, he complained of numbness in the lower extremities and both femoral pulsations were not palpable. Emergency surgery was undertaken. The aneurysm was adhered to the IVC and the ileum and there was a large thrombotic mass in it. Aneurysmectomy and Y-graft interposition were done uneventfully. Pathology revealed marked thickness of the aorta and infiltration of lots of inflammatory cells. The culture of aneurysmal wall was negative. This is the very rare case because of sudden thrombotic occlusion of the mycotic abdominal aneurysm. Several important features of this disease have been also discussed.

Aneurysm, Infected↗

A novel growth factor in rat spleen which promotes proliferation of hepatocytes in primary culture.

We have identified a factor from adult rat spleen which stimulates the proliferation of rat hepatocytes. The activity was found in the spleen soluble matrix fraction (1,300xg supernatant of inter-cellular fraction). No activity was found in the spleen cell homogenate, in the spleen insoluble matrix fraction or rat serum. After 4 days of incubation with the spleen factor, the cell number increased 4-fold higher than that at inoculation. The growth stimulation were observed in both fetal bovine serum supplemented medium and hormonally defined medium which contains insulin, epidermal growth factor, glucagon, growth hormone and prolactin. The level of activity in the spleen soluble matrix was not affected by partial hepatectomy or trypsinization. These data indicate that the spleen factor is different from previously characterized effectors of hepatocyte proliferation. The novel factor has been named spleen derived growth factor (SDGF).

Animals↗

Surgical treatment of coronary aneurysm developed after PTCA.

Two patients who developed coronary aneurysm at the site of Percutaneous Transluminal Coronary Angioplasty (PTCA) in proximal LAD accompanied by severe re-stenosis just proximal to the aneurysm are described. Both patients underwent Coronary Arterial Bypass Grafting (CABG) to distal LAD to stop anginal attacks refractory to any anti-anginal drugs and to prevent a rupture of a coronary aneurysm. After the operation the anginal attacks disappeared and no trace of coronary aneurysm was visible in the coronary angiogram.

Angioplasty, Balloon↗

Purification and characterization of two forms of chicken liver cytochrome P-450 induced by 3,4,5,3',4'-pentachlorobiphenyl.

3,4,5,3',4'-Pentachlorobiphenyl (PenCB), one of the most potent 3-methylcholanthrene (MC)-type inducers of hepatic enzymes in animals, caused a remarkable induction of liver microsomal monooxygenases, particularly 7-ethoxyresorufin (7-ER) O-deethylase, benzo(a)pyrene (BP) 3-hydroxylase, and testosterone 16 alpha-hydroxylase in chickens, but not NADPH-cytochrome c(P-450) reductase and cytochrome b5. Two forms of cytochrome P-450 (P-450) in liver microsomes of PenCB-treated chickens were purified and characterized. The absorption maxima of the CO-reduced difference spectra of both enzymes (chicken P-448 L and chicken P-448 H) were at 448 nm. From the oxidized form of their absolute spectra, chicken P-448 L was a low-spin form and chicken P-448 H was a high-spin form. They had molecular masses of 56 and 54 kDa, respectively. In a reconstituted system, 7-ER O-deethylation, BP 3-hydroxylation, and testosterone 16 alpha-hydroxylation were catalyzed at high rates by chicken P-448 L but not by chicken P-448 H. Chicken P-448 L also catalyzed N-demethylation of aminopyrine, benzphetamine, and ethylmorphine with relatively low activity. On the other hand, chicken P-448 H functioned only in catalyzing estradiol 2-hydroxylation. These results were supported by an inhibition study of microsomal monooxygenases using an antibody against each enzyme. Immunochemical studies revealed that the enzymes differ from each other but are both inducible by PenCB-treatment. Chicken P-448 L and chicken P-448 H respectively comprise about 82 and 7% of the total P-450 content in chicken liver microsomes.

Animals↗

4-Hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (PI-OH): a new potentiator of sympathomimetic amines on the rat anococcygeus muscle.

1. The potentiating effects of racemic 4-hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (PI-OH), cocaine, desipramine and nomifensine on the concentration-response curves of the rat anococcygeus muscle to noradrenaline (NA) and field stimulation were examined. 2. PI-OH and cocaine concentration-dependently potentiated the responses of anococcygeus muscle to NA and field stimulation, but the activity of PI-OH was stronger than that of cocaine on both responses. 3. At high concentrations the potentiating activities of desipramine and nomifensine were less, a fact that was explained by their postsynaptic inhibitory properties; the actions of nomifensine and desipramine as antagonists against NA were competitive and non-competitive, respectively. 4. It is concluded that PI-OH may be an ideal potentiator of the response to NA in adrenergically-innervated tissues because it has no side effects such as postsynaptic inhibition.

Animals↗

Enhanced faecal excretion of 2,3,4,7,8-pentachlorodibenzofuran in rats by a long-term treatment with activated charcoal beads.

1. The effect of activated charcoal beads on the faecal excretion of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), a causal agent of yusho, which accumulates in the body, was studied for 12 weeks in rats. 2. Diets supplemented with 1% and 5% activated charcoal beads stimulated faecal excretion of PenCDF about 2- and 4-fold, respectively. The concentration of PenCDF in liver, the major storage site, was decreased significantly and dose-dependently by the treatment. 3. The charcoal bead treatment decreased the extent of fatty liver, thymic atrophy, and induction of hepatic benzo[a]pyrene hydroxylase.

Animals↗

Metabolic fate of fenetylline in rat and man.

1. Metabolic fate of 7-[2-(alpha-methylphenylethylamino)ethyl]theophylline hydrochloride (fenetylline) was investigated in male Sprague-Dawley rats and three male volunteers. 2. Six metabolites were identified in the rat urine as amphetamine(AP), p-hydroxy-AP, acetylaminoethyl-theophylline(TP), aminoethyl-TP, hydroxyethyl-TP and carboxymethyl-TP by comparison of their spectral properties and h.p.l.c. and g.l.c. characteristics with those of authentic samples. All these metabolites was also detected in the urine of humans receiving fenetylline. 3. Quantification of these metabolites using h.p.l.c. and g.l.c. showed that carboxymethyl-TP, p-hydroxy-AP and acetylaminoethyl-TP were the major metabolites in 0-24 h rat urine at 13.7%, 11.2% and 9.3% of dose, respectively. In men, carboxymethyl-TP(39-43% dose) and AP(23-33% dose) were the major metabolites in 0-48 h urine. 4. These results suggest that fenetylline metabolism proceeds via oxidative cleavage at two different sites to produce aminoethyl-TP and AP, respectively. The pathway producing AP predominates, in both man and rat, but is more predominant in the former.

Adult↗

[A case of clivus chordoma showing hemorrhage in the posterior fossa].

We are reporting a rare case of clivus chordoma with fatal hemorrhage in the posterior fossa. A 38-year-old woman afflicted with sudden onset of severe headache and vomiting. On neurological examination, she was mildly lethargic. She had slight dysarthria and nystagmus, but no cranial nerve abnormalities. Craniogram revealed erosive changes in the right petrous bone. CT scan showed a massive intracerebellar hemorrhage and isodense mass in the sphenoid sinus, which were not enhanced by contrast medium. She became comatose and died 3 days later. No operation was performed. Autopsy revealed massive hemorrhage in the posterior fossa and yellowish, gelatinous tumor extending from the right clivus to the sphenoid sinus. Histological examination showed a chordoma. This case demonstrates that the hemorrhage associated with brain tumor, especially in posterior fossa, produces a significant sudden elevation of intracranial pressure and leads clinically to a rapid loss of consciousness and death soon after the onset.

Adult↗

Comparison of DT-diaphorases purified from the liver cytosol of untreated, and 3,4,5,3',4'-pentachlorobiphenyl- and 3-methylcholanthrene-treated rats.

DT-Diaphorase purified from the liver cytosol of rats treated with a highly toxic PCB congener, 3,4,5,3',4'-pentachlorobiphenyl (PenCB), was compared to those from 3-methylcholanthrene (MC)-treated and untreated rats. Treatments with PenCB and MC resulted in about 8- and 7-fold increases of cytosolic DT-diaphorase activity, respectively. Purification of the enzyme preparations from untreated, and PenCB- and MC-treated rats were conducted by using DE-52, DEAE-Sephadex A-50, hydroxylapatite, and Bio-Gel P-150 column chromatographies. Both Sephadex G-100 gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that all of the final preparations from the three origins were homogeneous and had the same molecular weight of 59,000, consisting of two subunits with molecular weights of 30,000. Further studies on amino acid composition, Km value, optimum pH, and catalytic activities for various substrates also indicated that both PenCB- and MC-inducible DT-diaphorases were identical with that from the untreated rats. All three DT-diaphorases contained about 2 mol of FAD per mol of enzyme. Partial digestion of the enzymes by trypsin and subsequent analysis by HPLC revealed that the three preparations were indistinguishable. The identity among the three purified DT-diaphorases was finally confirmed by Ouchterlony immunodiffusion employing anti-serum raised against each enzyme preparation.

Amino Acids↗

Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts.

Ethylene dibromide (1,2-dibromoethane, EDB) can be activated to electrophilic species by either oxidative metabolism or conjugation with glutathione. Although conjugation is generally a route of detoxication, in this case it leads to genetic damage. The major DNA adduct has been identified as S-[2-(N7-guanyl)ethyl]glutathione, which is believed to arise via half-mustard and episulfonium ion intermediates. The adduct has a half-life of about 70 to 100 hr and does not appear to migrate to other DNA sites. Glutathione-dependent DNA damage by EDB was also demonstrated in human hepatocyte preparations. The possible relevance of this DNA adduct to genetic damage is discussed.

Animals↗

Metabolism in vivo of 3,4,3',4'-tetrachlorobiphenyl and toxicological assessment of the metabolites in rats.

1. Metabolism in vivo of 3,4,3',4'-tetrachlorobiphenyl (TCB) and toxicological assessment of the metabolites were investigated in the rat. 2. Four metabolites were isolated from faeces of rats dosed with 3,4,3',4'-TCB. Two were identified as 5-hydroxy-3,4,3',4'-TCB and a chlorine-shift metabolite, 4-hydroxy-3,5,3',4'-TCB, by comparison of melting points, chromatographic mobilities and spectral features with those of the synthetic samples. A dihydroxy-TCB and monohydroxy-trichlorobiphenyl were also indicated by mass spectrometry to be excreted in faeces as minor metabolites. 3. Faecal excretion of unchanged 3,4,3',4'-TCB, 5-hydroxy-3,4,3',4'-TCB and 4-hydroxy-3,5,3',4'-TCB was 0.8%, 19.6% and 11.6% of dose, respectively, in 5 days after i.p. injection of 3,4,3',4'-TCB at a dose of 50 mg/kg. 4. From the inability to cause the liver hypertrophy and thymus atrophy, both monohydroxy-metabolites of 3,4,3',4'-TCB are much less toxic than the parent 3,4,3',4'-TCB. In addition, these phenolic metabolites did not induce the activities of benzo[a]pyrene hydroxylase and DT-diaphorase, whereas 3,4,3',4'-TCB greatly induced these activities. These results indicated that unlike PCB congeners with phenobarbital-type inducing ability, 3,4,3',4'-TCB, a prototype of 3-methylcholanthrene-type inducers, is detoxified by metabolic hydroxylation.

Animals↗