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Biomedical subjects

F Kanai

Publications and source records attributed to F Kanai.

At least 73 records · Page 4Linked to original sources

A cluster of four Sp1 binding sites required for efficient expression of the human insulin receptor gene.

Fragments of 5'-flanking sequences of the human insulin receptor gene were analyzed in transient expression assays after transfection of cell lines with expression assays after transfection of cell lines with an improved low background chloramphenicol acetyl-transferase vector system pSVOOCAT (Araki, E., Shimada, F., Shichiri, M., Mori, M., and Ebina, Y. (1988) Nucleic Acids Res. 16, 1627). Transfection of chimeric chloramphenicol acetyltransferase plasmids containing various deletions and insertions of the promoter of HIR gene into CHO and COS cells indicated that the region between -629 and -1 (initiator ATG is +1) is sufficient for maximal promoter activity. The DNA element of the cluster of four G-C boxes (-593 to -618) enhanced the transcription, examined by the low background pSVOOCAT vector system in vivo. DNase I footprinting and gel retardation experiments using partially purified LacZ-Sp1 hybrid proteins showed that the transcription factor Sp1 can bind to the cluster of the four G-C boxes of the promoter. Thus, the efficient expression of the human insulin receptor gene possibly requires the binding of transcriptional factor Sp1 to four G-C boxes located -593 to -618 base pairs upstream of the ATG translation initiation codon.

Animals↗

Effect of oral adsorbent on blood metabolites in hepatic failure dogs.

AST-120 is a specially synthesized carbonaceous adsorbent for oral use. It mainly adsorbs low to middle molecules in the alimentary tract. In the present study, AST-120 was administered to hepatic failure dogs, and blood metabolites were analyzed by high performance liquid chromatography (HPLC). Thirty adult mongrel dogs underwent posta-cavae (P-C) shunts with 40% and 70% hepatectomies. They were divided into two groups, the AST group (n = 19) and control group (n = 11). The AST group received about 0.5 g/kg of the adsorbent intermittently with diet after the operation. The control group was fed the ordinary diet. Body weight, blood ammonia, plasma bile acids were measured, and blood metabolites were analyzed by the multi-column HPLC system. P-C shunt dogs with 70% hepatotectomies died within three months showing about 40-50% body weight loss. HPLC analysis of their plasma showed some specific peaks for middle molecules, about 3000-5000 daltons. After administration of the adsorbent, these peaks were not detected, so it was considered that these substances had been adsorbed.

Administration, Oral↗

Plasma collection using nafamostat mesilate and dipyridamole as an anticoagulant.

Nafamostat mesilate (FUT-175) is a strong protease inhibitor and is used as an anticoagulant in extracorporeal circulation. In the present study, we administered FUT and dipyridamole as anticoagulants during donor plasmapheresis, and the additional effect of dipyridamole was examined. In dogs weighing about 15 Kg, donor plasmapheresis was performed using a cellulose triacetate membrane plasmaseparator (PEX-15, Nipro), and 300 ml of filtrated plasma was obtained within 30 minutes. These dogs were divided into two groups, 50 mg/h of FUT alone was infused (group A, n = 10), and the same dose of FUT and 25 mg/h of dipyridamole were infused (group B, n = 5) during plasmapheresis. Changes of the coagulation system, blood cell counts and complement system were investigated. In clinical cases, an artificial liver support therapy using FUT as an anticoagulant was performed on 8 patients with acute liver failure, and blood compatibility was examined. In dogs, RBC counts and hematocrits were almost stable, but WBC counts were decreased to about 70% of the previous value. Platelets counts were about 60% and 80% of the previous value, in group A and group B, respectively, at the end of the plasmapheresis (P less than 0.01). Clotting factor VII was diminished to about 20% and 35% of the previous value in group A and B, respectively. In clinical cases, all patients received the plasma exchange combined with hemodialysis using FUT as an anticoagulant, and no distinct side effect was observed during plasma exchange.

Adult↗

Vanoxonin, a new inhibitor of thymidylate synthetase. II. Structure determination and total synthesis.

Acid hydrolysis of vanoxonin yielded one mol each of 2,3-dihydroxybenzoic acid, L-threonine, L-N omega-hydroxyornithine. Presence of acetyl group in vanoxonin was suggested by the 1H NMR. Periodate oxidation of vanoxonin liberated one mol of acetic acid suggesting that the acetyl group bound to the omega-nitrogen of N omega-hydroxyornithine. The sequence of three components was determined to be L-N-(2,3-dihydroxybenzoyl)threonyl-L-(N omega-acetyl-N omega-hydroxy)ornithine by mass spectrometric analysis. This structure was confirmed by the total synthesis of vanoxonin.

Dipeptides↗

Vanoxonin, a new inhibitor of thymidylate synthetase. III. Inhibition of thymidylate synthetase by vanoxonin-vanadium complex.

Quinquevalent vanadium complex with two mol of vanoxonin ligated by the two catechols was shown to be the active structure for inhibition of thymidylate synthetase. The catechol group of vanoxonin as the essential moiety for the inhibition of enzyme was further confirmed by studies of structure-activity relationships using the enzyme obtained from Ehrlich ascites carcinoma cells of mice. Vanoxonin-vanadium complex showed competitive inhibition with respect to deoxyuridylic acid but uncompetitive to 5,10-methylenetetrahydrofolate.

Dipeptides↗

[Artificial liver].

An artificial liver should in fact be called an artificial liver assist device or system because at this point in its development it is unable to prolong the life of an ahepatic animal, whereas, an artificial heart or an artificial kidney enables the animal to live without a heart or kidneys for a long period of time. The hepatic assist devices are classified into three types: Artificial (charcoal hemoperfusion, PAN membrane dialysis or filtration); biological (baboon liver perfusion, cross dialysis between pig liver and patients systemic circulation); and hybrid (combined form of artificial and biological). Our hepatic support system is composed of a membrane plasma separator, blood and plasma pumps, hemodialyzer and controller. Using this system, the patients plasma is replaced with fresh donor plasma in amount of 5,000 ml daily. This procedure are taken place in the intensive care unit, until the patient recovers consciousness or his cerebral death is confirmed. A national survey of the patients with fulminant hepatic failure, revealed that the survival rate of the patients treated with plasma exchange was 34.1% (15/45), while that of the patient untreated with plasma exchange was 14.3% (5/35). The difference is statistically significant. However, plasma exchange requires a large amount of fresh plasma which occasionally induce hepatitis or allergy and its detoxication of the patients plasma was insufficient in severe cases. To overcome these problems, specific adsorpton of hepatic toxins and a combined therapy of blood purification with plasma exchange will be studied further.

Adult↗

[A case of alpha-fetoprotein-producing gastric carcinoma with unique macroscopical configuration].

A gastric carcinoma with unique macroscopical configuration was resected from a 63-year-old male patient. Serum level of alpha-fetoprotein (AFP) was markedly elevated (19,000 ng/ml), and AFP-positive cells were found in the carcinomatous tissues. The cytoplasm of the carcinoma cells appeared to be watery-clear by light microscopy, however, electron microscopy revealed abundant amorphous substances in their cytoplasmic matrix. The unique macroscopical configuration of the gastric carcinoma may reflect its biological resemblance to hepatocellular carcinoma. Such a case may be rare, but AFP production, per se, seems to be a rather universal phenomenon of gastric carcinomas.

Carcinoma↗