Human immunodeficiency virus (HIV), an ethiologic agent of AIDS, belongs to lentivirus subfamily of retroviruses. In striking contrast to oncoviruses HIV does not transform cells but instead causes chronic progressive diseases. This feature is demonstrable in vitro by dramatic cytopathic effects upon virus/cell coculture. Since virus-producing cells are generally destroyed, HIV must be transmitted to other cells after replication in order to maintain the infection. However, after viral infection, AIDS requires a long period of time before becoming full-brown. The virus appears to establish latent infection and stay dormant in many cells until activation signals have been received. We found that tumor necrosis factor can activate such latent HIV and selectively kill HIV-infected cells. The mechanism of cell death was recently cleared as Apoptosis.
Methods for modifying nucleic acids and their components with permanganate and with bisulfite are reviewed, with emphasis on work developed by the author's group of investigators. N (4) Aminocytidine, a nucleoside analog obtainable on bisulfite-hydrazine modification of cytidine, is a potent mutagen, and the mechanism of its action in the mutagenesis is discussed.
By the reaction of 2-benzoylmethyl-4-methylthiazole (6) with polarized olefins (3, 4) in the presence of base (K2CO8 or NaH), the corresponding thiazolo[3, 2-α]pyridine derivatives (7, 8) were obtained, Methylsulfinylthiazolopyridine derivative (11) obtained by the reaction of 8b with m-chloroperbenzoic acid (MCPBA), easily underwent nucleophilic substitution to give the corresponding substituted compounds (10, 12).
4, 5-Diphenyl-2-ethoxypyrimidine (1), 3, 4-diphenyl-6-ethoxypyridazine (2) and 2, 3-diphenyl-5-ethoxypyrazine (3) were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. 2, 3-Diphenyl-5-ethoxypyrazine (3) exhibited significant inhibitory activity. Thus, various 5-substituted 2, 3-bis(4-methoxyphenyl)pyrazines were synthesized by the nucleophilic substitution reaction of 5-chloro-2, 3-bis(4-methoxyphenyl)pyrazine (9). In a similar manner, substituted 2, 3-bis(4-methoxyphenyl)pyridines were prepared from 2, 3-bis(4-methoxyphenyl)-6-methylsulfonylpyridine (17), which was synthesized by the cycloaddition retro Diels-Alder reaction of 5, 6-bis(4-methoxyphenyl)-3-methylsulfonyl-1, 2, 4-triazine (16) with norbornadiene. Among the compounds prepared, 6-isopropoxy-2, 3-bis(4-methoxyphenyl)-pyrazine (10f) showed the most potent inhibitory activity, which was more than the activity of anitrazafen[5, 6-bis(4-methoxyphenyl)-3-methyl-1, 2, 4-triazine].
The possibility of the biomimetic transformation of (+)-matrine N-oxide, a main alkaloid in Sophora flavescens var. angustifolia, under various oxidative conditions was examined by the use of several metallic ions. When (+)-matrine N-oxide was warmed with FeSO4, or Fe(COOH)2 in MeOH-H2O at 40°C, (-)-7, 11-didehydromatrine [(-)-leontalbinine], a minor alkaloid in the same plant, was obtained along with (+)-matrine. This selective formation of (-)-leontalbinine seems to be specific to the reaction of (+)-matrine N-oxide with ferrous reagents. In addition, the structure of the newly isolated minor lupin alkaloid from the seeds of S.flavescens. was determined as (-)-leontalbinine N-oxide from its spectral comparison with the authentic sample.
The present study was carried out to evaluate the bioequivalence between Coptidis Rhizoma and the cultured cells of Coptis japonica MAKINO var. dissecta NAKAI to compare the concentration of berberine in the rat plasma after oral administration of both aqueous extracts. The concentration of berberine in the plasma after oral administration of both extracts was determined by HPLC. It was found that the values of time required for the maximum concentration (Tmax), the maximum concentration (Cmax) and the area under the plasma-time curve (AUC24h) of berberine in the rat plasma after oral administration of both extracts were about the same. It was also found that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts and an aqueous extract of Glycyrrhizae Radix were about the same as that of individual administration of both extracts. From these results, to evaluate the bioequivalence between Coptidis Rhizoma and cultured cells, it is important that the values of Tmax, Cmax andAUC24h of berberine after oral administration of both extracts are not different, and about the same values of berberine by the combined use of both extracts and the aqueous extract of other crude drugs are required.
The variation of constituent of Microlepia marginata in the southwestern part of Kyushu was observed. According to the constituent pattern, it was divided into the following four strains; 1 : microlepin and/or 4-epimicrolepin, 2 : microlepin and/or 4-epimicrolepin and a new flavanone glycoside, 3 : a new flavanone glycoside, 4 : two new pimarane glycosides. The structures of these new compounds were respectively determined as naringenin 7-O-α-L-rhamnopyranosyl-(1→2)-(4-O-methyl)-β-D-glucoside, 3α-α-L-arabinofuranosyloxy-12α-β-D-xylopyranosyloxy-ent-pimara-8(14), 15-diene and 3α-α-L-arabinofuranosyloxy-12α-(β-D-4-O-acetylxylopyranosyloxy)-ent-pimara-8(14), 15-diene.
We described in our previous paper that the cell-free extract from Hyphomicrobium neptunium ATCC 15444 oxidized hydrogen sulfide to sulfur. We tried to purify the enzyme used for this oxidation to determine the molecular nature of this enzyme. The 40% ammonium sulfate precipitate from the supernatant of cell sonicate of H.neptunium was chromatographed on a column of Phenyl Sepharose CL-4B and its active fractions were collected. These fractions were further purified through Superose 12 and then TSK gel G3000SW column chromatographies. A protein of molecular weight about 54000 and isoelectric point pI 6.8 was isolated. However, this final protein was found to reduce its activity to less than one-tenth of those of ammonium sulfate precipitate and of the fraction from Phenyl Sepharose CL-4B column chromatography. This might be caused either by the loss of accessory component or by its requirement of low molecular factors necessary for its activation at the stage of gel filtration. The neutral isoelectric point of this enzyme could be suitable as the function of H.neptunium because its final product was S0, and it grows at neutral pH. In contrast, the final oxidative product of hydrogen sulfide by Thiobascillus is sulfric acid, and they grow at acidic pH.
We studied the disposition of cyclosporine (CyA) in 8 living related donor partial liver transplant recipients (patient A-H). CyA blood levels were determined by fluorescence polarization immunoassay with specific monoclonal antibody (m-FPIA) and fluorescence polarization immunoassay with non-specific polyclonal antibody (p-FPIA). The ratio of the blood levels of CyA determined by p-FPIA to those by m-FPIA varied significantly, because the levels determined by p-FPIA were influenced by the function of graft liver. Thus, the levels of CyA determined by p-FPIA could not be used for the adjustment of CyA dose. The CyA dose ratios [DR ; CyA blood level (mg/l)/dose (mg/kg)] of 3 in 8 patients were relatively large in 1-4 d after the transplant operation, however, it decreased within 2-5 d after the operation. CyA DR gradually increased from 5-8 d after the transplantation, and it reached to a maximum in 10-13 d in 5 patients to whom CyA was administered intravenously over 12 d after transplantation. The average ratio of DR in oral administration to that in intravenous one was about 43%. CyA bioavailability in the patient of living related partial liver transplantation was as usual as that in other organ transplant patient except for cadaveric liver transplant patients. The average DR of intravenous CyA administration in liver transplant recipients was 1.5 times larger than that in bone marrow transplant patients. CyA disposition had large inter-individual and intra-individual variation, and CyA blood level and DR varied in clinical time course at least within 1.5 month after operation. Therefore, it is necessary to measure CyA blood level frequently and to adjust CyA dose.