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Biomedical subjects

A Ota

Publications and source records attributed to A Ota.

At least 73 records · Page 4Linked to original sources
PubMed1993

Synthesis and pharmacological activities of novel cyclic disulfide and cyclic sulfide derivatives as hepatoprotective agents.

In order to search for anti-hepatitis drugs, we synthesized a series of eight- and nine-membered cyclic disulfides (1) and six- and seven-membered cyclic sulfides (2) and evaluated them for ability to reduce mortality in the model of acute hepatic failure induced by Propionibacterium acnes-lipopolysaccharide in mice. Compounds 1 were synthesized by oxidative cyclization of the corresponding dithiol derivatives (3) with diethyl bromomalonate or iodine. Compounds 2 were prepared from the methyl esters of 1 by desulfurization with tris(diethylamino)phosphine followed by deprotection. Compounds 1 were generally found to be more active than compounds 2. Compound 1b (SA3443) was found to exhibit potent protective activity. The synthesis and structure-activity relationships are discussed.

Animals↗
PubMed1993

Synthesis of thiazolidine-2-thione derivatives and evaluation of their hepatoprotective effects.

A series of N-(mercaptoalkyl)thiazolidine-2-thiones and their derivatives were synthesized and evaluated for hepatoprotective activities against Propionibacterium acnes-lipopolysaccharide (P. acnes-LPS)-induced liver injury in mice and in vitro lipid peroxide (LPO) formation in rat liver microsomes. Reaction of N-(p-methoxybenzylthioalkyl)cysteine methyl ester (11) with 1,1'-thiocarbonyldiimidazole followed by deprotection gave the corresponding thiazolidine-2-thione derivatives. Among the compounds synthesized, 1a and 2a showed the most potent hepatoprotective activities against P. acnes-LPS-induced liver injury. Compounds 1a-f and 4 inhibited LPO formation in vitro. Compounds 1a and 2a were chosen for further pharmacological evaluations.

Animals↗
PubMed1993

A pH- and Co(2+)-dependent dipeptidase from Escherichia coli.

The pH dependency of a Co(2+)-dependent dipeptidase from Escherichia coli AJ005, a peptidase-deficient mutant strain K12, was examined with purified dipeptidase, which was about 106-fold in specific activity. The peptidase had a very sharp optimal pH at 7.5. It is suggested that the peptidase plays an important role in the process of cell division and growth.

Cobalt↗
PubMed1993

Effect of NaCl on the growth and morphology of Saccharomycopsis fibuligera.

The effect of NaCl on mycelial growth of Saccharomycopsis fibuligera was examined. Cells were able to grow in medium containing 1 M or 2 M NaCl after adaptation to the salt under standing culture conditions. It took more time to adapt to 2 M NaCl than to 1 M NaCl. Hollow-looking regions in the cells increased during incubation for 20 days in medium without salt, but diminished in cells incubated in medium containing either of the two concentrations of NaCl. The mycelial cells incubated in the medium containing salt were slimmer, and bubble shaped, and malformed cells were observed. The extent of the change was greater in 2 M NaCl than that in 1 M NaCl. NaCl protected cells from leaking, and produced malformed cells.

Saccharomycopsis↗
PubMed1993

Glucose uptake in the yeast Saccharomyces cerevisiae.

The glucose uptake of Saccharomyces cerevisiae cells in sporulation medium for 3 h was higher than that of cells in 5.5 mM glucose medium. This difference might be due to the change in cell structure which is necessary for the sporulation process. In both types of cells, the glucose uptake activity became higher as the glucose concentration of the medium decreased.

Culture Media↗
PubMed1992

Inducibility of protein-reactive antibodies by peptide immunization: comparison of three epitope peptides of hen egg-white lysozyme.

Three epitope peptides of hen egg-white lysozyme (HEL) were tested for ability to induce antibodies reactive with native HEL. Each peptide was coupled to bovine gamma-globulin (B gamma G) and 4 rabbits were immunized with each peptide-B gamma G conjugate in complete Freund's adjuvant. The mean association constants (K0s) of HEL-reactive antibodies (HEL-R-Abs) from each immunizing group to [3H]acetyl HEL or to [3H]acetyl-peptide were measured in solution by a double antibody method. Only peptide loop I.II (sequences 57-107 containing Cys64-Cys80 and Cys76-Cys94) induced high-affinity antibodies to HEL (K0 = 2.5 x 10(6)-2.3 x 10(7) M-1) among the three epitope peptides tested. The association constants of antipeptide loop I.II to [3H]acetyl peptide loop I.II were always one to two orders of magnitude higher than those to HEL. In addition, 50 to 80% of the anti-peptide loop I.II antibodies were reactive with native HEL. The specificity of anti-peptide loop I.II was directed to a conformational feature of the peptide rather than to native HEL and reactivity of the antibody to HEL was interpreted as a kind of cross-reaction. The HEL-R-Abs from anti-Ploop I.II antisera also manifested neutralizing activities against the enzymic activity of HEL when Micrococcus luteus was used as the substrate.

Animals↗
PubMed1992

Serum immunoglobulin and complement C3 levels in workers exposed to lead.

Serum immunoglobulin and complement C3 levels were measured in workers exposed to lead at a secondary lead refinery and a solder factory. In the first survey, significant correlations were found between blood lead and IgA with a correlation coefficient of 0.296, and between blood lead and IgE with a correlation coefficient of 0.314. No other significant correlations were found among the indicators of lead exposure and humoral immunity. In the second survey, no significant correlations were found between blood lead and IgG and IgA. A significantly higher number of subjects with IgE of more than 400 IU/ml was found in the group with blood lead of more than 60 micrograms/100 g.

Adolescent↗
PubMed1991

Reduction of enzymatic activity of tyrosine hydroxylase by a heterocyclic amine, 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (Trp-P-1), was due to reduced affinity to a cofactor biopterin.

A carcinogenic, food-derived heterocyclic amine, 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (Trp-P-1) was found to reduce the enzymatic activity of tyrosine hydroxylase in clonal rat pheochromocytoma PC12h cells, by its supplement to the culture medium. The reduction was observed with 10 microM Trp-P-1, and at this concentration the amount of cell protein and the activity of a non-specific enzyme, beta-galactosidase, were not affected. The mechanism of the reduction of the enzyme activity was clarified by kinetical studies. The amine reduced the affinity of tyrosine hydroxylase to a cofactor, tetrahydrobiopterin. The alteration of the enzymatic properties by Trp-P-1 was discussed in relation to the possible effect on catecholamine metabolism in the brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

The regulation of cytosolic Ca2+ concentration in a mammalian cell.

The assumptions governing the regulation of free Ca2+ in a mammalian cell are presented. There is a possibility that mitochondria, microsomes and plasma membrane play a major role, by regulation of the very low concentration of free Ca2+ in cytosol, as the signal to biochemical activities. The possibility of the loss of very high-affinity Ca2(+)-binding and the number of its sites by preparation has not been taken into consideration in previous hypotheses.

Animals↗
PubMed1990

Synthesis and Ca2+ antagonistic activity of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H- 1,4-benzothiazines.

As an extension of the previous investigation (J. Med. Chem. 1988, 31, 919), we synthesized a series of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H- 1,4-benzothiazines (3) and evaluated their Ca2+ antagonistic activities. Ca2+ antagonistic activity was measured with isolated depolarized guinea pig taenia cecum. On the basis of their potent Ca2+ antagonistic activity, six benzothiazines were selected and further evaluated for their vasocardioselectivity. Among these six compounds, the key compound 15 [3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[3,4- (methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo- 2H-1,4-benzothiazine hydrogen fumarate] was recognized as having the lowest cardioselectivity. Following optical resolution, the absolute configuration of the compound's optically active enantiomer was determined by means of X-ray crystallography of a synthetic precursor (+)-4a. The Ca2+ antagonistic activity of 15 was found to reside primarily in (+)-15 (which was about 7 times more potent than (-)-15). The in vitro study showed that (+)-15 had a low cardioselectivity compared to verapamil and diltiazem. This result suggests that (+)-15 would exhibit less adverse effects due to cardiac inhibition than diltiazem and verapamil in therapeutic use.

Animals↗
PubMed1990

Synthesis and calcium antagonistic activity of (+)-(R)- and (-)-(S)-3-acetyl-2-[5-methoxy-2-[4-[N-methyl-N-(3,4,5- trimethoxyphenethyl)amino]butoxy]phenyl]benzothiazoline hydrochloride.

SA2572 ((+)-1), 3-acetyl-2-[5-methoxy-2-[4-[N-methyl-N-(3,4,5-trimethoxyphenethyl) amino] butoxy]phenyl]-benzothiazoline hydrochloride is a newly synthesized Ca2+ antagonist having a inhibitory effect on the fast Na+ inward channel. In order to clarify the absolute configurations and the pharmacological properties of both enantiomers, compounds ((+)-1 and (-)-1) were synthesized. The configurations of these compounds were assigned on the basis of an X-ray crystallographic analysis of synthetic precursor (5). The in vitro Ca2+ channel blocking activities of (+)-1 and (-)-1 were evaluated in terms of the inhibitory activities on depolarization-induced contraction of guinea pig taenia cecum and rabbit aorta. The in vivo efficacy of the enantiomers was evaluated with their hypotensive effects in spontaneously hypertensive rats. Compound (-)-1 showed more potent Ca2+ antagonistic activities on guinea pig taenia cecum and rabbit aorta and the hypotensive effect than those activities of (+)-1. In the electrophysiological study of Langendorff perfused rabbit hearts, compound (+)-1 showed more potent inhibitory effect on the fast Na+ inward channel than that of compound (-)-1, and an approximately equal potent inhibitory effect on the slow Ca2+ inward channel as compared with compound (-)-1. Stereoselectivity of the pharmacological activity was found.

Animals↗
PubMed1990

Tetralysine endopeptidase activity in a cell-free extract of Escherichia coli AJ005.

The activity of tetralysine endopeptidase was examined with cell-free extracts of Escherichia coli AJ005. The peptidase activity of cell-free extracts increased as the concentration became higher, and reached its maximum at about 30 mg protein/ml. The peptidase activity was stable and maintained most of its activity throughout a 5 h period of observation during incubation at 35 degrees C.

Endopeptidases↗
PubMed1990

Activation of idiotype-specific CD4+ T-cell line: cellular processing of exogenous self-immunoglobulin.

An idiotype (Id)-specific long-term cultured T-cell line has been generated from BALB/c mice immunized with M315 (alpha, lambda 2). The cell line comprises both CD3+ and CD4+ but CD8- cells. The T-cell line is stimulated in a class II major histocompatibility complex (MHC)-restricted manner, and is capable of producing interleukin-2 (IL-2) in response to the Id along with Iad-bearing antigen-presenting cells (APC). Fine Id specificity analysis has shown that changes in amino acid residues, Phe-94, Arg-95 and Asn-96, located on the VL-315, resulting from a somatic mutation mechanism of the mouse V lambda 2 gene, contribute to the T-cell activation. Pretreatment of APC with either glutaraldehyde or paraformaldehyde prevented both Fv-315 and VL-315 from triggering the T cells. This suggested that further processing of VL is required for T-cell activation. To clarify this point, we have generated a synthetic peptide, designated P18, which spans residues 91-108 of VL-315. In sharp contrast to VL, prefixed APC were capable of presenting P18 to stimulate the T-cell line to induce IL-2.

Animals↗
PubMed1989

Insulin and IGF-I receptors in neuroblastoma cells: increases in mRNA and binding produced by glyburide.

Insulin and IGF-I binding to neuroblastoma cells (SK-N-MC) was increased by 13% and 7% respectively following a 24hr, incubation with the sulphonylurea glyburide. This increase in binding was associated with increased steady-state levels of insulin receptor and IGF-I receptor mRNA levels. Though insulin and IGF-I both stimulate glucose uptake into these cells, the increased binding following glyburide treatment was not associated with any change in glucose uptake.

Deoxyglucose↗
PubMed1988

Insulin-like growth factor I receptors on mouse neuroblastoma cells. Two beta subunits are derived from differences in glycosylation.

We have characterized receptors for the insulin-like growth factor (IGF-I) on the mouse neuroblastoma cell line N18 as well as NG108, the hybrid cell line of N18 and rat glioma (C6). In this cell-free system, IGF-I and insulin stimulated the phosphorylation of 95-kDa and 105-kDa proteins. Using appropriate antibodies we were able to demonstrate that the IGF-I receptor beta subunit has two subtypes of 95 kDa and 105 kDa. On the other hand, insulin receptor beta subunit is a separate single 95-kDa protein. Enzymatic digestion of IGF-I receptor beta subunit subtypes by glycopeptidase F resulted in similar molecular masses (84 kDa and 86 kDa) on SDS-PAGE, which suggests that the difference in molecular masses between two subtypes is attributable to the differences in N-linked complex-type carbohydrate chains on the extracellular domain of beta subunits. This conclusion is further supported by peptides of similar molecular mass following staphylococcal V8 protease digestion. Analysis of IGF-I receptor beta subunit subtypes in these cells may provide insights into the mechanism of action of IGF-I on neural tissues.

Animals↗