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Biomedical subjects

M Takasugi

Publications and source records attributed to M Takasugi.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of diltiazem on suppression and regression of experimental atherosclerosis.

The effects of diltiazem (a calcium antagonist) on the suppression and regression of atherosclerosis were studied. Thirty-one rabbits were fed a 1% cholesterol (atherogenic) diet together with saline (n = 22) or diltiazem (n = 9) injections. After 10 weeks, seven rabbits that received saline and nine rabbits that received diltiazem were killed. The remaining 15 saline-treated rabbits were then put on a standard (regression) diet for the next 15 weeks with saline (n = 7) or diltiazem (n = 8) injections. Sixteen rabbits given a standard diet were used as controls. At 5 and 10 weeks, the plasma LDL cholesterol level in rabbits on the atherogenic diet with diltiazem was significantly lower than in those on the atherogenic diet with saline. The aortic total cholesterol, esterified cholesterol and calcium contents were also significantly lower in rabbits on the atherogenic diet with diltiazem. After 25 weeks (15 weeks on the regression diet), the differences in aortic total cholesterol and calcium contents between the two groups on the regression diet were not significant; however, the aortic esterified cholesterol content was significantly lower in the regression diet with diltiazem. The results suggest that diltiazem has a favourable effect both on regression and on suppression of atherosclerosis.

Animals↗
PubMed1987

Double helices with parallel strands are formed by nuclease-resistant oligo-[alpha]-deoxynucleotides and oligo-[alpha]-deoxynucleotides covalently linked to an intercalating agent with complementary oligo-[beta]-deoxynucleotides.

Oligo-[alpha]-thymidylates have been synthesized and covalently linked to an intercalating agent (an acridine derivative) and/or to a p-azidophenacyl group. These molecules bind to a complementary oligo-[beta]-deoxynucleotide. A strong stabilization is obtained by covalent attachment of the acridine derivative at the 5' end of the oligo-[alpha]-deoxynucleotide. Upon excitation of the p-azidophenacyl group with ultraviolet light, the oligo-[alpha]-thymidylate is crosslinked to its target sequence. These crosslinks are converted to chain breaks under alkaline conditions. This allows an unambiguous assignment of the orientation of the two oligonucleotide chains. As expected, beta-beta hybrids have an antiparallel orientation, whereas the two chains of alpha-beta hybrids are parallel independently of whether an intercalating agent is covalently linked to the alpha-oligo-nucleotide. Oligo-[alpha]-thymidylates covalently linked to an acridine derivative are highly resistant to endo- and exonucleases. Therefore, they could be used as anti-messengers to block mRNA translation in vivo under conditions where oligo-[beta]-deoxynucleotides are usually hydrolysed.

Exonucleases↗
PubMed1987

Oligo(alpha-deoxynucleotide)s covalently linked to intercalating agents: differential binding to ribo- and deoxyribopolynucleotides and stability towards nuclease digestion.

An octathymidylate was synthesized with the alpha anomer of thymidine instead of the naturally occurring beta anomer. This oligonucleotide binds to complementary sequences containing beta-nucleosides. Binding to ribose-containing oligomers and polymers is much stronger than binding to deoxyribose-containing analogs. A derivative of acridine (9-amino-6-chloro-2-methoxyacridine) was covalently attached either to the 5' phosphate or to the 3' phosphate of the alpha-octathymidylate. A pentamethylene linker was used to bridge the phosphate group and the 9-amino group of the acridine derivative. In both cases the complexes with the complementary sequences were strongly stabilized due to the additional binding energy provided by intercalation of the acridine ring within the miniduplex structure formed by the oligonucleotide with its target sequence. The acridine-substituted alpha-oligothymidylates did not lose their discrimination between ribose and deoxyribose-containing complementary sequences. The alpha-oligothymidylates were much more resistant towards endonucleases than their beta analogs, independently of whether they were linked to the acridine derivative. Acridine substitution provided additional protection against the corresponding exonucleases. alpha-Oligodeoxynucleotides covalently linked or not to intercalating agents represent families of molecules that open possibilities to block mRNA translation or viral RNA expression in vitro and in vivo.

Aminoacridines↗
PubMed1987

Nodular regenerative hyperplasia of the liver associated with idiopathic membranous glomerulonephritis.

Nodular regenerative hyperplasia of the liver was found in a 67-yr-old man who had been suffering from nephrotic syndrome for years. Main clinical symptoms and signs were edema, proteinuria, hypertension, and abnormal studies of electrocardiogram. His renal disease had been relatively well controlled by administration of corticosteroids, but he died suddenly on March 12, 1986. Autopsy revealed fresh and old myocardial infarct and membranous glomerulonephritis. The liver weighed 1530 g and showed a diffuse nodular configuration except for in the area of Zahn's red infarct. Fibrosis was minimal in most areas, and each nodule was circumscribed by compressed atrophic parenchyma. However, this case was unusual compared to most cases of nodular regenerative hyperplasia because there was prominent fibrosis in the perihilar portion. Paucity of interlobular arterial branches was confirmed by a crude morphometry. We describe herein this somewhat unusual nodular regenerative hyperplasia case with some discussion concerning the histogenesis.

Aged↗
PubMed1986

An enzymatic method for the synthesis of [14C]pyridoxal 5'-phosphate from [14C]pyridoxine.

A new enzymatic method for the synthesis of [14C]pyridoxal 5'-phosphate is presented. [14C]Pyridoxal 5'-phosphate was synthesized from [14C]pyridoxine through the successive actions of pyridoxal kinase and pyridoxamine 5'-phosphate oxidase in a reaction mixture containing ATP, [14C]pyridoxine, and both enzymes. [14C]Pyridoxal 5'-phosphate was isolated by omega-aminohexyl-Sepharose 6B column chromatography. The overall yield of the product was more than 60%, starting from 550 nmol of [14C]pyridoxine. The radiochemical purity of the products, as determined by thin-layer and ion-exchange chromatography, was greater than 98%.

Aspartate Aminotransferases↗
PubMed1986

Autopsy findings of the coronary arteries of variant angina with Raynaud's phenomenon of the tongue.

A 42 year old man with variant angina occasionally associated with syncopal attacks died of acute myocardial infarction 17 months after the onset of angina. Prior to the onset of variant angina, he had Raynaud's phenomenon of the tongue for 2 years. Both Valsalva maneuver and hyperventilation could repeatedly provoke chest pain and ST segment elevation in leads II, III and aVF. The infusion of prostaglandin E1 at a rate of 0.05 microgram/kg/min, was able to prevent the attack of variant angina induced by these maneuvers. Although coronary angiography performed 15 months prior to death revealed no organic lesions except for complete spastic occlusion at segment 1 following intravenous ergonovine, autopsy revealed marked intimal proliferation and accumulation of abundant glycosaminoglycans in three coronary vessels, as well as in small and muscular arteries of other organs. This suggests that a rapid systemic progression of narrowing due to proliferation of the intima might occur in some cases of variant angina.

Adult↗
PubMed1985

Effects of nifedipine on platelet function.

Effects of nifedipine on platelet aggregation were studied both in vitro and in vivo. From in vitro experiments, nifedipine inhibited platelet aggregation in a dose-dependent manner. The inhibition by nifedipine (final concentration 10 micrograms/ml) on epinephrine-induced and collagen-induced platelet aggregation was more than 90%, greater than that on adenosine diphosphate (ADP)-induced aggregation. The consumption ratio of small platelets (less than or equal to 6.4 fL) was higher than that of large platelets (greater than 6.4 fL), suggesting that nifedipine inhibits the aggregation of large platelets more effectively. Changes in the effects of nifedipine on platelet aggregation associated with exercise were also studied in six healthy volunteers. While platelet aggregability increased after exercise without administration of nifedipine, it was inhibited 90 minutes after the drug's administration (10 mg). The inhibition of collagen-induced and ADP-induced (2 microM) aggregation by nifedipine was particularly significant.

Adenosine Diphosphate↗
PubMed1984

Platelet aggregation in variant angina: its relation to plasma catecholamines.

We concurrently measured plasma catecholamine levels and platelet aggregation in patients with variant angina, effort angina and old myocardial infarction. Platelet aggregability was lower in variant angina than in effort angina and old myocardial infarction. Plasma concentrations of epinephrine and norepinephrine in the variant angina group showed higher values than those in the effort angina group and the old myocardial infarction group. Moreover, there was a statistically significant negative correlation between plasma catecholamine concentration and ADP-induced platelet aggregation. These findings suggest that the lower platelet aggregation is related to the higher concentration of plasma catecholamine in variant angina.

Adenosine Diphosphate↗
PubMed1983

Excitation energy transfer from tryptophan residues of peptides and intrinsic proteins to diphenylhexatriene in phospholipid vesicles and biological membranes.

An efficient excitation energy transfer from tryptophan residues of intrinsic membrane proteins to an extrinsic fluorescent probe (diphenylhexatriene) has been demonstrated in rat erythrocyte ghosts. To correlate this transfer with the localization of the probe, a model system has been investigated. It consists of peptides containing lysine and tryptophan residues bound to negatively charged phosphatidylserine vesicles. Absorption and fluorescence spectroscopies were used to follow peptide binding and diphenylhexatriene incorporation. Peptide binding is accompanied by a blue shift of the tryptophan fluorescence together with an increase of the quantum yield and of the fluorescence decay time. An experimental Föster critical distance value of 4.0 nm was found for energy transfer from tryptophan residues of peptides to diphenylhexatriene which approaches the range of calculated values (3.1-3.7 nm) using a two-dimensional model. These results demonstrate that efficient energy transfer can occur from tryptophan residues of intrinsic proteins to diphenylhexatriene without any interaction between diphenylhexatriene and proteins in biological membranes.

Animals↗
PubMed1983

Immune function in aging atomic bomb survivors residing in the United States.

Immunologic parameters were studied among survivors of the 1945 atomic bombs who now reside in the United States. Of all known survivors living in the U.S., about 40% (n = 189) participated in this study. Of those survivors on whom radiation exposure information was available (n = 168), 96% were exposed to less than 50 rad at the time of the bomb (ATB). Survivors were divided into two groups; those exposed to varying low doses of radiation (S+ group, exposed at less than or equal to 2500 m from the hypocenter) were compared with those exposed to "O rad" (S0 group, exposed at greater than 2500 m from the hypocenter). Of the former group, 92% were exposed to less than 100 rad and 89% to less than 50 rad ATB. Cellular immune responses, including natural cell-mediated cytotoxicity (NCMC), interferon production, and the mitogenic response to PHA, tended to be higher among S+ individuals, although only the difference for NCMC was statistically significant. This was suggestive of a trend which was consistent with the higher serum interferon levels and lower frequencies of detectable immune complexes and antimitochondrial antibodies among the S+ group, although these differences were not statistically significant. Other immunologic parameters which showed no trend included frequency of antinuclear antibodies, rheumatoid factor, levels of serum immunoglobulins, levels of isoantibodies and heteroantibodies, and the magnitude of the mixed lymphocyte reaction.

Adolescent↗