Microscopic origin of quantum chaos in rotational damping.
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Journal Article↗
Biomedical subjects
M Matsuo
Publications and source records attributed to M Matsuo.
A novel regioselective desulfation of polysaccharide sulfates: Specific 6-O-desulfation with N,O-bis(trimethylsilyl)acetamide.
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Carbohydrate Sequence↗
Protective effect of lipophilic derivatives of ascorbic acid on lipid peroxide-induced endothelial injury.
The protective effects of ascorbic acid and its lipophilic derivatives on the cytotoxicity of linoleic acid hydroperoxide (LOOH), a primary product of lipid peroxidation, was investigated in cultured human umbilical vein endothelial cells. When cells were incubated with ascorbic acid for 24 h before treatment with LOOH, ascorbic acid did not protect cells from oxidative damage by LOOH. Its lipophilic derivatives such as 6-O-palmitoyl,6-O-stearoyl, and 2,6-O-dipalmitoyl esters and 2-O-octadecyl ether (CV3611) had an apparent protective effect on the toxicity of LOOH. When cells were incubated in medium containing both antioxidant and LOOH, the protective effect of lipophilic derivatives became weak. An interaction between alpha-tocopherol and ascorbic acid was not observed in this system using endothelial cells. However, in the case where the cells were preincubated with alpha-tocopherol and 6-O-palmitoylascorbic acid, the ascorbic acid derivative had a synergistic effect to alpha-tocopherol in protecting against LOOH-induced damage. These results suggest that lipophilic antioxidants incorporated into cellular membranes are effective protectors against LOOH, whereas lipophobic antioxidants located outside the membrane do not have any protective effect.
Ascorbic Acid↗
Brain- and muscle-type promoters of the dystrophin gene are selected in peripheral lymphocytes and Epstein Barr virus-transformed lymphoblastoid [correction of lymphoplastoid] cells.
Promoter-specific transcripts of the dystrophin gene in peripheral lymphocytes and Epstein Barr virus-transformed lymphoblastoid cells were analysed using reverse transcription-nested polymerase chain reaction. Two DNA fragments, corresponding to the alternative first exons transcribed from either brain- or muscle-type promoters, were both amplified from cDNA prepared from normal lymphocytes and lymphoblastoid cells. The nucleotide sequences of the amplified products were 100% homologous to the 5' termini of the cDNA of brain- and muscle-type dystrophins, respectively. Neither fragment was amplified from the lymphoblastoid cells of a patient with Duchenne muscular dystrophy, who has a partial deletion involving the brain- and muscle-type promoters in the dystrophin gene. These findings showed that the brain-type as well as the muscle-type promoter of the dystrophin gene was active in lymphocytes and lymphoblastoid cells.
B-Lymphocytes↗
Aging retards spin clearance from mouse brain and food restriction prevents its age-dependent retardation.
After the nitroxyl radical 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (carbamoylPROXYL) was intraperitoneally administered to mice, the time courses of changes in the intensity of signals in L-band electron spin resonance spectra from their brains were measured. The spin clearance rate of old, ad libitum-fed mice was lower than that of young, ad libitum-fed mice. The rate of old, food-restricted mice was significantly higher than that of old, ad libitum-fed mice and was comparable to that of young, ad libitum-fed mice. The spin clearance was found to be due to the one-electron reduction of the nitroxyl radical, because a decreased spin intensity of it in serum was restored to the original level by potassium hexacyanoferrate (III) oxidation in vitro. These results suggest that reducing capacity in the cardiovascular system of mice is decreased with advancing age, and that food restriction prevents an age-dependent decrease in the reducing capacity.
Aging↗
Oxygen dependency of life-span in the nematode.
1. The mean and maximum life-spans of both wild type Caenorhabditis elegans and the mev-1(kn1) mutant, whose cytoplasmic superoxide dismutase activity level is about half of the wild type, were increased and decreased under low and high concentrations of oxygen, respectively. 2. The Gompertz component, a parameter of ageing rate, of the wild type was smaller under 1% oxygen than under 2% or more oxygen. Further, the Gompertz component of the mutant increased with an increase in oxygen concentration. 3. The oxygen-dependent modulation of life-span and ageing rate seems to be enhanced by a genetic defect of the mutant in antioxidant defence.
Animals↗
Oxygen-dependent perturbation of life span and aging rate in the nematode.
The effects of atmospheric oxygen on the life span and aging rate of the nematode Caenorhabditis elegans were examined. The mean and maximum life spans of both the wild type and mev-1(kn1) mutant, whose cytoplasmic superoxide dismutase activity level is about half of the wild type, were increased and decreased under low and high concentrations of oxygen, respectively. The Gompertz component, a parameter of aging rate, of the wild type was smaller under 1% oxygen than under 2% or more oxygen. Further, the Gompertz component of the mutant increased with an increase in oxygen concentration. These effects of oxygen on the perturbation of life span and aging rate were more pronounced in the mev-1(kn1) mutant than in the wild type. The oxygen-dependent perturbation of life span and aging rate seems to be enhanced by a genetic defect of the mutant in antioxidant defense. A 1% oxygen exposure at the early phase of life span was ineffective for life span extension in the mutant, suggesting that the effect of oxygen concentrations on life span is not secondary to the effects of development and maturation. These results show that changes in oxygen concentration perturb aging rate, and hence oxygen is involved in the specification of life span of the nematode.
Aging↗
Food restriction suppresses an age-dependent increase in the exhalation rate of pentane from rats: a longitudinal study.
Longitudinal age changes in the exhalation rates of ethane and pentane, which are used as the indices of in vivo lipid peroxidation, from rats under ad libitum feeding and food restriction were measured. The exhalation rate of ethane or pentane from old, ad libitum-fed rats is higher than that of the corresponding hydrocarbon from young, ad libitum-fed rats, as reported previously. There is no difference between the exhalation rates of each hydrocarbon from young, ad libitum-fed and food-restricted rats. However, the exhalation rate of pentane from old, food-restricted rats is significantly lower than that from old, ad libitum-fed rats, while the exhalation rate of pentane from old, food-restricted rats tends to be lower than that from old, ad libitum-fed rats. In addition, the exhalation rate of pentane from old, food-restricted rats is equivalent to that from young, ad libitum-fed rats. These results are consistent with the views that in vivo lipid peroxidation in rats is increased during aging, and that the age-dependent increase in in vivo lipid peroxidation is suppressed by food restriction.
Aging↗
Interhemispheric correlation analysis of EEGs before and after corpus callosotomy.
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Adolescent↗
Measles without rash in an infant with pertussis.
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Female↗
Insertion of a 5' truncated L1 element into the 3' end of exon 44 of the dystrophin gene resulted in skipping of the exon during splicing in a case of Duchenne muscular dystrophy.
We report here the second evidence of retrotransposition of L1, which was found inserted into the dystrophin gene of a patient, causing Duchenne muscular dystrophy (DMD). When the PCR was used to amplify a region of the dystrophin gene encompassing exon 44 from genomic DNA of two Japanese brothers with DMD, it was found to be approximately 600 bp larger than expected. Both the normal and the abnormally large products were amplified from the DNA of their mother. However, the maternal grandparents did not have the abnormal allele, and the mutation must therefore have occurred in the mother. Analysis of nucleotide sequence of the amplified product from a patient disclosed that the insertion was present zero to two bases upstream from the 3' end of exon 44 and that two to four bases of the exon sequence were deleted from the insertion site. The insertion sequence was found to be composed of 606-608 bp and to be almost identical to the inverse complement of 3' portion of the L1 retrotransposon consensus sequence. The dystrophin gene transcript from peripheral lymphocytes of one of the patients was analyzed by using reverse transcription/semi-nested PCR. The size of the amplified product encompassing exon 42 to 46 was smaller than expected. Sequencing of the amplified product disclosed that the sequence of exon 43 was directly joined to that of exon 45. Exon 44 of the transcript was thus shown to be skipped during splicing. This novel mutation of the dystrophin gene has important implications regarding retrotransposition of an active L1 element and provides a new insight into the origins of mutations in the dystrophin gene.
Adult↗
Synthesis and pharmacological properties of N-[4-[4-(1H-indol-3-yl) piperidinoalkyl]-2-thiazolyl]alkanesulfonamides as novel antiallergic agents.
A number of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanesulfonamides (8--21) were synthesized and evaluated for their preventive effects on systemic anaphylaxis in guinea pigs. Structure-activity analysis revealed that methane- and ethanesulfonamide derivatives having a one to three methylene tether between the piperidine and thiazole rings exhibited potent activity but the introduction of a substituent on the indole part reduced the activity. Administration (100 mg/kg p.o.) of the four compounds 8, 9, 12, 13, together with ketotifen, oxatomide, terfenadine and azelastine as reference compounds, to mice revealed that only compound 8 caused no significant increase of the sleeping time induced by hexobarbital. In addition, compound 8 (10 mg/kg i.v.) did not change the electroencephalogram in conscious rabbits. These results led to the selection of N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]methanesulfon amide (8, FK613) for further development as a novel antiallergic agent. Clinical evaluation of FK613 is now in progress.
Anaphylaxis↗
Studies on antiinflammatory agents. III. Synthesis and pharmacological properties of metabolites of 4'-acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide (FK3311).
We synthesized putative metabolites of 4'-acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide (FK3311, 1), a novel antiinflammatory agent, in order to confirm their structures and also to investigate their pharmacological properties. The structures of the metabolites 2-5 were confirmed by direct comparison with the synthesized authentic compounds. We employed the following tests to assess pharmacological activities: zymosan-induced prostaglandin E2 production for in vitro activity, adjuvant-induced arthritis for antiinflammatory activity, and acetic acid-induced writhing for analgesic activity. Metabolite 2 is nearly equipotent to 1 in the in vivo tests and metabolite 3 is an active metabolite with in vitro activity comparable to that of 1.
Analgesics↗
Synthesis and antiinflammatory and analgesic properties of 2-amino-1H-benzimidazole and 1,2-dihydro-2-iminocycloheptimidazole derivatives.
2-Amino-1H-benzimidazoles (3) and 1,2-dihydro-2-iminocycloheptimidazoles (4) were synthesized and evaluated for antiinflammatory and analgesic activities. The compounds in the series 3 were synthesized via phenylthioureas (6) or 2-chloro-1H-benzimidazole (12). Most of 4 were synthesized by two methods. One was the reaction of carbodiimides (14) with 2-amino-2,4,6-cycloheptatrien-1-one (method A). The other was the reaction of guanidines (15) with 2-chloro-2,4,6-cycloheptatrien-1-one (method B). Some of the compounds 3 and 4 exhibited potent antiinflammatory and analgesic activities when compared to timegadine (1) or tiaramide hydrochloride (HCl) (17). It was of interest that 1-(2-benzothiazolyl)-2-cyclohexylimino-1,2-dihydrocycloheptimid azole (4e) showed superior analgesic activity to timegadine or tiaramide HCl (ED50 = 1.7 mg/kg p.o. in the acetic acid-induced writhing test, ED30 = 14.0 mg/kg p.o. in Randall-Selitto method) in spite of no effect on prostaglandin E2 synthesis.
Analgesics↗
Studies on antiinflammatory agents. II. Synthesis and pharmacological properties of 2'-(phenylthio)methanesulfonanilides and related derivatives.
The structure of the previously reported new antiinflammatory agent (1, FK3311) was chemically modified in an attempt to find novel compounds with more potent and broader-spectrum activities. Some 2'-(phenylthio) and 2'-(phenylamino)methanesulfonanilides (2 and 3), in particular those bearing an electron-attracting substituent at the 4'-position, potently inhibited adjuvant arthritis in rats as well as collagen-induced arthritis in mice when administered orally. 4'-Carbamoyl-2'-(2,4-difluorophenylthio)methanesulfonanilide (3b), which was selected as a candidate for further development from among the compounds synthesized herein, exhibited activity in reducing arthritis in a spontaneous autoimmune disease model (MRL/lpr mice) within the dose range of 10-100 mg/kg (p.o.).
Anilides↗
Multiple mediators and mechanisms are involved in the adaptive cytoprotection provided by certain mild irritants.
We investigated the participation of prostaglandins (PG) and nitric oxide (NO) in adaptive cytoprotection using 0.6 N HCl-induced gastric lesions in the rat stomach. Indomethacin reversed the protective effect of 0.2 N HCl more strongly than that of 0.35 N HCl, both of which markedly inhibited HCl ulcer. NG-Nitro-L-arginine (L-NNA) did not affect the protective effect afforded by either 0.2 N HCl or 0.35 N HCl. Combined pretreatment with indomethacin and L-NNA did not diminish the protective action induced by 0.35 N HCl, but almost completely abolished the indomethacin-resistant protection afforded by 0.1 N NaOH. Acid mild irritant increased the gastric fluid volume concentration-dependently, whereas alkaline mild irritant had little or no effect on the volume. These results suggest that: 1) The mediators involved in adaptive cytoprotection afforded by 0.1 N NaOH may be fully ascribed to PG and NO; 2) PG is a major mediator in the protection induced by 0.2 N HCl; 3) In the case of 0.35 N HCl, the mediators remain to be determined since increased gastric fluid volume could contribute to the protection through dilution. These findings thus may indicate that multiple mediators and mechanisms are implicated in adaptive cytoprotection.
Animals↗
Effects of hydrochloric acid on the development of enterochromaffin-like (ECL) cell hyperplasia in the rat stomach induced by omeprazole.
In the present study, gastric pH was lowered by hydrochloric acid to investigate whether the cause of enterochromaffin-like (ECL) cell hyperplasia was due to the inhibition of acid secretion by omeprazole or due to the direct action of the drug. Omeprazole was given to female Crj:CD (SD) rats in a daily oral dose of 2 or 8 mg/kg for 13 weeks, and 20 ml/kg of 0.12 N HCl was further given orally to the animals 3 and 6 hours after each dosing. The animals were killed at the end of the dosing period, and the stomach was removed and weighed. The thickness of the gastric wall was measured and ECL cell count and area rate of the cells were calculated with an image analyzer. There were no effects of the treatment with HCl on stomach weight or thickness of the gastric wall, but ECL cell count and area rate of the cells decreased markedly by the treatment with HCl. Therefore, the cause of gastric ECL cell hyperplasia induced by omeprazole was suggested to be sustained high gastric pH levels.
Animals↗
Hormonal disregulation mechanism in the rat thyroid tumor induced by diniconazole.
To assess the toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diniconazole, (E)-1-(2,4-dichlorophenyl)- 4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-ol, a 3-month subacute feeding study was conducted in male Crj: CD (SD) rats by administering diniconazole in diet at concentrations of 0, 100, 1,000, or 2,000 ppm. Examinations mainly for thyroid functions were performed at Weeks 2, 4 and 13. Measurement of serum hormone levels revealed continuous decreases in serum thyroxine (T4) and free T4 levels at and above 1,000 ppm and increase in serum thyroid stimulating hormone (TSH) level at 2,000 ppm concurrently with liver weight and hepatic UDP-glucuronyltransferase (UDP-GT) increases at and above 1,000 ppm. No changes were observed in serum triiodothyronine (T3) and free T3 levels. Increase in thyroid uptake of 125I and organification of 125I in the thyroid at 2,000 ppm and thyroid follicular cell hyperplasia at and above 1,000 ppm were also observed. However, no compound-related changes were observed in autopsy and organ weight in the thyroid. Based on the above results, diniconazole induces increases in the hepatic UDP-GT activity and the thyroid hormone excretion from the liver. The increased excretion of thyroid hormones causes decrease in serum T4 and free T4 levels, triggering the feedback mechanism of the pituitary gland, promotion of TSH release from the pituitary gland and increase in serum TSH level. The increased serum TSH level probably leads to increased 125I uptake of thyroid and thyroid follicular cell hyperplasia. Thus, the thyroid tumorigenesis in rats treated with diniconazole is due to the secondary overstimulant effect on the thyroid by increased serum TSH level. The toxicological significance in humans is extremely low and it is unlikely that diniconazole would increase thyroid tumor in humans even if diniconazole were to alter normal thyroid hormone level in humans.
Animals↗