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Biomedical subjects

M Kitazawa

Publications and source records attributed to M Kitazawa.

At least 37 records · Page 2Linked to original sources

Reversed circadian blood pressure rhythm is associated with occurrences of both fatal and nonfatal vascular events in NIDDM subjects.

To assess the significance of reversed circadian blood pressure (BP) rhythms as a predictive factor of vascular events in NIDDM, vital status after an average 4-year follow-up was determined in 325 NIDDM subjects in whom the circadian BP profile had been monitored between 1988 and 1996. Circadian BP rhythm was analyzed by the COSINOR (a compound word for cosine and vector) method, as previously described. After exclusion of 37 dropped-out subjects, 288 were recruited to the further analysis, of which 201 had a normal circadian BP rhythm (group N) and the remaining 87 had a reversed one (group R). There was no difference in sex, HbA1c, the prevalence of smokers, serum lipids, or serum electrolytes between groups N and R at baseline, whereas age, the prevalence of hypertension, serum creatinine, and diabetic complications were more pronounced in group R than in group N. During the follow-up period (which averaged 52 months in group N and 36 months in group R), fatal and nonfatal vascular (cerebrovascular, cardiovascular, peripheral vascular arteries, and retinal artery) events occurred in 20 subjects in group N and 56 in group R. Unadjusted survival times and event-free times were estimated by the Kaplan-Meier product-limit method, and there was a significant difference in both unadjusted survival and event-free survival rates between groups N and R (P < 0.001 each; log-rank test). The Cox proportional-hazards model adjusted for age, sex, circadian BP pattern, duration of diabetes, therapy for diabetes, various diabetic complications, and hypertension demonstrated that circadian BP pattern and age exhibited significant, high adjusted relative risks for fatal events, and that diabetic nephropathy, postural hypotension, and hypertension as well as circadian BP pattern exhibited significant, high adjusted relative risks with respect to the occurrence of various nonfatal vascular events. These results suggest that reversed circadian BP rhythm is associated with occurrences of both fatal and nonfatal vascular events in NIDDM subjects.

Blood Pressure↗

Extracellular matrix remodeling in coxsackievirus B3 myocarditis.

The connective tissue abnormality in relation to T lymphocytes was investigated in murine myocarditis. Inbred BALB/c-nu/+ (euthymic and normal T cell function) and BALB/c-nu/nu (athymic and T cell deficient) mice were inoculated with coxsackievirus B3 (CB3). Hearts were stained with hematoxylin-eosin, Malloryazan, and silver impregnation, for reticulin fiber abnormalities, and T lymphocyte subsets. In BALB/c-nu/+ mice, active myocardial necrosis appeared parallel with T lymphocyte infiltrates, that is, it was absent on day 0, increased until 14 days, and then decreased with time. In contrast, the abnormal reticulin fiber architecture and interstitial fibrosis increased with time until 60 days, when ventricular remodeling was noted. In the hearts of BALB/c-nu/nu mice, although minimal myocardial necrosis associated with infiltrating immature T lymphocytes was noted earlier, subsequent interstitial fibrosis and reticulin fiber abnormalities were not documented later. The abnormal reticulin fiber architecture seen in BALB/c-nu/+ mice may contribute to the extracellular matrix remodeling in murine CB3 myocarditis in which dilated cardiomyopathy develops later.

Animals↗

Enhancement of potassium-, and angiotensin II-stimulated aldosterone production by the calcium chelator EGTA in bovine adrenal glomerulosa cells in vitro.

The present study was designed to assess the effect of the calcium chelator EGTA (ethylenglycolbis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; 1.0 mM) on potassium (8 mM)- and angiotensin II (AII; 10 nM)-stimulated aldosterone production in bovine adrenal glomerulosa cells in vitro. The combined administration of EGTA and potassium, or of EGTA and AII, yielded a significant increase in the levels of aldosterone production. The net increment in aldosterone production after the combined administration of EGTA and potassium, or that after the combined administration of EGTA and AII was also significantly higher than the sum of that evoked by EGTA and potassium alone, or the sum of that evoked by EGTA and AII alone, respectively. At similar concentrations of extracellular ionized calcium ([Ca2+]out) or magnesium, the levels of agonist-stimulated aldosterone production were markedly elevated by the administration of EGTA. These results indicate that lowering [Ca2+]out concentrations with EGTA enhances potassium- and AII-stimulated aldosterone production in bovine adrenal glomerulosa cells in vitro. This enhancement may be predominantly due to another effect of EGTA, in addition to the stimulation of calcium entry into the cells.

Aldosterone↗

Interactions between vitamin E homologues and ascorbate free radicals in murine skin homogenates irradiated with ultraviolet light.

The mechanism of oxidation of ascorbic acid in mouse skin homogenates by UV light was investigated by measuring ascorbate free radical formation using electron spin resonance signal formation. Addition of vitamin E (alpha-tocopherol or alpha-tocotrienol) had no effect, whereas short-chain homologues (2,5,7,8-tetramethyl-6-hydroxychroman-2-carboxylic acid [Trolox] and 2,2,5,7,8-pentamethyl-6-hydroxychromane [PMC]) accelerated ascorbate oxidation. The similar hydrophilicity of ascorbate, Trolox and PMC increased their interaction, thus rapidly depleting ascorbate. When dihydrolipoic acid was added simultaneously with the vitamin E homologues, the accelerated ascorbate oxidation was prevented. This was due to the regeneration of ascorbate and PMC from their free radicals by a recycling mechanism between ascorbate, vitamin E homologues and dihydrolipoic acid. Potentiation of antioxidant recycling may be protective against UV irradiation-induced damage. The rate of ascorbate oxidation in the presence of vitamin E homologues was enhanced by a photosensitizer (riboflavin) but was not influenced by reactive oxygen radical quenchers, superoxide dismutase or 5,5-dimethyl-1-pyrroline-N-oxide. These experimental results suggest that the UV irradiation-induced ascorbate oxidation in murine skin homogenates is caused by photoactivated reactions rather than reactive oxygen radical reactions.

Animals↗

Intraocular pressure and central visual field of normal tension glaucoma.

AIM: To study whether damage in the central 30 degrees field of normal tension glaucoma (NTG) is relatively heterogeneous or homogeneous with respect to intraocular pressure (IOP) related damage. METHODS: Using the results of Humphrey perimeter examinations, the central 30 degrees field was divided into four subfields; superior and inferior hemifields excluding the caecocentral field (30-2 program) and superior and inferior 10 degrees hemifields (10-2 program). In 103 NTG cases, the intraindividual bilateral difference in the mean of total deviations (mean TD) in the four subfields was analysed by multiple linear regression to correct the effects of factors other than IOP. Explanatory variables were the intraindividual bilateral difference in the mean of clinic IOP (IOPmean), that in the ratio of area of peripapillary atrophy corresponding to each subfield to disc area, and that in myopic refraction. RESULTS: The intraindividual bilateral difference in the mean TD was significantly and negatively correlated with that in IOPmean in three of the above four subfields (p < 0.005) and correlation tended to be negative (p = 0.07) in the superior 10 degrees hemifield. CONCLUSIONS: Diffuse IOP related damage was suggested in the central 30 degrees field of NTG; greater extent of the damage in the above four subfields was correlated with higher mean IOP. The present findings may have clinical implications.

Glaucoma, Open-Angle↗

Isolation and some properties of sorbitol oxidase from Streptomyces sp. H-7775.

A sorbitol oxidase (SOX) was found in the cell-free extract of a strain isolated from soil. The strain was classified and designated as Streptomyces sp. H-7775. SOX is constitutively expressed in the cell. The molecular weight of SOX that purified from the cell-free extract was 45,000. The optimum pH and the K(m) for sorbitol were 6.5-7.5 and 0.26 mM, respectively. The prosthetic group was a covalently bound FAD. SOX catalyzed oxidation of D-sorbitol to glucose and hydrogen peroxide without any requirements of exogenous cofactors. SOX did not react with glucose, a reaction product of D-sorbitol. This feature is useful in its application for diagnosis.

Chromatography, Affinity↗

Isolation and characterization of chitinase from a flake-chitin degrading marine bacterium, Aeromonas hydrophila H-2330.

A flake-chitin degrading marine bacterium was isolated and identified as Aeromonas hydrophila. This strain secreted five chitinases and an beta-N-acetylglucosaminidase. The main chitinase (Chi-A) was purified and characterized. The optimum pH of Chi-A was 5-8, and the activity was inhibited by Hg2+ and Fe3+. Chi-A was different from chitinases of other Aeromonas species with respect to molecular weight (62,000) and insensitivity to monoiodoacetate. The amino-terminal amino acid sequence showed extensive similarity with chitinases from Gram-negative bacteria.

Aeromonas hydrophila↗

Potentiating effects of calcium chelators on basal and stimulated aldosterone production by bovine adrenal glomerulosa cells in vitro.

We previously reported the potentiation of basal aldosterone production by the addition of the calcium chelator ethyleneglycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to an extracellular solution of bovine adrenal glomerulosa cells in vitro. To assess whether the addition of the calcium chelators ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) and EGTA can potentiate basal and stimulated aldosterone production, we compared the effect of EDTA with that of EGTA on basal and the agonist (potassium; 8 mM, angiotensin II; 10 nM, ACTH; 10 nM)-stimulated aldosterone production by the cells in vitro. These two chelators lowered the extracellular ionized calcium ([Ca2+]o) concentration in a similar manner. The levels of basal and the agonist-stimulated aldosterone production in the presence of EDTA (1 mM) and EGTA (1 mM) were significantly (P < 0.01 or less) increased when compared with those in the absence of EDTA and EGTA, respectively. These results show that the addition of EDTA and EGTA to an extracellular solution potentiates basal and the agonist-stimulated aldosterone production in vitro. Although an increase in basal aldosterone production in the presence of EDTA (1 mM) and EGTA (1 mM) was completely inhibited by the voltage-dependent calcium channel antagonist nifedipine (1 microM) or the calmodulin antagonist pimozide (1 microM), the potentiation of the agonist-stimulated aldosterone production does not seem to be induced by CA2+/calmodulin-dependent nor cAMP-dependent systems. These findings suggest that calcium chelators such as EDTA and EGTA may possess activating effect on basal and stimulated aldosterone production in bovine adrenal glomerulosa cells.

Aldosterone↗

Rapidly progressive glomerulonephritis concomitant with diabetic nephropathy.

We describe a rare case of a rapidly progressive glomerulonephritis (RPGN) superimposed on diabetic nephropathy. A 68-year-old woman with non-insulin-dependent diabetes mellitus (NIDDM) complicated with diabetic triopathy demonstrated a rapid deterioration of renal function. Her urinary sediment contained many red blood cell (RBC) cells and casts, suggesting an additional renal disease accompanying diabetic nephropathy. Renal biopsy revealed crescent formation in many glomeruli characteristic of the pauci-immune type of RPGN. Steroid pulse therapy transiently halted the deterioration in renal function, but the patient died of pneumonia complicated with methicillin-resistant staphylococcus aureus (MRSA) infection. The unusual findings in diabetic nephropathy indicated the coexistence of primary glomerulonephritis and diabetic glomerulosclerosis in this case.

Aged↗

Effect of KMD-3213, an alpha 1a-adrenoceptor-selective antagonist, on the contractions of rabbit prostate and rabbit and rat aorta.

KMD-3213, (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy) phenoxy]ethyl]amino]propyl]indoline-7-carboxamide, a newly synthesized alpha 1-adrenoceptor antagonist, has been shown to have potent action toward, and to be selective for human cloned and native alpha 1-adrenoceptors. In the present study, we characterized the inhibitory effect of KMD-3213 on the phenylephrine (alpha 1-adrenoceptor-selective agonist)-induced contraction of rabbit prostate, rabbit thoracic aorta and rat thoracic aorta to functionally confirm the tissue selectivity of KMD-3213. The mean pA2 value for KMD-3213 for the inhibition of the rabbit prostatic contraction was 10.05, whereas the values for the rabbit and rat aortic contractions were 9.36 and 8.13, respectively. The order of mean pA2 values for the inhibition of the rabbit prostatic contraction was KMD-3213 > or = tamsulosin >> prazosin, whereas that for the rabbit and rat aortic contractions was tamsulosin > KMD-3213 > prazosin and tamsulosin > or = prazosin >> KMD-3213, respectively. KMD-3213 produced a sigmoidal inhibition curve for single-dose phenylephrine-induced contractions of rabbit prostate, whereas it produced a non-sigmoidal curve for that of rabbit aorta. KMD-3213 had no effect on isoproterenol-induced chronotropic action in guinea-pig atria, and 5-hydroxytryptamine-, histamine- and acetylcholine-mediated contractions of rabbit aorta. These results indicate that the potency of the inhibitory activity of KMD-3213 depends on the tissue subtype expression and that KMD-3213 preferentially antagonizes prostatic contraction.

Adrenergic alpha-Antagonists↗

Suppression of iron catalyzed free radical generation by iron tyrosinate protein models.

Novel antioxidants, N-(2-Hydroxy-1-naphthal)amino acids which mimic iron proteins, have been intensively studied for suppressive effect on iron-catalyzed free radical generation. These compounds exhibit inhibition of the Fenton reaction in electron spin resonance assessment. In addition, it is shown that the compounds inhibit iron-induced peroxidation by thiobarbituric acid test. Since these antioxidants form stable complexes with Fe3+, this antioxidative activity is expected to be derived from sequestration of catalytic iron.

Antioxidants↗

[Studies on the synthesis of cholecystokinin A receptor antagonists. I. synthesis and cholecystokinin A receptor inhibitory activities of malonamide derivatives].

2-Substituted malonamide derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity. Significant CCK-A receptor inhibitory activities were found in only three compounds (4g-i) which have carboxyl group. In order to study structure-activity relationships, carboxyethyl group was selected for 2-substituent and a number of N-substituted malonamides were prepared. After these compounds were tested for CCK-A receptor inhibitory activity, 4-(3,4-dichlorophenylcarbamoyl)-N,N-dipentylglutaramic acid (4h) was selected as the most preferred compound.

Malonates↗

[Studies on the synthesis of cholecystokinin A receptor antagonists. II. Synthesis and cholecystokinin A receptor inhibitory activities of sulfur-containing amide-carboxylic acid derivatives].

A number of sulfur-containing amide-carboxylic acid derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in only two series, that is, sulfoxide-carboxylic acid derivatives (9) and sulfone-carboxylic acid derivatives (10). As the most preferred compound, 5-(3,4-dichlorophenylsulfonyl)-4-(N,N-dipentylcarbamoyl)pent anoic acid (10n) was selected.

Animals↗

[Studies on the synthesis of cholecystokinin A receptor antagonists. III. Synthesis and cholecystokinin A receptor inhibitory activities of naphthyl sulfone derivatives].

A number of naphthyl sulfone derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in sulfone-carboxylic acid derivatives (7) having very hydrophobic sidechains. As the most preferred compound, (R)-4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulf onyl) pentanoic acid ((R)-7c) was selected.

Animals↗

Altered circadian blood pressure rhythm and progression of diabetic nephropathy in non-insulin dependent diabetes mellitus subjects: an average three year follow-up study.

BACKGROUND: In addition to autonomic dysfunction, diabetic nephropathy has been identified as another factor inducing a reversed circadian blood pressure (BP) rhythm in diabetic subjects. This study was carried out to assess the relationship between alterations in circadian BP rhythm and progression of diabetic nephropathy in subjects with non-insulin dependent diabetes mellitus (NIDDM). METHODS: Ambulatory 24-hour BP, 24-hour urinary albumin excretion rate (UAE), and plasma hormonal factors were measured during an average 3-year follow-up in 16 hospitalized subjects with NIDDM. Twelve age-matched control subjects were also studied. RESULTS: During an average 3-year follow-up, diabetic subjects had no significant progression of severe nephropathy and/or somatic neuropathy and showed no transition from a normal to a reversed mean blood pressure (mBP) pattern. However, mBP during whole day or nighttime, but not daytime, at baseline in diabetic subjects was high as compared with control subjects exhibiting an increased night/day mBP ratio and a decreased night/day mBP difference. The mBPs during various time periods (whole day, daytime, and nighttime) at follow-up in diabetic subjects were more elevated than those at baseline, showing a more increased night/day mBP ratio and a more decreased night/day mBP difference. In diabetic subjects, UAE during follow-up was increased, and UAE increments were well correlated with changes in mBP during whole day and nighttime. Plasma renin activity (PRA) and plasma aldosterone (PA) were decreased, while plasma alpha-atrial natriuretic peptide (ANP) was increased at follow-up, compared with at baseline. The mBP increments during various time periods were well correlated with changes in these hormonal factors, and UAE increments were well correlated with changes in PA and plasma ANP. CONCLUSIONS: The altered circadian BP rhythm observed in diabetic subjects may occur at the early stage of diabetic nephropathy with opposite changes in plasma renin-aldosterone and plasma ANP.

Blood Pressure↗

Effect of aging on spontaneous micronucleus frequencies in peripheral blood of nine mouse strains: the results of the 7th collaborative study organized by CSGMT/JEMS.MMS. Collaborative Study Group for the Micronucleus Test. Environmental Mutagen Society of Japan. Mammalian Mutagenesis Study Group.

The spontaneous frequencies of micronucleated reticulocytes (MNRETs) were examined monthly over the life spans of animals belonging to nine mouse strains for the 7th collaborative study organized by the CSGMT/JEMS.MMS. Both sexes of the BDF1 strain and females of the A/J strain showed a statistically significant increase in mean spontaneous MNRET frequency in their last month of life, suggesting the possibility of strain-specific, age-dependent chromosomal instability. SAMP6/Tan, an accelerated senescence-prone strain, showed the same tendency, although it was not statistically significant. The other strains studied, ddY, CD-1, B6C3F1, SAMR1, and MS/Ae, did not show significant age-related differences in mean of MNRET frequencies. More extensive statistical analyses are underway, and the outcomes will be reported separately.

Aging↗

[Angles among main cranial sutures in Japanese].

To examine a relation of angles among the coronal, sagittal and lambdoid sutures to the size of the calvaria as well as to the remains of the metopic suture, 158 adult Japanese calvae or calottes were observed. The calvae used consisted of four groups: group M composed of 74 male calvae without the metopic suture; group F, of 41 female calvae without the same suture; group Un, of 27 sex-unknown calvae without the same suture; and group Um, of 16 sex-unknown calvae with the same suture. The angles among the sutures were measured at both bregma and lambda. The size of the calvaria was represented by bistephanic arc and breadth (distance between the stephanions), and by parietal sagittal arc and chord (distance from the bregma to the lambda). Results obtained were as follows. The distances both between the stephanions and from the bregma to the lambda were larger in M than in F, though these distances in M, F and Un were much the same as those in Um. The bistephanic index (breadth/arc) was higher in Um than in F, whereas the sagittal parietal indices (arc/chrod) in M, F and Um were similar to one another. Apical angle of the frontal squama was larger in M than in F, and was larger in Um than in M and F. However, apical angle of the occipital squama showed no difference among M, F and Um.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗