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Biomedical subjects

N Miyata

Publications and source records attributed to N Miyata.

At least 55 records · Page 3Linked to original sources

Dog-bite injuries to the breast in children: deformities to secondary sex characteristics and their repair in an extended follow-up.

Injuries from dog bites are not uncommon among children. However, the site of the wound is rarely on the breast. The authors report two cases of nipple-areolar injuries caused by dog bites. The affected children were followed during the development of secondary sex characteristics. In one child, this follow-up period was more than 10 years. In treating such wounds to the breast, subsequent growth of the nipple-areolar complex should be considered, particularly in girls because of the area's importance as a secondary sex characteristic.

Animals↗

Elastofibroma dorsi: CT, MRI, and pathologic findings.

We report two cases of elastofibroma dorsi and discuss the CT and MR findings and histopathology of these tumors. Increased awareness of the characteristic MR patterns should lead to reduced misdiagnosis of such lesions as malignant and prevent unnecessary wide excision.

Female↗

Distribution of angiotensin AT1 and AT2 receptor subtypes in the rat kidney.

ANG II contributes importantly to the regulation of renal vascular resistance, glomerular filtration, and tubular epithelial transport, yet there remains a paucity of information regarding the localization of the ANG II type 1 and 2 (AT1 and AT2) receptors within the rat kidney particularly within the vasculature. The present study was designed to localize the transcriptional and translational site(s) of AT1 and AT2 receptor (AT1R and AT2R, respectively) expression within the rat kidney. Using immunohistochemistry, we detected the AT(1)R translational sites throughout the kidney, with the strongest labeling found in the vasculature of the renal cortex and the proximal tubules of the outer medulla. The AT2R protein expression was found throughout the rat kidney, although there was little to no expression found in the glomerulus and medullary thick ascending limbs of Henle (TAL). Gene-specific primers were then designed to distinguish between the receptor subtypes within microdissected renal tubular and vascular segments using RT-PCR. AT1AR, AT1BR, and AT2R mRNA were found within the renal vasculature (afferent arterioles, arcuate artery, and outer medullary descending vasa recta). The mRNA for both the AT1R isoforms was also detected in the glomeruli and the renal tubules (proximal tubules, TAL, and collecting ducts); however, no AT2R mRNA was detected within the glomerulus and was inconsistently found within the medullary TAL (MTAL). Taken together, these data show that mRNA for the AT1R subtypes was located in all of the renal tubular and vascular segments. Evidence for AT2R mRNA was also found in all but two of the vascular and tubular segments, the MTAL, and the glomeruli. These results are consistent with the whole tissue immunohistochemically localized receptors.

Angiotensin I↗

Renal intramedullary infusion of L-arginine prevents reduction of medullary blood flow and hypertension in Dahl salt-sensitive rats.

A role for reduced renal nitric oxide production has been proposed as a mechanism responsible for hypertension in Dahl "salt-sensitive" rats. The present study had 2 goals: first, to determine the relationship between changes in mean arterial pressure and renal cortical and medullary blood flows in unanesthetized Dahl/Rapp salt-sensitive (S) and Dahl/Rapp salt-resistant (R) rats as daily salt intake was increased from 0.4% to 4.0%; second, to determine if delivery of L- or D-arginine into the renal medulla of Dahl S rats would change the responses to high salt. Optical fibers were implanted into the renal cortex and inner medulla for daily recording of cortical and medullary blood flows using laser-Doppler flowmetry. Indwelling aortic catheters were used to record arterial pressure. Increasing salt intake to 4.0% in Dahl S rats increased mean arterial pressure from 128+/-2.0 to 155+/-5.0 mm Hg by day 5 of high salt diet; medullary blood flow was reduced 13% by day 2, 24% by day 3 (P<0.05), and 31% by day 5 (P<0.05), whereas cortical blood flow was unchanged. In Dahl R rats, mean arterial pressure averaged 117+/-5 mm Hg during the 0.4% salt control period and remained unchanged (as did cortical and medullary blood flows) during 5 days of 4.0% salt intake. Dahl S rats that received medullary L-arginine (300 microg. kg-1. min-1) exhibited no changes of mean arterial pressure or regional renal blood flow during the 5 days of 4.0% salt intake. Medullary infusion of D-arginine (300 microg. kg-1. min-1) did not prevent the development of hypertension in Dahl S rats that received 4.0% salt. The results are consistent with the view that Dahl S rats have a reduced capacity to generate nitric oxide within the renal medulla under conditions of high salt, which the administration of L-arginine can normalize. Furthermore, early reductions of medullary blood flow in Dahl S rats with high salt intake probably contribute to the development of hypertension.

Animals↗

Synergistic effect of naphthoquinones on the mutagenicity of nitroarene.

Nitro reduction is a critical step in the mutagenic activation of nitroarene. Nitroarene and quinone are known to be reduced by common enzymes, and thus, naphthoquinone (NQ) was studied for its effects on the mutagenicity of nitroarene in the Ames test using Salmonella typhimurium TA98 without S9. The mutagenicity of 1,3-dinitropyrene in TA98 was found to increase 9- and 6-fold as much in the presence of 70 nmol/plate of 2-methyl-1,4-NQ and 2-hydroxy-1,4-NQ, respectively. Mutagenicity also became greater in 1,3,5-trinitronaphthalene, 1-nitropyrene and 3-nitrofluoranthene. Seventy nmol/plate of 2-methyl-1,4-NQ increased the mutagenicity of 1-nitropyrene by 10.5-fold as much.

Drug Synergism↗

[Biological activity of photoexcited fullerene].

Fullerene (C60, C70, etc.) is a third carbon allotrope discovered in 1985, and a great deal of attention has been focused on its physical and chemical properties in recent years. We are very interested in its biological properties for use fullerene as a pharmacophore. We first developed a method of solubilizing fullerene itself in water to perform in vitro biological screening. The concentrations of aqueous C60 and C70 solution with 5% poly(vinylpyrorridone) (PVP) are 400 and 200 micrograms/mL, respectively. By using aqueous fullerene solutions prepared in this manner, we have clarified a series of biological activities of fullerene, consisting of DNA-cleavage, hemolysis, cancer-initiation, and cell-toxicity under photoirradiation, and chondrogenesis and inhibition of glutathione S-transferase activity without photoirradiation. The biological activity of photo-excited fullerene was found to be promising, because fullerene is a highly efficient photo-sensitizer. We synthesized a C60 derivative with an acridine moiety as a DNA-chelating function and assessed its effective DNA-cleaving activity. What kind of active species is involved in the biological action of photo-excited fullerene is our next concerns. Two pathways have been reported for the photo-excitation of fullerene. The so-called Type II energy transfer pathway generates singlet oxygen (1O2), while the Type I electron transfer pathway gives a fullerene radical anion (C60.-, C70.-). In order to clarify the effective oxygen species actually responsible for the biological action of photo-excited fullerene, we performed DNA-cleaving tests and EPR spectroscopic analyses under several conditions. The results showed that the photo-induced biological activity of fullerene is not caused by 1O2, but by reduced oxygen species (O2.-, .OH) generated by the electron transfer reaction of C60.-, with molecular oxygen. Its specificity is thought to be mainly attributed to the high-reducible property of fullerene. Since the reductive activation of molecular oxygen by photo-excited fullerene was observed at physiological concentrations of NADH as the reductant, fullerene can be classified as an oxyl-radical-generating photosensitizer. Pharmaceutical application of fullerene to cancer photo-dynamic therapy appears promising.

Carbon↗

[Computational study on antioxidation mechanism of catechins].

All C-H and O-H bond dissociation enthalpies (BDE's) in catechins, (-)-epigallocatechin) were calculated by semi-empirical molecular orbital calculation using the SPARTAN program. The BDE's of benzyl hydrogens (C-2 position in catechins) were found to be quite low. This suggests that abstraction of benzyl hydrogen is crucial step for antioxidative activity. This is corroborated by the reported results of LC/MS and spectrophotometric analysis of reaction intermediates from catechins treated with AAPH.

Antioxidants↗

[Molecular mechanics study on Conformation of a homooligopeptide constituted by isovalin].

Conformational energy computations on a homo-hexapeptide of (S)-isovaline were performed using molecular mechanics on MacroModel. Conformational search calculations were carried out by Monte Carlo method. AMBER* was used as the force field. The global minimum energy conformation was found to be a 3(10)-helix coordinated by four hydrogen bonds. The results of the theoretical analysis of the conformation of the peptide are in agreement with its reported conformational properties in the solid state determined by X-ray crystallographic analysis.

Crystallography, X-Ray↗

Resveratrol as a new type of DNA-cleaving agent.

The first demonstration of DNA cleavage by resveratrol '3,5,4'-trihydroxy-trans-stilbene' is presented. Resveratrol mediated relaxation of pBR322 at micromolar concentrations in the presence of Cu2+. Evidence is provided that resveratrol is capable of binding to DNA, and that the Cu(2+)-dependent DNA damage is more likely caused by a copper-peroxide complex rather than by a freely diffusible oxygen species.

Antineoplastic Agents, Phytogenic↗

Doubly entrapped baker's yeast survives during the long-term stereoselective reduction of ethyl 3-oxobutanoate in an organic solvent.

To attain long-term bioreaction in organic solvents with living microorganisms, we tried to protect the microorganisms from the toxicity of the solvent by immobilization. In this study, baker's yeast, which is not tolerant to organic solvents such as isooctane, was selected as a model microorganism and the immobilized living yeast cells were examined for activity in the steroselective reduction of ethyl 3-oxobutanoate to ethyl (S)-3-hydroxybutanoate in isooctane; an activity that correlated well with the viability of the yeast cells. It was found that double entrapment, that is, further entrapment of calcium-alginate-gel-entrapped cells with a urethane prepolymer, made it possible for the yeast to remain viable in isooctane, although other conventional immobilization methods, such as single entrapment using polysaccharide or synthetic resin prepolymers, were insufficient for its protection. Furthermore, doubly entrapped living yeast cells could carry out the stereoselective reduction in isooctane repeatedly for a long period (more than 1200 h) with occasional cultivation. Thus, double entrapment enabled a microorganism sensitive to organic solvents to survive over long-term bioreaction in an organic solvent.

Acetoacetates↗

Renal medullary interstitial infusion of L-arginine prevents hypertension in Dahl salt-sensitive rats.

Studies were designed to examine the effects of renal medullary interstitial infusion of L-arginine (L-Arg) on the development of high-salt-induced hypertension in Dahl salt-sensitive/Rapp (DS) rats. The threshold dose of L-Arg (300 micrograms . kg-1 . min-1) that increased the renal medullary blood flow without altering the cortical blood flow was first determined in anesthetized DS rats. Studies were then carried out to determine the effects of this dose of L-Arg on salt-induced hypertension in DS rats. In the absence of chronic medullary L-Arg infusion, mean arterial pressure (MAP) increased in DS rats from 125 +/- 2 to 167 +/- 5 mmHg by day 5 of a high-salt diet (4.0%), with no change observed in Wistar-Kyoto (WKY) or Dahl salt-resistant/Rapp (DR) rats. MAP did not change significantly with medullary infusion of L-Arg alone in DR rats (control = 104 +/- 1 mmHg) or in WKY rats (control = 120 +/- 3 mmHg) and was not significantly changed from these levels during the 7 days of L-Arg infusion combined with high-NaCl diet. The same amount of L-Arg that prevented salt-induced hypertension in DS rats when infused into the renal medulla (300 micrograms . kg-1 . min-1) failed to blunt salt-induced hypertension when administered intravenously to DS rats. DS rats receiving L-Arg (300 micrograms . kg-1 . min-1 iv) exhibited an increase in plasma L-Arg from control concentrations of 138 +/- 11 to 218 +/- 4 micromol/l, while MAP, which averaged 124 +/- 3 mmHg during the 3-day control period, rose to 165 +/- 5 mmHg by day 5 of high salt (4%) intake. These results indicate that the prevention of salt sensitivity in DS rats was due specifically to the action of L-Arg on renal medullary function and that DS rats may have a deficit of medullary substrate availability and NO production.

Animals↗

Hardness controlled enzymes and electronegativity controlled enzymes: role of an absolute hardness-electronegativity (eta-chi) activity diagram as a coordinate for biological activities.

We found that absolute hardness-absolute electronegativity (eta-chi) activity diagrams play an important role as a new coordinate of bioactivity in structure-activity relationships. In this paper, the eta-chi activity diagram, focusing on the molecular mechanism of bioactive compounds is used to discuss two major problems. First, the potency of bioactivities for xenobiotics such as polychlorinated dibenzo-p-dioxins (PCDDs) 3 and polychlorinated biphenyls (PCBs) 4, were found to be strongly related to their absolute hardness (eta). Second, the antibacterial activity of new quinolones such as norfloxacin 1 and enoxacin 2, was found to be strongly related to their absolute electronegativity (chi). These findings predict at least two chemical properties for a hardness-controlled or electronegativity-controlled enzyme.

4-Quinolones↗

(+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride) induces saliva and tear secretions in rats and mice: the role of muscarinic acetylcholine receptors.

We investigated effects of (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride), a rigid analogue of acetylcholine, on saliva and tear secretions in rats and mice to evaluate its therapeutical efficacy for xerostomia and xerophthalmia in patients with Sjogren's syndrome and X-ray exposure in the head and neck. Intraduodenal administrations of SNI-2011 increased saliva secretion in a dose-dependent manner at doses ranging from 3 to 30 mg/kg in normal rats and mice, two strains of autoimmune disease mice and X-irradiated saliva secretion defective rats. The salivation elicited by SNI-2011 was completely inhibited by atropine. A similar atropine-sensitive response was observed in tear secretion. In rat submandibular/sublingual gland membranes, [3H]quinuclidinyl benzilate (QNB) binding was saturable, and Scatchard plot analysis revealed a single population of binding sites with a Kd of 22 pM and a maximal binding capacity of 60 fmol/mg protein. The competitive inhibition curve of the [3H]QNB binding by SNI-2011 was obtained, and its dissociation constant value calculated from IC50 was 1-2 microM. These results suggest that SNI-2011 increases saliva and tear secretions through a direct stimulation to muscarinic receptors in salivary and lacrimal glands, and they suggest that SNI-2011 should be beneficial to patients with Sjögren's syndrome and X-ray exposure in the head and neck.

Animals↗

[Stereoselective epoxidation with bulky dioxiranes generated from substituted cyclohexanones].

Dioxiranes have recently been shown to be important and versatile oxidants, which are generated from potassium monoperoxysulfate (KHSO5) and ketones. Dimethyldioxirane, a dioxirane generated from acetone as a ketone, is particularly useful as an oxidation reagent with a broad scope of synthetic applications. Several papers have been reported about stereoselective epoxidation using dimethyldioxirane. However, there have been only a few examples using dioxiranes generated from other ketones. Dioxiranes derived from sterically hindered ketones are expected to be "bulky oxidant", and to be useful for stereoselective epoxidation. In a CH2Cl2-buffered water (two-phase system) in the presence of phase-transfer agent under neutral condition (pH 7.8) according to the reported procedure, the epoxidations with hindered alpha-substituted cyclohexanones proceeded in very low yields. After a survey of possible conditions we found that basic (pH 11) CH2Cl2-MeOH-buffer system was effective for the epoxidations of olefins with Oxone (active constituent KHSO5) and substituted cyclohexanones. We carried out epoxidation of cyclohexen derivatives with dioxiranes derived from alpha-substituted cyclohexanones in a CH2Cl2-MeOH-buffer solvent system at pH 11. High trans selectivities were obtained. Furthermore, according to this method acyclic silyl ethers were stereoselectively oxidized to afford erythro epoxides.

Chemistry, Organic↗

Quantitative evaluation of irregular astigmatism by fourier series harmonic analysis of videokeratography data.

PURPOSE: To assess quantitatively corneal irregular astigmatism in association with best spectacle-corrected visual acuity. METHODS: Refractive powers on a mire ring measured with computerized videokeratography were decomposed, using the Fourier series harmonic analysis. Extracting spherical and regular astigmatic components, the remaining irregular astigmatic component was quantified on rings 2 through 9. A weighted average was calculated by using the Stiles-Crawford effect on the basis of the radius of each ring of each eye and was used as an index of the irregular astigmatic component. Data analyses were carried out in 108 eyes, including 53 normal eyes, 34 eyes with keratoconus, and 21 eyes that had undergone penetrating keratoplasty for keratoconus. Keratoconic eyes and eyes after keratoplasty were included in the study only if visual acuity, corrected with a hard contact lens, was 20/20 or better. Logarithm of best spectacle-corrected visual acuity, age, type of disease, refractive astigmatism, irregular astigmatic component, surface regularity index, and surface asymmetry index were analyzed. RESULTS: In results of multiple regression analysis, the irregular astigmatic component was significantly correlated with best spectacle-corrected visual acuity (r = -0.744; adjusted R2 = 0.549; P < 0.001), whereas other explanatory variables showed no correlation with best spectacle-corrected visual acuity. CONCLUSIONS: This model of the irregular astigmatic component seems to be an efficient, quantitative means of describing corneal irregular astigmatism.

Adolescent↗

Promoting activity of 3-tert-butyl-4-hydroxyanisole (BHA) in BALB/3T3 cell transformation.

3-Tert-butyl-4-hydroxyanisole (BHA), a synthetic antioxidant, is an initiator in the transformation of BALB/3T3 mouse embryo cells, when cells are treated first with the chemical and then with a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. In the present study, BHA was examined for its promoting activity in BALB/3T3 cell transformation. BHA in a range of 5-20 microg/ml enhanced transformation induced by a subthreshold dose of 3-methylcholanthrene (MCA, 0.1 microg/ml) in a dose-dependent manner. Statistically significant increases were noted in the proportion of dishes with transformed foci in the cultures treated with 10 and 20 microg/ml BHA following MCA as compared to the cultures treated with MCA alone. When BHA was applied to the cultures both on initiating and promoting stages in the absence of another initiator or promoter, however, BHA did not increase the transformation frequency, suggesting that the transforming activities of BHA are too weak and require combination with a potent initiator or promoter to attain complete transformation in this assay system. BHA did not increase postconfluent cell density nor induce DNA synthesis in density-arrested cells, suggesting that cell proliferation is excluded from the causal events of transformation enhancement by BHA in BALB/3T3 cells.

3T3 Cells↗

Silver-stained nucleolar organizer regions in hypertrophic and keloid scars.

Silver-stained nucleolar organizer regions (AgNORs) have been widely used as a marker of cellular activity and proliferation. In a retrospective study, we investigated the potential value of AgNORs in 12 hypertrophic and 24 keloid scar tissues. Ten normal skin tissues served as controls. A standard silver-staining method was used, and the mean AgNOR count of dermal fibroblastic cells in each tissue was determined. In normal skin, the mean AgNOR count of dermal fibroblasts was 1.79+/-0.55, whereas fibroblastic cells in hypertrophic and keloid scars had mean AgNOR counts of 3.18+/-0.56 and 5.10+/-0.97, respectively. There was a statistically significant difference between the mean AgNOR counts of fibroblastic cells from normal skin, hypertrophic scar, and keloid scar [one-factor analysis of variance (ANOVA), p < 0.0001]. Our findings suggest that AgNOR count may be a useful marker for assessment of fibroblastic cell activity in hypertrophic and keloid scars, which may have potential value for histologic and biologic characterization of the two lesions.

Analysis of Variance↗