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Biomedical subjects

Y Shimomura

Publications and source records attributed to Y Shimomura.

At least 19 recordsLinked to original sources
PubMed2000

Preparation of a monoclonal antibody to N(epsilon)-(Hexanonyl)lysine: application to the evaluation of protective effects of flavonoid supplementation against exercise-induced oxidative stress in rat skeletal muscle.

The monoclonal antibody to N(epsilon)-(hexanonyl)lysine (HEL), a novel adduct formed by the reaction of linoleic acid hydroperoxide and lysine, has been prepared and characterized. The obtained antibody specifically recognized the HEL moiety. Using the monoclonal antibody, we evaluated the protective effects of feeding eriocitrin, which is one of flavonoids in lemon fruit, on oxidative modification induced by exercise in rats. The supplementation of eriocitrin significantly suppressed the increase in HEL in the skeletal muscle by exercise. The result suggests that the determination of HEL may be a good method for evaluation of the protective effect of beneficial food factors against oxidative stress.

Aldehydes↗
PubMed2000

Experimental hyperthyroidism causes inactivation of the branched-chain alpha-ketoacid dehydrogenase complex in rat liver.

Hyperthyroidism induced by 3-day treatment of rats with thyroid hormone (T(3); 3,5,3'-triiodothyronine) at 0.1 or 1 mg/kg body wt/day resulted in a reduced activity state (% of enzyme in its active, dephosphorylated state) of the hepatic branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. One treatment with 0.1 mg T(3)/kg body wt caused a significant effect on the activity state of BCKDH complex after 24 h, indicating that the reduction of the activity state was triggered by the first administration of T(3). Hyperthyroidism also caused a stable increase in BCKDH kinase activity, the enzyme responsible for phosphorylation and inactivation of the BCKDH complex, suggesting that T(3) caused inactivation of the BCKDH complex by induction of its kinase. Western blot analysis also revealed increased amounts of BCKDH kinase protein in response to hyperthyroidism. No change in the plasma levels of branched-chain alpha-keto acids was observed in T(3)-treated rats, arguing against an involvement of these known regulators of BCKDH kinase activity. Inactivation of the hepatic BCKDH complex as a consequence of overexpression of its kinase may save the essential branched-chain amino acids for protein synthesis during hyperthyroidism.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2000

Prediction of letter contrast sensitivity using videokeratographic indices.

PURPOSE: To analyze the relationship between corneal topography and letter contrast sensitivity. METHOD: Experiments were conducted on 59 eyes of 51 patients who had best spectacle-corrected visual acuity of 20/20 or better and no ocular pathology except for the corneal shape. Thirty-nine eyes had an abnormal topographic pattern resulting from keratoconus, and the other 20 eyes showed a normal topographic pattern. Videokeratography was performed with the TMS-2 videokeratoscope, and the surface regularity index, surface asymmetry index, and coefficient of variation of power were obtained for each subject. Letter contrast sensitivity was measured with the CSV-1000LV with spectacle correction. The correlation between the number of correct letters and topographic indices was calculated. RESULTS: The abnormal topography group had a significantly greater loss of letter contrast sensitivity (median = 20 letters) than the normal control (median = 23 letters; P =.0001). There were statistically significant correlations between number of correct letters and the coefficient of variation of power (r = -.77; P =. 001), number of correct letters and surface regularity index (r = -. 76, P =.001), and the number of correct letters and surface asymmetry index (r = -.64; P =.001). The linear regression equation between number of correct letters and the coefficient of variation of power was the number of correct letters = -0.05 x the coefficient of variation of power + 23.2. CONCLUSIONS: Our results suggest that subtle visual deteriorations, which are barely detected by contrast sensitivity testing, can be predicted objectively by the corneal topographic indices.

Adult↗
PubMed2000

Effects of penetrating keratoplasty rejection on the endothelium of the donor cornea and the recipient peripheral cornea.

PURPOSE: To determine the effects of penetrating keratoplasty rejection on the recipient endothelium. METHODS: Twenty transplanted corneas of 20 keratoconus patients were enrolled in this study. Ten of the corneas had undergone allograft rejection and the other 10 grafts had an uneventful postsurgical course. The endothelium of the donor cornea and the endothelium of the recipient peripheral cornea were evaluated by wide-field specular microscopy. RESULTS: The transplanted corneas that underwent allograft rejection showed a marked decrease in endothelial cell density not only in central donor cornea but also in the recipient peripheral cornea compared with that in the uneventful transplanted corneas. Additionally, the recipient endothelium had significant pleomorphism in the rejection group. There were no morphologic differences in the peripheral donor cornea between the control group and the rejection group. CONCLUSIONS: Our findings indicate that the recipient peripheral endothelium is also affected by allograft rejection, perhaps because of the contribution of recipient endothelium to the wound healing process after allograft rejection.

Adult↗
PubMed2000

Comparison of topographic indices that correlate with visual acuity in videokeratography.

OBJECTIVE: To evaluate the relationship between the best spectacle-corrected visual acuity (BSCVA) and two quantitative indices of the anterior corneal surface obtained by videokeratography. DESIGN: Prospective, single center, comparative, observational study. PARTICIPANTS: Eighty-nine normal eyes and 52 eyes with keratoconus with contact lens-corrected visual acuity of 20/20 or better. INTERVENTION: Videokeratography was performed with the TMS-2 and the CAS system 2000. MAIN OUTCOME MEASURES: The relationship between the BSCVA recorded in log minimal angle of resolution (logMAR) units, the surface regularity index (SRI), and the predicted corneal acuity (PCA) were assessed by linear regression analysis. RESULTS: The BSCVAs for all eyes ranged from 0.82 to -0.30 logMAR units. BSCVA was highly correlated with the SRI (r = 0.70, P < 0.0001) and the PCA (r = -0.61, P < 0.0001). There was no statistical difference in the regression slopes and the intercepts for the estimated BSCVA using the SRI and measured BSCVA, and the estimated BSCVA using PCA and measured BSCVA. CONCLUSIONS: Two quantitative topographic indices, SRI and PCA, are useful for estimating the effect of irregular astigmatism on visual acuity even though both indices quantify different aspects of the anterior surface of the cornea.

Adolescent↗
PubMed2000

The effects of binocular suture and dark rearing on the induction of c-fos protein in the rat visual cortex during and after the critical period.

It has been demonstrated in kittens that binocular lid suture has more deleterious and irreversible effects on plasticity of the developing visual system than rearing in complete darkness. The present study using immunocytochemistry focuses on the effects of the two types of visual deprivation on the inducibility of c-fos protein in visual cortical neurons of rats. Rats were subjected to binocular suture or dark rearing for 1 week during (postnatal days 14-21; P14-P21) and after (P50-P57) the critical period for activity-dependent modifiability of cortical ocular dominance. In rats of both age groups reared in the normal light-dark condition, only a small number of Fos-immunoreactive neurons was obtained in the visual cortex. By contrast, in dark-reared pups and adult rats, numerous c-fos neurons were detected in the layers II-IV and VI of the visual cortex following a brief light exposure (1 h). In rats of both ages subjected to binocular suture, Fos neurons were detected in the same layers as in the dark-reared rats, but significantly less in number. We speculate that the reduced plasticity of the visual cortex in the rats subjected to binocular suture may be due partly to the repressed AP-1 activity in visual cortical neurons. No significant difference was detected in c-fos expression in the visual cortex between visually manipulated pups and adult rats.

Aging↗
PubMed2000

Additive effects of estrogen deficiency and diabetes on bone mineral density in rats.

We investigated the combined effects of estrogen deficiency and diabetes on bone mineral density (BMD) and bone metabolism in rats. Ten-week-old, female rats were randomly divided into four groups: controls (C), an ovariectomized group (O), a streptozotocin-induced diabetic group (S), and a combined ovariectomy and streptozotocin-induced diabetic group (OS). The BMD of the lumbar spine and the femur were measured before grouping and at 23 weeks old. At the end of the experiment, blood samples were obtained via cardiac puncture, and bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP) and 1,25-dihydroxyvitamin D levels were measured. The rats in the C, O, S, and OS groups, in that order, had higher levels of BMD of the lumbar spine and femur at 23 weeks of age. The BGP levels in the S and OS groups were significantly lower than in C and O groups. Significantly higher 1,25-dihydroxyvitamin D was observed in the O group compared with the C, S and OS groups. No differences were obtained in TRAP among four groups. Our data suggest that the combined effects of estrogen deficiency and diabetes on BMD are not synergistic or counteractive but additive.

Alkaline Phosphatase↗
PubMed2000

Exercise training prevents maturation-induced decreases in insulin receptor substrate-1 and phosphatidylinositol 3-kinase in rat skeletal muscle.

We have previously reported that exercise training prevents a maturation-induced decrease in insulin sensitivity and suggested that an improvement of insulin sensitivity by exercise training was attributable, in part, to an increase in insulin-sensitive GLUT-4 on the skeletal muscle plasma membrane. In this study, we examined the effects of maturation and exercise training on the gene expression and protein content of the components of post-insulin receptor signal transduction in rat skeletal muscle. Rats aged 3 weeks were sedentary or trained by voluntary running through 4 or 27 weeks of age, and then the rats in both the sedentary and trained groups were killed and the gastrocnemius muscle was immediately removed for analysis of mRNA and protein content. The concentration of mRNA and protein for insulin receptor substrate-1 (IRS-1) in sedentary rats significantly decreased with maturation (49% and 63%, respectively, at age 27 weeks v age 4 weeks), but in trained rats they did not decrease with maturation. Although the level of phosphatidylinositol 3-kinase (PI 3-kinase) mRNA in sedentary rats was not altered with maturation, PI 3-kinase protein in sedentary rats significantly decreased with maturation (73% at 27 weeks v 4 weeks). However, PI 3-kinase protein in trained rats did not decrease with maturation. These results suggest that the prevention of maturation-induced decreases in the protein content of IRS-1 and PI 3-kinase is involved in the mechanisms responsible for the improvement of insulin sensitivity by exercise training, and exercise training may affect transcriptional regulation of the IRS-1 gene and posttranscriptional regulation of PI 3-kinase expression.

Animals↗
PubMed2000

The spectrum of beta ig-h3 gene mutations in Japanese patients with corneal dystrophy.

PURPOSE: This study was undertaken to identify beta ig-h3 gene mutations in Japanese patients with granular corneal dystrophy (GCD), Avellino corneal dystrophy (ACD), lattice corneal dystrophy (LCD), and Reis-Bücklers' corneal dystrophy (RBCD). R124H, R124C, R555W, and R555Q mutations have been reported in Europe to cause ACD, LCD type I, GCD, and RBCD, respectively. METHODS: In total, 91 Japanese patients who had been clinically diagnosed with GCD, LCD, or RBCD were investigated to determine whether they had mutations in the beta ig-h3 gene. Genomic DNA was amplified using the polymerase chain reaction and analyzed using single-strand conformation polymorphism techniques. Mutations were identified using the direct sequencing method. RESULTS: In 68 unrelated patients who had been diagnosed with GCD, 62 patients (91%) were found to have the R124H mutation, which has been reported to cause ACD, whereas only six patients (9%) had the R555W mutation. In LCD patients, 10 patients with type I disease had the R124C mutation, and 10 patients with type IIIA disease had a P501T mutation. One patient with atypical LCD had an L527R mutation. In two patients with RBCD, one had an R555Q mutation and the other patient with geographic opacities was found to have an R124L mutation. CONCLUSIONS: Depending on the specific mutation in the beta ig-h3 gene, the phenotypes of corneal dystrophy may differ. Our results indicate that assay of mutations in the beta ig-h3 gene is required to establish a correct diagnosis.

Corneal Dystrophies, Hereditary↗
PubMed2000

Corneal guttata associated with the corneal dystrophy resulting from a betaig-h3 R124H mutation.

AIMS: To investigate the frequency of corneal guttata in patients with a corneal dystrophy resulting from an Arg124His (R124H) mutation of betaig-h3 gene. METHODS: Slit lamp examination was performed on 30 eyes with corneal dystrophy from a genetically confirmed betaig-h3 R124H mutation and on 50 age matched control eyes. The stage of the corneal dystrophy was classified as stage 0, I, or II and the degree of guttata was classified as none, mild, or severe. Specular microscopic examinations were performed to evaluate the morphology of the corneal endothelium. RESULTS: Slit lamp examination disclosed the presence of corneal guttata in 21 eyes (70%) of the 30 eyes with the corneal dystrophy, but in only one (2%) of the 50 eyes in the age matched control group (p<0.001, chi(2) with Yates's correction). Of the 12 eyes with stage I betaig-h3 R124H corneal dystrophy, seven had no corneal guttata and five had a mild degree of guttata. Of the 18 eyes with stage II, the degree of guttata was none in two, mild in nine, and severe in seven. The degree of corneal guttata was significantly related to the stage of the corneal dystrophy (p<0.0001, Kruskul-Wallis test ANOVA on ranks). There was no significant differences between eyes with betaig-h3 R124H corneal dystrophy and normal eyes in cell density, coefficient of variation, and cell hexagonality of corneal endothelium. CONCLUSION: Corneal guttata are one of the characteristics of the corneal dystrophy resulting from betaig-h3 R124H mutation.

Aged↗
PubMed2000

The effect of mental loads on muscle tension, blood pressure and blink rate.

Surface electromyogram (EMG), blood pressure (BP), blink rate (BR) and heart rate (HR) were recorded before and during 4 types of mental task. The mental task involved 3 tasks that encompassed the memory (M), visual search (VS) and color-word (CW) tasks besides the control task (CT) of maintaining a similar posture while focusing on a single spot on the computer screen. Except for CW, any voluntary movement for response to visual stimuli given were not demanded. Slightly but significant increases in integrated EMG (iEMG) were shown in terapezius, biceps and gastrocnemius muscles during tasks except for CT. Especially in the trapezius muscle during M, the most remarkable enhancements of iEMG and BP were shown. In VS and CW tasks, significant decreases in BR were observed, although in M and CT tasks there were no significant changes in it. There were no significant changes in HR in any type of tasks. The present study demonstrated the increase in muscle tension due to mental needs of cognitive tasks per se accompanying changes in BP and BR. And, enhancement of these physiological responses by memory loads and eyeball movement was discussed as a possible mechanism.

Adult↗
PubMed2000

Suppression of glycogen consumption during acute exercise by dietary branched-chain amino acids in rats.

The effects of a diet supplemented with branched-chain amino acids (BCAA; 4.8% or 6.2%) on BCAA catabolism and glycogen metabolism in rats were examined. Rats were fed a BCAA diet or control diet for 4 wk and part of the rats were subjected to exercise training during the experimental period. Feeding the BCAA diet increased serum BCAA concentrations and activity of the hepatic branched-chain alpha-keto acid dehydrogenase complex, the rate-limiting enzyme in the catabolism of BCAA, suggesting that dietary BCAA promotes BCAA catabolism. Although the serum glucose concentration and glycogen contents in the liver and gastrocnemius muscle of rested rats were not significantly affected by feeding of the BCAA diet, those in rats exhausted by acute exercise were 2-4-fold higher in rats fed the BCAA diet than in rats fed the control diet. The activity of pyruvate dehydrogenase complex in the liver and gastrocnemius muscle after acute exercise showed reverse trends; the complex activities (especially in liver) tended to be less in the BCAA diet group than in the control diet group. These results suggest that dietary BCAA spares glycogen stores in liver and skeletal muscle during exercise and that the decrease in pyruvate dehydrogenase complex activity in these tissues by dietary BCAA is involved in the mechanisms.

Amino Acids, Branched-Chain↗
PubMed2000

[Ophthalmic area].

Although herpes simplex virus type 1 or herpes zoster virus is generally considered to cause ocular infection among alpha herpesviruses, herpes simplex virus type 2(HSV-2) retinitis has been recently reported. Acute retinal necrosis(ARN) syndrome is associated with herpesviruses, but the mechanisms remain unclear. The representative ocular infection by alpha herpesviruses is herpes simplex virus type 1(HSV-1) keratitis. The clinical types, ocular symptoms and therapy are reviewed in herpetic ocular infections(HSV-1 blephalitis, conjunctivitis, keratitis, retinitis). In addition, ocular infections caused by herpes zoster virus are reviewed.

Alphaherpesvirinae↗
PubMed2000

Rapid detection of M1S1 mutations by the protein truncation test.

PURPOSE: To determine a method of rapid detection of M1S1 gene mutations in patients with gelatinous droplike corneal dystrophy. METHODS: Forty-one patients from 35 families with gelatinous drop-like corneal dystrophy were studied. The entire coding region of the M1S1 gene was screened using the protein truncation test (PYT), with a polymerase chain reaction fragment amplified from genomic DNA serving as a template of in vitro translation. RESULTS: Homozygous or compound heterozygous mutations were detected in all patients by a single reaction of the PTT. This result matched those obtained using the polymerase chain reaction-restriction fragment length polymorphism and direct sequence analyses. The Q118X mutation was present in 63 of the 70 alleles, accounting for 90% of the disease-associated chromosomes in Japanese patients. CONCLUSIONS: The PTT is useful for detecting mutations in the M1S1 gene. This technique showed that the Q118X mutation is a founder mutation in Japanese patients with gelatinous droplike corneal dystrophy, and it reflects the linkage disequilibrium reported previously.

Antigens, Neoplasm↗
PubMed1999

Isolation and identification of melanin-concentrating hormone as the endogenous ligand of the SLC-1 receptor.

Melanin-concentrating hormone (MCH), which is an orexigenic peptide, was isolated and identified as the endogenous ligand of the SLC-1 receptor. We established a CHO cell line expressing the rat SLC-1 receptor to search for its endogenous ligand. The extract of rat whole brain showed inhibition of intracellular forskolin-induced cAMP accumulation in rat SLC-1-expressing CHO cells and was purified. Using HPLC purification, we isolated and identified MCH as the endogenous ligand of the SLC-1 receptor. The authentic MCH demonstrated a dose-dependent inhibitory effect on cAMP accumulation in forskolin-stimulated rat and human SLC-1-expressing CHO cells with an EC(50) value of 0.2 nM for both the rat and human SLC-1 receptors. This is the first description of the functional receptor for MCH.

Amino Acid Sequence↗
PubMed1999

BTEB2, a Krüppel-like transcription factor, regulates expression of the SMemb/Nonmuscle myosin heavy chain B (SMemb/NMHC-B) gene.

We have recently characterized the promoter region of the rabbit embryonic smooth muscle myosin heavy chain (SMemb/NMHC-B) gene and identified the 15-bp sequence, designated SE1, located at -105 from the transcriptional start site as an important regulatory element for its transcriptional activity in a smooth muscle cell (SMC) line. In this study, we attempted to isolate cDNA clones encoding for the transcription factors that control the expression of the SMemb gene through binding to this cis-regulatory element. We screened a lambdagt11 cDNA library prepared from C2/2 cells, a rabbit-derived SMC line, by using a radiolabeled concatenated oligonucleotide containing SE1 as a probe. Sequence analysis revealed that one of the cDNA clones corresponds to the rabbit homologue of basic transcriptional element binding protein-2 (BTEB2), which has previously been identified as one of the Krüppel-like transcription factor. Gel mobility shift assays and antibody supershift analyses with nuclear extracts from C2/2 cells indicate that BTEB2 is a major component of nuclear factor:SE1 complexes. Furthermore, a glutathione S-transferase-BTEB2 fusion protein binds to the SE1 in a sequence-specific manner. In support of the functionality of BTEB2 binding, basal promoter activity and BTEB2-induced transcriptional activation were markedly attenuated by the disruption of the SE1. In adult rabbit tissues, BTEB2 mRNA was most highly expressed in intestine, urinary bladder, and uterus. BTEB2 mRNA levels were downregulated in rabbit aorta during normal development. Moreover, immunohistochemical analysis indicated a marked induction of BTEB2 protein in the neointimal SMC after balloon injury in rat aorta. These results suggest that BTEB2 mediates the transcriptional regulation of the SMemb/NMHC-B gene and possibly plays a role in regulating gene expression during phenotypic modulation of vascular SMC.

Age Factors↗
PubMed1999

Urotensin II is the endogenous ligand of a G-protein-coupled orphan receptor, SENR (GPR14).

Two molecular species of urotensin II (UII) were isolated from porcine spinal cords and identified as the endogenous ligands of a G-protein-coupled orphan receptor, SENR (sensory epithelium neuropeptide-like receptor), which is identical to GPR14. We established a CHO cell line stably expressing the rat SENR and investigated several tissue extracts to evoke the response mediated by the SENR. Extract from porcine spinal cords showed an activity of arachidonic acid metabolites release from SENR-expressing cells and was purified using HPLC. Two active substances were isolated and their sequences were determined as GPTSECFWKYCV and GPPSECFWKYCV, which were revealed to be porcine UII. Synthetic UII peptides caused arachidonic acid metabolites release activity in the rat SENR-expressing cells with an EC(50) value of 1 nM. Three cDNAs encoding the precursor proteins of porcine UII were cloned from a porcine spinal cord cDNA library; 2 consist of 121 amino acid residues and the other, which seemed to be a splicing variant, consist of 85 residues.

Amino Acid Sequence↗