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Biomedical subjects

Yoshihiko Ito

Publications and source records attributed to Yoshihiko Ito.

At least 19 recordsLinked to original sources
PubMed2006

Fourteen-week feeding test of meat and milk derived from cloned cattle in the rat.

Agricultural application of cloned livestock produced by nuclear transfer requires public and governmental understanding of food-safety issues. To determine whether physiological effects occurred in animals fed products derived from cloned cattle, we conducted long-term (14 week) trials feeding Crj:CD(SD)IGS rats meat and milk from cloned cattle. Diets containing meat and milk were equal in nutritional value to the basal diet (AIN93G). Urinalysis was performed at Weeks 4, 8 and 12; at the end of the feeding period, blood sampling and autopsies were conducted. During the feeding periods, there were no significant differences in general condition, death loss, growth, battery of functional observational tests and estrous cycles among groups given diets containing meat and milk powder from non-clone, embryonic clone and somatic clone cattle. Furthermore, no significant changes attributed to consumption of clone meat or milk were detected in urinalysis, hematological and blood chemical, gross pathological or histological examinations. Therefore, we concluded that the physiologic conditions of the rats were not affected by consumption of meat and milk from bovine clones.

Animal Feed↗
PubMed2006

Susceptibility of newborn rats to 3-ethylphenol and 4-ethylphenol compared with that of young rats.

Newborn rat studies were conducted with oral administration of 3-ethylphenol (3EP) and 4-ethylphenol (4EP) on postnatal days (PND) 4-21 to allow comparison of no observed adverse effect level (NOAEL) and unequivocally toxic level (UETL) with those from 28-day studies of young rats starting at 5-6 weeks of age. In the newborn rat studies, slightly lowered body weight was observed after 3EP treatment, and deaths, hypoactivity, Straub tail, deep respiration and delayed righting reflex were clearly observed after 4EP treatment. In the young rat studies, salivation, staggering gait, changes in the liver including high values of liver weight and alanine aminotransferase or total cholesterol and the lesions in the forestomach were clearly observed after 3EP and 4EP treatments. NOAELs of 3EP and 4EP in the newborn rat studies appeared to be almost 3 times lower than those in the young rat studies. As a clear toxicity of 3EP was not observed in newborn rats, UETLs were not established for 3EP. Regarding 4EP, UETL of young rats was 4-5 times higher than that of newborn rats. In conclusion, newborn rats were 3-5 times more susceptible to 3EP and 4EP than young rats.

Administration, Oral↗
PubMed2005

Passive stretching produces Akt- and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice.

Muscle contraction is accompanied by passive stretching or deformation of cells and tissues. The present study aims to clarify whether or not acute passive stretching evokes glucose transporter 4 (GLUT4) translocation and glucose uptake in skeletal muscles of mice. Passive stretching mainly induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a plasma membrane-rich fraction (F2) and accelerated glucose uptake in hindlimb muscles; whereas electrical stimulation, which mimics physical exercise in vivo, and insulin, each induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a fraction rich in plasma membrane (F2), and to one rich in transverse tubules (PF3), along with subsequent glucose uptake. Mechanical stretching increased phosphorylation of Akt and p38 mitogen-activated protein kinase (p38 MAPK), but it had no apparent effect on the activity of AMP-activated protein kinase (AMPK). Electrical stimulation augmented the activity of not only AMPK but also phosphorylation of Akt and p38 MAPK. Our results suggest that passive stretching produces translocation of GLUT4 mainly from the fraction rich in intracellular membrane to that rich in plasma membrane, and that the glucose uptake could be Akt- and p38 MAPK-dependent, but AMPK-independent manners.

Animals↗
PubMed2005

Palladium-catalyzed addition of arylboronic acids to aldehydes.

[reaction: see text] Arylboronic acids react with aldehydes in the presence of a base and a catalytic amount of a palladium(0) complex with chloroform, affording the corresponding secondary alcohols in good yields. General palladium complexes have no catalytic activity without chloroform. Chloroform is essential for this reaction, and palladium complex that was prepared from Pd(PPh3)4 with CHCl3 showed good catalytic acitivity as well.

Journal Article↗
PubMed2005

Stereoselective synthesis of highly enantioenriched (E)-allylsilanes by palladium-catalyzed intramolecular bis-silylation: 1,3-chirality transfer and enantioenrichment via dimer formation.

Highly enantioenriched (E)-allylsilanes have been synthesized from optically active allylic alcohols on the basis of Pd-catalyzed intramolecular bis-silylation followed by highly stereospecific Si-O elimination reactions. The method involves three steps: 1) O-disilanylation of the allylic alcohols with chlorodisilanes, 2) intramolecular bis-silylation in the presence of a 1,1,3,3-tetramethylbutyl isocyanide/[Pd(acac)2] (acac = acetylacetonate) catalyst at 110 degrees C, and 3) treatment of the reaction mixture with organolithium reagents. The overall transformation proceeds with nearly complete conservation of the enantiopurity of the starting allyl alcohols by transposition of the C=C bond. For instance, (R)-(E)-3-decen-2-ol (99.6-99.7 % ee) produced (S)-(E)-4-(organosilyl)-2-decene of 98.8-99.4 % ee for a variety of silyl groups, including Me3Si, Me2PhSi, tBuMe2Si, Et3Si, and iPr3Si. In the bis-silylation step, the initially formed trans-1,2-oxasiletanes immediately dimerize to stereoselectively give 1,5-dioxa-2,6-disilacyclooctanes, which are isolated in high yield by carrying out the reaction at 70 degrees C. The eight-membered ring compounds undergo thermal extrusion of (E)-allylsilanes in high yield at 110 degrees C, along with formation of 1,3-dioxa-2,5-disilacyclohexane derivatives. These in turn undergo a Peterson-type elimination by treatment with nucleophiles such as BuLi and PhLi to give the (E)-allylsilanes. All of the steps involved in the sequence proceed with extremely high stereoselectivity and stereospecificity, leading to almost complete 1,3-chirality transfer through the overall transformation. The dimerization step, which forms diastereomeric intermediates, allows the synthesis of a highly enantioenriched allylsilane (99.4 % ee) from an optically active allylic alcohol with lower enantiopurity (79.2 % ee) by enrichment of enantiopurity. A general method for the determination of the enantiomeric excesses of (E)-allylsilanes is also described in detail.

Journal Article↗
PubMed2005

Elevated susceptibility of newborn as compared with young rats to 2-tert-butylphenol and 2,4-di-tert-butylphenol toxicity.

In order to determine the susceptibility of newborn rats to 2-tert-butylphenol (2TBP) and 2,4-di-tert-butylphenol (DTBP) toxicity, studies were conducted with oral administration from postnatal days (PND) 4 to 21 and the findings were compared with results for young rats exposed from 5 or 6 weeks of age for 28 days. In the newborn rats, specific effects on physical and sexual development and reflex ontogeny were not observed. While there were no clear differences in toxicological profiles between newborn and young rats, the no-observed-adverse-effect levels (NOAELs) differed markedly. For 2TBP, clinical signs such as ataxic gait, decrease in locomotor activity and effects on liver, such as increase in organ weight, were observed and the NOAELs were concluded to be 20 and 100 mg/kg/day in newborn and young rats, respectively. Based on hepatic and renal toxicity (histopathological changes and increase in organ weight with blood biochemical changes), the respective NOAELs for DTBP were concluded to be 5 and 20 mg/kg/day. Therefore, the susceptibility of newborn rats to 2TBP and DTBP was found to be 4-5 times higher than that of young rats.

Age Factors↗
PubMed2005

Susceptibility of newborn rats to hepatotoxicity of 1,3-dibromopropane and 1,1,2,2-tetrabromoethane, compared with young rats.

Newborn rat studies were conducted with oral administration of 1,3-dibromopropane (DBP) and 1,1,2,2-tetrabromoethane (TBE) from postnatal Days 4 to 21 to allow comparison of NOAELs and unequivocally toxic levels with those from 28-day young rat studies starting at 5-6 weeks of age. The unequivocally toxic level was estimated by our specified criteria, requiring simultaneous change of organ weights, histopathology, some biochemical parameters and body weights, because in this study only hypertrophy of hepatocytes was observed as a major histopathological change. DBP caused centrilobular hypertrophy of hepatocytes with alteration in biochemical parameters, as well as lowering of body weights, regardless of sex, in both newborn and young rats. NOAELs and unequivocally toxic levels were considered to be 50 and 150 mg/kg/day in newborn rats and 10 and 250 mg/kg/day in young rats, respectively. In the newborn rat study of TBE, some hepatic effects observed at the top dose of 50 mg/kg were not considered adverse because of the lack of histopathological changes. Significant lowering of body weight was noted at 200 mg/kg in the dose-finding study but histopathological data were not available. In the young rat study, there was no definite toxicity at 6 mg/kg and hypertrophic changes in liver and thyroids without body weight change occurred at 200 mg/kg. There were no clear sex differences in both the newborn and young rat studies. NOAELs were considered to be 50 and 6 mg/kg/day in newborn and young rats, respectively, but unequivocally toxic levels for both rats could not be estimated. Abnormalities of external and sexual development and reflex ontogeny in the newborn were not observed with either chemical. Based on these results, it can be concluded that the target organ of DBP and TBE is the liver in both newborn and young rats, and that while the doses at which toxic signs began to appear are higher in newborn rats, those causing clear toxicity may be paradoxically lower in the newborn case.

Age Factors↗
PubMed2004

Highly enantioselective synthesis of chiral 3-substituted indolines by catalytic asymmetric hydrogenation of indoles.

[reaction: see text] N-Tosyl 3-substituted indoles were hydrogenated with high enantioselectivities (95-98% ee) by use of a trans-chelating chiral bisphosphine, (S,S)-(R,R)-PhTRAP ligand. The chiral catalyst, which was generated in situ from [Rh(nbd)(2)]SbF(6), PhTRAP, and Cs(2)CO(3), is useful for enantioselectively synthesizing a range of diverse optically active indolines possessing a chiral carbon at the 3-position.

Journal Article↗
PubMed2004

Unexpected nephrotoxicity induced by tetrabromobisphenol A in newborn rats.

The repeated dose toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male and female newborn rats given TBBPA orally at 0, 40, 200, or 600 mg/kg per day for 18 days from 4 days of age until weaning at 21 days of age. Half the rats in each dose group were sacrificed for a full gross necropsy and a histopathology on the organs and the tissues at 22 days of age and the remaining rats were reared without any treatment from post-weaning until 84 days of age to examine the recovery and the delayed occurrence of toxic effects. Treatment with 200 or 600 mg/kg TBBPA-induced nephrotoxicity characterized by the formation of polycystic lesions, and some deaths occurred in the 600 mg/kg group. There was no gender difference of nephrotoxicity and there were no other critical toxicities. At 85 days of age, nephrotoxic lesions were still present in the 200 and 600 mg/kg groups, but no abnormalities indicating delayed occurrence of toxic effects were found in the treated groups. In order to investigate the specificity of the nephrotoxicity induced by TBBPA in newborn rats, TBBPA was given to male and female young rats (5 weeks old) by oral administration at 0, 2000, or 6000 mg/kg per day for 18 days. The kidneys showed no histopathological changes even at the high dose. These results clearly indicate that the nephrotoxicity of TBBPA is specific for newborn rats although the toxic dose level was relatively high. To gain insight into the possible effects on human infants, the mechanism of this unexpected nephrotoxicity of TBBPA in newborn rats should be examined.

Administration, Oral↗
PubMed2004

Evaluation of meat products from cloned cattle: biological and biochemical properties.

Agricultural utilization of cloned livestock produced by nuclear transfer and their products for food will require public and governmental acceptance. A series of studies of properties of meat derived from cloned cattle was carried out to collect data for the safety assessment of cloned cattle products. Meat samples obtained from embryonic cloned, somatic cloned and non-cloned cattle were analyzed for chemical composition, as well as amino acids and fatty acids. Digestibility, allergenicity, and mutagenicity of meat were also examined. There were no significant differences in these properties among embryonic cloned, somatic cloned and non-cloned cattle. The analyses and tests revealed that there were no significant biological differences in meat from a non-cloned, an embryonic cloned, or a somatic cloned animal. A 14-week feeding trial in rats showed there were no abnormalities in body growth, general condition, locomotor activity, reflexes, sexual cycle, urinalysis, hematology, blood biochemistry, and histology. This study showed for the first time that the biological/biochemical properties of meat of cloned cattle are similar to those of non-cloned cattle.

Amino Acids↗
PubMed2003

Asymmetric allylation of unsymmetrical 1,3-diketones using a BINAP-palladium catalyst.

[reaction: see text] The chiral palladium complex generated in situ from [Pd(eta(3)-allyl)Cl](2) and (R)-BINAP is a good catalyst for the catalytic asymmetric allylation of 1,3-diketones. The reaction provided chiral 2,2-dialkyl-1,3-diketones with 64-89% ee in high yields (13 examples). Enantiomeric excesses are strongly affected by the gamma-substituent of the allylic substrates. A variety of unsymmetrical 1,3-diketones were alkylated with cinnamyl acetate in good enantioselectivities via use of the BINAP-palladium catalyst (77-89% ee).

Journal Article↗
PubMed2003

Gender-specific knee extensor torque, flexor torque, and muscle fatigue responses during maximal effort contractions.

The purpose of this study was to examine gender differences in knee extensor and flexor peak torque, work, power, and muscle fatigue during maximal effort isokinetic contractions. Subjects included 19 healthy male and 20 healthy female volunteers. Following a dynamic warm-up period, subjects performed 30 reciprocal, concentric maximal knee extension and flexion contractions at a pre-set angular velocity of 3.14 rad x s(-1) on the Biodex Isokinetic Dynamometer. Values for knee extensor peak torque, work, and power were calculated for each repetition over an angular displacement of 1.05 rad for each repetition. The single highest repetition value for knee extensor and flexor peak torque, work, and power was then calculated relative to body mass (N x m x kg(-1), J x kg(-1), W x kg(-1)) and allometric-scaled (N x m x kg(-) (n), J x kg(-) (n), W x kg(-) (n)) units. The allometric-scaled units were derived from a log-log transformation and linear regression analysis to calculate the exponent to which body mass is raised. The rate of quadriceps femoris muscle fatigue was calculated as the decline in each isokinetic variable by the linear slope from the single highest repetition value through the 30th repetition, and by two different fatigue indexes. The results demonstrate higher knee extension and flexion peak torque, work, and power in absolute, relative, and allometric-scaled units for males compared to females. Males exhibited higher fatigue rates for both muscle groups of each isokinetic variable than females, as described by the slope and the fatigue index, except when adjusted for peak values via analysis of covariance. The findings suggest that during maximal-effort muscle contractions, males exhibit a higher susceptibility to muscle fatigue than females, a phenomenon that may be related to an inherent ability to generate higher knee extensor and flexor torque.

Adult↗
PubMed2003

Higher susceptibility of newborn than young rats to 3-methylphenol.

To determine susceptibility of infants to 3-methylphenol, a repeated dose toxicity study was conducted with oral administration to newborn and young rats. In an 18-day newborn study from postnatal days 4 to 21 at doses of 30, 100 and 300 mg/kg/day, various clinical signs including deep respiration, hypersensitivity on handling and tremors under contact stimulus, and depressed body weight gain were observed at 300 mg/kg. At 100 mg/kg, hypersensitivity and tremors were also noted in a small number of males only on single days during the dosing period. No adverse effects were observed in the 30 mg/kg group. There were no abnormalities of physical development, sexual maturation and reflex ontogeny. The no observed adverse effect level (NOAEL) for newborn rats was considered to be 30 mg/kg/day and the unequivocally toxic level 300 mg/kg/day. In a 28-day study starting at 5 weeks of age, clinical signs and depression of body weight gain, as observed in the newborn rats, appeared in both sexes at 1000 mg/kg but not 300 mg/kg. The NOAEL and the unequivocally toxic level were 300 mg/kg/day and 1,000 mg/kg/day, respectively. From these results, newborn rats were concluded to be 3 to 10 times more susceptible to 3-methylphenol than young rats. However, the realistic no adverse effect dose for the newborn must be slightly lower than 100 mg/kg/day, at which the toxicity incidence was very low, rather than 30 mg/kg/day. Based on this speculation and the equal toxicity at unequivocally toxic levels, the differences in the susceptibility to 3-methylphenol could be concluded to be 3 to 4 times. This is consistent with the results of our previous comparative studies on 4-nitrophenol, 2,4-dinitrophenol and 3-aminophenol, which showed 2 to 4 times differences in the susceptibility between newborn and young rats.

Aging↗
PubMed2002

Catalyzed intramolecular olefin insertion into a carbon-carbon single bond.

Intramolecular insertion of a C-C double bond into a C-C single bond was achieved by treatment of cyclobutanone bearing an o-styryl group at the 3-position with a catalytic amount of a cationic rhodium(I)-dppp complex. Initially, rhodium is inserted between the carbonyl carbon and the alpha-carbon of the cyclobutanone. Intramolecular coordination of the vinyl group results in its migratory insertion into the C-Rh linkage. Reductive elimination affords benzobicyclo[3.2.1]octan-3-one. Notably, a ring-opened alpha,beta-unsaturated ketone was obtained when dppe was used instead of dppp. In this reaction, rhodium cleaved the bond between the alpha sp3 carbon and the beta sp3 carbon of the cyclobutanone. The coordinating vinyl group directs this new regioselectivity of cleavage observed with the dppe ligand.

Journal Article↗