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Biomedical subjects

N Takeda

Publications and source records attributed to N Takeda.

At least 55 records · Page 3Linked to original sources
PubMed2001

Association of the mitochondrial DNA 5178 A/C polymorphism with serum lipid levels in the Japanese population.

As one approach to exploring whether the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is associated with atherosclerosis, we genotyped 461 healthy Japanese individuals and studied the relationship of mt5178 A/C genotypes to serum lipid levels. Blood specimens were obtained after at least a 12-h fasting period from the subjects. The mt5178 A/C was genotyped by the polymerase chain reaction/restriction fragment length polymorphism method. The relative frequency of mt5178 A was 41.6% (192/461) and of mt5178 C was 58.4% (269/461). After adjustments for age and body mass index, the high-density lipoprotein cholesterol concentration in males carrying mt5178 A was significantly higher than that in males carrying mt5178 C ( P=0.026). The tryglyceride (TG) concentration in females carrying mt5178 A was significantly lower than that in females carrying mt5178 C ( P=0.012). This difference in the TG level between the two genotypes was more evident in postmenopausal females than in premenopausal females. Mt5178 A seems to have an antiatherogenic effect. This is the first genetic epidemiological report on the association of mt5178 A/C polymorphism with serum lipid levels in the Japanese population.

Adenine↗
PubMed2001

Complementary functions of Otx2 and Cripto in initial patterning of mouse epiblast.

The development of the mammalian antero-posterior (A-P) axis is proposed to be established by distinct anterior and posterior signaling centers, anterior visceral endoderm and primitive streak, respectively. Knock-out studies in mice have shown that Otx2 and Cripto have crucial roles in the generation and/or functions of these anterior and posterior centers, respectively. In both Otx2 and Cripto single mutants, the initial formation of the A-P axis takes place in a proximal-distal (P-D) orientation, but subsequent axis rotation fails to occur. To examine the developmental consequences of the lack of these two genes, we have analyzed the Otx2(-/-);Cripto(-/-) double homozygous mutant phenotype. In the double mutants, the expression of the A-P axis markers Cer-l, Lim1, and Wnt3 was not induced, while expression of Fgf8 and T was expanded throughout the epiblast, indicating that the double mutants could not form the A-P axis even in its initial P-D orientation. In addition, the double mutants displayed defects in differentiation of the visceral endoderm overlying the epiblast, as well as in the extraembryonic ectoderm. Furthermore, differentiation of neuroectoderm was accelerated as judged by the reduction of Oct4 expression and emergence of Sox1 and Gbx2 expression in the double mutant epiblast. The resulting ectoderm only displayed characteristics of anterior hindbrain, implicating it as a ground state in the mammalian body plan. Our results indicate that complementary functions of Otx2 and Cripto are essential for initial patterning of the A-P axis in the mouse embryo.

Animals↗
PubMed2001

Oral administration of hepatitis E virus-like particles induces a systemic and mucosal immune response in mice.

We evaluated the potential of recombinant hepatitis E virus (rHEV) virus-like particles (VLPs) as an oral immunogen by analyzing the response of serum IgM, IgG, and IgA and fecal IgA in mice after oral administration. The capsid proteins of HEV with its N-terminal 111 amino acids truncated were expressed with a recombinant baculovirus in insect cells, where the capsid proteins self-assembled into VLPs. Mice were orally inoculated four times with purified rHEV VLPs in concentrations ranging from 10 to 100 microg without adjuvant. Serum IgM response was obtained with as little as 10 microg of the VLPs, and the level reached its maximum in all mice groups within 2 weeks after the first administration. Serum IgG was detected by 4 weeks post-immunization (p.i.) in the majority of mice given doses of 50 and 100 microg and continuously increased at least until the 10 week mark. Serum IgA was also detected by 4 weeks p.i. in the majority of mice given doses of 50 and 100 microg, and the level reached the maximum at 8 weeks p.i. Furthermore, the maximum level of intestinal IgA responses was detected in the groups of mice receiving 50 and 100 microg rHEV VLPs at 8 weeks p.i. All these antibody responses were obtained without a mucosal adjuvant. We therefore concluded that oral immunization of rHEV VLPs is capable of inducing systemic as well as intestinal antibody responses. Furthermore, serum IgG and fecal IgA thus induced were reactive to the native HEV antigen, as determined by Western blot assays and antigen-capture ELISA.

Administration, Oral↗
PubMed2001

Effect of AF64A, a cholinergic neurotoxin, on footshock stimulation-induced locus coeruleus excitation in rats.

We studied the effect of ethylcholine mustard aziridinium ion (AF64A), a cholinergic neurotoxin, on the footshock stimulation (FS)-induced excitation of the locus coeruleus (LC) neurons in rats. The FS-evoked LC excitation was significantly reduced in AF64A-treated rats, in comparison with normal rats. In particular, the early component of LC excitation was less pronounced. The number of choline acetyltransferase immunoreactive neurons in the septal complex was significantly lower than those in normal rats, except for in the ventral subgroup. These findings suggest that the cholinergic neuron system is involved in the early component of LC excitation in rats.

Action Potentials↗
PubMed2001

Genetic analysis of recent Taiwanese isolates of a variant of coxsackievirus A24.

Epidemics of acute hemorrhagic conjunctivitis (AHC) caused by a variant of coxsackievirus A24 (CA24v) reappeared in Taiwan in 1990 and 1994, following the first two epidemics of 1985--86 and 1988--89. To analyze the genetic diversity of recent CA24v in Taiwan, 7 Taiwanese strains isolated during the 1990--94 period were studied together with one Japanese and two Thai strains isolated in 1993. A fragment of 674 nucleotides between the carboxy terminal 3A and the amino terminal 3D polymerase, including the entire 3C protease (3C(pro)), was amplified by a reverse transcription-polymerase chain reaction (RT-PCR) and the nucleotide sequences were determined. In the 549 nucleotides (183 amino acids) of the entire 3C(pro), we found nucleotide differences at 80 positions between 10 strains and the prototype strain, EH24/70, one of the earliest strains of CA24v. Most of the nucleotide changes were synonymous substitutions and only nine amino acid changes were found. The nucleotide sequence homologies among 71 strains worldwide were 88-100%. These 71 nucleotide sequences were then analyzed by Neighbor-joining method and phylogenetically separated into three distinct genotypes. Genotype I consisted of early strains isolated in 1970--71 from Singapore and Hong Kong. Genotype II included isolates from Singapore and Thailand obtained in 1975. Genotype III comprised strains from the eastern hemisphere isolated in 1985--94 from Japan, Taiwan, China, Hong Kong, Thailand, Singapore, Pakistan and Ghana. They were further divided chronologically into six clusters. The recent isolates from Taiwan obtained in 1985/1986, 1988/1989 and 1990--94 were classified into genotype III Clusters 1, 5, and 6 respectively. The evolutionary rate was re-estimated to be 3 x 10(- 3) 30 years after the emergence of the virus.

Amino Acid Sequence↗
PubMed2001

Seroepidemiological study of hepatitis E virus infection in Japan using a newly developed antibody assay.

PURPOSE: A seroepidemiological study of hepatitis E virus (HEV) infection was conducted in Japan, where HEV infection is not considered endemic. METHODS: IgG and IgM class antibodies to HEV were measured with a newly developed enzyme-linked immunosorbent assay in which recombinant virus-like particles were used as an antigen. A total of 1253 individuals (401 males and 852 females; age range, 6-89 years) were enrolled from two different areas: area 1 (n = 478), in which hepatitis C was endemic; and area 2 (n = 775), in which it was not endemic. RESULTS: The HEV antibody (IgG class) positive rate was 6.7% in area 1 and 4.6% in area 2. Similarly, the HAV antibody (IgG class) positive rates were 65.3% and 72.3%. The age- and sex-specific prevalence of both HAV and HEV antibodies was quite similar in the two areas, and the HAV antibody positive rate clearly increased with age in both males and females. On the other hand, the HEV antibody positive rate showed a slight tendency to increase with age in males, but not in females. None of the 32 individuals with the HEV antibody who were interviewed had a history of visiting countries in which hepatitis E was endemic. In both areas, the mean age, percentage of males, and HAV antibody positive rate were significantly higher in the group of individuals with the HEV antibody than in the group of those without it, according to conventional statistical analyses. Of the three factors age, male sex, presence of HAV antibody, and the area factor, only male sex was statistically significant (P < 0.001) on multivariate logistic regression analysis. Two (0.2%) of the total of 1253 individuals were positive for the IgM class antibody to HEV. CONCLUSIONS: Our results suggest the possibility that HEV infection is circulating in Japan at a low level. HEV infection was associated with male sex, but not with HAV infection.

Adolescent↗
PubMed2001

Novel vitamin E derivative with 4-substituted resorcinol moiety has both antioxidant and tyrosinase inhibitory properties.

A novel vitamin E derivative, (6"-hydroxy-2",5",7",8"-tetramethylchroman-2"-yl)methyl 3-(2',4'-dihydroxyphenyl)propionate (TM4R), which has a chromanoxyl ring and 4-substituted resorcinol moieties, was synthesized; and its inhibitory effects on tyrosinase, antioxidant ability, and lightening effect of ultraviolet B (UVB)-induced hyperpigmentation were estimated. TM4R showed potent inhibitory activity on tyrosinase, which is the rate-limiting enzyme in melanogenesis. The scavenging activities of TM4R on 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals were found to be nearly the same as those of alpha-tocopherol. Furthermore, an efficient lightening effect was observed following topical application of TM4R to UVB-stimulated hyperpigmented dorsal skin of brownish guinea pigs. These results suggest that TM4R may be a candidate for an efficient whitening agent, possibly by inhibiting tyrosinase activity and biological reactions caused by reactive oxygen species.

Animals↗
PubMed2001

Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells: implications for long-term graft patency.

BACKGROUND: Serotonin can induce proliferation of vascular smooth muscle cells. We assessed the ability of a specific serotonin receptor antagonist, sarpogrelate, to inhibit proliferation of cultured porcine coronary artery smooth muscle cells. METHODS: Cell proliferation and mitotic activity were measured using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide. To determine the effect of sarpogrelate on DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and protein synthesis, radioactive incorporation of 3H-thymidine, 3H-uridine, and 3H-phenylalanine, respectively, was used. Synthesis of DNA was also assessed by flow cytometry with propidium iodide as a fluorochrome. RESULTS: Serotonin, platelet-derived growth factor, endothelin, and angiotensin II all induced proliferation of porcine coronary artery smooth muscle cells. Sarpogrelate specifically inhibited the serotonin-induced cytokine trigger but did not influence platelet-derived growth factor-, endothelin-, or angiotensin II-induced cell proliferation. Sarpogrelate inhibited the serotonin-induced increase in intracellular free ionized calcium concentration, prevented mitogen-activated protein kinase activation, and down-regulated expression of the protooncogenes c-fos and c-jun. Sarpogrelate acted at the G1 phase of the cell cycle. CONCLUSIONS: These data suggest that sarpogrelate could be used as a therapeutic agent to inhibit serotonin-induced neointimal hyperplasia and improve patency of coronary artery bypass grafts.

Animals↗
PubMed2001

An increased expression of Ca(2+) channel alpha(1A) subunit immunoreactivity in deep cerebellar neurons of rolling mouse Nagoya.

Rolling mouse Nagoya (RMN) is an ataxic mutant and carries a mutation in the gene coding for the alpha(1A) subunit of the P/Q-type Ca(2+) channel. We examined the immunohistochemical expression of the alpha(1A) subunit in deep cerebellar nuclei of RMN. The antibody used recognized residues 865-883 of the mouse alpha(1A) subunit not overlapping the altered sequences in RMN. In RMN, many neurons exhibited definite alpha(1A) subunit-staining in the medial nucleus, interposed nucleus, and lateral nucleus of deep cerebellar nuclei. The number of positive neurons in these nuclei was significantly higher in RMN than in controls. Increased expression of the alpha(1A) subunit in deep cerebellar neurons might compensate for the altered function of the P/Q-type Ca(2+) channel of RMN.

Animals↗
PubMed2001

Role of cholinergic mossy fibers in medial vestibular and prepositus hypoglossal nuclei in vestibular compensation.

Several lines of evidence have suggested that acetylcholine is a possible neurotransmitter/neuromodulator involved in vestibular compensation. Further, the central vestibular system, oculo- and spino-motor neurons and peripheral vestibular efferents contain abundant cholinergic neurons. However, details of cholinergic effective sites during vestibular compensation remain to be clarified. In the present study, we selectively damaged rat vestibulo-floccular and vestibulo-uvulonodular cholinergic mossy fibers using ethylcholine mustard aziridinium ions. In these treated animals, unilateral labyrinthectomy caused more severe vestibulo-ocular deficits especially during the initial stage. From these findings we suggest that vestibulo-floccular and vestibulo-uvulonodular cholinergic mossy fibers contribute to the restoration of a balance between intervestibular nuclear activities for the induction of vestibular compensation during the initial stage.

Acetylcholine↗
PubMed2001

Intravitreal phacoemulsification with pars plana vitrectomy and posterior chamber intraocular lens suture fixation for dislocated crystalline lenses.

This technique to manage a dislocated crystalline lens comprises intravitreal phacoemulsification with transscleral suture fixation of a posterior chamber intraocular lens (IOL). The dislocated lens in the vitreous cavity is removed using a standard phaco handpiece with the assistance of a fiber-optic light pipe. Then, the IOL is implanted. The technique was used in 10 eyes of 8 patients with lens luxation or subluxation. The postoperative best corrected visual acuity was 20/25 or better except in 1 eye, and no serious complications were observed. Increased intraocular pressure before surgery in 4 eyes was normalized in 3 eyes.

Aged↗
PubMed2001

Noradrenergic pathways involved in the development of vertigo and dizziness--a review.

In this study, vestibular caloric stimulation (CS) inhibited noradrenergic (NA) neurons of the locus coeruleus (LC) in rats. The vestibular input can be modified by the ventrolateral medulla (VLM), which then inhibits the LC neuronal activity via GABAA receptors. Clinically, CS induces vertigo in humans. Thus, LC-NA inhibition may be involved in the development of vertigo. Moreover, it is speculated that Sopite syndrome, one of the major symptom complexes of motion sickness, is also evoked by LC-NA inhibition. The central LC-NA neuronal system may participate in vertigo and motion sickness independent of the histaminergic neuronal system. In contrast, the cholinergic neuronal system may mediate LC-NA inhibition during the vestibulo-atonomic reflex. The LC-NA system projects to most higher centers and affects sensory information processing. Therefore, it is suggested that the suppression of sensory information processing induced by LC-NA inhibition causes drowsiness, one of the major symptoms of vertigo and motion sickness. It is also speculated that LC-NA inhibition participates in the development of sensory mismatch during vertigo and motion sickness.

Animals↗
PubMed2001

Role of cholinergic mossy fibers in vestibular nuclei in the development of vestibular compensation.

Several lines of evidence have suggested that acetylcholine is a possible neurotransmitter/neuromodulator involved in vestibular compensation. However, details of cholinergic effective sites during vestibular compensation remain unclear. In this study, we selectively damaged the rat vestibulo-floccular cholinergic mossy fibers using ethylcholine mustard aziridinium ion. In these animals, unilateral labyrinthectomy caused more severe vestibulo-ocular deficits, especially in the initial stage. These findings suggest that the vestibulo-floccular cholinergic mossy fibers serve to restore the balance between intervestibular nuclear activities in order to induce vestibular compensation in the initial stage.

Animals↗
PubMed2001

Information processing of visually-induced apparent self motion in the cortex of humans: analysis with magnetoencephalography.

The cortical site which processes information on whole-body linear displacement is unknown. In this study, neuromagnetic responses to a visually-induced linear vection were recorded in 5 healthy, right-handed, adult subjects using a 122-channel whole cortex neuromagnetometer. We presented expanding rectangles on the screen which came into view one after another and accelerated in expanding speed at random cycle, giving the subjects the sensation of linear self motion (linear vection) through an illusory tunnel with occasional acceleration. Clear responses of magnetic fields related to the accelerative event were obtained in both hemispheres around the parietal and temporal regions. The dipole sources of the component were estimated in the cortex around the superior temporal sulcus, insula and medial superior temporal area. Some parts of these regions may have been comprised in the vestibular cortex, suggesting that it processes the sensation of linear self motion and plays an important role in space perception.

Adult↗
PubMed2001

Recurrent septicemia caused by Streptococcus canis after a dog bite.

Human infection with Streptococcus canis is extremely rare. We describe herein a case of septicemia with cellulitis caused by S. canis in a 75-y-old woman, which developed 2 weeks after a dog bite. Macrorestriction analysis with pulsed-field gel electrophoresis demonstrated that the organism had been transmitted by means of a dog bite to her hand.

Aged↗