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Biomedical subjects

S Nakayama

Publications and source records attributed to S Nakayama.

At least 37 records · Page 2Linked to original sources

RET tyrosine kinase enhances hair growth in association with promotion of melanogenesis.

We first demonstrated that c-Ret protein is transiently expressed mainly in the inner and outer root sheaths of hair follicles soon after birth in the skin of normal C57BL/6 and BALB/c mice. A longer-lasting expression of activated RET protein overlapped the c-Ret expression with some preferential expression in the outer root sheath in close association with increase in the number of S-100 protein-containing cells in the area and excess melanogenesis in and around hair bulbs in the skin of RFP-RET-transgenic mice on a C57BL/6 background (RFP-RET/B6). Hair follicles in the skin of the transgenic mice continuously showed histology of the anagen phase, and the recovery period for the hair of the transgenic mice after shaving was shortened. Such growth promotion was not observed in the case of white hairs of RFP-RET-transgenic mice on a BALB/c background. These results suggest that RET works to extend the anagen phase in association with upregulation of melanin production.

Aged↗

Dipole excitation of alpha clusters in (6)Li and (7)Li.

Dipole excitations in highly excited energy regions of (6)He and (7)He nuclei were investigated via the ((7)Li,(7)Be) reaction with an incident energy of 65A MeV at forward scattering angles. The resonances at Q approximately equal to -30 MeV observed commonly for both (6)Li and (7)Li targets were found to be excited via both spin-flip and spin-nonflip transitions with DeltaL = 1. Based on the observed excitation energy, width, and cross section of each resonance, the relevant resonances are inferred to be analogs of the dipole resonances of alpha clusters in the (6)Li and (7)Li nuclei.

Journal Article↗

The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas.

Reduction of E-cadherin strongly relates to invasiveness and metastasis in vitro. To clarify CpG methylation around the promoter region of the E-cadherin gene in oral squamous cell carcinoma (SCC), we examined the DNA samples of various human SCC cell lines and primary oral SCC tissues by methylation-specific polymerase chain reaction (MSP). CpG methylation of the E-cadherin gene markedly correlated to the reduction of E-cadherin expression in human oral SCC cell lines. In primary oral SCC tissues, only 1 of 5 preserved E-cadherin-expressing tissues was methylated, whereas methylation was found in 17 (94.4%) of 18 E-cadherin-reduced tissues. Our results suggest that reduction of E-cadherin expression is associated with CpG methylation of the E-cadherin gene promoter. We recently established two cell lines with high and low metastatic potential, UM1 and UM2, from SCC primary tongue tissue of a patient. E-cadherin expression of high-metastatic UM1 was clearly lower than that of low-metastatic UM2, and MSP results showed CpG methylation in the UM1 but not the UM2 cell line. To investigate whether demethylation of CpG methylation of the E-cadherin gene could restore expression and function of E-cadherin, we treated UM1 with the demethylating agent 5-azacytidine (5-aza) and found that E-cadherin expression was indeed restored by demethylation. Moreover, in the demethylated UM1, invasion of the collagen gel was clearly suppressed compared with the untreated UM1. These results suggested that inactivation of E-cadherin expression resulted from CpG methylation of the gene promoter; a correlation between CpG methylation of the E-cadherin gene promoter and invasive potential was also suggested.

Antimetabolites, Antineoplastic↗

The Y chromosome in the liverwort Marchantia polymorpha has accumulated unique repeat sequences harboring a male-specific gene.

The haploid liverwort Marchantia polymorpha has heteromorphic sex chromosomes, an X chromosome in the female and a Y chromosome in the male. We here report on the repetitive structure of the liverwort Y chromosome through the analysis of male-specific P1-derived artificial chromosome (PAC) clones, pMM4G7 and pMM23-130F12. Several chromosome-specific sequence elements of approximately 70 to 400 nt are combined into larger arrangements, which in turn are assembled into extensive Y chromosome-specific stretches. These repeat sequences contribute 2-3 Mb to the Y chromosome based on the observations of three different approaches: fluorescence in situ hybridization, dot blot hybridization, and the frequency of clones containing the repeat sequences in the genomic library. A novel Y chromosome-specific gene family was found embedded among these repeat sequences. This gene family encodes a putative protein with a RING finger motif and is expressed specifically in male sexual organs. To our knowledge, there have been no other reports for an active Y chromosome-specific gene in plants. The chromosome-specific repeat sequences possibly contribute to determining the identity of the Y chromosome in M. polymorpha as well as to maintaining genes required for male functions, as in mammals such as human.

Amino Acid Sequence↗

Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0 MeV. The measured solar neutrino flux is 2.32+/-0.03(stat)+0.08-0.07(syst)x10(6) cm(-2) x s(-1), which is 45.1+/-0.5(stat)+1.6-1.4(syst)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry (Phi(n)-Phi(d))/Phi(average) is 0.033+/-0.022(stat)+0.013-0.012(syst). The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L. upper limit of 40x10(3) cm(-2) x s(-1), which is 4.3 times the BP2000 SSM prediction.

Journal Article↗

Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.

Journal Article↗

Synthesis and characterization of alkanethiolate-coordinated iron porphyrins and their dioxygen adducts as models for the active center of cytochrome p450: direct evidence for hydrogen bonding to bound dioxygen.

Two kinds of novel cytochrome P450 models, which have alkanethiolate axial ligands and hydroxyl groups inside molecular cavities, were designed and synthesized as functional O(2) binding systems. A superstructured porphyrin, designated as "twin-coronet" porphyrin, was used as the common framework of the model complexes. This porphyrin bears four binaphthalene bridges on the both sides and forms two pockets surrounded by the bulky aromatic rings. Thiobenzyloxy and thioglycolate moieties, which contain an alkanethiolate group exhibiting various electron-donating abilities and degrees of bulkiness, were covalently linked to twin-coronet porphyrin to yield thiolate-coordinated hemes, TCP-TB and TCP-TG (twin-coronet porphyrin with thiobenzyloxy and thioglycolate groups), respectively. Both ferric complexes exhibited high stability during usual experimental manipulation under air and were characterized by MS, UV/vis, ESR spectroscopies, and CV. The ESR spectra exhibited low-spin signals (TCP-TB: g = 2.334, 2.210, 1.959; TCP-TG: g = 2.313, 2.209, 1.966). The cyclic voltammogram of TCP-TB in CH(3)CN gave a quasi-reversible wave which corresponds to the Fe(III)/Fe(II) redox couple: E(p)()(/2) = -1.35 V (vs Fc/Fc(+)). On the other hand, TCP-TG showed a fine reversible wave: E(1/2) (Fe(III)/Fe(II)) = -1.12 V. The stable dioxygen adducts were formed in the reaction of the ferric complexes with KO(2) under an oxygen atmosphere and characterized by UV/vis and resonance Raman (RR) spectroscopies. In the RR spectra, the nu(O--O) bands of the dioxygen adducts were observed at 1138 cm(-1) (TCP-TB) and 1137 cm(-1) (TCP-TG). The hypothesis that hydrogen bonding between the bound oxygen and the hydroxyl groups of the binaphthyl moieties could increase their stability was verified by RR spectroscopy. When all hydroxyl groups were deuterated, only the frequencies of the nu(O--O) bands were upshifted by 2 cm(-1) without any perturbation in the porphyrin skeleton. This work shows the first direct evidence for a hydrogen bond to dioxygen in an oxy form of a thiolate-coordinated heme model system. These results are discussed in context of the process of dioxygen binding and activation in cytochrome P450.

Cytochrome P-450 Enzyme System↗

Comprehensive allelotype study of ovarian tumors of low malignant potential: potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma.

Ovarian tumors of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas (OC); however, the relevance of LMP to ovarian carcinogenesis is not clear. We performed a comparative analysis of allelotypes in 50 cases of LMP (42 mucinous and 8 serous) and 23 cases of OC (15 mucinous and 8 serous) to investigate any differences in genetic changes. Analysis of loss of heterozygosity (LOH) using 25 microsatellite markers reportedly associated with OC revealed that the total LOH frequency at each marker was significantly lower in LMP than in OC (p < 0.01). However, 9 (36%) loci showed higher LOH frequency in mucinous LMP than in mucinous OC. A genome-wide scan for LOH using 91 microsatellite markers and fine mapping revealed that LOH at D7S1805 (7q35) is characteristic of mucinous LMP (19.4% in mucinous LMP, 8.3% in mucinous OC). We further studied LOH in 3 cases of mucinous OC that were accompanied by mucinous LMP lesions. In 2 cases, LOH frequency was higher in the carcinoma portion than in the morphologically LMP portion. The other case showed microsatellite instability in the morphologically LMP portion and LOH in the carcinoma portion. Our results suggest the presence of an LMP-to-OC developmental sequence and the existence of a subset of LMP that does not develop into OC in the mucinous subtype of ovarian tumors.

Adenoma↗

Additional locus of rDNA sequence specific to the X chromosome of the liverwort, Marchantia polymorpha.

The molecular cytogenetic organization of 17S ribosomal RNA genes (17S rDNA), a part of the 45S rDNA repeat, was investigated on the chromosomes of the liverwort Marchantia polymorpha using fluorescence in-situ hybridization (FISH). The numbers of 17S rDNA loci visualized in female and male chromosomes were ten and nine. respectively. This heterogeneous localization was due to the presence of an additional 17S rDNA locus on the X chromosome and its absence on the Y chromosome. The signal on the X chromosome covered almost the entire region of its long arm. The other nine signals were observed on the same loci of respective autosomes in both sexes. Southern hybridization analysis revealed an additional band including 17S rDNA exclusively on EcoRI digested female genomic DNA supporting the existence of an additional 17S rDNA locus on the X chromosome.

Chromosomes↗

Phenotypic association of spontaneous ovulation and sexual receptivity in virgin females of Drosophila melanogaster mutants.

In Drosophila melanogaster females, mating stimulates ovulation/oviposition and switches off receptivity. To investigate the relationship between ovulation and receptivity, we searched for genetic variants in which ovulation occurs in virgins and characterized their behavioral phenotype. Among a collection of 333 P-element insertion lines, we identified eight lines that showed elevated ovulation in virgins. These females show ovipositor extrusion toward courting males, which is normally observed in mated females. To express the amount of rejection behavior, we defined the extrusion index (EI) as a percentage of time that each female extruded the ovipositor within the total time of being courted. There was a positive correlation between ovulation level and EI, suggesting that the two traits are physiologically associated. Genetic analysis of the variants revealed two regions on the third chromosome responsible for the phenotype.

Animals↗

Analysis of sputum taken from wheezy and asthmatic infants and children, with special reference to respiratory infections.

Children who are destined to develop asthma are considered to be susceptible to a variety of respiratory pathogens. To elucidate respiratory inflammation among these children, we measured the levels of eosinophil cationic protein (ECP) and tryptase in sputum taken from three different groups of wheezy infants and young children: those with a first wheeze (n = 15); those with recurrent wheeze (n = 27); and those with recurrent wheeze with respiratory distress, namely asthma (n = 56). The numbers of eosinophils or metachromatic cells determined by microscopic analysis of sputum samples were also evaluated in combination with the ECP and tryptase levels. Although neither sputum ECP nor tryptase was a clear discriminative marker that differentiated the three different types of wheezy disease, ECP levels in sputum from the asthma group were significantly higher (2,269.2 +/- 6,216.8 ng/g) than those in the recurrent wheezy group (440.3 +/- 1,199.8 ng/g) or in the first-wheeze group (209.0 +/- 172.9 ng/g). A similar trend was observed with tryptase levels in sputum, but there were no significant differences among the three groups. Sputum taken from asthmatic children showed a marked accumulation of eosinophils. However, an accumulation of eosinophils in sputum (even in the presence of an elevated level of sputum ECP) was not identified in the asthmatic infants < 1 year of age. An accumlation of eosinophils in sputum was not evident until children became > 1 year old and thereafter the eosinophils rapidly increased in number until the children reached 5 years of age. It was noteworthy that sputa positive for pathogenic bacteria, taken from the 1- and 2-year-old asthmatic infants, had a tendency to show high levels of ECP but a reduced number of eosinophils. Along with the wheezy episodes induced by viral infection, primarily and occasionally in combination with secondary bacterial infection, eosinophil activation and infiltration may develop. These predestined immune reactions to various pathogens might be associated with triggering the onset of asthma.

Asthma↗

Right internal jugular vein venography in infants and children.

UNLABELLED: We obtained venograms of the right internal jugular vein (RIJV) in 105 infants and children with congenital heart disease during cardiac catheterization. No major anomalies were found in the course of the RIJV. The diameter of the RIJV tended to increase with the patient's age, weight, and height. However, some disproportionately small vessels were seen in 8% of the patients. The depth from the skin to the RIJV varied from 2.5 to 20 mm and did not significantly correlate with age, weight, or height. Confirmation of the diameter or the depth of the RIJV by venography may facilitate clinical decisions and may be useful for performing percutaneous cannulation. IMPLICATIONS: We obtained venograms of the right internal jugular vein in children with congenital heart disease. Generally, the diameter increased with the patient's body size, but disproportionately small vessels were seen in 8% of the patients. Preoperative internal jugular venography may facilitate identifying those patients.

Catheterization, Peripheral↗

Plasma lidocaine concentrations during continuous thoracic epidural anesthesia after clonidine premedication in children.

UNLABELLED: There is no report concerning oral clonidine's effects on epidural lidocaine in children. Therefore, we performed a study to assess the concentrations of plasma lidocaine and its major metabolite (monoethylglycinexylidide [MEGX]) in children receiving continuous thoracic epidural anesthesia after oral clonidine premedication. Ten pediatric patients, aged 1-9 yr, were randomly allocated to the Control or Clonidine 4 microg/kg group (n = 5 each). Anesthesia was induced and maintained with sevoflurane in oxygen and air (FIO2 40%). Epidural puncture and tubing were carefully performed at the Th11-12 intervertebral space. An initial dose of 1% lidocaine (5 mg/kg) was injected through a catheter into the epidural space, followed by 2.5 mg x kg(-1) x h(-1). Plasma concentrations of lidocaine and MEGX were measured at 15 min, 30 min, and every 60 min for 4 h after the initiation of continuous epidural injection. The concentrations of lidocaine and MEGX were measured using high-pressure liquid chromatography with ultraviolet detection. Hemodynamic variables were similar between members of the Control and Clonidine groups during anesthesia. The Clonidine group showed significantly smaller lidocaine concentrations (p < 0.05) and the concentration of MEGX tended to be smaller in the plasma of the Clonidine group for the initial 4 h after the initiation of epidural infusion. In conclusion, oral clonidine preanesthetic medication at a dose of 4 microg/kg decreases plasma lidocaine concentration in children. IMPLICATIONS: Oral clonidine decreases the plasma lidocaine concentration in children. Our finding may have clinical implications in patients receiving continuous epidural anesthesia. Additionally, perhaps an additional margin of safety regarding lidocaine toxicity is gained through the use of oral clonidine in children who will receive epidural lidocaine.

Administration, Oral↗

Changes in myometrial and junctional zone thickness and signal intensity: demonstration with kinematic T2-weighted MR imaging.

PURPOSE: To demonstrate uterine contractions by evaluating changes during time in the thickness of the myometrium and junctional zone and in signal intensity of the uterus with T2-weighted fast magnetic resonance (MR) images in a kinematic fashion. MATERIALS AND METHODS: Sagittal MR imaging was performed with T2-weighted fast spin-echo (FSE) and multiphase-multisection single-shot FSE (SSFSE) in 60 premenopausal patients during free breathing. SSFSE MR images were evaluated with cine display. The pattern of uterine contractions and changes in signal intensities of the uterine structures were evaluated. Thickness of both myometrium and junctional zone, and their signal intensities, were measured during 15 phases of SSFSE and FSE MR imaging. RESULTS: Slow-massive (mean, 55%), middle-cycle (mean, 80%), and fine (mean, 93%) contractions were observed. Shape of junctional zones dynamically changed during time, showing focal (mean, 58%) and diffuse (mean, 82%) thickening and wavelike motions (mean, 88%). Ratio of thickness of the myometrium to junctional zone with FSE MR imaging was not significantly different from the mean ratio during 15 phases of SSFSE MR imaging, although maximum percentage of change of the ratio during 15 phases was 42.5%-56.8%. The signal intensities of the myometrium (97%) and junctional zone (75%) changed during time. CONCLUSION: Kinematic T2-weighted SSFSE MR images demonstrate uterine contractions related to dynamic changes in thickness and signal intensities of the myometrium and junctional zone, and these findings might affect the diagnosis of uterine disease.

Adolescent↗

Calcium waves in skinned cardiac myocytes evoked by two-photon excitation photolysis of caged calcium.

In rat ventricular myocytes chemically skinned with saponin, a local rise of [Ca2+] was achieved by two-photon excitation photolysis (TPP) of the caged Ca2+ compound 1-(2-nitro-4,5-dimethoxyphenyl)-N,N,N',N'-tetrakis[(oxycarbonyl)methyl]-1,2-ethanediamine (DM-nitrophen). Confocal Ca2+ images, by use of fluo-3, were simultaneously collected. TPP of DM-nitrophen induced Ca2+ waves propagating over the myocyte, and the local rise of [Ca2+] at the site of photolysis sustained for 50-60 ms. These TPP-induced Ca2+ events were completely suppressed by ryanodine (10 microM), suggesting that Ca2+ release resulting from TPP of DM-nitrophen triggered regenerative Ca2+ release from the neighboring sarcoplasmic reticulum. The present techniques should be useful to investigate the interaction of elementary Ca2+ events, the process leading to global Ca2+ movements, in cardiac myocytes and other types of cells.

Animals↗

[Anesthetic management for left ventricular assist device implantation in patients waiting for heart transplantation].

We report the anesthetic management of patients with dilated cardiomyopathy who underwent left ventricular assist device implantation (LVAD). Anesthesia was induced and maintained with midazolam and fentanyl. Transesophageal echocardiography (TEE) and a PA catheter were useful for hemodynamic monitoring and management of the patients. Furthermore, TEE is useful for the early detection of inflow of the air which is absorbed by negative pressure derived from high LVAD support pressure. On starting LVAD support, evaluation of right ventricular function and treatment for right ventricular failure were important and necessary for the patients. Added to conventional therapy using catecholamines, inhaled nitric oxide may provide a favorable effect for right ventricular failure.

Adult↗

[Evaluation of efficacy of ramosetron orally disintegrating tablets and patient preference as to the dosage form in gynecological cancer chemotherapy].

The efficacy of an oral 5-HT3 antagonist, ramosetron orally disintegrating tablet (ODT), in the treatment of chemotherapy-induced emesis was investigated in 21 female patients with cancer. Patient preference for the dosage form was also investigated. Eighteen (85.7%) of 21 patients answered that ODT is easy to take. Eleven (68.8%) of 16 patients who had previously taken granisetron tablets preferred ramosetron ODT to conventional tablets. The complete suppression rate of nausea or vomiting was more than 90% for 6 days. No adverse drug reactions associated with ramosetron were observed. As ambulatory or home chemotherapy becomes frequent, the use of oral 5-HT3 antagonists rather than intravenous agents will be increased. Chemotherapy for elderly cancer patients is becoming frequently used. Considering these circumstances, it is suggested that ramosetron ODT is a palatable and useful treatment of chemotherapy-induced emesis.

Administration, Oral↗

Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti.

The complete nucleotide sequence of the genome of a symbiotic bacterium Mesorhizobium loti strain MAFF303099 was determined. The genome of M. loti consisted of a single chromosome (7,036,071 bp) and two plasmids, designated as pMLa (351,911 bp) and pMLb (208, 315 bp). The chromosome comprises 6752 potential protein-coding genes, two sets of rRNA genes and 50 tRNA genes representing 47 tRNA species. Fifty-four percent of the potential protein genes showed sequence similarity to genes of known function, 21% to hypothetical genes, and the remaining 25% had no apparent similarity to reported genes. A 611-kb DNA segment, a highly probable candidate of a symbiotic island, was identified, and 30 genes for nitrogen fixation and 24 genes for nodulation were assigned in this region. Codon usage analysis suggested that the symbiotic island as well as the plasmids originated and were transmitted from other genetic systems. The genomes of two plasmids, pMLa and pMLb, contained 320 and 209 potential protein-coding genes, respectively, for a variety of biological functions. These include genes for the ABC-transporter system, phosphate assimilation, two-component system, DNA replication and conjugation, but only one gene for nodulation was identified.

ATP-Binding Cassette Transporters↗