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Biomedical subjects

T Komeda

Publications and source records attributed to T Komeda.

At least 19 recordsLinked to original sources

Ammonia adsorption on and diffusion into thin ice films grown on Pt(111).

Ammonia adsorption on and diffusion into thin ice films grown on a Pt(111) surface were studied using Fourier transform infrared spectroscopy (FTIR) and thermal desorption spectroscopy. After exposing the crystalline ice film to ammonia molecules at 45 K (ammonia/ice film), we have detected an intriguing feature at 1470 cm(-1) in the FTIR spectra, which is derived from the adsorption of ammonia on the ice with a characteristic structure which appears in thin film range. The peak intensity of this feature decreases gradually as the thickness of the substrate ice increases. In addition, we have detected a feature at 1260 cm(-1) which appears after annealing the ammonia/ice film. The feature corresponds to the ammonia molecules which reach the ice/Pt(111) interface through the ice film. Intriguingly, the intensity of this feature decreases with the ice thickness and there is a linear relation of the peak intensity of the features at 1470 and 1260 cm(-1). We propose a model in which the solubility of the ammonia molecules is much higher for the thin ice film than that for the ideal ice.

Journal Article↗

Inelastic tunneling spectroscopy using scanning tunneling microscopy on trans-2-butene molecule: spectroscopy and mapping of vibrational feature.

Inelastic tunneling spectroscopy (IETS) measurement using scanning tunneling microscopy (STM) with a commercially available STM set up is presented. The STM-IETS spectrum measured on an isolated trans-2-butene molecule on the Pd(110) shows a clear vibrational feature in d2I/dV2 at the bias voltage of 360 mV and -363 mV, which corresponds to the nu(C-H) mode (d2I/dV2 approximately 10 nA/V2). In addition, we have obtained an image by mapping the vibrational feature of nu(C-H) in d2I/dV2. The image is obtained by scanning the tip on the surface with the feedback loop activated while the modulation voltage is superimposed on the sample voltage. With the method that is readily performable with conventional software, we have clearly differentiated the molecules of trans-2-butene and butadiene through the mapping of the vibrational feature, demonstrating its capability of chemical identification in atomic scale.

Journal Article↗

Local chemical reaction of benzene on Cu110 via STM-induced excitation.

We have investigated the mechanism of the chemical reaction of the benzene molecule adsorbed on Cu(110) surface induced by the injection of tunneling electrons using scanning tunneling microscopy (STM). With the dosing of tunneling electrons of the energy 2-5 eV from the STM tip to the molecule, we have detected the increase of the height of the benzene molecule by 40% in the STM image and the appearance of the vibration feature of the nu(C-H) mode in the inelastic tunneling spectroscopy (IETS) spectrum. It can be understood with a model in which the dissociation of C-H bonds occurs in a benzene molecule that induces a bonding geometry change from flat-lying to up-right configuration, which follows the story of the report of Lauhon and Ho on the STM-induced change of benzene on the Cu(100) surface. [L. J. Lauhon and W. Ho, J. Phys. Chem. A 104, 2463 (2000)]. The reaction probability shows a sharp rise at the sample bias voltage at 2.4 V, which saturates at 3.0 V, which is followed by another sharp rise at the voltage of 4.3 V. No increase of the reaction yield is observed for the negative sample voltage up to 5 eV. In the case of a fully deuterated benzene molecule, it shows the onset at the same energy of 2.4 eV, but the reaction probability is 10(3) smaller than the case of the normal benzene molecule. We propose a model in which the dehydrogenation of the benzene molecule is induced by the formation of the temporal negative ion due to the trapping of the electrons at the unoccupied resonant states formed by the pi orbitals. The existence of the resonant level close to the Fermi level ( approximately 2.4 eV) and multiple levels in less than approximately 5 eV from the Fermi level, indicates a fairly strong interaction of the Cu-pi(*) state of the benzene molecule. We estimated that the large isotope effect of approximately 10(3) can be accounted for with the Menzel-Gomer-Redhead (MGR) model with an assumption of a shallow potential curve for the excited state.

Journal Article↗

Cis-acting elements sufficient for induction of FDH1 expression by formate in the methylotrophic yeast Candida boidinii.

The FDH1 gene of Candida boidinii encodes an NAD+-dependent formate dehydrogenase, which catalyzes the last reaction in the methanol dissimilation pathway. FDH1 expression is strongly induced by methanol, as are the promoters of the genes AOD1 (alcohol oxidase) and DAS1 (dihydroxyacetone synthase). FDH1 expression can be induced by formate when cells are grown on a medium containing glucose as a carbon source, whereas expression of AOD1 and DAS1 is completely repressed in the presence of glucose. Using deletion analyses, we identified two cis-acting regulatory elements, termed UAS-FM and UAS-M, respectively, in the 5' non-coding region of the FDH1 gene. Both elements were necessary for full induction of the FDH1 promoter by methanol, while only the UAS-FM element was required for full induction by formate. Irrespective of whether induction was achieved with methanol or formate, the UAS-FM element enhanced the level of induction of the FDH1 promoter in a manner dependent on the number of copies, but independent of their orientation, and also converted the ACT1 promoter from a constitutive into an inducible element. Our results not only provide a powerful promoter for heterologous gene expression, but also yield insights into the mechanism of regulation of FDH1 expression at the molecular level.

Base Sequence↗

Chromosomal instability and human hepatocarcinogenesis.

Recently, many studies have identified losses and gains of several chromosomal loci in human hepatocellular carcinoma (HCC) with fine microsatellite analysis and comparative genomic hybridization. Although distribution of aberrant chromosomal arms differs among HCCs, loss of 1p, 4q, 6q, 8p, 9p, 10q, 13q, 16q and 17p, and gain of 1q, 6p, 8q, 17q and 20q have been recurrently reported, and loss of 4q and 16q seems to occur preferentially in hepatitis B virus-related HCCs. Accumulation of these aberrant chromosomal regions is associated with tumor progression, and some chromosomal aberrations, such as loss of 1p, are frequently identified in well-differentiated HCCs and also detected even in dysplastic nodule and cirrhotic nodule. This evidence suggests that chromosomal instability (CIN) emerges at an early stage during hepatocarcinogenesis and is successively inherent to tumor cells, resulting in acquisition of malignant phenotype. The molecular basis of CIN is beginning to be explored; however, several mechanisms may be involved for CIN of HCC.

Allelic Imbalance↗

Production of active bovine cathepsin C (dipeptidyl aminopeptidase I) in the methylotrophic yeast Candida boidinii.

The heterologous production of active bovine cathepsin C (CTC; dipeptidyl aminopeptidase I) was investigated. Attempts to express CTC in Escherichia coli were hampered by formation of inclusion bodies that were partially degraded. To overcome this impediment, secretion of recombinant CTC was attempted in the methylotrophic yeast Candida boidinii. A DNA fragment encoding bovine procathepsin C was synthesized based on preferred codon usage in C. boidinii and placed downstream of the C. boidinii proteinase A signal sequence resulting in secretion of active CTC into the culture medium. The gene was expressed under the control of the methanol-inducible formate dehydrogenase gene promoter. Production levels were significantly improved by using a protease-deficient strain, changing medium composition, and by lowering the temperature of induction. When the recombinant C. boidinii was grown for 90 h in a jar-fermenter, active CTC was secreted with a yield of up to approximately 12 mg/l.

Amino Acid Sequence↗

Narrow photoemission peak at the Fermi level in Fe/Cu(111).

We have studied electronic states of Fe adatoms deposited on Cu(111) by photoemission spectroscopy and have found a narrow peak at the Fermi level in the Fe 3d spectral function. The Fe 3d spectral function would be consistent with the Anderson impurity model, which has been widely used for the interpretation of bulk Ce and Yb compounds. This result indicates a strong reduction of hybridization between the Fe 3d state and the conduction-band states and an enhancement of effective Coulomb interaction for the Fe 3d electrons in an Fe adatom on Cu(111).

Journal Article↗

Lateral hopping of molecules induced by excitation of internal vibration mode.

We demonstrate electron-stimulated migration for carbon monoxide (CO) molecules adsorbed on the Pd(110) surface, which is initiated by the excitation of a high-frequency (HF) vibrational mode (C-O stretching mode) with inelastic tunneling electrons from the tip of scanning tunneling microscopy. The hopping phenomenon, however, cannot be detected for CO/Cu(110), even though the hopping barrier is lower than in the CO/Pd(110) case. A theoretical model, which is based on the anharmonic coupling between low-frequency modes (the hindered-translational mode related to the lateral hopping) and the HF mode combined with electron-hole pair excitation, can explain why the hopping of CO is observed on Pd(110) but not on Cu(110).

Journal Article↗

Evaluation of the longitudinal arch of the foot with hallux valgus using a newly developed two-dimensional coordinate system.

The purposes of the present study were to establish a method for the evaluation of the longitudinal arch, using a two-dimensional coordinate system, and to clarify the main point of flattening of the foot in patients with hallux valgus. Measurements on a weight-bearing lateral radiograph of the foot were performed in 186 feet of 110 women with symptomatic hallux valgus and in 93 normal feet of 72 women. A two-dimensional coordinate system was used to perform the measurements. In this coordinate system, the line connecting the lowest point of the first metatarsal head and the lowest point (O) of the calcaneus is fixed as the x-axis, and the line that is perpendicular to the x-axis and intersects the x-axis at point O is fixed as the y-axis. The mean values of the y-coordinates at the points of the medial longitudinal arch of the foot in the patients with hallux valgus were significantly lower than those in the normal subjects (P < 0.001). The values were noticeably lower at points on the navicular. However, no change was observed in the posterior talus body. The new coordinate system indicated that the main points of flattening of the foot in patients with hallux valgus were the plantar flexion of the talus and the sinking of the navicular.

Adolescent↗

Postoperative detection of alpha-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma.

BACKGROUND: We tested for the presence of alpha-fetoprotein (AFP) mRNA by using nested RT-PCR in the peripheral blood of hepatocellular carcinoma (HCC) patients who had undergone curative surgery, and investigated the occurrence of intrahepatic and/or extrahepatic metastasis thereafter, to reveal the optimal timing of blood sampling for the prediction of metastatic recurrence. METHODS: Twenty-nine patients with HCC, who had been operated on were analyzed with RT-PCR at several points during the clinical course, and examined for metastatic recurrence for 3-28 months (mean = 18.7 months) after surgery. RESULTS: The presence of AFP mRNA before surgery was significantly correlated with the tumor size (P = 0.017). Metastatic recurrence was associated with the postoperative detection of AFP mRNA (P < 0.001), but not with the preoperative and/or perioperative detection. Furthermore, AFP mRNA was detected in some cases that showed low serum AFP levels at recurrence. The recurrence-free period after the detection of AFP mRNA varied from 1 to 12 months. CONCLUSIONS: The postoperative detection of AFP mRNA is useful for the prediction of metastatic recurrence, and long-term follow up with this method should be conducted.

Adult↗

Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas.

p16, cyclin D1 and retinoblastoma protein (pRB) regulate G1 to S transition and are commonly targeted in various cancers. However, few studies have simultaneously examined all components of the p16/cyclin D1/pRB pathway (RB pathway) in hepatocellular carcinoma (HCC). To clarify the role of the disruption of the RB pathway in HCC, we analyzed p16, pRB and cyclin D1 in 47 HCCs. Inactivation of p16 was detected in 30 of 47 HCCs (64%) by Western blot analysis and significantly correlated with hypermethylation of the promoter of this gene. pRB expression was found to be absent in 13 of 47 HCCs (28%) by immunohistochemistry. We found that 38 of 47 HCCs (81%) contained at least one inactivation in either pRB or p16. Furthermore, there was a significant inverse correlation between p16 and pRB inactivation (p = 0.041). Overexpression of cyclin D1 was detected in 5 of 47 HCCs (11%) by immunohistochemistry. The cases with cyclin D1 overexpression exhibited an advanced clinicopathological appearance and also contained inactivation of pRB and/or p16. These findings suggest that inactivation of pRB and/or p16 is a major event in human hepatocarcinogenesis, while cyclin D1 overexpression may confer additional growth advantages to the tumor in addition to pRB and/or p16 inactivation in HCC.

Adult↗

Effect of long-term bedrest on lower leg muscle activation patterns during quiet standing.

It has been well known that balance instabilities after long-term exposure to microgravity (e.g., Anderson et al. 1986) or bedrest (BR) can be related to alterations and/or adaptations to postural control strategies. Little is known, however, how the reduced muscular activity affects the activation pattern of the lower limb muscles during quiet standing (QS). The purpose of this study was to investigate whether or not any changes in the lower limb muscle activation patterns during QS would occur after BR.

Adult↗

Regulation and evaluation of five methanol-inducible promoters in the methylotrophic yeast Candida boidinii.

We isolated the promoter regions of five methanol-inducible genes (P(AOD1), alcohol oxidase; P(DAS1), dihydroxyacetone synthase; P(FDH1), formate dehydrogenase; P(PMP20), Pmp20; and P(PMP47), Pmp47) from the Candida boidinii genome, and evaluated their strength and studied their regulation using the acid phosphatase gene of Saccharomyces cerevisiae (ScPHO5) as the reporter. Of the five promoters, P(DAS1) was the strongest methanol-inducible promoter whose strength was approximately 1.5 times higher than that of the commonly used P(AOD1) in methanol-induced cells. Although the expression of P(AOD1) and P(DAS1) was completely repressed by the presence of glucose, formate-induced expression of P(FDH1) was not repressed by glucose. Expression under P(PMP47), another methanol-inducible promoter, was highly induced by oleate. The induction kinetics of P(PMP47) and P(DAS1) revealed that methanol induces the expression of peroxisome membrane protein Pmp47, earlier than the expression of matrix enzyme dihydroxyacetone synthase (Das1p), and that this information is contained in the promoter region of the respective gene. This is the first report which evaluates several methanol-inducible promoters in parallel in the methylotrophic yeast.

Acid Phosphatase↗

Crystal structure of glycosyltrehalose trehalohydrolase from the hyperthermophilic archaeum Sulfolobus solfataricus.

The crystal structure of glycosyltrehalose trehalohydrolase from the hyperthermophilic archaeum Sulfolobus solfataricus KM1 has been solved by multiple isomorphous replacement. The enzyme is an alpha-amylase (family 13) with unique exo-amylolytic activity for glycosyltrehalosides. It cleaves the alpha-1,4 glycosidic bond adjacent to the trehalose moiety to release trehalose and maltooligo saccharide. Unlike most other family 13 glycosidases, the enzyme does not require Ca(2+) for activity, and it contains an N-terminal extension of approximately 100 amino acid residues that is homologous to N-terminal domains found in many glycosidases that recognize branched oligosaccharides. Crystallography revealed the enzyme to exist as a homodimer covalently linked by an intermolecular disulfide bond at residue C298. The existence of the intermolecular disulfide bond was confirmed by biochemical analysis and mutagenesis. The N-terminal extension forms an independent domain connected to the catalytic domain by an extended linker. The functionally essential Ca(2+) binding site found in the B domain of alpha-amylases and many other family 13 glycosidases was found to be replaced by hydrophobic packing interactions. The enzyme also contains a very unusual excursion in the (beta/alpha)(8) barrel structure of the catalytic domain. This excursion originates from the bottom of the (beta/alpha)(8) barrel between helix 6 and strand 7, but folds upward in a distorted alpha-hairpin structure to form a part of the substrate binding cleft wall that is possibly critical for the enzyme's unique substrate selectivity. Participation of an alpha-beta loop in the formation of the substrate binding cleft is a novel feature that is not observed in other known (beta/alpha)(8) enzymes.

Amino Acid Sequence↗

Cloning and sequence analysis of the Candida boidinii ADE2 gene.

Candida boidinii ADE2 gene (phosphoribosyl-5-aminoimidazole carboxylase; AIRC, EC 4. 1. 1. 21) has been cloned by homology to the Saccharomyces cerevisiae ADE2 gene. The cloned C. boidinii ADE2 gene complemented the ade2 mutation of S. cerevisiae. Sequence analysis showed a single open reading frame of 1719 nucleotides coding for a polypeptide of 573 residues. Comparison of the deduced amino acid sequence with those of AIRC enzymes from other yeasts showed marked homology among yeast AIRCs.

Amino Acid Sequence↗

Treatment of extrinsic flexion deformity of the toes associated with previous removal of a vascularized fibular graft.

BACKGROUND: Complications from vascularized fibular bone-grafting are infrequent. We saw six patients who had a painful flexion deformity of the great and lesser toes after a free vascularized fibular graft had been obtained from the ipsilateral leg. In this report, we discuss our management of these patients. METHODS: Painful flexion deformity of the toes that had developed in six adults after removal of a free vascularized fibular graft was treated by cutting of the flexor hallucis longus alone in three patients, by lengthening of the flexor hallucis longus alone in one, and by cutting of both the flexor hallucis longus and the flexor digitorum longus in two. RESULTS: After an average duration of follow-up of six years and eleven months, the flexion deformity of the great and lesser toes had decreased or disappeared, leading to improved or full extension of the digits. Preoperative and postoperative measurements of muscle strength for plantar flexion of the interphalangeal joints did not change appreciably. CONCLUSIONS: Cutting or lengthening of the flexor hallucis longus behind the ankle provides an adequate release of digital flexion deformities that occur after removal of a vascularized fibular bone graft.

Adult↗

Selective activation of human soleus and medial gastrocnemius muscles during walking in water.

During walking in water (WW) the vertical component of ground reaction forces decreases, while the greater propulsive force is required to move forward against the greater resistance of water. In such reduced gravity environment, Hutchison et al. (1989) have demonstrated that the relative activation of rat medial gastrocnemius (MGAS) increased compared to that of the soleus (SOL) during swimming, suggesting different effects of peripheral information on motoneuron excitability of these muscles. It is conceivable that both buoyancy and resistance of water have different effects on the activation patterns of triceps surae muscles during WW, since the reduced weight in water might decrease the peripheral inflow relating load information while greater volitional command might be needed to propel a body forward against the water resistance. The present study was designed to assess each peripheral inflow and efferent input by adjusting the load and walking speed voluntarily during WW. The aim of this study is to investigate the dissociative activation pattern between the SOL and the MGAS during WW.

Adult↗

Incidence and characteristics of thyroid dysfunction following interferon therapy in patients with chronic hepatitis C.

Thyroid functions were analyzed before, during and after interferon (IFN) therapy in patients with chronic hepatitis C. According to the results of routine thyroid function tests and measurements of the levels of anti-thyroid autoantibody prior to the therapy, patients were divided into 2 groups; Group A (19 patients) had at least one abnormal finding related to the thyroid, and Group B (40 patients) did not show any abnormality. Five patients (26%) in Group A and 4 (10%) in Group B showed thyroid dysfunctions which were very clearly reflected by thyrotropin (TSH) measurements. Interestingly, the time of peak TSH elevation in Group A (mean +/- SD, 4.3 +/- 0.8 months) was significantly earlier than that in Group B (6.8 +/- 0.8). Most patients in Group B were diagnosed as having destructive thyroiditis. These findings may suggest that the pathogenesis of IFN-induced thyroid dysfunction consists not only of exacerbation of pre-existing thyroid autoimmunity but also of de novo destructive changes even in the intact thyroid before IFN therapy.

Adult↗