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Biomedical subjects

M Ishiguro

Publications and source records attributed to M Ishiguro.

At least 19 recordsLinked to original sources
PubMed2006

Detailed images of asteroid 25143 Itokawa from Hayabusa.

Rendezvous of the Japanese spacecraft Hayabusa with the near-Earth asteroid 25143 Itokawa took place during the interval September through November 2005. The onboard camera imaged the solid surface of this tiny asteroid (535 meters by 294 meters by 209 meters) with a spatial resolution of 70 centimeters per pixel, revealing diverse surface morphologies. Unlike previously explored asteroids, the surface of Itokawa reveals both rough and smooth terrains. Craters generally show unclear morphologies. Numerous boulders on Itokawa's surface suggest a rubble-pile structure.

Journal Article↗
PubMed2006

Touchdown of the Hayabusa spacecraft at the Muses Sea on Itokawa.

After global observations of asteroid 25143 Itokawa by the Hayabusa spacecraft, we selected the smooth terrain of the Muses Sea for two touchdowns carried out on 19 and 25 November 2005 UTC for the first asteroid sample collection with an impact sampling mechanism. Here, we report initial findings about geological features, surface condition, regolith grain size, compositional variation, and constraints on the physical properties of this site by using both scientific and housekeeping data during the descent sequence of the first touchdown. Close-up images revealed the first touchdown site as a regolith field densely filled with size-sorted, millimeter- to centimeter-sized grains.

Journal Article↗
PubMed2006

cDNA microarray analysis of cancer associated gene expression profiles in malignant peripheral nerve sheath tumours.

BACKGROUND: Malignant peripheral nerve sheath tumour (MPNST) is a highly aggressive malignancy that arises within peripheral nerves, and is associated with poor prognosis. Little is known about the underlying biology of MPNST, especially the mechanisms involved in cell proliferation, invasion, or escape from apoptosis. AIMS: To identify genes differentially expressed in MPNST compared with benign tumours, such as neurofibromas and schwannomas, by means of cDNA microarray analysis. METHODS: Six MPNST cases and five benign cases (three schwannomas and two neurofibromas) were analysed. RESULTS: Six genes (keratin 18, survivin, tenascin C, adenosine deaminase, collagen type VIa3, and collagen type VIIa1) were significantly upregulated in MPNST, whereas one gene, insulin-like growth factor binding protein 6, was downregulated in MPNST. Survivin and tenascin C expression was validated by reverse transcription polymerase chain reaction. Immunohistochemistry confirmed upregulation of survivin in MPNST at the protein level in six of eight cases compared with benign tumours. Tenascin C was also expressed at the invasive front and tumorous stroma in all MPNST cases. MPNST cells expressed tenascin C in four of nine cases. CONCLUSIONS: Survivin and tenascin C may be associated with the malignant potential of MPNST and could be considered as potential therapeutic targets.

Adult↗
PubMed2001

Reaction of Lys-Tyr-Lys triad mimics with benzylpenicillin: insight into the role of Tyr150 in class C beta-lactamase.

Small and simple molecules mimicking a Lys-Tyr-Lys triad and some 'mutant' derivatives were designed and synthesized. These-compounds react with benzylpenicillin in water (75mM phosphate buffer, pH 7), apparently through general base assistance by the phenolic moiety. Class C beta-lactamase has a Lys-Tyr-Lys triad in its active site, and our finding gives some insight into the role of this triad in the enzymatic beta-lactam hydrolysis mechanism.

Enzyme Inhibitors↗
PubMed2001

Modification of pharmacokinetic sampling schedules in clinical phase I trials: a use of Kullback-Leibler information.

In clinical phase I trials, pharmacokinetic sampling schedules often have to be modified while the trials proceed. The modifications are based on the observations from a limited number of subjects or only one subject in extreme cases. This paper describes a Kullback-Leibler information approach for modifying pharmacokinetic sampling schedules in clinical phase I trials. The proposed approach presupposes that the pharmacokinetic profile for each subject is specified by an appropriate pharmacokinetic model and the subject-specific parameters. The best modification plan is selected from arbitrarily chosen candidates based on the Kullback-Leibler information. Applications are given to a simulation study and an actual phase I trial of an anti-cancer drug.

Clinical Trials, Phase I as Topic↗
PubMed2001

A model of photoprobe docking with beta1,4-galactosyltransferase identifies a possible carboxylate involved in glycosylation steps.

A molecular docking study has been performed on the interaction of beta1,4-galactosyltransferase with an acceptor site photoprobe. This is based on an acceptor site peptide fragment which was recently identified by the use of a photoprobe. The present model strongly suggests that the carboxylate group of Asp318 could be involved in the activation of the acceptor sugar 4-OH for the efficient galactosyltransfer. The result also exemplified that the combination of photoaffinity labeling with crystallography is a powerful method for the detailed structural analysis of ligand protein complex.

Aspartic Acid↗
PubMed2001

Identification of syt-ssx fusion transcripts in both epithelial and spindle cell components of biphasic synovial sarcoma in small tissue samples isolated by membrane-based laser microdissection.

In order to confirm the presence of SYT-SSX fusion gene in epithelial and spindle cell components of synovial sarcoma, we performed a nested reverse transcriptase-polymerase chain reaction (RT-PCR) using microbeam microdissection of membrane-mounted native tissue (MOMeNT) technique applied on formalin-fixed, paraffin-embedded tumor specimens from two biphasic synovial sarcomas and a control tissue of adamantinoma. Small targeted portions of either an epithelial or spindle cell component of the tumor tissue were microdissected together with the supporter membrane, by using an ultraviolet (337-nm) pulsed laser microbeam coupled into a robot-stage microscope with infinity optics. The SYT-SSX fusion transcript was detected in epithelial and spindle cell components of both biphasic synovial sarcomas, but not in the control tissue. Southern blot analysis also confirmed that the detected messages were derived from the SYT-SSX fusion gene. In conclusion, the microbeam MOMeNT is a useful method for isolating selected small portions from tissue sections. The SYT-SSX fusion gene is present in both cellular components of biphasic synovial sarcoma and is involved in oncogenesis of the synovial sarcoma rather than in morphologic epithelial differentiation. Therefore, in spite of the variable proportions of each component, our results confirm that the synovial sarcoma is of monoclonal origin.

Adult↗
PubMed2001

Characteristics of aneurysms arising from the horizontal portion of the anterior cerebral artery.

BACKGROUND: Aneurysms arising from the proximal portion of the anterior cerebral artery (A1: horizontal portion) are quite rare and are considered to be unique, because they are usually connected with other vascular anomalies and are sometimes part of a multiple aneurysm occurrence. A1 aneurysm cases experienced over the past seven and a half years are summarized in this paper. METHODS: A total of 413 patients were surgically treated including 142 patients with subarachnoid hemorrhage (SAH); the remaining 271 patients had unruptured aneurysms. Among them, nine cases were categorized as constituent A1 aneurysms, three with SAH and six with unruptured aneurysms. RESULTS: The shape of the aneurysm was saccular in all nine cases. Three of the nine cases had associated vascular malformations. The average aneurysm diameter in the three cases with SAH was 4.0 mm, which is smaller than other common aneurysms presenting with SAH. Eight aneurysms developed at the takeoff point of perforating arteries-the medial lenticulostriate artery in five cases and the recurrent artery of Heubner in three cases. In the remaining case, the aneurysm originated from the proximal end of the associated A1 fenestration. All nine patients had an excellent outcome after surgery. CONCLUSION: A1 aneurysms require surgical elimination even if they are small. We emphasize the importance of preserving the blood flow of these perforating arteries by avoiding compression with either the clip blade or the clip body itself.

Adult↗
PubMed2001

Supernumerary ring chromosomes in dermatofibrosarcoma protuberans may contain sequences from 8q11.2-qter and 17q21-qter: a combined cytogenetic and comparative genomic hybridization study.

Dermatofibrosarcoma protuberans (DFSP) presents with characteristic cytogenetic features such as reciprocal t(17;22)(q22;q13) or, more commonly, supernumerary ring chromosomes containing sequences from chromosomes 17 and 22. Here, we report the identification of a novel abnormality in a 43-year-old woman with DFSP. Cytogenetic analysis of tumor cells showed the presence of a supernumerary ring chromosome as the sole anomaly. Amplification of 8q11.2 approximately qter and 17q21 approximately qter sequences was confirmed by comparative genomic hybridization (CGH); the present case apparently lacked amplification of chromosome 22. To our knowledge, this is the first case indicating that the ring chromosome in DFSP is possibly associated with amplified material from chromosomes 8 and 17.

Adult↗
PubMed2001

New method for obliterative treatment of an anterior wall aneurysm in the internal carotid artery: encircling silicone sheet clip procedure--technical case report.

OBJECTIVE AND IMPORTANCE: Aneurysms on the anterior surface of the internal carotid artery (ICA) have been shown to be somewhat different from ordinary berry aneurysms because they are rather small, grow rapidly in a short time, and easily lead to rupture, especially during surgery. The most difficult problem is that this type of aneurysm cannot be eliminated easily by an ordinary clipping procedure without causing apparent arterial stenosis or occlusion. CLINICAL PRESENTATION: A 52-year-old man experienced a subarachnoid hemorrhage because of a ruptured aneurysm located on the anterior surface of the ICA. The tiny aneurysmal body, which was covered with a layer of brain tissue, was successfully exposed. The ICA seemed to be atherosclerotic, and the aneurysmal portion was solitary and had a reddish color. TECHNIQUE: A large silicone sheet encircling clip (Vascwrap; Mizuho Ikakogyo Co., Ltd., Tokyo, Japan) was selected for this patient. The proximal margin of the silicone sheet was incised with a V-shaped cut, and the middle part of the sheet, which covered the diagonal part of the ICA, was trimmed to make it shorter. The blade of the fenestrated clip was applied to obliterate the aneurysm and was attached to the normal arterial wall together with this modified Vascwrap sheet to create a small space between the normal arterial wall and the surrounding Vascwrap sheet. Then tiny pieces of Teflon fiber (E.I. duPont de Nemours and Co., Wilmington, DE) was inserted from both margins, and the whole Vascwrap sheet was sealed with fibrin glue to ensure good adhesion. CONCLUSION: This method seemed adequate in treating this difficult aneurysm without causing postoperative regrowth or occlusion of the patient's ICA.

Carotid Artery, Internal↗
PubMed2001

Bopindolol: pharmacological basis and clinical implications.

Bopindolol, a non-selective antagonist of beta 1- and beta 2-adrenoceptors (ARs), has been found by pharmacological, molecular biological techniques and molecular modeling to have several unique properties. Bopindolol produces sustained blockade of beta 1- and beta 2-ARs, has intrinsic sympathomimetic as well as membrane stabilizing actions, inhibits renin secretion, and interacts with 5-HT receptors. Also, our recent molecular modeling studies identified possible interaction sites between bopindolol and beta-AR subtypes. The reviewed studies support our findings that bopindolol is non-selective for beta 1- and beta 2-ARs, has low affinity for beta 3-AR subtype and has pharmacological properties that are likely to be beneficial in the treatment of cardiovascular diseases.

Adrenergic beta-Antagonists↗
PubMed2001

Purification and characterization of the recombinant Thermus sp. strain T2 alpha-galactosidase expressed in Escherichia coli.

The nucleotide sequence of the Thermus sp. strain T2 DNA coding for a thermostable alpha-galactosidase was determined. The deduced amino acid sequence of the enzyme predicts a polypeptide of 474 amino acids (M(r), 53,514). The observed homology between the deduced amino acid sequences of the enzyme and alpha-galactosidase from Thermus brockianus was over 70%. Thermus sp. strain T2 alpha-galactosidase was expressed in its active form in Escherichia coli and purified. Native polyacrylamide gel electrophoresis and gel filtration chromatography data suggest that the enzyme is octameric. The enzyme was most active at 75 degrees C for p-nitrophenyl-alpha-D-galactopyranoside hydrolysis, and it retained 50% of its initial activity after 1 h of incubation at 70 degrees C. The enzyme was extremely stable over a broad range of pH (pH 6 to 13) after treatment at 40 degrees C for 1 h. The enzyme acted on the terminal alpha-galactosyl residue, not on the side chain residue, of the galactomanno-oligosaccharides as well as those of yeasts and Mortierella vinacea alpha-galactosidase I. The enzyme has only one Cys residue in the molecule. para-Chloromercuribenzoic acid completely inhibited the enzyme but did not affect the mutant enzyme which contained Ala instead of Cys, indicating that this Cys residue is not responsible for its catalytic function.

Amino Acid Sequence↗
PubMed2001

[New orally active penem antibiotic: Farom].

An orally active penem antibiotic, Farom (generic name: faropenem), was designed by the conformational analysis of active and inactive penem derivatives. Faropenem showed potent activity against a wide variety of bacteria including extended-spectrum beta-lactamase (ESBL)-producing ones. The mechanism of the stability against ESBL was elucidated by modeling the Michaelis complex of faropenem and Toho-1, an ESBL. Modeling of a complex of faropenem at the active site of a penicillin-binding protein 2 (PBP2) model suggested the characteristic affinity for faropenem with PBP2 of Escherichia coli. Faropenem has been totally synthesized from (R)-1,3-butanediol. The synthetic intermediate, a 3-hydroxyethyl-4-acetoxyazetidinone derivative, was efficiently prepared by the 2 + 2 coupling of a optically active vinylsulfide derivative and chlorosulfonyl isocyanate, followed by the substitution of the acetoxy group for the thiophenyl group at the C-4 position.

Anti-Bacterial Agents↗
PubMed2001

Beta-adrenoceptors: three-dimensional structures and binding sites for ligands.

Recent progress in analyzing the structures and functions of G-protein coupled receptors (GPCRs) including beta-adrenoceptors (beta-ARs) has been made by pharmacological, physiological and molecular biological techniques. The three-dimensional (3D) structures, interaction sites with ligands and conformational changes of these receptor subtypes due to ligand binding are now better understood by the simulation of these receptors using computer-aided molecular modeling. Based on these techniques, numbers and conformations of amino acid sequences of each subtype (beta1-, beta2- and beta3-ARs) were defined and also interaction sites or modes of interaction between ligands and beta-ARs could be analyzed three-dimensionally. In addition, simulation of 3D structures of beta-ARs by molecular modeling could clearly determine the limited size, space or pocket for fitting with ligands. These studies will give some clues for the clarification of other GPCRs. Thus, this review summarizes current findings on chemical structures of ligands, amino acid sequences, 3D structures and important amino acids of beta-AR subtypes for interacting with ligands obtained from mutagenesis, chimeric studies and molecular modeling techniques.

Amino Acid Sequence↗
PubMed2001

Localization, accumulation, and antifungal activity of chitinases in rye (Secale cereale) seed.

In order to understand a physiological role of chitinases in rye, the localization and accumulation of rye seed chitinase-a and -c (RSC-a and -c) in the seeds were studied by immunochemical methods. An antiserum specific to the chitin-binding domain (CB-domain), which is an N-terminal part of RSC-a, and an antiserum specific to the catalytic region of RSC-a and RSC-c were used. An immunoblot analysis detected both RSC-a and RSC-c in the endosperm of the rye seed. Immunohistochemical staining indicated that RSC-a was localized in only the aleurone cells, whereas RSC-c existed at least in the starchy endosperm and was also likely to exist in the aleurone cells. It was found by ELISA and an immunoblot analysis that RSC-a and -c accumulated in the seed during the later stage of development. Both chitinases and the Cat-domain exhibited antifungal activity toward Trichoderma species, while the CB-domain did not. Observation of the inhibition of hyphal growth of the T. species suggests that the two chitinases acted in different ways.

Antifungal Agents↗
PubMed2001

Thermally induced changes of lipoate acetyltransferase inner core isolated from the Bacillus stearothermophilus pyruvate dehydrogenase complex.

Incubation at 70 degrees C converted the Bacillus stearothermophilus lipoate acetyltransferase inner core into an unidentified active molecular form, X, yielding an inactive aggregate. The core and X showed similar thermostabilities, but they were different in the recovery of enzyme activity after incubation with 1.2-2.0 M guanidine hydrochloride and its subsequent removal; the core was hardly recovered, but X was well recovered.

Acetyltransferases↗
PubMed2001

CJ-15,801, a novel antibiotic from a fungus, Seimatosporium sp.

A novel antibiotic, CJ-15,801 (I), was isolated from the fermentation broth of a fungus, Seimatosporium sp. CL28611. The structure was determined to be a pantothenic acid analog having an alpha,beta-unsaturated carboxylic acid moiety by spectroscopic analyses. The compound inhibits the growth of multi-drug resistant (MDR) Staphylococcus aureus strains with MIC ranging from 6.25 to 50 microg/ml.

Anti-Bacterial Agents↗