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H Shirai

Publications and source records attributed to H Shirai.

At least 37 records · Page 2Linked to original sources
PubMed2001

Sequence-structure homology recognition by iterative alignment refinement and comparative modeling.

Our approach to fold recognition for the fourth critical assessment of techniques for protein structure prediction (CASP4) experiment involved the use of the FUGUE sequence-structure homology recognition program (http://www-cryst.bioc.cam.ac.uk/fugue), followed by model building. We treat models as hypotheses and examine these to determine whether they explain the available data. Our method depends heavily on environment-specific substitution tables derived from our database of structural alignments of homologous proteins (HOMSTRAD, http://www-cryst.bioc.cam.ac.uk/homstrad/). FUGUE uses these tables to incorporate structural information into profiles created from HOMSTRAD alignments that are matched against a profile created for the target from multiple sequence alignment. In addition, environment-specific substitution tables are used throughout the modeling procedure and as part of the model evaluation. Annotation of sequence alignments with JOY, to reflect local structural features, proved valuable, both for modifying hypotheses, and for rejecting predictions when the expected pattern of conservation is not observed. Our stringency in rejecting incorrect predictions led us to submit a relatively small number of models, including only a low number of false positives, resulting in a high average score.

Amino Acid Sequence↗
PubMed2001

Gastrointestinal stromal tumor of the stomach: report of a case.

We report herein the case of a 70-year-old woman found to have a gastrointestinal stromal tumor (GIST) of the stomach. Preoperative X-ray and endoscopic examination revealed a hemispheric submucosal tumor with central depression in the anterior wall of the gastric fornix. The tumor, which was 3 cm in diameter, was resected by a laparoscopy-assisted procedure. Histologic examination revealed that it was composed of spindle-shaped cells with elongated nuclei, and few mitoses. Most of the tumor cells showed immunoreactivity for vimentin and CD34, but not for alpha-smooth muscle actin, desmin, or S-100 protein. The PCNA index was 40.5%. Thus, the GIST did not show differentiation toward smooth muscle or neural cells. A gastrectomy was not performed because the small size of the tumor, and the paucity of the mitoses indicated that it was benign. Nevertheless, careful and long-term follow-up is needed to monitor for signs of possible local recurrence or distant metastases.

Aged↗
PubMed2001

Effects of ovariectomy and/or dietary calcium deficiency on bone dynamics in the rat hard palate, mandible and proximal tibia.

The effects of ovariectomy and/or dietary calcium deficiency on bone dynamics were examined by comparing the histomorphometric changes in these bones. Five groups of rats were studied, (1) unoperated basal controls; (2) sham-operated, fed on a normal-calcium diet; (3) ovariectomized, fed on a normal-calcium diet; (4) sham-operated, fed on a calcium-deficient diet; (5) ovariectomized, fed on a calcium-deficient diet. The basal controls were killed at 6 weeks of age, and the remaining groups were killed at 18 weeks of age. The hard palate, mandible and proximal tibia were processed undemineralized for quantitative bone histomorphometry. Bone volume, eroded surface, osteoid surface and bone-formation ratio were calculated. A significant age-related increase in bone volume and a significant decrease in bone formation were observed in the hard palate and mandible, whereas no significant age-related increase in bone volume could be found in the tibia. In the hard palate, ovariectomy neither inhibited age-related increases in bone volume nor affected bone dynamics, while both the combined ovariectomy and dietary calcium deficiency and dietary calcium deficiency alone led to bone loss and increased bone turnover. In contrast, in the mandible and proximal tibia, ovariectomy alone as well as dietary calcium deficiency led to bone loss and increased bone turnover. Ovariectomy, therefore, produced no significant changes in the hard palate, but affected bone dynamics in the mandible and tibia. However, dietary calcium deficiency induced bone loss and increased bone turnover in the hard palate, mandible and proximal tibia, independently of ovariectomy.

Analysis of Variance↗
PubMed2001

A novel superfamily of enzymes that catalyze the modification of guanidino groups.

Three enzymes, peptidyl-arginine deiminase from Porphyromonas gingivalis, arginine deiminase and amidinotransferase are traditionally classified separately. By combining PSI-BLAST and FUGUE, data presented in this article describe how these enzymes belong to a novel superfamily, adopting a common fold and sharing similar catalytic mechanisms.

Amidinotransferases↗
PubMed2001

A histomorphometric analysis on bone dynamics in denture supporting tissue under continuous pressure in streptozotocin-induced diabetic rat.

The purpose of this study was to investigate bone dynamics in denture supporting tissue under continuous pressure in the diabetic condition by using bone histomorphometry in relation to initial intensity of continuous pressure exerted through the denture base. The experimental denture base, which was designed to load initial continuous pressure of 0.0, 1.0, 10.0 or 20.0 kPa to the denture supporting tissue, was applied to the molar region of hard palate of streptozotocin-induced diabetic rats. Fluorescent labelled palatal bone tissue was stained with Villanueva bone stain and was prepared for the undecalcified grinding section. In 0.0 kPa group, no bone resorption was observed and bone formation was transiently inhibited after the denture insertion. In 1.0 kPa group, although no bone resorption was observed, the beginning of bone formation after the inhibition of bone formation was later than that in 0.0 kPa group and bone formation dynamics after the resumption of bone formation was similar to that in 0.0 kPa group. In 10.0 and 20.0 kPa groups, bone resorption was observed until 3 and 4 weeks, respectively, and the amount of bone resorption for each group was 60 +/- 16 and 87 +/- 18 microm, respectively. The resumption of bone formation in 10.0 and 20.0 kPa groups were observed at the same stage with 1.0 kPa group, and the bone formation dynamics after the resumption of bone formation in 10.0 and 20.0 kPa groups were also similar to that in 0.0 kPa group. From the results of this study, it was revealed that bone formation following bone resorption did not cause equivalent recovery of the bone surface level to the level observed in the case without bone resorption in the diabetic condition.

Animals↗
PubMed2001

CYP3A activity in European American and Japanese men using midazolam as an in vivo probe.

OBJECTIVE: To investigate putative differences in CYP3A activity between European American and Japanese subjects using midazolam as an in vivo probe. METHODS: Midazolam was administered orally (2 mg) to 22 young healthy Japanese men and, on a separate occasion, to 19 of these by the intravenous route (1 mg). The disposition of the drug and its 1'-hydroxy metabolite were determined and compared with data collected in a similar fashion in 20 young healthy European American men. RESULTS: Plasma concentrations of midazolam, especially those attained soon after drug administration, were higher after intravenous injection in Japanese subjects than those in European American men. This observation was associated with smaller initial (2.5-fold) and steady-state (1.8-fold) volumes of distribution for the drug; normalization for body weight only modestly reduced these differences. The systemic clearance value of midazolam was 25% lower (P < .03) in Japanese subjects, but this difference was not apparent after accounting for the smaller body weights of that group. No statistical differences were noted in the elimination half-life (t 1/2) of midazolam between European American and Japanese subjects. Much greater interindividual variability was observed after oral administration compared with intravenous administration, but significant differences were not found between the 2 groups with respect to the maximum midazolam plasma level or its oral clearance. Absolute oral bioavailability and its associated gastrointestinal and hepatic extraction ratios also showed no statistically significant interracial differences. CONCLUSIONS: On average, hepatic CYP3A, as measured by the metabolism of midazolam, is lower in young healthy Japanese men compared with similar European Americans. However, there is considerable interindividual variability, and body size appears to be an important determinant. After oral administration, even greater variability in the plasma level-time profile of midazolam is present, and no statistically significant or clinically important interracial/ethnic difference is present. Possibly because of smaller body mass and differences in body composition, midazolam has a smaller distribution volume(s) in Japanese men than in European American men that might be an important factor when drugs are administered intravenously.

Administration, Oral↗
PubMed2001

HOMSTRAD: adding sequence information to structure-based alignments of homologous protein families.

summary: We describe an extension to the Homologous Structure Alignment Database (HOMSTRAD; Mizuguchi et al., Protein Sci., 7, 2469-2471, 1998a) to include homologous sequences derived from the protein families database Pfam (Bateman et al., Nucleic Acids Res., 28, 263-266, 2000). HOMSTRAD is integrated with the server FUGUE (Shi et al., submitted, 2001) for recognition and alignment of homologues, benefitting from the combination of abundant sequence information and accurate structure-based alignments. AVAILABILITY The HOMSTRAD database is available at: http://www-cryst.bioc.cam.ac.uk/homstrad/. Query sequences can be submitted to the homology recognition/alignment server FUGUE at: http://www-cryst.bioc.cam.ac.uk/fugue/.

Computational Biology↗
PubMed2001

Inverse correlation between macrophage-colony stimulating factor, cholesterol and high density lipoprotein cholesterol in Kawasaki disease.

Kawasaki disease (KD) is a childhood-onset vascular disease. We assessed the concentrations of macrophage-colony stimulating factor (M-CSF) and those of lipids in sera from patients with KD. The M-CSF concentration in patients with acute-phase KD was 2,914+/-159 U/ml, significantly higher than that in control subjects with Infectious diseases (1,241+/-96 U/ml). The elevated levels of this cytokine in the acute phase fell to 1,319+/-138 U/ml in the convalescent phase. Total and high-density lipoprotein cholesterol concentrations in acute phase KD (113.8+/-8.4 and 21.5+/-2.3 mg/dl, respectively) were lower than in the infectious disease controls (195.8+/-7.0 and 62.5+/-1.8 mg/dl). The elevation of M-CSF correlated with the decrease of total and high-density lipoprotein cholesterol. Overproduction of macrophage-colony stimulating factor activates macrophages and monocytes and may disturb the lipid metabolism. Both effects could contribute to vasculitis in KD.

Child Welfare↗
PubMed2000

Low Molecular Weight Gelators for Organic Fluids: Gelation Using a Family of Cyclo(dipeptide)s.

Simple cyclo(dipeptide)s consisting of diverse amino acids are able to cause physical gelation in a wide variety of organic fluids, including edible oils, glyceryl esters, alcohols, and aromatic molecules. Minimum gel concentrations, FTIR spectroscopy, NMR spectroscopy, and electron micrograph are used to characterize gel phenomenon. The intermolecular hydrogen bonding between N-H and C=O in cyclo(dipeptide)s plays an important role in gelation. FTIR and X-ray diffraction data suggest that the aggregate responsible for gel is an assembly of hydrogen-bonded molecular ladders, which are initially formed from numerous molecules through intermolecular hydrogen bonding. The ladder-like aggregates are intertwined and interlocked, and finally immobilize organic fluids. The gelation ability is discussed in connection with the three-component solubility parameters of solvents. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Argyrophilic nucleolar organizer regions (AgNORs) in mucosal epithelium under experimental denture bases in rats.

The purpose of this study was to evaluate changes in the argyrophilic nucleolar organizer region (AgNOR) counts in mucosal epithelium induced by continuous or intermittent compressive pressure exerted through experimental denture bases and to examine the relationships between the AgNOR count, histopathological changes and the intensity of the pressure under denture bases. Continuous or intermittent compressive pressure exerted through the denture bases was applied to the hard palate of the molar region in rats. A morphometric analysis of AgNORs was performed in denture-supporting tissue 3 days and 1, 2, 4, 8, 12 and 20 weeks after the denture insertion. From the results of this study, it was found that non-pressure contact of the denture bases with palatal tissues did not change the AgNOR count. The AgNOR count was decreased by continuous or intermittent compressive pressure, and then recovered to almost the same level as with the non-pressure contact at 20 weeks following a decrease of the pressure. The AgNOR counts in the epithelium under the denture bases were revealed to be related to the histopathological changes in the denture-supporting tissues and the intensity of the pressure under the denture bases.

Acrylic Resins↗
PubMed2000

Morphology and dynamics of the ulnar nerve in the cubital tunnel. Observation by ultrasonography.

We examined 200 normal elbows to assess the usefulness of ultrasonography in examining the ulnar nerve in the cubital tunnel. On longitudinal images in elbow extension, the nerve changed its course at the fibrous band region 11.5 (SD 2.8) mm distal to the medial epicondyle. On axial images, the diameter of the major axis of the nerve was 3.1 (0.5) mm and that of the minor axis was 1.9 (0.4) mm in men. The respective values were 2.7 (0.4) mm and 1.8 (0.4) mm in women. Dynamic studies showed that in 53 elbows (27%), the nerve moved on to the tip of the epicondyle with the elbow flexed and in 39 elbows (20%), the nerve dislocated anteriorly. The diameters of the hypermobile nerves were significantly larger than nerves that did not displace.

Adult↗
PubMed2000

Diagnostic ultrasonography of the ulnar nerve in cubital tunnel syndrome.

Thirty-two elbows in 31 patients diagnosed as having cubital tunnel syndrome underwent ultrasonographic examination to assess morphological changes in the ulnar nerve and its surrounding tissues. On longitudinal images, the site of constriction due to the fibrous band and proximal swelling of the nerve were observed by ultrasonography and were confirmed intraoperatively. On axial images, the lengths of the major axis [7.2 (SD 1.6) mm] and the minor axis [3.7 (0.9) mm] of the nerve at the medial epicondyle were greater than those in normal subjects. There was a correlation between the stage of ulnar nerve palsy and the diameter of the major axis. Preoperatively, ganglia were detected by ultrasonography in the cubital tunnel in three cases and an anconeus epitrochlearis muscle in two.

Cubital Tunnel Syndrome↗
PubMed1999

Enhanced conformational diversity search of CDR-H3 in antibodies: role of the first CDR-H3 residue.

Through a conformation search by a simulation calculation, the relationships between the amino acid sequences and the conformations of the third complementarity-determining region of the antibody heavy chain (CDR-H3) were investigated to characterize the large conformational varieties of antibodies. Here, we focused on the structural role of the first CDR-H3 residue, and we selected two antibodies, 28B4 and PLG, whose CDR-H3 conformations are significantly different, having Trp and Gly at the first position, respectively. Multicanonical molecular dynamics simulations, with the advantage of enhanced sampling efficiency, were performed for the CDR-H3 fragments of 28B4 and PLG, and a modified CDR-H3 model of 28B4, where the first Trp residue was substituted with Gly. When the first CDR-H3 residue is Trp, almost all of the observed CDR-H3 loops were bent at the first residue. In contrast, when the first residue is Gly, large varieties of loop conformations were observed. The structural role of this Gly residue is discussed from the perspective of the other antibody structures in the database. When the surrounding residues were included in the calculations, CDR-H3 loop structures similar to those in the crystal structures were reproduced as the major conformations for both the 28B4 and PLG antibodies.

Algorithms↗
PubMed1999

H3-rules: identification of CDR-H3 structures in antibodies.

For the third complementarity determining region of the antibody heavy chain (CDR-H3), we propose the 'H3-rules', which should identify the tertiary structure from the amino acid sequence of the CDR-H3 segment. A total of 100 CDR-H3 segments from well-determined crystal structures were analyzed. Distinctive relationships between the structures and the sequences were revealed from 55 segments, and the rules were examined for the other 45 segments and were verified. In some antibodies, basic residues at specific positions were revealed to be notable signals, with their ability to form salt bridges and to assume conformations inconsistent with the rules.

Amino Acid Sequence↗
PubMed1999

Characterization of cleavage enzymes for sterol regulatory element binding protein in hamster liver microsomes.

Sterol regulatory element binding proteins (SREBP-1 and SREBP-2) are the key transcription factors for the regulation of the cellular cholesterol level. To identify proteolytic enzymes for SREBPs, a fluorogenic peptide substrate, MOCAc-GRSVLSFK(Dnp)rr-NH2, was synthesized according to the proposed cleavage site of human SREBP-2. In microsome fractions from hamster liver, we found a peptidase activity inhibitable by the synthetic inhibitor Ac-GRSVL-aldehyde with an IC50 of 40 nM. This peptidase separated into three peaks of approximately 400 kDa, 60 kDa, and 30 kDa (Mp400, Mp60 and Mp30 respectively) upon gel permeation chromatography. Mp30 was purified to apparent homogeneity with an Mr of 32 kDa. The partial amino acid sequence of Mp30 possessed homology to cathepsin B (EC 3.4.22.1). A 109 kDa protein band on SDS-PAGE which corresponded to Mp400 exhibited homology to neprilysin (EC 3.4.24.11) in partial amino acid sequence. These findings suggest several degradative pathways for SREBP in liver microsome membranes.

Amino Acid Sequence↗
PubMed1999

Structure and function of type I and II macrophage scavenger receptors.

Type I and II macrophage scavenger receptors are implicated in the pathologic deposition of cholesterol during the atherogenesis. There is a charged collagen structure of type I and II receptors identified as a ligand binding domain, which can recognize a wide range of negatively charged macromolecules including oxidized LDL as well as damaged or apoptotic cells and pathogenic micro-organisms. After binding these ligands can be either internalized by endocytosis, phagocytosis, or remain at cell surface and mediate the adhesion. Under physiological condition, scavenger receptors serve to scavenge or clean up cellular debris and other related materials, as well as playing a role in the hosts defence. In pathological condition, they mediate the recruitment, activation and transformation of macrophages and other cells, which may be related to the development of atherosclerosis and to disorders caused by the accumulation of denatured materials, such as Alzheimer's disease.

Alzheimer Disease↗