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Biomedical subjects

K Mizuguchi

Publications and source records attributed to K Mizuguchi.

At least 19 recordsLinked to original sources
PubMed2006

Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia.

Disrupted in Schizophrenia 1 (DISC1) is a schizophrenia risk gene associated with cognitive deficits in both schizophrenics and the normal ageing population. In this study, we have generated a network of protein-protein interactions (PPIs) around DISC1. This has been achieved by utilising iterative yeast-two hybrid (Y2H) screens, combined with detailed pathway and functional analysis. This so-called 'DISC1 interactome' contains many novel PPIs and provides a molecular framework to explore the function of DISC1. The network implicates DISC1 in processes of cytoskeletal stability and organisation, intracellular transport and cell-cycle/division. In particular, DISC1 looks to have a PPI profile consistent with that of an essential synaptic protein, which fits well with the underlying molecular pathology observed at the synaptic level and the cognitive deficits seen behaviourally in schizophrenics. Utilising a similar approach with dysbindin (DTNBP1), a second schizophrenia risk gene, we show that dysbindin and DISC1 share common PPIs suggesting they may affect common biological processes and that the function of schizophrenia risk genes may converge.

Biological Transport↗
PubMed2005

[Autologous fibrin sealant preparing system in coronary artery bypass grafting].

Autologous fibrin sealant (AFS) which is not based on the conventional method of co-administering fibrinogen, thrombin and aprotinin was prepared by Vivostat system, and was used in coronary artery bypass grafting (CABG). The purpose of this study was to investigate the safety and efficacy of the AFS prepared by the Vivostat system. In 6 of 68 cases of CABG, normal AFS was not prepared due to device failures. AFS was prepared and sprayed in 62 cases. There were the total of 230 anastomosis sprayed AFS and the bleeding could not seen in 225 anastomosis. Surgical hemostatic procedures (4 cases) were or other sealant usage (1 case) was performed 5 bleeding anastomosis sites. The rate of hemostasis at the anastomosis using AFS was 97.8%. This study was conducted in patients undergoing CABG. In this group of patients, a number of commercial available fibrin sealant products are routinely used. The usefulness of Vivostat as medical device to prepare and administer AFS was confirmed in this study.

Adult↗
PubMed2002

[Off-pump coronary artery bypass grafting for patients with cardiogenic shock due to acute myocardial infarction].

UNLABELLED: Off-pump coronary artery bypass (OPCAB) is less invasive, so we have recently been expanding the indication. We performed OPCAB for 3 patients with cardiogenic shock due to acute myocardial infarction (AMI). PATIENTS: All patients were supported hemodynamically by intra-aortic balloon pumping (IABP) prior to surgery. RESULTS: We performed the revascularization of territories for the left anterior descending artery (LAD) and right coronary artery (RCA) in these high risk patients using OPCAB technique to improve the hemodynamic state. In all patients, IABP was removed within 48 hours after surgery and the postoperative course was uneventful. CONCLUSIONS: It seems that OPCAB is a useful and effective procedure for a selected patient even with cardiogenic shock due to AMI.

Aged↗
PubMed2001

Effect of trapidil on effector functions of monocytes related to atherosclerotic plaque.

The infiltration and activation of inflammatory cells play an important role in the formation and stability of coronary atherosclerotic plaque in patients with acute coronary syndrome. In this study, we evaluated the effect of trapidil, an anti-platelet agent, on atheroma-related functions of human T cells and monocytes. Trapidil and anti-CD154 (CD40 ligand) antibody inhibited the increase of procoagulant activity in the mixed lymphocyte reaction; trapidil also suppressed the induction of tissue factor, monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 in the mixed lymphocyte reaction. Trapidil did not alter CD154 expression on isolated T cells, but it diminished CD40 expression on isolated monocytes and human monocytic leukemia THP-1 cells stimulated with interferon-gamma. Moreover, trapidil reduced MCP-1 production of isolated monocytes and THP-1 cells stimulated with interferon-gamma plus CD154-transfected cells. This effect was not seen with other tested anti-platelet agents and coronary vasodilators. In conclusion, trapidil directly acts on monocytes/macrophages to lower their susceptibility to CD154 on T cells.

Animals↗
PubMed2001

A family of proteins related to Spätzle, the toll receptor ligand, are encoded in the Drosophila genome.

The Drosophila gene Spätzle encodes the activating ligand for the Toll receptor. This signaling pathway is required for dorso-ventral patterning in the early embryo and an antifungal immune response in larvae and adults. The genome sequence of Drosophila shows that there are a total of eight Toll-like receptors and these may function in other aspects of embryonic development and innate immunity. Here we describe five Drosophila homologues of Spätzle (Spz2-6) found using an iterative searching method. All five appear to encode proteins containing neurotrophin-like cystine-knot domains. In addition, most retain a characteristic intron-exon structure shared with the prototype Spätzle gene. This provides evidence that the family arose by ancient gene duplication events and indicates that the gene products may represent activating ligands for corresponding Toll receptors. Expression studies show that only Spz4 is expressed strongly in larvae and adults and thus may be involved in an ancillary antifungal response mediated by Toll-5. By contrast, Spz6 shows a complex spatial and temporally regulated expression pattern in the late embryo. Thus the new Toll/Spätzle families of signaling molecules may have important roles in other aspects of development and immunity.

Amino Acid Sequence↗
PubMed2001

FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties.

FUGUE, a program for recognizing distant homologues by sequence-structure comparison (http://www-cryst.bioc.cam.ac.uk/fugue/), has three key features. (1) Improved environment-specific substitution tables. Substitutions of an amino acid in a protein structure are constrained by its local structural environment, which can be defined in terms of secondary structure, solvent accessibility, and hydrogen bonding status. The environment-specific substitution tables have been derived from structural alignments in the HOMSTRAD database (http://www-cryst.bioc. cam.ac.uk/homstrad/). (2) Automatic selection of alignment algorithm with detailed structure-dependent gap penalties. FUGUE uses the global-local algorithm to align a sequence-structure pair when they greatly differ in length and uses the global algorithm in other cases. The gap penalty at each position of the structure is determined according to its solvent accessibility, its position relative to the secondary structure elements (SSEs) and the conservation of the SSEs. (3) Combined information from both multiple sequences and multiple structures. FUGUE is designed to align multiple sequences against multiple structures to enrich the conservation/variation information. We demonstrate that the combination of these three key features implemented in FUGUE improves both homology recognition performance and alignment accuracy.

Algorithms↗
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

Reoperative coronary artery bypass grafting using a minimally invasive direct coronary artery bypass procedure.

OBJECTIVE: Reoperative coronary artery bypass grafting with cardiopulmonary bypass tends to cause a higher mortality and morbidity than the primary operation. The purpose of this study was to discuss the effectiveness and safety of a minimally invasive coronary artery bypass procedure for patients who had previously undergone coronary artery bypass surgery. METHODS: We performed redo single coronary artery bypass grafting to the left anterior descending coronary artery in 9 patients and to the right coronary artery in 3 patients using minimally invasive cardiac surgery. The graft to the left anterior descending coronary artery was taken from the left internal thoracic artery in 5 patients, the right gastroepiploic artery in 3 patients, and from the saphenous vein in the other 1 patient. The graft to the right coronary artery was from the right gastroepiploic artery in all 3 patients. RESULTS: All grafts were patent. There was no major postoperative complication and no surgical or hospital death except one late death. CONCLUSIONS: In selected patients, we could safely and completely perform coronary artery bypass re-grafting to the left descending coronary artery or right coronary artery using a minimally invasive operation.

Aged↗
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

Solitary fibrous tumor of the prostate.

An extremely rare case of solitary fibrous tumor of the prostate is presented. The patient underwent a radical retropubic prostatectomy and has remained well with no evidence of recurrence during the last 18 months. This is the fifth reported case of such a lesion arising in the prostate.

Adult↗
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

Regulation of perfusion pressure during cardiopulmonary bypass using sevoflurane.

In hypothermic cardiopulmonary bypass (CPB), various vasodilators are used to control the perfusion pressure. These agents, however, often decrease the pressure excessively, and the low perfusion pressure may persist until the end of CPB. In this study we evaluate the safety and characteristics of the regulation of perfusion pressure during CPB using a volatile anesthetic, sevoflurane which has an extremely low partition coefficient. Twenty adult patients who underwent cardiac surgery were studied. Sevoflurane was applied by a vaporizer inserted into the oxygenator gas supply line. Pump flows were fixed at 2.4 L/min/m2 during the hypothermic period. Sevoflurane concentration was adjusted to keep mean arterial pressure (MAP) between 40 and 70 mmHg during CPB. Hemodynamic and metabolic parameters were measured and compared to the group we previously treated with chlorpromazine. In all cases, MAP could be maintained adequately. In the sevoflurane group, systemic vascular resistance indices (SVRI) during the rewarming period and at the end of CPB were higher, and doses of norepinephrine needed at the end of CPB were significantly lower than in the chlorpromazine group. The regulation of perfusion pressure during CPB using sevoflurane was safe and could easily maintain adequate SVRI.

Aged↗
PubMed2001

Differences in adaptation to growth of children between internal thoracic artery and saphenous vein coronary bypass grafts.

BACKGROUND: It is not known how the internal thoracic artery (ITA) and saphenous vein graft (SVG) adapts to somatic growth of pediatric patients who underwent coronary artery bypass grafting (CABG). METHODS: Twenty-two ITAs and 6 SVGs in 17 patients who underwent at least three postoperative catheterizations with biplanar cineangiography and followed for a minimum of 5 years were evaluated. We evaluated the length, diameter and curvature of the grafts by cineangiographies which were performed at 1 month, 1 year, 5 years and more than 5 years postoperatively. RESULTS: The length of the ITA (1-month: 117+/-31 mm, 1-year: 134+/-32 mm, 5-years: 146+/-28 mm, and >5-years: 155+/-34 mm, p=0.032) and diameter of the ITA (1.4+/-0.4 mm, 2.0+/-0.7 mm, 2.3+/-0.6 mm and 2.6+/-0.6 mm, p<0.0001) significantly increased over time, but neither the length nor diameter of the SVG length: 121+/-33 mm, 119+/-29 mm, 119+/-25 mm and 126+/-1 mm, p=0.9907; diameter: 4.1+/-1.0 mm, 3.9+/-0.7 mm, 4.0+/-0.8 mm and 3.3+/-0.4 mm, p=0.5784) increased. Although the ITA exhibited no change in curvature over time (1 month: 1.15+/-0.07, late: 1.15+/-0.07, p=0.8490), the curvature of the SVG significantly decreased over time (1 month: 1.42+/-0.19 and late: 1.25+/-0.16, p=0.0277). The percent segmental length of ITAs were changed little from early to late after CABG (1 month: proximal: 33.7+/-7.0%, middle: 33.3+/-7.9% and distal: 32.9+/-7.9%, vs late: 34.3+/-7.2%, 33.2+/-7.9% and 32.5+/-7.9%, p=0.937). CONCLUSIONS: ITAs grow in proportion to somatic growth, while SVGs course in a more linear fashion in adapting to patient growth.

Adaptation, Physiological↗
PubMed2001

Functional and perfusional assessment with electrocardiograph-gated single photon emission computed tomography after minimally invasive direct coronary artery bypass grafting.

BACKGROUND: Because of limited surgical field, minimally invasive coronary artery bypass grafting (MIDCAB) requires anastomosis to the distal portion of the left anterior descending artery (LAD) of the left internal thoracic artery (LITA) with the heart beating. Though the diameters of these arteries are very small, it is unknown whether blood flow sufficient for the LAD territory is obtained by bypass grafting. METHOD: Eight patients with single-vessel disease of the LAD underwent MIDCAB with the LITA to the LAD and we evaluate the perfusion and function in the LAD territory by quantitative ECG-gated SPECT (QGS) with 99m-technetium sestamibi (MIBI) before and after operation. RESULT: The intraoperatively measured diameters of the LITA and LAD at the site of anastomosis were 1.1+/-0.2 mm and 1.3+/-0.4 mm, respectively. The percentage increases in end-diastolic perfusion, regional ejection fraction and regional wall thickening in the anteroseptal area after MIDCAB were 136.3+/-11.7(p=0.071), 148.4+/-6.6(p=0.007) and 133.0+/-5.6(p=0.029), respectively (paired t-test, mean +/- SD %). Stress-rest MIBI SPECT indicated no ischemia in anteroseptal wall. CONCLUSION: The MIDCAB technique thus appeared to improve perfusion and function in the LAD territory despite bypass to the distal LAD, and ECG-gated MIBI SPECT using QGS software was very useful for evaluating the quality of anastomosis after MIDCAB.

Aged↗
PubMed2000

beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics.

The voltage-sensitive sodium channel confers electrical excitability on neurons, a fundamental property required for higher processes including cognition. The ion-conducting alpha-subunit of the channel is regulated by two known auxiliary subunits, beta1 and beta2. We have identified rat and human forms of an additional subunit, beta3. It is most closely related to beta1 and is the product of a separate gene localized to human chromosome 11q23.3. When expressed in Xenopus oocytes, beta3 inactivates sodium channel opening more slowly than beta1 does. Structural modeling has identified an amino acid residue in the putative alpha-subunit binding site of beta3 that may play a role in this difference. The expression of beta3 within the central nervous system differs significantly from beta1. Our results strongly suggest that beta3 performs a distinct neurophysiological function.

Amino Acid Sequence↗
PubMed2000

Characterisation of the gene for Drosophila amphiphysin.

A sequence similarity search of the Drosophila nucleotide database using vertebrate amphiphysin as a query identified a cDNA that encodes a Drosophila amphiphysin. The predicted protein has conserved sequence domains that should enable it to dimerise and bind to dynamin. Structural modelling suggests that the Src-homology-3 (SH3) domains of vertebrate and Drosophila amphiphysins are highly similar, supporting the putative ability of the latter to bind dynamin. However, the fly amphiphysin shows less conservation to sequences in the vertebrate amphiphysins that bind other endocytic components such as clathrin, AP-2 and endophilin. Amphiphysin is a single-copy gene that maps to position 49B on polytene chromosomes. Messenger RNA of this amphiphysin is expressed widely during embryogenesis and has elevated expression in a number of sites including the foregut, hindgut and epidermis, but not in the central nervous system. Taken together, these data are consistent with a role for Drosophila amphiphysin in endocytosis, but the details of this role may differ from that of vertebrate amphiphysins.

Amino Acid Sequence↗