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Biomedical subjects

Toshio Shimizu

Publications and source records attributed to Toshio Shimizu.

At least 19 recordsLinked to original sources
PubMed2006

Influence of overweight on surgical complications for gastric cancer: results from a randomized control trial comparing D2 and extended para-aortic D3 lymphadenectomy (JCOG9501).

BACKGROUND: The impact of overweight on the outcome of gastrectomy with lymphadenectomy is controversial, and data from a well-controlled, randomized study are needed to identify a possible relationship. METHODS: We used data from 523 patients registered for a prospective randomized trial comparing D2 and extended para-aortic D3 lymphadenectomy to compare the effects of body mass index (BMI) and the extent of lymphadenectomy for the development of general or major surgical complications (anastomotic leakage, abdominal abscess, and pancreatic fistula). RESULTS: Seventy-seven patients were classified as overweight with BMI >or= 25, and 38 and 39 of these patients underwent a D2 or D3 lymphadenectomy, respectively. Among the 446 patients classified as nonoverweight with BMI < 25, 225 received D2 and 221 received D3 lymphadenectomy. Surgical complications, operation time, and blood loss were statistically significantly associated with BMI, and logistic regression analysis revealed that overweight directly affected the occurrence of surgical complications even after considering operation time and blood loss as intermediate factors instead of outcome variables. Among patients undergoing D2 lymphadenectomy, being overweight increased the risk for surgical complications and blood loss, whereas overweight was associated with only blood loss and operation time among patients receiving D3 lymphadenectomy. CONCLUSIONS: Overweight increased the risk of surgical complications in patients undergoing gastrectomy both directly and indirectly through operation time and blood loss. The impact of overweight on surgical complications was more evident in patients undergoing a D2 dissection.

Aged↗
PubMed2006

Phase 1 clinical study of pegylated liposomal doxorubicin (JNS002) in Japanese patients with solid tumors.

BACKGROUND: Pegylated liposomal doxorubicin (PLD, JNS002) is a formulation of doxorubicin encapsulated polyethylene-glycol coated liposomes with prolonged circulation time and unique toxicity profile. This phase 1 study was aimed at investigating the maximum tolerated dose (MTD), recommended dose, toxicity, pharmacokinetics, and antitumor activity in Japanese patients with solid tumors. METHODS: Patients with solid tumors not amenable to standard forms of treatment were eligible. PLD was administered as an intravenous infusion every 4 weeks. Dose escalation of PLD was planned from 30 to 60 mg/m(2) in 10 mg/m(2) increments. The pharmacokinetics of total doxorubicin (encapsulated plus non-encapsulated) in plasma were examined for the first cycle of treatment. RESULTS: Fifteen patients, aged 49-69 (median; 56) years with advanced solid tumors were enrolled. The major non-hematological toxicities were hand-foot syndrome (HFS), rash and stomatitis. Myelosuppression, especially leukopenia and neutropenia were major hematological toxicities. Although HFS was not severe, a delay of doses for subsequent cycles was required with multiple dosing. The peak plasma concentration and the area under the concentration time curve of PLD increased proportionally to the dose. Objective response was observed in one patient and the normalization of tumor marker values in another. These two patients had been diagnosed with ovarian cancer. CONCLUSION: The recommended dose for phase 2 clinical studies of PLD in Japanese patients was 50 mg/m(2) every 4 weeks. The encouraging results prompted us to plan a subsequent clinical study of PLD against ovarian cancer.

Aged↗
PubMed2006

Acute cervical motor radiculopathy induced by neck and limb immobilization in a patient with Parkinson disease.

A 68-year-old woman with Parkinson disease (PD) presented with acute monoplegia of her left upper extremity after the neck and limb immobilization for several hours. Her sensory function was normal, and the chest X-ray showed left phrenic nerve palsy. Electrophysiological studies showed multi-segment muscle involvement (C3 to T1) including denervation potentials and reduced interference of motor units in needle electromyography. M wave amplitude in peripheral nerve stimulation was preserved except for the ulnar nerve, suggesting both axonal injury and conduction block at the anterior spinal roots. The patient showed fair recovery in several months, suggesting sufficient reinnervation and recovery of conduction block. Incomplete root avulsion was thought to be the pathomechanism of acute cervical motor radiculopathy.

Aged↗
PubMed2006

EFA6A-like antibodies in paraneoplastic encephalitis associated with immature ovarian teratoma: a case report.

We describe a 19-year-old patient with paraneoplastic encephalitis associated with immature ovarian teratoma (OT), who presented with psychiatric symptoms, prolonged disturbance of consciousness, refractory status epilepticus, central hypoventilation, and various abnormal involuntary movements. Immunological characterization of the patient's serum and cerebrospinal fluid (CSF) demonstrated the presence of an autoantibody that colocalized with EFA6A, a brain-specific protein involved in the regulation of dendritic development of hippocampal neurons. Despite the severity of the symptoms, the patient showed significant neurological improvement following removal of the tumor and chemotherapy. This case suggests that physicians should rule out an OT in young women with encephalitis who present with the subacute-onset of psychiatric symptoms. Antibodies that colocalize with EFA6A are a valuable marker for early diagnosis of a potentially reversible paraneoplastic encephalitis associated with OT.

Adult↗
PubMed2006

Analysis of tandem repeats found in 44 prokaryotic genomes.

Genomes contain various types of repetitive sequences. They may be used as probes for seeking genome rearrangements because they are rather free from the natural selection if they are located in the intergenic regions. In this study, we searched for tandem repeats (TRs) in 44 prokaryotic genomes by the color-coding method and sought the signs of genome rearrangements by detailed analysis of the detected TRs. We found 13,542 tandem repeats from 44 prokaryotic genomes in total ranging from several tens to one thousand per genome. The results of statistical analysis show that TRs tend to exist on high base composition bias regions in some genomes. Moreover, we recognized the characteristic distribution patterns of equivalent TR-pairs in 12 genomes, which are expected to indicate the occurrence of whole-genome duplication (WGD) on the genomes. It is demonstrated that TRs could indeed be used for seeking genome rearrangements. Although it has not been made clear at this time whether or not WGD had occurred in prokaryotic genomes, the results of the analyses of equivalent TR-pairs in this study are thought to be evidences of WGD in these genomes.

Base Sequence↗
PubMed2005

How accurately can we discriminate G-protein-coupled receptors as 7-tms TM protein sequences from other sequences?

The group of 2502 transmembrane (TM) protein sequences with seven TM segments (7-tms) registered in SWISS-PROT 46.0 contains 2200 G-protein-coupled receptors (GPCRs), indicating that GPCR candidates can be detected with a reliability of 87.9% in the eukaryotic genomes merely by correctly predicting the number of TM segments as 7-tms. The predictive accuracies of TM topology-prediction methods proposed so far are not as high as expected; even the best method, HMMTOP 2.0, can only achieve a capture rate of 7-tms sequences of 77.6%. It is necessary to improve this performance as much as possible, even if by only a few percentage points, in order to identify as many novel GPCR candidate genes as possible among the increasing number of newly sequenced genomes. In this study, we propose a simple but useful prediction method for detecting as many 7-tms TM protein sequences as GPCR candidates in eukaryotic genomes as possible. This is achieved by employing a two-step prediction procedure. The first step involves collecting 7-tms sequences by the best prediction method (HMMTOP 2.0), and the second involves picking up the remaining 7-tms sequences by the second-best method (TMHMM 2.0). By this procedure, the capture rate of 7-tms TM protein sequences in SWISS-PROT can be improved considerably from 77.6% to 84.5%, and the number of GPCR candidate sequences predicted as 7-tms in the human genome (Build 35) is increased from 790 (by HMMTOP 2.0) to 903. These 790 and 903 candidate sequences include, respectively, 587 and 636 of the known human GPCRs of the 717 registered in SWISS-PROT 46.0, demonstrating that the proposed combinatorial method is effective in detecting GPCR candidate genes in eukaryotic genomes.

Amino Acid Sequence↗
PubMed2005

A proteome-wide analysis of domain architectures of prokaryotic single-spanning transmembrane proteins.

We performed a proteome-wide survey of the domain architectures in single-spanning transmembrane (TM) proteins (single-spannings) from 87 sequenced prokaryotic (Bacterial and Archaean) genomes by assigning Pfam domains to their N-tail and C-tail loops. Out of 14,625 single-spannings, 3,516 sequences have at least one domain assigned, and no domains were assigned to 7,850, with the remaining 3,259 with less reliable assignment. In the domain-assigned sequences, 3116 sequences are with at most two domains, and the other 400 sequences with more than two. The assigned domains distribute over 651 Pfam families, which account for 11.4% of the total Pfam-A families. Among the 651 families are mostly soluble-protein-originated ones, but only 21 families are unique to TM proteins. The occurrence frequency of the individual domain families follows a power-law, that is, 264 families occur only once, 106 just twice, and the families appeared more than 30 times are counted by only 39. It is found that the great majority of the sequences having one or two domains are of the type II topology with the C-tail loop containing domains on it. On the contrary, the N-tail loop of the same type topology seldom carries domains. Importantly, the assigned domains are always found on the tail loops longer than 60 residues, even for the small domains with less than 30 residues. There are still as many as 5,800 sequences without assigned domains in spite of having at least one long tail, on which no less than 1,000 novel domain families are expected most likely to lie concealed unknown yet. We also investigated the domain arrangement preference and the domain family combination patterns in 'singlets' (single-spannings with one assigned domain) and 'doublets' (with two domains).

Computational Biology↗
PubMed2005

Model analysis of surfactant--polymer interaction as cooperative ligand binding to linear lattice.

An improved model of the cooperative binding of monomeric ligands to a linear lattice is proposed for the analysis of surfactant association on the polymer. The interaction between bound ligands across an unoccupied site as well as the steric hindrance effect in consecutive bindings is taken into account here. Typical results of the model calculations are represented, and several least squares fittings of the binding isotherms of the ionic surfactant-polyelectrolyte systems are attempted. The characteristic binding behavior in those systems is interpretable by the feasible model of the interactions between surfactant molecules. The advantages and limitations of the analysis using this model also are discussed.

Binding Sites↗
PubMed2005

Introduction of Sd(a) carbohydrate antigen in gastrointestinal cancer cells eliminates selectin ligands and inhibits metastasis.

The Sd(a) blood group carbohydrate structure is expressed in the normal gastrointestinal mucosa. We reported previously that the expression of Sd(a) carbohydrate structures and beta1,4-N-acetylgalactosaminyltransferase (beta1,4GalNAcT) activity responsible for Sd(a) synthesis were remarkably decreased in cancer lesions of the gastrointestinal tract. In this study, we found that Sd(a) antigen was expressed mainly in chief cells of normal stomach but not in cancer tissue by immunohistologic staining. In separated gastric mucosal cells, the Sd(a) glycolipids and beta1,4GalNAcT activity were concentrated in a fraction that contained chief cells as a major population. We cloned the cDNA encoding the glycosyltransferase that catalyzes the synthesis of Sd(a) (Sd(a)-beta1,4GalNAcT). Introduction of this cloned cDNA into KATO III gastric or HT29 colonic cancer cell lines, which originally expressed the E-selectin ligands, sialyl Lewis(x) and sialyl Lewis(a), resulted in a marked increase in cell-surface expression of Sd(a) along with the concomitant total loss of both sialyl Lewis(x) and sialyl Lewis(a). Both KATO III and HT29 cells transfected with the Sd(a)-beta1,4GalNAcT gene showed significantly decreased adhesion to activated human umbilical vein endothelial cells when compared with mock-transfected cells. Sd(a) determinants showed no direct binding to Siglec-3, -5, -7, and -9. These Sd(a)-beta1,4GalNAcT-transfected cells showed strikingly reduced metastatic potential in vivo when compared with mock-transfected cells. In summary, forced expression of Sd(a) carbohydrate determinant caused remarkable elimination of carbohydrate ligands for selectin and reduced metastasis of human gastrointestinal tract cancer cells.

Animals↗
PubMed2005

Unsaturated selenacrown ethers: synthesis, structure, and formation of silver complexes.

The unsaturated selenacrown ethers, (Z,Z,Z,Z,Z)-1,4,7,10,13-pentaselenacyclopentadeca-2,5,8,11,14-pentaene (15-US-5) (2), (Z,Z,Z,Z,Z,Z)-1,4,7,10,13,16-hexaselenacyclooctadeca-2,5,8,11,14,17-hexaene (18-US-6) (3), (Z,Z,Z,Z,Z,Z,Z)-1,4,7,10,13,16,19-heptaselenacycloheneicosa-2,5,8,11,14,17,20-heptaene (21-US-7) (4), (Z,Z,Z,Z,Z,Z,Z,Z)-1,4,7,10,13,16,19,22-octaselenacyclotetracosa-2,5,8,11,14,17,20,23-octaene (24-US-8) (5), and (Z,Z,Z,Z,Z,Z,Z,Z,Z)-1,4,7,10,13,16,19,22,25-nonaselenacycloheptacosa-2,5,8,11,14,17,20,23,26-nonaene (27-US-9) (6), were obtained together with 1,4-diselenin (1) by reacting sodium selenide with cis-dichloroethene in the presence of a phase-transfer catalyst. The crystal structures of 2-5 were determined by X-ray crystallographic analysis. The UV spectra of the selenacrown ethers showed absorption maximums in the range of 251-262 nm, which were assigned to n-->pi transitions. The cyclic voltammograms indicated that the large unsaturated selenacrown ethers were oxidized more easily than the small ones. The thermal reactions of the unsaturated selenacrown ethers afforded 1,4-diselenin (1) along with polymeric materials, whereas 1 was thermally stable even at 100 degrees C. The reactions of 1 or unsaturated selenacrown ethers 2-5 with silver ion yielded various novel silver complexes, Ag(C(4)H(4)Se(2))(CF(3)COO) (7), Ag(C(4)H(4)Se(2))(2)(CF(3)COO) (8), Ag(15-US-5)(CF(3)COO) (9), Ag(5)(18-US-6)(3)(CF(3)COO)(5) (10), Ag(7)(21-US-7)(CF(3)COO)(5) (11), Ag(24-US-8)(2)(CF(3)COO) (12), Ag(2)(24-US-8)(CF(3)COO)(2) (13), Ag(3)(24-US-8)(2)(CF(3)COO)(3) (14), Ag(15-US-5)NO(3) (15), and Ag(21-US-7)BF(4) (16). The stoichiometry for the complexation with silver trifluoroacetate in solution was examined by (1)H NMR measurement. The titration plots of 2 and 5 under the dilution conditions showed a distinct inflection point at the 1/1 metal/macrocycle ratio, whereas the plots of 1 and 3 showed gradual change.

Journal Article↗
PubMed2005

Optically active seleninate esters: isolation, absolute configuration, racemization mechanism, and transformation into chiral selenoxide.

Optically active seleninate esters were obtained for the first time by chromatographic resolution on an optically active column. The absolute configurations of the optically active seleninate esters were determined by comparing their chiroptical properties with those of two analogous sulfinate esters, the absolute configuration of one of which is known and that of the other was determined by X-ray crystallographic analysis. The optically active seleninate esters were found to racemize in solution. Kinetic studies of the racemization, the oxygen exchange reaction with H(2)(18)O, and theoretical studies clarified that the racemization of the optically active seleninate esters in solution proceeded via an achiral hypervalent selenurane intermediate that was formed by the reaction with water. The reaction of the optically active seleninate ester and the sulfinate ester having bulky substituents with Grignard reagents was found to proceed with the retention of stereochemistry to give an optically active selenoxide and sulfoxides, respectively.

Journal Article↗
PubMed2005

Optically active seleninamides: isolation, absolute configuration, and racemization mechanism.

Optically active seleninamides were obtained for the first time by chromatographic resolution on an optically active column. The absolute configurations of the optically active seleninamides were determined by comparing their chiroptical properties with those of analogous sulfinamides, the stereochemistry of which was determined by transformation into chiral sulfoxides of known configurations. The optically active seleninamides were found to racemize in solution. Kinetic studies of the racemization and theoretical studies clarified that the racemization of the optically active seleninamides in solution proceeds via hypervalent hydrates formed by the reaction with water.

Journal Article↗
PubMed2005

A recurrent duodenal gastrointestinal stromal tumor with a frameshift mutation resulting in a stop codon in KIT exon 13.

Gastrointestinal stromal tumors (GISTs) are a specific and rare subset of human gastrointestinal tract tumors. Most GISTs show gain-of-function mutations of KIT, mainly in exon 11, that always maintain the reading frame. We report on data from a 43-year-old Japanese man with recurrent duodenal GIST and a frameshift mutation in KIT exon 13 together with an in-frame deletion in KIT exon 11 detected by genomic DNA sequencing. Deletion of 48 base pairs of KIT exon 11, which preserved the reading frame, was identified in both primary and recurrent tumors, whereas deletion of one nucleotide of codon 642 of KIT exon 13, which changed the reading frame and induced a novel stop codon at amino acid 644, was found only in the recurrent tumor. The predicted protein resulting from the latter would lack part of the kinase domain. To the best of our knowledge, this is the first documentation of a GIST with a frameshift mutation of KIT.

Adult↗
PubMed2005

Changes in causes of sudden deaths by decade in patients with coronary arterial lesions due to Kawasaki disease.

Over a 25-year period, we encountered 12 patients who died suddenly with coronary arterial lesions due to Kawasaki disease. We report their clinical course, and analyze the happenings of their deaths. Of the 12 patients, 10 were dead on arrival at hospital. Their age at death ranged from 13 months to 27 years, with a median of 16 years, and the interval from the onset of Kawasaki disease to death ranged from 2 months to 24 years. In 4 patients, death was found to be due to myocardial infarction, while in the remaining 8, it could not be determined. In 7 patients, coronary angiograms obtained less than 4 months after the acute onset of Kawasaki disease showed lesions bilaterally, most being giant aneurysms. Myocardial infarction had occurred in 6 patients prior to their death. In 1 patient of the late 1970s, who collapsed after running, cardiac sequels had not been suspected prior to autopsy. During the 1980s, 3 infants with bilateral giant aneurysms died within a year of the initial onset of Kawasaki disease, with acute myocardial infarction being the cause in 2 of them. In the late 1990s, and the 2000s, 5 patients died suddenly with left ventricular dysfunction, their ejection fractions being less than 40 percent more than 20 years after the initial onset of Kawasaki disease. Prior to their sudden deaths, they had had no cardiac events for many years, but had suffered previous myocardial infarctions. Multifocal premature ventricular contractions, and non-sustained ventricular tachycardia, are probable risk factors in such patients. Careful follow-up, checking for ventricular arrhythmia, is needed to prevent sudden death in patients suffering left ventricular dysfunction in the setting of Kawasaki disease.

Adolescent↗
PubMed2004

Optical resolution and racemization mechanism of a tellurinic acid.

[reaction: see text] Optically active tellurinic acid was obtained for the first time by chromatographic resolution of racemic 2,4,6-triisopropylbenzenetellurinic acid (1) using a chiral column. Optically active tellurinic acid (+)-1 was stable toward racemization in hexane, although racemization occurred in hexane/2-propanol. The kinetic studies for the racemization, oxygen exchange reaction using H(2)(18)O, and theoretical studies clarified that the racemization of the optically active tellurinic acid in solution proceeds via a hypervalent tellurane formed by addition of water remaining in solvent.

Kinetics↗
PubMed2004

ConPred II: a consensus prediction method for obtaining transmembrane topology models with high reliability.

ConPred II (http://bioinfo.si.hirosaki-u.ac.jp/~ConPred2/) is a server for the prediction of transmembrane (TM) topology [i.e. the number of TM segments (TMSs), TMS positions and N-tail location] based on a consensus approach by combining the results of several proposed methods. The ConPred II system is constructed from ConPred_elite and ConPred_all (previously named ConPred), proposed earlier by our group. The prediction accuracy of ConPred_elite is almost 100%, which is achieved by sacrificing the prediction coverage (20-30%). ConPred_all predicts TM topologies for all the input sequences with accuracies improved by up to 11% over individual proposed methods. In the ConPred II system, the TM topology prediction of input TM protein sequences is executed following a two-step process: (i) input sequences are first run through the ConPred_elite program; (ii) sequences for which ConPred_elite does not give the TM topology are delivered to the ConPred_all program for TM topology prediction. Users can get access to the ConPred II system automatically by submitting sequences to the server. The ConPred II server will return the predicted TM topology models and graphical representations of their contents (hydropathy plots, helical wheel diagrams of predicted TMSs and snake-like diagrams).

Algorithms↗
PubMed2004

Internal gene duplication in the evolution of prokaryotic transmembrane proteins.

We investigated the evolution of transmembrane (TM) topology by detecting partial sequence repeats in TM protein sequences and analyzing them in detail. A total of 377 sequences that seem to have evolved by internal gene duplication events were found among 38,124 predicted TM protein sequences (except for single-spannings) from 87 prokaryotic genomes. Various types of internal duplication patterns were identified in these sequences. The majority of them are diploid-type (including quasi-diploid-type) duplication in which a primordial protein sequence was duplicated internally to become an extant TM protein with twice as many TM segments as the primordial one, and the remaining ones are partial duplications including triploid-type. The diploid-type repeats are recognized in many 8-tms, 10-tms and 12-tms TM protein sequences, suggesting the diploid-type duplication was a principle mechanism in the evolutionary development of these types of TM proteins. The "positive-inside" rule is satisfied in whole sequences of both 10-tms and 8-tms TM proteins and in both halves of 10-tms proteins while not necessarily in the second half of 8-tms proteins, providing fit examples of "internal divergent topology evolution" likely occurred after a diploid-type internal duplication event. From analyzing the partial duplication patterns, several evolutionary pathways were recognized for 6-tms TM proteins, i.e. from primordial 2-tms, 3-tms and 4-tms TM proteins to extant 6-tms proteins. Similarly, the duplication pattern analysis revealed plausible evolution scenarios that 7-tms TM proteins have arisen from 3-tms, 4-tms and 5-tms TM protein precursors via partial internal gene duplications.

Amino Acid Sequence↗