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S Imai

Publications and source records attributed to S Imai.

At least 73 records · Page 4Linked to original sources
PubMed2000

M-S vibrational study in three-coordinate thiolato compounds (NEt4)2[M(SC6H4-p-X)3] and (NEt4).

By using p-substituted benzenethiolate ligands, the novel three-coordinate copper(I) and silver(I) thiolato complexes (NEt4)2[Cu(SC6H4-p-X)3] (X=Cl (1) and Br (2)), (NEt4)2[Ag(SC6H4-p-X)3] (X=Cl (3) and Br (4)) and novel clusters (NEt4)2[M4(mu-SC6H4-p-Cl)6] (M=Cu (5) and Ag(6)) have been prepared and structurally characterized by single crystal X-ray diffraction. All the complexes have three-coordinate sites having point-group D3h symmetry. The three-coordinate mononuclear silver(I) complexes 3 and 4 are the first examples. The M-S stretching bands were determined by far-IR and FT-Raman spectroscopies; nu(Cu-S) 363-372 cm(-1) and nu(Ag-S) 353-363 cm(-1). These results indicate that M-S stretching vibration energy in the three-coordinate metal(I) site of the mononuclear compounds or clusters is around 340-380 cm(-1), and it is a useful tool for determining their coordination modes.

Benzene Derivatives↗
PubMed2000

Effects of three different Ca(2+) pump ATPase inhibitors on evoked contractions in rabbit aorta and activities of Ca(2+) pump ATPases in porcine aorta.

Using vascular smooth muscle, we describe the actions of three pharmacological tools, cyclopiazonic acid (CPA), thapsigargin (TG) and 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBHQ), which are presumed to act as selective inhibitors of the sarco-endoplasmic reticulum Ca(2+)-ATPases (SERCAs). In porcine aortic smooth muscle microsomes two Ca(2+)-ATPase activities have been described, one vanadate-sensitive and one vanadate-resistant, representing the Ca(2+)-ATPase activities of the plasma membrane and SERCAs, respectively. In agreement, CPA, TG and tBHQ, in the concentration range 0.1 microM to 0.1 mM, dose-dependently inhibit the Ca(2+)-ATPase activity only in the vanadate-resistant microsomes. However, 0.1 mM tBHQ also significantly inhibited the Ca(2+)-ATPase activity of vanadate-sensitive microsomes. In rabbit aortic rings, all three SERCA inhibitors produced a dose-dependant inhibition of contractions evoked by 20 mM caffeine or 1 microM phenylephrine (PE) in a Ca(2+)-free physiological solution. However, in PE-contracted rings, tBHQ (> or =30 microM) also significantly inhibited the ability of cromakalim to induce relaxation. In conclusion, the data suggest that CPA, TG and tBHQ can all act as selective SERCA inhibitors in both porcine and rabbit aortic smooth muscle. However, in contrast to CPA and TG, high concentrations of tBHQ can exhibit some nonspecific effects, which include inhibition of the plasma membrane Ca(2+)-ATPase and possibly K(+) channels regulated by cromakalim.

Animals↗
PubMed2000

Transposon-mediated insertional mutagenesis of the D-alanyl-lipoteichoic acid (dlt) operon raises methicillin resistance in Staphylococcus aureus.

Two independent mutants of methicillin-resistant Staphylococcus aureus (MRSA), KAN96H1 and KAN96H2, were isolated by insertional mutagenesis with conjugative transposon Tn918. In both, the minimal inhibitory concentration (MIC) of methicillin was increased to 128 compared to 16 mg/L for the parental strain KAN96. By transduction experiments, we verified that the insertion of Tn918 conferred higher methicillin resistance on KAN96H1, but not on KAN96H2. In KAN96H1, the integration site of Tn918 was located in the 6.1-kb HindIII fragment of the KAN96 chromosomal DNA. We identified a novel D-alanyl-lipoteichoic acid (dlt) operon of S. aureus in this fragment. The amino acid sequences of four open reading frames of this operon were highly homologous to those of the dlt operon genes of Bacillus subtilis. The nucleotide sequence of the staphylococcal dlt operon is under the accession number D86240 in the DDBJ/GenBank/EMBL databases. In KAN96H1, Tn918 was inserted in the 5'-terminal region of the putative dltB gene which encoded a hypothetical membrane transporter. dlt transcripts of 4.7 kb were detected in KAN96, but were truncated to 2.3 kb in KAN96H1. No corresponding transcripts were observed in KAN96H2. Our results clearly demonstrated that defects in functions of the putative dlt operon resulted in increased methicillin resistance in MRSA.

Amino Acid Sequence↗
PubMed2000

Heparin-binding proteins HB-GAM (pleiotrophin) and amphoterin in the regulation of cell motility.

Fractionation of proteins from perinatal rat brain was monitored using a neurite outgrowth assay. Two neurite-promoting proteins, HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin) and amphoterin, were isolated, cloned and produced by baculovirus expression for structural and functional studies. HB-GAM is highly expressed in embryonic and early post-natal fiber pathways of the nervous system, and it enhances axonal growth/guidance by binding to N-syndecan (syndecan-3) at the neuron surface. N-syndecan in turn communicates with the cytoskeleton through the cortactin/src-kinase pathway to enhance neurite extension. In addition to N-syndecan, the chondroitin sulfate proteoglycan RPTP beta/zeta (receptor-type tyrosine phosphatase beta/zeta) is implicated in the receptor mechanism of HB-GAM. HB-GAM is also prominently expressed in developing and regenerating bone as a matrix-bound cue for migration of osteoblasts/osteoblast precursors to the site of bone deposition. HB-GAM is suggested to regulate motility in osteoblasts through a similar mechanism as in neurons. Structural studies using heteronuclear NMR reveal two similar protein domains in HB-GAM, both consisting of three anti-parallel beta-strands. Search of sequence databases shows that the beta structures of HB-GAM and of the similar domains of MK (midkine) correspond to the thrombospondin type I (TSR) sequence motif. We suggest that the TSR sequence motif, found in several neurite outgrowth-promoting and other cell surface and matrix-binding proteins, defines a beta structure similar to those found in HB-GAM and MK. In general, amphoterin is highly expressed in immature and transformed cells. We suggest a model, according to which amphoterin is an autocrine/paracrine regulator of invasive migration. Amphoterin binds to RAGE (receptor of advanced glycation end products), an immunoglubulin superfamily member related to N-CAM (neural cell adhesion molecule), that communicates with the GTPases Cdc42 and Rac to regulate cell motility. In addition, ligation of RAGE by amphoterin activates NF-kappaB to regulate transcription.

Animals↗
PubMed2000

Characterization of a novel Vibrio parahaemolyticus phage, KVP241, and its relatives frequently isolated from seawater.

A vibriophage, KVP241, and six of its relatives were isolated independently from seawater using Vibrio parahaemolyticus as the host. All of the phages had the same morphology (a hexagonal head and a tail with a contractile sheath) and the same host range (specific for some V. parahaemolyticus strains). DNA-DNA hybridization experiments elucidated that their genomes are highly homologous to each other. Analyses of amino acid sequences of putative major capsid proteins indicated that KVP241 may be weakly related to T4-type phages having a more elongated head.

Amino Acid Sequence↗
PubMed2000

Altered postnatal expression of insulin-like growth factor-I (IGF-I) and type X collagen preceding the Perthes' disease-like lesion of a rat model.

The spontaneously hypertensive rat (SHR) is a widely used animal model for the study of hypertension. It also exhibits an osteonecrosis of the femoral epiphysis that resembles the clinical features of Perthes' disease in humans. In this rat model, occlusion of the epiphyseal vessels occurs as a result of a breakdown of the mechanically vulnerable epiphysis. The postnatal development of the epiphysis recapitulates the serial events of the endochondral ossification (i.e., cartilage formation), chondrocyte hypertrophy, cartilage mineralization, vascularization, and introduction of osteoblasts that form the secondary ossification center within the epiphysis. In the present study, a detailed radiographic and histological analysis demonstrates that the osteonecrosis is preceded by a disturbance of the cartilage mineralization and a disturbance of the ossification, despite a normal hypertrophy of the epiphyseal cartilage. These observations suggest that abnormal development of the femoral epiphysis occurs much earlier than manifestation of the osteonecrosis. They lead us to a hypothesis that yet-unclarified transitional events between the cartilage hypertrophy and the cartilage mineralization may be affected in SHRs. Type X collagen is a developmentally regulated matrix molecule that is implicated in the mineralization of the hypertrophied chondrocytes. We show that the expression of type X collagen during epiphyseal ossification is delayed in SHRs (vs. normal controls), suggesting disturbed growth and/or differentiation of the epiphyseal chondrocytes. Postnatal growth and differentiation of the chondrocytes at least partly depend on insulin-like growth factor-I (IGF-I), which is produced by the chondrocytes in response to the pituitary growth hormone and stimulates cartilage growth in situ. The present study demonstrates an altered IGF-I expression during early postnatal life in SHRs and suggests that the altered IGF-I expression as well as the following delay in upregulation of type X collagen may cause the mechanical vulnerability of the femoral epiphysis in SHRs.

Animals↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 23). A comparative 2- and 4-week repeated oral dose testicular toxicity study of boric acid in rats.

To assess the validity and limitations of 2-week repeated daily dosing to detect toxic effects on male reproductive organs in rodents, a comparative 2- and 4-week oral repeated dosing study of boric acid, a known testicular toxicant, was given to 6- or 8-week-old Crj:Wistar rats at daily levels of 0, 125, 250 and 500 mg/kg. The ages of the rats were selected so that they were all sacrificed at 10 weeks of age. The testes and epididymides were weighed at necropsy; histopathological specimens were prepared in a routine manner and stained with H&E or PAS-H. In addition, the sperm number and motility rates were evaluated. There were no boric acid-induced effects on reproductive organ weights and on gross behavior/appearance in any groups in either the 2- or 4-week studies. The sperm number and motility rate were not decreased in any group after 2 weeks, while both decreased in the 250 and 500 mg/kg groups after 4 weeks. Histopathologically, as evidence of toxicity at the early stage of boric acid exposure, retention of step 19 spermatids of stages IX-XI was observed in the testes of almost all rats treated with 500 mg/kg after both 2 weeks and 4 weeks. Degenerative/necrotic germ cells and multinucleated giant cell formation were observed in 2 weeks, though to a lesser extent than in 4 weeks. On stage analysis of germinal cells in 2 weeks, spermatogonia and spermatids of stage VII were found to be decreased, and pachytene spermatocytes of stage X were increased. In conclusion, the results indicate that if the selection of doses is appropriate, testicular toxicity of boric acid can be detected even after only 2 weeks of repeated daily oral treatment.

Administration, Oral↗
PubMed2000

[Comparison of whole-body MR imaging and bone scintigraphy in the detection of bone metastases from breast cancer].

The aim of this study was to investigate the usefulness of whole body MR imaging (WB-MRI) in the detection of bone metastases from breast cancer and to compare the results with those from bone scintigraphy. In 21 patients with suspected bone metastasis from breast cancer, both bone scintigraphy and WB-MRI were performed. With WB-MRI, coronal images were obtained using a body coil in an FOV of 48 cm, and sequences of fast short TI inversion recovery (STIR) and gadolinium-enhanced fast spoiled GRASS (SPGR) were used in three parts: from the head to the thorax, the abdomen to the pelvis, and the lower extremities. Of the total 105 metastatic bone lesions, 65 (61.9%) were detected by bone scintigraphy, 98 (93.3%) by fast STIR, and 74 (70.5%) by fast SPGR. Thus, the detection of bone metastases by WB-MRI was excellent. However, detectability in the ribs was lower for WB-MRI than for bone scintigraphy. Contrast-enhanced MRI was useful in the differentiation of osteosclerotic lesions, in which high signal intensity is rare, pleural effusion, which has high signal intensity on STIR, and bone metastatic lesions. In conclusion, WB-MRI showed high reliability in the detection of bone metastatic lesions from breast cancer.

Adult↗
PubMed2000

[Neoadjuvant chemotherapy for advanced gastric cancer using FLEP therapy].

Combination chemotherapy with 5-FU, LV, ETP and CDDP (FLEP) for advanced gastric cancer uses a combination of regional and systemic delivery for the control of both local and disseminated disease in the intra- and extra-abdominal regions. We performed this regimen as neoadjuvant chemotherapy (NAC). Fifteen patients with unresectable primary advanced gastric cancer underwent FLEP. The treatment regimen was 5-FU at 370 mg/m2, LV at 30 mg/body (days 1 to 5, i.v. 24 h) and ETP and CDDP each at 70 mg/m2 (days 7 and 21, ia 2 h). This regimen was repeated every four weeks. The overall response rate was 46.7% (7/15), and the 50% and median survival times were 11.43 and 12.35 months, respectively. The adverse events were Grade 3 leukocytopenia, Grade 3 thrombocytopenia, and Grade 3 stomatitis in 20.0%, 13.3%, and 6.7% of the patients, respectively. The 50% and median survival time overall were 11.43 and 12.35 months, respectively. Of the 15 NAC patients, curability B patients showed a statistically higher survival rate than curability C and unresected patients. In conclusion, FLEP was effective for unresectable advanced gastric cancer.

Adult↗
PubMed2000

Occurrence of amphoterin (HMG1) as an endogenous protein of human platelets that is exported to the cell surface upon platelet activation.

Amphoterin (HMG1) is a 30-kD heparin-binding protein which is functionally associated with the outgrowth of cytoplasmic processes in developing neurones. Amphoterin has been shown to mediate adhesive and proteolytic interactions at the leading edge of motile cells. Recently it was shown that inhibition of amphoterin interactions with its cell surface receptor (RAGE) suppresses tumour growth and metastasis. In this work we have identified amphoterin polypeptide and its mRNA in human platelets. Amphoterin had a cytoplasmic localisation in resting platelets according to subcellular fractionation studies and immunogold electronmicroscopy. After platelet activation, part of amphoterin was associated with the external surface of plasma membrane. Externalisation of amphoterin during platelet activation was also detected in immunofluorescence studies. Amphoterin was detectable in human serum (0.2 ng/ml) but not in plasma. Resting platelets treated with PGI2 and forskolin bound to immobilised recombinant amphoterin independently of divalent cations. The binding induced a spicular morphology in platelets, and was effectively inhibited by heparin. Amphoterin-binding protein components on the platelet surface were not identified, but amphoterin bound to phosphatidylserine and sulfatide in lipid binding assays. Our results suggest that amphoterin is an endogenous protein in human platelets, which is exported to the cell surface during platelet activation. Interaction of amphoterin with the platelet surface may be mediated by sulfoglycolipids and phospholipids.

Blood Platelets↗
PubMed2000

Na+/H+ exchange inhibitor reduces vascular injury caused by ischemia-reperfusion in the rat hind limb.

This study was designed to evaluate the effects of an Na+/H+ exchange inhibitor, SM-20550, on ischemia-reperfusion injury in the skeletal muscle. Male Sprague-Dawley rats were exposed to ischemia and reperfusion by clamping and releasing clamps both at the abdominal aorta and the bilateral femoral arteries. Rats were divided into three groups; the sham, the SM-20550 treated (SM), and the untreated control (Control) groups. In the SM and control groups, rats were exposed to 5-hr ischemia and 5-hr reperfusion. In the sham group, vessel isolation only was performed. SM-20550 (2.8 mg/kg/hr) in the SM group or vehicle in the sham and control group was continuously administered during ischemia and reperfusion periods. The wall thickness of the vessels were significantly (p<0.01) decreased in the control group than any other group. The internal diameter was significantly (p<0.01) higher in the control and SM group than in the sham group. The wall thickness/internal diameter ratio was significantly (p<0.05) lower in the control group than in the SM group. Thus, an Na+/H+ exchange inhibitor, SM-20550, ameliorated the morphological change due to ischemia reperfusion. These findings provide a clue into the mechanism of ischemia reperfusion injury.

Animals↗
PubMed1999

Effects of quinine on three different types of potassium currents in bullfrog sympathetic neurons.

Whole-cell/voltage-clamp recordings were made from dissociated bullfrog sympathetic neurons to examine the sensitivity of potassium currents to a potassium channel blocker quinine (1-500 microM). Among three currents tested, a rapidly inactivating A-type current (I(A)) was the most sensitive to the block by quinine (IC50 approximately 22 microM). A non-inactivating M-type current (I(M)) was the least sensitive (IC50 approximately 445 microM), and the sensitivity of a slowly inactivating delayed rectifier-type current (I(K)) was in between (IC50 approximately 115 microM). Results suggest that the ability of quinine to block different types of potassium currents such as I(A) and I(M) with significantly different IC50 values would be of help for the potassium channel pharmacology in amphibian autonomic ganglion cells.

Animals↗
PubMed1999

Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig.

The effects of TAK-637 ((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8, 9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2 , 1-g][1,7]naphthyridine-6,13-dione), a novel tachykinin NK(1) receptor antagonist, on the micturition reflex in guinea pigs were studied in comparison with those of anti-pollakiuria agents. Cystometry was performed under urethane anesthesia. TAK-637 increased the volume threshold with a minimum effective dose of 0.03 mg/kg, i.v. without affecting voiding pressure. Oxybutynin, tolterodine, propiverine and inaperisone also increased the volume threshold in urethane-anesthetized guinea pigs, but they decreased voiding pressure, although the effect of propiverine was not statistically significant. A structurally unique tachykinin NK(1) receptor antagonist, (+/-)-CP-99,994 ((+/-)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), increased the volume threshold with a minimum effective dose of 0.3 mg/kg, i.v. TAK-637 increased the volume threshold with a minimum effective dose of 0.01 mg/kg, p.o. in unanesthetized guinea pigs. These results indicate that TAK-637 may be useful as pharmacotherapy for detrusor overactivity without decreasing voiding pressure or causing voiding difficulties.

Animals↗
PubMed1999

A Na+-H+ exchange inhibitor (SM-20550) protects from microvascular deterioration and myocardial injury after reperfusion.

Na+-H+ exchange inhibitors may reduce myocardial damage after reperfusion. However, their effects on microvascular deterioration are not known. We examined the potency of a novel Na+-H+ exchange inhibitor, SM-20550 [ N-(Aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate], and its effects on microvascular damage after reperfusion. In an in vitro study, the Na+-H+ exchange inhibiting activity of SM-20550 was about 10 times greater than that of ethylisopropyl amiloride. In in vivo experiments, we occluded the left circumflex coronary artery in 29 dogs for 2 h and then reperfused for 5 h. SM-20550 was administered either before ischemia (n = 11) or before reperfusion (n = 7). Another 11 dogs served as controls. We found that SM-20550 not only improved coronary vasodilator responses to acetylcholine and adenosine after reperfusion, but also reduced infarct size (P < 0.01). Intramyocardial bleeding, which should reflect microvascular damage, was not found in dogs with SM-20550 treatment. Infarct size was correlated inversely with collateral blood flow in control (both, P < 0.01) but not in SM-20550-treated animals. Furthermore, SM-20550 significantly suppressed ventricular fibrillation during both ischemia and reperfusion. These results suggest that protective effects of Na+-H+ exchange inhibitors on reperfused myocardium are due at least in part to microvascular protection.

Acetylcholine↗
PubMed1999

Inhibitory effect of a self-derived peptide on glucosyltransferase of Streptococcus mutans. Possible novel anticaries measures.

Glucosyltransferase (GTF) plays an important role in the development of dental caries. We examined the possible presence of self-inhibitory segments within the enzyme molecule for the purpose of developing anticaries measures through GTF inhibition. Twenty-two synthetic peptides derived from various regions presumably responsible for insoluble-glucan synthesis were studied with respect to their effects on catalytic activity. One of them, which is identical in amino acid sequence to residues 1176-1194, significantly and specifically inhibited both sucrose hydrolysis and glucosyl transfer to glucan by GTF-I. Double-reciprocal analysis revealed that the inhibition is noncompetitive. Scramble peptides, composed of the identical amino acids in randomized sequence, had no effect on GTF-I activity. Furthermore, the peptide is tightly bound to the enzyme once complexed, even in the presence of sodium dodecyl sulfate (SDS). Kinetic analysis using an optical evanescent resonant mirror cuvette system demonstrated that the enzyme-peptide interaction was biphasic. These results indicate that the peptide directly interacts with the enzyme with high affinity and inhibits its activity in a sequence-specific manner. This peptide itself could possibly be an effective agent for prevention of dental caries, although its effectiveness may be improved by further modification.

Amino Acid Sequence↗