Biomedical subjects

T Ishida

Publications and source records attributed to T Ishida.

At least 253 records · Page 14Linked to original sources

PubMed1999

TEMPO radicals showing magnetic interactions. II. 4-(Benzylideneamino)-TEMPO and related compounds.

X-ray crystal structure analyses were performed on 4-(Ar-methyleneamino)-TEMPO radicals at room temperature (TEMPO = 2,2,6,6-tetramethylpiperidyl-1-oxyl): Ar = Ph [4-(benzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl], 4-MeS-Ph [2,2,6,6-tetramethyl-4-(4-methylthiobenzylideneamino)piperidyl-1-oxyl], 4-Me-Ph [4-(4-methylbenzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl], 4-PhO-Ph [2,2,6,6-tetramethyl-4-(4-phenoxybenzylideneamino)piperidyl-1-oxyl], 4-MeSO(2)-Ph [2,2,6,6-tetramethyl-4-(4-methylsulfonylbenzylideneamino)piperidyl-1-oxyl], 3-Py [2,2,6,6-tetramethyl-4-(3-pyridylmethylideneamino)piperidyl-1-oxyl] and 2-Naph [2,2,6,6-tetramethyl-4-(2-naphthylideneamino)piperidyl-1-oxyl]. Structures of Ph and 4-Me-Ph derivatives were also determined at 100 K. Some of these crystals have been revealed to show intermolecular ferromagnetic interactions at an extremely low temperature. Structural features of crystals of Ph, 4-MeS-Ph and 3-Py derivatives, which show ferromagnetic interactions, are very similar to each other. In these crystals, O atoms are arranged to form a sheet. The ferromagnetic interactions are considered to be transferred through O.H van der Waals' interactions of the beta-H atoms of the neighboring TEMPO rings within the sheet. Between O.O sheets, the aryl groups are arranged in a herringbone manner. The crystal structure of the 4-Me-Ph derivative, which shows an antiferromagnetic interaction, is also pseudo-isostructural with those of Ph, 4-MeS-Ph and 3-Py derivatives, while the arrangement of the aryl groups is different. The packing mode of the crystals of the 4-MeSO(2)-Ph derivative, of which the Weiss constant straight theta is nearly zero, is very different from those of the other derivatives showing magnetic interactions. The fact that the crystal structure of the paramagnetic 4-MeSO(2)-Ph derivative does not show the O.O sheet structure accompanying the O.beta-H interactions indicates that the intermolecular ferromagnetic interactions through beta-H atoms within the O.O sheet are important for these TEMPO radical crystals.

Journal Article↗

PubMed1999

A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs.

We have developed a method for producing sterically stabilized immunoliposomal drugs (SIL) readily applicable to a 'mix and match' combinatorial approach for the simple manufacture of a variety of ligand-targeted liposomal drugs. Ligands coupled to the terminus of polyethylene glycol (PEG) in micelles formed from PEG-lipid derivatives (mPEG2000-DSPE) could be transferred into preformed, drug-containing liposomes from the micelles in a temperature- and time-dependent manner. Antibody densities up to 100 microg antibody/micromol of phospholipid, and up to 3 mol% of mPEG2000-DSPE, could be simultaneously transferred from the ligand-coupled micelles into the liposomal outer monolayer with negligible drug leakage from liposomes during transfer and good stability in human plasma. Transfer of anti-CD19 into SIL resulted in a three-fold increase in binding of these liposomes to CD19+ human B cell lymphoma cells.

Antibodies↗

PubMed1999

A product of growth arrest-specific gene 6 modulates scavenger receptor expression in human vascular smooth muscle cells.

Although Gas6 is identified as a growth factor for vascular smooth muscle cells (VSMCs), its roles in these cells have not been clearly elucidated. To examine the role of Gas6 in atherosclerosis, we examined the effects of Gas6 on scavenger receptor family expression in VSMCs. Scavenger receptor class A, one of the scavenger receptor family members, was upregulated in VSMCs by Gas6. Furthermore, the atherogenic lipoprotein, oxidized LDL, induced Gas6 production in these cells. These results indicate that Gas6 plays an important role in foam cell formation in human VSMCs.

Cell Line↗

PubMed1999

Shear stress-mediated extracellular signal-regulated kinase activation is regulated by sodium in endothelial cells. Potential role for a voltage-dependent sodium channel.

Fluid shear stress is an important regulator of endothelial cell (EC) function. To determine whether mechanosensitive ion channels participate in the EC response to shear stress, we characterized the role of ion transport in shear stress-mediated extracellular signal-regulated kinase (ERK1/2) stimulation. Replacement of all extracellular Na+ with either N-methyl-D-glucamine or choline chloride increased the ERK1/2 stimulation in response to shear stress by 1.89 +/- 0.1-fold. The Na+ effect was concentration-dependent (maximal effect, </=12.5 mM) and was specific for shear stress-mediated ERK1/2 activation as epidermal growth factor-stimulated ERK1/2 activation was unaffected by removal of extracellular Na+. Shear stress-mediated ERK1/2 activation was potentiated by the voltage-gated sodium channel antagonist, tetrodotoxin (100 nM), to a magnitude similar to that achieved with extracellular Na+ withdrawal. Transfection of Chinese hamster ovary cells with a rat brain type IIa voltage-gated sodium channel completely inhibited shear stress-mediated ERK1/2 activation in these cells. Inhibition was reversed by performing the experiment in sodium-free buffer or by including tetrodotoxin in the buffer. Western blotting of bovine and human EC lysates with SP19 antibody detected a 250-kDa protein consistent with the voltage-gated sodium channel. Degenerate polymerase chain reaction of cDNA from primary human EC yielded transcripts whose sequences were identical to the sodium channel SCN4a and SCN8a alpha subunit genes. These results indicate that shear stress-mediated ERK1/2 activation is regulated by extracellular sodium and demonstrate that ion transport via Na+ channels modulates EC responses to shear stress.

Animals↗

PubMed1999

Thiazolidinedione inhibits the production of monocyte chemoattractant protein-1 in cytokine-treated human vascular endothelial cells.

The chemokine monocyte chemoattractant protein-1 is a potent chemoattractant for monocytes. Monocyte chemoattractant protein-1 is produced by vascular endothelial cells during inflammatory diseases such as atherosclerosis. In this study, we examined the effects of a thiazolidinedione on monocyte chemoattractant protein-1 expression in human vascular endothelial cells. In human vascular endothelial cells, interleukin-1beta and tumor necrosis factor-alpha induced endogenous monocyte chemoattractant protein-1 protein secretion, mRNA expression and promoter activity. The thiazolidinedione inhibited these effects. In summary, our results indicated that the suppression of the expression of monocyte chemoattractant protein-1 can be accomplished by thiazolidinedione treatment, raising the possibility that thiazolidinedione may be of therapeutic value in the treatment of diseases such as atherosclerosis.

Chemokine CCL2↗

PubMed1999

Multiple gigantic arteriovenous malformations with destruction of lumbar vertebral bodies. A case report.

STUDY DESIGN: This case report describes a patient with massive intramuscular and paravertebral arteriovenous malformations with destruction of vertebral bodies. OBJECTIVES: To demonstrate successful interbody fusion of the involved vertebral bodies after embolization for arteriovenous malformation. SUMMARY OF BACKGROUND DATA: Although arteriovenous malformations in the spinal cord are well documented in the literature, arteriovenous malformation in the paravertebral and iliopsoas muscles with destruction of vertebral bodies is an extremely rare clinical condition. METHODS: After careful investigation with angiography, the arteriovenous malformations were managed with embolization, and the scoliosis caused by the collapsed vertebral bodies was managed surgically by anterior spinal fusion with segmental spinal instrumentation. RESULTS: The patient's scoliosis caused by vertebral collapse was corrected by surgery, and good alignment of the lumbar spine was achieved. The preoperation pain had subsided completely by follow-up assessment 1 year and 10 months after fusion. However, the arteriovenous malformations still remained. Careful observation should be maintained continuously in the coming days. CONCLUSION: In arteriovenous malformations with destruction of the vertebral bodies, embolization and spinal fusion with segmental instrumentation may be necessary to relieve pain and prevent the progression of spinal deformity. Arteriovenous malformation should be considered in the diagnostic evaluation of a patient who has experienced vertebral collapse with no inflammatory signs.

Adult↗

PubMed1999

Thiazolidinedione inhibits production of RANTES in a cytokine-treated human lung epithelial cell line.

The chemokine RANTES is a potent chemoattractant for eosinophils. RANTES is produced by lung epithelial cells during eosinophil-rich inflammatory diseases such as asthma. In this study, we examined the effects of thiazolidinediones (TZD) on RANTES expression in a human lung epithelial cell line, A549. In A549 cells, interleukin-1beta and tumor necrosis factor-alpha induced endogenous RANTES protein secretion, mRNA expression, and promoter activity. The TZD inhibited these effects. Our data indicate that the suppression of the expression of RANTES can be accomplished by TZD treatment, raising the possibility that TZD might be of therapeutic value in diseases such as asthma.

Cell Line↗

PubMed1999

Microwave Dielectric Relaxation of Bound Water to Silica, Alumina, and Silica-Alumina Gel Suspensions.

By the use of a time domain reflectomery method, dielectric measurements were carried out on silica, alumina, and silica-alumina gel suspensions (five types with composition varying between 0.3 < Si/Al atomic ratio <0.8) in the frequency range of 100 kHz to 20 GHz. For all the gels, a relaxation peak due to bound water was observed. This peak locates at around 1-10 MHz, indicating that the peak is a decade or 10 decades lower than those of biological polymers such as an aqueous DNA solution. The silica and alumina gels have a different bound water structure, judging from the fact that the peaks are different in their locations and shapes between the two gels. The silica-alumina gels exhibit two different peaks other than the peak of bulk water. The sum of the relaxation strength on the two peaks is proportional to the monolayer capacity obtained from water vapor isotherms. The shape of the one peak holds that of the silica gel, whereas the other retains that of alumina gel, and furthermore the ratio of the relaxation strength on the former peak to that on the latter depends on Si/Al atomic ratio. It is suggested that both peaks are caused by the orientation of bound water molecules. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Effects of pH on Dielectric Relaxation of Montmorillonite, Allophane, and Imogolite Suspensions.

Dielectric measurements were performed on montmorillonite, allophane, and imogolite suspensions under various pH conditions, using time domain reflectometry over the frequency range 10 kHz-20 GHz. A dielectric relaxation peak due to bound water could be observed for all the clays. Allophane has two peaks, indicating that its peaks are very similar to those of silica-alumina gels. Although imogolite has a similar chemical composition, only one peak was found. The relaxation strength of montmorillonite is greater than that of the other two clays. For all the clays, the relaxation strength depended on the pH. A change in the relaxation strength according to a change in pH is explained in terms of the different network structures of the clay particles. It is suggested that bound water influences the network structure formation. In montmorillonite, a great relaxation process detected at low frequency is caused by surface polarization of counterions. The change in measure of the structural unit with the pH, identified from Schwartz's theory, has a tendency similar to that postulated by other experimental techniques, and surface charge densities identified are close to those estimated from CEC. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

TEMPO radicals showing magnetic interactions. I. 4-(4-Halobenzylideneamino)TEMPO and related compounds.

X-ray crystal structure analyses of the 4-(4-halobenzylideneamino)TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidyl-1-oxyl) radicals 4-(4-fluorobenzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl, 4-(4-chlorobenzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl, 4-(4-bromobenzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl and 4-(4-iodobenzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl, and other 4-Ar-CH=N-TEMPO [Ar = 4-Ph-Ph, 2,2,6,6-tetramethyl-4-(4-phenylbenzylideneamino)piperidyl-1-oxyl, 4-Py, 2,2,6,6-tetramethyl-4-(4-pyridylmethylideneamino)piperidyl-1-oxyl, and 3,5-diCl-Ph, 4-(3,5-dichlorobenzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl] radicals have been performed at room temperature. Some of these radicals show intermolecular ferromagnetic interactions at extremely low temperatures. X-ray analysis revealed that crystals of the 4-I-Ph derivative showed two modifications [(a) and (b)]; measurements of the magnetic properties of these crystals showed a ferromagnetic transition at an extremely low temperature for modification (a) and an antiferromagnetic interaction for modification (b). The structural features of these TEMPO radical crystals can be classified into three groups: (i) the crystal structures of the 4-Cl-Ph, 4-I-Ph(a) and 4-Ph-Ph derivatives, which show a ferromagnetic transition; (ii) the structures of the 4-Br-Ph and 4-Py derivatives, which show a ferromagnetic interaction (straight theta > 0); (iii) miscellaneous: the antiferromagnetic 4-F-Ph and 4-I-Ph(b) derivatives (straight theta < 0) and the ferromagnetic 3,5-diCl-Ph (straight theta > 0) derivative. Sheet-like arrangements of O atoms and intra-sheet interactions through the CH(2) or CH(3) groups of the TEMPO rings are related to the mechanisms of the ferromagnetic interactions.

Journal Article↗

PubMed1999

An archetypical extradiol-cleaving catecholic dioxygenase: the crystal structure of catechol 2,3-dioxygenase (metapyrocatechase) from Ppseudomonas putida mt-2.

BACKGROUND: Catechol dioxygenases catalyze the ring cleavage of catechol and its derivatives in either an intradiol or extradiol manner. These enzymes have a key role in the degradation of aromatic molecules in the environment by soil bacteria. Catechol 2, 3-dioxygenase catalyzes the incorporation of dioxygen into catechol and the extradiol ring cleavage to form 2-hydroxymuconate semialdehyde. Catechol 2,3-dioxygenase (metapyrocatechase, MPC) from Pseudomonas putida mt-2 was the first extradiol dioxygenase to be obtained in a pure form and has been studied extensively. The lack of an MPC structure has hampered the understanding of the general mechanism of extradiol dioxygenases. RESULTS: The three-dimensional structure of MPC has been determined at 2.8 A resolution by the multiple isomorphous replacement method. The enzyme is a homotetramer with each subunit folded into two similar domains. The structure of the MPC subunit resembles that of 2,3-dihydroxybiphenyl 1,2-dioxygenase, although there is low amino acid sequence identity between these enzymes. The active-site structure reveals a distorted tetrahedral Fe(II) site with three endogenous ligands (His153, His214 and Glu265), and an additional molecule that is most probably acetone. CONCLUSIONS: The present structure of MPC, combined with those of two 2,3-dihydroxybiphenyl 1,2-dioxygenases, reveals a conserved core region of the active site comprising three Fe(II) ligands (His153, His214 and Glu265), one tyrosine (Tyr255) and two histidine (His199 and His246) residues. The results suggest that extradiol dioxygenases employ a common mechanism to recognize the catechol ring moiety of various substrates and to activate dioxygen. One of the conserved histidine residues (His199) seems to have important roles in the catalytic cycle.

Amino Acid Sequence↗

PubMed1999

New DNA polymorphisms of human MMH/OGG1 gene: prevalence of one polymorphism among lung-adenocarcinoma patients in Japanese.

MMH/OGG1 is an 8-hydroxyguanine-specific DNA glycosylase/AP-lyase, one of the mutator enzymes for the excision repair of 8-hydroxyguanine. DNA polymorphisms in human MMH/OGG1 gene were newly identified and analyzed to examine a possible association with lung-cancer risk by a population-based study. Polymorphic allele 3 in hMMH/OGG1 exon 1 was significantly prevalent among Japanese patients with adenocarcinoma of the lung [odds ratio (OR): 3.152, 95% confidence interval (CI): 1.266-7.845], indicating that the excision repair of 8-hydroxyguanine may play a role in predisposition to lung cancer.

Adenocarcinoma↗

PubMed1999

Accelerated rejection of Fas ligand-expressing heart grafts.

The Fas/Fas ligand (FasL) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. Recently, there has been renewed interest in immune privilege, as it was shown that two privileged sites (the eye and testes) constitutively express FasL, which kills lymphoid cells that invade these areas. We have established murine FasL-transgenic mice (B6) under the control of the cardiac alpha-myosin heavy chain promotor, and transplanted FasL-expressing F1(B6 x C3H/HeJ) heart grafts into syngeneic (F1) and allogeneic (C3H/HeJ) recipients. FasL-expressing F1 heart allografts placed in C3H/HeJ recipients as well as FasL-expressing F1 isografts placed in nontransgenic and FasL-transgenic F1 were more rapidly rejected, and their survival was much shorter than that of nontransgenic control F1 allografts placed in C3H/HeJ. Native control and FasL-expressing hearts looked normal in mice up to 8 wk of age on hematoxylin-eosin staining. Control heart allografts undergoing ordinally acute rejection showed moderate focal lymphocyte infiltrates, while FasL-expressing F1 allografts and isografts showed massive hemorrhage, edema, and massive neutrophil infiltration as early as 1 day after transplantation. In conclusion, FasL expression and surgical procedure (ischemia/reperfusion) were synergistic in the induction of accelerated heart graft rejection, while allogenicity was not necessary. It may be necessary to find ways of controlling neutrophilic reaction/apoptosis in infiltrating lymphocytes to use FasL in clinical organ transplantation.

Animals↗

PubMed1999

Structural basis of inhibition of cysteine proteases by E-64 and its derivatives.

This paper focuses on the inhibitory mechanism of E-64 and its derivatives (epoxysuccinyl-based inhibitors) with some cysteine proteases, based on the binding modes observed in the x-ray crystal structures of their enzyme-inhibitor complexes. E-64 is a potent irreversible inhibitor against general cysteine proteases, and its binding modes with papain, actinidin, cathepsin L, and cathepsin K have been reviewed at the atomic level. E-64 interacts with the Sn subsites of cysteine proteases. Although the Sn-Pn (n = 1-3) interactions of the inhibitor with the main chains of the active site residues are similar in respective complexes, the significant difference is observed in the side-chain interactions of S2-P2 and S3-P3 pairs because of different residues constituting the respective subsites. E-64-c and CA074 are representative derivatives developed from E-64 as a clinical usable and a cathepsin B-specific inhibitors, respectively. In contrast with similar binding/inhibitory modes of E-64-c and E-64 for cysteine proteases, the inhibitory mechanism of cathepsin B-specific CA074 results from the binding to the Sn' subsite.

Binding Sites↗

PubMed1999

Conformational change of ascidiacyclamide caused by asymmetric modification for an isoleucine residue: structural analyses of [Gly], [Leu], and [Phe]ascidiacyclamides by x-ray diffraction and NMR spectroscopy.

Ascidiacyclamide, a cytotoxic cyclic peptide from tunicate, is composed of unusual amino acids and has a repeated sequence, c[-thiazole-D-Val-oxazoline-L-Ile-]2 ([Ile]ASC). The symmetric chemical structure has been assumed to be correlated with the cytotoxicity, and it is reasonable to consider that the disturbance of its structure from the C2 symmetry results in the changes of conformation and activity. In order to quantitatively estimate the molecular conformation-activity relationship, an isoleucine residue was substituted by Gly, Leu, or Phe to disturb the C2 symmetry. The conformations of three derivatives were examined by nmr spectroscopy and the crystal structure of [Leu]ASC was also analyzed by x-ray diffraction method. The 1H-nmr experiments and the constrained molecular dynamics simulations showed the twisted "figure 8" conformers for [Gly] and [Phe]ASCs and the "square" conformer for [Leu]ASC in the DMSO solution. The x-ray crystal analysis of [Leu]ASC also revealed the square form similar to the solution structure. On the other hand, their cytotoxic activities were measured using L1210 leukemia cells and were related with the bulkiness and/or hydrophobicity of the side chain of the substituted amino acid; [Phe] > or = [Ile] > [Leu] >> [Gly]ASCs. As an attempt to consider the correlation between the activity and conformer, the accessible surface area (ASA) was calculated for each derivative to estimate the size or bulkiness of its conformation. Although the ASAs of nmr structures were not directly related to the type of conformer (figure 8 or square form), it was an important probe to consider the cytotoxicity of each derivative.

Amino Acid Substitution↗

PubMed1999

Gas-phase oxidation of nitric oxide: chemical kinetics and rate constant.

Inhaled nitric oxide (NO) is gaining popularity as a selective pulmonary vasodilator. Because of the potential toxicity of NO and its oxidizing product nitrogen dioxide (NO2), any system for the delivery of inhaled NO must aim at predictable and reproducible levels of NO and at as low concentrations of NO2 as possible. This review describes the chemical kinetics and rate constant values k for the reaction 2NO + O2 = 2NO2. This reaction has been well established as a third-order homogeneous reaction. Published data support two equally plausible two-step mechanisms for the reaction between NO and O2 over a wide range of temperature and pressure. The Arrhenius equation k (L2 x mol(-2) x s(-1)) = 1.2 x 10(3) e(530/T) (=1.2 x 10(3) x 10(230/T)) gives the best fit to the experimental values of the rate constant thus far reported in a temperature range of 273 to 600 K. Using the reaction mechanism and the rate constant k, one can make reliable predictions about NO2 formation in any set of NO inhalation therapy conditions. It is also pointed out that NO3, the intermediate of one of the two mechanisms, deserves serious attention in NO inhalation therapy.

Administration, Inhalation↗

PubMed1999

Immunohistochemical evidence that P-glycoprotein in non-small cell lung cancers is associated with shorter survival.

The expression of P-glycoprotein in 159 non-small cell lung cancers was immunohistochemically examined using a monoclonal antibody (MoAb C219). A total of 93 (60%) cancers were found to be positive for P-glycoprotein. The 5-year survival rates of patients with P-glycoprotein (P-gp+) and those without P-glycoprotein (P-gp-) were 47.6% and 73.6%, respectively (P < 0.05). According to a univariate analysis, P-gp+ was associated with a poor prognosis for males, those with stage I cancer, those who underwent complete resection, and those with adenocarcinoma or squamous cell carcinoma. A multivariate study using the Cox regression analysis indicated that the expression of P-glycoprotein is useful for predicting the prognosis. Among 24 patients who underwent complete resection and postoperative adjuvant chemotherapy, 18 were P-gp+ and the remaining 6 were P-gp-. Of the 18 with P-gp+ cancer, 11 relapsed and 9 died from tumor-related causes, while the other 7 remain free from tumor recurrence; however, all with P-gp- cancer are alive without recurrence. These observations suggest a bias toward a shorter survival for patients with P-gp+ cancer because P-glycoprotein may be associated with chemoresistance. Thus, detection of the expression of P-glycoprotein will aid in planning appropriate adjuvant chemotherapy for patients with non-small cell lung cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Serum levels of NCC-ST-439 in Dukes' C colorectal cancer patients: a preliminary report.

The serum levels of NCC-ST-439, a monoclonal antibody raised against a human gastric cancer xenograft (ST-439), were determined in 28 patients who had undergone a curative resection of Dukes' C colorectal carcinoma. The preoperative mean levels of NCC-ST-439 were 14.4 U/ml (range 1.0-280.0) and positive (>7.0 U/ml for women under the age of 49, >4.5 U/ml for women over the age of 50, and men at any age) in 6 patients. Recurrence of the disease after a curative resection was encountered in 7 patients (serum NCC-ST-439 was positive in 5 and negative in 2 patients). The positive serum NCC-ST-439 was associated with a significantly poorer disease-free survival time (P < 0.0001). In patients who had undergone a curative resection of Dukes' C colorectal cancer, the sensitivity of NCC-ST-439 in the sera for recurrent disease was 71.4% and specificity was 95.2%. The results of a preliminary study suggested NCC-ST-439 to be a novel marker for predicting recurrence after a curative resection of Dukes' C colorectal carcinoma.

Adolescent↗