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Biomedical subjects

Kenji Kanazawa

Publications and source records attributed to Kenji Kanazawa.

13 recordsLinked to original sources
PubMed2006

Sumatriptan provokes coronary artery spasm in patients with variant angina: possible involvement of serotonin 1B receptor.

BACKGROUND: Serotonin (5HT) can induce coronary artery spasm (CAS) in patients with variant angina (VA). We have previously reported that 5HT(1B) and 5HT(2A) receptors gene were expressed in human coronary arterial smooth muscle cells and that isolated coronary artery from a patient with VA showed the supersensitivity to sumatriptan (SMT), a 5HT(1B/1D) receptor agonist. The aim of the present study was to determine whether SMT can provoke CAS directly or indirectly through platelet aggregation in patients with VA. METHODS: We evaluated the effects of intracoronary infusion of graded concentrations of SMT on coronary arteries in 9 patients, including 5 documented VA and 4 participants with atypical chest pain as control. RESULTS: SMT provoked CAS in all patients with VA. SMT could not induce CAS in control. SMT (10(-4) M) caused significant contractions (%diameter of baseline; median [interquartile range], 0 [0-18.4]% in VA, as compared with control (proximal segments; 92.6 [77.9-118.9]%, p<0.05 vs. VA, distal segments; 92.9 [65.3-158.5]%, p<0.01 vs. VA). In control, minor dilation occurred at SMT concentration up to 10(-5) M. SMT could induce in vitro platelet aggregation neither in healthy subjects nor in patients with VA. CONCLUSIONS: These findings suggest that activation of 5HT(1B) receptor by SMT can induce CAS directly in patients with VA without platelet activation. This is the first report directly demonstrating the effect of 5HT(1B) receptor activation on human coronary arteries in vivo.

Adult↗
PubMed2005

Low-barrier hydrogen bond between phosphate and the amide group in phosphopeptide.

As the conversion between the monoionic (1) and diionic (2) form of the phosphate occurs, the phosphorylated peptides or proteins can not only cause the formation of a hydrogen bond between the phosphate group and the amide group but also change the strength of the hydrogen bond to form low-barrier hydrogen bonds (LBHBs). This reversible protonation of the phosphate group, which changes both the electrostatic properties of the phosphate group and the strength of the hydrogen bond, provides a possible mechanism in regulating protein function.

Amides↗
PubMed2005

Ab initio fragment molecular orbital (FMO) method applied to analysis of the ligand-protein interaction in a pheromone-binding protein.

Full quantum computation of the electronic state of proteins has recently become possible by the advent of the ab initio fragment molecular orbital (FMO) method. We applied this method to the analysis of the interaction between the Bombyx mori pheromone-binding protein and its ligand, bombykol. The protein-ligand interaction of this molecular complex was minutely analyzed by the FMO method, and the analysis revealed several important interactions between the ligand and amino acid residues.

Animals↗
PubMed2005

Copper binding properties of a tau peptide associated with Alzheimer's disease studied by CD, NMR, and MALDI-TOF MS.

We have previously reported the copper binding properties of R3 peptide (residues 318-335: VTSKCGSLGNIHHKPGGG, according to the longest tau protein) derived from the third repeat microtubule-binding domain of water-soluble tau protein. In this work, we have investigated copper binding properties of R2 peptide (residues 287-304: VQSKCGSKDNIKHVPGGG) derived from the second repeat region of tau protein. Similar to R3 peptide, R2 peptide also plays an important role in the formation of neurofibrillary tangles (NFTs) which is one of the two main biological characteristics of Alzheimer's disease (AD). Based on the copper binding properties of R2 peptide, the possible influences of the binding on the formation of NFTs were investigated. Results from circular dichroism (CD) spectra, nuclear magnetic resonance (NMR) spectroscopy, and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) suggest that the binding is pH-dependent and stoichiometry-determined. In addition, these results also reveal that R2 peptide adopts a monomeric alpha-helical structure in aqueous solutions at physiological pH after the addition of 1 mol equiv. of Cu2+. Since alpha-helix structure is responsible for the formation of paired helical filaments (PHFs) which aggregate into NFTs, it is hypothesized that Cu2+ induces R2 peptide to self-assemble into a PHFs-like structure. Hence, it is postulated that Cu2+ plays an important role in the aggregation of R2 peptide and tau protein and that copper binding to R2 peptide may be another possible involvement in AD.

Alzheimer Disease↗
PubMed2005

Binding of copper (II) ion to an Alzheimer's tau peptide as revealed by MALDI-TOF MS, CD, and NMR.

The tau protein plays an important role in some neurodegenerative diseases including Alzheimer's disease (AD). Neurofibrillary tangles (NFTs), a biological marker for AD, are aggregates of bundles of paired helical filaments (PHFs). In general, the alpha-sheet structure favors aberrant protein aggregates. However, some reports have shown that the alpha-helix structure is capable of triggering the formation of aberrant tau protein aggregates and PHFs have a high alpha-helix content. In addition, the third repeat fragment in the four-repeat microtubule-binding domain of the tau protein (residues 306-336: VQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQ, according to the longest tau protein) adopts a helical structure in trifluoroethanol (TFE) and may be a self-assembly model in the tau protein. In the human brain, there is a very small quantity of copper, which performs an important function. In our study, by means of matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), circular dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy, the binding properties of copper (II) ion to the R3 peptide derived from the third repeat fragment (residues 318-335: VTSKCGSLGNIHHKPGGG) have been investigated. The results show that copper ions bind to the R3 peptide. CD spectra, ultraviolet (UV)-visible absorption spectra, and MALDI-TOF MS show pH dependence and stoichiometry of Cu2+ binding. Furthermore, CD spectra and NMR spectroscopy elucidate the copper binding sites located in the R3 peptide. Finally, CD spectra reveal that the R3 peptide adopts a mixture structure of random structures, alpha-helices, and beta-turns in aqueous solutions at physiological pH. At pH 7.5, the addition of 0.25 mol eq of Cu2+ induces the conformational change from the mixture mentioned above to a monomeric helical structure, and a beta-sheet structure forms in the presence of 1 mol eq of Cu2+. As alpha-helix and beta-sheet structures are responsible for the formation of PHFs, it is hypothesized that Cu2+ is an inducer of self-assembly of the R3 peptide and makes the R3 peptide form a structure like PHF. Hence, it is postulated that Cu2+ plays an important role in the aggregation of the R3 peptide and tau protein and that copper (II) binding may be another possible involvement in AD.

Alzheimer Disease↗
PubMed2005

Synthesis and conformational properties of phosphopeptides related to the human tau protein.

In the brains of Alzheimer's disease patients, the tau protein dissociates from the axonal microtubule and abnormally aggregates to form a paired helical filament (PHF). One of the priorities in Alzheimer research is to determine the effects of abnormal phosphorylation on the local structure. A series of peptides corresponding to isolated regions of tau protein have been successfully synthesized using Fmoc-based chemistry and their conformations were determined by 1H NMR spectroscopy and circular dichroism (CD) spectroscopy. Immunodominant peptides corresponding to tau-(256-273), tau-(350-367) and two phosphorylated derivatives in which a single Ser was phosphorylated at positions 262 and 356, respectively, were the main focus of the study. A direct alteration of the local structure after phosphorylation constitutes a new strategy through which control of biological activity can be enforced. In our study on Ser262 in R1 peptide and Ser356 in R4 peptide, phosphorylation modifies both the negative charge and the local conformation nearby the phosphorylation sites. Together, these structural changes indicate that phosphorylation may act as a conformational switch in the binding domain of tau protein to alter specificity and affinity of binding to microtubule, particularly in response to the abnormal phosphorylation events associated with Alzheimer's disease.

Alzheimer Disease↗
PubMed2005

Application of ultra-high magnetic field for saccharide molecules: 1H NMR spectra of 6-O-alpha-D-glucopyranosyl-cyclomaltoheptaose and -cyclomaltohexaose.

1H NMR spectra of G1-alpha-CD and G1-beta-CD were recorded using a spectrometer equipped with a 21.6 T magnet. An ultra-high magnetic field was effective for detecting 1H NMR signals with a small difference in chemical shifts. Introducing a glucosyl group onto CDs as a branch caused deformation of equilibrated 1H signals of cyclodextrin. Particularly, 1H signals in branched glucose were shifted greatly.

Cyclodextrins↗
PubMed2004

1H NMR spectra of branched-chain cyclomaltohexaoses (alpha-cyclodextrins).

The 1H NMR spectra of seven branched alpha-cyclodextrins (alpha-CDs) were observed and analyzed in detail. They were compared with spectra of alpha-CD and amylose. Although these branched alpha-CDs consist only of alpha-D-glucose with the same alpha-(1-->4) O-glucosyl binding, aside from one exception, differences in chemical shifts of corresponding signals were significantly large. Especially, differences in the chemical shift in anomeric protons were considerably large. Subtle differences in glucosyl binding directly influences chemical shifts of these protons because anomeric protons are located adjacent to the glucosyl binding sites.

Amylose↗
PubMed2004

High-grade neuroendocrine carcinoma of the lung presenting an unusual spread mimicking pleural mesothelioma associated with dermatomyositis.

Neuroendocrine tumors of the lung comprise a heterogeneous group of tumors that represents a spectrum of disease from typical carcinoid tumors to the high-grade neuroendocrine carcinomas (large-cell neuroendocrine carcinomas and small-cell carcinomas). The high-grade neuroendocrine carcinomas are characterized by early metastasis and poor prognosis. The peripheral location and especially the massive pleural spread are rare for a high-grade neuroendocrine carcinoma. We report a case in which a high-grade neuroendocrine carcinoma, associated with dermatomyositis, presented an unusual pattern of progression, mimicking malignant pleural mesothelioma on diagnostic imaging.

Carcinoma, Neuroendocrine↗
PubMed2003

Arg389Gly polymorphism of the human beta1-adrenergic receptor in patients with nonfatal acute myocardial infarction.

BACKGROUND: We sought to investigate the relation between the Arg389Gly polymorphism in the human beta1-adrenergic receptor (ADRB1) gene and acute myocardial infarction (AMI). It was previously reported that augmented sympathetic activity might play an important role as a trigger of AMI by enhanced hemodynamic or mechanical forces through ADRB1 activation. Recently, a common polymorphism has been identified at amino acid position 389 (Arg or Gly) of the human ADRB1, within a region important for receptor-Gs protein coupling and subsequent agonist-stimulated adenylyl cyclase activation. METHODS: To investigate the relation between the Arg389Gly polymorphism in the ADRB1 gene and AMI, we genotyped 354 patients with AMI and 354 age- and sex-matched control subjects by use of polymerase chain reaction amplification and the restriction fragment length polymorphism analysis. RESULTS: The prevalence of the Arg389 homozygote (CC) genotype was significantly more frequent in patients with AMI than in control subjects (68.1% vs 47.2%, P <.0001). In logistic regression models, the odds ratio (OR) of Arg389 homozygote (CC) versus Arg389Gly heterozygote (CG) + Gly389 homozygote (GG) genotypes between control subjects and patients with AMI was 2.86 (95% CI 1.92-4.26, P =.0001). The association of the Arg389Gly polymorphism of ADRB1 with AMI was statistically significant and independent of other risk factors. CONCLUSION: Our findings suggest that the genotype of Arg389Gly polymorphism in the human ADRB1 gene is associated with AMI.

Aged↗
PubMed2002

Three-dimensional structure of the inclusion complex between phloridzin and beta-cyclodextrin.

The inclusion of phloridzin into beta-cyclodextrin was studied as a model of molecular recognition in membranes. Effects on 1H NMR spectra and NOE correlational peaks between phloridzin and beta-cyclodextrin were observed in the complex. Strong NOEs were observed between hydrogens of a phenol group in phloridzin and beta-cyclodextrin. The three-dimensional structure of the inclusion complex between phloridzin and beta-cyclodextrin was simulated with distance constraints estimated by the intensity of NOE peaks using the DADAS90 programs. Two inclusion possibilities were suggested-the large rim of beta-cyclodextrin as an entrance of the inclusion and the small rim of beta-cyclodextrin as the entrance. In both cases, the phenol group of phloridzin was included in the hydrophobic space of beta-cyclodextrin.

Computer Simulation↗
PubMed2002

Circulating T-lymphocyte activation in patients with variant angina.

BACKGROUND: Both experimental and pathological studies suggest that immune response and inflammation may play an important role in the pathogenesis of coronary spasm. DESIGN: To elucidate the role of systemic immune and inflammatory responses in the pathogenesis of coronary spasm, we studied circulating T-lymphocyte activation in variant angina patients (VAPs), stable effort angina patients (EAPs) and in control participants. METHODS: Twenty documented VAPs, 13 EAPs and 20 control participants were studied. To evaluate T-lymphocyte activation, T-lymphocyte surface antigen expression, including CD3, CD4, CD8 and HLA-DR, was measured by two-colour flow cytometric analysis. Serum-soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were also measured by enzyme-linked immunosorbent assay. We restudied 10 of the VAPs to investigate the relationship between the disease activity of variant angina and T-lymphocyte activation. RESULTS: The percentage of CD3+/DR+ T-lymphocytes in VAPs (14.8%) was significantly higher than in EAPs (10.7%, P < 0.05) and control participants (9.7%, P < 0.005); however, levels of sIL-2R were the same among the three groups. Levels of CRP were within normal range in all VAPs. The percentage of CD8+/DR+ T-lymphocytes was significantly higher in VAPs (9.5%, P < 0.005) than in EAPs (5.5%) and control participants (5.9%), whereas the percentage of CD4+/DR+ T-lymphocytes was similar among the three groups. The percentage of activated T-lymphocytes in VAPs was unchanged during the follow-up period (mean intervals, 10 months). CONCLUSIONS: These results indicate that the chronic activation of T-lymphocytes, especially CD8+ T-lymphocytes, may be involved in the pathogenesis of coronary spasm.

Adult↗