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Biomedical subjects

S Saito

Publications and source records attributed to S Saito.

At least 127 records · Page 7Linked to original sources
PubMed2001

Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of the aortic wall resulting from degradation of collagen and elastin. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in AAAs (n = 8), atherosclerotic occlusive diseases (AOD) (n = 8), and normal subjects (n = 8) using the reverse transcription-polymerase chain reaction (RT-PCR). We also analyzed the gelatinolytic activity of these metalloproteinases using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in the AAA group compared with those in the AOD group and normal subjects. The levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in the AOD and normal groups. Only in the case of MT-MMP-1 was the difference between AAA and AOD not statistically significant. By gelatin zymography with the same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups and did not differ significantly between them. Linear regression analysis demonstrated a significant positive correlation between mRNA levels of MMPs and those of TIMPs. These observations suggest that aneurysm formation in patients with atherosclerosis is related to the degree of MMP-9 expression.

Aged↗
PubMed2001

Comparison of perceptional nasal obstruction with rhinomanometric and acoustic rhinometric assessment.

Perception of nasal stuffiness, together with rhinomanometric and acoustic rhinometric assessments were evaluated before and after nasal and/or sinus surgery in 50 Japanese adult patients. Nasal resistance on both expiration and inspiration correlated well with the patients' perceptions (P<0.05). Nasal volumes (0-4 cm and 0-7 cm) obtained from acoustic rhinometry measurements also correlated well with perception (P<0.05). No significant relationships were found between rhinomanometric and acoustic rhinometric results. Perceptional nasal obstruction, rhinomanometric and acoustic rhinometric results (except for the sectional areas at the I-notch) improved significantly after the operations. Rhinomanometry and acoustic rhinometry are valuable methods for assessing nasal stuffiness, but we must take account of the differences between the two methods.

Adult↗
PubMed2001

The combination of a fiberoptic stylet and a McCoy laryngoscope facilitates tracheal intubation in difficult airway cases.

PURPOSE: Fiberoptic stylets are considered useful for difficult airway management. In the present study, we assessed the usefulness of a fiberoptic stylet when the stylet was used with a Macintosh or a McCoy laryngoscope. METHODS: Twenty-four patients, whose airways were graded as Cormack grade III, were studied. We compared the times required for tracheal intubation when the fiberoptic stylet was used with a Macintosh direct laryngoscope and when it was used with a McCoy laryngoscope. Cormack grade III was subdivided into IIIa (with distance between the epiglottis and the posterior wall of the pharynx) and IIIb (with no distance between the epiglottis and the posterior wall of the pharynx), according to the view of the vocal cords by the laryngoscope. RESULTS: The intubation time in grade IIIb patients, who were intubated by the concurrent use of the fiberoptic stylet and the McCoy laryngoscope (28 +/- 4 s), was not significantly different from that in grade IIIa patients (28 +/- 10 s). The intubation time in grade IIIb patients, who were intubated by the concurrent use of the fiberoptic stylet and the Macintosh laryngoscope (52 +/- 8 s), was significantly longer than that in grades IIIa (28 +/- 10 s; P < 0.01) or IIIb with the McCoy laryngoscope (28 +/- 4 s; P < 0.01). CONCLUSION: The combination of a new handy fiberoptic stylet and a McCoy laryngoscope facilitated tracheal intubation of patients whose airway had no distance between the epiglottis and the posterior wall of the pharynx in laryngoscopic vocal cord view.

Journal Article↗
PubMed2001

Catalog of 258 single-nucleotide polymorphisms (SNPs) in genes encoding three organic anion transporters, three organic anion-transporting polypeptides, and three NADH:ubiquinone oxidoreductase flavoproteins.

We present here a series of high-density maps of single-nucleotide polymorphisms (SNPs) detected in genes encoding three organic-anion transporters, three organic anion-transporting polypeptides, and three nicotinamide adenine dinucleotide, reduced:ubiquinone oxidoreductase flavoproteins. A total of 258 SNPs were identified among these nine genes through systematic screening of DNA from 48 Japanese individuals: 17 in 5' flanking regions, three in 5' untranslated regions, 13 in coding regions, 211 in introns, six in 3' untranslated regions, and 8 in 3' flanking regions. By comparing our data with SNPs deposited in the dbSNP database in the National Center for Biotechnology Information, we determined that 236 (91.5%) were novel. In addition, 46 genetic variations of other types were discovered within these loci. These high-resolution maps will serve as a useful resource for analyzing potential associations between variations in these nine genes and differences in human susceptibilities to common diseases or response to drug therapies.

Chromosome Mapping↗
PubMed2001

Catalog of 46 single-nucleotide polymorphisms (SNPs) in the microsomal glutathione S-transferase 1 (MGST1) gene.

A major goal in our laboratory is to understand the role of common genetic variations among individual patients as regards susceptibility to common diseases and differences in therapeutic efficacy and/or side effects of drugs. As an addition to the high-density SNP (single-nucleotide polymorphism) maps of 12 glutathione S-transferase and related genes reported earlier, we provide here an SNP map of the microsomal glutathione S-transferase 1 (MGST1) gene. Among 48 healthy Japanese volunteers examined. we identified a total of 46 SNPs at this locus, 36 of which had not been reported before: 4 in the promoter region, 34 in introns, 3 in the 3' untranslated region, and 5 in the 3' flanking region. No SNP was found in 5'untranslated or coding regions. The ratio of transition to transversion was approximately 1.2:1. Among the 13 insertion-deletion polymorphisms was a 2-bp deletion in the coding region of MGST1 in DNA from one of the volunteers, which resulted in a frame-shift mutation. Since the gene product encoded by this mutant allele would lack the C-terminal half including the MAPEG (membrane-associated proteins in eicosanoid and glutathione metabolism) domain, MGST1 activity is likely to be reduced in the carrier's cells. The SNP map presented here adds to the archive of tools for studying complex genetic diseases, population migration patterns, and a variety of pharmacogenetic possibilities.

3' Untranslated Regions↗
PubMed2001

High-density single-nucleotide polymorphism (SNP) map of the 150-kb region corresponding to the human ATP-binding cassette transporter A1 (ABCA1) gene.

Highly dense catalogs of human genetic variations, in combination with high-throughput genotyping technologies, are expected to clarify individual genetic differences in pharmacological responsiveness and predispositions to common diseases. Here we report single-nucleotide polymorphisms (SNPs) present among 48 Japanese individuals at the locus for the human ATP-binding cassette transporter A1 (ABCA1) gene. ABCA1 plays a key role in apolipoprotein-mediated cholesterol transport, and mutations in this gene are responsible for Tangier disease and familial high-density lipoprotein deficiency associated with reduced cholesterol efflux. We identified a total of 162 SNPs, 149 of which were novel, within the 150-kb region encompassing the entire ABCA1 gene. Eight of the SNPs lie within coding elements, two in 5' flanking regions, 147 in introns, and five in 3' untranslated regions, but none were found in 5' untranslated or 3' flanking regions. The ratio of transitions to transversions was approximately 2.37 to 1. Our dense SNP map of this region could serve as a powerful resource for studies of complex genetic diseases that may be associated with ABCA1 and of individual responses to drug therapy.

ATP Binding Cassette Transporter 1↗
PubMed2001

Identification of 197 genetic variations in six human methyltranferase genes in the Japanese population.

Methylation is an important event in the biotransformation pathway for many drugs and xenobiotic compounds. We screened DNA from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in six methyltransferase (MT) genes (catechol-O-MT, COMT; guanidinoacetate N-MT, GAMT; histamine N-MT, HNMT; nicotinamide N-MT, NNMT; phosphatidylethanolamine N-MT, PEMT; and phenylethanolamine N-MT, PNMT) by direct sequencing of their entire genomic regions except for repetitive elements. This approach identified 190 SNPs and seven insertion/deletion polymorphisms among the six genes. Of the 190 SNPs, 33 were identified in the COMT gene, 6 in GAMT, 41 in HNMT, 8 in NNMT, 98 in PEMT, and 4 in PNMT. Nine were located in 5' flanking regions, 156 in introns, 10 in exons, and 15 in 3' flanking regions. These variants may contribute to a more precise understanding of possible correlations between genotypes and disease-susceptibility phenotypes or risk for side effects from drugs.

3' Untranslated Regions↗
PubMed2001

Catalog of 434 single-nucleotide polymorphisms (SNPs) in genes of the alcohol dehydrogenase, glutathione S-transferase, and nicotinamide adenine dinucleotide, reduced (NADH) ubiquinone oxidoreductase families.

An approach based on development of a large archive of single-nucleotide polymorphisms (SNPs) throughout the human genome is expected to facilitate large-scale studies to identify genes associated with drug efficacy and side effects, or susceptibility to common diseases. We have already described collections of SNPs present among various genes encoding drug-metabolizing enzymes. Here we report SNPs for such enzymes at additional loci, including 8 alcohol dehydrogenases, 12 glutathione S-transferases, and 18 belonging to the NADH-ubiquinone oxidoreductase family. Among DNA samples from 48 Japanese volunteers, we identified a total of 434 SNPs at these 38 loci: 27 within coding elements, 52 in 5' flanking regions, five in 5' untranslated regions, 293 in introns, 20 in 3' untranslated regions, and 37 in 3' flanking regions. The ratio of transitions to transversions was approximately 2.1 to 1. Among the 27 coding SNPs, 13 were nonsynonymous changes that resulted in amino acid substitutions. Our collection of SNPs derived from this study should prove useful for investigations designed to detect associations between genetic variations and common diseases or responsiveness to drug therapy.

Alcohol Dehydrogenase↗
PubMed2001

Identification of single-nucleotide polymorphisms (SNPs) of human N-acetyltransferase genes NAT1, NAT2, AANAT, ARD1 and L1CAM in the Japanese population.

By direct sequencing of regions of the human genome containing five genes belonging to the acetyltransferase family, arylamine N-acetyltransferase (NAT1), arylamine N-acetyltransferase (NAT2), arylalkylamine N-acetyltransferase (AANAT), L1 cell adhesion molecule (L1CAM), and the human homolog of Saccharomyces cerevisiae N-acetyltransferase ARD1, we identified 53 single-nucleotide polymorphisms (SNPs) and two insertion/ deletion polymorphisms in 48 healthy Japanese volunteers. NAT1 and NAT2 are so-called drug-metabolizing enzymes. In the NAT1 gene we found two SNPs and a 3-bp insertion/ deletion polymorphism that corresponded to the NAT1*3, *10, and *18A/*18B alleles reported in other populations. The frequencies of NAT1* alleles in our Japanese subjects were 52.6% for NAT1*4, 1.0% for NAT1*3, 40.6% for NAT1*10, 2.6% for NAT1*18A and 3.1% for NAT1*18B. In the NAT2 gene we found 32 SNPs and a 1-bp insertion/ deletion polymorphism; 6 SNPs within the coding region were reported previously and belonged to the slow acetylator group (NAT2*5, NAT2*6 and NAT2*7), and 2 of the 8 SNPs in the 5' flanking region were reported in the dbSNP of GenBank, but the remaining 24 SNPs and the insertion/deletion polymorphism were novel. The frequencies of NAT2* alleles in Japanese (51.3% for NAT2*4, 1.6% for *5B, 26.1% for *6A, 2.2% for *6B, 1.2% for *7A, 10.1% for *7B, 7.4% for *12A, and 1.1% for *13) were significantly different from those reported in Caucasian populations. In the AANAT gene we found 4 novel SNPs: 2 in the 5' flanking region, 1 in exon 4, and 1 in intron 3. In the two genes belonging to the N-terminal N-acetyltransferase family, we identified 9 SNPs, 7 of them novel, for ARD1, and six novel SNPs for L1CAM. Variations at these loci may contribute to an understanding of the way in which different genotypes may affect the activities of human N-acetyltransferases, especially as regards the therapeutic efficacy of certain drugs and antibiotics.

Acetyltransferases↗
PubMed2001

Seventy genetic variations in human microsomal and soluble epoxide hydrolase genes (EPHX1 and EPHX2) in the Japanese population.

Human microsomal and soluble epoxide hydrolases (mEH and sEH) are enzymes that metabolize xenobiotic molecules. We screened DNA from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in both genes by direct sequencing of the entire genomic regions containing EPHX1 and EPHX2, except for repetitive elements. This approach identified 33 SNPs in the EPHX1 gene; 6 of them were located in the 5' flanking region, 17 in introns, 8 in exons, and 2 in the 3' flanking region. In the EPHX2 gene, we identified 36 SNPs, including 4 in the 5' flanking region, 24 in introns, 5 in exons, and 3 in the 3' flanking region, as well as one insertion/deletion polymorphism in the 5' flanking region. These variants may contribute to a more precise understanding of the nature of correlations between genotypes and disease-susceptibility phenotypes that have been postulated in regard to human microsomal and soluble epoxide hydrolases.

Alleles↗
PubMed2001

Catalog of 320 single nucleotide polymorphisms (SNPs) in 20 quinone oxidoreductase and sulfotransferase genes.

Single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes, transporters, receptors, and other drug targets have been widely implicated as contributors to differences among individuals as regards the efficacy and toxicity of many medications, as well as the susceptibility to complex diseases. By combining the polymerase chain reaction (PCR) technique with direct sequencing, we screened genomic DNAs from 48 Japanese volunteers for SNPs in genes encoding three quinone oxidoreductases (NQO1, NQO2, and PIG3) and 17 sulfotransferases (SULT1A1, SULT1A2, SULT1A3, SULT1C1, SULT1C2, SULT2A1, SULT2B1, ST1B2, TPST1, TPST2, SULTX3, STE, CST, HNK-1 ST, CHST2, CHST4, and CHST5). In all, we identified 320 SNPs from these 20 loci: 22 within coding elements, 21 in 5' flanking regions, 10 in 5' untranslated regions, 223 in introns, 19 in 3' untranslated regions, and 25 in 3' flanking regions. The ratio of transitions to transversions was approximately 2.3 to 1. Of the 22 coding SNPs, 6 were nonsynonymous substitutions that resulted in amino-acid substitutions. The high-density SNP maps we constructed from this data for each of the quinone oxidoreductases and sulfotransferases examined here should provide useful information for investigations designed to detect association(s) between genetic variations and common diseases or responsiveness to drug therapy.

Base Sequence↗
PubMed2001

Dental bar tracheopexy in a neonate.

Double aortic arch often presents with tracheoesophageal compression. Management requires division of the vascular ring and, if tracheomalacia is present, some form of tracheopexy. We report here the use of a dental bar as an external splint for tracheopexy in a neonate. Follow-up to 18 months shows good tracheal growth and no erosion.

Aorta↗
PubMed2001

Correlation of binding sites for diisopropyl phosphorofluoridate with cholinesterase and neuropathy target esterase in membrane and cytosol preparations from hen.

To find new putative target(s) for organophosphorus induced delayed neurotoxicity (OPIDN), we investigated the biochemical and pharmacological characteristics of [3H] diisopropyl phosphorofluoridate (DFP) binding to membrane and cytosol preparations from the brain and spinal cord of hens. Specific [3H]DFP binding was determined by subtracting non-specific binding from total binding. The binding sites of [3H]DFP, an organophosphate that induces OPIDN, were found not only on membrane but also in cytosol. Reduction of subsequent ex vivo specific [3H]DFP binding by in vivo pretreatment with unlabeled DFP was found in cytosol, not membrane. The reduced binding lasted to the onset of OPIDN, especially in spinal cord. These results suggest that the specific DFP binding sites in cytosol, rather than on membrane, are the most important with regard to the initiation of OPIDN. Inhibitors of cholinesterase (ChE) and neuropathy target esterase (NTE) other than DFP did not affect specific [3H]DFP binding to either membranes or cytosol in vivo. Additionally, inhibition of the activities of these esterases by these compounds was not consistent with either the degree of inhibition of the [3H]DFP binding or a time-dependent manner of OPIDN. These results suggest that DFP binding site(s) involved in the initiation of OPIDN may be different from the active sites of ChE and NTE.

Animals↗
PubMed2001

IgE reactivity and cross-reactivity to Japanese cedar (Cryptomeria japonica) and cypress (Chamaecyparis obtusa) pollen allergens in dogs with atopic dermatitis.

The natural occurrence of Japanese cedar (Cryptomeria japonica) pollinosis has been reported in dogs with atopic dermatitis. However, the reactivity to Japanese cypress (Chamaecyparis obtusa) pollen allergens in these dogs has not been reported. The present study was designed to investigate the reactivity to Japanese cypress pollen allergens in dogs sensitized to Japanese cedar pollen allergens. In 19 dogs with specific IgE to C. japonica pollen allergen, we measured the specific IgE to C. obtusa pollen allergen and examined the reactivity to the allergen by intradermal test. Of the 19 dogs, 18 had specific IgE to crude and purified major allergens (Cha o 1) of C. obtusa pollen. Most of the dogs showed a positive reaction to C. obtusa pollen allergens in the intradermal test. Allergenic cross-reactivity between Cha o 1 and Cry j 1 (a major allergen in C. japonica pollen) was observed by the ELISA inhibition method. Dogs sensitized to Japanese cedar pollen allergens demonstrate reactivity to Japanese cypress pollen allergens.

Allergens↗
PubMed2001

Intracoronary electrocardiogram for early detection of myocardial viability during coronary angioplasty in acute myocardial infarction.

PURPOSE: The clinical value of the intracoronary electrocardiogram (ECG) for detecting myocardial viability in acute myocardial infarction was evaluated by thallium-201 scintigraphy and left ventriculogram at the chronic stage. METHODS: Intracoronary ECGs, recorded from the tip of a guidewire during emergency coronary angioplasty, were obtained in 65 patients with reperfused anterior myocardial infarction. Further ST segment elevation of greater than 0.2 mV detected during the balloon inflation was taken as significant. The left ventricular segmental shortening was measured from left ventriculograms recorded at acute and chronic stages. The infarct area was defined as viable when a thallium uptake of more than 50% was detected on thallium-201 myocardial scintigraphy at the chronic stage. RESULTS: During emergency coronary angioplasty, significant ST segment elevation was noted in 45 patients (Group A); however, the ST segment was not significantly elevated in the other 20 patients (Group B). The infarct area of 42 patients in Group A and three patients in Group B was viable on scintigraphy. Improvement left ventricular wall motion of the infarct area was observed in 39 of the 42 patients in Group A and the three patients in Group B. Therefore, intracoronary ECG can predict reversible dysfunction with excellent sensitivity (92.9%) and specificity (73.9%). CONCLUSIONS: The myocardium within an infarct area can be regarded as viable when a further ST segment elevation occurs on intracoronary ECG during emergency coronary angioplasty. It is useful, therefore, to monitor the intracoronary ECG during coronary angioplasty balloon inflation to assess the myocardial viability of the infarct area.

Angioplasty, Balloon, Coronary↗
PubMed2001

Identification of hepatitis B virus-specific CTL epitopes presented by HLA-A*2402, the most common HLA class I allele in East Asia.

BACKGROUND/AIMS: The aim of this study was to identify and characterize hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTL) epitopes presented by human leukocyte antigen (HLA)-A*2402, most common HLA class I allele in East Asia. METHODS: HLA-A*2402-restricted CTL epitopes were identified by reverse immunogenetics. Immunogenecity of these epitopes was investigated using peripheral blood mononuclear cell (PBMC) from HLA-A24+ patients with acute hepatitis B. RESULTS: An HLA-A*2402 stabilization assay demonstrated that 36 of 63 HBV peptides carrying HLA-A*2402 anchor residues have high- and medium-HLA-A*2402 binding affinity. Two (C117-125 and P756-764) of the 36 peptides induced peptide-specific CTLs. CTL clones and lines specific for these peptides killed HBV recombinant vaccinia virus-infected target cells expressing HLA-A*2402, indicating that these two peptides are CTL epitopes presented by HLA-A*2402. These two peptides were able to induce specific CTLs in 7 and 11 of 12 HLA-A24+ patients with acute hepatitis B, respectively. CONCLUSIONS: We identified two immunodominant CTL epitopes restricted by HLA-A*2402. Because HLA-A*2402 is the most common allele in East Asia, a region in which there are approximately 200 million HBV carriers, these epitopes will be useful for analysis of CTL responses in patients from East Asia.

Acute Disease↗
PubMed2001

A new radiofrequency thermal balloon catheter for pulmonary vein isolation.

OBJECTIVES: We sought to evaluate whether porcine pulmonary vein (PV) isolation (PVI) can be produced by ablation using our novel radiofrequency (RF) thermal balloon catheter (RBC). BACKGROUND: It has been proposed that PVI can prevent focal atrial fibrillation (AF) originating in or close to the PV. METHODS: The RBC is composed of a 12F main shaft, a 4F inner tube and a balloon. Inside the balloon, there is a unipolar coil electrode with a thermocouple sensor mounted along the tube, the former to deliver RF energy (13.56 MHz) and the latter to monitor the temperature. After the presence of a PV potential was confirmed, the RBC was safely inserted into the left atrium (LA) by the trans-septal approach. Once the balloon was inflated and optimally wedged at the junction between the PV and LA, RF energy was applied for 5 min. Radiofrequency catheter ablation (RFA) was repeated up to three times, until elimination of the PV potential or dissociation between the LA and PV was observed. Finally, each heart was examined histologically. RESULTS: In 18 PVs that had PV potentials, PVI was performed, resulting in success in 15 (success rate 83%, 95% confidence interval [CI] 58.0% to 96.3%; failure rate 17%, 95% CI 3.7% to 42.0%). After successful PVI, the PV potentials completely disappeared and the histologic examination revealed circumferential, transmural necrosis around the PV trunks. No major complications, such as PV stenosis or macroscopic thrombosis, were observed. CONCLUSIONS: The RBC was useful for PVI.

Animals↗