Search PubMed⌕ Search

Biomedical subjects

M Suwa

Publications and source records attributed to M Suwa.

At least 19 recordsLinked to original sources
PubMed2001

HUNT: launch of a full-length cDNA database from the Helix Research Institute.

The Helix Research Institute (HRI) in Japan is releasing 4356 HUman Novel Transcripts and related information in the newly established HUNT database. The institute is a joint research project principally funded by the Japanese Ministry of International Trade and Industry, and the clones were sequenced in the governmental New Energy and Industrial Technology Development Organization (NEDO) Human cDNA Sequencing Project. The HUNT database contains an extensive amount of annotation from advanced analysis and represents an essential bioinformatics contribution towards understanding of the gene function. The HRI human cDNA clones were obtained from full-length enriched cDNA libraries constructed with the oligo-capping method and have resulted in novel full-length cDNA sequences. A large fraction has little similarity to any proteins of known function and to obtain clues about possible function we have developed original analysis procedures. Any putative function deduced here can be validated or refuted by complementary analysis results. The user can also extract information from specific categories like PROSITE patterns, PFAM domains, PSORT localization, transmembrane helices and clones with GENIUS structure assignments. The HUNT database can be accessed at http://www.hri.co.jp/HUNT.

Computational Biology↗
PubMed2001

Identification and quantification of tamoxifen-DNA adducts in the liver of rats and mice.

A new HPLC gradient system was developed for (32)P-postlabeling analysis to identify and quantify hepatic tamoxifen-DNA adducts of rats and mice treated with tamoxifen. Four stereoisomers of alpha-(N(2)-deoxyguanosinyl)tamoxifen (dG(3')(P)-N(2)-TAM), alpha-(N(2)-deoxyguanosinyl)-N-desmethyltamoxifen (dG(3')(P)-N(2)-N-desmethyl-TAM), and alpha-(N(2)-deoxyguanosinyl)tamoxifen N-oxide (dG(3')(P)-N(2)-TAM N-oxide) were prepared by reacting either alpha-acetoxytamoxifen, alpha-acetoxy-N-desmethyltamoxifen or alpha-acetoxytamoxifen N-oxide with 2'-deoxyguanosine 3'-monophosphate, and used as standard markers for (32)P-postlabeling/HPLC analysis. Our HPLC gradient system can separate the above 12 nucleotide isomers as nine peaks; six peaks representing two each trans epimers (fr-1 and fr-2) of dG(3')(P)-N(2)-TAM, dG(3')(P)-N(2)-N-desmethyl-TAM and dG(3')(P)-N(2)-TAM N-oxide, and three peaks representing a mixture of two cis epimers (fr-3 and fr-4) of nucleotides. Tamoxifen was given to female F344 rats and DBA/2 mice by gavage at doses of 45 mg/kg/day and 120 mg/kg/day, respectively, for 7 days. Totally 15 and 17 tamoxifen-DNA adducts were detected in rats and mice, respectively; among them 13 adducts were observed in both rats and mice. trans-dG-N(2)-TAM (fr-2) and trans-dG(3')(P)-N(2)-N-desmethyl-TAM (fr-2) were two major adducts in both animals. Except for these two adducts, trans-dG-N(2)-TAM N-oxide (fr-2) was the third abundant adduct that accounted for 6.4% of the total adducts in mice, while this accounted for only 0.3% in rats. A trans-isomer (fr-1) and cis-isomers (fr-3 and -4) of dG(3')(P)-N(2)-TAM, dG(3')(P)-N(2)-N-desmethyl-TAM and dG(3')(P)-N(2)-TAM N-oxide were also detected as minor adducts in both animals except for cis-form of dG-N(2)-TAM N-oxide in rats. Although the administered dose for rats was 2.7-fold less than that for mice, the total adduct level of rats (216 adducts/10(8) nucleotides) were 3.8-fold higher than mice (56.2 adducts/10(8) nucleotides). Thus, these three types of tamoxifen adducts accounted for 95.0 and 92.5% of the total DNA adducts of the rats and mice, respectively. The formation of tamoxifen adducts primarily resulted from alpha-hydroxylation of tamoxifen.

Animals↗
PubMed2001

A case of cardiomyopathy showing progression from the hypertrophic to the dilated form: association of Mt8348A-->G mutation in the mitochondrial tRNA(Lys) gene with severe ultrastructural alterations of mitochondria in cardiomyocytes.

This report describes a case of cardiomyopathy with a novel point mutation of mitochondrial DNA coding lysine tRNA in association with severe ultrastructural alterations of the mitochondria in the cardiomyocytes. Abnormalities of energy production and/or abnormal protein synthesis because of the mutation of mitochondrial DNA may have played an important role in the pathogenesis of this case, which showed severe cardiomyocyte degeneration and deterioration from hypertrophic cardiomyopathy to severe dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed2001

Role of transesophageal echocardiography in the prediction of thromboembolism in patients with chronic nonvalvular atrial fibrillation.

The purpose of this study was to determine whether parameters derived from transesophageal echocardiography (TEE) could predict thromboembolism in patients with chronic nonvalvular atrial fibrillation (AF). Eighty-nine patients, mean age 66+/-9 years, who underwent TEE in 1996 to 1999 were studied. The clinical endpoint was a thromboembolic event, including transient ischemic attack (TIA). Sixty-seven patients (75%) were anticoagulated with warfarin after TEE. After a follow-up period of 29+/-10 months, 1 patient died suddenly, 4 had a thromboembolism, and 3 had a TIA; the annual embolic event rate was 3.3%. Left atrial appendage (LAA) thrombus (86% vs 17%, p<0.001), LAA dysfunction (LAA velocity <20 cm/s; 71% vs 25%, p=0.009), and severe LA spontaneous echo contrast (29% vs 2%, p=0.002) were more prevalent in patients with an embolic event than in those without. In patients with LAA thrombus, the annual event rate was 11% as compared with 1.2% in those without (p=0.004). On the Cox proportional hazards model analysis, LAA thrombus (chi-square 7.0, p=0.008), severe LA spontaneous echo contrast (chi-square 7.0, p=0.008), and LAA dysfunction (chi-square 5.9, p=0.015) were significantly related to thromboembolism. Multivariate analysis revealed that LAA thrombus (chi-square 5.5, p=0.019) and LAA dysfunction (chi-square 4.0, p=0.045) were the independent predictors. In conclusion, TEE parameters, particularly the presence of LAA thrombus, can be used to assess thromboembolic potential in patients with chronic nonvalvular AF.

Aged↗
PubMed2001

Quantification of left atrial appendage spontaneous echo contrast in patients with chronic nonalvular atrial fibrillation.

OBJECTIVES: The left atrial (LA) appendage is the most common site of thrombus formation in patients with atrial fibrillation, and integrated backscatter allows the quantiative assessment of LA spontaneous echo contrast (SEC). Integrated backscatter was used to examine the significance of measuring appendage SEC, specifically in relation to echocardiographic variables implying thromboembolism, in patients with chronic nonvalvular atrial fibrillation. METHODS: Fifty-two patients with chronic nonvalvular atrial fibrillation and no prior anticoagulant therapy (35 men, 17 women, mean age 66 +/- 7 years) underwent transesophageal echocardiography with integrated backscatter analysis. The LA and LA appendage integrated backscatter intensity were measured with the regions of interest placed in the LA cavity and the appendage, respectively. The integrated backscatter intensity values for these two chambers (corrected "LA" and "LA appendage" integrated backscatter intensity, respectively) were corrected using values from the left ventricular cavity. RESULTS: The LA appendage integrated backscatter intensity values were available in 44 patients (85%). Overall, the corrected LA appendage integrated backscatter intensity was significantly increased compared with the corrected LA integrated backscatter intensity (2.8 +/- 2.2 vs 2.0 +/- 1.8 dB, p < 0.001). The corrected LA appendage integrated backscatter intensity was inversely correlated with the LA appendage velocity (r = -0.37, p < 0.05), but not with the LA dimension, appendage size, or left ventricular function. The corrected appendage integrated backscatter intensity (4.5 +/- 2.3 vs 2.4 +/- 1.9 dB, p < 0.01) and LA integrated backscatter intensity (3.2 +/- 2.1 vs 1.7 +/- 1.7 dB, p < 0.05) were higher in patients who had LA appendage thrombus (n = 8) than those who did not. With the corrected appendage integrated backscatter intensity set at > or = 2.5 dB, the sensitivity for the presence of appendage thrombus was 88% and the specificity was 64%. CONCLUSIONS: Patients with chronic nonvalvular atrial fibrillation had a denser SEC in the LA appendage compared with SEC in the main LA cavity. The severity of the appendage SEC was influenced by the LA appendage function rather than its size. Quantification of SEC in the appendage, rather than main LA cavity, was more valuable for assessing embolic potential.

Aged↗
PubMed2001

Doppler evaluation of systolic and diastolic heart failure in patients with cardiomyopathy.

BACKGROUND AND OBJECTIVES: Analysis of transmitral flow with Doppler echocardiography can currently evaluate left ventricular diastolic function noninvasively and easily. In addition, measurement of pulmonary venous flow and left atrial appendage flow clarifies not only left ventricular diastolic function but also left atrial systolic function in patients with left ventricular systolic failure and diastolic failure. METHODS AND RESULTS: Doppler echocardiography was used to investigate the differences in left ventricular diastolic dysfunction. In patients with systolic heart failure, left atrial dysfunction due to afterload mismatch to the left ventricle was related to the reduction of transmitral atrial filling wave in a restrictive pattern. In contrast, in patients with diastolic heart failure, transmitral flow seldom indicated a restrictive pattern because left atrial systolic function was preserved even with high pulmonary wedge pressure. CONCLUSIONS: Left ventricular diastolic dysfunction is somewhat distinct between patients with left ventricular systolic failure and patients with left ventricular diastolic failure. Atrial reversal flow in pulmonary vein has the potential to predict left ventricular filling pressure in patients with diastolic failure.

Cardiomyopathies↗
PubMed2001

Occurrence of Cryptosporidium in Japan and counter-measures in wastewater treatment plants.

The outbreak of cryptosporidiosis in Ogose in 1996 forced the wastewater treatment authorities to rethink the level of contamination by Cryptosporidium of wastewater and waters in the watersheds and counter-measures in wastewater treatment plants. A survey of Cryptosporidium concentrations in wastewater and treated wastewater conducted nationwide showed relatively low levels. Also, evaluation of wastewater treatment showed a 2 log oocyst removal with an activated sludge process and an additional 1 log removal with coagulant dosing.

Animals↗
PubMed2000

A novel measure characterized by a polar energy surface approximation for recognition and classification of transmembrane protein structures.

A new theoretical method has been developed for recognition and classification of membrane proteins. The method is based on computation of a polar energy surface that can reveal characteristic interaction patterns for individual helices even if crystal or NMR structure coordinates are not available. A protein with N transmembrane helices is described as a set of N vectors that are derived from a Fourier analysis of this polar energy surface computed for each helix. We then derive a polarity difference score (PDS) for any two proteins computed as the root mean square deviation between the respective vector coordinate sets. The score was found to correlate with the degree of structural similarity between the following three protein families for which tertiary structures have been determined: bacteriorhodopsin, rhodopsin, and the cytochrome c oxidase III subunit.

Algorithms↗
PubMed2000

Synthesis of derivatives of NK109, 7-OH benzo[c]phenanthridine alkaloid, and evaluation of their cytotoxicities and reduction-resistant properties.

The N5-C6 double bond of NK109 (an antitumor benzo[c]phenanthridine alkaloid) is easily reduced under biological environment. To suppress the inactivation caused by reduction, we synthesized 5-, 6-, and 8-substituted NK109. 5-Substituted derivatives (4a-c) were reduced more easily than NK109. 6-Substituted ones (10a-f) inhibited biological reduction, but showed weak cytotoxic activity. 8-O-Substituted ones (13a-h), especially 8-O-hydroxyethyl NK109 (13d), suppressed biological reduction and exhibited strong cytotoxic activity.

Antineoplastic Agents↗
PubMed2000

Identification of two polyketide synthase gene clusters on the linear plasmid pSLA2-L in Streptomyces rochei.

The 200kb linear plasmid pSLA2-L was suggested to be involved in the production of two macrolide antibiotics, lankamycin (Lm) and lankacidin (Lc), in Streptomyces rochei 7434AN4. Hybridization experiments with the polyketide synthase (PKS) genes for erythromycin and actinorhodin identified two eryAI-homologous regions and an actI-homologous region on pSLA2-L. The nucleotide sequence of a 3.6kb SacI fragment carrying one of the eryAI-homologs revealed that it codes for part of a large protein with four domains for ketoreductase, acyl carrier protein, ketosynthase, and acyltransferase. Gene disruption confirmed that the two eryAI-homologs are parts of a large type-I PKS gene cluster for Lm. A 4.8kb DNA carrying the actI-homologous region contains four open reading frames (ORF1-ORF4) as well as an additional ORF, i.e. ORF5, which might code for a thioesterase. Deletion of the ORF2-ORF4 region showed that it is not involved in the synthesis of Lm or Lc. Thus, it was confirmed that pSLA2-L contains two PKS gene clusters for Lm and an unknown type-II polyketide.

Amino Acid Sequence↗
PubMed2000

Myocardial integrated ultrasonic backscatter in patients with dilated cardiomyopathy: prediction of response to beta-blocker therapy.

BACKGROUND: Myocardial integrated backscatter (IB) imaging has been reported to be useful for ultrasonic tissue characterization and delineation of myocardial viability or fibrosis. beta-Blocker therapy has beneficial effects for patients with dilated cardiomyopathy (DCM), but there are no clear findings that indicate which patients with DCM will respond to this therapy. This study was performed to evaluate whether myocardial IB analysis can predict the response to beta-blocker therapy. METHODS AND RESULTS: We prospectively performed echocardiographic examination with IB analysis in 29 patients with DCM (20 men, 9 women) before starting bisoprolol therapy and in 15 normal subjects. Standard echocardiographic examination and IB analysis in the left ventricular wall in the 2-dimensional short-axis view were performed and the magnitude of cyclic variation (CV) of IB and calibrated myocardial IB intensity (subtracted pericardial) were obtained from the interventricular septum and the left ventricular posterior wall. Sixteen patients responded to bisoprolol therapy and 13 did not respond after 12 months of full-dose therapy. Calibrated myocardial IB intensity was lower in responders relative to nonresponders in both the interventricular septum (responders, -20.1 +/- 3.6 dB vs nonresponders, -9.8 +/- 5.1 dB, P <.0001; controls, -20.1 +/- 4.4 dB) and posterior wall (responders, -20.6 +/- 3.6 dB vs nonresponders, -14.6 +/- 4.2 dB, P =.0002; controls, -22.7 +/- 3.3 dB). Also, the lower the myocardial intensity in the interventricular septum or posterior wall, the better left ventricular systolic function improved after beta-blocker therapy. However, CV was lower in both DCM groups than in the controls, and CV in the interventricular septum was lower in nonresponders than in responders (responders, 4.0 +/- 4.1 dB vs nonresponders, -0.8 +/- 6. 1 dB, P <.02; controls, 8.3 +/- 2.4 dB). In addition, CV in the posterior wall showed no difference between the 2 DCM groups (responders, 5.6 +/- 1.3 dB vs nonresponders, 5.1 +/- 3.5 dB, P = not significant; controls, 9.6 +/- 2.5 dB). Also, the percent fibrosis on right ventricular endomyocardial biopsy specimens showed no distinctions between these 2 groups (responders, 25.1% +/- 16.1% vs nonresponders, 24.9% +/- 15.0%, P = not significant). CONCLUSIONS: These findings suggest that left ventricular myocardial IB data, especially IB intensity, provide useful information for predicting the response to beta-blocker therapy in patients with DCM. However, right ventricular endomyocardial biopsy findings do not appear to contribute to discriminating between the 2 groups.

Adrenergic beta-Antagonists↗
PubMed2000

Prediction of mean pulmonary wedge pressure using doppler pulmonary venous flow variables in hypertrophic cardiomyopathy.

We examined whether pulmonary venous flow variables, assessed by transthoracic Doppler echocardiography, could predict mean pulmonary wedge pressure in hypertrophic cardiomyopathy. Forty-four patients with no left ventricular systolic dysfunction (left ventricular fractional shortening > or =25%) were studied. Forty patients with systolic dysfunction (dilated cardiomyopathy group) served as control. Mitral and pulmonary venous flow velocity curves were recorded with the pulsed-Doppler method and were related to mean pulmonary wedge pressure obtained by right heart catheterization. In hypertrophic cardiomyopathy group, the systolic (r=-0.15, P=0.335) and diastolic (r=0.35, P=0.022) forward flow velocity were poorly related to mean pulmonary wedge pressure, whereas the velocity of atrial reversal (r=0.68, P<0.001) correlated well with mean pulmonary wedge pressure. In dilated cardiomyopathy group, the systolic (r=-0.51, P=0.001) and diastolic (r=0.60, P<0.001) forward flow velocity were strongly related to mean pulmonary wedge pressure. With the cut-off value set at the velocity of atrial reversal >30 cm/s in hypertrophic cardiomyopathy group, the sensitivity for predicting mean pulmonary wedge pressure >15 mmHg was 79% and the specificity was 73%. In conclusion, the atrial component of the pulmonary venous flow can be used to predict mean pulmonary wedge pressure in hypertrophic cardiomyopathy.

Adult↗
PubMed2000

Using the CATH domain database to assign structures and functions to the genome sequences.

The CATH database of protein structures contains approximately 18000 domains organized according to their (C)lass, (A)rchitecture, (T)opology and (H)omologous superfamily. Relationships between evolutionary related structures (homologues) within the database have been used to test the sensitivity of various sequence search methods in order to identify relatives in Genbank and other sequence databases. Subsequent application of the most sensitive and efficient algorithms, gapped blast and the profile based method, Position Specific Iterated Basic Local Alignment Tool (PSI-BLAST), could be used to assign structural data to between 22 and 36 % of microbial genomes in order to improve functional annotation and enhance understanding of biological mechanism. However, on a cautionary note, an analysis of functional conservation within fold groups and homologous superfamilies in the CATH database, revealed that whilst function was conserved in nearly 55% of enzyme families, function had diverged considerably, in some highly populated families. In these families, functional properties should be inherited far more cautiously and the probable effects of substitutions in key functional residues carefully assessed.

Algorithms↗
PubMed2000

Epidermoid cyst of the penis: a case report and review of the literature.

Penile cysts are uncommon. A case of a 7-year-old boy with an epidermoid cyst of the penis is reported. He had an asymptomatic, slowly growing soft mass in the frenulum of the penis. Excision of the mass was performed, and the diagnosis was epidermoid cyst of the penis. No recurrence has been noted within the year since excision. To our knowledge, there have been no previous reports of malignancy developing in cystic disease of the penis. In such cases, clinicians should attempt more appropriate management, involving either watchful observation or complete excision of the cyst, by considering the embryogenesis and nature of the disease.

Child↗
PubMed2000

Integrated backscatter assessment of left atrial spontaneous echo contrast in chronic nonvalvular atrial fibrillation: relation with clinical and echocardiographic parameters.

Integrated backscatter (IB) provides the quantitative assessment of left atrial spontaneous echo contrast (SEC). The IB intensity of the left atrial cavity relative to the left ventricular cavity is related to atrial thrombus in patients with atrial fibrillation (AF) or sinus rhythm. However, little is known about the relation between the quantitative SEC value of the left atrial cavity and variables implying thromboembolism in nonvalvular AF. To examine this relation, we performed transesophageal echo-cardiography with IB analysis in 65 patients with chronic nonvalvular AF. The quantitative SEC value of the left atrial cavity was defined as the difference between atrial IB intensity and ventricular IB intensity (corrected IB intensity). The corrected IB intensity was correlated with the left atrial dimension (r = 0.25, P =.049), the left atrial appendage velocity (r = -0.41, P <.001), and the duration of AF (r = 0.23, P =. 023). The corrected IB intensity was higher in patients who had a history of hypertension (3.2 +/- 2.2 dB versus 2.0 +/- 1.6 dB, P =. 018), SEC (3.9 +/- 1.9 dB versus 1.4 +/- 1.1 dB, P =.002), and left atrial thrombus (4.5 +/- 2.7 dB versus 2.2 +/- 1.7 dB, P <.001) when compared with those who did not have these abnormalities. The corrected IB intensity was significantly lower in patients with significant mitral regurgitation than in those without it (1.1 +/- 1. 2 dB versus 2.7 +/- 2.0 dB, P =.036). When the cutoff value of the corrected IB intensity was set at >/=2.0 dB, the sensitivity for left atrial thrombus was 78% and the specificity was 55%. In patients with chronic nonvalvular AF, the quantitative SEC value of the left atrial cavity depends on the duration of AF as well as the left atrial dimension and appendage velocity. Although IB may be capable of identifying patients with higher risk of cardiogenic embolism, a large-scale prospective study is needed to actually establish this.

Adult↗
PubMed2000

Identification of hepatic tamoxifen-DNA adducts in mice: alpha-(N(2)-deoxyguanosinyl)tamoxifen and alpha-(N(2)-deoxyguanosinyl)tamoxifen N-oxide.

Tamoxifen-DNA adducts detected in the liver of mice treated with tamoxifen have not yet been identified. In the present study a new type of tamoxifen-DNA adduct, four stereoisomers of alpha-(N:(2)-deoxyguanosinyl)tamoxifen N:-oxide 3'-monophosphate (dG(3'P)-N:(2)-TAM N:-oxide) were prepared as standard DNA adducts by reacting 2'-deoxyguanosine 3'-monophosphate with trans-alpha-acetoxytamoxifen N:-oxide in addition to four stereoisomers of alpha-(N:(2)-deoxyguano- sinyl)tamoxifen 3'-monophosphate (dG(3'P)-N:(2)-TAM) that was reported previously. Liquid chromatography-electrospray ionization-mass spectrometry of the reaction products gave the most abundant ion at m/z 731 ([M - H](-)), which corresponded to dG(3'P)-N:(2)-TAM N:-oxide. The modified products digested by alkaline phosphatase corresponded to the isomers of dG-N:(2)-TAM N:-oxide whose structures were identified previously by mass spectrometry and nuclear magnetic resonance. Using these standard markers, we analyzed the hepatic DNA adducts of female DBA/2 mice treated with tamoxifen at a dosage of 120 mg/kg/day for 7 days by (32)P-post-labeling coupled with an HPLC/radioactive detector. Mixtures of eight isomers of dG(3'P)-N:(2)-TAM and dG(3'P)-N:(2)-TAM N-oxide were separated into six peaks, since each of the cis epimers were not separated under the present HPLC conditions. Nine adducts were detected in all liver samples of mice. An epimer of trans-dG(3'P)-N:(2)-TAM was detected as the principal DNA adduct at a level of 29.0 adducts/10(8) nucleotides, which accounted for 53.3% of the total tamoxifen-DNA adducts. Lesser amounts of cis-dG(3'P)-N:(2)-TAM (2.8%) were also observed. An epimer of the trans-dG(3'P)-N:(2)-TAM N:-oxide (3.9 adducts/10(8) nucleotides) was detected as the third biggest adduct (7.2% of the total). The cis-dG(3'P)-N:(2)-TAM N:-oxide (0.4 adducts/10(8) nucleotides) accounted for 0.7% of the total. Thus, dG(3'P)-N:(2)-TAM and dG(3'P)-N:(2)-TAM N:-oxide were identified in tamoxifen-treated mouse liver.

Animals↗
PubMed2000

A triangle lattice model that predicts transmembrane helix configuration using a polar jigsaw puzzle.

We developed a method of predicting the tertiary structures of seven transmembrane helical proteins in triangle lattice models, assuming that the configuration of helices is stabilized by polar interactions. Triangle lattice models having 12 or 11 nearest neighbor pairs were used as general templates of a seven-helix system, then the orientation angles of all helices were varied at intervals of 15 degrees. The polar interaction energy for all possible positions of each helix was estimated using the calculated polar indices of transmembrane helices. An automated system was constructed and applied to bacteriorhodopsin, a typical membrane protein with seven transmembrane helices. The predicted optimal and actual structures were similar. The top 100 predicted helical configurations indicated that the helix-triangle, CFG, occurred at the highest frequency. In fact, this helix-triangle of bacteriorhodopsin forms an active proton-pumping site, suggesting that the present method can identify functionally important helices in membrane proteins. The possibility of studying the structure change of bacteriorhodopsin during the functional process by this method is discussed, and may serve to explain the experimental structures of photointermediate states.

Algorithms↗