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Biomedical subjects

T Akasaka

Publications and source records attributed to T Akasaka.

At least 55 records · Page 3Linked to original sources

Value of acceleration flow and the prestenotic to stenotic coronary flow velocity ratio by transthoracic color Doppler echocardiography in noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty.

OBJECTIVES: The study evaluated the value of coronary flow velocity measurement by transthoracic color Doppler echocardiography (TTCDE) for the noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty (PTCA) for left anterior descending coronary artery (LAD) lesions. BACKGROUND: Recent advances in TTCDE provide coronary flow velocity measurements in the LAD under the guidance of color flow mapping. METHODS: We studied 53 patients who underwent successful PTCA for LAD lesions and follow-up coronary angiography (18 patients with restenosis [Group-R], 35 patients without restenosis [Group-N]). We searched localized color aliasing corresponding to local flow acceleration to obtain coronary flow velocity at PTCA sites in the LAD. When localized aliasing was detected, we measured coronary flow velocity at the aliasing (stenotic site) and the prestenotic site. RESULTS: Using TTCDE, it was possible to measure mean diastolic velocity (MDV) in the LAD in 41 (77%) of 53 patients (14 of 18 patients in Group-R; 27 of 35 patients in Group-N). Localized aliasing was displayed by color flow mapping in 14 (100%) of 14 patients in Group-R, and 15 (56%) of 27 patients in Group-N. Stenotic MDV in Group-R was significantly higher than that in Group-N (60.3 +/- 21.1 vs. 35.1 +/- 7.6 cm/s, p < 0.01), although prestenotic MDV did not differ between Group-R and Group-N (20.2 +/- 3.0 vs. 19.6 +/- 2.3 cm/s). There were significant differences in the prestenotic to stenotic MDV ratio between Group-R and Group-N (0.36 +/- 0.10 vs. 0.57 +/- 0.09, p < 0.001). Localized aliasing with the prestenotic to stenotic MDV ratio <0.45 as the optimal cutoff value had a sensitivity of 86% and a specificity of 93% for the presence of restenosis in LAD lesions. CONCLUSIONS: Detection of localized color aliasing and measurement of the prestenotic to stenotic MDV ratio in the LAD by TTCDE are useful in the noninvasive diagnosis of restenosis after PTCA for LAD lesions.

Aged↗

Deficiency of the macrophage migration inhibitory factor gene has no significant effect on endotoxaemia.

By targeted disruption of the MIF gene, we have established a mouse strain deficient in macrophage (Mphi) migration inhibitory factor (MIF). Despite previous reports indicating an essential role of MIF in endotoxaemia, an injection of lipopolysaccharide (LPS) into the MIF-deficient mice (maintained under specific pathogen-free conditions) caused shock. No significant difference was detected between the MIF-deficient mutant and normal mice in susceptibility to LPS for endotoxaemia or tumour necrosis factor-alpha (TNF-alpha) formation upon LPS injection. Peritoneal Mphi from the two strains produced TNF-alpha in response to LPS with similar dose responses. Dexamethasone suppressed the LPS-induced TNF-alpha response of Mphi, but no difference was detected between the Mphi from the two strains. These results suggest that endogenous MIF has no significant effect on the LPS-induced TNF-alpha production and no effect on suppression of the response by glucocorticoids. Thus, MIF is not crucial for LPS-induced immune responses leading to shock.

Animals↗

Molecular and clinical features of non-Burkitt's, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene.

PURPOSE: t(8;14)(q24;q32) and/or c-MYC/immunoglobulin heavy-chain (IGH) fusion gene have been observed not only in Burkitt's lymphoma (BL) but also in a proportion of non-BL, diffuse large-cell lymphoma of B-cell type (DLCL). We explored molecular features of DLCL with c-MYC/IGH fusion and the impact of this genetic abnormality on clinical outcome of DLCL. PATIENTS AND METHODS: A total of 203 cases of non-BL DLCL were studied. Genomic DNA extracted from tumor tissues was subjected to long-distance polymerase chain reaction (LD-PCR) using oligonucleotide primers for exon 2 of c-MYC and for the four constant region genes of IGH. RESULTS: Twelve cases (5.9%) showed positive amplification; one had a c-MYC/Cmicro, nine had a c-MYC/Cgamma, and two had a c-MYC/Calpha fusion sequence. Restriction and sequence analysis of the LD-PCR products, ranging from 2.3 to 9.4 kb in size, showed that breakage in the 12 cases occurred within a 1.5-kb region that included exon 1 of c-MYC in combination with breakpoints at the switch regions of IGH (10 of 12). In 10 cases, Myc protein encoded by the fusion genes demonstrated mutations and/or deletions. Six cases had additional molecular lesions in BCL-2 or BCL-6 and/or p53 genes. The age range of the 12 patients was 44 to 86 years, with a median age of 65.5 years. Five patients had stage I/II disease, and seven had stage III/IV disease. Lactate dehydrogenase was elevated in nine of 11 subjects. Seven showed involvement of the gastrointestinal tract. All patients were treated by surgery and/or chemoradiotherapy; six died of the disease within 1 year, resulting in the poorest 1- and 2-year survival rates among DLCL subgroups. CONCLUSION: The c-MYC/IGH fusion gene of DLCL is identical to that of the sporadic type of BL (sBL). DLCL with c-MYC/IGH shares clinical features with sBL but is characterized further by an older age distribution.

Adult↗

Pulse dispersion due to atrial fibrillation causes arterial thrombosis in a rabbit experimental model.

Thrombosis associated with atrial fibrillation (AF) is usually caused by a left atrial (LA) thrombus, but it is not always detected. The present study was based on the hypothesis that abnormalities in peripheral artery are responsible for the ischemic stroke associated with AF. Peripheral arterial coagulability was investigated in a rabbit experimental model in which AF was induced by high-frequency stimulation of the right atrium, creating stenosis of the carotid artery together with endothelial damage. The rabbits were classified into 4 groups: (i) sinus rhythm only (group 1), (ii) sinus rhythm after 6 h of pacing (group 2), (iii) short AF (continuous pacing for 5 min; group 3) and (iv) long AF (continuous pacing for 6 h: group 4). The carotid blood flow developed a typical pattern, called cyclic flow reductions (CFRs), the frequency of which (CFRF) was 18.59+/-2.85 in AF (group 3+4) compared with 14.46+/-2.1 in sinus rhythm (group 1+2) (p<0.0005). Among the groups with AF, correlation analysis showed an association between CFRF and pulse dispersion (p<0.02, r=0.58). This study suggests that the distinctive hemodynamic effects with AF, in particular pulse dispersion, substantively influence thrombus formation on injured vascular endothelium.

Animals↗

The t(9;14)(p13;q32) translocation in B-cell non-Hodgkin's lymphoma.

t(9;14)(p13;q32) is a rare but recurring translocation found in a subset of B-cell non-Hodgkin's lymphoma (B-NHL). These lymphomas share clinical features with chronic lymphocytic leukemia and are further characterized by plasmacytoid differentiation of lymphoma cells. Molecular cloning of t(9;14)(p13;q32) revealed juxtaposition of the PAX5 to the immunoglobulin heavy chain gene (IGH), although breakpoints on both genes were variable. The PAX5 gene encodes the BSAP (B-cell-specific activator protein) transcription factor, which is expressed throughout the process of B-cell development except in terminally differentiated plasma cells. t(9;14)(p13;q32) consistently leaves the PAX5 coding region intact, most likely resulting in deregulated expression of the gene product due to the proximity of IGH. The majority cases of B-cell tumors expressed considerable levels of PAX5/BSAP irrespective of whether they exhibited t(9;14)(p13;q32), suggesting that quantitative differences in expression level alone may not account for the development of this particular subtype of B-NHL.

Amino Acid Sequence↗

Prediction of progression or regression of type A aortic intramural hematoma by computed tomography.

BACKGROUND: It has been reported that early surgery should be required for patients with type A aortic intramural hematoma (IMH) because it tends to develop classic aortic dissection or rupture. However, the anatomic features of type A IMH that develops dissection or rupture are unknown. The purpose of this study was to investigate the predictors of progression or regression of type A IMH by computed tomography (CT). METHODS AND RESULTS: Twenty-two consecutive patients with type A IMH were studied by serial CT images. Aortic diameter and aortic wall thickness of the ascending aorta were estimated in CT images at 3 levels on admission and at follow-up (mean 37 days). We defined patients who showed increased maximum aortic wall thickness in the follow-up CT (n=9) or died of rupture (n=1) as the progression group (n=10). The other 12 patients, who all showed decreased maximum wall thickness, were categorized as the regression group. In the progression group, the maximum aortic diameter in the initial CT was significantly greater than that in the regression group (55+/-6 vs 47+/-3 mm, P=0.001). A Cox regression analysis revealed that the maximum aortic diameter was the strongest predictor for progression of type A IMH. We considered the optimal cutoff value to be 50 mm for the maximum aortic diameter to predict progression (positive predictive value 83%, negative predictive value 100%). CONCLUSIONS: Maximum aortic diameter estimated by the initial CT images is predictive for progression of type A IMH.

Aged↗

Can coronary blood flow velocity pattern after primary percutaneous transluminal coronary angioplasty [correction of angiography] predict recovery of regional left ventricular function in patients with acute myocardial infarction?

BACKGROUND: In the era of primary percutaneous transluminal coronary angioplasty (PTCA), it is important to judge whether myocardium within acute ischemic injury is viable. This study sought to investigate parameters derived from the coronary blood flow velocity spectrum immediately after primary PTCA in patients with acute myocardial infarction and to elucidate the clinical value of coronary blood flow measurement in predicting myocardial viability. METHODS AND RESULTS: Using a Doppler guidewire, we measured coronary blood flow velocity after successful completion of primary PTCA in 23 consecutive patients with acute anterior myocardial infarction. Regional wall motion was analyzed to estimate anterior wall motion score index (A-WMSI) by echocardiography before PTCA and 1 month after the onset of symptoms. Average systolic peak velocity (ASV) and deceleration time of diastolic flow velocity (DDT) significantly correlated to 1-month A-WMSI (r=-0.54, P=0.007 and r=-0.62, P=0.002, respectively), and optimal cutoff values to predict viable myocardium (defined as 1-month A-WMSI </=2.0) were 6.5 cm/s for ASV and 600 ms for DDT (sensitivity=0.79, specificity=0.89 and sensitivity=0.86, specificity=0.89, respectively). ASV and DDT also correlated weakly to the change in A-WMSI (r=0.46, P=0.03 and r=0.49, P=0.02, respectively). CONCLUSIONS: Low ASV and rapid DDT of coronary blood flow spectrum immediately after primary PTCA reflects a greater degree of microvascular damage in the risk area. Analysis of coronary blood flow spectrum immediately after primary PTCA by use of a Doppler guidewire is useful in predicting recovery of regional left ventricular function.

Aged↗

Conjugation of plasmid DNAs with lactose via diazocoupling enhances resistance to restriction enzymes and acquires binding affinity to galactose-specific lectin.

Oligosaccharide-plasmid DNA conjugates were synthesized simply and effectively via the diazocoupling method. Plasmids (pUC19, pTRI-beta-actin, and pEGFP-C1) were treated with an N-beta-lactoside-substituted diazonium salt to yield diazocoupling products with degree of substitutions of 2.5-3.1 mol% of overall nucleobases. The lactose-pUC19 conjugate was found to resist restriction enzymes more strongly than the nonconjugated plasmid DNA and to acquire a strong binding affinity to galactose-specific lectin RCA(120). The diazocoupling modification of pTRI-beta-actin plasmid DNA little influenced in vitro transcription with T7 RNA polymerase. When lactose-pEGFP-C1 conjugate was transfected to baby hamster kidney (BHK) cells by means of cationic lipids, transduced gene was expressed in BHK cells similarly with the nonconjugated pEGFP-C1. The modification of plasmid DNA with carbohydrate enhanced the resistance to restriction enzymes and developed a strong binding affinity to galactose-specific lectin.

Actins↗

Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development.

During axial skeleton development, the notochord is essential for the induction of the sclerotome and for the subsequent differentiation of cartilage forming the vertebral bodies and intervertebral discs. These functions are mainly mediated by the diffusible signaling molecule Sonic hedgehog. The products of the paired-box-containing Pax1 and the mesenchyme forkhead-1 (Mfh1) genes are expressed in the developing sclerotome and are essential for the normal development of the vertebral column. Here, we demonstrate that Mfh1 like Pax1 expression is dependent on Sonic hedgehog signals from the notochord, and Mfh1 and Pax1 act synergistically to generate the vertebral column. In Mfh1/Pax1 double mutants, dorsomedial structures of the vertebrae are missing, resulting in extreme spina bifida accompanied by subcutaneous myelomeningocoele, and the vertebral bodies and intervertebral discs are missing. The morphological defects in Mfh1/Pax1 double mutants strongly correlate with the reduction of the mitotic rate of sclerotome cells. Thus, both the Mfh1 and the Pax1 gene products cooperate to mediate Sonic hedgehog-dependent proliferation of sclerotome cells.

Animals↗

Noninvasive assessment of hemodynamic subsets in patients with acute myocardial infarction using digital color Doppler velocity profile integration and pulmonary venous flow analysis.

Four major hemodynamic subsets from cardiac index (CI) and mean pulmonary artery (PA) wedge pressure with a PA catheter usually reflect clinical status and prognosis of patients with acute myocardial infarction (AMI). Recently, a new color Doppler technique has been developed for automated cardiac output measurements (ACOM). Color Doppler echocardiography also provides noninvasive estimation of PA wedge pressure from pulmonary venous (PV) flow analysis. This study evaluates the value of ACOM and PV flow analysis by color Doppler echocardiography for the assessment of hemodynamic subsets in patients with AMI. We performed ACOM and PV flow analysis by color Doppler echocardiography in 55 patients with AMI who underwent hemodynamic assessment with a PA catheter. From both noninvasive and invasive methods, we classified hemodynamic subsets as follows: subset I: normal hemodynamics (CI >2.2 L/min/m2, PA wedge pressure < or =18 mm Hg); subset II: pulmonary congestion (CI >2.2 L/min/m2, PA wedge pressure >18 mm Hg); subset III: peripheral hypoperfusion (CI < or =2.2 L/min/m2, PA wedge pressure < or =18 mm Hg); and subset IV: pulmonary congestion and peripheral hypoperfusion (CI < or =2.2 L/min/m2, PA wedge pressure >18 mm Hg). Doppler assessment of hemodynamic subsets was possible in 50 of 55 patients (91%). CI from ACOM correlated well with that from the thermodilution method (r = 0.94) with close agreement. There was a good correlation between the systolic fraction (systolic velocity-time integral expressed as a fraction of the sum of systolic and diastolic velocity-time integrals) of PV flow and PA wedge pressure measured from cardiac catheterization (r = -0.83). When we determined the value of 45% in the systolic fraction as the cut-off point in predicting >18 mm Hg in PA wedge pressure, there was 90% (45 of 50 patients) agreement between noninvasive and invasive hemodynamic subsets. Thus, ACOM and PV flow analysis by color Doppler echocardiography is useful in the noninvasive assessment of hemodynamic subsets in patients with AMI.

Adult↗

Noninvasive evaluation of pulmonary capillary wedge pressure in patients with acute myocardial infarction by deceleration time of pulmonary venous flow velocity in diastole.

OBJECTIVES: This study investigates the correlation between deceleration time of diastolic pulmonary venous flow (PV-DT) and of early filling mitral flow (LV-DT), and pulmonary capillary wedge pressure (PCWP) in patients with acute myocardial infarction (AMI). BACKGROUND: An earlier study suggests that Doppler-derived LV-DT provides an accurate means of estimating PCWP in postinfarction patients with left ventricular systolic dysfunction. Furthermore, recent studies have suggested that PCWP correlates better with PV-DT than with LV-DT. However, the value of PV-DT and LV-DT for assessment of PCWP in patients with AMI has not been evaluated. METHODS: In 141 consecutive patients with AMI, we measured PV-DT and LV-DT by Doppler echocardiography, and compared these variables with PCWP measured using a Swan-Ganz catheter. RESULTS: There was a weak negative correlation between the LV-DT and PCWP (r = -0.54). Although the sensitivity of < or =130 ms in LV-DT in predicting > or =18 mm Hg in PCWP was high (86%), its specificity was low (59%). On the other hand, a very close negative correlation was found between PV-DT and PCWP (r = -0.89). The sensitivity and specificity of < or =160 ms in PV-DT in predicting > or =18 mm Hg in PCWP were 97% and 96%, respectively. CONCLUSIONS: In patients with AMI, Doppler-derived PV-DT showed a stronger correlation with PCWP than LV-DT.

Adult↗

CD44 variant isoform CD44v10 expression of human melanoma cell lines is upregulated by hyaluronate and correlates with migration.

CD44, a multifunctional adhesion receptor involved in cell-cell and cell-matrix interactions, plays an important role in the local progression and metastasis of malignant tumours. We investigated relative CD44 variant isoform mRNA expression in six human melanoma cell lines and determined cell migration on hyaluronic acid (HA) coated substrates. Haematopoietic form (CD44H) mRNA expression increased in all melanoma cell lines after plating on HA, whereas the relative CD44 variant exon 10 (CD44v10) mRNA expression increased in only three of the cell lines. Cell migration rates increased on substrates coated with HA in the three CD44v10-positive cell lines, whereas the three CD44v10-negative cell lines showed no modification in migration rates. Immunofluorescent labelling of CD44v10 revealed increased expression with plaques localized to the periphery of cells. Cell lines with increased relative CD44v10 expression exhibited significantly higher mean migration rates on HA. These results indicate that CD44v10 expression functionally relates to melanoma cell migration and suggest that interaction between CD44v10 and HA plays a role in the variable tissue invasion and aggressiveness of different melanoma clones.

Adjuvants, Immunologic↗

A case of systemic sclerosis associated with gastric cancer.

We report the case of a 47-year-old woman who began to experience stiffness and Raynaud's phenomenon of her fingers and toes as well as easy fatigability approximately one year before initial evaluation. Histopathologic examination revealed dense fibrosis and perivascular lymphoid cell infiltration in the dermis. The patient's diagnosis was systemic sclerosis (SSc). Esophageal sclerosis was not revealed, but an early type IIb carcinoma of the gastric antrum was noted by endoscopic examination. Other recent reports have discussed the association of SSc with various malignant carcinomas. We also reviewed the literature for associations between SSc and gastric cancer in Japanese patients.

Biopsy, Needle↗

Cloning, expression, and enzymatic characterization of Pseudomonas aeruginosa topoisomerase IV.

The topoisomerase IV subunit A gene, parC homolog, has been cloned and sequenced from Pseudomonas aeruginosa PAO1, with cDNA encoding the N-terminal region of Escherichia coli parC used as a probe. The homolog and its upstream gene were presumed to be parC and parE through sequence homology with the parC and parE genes of other organisms. The deduced amino acid sequence of ParC and ParE showed 33 and 32% identity with that of the P. aeruginosa DNA gyrase subunits, GyrA and GyrB, respectively, and 69 and 75% identity with that of E. coli ParC and ParE, respectively. The putative ParC and ParE proteins were overexpressed and separately purified by use of a fusion system with a maltose-binding protein, and their enzymatic properties were examined. The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. So, the cloned genes were identified as P. aeruginosa topoisomerase IV genes. The inhibitory effects of quinolones on the activities of topoisomerase IV and DNA gyrase were compared. The 50% inhibitory concentrations of quinolones for the decatenation activity of topoisomerase IV were from five to eight times higher than those for the supercoiling activities of P. aeruginosa DNA gyrase. These results confirmed that topoisomerase IV is less sensitive to fluoroquinolones than is DNA gyrase and may be a secondary target of new quinolones in wild-type P. aeruginosa.

4-Quinolones↗

[Evaluation of mitral valve lesions in patients with infective endocarditis by three-dimensional echocardiography].

Recognition of the involved lesions is extremely important in mitral valve repair for infective endocarditis. Transesophageal echocardiography (TEE) is more sensitive for the detection of lesions than transthoracic echocardiography, but localization of the lesions is sometimes difficult by TEE. Three-dimensional (3D) TEE provides images of the mitral valve similar to the view from the left atrium. This study evaluated the value of 3D echocardiography for the diagnosis of involved lesions in 12 patients who underwent surgery for mitral regurgitation due to infective endocarditis. The location of the lesion in the mitral valve was classified as the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet, respectively. In all patients, the involved sites were confirmed at operation. The sensitivities of 3D TEE for detecting the lesions at the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet were 100%, 78% and 67%, and 100%, 100% and 100%, respectively. The specificities were 90%, 100% and 78%, and 100%, 100% and 100%, respectively. The lesions diagnosed by 3D TEE coincided with lesions confirmed at operation in 23 (92%) of 25 lesions. 3D TEE is useful for the assessment of the involved lesion of the mitral valve in patients with infective endocarditis.

Echocardiography, Three-Dimensional↗

[Usefulness of tissue harmonic imaging for the detection of left ventricular endocardial border].

Assessment of segmental wall motion is one of the most challenging tasks in echocardiography. One major limitation is impairment of echocardiographic regional wall motion by incomplete endocardial definition. The newly developed tissue harmonic imaging method may improve the detection of left ventricular endocardial border. This study examined the impact of native tissue harmonic imaging on endocardial border definition. Fundamental and harmonic imaging were compared for detecting the endocardial border in 96 segments of 16 patients (age 54 +/- 8 years). Visualization of endocardial border was better with harmonic imaging than with fundamental mode in 49% (47 of 96 segments). Thus, tissue harmonic imaging has a significant impact on endocardial border definition.

Cardiomyopathies↗

[Appropriate duration of postoperative pain relief by continuous epidural infusion in patients receiving hysterectomy or ovarian tumor resection: comparison of three methods].

We evaluated effects of continuous epidural infusion on postoperative pain, and frequency of its side effects. Patients who had undergone elective gynecological operations were randomly allocated into three groups by difference in duration of indwelling of epidural catheters: patients receiving epidural block only during operations (group M); patients receiving continuous epidural infusion for 2 postoperative days (group B 2); patients receiving continuous epidural infusion for 4 postoperative days (group B 4). In group M, morphine 3 mg and 1 or 2% lidocaine 5-7 ml were given before the start of operation, and epidural catheter was removed after the end of operations. In group B 2 and B 4, morphine 2 mg and 1 or 2% lidocaine 5-7 ml were given before the start of operation, and morphine 8 mg in 50 ml of 0.25% bupivacaine was continuously infused at a rate of 0.5-1 ml.hr-1. We evaluated visual analogue scale (VAS) at rest and moving, and verbal descriptor pain score. Frequencies of supplementary analgesics, vomiting and nausea, residual urine volume after removal of bladder catheter, and timing to initiation of bowel movement after operation were also recorded. VAS at rest was significantly higher in group M than in groups B 2 and B 4 for 2 postoperative days, but no significant difference was seen between the three groups for three postoperative days. VAS at moving did not differ between the 3 groups. Verbal descriptor pain score was significantly higher in group M than in groups B 2 and B 4 for 3 postoperative days, but it was not different between groups B 2 and B 4. In group B 2, patients complained increased abdominal pain after removing catheters. Frequencies of supplementary analgesics were 3.7, 0.6 and 0.4 times in group M, B 2, B 4, respectively. Times to initiation of bowel movement after operation were 39.8, 46.5 and 61.7 hrs in group M, B 2, and B 4, respectively, and most patients in group B 4 felt uncomfortable. These results suggest that continuous epidural analgesia for 2 postoperative days is appropriate, but the duration should be determined according to patient's conditions and complications.

Adult↗