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Biomedical subjects

T Akasaka

Publications and source records attributed to T Akasaka.

At least 127 records · Page 7Linked to original sources

Improved visualization of pulmonary venous flow Doppler signal by intravenous injection of sonicated albumin.

Color Doppler signal of pulmonary venous flow was enhanced, and the optimal recordings could be detected in most cases after intravenous injection of sonicated albumin. Improved visualization of pulmonary venous flow Doppler signal by intravenous injection of sonicated albumin should have important clinical implications for the assessment of left ventricular diastolic function by using Doppler technique.

Adult↗

Application of long-distance polymerase chain reaction to detection of junctional sequences created by chromosomal translocation in mature B-cell neoplasms.

Junctional sequences created by chromosomal translocations in mature B-cell neoplasms, which involve immunoglobulin gene loci (IG) and putative proto-oncogenes on reciprocal partner chromosomes, are unique to neoplastic cells characterized by particular histological and immunological phenotypes. To establish a rapid and sensitive method to detect neoplastic cells carrying a specific chromosomal translocation, we have developed a novel strategy based on long-distance polymerase chain reaction (LD-PCR) amplification. Genomic DNA was extracted from tumor cells carrying t(14;19)(q32;q13), t(8;14)(q24;q32), t(3;22)(q27;q11), t(2;3)(p12;q27), or t(3;14)(q27;q32). Thirty-two to 35-mer oligonucleotide primer pairs were designed to be complementary to exons or flanking sequences of the BCL3, c-MYC and BCL6 oncogenes, and to IG constant region genes. LD-PCR with a newly available Taq polymerase for longer product synthesis successfully amplified fragments representing BCL3/C alpha junctional sequences for t(14;19); c-MYC/C mu, c-MYC/C gamma, and c-MYC/C alpha for t(8;14); BCL6/C lambda for t(3;22); BCL6/C kappa for t(2;3); 5'-BCL6/C mu, and 5'-BCL6/C gamma for t(3;14). In Burkitt's lymphoma/leukemia, all materials in which c-MYC rearrangements were detectable by conventional Southern blot hybridization showed positive LD-PCR amplification. The sizes of the amplified fragments varied from 1.8 kb to 12 kb, and these were specific to each material. Serial dilution of tumor cells or DNA in negative materials demonstrated a single band on agarose gel electrophoresis stained with ethidium bromide at a level of sensitivity of 10(-3), and hybridization with radioactive probe improved the level by one order of magnitude (1 cell in 10(4)), indicating that this LD-PCR approach is a sensitive technique capable of detecting minimal residual disease. Thus, the present study provided a useful tool for diagnosis and subsequent management of B-cell neoplasms characterized by specific chromosomal translocations.

Base Sequence↗

Comparison of relation of systolic flow of the right coronary artery to pulmonary artery pressure in patients with and without pulmonary hypertension.

Systolic flow velocity is relatively predominant over diastolic velocity in the proximal right coronary artery and right ventricular branch in patients with normal systolic pulmonary artery pressure. The amount of systolic flow velocity reduction in the proximal right coronary artery and right ventricular branch is inversely related to the level of pulmonary hypertension.

Adolescent↗

Flow reserve capacity of left internal thoracic artery 23 years after Vineberg procedure.

Graft flow volume and flow reserve were assessed by Doppler echocardiography 23 years after Vineberg left internal thoracic artery implantation. Angiography showed good patency of the left internal thoracic artery, and the flow velocity profile was as biphasic as that of the coronary circulation. Drug-stressed test showed a physiologic reactivity of the Vineberg left internal thoracic artery but less response than that of a directly anastomosed left internal thoracic artery.

Blood Flow Velocity↗

Rearrangement of the BCL6 gene in B-cell lymphoid neoplasms: comparison with lymphomas associated with BCL2 rearrangement.

We report a series of B-cell neoplasms with regard to rearrangement of the BCL6 gene on chromosome band 3q27. Southern blot analysis using probes from the major translocation cluster (MTC) region of the BCL6 revealed rearrangement in 21/197 patients (10.7%) with B-cell neoplasms studied at presentation, and 11/25 patients (44%) first studied at relapse. In non-Hodgkin's lymphoma (NHL) studied at diagnosis, rearrangements of the BCL6 gene were not closely associated with a specific histopathologic subtype but distributed in subcategories in the Working Formulation. The incidence in follicular lymphoma was 12.1%, with significantly higher frequency in mixed and large cell subtypes, and that in diffuse aggressive lymphoma was 14.1%. Comigration analysis using probes from the immunoglobulin genes revealed association of the BCL6 gene with one of the three immunoglobulin loci in 9/25 cases analysed. A comparative study between NHL associated either with BCL2 or BCL6 rearrangement showed that advanced disease and bone marrow involvement were more frequent in BCL2(+) NHL. In contrast, extranodal involvement was more frequently observed in the BCL6(+) NHL. The survival curve of BCL6(+) NHL was characterized by a rapid decline followed by a plateau. Of the total of 32 BCL6(+) patients, six carried both BCL2 and BCL6 rearrangements; five of these six showed clinicopathological properties characteristic of follicular lymphoma, suggesting that the presence of the two genetic abnormalities does not necessarily have synergistic effects on malignant phenotypes. The high level of BCL6 expression in follicular lymphoma cell lines carrying a BCL2 rearrangement suggests that the deregulated BCL2 gene may have an effect on the development of genetic abnormalities of the BCL6 gene. The present study suggests that BCL6 gene rearrangement is primarily involved in large cell lymphoma irrespective of growth pattern of neoplastic cells, and that BCL6(+)BCL2(-) NHL could be curable with modern intensive chemotherapy.

Aged↗

Multiple basaloid cell hamartoma with alopecia and autoimmune disease (systemic lupus erythematosus).

We report a 22-year-old Japanese woman with multiple basaloid cell hamartoma with alopecia and autoimmune disease (systemic lupus erythematosus). She presented with infiltrated large annular, brown-violet, erythematous plaques with atrophic areas in the center on her right cheek, left abdomen and left knee. She also had progressive multiple follicular keratotic papules on her scalp, face, neck, and both axilla and hair loss from her scalp, eyebrow, and axilla. Serologically, rheumatoid factor (+ + +), rheumatoid arthritis hemagglutination test (x1280), and anti-nuclear antigen (x160) were positive. Histological findings of the annular lesion showed liquefaction degeneration of basal cells, lymphocytic infiltration around hair follicles and capillaries, and panniculitis with lymphoid cell infiltration, which was diagnosed as lupus erythematosus profundus. The histological findings of multiple follicular papular lesions of the scalp and neck showed aggregations of basaloid cells, partially with hair-bulb-like structures, which was diagnosed as trichoepithelioma. Taken together, the histogenesis of multiple basaloid cell hamartoma is thought to share the same basis with autoimmune disease.

Adult↗

p53 mutation in B-cell lymphoid neoplasms with reference to oncogene rearrangements associated with chromosomal translocations.

We investigated mutations of the p53 tumor suppressor gene in B-cell lymphoid neoplasms with reference to oncogene rearrangements associated with specific chromosomal translocations. These included 15 patients with a BCL1/PRAD1 gene rearrangement and/or PRAD1 overexpression, 45 with a BCL2 rearrangement, 2 with a BCL3 rearrangement, 24 with a BCL6 rearrangement, and 6 with both BCL2 and BCL6 rearrangements. Thirty-six patients lacked detectable oncogene rearrangements. Genomic DNA was isolated from involved tissues or leukemic cells obtained at diagnosis and/or at relapse, and established cell lines. Polymerase chain reaction-mediated single-strand conformation polymorphism analysis and direct sequencing were performed to analyze abnormalities of the p53 gene. We detected p53 gene alterations in 18 of 128 patients, representing 21 of the total 151 materials analyzed. In the total of 66 patients with an oncogene rearrangement studied at diagnosis, only one had a mutation; however, 6 of 37 patients studied at relapse showed p53 mutations. Sequential analysis revealed that the p53 mutation was closely associated with transformation from follicular lymphoma to large cell lymphoma, exclusively in BCL2-positive lymphoma cases. Two of 13 mutations observed in oncogene rearrangement-positive cases and cell lines were transitions at CpG dinucleotides. In contrast, the relationship between p53 mutations and clinical behavior in oncogene rearrangement-negative cases was variable; 5 patients including one with indolent follicular lymphoma were positive for p53 mutation at initial presentation, and 2 of the 5 showed prolonged disease-free survival. Our findings suggest that p53 alteration exhibits diverse functions in the development and progression of B-cell tumors related to the presence or absence of oncogene rearrangement, and that chemotherapy-related influences may be involved in the occurrence of progression-associated p53 mutations.

Cyclin D1↗

Attachment, spreading and migration of melanoma cells on vitronectin. The rôle of alpha V beta 3 and alpha V beta 5 integrins.

Recent in situ studies suggest the alpha V beta 3 integrin is a tumour progression marker in melanoma. We analyzed 5 human melanoma cell lines for their expression of the vitronectin binding alpha V beta 3 and alpha V beta 5 integrins using flow cytometry. The role of these receptors in cell attachment, spreading and migration was investigated using attachment assays, video time lapse spreading and migration assays and with function blocking monoclonal antibodies. Cell lines derived from later stages of tumor progression exhibited high levels of alpha V beta 3 expression, whereas no similar correlation with alpha V beta 5 expression was identified. Cell attachment, spreading and migration response on vitronectin correlated well with the expression level of the alpha V beta 3 but not the alpha V beta 5 vitronectin receptor. Blocking of the alpha V beta 3 integrin resulted in a significant decrease in cell attachment, spreading and motility whereas the function blocking antibody against the alpha V beta 5 integrin only inhibited cell attachment in cell lines with the highest level of expression of this integrin. Taken together, our study indicates that the level of expression of the alpha V beta 3 and alpha V beta 5 integrins is heterogeneous in melanoma cell lines and that the alpha V beta 5 integrin, if present, may function only during the initial cell attachment whereas the alpha V beta 3 plays an important role in cell spreading and cell migration as well.

Antibodies, Blocking↗

Quinolone-resistant mutants of escherichia coli DNA topoisomerase IV parC gene.

Escherichia coli quinolone-resistant strains with mutations of the parC gene, which codes for a subunit of topoisomerase IV, were isolated from a quinolone-resistant gyrA mutant of DNA gyrase. Quinolone-resistant parC mutants were also identified among the quinolone-resistant clinical strains. The parC mutants became susceptible to quinolones by introduction of a parC+ plasmid. Introduction of the multicopy plasmids carrying the quinolone-resistant parC mutant gene resulted in an increase in MICs of quinolones for the parC+ and quinolone-resistant gyrA strain. Nucleotide sequences of the quinolone-resistant parC mutant genes were determined, and missense mutations at position Gly-78, Ser-80, or Glu-84, corresponding to those in the quinolone-resistance-determining region of DNA gyrase, were identified. These results indicate that topoisomerase IV is a target of quinolones in E. coli and suggest that the susceptibility of E. coli cells to quinolones is determined by sensitivity of the targets, DNA gyrase and topoisomerase IV.

Anti-Infective Agents↗

Use of intravascular ultrasound for in vivo assessment of changes in intimal thickness of angiographically normal saphenous vein grafts one year after aortocoronary bypass surgery.

OBJECTIVE: To use intravascular ultrasound in vivo to evaluate changes in the intimal thickness of angiographically normal saphenous vein grafts one year after implantation. DESIGN: Fifteen saphenous vein grafts in 12 patients were examined one month and 12 months after aortocoronary bypass graft surgery with intravascular ultrasound using a 30 MHz transducer. None of the grafts examined showed any angiographic abnormalities. The intimal thickness and intimal area of the graft in the proximal portion were measured on intravascular ultrasound images obtained one month and 12 months after operation. SETTING: General hospital. PATIENTS: Twelve patients who underwent aortocoronary bypass graft surgery. RESULTS: The ultrasound images showed a thin-walled graft with a thin intima one month after operation (mean (SD)) (0.31 (0.09) mm). The intimal thickness of the graft increased significantly to 0.65 (0.08) mm (P < 0.001) 12 months after operation. The intimal area of the graft was 0.90 (0.80) mm2 one month after operation. 12 months after operation the intimal area had increased significantly to 5.26 (1.38) mm2 (P < 0.001). CONCLUSION: Intravascular ultrasound in vivo showed that one year after implantation angiographically normal saphenous vein grafts had a thicker intima than one month after implantation.

Coronary Artery Bypass↗

A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton.

Segment identity in both invertebrates and vertebrates is conferred by spatially restricted distribution of homeotic gene products. In Drosophila, the expression of Homeobox genes during embryogenesis is initially induced by segmentation gene products and then maintained by Polycomb group and Trithorax group gene products. Polycomb group gene homologs are conserved in vertebrates. Murine mel-18 and closely related bmi-1 are homologous to posterior sex combs and suppressor two of zeste. Mel-18 protein mediates a transcriptional repression via direct binding to specific DNA sequences. To gain further insight into the function of Mel-18, we have inactivated the mel-18 locus by homologous recombination. Mice lacking mel-18 survive to birth and die around 4 weeks after birth after exhibiting strong growth retardation. Similar to the Drosophila posterior sex combs mutant, posterior transformations of the axial skeleton were reproducibly observed in mel-18 mutants. The homeotic transformations were correlated with ectopic expression of Homeobox cluster genes along the anteroposterior axis in the developing paraxial mesoderm. Surprisingly, mel-18-deficient phenotypes are reminiscent of bmi-1 mutants. These results indicate that the vertebrate Polycomb group genes mel-18 and bmi-1, like Drosophila Polycomb group gene products, might play a crucial role in maintaining the silent state of Homeobox gene expression during paraxial mesoderm development.

Animals↗

Specific binding of allergenic soybean protein Gly m Bd 30K with alpha'- and alpha-subunits of conglycinin in soy milk.

When defatted soy milk was ultracentrifuged, 34kDa allergenic soyabean protein Gly m Bd 30 K was more abundant in the precipitate than in the supernatant by an SDS-PAGE analysis. The addition of more than 10 mM of 2-mercaptoethanol (2-ME) to the soy milk resulted not only in further removal of the 34kDa allergenic protein to the precipitate, but also in better recovery of conglycinin in the supernatant. After a two-dimensional SDS-PAGE analysis (the first dimension, minus 2-ME; the second, plus 2-ME) of the precipitates, superimposition between the CBB-stained gel and the eletroblotted membrane stained with a monoclonal antibody specific to Gly m Bd 30 K indicated that part of Gly m Bd 30 K was preferentially bound to the alpha'- and alpha-subunits of conglycinin, and that part of them had formed the dimer through a disulfide bond.

Allergens↗

[Evaluation of left ventricular volume and ejection fraction using three-dimensional transesophageal echocardiography].

Left ventricular (LV) volume and ejection fraction (EF) derived from three-dimensional echocardiography using a multiplane transesophageal probe (3D-TEE) were compared with LV volume and EF obtained from left ventriculography (LVG) in 14 patients (mean age: 61 years). Left ventricular volumes were calculated using a summation of disks algorithm based on multiple reconstructed short-axis cross-sections from 3D data. Left ventricular volume (end-diastole and end-systole) and EF from 3D-TEE were compared with those from LVG using linear regression analysis. Three-dimensional TEE demonstrated excellent correlations with LVG for measuring LV volume (r = 0.97, SEE = 11 ml) and EF (r = 0.95, SEE-4%), respectively. Three-dimensional TEE is useful for the measurement of LV volume and EF in the clinical setting.

Echocardiography, Transesophageal↗

[Phasic flow velocity characteristics of the right coronary artery in patients with aortic stenosis: a Doppler guide wire study].

This study investigated the characteristics of the phasic flow velocity pattern of the right coronary artery and the relationship to hemodynamic parameters in patients with aortic stenosis. Coronary flow velocities were recorded at the proximal (segment 1) and the distal (segment 4PD) portion of the right coronary artery using a Doppler guide wire (0.014-in, 15 MHz) in 10 patients with aortic stenosis and 8 control subjects with normal coronary arteries. The diastolic to systolic peak velocity ratio at both the proximal and distal portion were significantly greater in patients with aortic stenosis than in control subjects. Systolic flow reversal was not seen in the right coronary artery in control subjects, but it was observed in 5 patients (50%) at the proximal portion and in 10 patients (100%) at the distal portion. Peak velocity of flow reversal at the distal portion showed a significant correlation with mean pressure gradient across the aortic valve (y = -1.3x + 37.3, r = 0.71, p = 0.02). Systolic flow reversal is characteristic in the right coronary artery, especially at the distal portion, in patients with aortic stenosis. This may be related to the pressure difference across the aortic valve through the posterior descending artery.

Aged↗

Rearrangement of the 5' cluster region of the BCL2 gene in lymphoid neoplasm: a summary of nine cases.

Rearrangement of the BCL2 gene with the immunoglobulin (IG) genes is the most frequent genetic abnormality in B cell lymphoid neoplasms. In the majority of cases, breakages occur at two breakpoint cluster regions; major breakpoint cluster (MBR) and minor cluster region (mcr). In a minority of cases with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), rearrangements involving the 5' flanking region of the BCL2 (5'-BCL2) have been reported. Here, we investigated 196 patients with NHL and 31 with CLL, with regard to rearrangement of the BCL2 gene. Hybridization analyses using probes representing the three cluster regions revealed that a total of 57 patients had a rearrangement of the BCL2; 42 (73.7%) were within the MBR, seven (12.2%) were within the mcr, and nine (15.8%) had a rearrangement at the 5'-BCL2. The nine patients with 5'BCL2 rearrangement included two with follicular lymphoma, four with diffuse large cell lymphoma and immunoblastic variant, two with leukemic phase of follicular lymphoma, and one with CLL. Comigration analysis with probes for the IG heavy chain gene (IGH), kappa-chain gene (IG kappa) and lambda-chain gene (IG lambda), demonstrated a 5'-BCL2/IGH junction at the JH region in four patients with NHL derived from follicular center B cell. Thus, the 5'flanking region is a third cluster for recombination between the BCL2 and IGH, which is closely associated with the development of follicular center cell lymphoma. Molecular cloning of a 5'-BCL2/IGH junction demonstrated recombination of the two affected genes in divergent orientation. A 5'-BCL2/IG kappa junction was observed in two patients with immunoblastic lymphoma, and one with CLL had a 5'-BCL2/IG lambda recombination. Two patients, including one with a BCL2-MBR/JH junction, lacked obvious recombination of the 5'-BCL2 with IG genes, suggesting the presence of a deletion at the 5'-BCL2. Our findings demonstrated heterogeneity not only in clinicopathological presentation of B cell disease with rearrangement of 5'-BCL2, but also in molecular lesions resulting from the rearrangement.

Adult↗

[Assessment of Japanese patients receiving heart transplants overseas].

No heart transplants have been performed in Japan due to various obstacles since the only operation performed in 1968. Since 1981, a number of patients requiring heart transplants have been accepted by foreign transplantation centers in England, the U.S.A., and Germany. This report describes an investigation of the postoperative course of these Japanese heart transplant patients and discusses the problems regarding transplantation in Japan. Of the 21 transplant patients, the diagnosis was dilated cardiomyopathy in 17, restrictive cardiomyopathy in 1, hypertrophic cardiomyopathy in 2, and congenital muscle dystrophy in 1. All patients survived surgery but three died in the long-term period. The causes of death were acute rejection (after 3 months), chronic rejection (after 50 months) and infection (after 30 months). The actuarial survival curve of these patients was 95.0% for one-year survival and 86.4% for three-year survival. The postoperative functional class was NYHA classification I in all patients (100%). Ninety-three percent of patients returned to work. Immunosuppressive therapies included triple drug therapy in 14 patients (66.7%), double drug therapy in 4 (19.0%), ciclosporin alone in 2 (9.5%) and FK506 in 2 (5.0%). The incidence of acute rejection was 1.56 episodes per patient per year within 3 months and 2.9 episodes per patient per year within 1 year. The postoperative courses of Japanese patients who underwent heart transplantation at foreign transplantation centers were satisfactory. These results will encourage heart transplantation in Japan.

Adolescent↗