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Biomedical subjects

Ryuzo Ueda

Publications and source records attributed to Ryuzo Ueda.

At least 91 records · Page 5Linked to original sources

Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene.

The present study aimed to characterize the clinical and molecular-cytogenetic features of non-Hodgkin's lymphoma (NHL) with double translocation of the immunoglobulin heavy chain (IGH) gene. G-banding analysis, fluorescence in situ hybridization (FISH) with the IGH (Cgamma and VH) and oncogene (c-MYC, BCL1, BCL2, and BCL6) probes, and long-distance polymerase chain reaction (LD-PCR) were performed on 6 patients with B-cell lymphoma, one with angioimmunoblastic T-cell lymphoma, and one with acute lymphoblastic leukemia (ALL) with B-cell phenotype. G-banding analysis detected two different 14q32 translocations, t(14,18) and add (14)(q32) in a patient with ALL. Two distinct partners of double IGH translocation identified by FISH were as follows: c-MYC + BCL2 in 3 patients, c-MYC + BCL1 in 2, c-MYC + BCL6 in one, BCL2 + 9q22 in one, and 1q21 + 6q27 in one. Colocalization of BCL1 and c-MYC probes was demonstrated in a patient with mantle cell lymphoma. LD-PCR detected c-MYC/Cmu, c-MYC/Calpha and BCL6/Cmu, and c-MYC/Calpha fusion in each one patient. Seven of 8 patients showed high serum LDH. Central nervous system and leukemic involvement was observed in 5 and 6 patients, respectively. Median survival time of patients with c-MYC/IGH translocation was 9 months. The results defined a clinical subset of B-cell lymphoma/leukemia showing extremely poor prognosis. C-MYC/IGH translocation is possibly an evolutionary alteration following the primary IGH translocation with BCL1, BCL2, or BCL6. Furthermore, FISH identified one novel (9q22) and one cryptic chromosomal breakpoints (6q27) involved in IGH translocation.

Adult↗

Coronary stenting in an elderly patient with an acute myocardial infarction at left main trunk.

Acute myocardial infarction (AMI) caused by an occlusion of the left main trunk (LMT) is a rare angiographic finding. The prognosis is usually extremely poor, particularly in an elderly patient, unless complete reperfusion is rapidly established. We experienced a survival case of an elderly man with AMI at the LMT. A 91-year-old man with cardiogenic shock was referred to our hospital for the treatment of AMI. Left ventriculograms showed that akinesis in the anterolateral and apical wall segments had resulted in an ejection fraction of 30.8%. Coronary angiograms revealed a 90% narrowing at the ostium of the LMT. Intravascular ultrasound images showed a circumferential calcification at the site of the minimum lumen diameter of the LMT. We successfully dilated this calcified narrowing using a coronary stent, and the patient was discharged without complications 1 month later. The patient was asymptomatic 6 months later.

Aged↗

Gastric MALT lymphomas are divided into three groups based on responsiveness to Helicobacter Pylori eradication and detection of API2-MALT1 fusion.

Gastric MALT lymphoma shows unique features including regression by Helicobacter pylori eradication and API2-MALT1 fusion. We performed a molecular and clinicopathologic study for 115 cases. All eradication-responsive cases were devoid of API2-MALT1 fusion. All tumors positive for the fusion and all negative for H. pylori infection were nonresponsive to the eradication. Consequently, gastric MALT lymphomas were divided into three groups: Eradication-responsive and fusion-negative (group A, n = 72), eradication-nonresponsive and fusion-negative (group B, n = 22), and eradication-nonresponsive and fusion-positive (group C, n = 21). Group A tumors were characterized by low clinical stage and superficial gastric wall involvement, and group C tumors by low H. pylori infection rate, advanced clinical stage, and nuclear BCL10 expression. All group C tumors showed exclusively low-grade histology. Group B tumors, which have not been well recognized, frequently showed nodal involvement, deep gastric wall involvement, and advanced clinical stage, and sometimes an increased large cell component. A multivariate discriminant analysis revealed that responsiveness to the eradication could be predicted accurately by negative API2-MALT1 fusion, positive H. pylori infection, low clinical stage, and superficial gastric wall invasion, the former being the most important factor for the prediction. This 3-group categorization may be helpful for a comprehensive understanding of gastric MALT lymphoma.

Adaptor Proteins, Signal Transducing↗

Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A.

Complete nucleotide sequences of 19 hepatitis B virus (HBV) isolates of genotype A (HBV/A) were determined and analysed along with those of 20 previously reported HBV/A isolates. Of the 19 HBV/A isolates, six including three from Japan and three from the USA clustered with the 14 HBV/A isolates from Western countries. The remaining 13 isolates including four from The Philippines, two from India, three from Nepal and four from Bangladesh clustered with the six HBV/A isolates reported from The Philippines, South Africa and Malawi. Due to distinct epidemiological distributions, genotype A in the 20 HBV isolates was classified into subtype Ae (e for Europe), and that in the other 19 into subtype Aa (a for Asia and Africa) provisionally. The 19 HBV/Aa isolates had a sequence variation significantly greater than that of the 20 HBV/Ae isolates (2.5+/-0.3 % vs 1.1+/-0.6 %, P<0.0001); they differed by 5.0+/-0.4 % (4.1-6.4 %). The double mutation (T1762/A1764) in the core promoter was significantly more frequent in HBV/Aa isolates than in HBV/Ae isolates (11/19 or 58 % vs 5/20 or 25 %, P<0.01). In the pregenome encapsidation (epsilon) signal, a point mutation from G to A or T at nt 1862 was detected in 16 of the 19 (84 %) HBV/Aa isolates but not in any of the 20 HBV/Ae isolates, which may affect virus replication and translation of hepatitis B e antigen. Subtypes Aa and Ae of genotype A deserve evaluation for any clinical differences between them, with a special reference to hepatocellular carcinoma prevalent in Africa.

Africa↗

Determinants of sensitivity and resistance to gemcitabine: the roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer.

Gemcitabine is one of the most commonly used agents for lung cancer chemotherapy, but the determinants of sensitivity and/or resistance to this agent are not yet fully understood. In this study we used quantitative RT-PCR to examine the expression levels of human equilibrative nucleoside transporter 1 (hENT1) and deoxycytidine kinase (dCK) genes in non-small cell lung cancer (NSCLC) cell lines in relation to sensitivity and resistance to gemcitabine. The basal expression levels of hENT1 were significantly correlated with the IC50 values for gemcitabine (r =-0.6769, P = 0.0005), whereas dCK expression levels were not. In a highly gemcitabine-sensitive cell line, NCI-H23, the sensitivity to gemcitabine was inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), an inhibitor of hENT1, without significant modulation of hENT1 expression. These data suggest that hENT1 is associated with gemcitabine sensitivity in lung cancer. We also continuously exposed NCI-H23 cells to gemcitabine and subsequently established the drug-resistant clone H23/GEM-R, which showed a significant decrease of dCK expression; however, hENT1 expression was not altered in the continuously exposed sublines or in the resistant clone. We conclude that increased hENT1 expression is a determinant of gemcitabine sensitivity, while decreased dCK expression is associated with acquired resistance to gemcitabine in NSCLC cells. Thus, hENT1 and dCK might be useful as predictive markers for efficacy of gemcitabine therapy in NSCLC.

Affinity Labels↗

Lack of association between occult hepatitis B virus DNA viral load and aminotransferase levels in patients with hepatitis C virus-related chronic liver disease.

BACKGROUND AND AIM: Occult hepatitis B virus (HBV) infection in hepatitis C virus (HCV)-infected patients might enhance the severity of chronic liver disease (CLD). To elucidate the correlation between occult HBV infection and the clinical course of HCV-related CLD, we evaluated whether the fluctuation of occult HBV-DNA directly affects the serum alanine aminotransferase (ALT) level. METHODS: Forty-one patients with HCV-related CLD who received regular outpatient treatment and 42 age-, sex-, and antibody to hepatitis B core antigen positivity-matched healthy volunteers were enrolled. Serum HBV-DNA was quantitatively detected using real-time detection polymerase chain reaction (RTD-PCR). Serial serum samples in three patients were measured for HBV-DNA, ALT and HCV core antigen. RESULTS: Hepatitis B virus DNA was amplified in eight of the HCV-related CLD patients (19.5%), which was significantly higher than that of healthy volunteers (2.4%). No significant difference between the genotype 1 HCV-related CLD group and the genotype 2 group was found. Based on the analyses using serial serum samples, the elevation of HBV-DNA did not occur before the ALT flares, but occurred at the same time or after the ALT flares. CONCLUSIONS: The prevalence of occult HBV infection of HCV-related CLD is significantly higher than that of control. Occult HBV infection has no influence on ALT flares among patients with HCV-related CLD.

Adult↗

Novel hepatitis B virus genotype a subtyping assay that distinguishes subtype Aa from Ae and its application in epidemiological studies.

The eight genotypes of hepatitis B virus (HBV) have different geographical distributions, virological characteristics, and clinical manifestations. A unique subtype of HBV genotype A (HBV/A) was reported in sub-Saharan Africa, raising the possibility that patients infected with this subtype (HBV/Aa ["a" for African and Asian]) may have different clinical outcomes than other HBV/A isolates (HBV/Ae ["e" for European]). Comparison between 30 HBV/Aa and 30 HBV/Ae isolates indicated that almost all HBV/Ae isolates had G at nucleotide (nt) 1809 and C at nt 1812, whereas HBV/Aa isolates had T1809/T1812. Taking advantage of these two single nucleotide polymorphisms (SNPs), a novel subtype-specific PCR assay in the X/precore/core region was developed. This assay was combined with a restriction fragment length polymorphism assay using BglII in a different region (nt 1984 to 1989), which has a SNP distinguishing HBV/Aa from HBV/Ae, resulting in 100% specificity for the combined assay. Application of the subtyping assay using sera from 109 paid donors in the United States indicated significantly different distributions of HBV/A subtypes among races; African-Americans, Caucasians, and Hispanics had HBV/Ae, whereas Asians had mainly HBV/Aa, suggesting that the HBV/Aa isolates may have been imported by recent immigration from Asia. In conclusion, the specificity and sensitivity of the combined subtyping assay were confirmed, and its usefulness was demonstrated in a practical context.

Adolescent↗

Antihypertensive effects of long-acting calcium channel blockers on hemodialysis days--a randomized crossover trial between benidipine and nifedipine CR.

BACKGROUND/AIMS: Since antihypertensive effects of most calcium channel blockers largely depend on their plasma concentrations, a rapid increase in blood pressure may occur as circulating levels of such blockers decrease after hemodialysis. Thus, the effects of benidipine and nifedipine CR (extended-release coated tablets, Adalat CR), which are long-acting calcium channel blockers, on post-hemodialytic blood pressures were investigated. METHODS: A randomized crossover trial was carried out with 10 hypertensive patients on chronic maintenance hemodialysis. Patients were assigned to receive benidipine (4-8 mg/day) or nifedipine CR (20-40 mg/day), and after 4 weeks, 24-hour ambulatory blood pressure monitoring was performed on the day of hemodialysis and blood samples were obtained before and after hemodialysis to measure plasma concentrations of the blockers. The calcium channel blockers were then exchanged in each patient and the same protocol was repeated. RESULTS: The pattern of fluctuation of blood pressure differed markedly between the treatment with benidipine and nifedipine CR. Under treatment with nifedipine CR, rapid increase in blood pressure was observed after hemodialysis, while blood pressure remained at favorable levels with benidipine. Plasma concentrations of the blockers were significantly decreased by hemodialysis. CONCLUSION: Benidipine exerts more sustained antihypertensive effects than expected from its disposition in plasma. The stable depressor effects of benidipine even after hemodialysis may contribute to favorable control of blood pressure in this population.

Aged↗

Usefulness of dual 67Ga and 99mTc-sestamibi single-photon-emission CT scanning in the diagnosis of cardiac sarcoidosis.

Cardiac sarcoidosis is potentially fatal and hence requires a precise diagnosis. We performed dual (67)Ga (Ga)-(99m)Tc-sestamibi (Tc) single-photon emission CT (SPECT) scans by superimposing a Ga-SPECT image on the myocardial outline traced with Tc. The usefulness of this imaging technique in the diagnosis of cardiac sarcoidosis was studied. The subjects in this study were 14 patients with sarcoidosis (mean [+/- SD] age, 52 +/- 16 years; 5 men and 9 women). An IV dose of Tc (74 MBq per 2 mL) was injected into patients 72 h after an IV dose of Ga (111 MBq per 3 mL) was injected. The dual SPECT scan was performed 30 min after the Tc dose was administered. The energy used for collection was 93 keV for Ga and 140 keV for Tc. The myocardial outline was successfully traced in all subjects, allowing us to check for myocardial Ga uptake and to identify its location. Abnormal Ga uptake in the myocardium was observed in 9 of the 14 subjects. In seven of these nine subjects, the location of the abnormal myocardial Ga uptake was identical to the location of reduced Tc uptake. Abnormal Ga uptake disappeared in all cases following steroid therapy. Of the five subjects who were free of abnormal Ga uptake, two showed reduced Tc uptake, and these two subjects had been receiving steroid therapy. These results suggest that dual SPECT scanning using Ga and Tc represents a very useful diagnostic imaging technique since it improves the diagnostic capability of Ga-SPECT to allow the highly specific diagnosis of cardiac sarcoidosis.

Adult↗

Microscopic polyangiitis associated with diffuse panbronchiolitis.

There are several case reports of systemic vasculitis associated with chronic suppurative lung diseases. We describe a 46-year-old female, previously diagnosed as having diffuse panbronchiolitis (DPB), presenting with hemosputum and dyspnea. Her serum titer of MPO-ANCA was positive together with a high titer of BPI-ANCA. Chest X-ray and chest CT scan showed pulmonary hemorrhage, and the renal biopsy specimen revealed necrotizing, crescentic glomerulonephritis. She was diagnosed as having ANCA-associated vasculitis, and more specifically, microscopic polyangiitis accompanied by DPB. She was treated with methylprednisolone pulse therapy, followed by intravenous cyclophosphamide. This case suggested a possible association with chronic bacterial infection, which may play a role in the pathogenesis of ANCA-associated vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗

Cognitive event-related potentials: useful clinical information in Alzheimer's disease.

Cognitive event-related potentials (ERPs) have been used as a marker of cognitive function in patients with psychiatric and neurological disorders. In particular, the P300 potential has been widely utilized to study dementia and aging, because the P300 ERP component is easily observed and reflects attention and memory processing. However, the relationship between parameters of the P300 potential and the severity or type of cognitive impairment in patients with Alzheimer's disease (AD) remains controversial. Because specific and effective anti-dementia treatments have recently become available for AD, more useful information is needed about the clinical aspects of this disease, including methods of making an accurate and early diagnosis, differentiation from vascular dementia and other degenerative dementias, assessment of severity, assessment of disease progression, evaluation of the response to treatment, and prediction of the prognosis. This mini-review described new discoveries on recent clinical application of ERPs in AD with respect to the above-mentioned areas. Although the definition of normal ERP values and the most appropriate method of ERP recording in AD patients have not been well defined, recent findings suggest that ERP analysis may be a clinically useful, inexpensive, noninvasive, and reliable method of assessing AD.

Alzheimer Disease↗

[CD5- CD11c+ CD23- small lymphocytic lymphoma evolving from aplastic anemia].

A 91-year-old woman was hospitalized with acute respiratory distress syndrome due to pneumonia in June 1997. Since she had pancytopenia and a bone marrow aspirate indicated hypocellularity with no increase in myeloblasts, dysplasia or abnormal chromosomes, aplastic anemia (AA) was diagnosed. Pulse therapy with methylprednisolone and antibiotics proved successful, and blood cell numbers stabilized. In June 2001, she was readmitted to our hospital with persistent low grade fever and leukopenia. A bone marrow aspirate from the sternum and iliac bone biopsy revealed compact proliferation of small lymphocytes, and the surface marker CD5- CD10- CD11c+ CD19+ CD20+ CD23- was detected through immune staining and flowcytometry. CD30+, CD34+and CD56+cells were scarce. Tests for surface immunoglobulins, IgG, IgA, IgM and IgD, were negative. No nodal or extranodal lesions were evident. Since Southern blot analysis of bone marrow cells indicated rearrangement of the immunoglobulin heavy chain and abnormal chromosomes were evident, small lymphocytic lymphoma (SLL) was diagnosed. Four intravenous infusions of rituximab (375mg/m2) were administered without critical adverse effects. Tests conducted four weeks later revealed saturation of CD20+ antigens of lymphoma cells and chromosomal abnormalities and rearrangement of the immunoglobulin heavy chain were still apparent. Though complete remission of the pancytopenia was not achieved, serum concentrations of lactate dehydrogenase and soluble interleukin-2 receptor decreased, and the numbers of platelets and erythrocytes increased. There was also an improvement in systemic condition. This was a rare case of SLL having the surface marker of CD5- CD10- CD11c+ CD19+ CD20+ CD23-, which had evolved from AA and infiltrated bone marrow.

Aged↗

Analysis of beta-tubulin gene alteration in human lung cancer cell lines.

We examined lung cancer cell lines for the presence of beta-tubulin gene alteration based on a previous report of a relationship between frequent beta-tubulin gene mutation in non-small-cell lung cancer and clinical response to taxanes as well as the prognosis. The mutation was defined by analyzing genomic DNA from 31 lung cancer cell lines by direct genomic sequencing using specific primers for the beta-tubulin class I gene. We detected only three genetic alterations at nonsplice sites in two introns, and a silent genetic alteration at codon 217 in exon 4. The mutation of the beta-tubulin gene was rare; moreover, these genetic alterations were predicted to evoke no biological alteration of the cancer cells. Our data suggest that the beta-tubulin gene mutation does not play a major role in the genetic mechanism of resistance to taxanes. In addition, the presence of a closely related family of beta-tubulins or pseudogenes was thought to hinder accurate evaluation of the beta-tubulin gene.

Codon↗

Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia.

Although FLT3 mutations are essentially found in myeloid-lineage leukemia cells, a high level of FLT3 expression was recently observed in MLL gene-rearranged acute lymphoblastic leukemia without FLT3 mutations. Here, we analyzed the biologic and clinical significance of the FLT3 transcript level in comparison with several gene alterations in 181 de novo acute myeloid leukemia (AML) cases. The mean expression level in AML was higher than that in normal mononuclear cells, whereas the range varied widely. A high level of FLT3 is related to internal tandem duplication of the FLT3 gene (FLT3/ITD), the mutations within the activation loop of FLT3 (FLT3/D835Mt), and tandem duplication of the MLL gene (MLL-TD) but not to p53 or N-RAS gene mutations. Furthermore, a high expression level in AML cases with FLT3 mutations was not related to MLL-TD. Overexpressed FLT3 revealed autophosphorylation and had the same sensitivity to the FLT3 inhibitor as FLT3/ITD. Overexpression of FLT3 (more than 200,000 copies/microgRNA) was an unfavorable prognostic factor for overall survival in 91 AML cases without FLT3/ITD. These results indicated that FLT3 overexpression may distinguish a novel disease entity in AML without FLT3 mutations and serve as a therapeutic target for FLT3 inhibitors.

Adult↗

Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome.

Adult T-cell leukemia/lymphoma (ATLL) is a distinct clinical entity among mature T-cell neoplasms, and its causative agent has been confirmed to be long-term infection by human T-lymphotropic virus type 1. A recent study demonstrated frequent expression of a chemokine receptor, CC chemokine receptor (CCR)4, which is known as a Th2 marker but not CXC chemokine receptor (CXCR)3, which is known as a Th1 marker, among both ATLL- and human T-lymphotropic virus type 1-immortalized T cells. In this study, immunostaining analysis for CCR4 and CXCR3 expression in ATLL cells obtained from 103 patients with ATLL was performed, and the clinical parameters and overall survival of the CCR4-positive and -negative cases were compared. Ninety-one (88.3%) of the 103 cases were positive for CCR4 staining, whereas only 5 (4.9%) were positive for CXCR3 staining. Positivity for CCR4 was significantly associated with skin involvement (P < 0.05), although there were no significant differences in clinical characteristics between the CCR4-positive and -negative cases at the time of initial diagnosis. CCR4(+) ATLL cells may accumulate in the skin because of the expression of a CCR4 ligand, thymus and activation-regulated chemokine (TARC), on normal and inflamed cutaneous endothelia. As for survival analysis, positivity for CCR4 expression was extracted as an unfavorable prognostic factor as well as other factors, including the presence of B symptoms and extranodal involvement of more than one site. Multivariate analysis confirmed that CCR4 expression was an independent and significant prognostic factor (P < 0.05). Thus, our finding may provide a novel insight into not only the biological but also the clinical features of ATLL.

Adult↗

Different antiapoptotic pathways between wild-type and mutated FLT3: insights into therapeutic targets in leukemia.

An internal tandem duplication (ITD) of the juxtamembrane (JM) domain of FLT3 (FLT3/ITD) has been found in 20% of patients with acute myeloid leukemia (AML) and is correlated with leukocytosis and a poor prognosis. Here, we compared the antiapoptotic effects of wild-type FLT3 (WtFLT3) and FLT3/ITD in terms of the regulation of Bcl-2 family members. In a murine myeloid cell line, 32D, interleukin-3 (IL-3) deprivation induced apoptosis following the down-regulation of Bcl-XL and the dephosphorylation of Bad. However, the expression levels of Bcl-2, Bax, Bak, and Mcl-1 were unchanged. In WtFLT3-transfected 32D (WtFLT3-32D) cells, FLT3 ligand (FL) stimulation did not restore the down-regulation of Bcl-XL but maintained the phosphorylation of Bad. Combined treatment with phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, and mitogen-activated protein kinase kinase (MEK) inhibitor, PD98059, dephosphorylated Bad and induced apoptosis in WtFLT3-32D cells stimulated with FL. Induction of nonphosphorylated Bad induced remarkable apoptosis. These findings suggest that the FL stimulation is associated with antiapoptosis through Bad phosphorylation. On the other hand, FLT3/ITD-transfected 32D (FLT3/ITD-32D) cells survived in an IL-3-or FL-deprived state. Furthermore, the dephosphorylation of Bad using LY294002 and PD98059 was insufficient for apoptosis, and the down-regulation of Bcl-XL using antisense treatment was needed to induce apoptosis. FLT3 kinase inhibitor, AG1296, alone not only dephosphorylated Bad but also down-regulated Bcl-XL, leading FLT3/ITD-32D cells into apoptosis. These findings suggest that the antiapoptotic pathways from FLT3/ITD are more divergent than those from WtFLT3 and may represent targets for drug discovery with the potential of inducing selective cell death of human leukemia cells.

Apoptosis↗

A xeno-transplantable plasma cell leukemia line with a split translocation of the IgH gene.

A novel cell line, SACHI, was established from a pericardial effusion developed during the course of primary plasma cell leukemia (PCL). The cell line SACHI cells were the same as the infiltrating plasma cells with regard to surface markers (CD38(+)CD19(-)PCA-1(+)VLA-5(-)CD56(-)TdT(+)) and immunoglobulin gene rearrangements. Analysis of SACHI cells showed a complex hypertriploid (karyotype mode 70-73) including 7p32, 14q32, and Xq24 structural abnormalities, which were found also in the original leukemia cells. Dual-color fluorescence in situ hybridization revealed that the c-MYC gene was juxtaposed with a constant region of IgG (Cgamma) on 14q32. The split Cgamma locus was fused near the MAFB gene on chromosome 20. The SACHI cells had increased amounts of c-MYC and MAFB transcripts. Injection of SACHI cells into NOD/SCID mice generated leukemic plasmacytosis with invasion to liver, spleen, and bone marrow. This cell line may be useful for therapeutic testing as well as analyzing the molecular pathogenesis of PCL.

Female↗