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Biomedical subjects

S Tagawa

Publications and source records attributed to S Tagawa.

At least 37 records · Page 2Linked to original sources

Multicolor spectral karyotyping identifies new recurring breakpoints and translocations in multiple myeloma.

Karyotypic information on multiple myeloma (MM) is less extensive than that on other myeloid or lymphoid malignancies due to low mitotic activity of plasma cells. An add(14)(q32) marker chromosome has been reported to be the most frequent recurring abnormality in clonally abnormal cases; in approximately one third of the latter cases, this marker has been identified as a der(14)t(11;14)(q13;q32) chromosome. To map chromosomal breakpoints, characterize the add(14)(q32) marker chromosomes, and to identify other recurring translocations in MM, we used spectral karyotyping (SKY) to analyze a panel of nine bone marrow (BM) biopsy samples from eight patients and 10 tumor cell lines derived from MM patients. SKY involves hybridization of 24 fluorescently labeled chromosome painting probes to metaphase spreads in such a manner that simultaneous visualization of each of the chromosomes in a different color is accomplished. By this method, it was possible to define all chromosomal rearrangements and identify all of the clonal marker chromosomes in tumor cells. By detailed mapping of breakpoints of rearrangement, it was also possible to identify several novel recurring sites of breakage that map to the chromosomal bands 3q27, 17q24-25, and 20q11. The partner chromosomes in translocations that generated the add (14)(q32) marker chromosomes were identified in all cases in which they were detected by G-banding (one biopsy and six cell lines). In addition, two new translocations involving band 14q32, ie, t(12;14)(q24;q32) and t(14;20)(q32;q11) have also been identified. These studies demonstrate the power of SKY in resolving the full spectrum of chromosome abnormalities in tumors.

Aged↗

Distinct roles of two heme centers for transmembrane electron transfer in cytochrome b561 from bovine adrenal chromaffin vesicles as revealed by pulse radiolysis.

The reaction of monodehydroascorbate (MDA) radical with purified cytochrome b561 from bovine adrenal chromaffin vesicles was investigated by the technique of pulse radiolysis. Radiolytically generated MDA radical oxidized rapidly the reduced form of cytochrome b561 to yield the oxidized form. Subsequently the oxidized form of cytochrome b561 was re-reduced by ascorbate in the medium. The second-order rate constants of the reaction of MDA radical were increased with decreasing pH, whereas a maximum of the second-order rate constant for the reaction with ascorbate was obtained around pH 6.8. At excess MDA radical to cytochrome b561 concentration, only half of the heme in cytochrome b561 was oxidized, indicating that only one of the two heme centers can react with MDA radical. On the other hand, when the reactions were examined using cytochrome b561 pretreated in a mild alkaline condition in the oxidized state, the cytochrome b561 could not be oxidized with MDA radical, suggesting that the heme center specific for the electron donation to MDA radical is selectively modified upon the alkaline treatment. These results suggest that the two heme b centers have distinct roles for the electron donation to MDA radical and the electron acceptance from ascorbate, respectively.

Adrenal Glands↗

Natural killer cell-derived large granular lymphocyte lymphoma of lung developed in a patient with hypersensitivity to mosquito bites and reactivated Epstein-Barr virus infection.

A 17-year-old female developed natural killer (NK) cell-derived large granular lymphocyte (LGL) lymphoma of the lung. She had a past history of hypersensitivity to mosquito bites (HMB). After an eight-year chronic, active Epstein-Barr virus (EBV) infection, she developed multiple lung lesions and pleural effusion. In the effusion, 60% of the cells were LGL. They were CD2+, 3-, 16+, 56+, 57+, 45RO+/RA + weak, and possessed strong NK activity. No rearrangement of T-cell-receptor genes was detected. From all these results, a diagnosis of NK-LGL lymphoma of the lung was made. EB virus DNA was detected in cells infiltrating the pleural effusion. The clonality of the LGLs was determined by Southern blot hybridization with the terminal repeat sequence of EB virus as a probe, and by chromosomal abnormalities. The patient died from respiratory failure. Necropsy of the lung revealed diffuse lymphoma composed of polymorphic cells with typical angiocentric lesions. Reportedly, lymphomas of NK lineage show predominantly extranodal involvement, and primary lung lesions are rare. In the pleural effusion of the present case, abnormally high levels of soluble Fas ligand, interleukin-10 and interferon gamma were detected. This hypercytokinemia, reflecting the microenvironment of lymphoma cells, may play a role in the progression of the lymphoma and organ injury in the lung.

Adolescent↗

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia.

Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4+CD8+ double-positive (DP) phenotype is seen in a few cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a matter of controversy. To address this issue, we studied phenotypical features in eight cases of DP T cell leukemia. Thymic DP T cells and peripheral CD8+ T cells have CD8 of alphabeta subunit, while CD8alphaalpha is induced in CD4+ T cells on activation with IL-4. We found that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim expression of CD8alphaalpha, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high levels of IL-4. These findings suggest that they may be derived from peripheral CD4+ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed CD8alphaalpha, suggestive of an activated peripheral T cell origin. One case expressed CD8alphaalpha dim and IL-4 mRNA, while the other two cases expressed no IL-4 mRNA and showed CD8alphaalpha bright phenotype, features not found in normal T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL) expressed CD8alphabeta. The DP phenotype is relatively common in T-PLL, and CD4+CD8alphabeta+ is characteristic of thymic T cells. The DP T-PLL cells did not express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down-regulated at the late stage of thymic T cell development. On the basis of these findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.

Adult↗

Pulse radiolysis studies on cytochrome cd1 nitrite reductase from Thiosphaera pantotropha: evidence for a fast intramolecular electron transfer from c-heme to d1-heme.

Electron transfer within cytochrome cd1 from Thiosphaera pantotropha was investigated by the technique of pulse radiolysis. The reduction of the heme centers in this nitrite reductase occurred in two phases as judged from kinetic difference spectra. In the faster phase, radiolytically generated N-methylnicotinamide (NMA) radicals selectively reduced the c-heme of the enzyme. From the absorbance increase at 420 nm, a characteristic of formation of the ferrousc-heme, the second-order rate constant for this electron transfer process was estimated to be 3.8 x 10(9) M-1 s-1 at pH 7.0. In the slower phase, a decrease of absorption around 420 and 550 nm, corresponding to a reoxidation of the c-heme, was accompanied by an increase of absorption around 460 and 640 nm, characteristic of formation of the reduced d1-heme. This indicated that an intramolecular electron transfer from the c-heme to the d1-heme occurred. The first-order rate constant of this process was calculated to be 1.4 x 10(3) s-1 at pH 7.0 and was independent of the enzyme concentration. In the presence of nitrite the interheme electron transfer rate was not affected, but on a time scale of seconds a new species associated with the d1-heme, having an absorption maximum at 640 nm, was detected and is proposed to reflect ligand binding to this heme. These results suggest the role of the c-heme as the electron acceptor site in cytochrome cd1 and in mediating the electron transfer to the catalytic site of the enzyme. Moreover, the fast interheme electron transfer rate argues against this process being the rate determining step in catalysis.

Cytochrome c Group↗

Antioxidant activity of polyphenolics in diets. Rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen.

Phenolic non-flavonoid compounds in diets, such as chlorogenic acid and caffeic acid are widely recognized to be antioxidants. However, it is not known how these phenolics scavenge reactive species of oxygen and nitrogen. We determined the rate constants of the reactions between the phenolics with superoxide and hydroxyl radical with a pulse radiolysis. The second-order rate constants of the reactions of chlorogenic acid with superoxide and hydroxyl radical were 1.67 +/- 0.14 x 10(6) M(-1) s(-1) and 3.34 +/- 0.19 x 10(9) M(-1) s(-1), respectively, while those of caffeic acid with superoxide and hydroxyl radical were 0.96 +/- 0.01 x 10(6) M(-1) s(-1) and 3.24 +/- 0.12 x 10(9) M(-1) s(-1), respectively. By scavenging peroxy radical chlorogenic acid inhibited the initiation of chain lipid peroxidations by organic free radical. The second-order rate constant of the reaction of chlorogenic acid with peroxy radical was estimated to be 1.28 +/- 0.11 x 10(5) M(-1) s(-1). Chlorogenic acid was rapidly oxidized by peroxynitrite in concentration- and pH-dependent manners and its rate constant was determined to be 1.6 +/- 0.7 x 10(5) M(-1) s(-1), using competitive inhibitions by glutathione and methionine.

Antioxidants↗

Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is caused by the hyperactivation of T cells and macrophages. The clinical characteristics associated with this disease result from overproduction of Th1 cytokines including interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-alpha). In this study, we analyzed the production of IL-12 and IL-4, which determine Th1 and Th2 response, respectively, and IL-10, which antagonizes Th1 cytokines, in 11 patients with HLH. IL-12 was detected in plasma in all patients (mean peak value, 30.0 +/- 5.0 pg/mL), while IFN-gamma was massively produced in nine patients (mean peak value, 79.2 +/- 112.0 U/mL). IL-4 was not detected in any of the patients. Plasma IL-10 levels were elevated in all patients (mean peak value, 2,698.0 +/- 3,535.0 pg/mL). There was a positive correlation between the levels of IFN-gamma and IL-10 (P < .01). The plasma concentrations of these cytokines were initially high, before decreasing after the acute phase. However, the decrease in IL-10 levels was slower than that of IFN-gamma. Although the concentration of IL-12 was high at the acute phase, in some patients, a peak in the level was delayed until the chronic phase. Thus, in HLH, production of cytokines that promote development of Th1 cells appears to be predominant over that for Th2 cell development. Overproduction of IL-10 was also observed indicating that a mechanism suppressing hyperactivation of Th1 cells and monocytes/macrophages functions in patients with this disease.

Child↗

Successful treatment for active cytomegalovirus infection by cytomegalovirus antibody-enriched immunoglobulin in a renal transplant recipient.

Active cytomegalovirus (CMV) infection was treated successfully by only CMV antibody-enriched immunoglobulin (CMV-IG) in a renal transplant recipient. CMV-IG was injected at 86 mg/kg i.v. twice a day for a total of 16 days (4 plus 12 days, interrupted by a pause of 4 days), followed by weekly i.v. injection of 86 mg/kg (7 weeks). Active CMV infection was diagnosed on the basis of DNAemia in plasma, by a newly developed CMV polymerase chain reaction (PCR) test (AMPLICOR CMV). The disappearance of CMV from plasma was confirmed by this PCR test. It seems that single CMV-IG therapy is worth consideration for the treatment of CMV infection.

Antibodies, Viral↗

Evaluation of the AMPLICOR CMV test for direct detection of cytomegalovirus in plasma specimens.

We evaluated the AMPLICOR CMV test (PCR) for the direct detection of cytomegalovirus in plasma. Sixty-eight specimens were involved for the comparison between the AMPLICOR test and the antigenemia assay. The sensitivities, specificities, and positive and negative predictive values were 97.1, 100, 100, and 97.1%, respectively, for the AMPLICOR test and 79.4, 100, 100, and 82.9%, respectively, for the antigenemia assay.

Antigens, Viral↗

Pheochromocytoma in a long-term hemodialysis patient, discovered as an adrenal incidentaloma.

A case of pheochromocytoma was discovered incidentally during long-term hemodialysis for chronic renal failure due to acquired cystic kidney disease. A 52-year-old male patient was examined for weight loss of 3 kg during over a period of 3 months. Abdominal computed tomography (CT) revealed a left adrenal mass (3.0 cm in size). Plasma adrenaline and noradrenaline were increased to 521 pg/ml and 1,341 pg/ml, respectively, and the metoclopramide provocative test was positive. Further, in the scintiscan using 123I-metaiodobenzylguanidine (MIBG), an accumulation of the radionuclide in the left adrenal tumor region was confirmed. The patient is currently under observation and conservative treatment due to the possible occurrence of arterial hypotension after resection of the tumor and to lesser possibility of the malignancy.

3-Iodobenzylguanidine↗

Establishment of a new cell line from a patient with hairy cell leukemia-Japanese variant.

A cell line, JHC-2, was established from the peripheral blood of a patient with hairy cell leukemia (HCL)-Japanese variant. The JHC-2 cells have cytologic features similar to those of the original tumor cells. They displayed hairy cytoplasmic projections by phase contrast and scanning electron microscopy. The tartrate-resistant acid phosphatase reaction was weakly positive. The immunophenotype of the JHC-2 cells was CD5-, CD10-, CD11c+/-, CD19+, CD21+, CD23+, CD24-, CD25+/-, CD38- and FMC-7+. The expression of surface immunoglobulin (IgG, kappa) and the configuration of Ig gene rearrangements in the JHC-2 cells were identical to those in the original leukemic cells, and the JHC-2 cells displayed trisomy 9 on cytogenetic examination. Southern blot analysis for the Epstein-Barr virus (EBV) genome showed that the JHC-2 cells contained the EBV genome, although the freshly isolated leukemic cells did not. These results indicate that the JHC-2 cell line is an EBV spontaneously transformed B cell line originating from HCL cells.

Acid Phosphatase↗

[Chronic myelogenous leukemia expressing two bcr-abl chimeric mRNA; a case report].

Chronic myelogenous leukemia (CML) expresses two types of bcr-abl chimeric mRNA. One is b3a2 type in which bcr exon 3 binds to abl exon 2, the other is b2a2 type that bcr exon 2 binds to abl exon 2. Either bcr-abl is normally expressed, but both types of bcr-abl mRNA can be expressed at the same time in a patient. We report here a rare case of CML expressing two types of bcr-abl mRNA and discuss the possibility that this double expression would help to monitor the clinical course of CML.

Adult↗