Detection of ETV6/MDS1/Evi-1 chimeric transcripts in a patient with acute myelocytic leukemia and t(3;12)(q26;p13)
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Biomedical subjects
Publications and source records attributed to H Wada.
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Changes in serum concentrations of propofol after administration of three different fluids were investigated in 42 scheduled surgical patients. Anesthesia was induced with propofol 2 mg.kg-1 and maintained with constant rate infusion of propofol 6 mg.kg-1.hr-1. After achieving a stable depth of anesthesia, 5 ml.kg-1 of acetate Ringer's solution, 6% hydroxyethyl starch saline solution or 20% mannitol solution was infused in 15 minutes. Blood samples each 2 ml were taken before and 0, 5, 15, 30 and 60 minutes after fluid treatment. We measured hemoglobin and hematocrit of the samples for calculating the dilution rate of the plasma with infusion treatment, and determined the serum concentration of propofol by HPLC-spectrofluorometry. After administration of each fluid, the serum concentrations of propofol decreased significantly to 17 +/- 15, 25 +/- 10 and 35 +/- 8%, respectively (mean +/- SEM). The dilution rate of the plasma from the fractional change in blood hemoglobin increased to 0.08 +/- 0.02, 0.24 +/- 0.03, and 0.36 +/- 0.03, respectively. Administration of mannitol might markedly increase distribution volume of propofol, and this can be attributed to osmotic action of mannitol and resultant expansion of extracellular fluid volume. The results of the present investigation suggest that this pharmacokinetic change decreased the concentration of propofol more significantly in mannitol treatment patients than in Ringer's solution or 6% hydroxyethyl starch saline treatment patients.
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To clarify cellular biological varieties of myeloma cells, biological differences were analyzed between 2 human myeloma cell lines, KMS-12-PE and KMS-12-BM, derived from pleural effusion and bone marrow, respectively, of a single patient. Although both lines were considered to be derived from the same clone because both had the same chromosomal marker and immunoglobulin H rearrangement, several biological differences were noted. CD11a and CD20 were highly expressed in the KMS-12-BM line, whereas the KMS-12-PE line showed a higher expression of CD7 and CD95/Fas. Although growth was stimulated in KMS-12-BM by interleukin-6 and interferon-alpha, it was inhibited in KMS-12-PE. In addition, apoptosis inhibitors Bcl-2 and Bcl-X(L) were highly expressed in KMS-12-BM cells. Because KMS-12-PE was cultivated 2 months before KMS-12-BM, these differences might be related to their origin (pleural effusion and bone marrow) or the phases of disease progression. However, these biological differences may help clarify myeloma cell biology and lead to improvement in treatment for myeloma patients.
We investigated the effect of propofol anesthesia on the level of interstitial dopamine in vivo awake free moving and anesthetized rats brain striatum using microdialysis techniques. Rats were implanted a microdialysis probe to right striatum of the brain and administered intravenously 20 mg.kg-1 of propofol for induction and followed by continuous infusion at 12.5, 25 and 50 mg.kg-1.hr-1 up to 1 hour. The microdialysis probe was perfused with artificial cerebrospinal fluid and dialysates from the probe were determined every 20 minutes by high performance liquid chromatography and electrochemical detection. Propofol anesthesia reduced the amount of dopamine derived from dialysate, but no prolonged increases of dopamine metabolites were observed, as we demonstrated in previous investigation for halothane, isoflurane or sevoflurane anesthesia. We hypothesize that the characteristics of propofol anesthesia for dopamine and its metabolites might contribute to low incidence of postoperative nausea and vomiting in its clinical use.
The contents of the chloroplast acidic lipids, SQDG (sulphoquinovosyldiacylglycerol) and PG (phosphatidylglycerol), were reduced in the cells of Chlamydomonas reinhartdtii with exposure to sulphur- or phosphorus-source limitation, respectively. The decrease in the content of one acidic lipid was accompanied by an increase in the content of the other acidic lipid, which resulted in the maintenance of a certain level of total acidic lipids of chloroplast membranes. On the other hand, the content of each acidic lipid was little affected by temperature stresses during cell growth.
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In yeast, RAD52 has been shown to be essential for homologous recombination of DNA and to be involved in the repair of double-stranded DNA breaks. Recently, the human homologue of yeast RAD52, a 418-amino-acid protein, has been identified. In this study, we report three different isoforms of human RAD52 isolated from brain and testis cDNA libraries. cDNAs of these isoforms contain distinct insertions and encode truncated proteins due to translational frame-shifts. The three isoforms consist of 226-, 139-, and 118-amino-acid residues, and are designated as RAD52beta, gamma, and delta, respectively. The original RAD52 is termed as RAD52alpha in this paper. Messages of these isoforms have been detected in various human tissues. We found that the RAD52 isoforms were unable to interact with RAD52alpha because of partial defect of the self-interaction domain. Furthermore, like RAD52alpha, the isoforms have been shown to bind to both single-stranded and double-stranded DNA. These results suggest that RAD52beta, gamma, and delta might affect RAD52alpha function through their DNA-binding property and their inability to bind to RAD52alpha. Thus, these isoforms might act as dominant negative mutants or negative regulators of RAD52alpha.
We have previously shown that human cullin-2 (Cul-2) is covalently modified at Lys-689 by NEDD8 (Wada, H., Yeh, E. T. H., and Kamitani, T. (1999) Biochem. Biophys. Res. Commun. 257, 100-105). Cul-2 has also been reported to form a multiprotein complex, Cul-2.VBC, with the von Hippel-Lindau tumor suppressor gene product (pVHL) and elongins B and C. In this study, using an in vivo coexpression system in COS cells, we show that NEDD8 conjugation to Cul-2 is promoted by coexpression with wild-type pVHL and elongins B and C. Interestingly, tumorigenic mutants and deletion mutants of pVHL, which are unable to form a Cul-2.VBC complex, do not have the activity to promote NEDD8 conjugation to Cul-2. These results suggest that the complex formation is required for NEDD8 conjugation to Cul-2. Furthermore, we used a pVHL-deficient cell line, 786-0, to show that Cul-2 is poorly but clearly conjugated by NEDD8, indicating that pVHL is not the only molecule that promotes NEDD8 conjugation to Cul-2. Taken together, the VBC complex appears to have ligase activity in the conjugation of NEDD8 to Cul-2.
An error in the figures is reported. In the paper by Onoda et al. [Acta Cryst. (1999), B55, 721-725] the figures are given in the wrong order. Fig. 1 on p. 723 should in fact be Fig. 2 on p. 724 and vice versa. The figure captions are given correctly.
A cellular target of adenovirus E1A oncoprotein, p300 is a transcriptional coactivator and a negative regulator of cellular proliferation. A previous study suggests that the p300 family is also involved in cell type-specific transcription in cardiac myocytes. However, nothing is known about which cardiac transcription factor(s) interact with and transactivate through these proteins. The transcription factors GATA-4/5/6 have been implicated as key regulators of cardiogenesis, and they participate in the transcription of many cardiac-specific genes. Here we show that E1A represses the GATA-5-dependent transactivation of a promoter derived from the cardiac-restricted atrial natriuretic factor gene. This repression is correlated with the interaction of E1A with p300, indicating that p300 participates in GATA-5-dependent transactivation. E1A markedly down-regulates endogenous atrial natriuretic factor expression, as well as disrupts the interaction between p300 and GATA-5. A small fragment of p300 containing the carboxyl-terminal cysteine/histidine-rich domain, sufficient to interact with GATA-5, prevents transcriptional activation by GATA-5 as a dominant-negative mutant. Consistent with its role as a coactivator, p300 markedly potentiates GATA-5-activated transcription. These results implicate p300 as an important component of myocardial cell differentiation and provide an insight into the relationship between mechanisms that mediate cell type-specific transcription and cell cycle regulation during cardiogenesis.
Primary leiomyosarcoma of the thyroid gland is rare, and to the best of our knowledge only nine well-documented cases have been previously reported in the world literature. We herein report a 90-year-old female patient with primary leiomyosarcoma of the thyroid gland who showed a rapid tumor growth and tracheal obstruction. The patient was successfully treated by a partial resection of the thyroid gland using an ultrasonically activated scalpel and emergency tracheostomy. Immunohistochemically, the tumor cells showed positive reactivity to smooth muscle actin and negative reactivity to thyroglobin. Palliative surgery successfully allowed the patient to recover from the symptoms of dyspnea related to this rare disease. The use of an ultrasonically activated scalpel and tracheostomy thus allowed us to safely perform a thyroidectomy with substantially less bleeding than normal.
BACKGROUND: Adult respiratory distress syndrome-like respiratory disorders are a serious, but uncommon, complication of bone marrow transplantation. METHODS: We measured various cytokines in 2 patients with respiratory disorders and 11 patients without respiratory problems after allogeneic bone marrow transplantation. RESULTS: The patients with respiratory disorders had elevated levels of interferon-gamma and interleukin-2 in the aplastic phase, and elevation of tumor necrosis factor-alpha, intercellular adhesion molecule-1, and interleukin-8 at the time of leukocyte recovery. Both patients with respiratory disorders developed fever during the aplastic phase, whereas none of the patients without fever had respiratory disorders. Among patients who had fever during the aplastic phase but no respiratory disorders, there was no elevation of cytokines from the aplastic phase to the recovery phase. CONCLUSIONS: Respiratory disorders may occur after bone marrow transplantation when an inflammatory response during the aplastic phase stimulates cytokines that cause vascular endothelial damage and increases the levels of chemokines and adhesive molecules along with elevation of the leukocyte count.
BACKGROUND: To the authors' knowledge the prognosis of patients with intrapulmonary metastases (PM) of nonsmall cell lung carcinoma (NSCLC) has not yet been clarified fully and little is known regarding the characteristic changes that occur during the metastatic process, nor of their clinical significance. METHODS: Formalin fixed and paraffin embedded material of primary and metastatic lesions resected from 34 patients with PM of NSCLC were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44 and its variant isoforms. RESULTS: Patients with NSCLC expressing PCNA in the primary tumor site (79.4%) showed a significantly poorer survival (5-year survival rate of 20.2%) compared with the 5-year survival rate of 57.1% for patients not expressing PCNA in the primary tumor site (P = 0.048). Patients expressing PCNA in the metastatic site (88.2%) also showed a significantly poorer prognosis than those not expressing PCNA (P = 0. 036). Patients with squamous cell carcinoma expressed CD44 variant exon 6 (CD44v6) at a significantly higher rate than adenocarcinoma patients (P = 0.0164), but expression of CD44v6 was not a significant prognostic factor. Concordance of PCNA and CD44v6 expression between the primary and corresponding metastatic sites was observed in 65% of patients (22 of 34 patients) but no difference in prognosis was observed in relation to this concordance. Cox multivariate analyses indicated that expression of PCNA was a significant prognostic indicator for both primary and metastatic sites (P = 0.014 and P = 0.0095, respectively). CONCLUSIONS: This study demonstrated that PCNA expression was a significant prognostic factor for both primary and metastatic lesions in PM patients. CD44v6 showed histogenesis of the tumor, but no relation with the prognosis could be ascertained.
The structure of the orthorhombic room-temperature phase of Cu(8)GeS(6) (copper germanium sulfide), M(r) = 773.27, has been refined on the basis of X-ray diffraction data from a 12-fold twinned crystal applying a six-dimensional twin refinement technique. For 1804 unique reflections measured using Mo Kalpha radiation, R(F) was 0.083 with 77 structure parameters and 12 scale factors. The symmetry operations, the unit cell and other crystal data are (0, 0, 0; (1/2), (1/2), 0) + x, y, z; y, x, z; (1/4) - x, (3/4) - y, (1/2) + z; (3/4) - y, (1/4) - x, (1/2) + z; a = b = 9.9073 (3) Å, c = 9.8703 (4) Å, alpha = beta = 90 degrees, gamma = 90.642 (4) degrees; V = 968.7 (1) Å(3), Z = 4, D(x) = 5.358 Mg m(-3), µ = 21.70 mm(-1). The standard setting of the space group and the reduced unit cell are Pmn2(1); a = 7.0445 (3), b = 6.9661 (3), c = 9.8699 (5) Å; Z = 2.
The cephalochordate amphioxus has a single Hox gene cluster. Here we describe the genomic organization of four adjacent amphioxus genes, AmphiHox-1 to AmphiHox-4, together with analysis of their spatiotemporal expression patterns. We demonstrate that these genes obey temporal colinearity and that three of the genes also obey spatial colinearity in the developing neural tube. AmphiHox-1, AmphiHox-3, and AmphiHox-4 show segmental modulation of their expression levels, a two-segment phasing of spatial colinearity, and, at least for AmphiHox-4, asymmetrical expression. AmphiHox-2 is unlike other amphioxus Hox genes: it does not obey spatial colinearity and it has no positional expression in the neural tube. AmphiHox-2 is expressed in the preoral pit of larvae, from which the homologue of the anterior pituitary develops. We suggest that the ancestral role of chordate Hox genes was primarily in the neural tube and that chordate Hox genes can functionally diverge in a manner analogous to that of Drosophila ftz or zen.
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BACKGROUND: Saccharides are considered to play a role as osmotic impermeants and serve as an energy source for the organ during ischemia. However, previous studies on the effectiveness of saccharides on organ preservation have yielded conflicting results. We compared the preservative effects of a monosaccharide (glucose), disaccharides (trehalose, maltose, sucrose), and a trisaccharide (raffinose) to investigate whether the effects of saccharides on lung preservation depend on their molecular weight, energy-level maintenance, and cytoprotective effects. METHODS: We used an ex vivo rat lung model using homologous blood as the perfusate. In the fresh group, the lungs were reperfused immediately after flush. In the other groups, the lungs were flushed with one of the solutions containing glucose, trehalose, maltose, sucrose, or raffinose and preserved for 14 hours. RESULTS: The results of the trehalose group were comparable to those of the fresh group. The glucose, maltose, and raffinose groups showed significantly higher levels of shunt fraction, pulmonary artery pressure, and peak inspiratory pressure compared with the fresh and trehalose groups. There were no differences among the groups in the levels of total adenine nucleotides, adenosine triphosphate of the lung after flush, and preservation. However, after reperfusion, levels of total adenine nucleotides became significantly lower in the glucose, sucrose, maltose, and raffinose groups. Ultrastructural examination revealed endothelial cell injury in the glucose, sucrose, maltose, and raffinose groups. CONCLUSIONS: These results show that the effects of saccharides may depend on their cytoprotective effect rather than on impermeant activity or energy-level maintenance of the preserved lung. Trehalose proved to be superior to the other saccharides.