A family of severe congenital neutropenia with -199C to A substitution in ELA2 promoter.
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Adolescent↗
Biomedical subjects
Satomi Asai
Publications and source records attributed to Satomi Asai.
A cost-effectiveness evaluation of reticulocyte measurement in new outpatients with or without hematologic disorders.
BACKGROUND: Although reticulocyte counts provide very useful information, few studies have analyzed the cost-effectiveness of this testing. METHODS: The yield and cost of reticulocyte count testing were analyzed in 719 new outpatients who visited the comprehensive medicine clinics and received both reticulocyte and complete blood count (CBC) testing. A "useful result" (UR) of the testing was defined as a finding that contributed to a change in a physician's diagnosis or decision-making between the pre- and post-test diagnosis. Patients' medical records were thoroughly reviewed for the assignment of URs. A simulation study was performed, blinding the reticulocyte data to the examiners, for the determination of URs generated by CBC alone. RESULTS: CBC and reticulocyte testing generated a total of 838 URs in 719 patients, while the simulation study demonstrated 612 URs with CBC testing alone. When patients were grouped into 11 major disease categories according to a pre-test diagnosis, clinical effectiveness (UR/patient) varied from 1.69 (hematologic) to 0.13 (metabolic/endocrine patients), with a cost disparity from 206yen to 2784yen/UR. The cost-effectiveness (Deltacost/DeltaUR) of reticulocyte addition against CBC alone was 515yen per additional UR as a whole. Reticulocyte testing showed favorable cost-effectiveness in gastrointestinal ( 234yen) and hematologic patients ( 338yen/additional UR), while the test added few URs in metabolic/endocrine and neurologic patients, resulting in possibly unacceptable cost-effectiveness ( 3240yen and 2916yen/additional UR, respectively). CONCLUSIONS: Wide disparity in its cost-effectiveness among patients apparently indicated that reticulocyte count testing should be performed for selected patient groups on the basis of its cost-effectiveness.
Cost-Benefit Analysis↗
Clubbed fingers in a patient with inflammatory gingival hyperplasia.
The association of clubbing with miscellaneous diseases and its diagnostic implications are such that its detection should prompt consideration of the underlying etiology. We encountered a 48-year-old woman with clubbed fingers and a cauliflower-like gingival swelling on the hard palate of the upper jaw. There were no conventionally well-known causes for clubbing. Histological examination of gum biopsy specimen revealed a diagnosis of inflammatory gingival hyperplasia. As an etiology of clubbed fingers, gingivitis was suggested, since clubbing was regressed in parallel with remission of the gingivitis after the treatment by extraction of anterior teeth. Possible involvement of an autoimmune process in the pathogenesis was also considered, because of concomitant elevation of serum anti-double strand DNA antibodies. We recommend examination of the oral cavity for search of an inflammatory disease in cases with clubbed fingers, particularly when other common causes are not apparent.
Antibodies, Antinuclear↗
Virus-associated hemophagocytic syndrome in an international traveler as a differential diagnosis of SARS.
During the epidemic of severe acute respiratory syndrome in 2003, a 27-year- old Japanese woman presented a high fever and acute respiratory distress with pulmonary infiltrates after traveling to a high-risk area. An alternative diagnosis was made as Epstein-Barr virus-associated hemophagocytic syndrome, based on the proliferation of macrophages with hemophagocytosis in the bone marrow and Epstein-Barr viral marker profiles. Virus-associated hemophagocytic syndrome in an international traveler should be included in the differential diagnosis of severe acute respiratory syndrome.
Adult↗
[Methods for the specimen preparation for molecular diagnostic tests].
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Automation↗
Large diversity in transport-mediated methotrexate resistance in human leukemia cell line CCRF-CEM established in a high concentration of leucovorin.
To elucidate the mechanism(s) of methotrexate (MTX) resistance as a possible reason underlying treatment failure in high-dose MTX regimens combined with leucovorin (LV) rescue, we established MTX-resistant human T-cell leukemia cell line CCRF-CEM cells in the presence of excess LV, and characterized their properties. Continuous exposure of the cells to escalating concentrations of MTX up to 20 microM in the presence of 1000 nM LV resulted in establishment of three MTX-resistant sublines with a wide disparity of resistance degree over a 4 logarithmic range (approximately 40-, 900- and 44,000-fold, respectively). Transmembrane transport of MTX in these sublines was diminished to 52%, 35% and 12%, respectively. Intracellular retention of MTX in these sublines was not different from that of the parent cells. A cell growth study in various concentrations of LV showed that cells with higher resistance to MTX required more LV for optimal growth. In parallel with the resistance levels, there was an increase in mRNA expression of dihydrofolate reductase gene and a decrease in that of thymidylate synthase gene, but no change in that of reduced folate carrier (RFC1) gene, as assessed by northern blot analysis. Sequencing of the RFC1 gene in all 3 sublines revealed a point mutation in codon 47 (TCC-->TTC) resulting in substitution of Phe for Ser residue, and additional deletion of CTG of codon 112 in the subline with the highest resistance. In summary, MTX exposure to CCRF-CEM cells in the presence of 1000 nM LV resulted in the establishment of heterogeneous cell populations with a wide range of transport-mediated MTX resistance, which was associated with differential alterations of RFC gene. These cell lines may serve as models for investigation of the molecular mechanism(s) underlying refractory tumors in high-dose MTX regimens with LV rescue.
Amino Acid Substitution↗
Quantitative assay of hepatitis C virus RNA using an automated extraction system for specific capture with probes and paramagnetic particle separation.
A commercially available automated specimen preparation instrument for specific probe capture and paramagnetic separation has been developed (AmpliCap/GT-12; Roche Molecular Systems). We evaluated assay performance of the AmpliCap/GT-12 in the quantitative assay for hepatitis C virus (HCV) RNA with the AMPLICOR HCV MONITOR Test (version 2.0). Assay linearity using serial dilutions from a serum panel was observed in the range of 500 to 850000 IU/ml, with a slightly compromised slope in the higher viral titers. The overall within-run and between-run reproducibility of the entire detection process for 3 and 5 log(10) (IU/ml) of HCV RNA in samples had a standard deviation of <0.2, which was comparable to a manual method based on organic extraction and isopropanol precipitation (Roche Molecular Systems). Comparison of the test results with those obtained by the manual method showed a good correlation (R(2) = 0.972, n = 86). Using heparin (3, 6.5, and 13 U/ml), dextran sulfate (0.1, 1, and 5 mM), hemoglobin (1.13, 2.25, and 4.5 g/liter), conjugated or unconjugated bilirubin (7.5, 15, and 30 mg/dl), and ATP (1.25, 2.5, and 5.0 mM) as known inhibitors, inhibition was only detected at a dextran sulfate concentration of 1 mM with the manual method but not with the AmpliCap/GT-12 extraction. In summary, the AmpliCap/GT-12 system was shown to permit a stable extraction process and accurate results for the quantitative assay of HCV RNA, successfully eliminating the inhibitory effect of dextran sulfate. This automated extraction system provides reliable and reproducible test results and saves labor; thus, it is suitable for routine diagnostic PCR.
Automation↗
Reversal of drug resistance mediated by hammerhead ribozyme against multidrug resistance-associated protein 1 in a human glioma cell line.
We examined the effects of suppressing multidrug resistance-associated protein 1 (MRP1) gene expression in a human glioma cell line U87MG. Hammerhead ribozymes, designed to cleave MRP1 mRNA (alphaMRP1-Rz), were transfected into the U87MG cells. The U87MG/alphaMRP1-Rz cells were significantly sensitive to nitrosourea (ACNU) and doxorubicin (DOX) compared with the U87MG cells (p<0.01 and p<0.05, respectively, unpaired t-test). There was no significant difference in the expression of other human genes between the U87MG/alphaMRP1-Rz and controls by cDNA array. The hammerhead ribozyme-mediated specific suppression of MRP1 was sufficient to reverse the resistance of ACNU and DOX in the human glioma cell line.
Antibiotics, Antineoplastic↗
[Genetic tests for molecular markers of cancer].
Based on recent advancements in biotechnology and molecular oncology, genetic tests for molecular markers have been widely used for diagnosis and therapeutic monitoring in patients with hematological malignancies. However, incorporation of such tests has been limited in the care of patients with non-hematopoietic malignancies. The reasons for this include difficulty in sampling of the tumor tissue, and a lack of evidence for cost-effectiveness in the test utilization. A practical approach is the use of bodily fluids, such as blood, sputum, urine and feces, as specimens for early detection and monitoring of tumor-derived nucleic acid sequences. The prospect has been raised for development of tests for individualized medicine based on genetic information such as prediction of responsiveness to chemotherapeutic agents for selection of treatment, which will be promoted by gene expression profiling using DNA microarray.
Biomarkers, Tumor↗
Smoldering myeloma associated with zonisamide treatment.
A 39-year-old man was found to have hyperproteinemia after being treated with zonisamide for 10 years. Laboratory examination revealed a serum M-protein which consisted of IgG (lambda) and an increased number of plasma cells in the bone marrow, resulting in a diagnosis of smoldering myeloma. Considering his age, zonisamide was suspected to play an etiologic role in the occurrence of smoldering myeloma. Zonisamide was changed to sodium valproate. Subsequently the M-protein did not increase over 13 months. When zonisamide is used, the monitoring of serum levels of M-protein and patterns of gammaglobulin is warranted.
Adult↗
Extensive wall thickening in intestinal Burkitt lymphoma.
OBJECTIVE: To evaluate intestinal lesions in Burkitt lymphoma. METHODS: Ultrasonography was used in the initial evaluation of 6 Japanese patients with intestinal Burkitt lymphoma. RESULTS: Ultrasonography revealed marked wall thickening of the colon from the cecum through either the ascending or the transverse colon, which led to a target sign (4 cases) or a pseudokidney sign (2 cases). The target sign histopathologically corresponded to invagination of an occult tumor of the cecum into the ascending colon. Wall thickening of the colon when associated with a target or pseudokidney sign corresponded to marked lymph edema or a diffuse infiltration of Burkitt lymphoma cells into the intramural layers, respectively CONCLUSIONS: Ultrasonography provides useful information in the initial evaluation of intestinal lesions with distinctive histopathologic characteristics in Burkitt lymphoma.
Adolescent↗
[cDNA microarray technology as a laboratory examination method: a gene expression profiling test for analysis of drug resistance in tumor cells].
cDNA microarray technology permits the simultaneous measurement of the expressions of thousands of genes. The technology is now an indispensable research tool in molecular biology, and the challenge is its development and usage as clinical diagnostic tools. cDNA microarray can be used to identify gene expression profiles in tumor cells which correlate strongly with the treatment responsiveness such as drug resistance and clinical outcome of the disease despite similar phenotypes. For the introduction of cDNA microarray into laboratory examination, many issues need to be resolved. Design of a diagnostic array must be developed with defined sequences based on interpretation of huge quantities of data from experimental arrays to predict treatment responsiveness. Assay quality must be improved in terms of detection sensitivity, reproducibility, and linear dynamic range for RNA quantitation. Generally available instruments, which are much less expensive and more practical, need to be developed. Along with the improvement of the assay as a laboratory examination method, cDNA microarray will facilitate the integration of diagnosis and therapeutics, and the introduction of individual medicines.
Clinical Laboratory Techniques↗
Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene.
We examined the effects of suppressing multidrug resistance-associated protein (MRP) and multidrug resistance 1 (MDR1) gene expression in HCT-8DDP human colon cancer cell lines, which showed both cisplatin and multidrug resistance. Hammerhead ribozymes, designed to cleave MRP mRNA (anti-MRP Rz) and MDR1 mRNA (anti-MDR1 Rz), were transfected into the HCT-8DDP cells. Drug sensitivity was estimated by MTT assay in vitro. The HCT-8DDP/anti-MRP Rz cells were more sensitive to doxorubicin (DOX) and etoposide (VP-16) by 2.5- and 4.1-fold, respectively, compared with HCT-8DDP cells. The HCT-8DDP/anti-MDR Rz cells were more sensitive to DOX and VP-16 by 2.3- and 3.8-fold, respectively. The anti-MRP Rz and anti-MDR1 Rz significantly down-regulated resistance to DOX and VP-16, while anti-MRP Rz and anti-MDR1 Rz did not affect resistance to cisplatin, methotrexate and 5-fluorouracil. The hammerhead ribozyme-mediated specific suppression of MRP or MDR1 was sufficient to reverse multidrug resistance in the human colon cancer cell line.
ATP Binding Cassette Transporter, Subfamily B, Mem↗