Biomedical subjects

Tadao Funato

Publications and source records attributed to Tadao Funato.

26 records · Page 2Linked to original sources

PubMed2002

Nucleotide alteration of retinoblastoma protein-interacting zinc finger gene, RIZ, in human leukemia.

The retinoblastoma protein-interacting zinc finger gene (RIZ) is a zinc-finger type DNA binding protein and is postulated as a member of the nuclear protein-methyltransferase superfamily. RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the N-terminal PR (PRDI-BF1 and RIZ homologous)-domain, RIZ2 lacks it. RIZ1 is now considered as a tumor suppressor. We analyzed nucleotide alteration of RIZ gene in human leukemia. The results revealed a single nucleotide polymorphism (SNP), T1704 to A, near the conserved Rb-binding domain, leading to an amino acid change, Asp283 to Glu. Interestingly, 17 of 21 leukemia cell lines are homozygous for the T1704 allele whereas only 2 of 20 normal subjects are homozygous for the allele. In addition, one base pair deletion in the poly (A)9 tract in the coding region near the C-terminal zinc-fingers was identified, resulting in frameshift, in 1 out of 17 leukemia cell lines, but no mutation in samples from 15 patients with acute lymphoblastic leukemia (ALL) and 6 patients with adult T cell leukemia (ATL). In the PR or SH3 (src homology 3) domain of the RIZ gene, no mutation was found. These findings suggest that RIZ may be a possible target of structural alteration leading to leukemia.

Alleles↗

PubMed2002

[Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced influenza-virus-associated encephalopathy].

The mechanism causing influenza-virus-associated encephalopathy is unclear, even though diclofenac metabolites may induce this pathogenesis. CYP2C9 is known as the major cytochrome P450 gene product that catalyzes diclofenac in human liver. It is uncertain whether the mutation of CYP2C9 is associated the pharmacologic effects of diclofenac in influenza infection. Therefore, we applied a simple and rapid procedure involving real-time fluorescence allele-specific PCR(TaqMan-ASA) assay and denaturing HPLC assay to detect the mutation of CYP2C9 gene. A single-base mutation in the CYP2C9 gene was found in one of thirty subjects in the healthy population. We suggest that this mutation in the CYP2C9 gene may be related to diclofenac-induced influenza-virus-associated encephalopathy.

Aryl Hydrocarbon Hydroxylases↗

PubMed2002

[Comparative study of T-wave alternans, QT c dispersion and late potential for predicting ventricular tachycardia in patients with ischemic heart disease].

Ventricular tachycardia(VT) is well known as the life-threatening arrhythmia. It would be important for predicting the risk of VT to prevent sudden death caused by VT after myocardial damage such as old myocardial infarction and dilated cardiomyopathy. In this study, we examined late potential(LP), TWA alternans(TWA), and QTc dispersion(QTcd) measured by Holter ECG, in 21 patients with old myocardial infarction(OMI) and 21 patients with dilated cardiomyopathy(DCM), and evaluated these parameters in relation with the occurrence of VT on these patients. The sensitivities of LP, TWA, and QTcd in patients with OMI in relation with VT were 82%, 73%, and 82%, respectively, and those in patients with DCM were 82%, 93%, and 73%, respectively. The specificities of LP, TWA, and QTcd in patients with OMI in relation with VT were 100%, 40%, and 100%, respectively, and those in patients with DCM were 100%, 30%, and 100%, respectively. The data demonstrated that LP and TWA were the useful predictive parameters for the VT on myocardial damage such as OMI and DCM.

Adult↗

PubMed2002

Quantitative analysis of a MDR1 transcript for prediction of drug resistance in acute leukemia.

BACKGROUND: Assessing the drug resistance of leukemic cells is important for treatment of leukemia. We developed a quantitative reverse transcription (RT)-PCR method for multidrug resistance 1 (MDR1) and multidrug resistance-related protein 1 (MRP1) transcripts to evaluate drug resistance, and applied it to clinical samples. METHODS: The cutoffs for copy numbers of MDR1 and MRP1 transcripts were defined based on copy numbers in healthy bone marrow mononuclear cells. To confirm that the cutoffs reflected biological resistance, we established vincristine (VCR)-resistant K562 sublines that showed various degrees of drug resistance and examined the correlation between the copy numbers of these transcripts and the biological resistance of these clones. In addition, we compared the sensitivity and specificity of quantitative RT-PCR to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric (FCM) analysis. RESULTS: The defined cutoff for copy numbers of MDR1 transcripts corresponded with the degree of biological resistance of VCR-resistant K562 sublines. Clinical study revealed that the concentrations of MDR1 mRNA in all relapsed patients with acute myelogenous leukemia (AML) were above the cutoff. Moreover, both AML and acute lymphoblastic leukemia patients with high MDR1 mRNA expression at diagnosis tended to show a low remission rate and short remission periods. No association was observed between the amounts of MRP1 transcripts and clinical outcomes. The specificity and sensitivity of quantitative RT-PCR for MDR1 were superior to the MTT assay and FCM analysis. CONCLUSION: These results suggest the efficacy of this quantitative analysis of MDR1 transcripts for the prediction of clinical drug resistance in acute leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

[Molecular diagnosis for diagnosis of leukemia].

Molecular methods are emerging as important tools for diagnosis and therapy of patients with leukemia. First, the development of conventional Southern blot analysis has facilitated the detection of rearrangements in immunoglobulin and T-cell receptor genes. Moreover, many chimeric genes involved in balanced translocation have identified significant classifications of leukemia patients by cytogenetic techniques such fluorescent in situ hybridization (FISH) and reverse-transcriptase polymerase chain reaction (RT-PCR). These techniques provide an advantage in monitoring minimal residual disease (MRD). Furthermore, recent gene expression analysis with quantitative PCR assays such as real-time PCR have developed the early diagnosis and monitoring of MRD. These molecular-based diagnoses have contributed to the clinical decision-making process in the diagnosis of leukemia.

Humans↗

PubMed2002

[Genetic education in pre- and post-graduation].

Molecular genetics is now integral to all aspects of biomedical science. Every medical school should have a best program of basic and practical genetics education as one of the core curriculum. Genetic information includes DNA, chromosome analysis and clinical tests, as well as family history. The benefit of patient received genetic tests is counseling by counselors well educated. Thus each medical and technological school must find the best way to incorporate genetics teaching into its own curriculum.

Bioethics↗

PubMed2002

[The ethical implications, guidelines, and standardization of genetic tests].

Laboratory advances in molecular genetics have resulted in numerous clinical applications for DNA analysis. Genetic tests can contribute a great deal of information to clinical diagnosis. These genetic tests including PCR, fluorescence detection, real-time PCR, and automated sequencing have developed into both simple and time-consuming laboratory techniques. Currently, DNA diagnosis is not used routinely because of cost, complexity, and resources. We have focused on the ethical implications and proper standardization in DNA diagnosis. This review is to discuss a guide to proceed genetic tests for their efficiency, accessibility and quality in laboratory.

Genetic Counseling↗

PubMedDate not supplied

Microsatellite instability in gonadal tumors of XY pure gonadal dysgenesis patients.

To investigate genetic alternation accompanied by malignant transformation in gonadal tumors of XY pure gonadal dysgenesis patients, we investigated microsatellite instability in the hMSH1, hMSH2, TP53, and DCC loci, and ras mutations in two patients. The gonadal tumors from the patients were combined gonadoblastoma and dysgerminoma. Microsatellite instability and/or loss of heterozygotes (LOH) at hMSH1, hMSH2, and TP53 were detected in the dysgerminoma lesions of the both patients, but were not observed in any normal tissues. In the analyses of the H-, K-, or N-ras genes, where specific mutations have been frequently reported, no mutations were observed in the tumors. It is suggested therefore that microsatellite instability plays an important role in malignant transformation of gonadal tumors in patients with XY pure gonadal dysgenesis.

Adolescent↗