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Biomedical subjects

M Ohki

Publications and source records attributed to M Ohki.

At least 73 records · Page 4Linked to original sources
PubMed1997

Translocation (8;12;21)(q22.1;q24.1;q22.1): a new masked type of t(8;21)(q22;q22) in a patient with acute myeloid leukemia.

The translocation t(8;21)(q22;q22) is found in 40% of cases of acute myeloid leukemia (AML) designated as the subtype M2 in the French-American-British (FAB) classification. The 8;21 translocation is clinically of interest because patients with this subtype have a good prognosis. We describe a masked type of the translocation, t(8;12;21)(q22.1;q24.1;q22.1). The translocation was first interpreted as t(8;12)(q22;q24) based on cytogenetics, but was reevaluated as a result of Southern blot and fluorescence in situ hybridization (FISH) analyses.

Acute Disease↗
PubMed1997

The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10.

The inv(11)(p15q22) is a recurrent chromosomal abnormality associated with de novo and therapy-related myeloid malignancies. Here we report the molecular definition of this chromosomal aberration in four patients. Positional cloning showed the consistent rearrangement of the DDX10 gene on chromosome 11q22, which encodes a putative RNA helicase. The translocation targets the NUP98 gene on 11p15, a member of the FG peptide repeat nucleoporin family. In DDX10 and NUP98, the inv(11) breakpoints occurred within two introns of each gene and the two genes merged in-frame to produce the chimeric transcripts characteristic of this translocation. Although two reciprocal chimeric products, NUP98-DDX10 and DDX10-NUP98, were predicted, only NUP98-DDX10 appears to be implicated in tumorigenesis. DDX10 is predicted to be involved in ribosome assembly. NUP98 has been identified as a nuclear pore complex protein and a target of chromosomal translocation in acute myeloid leukemia through the t(7;11)(p15;p15) translocation. The predicted NUP98-DDX10 fusion protein may promote leukemogenesis through aberrant nucleoplasmic transport of mRNA or alterations in ribosome assembly.

Amino Acid Sequence↗
PubMed1997

Hematologic malignancies with the t(10;11) (p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes.

Previous studies described the t(10;11)(p13-14;q14-21) as a recurring translocation associated with T-cell acute lymphoblastic leukemia (ALL). This translocation has also been reported in monocytic leukemia or ALL with a very early pre-B phenotype. However, whether these cytogenetically similar translocations involve the same molecular breakpoint is unknown. Using fluorescence in situ hybridization (FISH) with a series of probes on 11q, we mapped the 11q breakpoint of the U937 cell line, which was derived from a patient with diffuse histiocytic lymphoma and was shown by FISH to have the t(10;11)(p13-14;q14-21). Subsequently, we identified a yeast artificial chromosome (YAC) clone, y960g8, that included the breakpoint on 11q. From this YAC, we isolated a PI clone, P91B1, that was split by the 10;11 translocation. We studied four patients with a t(10;11), one of whom had acute monocytic leukemia (AMoL), one had acute lymphoblastic leukemia (ALL), one had lymphoblastic lymphoma (LBL), and one had granulocytic sarcoma, by using FISH with y960g8 and P91B1. Y960g8 and P91B1 were split by the translocation in each patient. We showed that P91B1 included a recently identified gene, CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene), and that AF10 was also rearranged in each patient by FISH when we used y807b3, which contains the AF10 gene. These findings indicate that hematologic malignant diseases with fusion of AF10 and CALM show various morphologic and immunologic phenotypes, suggesting that this fusion occurs in multipotential or very early precursor cells.

Adult↗
PubMed1997

Anastomotic intimal hyperplasia: a comparison between conventional and endovascular stent graft techniques.

Endovascular grafts (EVGs) have been proposed as a treatment for a variety of vascular diseases; however, the impact of EVGs on graft healing has not been fully evaluated. The aim of this study is to compare anastomotic intimal hyperplasia (AIH) and endothelialization in EVGs and conventional bypass grafts (CGs). Seven mongrel dogs received an EVG in one iliac artery and a CG in the other iliac artery using a 5 mm x 4 cm polytetrafluoroethylene graft. The EVG was secured to the native vessel wall, with balloon expandable stents at either ends of the graft. CGs were anastomosed using running sutures. Intravascular ultrasound was performed at the time of sacrifice (8 weeks) to determine percentage of stenosis at the distal anastomosis. Specimens were divided longitudinally for light microscopic analysis (thickness of distal AIH) and scanning electron microscopic studies (percentage of endothelial coverage of the graft). Percentage of stenosis at the distal anastomosis was significantly higher in EVGs compared with CGs (28.2 +/- 18.2% versus 1.8 +/- 2.8%; P < 0.01) due to significantly greater mean intimal thickness in the EVGs (441.1 +/- 101.1 microns versus 82.4 +/- 41.9 microns; P < 0.01). The total percentage of area covered by endothelial cells was also significantly greater in EVGs compared with CGs (80.5 +/- 37.5% versus 30.3 +/- 37.1%; P < 0.05). Intraluminal location enhanced endothelialization of the polytetrafluoroethylene graft; however, it also resulted in greater AIH. Further device refinements including stent design may be required to maximize the potential of these endovascular procedures.

Anastomosis, Surgical↗
PubMed1997

Discrimination of spinal fracture with various bone mineral measurements.

For several different bone mineral measurements and various skeletal sites, we compared capability to discriminate between women in various age decades with and without spinal fracture, and attempted to identify the most effective cutoff level in discrimination of spinal fracture. The subjects were 88 women aged 50-59 years (including 32 with fracture), 95 women aged 60-69 years (including 54 with fracture), and 34 women aged 70-79 years (including 18 with fracture). Spinal trabecular and cortical bone mineral density (BMD) were measured using quantitative computed tomography (CT), and spinal, radial (ultra-distal, 10% distal and 33% distal), and calcaneal BMD were measured by dual X-ray absorptiometry. These BMD values were obtained in each subject on the same day. Three statistical techniques-Student's t-test, the logistic regression analysis, and the receiver operating characteristics (ROC) analysis- were applied and accuracy was calculated using the various cutoff values. The capability to discriminate between women with and those without fracture using these BMD values was different among the three age groups. In women aged 50-59 and 60-69 years, all measurements showed good capabilities for discriminating women with fracture. In women aged 70-79 years, these measurements showed lower capability than in those aged 50-59 and 60-69 years, but among them, the calcaneal and ultradistal radial BMD showed relatively good capability. The 10% and 33% distal radial BMD values were not useful in the detection of the high risk women with fracture. The cutoff BMD values for discrimination of women with fracture varied according to the sites and methods of measurement. For each specific age group, the most suitable measurement methods and the appropriate skeletal sites should be considered, and the effective cutoff values to discriminate those with fracture may differ according to the measurement methods, the skeletal sites examined, and age.

Absorptiometry, Photon↗
PubMed1997

Relationship of spinal fracture to bone density, textural, and anthropometric parameters.

To investigate risk factors for spinal fracture, we studied the relationship between the prevalence of asymptomatic spinal fracture and various morphological measures including spinal bone mineral density (BMD) in women. A total of 122 women ranging in age from 55 to 79 years were studied. The group consisted of 46 women aged 55-59 years (18 with fracture), 51 women aged 60-69 years (26 with fracture), and 26 women aged 70-79 years (14 with fracture). BMD of cortical and trabecular bone from L1 to L3 was measured using quantitative computed tomography (QCT). Run-length analysis was applied to evaluate the spinal trabecular textural features using CT images; the texture indices which represent the mean width of trabecular (the T-texture) and that of intertrabecular spaces (the I-texture) were obtained. Anthropometric factors including body weight and height, psoas muscle area, and vertebral bone volume were measured using CT images. Among the various factors, trabecular BMD in women aged 55-69 years showed the highest odds ratio for the presence of fracture per standard deviation (SD) decrease in bone density. However, in women aged 70-79 years, the highest odds ratio was observed for trabecular texture index but not for trabecular BMD. The I-texture in women aged 55-59 years, the muscle area in women aged 60-69 years, and cortical BMD and muscle area in women aged 70-79 years were also considered significantly related to the risk of fracture.

Age Distribution↗
PubMed1997

Spinal trabecular bone loss and fracture in American and Japanese women.

This study examined trabecular bone mineral density (BMD) in Japanese women with and without spinal fracture, and compared the results to American women with and without fracture. The quantitative computed tomography (QCT) systems used at the University of California, San Francisco (UCSF) and at Nagasaki University were cross-calibrated. Normative BMD was assessed with the K2HPO4 liquid phantom in 538 Americans aged 20-85 years, and with the B-MAS200 phantom in 577 Japanese aged 20-83 years. These BMD were adjusted for use with the Image Analysis solid phantom using the result of cross-calibration. The trabecular BMD in 111 postmenopausal American women (55 with fracture), and in 185 postmenopausal Japanese women (67 with fracture) were compared for investigation of the difference in BMD values relative to fracture status. The absolute BMD values in Japanese were lower than those in Americans, and the differences were greater with advancing age. The magnitude of the BMD difference was 8.6, 20.5, 38.1 mg/cm3 in women aged 20-24 years, 40-44 years, 60-64 years, respectively. In premenopausal women, BMD began to decrease at the age of 20 in Japanese, whereas the peak bone mass was maintained until the age of 35 in the American women. In immediate postmenopausal women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age in the Japanese women but decreased less rapidly in the American women. The aging decrease of BMD was 1.4% and 2.2% per year in the later postmenopausal American and Japanese women, respectively. The fracture threshold is considered to be lower in Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without fracture. The Z-scores of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese women. In conclusion, Japanese women were found to have a lower BMD and lower fracture threshold than American women. The significant decrease of spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese women.

Adult↗
PubMed1997

Glucocorticoids induce apoptosis in acute myeloid leukemia cell lines with A t(8;21) chromosome translocation.

The t(8;21) chromosome translocation frequently occurs in the AML, acute myeloid leukemia, M2 sub-type. This translocation juxtaposes the AML1 gene on chromosome 21 with the MTG8(ETO) gene on chromosome 8, resulting in the expression of the AML1-MTG8(ETO) fusion transcript. The fusion product is thought to play a critical role in the abnormal proliferation and differentiation of myeloid leukemia cells. We investigated the effects of various differentiation inducers of myeloid leukemia cells on the growth and differentiation of Kasumi-1 and SKNO-1 cells, AML cell lines with t(8;21). These cells resisted differentiation into mature granulocytes and macrophages in response to various inducers of myelomonocytic differentiation, such as dimethyl sulfoxide, retinoic acid, butyrate, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1alpha,25-dihydroxyvitamin D3. On the other hand, dexamethasone can induce apoptosis in these cells at low concentrations, whereas other myelomonocytic leukemia cell lines tested were resistant to glucocorticoid-induced apoptosis. The levels of glucocorticoid receptor gene expression were high in Kasumi-1 and SKNO-1 cells. Expression of the AML1-MTG8(ETO), bcl-2, and c-myc genes was unchanged following exposure to dexamethasone. Glucocorticoids might induce the apoptosis of some types of AML cells, just like that of some lymphoid leukemia cells.

Acute Disease↗
PubMed1997

CBFA2, frequently rearranged in leukemia, is not responsible for a familial leukemia syndrome.

We have identified a family with an autosomal dominant platelet disorder with a predisposition for developing myeloid malignancies and have previously demonstrated linkage of this trait to chromosome 21q22.1-22.2. The nearest flanking markers, D21S1265 and D21S167, define the familial platelet disorder (FPD) critical region at a genetic distance of approximately 15.2 centimorgans and physical distance of approximately 6 megabases. This locus is of particular interest as it has previously been implicated in the pathogenesis of acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) through the (8;21), (3;21) and (12;21) chromosomal translocations. In each of these cases, the CBFA2 gene is rearranged. As well, there is a potential association of this locus with the hematologic abnormalities seen in Down syndrome (trisomy 21). To identify the mutant gene in this pedigree, a positional cloning strategy has been undertaken. Several candidate genes map to this locus including: CBFA2, IFNAR1, IFNAR2, CRFB4, GART, SON, KCNE1, SCL5A3 and ATP50. CBFA2, as well as IFNAR1 and CRFB4, were the focus of initial mutational analysis efforts. In this report, we exclude CBFA2 as a candidate by Northern and Southern blotting, RNase protection, single-strand conformational polymorphism (SSCP), direct sequencing and gel-shift analysis. Exons of the IFNAR1 and CRFB4 genes were also analyzed by SSCP and demonstrated no evidence of mutation. SSCP analysis identified a new polymorphism in the second exon of the CRFB4 gene and confirmed a previously described polymorphism in the fourth exon of IFNAR1. Efforts are currently underway to delimit further the FPD critical region and to analyze the other known candidate genes, as well as novel candidate genes, which map to this locus.

Core Binding Factor Alpha 2 Subunit↗
PubMed1997

Genetic analysis of 8;21 chromosomal translocation without AML1 gene involvement in MDS-AML.

We have investigated a case of acute myelocytic leukaemia derived from myelodysplastic syndrome (MDS-AML) with an 8;21 translocation. In this case the AML1/MTG8 (ETO) fusion transcript was not detected by reverse transcriptase-polymerase chain reaction (RT-PCR), and the rearrangement of the AML1 gene locus was not detected by Southern blot nor pulse field gel electrophoresis (PFGE) analyses using specific probes for the AML1 gene. Fluorescence in-situ hybridization (FISH) study using cosmid probes for 21q22 revealed that the breakpoint of 21q22 was telomeric to the AML1 gene locus and centromeric from D21S259, 351, 3421 loci. This is the first report concerning the t(8;21)(q22;q22) carrying AMLs (de novo AML, MDS-AML and therapy-related AML) to show that the breakpoint at 21q22 is located outside the AML1 gene locus. It is also noteworthy that the cell-surface antigen expression pattern of the bone marrow (BM) blasts was changed from CD7+ CD2+ CD13+ CD33+ CD19- CD11b+ CD14+ CD36+ to CD7- CD2- CD13+ CD19+ CD11b- CD14- CD33+ CD34+ CD36- CD56+ during leukaemic progression, and the pattern in leukaemic phase was similar to the characteristic phenotype of de novo AML cases with t(8;21), when the AML1/MTG8 fusion transcripts are always detected by RT-PCR.

Blotting, Southern↗
PubMed1997

A complete NotI restriction map covering the entire long arm of human chromosome 11.

BACKGROUND: Human chromosome 11 is one of the autosomes on which many disease genes have been mapped. Many different types of map, including a radiation hybrid map, a genetic map, and an STS-content YAC map, have been constructed for the chromosome. However, a physical map providing accurate physical distances has not yet been established. A chromosome-wide NotI restriction map was constructed to understand the overall feature of the genome organization and to facilitate the positional cloning of disease genes. RESULTS: A complete NotI restriction map of the entire long arm of human chromosome 11 was constructed using linking-clone mapping. This physical map covers 77.6Mb, from a pericentromeric NotI site to the terminus, and provides the most accurate ordering and distance estimation to date. We also mapped 138 sequence markers in the q13 region that have been poorly mapped previously. CONCLUSIONS: The restriction map of the entire long arm of human chromosome 11 is the longest restriction map of the human genome. This mapping has disclosed unique features regarding the organization of the chromosome, indicating that restriction sites of NotI, a CpG-recognition enzyme, are primarily distributed in R (or T) bands and that genetic distance is considerably longer in R (or T) bands than in G bands. The mapping, as well as the dense concentration of mapped markers within the q13 region, should help with positional cloning of the genes associated with various diseases.

Bacteriophage P1↗
PubMed1997

The genomic analysis of human DAN gene.

DAN gene is shown to be localized at human chromosome 1p36.11-p36.13, which resides within the consensus deletion observed in neuroblastoma. In the present study, we have isolated the genomic DNA containing the entire human DAN gene and determined its nucleotide sequence. Structural analysis revealed that DAN gene is composed of four exons and spans approximately 15 kb. Its overall structure was basically the same as that of rat DAN gene. Two distinct transcription initiation sites (major and minor) were identified by the primer extension experiment. Putative TATA and CAAT-like elements are present 38 and 366 bp upstream from the major transcription start site, respectively, however, no apparent TATA-like sequence was found in the upstream region of the minor transcription start site. The 400-bp region immediately upstream from the major transcription initiation site was strongly GC-rich (79% GC). Genomic Southern experiments demonstrated that the allelic loss of DAN gene might occur in neuroblastoma. Interestingly, there exist two dinucleotide repeats, (CA)7 and (CA)8, in the first intron of DAN gene, raising the possibility to distinguish two alleles of DAN gene in some of the cancer cells.

Base Composition↗
PubMed1997

Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21.

The Down syndrome (DS) region has been defined by analyses of partial trisomy 21. The 2.5-Mb region between D21S17 and ERG is reportedly responsible for the main features of DS. Within this 2.5-Mb region, we focused previously on a distal 1.6-Mb region from an analysis of Japanese DS patients with partial trisomy 21. Previously we also performed exon-trapping and direct cDNA library screening of a fetal brain cDNA library and identified a novel gene TPRD. Further screening of a fetal heart cDNA library was performed and a total of 44 possible exons and 97 cDNA clones were obtained and mapped on a BamH1 map. By rescreening other cDNA libraries and a RACE reaction, we isolated nearly full-length cDNAs of three additional genes [holocarboxylase synthetase (HCS), G protein-coupled inward rectifier potassium channel 2 (GIRK2), and a human homolog of Drosophila minibrain gene (MNB)] and a coding sequence of a novel inward rectifier potassium channel-like gene (IRKK). The gene distribution and direction of transcription were determined by mapping both ends of the cDNA sequences. We found that these genes, except IRKK, are expressed ubiquitously and are relatively large, extending from 100 kb to 300 kb on the genome. These nearly full-length cDNA sequences should facilitate understanding of the detailed genome structure of the DS region and help to elucidate their role in the etiology of DS.

Amino Acid Sequence↗
PubMed1997

A remote conference system for image diagnosis on the World-Wide Web.

OBJECTIVE: The World-Wide Web on the Internet enables an exchange of multimedia information among remote desktop computers. Therefore, a teleradiology system using the Web would allow remote consultation with expert radiologists. Our objective was to establish a Web-based prototype system for image interpretation. CONCLUSION: Our system allows a physician to transmit clinically useful images to an expert radiologist at a different location, who can see them on a Web browser and discuss diagnoses with the physician.

Computer Communication Networks↗
PubMed1997

[The relationship between ocular abnormalities and MRI findings in patients with spinocerebellar degeneration].

We studied the relationship between MRI findings and ocular abnormalities in 46 patients with spinocerebellar degeneration. MRI was performed for all patients. In order to evaluate the severity of atrophy in the brainstem and cerebellum, we delineated the region of the pons, mesencephalic tegmentum, medulla oblongata, cerebellar hemisphere, and vermis on a typical section of their T1 weighted image. Each area or the longest diameter of each regions were measured by using a computed graphic analyzer. The data were compared with those of 10 normal subjects and the severity of atrophy in each region was quantitatively estimated. In all of the patients, electro-oculographic tests including gaze nystagmus, positional and positioning nystagmus, smooth pursuit eye movements (smooth pursuit), optokinetic nystagmus test (OKN), horizontal saccade test, and visual suppression of the caloric nystagmus test (VS test) were examined. Eight patients with rebound nystagmus showed more severe atrophy than those of 38 patients without rebound nystagmus in the cerebellar hemisphere and vermis. Nine patients with apogeotrophic derection changing nystagmus indicates more severe atrophy than those of 35 patients without it in the cerevellar hemisphere, pons, mesencephalic tegmentum, medulla oblongata. Twenty three patients who showed severe impairments of OKN, 11 patients with a burst phenomenon on VS test and 19 patients with significantly reduced saccade velocity showed particularly severe pontine atrophy. A significant atrophic change in the pons and medulla oblongata was seen in 4 patients with severely impaired pursuit eye movements. Our finding that there is good correlation between ocular abnormalities and markedly atrophic regions on MRI support the neurophysiological findings which had been reported concerning the generation of ocular abnormalities in humans and animals.

Adult↗
PubMed1997

AML1a but not AML1b inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of K562 leukemia cells.

AML1 may play a role in growth and differentiation of cells along erythroid and/or megakaryocytic lineages, because a significant level of the AML1 gene is expressed in these cells. We overexpressed AML1a (without the transcription-activating domain) and AML1b (with the domain) proteins in K562 leukemia cells, which can be induced to differentiate into hemoglobin-producing cells and megakaryocytes. The AML1a-transfected K562 cells had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers, such as hemin, 1-beta-D-arabinofuranosylcytosine, and herbimycin A. The AML1 antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate. On the other hand, AML1b conferred a similar differentiation-inducing capacity upon K562 cells transfected with vector alone. AML1a expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester. These results provide evidence that AML1 proteins play a role in erythroid and megakaryocytic differentiation.

Antigens, CD↗