PubMed Health⌕ Search

Biomedical subjects

Q H Huang

Publications and source records attributed to Q H Huang.

At least 19 recordsLinked to original sources
PubMed2006

Assessment of muscle fatigue using sonomyography: muscle thickness change detected from ultrasound images.

Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. As the surface electromyography (SEMG) can be used to estimate the features of neuromuscular activations associated with muscle contractions, it has been widely employed as an objective tool to evaluate muscle fatigue. On the other hand, ultrasound imaging can inherently provide the morphological information of individual muscle, thus the architectural changes of muscles during fatigue can be obtained. In this study, we demonstrated the feasibility of using the dimensional change of muscles detected by ultrasound images, named as sonomyography (SMG), to characterize the behavior of muscles when they were in fatigue. The SEMG signals of the muscles were also recorded simultaneously and used for comparison. The right biceps brachii muscles of 8 normal young male adult subjects were tested for 30s under 80% of the maximal voluntary isometric contraction. The muscle fatigue was indicated by the change of the root-mean-square (RMS) and median frequency (MDF) of the SEMG signals. The results showed that the SEMG RMS had a linear increase with time with a rate of 2.9+/-1.9%/s (mean+/-S.D.), while the MDF decreased linearly with a rate of -0.60+/-0.26Hz/s. The muscle thickness, detected from the ultrasound images, continuously increased during the muscle fatigue but with a nonlinear increase with time, which was rapid during the initial 8.1+/-2.1s with a mean deformation rate of 0.30+/-0.19%/s and then became slower with a rate of 0.067+/-0.024%/s up to 20s after the contraction. The muscle deformation at 20s was 3.5+/-1.6%. The results demonstrated that the architectural change of muscles detected using SMG could potentially provide complementary information for SEMG for the muscle fatigue assessment.

Adult↗
PubMed2006

Ultrasound palpation sensor for tissue thickness and elasticity measurement--assessment of transverse carpal ligament.

Palpation is a traditional diagnostic procedure for health care professionals to use their fingers to touch and feel the body soft tissues. It is a common clinical approach, though it is rather subjective and qualitative and the palpation results may vary among different people. Tissue ultrasound palpation sensor (TUPS) provides a feasible solution that makes the palpation of soft tissues not subjective feeling any more. It is comprised of an ultrasound transducer together with a load cell to form the finger-sized probe. The probe is used to push against the soft tissue surface to measure the thickness and elasticity of the soft tissues. TUPS has been successfully applied to the assessment of various human tissues. Recently, we have improved TUPS, which can now be linked to personal computer (PC) via universal serial bus (USB) and provide a better user-interface. The information of ultrasound signal and indentation force is displayed on PC in real time during measurement. In this paper, we introduce the recent application of TUPS for the assessment of the transverse carpal ligament. The tissues at the carpal tunnel regions of five normal male subjects were tested using TUPS. The results showed that the average thickness of the tissues covering the carpal tunnel ligament and the tunnel region was 7.98+/-1.05 mm and 9.59+/-1.12 mm, respectively. Under a compression force of 20 N applied by a cylindrical ultrasound indentor with a diameter of 9 mm, the stiffness of the soft tissue layer and the tunnel region was 6.72+/-2.10 N/mm and 15.63+/-8.42 N/mm, respectively. It is expected that TUPS can be a potential tool for non-invasive assessment of carpal tunnel syndrome.

Algorithms↗
PubMed2006

SLC11A1 (formerly NRAMP1) gene polymorphisms and tuberculosis susceptibility: a meta-analysis.

OBJECTIVE: Although many case-control studies have investigated the association between the SLC11 A1 gene polymorphisms and tuberculosis (TB) susceptibility, results were conflicting due to limited power. We reviewed the literature systematically by means of meta-analysis, provided a quantitative summary estimate on the association with TB, and examined some sources of between-study heterogeneity. DESIGN: We searched databases (MEDLINE, PUBMED and OVID) from January 1995 to December 2004 using 'gene' or 'SLC11A1' or 'NRAMP1', in combination with 'tuberculosis', performed a manual search of citations from relevant original studies and review articles, or corresponded with authors. RESULTS: The summary ORs for studies with 3'UTR, D543N, INT4 and 5'(GT)n loci allele variants in the SLC11A1 gene were 1.33 (95%CI 1.08-1.63), 1.67 (95%CI 1.36-2.05), 1.14 (95%CI 0.96-1.35) and 1.32 (95%CI 1.03-1.68), respectively, compared with their corresponding common alleles. The pooled ORs by sub-group analyses for the four loci described above were 1.20 (95%CI 0.86-1.68), 1.69 (95%CI 1.14-2.50), 1.50 (95%CI 1.17-1.91), and 1.31 (95%CI 1.05-1.64) in subjects of African descent, 1.46 (95%CI 1.10-1.94), 1.65 (95%CI 1.29-2.12), 0.91 (95%CI 0.66-1.25) and 1.86 (95%CI 1.33-2.62) in Asian subjects, 1.81 (95%CI 0.66-4.93), 1.79 (95%CI 0.72-4.47), 0.87 (95%CI 0.61-1.22) and 1.02 (95%CI 0.35-2.99) in European subjects. CONCLUSIONS: Polymorphisms at the four loci had no statistically significant association between the SLC11A1 variants and susceptibility to TB in subjects of European descent, while they showed a statistically significant association in Asian subjects (except the INT4 variant), African subjects (except the 3'UTR variant) and the population as a whole (except the INT4 variant).

Asian People↗
PubMed2005

Sonomyography: monitoring morphological changes of forearm muscles in actions with the feasibility for the control of powered prosthesis.

Electromyography (EMG) has been widely used for the assessment of musculoskeletal functions and the control of electrical prostheses, which make use of the EMG signal generated by the contraction of the residual muscles. In spite of the successful applications of EMG in different fields, it has some inherent limitations, such as the difficulty to differentiate the actions of neighboring muscles and to collect signals from deep muscles using the surface EMG. The majority of current EMG controlled prostheses can only provide sequential on-off controls using signals from two groups of muscles, so the users are required to put many conscious efforts in monitoring the speed and range of motion of the terminal devices being controlled. Recently, many alternative signals based on the detection of dimensional changes of muscles or tendons during actions have been reported. The objective of this study was to investigate the potential of the dimensional change of muscles detected using sonography for musculoskeletal assessment and control. A portable B-mode ultrasound scanner was used to collect the dynamic ultrasound images of the forearm muscles of six normally limbed young adults and three amputee subjects. A motion analysis system was used to collect the movement of the wrist angle during the experiments for the normal subjects. It was demonstrated that the morphological changes of forearm muscles during actions can be successfully detected by ultrasound and linearly correlated (R(2)=0.876+/-0.042, mean+/-S.D.) with the wrist angle. We named these sonographically detected signals about the architectural change of the muscle as sonomyography (SMG). The mean ratio between the wrist angle and the percentage deformation of the forearm muscle was 7.2+/-3.7 degrees /% for the normal subjects. The intraclass correlation coefficient (ICC) of this ratio among the three repeated tests was 0.868. The SMG signals from the residual forearms were also successfully detected when the three amputee subjects contracted their residual muscles. The results demonstrated that SMG had potentials for the musculoskeletal control and assessment.

Amputees↗
PubMed2005

Development of a portable 3D ultrasound imaging system for musculoskeletal tissues.

3D ultrasound is a promising imaging modality for clinical diagnosis and treatment monitoring. Its cost is relatively low in comparison with CT and MRI, no intensive training and radiation protection is required for its operation, and its hardware is movable and can potentially be portable. In this study, we developed a portable freehand 3D ultrasound imaging system for the assessment of musculoskeletal body parts. A portable ultrasound scanner was used to obtain real-time B-mode ultrasound images of musculoskeletal tissues and an electromagnetic spatial sensor was fixed on the ultrasound probe to acquire the position and orientation of the images. The images were digitized with a video digitization device and displayed with its orientation and position synchronized in real-time with the data obtained by the spatial sensor. A program was developed for volume reconstruction, visualization, segmentation and measurement using Visual C++ and Visualization toolkits (VTK) software. A 2D Gaussian filter and a Median filter were implemented to improve the quality of the B-scan images collected by the portable ultrasound scanner. An improved distance-weighted grid-mapping algorithm was proposed for volume reconstruction. Temporal calibrations were conducted to correct the delay between the collections of images and spatial data. Spatial calibrations were performed using a cross-wire phantom. The system accuracy was validated by one cylinder and two cuboid phantoms made of silicone. The average errors for distance measurement in three orthogonal directions in comparison with micrometer measurement were 0.06+/-0.39, -0.27+/-0.27, and 0.33+/-0.39 mm, respectively. The average error for volume measurement was -0.18%+/-5.44% for the three phantoms. The system has been successfully used to obtain the volume images of a fetus phantom, the fingers and forearms of human subjects. For a typical volume with 126 x 103 x 109 voxels, the 3D image could be reconstructed from 258 B-scans (640 x 480 pixels) within one minute using a portable PC with Pentium IV 2.4 GHz CPU and 512 MB memories. It is believed that such a portable volume imaging system will have many applications in the assessment of musculoskeletal tissues because of its easy accessibility.

Equipment Design↗
PubMed2005

A novel noncontact ultrasound indentation system for measurement of tissue material properties using water jet compression.

This study is aimed to develop a novel noncontact ultrasonic indentation system for measuring quantitative mechanical properties of soft tissues, which are increasingly important for tissue assessment and characterization. The key idea of this method is to use a water jet as an indenter to compress the soft tissue while at the same time as a medium for an ultrasound beam to propagate through. The use of water jet indentation does not require a rigid compressor in front of the focused high frequency ultrasound transducer to compress the tissue, so that the additional attenuation caused by the rigid compressor and the strong echoes reflected from its surfaces can be avoided. The indentation deformation was estimated from the ultrasound echoes using a cross-correlation algorithm and the indentation force was calculated from the water pressure measured inside the water pipe. Experiments were performed on uniform tissue-mimicking phantoms with different stiffness. The Young's moduli and Poisson's ratios of these phantoms were measured using a uniaxial ultrasound compression system. The ratio of the indentation pressure to the tissue relative deformation was obtained from the water indentation. This ratio was well correlated with the Young's modulus (r = 0.87). The results also demonstrated that the water indentation approach could differentiate materials with different stiffness in a combined phantom (288 kPa and 433 kPa). This novel noncontact water indentation approach could be potentially used for the measurement of the elasticity of small samples and with a fast scanning speed.

Algorithms↗
PubMed2005

A new scanning approach for limb extremities using a water bag in freehand 3-D ultrasound.

3-D ultrasound (US) can significantly improve the visualization of musculoskeletal tissues, such as residual limbs, feet and hands. Traditionally, mechanical scanning is normally required to obtain the entire volume of these limb extremities. In this paper, a new scanning approach using a water bag was described to collect the complete volume of various tissues surrounding bones. The water bag was used to contain the limb extremity and the scanning was conducted on its external surface from different directions. The recorded 2-D US images containing complete anatomic information surrounding the bones from different directions were used to form full 3-D volumes of the limb extremities. A plastic auxiliary apparatus was designed to hold the water bag and support the subject's limb part with an armrest. A corresponding algorithm was proposed to remove invalid image information within each sweep by a separating plane defined semiautomatically. Two phantoms were used to test the repeatability and accuracy of the imaging. The distance between two plastic bands attached to a plastic tube filled with US gel measured by a micrometer and from the four reconstructed volumes were 39.03 +/- 0.36 mm and 39.2 +/- 0.5 mm, respectively. The diameter, height and volume of a silicone cylinder phantom measured for the 10 reconstructed volumes were 40.2 +/- 1.4 mm, 12.9 +/- 1.0 mm and 16400 +/- 1600 mm(3), respectively. They agreed with the corresponding results obtained by the micrometer, which were 41.29 +/- 0.13 mm, 12.98 +/- 0.17 mm and 17370 +/- 140 mm(3), respectively. The reconstructed volumes of the two phantoms, a chicken leg in vitro, and human fingers in vivo were also reported. The preliminary results obtained in this study demonstrated that this new scanning approach should have potential for the 3-D US imaging of musculoskeletal extremities using freehand scanning.

Algorithms↗
PubMed2003

Structural genomics efforts at the Chinese Academy of Sciences and Peking University.

Structural genomics efforts at the Chinese Academy of Sciences and Peking University are reported in this article. The major targets for the structural genomics project are targeted proteins expressed in human hematopoietic stem/progenitor cells, proteins related to blood diseases and other human proteins. Up to now 328 target genes have been constructed in expression vectors. Among them, more than 50% genes have been expressed in Escherichia coli, approximately 25% of the resulting proteins are soluble, and 35 proteins have been purified. Crystallization, data collection and structure determination are continuing. Experiences accumulated during this initial stage are useful for designing and applying high-throughput approaches in structural genomics.

Academies and Institutes↗
PubMed2001

Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Carcinoma, Hepatocellular↗
PubMed2001

Lineage restriction of the RARalpha gene expression in myeloid differentiation.

To better understand the role of retinoids in myelopoiesis, expression of the retinoid receptor genes (retinoic acid receptors [RARs] and retinoid X receptors [RXRs]) were examined during differentiation of factor-dependent cell-Paterson (FDCP)-mixA4 murine progenitor cells. The major receptor expressed in undifferentiated A4 cells was RARalpha (primarily the RARalpha1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARalpha expression (particularly the RARalpha2 isoform) was seen. In contrast, expression of both RARalpha isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRalpha expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARgamma2 and RXRbeta remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARalpha agonists and antagonists stimulated myelomonocytic and erythroid differentiation of FDCP-mixA4 cells, respectively. Taken together, these results suggest that erythropoiesis and granulopoiesis require diminished and enhanced RARalpha activities, respectively, which at physiological all-trans-retinoic acid (RA) concentrations may be accomplished by reciprocal effects of EPO and myelomonocytic growth factors on its expression. This hypothesis is corroborated by data showing that RA, which positively regulates RARalpha2 expression, can exert inhibitory effects on erythroid differentiation.

Bone Marrow↗
PubMed2000

Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.

The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life.

Alternative Splicing↗
PubMed2000

alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression.

The hypothalamic arcuate nucleus has an essential role in mediating the homeostatic responses of the thyroid axis to fasting by altering the sensitivity of prothyrotropin-releasing hormone (pro-TRH) gene expression in the paraventricular nucleus (PVN) to feedback regulation by thyroid hormone. Because agouti-related protein (AGRP), a leptin-regulated, arcuate nucleus-derived peptide with alpha-MSH antagonist activity, is contained in axon terminals that terminate on TRH neurons in the PVN, we raised the possibility that alpha-MSH may also participate in the mechanism by which leptin influences pro-TRH gene expression. By double-labeling immunocytochemistry, alpha-MSH-IR axon varicosities were juxtaposed to approximately 70% of pro-TRH neurons in the anterior and periventricular parvocellular subdivisions of the PVN and to 34% of pro-TRH neurons in the medial parvocellular subdivision, establishing synaptic contacts both on the cell soma and dendrites. All pro-TRH neurons receiving contacts by alpha-MSH-containing fibers also were innervated by axons containing AGRP. The intracerebroventricular infusion of 300 ng of alpha-MSH every 6 hr for 3 d prevented fasting-induced suppression of pro-TRH in the PVN but had no effect on AGRP mRNA in the arcuate nucleus. alpha-MSH also increased circulating levels of free thyroxine (T4) 2.5-fold over the levels in fasted controls, but free T4 did not reach the levels in fed controls. These data suggest that alpha-MSH has an important role in the activation of pro-TRH gene expression in hypophysiotropic neurons via either a mono- and/or multisynaptic pathway to the PVN, but factors in addition to alpha-MSH also contribute to the mechanism by which leptin administration restores thyroid hormone levels to normal in fasted animals.

Animals↗
PubMed2000

The impact of differential binding of wild-type RARalpha, PML-, PLZF- and NPM-RARalpha fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia.

Retinoic acid receptor (RA) heterodimer (RAR/RXR) activities have been shown to be repressed by transcriptional co-repressor, SMRT/N-CoR, in the absence of the ligand while upon all-trans retionic acid (ATRA) treatment, SMRT/N-CoR is dissociated from RARalpha leading to gene expression by the recruitment of transcriptional co-activators to the transcriptional complex. The difference in response to ATRA therapy between acute promyelocytic leukemia (APL) patients with PML-RARalpha fusion and PLZF-RARalpha fusion has recently been found to be partially due to the strong association of the transcriptional co-repressor, SMRT/N-CoR, with PLZF domain. We demonstrate that SMRT association, as with PML-RARalpha, can be released from NPM-RARalpha at pharmacological concentration of ATRA (10-6 M). Moreover, we show for the first time that the interaction between the transcriptional co-activator, RIP-140, and PML-, PLZF- or NPM-RARalpha fusion proteins can be positively stimulated by ATRA although they are less sensitive as compared with the wild-type RARalpha. Our results suggest that the dissociation of transcriptional co-repressors, SMRT/N-CoR, and recruitment of co-activators, eg RIP-140, to APL-associated fusion proteins constitute a common molecular mechanism in APL and underlie the responsiveness of the disease to RA therapy. Leukemia (2000) 14, 77-83.

Dimerization↗
PubMed2000

Gene expression in CD34(+) cells from normal bone marrow and leukemic origins.

INTRODUCTION: To address the molecular regulation of hematopoiesis and the complex mechanism in leukemogenesis, we established the first catalogs of genes expressed in normal bone marrow and leukemia CD34(+) cells. MATERIALS AND METHODS: CD34(+) cell cDNA libraries were constructed using mRNA from adult bone marrow and from a case of acute myeloid leukemia-M5 transformed from myelodysplastic syndrome (MDS-AML). Expressed sequence tags (ESTs) and full-length cDNAs were generated by sequencing and were annotated using bioinformatic tools. RESULTS: From a total of 4142 ESTs obtained from normal bone marrow, 3424 meaningful tags were integrated into 1630 clusters, representing 622 known genes, 522 dbEST entries and 486 novel sequences. Out of 5382 ESTs from MDS-AML, 1985 clusters were produced based on the analysis of 4321 useful ESTs, including 711 known genes, 657 known ESTs and 617 novel sequences. Among 251 transcripts found in both bone marrow and MDS-AML EST datasets and those present in only one dataset, 58 showed statistically significant differences in EST copy numbers between the two tissues (P<0.05). Twenty putative full-length cDNAs for novel genes were also cloned from the MDS-AML library. CONCLUSION: The distinct gene expression patterns in MDS-AML-CD34(+) cells as compared to normal control cells may contribute to the development and/or maintenance of the malignant phenotypes of leukemia cells.

Adult↗
PubMed2000

Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.

Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3' UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation.

Alternative Splicing↗
PubMed1999

Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARalpha and NPM-RARalpha.

Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARalpha and one of four fusion partners: PML, PLZF, NPM, and NuMA genes. To study the leukemogenic potential of the fusion genes in vivo, we generated transgenic mice with PLZF-RARalpha and NPM-RARalpha. PLZF-RARalpha transgenic animals developed chronic myeloid leukemia-like phenotypes at an early stage of life (within 3 months in five of six mice), whereas three NPM-RARalpha transgenic mice showed a spectrum of phenotypes from typical APL to chronic myeloid leukemia relatively late in life (from 12 to 15 months). In contrast to bone marrow cells from PLZF-RARalpha transgenic mice, those from NPM-RARalpha transgenic mice could be induced to differentiate by all-trans-retinoic acid (ATRA). We also studied RARE binding properties and interactions between nuclear corepressor SMRT and various fusion proteins in response to ATRA. Dissociation of SMRT from different receptors was observed at ATRA concentrations of 0.01 microM, 0.1 microM, and 1.0 microM for RARalpha-RXRalpha, NPM-RARalpha, and PML-RARalpha, respectively, but not observed for PLZF-RARalpha even in the presence of 10 microM ATRA. We also determined the expression of the tissue factor gene in transgenic mice, which was detected only in bone marrow cells of mice expressing the fusion genes. These data clearly establish the leukemogenic role of PLZF-RARalpha and NPM-RARalpha and the importance of fusion receptor/corepressor interactions in the pathogenesis as well as in determining different clinical phenotypes of APL.

Animals↗
PubMed1999

Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene.

BTB/POZ-domain C2H2 zinc(Zn)-finger proteins are encoded by a subfamily of genes related to the Drosophila gap gene krüppel. To date, two such proteins, PLZF and LAZ-3/BCL-6, have been implicated in oncogenesis. We have now identified a new member of this gene subfamily which encodes a 62 kDa Zn-finger protein, termed LRF, with a BTB/POZ domain highly similar to that of PLZF. Both human and mouse LRF genes, which localized to syntenic chromosomal regions (19p13.3 and 10B5.3, respectively), were widely expressed in adult tissues and cell lines. At approximately 9.5-10.0 days of embryonic development, the mouse LRF gene was expressed in the limb buds, pharyngeal arches, tail bud, placenta and neural tube. The LRF protein associated in vivo with LAZ-3/BCL-6, but not with PLZF to which it was more related. Although the LRF, or LAZ-3/BCL-6, BTB/POZ domain could readily homodimerize, no heterodimerization was detected in vivo between the LRF and LAZ-3/BCL-6 BTB/POZ domains and interaction between full length LRF and LAZ-3/BCL-6 required the presence of both the BTB/POZ domain and Zn-fingers in each partner protein. As expected from the above results, LRF and LAZ-3/BCL-6 also colocalized with each other in the nucleus. Taken together, our findings suggest that BTB/ POZ-domain Zn-finger proteins may function as homo and heterodimeric complexes whose formation, and hence the resultant effect on transcription of their downstream target genes, is determined by the levels and expression domains of a given partner protein.

Amino Acid Sequence↗