Nfl gene inactivation in acute myeloid leukemia cells confers cytarabine resistance through MAPK and mTOR pathways.
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Biomedical subjects
Publications and source records attributed to B Yin.
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OBJECTIVE: To evaluate the effect of distraction osteogenesis in correction of mandibular micrognathia accompanying obstructive sleep apnea syndrome (OSAS). METHODS: A total of 15 patients, aged 9 to 43 years, 11 males and 4 females, were treated. 7 patients suffered from bilateral ankylosis of temporo manclibular joint inducing severe mandibular micrognathia and accompanying severe OSAS. 3 cases suffered from unilateral TMJ ankylosis with OSAS. 3 patients suffered from congenital developmental micrognathia with OSAS. 2 cases were caused by trauma. Among the 15 patients, 12 were treated by synchronous bilateral mandibular distraction, 3 patients were distracted unilaterally. Every patient had been evaluated pre- and postoperatively with cephalometry and polysomnography. RESULTS: The minimum distance of distraction was 9 mm, the maximum was 30 mm, with a mean of 20.4 mm, in mandible of 15 patients with 27 sides. The distraction process was smooth in all the cases. The osteogenesis was good, without infection and other complications. Complete curative effect was achieved in 4 severe, 3 moderate, and 4 mild cases. The posterior airway space was increased from averaged 4.5 mm preoperatively to 12.4 mm. The increase of SNB angle was from preoperative 66 degrees to 75 degrees on average postoperatively. The vast majority of the patients had their subjective symptoms alleviated gradually or disappeared completely. The results were stable without relapse during a follow-up period of 12 months. CONCLUSION: The distraction osteogenesis can not only be used to effectively correct severe mandibular micrognathia deformity, but also can cure its accompanying OSAS. The procedure is simple, with low risk, high curative rate, low relapse rate, and stable result. Up to now, it is the most effective method in the treatment of this difficult and complicated kind of disorder.
Abstract Drosophila ash2 is a member of the trxG gene super family, some human homologues of which are involved in hematopoiesis and leukemia. We report here the identification of the human homologue of Drosophila ash2 and its alternative splicing isoform, ASH2L1 and ASH2L2. ASH2L proteins are 60% homologous to Drosophila ash2. ASH2L also has a zinc finger motif (C2C2) although it is not identical to that in ASH2. Expression profile analysis showed that the amount of ASH2L transcripts is extremely high in fetal liver, testis, and leukemia cell lines with erythroid and megakaryocytic potential such as K562, Hel, and Dami. We treated these cells with differentiation inducers phorbol ester and hemin. We found that ASH2L is downregulated rapidly and dramatically in K562, Hel, and Dami cells during phorbol ester induced differentiation with megakaryocytic features. However, its expression is maintained at a high level during erythroid differentiation of K562 cells induced with hemin. These results suggest that ASH2L plays a role in hematopoiesis and is associated with some special kinds of leukemia.
BACKGROUND: Controversy exists regarding the perfusion status of chronically dysfunctional yet viable myocardium. Studies investigating the pathophysiology of this condition have reached different conclusions, with some suggesting that myocardial blood flow (MBF) in these regions is normal at rest with regional dysfunction resulting from repetitive stress-induced ischemia (stunned myocardium), whereas others have proposed that MBF is chronically reduced at rest (hibernating myocardium). However, adequately powered experimental studies investigating this question in an appropriate animal model using clinically available techniques have not been performed. Based on the mixed results of prior studies, we hypothesized that these chronically dysfunctional yet viable regions may actually represent a mixture of hibernation and stunning. Consequently, the purpose of this study was to quantitatively determine the distribution of MBF in left ventricular regions with chronically impaired resting function but preserved viability in a large population of animals with single-vessel coronary stenosis in an attempt to further elucidate the mechanism(s) responsible for chronic, reversible myocardial dysfunction. METHODS: Fifty-two adult mini-swine with 90% proximal left circumflex (LCx) stenosis underwent dynamic positron emission tomography (PET) with 13N-ammonia and 18F-fluorodeoxyglucose and dobutamine stress echocardiography (DSE) (5 to 40 microg/kg/min) 1 month after stenosis creation. Values of MBF and FDG uptake by PET and wall motion score index (WMSI) by DSE were compared using a standard 16-segment model. RESULTS: Of 312 possible LCx segments seen on PET, 303 (97.1%) were visualized by DSE. Of the 303 LCx segments, 279 (92.1%) had rest dysfunction (WMSI > or = 2) by DSE. One hundred eighty-two segments (60.1%) had decreased (< 85% reference) MBF at rest with preserved to increased (> 60% reference) FDG uptake and were classified as hibernating. Ninety-two segments (30.4%) had preserved MBF (> or = 85% reference) and were classified as stunned. Five segments (1.7%) with reduced (< or = 60% reference) FDG uptake by PET and akinesis or dyskinesis at rest (WMSI > or = 3) and no contractile reserve were considered infarcted. Hibernating segments had significantly higher FDG uptake at rest (360.7+/-48.3 vs 212.3+/-17.7% septal values; p < 0.001) than stunned segments consistent with greater resting ischemia. Likewise, mean rest WMSI was also worse in hibernating versus stunned segments (2.35+/-0.04 vs 2.13+/-0.04; p < 0.001). There was no difference in the percentage of hibernating versus stunned segments exhibiting contractile reserve during dobutamine infusion (55.5 vs 63.7%; p = 0.4), indicating similar degrees of viability. CONCLUSIONS: Myocardial hibernation and stunning appear to frequently coexist in regions served by a stenotic coronary vessel. Hibernating regions appear to have greater resting ischemia based on higher values of FDG uptake and greater resting dysfunction. Reversible left ventricular dysfunction in the setting of chronic coronary artery disease is likely due to a combination of these two mechanisms.
This paper introduces an ECG computing algorithm that computes ECG based on the action potential of single cardiac cell. Taking solid angle analysis as tool, this algorithm analyzes the field potential of a cardiac cell that connects and communicates with neighboring cells. This algorithm has been implemented in our electrophysiological model CardioAuto, which was built with extended Cellular 3.0-a cellular automata system. Algorithm and simulation results reveal that it is the transmembrane potential slope among cell group that contributes to ECG waveform generation and determines the waveform deflection. To a specific lead location, whenever cell group has a transmembrane potential slope that proximal end is higher than distal end, a downward ECG deflection is generated. Whenever cell group has a reverse transmembrane potential slope, an upward ECG deflection is generated. Whenever there is no transmembrane potential slope, ECG keeps on baseline. According to our algorithm, the significance of normal and many abnormal ECG waveforms can be analyzed and interpreted at cellular level.
OBJECTIVE: To observe the variability of lipopolysaccharide binding protein (LBP) in patients with chronic hepatitis and severe hepatitis. METHODS: Using ELISA the authors detected the serum LBP of 71 patients including 16 with chronic hepatitis, 15 with post hepatitis cirrhosis, 12 with severe hepatitis and 17 healthy controls. RESULTS: The serum LBP of chronic liver disease group was 35 166.25 micrograms/L, which was higher than that of healthy control group (18 590.00 micrograms/L). The serum LBP of chronic hepatitis and cirrhosis patients was higher than that of severe hepatitis cases. These differences were significant. The serum LBP had positive correlation with prothrombin activity (PTA) (r =0.395 8,P <0.01), while it had no significant correlation with serum ALT and total bilirubin levels (r =0.164 5,0.189 4, respectively, P <0.05). CONCLUSIONS: Serum LBP could be used as an index for predicting liver function compensation.
OBJECTIVES: The purpose of this study was to determine the short-term effects of transmyocardial laser revascularization (TMR) on regional left ventricular systolic and diastolic function, myocardial blood flow (MBF) and myocardial water content (MWC). BACKGROUND: Clinical studies of TMR have noted a significant incidence of cardiac complications in the early postoperative period. However, the early post-treatment effects of laser therapy on the myocardium and their potential contribution to postoperative cardiac morbidity are unknown. METHODS: Swine underwent holmium:yttrium-aluminum-garnet (holmium:YAG) (n = 12) or carbon dioxide (CO2) (n = 12) laser TMR. Regional systolic function for the lased and nonlased regions was quantitated using preload recruitable work area (PRWA) and regional diastolic function with the ventricular stiffness constant alpha. RESULTS: Preload recruitable work area was significantly decreased in the lased regions both 1 (59.8+/-13.0% of baseline, p = 0.02) and 6 h (64.2+/-9.4% of baseline, p = 0.02) after holmium:YAG TMR. This decreased PRWA was associated with a significant reduction in MBF to the lased regions (13.2% reduction at 1 h, p = 0.02; 18.4% decrease at 6 h post-TMR, p = 0.01). These changes were not seen after CO2 laser TMR. A significant increase in MWC (1.4+/-0.3% increase with holmium:YAG, p = 0.004; 1+/-0.2% increase with CO2, p = 0.002) and alpha (217.4+/-44.2% of baseline 6 h post-holmium:YAG TMR, p = 0.05; 206+/-36.7% of baseline 6 h post-CO2 TMR, p = 0.03) was seen after TMR with both lasers. CONCLUSIONS: In the early postoperative setting, impaired regional systolic function in association with regional ischemia is seen after TMR with a holmium:YAG laser. Both holmium:YAG and CO2 lasers are associated with increased MWC and impaired diastolic relaxation in the lased regions. These changes may explain the significant incidence of early postoperative cardiac morbidity. The impact of these findings on anginal relief and long-term outcome are not known.
BACKGROUND: Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. METHODS: Miniswine underwent 90% stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. RESULTS: Positron emission tomography (13N-labeled-ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8% +/- 2% infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. CONCLUSIONS: Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart.
BACKGROUND: Transmyocardial laser revascularization (TMR) is an emerging treatment for end-stage coronary artery disease. A variety of lasers are currently available to perform the procedure, although their relative efficacy is unknown. The purpose of this study was to compare changes in myocardial blood flow and function 6 months after TMR with holmium:yttrium-aluminum-garnet (holmium:YAG), carbon dioxide (CO2), and xenon chloride excimer lasers in a model of chronic ischemia. METHODS: Miniswine underwent subtotal (90%) left circumflex coronary stenosis. Baseline positron emission tomography and dobutamine stress echocardiography were performed to document hibernating myocardium in the left circumflex coronary artery distribution. Animals were then randomized to sham redo-thoracotomy (n = 5) or TMR using a holmium:YAG (n = 5), CO2 (n = 5) or excimer (n = 5) laser. Six months postoperatively, the positron emission tomography and dobutamine stress echocardiography studies were repeated and the animals sacrificed. RESULTS: In animals undergoing TMR with holmium: YAG and CO2 lasers, a significant improvement in myocardial blood flow to the lased left circumflex regions was seen. No significant change in myocardial blood flow was seen in sham- or excimer-lased animals. There was a significant improvement in regional stress function of the lased segments 6 months postoperatively in animals undergoing holmium:YAG and CO2 laser TMR that was consistent with a reduction in ischemia. There was no change in wall motion in sham- or excimer-lased animals. Significantly greater neovascularization was observed in the holmium:YAG and CO2 lased regions than with either the sham procedure or excimer TMR. CONCLUSIONS: Transmyocardial laser revascularization with either holmium:YAG or CO2 laser improves myocardial blood flow and contractile reserve in lased regions 6 months postoperatively. These changes were not seen following excimer TMR or sham thoracotomy, suggesting that differences in laser energy or wavelength or both may be important in the induction of angiogenesis.
A strategy to measure bacterial functional redundancy was developed and tested with soils collected along a soil reclamation gradient by determining the richness and diversity of bacterial groups capable of in situ growth on selected carbon substrates. Soil cores were collected from four sites along a transect from the Jamari tin mine site in the Jamari National Forest, Rondonia, RO, Brazil: denuded mine spoil, soil from below the canopy of invading pioneer trees, revegetated soil under new growth on the forest edge, and the forest floor of an adjacent preserved forest. Bacterial population responses were analyzed by amending these soil samples with individual carbon substrates in the presence of bromodeoxyuridine (BrdU). BrdU-labeled DNA was then subjected to a 16S-23S rRNA intergenic analysis to depict the actively growing bacteria from each site. The number and diversity of bacterial groups responding to four carbon substrates (L-serine, L-threonine, sodium citrate, and alpha-lactose hydrate) increased along the reclamation-vegetation gradient such that the preserved forest soil samples contained the highest functional redundancy for each substrate. These data suggest that bacterial functional redundancy increases in relation to the regrowth of plant communities and may therefore represent an important aspect of the restoration of soil biological functionality to reclaimed mine spoils. They also suggest that bacterial functional redundancy may be a useful indicator of soil quality and ecosystem functioning.
OBJECTIVE: To analyse TBX5 mutation in Chinese patients with Holt-Oram syndrome(HOS). METHODS: Seven HOS families were analysed with single strand conformation polymorphism(SSCP) and sequencing. RESULTS: Three SSCP changes were detected and identified as the TBX5 gene mutation at three new sites. One of the changes is a frameshift mutation caused by a base cytidine deletion at the cDNA sequence of 416, which altered all the codons after the point, thus it can not encode the protein of normal amino acid sequence; another is a missense mutation induced by a base substitution(C-->A) at the cDNA sequence of 145, which made the codon of that point change from CAG-->AAG, and encoded amino acid changed from glutamine(Gln) to lysine(Lys), consequently the change weakened the function of TBX5 protein; the third is also a missense mutation which resulted from a base substitution (T-->C) at the cDNA sequence of 161, this change made the codon of that point change from ATC-->ACC, it changed the encoded amino acid from isoleucine(Ile) to threonine(Thr), which reduced the function of TBX5 protein. CONCLUSION: HOS in Chinese is caused by mutation in TBX5.
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OBJECTIVE: To unravel the biological significance of the alternative splicing of de novo methyltransferase 3b, expression of the Dnmt3b gene in various tissues and developmental stages was investigated in postnatal mice. METHODS: RT-PCR and capillary electrophoresis were employed to analyze the alternative splicing pattern of Dnmt3b in tissues of newborn and adult mice. The results had been further reaffirmed by repeating and statistics analysis. Bioinformatics tools were used to predict the structure and hydrophobicity of the Dnmt3b exon10 coding sequence. RESULTS: Isoform with Dnmt3b exon10 was the abundant form in lung of newborn mice and in liver of both newborn and adult mice, while in other tissues of newborn and adult mice, the spliced isoform was presented as the predominant one. Peptide encoded by Dnmt3b exon10 was mainly random coil on the surface of Dnmt3b protein. CONCLUSIONS: The data demonstrate that the specific expression of Dnmt3b exists in tissues and developmental stages of postnatal mice. The alternative splicing of the exon 10 of Dnmt3b is possibly involved in the regulation of Dnmt3b's catalytic function. These results provide an insight into the developmental regulation and physiological function of the alternative splicing of the Dnmt3b gene.
OBJECTIVE: Transmyocardial laser revascularization (TMR) is emerging as a potential treatment option for patients with end-stage CAD, and adjuvant gene therapy may be helpful in further improving the results of the procedure. However, the effects of TMR on gene transfer are unknown. METHODS: Swine underwent left thoracotomy. TMR was performed to create five channels at 2-cm intervals in the anterolateral free wall of the left ventricle (LV) followed by injection of 1 x 10(9) plaque-forming units (pfu) of a replication-deficient adenovirus vector carrying the reporter gene beta-galactosidase (Ad.Pac beta-gal). An additional five direct injections of 1 x 10(9) pfu Ad.Pac beta-gal were made at 2-cm intervals in the posterolateral LV of each heart. Control animals underwent TMR alone/vehicle alone (n = 3) or empty virus alone/no treatment (n = 3) of the anterolateral/posterolateral LV, respectively. RESULTS: ELISA revealed significantly greater transgene expression in the direct Ad.Pac beta-gal injection versus TMR plus Ad.Pac beta-gal inject regions at both 3 (n = 6) (273.0 +/- 58.5 vs. 133.4 + 28.1 pg beta-gal/g protein, P = 0.02) and 7 days (n = 6) (180.0 + 59.9 vs. 56.7 + 18.1 pg beta-gal/g protein, P = 0.02) postoperatively. At 14 days postoperatively (n = 2), no transgene expression was detected in either region. No transgene expression was detected in any of the control regions at 3 days postoperatively. CD-18 staining revealed significantly greater inflammation in the TMR plus Ad.Pac beta-gal and TMR alone regions as compared to Ad.Pac beta-gal or vehicle (P < 0.001). CONCLUSIONS: Adenoviral-mediated gene transfer in conjunction with TMR is possible, although TMR appears to limit the degree of transgene expression attained as compared to direct intramyocardial injection alone, likely due to the greater immune response observed with the former. These findings may have important implications for therapeutic strategies aimed at combining TMR with gene therapy for CAD.
A patient developed an epidural haematoma 6 days after removal of an epidural catheter resulting in paraplegia and death. Insertion and removal of the epidural catheter during anticoagulation with prophylactic unfractionated heparin and subsequent administration of high-dose enoxaparin (Clexane), which commenced 3 days after catheter removal, were implicated.
OBJECTIVE: Four B and Th cell epitopes were selected from conservative domain of Plasmodium falciparum antigens to construct two groups of chimeric malaria DNA vaccines with different configurations and their antigenicities were studied. METHODS: The partially synthesized oligonucleotide was annealed, PCR amplified and cloned into a mammalian cell expression vector. By using a pair of isocaudamers on the vector, different single copies of B epitopes were multiplied and were tenderly stringed into two groups of chimeric DNA vaccine with different configurations. BALB/c mice were immunized with these DNA plasmids by either intramuscular or intradermal injections. RESULTS: The antisera from the immunized mice tested by ELISA showed that only the configuration which had a single copy of universal T helper cell epitope, CS. T3, located at the C terminal of the multi-copy B cell epitopes induced a high antibody response. The T helper cell epitope at any other position of the peptide, or the double T helper cell epitopes configured with the B cell epitopes did not enhance antibody response, and some configurations even decreased the humoral response to a B cell epitope. CONCLUSION: This study demonstrated that both combination and configuration of the epitope may affect the antigenicity of a chimeric multiple antigen.
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