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Biomedical subjects

H Shi

Publications and source records attributed to H Shi.

At least 19 recordsLinked to original sources
PubMed2007

Antitumor activity of sorafenib in FLT3-driven leukemic cells.

Activating internal tandem duplication (ITD) insertions in the juxtamembrane domain of the FLT3 tyrosine kinase are found in about one fourth of patients with acute myeloid leukemia and have been shown to be an independent negative prognostic factor for survival. We show that sorafenib (BAY 43-9006, Nexavar) potently inhibits FLT3 enzymatic and signaling activities. In HEK293 cells stably transfected with FLT3-WT or FLT3-ITD, sorafenib blocked basal and ligand dependent FLT3-mediated tyrosine autophosphorylation as well as extracellular signal-regulated kinase1/2 and Stat5 phosphorylation. In leukemia cell lines MV4-11 and EOL-1, sorafenib treatment resulted in decreased cell proliferation and inhibition of FLT3 signaling. The growth of the FLT3-independent RS4-11 cell line was only weakly inhibited by sorafenib. Cell cycle arrest and induction of apoptosis were observed upon treatment with sorafenib in MV4-11 and EOL-1 cells. The antitumor efficacy of sorafenib was evaluated against the MV4-11 leukemia grown subcutaneously in NCr nu/nu mice. Doses of 3 and 10 mg/kg administered orally for 14 days resulted in six and nine out of 10 animals with complete responses, respectively. The demonstration that sorafenib exhibits potent target inhibition and efficacy in FLT3-driven models suggests that this compound may have a therapeutic benefit for patients with FLT3-driven leukemias.

Animals↗
PubMed2007

Normal and shear strain estimation using beam steering on linear-array transducers.

In current ultrasound elastography, only the axial component of the displacement vector is estimated and used to produce strain images. A method was recently proposed by our group to estimate both the axial and lateral components of a displacement vector following a uniaxial compression. Previous work evaluated the technique using both simulations and a mechanically translated phased array transducer. In this paper, we present initial results using beam steering on a linear array transducer attached to a commercial scanner to acquire echo signals for estimating 2-D displacement vectors. Single-inclusion and anthropomorphic breast phantoms with different boundary properties between the inclusion and background material are imaged by acquiring echo data along beam lines ranging from -15 degrees to 15 degrees relative to the compression direction. 1-D cross-correlation is used to calculate "angular displacements" in each acquisition direction, yielding axial and lateral components of the displacement vector. Strain tensor components are estimated from these displacements. Features on shear strain images generated for the inclusion phantom agree with those predicted using FEA analysis. Experimental results demonstrate the utility of this technique on clinical scanners. Shear strain tensors obtained using this method may provide useful information for the differentiation of benign from malignant tumors. For the linear array transducer used in this study, the optimum angular increment is around 3 degrees. However, more work is required for the selection of an appropriate value for the maximum beam angle for optimal performance of this technique.

Humans↗
PubMed2007

Incidence of changes and predictive factors for sexual function after coronary stenting.

The study was aimed at determining the incidence of changes in sexual function and identifying the possible associated variables of erectile dysfunction (ED) in coronary artery disease (CAD) patients undergoing coronary stenting. Four hundred and sixty-seven patients were retrospectively contacted with a questionnaire regarding sexual function from 6 months pre-stenting to 6 months post-stenting by telephone follow up. Univariate analyses were used to determine prognostic variables. ED changed following stenting in CAD (P < 0.05), in acute coronary syndrome (ACS) (P > 0.05) and in chronic coronary syndrome (CCS) (P < 0.05). Sexual activity was not resumed in 8.1%, was unchanged in 33.8%, increased in 0% and decreased in 58.0%. The average frequency of sexual activity decreased every month in CAD (P < 0.05), in ACS (P < 0.05) and in CCS (P < 0.01) after undergoing coronary stenting respectively. The mean time interval between the onset of ED and CAD was 33 months. Resuming sexual activity after stenting varied from 2 weeks to 30 months. Significant predictors of ED after coronary stenting were mean age, diabetes mellitus, 2,3-vessel disease or current smoking status. It was concluded that coronary stenting had a significant incidence of ED. Mean age, diabetes mellitus, 2,3-vessel disease or current smoking status showed to be the main variables associated with ED. Attempts to improve individual secondary prevention outcomes (controlling serum glucose and smoking cessation) should be designed.

Coronary Artery Disease↗
PubMed2006

Extracellular signal-regulated kinase pathway is differentially involved in beta-agonist-induced hypertrophy in slow and fast muscles.

The molecular mechanisms controlling beta-adrenergic receptor agonist (BA)-induced skeletal muscle hypertrophy are not well known. We presently report that BA exerts a distinct muscle- and muscle fiber type-specific hypertrophy. Moreover, we have shown that pharmacologically or genetically attenuating extracellular signal-regulated kinase (ERK) signaling in muscle fibers resulted in decreases (P < 0.05) in fast but not slow fiber type-specific reporter gene expressions in response to BA exposure in vitro and in vivo. Consistent with these data, forced expression of MAPK phosphatase 1, a nuclear protein that dephosphorylates ERK1/2, in fast-twitch skeletal muscle ablated (P < 0.05) the hypertrophic effects of BA feeding (clenbuterol, 20 parts per million in water) in vivo. Further analysis has shown that BA-induced phosphorylation and activation of ERK occurred to a greater (P < 0.05) extent in fast myofibers than in slow myofibers. Analysis of the basal level of ERK activity in slow and fast muscles revealed that ERK1/2 is activated to a greater extent in fast- than in slow-twitch muscles. These data indicate that ERK signaling is differentially involved in BA-induced hypertrophy in slow and fast skeletal muscles, suggesting that the increased abundance of phospho-ERK1/2 and ERK activity found in fast-twitch myofibers, compared with their slow-twitch counterparts, may account, at least in part, for the fiber type-specific hypertrophy induced by BA stimulation. These data suggest that fast myofibers are pivotal in the adaptation of muscle to environmental cues and that the mechanism underlying this change is partially mediated by the MAPK signaling cascade.

Adrenergic beta-Agonists↗
PubMed2006

Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior.

Non-Hodgkin's lymphoma (NHL) is a group of malignancies of the immune system with variable clinical behaviors and diverse molecular features. Despite the progress made in classification of NHLs based on classical methods, molecular classifications are a work in progress. Toward this goal, we used an array-based technique called differential methylation hybridization (DMH) to study small B-cell lymphoma (SBCL) subtypes. A total of 43 genomic DMH experiments were performed. From these results, several statistical methods were used to generate a set of differentially methylated genes for further validation. Methylation of LHX2, POU3F3, HOXC10, NRP2, PRKCE, RAMP, MLLT2, NKX6.1, LRP1B and ARF4 was validated in cell lines and patient samples and demonstrated subtype-related preferential methylation patterns. For LHX2 and LRP1B, bisulfite sequencing, real-time reverse transcriptase-polymerase chain reaction and induction of gene expression following treatment with the demethylating agent, 5'-aza-2'-deoxycytidine, were confirmed. This new epigenetic information is helping to define molecular portraits of distinct subtypes of SBCL that are not recognized by current classification systems and provides valuable potential insights into the biology of these tumors.

Adult↗
PubMed2006

Single marker and haplotype analysis of the chicken apolipoprotein B gene T123G and D9500D9- polymorphism reveals association with body growth and obesity.

Apolipoprotein B (apoB) is synthesized in the mammalian small intestine and liver, where it serves an essential role in the assembly and secretion of triglyceride-rich lipoproteins and is the constituent of very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein (LDL), and is the ligand for the LDL receptor. The present study was designed to investigate the effects of the apoB gene on chicken growth and deposition of adipose tissues. The Northeast Agricultural University broiler lines divergently selected for abdominal fat were used. Two novel polymorphisms, a synonymous mutation T-->G at 123 of 26th exon, and a 9 bp deletion at 500 bp after the stop code TGA of the apoB gene were found, and then the association between these 2 polymorphisms and traits were detected using both single marker and haplotype analysis. Results showed that the haplotype of the 2 polymorphisms of apoB gene was linked with potential major loci or genes affecting the body growth and fatness traits. The results of the present study not only suggest a primary function of apoB gene in the chicken, but also suggest that the use of molecular genetic markers associated with the apoB gene can be used in a selection program for low abdominal fat.

Abdomen↗
PubMed2006

Laminar airflow and nanoparticle or vapor deposition in a human nasal cavity model.

The transport and deposition of nanoparticles, i.e., dp = 1-2 nm, or equivalent vapors, in the human nasal cavities is of interest to engineers, scientists, air-pollution regulators, and healthcare officials alike. Tiny ultrafine particles, i.e., dp < or = 5 nm, are of special interest because they are most rapidly absorbed and hence have an elevated toxic or therapeutic impact when compared to larger particles. Assuming transient laminar 3-D incompressible flow in a representative human nasal cavity, the cyclic airflow pattern as well as local and overall nanoparticle depositions were computationally simulated and analyzed. The focus was on transient effects during inhalation/exhalation as compared to the steady-state assumption typically invoked. Then, an equation for a matching steady-state inhalation flow rate was developed that generates the same deposition results as cyclic inhalation. Of special interest is the olfactory region where the narrow channel surfaces receive only about one-half of a percent of the inhaled nanoparticles because the airflow bypasses these recesses located in the superior-most portions in the geometrically complex nasal cavities.

Absorption↗
PubMed2005

Femtosecond multidimensional imaging of a molecular dissociation.

The coupled electronic and vibrational motions governing chemical processes are best viewed from the molecule's point of view-the molecular frame. Measurements made in the laboratory frame often conceal information because of the random orientations the molecule can take. We used a combination of time-resolved photoelectron spectroscopy, multidimensional coincidence imaging spectroscopy, and ab initio computation to trace a complete reactant-to-product pathway-the photodissociation of the nitric oxide dimer-from the molecule's point of view, on the femtosecond time scale. This method revealed an elusive photochemical process involving intermediate electronic configurations.

Journal Article↗
PubMed2004

IAL-CHS (internal airlift loop--ceramic honeycomb supports) reactor used for biodegradation of 2,4-dichlorophenol and phenol.

The internal airlift loop reactor with ceramic honeycomb supports (IAL-CHS) was applied for biodegradation of 2,4-dichlorophenol (2,4-DCP) and phenol. A strain of DCP-degrading bacteria isolated from activated sludge, Achromobacter sp., was rapidly immobilized onto the ceramic honeycomb supports. The immobilized cells effectively biodegraded 2,4-DCP alone and together with phenol in batch and continuous-flow experiments. For example, 2,4-DCP was biodegraded from an influent concentration of 50 mg/L to less than 1 mg/L with a 6-h hydraulic retention time (HRT) in continuous flow tests. The immobilized biomass grew and accumulated through 2,4-DCP biodegradation, and the rate of degradation increased accordingly.

Anthelmintics↗
PubMed2003

Correction for simultaneous catheter eccentricity and tilt in intravascular elastography.

Intravascular elastography can provide significant new information about the elastic properties of vascular tissue and plaque, useful for the diagnosis of disease and appropriate selection of interventional methods. Knowledge of the plaque composition, vulnerability and its elastic properties can assist the clinician in selecting appropriate interventional techniques. However, several noise sources have to be addressed to obtain quality intravascular elastograms. Misalignment of the vessel lumen and the ultrasound beam can produce erroneous strain estimates in elastography. Errors in the strain estimate are introduced due to the eccentricity and tilt of the intravascular transducer within the vessel lumen. Previous work in this area has provided theoretical expressions for the correction of eccentricity and tilt errors when they occur independent of each other. However, under most imaging conditions, both eccentricity and tilt errors are simultaneously present. In this paper, we extend the theoretical correction factor by accounting for the influence of both of these errors occurring simultaneously in the positioning of the catheter within the vessel lumen.

Blood Vessels↗
PubMed2003

Biological treatment of printing ink wastewater.

Printing ink wastewater is usually very difficult to treat biologically and its chemical oxygen demand (COD) far exceeds standards of discharge. The COD in wastewater is usually 3,000 to 8,000 mg/L after flocculation and sedimentation. Herein, a strain of bacterium was isolated from the sludge and identified as Bacillus sp. and utilized to treat printing ink wastewater. The application of bacteria to degrade printing ink in wastewater is discussed in this paper. The influence of N and P sources on COD removal, and COD removal in combination with glucose was also discussed. More than 85 per cent of the COD could be removed using the proposed biological process. A novel internal airlift loop bioreactor with bacteria immobilized onto ceramic honeycomb support was used for the wastewater treatment.

Bacteria↗
PubMed2002

Analysis of intra-operative bleeding and recurrence of juvenile nasopharyngeal angiofibromas.

The purpose of this study is to present our experience with 34 patients diagnosed with juvenile nasopharyngeal angiofibromas and treated in the Chinese PLA General Hospital between 1986 and 1999, and to examine the factors influencing intra-operative bleeding and tumour recurrence. The age of the patient, the duration of symptoms and tumour stage were related to the amount of intra-operative bleeding. The tumours were totally resected in 30 patients and recurred in five patients (16.7%), with a mean follow-up time of 77 months. The mean time to tumour recurrence after operation was 3.2 months (1-6 months). The incidence of recurrence had no correlation with the age of the patient, duration of symptoms, peri-operative treatment or surgical approaches (P > 0.05); but strongly correlated with tumour stage (P < 0.05).

Adolescent↗
PubMed2001

Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays.

It is now clear that aberrant DNA methylation observed in cancer cells is not restricted to a few CpG islands, but affects multiple loci. When this epigenetic event occurs at the 5'-end of the regulatory region of genes, it is frequently associated with transcriptional silencing. To investigate further this widespread event in the tumor genome, we developed a novel microarray containing 7776 short GC-rich tags tethered to glass slide surfaces. This DNA chip was used to study 17 paired tissues of breast tumors and normal controls. Amplicons, representing differential pools of methylated DNA fragments between tumors and normal controls, were cohybridized to the microarray panel. Hypermethylation of multiple CpG island loci was then detected in a two-color fluorescence system. Approximately 1% (on average, 83 loci) of these CpG islands examined were hypermethylated in this patient group. Hierarchical clustering segregated these tumors based on their methylation profiles and identified a group of CpG island loci that corresponds to the hormone-receptor status of breast cancer. This observation was independently confirmed by examining a single locus, the promoter of the human glypican 3 gene, which was predominately hypermethylated in the hormone receptor-negative tumors. Our findings support the notion that hypermethylation of critical CpG island loci influences cancer development and produces distinct epigenetic signatures for particular tumor subtypes.

Breast Neoplasms↗
PubMed2001

1alpha,25-Dihydroxyvitamin D3 modulates human adipocyte metabolism via nongenomic action.

We reported recently that suppression of the renal 1alpha,25-dihyroxyvitamin D3 (1lpha,25-(OH)2-D3) production in aP2-agouti transgenic mice by increasing dietary calcium decreases adipocyte intracellular Ca2+ ([Ca2+]i), stimulates lipolysis, inhibits lipogenesis, and reduces adiposity. However, it was not clear whether this modulation of adipocyte metabolism by dietary calcium is a direct effect of inhibition of 1alpha,25-(OH)2-D3-induced [Ca2+]i. Accordingly, we have now evaluated the direct role of 1alpha,25-(OH)2-D3. Human adipocytes exhibited a 1alpha,25-(OH)2-D3 dose-responsive (1-50 nM) increase in [Ca2+]i (P<0.01). This action was mimicked by 1alpha,25-dihyroxylumisterol3 (1alpha,25-(OH)2-lumisterol3) (P<0.001), a specific agonist for a putative membrane vitamin D receptor (mVDR), and completely prevented by 1b,25-dihydroxyvitamin D3 (1beta,25-(OH)2-D3), a specific antagonist for the mVDR. Similarly, 1alpha,25-(OH)2-D3 (5 nM) caused 50%-100% increases in adipocyte fatty acid synthase (FAS) expression and activity (P<0.02), a 61% increase in glycerol-3-phosphate dehydrogenase (GPDH) activity (P<0.01), and an 80% inhibition of isoproterenol-stimulated lipolysis (P<0.001), whereas 1beta,25-(OH)2-D3 completely blocked all these effects. Notably, 1alpha,25-(OH)2-lumisterol3 exerted more potent effects in modulating adipocyte lipid metabolism, with 2.5- to 3.0-fold increases in FAS expression and activity (P<0.001) and a threefold increase in GPDH activity (P<0.001). Also 1alpha,25-(OH)2-lumisterol3 was approximately twice as potent in inhibiting basal lipolysis (P<0.025), whereas 1beta,25-(OH)2-D3 completely blocked all these effects. These data suggest that 1alpha,25-(OH)2-D3 modulates adipocyte Ca2+ signaling and, consequently, exerts a coordinated control over lipogenesis and lipolysis. Thus, a direct inhibition of 1alpha,25-(OH)2-D3-induced [Ca2+]i may contribute to an anti-obesity effect of dietary calcium, and the mVDR may represent an important target for obesity.

Adipocytes↗
PubMed2001

A recombinant glycine receptor fragment forms homo-oligomers distinct from its GABA(A) counterpart.

The ligand-gated ion channel receptor superfamily includes receptors for glycine, GABA, acetylcholine and serotonin. Whereas the acetylcholine and serotonin receptors mediate excitory neurotransmissions, both glycine and GABA(A) receptors are inhibitory. In this study, a fragment of the human glycine receptor alpha1 subunit, consisting of residues Ala165-Met291 (numbering based on the precursor protein), was hyperexpressed for the first time in Escherichia coli. This fragment is highly homologous in sequence to the corresponding fragment of the GABA(A) receptor. The recombinant fragment was found to have stable beta-rich secondary structure, similar to that found for the homologous GABA(A) receptor fragment, and ordered tertiary packing, suggesting a stable structural domain. Results from laser scattering studies suggest that the fragment forms trimers in solution. In addition, SDS-induced changes in secondary structure were found to occur prior to changes in oligomerization status, suggesting that oligomerization was secondary structure dependent. A study of quaternary structure using single particle analysis electron microscopy (EM) also suggested that the fragment formed homo-trimers. One trimer measures approximately 7.5 nm in diameter with a central cavity approximately 1.5 nm across. This is the first EM study on a single domain of the glycine receptor and the result is in contrast to the pentameric assembly of the equivalent GABA(A) receptor fragment reported by us earlier. The fact that this fragment alone could form oligomers in vitro suggests that amino acid residues within this segment may be involved in the oligomerization of the glycine receptor in vivo. Furthermore, the finding that two cousin receptor fragments form distinct quaternary structures indicates that sequence similarity does not necessarily imply quaternary structure similarity and, hence, care must be taken when applying a structure model derived from studies of individual receptors to the whole ligand-gated ion channel superfamily.

Amino Acid Sequence↗
PubMed2001

Different subtypes of alpha1-adrenoceptor modulate different K+ currents via different signaling pathways in canine ventricular myocytes.

Multiple subtypes (alpha1A, alpha1B, and alpha1D) of alpha1-adrenoreceptors (alpha1ARs) co-exist in the heart and mediate a variety of cellular functions. We studied alphaAR modulation of inward rectifier (IK1) and transient outward (Ito) K(+) currents in canine ventricular myocytes. Phenylephrine at 10 microM depressed only Ito without affecting IK1 and at 100 microM inhibited both Ito and IK1. The effect of phenylephrine on Ito was abolished by (+)niguldipine (10 nm) to inhibit alpha1AARs but not by chloroethyclonidine (10 microM) to inactivate alpha1BARs nor by BMY-7378 to antagonize alpha1DARs. In contrast, phenylephrine inhibition of IK1 was reversed only by BMY-7378 (1 nm). PDD (100 nm, phorbol ester activator of protein kinase C (PKC)) simulates and bisindolylmaleimide (50 nm, PKC inhibitor) weakens phenylephrine modulation of Ito but not IK1. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 and inhibitor peptides abolished the effects of phenylephrine on IK1. Enhancement of PKC or CaMKII activities was seen in alpha1aAR- or alpha1dAR-transfected HEK293 cells and in myocytes pretreated with 10 or 100 microM phenylephrine, respectively. Our data suggest that different subtypes of alpha1ARs selectively modulate different cardiac K(+) currents via different signal transduction mechanisms; alpha1AARs mediate Ito regulation via PKC, and alpha1DARs mediate IK1 regulation via CaMKII.

Adrenergic alpha-Agonists↗
PubMed2001

[Antigen presentation of eosinophils in mice].

OBJECTIVE: To explore whether or not eosinophils can present antigen to T lymphocytes in vivo, and to further elucidate the process and characteristics of antigen-presentation by eosinophils in vivo. METHODS: BALB/c mice were sensitized and challenged by ovalbumin to recruit eosinophil infiltration into the airways. The airway eosinophils were purified and were labeled with a fluorescent dye. The labeled eosinophils were instilled into the mouse tracheas, fluorescent microscope was used to observe the migration of endobronchial eosinophils in vivo. Single cell suspension was prepared from paratracheal lymph nodes of mice receiving antigen-exposed eosinophil instillation, and flow cytometry was used to determine proliferation response of T cells and to identify the subset of responding T cells. RESULTS: By 8 h after tracheal instillation, labeled eosinophils were visible in the subcapsular region and streaming through the subcapsular sinus (19.0 +/- 1.8/mm(2)). With increasing time, the numbers of eosinophils entering the regional lymph nodes increased, peaking at 24 h (59.2 +/- 7.2/mm(2)) and persisting for at least 120 h (29.6 +/- 2.8/mm(2)). In sensitized mice that received 5 x 10(5) antigen-exposed eosinophils, in vivo percentage of proliferating T cell in the paratracheal lymph nodes 1 d after eosinophil instillation (6.9% +/- 0.5%) were much higher than basic control value (3.2% +/- 0.3%, P < 0.01), peaked at day 3 (10.8% +/- 0.8%, P < 0.01), and then declined over 7 d (6.1% +/- 0.6%, P < 0.05). Eosinophil-induced in vivo T cell proliferation was antigen-specific, and the responding T cells were limited to CD4(+) cells. CONCLUSIONS: Eosinophils within the lumina of airways can process inhaled antigens, traffick to regional lymph nodes and function in vivo as antigen-presenting cells to stimulate responses of CD4(+) T cells.

Animals↗