Biomedical subjects

Ming Zhang

Publications and source records attributed to Ming Zhang.

At least 37 records · Page 2Linked to original sources

PubMed2006

Sno/scaRNAbase: a curated database for small nucleolar RNAs and cajal body-specific RNAs.

Small nucleolar RNAs (snoRNAs) and Cajal body-specific RNAs (scaRNAs) are named for their subcellular localization within nucleoli and Cajal bodies (conserved subnuclear organelles present in the nucleoplasm), respectively. They have been found to play important roles in rRNA, tRNA, snRNAs, and even mRNA modification and processing. All snoRNAs fall in two categories, box C/D snoRNAs and box H/ACA snoRNAs, according to their distinct sequence and secondary structure features. Box C/D snoRNAs and box H/ACA snoRNAs mainly function in guiding 2'-O-ribose methylation and pseudouridilation, respectively. ScaRNAs possess both box C/D snoRNA and box H/ACA snoRNA sequence motif features, but guide snRNA modifications that are transcribed by RNA polymerase II. Here we present a Web-based sno/scaRNA database, called sno/scaRNAbase, to facilitate the sno/scaRNA research in terms of providing a more comprehensive knowledge base. Covering 1979 records derived from 85 organisms for the first time, sno/scaRNAbase is not only dedicated to filling gaps between existing organism-specific sno/scaRNA databases that are focused on different sno/scaRNA aspects, but also provides sno/scaRNA scientists with an opportunity to adopt a unified nomenclature for sno/scaRNAs. Derived from a systematic literature curation and annotation effort, the sno/scaRNAbase provides an easy-to-use gateway to important sno/scaRNA features such as sequence motifs, possible functions, homologues, secondary structures, genomics organization, sno/scaRNA gene's chromosome location, and more. Approximate searches, in addition to accurate and straightforward searches, make the database search more flexible. A BLAST search engine is implemented to enable blast of query sequences against all sno/scaRNAbase sequences. Thus our sno/scaRNAbase serves as a more uniform and friendly platform for sno/scaRNA research. The database is free available at http://gene.fudan.sh.cn/snoRNAbase.nsf.

Base Sequence↗

PubMed2006

Total and free mycophenolic acid and its 7-O-glucuronide metabolite in Chinese adult renal transplant patients: pharmacokinetics and application of limited sampling strategies.

OBJECTIVE: This study aimed to investigate the pharmacokinetic characteristics of total and free mycophnolic acid (MPA) and its 7-O-glucuronide metabolite (MPAG) in Chinese renal transplant recipients. In addition, limited sampling strategies were developed to estimate the individual area under concentration curve (AUC) of total and free MPA. METHODS: Total and free MPA and MPAG concentrations were determined by high performance liquid chromatography. Whole 12-h pharmacokinetic profiles were obtained on the 10th day after operation in 12 adult Chinese de novo renal transplant recipients administrated with mycophenolate mofetil (MMF, 750 mg bid), cyclosporine and corticosteroids. Limited sampling strategies with jackknife technique, a resampling method, and Bland-Altman analysis were employed to develop equations to estimate total and free MPA AUC. RESULTS: The pattern of total and free MPA and MPAG plasma concentration-time curves in the cohort of patients taking lower doses of MMF was consistent with previous reports of Caucasian patients taking MMF 1 g bid, except that dose-normalized exposure of total and free MPAG was much lower in the current study than in those of the Caucasians. The mean C (max) and AUC(0-12h) of total and free MPA were 9.4 +/- 3.4 mg/L, 20.2 +/- 6.5 mg x h/L and 0.4 +/- 0.4 mg/L, 0.7 +/- 0.5 mg x h/L, respectively, whereas mean C (max) and AUC(0-12h) of total and free MPAG were 97.3 +/- 32.6 mg/L, 656.0 +/- 148.0 mg.h/L and 29.9 +/- 8.5 mg/L, 222.0 +/- 58.1 mg x h/L respectively. The mean fractions of free MPA and MPAG were 3.5 +/- 2.0 and 34.6 +/- 8.0%, respectively. No determinant was identified to influence the pharmacokinetics of total and free MPA and MPAG or the free fraction of MPA and MPAG. The combinations of C (2h)-C (4h) and C (1h)-C (2h)-C (3h) were the best to estimate free and total MPA AUC(0-12h) respectively, whereas the combination of C (2h)-C (3h)-C (4h) and C (1h)-C (2h)-C (4h) was the best to estimate both simultaneously. CONCLUSION: This is the first time that the pharmacokinetics profile of total and free MPA and its main metabolite MPAG has been examined in Chinese adult renal transplant patients. The limited sampling strategies proposed to estimate individual free and total MPA AUC could be useful in optimizing patient care.

Adult↗

PubMed2006

Using computational simulation to aid in the prediction of socket fit: a preliminary study.

This study illustrates the use of computational analysis to predict prosthetic socket fit. A simple indentation test is performed by applying force to the residual limb of a trans-tibial amputee through an indenter until the subject perceives the onset of pain. Computational finite element (FE) analysis is then applied to evaluate the magnitude of pressure underlying the indenter that initiates pain (pain threshold pressure), and the pressure at the prosthetic socket-residual limb interface. The assessment of socket fit is examined by studying whether or not the socket-limb interface pressure exceeds the pain threshold pressure of the limb. Based on the computer-aided assessment, a new prosthetic socket is then fabricated and fitted to the amputee subject. Successful socket fit is achieved at the end of this process. The approach of using computational analysis to aid in assessing socket fit allows a more efficient evaluation and re-design of the socket even before the actual fabrication and fitting of the prosthetic socket. However, more thorough investigations are required before this approach can be widely used. A subsequent part of this paper discusses the limitations and suggests future research directions in this area.

Amputation, Surgical↗

PubMed2006

Monocyte chemotactic protein-3 is a myocardial mesenchymal stem cell homing factor.

MSCs have received attention for their therapeutic potential in a number of disease states, including bone formation, diabetes, stem cell engraftment after marrow transplantation, graft-versus-host disease, and heart failure. Despite this diverse interest, the molecular signals regulating MSC trafficking to sites of injury are unclear. MSCs are known to transiently home to the freshly infarcted myocardium. To identify MSC homing factors, we determined chemokine expression pattern as a function of time after myocardial infarction (MI). We merged these profiles with chemokine receptors expressed on MSCs but not cardiac fibroblasts, which do not home after MI. This analysis identified monocyte chemotactic protein-3 (MCP-3) as a potential MSC homing factor. Overexpression of MCP-3 1 month after MI restored MSC homing to the heart. After serial infusions of MSCs, cardiac function improved in MCP-3-expressing hearts (88.7%, p < .001) but not in control hearts (8.6%, p = .47). MSC engraftment was not associated with differentiation into cardiac myocytes. Rather, MSC engraftment appeared to result in recruitment of myofibroblasts and remodeling of the collagen matrix. These data indicate that MCP-3 is an MSC homing factor; local overexpression of MCP-3 recruits MSCs to sites of injured tissue and improves cardiac remodeling independent of cardiac myocyte regeneration.

Animals↗

PubMed2006

Differentiation of human embryonic stem cells into smooth muscle cells in adherent monolayer culture.

Smooth muscle cell (SMC) plays critical roles in many human diseases, an in vitro system that recapitulates human SMC differentiation would be invaluable for exploring molecular mechanisms leading to the human diseases. We report a directed and highly efficient SMC differentiation system by treating the monolayer-cultivated human embryonic stem cells (hESCs) with all-trans retinoid acid (atRA). When the hESCs were cultivated in differentiation medium containing 10microM RA, more than 93% of the cells expressed SMC-marker genes along with the steadily accumulation of such SMC-specific proteins as SM alpha-actin and SM-MHC. The fully differentiated SMCs were stable in phenotype and capable of contraction. This inducible and highly efficient in vitro human SMC system could be an important resource to study the mechanisms of SMC phenotype determination in human.

Biomarkers↗

PubMed2006

Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury.

Reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement, which is activated by circulating natural IgM specific to self-Ags exposed by ischemia. Recent reports demonstrating a role for the lectin pathway raise a question regarding the initial events in complement activation. To dissect the individual roles of natural IgM and lectin in activation of complement, mice bearing genetic deficiency in early complement, IgM, or mannan-binding lectin were characterized in a mesenteric model of ischemia reperfusion injury. The results reveal that IgM binds initially to ischemic Ag providing a binding site for mannan-binding lectin which subsequently leads to activation of complement and injury.

Amino Acid Sequence↗

PubMed2006

Spatial and nonspatial peripheral auditory processing in congenitally blind people.

Congenitally blind adults' performance in spatial and nonspatial peripheral auditory attention tasks was compared with that of sighted adults in a paradigm manipulating location-based and frequency-based inhibition of return concurrently. Blind study participants responded faster in spatial attention tasks (detection/localization) and slower in the nonspatial frequency discrimination task than sighted participants. Both groups, however, showed the same patterns of interaction between location-based and frequency-based inhibition of return. These results suggest that early vision deprivation enhances the function of the posterior-dorsal auditory 'where' pathway but impairs the function of the anterior-ventral 'what' pathway during peripheral auditory attention. The altered processing speed in the blind, however, is not accompanied by alteration in attentional orienting mechanisms that may be localized to higher cortices.

Acoustic Stimulation↗

PubMed2006

Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in Southern Africa.

A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.

Gene Products, env↗

PubMed2006

Nature of zinc(II)-induced ionochromic effect of bipyridine-containing conjugated polymers: an electrostatic interaction mechanism.

To reveal the nature of the zinc(II)-ion-induced ionochromic effect of bipyridine (bpy)-containing pi-conjugated polymers, we proposed an electrostatic interaction mechanism to illustrate our recent experimental findings [Tian, L., et al. J. Phys. Chem. B 2005 109 (15), 6944]. Our theoretical analysis was based on the semiempirical (INDO/2) calculation of spectral properties and electronic structures of difluorene-substituted bpy model compounds. Our calculations show that the zinc(II)-induced ionochromic effect can be attributed to the electrostatic interaction between the zinc(II) ion and the polymer. Zinc(II) ion acts as a positive point charge with varied charge quantities, which is responsible for the red-shifted absorption spectra compared with those of the metal-free compound. The counterion ionochromic effect of the zinc(II) ion is also discussed. The proposed mechanism is possibly applied to the ionochromic effect induced by other metal ions such as Cd(II) and Hg(II).

Journal Article↗

PubMed2006

Interaction between location- and frequency-based inhibition of return in human auditory system.

Using a cue-target paradigm, this study investigated the interaction between location and frequency information processing in human auditory inhibition of return (IOR). The cue and the target varied in terms of location and frequency and participants were asked to perform a target detection, localization or frequency discrimination task. Results showed that, when neither location nor frequency of auditory stimuli was particularly relevant to the target detection task, there was a location-based IOR only if the cue and the target were identical in frequency and there was a frequency-based IOR only if the cue and the target were presented at the same location. When a particular feature of auditory stimuli, whether location or frequency, was directly relevant to the current task, the IOR effect was evident for this feature only if the cue and the target differed on the task-irrelevant feature, while the IOR effect was eliminated for the task-relevant feature when the cue and the target had the same task-irrelevant feature. Similarly, the IOR effect based on the task-irrelevant feature was evident when the cue and the target differed on the task-relevant feature, and was eliminated or reversed when the cue and the target shared the task-relevant feature. Theoretical implications of these findings for auditory IOR are discussed.

Acoustic Stimulation↗

PubMed2006

Pressure distribution at the stump/socket interface in transtibial amputees during walking on stairs, slope and non-flat road.

BACKGROUND: Studies examining the stump/socket interface stresses have been restricted to unsupported stance and natural gait, i.e. walking at a comfortable speed on flat and straight walkway. However, the pressure behaviour as to the interface in unilateral transtibial amputees during walking on stairs, slope and non-flat road is unclear. METHODS: Pressure distribution changes at multiple points, expressed as mean peak stump/socket interface pressure, mean pressure level over 90% of peak pressure, time in which pressure exceeded 90% of peak pressure and time-pressure integral at the period of sustained sub-maximal load, were measured during natural ambulating and walking on stairs, slope and non-flat road. FINDINGS: Compared with natural gait, the mean peak pressure and sustained sub-maximal load increase notably over the patellar tendon during walking on stairs and non-flat road, and however decrease or change insignificantly at the patellar tendon on slope and over other measured areas in all conditions; moreover the time period of sustained sub-maximal load changes remarkably, except over the patellar tendon during walking up slope and over the popliteal area on non-flat road; finally, the time-pressure integral in the time period of sustained sub-maximal load changes considerably, except at the patellar tendon during walking up slope. INTERPRETATION: The pressure characteristics during natural ambulating seem not to be highly predictive of what occurs in the conditions of walking on stairs, slope and non-flat road, which leads to significant increase in amplitude domain of tissue loading only at the patellar tendon, and however to remarkable changes in temporal sequences of tissue (un-)loading almost in all measured regions.

Adult↗

PubMed2006

[Anterior cingulate cortex involving in pain modulation-an functional magnetic resonance imaging study].

OBJECTIVE: To investigate the functional activation patterns of the subregions of anterior cingulate cortex (ACC) in human to electrical stimulation of different intensity with functional Magnetic Resonance Imaging (fMRI) and probe the contribution of this area in pain modulation network. METHODS: 10 healthy right-handed volunteers were studied with different electrical intensity stimulation of 1-, 2-, or 3-time pain threshold. The fMRI data were collected by GE signa 1.5T MRI system and postprocessed with software of Analysis of Functional Neuroimages (AFNI) to generate the regional activation maps of ACC, furthermore, the distinctive characteristics of stimulation-BOLD signal in ACC subregions were analyzed according to the fMRI maps from the average of the 10 subjects. RESULTS: The anterior portion of ACC (aACC) showed moderate pain-attention-related activation but not statistically related to the strength of stimulation (average activated pixels of P1, P2, P3 amounted to 324, 429, 562 respectively). The BOLD signal showed a positive linear relation with the increasing stimulation at the dorsal-posterior portion of ACC (average activated pixels of P1, P2, P3 were 311, 964, 1414), which indicated stimulus intensity-dependent responses. The ventral-posterior area of ACC (vpACC) demonstrated pain intensity encoding because the BOLD signal had no significant difference during innocuous condition but displayed remarkable distinction during noxious stimulation in this area (average activated pixels of P1, P2, P3 were 324, 429, 562). CONCLUSION: Subregions in ACC may play a varied role in the network of pain modulation. Each area of ACC displays segregated activation patterns in response to electrical stimulation with different strength.

Adult↗

PubMed2006

Interactions of daidzin with intramolecular G-quadruplex.

The potential interaction of daidzin, an ingredient of soy isoflavones, with human telomeric antiparallel G-quadruplex dAG(3)(T(2)AG(3))(3) was studied using ESI-MS, PAGE, CD and molecular simulation. Experimental studies indicated that daidzin molecules interacted with dAG(3)(T(2)AG(3))(3) and formed DNA-daidzin complex with the stoichiometric ratio of 1:1 and 1:2. The transition temperature of the G-quadruplex increased at higher ratio of daidzin to DNA. Under molecular crowding conditions the interactions between daidzin and the G-quadruplex become much stronger. Combining computational simulation and experimental results, it is demonstrated that the dAG(3)(T(2)AG(3))(3)/daidzin complex with a stoichiometric ratio of 1:1 is stabilized through the pi-pi conjugacy interactions and hydrogen bondings between daidzin and the bases of G-quadruplex. This work provides guidance not only on exploring the molecular anti-cancer mechanism of dietary isoflavones, but also searching small natural products as promising anticancer candidates that can inhibit telomerase activity.

Circular Dichroism↗

PubMed2006

Reduction of intracellular pH inhibits the expression of VEGF in K562 cells after targeted inhibition of the Na+/H+ exchanger.

To explore the effect of inhibition of Na(+)/H(+) exchanger isoform 1 (NHE1) on the expression of vascular endothelial growth factor (VEGF) mRNA and protein in human myeloid K562 cells. The expression of VEGFmRNA was detected by RT-PCR technique. The levels of VEGF protein were measured by Western blotting and immunocytochemistry assay. pHi values were measured with fluorescence spectrophotometer. The three RT-PCR products detected were VEGF121, VEGF165, and VEGF189, respectively. Treatment of K562 cells either with amiloride (an inhibitor of NHE1) or with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA, a selective inhibitor of NHE1) resulted in significant decrease of VEGF mRNA and VEGF protein levels. Either amiloride or EIPA decreased intracellular pH (pHi) values in K562 cells. These data strongly suggested that the expression of VEGF mRNA and protein in K562 cells was inhibited accompanying its reduction in pHi value after targeted inhibition of NHE1.

Amiloride↗

PubMed2006

Natural antibody mediated innate autoimmune response.

Recent advance in autoimmunity research reveals that the innate immune system is able to recognize self-targets and initiate inflammatory response in a similar way as with pathogens. This review describes one novel example of this innate autoimmunity, ischemia-reperfusion (I/R) injury. Studies of intestinal, skeletal muscle, and heart I/R models showed that reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement system which is activated by natural IgM. The recent identification of a monoclonal natural IgM that initiates I/R led to the identification of non-muscle myosin heavy chain type II A and C as the self-targets in two different tissues. New evidence further suggests that IgM binds initially to ischemic antigen providing a binding site for mannan binding lectin (MBL) which subsequently leads to activation of complement and results in tissue injury. Therefore, natural IgM mediated innate autoimmunity is likely responsible for the detrimental consequences in ischemic diseases.

Animals↗

PubMed2006

Genome sequence diversity and clues to the evolution of variola (smallpox) virus.

Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.

DNA, Viral↗

PubMed2006

Effects of spatial distribution of attention during inhibition of return (IOR) on flanker interference in hearing and congenitally deaf people.

This study explored the interaction between the spatial distribution of attention during inhibition of return (IOR) and different levels of flanker interference in congenitally deaf subjects as compared with hearing subjects. Color (Experiment 1) and alphanumeric (Experiment 2) flanker interference effects were differentiated into the pre-response and the response levels. The spatial distribution of attention was manipulated through IOR. Subjects were asked to either make color or letter/digit discriminations to the central targets or detect the abrupt-onset peripheral targets. Deaf subjects were significantly faster than hearing subjects at detecting peripheral targets irrespective of the cue validity, while the two groups had comparable sizes of IOR. In the central discrimination tasks, deaf subjects showed significant response level, but not pre-response level, flanker effects irrespective of the type of stimuli and the spatial location of the flanker. For hearing subjects, however, spatial attention interacted with the pre-response and response flanker effects in different ways. While flankers at the cued location caused interference effects at the response level and facilitatory effects at the pre-response level, those at the uncued location caused different effects depending on the type of stimuli. Moreover, increasing the peripheral attention for hearing subjects, by increasing the proportion of peripheral detection trials, made hearing subjects behave like deaf subjects. These results demonstrate that deaf people possess enhanced peripheral attentional resources as compared with hearing people. The spatial distribution of attention modulates mainly the resolution of the pre-response flanker interference in hearing people, but affects neither the pre-response nor the response level interference in deaf people.

Acoustic Stimulation↗

PubMed2006

Hydroxyl-directed conjugate additions of carbon nucleophiles to cyclopentadienones.

[Structure: see text] The conjugate additions of different carbon nucleophiles to cyclopentadienone substrates (1 and 2) with one free hydroxyl functional group were investigated to determine the role of the hydroxyl group in controlling regiochemistry. During this reaction an unexpected intramolecular displacement of OTBS by the enolate intermediate occurs, to afford cyclopropane derivatives.

Journal Article↗