Biomedical subjects

Jing Wang

Publications and source records attributed to Jing Wang.

At least 415 records · Page 23Linked to original sources

PubMed2003

The structural characterization and antigenicity of the S protein of SARS-CoV.

The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and positions, thus establishing the structural connection with these two important structural proteins, if confirmed. Phylogenetic analysis reveals several conserved regions that might be potent drug targets.

Amino Acid Sequence↗

PubMed2003

The M protein of SARS-CoV: basic structural and immunological properties.

We studied structural and immunological properties of the SARS-CoV M (membrane) protein, based on comparative analyses of sequence features, phylogenetic investigation, and experimental results. The M protein is predicted to contain a triple-spanning transmembrane (TM) region, a single N-glycosylation site near its N-terminus that is in the exterior of the virion, and a long C-terminal region in the interior. The M protein harbors a higher substitution rate (0.6% correlated to its size) among viral open reading frames (ORFs) from published data. The four substitutions detected in the M protein, which cause non-synonymous changes, can be classified into three types. One of them results in changes of pI (isoelectric point) and charge, affecting antigenicity. The second changes hydrophobicity of the TM region, and the third one relates to hydrophilicity of the interior structure. Phylogenetic tree building based on the variations of the M protein appears to support the non-human origin of SARS-CoV. To investigate its immunogenicity, we synthesized eight oligopeptides covering 69.2% of the entire ORF and screened them by using ELISA (enzyme-linked immunosorbent assay) with sera from SARS patients. The results confirmed our predictions on antigenic sites.

Amino Acid Sequence↗

PubMed2003

The E protein is a multifunctional membrane protein of SARS-CoV.

The E (envelope) protein is the smallest structural protein in all coronaviruses and is the only viral structural protein in which no variation has been detected. We conducted genome sequencing and phylogenetic analyses of SARS-CoV. Based on genome sequencing, we predicted the E protein is a transmembrane (TM) protein characterized by a TM region with strong hydrophobicity and alpha-helix conformation. We identified a segment (NH2-_L-Cys-A-Y-Cys-Cys-N_-COOH) in the carboxyl-terminal region of the E protein that appears to form three disulfide bonds with another segment of corresponding cysteines in the carboxyl-terminus of the S (spike) protein. These bonds point to a possible structural association between the E and S proteins. Our phylogenetic analyses of the E protein sequences in all published coronaviruses place SARS-CoV in an independent group in Coronaviridae and suggest a non-human animal origin.

Amino Acid Sequence↗

PubMed2003

Complete genome sequences of the SARS-CoV: the BJ Group (Isolates BJ01-BJ04).

Beijing has been one of the epicenters attacked most severely by the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) since the first patient was diagnosed in one of the city's hospitals. We now report complete genome sequences of the BJ Group, including four isolates (Isolates BJ01, BJ02, BJ03, and BJ04) of the SARS-CoV. It is remarkable that all members of the BJ Group share a common haplotype, consisting of seven loci that differentiate the group from other isolates published to date. Among 42 substitutions uniquely identified from the BJ group, 32 are non-synonymous changes at the amino acid level. Rooted phylogenetic trees, proposed on the basis of haplotypes and other sequence variations of SARS-CoV isolates from Canada, USA, Singapore, and China, gave rise to different paradigms but positioned the BJ Group, together with the newly discovered GD01 (GD-Ins29) in the same clade, followed by the H-U Group (from Hong Kong to USA) and the H-T Group (from Hong Kong to Toronto), leaving the SP Group (Singapore) more distant. This result appears to suggest a possible transmission path from Guangdong to Beijing/Hong Kong, then to other countries and regions.

Genome, Viral↗

PubMed2003

Evolution and variation of the SARS-CoV genome.

Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.

Amino Acid Motifs↗

PubMed2003

Genome organization of the SARS-CoV.

Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or developed by ourselves. Totally, 21 open reading frames (ORFs) of genes or putative uncharacterized proteins (PUPs) were predicted. Seven PUPs had not been reported previously, and two of them were predicted to contain transmembrane regions. Eight ORFs partially overlapped with or embedded into those of known genes, revealing that the SARS-CoV genome is a small and compact one with overlapped coding regions. The most striking discovery is that an ORF locates on the minus strand. We have also annotated non-coding regions and identified the transcription regulating sequences (TRS) in the intergenic regions. The analysis of TRS supports the minus strand extending transcription mechanism of coronavirus. The SNP analysis of different isolates reveals that mutations of the sequences do not affect the prediction results of ORFs.

Amino Acid Substitution↗

PubMed2003

Decolorization of azo dyes by Rhodobacter sphaeroides.

Rhodobacter sphaeroides AS1.1737 decolorized more than 90% of several azo dyes (200 mg dyes l(-1)) in 24 h. The optimal culture conditions were: anaerobic illumination (1990 1x), peptone as carbon source, temperature 35-40 degrees C and pH 7-8. Intracellular crude enzyme from this strain had azoreductase activity, optimized temperature as 45-50 degrees C, and decolorization kinetics which were consistent with a ping-pong mechanism.

Azo Compounds↗

PubMed2003

Structure-based prediction of free energy changes of binding of PTP1B inhibitors.

The goals were (1) to understand the driving forces in the binding of small molecule inhibitors to the active site of PTP1B and (2) to develop a molecular mechanics-based empirical free energy function for compound potency prediction. A set of compounds with known activities was docked onto the active site. The related energy components and molecular surface areas were calculated. The bridging water molecules were identified and their contributions were considered. Linear relationships were explored between the above terms and the binding free energies of compounds derived based on experimental inhibition constants. We found that minimally three terms are required to give rise to a good correlation (0.86) with predictive power in five-group cross-validation test (q2 = 0.70). The dominant terms are the electrostatic energy and non-electrostatic energy stemming from the intra- and intermolecular interactions of solutes and from those of bridging water molecules in complexes.

Binding Sites↗

PubMed2003

Lymphoid microenvironment in the gut for immunoglobulin A and inflammation.

Signaling through lymphotoxin beta receptor (LTbetaR) initiates the unfolding of a host of developmental programs ranging from the organogenesis of lymph nodes and Peyer's patches (PPs) to the coordination of splenic microarchitecture. While investigating an alternative pathway to immunoglobulin A (IgA) production, it was uncovered that LTbetaR signaling in the lamina propria (LP) stroma orchestrates the coordinated expression of key chemokines and adhesion molecules, creation of a cytokine milieu, and stroma development that facilitates robust IgA production independent of secondary lymphoid structures. Simultaneously, this same infrastructure can be commandeered by autoreactive T cells to organize both the acute destruction of the intestinal mucosa and chronic intestinal inflammation via the ligands for LTbetaR. The ability to modulate LTbetaR signaling may alternatively permit the suppression of autoimmune responses and augmentation of gut defenses.

Animals↗

PubMed2003

Construction, expression and characterization of the engineered antibody against tumor surface antigen, p185(c-erbB-2).

The c-erbB-2 proto-oncogene encodes a 185kDa protein p185, which belongs to epidermal growth factor receptor family. Amplification of this gene has been shown to correlate with poor clinical prognosis for certain cancer patients. The monoclonal antibody A21 which directed against p185 specifically inhibits proliferation of tumor cells overexpressing p185, hence allows it to be a candidate for targeted therapy. In order to overcome several drawbacks of murine MAb, we cloned its VH and VL genes and constructed the single-chain Fv (scFv) through a peptide linker. The recombinant scFvA21 was expressed in Escherichia coli and purified by the affinity column. Subsequently it was characterized by ELISA, Western blot, cell immunohistochemistry and FACS. All these assays showed the binding activity to extracellular domain (ECD) of p185. Based on those properties of scFvA21, we further constructed the scFv-Fc fusion molecule with a homodimer form and the recombinant product was expressed in mammalian cells. In a series of subsequent analysis this fusion protein showed identical antigen binding site and activity with the parent antibody. These anti-p185 engineered antibodies have promised to be further modified as a tumor targeting drugs, with a view of application in the diagnosis and treatment of human breast cancer.

Amino Acid Sequence↗

PubMed2003

Degeneration of sensory outer hair cells following pharmacological blockade of cochlear KCNQ channels in the adult guinea pig.

In the inner ear, hair cell function is inextricably linked with intracellular potassium homeostasis. KCNQ potassium channels may play an important role by preventing accumulation of potassium in the hair cells. Linopirdine, a tool useful in targeting native or heterologous KCNQ channels, was used to study the role of KCNQ channels in the guinea pig cochlea. When perfused into intact cochlea, linopirdine transiently increases the summating potential and endocochlear potential, suggesting that it alters K+ homeostasis. The concomitant decrease in cochlear microphonic potential and distortion product otoacoustic emission amplitude indicates that linopirdine has an effect on the outer hair cells (OHCs). To determine the pathological consequences of the inhibition of cochlear KCNQ channels, we developed a hearing loss model based on a chronic intracochlear perfusion of linopirdine via an osmotic minipump. Ultrastructural analysis reveals that KCNQ channel blockade leads to OHC degeneration. Together, these results demonstrate that KCNQ channels, most probably of the KCNQ4 subtype, are crucial for the function and survival of sensory OHCs. Clinically, KCNQ4 channel dysfunction is known to be associated with the DFNA2 form of nonsyndromic dominant deafness. Our study shows that OHC KCNQ4 dysfunction could contribute to the early (40dB) hearing loss, but not for the profound deafness observed at the final stage of this disease.

Acoustic Stimulation↗

PubMed2003

Detection of occupational allergic contact dermatitis by patch testing.

Occupational allergic contact dermatitis (OACD) is an important medical and occupational health problem. If undiagnosed, the disease may persist and even spread widely, resulting in severe and permanent disability to the worker, who may be deprived of his legal right to compensation. OACD is not uncommon in China, although many dermatologists fail to establish the connection between disease and working conditions, because they think that the diagnosis of OACD is the work of occupational medicine and that special diagnostic methods are required. The Ministry of Health and Ministry of Labour and Social Security of China have issued a new law recently to emphasize the prevention and treatment of occupational disease. It requires physicians to make an accurate diagnosis and report of occupation-related diseases. In this study, we have successfully investigated 14 cases of OACD in our hospital by patch testing the patients with a standard series of allergens and investigating by questionnaire the suspected offending occupational allergens. During a 2-year period (2001-2003), 14 patients with suspected allergic contact dermatitis were investigated and confirmed as having OACD. OACD may develop in many different occupations. In this study, nickel, 4-phenylenediamine, fragrance mix, black rubber mix, colophonium, epoxy resin and thiuram mix were identified by patch testing as the main offending allergens in such patients. These results indicate that patch testing plays a vital role in the diagnosis and identification of occupational allergens, and our study shows that OACD can often be diagnosed by patch testing patients with a standard series. The clinician should be alert to recognize the offending allergens of OACD by referring to patch testing all patients with clinically suspected contact dermatitis, and then educating the sensitized worker in how to avoid further exposure to the causative allergens.

Adult↗

PubMed2003

Age-dependent changes in the basal retinovitreous adhesion.

PURPOSE: To determine the width of the posterior vitreous base in human eyes of different ages and to clarify the nature of the postoral retinovitreous adhesion that underlies the development of juxtabasal retinal tears and retinal detachment after posterior vitreous detachment (PVD). METHODS: The posterior limit of the vitreous base was delineated with indocyanine green after mechanical peeling of the postbasal vitreous cortex from the retina in 58 pairs of donor eyes. The area of residual retinovitreous adhesion was measured by image analysis. Scanning electron microscopy was performed on the undersurface (or retinal aspect) of the inner limiting lamina (ILL) after trypsin digestion of the peripheral retina. RESULTS: An age-dependent increase in the anteroposterior dimension of the posterior vitreous base was revealed that became progressively wider in eyes of male donors than in those of female donors and in the nasal half compared with the temporal half of the globe. Ultrastructural studies showed progressive invasion of the innermost peripheral retina by bundles of collagen fibrils, initially in the form of characteristic braids splaying out beneath the ILL and eventually as a dense sublaminar mat in the elderly. The collagen fibrils penetrated the ILL through localized defects and intertwined with those in the basal gel. CONCLUSIONS: With aging, the posterior border of the vitreous base migrates posteriorly so that an annular band of firm adhesion eventually straddles the ora serrata eccentrically. Intraretinal synthesis of collagen fibrils, their penetration of the ILL, and their splicing with cortical vitreous fibrils, underlie the slowly evolving retinovitreous adhesion.

Adhesiveness↗

PubMed2003

Synthesis and antiviral activity of a series of new cyclohexenyl nucleosides.

A series of new cyclohexenyl nucleosides is synthesized by coupling the heterocyclic bases with a protected cyclohexenyl precursor under Mitsunobu conditions. The compounds were evaluated for their antiviral and cytostatic activity. Pronounced activity against herpes simplex virus type 1 and type 2 was observed for the 2,6-diaminopurine analogue.

Antiviral Agents↗

PubMed2003

The MPN mag: introducing a critical area mediating pheromonal and hormonal regulation of male sexual behavior.

Mating behavior in male hamsters is regulated by a chemosensory pathway that converges on the bed nucleus of the stria terminalis (BST) and the medial nucleus of the amygdala (Me). Both the BST and the Me project to the lateral part of the medial preoptic area. Lesion studies have identified a small group of large cells referred to as the magnocellular medial preoptic nucleus (MPN mag) whose integrity is required for normal mating behavior. Our data, summarized within, indicate that the MPN mag is a sexually differentiated nucleus in a large steroid-responsive network that relays pheromonal signals from the sensory systems to the motor areas to affect behavior.

Animals↗

PubMed2003

An amperometric biosensor for glucose based on electrodeposited redox polymer/glucose oxidase film on a gold electrode.

In this paper, we described a glucose biosensor based on the co-electrodeposition of a poly(vinylimidazole) complex of [Os(bpy)2Cl](+/2+) (PVI-Os) and glucose oxidase (GOX) on a gold electrode surface. The one-step co-electrodeposition method provided a better control on the sensor construction, especially when it was applied to microsensor construction. The modified electrode exhibited the classical features of a kinetically fast redox couple bound to an electrode surface and the redox potential of the redox polymer/enzyme film was 0.14 V (vs. SCE). For a scan rate of up to 200 mV s(-1), the peak-to-peak potential separation was less than 25 mV. In the presence of glucose, a typical catalytic oxidation current was observed, which reached a plateau at 0.25 V (vs. SCE). Under the optimal experimental conditions, the steady-state electrooxidation current measured at 0.30 V (vs. SCE) was linear to the glucose concentration in the range of 0-30 mM. Successful attempts were made in blood sample analysis.

2,2'-Dipyridyl↗

PubMed2003

Hemopoietic cells with features of the mast cell and basophil lineages and their potential role in allergy.

Human mast cells (MCs) and basophils play a key role in the pathogenesis of allergic disorders, not only by producing inflammatory and fibrogenic mediators, but also by directly and indirectly secreting various cytokines and chemokines. Although mast cells and basophils have differences in many properties, recent evidence suggests that human MCs and basophils may be derived from a common progenitor, and their contents and phenotypes may be reversibly altered in a variety of allergic disorders. The study of FcetaRI signalling of mast cell and basophils offers new opportunities for therapeutic interventions based on the specific inhibition of the earliest events in allergic diseases. This article reviews the origin, differentiation, morphology and phenotypic properties of MCs and basophils, focussing particularly on the possible pathogenic role of MCs and basophils in allergy and biochemical targets for therapeutic interventions in allergic diseases.

Animals↗

PubMed2003

Excess physical limitations among adults with diabetes in the U.S. population, 1997-1999.

OBJECTIVE: To estimate the prevalence of physical limitations associated with diabetes among U.S. adults > or =18 years of age. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis of the association between diabetes status and physical limitations using the 1997-1999 National Health Interview Survey (NHIS). Physical limitation was defined from self-reported degree of difficulty with nine tasks. RESULTS: People with diabetes had a higher proportion of any physical limitation than did people without diabetes overall (66 vs. 29%, P < 0.001), for both men (59 vs. 24%, P < 0.001) and women (72 vs. 34%, P < 0.001). Compared with those without diabetes, a higher proportion of people with diabetes had some physical limitation among all age groups, and the difference declined (all P < 0.001) with increasing age (46 vs. 18% for 18-44 years, 63 vs. 35% for 45-64 years, 74 vs. 53% for 65-74 years, and 85 vs. 70% for those 75 years and older). After controlling for demographic characteristics and several other confounders, the odds ratio of physical limitation among adults with diabetes versus those without diabetes was 1.9 (95% CI: 1.8-2.1). CONCLUSIONS: People with diabetes are much more likely to have a physical limitation than those without diabetes. Interventions are needed in this population to reduce progression from impairment to physical limitation and from physical limitation to disability, especially because the prevalence of diabetes is projected to increase dramatically in the next several decades.

Activities of Daily Living↗