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Biomedical subjects

Xiaoping Tang

Publications and source records attributed to Xiaoping Tang.

17 recordsLinked to original sources
PubMed2006

Glycosynthase-mediated synthesis of glycosphingolipids.

Glycosphingolipids play crucial roles in virtually every stage of the cell cycle, and their clinical administration has been proposed as a treatment for Alzheimer's, Parkinson's, stroke, and a range of other conditions. However, lack of supply has severely hindered testing of this potential. A novel glycosynthase-based synthetic strategy is demonstrated, involving a mutant of an endoglycoceramidase in which the catalytic nucleophile has been ablated. This mutant efficiently couples a range of glycosyl fluoride donors with a range of sphingosine-based acceptors in yields around 95%. This technology opens the door to large-scale production of glycosphingolipids and, thus, to clinical testing.

Catalysis↗
PubMed2005

Response of memory CD8+ T cells to severe acute respiratory syndrome (SARS) coronavirus in recovered SARS patients and healthy individuals.

To date, the pathogenesis of severe acute respiratory syndrome (SARS) in humans is still not well understood. SARS coronavirus (SARS-CoV)-specific CTL responses, in particular their magnitude and duration of postinfection immunity, have not been extensively studied. In this study, we found that heat-inactivated SARS-CoV elicited recall CTL responses to newly identified spike protein-derived epitopes (SSp-1, S978, and S1202) in peripheral blood of all HLA-A*0201(+) recovered SARS patients over 1 year postinfection. Intriguingly, heat-inactivated SARS-CoV elicited recall-like CTL responses to SSp-1 but not to S978, S1202, or dominant epitopes from several other human viruses in 5 of 36 (13.8%) HLA-A*0201(+) healthy donors without any contact history with SARS-CoV. SSp-1-specific CTLs expanded from memory T cells of both recovered SARS patients, and the five exceptional healthy donors shared a differentiated effector CTL phenotype, CD45RA(+)CCR7(-)CD62L(-), and expressed CCR5 and CD44. However, compared with the high avidity of SSp-1-specific CTLs derived from memory T cells of recovered SARS patients, SSp-1-specific CTLs from the five exceptional healthy donors were of low avidity, as determined by their rapid tetramer dissociation kinetics and reduced cytotoxic reactivity, IFN-gamma secretion, and intracellular production of IFN-gamma, TNF-alpha, perforin, and granzyme A. These results indicate that SARS-CoV infection induces strong and long-lasting CTL-mediated immunity in surviving SARS patients, and that cross-reactive memory T cells to SARS-CoV may exist in the T cell repertoire of a small subset of healthy individuals and can be reactivated by SARS-CoV infection.

Adolescent↗
PubMed2005

New glycosidase activated nitric oxide donors: glycose and 3-morphorlinosydnonimine conjugates.

[reaction: see text] To achieve site specific delivery of nitric oxide (NO), a new class of glycosidase activated NO donors has been developed. Glucose, galactose, and N-acetylneuraminic acid were covalently coupled to 3-morphorlinosydnonimine (SIN-1), a mesoionic heterocyclic NO donor, via a carbamate linkage at the anomeric position. The beta-glycosides were successfully prepared for these conjugates, while the alpha-glycosidic compounds were very unstable. The new stable sugar-NO conjugates could release NO in the presence of glycosidases. Such NO prodrugs may be used as enzyme activated NO donors in biomedical research.

Catalysis↗
PubMed2005

A new approach for simultaneous measurement of ADC and T2 from echoes generated via multiple coherence transfer pathways.

The study of rotational and translational diffusion requires the measurement of both T2 and apparent diffusion coefficient (ADC), quantities that are typically measured in separate experiments. The exploitation of echoes generated via multiple coherence transfer pathways offers an opportunity for measuring T2 and ADC values simultaneously in a single experiment. A series of RF pulses can generate multiple echoes via different coherence pathways with each one being uniquely encoded. Here, we demonstrate one pulse sequence that uses an initial theta; RF pulse to generate three coherence orders (C = 0, -1, +1). In the particular version of the method discussed here only two are used (C = 0, +1). Each order is encoded with a different b value from which the ADC is derived. The coherence order echo C = 0 is refocused to quantify T2. The performance of the method--dubbed simultaneous measurement of ADC and relaxation time (SMART)--is demonstrated on a set of samples differing in T2 and ADC achieved by varying the relative volume fractions in mixtures of gadolinium-doped H2O and D2O. The regional SMART derived T2 and ADC agree well with those obtained with conventional double-spin-echo and pulsed gradient spin-echo methods.

Contrast Media↗
PubMed2004

A one-shot method for measurement of diffusion.

This paper describes an NMR method capable of determining the diffusion constant of a material within a few milliseconds and without the need of multiple scans. The method can be used with static or pulsed magnetic field gradients. It may be used to detect time-dependent processes, such as in chemical reactions, production monitoring, and medical MRI.

Diffusion↗
PubMed2003

Synthesis of beta-lactamase activated nitric oxide donors.

In order to achieve site specific delivery of NO, we designed conjugates of cephalosporin with NO donors. NO donors such as cupferron and SIN-1 were evaluated as potential choices for conjugates. Cephalosporin conjugated with SIN-1 demonstrated promising beta-lactamase dependent NO releasing ability.

Cephalosporins↗
PubMed2003

Isolating quantum coherences in structural imaging using intermolecular double-quantum coherence MRI.

Intermolecular multiple-quantum coherence (iMQC) MR imaging provides a fundamentally different contrast mechanism. It allows probing tissue microstructure by tuning the direction and strength of the correlation gradient. However, iMQC images of a specific quantum-coherence can easily be contaminated by leakage signals from undesired quantum coherences (zero, single, and triple quantum coherence in this work). Using a modified double-quantum CRAZED imaging sequence, we show that signals originating from various coherence orders (M=0, 1, 2, 3) can be predicted in k-space and effectively isolated by means of a four-step phase cycling scheme and judicious choice of flip angles. Finally, preliminary data suggest the method to be able to provide information on trabecular bone architecture such as regional mean trabecular plate separation.

Algorithms↗
PubMed2003

Simultaneous acquisition of multiple orders of intermolecular multiple-quantum coherence images.

Recent studies have demonstrated the ability to detect images based on intermolecular multiple-quantum coherences (iMQCs) that correspond to flipping of two or more separated spins simultaneously, as opposed to conventional magnetic resonance where only one spin is flipped at a time. Until now, iMQC imaging has only acquired one coherence signal per pulse sequence. Here we report a new sequence that successfully detects five orders of coherence (2, 1, 0, -1, and -2-quantum coherence images) in one pulse sequence, with each signal having its full intensity. The simultaneous acquisition highlights substantial contrast differences between conventional and iMQC images, and between the different types of iMQC images.

Humans↗
PubMed2003

Magnetic alignment in nominally non-magnetic hexagonal metal hydrides: NMR.

Powders of three hexagonal metal-hydrides or -deuterides are found to align in 4.4-8.3 T magnetic fields used for NMR. The field-alignment is unexpected, since all three systems have very small susceptibilities, as demonstrated by sharp NMR lines. The extent of alignment runs from nearly complete to barely detectable in ZrBe2(H,D)x, LuD3, and YD3, respectively. The preferred alignment direction in ZrBe2(H,D)x is with the crystallites' c-axis perpendicular to B, while the c-axis and B tend to be parallel in LuD3 and YD3. The susceptibilities chi parallel and chi perpendicular are determined from bulk magnetization measurements in aligned ZrBe2H1.4 powder. The alignment must be considered for proper analysis of NMR spectra in these and related materials.

Journal Article↗
PubMed2003

Measurement of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome and its clinical significance.

OBJECTIVE: To investigate the changes of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome (SARS) and its clinical significance. METHODS: Subgroups of blood T lymphocytes in 93 patients with SARS were detected by flow cytometer. The results detected in 64 normal subjects and 50 patients with AIDS served as controls. RESULTS: The numbers of CD(3)(+), CD(4)(+), and CD(8)(+) lymphocytes all significantly decreased in acute phase of patients with SARS [(722 +/- 533)/microliter, (438 +/- 353)/microliter, (307 +/- 217)/microliter] compared with those in normal controls [(1527 +/- 470)/microliter, (787 +/- 257)/microliter, (633 +/- 280)/microliter, all P <0.01], which was different from what we observed in patients with AIDS who had decreased CD(4)(+) [(296 +/- 298)/microliter] but increased CD(8)(+) [(818 +/- 566)/microliter] counts. The counts of CD(3)(+), CD(4)(+), and CD(8)(+) lymphocytes decreased more apparently in patients with severe SARS. All the five patients who died had CD(4)(+) counts less than 200/microliter. As the patients' condition improved, CD(3)(+), CD(4)(+), and CD(8)(+) counts gradually returned to normal ranges. CONCLUSION: The damage of cellular immunity is probably an important mechanism of pathogenesis of SARS.

Acquired Immunodeficiency Syndrome↗
PubMed2003

The chest X-ray image features of patients with severe SRAS: a preliminary study.

OBJECTIVE: To study the chest X-ray image features of patients with severe SARS. METHODS: Chest X-ray image features in 36 patients with severe SARS were retrospectively analyzed. The image characteristics were compared with those of 224 patients with common SARS. RESULTS: The important chest X-ray imaging features of 36 patients with severe SARS included small patch of infiltration (n = 27, 75.0%), large patch of infiltration (n = 22, 61.1%), large area of lung consolidation (n = 10, 27.3%), interstitial lung lesion (n = 26, 72.2%), ground-glass shadow (n = 28, 77.8%), irregular linear opacity (n = 15, 41.7%), diffuse lung lesion (n = 12, 33.3%), with single lung involved (n = 9, 25.0%), and both lungs involved (n = 32, 88.9%). The rates of large patch of infiltration, large area of lung consolidation, ground-glass shadow, diffuse lung lesion and involvement of both lungs in patients with severe SARS were significantly higher than those in patients with common type of SARS (all P < 0.01). Out of the 11 severe SARS patients who died, nine had large area of ground-glass shadow with air bronchogram in both lungs before death. CONCLUSIONS: Large patch of infiltration, large area of consolidation, ground-glass shadow, diffuse lung lesion and involvement of both lungs were the main X-ray image characteristics of patients with severe SARS. Large area of ground-glass shadow with air bronchogram in both lungs indicated a bad prognosis.

Adolescent↗
PubMed2002

Conformational characterization of ceramides by nuclear magnetic resonance spectroscopy.

Ceramide (Cer) has been identified as an active lipid second messenger in the regulation of cell growth, differentiation, and apoptosis. Its analog, dihydroceramide, without the 4 to 5 trans double bond in the sphingoid backbone lacks these biological effects. To establish the conformational features that distinguish ceramide from its analogs, nuclear magnetic resonance spectral data were acquired for diluted samples of ceramides (C2- and C18-Cer), dihydroceramide (C16-DHCer), and deoxydihydroceramide (C18-DODHCer). Our results suggest that in both C2- and C18-Cer, an H-bond network is formed in which the amide proton NH is donated to the OH groups on carbons C1 and C3 of the sphingosine backbone. Two tightly bound water molecules appear to stabilize this network by participating in flip-flop interactions with the hydroxyl groups. In DHCer, the lack of the trans double bond leads to a conformational distortion of this H-bonding motif. Without the critical double bond, the degree with which water molecules stabilize the H bonds between the two OH groups of the sphingolipid is reduced. This structural alteration might preclude the participation of DHCer in signaling-related interactions with cellular targets.

Amino Acid Motifs↗
PubMed2002

Novel substrates for nitric oxide synthases.

Enzymatic generation of nitric oxide (NO) by nitric oxide synthase (NOS) consists of two oxidation steps. The first step converts L-arginine to N(G)-hydroxy-L-arginine (NOHA), a key intermediate, and the second step converts NOHA to NO and L-citrulline. To fully probe the substrate specificity of the second enzymatic step, an extensive structural screening was carried out using a series of N-alkyl (and N-aryl) substituted-N'-hydroxyguanidines (1-14). Among the eleven N-alkyl-N'-hydroxyguanidines evaluated, N-n-propyl (2), N-iso-propyl (3), N-n-butyl (4), N-s-butyl (5), N-iso-butyl (6), N-pentyl (8) and N-iso-pentyl (9) derivatives were efficiently oxidized by the three isoenzymes of NOS (nNOS, iNOS and eNOS) to generate NO. N-Butyl-N'-hydroxyguanidine (4) was the best substrate for iNOS (K(m)=33 microM) and N-iso-propyl-N'-hydroxyguanidine (3) was the best substrate for nNOS (K(m)=56 microM). When the alkyl substituents were too small (such as ethyl 1) or too large (such as hexyl 10 and cyclohexyl 11), the activity decreased significantly. This suggests that the van der Waals interaction between the alkyl group and the hydrophobic cavity in the NOS active site contributes significantly to the relative reactivity of compounds 3-11. Moreover, five N-aryl-N'-hydroxyguanidines were found to be good substrates for iNOS, but not substrates for eNOS and nNOS. N-phenyl-N'-hydroxyguanidine was the best substrate among them (K(m)=243 microM). This work demonstrates that N-alkyl substituted hydroxyguanidine compounds are novel NOS substrates which 'short-circuit' the first oxidation step of NOS, and N-aryl substituted hydroxyguanidine compounds are isoform selective NOS substrate.

Animals↗
PubMed2002

[Relationship between diversity of hepatitis C virus quasispecies and viremia, activity of liver disease and response to interferon therapy].

BACKGROUND: To determine the relationship between diversity of hepatitis C virus quasispecies and viremia, activity of liver disease and response to interferon therapy. METHODS: HCV quasispecies heterogeneity in 68 patients with chronic hepatitis C were detected by single stranded conformational polymorphism (SSCP) analysis of the HCV E2 hypervaribale region 1 (HVR1); of these, 48 were subsequently treated with interferon-alpha for 6 months. RESULTS: HVR1 was amplified in 61 patients. The average number of SSCP bands was 6.2+/-2.4. Quasispecies heterogeneity significantly correlated with serum HCV RNA levels (P<0.01), but not with serum ALT, AST levels and histological activity index (P>0.05). Of the patients who received interferon therapy, 43 were HVR1 positive. Patients who gained sustained response (n=11) had lower pre-treatement quasispecies heterogeneity (3.3+/-1.2) compared to those who had complete end-of-treatment response (ETR) with relapse (6.3+/-2.2, n=12, P<0.5) or no response (8.0+/-3.3, n=20, P<0.01). At the end of treatment, HVR1 could still be detected in 16 patients. The number of quasispecies heterogeneity in these patients decreased to 3.4+/-1.2, which was significantly lower than that in the patients who didn't receive interferon therapy (6.8+/-2.5, P<0.01). Of these 16 patients, 10 had change in quasispecies patterns. CONCLUSIONS: Increased quasispecies heterogeneity can cause high HCV viremia, but it is not related to severity of liver disease. Quasispecies heterogeneity is another marker to predict the response to interferon-alpha in patients with chronic hepatitis C.

Adolescent↗