Biomedical subjects

Wei Zhao

Publications and source records attributed to Wei Zhao.

At least 91 records · Page 5Linked to original sources

PubMed2006

[Observation on two kinds of recombinant hepatitis B vaccines used in populations with different immunity].

OBJECTIVE: To evaluate the immunity status on different hepatitis B vaccines currently being used in Beijing. METHODS: College students who had not received hepatitis B vaccine and children who had received whole-course immunization at birth, were tested HBsAg, anti-HBs and anti-HBc. All the test-negative cases were served as research subjects. 3 doses recombinant hepatitis B vaccines were given to the college students, following the 0, 1, 6 months schedule. Among which, 140 cases received recombinant beer yeast hepatitis B vaccine (BY vaccine, 10 microg, 5 microg, 5 microg), and 140 cases with recombinant hansenula polymorpha hepatitis B vaccine (HP vaccine, 10 microg, 10 microg, 10 microg). 1 dose was given for boosting immunization to 98 children, in which 49 cases with BY vaccine (5 microg) and 49 cases with HP vaccine (10 microg). Anti-HBs was tested 1 month after. RESULTS: The total positive (> or = 10 mIU/ ml) rate was lower among BY vaccine group than HP vaccine group for the college students (93.5 %, 99.3% , P<0.05), but no statistical difference on GMT(81.2 mIU/ml, 94.6 mIU/ml, P>0.05) was found. For males, the positive rate and GMT were lower in BY vaccine group than in HP vaccine group (85.7% ,100.0%, P<0.01)(56.6 mIU/ml, 98.6 mIU/ml, P<0.01), but with no statistical difference for females (98.8%, 98.5%, P> 0.05) (103.4 mIU/ml, 90.3 mlU/ml, P> 0.05). For the same vaccine, the positive rate and GMT were lower in males than in females when using BY vaccine (85.7% , 98.8%, P<0.01)(56.6 mIU/ml,103.4 mIU/ml, P< 0.01), but no statistical difference was found on HP vaccine(100.0%, 98.5%, P>0.05)(98.6 mIU/ml, 90.3 mIU/ml, P>0.05). The positive rate of anti-HBs was decreasing along with age among the children who had received a whole-course immunization at birth (P <0.01). 98.6 % of the 70 negative cases appeared positive conversion after receiving 1 dose and the GMT raised significantly by 15 times. No statistical difference was found between the two kinds of vaccines(100.0%, 97.4%, P>0.05)(80.5 mIU/ml, 68.5 mIU/ml, P>0.05). CONCLUSIONS: The type of vaccine and sex were related to the effects, better with HP vaccine than BY vaccine in males but was the same for females in adults receiving basic immunization according to the conventional doses. Both kinds of vaccines were ideal when children receiving boosting immunization. The immune memory was good for persons who had received primary immunization with recombinant vaccine but antibody appeared negative conversion. It was not necessary to boost immunization within 6 years after a whole-course immunization with recombinant hepatitis B vaccine in infancy.

Antibodies, Viral↗

PubMed2005

[Antiviral effects of dual-target antisense rna: an experimental study with hepatitis B virus transgenic mice].

OBJECTIVE: To investigate the curative effects of dual-target antisense RNA targeting the X and P regions in the genome of hepatitis B virus (HBV). METHODS: Retrovirus vector pLXSN was used to construct 4 kinds of recombinant vector plasmids expressing dual-target antisense RNA complementary to the X and P regions in the genome of HBV, namely, pLXSN-asX, pLXSN-asP, pLXSN-asXP, and pLXSN-seX. 48 HBV transgenic mice were randomly divided into 6 equal groups: pLXSN-asX group, pLXSN-asX group, pLXSN-asX group, pLXSN-asX group, and blank plasmid blank (pLXSN) group, to be injected into the caudal vein with corresponding plasmids thrice for every other day, and blank control group. Venous blood samples were collected before, 1 day and 3 days, and 2, 4, and 8 weeks after the injection to undergo detection of serum HBV DNA and HBsAg. Eight weeks later the mice were killed and immunohistochemistry was used t examine the HBsAg and HBcAg in the tissues. Pathological examination of the tissues was performed. RESULTS: The serum HBsAg concentrations 4 and 8 weeks after injection were significantly lower than that before injection in the.pLXSN-asX and pLXSN-asXP groups (all P <0.05) with an inhibition rate of 24% and 27% respectively. In comparison with that before injection, the HBV DNA expression level 2 weeks after injection was significantly lower in the pLXSN-asX group (P < 0.05) with an inhibition rate of 58%. In comparison with that before injection, the HBV DNA expression level 8 weeks after injection was significantly lower in the pLXSN-asP group (P <0.05) with an inhibition rate of 58%. In comparison with that before injection, the HBV DNA expression level in the pLXSN-asXP group showed 2 times of significant decrease 1 week and 8 weeks after injection (both P < 0.05) with the inhibition rates of 66% and 77% respectively. HBsAg and HBcAg were expressed in liver were significantly lower in the pLXSN-asX, pLXSN-asP, and pLXSN-asXP groups than in other groups (P < 0.05). No significant abnormality was found in the tissues in all groups. CONCLUSION: Dual-target antisense RNA targeting the X and P regions in the genome of HBV inhibits the replication and expression of HBV, significantly stronger than single-target antisense-RNA.

Animals↗

PubMed2005

SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans.

Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved ancestral allele of a human coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation.

Black or African American↗

PubMed2005

Nucleolar localization of Aspergillus fumigatus CgrA is temperature-dependent.

Pathogenic fungi must adapt to multiple adverse environmental conditions during the transition from the environment to a mammalian host, one of which is temperature. The ability of Aspergillus fumigatus to grow optimally under conditions of thermal stress requires the nucleolar protein CgrA. In this study, we have determined how temperature affects the intracellular localization of CgrA in A. fumigatus using a green fluorescent protein (GFP)-tagging approach. At 22 degrees C, CgrA was almost exclusively in the nucleolus, with a ratio of nucleolar to cytoplasmic fluorescence of 10:1. At 37 degrees C, the ratio of nucleolar to cytoplasmic fluorescence was reduced fivefold, and increased correspondingly in the cytoplasm. This effect was not seen with the nucleolar protein NopA in wild-type A. fumigatus. However, in a DeltacgrA mutant NopA was delocalized from the nucleolus at 37 degrees C but not at 22 degrees C. These results provide evidence for a temperature-dependent mechanism of intracellular localization for CgrA, and suggest that CgrA facilitates nucleolar compartmentalization of NopA at higher temperature.

Aspergillus fumigatus↗

PubMed2005

Recoverable solution reaction of HiPco carbon nanotubes with hydrogen peroxide.

There is increasing interest in developing single-walled carbon nanotubes (SWNTs)-based optical biosensors for remote or in vitro and in vivo sensing because the near-IR optical properties of SWNTs are very sensitive to surrounding environmental changes. Many enzyme-catalyzed reactions yield hydrogen peroxide (H(2)O(2)) as a product. To our knowledge, there is no report on the interaction of H(2)O(2) with SWNTs from the optical sensing point of view. Here, we study the reaction of H(2)O(2) with an aqueous suspension of water-soluble (ws) HiPco SWNTs encased in the surfactant sodium dodecyl sulfate (SDS). The SWNTs are optically sensitive to hydrogen peroxide in pH 6.0 buffer solutions through suppression of the near-IR absorption band intensity. Interestingly, the suppressed spectral intensity of the nanotubes recovers by increasing the pH, by decomposing the H(2)O(2) into H(2)O and O(2) with the enzyme catalase, and by dialytically removing H(2)O(2). Preliminary studies on the mechanisms suggest that H(2)O(2) withdraws electrons from the SWNT valence band by charge transfer, which suppresses the nanotube spectral intensity. The findings suggest possible enzyme-assisted molecular recognition applications by selective optical detection of biological species whose enzyme-catalyzed products include hydrogen peroxide.

Journal Article↗

PubMed2005

Structured antedependence models for functional mapping of multiple longitudinal traits.

In this article, we present a statistical model for mapping quantitative trait loci (QTL) that determine growth trajectories of two correlated traits during ontogenetic development. This model is derived within the maximum likelihood context, incorporated by mathematical aspects of growth processes to model the mean vector and by structured antedependence (SAD) models to approximate time-dependent covariance matrices for longitudinal traits. It provides a quantitative framework for testing the relative importance of two mechanisms, pleiotropy and linkage, in contributing to genetic correlations during ontogeny. This model has been employed to map QTL affecting stem height and diameter growth trajectories in an interspecific hybrid progeny of Populus, leading to the successful discovery of three pleiotropic QTL on different linkage groups. The implications of this model for genetic mapping within a broader context are discussed.

Journal Article↗

PubMed2005

AKT induces erythroid-cell maturation of JAK2-deficient fetal liver progenitor cells and is required for Epo regulation of erythroid-cell differentiation.

AKT serine threonine kinase of the protein kinase B (PKB) family plays essential roles in cell survival, growth, metabolism, and differentiation. In the erythroid system, AKT is known to be rapidly phosphorylated and activated in response to erythropoietin (Epo) engagement of Epo receptor (EpoR) and to sustain survival signals in cultured erythroid cells. Here we demonstrate that activated AKT complements EpoR signaling and supports erythroid-cell differentiation in wild-type and JAK2-deficient fetal liver cells. We show that erythroid maturation of AKT-transduced cells is not solely dependent on AKT-induced cell survival or proliferation signals, suggesting that AKT transduces also a differentiation-specific signal downstream of EpoR in erythroid cells. Down-regulation of expression of AKT kinase by RNA interference, or AKT activity by expression of dominant negative forms, inhibits significantly fetal liver-derived erythroid-cell colony formation and gene expression, demonstrating that AKT is required for Epo regulation of erythroid-cell maturation.

Animals↗

PubMed2005

Antiviral therapeutic efficacy of foscarnet in hepatitis B virus infection.

Foscarnet (PFA), a viral DNA polymerase inhibitor, is a clinical agent for herpes viruses. The goal of the study was to evaluate the therapeutic efficacy of PFA in hepatitis B virus (HBV) infection. Intravenous infusion of PFA (1 g/day) for 4 weeks significantly reduced serum HBeAg (p<0.01) and HBV DNA copies (p<0.05) in 31 patients who were diagnosed with active chronic HBV infection (CHB) and had not received antiviral treatment previously. Alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and gamma glutamyl transpeptidase (gamma-GT) of the patients declined (p<0.001, 0.001 and 0.01, respectively). Kidney function (blood creatinine and urea nitrogen) remained unchanged. Another 21 lamivudine-resistant CHB patients with mutations at the tyrosine-methionine-aspartate-aspartate motif (YMDD) displayed a response to PFA similar to that mentioned above, with reductions in HBeAg (p<0.05), HBV DNA (p<0.01) and liver enzymes (ALT and AST, p<0.001; gamma-GT, p<0.05). Moreover, PFA reduced serum HBeAg (p<0.01), HBV DNA (P<0.05), AST (p<0.05) and ALT (p<0.02) in a cohort of 13 severe CHB patients with advanced liver damage. PFA was also evaluated in vitro and in vivo. PFA inhibited HBV DNA replication in HBV-transfected human HepG2 cells (2.2.15 cells) with reduced amount of HBV RC-DNA and DS-DNA. In the duck HBV-infected ducklings, PFA reduced viral DNA and duck HBsAg in the serum (p<0.01 for both).

Adult↗

PubMed2005

Crystal structure and carbon vacancy hardening of (W0.5Al0.5)C1-x prepared by a solid-state reaction.

Novel solid solutions of aluminum in tungsten carbide (WC) with or without carbon vacancies, which can be expressed by the chemical formula (W(0.5)Al(0.5))C(1-x) (x=0.0-0.5), have been synthesized by the solid-state reaction of W(0.5)Al(0.5) alloy and the proper amount of carbon at around 1673 K in vacuum. The reaction time decreases from 73 to 50 h on increasing the carbon vacancy concentration from 0 to 50 %. The formation of the intended products is certified, by X-ray diffraction, environmental scanning electron microscopy-energy-dispersive X-ray analysis, and inductively coupled plasma-atomic emission spectroscopy, even though the carbon vacancy concentration reaches the astonishing value of 50 %. The as-prepared (W(0.5)Al(0.5))C(1-x) samples have been identified as the hexagonal WC-type structure belonging to the space group P6m2 (Z=1). Moreover, the crystallographic results reveal that the substituting aluminum atoms in the WC are located in the 1a site (the W atom position of the WC structure) and the cell parameters decrease slightly with increasing vacancy concentration. The hardness of the (W(0.5)Al(0.5))C(1-x) system increases up to a maximum 2659 kg mm(-2) at a carbon vacancy concentration of about 35 %, and the density of (W(0.5)Al(0.5))C(1-x) is far lower than that of WC.

Journal Article↗

PubMed2005

[Molecular cloning and identify expression of the novel human LNX gene in gliomas].

OBJECTIVE: To clone and identify expression pattern of the novel LNX gene, and characterize its molecular mechanism in all grades of human gliomas. METHODS: From a fetal brain cDNA library, we isolated the novel human LNX gene. The expression pattern of LNX gene in 16 normal tissues was examined by MTC panel (Clontech). Microarray were adopted and hybridized with LNX probes to examine the expression of novel gene in gliomas. Northern hybridization was used for verifying expression of LNX gene in gliomas. Two-hybrid screen in yeast was used to identify human LNX interacting proteins. Pull-down assays and Co-immunoprecipitation were transfected in HEK293 cells according to the lipofectAMINE protocol. RESULTS: We isolated a 3.7 kb cDNA containing an open reading frame (ORF) of 1,899 bp and a putative 632 amino acids protein, which was located on 4q12. cDNA microarray showed LNX was down-regulated in all 18 glioma samples and it was testified by Northern-blot. The MTC panel showed a ubiquitous expression pattern which highly expressed in adult brain, kidney and pancreas, while weak expression in heart, lung, etc. The two-hybrid screen in yeast revealed that LNX interacted with SKIP (Ski interacting protein) via PDZ domains. The co-immunoprecipation suggested that LNX interacted with SKIP in HEK293 cells and could affect the subcellular localization of Numb, which indicated that LNX might function as a molecular anchor that localized Numb to the subcellular site of its interaction with Notch. CONCLUSION: cDNA microarray technology is a powerful technique in screening and locking differentially expressed genes in gliomas, LNX was closely related to human gliomas and suggested playing an important role in gliomas by notch signal approach.

Cloning, Molecular↗

PubMed2005

Multilayer membranes via layer-by-layer deposition of organic polymer protected Prussian blue nanoparticles and glucose oxidase for glucose biosensing.

Polyelectrolyte multilayers (PEMs) are now widely used for bioanalytical applications. In this work, a bilayer of poly(diallydimethylammonium chloride) (PDDA) and poly(sodium 4-styrenesulfonate) (PSS) is consecutively adsorbed on 3-mercapto-1-propanesulfonic acid modified Au electrode surfaces, forming stable, ultrathin multilayer films. Subsequently, Prussian blue nanoparticles protected by PDDA (denoted as P-PB) and negatively charged glucose oxidase (GOx) are consecutively adsorbed onto the PSS-terminated bilayer. The growth of each of the P-PB/GOx bilayers is followed quantitatively using UV-visible absorption spectroscopy and the electrochemical method. The P-PB nanoparticles can catalyze the electroreduction of hydrogen peroxide formed from enzymatic reaction at lower potential and inhibit the responses of interferents, such as ascorbic acid (AA) and uric acid (UA). Performance of the multilayer films can be tailored by controlling the number of bilayers. Under optimal conditions, a linear range of 0.10 to 11.0 mM and a detection limit of 10 microM were achieved. The glucose biosensor has good stability and reproducibility.

Biosensing Techniques↗

PubMed2005

Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway.

Erythropoietin (Epo) stimulation of its receptor's downstream signaling pathways and optimum function of GATA-1 transcription factor are both essential for normal erythroid cell development. Epo-receptor (EpoR) signaling and GATA-1 regulate proliferation, survival, differentiation, and maturation of erythroid cells. Whether any signal that is generated by EpoR targets GATA-1 or affects GATA-1 transcriptional activity is not known. Here, we demonstrate that stimulation of EpoR results in phosphorylation of GATA-1 at serine 310 (S310) in primary fetal liver erythroid progenitors and in cultured erythroid cells. We show that phosphorylation of GATA-1 is important for Epo-induced maturation of fetal liver erythroid progenitor cells. The PI3-kinase/AKT signaling pathway is identified as a mediator of Epo-induced phosphorylation of GATA-1. AKT serine threonine kinase phosphorylates GATA-1S310 in vitro and in erythroid cells and enhances GATA-1 transcriptional activity. These data demonstrate that EpoR signaling phosphorylates GATA-1 and modulates its activity via the PI3-kinase/AKT signaling pathway.

Animals↗

PubMed2005

Modelling clinical trials in heterogeneous samples.

Individual variation in genetic, phenotypic and environmental factors could lead to significant differences in rates of drug metabolism, in clinical responses to drugs, and in drug side effects. The impact of population heterogeneity on treatment effect estimation and on assessment and application of clinical trial findings has been less than fully studied. In this paper, we studied the properties of models that reflect population heterogeneity of clinical trial samples by unmeasured covariates such as genetic susceptibility. The impact of heterogeneity on the estimation of treatment effect in a two-armed placebo or active-controlled clinical trial was quantified using logistic regression models. We also proposed a two-stage clinical trial, where the effects of individual drug-response-related covariates were estimated in a 'training data set' in the first stage of the trial. In the second stage of the trial, a subgroup of individuals with enhanced (or reduced) sensitivity to drug treatments in a heterogeneous risk cohort was identified based on information about their drug-related characteristics. Only these 'responders' were included in the subsequent efficacy test. Our simulation results showed that population heterogeneity could lead to biased estimation of treatment effect not only in the contaminated groups but also in the uncontaminated groups. A two-stage trial could greatly increase the power of an efficacy test over a 'full trial' even with fewer individuals enrolled in the trial; results would apply to a more highly specified population. The bigger the covariate effects, the more efficient the two-stage trial is compared to a 'full trial'.

Biometry↗

PubMed2005

Loss of epigenetic control of synuclein-gamma gene as a molecular indicator of metastasis in a wide range of human cancers.

Metastasis is a major contributing factor to poor prognosis in cancer. Reliable and sensitive biomarkers that indicate the development of metastasis of primary tumors would be of great clinical use. In this study, we show that the neuronal protein synuclein-gamma (SNCG) is abnormally expressed in a high percentage (67.5%) of tumor tissues of diversified cancer types, including liver, esophagus, colon, gastric, lung, prostate, cervical, and breast cancer, but rarely expressed in tumor-matched nonneoplastic adjacent tissues (0.6%). Expressions of SNCG protein in different cancer types all display stage-specific patterns of very low expression in stage I and high expression in stages II to IV. Importantly, we observe a strong association between SNCG protein expression in primary tumors with distant metastasis in patients regardless of the cancer type (60.6%, P < 0.001). By performing genomic sequencing and methylation-specific PCR assays, we identify an inclusive demethylation of CpG sites within the CpG island of SNCG gene in every tumor sample (100%) across all cancer types, illustrating a universal loss of the epigenetic control of SNCG gene expression in tumors and further demonstrating that the demethylation of SNCG CpG island is primarily responsible for the aberrant expression of SNCG protein in cancerous tissues. These new findings strongly suggest that reactivation of SNCG gene expression by DNA demethylation is a common critical contributing factor to malignant progression of many solid tumors and its expression in primary carcinomas is an effective molecular indicator of distant metastasis. Our studies also suggest that the methylation status of SNCG gene can be used as a sensitive molecular tool in early detections of tumorigenesis.

Aged↗

PubMed2005

A selective HPLC method for the determination of indapamide in human whole blood: application to a bioequivalence study in Chinese volunteers.

Indapamide was extracted from human whole blood with diethyl ether and was determined by a HPLC-UV method using an Inertsil ODS-3 column and an isocratic mobile phase consisting of 55% buffer solution (2 g KH(2)PO(4), 3 ml H(3)PO(4) and 3.5 ml triethylamine in 1l of H(2)O), 40% acetonitrile and 5% methanol for 12.5 min, and then a gradient flush from 100% isocratic to a mixture of 20% isocratic mobile phase and 80% methanol for 3 min. Indapamide and glipizide (internal standard) were eluted from the column at about 10.5 and 12.8 min, respectively. The method had within day precision values in the range +/- 1.2 to +/- 9.7% (n = 5) and between day precision in the range +/- 3.3 to +/- 9.7%. The method was linear over the range of 10-400 ng/ml of indapamide in blood (R = 0.999). The LOQ (s/n = 10) of the method was 10 ng/ml. The method was applied in a study of the pharmacokinetics and bioequivalence of generic indapamide capsules (2.5 mg) in comparison with reference indapamide tablets (2.5mg), in 20 healthy male Chinese volunteers. The mean values of major pharmacokinetic parameters of C(max), AUC(0-48), AUC(0-infinity), T(max), and t(1/2) of indapamide in healthy male Chinese volunteers after po a single 5 mg dose for the test product were 331.0 +/- 39.2 ng/ml, 6,193.7+/-873.5 ng h/ml, 7311.8+/-1,232.3 ng h/ml, 3.2+/-0.9h, and 17.3+/-2.8 h, respectively. There was no significant differences between the two formulations.

Area Under Curve↗

PubMed2005

Cytokine production by skin-derived mast cells: endogenous proteases are responsible for degradation of cytokines.

The current study characterizes the cytokine protein (ELISA) and mRNA (gene array and RT-PCR) profiles of skin-derived mast cells cultured under serum-free conditions when activated by cross-linking of Fc epsilonRI. Prior to mast cell activation, mRNA only for TNF-alpha was detected, while after activation mRNA for IL-5, IL-6, IL-13, TNF-alpha, and GM-CSF substantially increased, and for IL-4 it minimally increased. However, at the protein level certain recombinant cytokines, as measured by ELISAs, were degraded by proteases released by these skin-derived mast cells. IL-6 and IL-13 were most susceptible, followed by IL-5 and TNF-alpha; GM-CSF was completely resistant. These observations also held for the endogenous cytokines produced by activated mast cells. By using protease inhibitors, chymase and cathepsin G, not tryptase, were identified in the mast cell releasates as the likely culprits that digest these cytokines. Their cytokine-degrading capabilities were confirmed with purified chymase and cathepsin G. Soy bean trypsin inhibitor, when added to mast cell releasates, prevented the degradation of exogenously added cytokines and, when added to mast cells prior to their activation, prevented degradation of susceptible endogenous cytokines without affecting either degranulation or GM-CSF production. Consequently, substantial levels of IL-5, IL-6, IL-13, TNF-alpha, and GM-CSF were detected 24-48 h after mast cells had been activated, while none were detected 15 min after activation, by which time preformed granule mediators had been released. IL-4 was not detected at any time point. Thus, unless cytokines are protected from degradation by endogenous proteases, cytokine production by human mast cells with chymase and cathepsin G cells may be grossly underestimated.

Antibodies, Monoclonal↗

PubMed2005

Evaluation of rotavirus dsRNA load in specimens and body fluids from experimentally infected juvenile macaques by real-time PCR.

We recently established a non-human primate model of rotavirus infection that is characterized by consistent and high levels of virus antigen shedding in stools. Here, we report that starting from post challenge day (PCD) 2, 6 x 10(3) to 1.5 x 10(6) copies of rotavirus double-stranded RNA per nanogram of total RNA were detected by real-time PCR in MA104 cells that were 48 h pre-incubated with filtered stool suspensions of three experimentally infected juvenile macaques. The peak of virus load was detected at PCD 4-5, followed by decreased load at PCD 6-11, and very low levels at PCD 12. Such a pattern corresponded to virus shedding in stools as reported recently based on enzyme-linked immunosorbent assay (ELISA) results. In addition, plasma and cerebrospinal fluids (CSF) from six infected animals were tested for the presence of rotavirus. Rotavirus extraintestinal escape was revealed in three out of six animals by a combination of real-time and nested PCR. However, very low quantities of detected viral RNA (approximately 20 copies/ng of total RNA) were not suggestive of viremia. Thus, the rhesus model of rotavirus infection can be exploited further in studies with vaccine candidates designed to prevent or abrogate rotavirus infection.

Animals↗

PubMed2005

Synthesis of a heptasaccharide fragment of the O-deacetylated GXM of C. neoformans serotype C.

Beta-D-Xylp-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->4)]-alpha-D-Manp, the fragment of the exopolysaccharide from Cryptococcus neoformans serovar C, was synthesized as its methyl glycoside. Thus, chloroacetylation of allyl 3-O-acetyl-4,6-O-benzylidene-alpha-D-mannopyranoside (1) followed by debenzylidenation and selective 6-O-benzoylation afforded allyl 2-O-chloroacetyl-3-O-acetyl-6-O-benzoyl-alpha-D-mannopyranoside (4). Glycosylation of 4 with 2,3,4-tri-O-benzoyl-D-xylopyranosyl trichloroacetimidate (5) furnished the beta-(1-->4)-linked disaccharide 6. Dechloroacetylation gave the disaccharide acceptor 7 and subsequent coupling with 5 produced the trisaccharide 8. Deacetylation of 8 gave the trisaccharide acceptor 9 and subsequent coupling with a disaccharide 10 produced the pentasaccharide 11. Reiteration of deallylation and trichloroacetimidate formation from 11 yielded the pentasaccharide donor 12. Coupling of a disaccharide acceptor 13 with 12 afforded the heptasaccharide 14. Subsequent deprotection gave the heptaoside 16, while selective 2-O-deacetylation of 14 gave the heptasaccharide acceptor 15. Condensation of 15 with glucopyranosyluronate imidate 17 did not yield the expected octaoside, instead, an orthoester product 18 was obtained. Rearrangement of 18 did not give the target octaoside; but produced 15. Meanwhile, there was no reaction between 15 and the glycosyl bromide donor 19.

Acetylation↗