A human genome diversity cell line panel.
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Biological Specimen Banks↗
Biomedical subjects
S Zhu
Publications and source records attributed to S Zhu.
Models for improving cataract surgical rates in southern China.
BACKGROUND/AIMS: Unoperated cataract is the main challenge to blindness reduction in China. This demonstration project in Guangdong Province was designed to test various strategies to improve the cataract surgical rate. METHODS: Two strategies (reduction of the cataract surgical fee and training of country doctors in the detection of cataract blindness) were implemented in each of two counties. Both interventions were introduced in a third county. RESULTS: The cataract surgery rate (CSR) per million was 366 in the county where training took place, 588 where the fee was lowered, and 1140 where both interventions took place. The improvement in CSR was highly significant (p<0.001). CONCLUSIONS: In southern China, CSR can be increased with community based measures. Sustainability for such measures will be the major future challenge.
Aged↗
Directed evolution of alpha-aspartyl dipeptidase from Salmonella typhimurium.
Model-free approaches (error-prone PCR to introduce random mutations, DNA shuffling to combine positive mutations, and screening of the resultant mutant libraries) have been used to enhance the catalytic activity and thermostability of alpha-aspartyl dipeptidase from Salmonella typhimurium, which is uniquely able to hydrolyze Asp-X dipeptides (where X is any amino acid) and one tripeptide (Asp-Gly-Gly). Under double selective pressures of activity and thermostability, through two rounds of error-prone PCR and three sequential generations of DNA shuffling, coupled with screening, a mutant pepEM3074 with approximately 47-fold increased enzyme activity compared with its wild-type parent was obtained. Moreover, the stability of pepEM3074 is increased significantly. Three amino acid substitutions (Asn89His, Gln153Glu, and Leu205Arg), two of them are near the active site and substrate binding pocket, were identified by sequencing the genes encoding this evolved enzyme. The mechanism of the enhancement of activity and stability was analyzed in this paper.
Amino Acid Substitution↗
A naturally occurring non-coding fusion transcript derived from scorpion venom gland: implication for the regulation of scorpion toxin gene expression.
Scorpion venom glands synthesize and secrete a great number of low molecular mass toxic peptides for prey and defense. Many cDNAs and genomic genes encoding these toxins have been isolated and sequenced. However, their expression regulation mechanism is not yet known at present. During screening of a cDNA library prepared from venom glands of the scorpion Buthus martensii Karsch, we isolated a natural fusion cDNA composed of the 5'-untranslated region (UTR) and upstream coding sequence of a long-chain toxin transcript and the downstream coding sequence and 3'-UTR of a short-chain toxin transcript. The junction site is just the overlapping region of 11 nucleotides (GGCAAGGAAAT) between the two wild transcripts, and thus leads to the formation of an early stop codon, which will cause premature translation. Based on the above observations, combined with the genomic data, we proposed a characteristic regulation mechanism of scorpion toxin genes, in which trans-splicing and nonsense mediated mRNA decay are involved.
3' Untranslated Regions↗
Fluorine-containing donor-acceptor complex: infinite chain formed by oxygen...iodine interaction.
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Journal Article↗
[Construction of attenuated Salmonella typhimurium vaccine strain expressing Helicobacter pylori catalase and observation on its protective immunity].
OBJECTIVE: To investigated the effect of attenuated Salmonella typhimurium vaccine strain expressing Helicobacter pylori (Hp) catalase (KatA) on protection against Hp infection. METHODS: Recombinant plasmid expressing KatA was constructed. Expression of KatA was induced with IPTG, and analyzed by SDS-PAGE and Western blot. The recombinant plasmid were introduced into attenuated Salmonella typhimurium SL3261 strain to construct live oral vaccine strain. C57BL/6 mice was orally immunized with this vaccine strain and then given orogastric challenge with live Hp Sydney strain. The stomach samples were submitted to a rapid urease test and quantitative culture. RESULTS: The SDS-PAGE showed a dominant additional protein with molecular weight of 79kDa which could specially react with antibody against GST and accounted for 19% of total bacteria proteins. Animal experiment indicated that this vaccine strain could protect mice against Hp infection. CONCLUSION: Attenuated Salmonella typhimurium vaccine strain expressing KatA could induce effective immune response in protection against Hp infection,which may play an important role in preventing and treating Hp infection and related diseases.
Administration, Oral↗
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade enhances incidence and severity of experimental autoimmune neuritis in resistant mice.
Experimental autoimmune neuritis (EAN), an autoimmune inflammatory demyelinating disease of the peripheral nervous system, represents an animal model of the human Guillain-Barré syndrome. EAN can be induced by active immunization in several animals, including Lewis rats. In contrast, most strains of mice including the widely used C57BL/6 (B6) strain are reputedly resistant to the induction of EAN. In the present study, we demonstrate that in B6 mice, anti-CTLA-4 monoclonal antibody administration in conjunction with immunization with the P0 protein derived peptide 180-199 can induce clinical and pathological definite EAN. Upregulating effects of CTLA-4 blockade on initial and ongoing EAN are demonstrated. CTLA-4 blockade augmented cellular infiltration and enhanced demyelination in the target organ sciatic nerves as well as increased T cell proliferation in lymph node cells. Moreover, serum levels of IFN-gamma and IL-4 were increased. Thus, manipulation of CTLA-4/B7 costimulatory pathway by CTLA-4 blockade can promote autoreactivity and break the relative tolerance to peripheral autoantigen P0 in resistant B6 mice.
Abatacept↗
Double-strand hydrolysis of plasmid DNA by dicerium complexes at 37 degrees C.
Significant effort has been made to develop synthetic metal complexes that hydrolyze DNA. Here we report a new dicerium complex, Ce(2)(HXTA) (HXTA = 5-methyl-2-hydroxy-1,3-xylene-alpha,alpha-diamine-N,N,N',N'-tetraacetic acid), which can hydrolyze DNA at pH 8 and 37 degrees C. This complex hydrolyzes DNA restriction fragments to give products with high regioselectivity, affording >90% 5'-OPO(3) and 3'-OH ends, like the products of DNA hydrolyzing enzymes. Ce(2)(HXTA) also hydrolyzes Litmus 29 plasmid DNA to afford both nicked and linear DNA. Analysis of the relative amounts of supercoiled, nicked, and linear DNA present show that there is one double-strand cleavage per ten single-strand cleavages, indicating that the linear DNA formed cannot be the result of two random single-strand cleavage events. The kinetics of nicked and linear DNA formation are comparable, both being associated with apparent first-order rate constants of approximately 1 x 10(-)(4) s(-)(1) for complex concentrations of 10(-)(5)-10(-)(4) M. These observations suggest that similar factors affect the hydrolysis of the first and second DNA strands and that cleaving the phosphodiester bond is likely the rate determining step in both cases. This is the first detailed study of a metal complex shown to mimic DNA hydrolases in their capability to effect double-strand DNA hydrolysis regioselectively at the 3'-O-P bond.
Cerium↗
Inhibition of N-myc expression and induction of apoptosis by iron chelation in human neuroblastoma cells.
Neuroblastoma is the second most common solid malignancy of childhood. Enhanced expression of the amplified N-myc gene in the tumor cells may be associated with poor patient prognosis and may contribute to tumor development and progression. The use of deferoxamine mesylate (DFO), an iron chelator, to treat neuroblastoma is being investigated in national clinical studies. We show here by TUNEL assay and DNA laddering that DFO induces apoptosis in cultured human neuroblastoma cells, which is preceded by a decrease in the expression of N-myc and the altered expression of some other oncogenes (up-regulating c-fos and down-regulating c-myb) but not housekeeping genes. The decrease in N-myc expression is iron-specific but does not result from inhibition of ribonucleotide reductase, because specific inhibition of this iron-containing enzyme by hydroxyurea does not affect N-myc protein levels. Nuclear run-on and transient reporter gene expression experiments show that the decrease in N-myc expression occurs at the level of initiation of transcription and by inhibiting N-myc promoter activity. Comparison across neuroblastoma cell lines of the amount of residual cellular N-myc protein with the extent of apoptosis measured as pan-caspase activity after 48 h of iron chelation reveals no correlation, suggesting that the decrease in N-myc expression is unlikely to mediate apoptosis. In conclusion, chelation of cellular iron by DFO may alter the expression of multiple genes affecting the malignant phenotype by multiple pathways. Given the clinical importance of N-myc overexpression in neuroblastoma malignancy, decreasing N-myc expression by DFO might be useful as an adjunct to current
Aphidicolin↗
The magnesium-ene cyclization stereochemically directed by an allylic oxyanionic group and its application to a highly stereoselective synthesis of (+/-)-matatabiether. Allylmagnesium compounds by reductive magnesiation of allyl phenyl sulfides.
The first example of a magnesium-ene cyclization stereochemically directed by an allylic oxyanionic group is demonstrated by a highly stereoselective synthesis of the bicyclic terpene matatabiether 10. The synthetic method is particularly valuable, not only because of the stereochemical control and the utility of the versatile hydroxyl group introduced into the product, but also because the precursor of the allylmagnesium is an allyl phenyl sulfide, which is more stable and more easily prepared in a connective fashion than the usual allyl halide precursor. Since the presence of lithium ions encourages undesirable proton transfer to the cyclized organometallic and is detrimental to the stereochemical control, the conversion of the allylic thioether to the allylmagnesium utilizes a lithium-free method involving direct reductive magnesiation in the presence of the magnesium-anthracene complex.
Journal Article↗
A new vascularized adrenal transplantation model in the rat.
A new microsurgical model of adrenal transplantation in the rat is described. An adrenal graft with its vascular supply, adrenal artery and vein, and the attachment of a segment of aorta and inferior vena cava (IVC) was transplanted to a recipient rat with end-to-side anastomoses between the donor IVC segment and the recipient IVC and between the donor aortic segment and the recipient aorta using 10-0 nylon sutures. Using this model, different groups of recipient rats received iso- or allograft with or without immunosuppressive treatment were tested. This model provides a reliable and useful tool for research on endocrinology.
Adrenal Glands↗
Inhibitory effects of gynostemma pentaphyllum on the UV induction of bacteriophage lambda in lysogenic Escherichia coli.
Effects of gynostemma pentaphyllum (GP) on the bacteriophage lambda induced by ultraviolet (UV) irradiation have been studied. The results showed that GP could inhibit the UV induction of bacteriophage lambda in lysogenic cells. The inhibitory effects were dependent on the concentration and the reaction time of GP, and were efficient at 40 to approximately 125 microg ml(-1) for 10 min. The inhibitory rate was higher than 70% when the GP concentration was 50 microg ml(-1). By electron spin resonance (ESR) and spin-trapping techniques, the signals of free radicals were detected in the suspension of the lambda lysogenic bacteria induced by ultraviolet irradiation, but after the addition of GP the signals were decreased. These results indicate that gynostemma pentaphyllum not only is a scavenger of free radicals, but also possesses the biological function of anti-irradiation, and that there is a close relation between the UV irradiation of the bacteriaphage lambda and free radicals.
Bacteriophage lambda↗
Mutational analysis of patients with p47-phox-deficient chronic granulomatous disease: The significance of recombination events between the p47-phox gene (NCF1) and its highly homologous pseudogenes.
OBJECTIVE: The aim of this study was to determine the molecular basis of p47-phox-deficient chronic granulomatous disease (CGD), the most common autosomal recessive form of the disease. CGD is an inherited condition characterized by defective oxygen radical production due to defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Mutational analysis of p47-phox-deficient CGD patients previously demonstrated that the majority of patients have a GT dinucleotide (Delta GT) deletion at the start of exon 2, a signature sequence also observed in the highly homologous pseudogenes of NCF1. MATERIALS AND METHODS: We performed genetic analysis of NCF1 and its pseudogenes using genomic DNA in 29 p47-phox-deficient CGD patients from 22 separate families. First-strand cDNA analysis was performed in 17 of the 29 patients. RESULTS: We confirmed the significance of the Delta GT mutation; in 27 of 29 patients, only the Delta GT sequence was detectable. All but one of the 27 had at least one additional signature sequence, specific to the pseudogene, in either intron 1 and/or intron 2. We extended our analysis to look at signature sequence differences in exons 6 and 9 and detected both the wild-type and pseudogene sequences in all patients tested. CONCLUSIONS: Although detection of only Delta GT sequence accounts for over 85% of affected patients, the molecular basis is most likely due to partial cross-over events between the wild-type and pseudogene(s) of p47-phox at different recombination sites. Our results suggest that complete gene conversion or deletion of the p47-phox gene (NCF1) occurs rarely, if it all.
Base Sequence↗
Dynamics of bubble oscillation in constrained media and mechanisms of vessel rupture in SWL.
Rupture of small blood vessels is a primary feature of the vascular injury associated with shock-wave lithotripsy (SWL) and cavitation has been implicated as a potential mechanism. To understand more precisely the underlying mechanical cause of the injury, the dynamics of SWL-induced bubble dynamics in constrained media were investigated. Silicone tubing and regenerated cellulose hollow fibers of various inner diameters (0.2 to 1.5 mm) were used to fabricate vessel phantoms, which were placed in a test chamber filled with castor oil so that cavitation outside the phantom could be suppressed. Degassed water seeded with 0.2% Albunex contrast agent was circulated inside the vessel phantom, and intraluminal bubble dynamics during SWL were examined by high-speed shadowgraph imaging and passive cavitation detection via a 20-MHz focused transducer. It was observed that, in contrast to the typical large and prolonged expansion and violent inertial collapse of SWL-induced bubbles in a free field, the expansion of the bubbles inside the vessel phantom was significantly constrained, leading to asymmetric elongation of the bubbles along the vessel axis and, presumably, much weakened collapse. The severity of the constraint is vessel-size dependent, and increases dramatically when the inner diameter of the vessel becomes smaller than 300 microm. Conversely, the rapid, large intraluminal expansion of the bubbles causes a significant dilation of the vessel wall, leading to consistent rupture of the hollow fibers (i.d. = 200 microm) after less than 20 pulses of shock wave exposure in a XL-1 lithotripter. The rupture is dose-dependent, and varies with the spatial location of the vessel phantom in the lithotripter field. Further, when the large intraluminal bubble expansion was suppressed by inversion of the lithotripter pressure waveform, rupture of the hollow fiber could be avoided even after 100 shocks. Theoretical calculation of SWL-induced bubble dynamics in blood confirms that the propensity of vascular injury due to intraluminal bubble expansion increases with the tensile pressure of the lithotripter shock wave, and with the reduction of the inner diameter of the vessel. It is suggested that selective truncation of the tensile pressure of the shock wave may reduce tissue injury without compromising the fragmentation capability of the lithotripter pulse.
Acoustics↗
Upregulation of PAI-1 is mediated through TGF beta /SMAD pathway in transplant arteriopathy.
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Journal Article↗
Angiotensin II induces PAI-1 expression through MAP kinase-dependent, but TGF beta and PI3 kinase-independent pathway.
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Journal Article↗
Development of a synthetic cyclized peptide derived from alpha-fetoprotein that prevents the growth of human breast cancer.
The peptide, EMTPVNPG, derived from alpha-fetoprotein, inhibits estrogen-stimulated growth of immature mouse uterus and estrogen-dependent proliferation of human breast cancer cells. However, the biological activities of the peptide diminish over time in storage, even when in the lyophilized state, probably because of peptide aggregation through hydrophobic interaction among monomers. Two analogs of EMTPVNPG were designed with the intent of minimizing aggregation and retaining biological activity during prolonged storage. EMTOVNOG, where O is 4-hydroxyproline, is a linear peptide generated by substituting 4-hydroxyproline for the two prolines, thereby increasing peptide hydrophilicity. This analog exhibited a dose-dependent inhibition of estrogen-stimulated growth of immature mouse uterus similar to that of EMTPVNPG (maximal activity at 1 microg/mouse). A second analog, cyclo-(EMTOVNOGQ), a hydrophilic, cyclic analog with increased conformational constraint, was as potent as the other peptides in its inhibition of estrogen-dependent growth of immature mouse uterus, and had an expanded effective dose range. Both linear and cyclized hydroxyproline-substituted analogs exhibited indefinite shelf-life. Furthermore, both analogs inhibited the estrogen-dependent growth of MCF-7 human breast cancer growing as a xenograft in SCID mice. These analogs may become significant, novel agents for the treatment of breast cancer.
Amino Acid Substitution↗
Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India.
A pilot study was conducted to determine if host genetic factors influence susceptibility and outcomes in human filariasis. Using the candidate gene approach, a well-characterized population in South India was studied using common polymorphisms in six genes (CHIT1, MPO, NRAMP, CYBA, NCF2, and MBL2). A total of 216 individuals from South India were genotyped; 67 normal (N), 63 asymptomatic microfilaria positive (MF+), 50 with chronic lymphatic dysfunction/elephantiasis (CP), and 36 tropical pulmonary eosinophilia (TPE). An association was observed between the HH variant CHIT1 genotype, which correlates with decreased activity and levels of chitotriosidase and susceptibility to filarial infection (MF+ and CP; P = 0.013). The heterozygosity of CHIT1 gene was over-represented in the normal individuals (P = 0.034). The XX genotype of the promoter region in MBL2 was associated with susceptibility to filariasis (P = 0.0093). Since analysis for MBL-sufficient vs insufficient haplotypes was not informative, it is possible the MBL2 promoter association results from linkage disequilibrium with neighboring loci. We have identified two polymorphisms, CHIT1 and MBL2 that are associated with susceptibility to human filarial infection, findings that merit further follow-up in a larger study.
Animals↗