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Lixin Zhang

Publications and source records attributed to Lixin Zhang.

At least 37 records · Page 2Linked to original sources
PubMed2005

Escherichia coli mediated urinary tract infections: are there distinct uropathogenic E. coli (UPEC) pathotypes?

A variety of virulence genes are associated with Escherichia coli mediated urinary tract infections. Particular sets of virulence factors shared by bacterial strains directing them through a particular pathogenesis process are called a "pathotype." Comparison of co-occurrence of potential urinary tract infection (UTI) virulence genes among different E. coli isolates from fecal and UTI collections provides evidence for multiple pathotypes of uropathogenic E. coli, but current understanding of critical genetic differences defining the pathotypes is limited. Discovery of additional E. coli genes involved in uropathogenesis and determination of their distribution and co-occurrences will further define UPEC pathotypes and allow for a more detailed analysis of how these pathotypes might differ in how they cause disease.

Animals↗
PubMed2005

Decreased stability of photosystem I in dgd1 mutant of Arabidopsis thaliana.

The dgd1 mutant of Arabidopsis thaliana provides us with a powerful tool for revealing the specific role of digalactosyldiacylglycerol (DGDG) in photosynthesis. Blue-native polyacrylamide gel electrophoresis analysis revealed that photosystem I (PSI) subunits are assembled into a PSI complex, and that a PSI subcomplex lacking stroma side subunits was also present. PSI subunits in the dgd1 mutant were decreased to a similar level compared with that in the wild type (WT) Arabidopsis. Further experiments showed that PSI subunits in the stroma side, PsaD and PsaE, in the dgd1 mutant were more susceptible to removal by chaotropic agents than those in the WT plant, indicating that the stability of PsaD and PsaE is impaired in the dgd1 mutant. These results provide evidence that DGDG is important for the stability of the PSI complex.

Arabidopsis↗
PubMed2005

Clinical relevance of Mycobacterium tuberculosis plcD gene mutations.

To identify Mycobacterium tuberculosis virulence factors, we integrated comparative genomics and epidemiologic data analysis to investigate the relationship between certain genomic insertions and deletions in the phospholipase-C gene D (plcD) with the clinical presentation of tuberculosis (TB). Four hundred ninety-six well-characterized M. tuberculosis clinical isolates were studied. Approximately 30% (147) of the isolates had an interruption of the plcD gene. Patients infected with the plcD mutant were twice as likely to have extrathoracic disease as those infected by a strain without an interruption (adjusted odds ratio, 2.19; 95% confidence interval, 1.27, 3.76). When we limited the analysis to the 275 isolates with distinct DNA fingerprint patterns, we observed the same association (adjusted odds ratio, 2.74; 95% confidence interval, 1.35, 5.56). Furthermore, the magnitude of the association appeared to differ with the type of extrathoracic TB. Our findings suggest that the plcD gene of M. tuberculosis is potentially involved in the pathogenesis of TB, and the clinical presentation of the disease may be influenced by the genetic variability of the plcD region.

Adult↗
PubMed2005

Clonal groups and the spread of resistance to trimethoprim-sulfamethoxazole in uropathogenic Escherichia coli.

BACKGROUND: Antibiotic resistance is increasingly complicating the management of urinary tract infection. We investigated the extent to which a group of Escherichia coli called clonal group A (CGA), which is associated with resistance to trimethoprim-sulfamethoxazole (TMP-SMZ), accounted for TMP-SMZ resistance among a prospectively collected set of uropathogenic and rectal E. coli isolates from a university population in Michigan. METHODS: Resistant and susceptible uropathogenic E. coli isolates (45 each) and 79 randomly selected rectal E. coli isolates were evaluated for CGA status by use of 2 definitions of this group-- the enterobacterial repetitive intergenic consensus sequence 2 (ERIC2)-polymerase chain reaction (PCR) pattern A fingerprint and the C288T single nucleotide polymorphism (SNP) in the fumC gene. We compared virulence gene profiles and molecular mechanisms of resistance to TMP-SMZ between isolates classified as CGA by both approaches to better characterize the relationship between isolates. RESULTS: Of the 45 isolates that exhibited ERIC2-PCR pattern A, one-half (23 of 45) were resistant to TMP-SMZ, and 16 contained the C288T SNP. The pattern A isolates were diverse, exhibiting multiple mechanisms of resistance to TMP-SMZ and various combinations of virulence factors. C288T SNP isolates showed less variation, with 15 of 16 resistant to TMP-SMZ and a 1.8-kb class I integron bearing the dfrA17 gene present in 14 of 15 resistant isolates. Twelve of 16 exhibited the same combination of virulence genes. Pulsed-field gel electrophoresis patterns for these 12 isolates were unique. CONCLUSION: CGA, as defined by the fumC C288T SNP, appears to be distantly clonal but is not an outbreak-related group. The widespread group has likely evolved through lateral transfer of genes conferring virulence and antibiotic resistance.

Adolescent↗
PubMed2005

Exploring novel bioactive compounds from marine microbes.

The historical paradigm of the deep ocean as a biological 'desert' has shifted to one of a 'rainforest' owing to the isolation of many novel microbes and their associated bioactive compounds. Recently, there has been an explosion of information about novel bioactive compounds that have been isolated from marine microbes in an effort to further explore the relatively untapped marine microbes and their secondary metabolites for drug discovery. The microbes are recovered and purified from the ocean by both conventional and innovative isolation methods to obtain those previously thought to be 'uncultivable'. To overcome the difficulties and limitations associated with cultivation techniques, several DNA-based molecular methods have been developed to bypass the culture-dependent bottleneck. Bioactive compounds isolated using the above strategies have not only shown importance in biotechnological and pharmaceutical applications but have also increased our understanding of the diversity of marine microbiota, ecosystem functions and the exploitable biology.

Anti-Infective Agents↗
PubMed2005

Protective effect of nitric oxide against oxidative stress under ultraviolet-B radiation.

The response of bean leaves to UV-B radiation was extensively investigated. UV-B radiation caused increase of ion leakage, loss of chlorophyll, and decrease of the maximum efficiency of PSII photochemistry (Fv/Fm) and the quantum yield of PSII electron transport (PhiPSII) of bean leaves. H2O2 contents and the extent of thylakoid membrane protein oxidation increased, indicated by the decrease of thiol contents and the increase of carbonyl contents with the duration of UV-B radiation. Addition of sodium nitroprusside, a nitric oxide (NO) donor, can partially alleviate UV-B induced decrease of chlorophyll contents, Fv/Fm and PhiPSII. Moreover, the oxidative damage to the thylakoid membrane was alleviated by NO. The potassium salt of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a specific NO scavenger, arrested NO mediated protective effects against UV-B induced oxidative damage. Incubation of thylakoid membrane with increasing H2O2 concentrations showed a progressive enhancement in carbonyl contents. H2O2 contents were decreased in the presence of NO under UV-B radiation through increased activities of superoxide dismutases, ascorbate peroxidases, and catalases. Taken together, the results suggest that NO can effectively protect plants from UV-B damage mostly probably mediated by enhanced activities of antioxidant enzymes.

Antioxidants↗
PubMed2005

Challenges in prostate cancer research: animal models for nutritional studies of chemoprevention and disease progression.

Prostate cancer is the second leading cause of cancer-related death in the United States. The American Cancer Society estimates that there will be over 232,000 new cases of prostate cancer in 2005. Evidence suggests that diet can act as a chemopreventive agent to reduce the incidence of prostate cancer as well as to reduce the mortality of the disease. Epidemiologic studies suggest that diets rich in specific vitamins, grains, fruits, and vegetables may be associated with lower cancer rates than high-fat diets, yet the molecular bases for these positive nutritional actions are largely unknown. The interactions of diet in combination with genetic determinants of disease progression are unclear because prostate cancer is also a disease resulting from abnormal gene expression. Hence, the biology of normal prostate development and the mechanisms underlying the initiation, progression, and metastatic spread of prostate cancer must be understood at the molecular level to develop effective nutritional prevention and intervention strategies to control and treat this malignant disease. However, progress toward understanding the biology of prostate cancer and the development of new therapies has been hampered by the lack of in vivo model systems that adequately capitulate the spectrum of benign, latent, aggressive, and metastatic forms of the human disease. In this review we discuss the diverse animal models of prostate cancer available and their applicability for nutritional studies of cancer prevention.

Animal Nutritional Physiological Phenomena↗
PubMed2005

Variation of the Mycobacterium tuberculosis PE_PGRS 33 gene among clinical isolates.

PE_PGRS 33, one of about 60 PE_PGRS genes in the Mycobacterium tuberculosis genome, encodes a surface-expressed protein that may be involved in the antigenic variation of M. tuberculosis strains and evasion of the host immune system. While genetic differences between the PE_PGRS 33 genes of H37Rv and CDC 1551 have been noted, genetic variation in this gene among clinical isolates has not been evaluated. In order to gain a better understanding of the genetic basis for the role of PE_PGRS in antigenic variation and evasion of the host immune system, we investigated the genetic diversity of the PE_PGRS 33 gene among 123 clinical M. tuberculosis isolates from a population-based study, using PCR and DNA sequencing. The 123 isolates belonged to principal genetic groups 1, 2, and 3 and had IS 6110 copy numbers ranging from 1 to 22. Eighty-four (68.3%) of the 123 isolates were found to have at least one sequence variation in the PE_PGRS 33 gene, relative to that of H37Rv. Twenty-five different sequence variations were observed and included three insertions (ranging from 9 to 87 bp), nine deletions (ranging from 1 to 273 bp), one insertion-and-deletion event, and 12 single-nucleotide polymorphisms (six synonymous and six nonsynonymous). Analysis of the relationships among the different PE_PGRS 33 gene sequence variations suggests that polymorphisms in the gene are shifting along evolutionary lineages. The observed genetic diversity of the PE_PGRS 33 gene supports its role in antigenic variation and can serve as a basis for future investigations of the function of the PE_PGRS 33 gene among clinical isolates.

Antigens, Bacterial↗
PubMed2004

Supranigral injection of neuregulin1-beta induces striatal dopamine overflow.

Previous studies have provided anatomical evidence that the functional neuregulin receptor, ErbB4, is present within the ventral midbrain where it is co-localized to dopamine neurons of the substantia nigra and ventral tegmental area. In this study, we provide evidence that neuregulin1-beta (a.k.a. heregulin1-beta), a neuregulin-1 gene isoform that preferentially binds to and activates the ErbB4 receptor, evokes an almost immediate overflow of striatal dopamine when injected into a region just dorsal to the ipsilateral substantia nigra. These data are indicative that neuregulins can modulate the activity of mesostriatal dopaminergic neurons.

Animals↗
PubMed2004

Vector targeting makes 5-fluorouracil chemotherapy less toxic and more effective in animal models of epithelial neoplasms.

PURPOSE: 5-fluorouracil (5-FU) has been combined in the past with other drugs for the combination chemotherapy for cancers of the breast, ovary, and colon. These drug regimens were limited by the fact that 5-FU fails to kill nondividing cancer cells at the doses that are safe to deliver. The goal of the present study is to test the feasibility of replacing 5-FU in established 5-FU combination chemotherapy with the Ad-LpCDIRESE1A/5-fluorocytosine (5-FC) system for the purpose of reducing toxicity and increasing efficacy. EXPERIMENTAL DESIGN: We have replaced 5-FU in the weekly combination of CPT-11, folinic acid (FA) and 5-FU chemotherapy by 5-FC and an adenoviral vector that carries the L-plastin (Lp) tumor-specific promoter-driven transcription unit encoding the cytosine deaminase gene linked to the E1A gene by an internal ribosomal entry site element. This combination is called "genetic combination therapy." The goal of using the vector was to decrease the toxicity to normal tissue and to increase the efficacy of therapy in the cancer cells by increasing the concentration of 5-FU sufficiently high that even nondividing cancer cells would be killed by 5-FU through its incorporation into mRNA and consequent inhibition of synthesis of functional proteins. We compared the in vivo efficacy of the genetic combination therapy with the conventional combination chemotherapy in a mouse colon cancer model. RESULTS: Both replication-competent and -noncompetent adenoviral vectors carrying an L-plastin-driven cytosine deaminase transcription unit when combined with 5-FC, CPT-11, and FA showed increased in vitro therapeutic activity that was significantly higher than that of the conventional chemotherapy combination. Tumor-bearing mice treated with the genetic combination therapy showed a statistically significant advantage in terms of increased response rate, response duration, survival, and reduced toxicity when compared with tumor-bearing mice treated with the conventional combination chemotherapy. CONCLUSIONS: Replacement of 5-FU in 5-FU-based combination chemotherapy with the Ad-LpCDIRESE1A vector and 5-FU reduces toxicity and increases efficacy. This is a concept that could be potentially applied widely for many forms of cancer treatment.

Adenoviridae↗
PubMed2004

Ferrocenyl monophosphine ligands: synthesis and applications in the Suzuki-Miyaura coupling of aryl chlorides.

Ferrocenyl monophosphine ligands have been developed by a method based on palladium-catalyzed Suzuki-Miyaura coupling. The modular procedure creates a rapid synthesis of phosphines with diverse properties. The electron-rich phosphines have been successfully applied to the Suzuki-Miyaura coupling of activated and deactivated aryl chlorides, with low catalyst loading being feasible in the synthesis of tris-ortho-substituted biaryls.

Journal Article↗
PubMed2004

Multistep process through which adenoviral vector vaccine overcomes anergy to tumor-associated antigens.

Our goal in the present work was to characterize the multiple steps involved in overcoming the anergy that exists in tumor hosts to tumor-associated antigen (TAA). Our studies showed that the subcutaneous injection of the Ad-sig-TAA/ecdCD40L vector resulted in secretion of the TAA/ecdCD40L protein for at least 10 days from infected cells. Binding of the TAA/ecdCD40L protein to dendritic cells (DCs) resulted in the induction of CCR-7 chemokine receptor expression and cytokine release. This was followed by migration of the DCs to regional lymph nodes. Tetramer staining, enzyme-linked immunospot (ELISPOT) assay, and cytotoxicity assay all showed that the Ad-sig-TAA/ecdCD40L vector increased the levels of splenic CD8(+) T cells specific for the 2 TAAs (human MUC1 [hMUC1] and HPV E7) tested. Vaccination with the Ad-sighMUC1/ecdCD40L vector suppressed the growth of hMUC1 antigen-positive tumor cells in 100% of the test mice that were previously anergic to the hMUC1 antigen. These data suggest that Ad-sig-TAA-ecd/ecdCD40L vector injections may be of value in treating the many epithelial malignancies in which TAA-like hMUC1 is overexpressed.

Adenoviridae↗
PubMed2004

Negative control of apoptosis signal-regulating kinase 1 through phosphorylation of Ser-1034.

Apoptosis signal-regulating kinase 1 (ASK1) is a serine/threonine kinase that mediates cell stress signaling initiated by diverse stimuli, such as H(2)O(2) and TNF alpha. Owing to its critical role in promoting apoptosis, ASK1 activity is highly controlled in cells. Phosphorylation of ASK1 at Thr-845 has been correlated with its activation, while phosphorylation at Ser-967 negatively controls its death promoting activity. Here, we report the identification of a novel phosphorylation site at Ser-1034 in the C-terminal regulatory domain of ASK1. Mutating Ser-1034 to an unphosphorylatable Ala led to increased catalytic activity of ASK1 and enhanced proapoptotic function of ASK1. Thus, the proapoptotic function of ASK1 is suppressed in part by phosphorylation at its C-terminal regulatory domain, which may couple upstream survival kinases to the death regulatory machinery.

Apoptosis↗
PubMed2004

Library on a slide for bacterial comparative genomics.

BACKGROUND: We describe a novel application of microarray technology for comparative genomics of bacteria in which libraries of entire genomes rather than the sequence of a single genome or sets of genes are arrayed on the slide and then probed for the presence or absence of specific genes and/or gene alleles. RESULTS: We first adopted a 96-well high throughput working protocol to efficiently isolate high quality genomic DNA. We then optimized conditions to print genomic DNA onto a glass slide with high density (up to 15000 spots) and to sensitively detect gene targets in each genome spot using fluorescently labeled DNA probe. Finally, we created an E. coli reference collection array and probed it for the presence or absence of the hemolysin (hly) gene using a dual channel non-competing hybridization strategy. Results from the array hybridization matched perfectly with previous tests. CONCLUSIONS: This new form of microarray technology, Library on a Slide, is an efficient way for sharing and utilizing large strain collections in comparative genomic analyses.

Bacterial Typing Techniques↗
PubMed2004

Nitric oxide functions as a signal in salt resistance in the calluses from two ecotypes of reed.

Calluses from two ecotypes of reed (Phragmites communis Trin.) plant (dune reed [DR] and swamp reed [SR]), which show different sensitivity to salinity, were used to study plant adaptations to salt stress. Under 200 mm NaCl treatment, the sodium (Na) percentage decreased, but the calcium percentage and the potassium (K) to Na ratio increased in the DR callus, whereas an opposite changing pattern was observed in the SR callus. Application of sodium nitroprusside (SNP), as a nitric oxide (NO) donor, revealed that NO affected element ratios in both DR and SR calluses in a concentration-dependent manner. N(omega)-nitro-l-arginine (an NO synthase inhibitor) and 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxyde (a specific NO scavenger) counteracted NO effect by increasing the Na percentage, decreasing the calcium percentage and the K to Na ratio. The increased activity of plasma membrane (PM) H(+)-ATPase caused by NaCl treatment in the DR callus was reversed by treatment with N(omega)-nitro-l-arginine and 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxyde. Western-blot analysis demonstrated that NO stimulated the expression of PM H(+)-ATPase in both DR and SR calluses. These results indicate that NO serves as a signal in inducing salt resistance by increasing the K to Na ratio, which is dependent on the increased PM H(+)-ATPase activity.

Adaptation, Physiological↗
PubMed2004

Diversity and sharing of Haemophilus influenzae strains colonizing healthy children attending day-care centers.

BACKGROUND: Children attending day-care centers (DCCs) are at risk for Haemophilus influenzae nasopharyngeal colonization and acute otitis media. The degree to which a given strain circulates within a day-care center and the heterogeneity of strains among DCCs in a geographic area are not well-characterized. This study describes the prevalence rates of H. influenzae colonization in a large number of children attending day-care centers and examines the genetic diversity of colonizing strains and the degree of sharing among children. METHODS: Throat cultures were collected from 198 healthy children <3 years old attending 16 day-care centers in Michigan. All H. influenzae isolates were genetically typed by enterobacterial repetitive intergenic consensus PCR as the initial screening technique to identify unique strains within each child. Pulsed field gel electrophoresis was used subsequently to examine the genetic diversity of strains between children. RESULTS: There were 127 (64%) children colonized with H. influenzae. Wide variation in rates of colonization was identified among day-care centers (0 to 95%). A total of 179 genetically unique H. influenzae strains were isolated, and 47 children (37%) were colonized with 2 or more genetically distinct H. influenzae organisms. Evidence of sharing of the same strain in different children was found in 13 of 15 colonized DCCs and 23% of genotypically unique strains were shared. CONCLUSION: The degree of sharing of H. influenzae among children in this study suggests transmission of these potentially pathogenic microorganisms in day-care centers.

Carrier State↗