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Biomedical subjects

L H Xu

Publications and source records attributed to L H Xu.

At least 19 recordsLinked to original sources
PubMed2005

Formation of MTBE-DNA adducts in mice measured with accelerator mass spectrometry.

Methyl tert-butyl ether (MTBE) is a gasoline oxygenate and antiknock additive substituting for lead alkyls currently in use worldwide. Previous studies have shown that MTBE at very high doses induces tumors in rodents. The aim of the present study was to examine directly the binding ability of MTBE onto DNA, demonstrating its potential genotoxicity. MTBE-DNA adducts and their decay kinetics in mice have been measured by using doubly 14C-labeled MTBE with an advanced, ultrasensitive technique: accelerator mass spectrometry (AMS). It was found that MTBE definitely formed adducts with DNA in mouse lung, liver, and kidney in a log/log linear dose-response relationship. The distribution sequence of DNA adducts in these tissues is: lung > liver > kidney. The level of MTBE-DNA adducts peaked at 12 h postadministration in the lung and peaked at 6 h postadministration in the liver. Then the adducts declined rapidly until 5 days postadministration and thereafter declined much more slowly. To our knowledge, this is the first report on DNA adduction with MTBE in vivo. The mechanism of the formation of MTBE-DNA adducts also is discussed.

Animals↗
PubMed2001

Organic composition of C/1999 S4 (LINEAR): a comet formed near Jupiter?

In the current paradigm, Oort cloud comets formed in the giant planets' region of the solar nebula, where temperatures and other conditions varied greatly. The measured compositions of four such comets (Halley, Hyakutake, Hale-Bopp, and Lee) are consistent with formation from interstellar ices in the cold nebular region beyond Uranus. The composition of comet C/1999 S4 (LINEAR) differs greatly, which suggests that its ices condensed from processed nebular gas, probably in the Jupiter-Saturn region. Its unusual organic composition may require reevaluation of the prebiotic organic material delivered to the young Earth by comets.

Journal Article↗
PubMed2001

Streptimonospora salina gen. nov., sp. nov., a new member of the family Nocardiopsaceae.

Actinomycete strain YIM 90002T (= CCTCC 99003T = CCRC 16284T) was isolated from a soil sample collected from a salt lake in the west of China. The aerial mycelium of this organism is well developed but not fragmented and, at maturity, forms short chains of spores. Spores in short chains are oval- to rod-shaped and have wrinkled surfaces. Substrate mycelium is branched with non-fragmenting hyphae and forms single oval to round spores borne on sporophores or dichotomously branching sporophores. Single spores have wrinkled surfaces. Single spores and spores in short chains are non-motile. Strain YIM 90002T contains meso-diaminopimelic acid, DD-diaminopimelic acid, glycine, lysine and aspartic acid in its cell wall and has glucose, galactose, ribose, xylose, arabinose and mannose as whole-cell sugars (no diagnostic sugars). The phospholipids are phosphatidylglycerol, phosphatidylinositol and phosphatidylethanolamine. The major menaquinones are MK-9(H6), MK-10(H2) and MK-10(H4). Phylogenetic data indicate that this strain belongs to the family Nocardiopsaceae. The morphological and physiological characteristics and chemotaxonomic and phylogenetic data for this strain differ from those of previously described actinomycetes. Therefore, a new genus, Streptimonospora, is proposed for this organism; the type species of the genus is Streptimonospora salina gen. nov., sp. nov., and the type strain of S. salina is strain YIM 90002T.

Actinomycetales↗
PubMed2001

[Transplantation of cultured human keratinocyte on collagen sponge].

OBJECTIVE: To investigate the skin regeneration using cultured human keratinocytes with collagen sponge transplanted into thickness wound of nude mice. METHODS: Human foreskin from foreskin ectomy procedures was detached with 0.5% Dispase II. Epidermis sheets were separated from dermis and digested with 0.05% Trypsin into single cell suspension. Keratinocytes were cultured and seeded into collagen sponge during logarithmic growth phase. After 3 days, the keratinocytes-collagen sponge were grafted on full thickness wound of nude mice, compared with simple collagen sponge without keratinocytes. The histological, immunohistochemical examination and electron microscopy were detected. RESULTS: After the epidermal substitute was grafted onto wound, the human keratinocytes were able to further proliferate and differentiate and develop into new epithelia. Compared with the control group, the wound healed earlier and contracted less, epithelia matured earlier, and the collagen fiber was less beneath epithelia. CONCLUSION: Keratinocytes can grow on collagen sponge and migrate onto wound to develop into stratified epithelia and inhibit wound contract. The keratinocyte graft can be used to repair skin defect.

Animals↗
PubMed2001

Detection of head and neck squamous cell carcinoma among exfoliated oral mucosal cells by microsatellite analysis.

Prompt detection of head and neck squamous cell carcinoma (HNSCC) is vital to successful patient management. In this feasibility study, we used microsatellite analysis to detect tumor-specific genetic alterations in exfoliated oral mucosal cell samples from patients with known cancer. Exfoliated mucosal cells in pretreatment oral rinse and swab samples were collected from 44 HNSCC patients and from 43 healthy control subjects (20 nonsmokers and 23 smokers). We tested a panel of 23 informative microsatellite markers to assay DNA from the matched lymphocyte, tumor (from cancer cases), and oral test samples. Loss of heterozygosity or microsatellite instability of at least one marker was detected in 38 (86%) of 44 primary tumors. Identical alterations were found in the saliva samples in 35 of these 38 cases (92% of those with markers; 79% overall) including 12 of 13 cases with small primaries [stage Tt or Tx (occult primary)] and 4 of 4 cases of patients that had undergone prior radiation. Microsatellite instability was detectable in the saliva in 24 (96%) of 25 cases in which it was present in the tumor, and loss of heterozygosity was identified in the test sample in 19 (61%) of 31 cases. No microsatellite alterations were detected in any of the samples from the healthy control subjects. This approach must now be refined and validated for the detection of clinically occult disease. Microsatellite analysis of oral samples may then become a valuable method for detecting and monitoring HNSCC.

Carcinoma, Squamous Cell↗
PubMed2000

The focal adhesion kinase suppresses transformation-associated, anchorage-independent apoptosis in human breast cancer cells. Involvement of death receptor-related signaling pathways.

The focal adhesion kinase (FAK) is a mediator of cell-extracellular matrix signaling events and is overexpressed in tumor cells. In order to rapidly down-regulate FAK function in normal and transformed mammary cells, we have used adenoviral gene transduction of the carboxyl-terminal domain of FAK (FAK-CD). Transduction of adenovirus containing FAK-CD in breast cancer cells caused loss of adhesion, degradation of p125(FAK), and induced apoptosis. Furthermore, breast tumor cells that were viable without matrix attachment also underwent apoptosis upon interruption of FAK function, demonstrating that FAK is a survival signal in breast tumor cells even in the absence of matrix signaling. In addition, both anchorage-dependent and anchorage-independent apoptotic signaling required Fas-associated death domain and caspase-8, suggesting that a death receptor-mediated apoptotic pathway is involved. Finally, FAK-CD had no effect on adhesion or viability in normal mammary cells, despite the loss of tyrosine phosphorylation of p125(FAK). These results indicate that FAK-mediated signaling is required for both cell adhesion and anchorage-independent survival and the disruption of FAK function involves the Fas-associated death domain and caspase-8 apoptotic pathway.

Apoptosis↗
PubMed2000

Engineering of a mini-trichosanthin that has lower antigenicity by deleting its C-terminal amino acid residues.

Trichosanthin is a ribosome-inactivating protein that possesses antitumor and antiviral activities. Clinical trials of trichosanthin on AIDS patients, however, elicit anaphylactic reactions. To reduce the antigenicity of trichosanthin as a drug while preserving its biological activity, the C-terminal domain (residues 203 to 247), which contains a putative antigenic site, was systemically deleted. We have found that the minimum length of trichosanthin that can fold into an active conformation is residue 1 to 240. The mini-trichosanthin (C7) generated by deleting the last seven C-terminal amino acid residues has 2.7-fold decrease in antigenicity, 10-fold reduction in in vitro ribosome-inactivation activity, and in vivo cytotoxicity toward K562 cells, and 2-fold reduction in abortificient activity. Structural analyses of C7 indicate decrease in the helix content, increased exposure of Trp192, and lower thermodynamic stability. The deletion of the C-terminal residues (Leu241 to Ala247) probably perturbs local structure of the C-terminal antigenic epitope that results in the decrease in antigenicity and activities of C7.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

Use of protein phosphatase inhibition assay to detect microcystins in Donghu Lake and a fish pond in China.

Seasonal variations in the level of total microcystins in water samples collected from Donghu Lake and a fish pond in Wuhan, China, were studied between March 1995 and February 1996 using a protein phosphatase inhibition assay involving a radioactive 32P-labelled substrate. The assay is highly reliable and repeatable, and is probably the most sensitive assay for microcystin detection to date. Results of the survey indicated the presence of microcystins in the water samples, and the concentration of microcystins appeared to be related to the degree of eutrophication and water temperature. There is also a correlative relationship between the quantity of microcystins and the abundance of microcystin-producing cyanobacteria (Anabaena and Oscillatoria) in the water bodies over a year cycle. In the present study, the positive detection of microcystins in water bodies having no signs of algal bloom warns of considerable potential threat of these waters to public health.

Animals↗
PubMed1999

Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer.

BACKGROUND: Conventional cytologic analysis of sputum is an insensitive test for the diagnosis of non-small-cell lung cancer (NSCLC). We have recently demonstrated that polymerase chain reaction (PCR)-based molecular methods are more sensitive than cytologic analysis in diagnosing bladder cancer. In this study, we examined whether molecular assays could identify cancer cells in bronchoalveolar lavage (BAL) fluid. METHODS: Tumor-specific oncogene mutations, CpG-island methylation status, and microsatellite alterations in the DNA of cells in BAL fluid from 50 consecutive patients with resectable (stages I through IIIa) NSCLC were assessed by use of four PCR-based techniques. RESULTS: Of 50 tumors, 28 contained a p53 mutation, and the identical mutation was detected with a plaque hybridization assay in the BAL fluid of 39% (11 of 28) of the corresponding patients. Eight of 19 adenocarcinomas contained a K-ras mutation, and the identical mutation was detected with a mutation ligation assay in the BAL fluid of 50% (four of eight) of the corresponding patients. The p16 gene was methylated in 19 of 50 tumors, and methylated p16 alleles were detected in the BAL fluid of 63% (12 of 19) of the corresponding patients. Microsatellite instability in at least one marker was detected with a panel of 15 markers frequently altered in NSCLC in 23 of 50 tumors; the identical alteration was detected in the BAL fluid of 14% (three of 22) of the corresponding patients. When all four techniques were used, mutations or microsatellite instability was detected in the paired BAL fluid of 23 (53%) of the 43 patients with tumors carrying a genetic alteration. CONCLUSION: Although still limited by sensitivity, molecular diagnostic strategies can detect the presence of neoplastic cells in the proximal airway of patients with surgically resectable NSCLC.

Alleles↗
PubMed1999

Site-directed polyethylene glycol modification of trichosanthin: effects on its biological activities, pharmacokinetics, and antigenicity.

Trichosanthin (TCS), a type I ribosome-inactivating protein (RIP), was modified with polyethylene glycol (PEG) in order to reduce its antigenicity and prolong its half-life. Computer modeling identified three potential antigenic sites namely Q219, K173 and S7. By site-directed mutagenesis, these sites were changed into cysteine through which PEG can be covalently attached. The resulting TCS had a PEG coupled directly above one of its potential antigenic determinants, hence masking the antigenic region and prevent binding of antibodies specific to this site. In general, mutation did not bring about significant changes in ribosome-inactivating activity, cytotoxicity, and abortifacient activity of TCS. However, the in vitro activities of PEG modified (PEGylated) TCS muteins were 3-20 folds lower and the in vivo activity 50% less than that of nTCS. Pharmacokinetics study indicated that all three PEGylated TCS muteins showed 6-fold increase in mean residence time as compared to unmodified muteins. The binding affinity of an IgE monoclonal antibody (TE1) to TCS was greatly reduced after PEG modification (PEGylation) at position Q219, suggesting that TE1 recognized an epitope very near to residue Q219. PEGylated TCS muteins induced similar IgG response but 4-16 fold lower IgE response in mice compared with nTCS.

Animals↗
PubMed1999

Three new species of the genus Actinobispora of the family Pseudonocardiaceae, Actinobispora alaniniphila sp. nov., Actinobispora aurantiaca sp. nov. and Actinobispora xinjiangensis sp. nov.

The genus Actinobispora Jiang et al. is characterized by the formation of longitudinally paired spores on both the vegetative and the aerial mycelium, absence of mycolic acid, cell wall chemotype IV (containing meso-diaminopimelic acid as the diamino acid, galactose and arabinose), PVI and MK-9(H2). Comparative studies of morphology, chemical classification and phylogenetic analysis based on the 16S rRNA sequences among the four type strains of the genus Actinobispora and type strains of related genera were carried out. The results indicated that the genus Actinobispora is different from these other genera and should be placed in the family Pseudonocardiaceae Embley et al. 1988 with the genera Amycolatopsis, Pseudonocardia, Saccharomonospora, Saccharopolyspora and Actinopolyspora. On the bases of these results, three new species under the names of Actinobispora alaniniphila sp. nov., Actinobispora aurantiaca sp. nov. and Actinobispora xinjiangensis sp. nov. are proposed; the type strains are CCTCC AA97001T, CCTCC AA97002T and CCTCC AA97020T.

Actinomycetales↗
PubMed1998

Establishment and characterization of a SV40T-transformed human bronchial epithelial cell line.

The majority of human lung cancers originate from the carcinogenesis of bronchial epithelial cells. To study the malignant progression of human bronchial epithelial cells, we established a SV40T-transformed human bronchial epithelial cell line, and observed some biological and genetic changes of the cell line at different passages. In a 2-year culture, this cell line was approaching malignancy without obvious senescence. Cells in a later passage proliferated faster and required less growth factors than those of an early passage. After continued passaging, these cells were resistant to the terminal squamous differentiation effects of serum, and many of the cells grew anchorage independently. However, no tumor formed after cells were injected into nude mice. Some genetic alterations were found accompanying those morphological changes, such as 3p- and activation of c-myc, c-erbB-2 and bcl2, suggesting that those genetic alterations may contribute to the carcinogenesis of human bronchial epithelial cells at an early stage. This cell line should be particularly useful for studying the progression of human lung cancers.

Animals↗
PubMed1998

Streptomyces thermogriseus, a new species of the genus Streptomyces from soil, lake and hot-spring.

Many thermophilic actinomycetes were isolated from samples collected from a hot-spring, lake and soil in Yunnan, China. Chemical and molecular classification of four selected strains of thermophilic Streptomyces with an upper limited growth temperature of 65-68 degrees C and autolytic characteristics was carried out. A new species, Streptomyces thermogriseus sp. nov. is described. The type strain is Y-14046T (= CCTCC AA97014T).

China↗
PubMed1998

Description of Saccharomonospora xinjiangensis sp. nov. based on chemical and molecular classification.

Comparative studies of morphology, physiology, biochemistry and chemical composition of cells, and phylogenetic analysis based on 16S rRNA gene sequences were carried out with strains XJ-54T and XJ-58 of the genus Saccharomonospora and type strains of related genera. The results indicated that the two strains are different from known members of the genus Saccharomonospora. A new species with the name Saccharomonospora xinjiangensis sp. nov. is proposed. The new species is characterized by the presence of longitudinal pairs of spores on both the aerial and the vegetative hyphae and contains phosphatidyl ethanolamine, phosphatidyl choline and unknown glucosamine-containing phospholipids, and the major menaquinones MK-9(H2), MK-9(H4) and MK-7(H4).

Actinomycetales↗
PubMed1998

The COOH-terminal domain of the focal adhesion kinase induces loss of adhesion and cell death in human tumor cells.

Focal adhesion kinase (FAK) is a tyrosine kinase that is linked to signaling pathways between cells and their extracellular matrix. An alternate transcript of the COOH-terminal region of the FAK gene, called FAK-related nonkinase, has been shown to act as an inhibitor of FAK in chicken embryo fibroblasts. We have designed an analogous segment of human FAK, FAK COOH-terminal domain (FAK-CD), and transfected this construct into human tumor cells. Expression of FAK-CD inhibited cell growth in BT474 human breast cancer cells and C8161 human melanoma cells. To characterize the nature of growth inhibition, we developed an inducible system of FAK-CD expression and demonstrated that the induced FAK-CD protein localized to focal adhesions, causing cellular rounding, an irreversible loss of adhesion, and subsequent cell death. In addition, expression of FAK-CD reduced tyrosine phosphorylation of FAK, suggesting that FAK-CD may be a potent inhibitor of FAK in human tumor cells.

Alternative Splicing↗
PubMed1996

Diethylstilbestrol-induced immortalization of human endometrial cells: alterations in p53 and estrogen receptor.

Carcinogenesis is a process requiring multiple steps. Immortalization is one step in this process and may be rate limiting. To further our understanding of estrogen-induced carcinogenesis, we evaluated diethylstilbestrol (DES)-induced immortalization of human endometrial stromal cells. This was achieved by assessing at the restrictive temperature the colony-forming efficiency of cells that were conditionally immortalized with a temperature-sensitive simian virus 40 large T antigen. Treatment with DES for 1 wk did not increase the immortalization frequency; however, cultures that were treated for 20 wk had a twofold increase in immortalization frequency, and continued treatment for a total of 44 wk produced a threefold increase in immortalization frequency that was dose dependent. DES-treated restrictive temperature variants (RTVs) but not spontaneous RTVs lost the temperature-sensitive phenotype. DES-RTVs also had a shorter doubling time than spontaneous RTVs did. p53 expression was increased in DES-RTVs, and its localization within the cell was altered. Conversely, expression of the estrogen receptor was decreased in DES-immortalized cells. These changes in gene expression often occur in estrogen-related malignancies, and our results are consistent with a causal role for estrogens in these p53 and the estrogen receptor alterations. Immortalization of human cells may be analogous to initiation of rodent cells, and our results suggest that estrogen-induced alterations in p53 or other genes that regulate life span could contribute to estrogen-induced initiation.

Base Sequence↗
PubMed1996

2q-, a non-random chromosomal abnormality in human non-small-cell lung cancer.

Many cytogenetic studies have been carried out on human lung cancer. However the chromosomal alterations in human lung cancers are often complex, making it difficult to identify some abnormal chromosomes by routine cytogenetic studies. Using FISH (fluorescence in situ hybridization), we studied the alterations of chromosome 2, 3, and 17 in four human bronchial epithelial cell lines, two human non-small-cell lung cancer (NSCLC) cell lines, and 12 primary NSCLC specimens. 2q- was found in three out of four human bronchial epithelial cell lines, two NSCLC cell lines, and three out of seven primary NSCLC specimens tested. 3p- was noted in five cases of twelve primary NSCLC patients examined. 3p- was the first cytogenetic discovery and the most prominent abnormality in lung cancer. 2q- has rarely been reported in human lung cancer but loss of heterozygosity by RFLP analysis for 2q had been reported in human NSCLC. Our results indicate that 2q- was also a non-random chromosomal abnormality in the early stage of the development of human NSCLC. There would be one or more putative tumor suppressor gene(s) on the long arm of chromosome 2. Loss of the gene(s) presumably contributes to the carcinogenesis of human non-small-cell lung cancer.

Adult↗