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Biomedical subjects

L H Xu

Publications and source records attributed to L H Xu.

36 records · Page 2Linked to original sources
PubMed1996

Attenuation of the expression of the focal adhesion kinase induces apoptosis in tumor cells.

The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase implicated in integrin-mediated signal transduction pathways, oncogenic transformation by v-src, and the invasion of human tumors. The overexpression of p125FAK in a variety of human tumors and tumor cell lines in comparison to their nontransformed counterparts suggested that attenuation of p125FAK expression might have an effect on tumor cell proliferation. In this study, we have treated tumor cell lines that expressed high levels of p125FAK with different antisense oligonucleotides to FAK, and have specifically attenuated p125FAK expression. The cells treated with antisense oligonucleotides not only lost their attachment, but also underwent apoptosis. Extensive control oligonucleotide experiments suggested that this attenuation was highly FAK specific. Furthermore, normal human fibroblasts, which did not express high levels of p125FAK, did not lose their attachment or become apoptotic with FAK antisense treatment. These results suggested that FAK is involved in adhesion-mediated growth in tumor cells and that FAK may be a rational gene-directed target for disrupting tumor cell growth.

Apoptosis↗
PubMed1995

Estrogen-induced anchorage-independence in human endometrial stromal cells.

Estrogens are important etiologic agents for most gynecologic malignancies, and chronic exposure to estrogen that is unopposed by progestins conveys the greatest risk. Treatments with estrogen facilitate the process of malignant transformation in rodents, but relatively few studies of estrogen-induced carcinogenesis have been performed using human cells. Most malignancies in estrogen-responsive tissues arise from epithelial cells, but an increasing body of evidence emphasizes the role of stromal cells as mediators of the effects of estrogens on epithelial cells. Our studies were designed to assess estrogens as carcinogens for human endometrial stromal cells and to provide a basis for studies of the role of stroma in estrogen-induced carcinogenesis in humans. Acute treatments with the estrogens diethylstilbestrol (DES), 17 beta-estradiol (E2) and beta-dienestrol enhance anchorage-independent proliferation (AIP) of SV40-immortalized human endometrial stromal cells in the rank order of DES > E2 > beta-dienestrol. The anti-estrogenic compound tamoxifen inhibits DES-induced AIP. The magnitude of DES-induced AIP increases with prolonged duration of treatment. After 11 months of chronic treatment with 0.1 nM DES, AIP was 20-fold higher than in vehicle-treated control cultures. Expression of the estrogen receptor was altered by treatments with DES in parallel with increased capacity for AIP. These conditionally immortal human endometrial stromal cells appear to be a good model for estrogen-induced transformation of human cells.

Base Sequence↗
PubMed1995

Receptor tyrosine kinases expressed in metastatic colon cancer.

Using a PCR-based cloning technique, we have isolated a series of DNA fragments coding for tyrosine kinases that are expressed in a metastatic human colon tumor, and have subsequently analyzed their expression pattern at the protein level in human tumors. We identified both the alpha and the beta forms of the platelet-derived growth factor receptor (PDGFR), axl and 8 other genes, including 3 cytoplasmic tyrosine kinases. To study their expression in human colon cancer, we performed Western blots of matched sets of normal tissues and of carcinomas from the same patient. These revealed that the alpha-PDGFR migrates predominantly as a 200-kDa band in 8/8 normal tissues, and as a 170-kDa band in 17/17 malignant tissues, as well as in colonic polyps, suggesting that expression of an isoform of this receptor may be a marker for the progression of colon cancer. Additional studies showed that the Axl receptor tyrosine kinase was expressed at 10-fold higher levels in a peritoneal metastatic nodule than in other normal and malignant tissues. Immunohistochemistry revealed Axl over-expression specifically in the malignant cells of the tumor. This indicates that over-expression and possibly a differential processing event of tyrosine kinase receptors may be involved in colon cancer, and that they are potential markers for the progression of this disease.

Amino Acid Sequence↗
PubMed1994

Electron microscopic observations of tegumental damage in adult Schistosoma japonicum after in vivo treatment with levo-praziquantel.

The in vivo effects of a single dose of levo-praziquantel, 75 mg/kg in PEG 400, on the tegumental surface of adult S. japonicum were compared with the effects of a single dose (150 mg/kg) of the mixed isomer preparation, using scanning and transmission electron microscope. Worms were recovered from mice at 10 min, 30 min, 1 hr, 4 hr, 12 hr, 24 hr and 48 hr after treatment. After 10 min exposure to either compound, the tegumental folds and sensory organelles were swollen and the tegument vacuolated. After 12-24 hr, the surface was eroded and exfoliated with exposure of intrategumental and/or subtegumental tissues and attachment of leukocytes to the denuded areas. Vehicle controls were normal throughout the time period examined. These studies demonstrate that the levo isomer of praziquantel causes acute structural damage to the tegument similar to that seen with the mixed isomer preparation.

Animals↗
PubMed1993

Hypothalamic and gastric myoelectrical responses during vection-induced nausea in healthy Chinese subjects.

The physiology of nausea, a uniquely human symptom, is poorly understood. The purpose of this study was to measure the temporal sequences of neurohormonal responses and gastric myoelectrical activity in healthy subjects during the rotation of an optokinetic drum that produced nausea and other symptoms of motion sickness. Plasma catecholamines, vasopressin, and cortisol were measured at baseline, during minutes 1-5, 6-10, and 11-15 of drum rotation, and after rotation stopped. Electrogastrograms were recorded throughout the study. Twelve subjects (80%) developed nausea and 4-9 cycles/min of gastric tachyarrhythmias; three subjects had no nausea and no gastric dysrhythmias. Tachyarrhythmias began 3.4 +/- 0.8 min after the onset of drum rotation, and nausea was reported, on average, 3 min later. During minutes 6-10 of drum rotation, vasopressin levels significantly increased in the subjects with nausea compared with subjects without nausea (P < 0.04). In the subjects with nausea, epinephrine and vasopressin increased significantly (P < 0.05) compared with baseline during minutes 6-10 and 11-15 of drum rotation. As nausea resolved during recovery, vasopressin decreased by 74%, whereas epinephrine increased 13%. We conclude that 1) in nauseated subjects, endogenous vasopressinergic and sympathetic circuits are activated before hypothalamic-pituitary-adrenal pathways, 2) plasma vasopressin levels correlate most closely with the temporal onset and resolution of nausea, and 3) peripheral gastric dysrhythmias may have a role in activating central vasopressinergic neurons.

Adult↗
PubMed1993

Expression of tissue kallikrein in normal and SV40-transfected human endometrial stromal cells.

The polymerase chain reaction with specific tissue kallikrein primers was utilized to demonstrate the presence of tissue kallikrein mRNA in human endometrial stromal cells. Enzymatic analysis measured with a specific tripeptide nitroanilide substrate demonstrated the presence of tissue kallikrein in the conditioned medium obtained from both normal stromal cells and stromal cells transfected with an origin-defective temperature-sensitive SV40 large T antigen. The transfected stromal cell supernatant exhibited approximately twice as much tissue kallikrein activity as normal stromal cells at 60-100% of cell confluence. The release of tissue kallikrein from transfected stromal cells was confirmed by Western blot analysis and [35S]-methionine incorporation into a 35-kD protein which retains tissue kallikrein activity. These results demonstrate for the first time the expression and secretion of tissue kallikrein in human endometrial stromal cells and provide evidence of possible involvement of tissue kallikrein in cell transformation.

Base Sequence↗
PubMed1990

Synthesis and antiviral and cytotoxic activity of iodohydrin and iodomethoxy derivatives of 5-vinyl-2'-deoxyuridines, 2'-fluoro-2'-deoxyuridine, and uridine.

A series of new 5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine and uridine compounds (11, 16) was synthesized by the regiospecific addition of HOI to the vinyl substituent of 5-vinyl-2'-deoxyuridine (10a), 5-vinyl-2'-fluoro-2'-deoxyuridine (10b), 5-vinyluridine (10c), and (E)-5-(2-iodovinyl)-2'-deoxyuridine (4b). Treatment of the iodohydrins 11a-c with methanolic sulfuric acid afforded the corresponding 5-(1-methoxy-2-iodoethyl) derivatives (12a-c). In contrast, reaction of 5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine (11a) with sodium carbonate in methanol afforded a mixture of 5-(1-hydroxy-2-methoxyethyl)-2'-deoxyuridine (13) and 2,3-dihydro-3-hydroxy-5-(2'-deoxy-beta-D-ribofuranosyl)- furano[2,3-d]pyrimidin-6(5H)-one (14). The most active compound, 5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine (12a, ID50 = 0.1 micrograms/mL), which exhibited antiviral activity (HSV-1) 100-fold higher than that of the 5-(1-hydroxy-2-iodoethyl) analogue (11a), was less active than IVDU or acyclovir (ID50 = 0.01-0.1 micrograms/mL range). The C-5 substituent in the 2'-deoxyuridine series was a determinant of cytotoxic activity, as determined in the in vitro L1210 screen, where the relative activity order was CH(OH)CHI2 (16) greater than CH(OMe)CH2I (12a) greater than CH(OH)CH2I (11a) congruent to CH(OH)CH2OMe (13). The 2'-substituent was also a determinant of cytotoxic activity in the 5-(1-hydroxy-2-iodoethyl) (11a-c) and 5-(1-methoxy-2-iodoethyl) series of compounds, where the relative activity profile was 2'-deoxyuridine greater than 2'-fluoro-2'-deoxyuridine greater than uridine (11a greater than 11b greater than or equal to 11c; 12a greater than 12b greater than 12c). The most active cytotoxic agent (16), possessing a 5-(1-hydroxy-2,2-diiodoethyl) substituent (ED50 = 0.77 micrograms/mL), exhibited an activity approaching that of melphalan (ED50 = 0.15 micrograms/mL). All compounds tested, except for 13 and 14, exhibited high affinity (Ki = 0.035-0.22 mM range relative to deoxyuridine, Ki = 0.125) for the murine NBMPR-sensitive erythrocyte nucleoside transport system, suggesting that these iodohydrins are good permeants of cell membranes.

Animals↗
PubMed1990

Prevalence of age-related cataract in Ganzi and Shanghai. The Epidemiological Study Group.

It has been reported that the prevalence of cataract is much higher in plateau than that in plain regions. But the data are incomplete and can not be compared because of different examination methods and different diagnostic criteria. A small group of ophthalmologists was sent to Ganzi, Sichuan Province at the altitude of 3.393 m, and to Qinpu in the suburb of Shanghai which is at the sea level. In Ganzi 3,905 (91.97%) people including 822 Hans and 3,083 Zang and in Qinpu 3,101 (93.20%) were studied. Age-related cataract was diagnosed when there are cortical or nuclear, or mixed opacities; and aphakia due to previous extraction of age-related cataract. Direct method was used to standardize the data. The prevalence of age-related cataract in Ganzi is about 82% higher than that in Qinpu in all age groups; from age 16-60, the prevalence of age-related cataract in Ganzi is about 180% (in Hans) and 160% (in Zangs) higher than that in Qinpu. There is no significant difference in the prevalence of age-related cataract between the ethnic groups in Ganzi. In Ganzi, the sunshine hours per year are 1.28 times that in Qinpu, and the global radiation in Ganzi is 1.47 times that in Qinpu. The higher prevalence of cataract in Ganzi than in Qinpu may be due to the greater exposure to the sunshine on the Tibetan plateau. The differences in prevalence between males and females and between indoor and outdoor work are discussed.

Adolescent↗
PubMed1989

Synthesis and tumor uptake of 5-82Br- and 5-131I-labeled 5-halo-1-(2-fluoro-2-deoxy-beta-D-ribofuranosyl)uracils.

A synthesis of 5-bromo- and 5-iodo-1-(2-fluoro-2-deoxy-beta-D-ribofuranosyl)uracil (3 and 4) and their 5-82Br and 5-131I analogues has been developed. The tissue distribution of the radiolabeled compounds in BDF1 mice bearing Lewis lung tumors has been investigated. After injection of the radiolabeled analogues of compounds 3 and 4 there was a rapid initial excretion of activity. Compound 3 was excreted unchanged in the urine. Residual activity in mice after 4 h showed a distribution characteristic of bromide (Br-). Compound 4 was excreted mainly as unchanged starting material with increasing amounts of iodide (I-) detected at later time periods, in addition to 5-iodouridine and unidentified metabolites at shorter time periods. Both 3 and 4 demonstrated a remarkable in vivo stability relative to related 5-substituted nucleosides that do not contain the 2'-fluoro group. The tumor uptake was minimal, with only the 5-bromo analogue demonstrating a slight elevation in tumor to blood ratios relative to other tissues. Compounds 3 and 4 were shown to compete with thymidine for the same binding site in the transport of nucleosides across the cell membrane in mouse erythrocytes. The inhibition constants (Ki) show that the compounds were weak competitors of thymidine binding to pyrimidine nucleoside transporter compared to physiological nucleosides. Other evidence indicates that compounds 3 and 4 are not substrates for mammalian kinase enzymes.

Animals↗
PubMed1989

[Studies on actinomycete flora and resources in the plateau lakes in Yunnan].

During the period of 1983 to 1987 mud and water samples were collected from 12 larger lakes on the Yunnan Plateau. The actinomycetes in both sediment and water samples were investigated. Strains producing metabolites were screened by various procedures. The results are as follow: 1. The number and composition of actinomycetes in a lake were found to have relation to the physical and chemical features of the water-body. On the basis of the number and generic diversity of actinomycetes, lakes were thus divided into four groups. 2. Micromonospora occupied a notable domonance in benthic samples taken from all 12 lakes. This is a conspicuous characteristics of actinomycete flora in these lakes. 3. The population of actinomycetes in Lakes Qilu, Yilong and Datun ranges from 2991 to 3542 X 10(3)/g dry wt. of mud. 4. Strains of Actinomadura, Microtetraspora, Micropolyspora, Saccharomonospora and Saccharopolyspora were isolated. These genera were not previously reported in similar studies abroad. In addition, five species were considered to be new to science: Micromonospora phaeovirida Jiang et Xu, 1985 Saccharomonospora yunnanensis Jiang et Xu, 1985 Microtetraspora flavorosea Jiang et Xu, 1986 Actinomadura chenghaiensis Jiang et Xu, 1986 Actinomadura viridoflava Jiang et Xu, 1986 5. Studies indicate that actinomycetes possibly play an important role in the decomposition of chitin, cellulose and some toxic substances in lakes. 6. As freshwater resources, actinomycetes produce various useful metabolites such as fibrinolysine, and milk-clotting enzyme.

Actinomycetaceae↗
PubMed1989

[Studies on the fine structure of Toxoplasma gondii tachyzoite].

Toxoplasma gondii tachyzoite was crescent-shaped. The pellicle of the parasite consisted of two membranes. The anterior end contained the polar ring and conoid, the former being the thickened inner membrane and the latter a cylindrical organelle which was made up of about 10 filaments arranged in an oblique row. The subpellicular microtubules numbering 22 originated at the polar ring and extended to the posterior end. The rhoptries extended from the conoid and terminated anterior to the nucleus with a narrow dense neck and an enlarged posterior portion with a glandular structure. The rhoptries perhaps had a secretory function and the conoid might be related to the invasion of the tachyzoite into the host cell.

Animals↗
PubMedDate not supplied

Asian hypersusceptibility to motion sickness.

A rotating optokinetic drum was used in three laboratory studies to test the hypothesis that Asian subjects are hypersusceptible to motion sickness. The results of the first study showed that Chinese women compared to European-American and African-American women experienced significantly more severe symptoms of motion sickness and greater disturbance of normal gastric myoelectric activity. A second study yielded similar results using American-born children of Asian parents. The results of a third study using Chinese men and women were similar and showed a significant increase in vasopressin during rotation. Possible genetic mechanisms that may account for these results are discussed.

Adolescent↗