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Biomedical subjects

Q Lu

Publications and source records attributed to Q Lu.

At least 127 records · Page 7Linked to original sources
PubMed1999

The effect of estrogen on aromatase and vascular endothelial growth factor messenger ribonucleic acid in the normal nonhuman primate mammary gland.

In the present study, the baboon was used as a model to investigate the effects of steroid hormones on vascular endothelial growth factor (VEG/PF) and aromatase expression and on proliferation of the normal mammary gland. Immunocytochemistry revealed that both aromatase and VEG/PF were expressed in the epithelial cells of the terminal ductal lobular units. Mammary tissue biopsies were obtained from female baboons during the follicular and luteal phases of the menstrual cycle, 4 weeks after ovariectomy (OVX), and after 2 weeks of treatment with estradiol benzoate (E2B; 500 microg/day, i.m.). Although there was little apparent difference in aromatase messenger ribonucleic acid (mRNA) in tissue from follicular and luteal phases or after ovariectomy, aromatase mRNA was decreased in tissue from ovariectomized (OVX) animals treated for 2 weeks with E2B. Furthermore, aromatase activity in tissue from these animals was markedly reduced compared to activity in tissue from the OVX animals before treatment (P < 0.001). In one animal in which mammary aromatase activity was measured sequentially during the follicular and luteal phases, aromatase activity was increased significantly after OVX and was reduced to the level in the intact animal by subsequent treatment with E2B. This effect on both aromatase activity and mRNA occurred rapidly 2 and 4 h after injection with E2B. In contrast to its effect on aromatase, E2B treatment of OVX animals stimulated VEG/PF mRNA 2 and 4 h after injection. In histoculture of mammary biopsies from these animals in the follicular and luteal phases of the menstrual cycle or after OVX, [3H]thymidine incorporation was increased significantly by incubation with testosterone (T) as well as estrogen (P < 0.01). The effect of T was blocked by aromatase inhibitor, 4-hydroxyandrostenedione, suggesting that the tissue is responsive to E produced by aromatization of T in the tissue. When mammary tissue from OVX animals was cultured with T, there was a significantly greater increase in [3H]thymidine incorporation than in histocultures of tissue from intact animals (P < 0.01). However, in histocultures of tissue from the OVX animals treated with E2B (500 microg) for 2 weeks, [3H]thymidine incorporation was similar to the level in tissue of intact animals incubated with T. No significant changes occurred in [3H]thymidine incorporation with the nonaromatizable androgen dihydrotestosterone or progesterone alone. These findings suggest that estrogens produced locally by aromatization of T have a functional role in mammary tissue. Aromatase expressed in the mammary gland could be important in maintaining local estrogen concentrations, particularly after menopause. Estrogen appears to regulate transcription of both aromatase and VEG/PF in the mammary gland, suggesting a regulatory loop by which local estrogens could stimulate VEG/PF production. Thus, paracrine/autocrine mechanisms that can enhance the proliferation of malignant cells and their metastatic spread already exist before transformation.

Animals↗
PubMed1999

Aromatase inhibitors and their antitumor effects in model systems.

The potential of aromatase (estrogen synthetase) within the breast to provide a significant source of estrogen mediating tumor proliferation is suggested by studies reporting 4- to 6-fold higher estrogen levels in tumors than in plasma of postmenopausal patients with breast cancer. Recent studies in our laboratory have identified aromatase and its mRNA in tumor epithelial cells using immunocytochemistry and in situ hybridization. In addition, significant aromatase activity, which was stimulated 7-fold by dexamethasone, was measured in metastatic cells isolated from a breast cancer patient. Increase in proliferation, as measured by proliferating cell nuclear antigen immunostaining in tumor sections and by thymidine incorporation into DNA in response to testosterone, was observed in histocultures of breast cancer samples. This latter effect could be inhibited by 4-hydroxyandrostenedione. These results imply that intratumoral aromatase has functional significance and may be an important target for successful inhibitor treatment of breast cancer patients. To investigate treatment strategies with aromatase inhibitors and antiestrogens, we developed an intratumoral aromatase model to simulate the hormone responsive postmenopausal breast cancer patient. Tumors of estrogen receptor positive human breast carcinoma cells (MCF-7) transfected with the human aromatase gene are grown in ovariectomized nude mice. These cells synthesize sufficient estrogen to stimulate tumor formation. We have utilized this model to investigate the effects on tumor growth of the antiestrogens, tamoxifen and ICI 182780, and the aromatase inhibitors, letrozole and anastrozole (arimidex), alone and in combination. Both the aromatase inhibitors and the antiestrogens were effective in suppressing tumor growth. However, letrozole was significantly more effective than the antiestrogens. When the aromatase inhibitors were combined with the antiestrogen, tamoxifen, tumor growth was suppressed to about the same extent as with the aromatase inhibitors alone. Furthermore, the results do not suggest any benefit from combining tamoxifen with the pure antiestrogen, ICI 182780. Thus sequential use of these agents is likely to be more advantageous to the patient in terms of longer duration of effective treatment.

Animals↗
PubMed1999

CNTF, not other trophic factors, promotes axonal regeneration of axotomized retinal ganglion cells in adult hamsters.

PURPOSE: To investigate the in vivo effects of trophic factors on the axonal regeneration of axotomized retinal ganglion cells in adult hamsters. METHODS: The left optic nerve was transected intracranially or intraorbitally, and a peripheral nerve graft was apposed or sutured to the axotomized optic nerve to enhance regeneration. Trophic factors were applied intravitreally every 5 days. Animals were allowed to survive for 3 or 4 weeks. Regenerating retinal ganglion cells (RGCs) were labeled by applying the dye Fluoro-Gold to the distal end of the peripheral nerve graft 3 days before the animals were killed. RESULTS: Intravitreal application of ciliary neurotrophic factor substantially enhanced the regeneration of damaged axons into a sciatic nerve graft in both experimental conditions (intracranial and intraorbital optic nerve transections) but did not increase the survival of distally axotomized RGCs. Basic fibroblast growth factor and neurotrophins such as nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 failed to enhance axonal regeneration of distally axotomized RGCs. CONCLUSIONS: Neurons of the adult central nervous system can regenerate in response to trophic supply after injury, and ciliary neurotrophic factor is at least one of the trophic factors that can promote axonal regeneration of axotomized RGCs.

Animals↗
PubMed1999

Population distributions of allele frequency of apolipoprotein E by age and gender in Han Chinese.

AIM: To study apolipoproteins E (ApoE) allele frequency in Han Chinese based on age and gender from Shanghai metropolitan area. METHODS: Healthy Han Chinese people (F: 237 and M: 412) were involved in this study. ApoE gene was amplified by PCR using the forward primer: 5'-GGC ACG GCT GTC CAA GGA GCT-3' and reverse primer: 5'-GAT GGC GCT GAG GCC GCG CT-3'. The PCR product was digested directly with 5 units of CfoI and separated by a 20% polyacrylamide nondenaturing gel. RESULTS: ApoE*3 was the commonest allele which accounted for 86.4% of the isoforms, and ApoE*2 and ApoE*4 accounted for 6.2% and 7.5%, respectively. The allele and genotype frequencies were in Hardy-Weinberg equilibrium by comparison with that of the corresponding theoretical distribution (P > 0.05). CONCLUSION: The frequencies of ApoE*2, ApoE*3, and ApoE*4 were demonstrated in the normal Chinese population.

Adult↗
PubMed1999

Gut-derived mesenteric lymph: a link between burn and lung injury.

BACKGROUND: Previously, we showed that mesenteric lymph generated following hemorrhagic shock increases endothelial cell permeability and contributes to lung injury. It has also been shown that lymph produced at the site of burn injury plays a role in altering pulmonary vascular hemodynamics. In addition, previous experimental work has suggested that organs and tissues distant from the injury site may contribute to pulmonary dysfunction. One explanation would be that gut-derived inflammatory factors (in addition to those produced locally at the site of injury) are reaching the pulmonary circulation, where they exert their effects via the gut lymphatics. HYPOTHESES: The 2 hypotheses herein were that (1) gut-derived factors carried in the mesenteric lymph of rats generated following thermal injury will contribute to lung injury and (2) intestinal bacterial overgrowth will potentiate the degree of burn-induced lung injury. These hypotheses were tested by examining the effect of mesenteric lymph flow interruption prior to thermal injury on burn-induced lung injury in rats with a normal intestinal bacterial flora and in rats with intestinal Escherichia coli overgrowth. These rats were termed E. coli-monoassociated rats. METHODS: Normal intestinal bacterial flora and monoassociated male Sprague-Dawley rats were subjected to sham burn, 40% total body surface area burn, or lymphatic division plus burn. After 3 hours, 10 mg of Evans blue was injected to measure lung permeability. After the rats were killed, a bronchoalveolar lavage was performed and the fluid analyzed spectrophotometrically. Bronchoalveolar lavage fluid protein content, pulmonary myeloperoxidase activity, and alveolar apoptosis served to further quantitate lung injury. RESULTS: Both normal intestinal bacterial flora and monoassociated-burned rats exhibited significant increases in lung permeability, bronchoalveolar lavage fluid protein content, myeloperoxidase activity, and alveolar apoptosis. The combination of monoassociation and thermal injury resulted in even further increases in lung injury over thermal injury alone. Lymphatic division prior to thermal injury ameliorated burn-induced increases in lung permeability, bronchoalveolar lavage fluid protein content, pulmonary myeloperoxidase accumulation, and alveolar apoptosis in both normal intestinal bacterial flora and monoassociated rats. CONCLUSIONS: The results of this study support the hypothesis that gut-derived factors carried in the mesenteric lymph contribute to burn-induced lung injury and may therefore play a role in postburn respiratory failure and suggest that intestinal bacterial overgrowth primes the host such that when animals are exposed to a second stimulus (such as thermal injury) an exaggerated response occurs.

Animals↗
PubMed1999

[Study on double antigens sandwich enzyme immunoassay for detection of Brucella specific antibodies in human and animals].

OBJECTIVE: In order to develop practicable methods for serodiagnosis, surveillance and epidemiological surveys in human and animals Brucellosis. METHODS: A double antigens sandwich Enzyme Immunoassay (DAgS-EIA include DAgS-ELISA and DAgS-DIEA) have been developed under the basis of first production conjugate of Brucella antigen with horseradish peroxidase. Serum samples from diagnosed patients, suspected patients of Brucellosis and sheep infected with Brucella in Henan and Hebei provinces as well as from experimental animals of infected with Brucella in laboratory detected through DAgS-EIA, I-ELISA, RBPT and SAT tests. RESULTS: Of the diagnosed and suspected Brucellosis patients, positive rates of DAgS-ELISA, RBPT, I-ELISA, DAgS-DIEA and SAT were 60.0%-62.9%, 48.6%-58.1%, 55.6%, 53.7% and 44.2% respectively; as for sheep with Brucella-infection, positive rate of the above mentioned 5 tests were 81.8%. CONCLUSION: Results showed that DAgS-EIA were not only specific and practicable but may use for Brucella specific antibodies detection in humans and various animals with only one conjugate of Brucella antigen with horseradish peroxidase.

Animals↗
PubMed1999

[A novel alternative splicing mode of the erythropoietin receptor gene in rats].

OBJECTIVE: To detect new alternative splicing mode of erythropoietin receptor (EpoR) gene in normal rats. METHODS: Total RNAs were isolated from bone marrow mononuclear cells of normal Wistar rats. Reverse transcriptase polymerase chain reaction (RT-PCR) of the total RNAs was done and the amplified products were sequenced. RESULTS: After RT-PCR with a pair of primers (sense: 637/657 bp, and antisence: 903/882 bp), two bands were detected, the expected band (267 bp) and a longer one (346 bp) which had a 79 bp insert between 736th and 737th bases from the first ATG of the rat EpoR nucleotide. Sequence analysis showed that the 79 bp insert was the retaining intron 5 with a C-to-T point mutation at 16th base and an insertion of G base between 49th and 50th base. The insertion of G base caused a shift in reading frame and resulted EpoR with a truncated intracellular domain. CONCLUSION: A new alternative splicing of EpoR mRNA encoding truncated intracellular domain was identified in normal Wistar rats. Its implication in rat erythropoiesis remains to be determined.

Alternative Splicing↗
PubMed1999

[Study on regulators of the cell cycle in cutaneous squamous cell carcinoma].

In order to investigate the relationship between the regulators of cell cycle and cutaneous squamous cell carcinoma(SCC), we used an immunohistochemical staining technique to examine the expression of cyclin D1, p16 and Rb in the paraffin embedded skin cancer tissues of 30 patients with SCC. The positive percentage of cyclin D1, CDK4, p16 and Rb was 66.7%, 53.3%, 33.3%, and 36.7%, respectively. The overexpression of cyclin D1 and CDK4 could be observed frequently in low grade of differentiated cells, especially in marginal cells of the cancer nest. The results indicate that the aberrant expression of positive and negative regulators of the cell cycle may be involved in the carcinogenesis and evolution of SCC.

Carcinoma, Squamous Cell↗
PubMed1998

Effects of some novel inhibitors of C17,20-lyase and 5alpha-reductase in vitro and in vivo and their potential role in the treatment of prostate cancer.

The effects of some novel steroidal compounds were evaluated against both human C17,20-lyase and 5alpha-reductase in vitro and also against androgen synthesis in normal male rats. L-2, L-36, L-37, and I-41 showed potent inhibition of human testicular C17,20-lyase, with IC50s of 43, 39, 42, and 58 nM, respectively. In contrast, ketoconazole, a competitive inhibitor of C17,20-lyase, had an IC50 of 76 n.M. L-36 also showed potent inhibitory activity against 5a-reductase in human prostatic microsomes, with an IC50 of approximately 31 nM. The inhibitory activities of L-2 and 1-41 on 5alpha-reductase were moderate, with IC50s of 75 and 151 nM, respectively, whereas L-37 showed little inhibitory activity against this enzyme. In comparison, finasteride, a potent inhibitor of 5alpha-reductase, had an IC50 of 33 nM. When normal male rats were treated with these novel compounds (50 or 100 mg/kg/day) for 14 consecutive days, the wet weight of the prostate was significantly reduced by L-36, L-37, and I-41, compared to the control group. Testosterone levels in rat serum were also reduced by L-36 (55%), L-37 (86%), and I-41 (53%). The concentrations of testosterone in rat testes were reduced by these novel compounds by 13-74%. The compounds also reduced the concentration of testosterone in rat prostates by 35-75%. Similarly, dihydrotestosterone (DHT) concentration in rat serum was reduced 30-89% by these compounds, compared to the control group. Prostatic DHT levels were also lower in rats treated with L-36 (48%), L-37 (54%), or I-41 (26%). In contrast, L-2 enhanced serum testosterone and prostatic DHT concentrations by >50%. These findings suggest that the dual activities of several of these novel inhibitors of C17,20-lyase and 5alpha-reductase accounts for the diminished levels of circulating androgens in vivo.

Androgens↗
PubMed1998

Antihyperglycemic activities of cryptolepine analogues: an ethnobotanical lead structure isolated from Cryptolepis sanguinolenta.

Cryptolepine (1) is a rare example of a natural product whose synthesis was reported prior to its isolation from nature. In the previous paper we reported the discovery of cryptolepine's antihyperglycemic properties. As part of a medicinal chemistry program designed to optimize natural product lead structures originating from our ethnobotanical and ethnomedical field research, a series of substituted and heterosubstituted cryptolepine analogues was synthesized. Antihyperglycemic activity was measured in vitro and in an NIDDM mouse model to generate the first structure-bioactivity study about the cryptolepine nucleus.

3T3 Cells↗
PubMed1998

Purification, characterization and molecular cloning of TGP1, a novel G-DNA binding protein from Tetrahymena thermophila.

G-DNA, a polymorphic family of four-stranded DNA structures, has been proposed to play roles in a variety of biological processes including telomere function, meiotic recombination and gene regulation. Here we report the purification and cloning of TGP1, a G-DNA specific binding protein from Tetrahymena thermophila. TGP1 was purified by three-column chromatographies, including a G-DNA affinity column. Two major proteins (approximately 80 and approximately 40 kDa) were present in the most highly purified column fraction. Renaturation experiments showed that the approximately 80 kDa protein contains TGP1 activity. Biochemical characterization showed that TGP1 is a G-DNA specific binding protein with a preference for parallel G-DNAs. The TGP1/DNA complex has a dissociation constant (Kd) of approximately 2.2 x 10(-8) M and TGP1 can form supershift in gel mobility shift assays. The cDNA coding TGP1 was cloned and sequenced based upon an internal peptide sequence obtained from the approximately 80 kDa protein. Sequence analyses showed that TGP1 is a basic protein with a pI of 10.58, and contains two extensively hydrophilic and basic domains. Homology searches revealed that TGP1 is a novel protein sharing weak similarities with a number of proteins.

Amino Acid Sequence↗
PubMed1998

Ethnobotanical-directed discovery of the antihyperglycemic properties of cryptolepine: its isolation from Cryptolepis sanguinolenta, synthesis, and in vitro and in vivo activities.

Using an ethnobotanical approach in combination with in vivo-guided fractionation as a means for lead discovery, cryptolepine was isolated as an antihyperglycemic component of Cryptolepis sanguinolenta. Two syntheses of cryptolepine, including an unambiguous synthesis, are reported. The hydroiodide, hydrochloride, and hydrotrifluoromethanesulfonate (hydrotriflate) salts of cryptolepine were synthesized, and a comparison of their spectral properties and their in vitro activities in a 3T3-L1 glucose transport assay is made. Cryptolepine and its salt forms lower blood glucose in rodent models of type II diabetes. While a number of bioactivities have been reported for cryptolepine, this is the first report that cryptolepine possesses antihyperglycemic properties.

3T3 Cells↗
PubMed1998

Laser assisted soldering: microdroplet accumulation with a microjet device.

BACKGROUND AND OBJECTIVE: We investigated the feasibility of a microjet to dispense protein solder for laser assisted soldering. STUDY DESIGN: Successive micro solder droplets were deposited on rat dermis and bovine intima specimens. Fixed laser exposure was synchronized with the jetting of each droplet. After photocoagulation, each specimen was cut into two halves at the center of solder coagulum. One half was fixed immediately, while the other half was soaked in phosphate-buffered saline for a designated hydration period before fixation (1 hour, 1, 2, and 7 days). After each hydration period, all tissue specimens were prepared for scanning electron microscopy (SEM). RESULTS: Stable solder coagulum was created by successive photocoagulation of microdroplets even after the soldered tissue exposed to 1 week of hydration. CONCLUSIONS: This preliminary study suggested that tissue soldering with successive microdroplets is feasible even with fixed laser parameters without active feedback control.

Animals↗
PubMed1998

Topographic guidance labels in a sensory projection to the forebrain.

Visual connections to the mammalian forebrain are known to be patterned by neural activity, but it remains unknown whether the map topography of such higher sensory projections depends on axon guidance labels. Here, we show complementary expression and binding for the receptor EphA5 in mouse retina and its ligands ephrin-A2 and ephrin-A5 in multiple retinal targets, including the major forebrain target, the dorsal lateral geniculate nucleus (dLGN). These ligands can act in vitro as topographically specific repellents for mammalian retinal axons and are necessary for normal dLGN mapping in vivo. The results suggest a general and economic modular mechanism for brain mapping whereby a projecting field is mapped onto multiple targets by repeated use of the same labels. They also indicate the nature of a coordinate system for the mapping of sensory connections to the forebrain.

Aging↗
PubMed1998

Isolation and unambiguous synthesis of cryptolepinone: An oxidation artifact of cryptolepine

Cryptolepinone (3) was isolated as an artifact of extraction from Cryptolepis sanguinolenta. Previously, this compound had been identified as the natural products hydroxycryptolepine (2) and 3. Synthesis via an unambiguous pathway has confirmed the structure of cryptolepinone. Spectroscopic studies in various solvents have shown that the natural product artifact or its synthetic equivalent can exist in the keto (cryptolepinone) or enol (hydroxycryptolepine) form.

Journal Article↗