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C Liu

Publications and source records attributed to C Liu.

At least 343 records · Page 19Linked to original sources
PubMed1999

beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation.

Regulation of beta-catenin stability is essential for Wnt signal transduction during development and tumorigenesis. It is well known that serine-phosphorylation of beta-catenin by the Axin-glycogen synthase kinase (GSK)-3beta complex targets beta-catenin for ubiquitination-degradation, and mutations at critical phosphoserine residues stabilize beta-catenin and cause human cancers. How beta-catenin phosphorylation results in its degradation is undefined. Here we show that phosphorylated beta-catenin is specifically recognized by beta-Trcp, an F-box/WD40-repeat protein that also associates with Skp1, an essential component of the ubiquitination apparatus. beta-catenin harboring mutations at the critical phosphoserine residues escapes recognition by beta-Trcp, thus providing a molecular explanation for why these mutations cause beta-catenin accumulation that leads to cancer. Inhibition of endogenous beta-Trcp function by a dominant negative mutant stabilizes beta-catenin, activates Wnt/beta-catenin signaling, and induces axis formation in Xenopus embryos. Therefore, beta-Trcp plays a central role in recruiting phosphorylated beta-catenin for degradation and in dorsoventral patterning of the Xenopus embryo.

Animals↗
PubMed1999

Interaction between terminal complement proteins C5b-7 and anionic phospholipids.

We have recently shown that C5b-6 binds to the erythrocyte membrane via an ionic interaction with sialic acid before the addition of C7 and subsequent membrane insertion. In this study we assessed the role of anionic lipids in the binding of the terminal complement proteins to the membrane and the efficiency of subsequent hemolysis. Human erythrocytes were modified by insertion of dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylserine (DPPS), dipalmitoyl phosphatidylethanolamine (DPPE), or dipalmitoyl phosphatidic acid (DPPA). Lipid incorporation and the hemolytic assays were done in the presence of 100 micromol/L sodium orthovanadate to prevent enzymatic redistribution of lipid. We found that the neutral lipids, DPPC and DPPE, did not affect C5b-7 uptake or hemolysis by C5b-9. In contrast, the two acidic phospholipids, DPPS and DPPA, caused a dose-dependent increase in both lysis and C5b-7 uptake. We conclude that the presence of anionic lipids on the exterior face of the membrane increases C5b-7 uptake and subsequent hemolysis. It is known that sickle cell erythrocytes have increased exposure of phosphatidylserine on their external face and are abnormally sensitive to lysis by C5b-9. The data presented here provide a plausible mechanism for this increased sensitivity.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Identification of a site of Hsp27 binding with Hsp27 and alpha B-crystallin as indicated by the yeast two-hybrid system.

The small heat-shock proteins (sHsp), including Hsp27 and alphaB-crystallin, usually form large oligomers in cells. It has been suggested that the sHsp form oligomers by binding either a conserved C-terminal amino acid sequence or the less conserved N-terminal region. However, the site of binding has not been precisely determined. We used the yeast two-hybrid system to investigate binding of full-length rat Hsp27 or fragments of Hsp27 to full-length rat Hsp27 or alphaB-crystallin molecules. A series of cDNAs coding for fragments of Hsp27 were generated and ligated with the coding sequence for the binding domain of the yeast Gal4p transcription factor. These cDNAs were each transfected into yeast that had been transfected to express full-length rat Hsp27 or alphaB-crystallin fused with the DNA binding domain of Gal4p. Yeast cells transfected with both plasmids were assayed, by both a beta-galactosidase (beta-gal) filter assay and a quantitative liquid assay, for activation of Gal4p-driven beta-gal expression. Results indicated that the N-terminal domain of Hsp27 consisting of amino acids 1-124 did not bind to Hsp27 or alphaB-crystallin. The predominant Hsp27-Hsp27/alphaB-crystallin binding domain was the conserved C-terminal region consisting of amino acids 141-206, particularly amino acids 141-176.

Animals↗
PubMed1999

The transcription factor EGR-1 suppresses transformation of human fibrosarcoma HT1080 cells by coordinated induction of transforming growth factor-beta1, fibronectin, and plasminogen activator inhibitor-1.

Re-expression of EGR-1 in fibrosarcoma HT1080 suppresses transformation including tumorigenicity (Huang, R.-P., Liu, C., Fan, Y., Mercola, D., and Adamson, E. (1995) Cancer Res. 55, 5054-5062) owing in part to up-regulation of the transforming growth factor (TGF)-beta1 promoter by EGR-1 which suppresses growth by an autocrine mechanism (Liu, C., Adamson, E., and Mercola, D. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 11831-11836). Here we show that enhanced cell attachment contributes to the suppression via increased secretion of fibronectin (FN) and also of plasminogen activator inhibitor-1 (PAI-1). The secretion of FN and PAI-1 is strongly correlated with EGR-1 expression (RPEARSON = 0.971 and 0. 985, respectively). Addition of authentic TGF-beta1 to parental cells greatly stimulated secretion of PAI-1 but not FN, whereas addition of TGF-beta antibody or lipofection with specific antisense TGF-beta1 oligonucleotides to EGR-1-regulated cells completely inhibits the secretion of PAI-1 but not FN. However, in gel mobility shift assays pure EGR-1 or nuclear extracts of EGR-1-regulated cells specifically bind to two GC-rich elements of the human FN promoter at positions -75/-52 and -4/+18, indicating that the increased secretion of FN is likely due to direct up-regulation by EGR-1. Moreover, adhesion was greatly enhanced in EGR-1-regulated cells and was reversed by treatment with Arg-Gly-Asp (RGD) or PAI-1 antibody indicating that the secreted proteins are functional. We conclude that EGR-1 regulates the coordinated expression of gene products important for cell attachment ("oikis" factor) and normal growth control.

Cell Adhesion↗
PubMed1999

Protein kinase calpha is an effector of hexamethylene bisacetamide-induced differentiation of Friend erythroleukemia cells.

The program of biochemical and molecular events necessary for commitment to erythroid cell differentiation is particularly well characterized in murine Friend erythroleukemia cell lines. Commitment to hemoglobin synthesis in response to a variety of chemical inducers, including hexamethylene bisacetamide and dimethyl sulfoxide is completed by 24 h and proceeds to terminal differentiation by 96 h. Phorbol 12-myristate 13-acetate, a classical tumor promoter phorbol ester that binds to protein kinase C, blocks differentiation in a reversible manner, suggesting an important role for protein kinase C signaling pathways. The classical protein kinase C isoforms alpha, betaI, and betaII, play distinct roles in the transduction of proliferative and differentiative signals in human, as well as in murine, erythroleukemia cells. Protein kinase Calpha has been implicated in differentiation of human erythroleukemia cells although its translocation to the nucleus has not been observed. Taking advantage of the ability of phorbol 12-myristate 13-acetate to block differentiation in Friend erythroleukemia cells, we determined the localization of the predominant protein kinase C isoforms alpha and betaI during differentiation and in response to their blockade. The ability of phorbol myristate acetate to preferentially diminish protein kinase Calpha-protein localization to the nucleus by 24 h and thereby block differentiation induced by hexamethylene bisacetamide was paralleled by the ability of protein kinase Calpha antisense transfection to block differentiation. In addition, beta-globin transcription, assessed by polymerase chain reaction, was significantly decreased in protein kinase Calpha antisense-transfected cells compared to that seen in vector transfected ones. Taken together, these data suggest an important temporal role for nuclear protein kinase Calpha localization in Friend erythroleukemia cell differentiation.

Acetamides↗
PubMed1999

Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke.

BACKGROUND: Epidemiologic studies have demonstrated that individuals who eat more fruits and vegetables and/or have high levels of serum beta-carotene have a lower risk of cancer, especially lung cancer. However, recent human intervention studies using beta-carotene supplements have shown an increase in the risk of lung cancer among smokers and asbestos workers. In this study, we used an animal model system to evaluate the hazard associated with a combination of high-dose beta-carotene supplementation and tobacco smoking. METHODS: Ferrets were given a beta-carotene supplement, exposed to cigarette smoke, or both for 6 months. Cell proliferation and squamous metaplasia in lung tissue were assessed by examination of proliferating-cell nuclear antigen expression and histopathologic examination, respectively. beta-Carotene and retinoid concentrations in lung tissue and plasma samples were analyzed by high-performance liquid chromatography. Expression of genes for retinoic acid receptors (RARs) and activator protein-1 (encoded by the c-Jun and c-Fos genes) in lung tissue specimens was examined by western blotting. RESULTS: A strong proliferative response in lung tissue and squamous metaplasia was observed in all beta-carotene-supplemented animals, and this response was enhanced by exposure to tobacco smoke. When compared with control groups, all three treatment groups had statistically significantly lower concentrations of retinoic acid in lung tissue, and they exhibited 18%-73% reductions in RARbeta gene expression; however, RARalpha and RARgamma gene expression was not reduced. Ferrets given a beta-carotene supplement and exposed to tobacco smoke had threefold to fourfold elevated expression of the c-Jun and c-Fos genes. CONCLUSIONS: Diminished retinoid signaling, resulting from the suppression of RARbeta gene expression and overexpression of activator protein-1, could be a mechanism to enhance lung tumorigenesis after high-dose beta-carotene supplementation and exposure to tobacco smoke.

Animals↗
PubMed1999

Development of an automated mass spectrometry system for the quantitative analysis of liver microsomal incubation samples: a tool for rapid screening of new compounds for metabolic stability.

There is a continuing need for increased throughput in the evaluation of new drug entities in terms of their pharmacokinetic parameters. One useful parameter that can be measured in vitro using liver microsomal preparations is metabolic stability. In this report, we describe an automated system that can be used for unattended quantitative analysis of liver microsomal samples for a series of compounds. This system is based on the Sciex API 150 (single quadrupole) liquid chromatography/mass spectrometry system and utilizes 96-well plate autosampler technology as well as a custom-designed AppleScript which executes the on-line data processing and report generation. It has the capability of analyzing at least 75 compounds per week or 300 compounds per month in an automated fashion.

Autoanalysis↗
PubMed1999

Single daily dosing of gentamicin: pharmacokinetic comparison of two dosing methodologies for postpartum endometritis.

OBJECTIVE: We compared the pharmacokinetics of two methods for dosing gentamicin for the treatment of postpartum endometritis with the goal of achieving adequate peak serum concentrations (>12 mg/L) and prolonged trough levels below 2 mg/L. METHODS: Group-I subjects (n = 5) received intravenous gentamicin, 5 mg/kg per total body weight over 60 min., with a maximum dose of 500 mg. Group-II subjects (n = 17) were dosed intravenously according to the following formula: Dose = desired peak concentration (fixed at 14 mg/L) * (volume of distribution, i.e., 0.35 L/kg) * adjusted body weight (in kilograms). Serum gentamicin levels were obtained 1 hr. and 8-12 hr. after infusion of the second dose. Pharmacokinetic parameters for the subjects in each group were calculated according to standard formulas. RESULTS: Subjects in Group I had significantly higher doses and peak drug concentrations (P < 0.01), while in Group II, 76% of patients had peak levels less than desired (<12 mg/L). Both groups maintained trough levels of <2 mg/L in excess of 12 hr. CONCLUSIONS: Changing to the adjusted body weight formula for Group I, while maintaining a dose between 4 and 5 mg/kg, would reduce excessive peak concentrations. Using a calculated volume of distribution of 0.4 L/kg in Group II would improve peak serum concentrations to the desired levels. Both dosing regimens ensure adequate aminoglycoside pharmacokinetic parameters and avoid the need for monitoring serial serum drug concentrations, provided the expected clinical response is also achieved. While the first dosing formula is simpler to calculate, the second dosing formula allows for more individualized dosing considerations.

Adolescent↗
PubMed1999

Synergistic effect of copper and lead uptake by fish.

Paracheirodon innesi was exposed (simultaneously or sequentially) to copper and lead in varying concentrations in a synthetic water solution. Metal accumulations in fish gills and the fish (without gills) were measured at the end of the exposure period. Results of the exposure experiment indicated that lead seems to facilitate the uptake of copper and vice versa when the exposure process is simultaneous. In the case of sequential exposure first to copper for 7 days then to lead for 20 days, lead accumulations in the fish and the gills were enhanced by copper, indicating a possible alteration of the physiological absorption process. The synergistic effects observed during either simultaneous or sequential exposure experiments can be described using logistic equations.

Animals↗
PubMed1999

Study on relationship between anticardiolipin antibody and cerebrovascular diseases.

Serum anticardiolipin antibody (ACA) was measured in 91 patients with cerebral infarction (CI), 42 patients with cerebral hemorrhage (CH) and 30 healthy controls. The results showed that the ACA in CI and CH patients was significantly higher than in controls and IgG-ACA was the most important isotype. Stroke in ACA positive group tended to be recurrent and of multi-focuses. Positive rate of IgG-ACA reached its peak within the first week after stroke onset. The results suggested that ACA was an independent risk factor in CI and CH and might be valuable in stroke prediction.

Aged↗
PubMed1999

Uptake of particulate lead via the gills of fish (Carassius auratus).

Carassius auratus were exposed to mixtures of constant free lead (0. 1 mg/L) and particulate lead (adsorbed on gibbsite particles) at varied concentrations (0, 0.4, 0.8, 1.2, 2.0, and 3.0 mg/L). The concentrations of lead and aluminum in the gills and intestines of the fish were determined after exposure. The gills were examined (after the exposure) with a light microscope for any particles adhering to the surface. The examination results revealed that lead accumulations on the gills increased with increased particulate lead concentrations in the ambient water (under conditions of a constant level of free lead), indicating the bioavailability of lead via the gills. Gibbsite particles were also observed on the gill surface after exposure. The ratio of lead and aluminum in the gills was much higher than that in the particles. Our results suggest that there was a two-step process involved in the uptake of particulate lead by fish gills: (1) adherence of the particles on the gill surface where mucus was attached; and (2) desorption of lead from the particles under conditions of the gill microenvironment.

Animals↗
PubMed1999

A modified technique to correct primary vesicoureteral reflux in children.

PURPOSE: The authors describe the experience of a modified technique to correct primary vesicoureteral reflux in children. METHODS: Twenty children (28 renal units) with primary vesicoureteral reflux (grade III to grade IV) were treated with this technique. The authors incised the bladder mucosa and muscle along the direction of the ureter using a right-angled probe as a guide. About 2 to 3 cm of extravesical ureter was freed and pulled into the bladder via the incision. The bladder muscle was closed under the ureter, and the mucosa was repaired over the ureter. RESULTS: One patient had residual reflux. All other patients, who underwent follow-up with sonogram and voiding cystourethrogram from 14 to 42 months after the operation, had neither recurrent reflux nor urinary tract obstruction. CONCLUSIONS: The advantages of this technique are (1) anastomosis of the ureteral orifice to the urinary bladder is not needed, so that the risk of orifice stenosis is minimized; (2) the ureteral orifice remains unchanged after the procedure, so that ureteroscopic procedures are easier to perform in future if required; and (3) pelvic dissection is not needed as in extravesical detrusorrhaphy. However, this procedure may not be suitable for patients with severe hydroureter.

Child↗
PubMed1999

Contralateral reflux after unilateral ureteral reimplantation--preexistent rather than new-onset reflux.

PURPOSE: The authors studied the preoperative Technetium 99m-dimercaptosuccinic acid renal scan (DMSA) of patients undergoing unilateral vesicoureteral antireflux surgery to compare the amount of renal scarring between the refluxing and the contralateral renal units. They sought to determine whether postoperative contralateral vesicoureteral reflux was preexistent or new onset. METHODS: Sixty-eight patients who underwent unilateral vesicoureteral antireflux surgery and had preoperative DMSA and postoperative voiding cystourethrography (VCUG) examinations were studied. Preoperative DMSA results were analyzed to determine the amount of renal scarring in each kidney. RESULTS: Sixty-four (94.1%) ipsilateral refluxing renal units had renal scars. Of the 68 contralateral renal units, scars were noted in 28 (41.2%). The rate of nonscar was 4 of 68 (5.9%) in reflux kidneys, which was significantly lower than 40 of 64 (62.5%, excluding 4 with a history of resolved reflux) in nonreflux kidneys (P<.001). Of 40 contralateral nonscarred kidneys, 1 of 40 (2.5%) had subsequent reflux, which was significantly lower than 5 of 28 (17.9%) of scarred kidneys (P<.005). Six patients (8.8%) had contralateral reflux, and 1 of them had a history of resolved reflux. Of the 6 contralateral kidneys with severe scarring involving 3 poles or contracted, 4 of 6 (66.7%) had subsequent reflux. CONCLUSIONS: Scar in the contralateral kidney seen on DMSA scan seems to predict contralateral reflux after unilateral antireflux surgery. The contralateral reflux may be preexistent. Postoperative VCUG should be performed routinely for patients who have contralateral renal scars. In patients with a history of contralateral reflux or severe contralateral renal scar, simultaneous contralateral ureteral reimplantation should be considered.

Adolescent↗
PubMed1999

Biodegradation of coplanar polychlorinated biphenyls by anaerobic microorganisms from estuarine sediments.

In this study, we investigated the biodegradability of biphenyl and 5 congeners (one non-planar and four coplanar) of polychlorinated biphenyl (PCB). Biphenyl, the non-planar congener 2,3',4',5-tetrachlorobiphenyl (25-34 CB), and the four coplanar congeners 3,3',4,4'-tetrachlorobiphenyl (34-34 CB), 3,4,4',5-tetrachlorobiphenyl (345-4 CB), 3,3',4,4',5-pentachlorobiphenyl (345-34 CB), and 3,3',4,4',5,5'-hexachlorobiphenyl (345-345 CB) were amended at a concentration of 10 mg/L into anoxic sediment slurries collected from the estuaries of the Tansui River and the Erjen River. During 2 years' incubation under sulfidogenic conditions, biphenyl was persistent, while all other chlorinated congeners, except for 345-345 CB, were dechlorinated with or without a lag period in sediment slurries collected from both rivers. Dechlorination of coplanar and non-planar congeners began with para chlorine removal. All para chlorines from the mono-, di-, and trichlorobiphenyl groups could be removed by sediment slurries from both rivers. Microbial communities in sediment from the Erjen River additionally fostered meta-dechlorination activity, but only after removal of all the para chlorines. Addition of Tween 20 (0.05%, v/v) into sediment slurries from the Tansui River did not enhance dechlorination rates or extents, but the addition of toluene- or 3-chlorobenzoate-adapted sediments enhanced dechlorination of 34-34 CB and 345-4 CB.

Anaerobiosis↗
PubMed1999

Cavernous hemangiomas in the cavernous sinus. Case reports.

BACKGROUND: Extra-axial cavernous hemangiomas are rare and have a propensity to develop within the cavernous sinus. Total removal of these vascular tumors is difficult due to the risk of severe intraoperative bleeding and the complicated neurovascular structures of the cavernous sinus. Only a small number of cases have been reported to be successfully totally removed. METHODS: Retrospective studies were done in three cases of extraaxial cavernous hemangiomas located in the cavernous sinus. All three patients presented with clinical symptoms common to other tumors located in the region, such as headache and impairment of cranial nerve function. Their preoperative MRI results showed significant hyperintensity on T2-weighted images and marked enhancement with gadolinium-DTPA that delineated a sharp tumor margin. RESULTS: All three patients underwent total tumor removal, with an uneventful postoperative course. There was no postoperative neurological deficit in one patient, and a complete ophthalmoplegia and diminished sensation in the V1 distribution in two patients. Three months after operation, follow-up MRI or CT scan showed no residual tumor. CONCLUSION: Surgical resection of these lesions was possible but difficult because of severe bleeding. Avoiding piecemeal removal before the main feeding arteries are interrupted can minimize intraoperative bleeding.

Adult↗
PubMed1999

Functional analysis of P-glycoprotein and multidrug resistance associated protein related multidrug resistance in AML-blasts.

Despite the high effectiveness of various P-glycoprotein (P-gp) modulating substances in vitro their clinical value e.g. for combination treatment of acute myelogenous leukemias (AML) remains still unclear. This might be explainable by recent findings that other factors than P-gp (e.g. the multidrug resistance associated protein (MRP)) may also be involved in clinical occurring drug resistance. To study P-gp and MRP mediated MDR in AML blasts from patients with relapses at the functional level we measured rhodamine 123 (RHO) efflux in combination with a P-gp specific (SDZ PSC 833) or a MRP specific (MK571) modulator, respectively. Furthermore, direct antineoplastic drug action was monitored by determination of damaged cell fraction of a blast population using flow cytometry. We generally found strongly modulated RHO efflux by SDZ PSC 833 but slight RHO-efflux modulation by MK571 in blasts from relapsed states of AML expressing MDR1 or MRP mRNA at various levels. We could not demonstrate, though, significant PSC 833 or MK571 mediated modulation of the cytotoxic effects of etoposide. The results point to the possibility that combination of etoposide and a modulator might not improve responses to chemotherapy by targeting P-gp or MRP exclusively.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

SZF1: a novel KRAB-zinc finger gene expressed in CD34+ stem/progenitor cells.

The identification and study of genes expressed in hematopoietic stem/progenitor cells should further our understanding of hematopoiesis. Transcription factors in particular are likely to play important roles in maintaining the set of genes that define the stem/progenitor cell. We report here the identification of a putative KRAB-zinc finger gene (SZF1) from a cDNA library prepared from human bone marrow CD34+ cells. Characterization of SZF1 implicates its role in hematopoiesis. The predicted protein contains a highly conserved KRAB domain at the NH2 terminus and four zinc fingers of the C2H2 type at the COOH terminus. Two alternatively spliced products of SZF1 were isolated, which predict proteins of 421 (SZF1-1) and 361 (SZF1-2) amino acids, differing from each other only at the carboxy terminus. The two transcripts of SZF1 have different expression patterns. SZF1-2 is ubiquitously expressed, as indicated by Northern blot, RNase protection, and reverse transcriptase polymerase chain reaction. SZF1-1 expression, in contrast, was detected only in CD34+ cells. We recently isolated the promoter region for the stem/progenitor cell expressed FLT3/FLK-2/STK-1 gene and used this region to generate a reporter construct to test the effect of SZF1 expression. Cotransfection of the reporter construct with SZF1 constructs showed that SZF1-2 repressed transcription three- to fourfold, whereas SZF1-1 showed a lower level of repression. The expression pattern of SZF1 transcripts and the transcriptional repression of a CD34+-specific promoter demonstrate a possible role for SZF1 in hematopoietic stem/progenitor cell differentiation.

Alternative Splicing↗