Biomedical subjects

S Zhou

Publications and source records attributed to S Zhou.

At least 163 records · Page 9Linked to original sources

PubMed2000

Comparison of an automated thrombolytic predictive instrument to both diagnostic software and an expert cardiologist for diagnosis of an ST elevation acute myocardial infarction.

Because the electrocardiograms (ECGs) of patients with symptoms suggesting an acute thrombotic coronary occlusion are typically read by physicians relatively inexperienced in this skill, it is important to develop automated decision support. A Thrombolytic Predictive Instrument (TPI) is now available along with the standard diagnostic software in a commercially available electrocardiograph. This study evaluates the performance of the predictive software in comparison to both an expert cardiologist and standard diagnostic software. True sensitivity and specificity cannot be determined because acute coronary angiography was not performed. The specificities determined by this study were excellent (98% and 99%), and the sensitivities were very good (72% and 78%). These results that the TPI will be only rarely applied to patients who do not indeed have an acute coronary thrombosis. However, the reasons for even this small number of presumably falsely TPI positive patients should be determined and analyzed. It is unlikely that alterations of the thresholds for TPI activation will significantly improve on this very good level of sensitivity, without prohibitively decreasing specificity.

Clinical Competence↗

PubMed2000

Preliminary evaluation of dual wavelength phased array imaging on neonatal brain function.

Imaging of human tissue using noninvasive techniques has been of great interest in biomedical fields. Optical imaging has attracted a lot of attention because of its portability and economy. The possibility that a highly portable, fast, safe, and affordable imaging system which could obtain interpretable images of brain function for pre- and full-term neonates in a few seconds, has been explored in this article. We have used a sensitive optical topography system, termed phased array, in which a pair of equal-amplitude and antiphase light sources are applied to generate a sharp amplitude null and phase transition plane. This two-wavelength (750 and 830 nm), frequency encoded (50 and 52 MHz) phased array imaging system can indicate the blood concentration and oxygenation changes in blood model studies and during parietal brain activation in neonates. Significant functional responses, particularly to parietal stimulation in normal and pathological states of neonatal brain, have been revealed in our study. The preliminary clinical results are presented in this article.

Blood Flow Velocity↗

PubMed2000

Synergistic hydrolysis of carboxymethyl cellulose and acid-swollen cellulose by two endoglucanases (CelZ and CelY) from Erwinia chrysanthemi.

Erwinia chrysanthemi produces a battery of hydrolases and lyases which are very effective in the maceration of plant cell walls. Although two endoglucanases (CelZ and CelY; formerly EGZ and EGY) are produced, CelZ represents approximately 95% of the total carboxymethyl cellulase activity. In this study, we have examined the effectiveness of CelY and CelZ alone and of combinations of both enzymes using carboxymethyl cellulose (CMC) and amorphous cellulose (acid-swollen cellulose) as substrates. Synergy was observed with both substrates. Maximal synergy (1.8-fold) was observed for combinations containing primarily CelZ; the ratio of enzyme activities produced was similar to those produced by cultures of E. chrysanthemi. CelY and CelZ were quite different in substrate preference. CelY was unable to hydrolyze soluble cellooligosaccharides (cellotetraose and cellopentaose) but hydrolyzed CMC to fragments averaging 10.7 glucosyl units. In contrast, CelZ readily hydrolyzed cellotetraose, cellopentaose, and amorphous cellulose to produce cellobiose and cellotriose as dominant products. CelZ hydrolyzed CMC to fragments averaging 3.6 glucosyl units. In combination, CelZ and CelY hydrolyzed CMC to products averaging 2.3 glucosyl units. Synergy did not require the simultaneous presence of both enzymes. Enzymatic modification of the substrate by CelY increased the rate and extent of hydrolysis by CelZ. Full synergy was retained by the sequential hydrolysis of CMC, provided CelY was used as the first enzyme. A general mechanism is proposed to explain the synergy between these two enzymes based primarily on differences in substrate preference.

Carbohydrate Conformation↗

PubMed2000

A role for SKIP in EBNA2 activation of CBF1-repressed promoters.

EBNA2 is essential for Epstein-Barr virus (EBV) immortalization of B lymphocytes. EBNA2 functions as a transcriptional activator and targets responsive promoters through interaction with the cellular DNA binding protein CBF1. We have examined the mechanism whereby EBNA2 overcomes CBF1-mediated transcriptional repression. A yeast two-hybrid screen performed using CBF1 as the bait identified a protein, SKIP, which had not previously been recognized as a CBF1-associated protein. Protein-protein interaction assays demonstrated contacts between SKIP and the SMRT, CIR, Sin3A, and HDAC2 proteins of the CBF1 corepressor complex. Interestingly, EBNA2 also interacted with SKIP in glutathione S-transferase affinity and mammalian two-hybrid assays and colocalized with SKIP in immunofluorescence assays. Interaction with SKIP was not affected by mutation of EBNA2 conserved region 6, the CBF1 interaction region, but was abolished by mutation of conserved region 5. Mutation of conserved region 5 also severely impaired EBNA2 activation of a reporter containing CBF1 binding sites. Thus, interaction with both CBF1 and SKIP is necessary for efficient promoter activation by EBNA2. A model is presented in which EBNA2 competes with the SMRT-corepressor complex for contacts on SKIP and CBF1.

Amino Acid Sequence↗

PubMed2000

A human condensin complex containing hCAP-C-hCAP-E and CNAP1, a homolog of Xenopus XCAP-D2, colocalizes with phosphorylated histone H3 during the early stage of mitotic chromosome condensation.

Structural maintenance of chromosomes (SMC) family proteins play critical roles in structural changes of chromosomes. Previously, we identified two human SMC family proteins, hCAP-C and hCAP-E, which form a heterodimeric complex (hCAP-C-hCAP-E) in the cell. Based on the sequence conservation and mitotic chromosome localization, hCAP-C-hCAP-E was determined to be the human ortholog of the Xenopus SMC complex, XCAP-C-XCAP-E. XCAP-C-XCAP-E is a component of the multiprotein complex termed condensin, required for mitotic chromosome condensation in vitro. However, presence of such a complex has not been demonstrated in mammalian cells. Coimmunoprecipitation of the endogenous hCAP-C-hCAP-E complex from HeLa extracts identified a 155-kDa protein interacting with hCAP-C-hCAP-E, termed condensation-related SMC-associated protein 1 (CNAP1). CNAP1 associates with mitotic chromosomes and is homologous to Xenopus condensin component XCAP-D2, indicating the presence of a condensin complex in human cells. Chromosome association of human condensin is mitosis specific, and the majority of condensin dissociates from chromosomes and is sequestered in the cytoplasm throughout interphase. However, a subpopulation of the complex was found to remain on chromosomes as foci in the interphase nucleus. During late G(2)/early prophase, the larger nuclear condensin foci colocalize with phosphorylated histone H3 clusters on partially condensed regions of chromosomes. These results suggest that mitosis-specific function of human condensin may be regulated by cell cycle-specific subcellular localization of the complex, and the nuclear condensin that associates with interphase chromosomes is involved in the reinitiation of mitotic chromosome condensation in conjunction with phosphorylation of histone H3.

Amino Acid Sequence↗

PubMed2000

Crk1, a novel Cdc2-related protein kinase, is required for hyphal development and virulence in Candida albicans.

Both mitogen-activated protein kinases and cyclin-dependent kinases play a role in hyphal development in Candida albicans. Using an oligonucleotide probe-based screen, we have isolated a new member of the Cdc2 kinase subfamily, designated Crk1 (Cdc2-related kinase). The protein sequence of Crk1 is most similar to those of Saccharomyces cerevisiae Sgv1 and human Pkl1/Cdk9. In S. cerevisiae, CRK1 suppresses some, but not all, of the defects associated with an sgv1 mutant. Deleting both copies of CRK1 in C. albicans slows growth slightly but leads to a profound defect in hyphal development under all conditions examined. crk1/crk1 mutants are impaired in the induction of hypha-specific genes and are avirulent in mice. Consistent with this, ectopic expression of the Crk1 kinase domain (CRK1N) promotes filamentous or invasive growth in S. cerevisiae and hyphal development in C. albicans. The activity of Crk1 in S. cerevisiae requires Flo8 but is independent of Ste12 and Phd1. Similarly, Crk1 promotes filamentation through a route independent of Cph1 and Efg1 in C. albicans. RAS1(V13) can also activate filamentation in a cph1/cph1 efg1/efg1 double mutant. Interestingly, CRK1N produces florid hyphae in ras1/ras1 strains, while RAS1(V13) generates feeble hyphae in crk1/crk1 strains.

Amino Acid Sequence↗

PubMed2000

A specificity and targeting subunit of a human SWI/SNF family-related chromatin-remodeling complex.

The SWI/SNF family of chromatin-remodeling complexes facilitates gene activation by assisting transcription machinery to gain access to targets in chromatin. This family includes BAF (also called hSWI/SNF-A) and PBAF (hSWI/SNF-B) from humans and SWI/SNF and Rsc from Saccharomyces cerevisiae. However, the relationship between the human and yeast complexes is unclear because all human subunits published to date are similar to those of both yeast SWI/SNF and Rsc. Also, the two human complexes have many identical subunits, making it difficult to distinguish their structures or functions. Here we describe the cloning and characterization of BAF250, a subunit present in human BAF but not PBAF. BAF250 contains structural motifs conserved in yeast SWI1 but not in any Rsc components, suggesting that BAF is related to SWI/SNF. BAF250 is also a homolog of the Drosophila melanogaster Osa protein, which has been shown to interact with a SWI/SNF-like complex in flies. BAF250 possesses at least two conserved domains that could be important for its function. First, it has an AT-rich DNA interaction-type DNA-binding domain, which can specifically bind a DNA sequence known to be recognized by a SWI/SNF family-related complex at the beta-globin locus. Second, BAF250 stimulates glucocorticoid receptor-dependent transcriptional activation, and the stimulation is sharply reduced when the C-terminal region of BAF250 is deleted. This region of BAF250 is capable of interacting directly with the glucocorticoid receptor in vitro. Our data suggest that BAF250 confers specificity to the human BAF complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions.

Amino Acid Sequence↗

PubMed2000

SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function.

Notch proteins are transmembrane receptors that mediate intercell communication and direct individual cell fate decisions. The activated intracellular form of Notch, NotchIC, translocates to the nucleus, where it targets the DNA binding protein CBF1. CBF1 mediates transcriptional repression through the recruitment of an SMRT-histone deacetylase-containing corepressor complex. We have examined the mechanism whereby NotchIC overcomes CBF1-mediated transcriptional repression. We identified SKIP (Ski-interacting protein) as a CBF1 binding protein in a yeast two-hybrid screen. Both CBF1 and SKIP are highly conserved evolutionarily, and the SKIP-CBF1 interaction is also conserved in assays using the Caenorhabditis elegans and Drosophila melanogaster SKIP homologs. Protein-protein interaction assays demonstrated interaction between SKIP and the corepressor SMRT. More surprisingly, SKIP also interacted with NotchIC. The SMRT and NotchIC interactions were mutually exclusive. In competition binding experiments SMRT displaced NotchIC from CBF1 and from SKIP. Contact with SKIP is required for biological activity of NotchIC. A mutation in the fourth ankyrin repeat that abolished Notch signal transduction did not affect interaction with CBF1 but abolished interaction with SKIP. Further, NotchIC was unable to block muscle cell differentiation in myoblasts expressing antisense SKIP. The results suggest a model in which NotchIC activates responsive promoters by competing with the SMRT-corepressor complex for contacts on both CBF1 and SKIP.

Amino Acid Sequence↗

PubMed2000

Effect of dietary fatty acids on tumorigenesis of colon cancer induced by methyl nitrosourea in rats.

We studied the effect of dietary fatty acid composition on the tumorigenesis of colon cancer induced by methyl nitrosourea (MNU) in rats. Five groups of Sprague-Dawley male rats were fed with semi-synthetic diets that contained different proportions of beef tallow, soybean oil, alkana oil, corn oil, and fish oil for 180 days. Each group was matched with a control group fed with the same diet. The experimental groups were given MNU in PBS i.p. 6 times at weekly intervals. The control groups were given PBS only. The incidence of colon cancer, the average volume of the tumors, PCNA, cell kinetics, membrane lipid fluidity, ALP activity, and the content of PGE2 in colonic mucous and the fatty acid distribution in the testis pad fat were measured at the end of the experiment. The results showed that the incidence of colon cancer and the average volume of the tumors in animals fed with diets that contained mainly beef tallow, soybean oil, or alkana oil were significantly higher than that in animals fed with diets that contained mainly fish oil. The diet containing 13.9% of SFA, 16.4% of MUFA, and 68.8% of PUFA showed the strongest inhibition effect. This may be due to the mechanism of protecting the membrane lipid fluidity, decreasing the amount of PCNA in colon cells, the number of propidium iodine-labeled cells in S phase, the activity of ALP and inhibiting the production of AA and thus decreasing the amount of PGE2.

Alkaline Phosphatase↗

PubMed2000

A re-evaluation of the antioxidant activity of purified carnosine.

The antioxidant activity of carnosine has been re-evaluated due to the presence of contaminating hydrazine in commercial carnosine preparations. Purified carnosine is capable of scavenging peroxyl radicals. Inhibition of the oxidation of phosphatidylcholine liposomes by purified carnosine is greater in the presence of copper than iron, a phenomenon likely to be due to the copper chelating properties of carnosine. Purified carnosine is capable of forming adducts with aldehydic lipid oxidation products. Adduct formation is greatest for alpha,beta-monounsaturated followed by polyunsaturated and saturated aldehydes. While the ability of carnosine to form adducts with aldehydic lipid oxidation products is lower than other compounds such as glutathione, the higher concentrations of carnosine in skeletal muscle are likely to make it the most important molecule that forms aldehyde adducts. Monitoring changes in carnosine concentrations in oxidizing skeletal muscle shows that carnosine oxidation does not occur until the later stages of oxidation suggesting that carnosine may not be as effective free radical scavenger in vivo as other antioxidants like alpha-tocopherol.

Animals↗

PubMed2000

Retinal degeneration is slowed in transgenic rats by AAV-mediated delivery of FGF-2.

PURPOSE: We evaluated adeno-associated virus (AAV)-mediated gene transfer of basic fibroblast growth factor (FGF-2) as a therapy for photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa. METHODS: Recombinant adeno-associated virus vector (rAAV) incorporating a constitutive cytomegalovirus (CMV) promoter was used to transfer the bovine FGF-2 gene to photoreceptors. AAV was administered by subretinal injection to transgenic rats (TgN S334ter-4) at postnatal day 15 (P15). Control eyes were uninjected, injected with PBS, or AAV-LacZ. Eyes were examined by histopathology, morphometric analysis, and electroretinography at P60. RESULTS: Expression of recombinant FGF-2 slowed the rate of photoreceptor degeneration. Morphologic studies demonstrated significantly more photoreceptors surviving in eyes injected with AAV-FGF-2 than in controls. Insignificant rescue effects were seen in retinas injected with buffer only. No significant inflammatory response or neovascularization was detected. Electroretinographic (ERG) responses of eyes injected with AAV-FGF-2 were increased compared with uninjected eyes; however, these amplitudes were not significantly larger than eyes receiving an AAV-LacZ control vector. CONCLUSIONS: Transduction of retinal cells with AAV-FGF-2 reduces the rate of photoreceptor degeneration in an S334ter-4 animal model. Despite the lack of significantly increased ERG amplitudes from eyes expressing FGF-2, a greater number of surviving photoreceptors was demonstrated. Delivery of FGF-2 using recombinant AAV has potential as a therapy for retinal degeneration.

Animals↗

PubMed2000

Chronic neural adaptations to unilateral exercise: mechanisms of cross education.

Cross education refers to the contralateral effect of chronic motor activity in one limb. The effect can enhance or diminish motor activity and is specific to the homologous muscles and the training task. The mechanisms underlying the phenomenon involve adaptations in the nervous system, probably at the level of the spinal cord.

Adaptation, Physiological↗

PubMed2000

Identification of the human liver cytochrome P450 isoenzyme responsible for the 6-methylhydroxylation of the novel anticancer drug 5,6-dimethylxanthenone-4-acetic acid.

In vitro studies were conducted to identify the hepatic cytochrome P450 (CYP) isoenzyme involved in the 6-methylhydroxylation of 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) by using a human liver library (n = 14). The metabolite 6-hydroxymethyl-5-methylxanthenone-4-acetic acid (6-OH-MXAA) was determined by HPLC with fluorescence detection. The metabolite formed in human liver microsomes and by cDNA-expressed CYP isoform was identified by liquid chromatography mass spectrometry as 6-OH-MXAA. In human liver microsomes (n = 14), 6-methylhydroxylation of DMXAA followed monophasic Michaelis-Menten kinetics, with a mean apparent K(m) of 21 +/- 5 microM and V(max) of 0.043 +/- 0.019 nmol/min/mg. An approximate 10-fold interindividual variation in the intrinsic clearance (V(max)/K(m)) of DMXAA 6-methylhydroxylation in human liver microsomes was observed. The involvement of CYP1A2 in DMXAA metabolism by human livers was demonstrated by the following: 1) the potent inhibition of DMXAA metabolism by furafylline (k(inact) = 0.23 +/- 0.04 min(-1), K'(app) = 15.6 +/- 6.7 microM) and alpha-naphthoflavone (K(i) = 0.036 microM), but not by cimetidine, ketoconazole, tolbutamide, quinidine, chlorzoxazone, diethyldithiocarbamate, troleandomycin, and sulfaphenazole; 2) when incubated with human lymphoblastoid cell microsomes containing cDNA-expressed CYP isoenzymes, DMXAA was metabolized only by CYP1A2, with an apparent K(m) of 6.2 +/- 1.5 microM and V(max) of 0.014 +/- 0.001 nmol/min/mg, but not by CYP2A6, CYP2B6, CYP2C9 (Arg(144)), CYP2C19, CYP2D6 (Val(374)), CYP2E1, and CYP3A4; 3) a significant correlation (r = 0.90; P <.001) between 6-methylhydroxylation of DMXAA and 7-ethoxyresorufin O-deethylation; and 4) a significant correlation (r = 0.75; P <.01) between the CYP1A protein level determined by Western blots and DMXAA 6-methylhydroxylation.

Adult↗

PubMed2000

[Different flow augmentations in coronary, carotid and renal arteries with ECP in experimental canines].

Different flow augmentations were found in canine's coronary, carotid and renal arteries with ECP because of their different anatomical locations in aorta. We used the Electromagnetic Blood Flowmeters to measure the blood flow pre-ECP and during ECP. The results showed ECP increased the diastolic flow of coronary, carotid and renal arteries by 24.48% +/- 1.29%, 27.18% +/- 0.94% and 20.68% +/- 0.80% respectively, decreased their systolic flow by 4.77% +/- 0.48%, 6.45% +/- 0.99% and 9.60% +/- 0.70%, but augmented their mean flow by 18.24% +/- 2.01%, 19.38% +/- 1.47% and 8.42% +/- 0.94% respectively in experimental dogs. These data demonstrate that ECP can greatly increase the mean flow of coronary and carotid arteries but at the same time patently decrease the systolic flow of renal artery.

Animals↗

PubMed2000

[Study of mdr1 antisense oligodeoxynucleotides on reversal of multidrug resistance in ovarian carcinoma cell line SKOV3].

OBJECTIVE: To investigate the effect of mdr1 antisense oligodeoxynucleotides (ASON) on reversal of multidrug resistance in ovarian carcinoma cells. METHODS: Drug resistance ovarian carcinoma cells SKOV3/mdr1 transducted with human multidrug resistance gene (mdr1) were served as models. The positive rate and function of the mdr1 gene product P-glycoprotein (P-gp) in SKOV3/mdr1 cells after mdr1-ASON (250 micrograms/ml) treatment were determined by flow cytometry and rhodamine 123 efflux trial. Drug resistance of SKOV3/mdr1 cells was also observed by cell colony culture. RESULTS: P-gp positive rate of SKOV3/mdr1 cells after mdr1-ASON treatment was decreased from 38.9% to 21.3% (P < 0.01). Intracellular rhodamine retension in SKOV3/mdr1 cells after mdr1-ASON treatment was increased from 32.1% to 50.7% (P < 0.01). Under effect of Taxol 5 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 8% and 63%, respectively, (P < 0.01). Under effect of Doxorubicin 100 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 34% and 79%, respectively, (P < 0.01). CONCLUSION: mdr1-ASON can reverse multidrug resistance of ovarian carcinoma cell in a certain extent so as to increase chemotherapeutic sensitivity of ovarian carcinoma cells.

Drug Resistance, Neoplasm↗

PubMed2000

[Histochemical study and classification of facial muscles fibers].

OBJECTIVE: To study the histological and histochemical characteristics of the facial muscle fiber. METHODS: Seven biopsy specimens of the facial muscle from twelve patients were stained with histochemical method. The diameter and the histochemical type of the fibers were analysed by staining of M-ATP ase and NADA-TR. Type I and type II fibers were evaluated respectively by means of computer-assisted image analysis. RESULTS: The fiber diameter is between 24.3-63.9 microns. According to the quantity of fiber I, facial muscles may be classified into three groups: 1. Phasic muscle contains less than 20 percent of type I fibers; 2. Intermediate muscle contains 21 to 40 percent of type I fibers; 3. Tonic muscle contains 41 to 69 percent of type I fibers. CONCLUSION: The results of the study show that the histological and histochemical difference of facial muscles may have significance in facial paralysis restoration.

Adult↗

PubMed2000

[Relationship between isometric exercise and myocardial ischemia in patients with coronary artery disease: an Echo-Doppler study].

OBJECTIVE: To study the relationship between isometric exercise and myocardial ischemia in patients with coronary artery disease (CAD). METHODS: Twenty CAD patients and 10 normal subjects were included in our study. All subjects performed maximal brief isometric exercise (BIE), maximal sustained isometric exercise (SIE) and dynamic exercise (DE). Hemodynamic parameters and cardiac function were measured by Echo-Doppler technique. To avoid influence of different baseline values, increment (delta%) of exercise response was used as parameter for significant analysis: delta% = (exercise values - baseline values)/baseline values x 100%. RESULTS: Positive exercise testing (PET) showed no evidence of myocardial ischemia during BIE and SIE even though their rates of perceived exertion (RPE) were similar to DE. delta% heart rate (HR) and delta% rate pressure product (RPP) were higher during DE than during SIE and BIE in negative exercise testing (NET) and normal controls (NOR) (P < 0.01), except PET during DE and SIE; delta% systolic blood pressure (SBP) was higher during DE than during BIE in NOR (P < 0.01). delta% SBP in NOR and NET during SIE was higher than during BIE (P < 0.05). delta% diastolic blood pressure (DBP) was the highest during SIE among exercises in all gropus (P < 0.05). There were no significant inter-group differences of delta% HR, delta% SBP, delta% DBP and delta% RPP during SIE, BIE and DE, except that delta% SBP during SIE was higher in NET than in NOR and PET (P < 0.05). In NOR, delta% ejection fraction (EF), delta% fractional shortening of the minor-semi axis (SF), delta% cardiac output (CO), delta% E/A was higher during DE than during SIE and BIE (P < 0.01). delta% stroke volume (SV) was similar during DE, SIE and BIE. There were no significant differences in delta% EF, delta% SF, delta% CO, delta% SV and delta% E/A during DE, SIE and BIE in both NET and PET, except lower delta% CO in NET during SIE and BIE than DE (P < 0.01). There were no inter-group differences in delta% EF, delta% SF, delta% CO and delta% E/A, except that delta% E/A was higher during SIE in NET than PET (P < 0.01). During DE, NOR and NET had higher delta% SV, delta% SF, delta% CO and delta% E/A than PET (P < 0.05). CONCLUSIONS: The incidence of myocardial ischemia in CAD patients was lower during isometric exercise than dynamic exercise at similar perceived exertion levels. Isometric exercise might protect the myocardium from ischemia through high coronary artery perfusion pressure and long perfusion duration. We suggest that application of isometric exercise in a cardiac rehabilitation program may have reasonable physiological background.

Aged↗

PubMed2000

[Chemoprotection of transfer of multidrug resistance gene into human hematopoietic progenitor cell].

OBJECTIVE: To observe the effect of the transfer of multidrug resistance gene (mdr1) into human hematopoietic progenitor cells (HPC) on the chemoprotection. METHODS: Human CD34+ cells served as a target of mdr1 gene transfer. Retroviral vector SF-mdr containing human total length mdr1cDNA was introduced into packing cells GP-envAM12 by liposome-mediated transfection. The mdr1 gene was transduced into human CD34+ cells by retroviral supernatants of packing cells. The integration and expression of the mdr1 gene and its protein (P170) in transduced cells were determined by PCR, RT-PCR, and flow cytometry. The drug resistance of chemotherapy in transduced HPC was determined by culturing colonies. RESULTS: The mdr1 gene was integrated and expressed in transduced CD34+ cells. The efficiency of mdr1 gene transfer was 10%-14%. Compared with untransduced controls, within a certain range of drug concentration, the number of drug-resistant colony in transduced HPC for taxol, doxorubicin, VCR and VP16 were increased by 3.6 +/- 2.1 fold, 2.9 +/- 0.3 fold, 1.9 +/- 0.4 fold, and 3.5 +/- 0.5 fold, respectively. CONCLUSION: The transfer of the mdr1 gene into human HPC can increase the drug resistance of the transduced cells to corresponding chemotherapeutic drugs that may provide some degree of chemoprotection for HPC.

Antigens, CD34↗