PURPOSE: We aim to compare the erythropoietic effects of epoetin-alpha (EA, 4000 IU SC thrice a week) with those of darbepoetin-alpha (DA, 60ug IV weekly, conversion rate to EA=200:1). METHODS: Forty one stable hemodialysis patients were enrolled in this randomized crossover study. After a washout period of erythropoietin stimulating agents (ESA), the patients with hemoglobin (Hb) level of < or =11.0 g/dL were randomly assigned to DA or EA and we measured Hb and reticulocyte levels. When Hb reached >11.0 g/dL, we stopped ESA. When Hb level decreased to < or =11.0 g/dL again, we switched to alternative ESA and repeated the rest of the steps. RESULTS: Thirty six patients (M:F=20:16, age 62+/-11 years, Kt/V 1.65, nPCR 1.13 g/kg/day) completed the study. No significant differences were observed in baseline parameters between DA and EA during the period of the clinical trial. The rate of Hb level increase (EA 0.29 g/dL/week, DA 0.30 g/dL/week, p=0.76) and decrease (EA 0.45 g/dL/week, DA 0.38 g/dL/week, p=0.14) were not different between two periods. After ESA stopped, the duration of decreased Hb level of < or =11.0 g/dL was not significantly different (4 weeks in EA vs. 3.9 weeks in DA, p=0.86). Erythropoietin resistance index was 10.59 in the EA period. It was not significantly different from 10.97 in DA period (p=0.49). Nine patients (25%) showed a >30% change in EA efficiency relative to DA efficiency. CONCLUSION: There was no significant difference in erythropoietic parameters for both EA and DA.
Anemia ; Cross-Over Studies ; Erythropoietin ; Hemoglobins ; Humans ; Recombinant Proteins ; Renal Dialysis ; Reticulocytes ; Darbepoetin alfa ; Epoetin Alfa

PURPOSE: This study was undertaken to examine whether differences exist in the hemoglobin variability according to the types of erythropoiesis stimulating agent (ESA) in hemodialysis (HD) patients. METHODS: Clinical data were retrospectively analyzed from 72 patients on maintenance hemodialysis who were using darbepoetin alfa (n=27), epoetin beta (n=27), and epoetin alpha (n=18). As parameters of hemoglobin variability, hemoglobin cycling, the variance of hemoglobin and the SD/mean of hemoglobin were analyzed. Hemoglobin cycling was defined as the presence of cycles with an amplitude >1.5 g/dL and lasting more than 2 months. RESULTS: Hemoglobin cycling was present in 53 (73.6%) out of 72 HD patients. Hemoglobin cycling in patients receiving darbepoetin alfa had greater frequency (1.63+/-0.93 vs. 1.00+/-0.88 times/year, p<0.05), amplitude (2.88+/-1.48 vs. 1.88+/-1.60 g/dL, p<0.05), and velocity (1.21+/-0.74 vs. 0.73+/-0.66 g/dL/month, p<0.05) than that in patients receiving epoetin beta. The variance of hemoglobin in patients receiving epoetin beta (0.79+/-0.53 g/dL) was smaller than that in patients receiving darbepoetin alfa (1.29+/-0.70 g/dL, p<0.05) and epoetin alfa (1.08+/-0.52 g/dL, p<0.05). Also, the ratio of SD/mean of hemoglobin in patients receiving epoetin beta (8.20+/-2.59%) was lower than that in patients receiving darbepoetin alfa (10.81+/-2.10%, p<0.05) and epoetin alfa (10.30+/-2.10%, p<0.05). CONCLUSION: Hemoglobin variability is differential according to various ESAs, and it may be less with epoetin beta compared with darbepoetin alpha and epoetin alpha.
Anemia ; Erythropoiesis ; Erythropoietin ; Hematinics ; Hemoglobins ; Humans ; Recombinant Proteins ; Renal Dialysis ; Retrospective Studies ; Darbepoetin alfa ; Epoetin Alfa

<p>OBJECTIVESTo detect the cholesterol ester transfer protein (CETP) levels in semen of infertile patients and evaluate the correlation between CETP in semial plasma and infertility.p><p>METHODSOne hundred and sixty-three infertile patients and fifteen fertile males were selected randomly. The routine examination of ejaculates was fulfilled by computer aided semen analysis (CASA). The CETP levels in all seminal plasma samples and fifty-five serum samples were detected by ELISA method.p><p>RESULTSThe CETP levels in infertile patients and fertile males were (2.21 +/- 1.23) microgram/L and (1.40 +/- 0.45) microgram/L, respectively. There were no significant differences between the two groups(P > 0.05). And there were no significant differences of CETP levels in seminal plasma among groups of azoospermia(n = 29), oligoasthenozoospermia (n = 58), oligospermia(n = 15), asthenozoospermia(n = 44) and normozoospermia(n = 17) in the infertile patients(P > 0.05). The CETP in seminal plasma and serum were detected in 55 infertile patients, and there was no correlation between CETP levels in seminal plasma and serum using Spearman analysis(r = 0.009, P > 0.05). The mean CETP level in seminal plasma was almost 1/1,000 of that in serum.p><p>CONCLUSIONSThe CETP level in seminal plasma is extremely low and has no relation with the changes of sperm density or motility. It may ensure the integrity of sperm membrane before the sperm enters into female genital tract.p>
Adult ; Carrier Proteins ; analysis ; blood ; Cholesterol Ester Transfer Proteins ; Glycoproteins ; Humans ; Infertility, Male ; metabolism ; Male ; Middle Aged ; Semen ; chemistry

<p>OBJECTIVETo detect cholesteryl ester transfer protein (CETP) levels, frequencies of CETP D442G and I 14A mutations and characteristics of abnormal lipids in patients with cardio-cerebro vascular diseases.p><p>METHODSNinety-four myocardial infarction (MI) patients, 110 stroke patients and 335 healthy controls were selected. The CETP concentration was determined using ELISA. The CETP activity was measured using a substrate of (14)C-radiolabeled discoidal bilayer particles. The CETP gene mutations were detected by PCR-RFLP.p><p>RESULTSThe CETP concentrations in the MI and stroke group, were higher than those in the controls. The gene mutation frequencies of D442G in the MI, stroke and control group were 3.5%, 3.6% and 5%, respectively, and the frequencies of I 14A were 1.05%, 0.91% and 1%, respectively. One case of D442G homozygote was detected in the healthy group. The frequency of two CETP gene mutations showed no significant difference among the patients and controls. The CETP concentration and activity in subjects with CETP mutations were one-third of those in the control group. The level of HDL-C, apo-A1 increased in the mutation subjects, while the TG level decreased.p><p>CONCLUSIONSThe CETP level increased significantly in patients with cardio-cerebrovascular diseases. The carriers of CETP deficiency had CETP and lipid abnormalities.p>
Carrier Proteins ; blood ; genetics ; Cholesterol Ester Transfer Proteins ; Glycoproteins ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Mutation ; Myocardial Infarction ; blood ; genetics ; Stroke ; blood ; genetics

<p>OBJECTIVETo study the distribution of cholesteryl ester transfer protein (CETP)-TaqIB polymorphism and plasma concentration in general population and the association between the two.p><p>METHODSA cross-sectional study was carried out in a general population of Beijing in 1999, using stratified-random sampling method. CETP-TaqIB polymorphism and plasma CETP concentration were determined in 719 individual aged 45 - 64 years.p><p>RESULTS(1) Frequencies of B1B1, B1B2 and B2B2 genotypes were 0.356, 0.478 and 0.166, respectively. The frequency of allele B2 was 0.405. Distributions of genotypes and alleles were homogeneous in both sexes. (2) Plasma CETP concentration manifested as a normal distribution, with the mean of 2.03 micro g/ml. The value of female was 20.3%, higher than that of male (P < 0.001). There were no differences among age groups. (3) Plasma CETP concentrations of B1B1 and B1B2 were 19.6% and 13.4% higher than that of B2B2 homozygotes. (4) Stratified by lipid levels, smoking and alcohol consumption, only when tryglyceride exceeded 150 mg/dl, with no significant difference among three genotypes. The effect of lipids, smoking and alcohol consumption status was more significant in B1B2 heterozygotes.p><p>CONCLUSIONCETP-TaqIB polymorphism was a determinant of plasma CETP concentration. However, the effect could be modified by other factors, such as lipids, smoking and alcohol consumption.p>
Carrier Proteins ; blood ; genetics ; Cholesterol Ester Transfer Proteins ; Cross-Sectional Studies ; Female ; Genotype ; Glycoproteins ; blood ; genetics ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic ; Sampling Studies

<p>BACKGROUNDThe Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD).p><p>METHODSGenomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package.p><p>RESULTSThe distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047).p><p>CONCLUSIONSGenetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.p>
Adult ; Aged ; Carrier Proteins ; genetics ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Disease ; blood ; genetics ; Female ; Gene Frequency ; Glycoproteins ; genetics ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic

<p>OBJECTIVETo obtain the nucleotide sequence and deduced amino acid sequence of cholesteryl ester transfer protein (CETP) cDNA from the tree shrew (Tupaia glis).p><p>METHODSThe cDNA sequence of the tree shrew CETP was obtained by utilizing the technique of switching mechanism at 5' end of RNA transcript (SMART) and rapid amplification of cDNA end (RACE) from the first strand of the cDNA. The amino acid sequence of CETP was deduced from the cDNA sequence and its primary and secondary structures were predicted.p><p>RESULTSThe sequence of CETP cDNA from tree shrew (GenBank accession number AF334033) covers 1636 bp, including 178 bp at the 3' end of the untranslated region and a 1458 bp fragment in a coding region, which provides the complete sequence of mature tree shrew CETP, although not the initiator methionine. The first 24 bp encodes a partial signal peptide. The mature protein consists of 477 amino acids and is longer than the human version by one amino acid (Gly318). Comparing this amino acid sequence with those of other animals' CETPs, the identity between tree shrew and human and rabbit CETP is 88% and 82%, respectively. The protein is extremely hydrophobic as it contains many hydrophobic residues, especially at the C-terminal, consistent with its function in the transfer of neutral lipids. The amino acid residues concerning with binding and transferring neutral lipids are highly conserved. There is a deletion of an N-linked glycosylation site at Asn342 in the tree shrew CETP protein that may participate in the removal of peripheral cholesterol and cholesteryl ester by increasing its activity of transferring cholesteryl ester.p><p>CONCLUSIONThe possible glycosylation in the tree shrew CETP may be involved in the molecular mechanism of its insusceptibility to atherosclerosis.p>
Amino Acid Sequence ; Animals ; Arteriosclerosis ; prevention & control ; Base Sequence ; Carrier Proteins ; chemistry ; genetics ; Cholesterol Ester Transfer Proteins ; Cloning, Molecular ; DNA, Complementary ; chemistry ; Glycoproteins ; Glycosylation ; Humans ; Molecular Sequence Data ; Protein Structure, Secondary ; Tupaiidae ; metabolism

<p>OBJECTIVETo study the major histocompatibility complex class II (MHC II) antigen and costimulatory molecules expression on the surface of breast cancer cells.p><p>METHODSMHC II antigen and costimulatory molecule expression on five breast cancer cell lines including MCF-7, SK-BR-3, T47D, MDA-MB-435 and ZR-75-30 were detected through flow cytometery analysis, with their expression level compared with that of normal mammary cell line HBL-100.p><p>RESULTSThe MHC II expression level of the five breast cancer cell lines were significantly different from that of HBL-100 (P < 0.05). MHC II antigen expression of MCF-7 cells which was about 20 percent of HBL-100 was the lowest. MDA-MB-435 and ZR-75-30 cell expression levels were twice as much as that of HBL-100, with the fluorescence intensity of MDA-MB-435 the highest of all cells. CD40 molecule expression on the surface of MDA-MB-435 cells was the lowest, which was nearly ten percent of that of MCF-7 and HBL-100 cells. CD80 and CD86 molecule expression showed no difference in MDA-MB-435 or HBL-100 cell (P > 0.05), and those of the other four breast cancer cells were lower than that of HBL-100 (P < 0.05).p><p>CONCLUSIONMHC II antigen and costimulatory molecule expression on the surface of breast cancer cells is abnormal, with different molecule expression in different cells. Breast cancer cells can escape immune surveillance through abnormal molecule expression.p>
Antigens, CD ; biosynthesis ; B7-1 Antigen ; biosynthesis ; B7-2 Antigen ; Breast Neoplasms ; immunology ; CD40 Antigens ; biosynthesis ; Cell Membrane ; immunology ; Female ; Histocompatibility Antigens Class II ; biosynthesis ; Humans ; Membrane Glycoproteins ; biosynthesis ; Tumor Cells, Cultured

<p>OBJECTIVETo determine the frequencies of 4 mutations of cholesteryl ester transfer protein (CETP) gene in Chinese population and to investigate the association of the mutations with lipid metabolism and the susceptibility to coronary atherosclerotic heart disease (CHD).p><p>METHODSThe target fragments of CETP gene were amplified and analyzed by PCR-restriction fragment length polymorphism technique in 209 unrelated control individuals and 203 CHD patients. The test for Hardy-Weinberg equilibrium was performed using HWE program and statistical analysis was implemented in statistical package SPSS.p><p>RESULTSIVS14A and 451Q mutant genes were not found in either control group or patient group. The frequencies of 405V mutant allele were 0.443 and 0.413 in controls and patients, respectively, while 442G mutant gene frequencies were 0.007 and 0.025, respectively. The observed allele frequencies of I405V and D442G mutation were in accord with Hardy-Weinberg equilibrium. The frequency of 442G mutant gene in patients was significantly higher than that in controls (P=0.043). Compared with the CHD patients without D442G mutation, the 442G heterozygous CHD patients exhibited a significant increase in plasma TC and LDL-C concentration (P=0.017; P=0.041).p><p>CONCLUSIONIVS14A and 451Q mutants of CETP gene were rare in Chinese population and 442G mutant gene was possibly one of the susceptibility factors to CHD in Chinese.p>
Aged ; Carrier Proteins ; genetics ; metabolism ; China ; Cholesterol Ester Transfer Proteins ; Coronary Artery Disease ; blood ; genetics ; DNA ; genetics ; metabolism ; DNA Restriction Enzymes ; metabolism ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Glycoproteins ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Mutation ; Polymorphism, Restriction Fragment Length

BACKGROUND: Lipocalin-2 (LCN2), a small glycoprotein, has a pivotal role in diverse biological processes such as cellular proliferation and differentiation. We previously reported that LCN2 is implicated in osteoclast formation induced by receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). In the present study, we used a knockout mouse model to further investigate the role of LCN2 in osteoclast development. METHODS: Osteoclastogenesis was assessed using primary bone marrow-derived macrophages. RANKL and M-CSF signaling was determined by immunoblotting, cell proliferation by bromodeoxyuridine (BrdU) enzyme-linked immunosorbent assay (ELISA), and apoptosis by cell death detection ELISA. Bone morphometric parameters were determined using a micro-computed tomography system. RESULTS: Our results showed that LCN2 deficiency increases tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclast formation in vitro, a finding that reflects enhanced proliferation and differentiation of osteoclast lineage cells. LCN2 deficiency promotes M-CSF-induced proliferation of bone marrow macrophages (BMMs), osteoclast precursors, without altering their survival. The accelerated proliferation of LCN2-deficient precursors is associated with enhanced expression and activation of the M-CSF receptor, c-Fms. Furthermore, LCN2 deficiency stimulates the induction of c-Fos and nuclear factor of activated T cells c1 (NFATc1), key transcription factors for osteoclastogenesis, and promotes RANKL-induced inhibitor of kappa B (IkappaBalpha) phosphorylation. Interestingly, LCN2 deficiency does not affect basal osteoclast formation in vivo, suggesting that LCN2 might play a role in the enhanced osteoclast development that occurs under some pathological conditions. CONCLUSIONS: Our study establishes LCN2 as a negative modulator of osteoclast formation, results that are in accordance with our previous findings.
Acid Phosphatase ; Animals ; Apoptosis ; Biological Processes ; Bone Marrow ; Bromodeoxyuridine ; Cell Death ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins ; Immunoblotting ; Macrophage Colony-Stimulating Factor ; Macrophages ; Mice ; Mice, Knockout ; NF-kappa B ; Osteoclasts* ; Phosphorylation ; RANK Ligand ; T-Lymphocytes ; Transcription Factors