PubMed Health⌕ Search

Biomedical subjects

Jian Liu

Publications and source records attributed to Jian Liu.

At least 127 records · Page 7Linked to original sources

[Phase II clinical trial on China manufactured recombinant human interleukin-11 derivative in the prevention and treatment of chemotherapy-induced thrombocytopenia].

OBJECTIVE: This phase II clinical trial was designed to evaluate the efficacy and toxicity of recombinant human interleukin-11 (rhIL-11) derivative manufactured in China in the prevention and treatment of chemotherapy-induced thrombocytopenia in cancer patients. METHODS: A total of 100 cancer patients with chemotherapy-induced thrombocytopenia (< or = 75 x 10(9)/L) were studied by self-cross control. Ninty-one of them received 2 cycles of chemotherapy. In the first cycle (control cycle) the patients received chemotherapy only, while in the second cycle (treatment cycle), the patients were given subcutaneous injection of rhIL-11 derivative (40 microg.kg(-1).d(-1)) once daily after chemotherapy for 10 consecutive days or more until platelet count reached > or = 300 x 10(9)/L. RESULTS: 1. The patients with platelet count of < or = 75 x 10(9)/L was 89/89 in the control cycle and 44/89 in the treatment cycle (P = 0.00). The recovery time to the normal platelet count was 1-47 days (median 9 days) in the control cycle, and 1-18 days (median 5.5 days) in treatment cycle (P = 0.00). 2. Patients with platelet count of < or = 50 x 10(9)/L was 56/89 in the control cycle and 20/89 in the treatment cycle (P = 0.00). The recovery time to normal platelet count was 1-31 days (median 9 days) in the control cycle and 3-13 days (median 6 days) in the treatment cycle (P = 0.05). 3. The median nadir platelet count was 44 x 10(9)/L (range: 10 x 10(9)/L-75 x 10(9)/L) in the control cycle, and 83 x 10(9)/L (range: 10 x 10(9)/L-310 x 10(9)/L) in the treatment cycle (P = 0.00). The time of recovery to the normal platelet count was 1-31 days (median 6 days) in the control cycle, and 0-13 days (median 2 days) in the treatment cycle (P = 0.00). 4. Nine of 89 evaluable patients required platelet transfusion in the control cycle versus 1 of 89 patients in treatment cycle (P = 0.01), and the total platelet transfusion was 10 times in the control cycle versus once in the treatment cycle (P = 0.01). 5. The major adverse events associated with rhIL-11 derivative were: headache, fatigue, myalgia/arthralgia, edema and palpitation, etc. CONCLUSION: rhIL-11 derivative can be safely and effectively used for the prevention and treatment for chemotherapy-induced thrombocytopenia.

Adult↗

[Cytotoxicity study of heparin coated polyvinyl chloride material].

In this study, heparin ionically coated polyvinyl chloride (PVC) material was prepared by heparin-benzalkonium chloride complex (Group A), heparin-benzalkonium bromide complex (Group B) and heparin-polyethyleneimine compound (Group C). Cytotoxicity evaluation was conducted by direct cell contact evaluation and MTT colorimetry method. The results showed Group A and Group B caused L-929 cells to die out while Group C showed good compatibility with cells. The OD levels of Group A and B were lower than that of the Group C in MTT test. Method A and method B of heparin coating had remarkable cytotoxicity, while method C had little cytotoxicity and could be further studied for clinical use.

Animals↗

Experimental study on establishing eukaryotic expression vector pcDNA3.1(+) TPA and its expressing activity in human skin fibroblists.

OBJECTIVE: To establish a cell line stably expressing the tissue plasminogen activator (TPA) in human skin fibroblasts so as to develop the function analysis and gene therapy of TPA in ischemic heart diseases. METHODS: Eukaryotic expression vector pcDNA3.1(+) TPA was constructed and transferred into human skin fibroblasts. After G418 selection, the exogenous expression and activity of TPA were observed subsequently by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and chromogenic substrate assay. RESULTS: Eukaryotic expression vector pcDNA3.1(+) TPA was expressed effectively in human skin fibroblasts. Quantitative ELISA showed that the expression of TPA protein of the experiment group was much higher than that of the control group (643.5 ng/10(6) cells per 24 hours vs. 19.2 ng/10(6) cells per 24 hours). And the chromogenic substrate assay showed that the exogenous TPA activity of the experimental group was also much higher than that of the control group (122.6 U/10(6) cells per 24 hours vs. 5.8 U/10(6) cells per 24 hours). CONCLUSION: The exogenous TPA gene can be expressed effectively after pcDNA3.1(+)TPA was transferred into human skin fibroblasts, suggesting that the cell model will become an important tool in the further study of TPA function and gene therapy in ischemic heart diseases.

Base Sequence↗

Ovariotomy and persistent pain affect long-term Fos expression in spinal cord.

Sex differences in pain have been confirmed both in clinical and experimental studies. Estrogen has a great role in this process and can affect response to noxious stimuli. In this study, we used Fos as a marker to investigate the mechanism underlying the phenomenon. Sprague-Dawley rats were randomly assigned to ovariotomy (OVX) or sham surgery (OVX-sham) group (n=20 rats/condition). All the rats received CCI surgery three weeks after ovariotomy. We used hot-plate test as a sign of neuropathic pain. On PO days 3, 7, 14, and 21, paw withdrawal latency was determined and 2 h later, the L4-L5 segments of the spinal cord were removed and immunostained for Fos protein. Number of Fos-like immunoreactive (Fos-LI) neurons of each section was counted bilaterally. We find that ovariotomy can regulate the sensitivity to thermal stimuli and Fos protein level will change in the spinal dorsal horn. However, the alternation of Fos expression does not extremely account for the behavior.

Animals↗

[Comparison of pharmacokinetics/pharmacodynamics of cefdinir, cefpodoxime proxetil and cefaclor against common bacteria of community acquired infections].

OBJECTIVE: To compare the pharmacokinetics/pharmacodynamics property of cefdinir, cefpodoxime proxetil and cefaclor against common bacteria of community acquired infections and evaluate the recommended regimens. METHODS: The antibacterial activities of 3 agents against 238 clinical isolates were determined by standard agar dilution test and the pharmacokinetics of these antibiotics in male healthy volunteers were conducted in Latin-square manner. The time over MIC (T > MIC) of serum antibiotic concentrations were calculated with pharmacokinetic equation and MIC. RESULTS: The value of MIC90 s cefdinir against these bacterial strains except penicillin non-sensitive pneumococci were 0.031-1 mg/L. Cefpodoxime held similar antibacterial activity with cefdinir, but was less potent against staphylococci. Cefaclor had much higher MIC values than other two drugs. After oral administration of 250 mg cefaclor, the drug concentration quickly reached peak concentration of 4.95 mg/L +/- 2.41 mg/L and the eliminative half time was 0.69 h +/- 0.6 h; the Tmax, Cmax and T1/2beta of cefdinir and cefpodoxime after oral administration of 100 mg were 2.5 h +/- 0.48 h, 0.81 mg/L +/- 0.19 mg/L, 1.73 h +/- 0.3 h and 2.38 h +/- 0.43 h, 1.12 mg/L +/- 0.28 mg/L, 1.92 h +/- 0.55 h, respectively. T > MIC of cefdinir in thrice daily administration were longer than 40% of medication interval against most of the tested isolates; no T > MIC period was found in cefpodoxime against staphylococci and the T > MICs of cefaclor after 250 mg oral administration were shorter than expected values against most bacteria. CONCLUSION: With powerful antibacterial activity, the T > MICs of cefdinir after 100 mg oral administration can meet with the clinical requirement in most infections; PK/PD value of cefpodoxime proxetil against staphylococci is lower than expectancy and 250 mg cefaclor 3 times daily is not enough to the treatment of common community acquired infections, the regimens of cefpodoxime proxetil and cefclor should be furtherly optimized.

Anti-Bacterial Agents↗

Double transfection improves small interfering RNA-induced thrombin receptor (PAR-1) gene silencing in DU 145 prostate cancer cells.

The efficiency of small interfering RNA (siRNA)-induced gene knockdown is hampered by low transfection efficiency. We established a novel and simple double transfection method using specific siRNA duplexes targeted against human thrombin receptor PAR-1 in DU 145 prostate cancer cells. The initial siRNA transfection of cell suspensions followed by re-transfection of adherent cells on the following day resulted in undetectable PAR-1 mRNA and absent receptor protein. PAR-1 mRNA expression was silenced for up to five days. Functional studies showed that PAR-1 gene silencing in DU 145 cells abolished the modulating effects of thrombin on cell adhesion to the extracellular matrix proteins, fibronectin and laminin, thus demonstrating the essential role of PAR-1 in mediating thrombin effects on DU 145 cell adhesion.

Base Sequence↗

Determination of icariin and metabolites in rat serum by capillary zone electrophoresis: rat pharmacokinetic studies after administration of icariin.

A simple and rapid method for determination of icariin (ICA) and its two metabolites, icaritin (ICT) and desmethylicaritin (DICT), by capillary zone electrophoresis has been developed and validated. Optimum separation of ICA, ICT, and DICT was obtained on 43.6 cm x 50 microm capillary using sodium tetraborate (30 mmol/L), monobasic sodium phosphate (50 mmol/L)-acetonitrile (50:50, v/v) (pH 10.0) as running buffer. Carbamazepine (CMP) was used as internal standard (IS). The temperature and voltage were optimized at 25 degrees C and 12 kV, respectively. The limit of detection of ICA was 1.0 mg/L (S/N = 3) by UV detection at 270 nm. The elaborated method was tested in vivo after administration of a single dose of 120 mg ICA/kg to healthy rats. Calculated parameters confirmed usefulness of the method in rat pharmacokinetic studies on ICA.

Animals↗

[Changes of discharge rate and pattern of 5-hydroxytrypamine neurons of dorsal raphe nucleus in a rat model of Parkinson's disease].

In the present study, changes of the neuronal activity of 5-hydroxytrypamine (5-HT) neurons of dorsal raphe nucleus(DRN) in a rat model of Parkinson's disease (PD) were investigated with glass microelectrode recording. The results showed that the discharge rates of 5-HT neurons in control and PD rats were (1.61+/-0.56) Hz and (2.61+/-1.97) Hz, respectively. The discharge rate of PD rats was significantly increased when compared to that of the control rats. In control rats, 79% of 5-HT neurons discharged regularly and 21% in bursts. In PD rats, however, 36% of 5-HT neurons discharged regularly, 16% irregularly and 47% in bursts. The percentage of 5-HT neurons discharging in bursts was obviously higher than that of the control rats (P<0.05). The data suggest that the discharge rate and bursting pattern of 5-HT neurons in DRN are increased in a rat model of Parkinson's disease.

Animals↗

Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer.

Vesicular stomatitis virus (VSV) has been shown to replicate rapidly in vitro and kill selectively a variety of tumor cell lines. The present study was designed to determine whether gemcitabine potentiates the antitumor activity of VSV in vitro and in vivo. A549 human lung adenocarcinoma cells and LLC Lewis lung carcinoma cells were treated with VSV (0.1-10 plaque-forming units per cell) plus gemcitabine (20 nM to 20 microM). Mice bearing A549 or LLC were treated with VSV (5 x 10(4) to 1 x 10(8) plaque-forming units) daily for 5 days plus gemcitabine (5-125 mg/kg/day) once every 3 days for 4 times. Induction of apoptosis and effects on growth inhibition were assessed. The lung cancer cells treated with VSV plus gemcitabine displayed the apparently increased apoptotic cells compared with treatment with VSV or gemcitabine alone. The combined treatment with VSV plus gemcitabine induced the apparent antitumor activity with complete regression of the established lung cancer in both A549 and LLC lung cancer models and augmented the induction of apoptosis in lung cancer cells in vivo as well. This study suggests that the combined treatment with VSV plus gemcitabine may augment the induction of apoptosis in lung cancer cells in vitro and in vivo, and that the augmented antitumor activity in vivo may result from the increased induction of apoptosis in lung cancer cells. The present findings may be of importance to the further exploration of the potential application of this combined approach in the treatment of lung cancer.

Adenocarcinoma↗

Hierarchical structure description of spatiotemporal chaos.

We develop a hierarchical structure (HS) analysis for quantitative description of statistical states of spatially extended systems. Examples discussed here include an experimental reaction-diffusion system with Belousov-Zhabotinsky kinetics, the two-dimensional complex Ginzburg-Landau equation, and the modified FitzHugh-Nagumon equation, which all show complex dynamics of spirals and defects. We demonstrate that the spatial-temporal fluctuation fields in the above-mentioned systems all display the HS similarity property originally proposed for the study of fully developed turbulence [Phys. Rev. Lett. 72, 336 (1994)]]. The derived values of a HS parameter beta from experimental and numerical data in various physical regimes exhibit consistent trends and characterize the degree of turbulence in the systems near the transition, and the degree of heterogeneity of multiple disorders far from the transition. It is suggested that the HS analysis offers a useful quantitative description for the complex dynamics of two-dimensional spatiotemporal patterns.

Journal Article↗

High-level mRNA quantification of proliferation marker pKi-67 is correlated with favorable prognosis in colorectal carcinoma.

PURPOSE: The present study retrospectively examines the expression of pKi-67 mRNA and protein in colorectal carcinoma and their correlation to the outcome of patients. METHODS: Immunohistochemistry and quantitative RT-PCR were used to analyze the expression of pKi-67 in 43 archival specimens of patients with curatively resected primary colorectal carcinoma, who were not treated with neo-adjuvant therapy. RESULTS: We determined a median pKi-67 (MIB-1) labeling index of 31.3% (range 10.3-66.4%), and a mean mRNA level of 0.1769 (DeltaC(T): range 0.01-0.69); indices and levels did not correlate. High pKi-67 mRNA DeltaC(T) values were associated with a significantly favorable prognosis, while pKi-67 labeling indices were not correlated to prognostic outcome. A multivariate analysis of clinical and biological factors indicated that tumor stage (UICC) and pKi-67 mRNA expression level were independent prognostic factors. CONCLUSION: Quantitatively determined pKi-67 mRNA can be a good and new prognostic indicator for primary resected colorectal carcinoma.

Adult↗

Structural basis of Rab5-Rabaptin5 interaction in endocytosis.

Rab5 is a small GTPase that regulates early endosome fusion. We present here the crystal structure of the Rab5 GTPase domain in complex with a GTP analog and the C-terminal domain of effector Rabaptin5. The proteins form a dyad-symmetric Rab5-Rabaptin5(2)-Rab5 ternary complex with a parallel coiled-coil Rabaptin5 homodimer in the middle. Two Rab5 molecules bind independently to the Rabaptin5 dimer using their switch and interswitch regions. The binding does not involve the Rab complementarity-determining regions. We also present the crystal structures of two distinct forms of GDP-Rab5 complexes, both of which are incompatible with Rabaptin5 binding. One has a dislocated and disordered switch I but a virtually intact switch II, whereas the other has its beta-sheet and both switch regions reorganized. Biochemical and functional analyses show that the crystallographically observed Rab5-Rabaptin5 complex also exists in solution, and disruption of this complex by mutation abrogates endosome fusion.

Amino Acid Sequence↗

High-throughput microarray detection of olfactory receptor gene expression in the mouse.

The large number of olfactory receptor genes necessitates high throughput methods to analyze their expression patterns. We have therefore designed a high-density oligonucleotide array containing all known mouse olfactory receptor (OR) and V1R vomeronasal receptor genes. This custom array detected a large number of receptor genes, demonstrating specific expression in the olfactory sensory epithelium for approximately 800 OR genes previously designated as ORs based solely on genomic sequences. The array also enabled us to monitor the spatial and temporal distribution of gene expression for the entire OR family. Interestingly, OR genes showing spatially segregated expression patterns were also segregated on the chromosomes. This correlation between genomic location and spatial expression provides unique insights about the regulation of this large family of genes.

Age Factors↗

Transcriptional activation of c-myc proto-oncogene by WT1 protein.

The Wilms' tumor 1 gene (WT1) plays an essential role in urogenital development and malignancy. Through DNA binding, WT1 can either enhance or repress transcription depending on the context of the DNA-binding sites or the cell type in which it is expressed. WT1 is overexpressed in a variety of human cancers, including leukemia and breast cancer; in these diseases, the expression of WT1 is associated with a poor prognosis. To determine how WT1 affects c-myc expression in the context of breast cancer cells, we have examined the ability of both endogenous and exogenous WT1 proteins in breast cancer cells to bind to the c-myc promoter in vivo. Using c-myc-promoter-driven luciferase constructs, we found that different forms of WT1 could enhance the expression of the reporter. Unlike other studies where WT1 is reported to be a negative regulator of c-myc, we found that both the - and + KTS forms of WT1 could act to enhance c-myc expression, depending on the cell type. The WT1-binding site near the second major transcription start site of the c-myc promoter was confirmed to be involved in upregulation of human c-myc by WT1. Finally, we demonstrated that overexpression of WT1 induced a significant increase in the abundance of endogenous c-myc protein in breast cancer cells, consistent with the upregulation of c-myc transcription following WT1 induction. These observations strongly argue that in the case of breast cancer WT1 is functioning as an oncogene in part by stimulating the expression of c-myc.

Base Sequence↗

Capillary high-performance liquid chromatography-electrospray ionization mass spectrometry using monolithic columns and carbon fiber electrospray ionization emitters.

Monolithic columns having long hydrocarbon chains were prepared by in-situ polymerization in capillary fused silica tubing. The capillary columns were coupled with a newly developed carbon fiber electrospray ionization (ESI) emitter for proteomic analysis using sheathless capillary HPLC-ESI mass spectrometry (MS). The sample loading capacity and chromatographic performance of the styrene-based monolithic column, which was prepared by photo-polymerization of octylstyrene (OS) and divinylbenzene (DVB) were compared with that of the methacrylate-based monolithic column composed of lauryl methacrylate (LMA) and ethylene dimethacrylate (EDMA). The sample loading ability of tryptic digested protein in poly-OS (POS)-DVB column was higher than that of poly-LMA (PLMA)-EDMA column, possibly due to the irregular and rugluous surface offering a greater surface area of POS-DVB stationary phase. The POS-DVB column also provided better separation efficiency in the separation of high concentration (10 microg) of tryptic digested albumin bovine serum (BSA). Due to the successful interface of a highly efficient monolithic column and a stable, durable carbon fiber emitter, low femtomole levels of peptides were successfully separated and identified in the presence of large amounts of tryptic digested protein.

Amino Acid Sequence↗

Structural analysis of the sulfotransferase (3-o-sulfotransferase isoform 3) involved in the biosynthesis of an entry receptor for herpes simplex virus 1.

Heparan sulfate (HS) plays essential roles in assisting herpes simplex virus infection and other biological processes. The biosynthesis of HS includes numerous specialized sulfotransferases that generate a variety of sulfated saccharide sequences, conferring the selectivity of biological functions of HS. We report a structural study of human HS 3-O-sulfotransferase isoform 3 (3-OST-3), a key sulfotransferase that transfers a sulfuryl group to a specific glucosamine in HS generating an entry receptor for herpes simplex virus 1. We have obtained the crystal structure of 3-OST-3 at 1.95 A in a ternary complex with 3'-phosphoadenosine 5'-phosphate and a tetrasaccharide substrate. Mutational analyses were also performed on the residues involved in the binding of the substrate. Residues Gln255 and Lys368 are essential for the sulfotransferase activity and lie within hydrogen bonding distances to the carboxyl and sulfo groups of the uronic acid unit. These residues participate in the substrate recognition of 3-OST-3. This structure provides atomic level evidence for delineating the substrate recognition and catalytic mechanism for 3-OST-3.

Amino Acid Sequence↗

Discovery of frequent homozygous deletions in chromosome 3p21.3 LUCA and AP20 regions in renal, lung and breast carcinomas.

We searched for chromosome 3p homo- and hemizygous losses in 23 lung cancer cell lines, 53 renal cell and 22 breast carcinoma biopsies using 31 microsatellite markers located in frequently deleted 3p regions. In addition, two sequence-tagged site markers (NLJ-003 and NL3-001) located in the Alu-PCR clone 20 region (AP20) and lung cancer (LUCA) regions, respectively, were used for quantitative real-time PCR (QPCR). We found frequent (10-18%) homozygous deletions (HDs) in both 3p21.3 regions in the biopsies and lung cancer cell lines. In addition, we discovered that amplification of 3p is a very common (15-42.5%) event in these cancers and probably in other epithelial malignancies. QPCR showed that aberrations of either NLJ-003 or NL3-001 were detected in more than 90% of all studied cases. HDs were frequently detected simultaneously both in NLJ-003 or NL3-001 loci in the same tumour (P<3-10(-7)). This observation suggests that tumour suppressor genes (TSG) in these regions could have a synergistic effect. The exceptionally high frequency of chromosome aberrations in NLJ-003 and NL3-001 loci suggests that multiple TSG(s) involved in different malignancies are located very near to these markers. Precise mapping of 15 independent HDs in the LUCA region allowed us to establish the smallest HD region in 3p21.3C located between D3S1568 (CACNA2D2 gene) and D3S4604 (SEMA3F gene). This region contains 17 genes. Mapping of 19 HDs in the AP20 region resulted in the localization of the minimal region to the interval flanked by D3S1298 and D3S3623 markers. Only four genes were discovered in this interval, namely, APRG1, ITGA9, HYA22 and VILL.

Breast Neoplasms↗