Biomedical subjects

Ning Liu

Publications and source records attributed to Ning Liu.

98 records · Page 6Linked to original sources

PubMed2002

Diagnosis and treatment of primary gastric non-Hodgkin's lymphoma: analysis of 157 patients.

OBJECTIVE: To seek the optimum treatment for patients with primary gastric non-Hodgkin's lymphoma and factors associated with prognosis. METHODS: A retrospective study was conducted on 157 primary gastric non-Hodgkin's lymphoma patients who had received operation for 45 years. RESULTS: The X-ray diagnosis rate was 39.4% before operation. The diagnosis rate by gastroscopy was 52.7%. Among the 157 patients, 32 belonged to stage I(E), 40 stage II(E), 29 stage III(E), and 56 stage IV(E). All of the patients were received chemotherapy or radiation. The 3-, 5-, 10-, 15-year survival rates were 51.1% (69/135), 42.3% (55/130), 20.7% (23/111), and 13.5% (14/104). CONCLUSIONS: The 3-, 5-year survival rates in stage I(E) and stage II(E) were 2 to 5 times higher than those in stage III(E) and IV(E) (P < 0.01). The 3-, 5-year survival rates of primary gastric non-Hodgkin's lymphoma were 60.2% (65/108) and 50.0% (52/104) respectively. The prognosis was better than the 5-year survival rate of gastric cancer patients with D(2) lymphodenectomy (33.3%). Early diagnosis and treatment are effective to prevent complications, enhance quality of patient's life, and prolong the survival.

Humans↗

PubMed2001

Differential aggregation of the Trembler and Trembler J mutants of peripheral myelin protein 22.

Mutations in the gene encoding the peripheral myelin protein 22 (PMP22), a tetraspan protein in compact peripheral myelin, are one of the causes of inherited demyelinating peripheral neuropathy. Most PMP22 mutations alter the trafficking of the PMP22 protein in Schwann cells, and this different trafficking has been proposed as the underlying mechanism of the disease. To explore this problem further, we compared the aggregation of wild-type Pmp22 with those of the two Pmp22 mutations found in Trembler (Tr) and Trembler J (TrJ) mice. All three Pmp22s can be crosslinked readily as homodimers in transfected cells. Wild-type Pmp22 also forms heterodimers with Tr and TrJ Pmp22, and these heterodimers traffic with their respective mutant Pmp22 homodimers. All three Pmp22s form complexes larger than dimers with Tr Pmp22 especially prone to aggregate into high molecular weight complexes. Despite the differences in aggregation of Tr and TrJ Pmp22, these two mutant Pmp22s sequester the same amount of wild-type Pmp22 in heterodimers and heterooligomers. Thus, the differences in the phenotypes of Tr and TrJ mice may depend more on the ability of the mutant protein to aggregate than on the dominant-negative effect of the mutant Pmp22 on wild-type Pmp22 trafficking.

Alleles↗

PubMedDate not supplied

Electrostatic binding with tat and other cationic peptides increases cell accumulation of 99mTc-antisense DNAs without entrapment.

UNLABELLED: An important limitation restricting antisense nuclear medicine imaging is low radioactivity accumulations in target cells. The Tat peptide (Tat), a basic domain of the HIV Tat protein, has been shown to enhance cell accumulation of various biomolecules. PURPOSE: The influence of Tat, as a cationic carrier, on the accumulation in cell culture of anionic antisense DNAs bound electrostatically rather than covalently was investigated. To establish specificity of the accumulation, antisense DNA and control sequence were studied along with four different peptides. The technique of in situ reverse transcription was used to assay the in vivo hybridization of antisense DNA to the target mRNA in cultured live cells when transducted with the Tat peptide. METHODS: Uniform phosphorothioated DNAs were radiolabeled with 99mTc via Hynic/tricine. This 18 mer antisense DNA against RI alpha mRNA along with its sense and random control was studied in ACHN cells with the four peptides as carriers. RESULTS: The addition of Tat significantly increased cell accumulations. At 12 hours accumulations went from 14% to 45% for the antisense DNA and from 4% to 12% for control. Furthermore, an antisense effect was again suggested, now with the Tat carrier, by the significantly higher accumulation of 99mTc on both antisense DNAs vs. controls. Moreover, the accumulated antisense DNA enhanced with the Tat carrier was capable of priming reverse transcription as determined by an in situ assay suggesting that the DNA could escape from entrapment in endosome or lysosome vesicles for hybridization. However, differences in cellular accumulation with either Tat compared to either scrambled peptide were not significant, showing that the Tat in this study was functioning merely as a cationic carrier. CONCLUSIONS: Although electrostatic binding of antisense DNA to Tat is convenient, the association may mask the unique transduction properties of the peptide. Nevertheless, a promising improvement in cellular accumulation of antisense DNA was observed through the use of these carriers. In addition, at least a fraction of the transducted DNA appears to be free of entrapment to hybridize to its mRNA target in live cells.

DNA, Antisense↗

PubMedDate not supplied

A comparison of in vitro and in vivo stability in mice of two morpholino duplexes differing in chain length.

UNLABELLED: The stability of hybridized duplexes is an important criterion for any radiopharmaceutical application of DNAs or their analogues such as phosphorodiamidate morpholinos (MORFs). OBJECTIVE: The stabilities in vitro and in mice of the duplex between MORF and its complement (cMORF) were investigated for two different chain lengths, a 15-mer MORF compared to the identical MORF but elongated to a 25-mer. METHODS: The hybridization characteristics of the 15-mer MORF with its complementary 15-mer and that of the 25-mer with its complementary 25-mer MORF were measured using surface plasmon resonance (SPR) analysis. For radiolabeling with (99m)Tc, the 15- and 25-mer MORF, both with a primary amine via a 10-member linker on the 3' equivalent end, were conjugated with NHS-MAG(3). The 15- and 25-mer cMORFs were conjugated via their amines to carbodiimidazole treated poly(methyl vinyl ether-alt-maleic acid) (PA) such that about 50 cMORFs were attached to each polymer molecule in both cases (estimated MWs about 300 and 450 kDa, respectively). After hybridization in vitro, both the PA-cMORF15-(99m)Tc-MORF15 and PA-cMORF25-(99m)Tc-MORF25 homoduplexes were evaluated by size exclusion HPLC in saline, after incubation in 37 degrees C serum and in urine obtained 30 min post IV administration to normal mice. Biodistributions were obtained up to 18 h post administration. RESULTS: By SPR, the affinity constants for the homoduplexes were both about 10(9) M(-)(1) with the 25/25 only about 25% higher than the 15/15. However, the affinity constants for the 15/25 and 25/15 heteroduplexes showed a surprisingly 13-fold difference. By HPLC analysis, all duplexes were stable in saline; however, analysis of serum incubates and urine containing PA-cMORF15-(99m)Tc-MORF15 showed an immediate and pronounced low molecular weight peak that was identified by a shift assay to be (99m)Tc-MORF15. The comparable peak in both fluids was much less pronounced in the case of PA-cMORF25-(99m)Tc-MORF25. Whole body radioactivity levels also fell much more rapidly in mice receiving the 15-mer conjugate (65 vs 30% eliminated at 18 h) and biodistribution results showed higher kidney levels for the 15-mer conjugate. Results with the PA-cMORF25-(99m)Tc-MORF15 heteroduplex were more similar to that obtained with the 15-mer homoduplex than the 25-mer homoduplex. CONCLUSION: Despite what is reported to be high hybridization affinities, both the homoduplex and heteroduplexes prepared with (99m)Tc-MORF15 were found to be unstable in serum and in vivo toward dissociation to free (99m)Tc-MORF15. By contrast, homoduplex prepared with (99m)Tc-MORF25 showed higher stability. These differences in hybridization stability may be important considerations in radiopharmaceutical design.

Animals↗

PubMedDate not supplied

Comparison of species differences of P-glycoproteins in beagle dog, rhesus monkey, and human using Atpase activity assays.

P-glycoprotein (P-gp) is a transmembrane efflux transporter which possesses many important functions in drug absorption, disposition, metabolism, and toxicity. The ultimate goal of investigating drug interactions between P-gp and drug molecules in early drug discovery is to understand the contribution of P-gp to the pharmacokinetic and pharmacodynamic properties of drug candidates and to project drug-drug interaction (DDI) potentials in humans. Understanding species differences in P-gp activities further helps the prediction of P-gp-mediated drug disposition and DDI in humans from preclinical pharmacokinetics data. The objective of the present study is to investigate the species difference in P-gp activities, via P-gp ATPase assays, using rhesus monkey Mdr1, beagle dog Mdr1, and human MDR1 expressed insect cell membranes. Twenty-one compounds with diverse chemical structures and different P-gp binding sites were chosen for the ATPase assays. P-gp ATPase binding affinities (alphaKa) and fold increases in P-gp ATPase activities (beta) of P-gp substrates were determined. Consistent with the gene and amino acid similarity, the binding affinities of test compounds to rhesus monkey P-gp were much closer to those of human P-gp than beagle dog P-gp. This is the first study which investigates the ligand affinities of P-gp from three different species. The result of this study provides an example of how to use membrane P-gp ATPase assays to evaluate interspecies P-gp differences.

ATP Binding Cassette Transporter, Subfamily B↗

PubMedDate not supplied

Two-dimensional phased arrays of sources and detectors for depth discrimination in diffuse optical imaging.

We present a multisource, multidetector phased-array approach to diffuse optical imaging that is based on postprocessing continuous-wave data. We previously showed that this approach enhances the spatial resolution of diffuse optical imaging. We now demonstrate the depth discrimination capabilities of this approach and its potential to perform tomographic sectioning of turbid media. The depth discrimination results from the dependence of the sensitivity function on the depth coordinate z. To demonstrate the potential of this approach, we perform an experimental study of a turbid medium containing cylindrical inhomogeneities that are placed 2.0, 3.0, and 4.0 cm from a seven-element, 2-D source array. A single detector element is placed at a distance of 6.0 cm from the source array, and the measurement is repeated after switching the positions of the detector and the source array to simulate the case where both sources and detectors consist of a 2-D array of elements. We find that the proposed phased-array method is able to separate cylinders at different depths, thus showing cross-sectioning capabilities.

Equipment Design↗

PubMedDate not supplied

Broad antiproliferative effects of benidipine on cultured human mesangial cells in cell cycle phases.

BACKGROUND AND PURPOSE: Recently, in vitro studies have shown that some calcium channel blockers inhibit the proliferation of mesangial cells. In the present study, we evaluated the antiproliferative effects of benidipine, a calcium channel blocker, in comparison with other calcium channel blockers, and attempted to further clarify its mechanism of action on cultured human mesangial cells in relation to cell cycle. METHODS: Human mesangial cells were cultured in medium containing 5% fetal calf serum (FCS), with or without benidipine, or other calcium channel blockers for 20 h, and [(3)H]thymidine incorporation were measured. Analysis of cell cycle dependency was carried out, using platelet-derived growth factor as a competence factor, which transfers cells from the G0 to the G1 (G0/G1) phase, and insulin as a progression factor, which transfers cells from the G1 to the S (G1/S) phase. Cells were also analyzed by flow cytometry. RESULTS: Benidipine and nifedipine showed significant inhibitory effects on FCS-induced proliferation (p < 0.001 and p < 0.01, respectively, by ANOVA), with 3.8 and 41.9% of the control level of [(3)H]thymidine incorporation at the concentration of 10 microM of the blockers, respectively. Diltiazem had no inhibitory effect at this concentration. Benidipine was found to inhibit cells in both the boundaries of G0/G1 and G1/S phases (p < 0.001 and p < 0.0001, respectively), whereas nifedipine inhibited only cells in G1/S phase (p < 0.05). The effects of benidipine (10 microM) on cells in G1/S were stronger than those on cells in the G0/G1 phase (p < 0.0001). Furthermore, flow cytometry showed that 10 mM benidipine significantly inhibited the G1 to S phase transition of FCS-stimulated mesangial cells (p < 0.03). CONCLUSIONS: Benidipine markedly inhibited the proliferation of mesangial cells, at both the G0/G1 and G1/S phases, and it might be effective to suppress the progression of mesangioproliferative glomerular diseases.

Calcium Channel Blockers↗

PubMedDate not supplied

Recent advances in parathyroid disease and parathyroid hormone assays.

Parathyroid hormone (PTH) regulates extracellular calcium. The physiology and pathology of PTH and the many circulating fragments of PTH are reviewed. Various PTH assays have been used, leading to the now standard intact PTH (iPTH). The recently discovered 7-84 fragment may have profound implications in PTH measurement and management, particularly in renal-failure patients. Newer assays measuring true PTH, exclusive of this fragment, are appearing on the market and may have use in monitoring calcitriol analogue therapy and other settings. Rapid PTH assays have application as intraoperative measures of success during excision of parathyroid adenomas.

Calcium↗