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Biomedical subjects

Feng Gao

Publications and source records attributed to Feng Gao.

At least 289 records · Page 16Linked to original sources

Human antibodies against amyloid beta peptide: a potential treatment for Alzheimer's disease.

Naturally occurring antibodies directed against beta-amyloid (Abeta) were detected in intravenous immunoglobulin preparations. After intravenous immunoglobulin treatment in patients with different neurological diseases, total Abeta and Abeta(1-42) in the cerebrospinal fluid was reduced significantly compared with baseline values. In the serum, total Abeta levels increased after intravenous immunoglobulin treatment, whereas no significant change was observed in Abeta(1-42) levels. Antibodies against Abeta were found to be increased in the serum and cerebrospinal fluid after intravenous immunoglobulin treatment. This study provides evidence that intravenous immunoglobulin or purified Abeta antibodies may modify Abeta and Abeta(1-42) levels, suggesting potential utility as a therapy for Alzheimer disease.

Adult↗

Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatment.

Relatively little is known concerning the magnitude of alterations of platelet activation and secretion markers of patients with major depression when compared to patients at increased risk for, or with current, clinically significant atherosclerosis. Markers of in vivo platelet stimulation and secretion were measured under basal conditions in normal comparison subjects (n = 12) and three patient groups: patients diagnosed with DSM-IV major depression (n = 15), dialysis-dependent patients (n = 12), and patients with severe thoracic aortic atherosclerosis (n = 10). In comparison to normal comparison subjects, depressed patients and patients with thoracic aortic atherosclerosis exhibited the greatest platelet stimulation as detected by increased anti-LIBS platelet binding. Dialysis-dependent patients exhibited the highest plasma concentrations of the renally-excreted platelet-specific secretion protein, beta-thromboglobulin. This study extends previous observations of increased platelet activation in patients with major depression and documents similar alterations in patients with transesophageal echocardiography (TEE)-documented thoracic aortic atherosclerosis. Future studies will determine whether the magnitude of platelet stimulation and secretion in patients with comorbid depression and atherosclerotic aortic disease is greater than that observed in nondepressed patients with atherosclerotic aortic disease or major depression alone. These findings provide further evidence for either increased platelet activation and/or intrinsic heightened platelet reactivity as one of the biological substrates underlying the increased risk of depressed patients for cardiovascular disease.

Adult↗

Regulation of cardiac fibroblast cellular function by leukemia inhibitory factor.

BACKGROUND: Previous studies have shown that leukemia inhibitory factor (LIF) provokes hypertrophic and cytoprotective effects in cardiac myocytes. However, the effects of LIF in cardiac fibroblasts are not known. Given that the cardiac fibroblast is the most abundant cell type in the heart, we sought to examine the functional effects of LIF on cardiac fibroblasts in vitro. RESULTS: Short-term LIF stimulation (24h) had no effect on fibroblast proliferation and/or cell differentiation. However, longer-term LIF stimulation (48-72h) increased fibroblast proliferation, and significantly inhibited cardiac fibroblast differentiation into myofibroblasts. Moreover, 72h of LIF stimulation significantly reduced collagen content in cardiac fibroblasts cultures, as well as decreased MMP activity in fibroblast culture supernatants. CONCLUSION: The results of this study suggest that LIF stimulation down-regulates several key components of the remodeling process, including collagen content and matrix metalloproteinase (MMP) activation, and thus suggest that LIF may play an important autocrine/paracrine role in preventing excessive extracellular matrix remodeling following acute myocardial injury.

Actins↗

Computational method for muscle-path representation in musculoskeletal models.

This paper presents a new and efficient method to calculate the line-of-action of a muscle as it wraps over bones and other tissues on its way from origin to insertion. The muscle is assumed to be a one-dimensional, massless, taut string, and the surfaces of bones that the muscle may wrap around are approximated by cross-sectional boundaries obtained by slicing geometrical models of bones. Each cross-sectional boundary is approximated by a series of connected line segments. Thus, the muscle path to be calculated is piecewise linear with vertices being the contact points on the cross-sectional boundaries of the bones. Any level of geometric accuracy can be obtained by increasing the number of cross sections and the number of line segments in each cross section. The algorithm is computationally efficient even for large numbers of cross sections.

Algorithms↗

FTY720 pretreatment reduces warm hepatic ischemia reperfusion injury through inhibition of T-lymphocyte infiltration.

Ischemia and reperfusion (IR) injury remains a significant problem in clinical liver transplantation. We investigated the effects of lymphocyte depletion with FTY720 in models of warm hepatic IR. Using 60-min partial warm hepatic IR, three groups of rats were studied: Sham--laparotomy alone; Control--water p.o. x 3 d before ischemia; Treatment--FTY720 p.o. x 3 d before ischemia. Animals were sacrificed for analysis at 6 h and 24 h post reperfusion. The effect of FTY720 pretreatment on survival was also studied using 150 min total hepatic IR with portojugular shunt. FTY720 treatment significantly reduced serum glutamic pyruvic transaminase and peripheral blood lymphocytes compared to controls at 6h and 24h (p < 0.0005). Histological grade was significantly improved in treated livers vs. controls (p < 0.05). CD3 immunocytochemical analysis revealed a significant reduction in T-cell infiltration in FTY720-treated livers (p < 0.0002). No difference in tissue myeloperoxidase levels was observed. Seven-day survival was significantly improved in treated rats vs. controls following total hepatic ischemia (p < 0.05). In conclusion, FTY720 ameliorates the biochemical and histological manifestations of hepatic IR by preventing T-lymphocyte infiltration and prolongs survival following a more severe ischemic insult. Myeloperoxidase data suggest this mechanism is independent of neutrophil activation. These results indicate that T lymphocytes are pivotal mediators in hepatic IR and may have important implications in liver transplantation.

Animals↗

Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy.

HIV-associated nephropathy is a clinicopathologic entity that includes proteinuria, focal segmental glomerulosclerosis often of the collapsing variant, and microcystic tubulointerstitial disease. Increasing evidence supports a role for HIV-1 infection of renal epithelium in the pathogenesis of HIV-associated nephropathy. Using in situ hybridization, we previously demonstrated HIV-1 gag and nef mRNA in renal epithelial cells of patients with HIV-associated nephropathy. Here, to investigate whether renal epithelial cells were productively infected by HIV-1, we examined renal tissue for the presence of HIV-1 DNA and mRNA by in situ hybridization and PCR, and we molecularly characterized the HIV-1 quasispecies in the renal compartment. Infected renal epithelial cells were removed by laser-capture microdissection from biopsies of two patients, DNA was extracted, and HIV-1 V3-loop or gp120-envelope sequences were amplified from individually dissected cells by nested PCR. Phylogenetic analysis of kidney-derived sequences as well as corresponding sequences from peripheral blood mononuclear cells of the same patients revealed evidence of tissue-specific viral evolution. In phylogenetic trees constructed from V3 and gp120 sequences, kidney-derived sequences formed tissue-specific subclusters within the radiation of blood mononuclear cell-derived viral sequences from both patients. These data, along with the detection of HIV-1-specific proviral DNA and mRNA in tubular epithelium cells, argue strongly for localized replication of HIV-1 in the kidney and the existence of a renal viral reservoir.

Base Sequence↗

Application of functionalized CdS nanoparticles as fluorescence probe in the determination of nucleic acids.

Nanometer-sized fluorescent particles were successfully synthesized. The nanoparticles have a narrow, tunable, symmetric emission spectrum and a broad, continuous excitation spectrum. They are also photochemically stable. A synchronous fluorescence method was developed for the rapid determination of DNA with functionalized CdS as a fluorescence probe, based on the synchronous fluorescence quenching of functionalized CdS in the presence of DNA. Maximum fluorescence is produced at pH 7.0, with maximum excitation and emission wavelengths of 360 and 620 nm, respectively. The maximum emission wavelength of synchronous fluorescence is 354 nm when delta lambda = 260 nm. Under optimum conditions, the calibration graphs are linear over the range 0-3.5 microg mL(-1) for calf thymus DNA (CT-DNA) and 0.2-3.0 microg mL(-1) for fish sperm DNA. The corresponding detection limit is 0.01 microg mL(-1) for CT-DNA and 0.02 microg mL(-1) for fish sperm DNA. The relative standard deviation of seven replicate measurements is 2.2% for 1 microg mL(-1) calf thymus DNA and 2.4% for 1 microg mL(-1) fish sperm DNA. The method is simple, rapid and sensitive. The recovery and relative standard deviation are very satisfactory.

Animals↗

Enhancement of glutathione cardioprotection by ascorbic acid in myocardial reperfusion injury.

The present experiment determined the effects of glutathione and ascorbic acid, the two most important hydrophilic antioxidants, on myocardial ischemia-reperfusion injury and evaluated their relative therapeutic values. Isolated rat hearts were subjected to ischemia (30 min) and reperfusion (120 min) and treated with ascorbic acid, glutathione monoethyl ester (GSHme), or their combination at the onset of reperfusion. Administration of 1 mM GSHme alone, but not 1 mM ascorbic acid alone, significantly attenuated postischemic injury (P < 0.05 versus vehicle). Most interestingly, coadministration of ascorbic acid with GSHme markedly enhanced the protective effects of GSHme (P < 0.01 versus vehicle). The protection exerted by the combination of GSHme and ascorbic acid at 1 mM each was significantly greater than that observed with 1 mM GSHme alone (P < 0.05). Moreover, treatment with GSHme alone or GSHme plus ascorbic acid markedly reduced myocardial nitrotyrosine levels, suggesting that these treatments attenuated myocardial peroxynitrite formation. These results demonstrated that 1) GSHme, but not ascorbic acid, exerted protective effects against ischemia-reperfusion injury; and 2) the protective effects of GSHme were further enhanced by coadministration with ascorbic acid, suggesting a synergistic effect between GSHme and ascorbic acid.

Animals↗

Molecular epidemiology of human immunodeficiency virus type 1 transmission in a heterosexual cohort of discordant couples in Zambia.

Most human immunodeficiency virus type 1 (HIV-1) transmissions in sub-Saharan Africa are believed to occur between married adults who are discordant for their HIV-1 infection status; however, no studies to date have investigated the molecular epidemiology of such transmission events. Here we report the genetic characterization of HIV-1 strains from 149 transmission pairs that were identified prospectively in a cohort of discordant couples in Lusaka, Zambia. Subgenomic gag, gp120, gp41, and/or long terminal repeat regions were amplified by PCR analysis of uncultured blood samples from both partners and sequenced without interim cloning. Pairwise genetic distances were calculated for the regions analyzed and compared to those of subtype-specific reference sequences as well as local controls. Sequence relationships were also examined by phylogenetic tree analysis. By these approaches, epidemiological linkage was established for the majority of transmission pairs. Viruses from 129 of the 149 couples (87%) were very closely related and clustered together in phylogenetic trees in a statistically highly significant manner. In contrast, viruses from 20 of the 149 couples (13%) were only distantly related in two independent genomic regions, thus ruling out transmission between the two partners. The great majority (95%) of transmitted viruses were of subtype C origin, although representatives of subtypes A, D, G, and J were also identified. There was no evidence for extensive transmission networks within the cohort, although two phylogenetic subclusters of viruses infecting two couples each were identified. Taken together, these data indicate that molecular epidemiological analyses of presumed transmission pairs are both feasible and required to determine behavioral, virological, and immunological correlates of heterosexual transmission in sub-Saharan Africa with a high level of accuracy.

Cohort Studies↗

Reduced folate carrier transports thiamine monophosphate: an alternative route for thiamine delivery into mammalian cells.

Although the reduced folate carrier RFC1 and the thiamine transporters THTR-1 and THTR-2 share approximately 40% of their identity in protein sequence, RFC1 does not transport thiamine and THTR-1 and THTR-2 do not transport folates. In the present study, we demonstrate that transport of thiamine monophosphate (TMP), an important thiamine metabolite present in plasma and cerebrospinal fluid, is mediated by RFC1 in L1210 murine leukemia cells. Transport of TMP was augmented by a factor of five in cells (R16) that overexpress RFC1 and was markedly inhibited by methotrexate, an RFC1 substrate, but not by thiamine. At a near-physiological concentration (50 nM), TMP influx mediated by RFC1 in wild-type L1210 cells was approximately 50% of thiamine influx mediated by thiamine transporter(s). Within 1 min, the majority of TMP transported into R16 cells was hydrolyzed to thiamine with a component metabolized to thiamine pyrophosphate, the active enzyme cofactor. These data suggest that RFC1 may be one of the alternative transport routes available for TMP in some tissues when THTR-1 is mutated in the autosomal recessive disorder thiamine-responsive megaloblastic anemia.

Animals↗

Anion channels influence ECC by modulating L-type Ca(2+) channel in ventricular myocytes.

Anion channels are extensively expressed in the heart, but their roles in cardiac excitation-contraction coupling (ECC) are poorly understood. We, therefore, investigated the effects of anion channels on cardiac ventricular ECC. Edge detection, fura 2 fluorescence measurements, and whole cell patch-clamp techniques were used to measure cell shortening, the intracellular Ca(2+) transient, and the L-type Ca(2+) current (I(Ca,L)) in single rat ventricular myocytes. The anion channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and niflumic acid reversibly inhibited the Ca(2+) transients and cell shortening in a dose-dependent manner. Comparable results were observed when the majority of the extracellular Cl(-) was replaced with the relatively impermeant anions glutamate (Glt(-)) and aspartate (Asp(-)). NPPB and niflumic acid or the Cl(-) substitutes did not affect the resting intracellular Ca(2+) concentration but significantly inhibited I(Ca,L). In contrast, replacement of extracellular Cl(-) with the permeant anions NO, SCN(-), and Br(-) supported the ECC and I(Ca,L), which were still sensitive to blockade by NPPB. Exposure of cardiac ventricular myocytes to a hypotonic bath solution enhanced the amplitude of cell shortening and supported I(Ca,L), whereas hypertonic stress depressed the contraction and I(Ca,L). Moreover, cardiac contraction was completely abolished by NPPB (50 microM) under hypotonic conditions. It is concluded that a swelling-activated anion channel may be involved in the regulation of cardiac ECC through modulating L-type Ca(2+) channel activity.

Animals↗

Optimizing higher throughput methods to assess drug-drug interactions for CYP1A2, CYP2C9, CYP2C19, CYP2D6, rCYP2D6, and CYP3A4 in vitro using a single point IC(50).

Drug-drug interactions involving cytochrome P(450) (CYP) are an important factor in whether a new chemical entity will survive through to the development stage. Therefore, the identification of this potential as early as possible in vitro could save considerable future unnecessary investment. In vitro CYP interaction screening data generated for CYP2C9, CYP2D6, and CYP3A4 were initially analyzed to determine the correlation of IC(50) from 10- and 3-point determinations. A high correlation (r = 0.99) prompted the further assessment of predicting the IC(50) by a single value of percent inhibition at either 10, 3, or 1 microM. Statistical analysis of the initial proprietary compounds showed that there was a strong linear relationship between log IC(50) and percent inhibition at 3 microM, and that it was possible to predict a compound's IC(50) by the percent inhibition value obtained at 3 microM. Additional data for CYP1A2, CYP2C19, and the recombinant CYP2D6 were later obtained and used together with the initial data to demonstrate that a single statistical model could be applicable across different CYPs and different in vitro microsomal systems. Ultimately, the data for all five CYPs and the recombinant CYP2D6 were used to build a statistical model for predicting the IC(50) with a single point. The 95% prediction boundary for the region of interest was about +/- 0.37 on log(10) scale, comparable to the variability of in vitro determinations for positive control IC(50) data. The use of a single inhibitor concentration would enable determination of more IC(50) values on a 96-well plate and result in more economical use of compounds, human liver or expressed enzyme microsomes, substrates, and reagents. This approach would offer the opportunity to increase screening for CYP-mediated drug-drug interactions, which may be important given the challenges provided by the generation of orders of magnitude more new chemical entities in the field of combinatorial chemistry. In addition, the algorithmic approach we propose would obviously be applicable for other in vitro bioactivity and therapeutic target enzyme and receptor screens.

Algorithms↗

[Effect of tetrandrine and droloxifene on the reversion of drug resistance of K562/A02 cell line and induction of apoptosis].

OBJECTIVE: To study the reversal effect of tetrandrine (Tet) and droloxifene (Drol) on multidrug resistant cell line K562/A02 and apoptosis induction. METHODS: The cytotoxicity of daunorubicin (DNR) was assayed by MTT method. The effects of Tet and DRL, alone or combined were detected through the apoptosis of K562/A02 by agarose gel electrophoresis. RESULTS: The cytotoxicity of DNR to K562/A02 was enhanced by 0.62 microg/ml Tet or 1.94 microg/ml Drol with IC(50) 7.28 +/- 2.06 microg/ml, 7.58 +/- 3.44 microg/ml, giving a reversal effect of 2.94 and 2.82. But IC(50) of combined Tet and Drol was 1.66 +/- 0.41 microg/ml with the reversal effect markedly increased to 12.9. Neither 0.62 microg/ml Tet nor 1.94 microg/ml Drol could induce apoptosis of K562/A02 cells. CONCLUSION: Multidrug resistance (MDR) can be partially reversed by Tet or Drol, of which the combination shows a great synergistic reversal effect. The mechanism of Tet and Drol reversing multidrug resistance is not correlated with the apoptosis of K562/A02 cells.

Alkaloids↗

[Preparation of surface functional magnetic microspheres and their application in nucleic acid separation and enzyme immobilization].

OBJECTIVE: To Prepare surface functional magnetic microspheres for the separation of vascular endothelial growth factor (VEGF) nucleic acid and lactase enzyme immobilization. METHODS: Using suspension polymerization methods to copolymerize MA-styrene containing magnetite nanoparticles and GMA-styrene also containing magnetite nanoparticles, respectively. Both the carboxyl-modified magnetic microspheres and epoxy-modified magnetic microspheres were obtained. In addition, the chloromethyl-modified magnetic microspheres were prepared by seedy microemulsion. The magnetic microspheres bound with b-gamma IgG were determined by radioimmunoassay (RIA), and the separation of VEGF nucleic acid and lactase enzyme immobilization were performed by carboxyl-modified magnetic microspheres. RESULTS: Transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS) and infrared (IR) spectra showed that the products of polymer magnetic microspheres were monodispersed and that the magnetic particles were uniformly distributed in the microsphere with special functional group on the surface of the microsphere. RIA showed that three kinds of magnetic microspheres could be bound with b-gamma IgG and the absorption of b-gamma IgG reached 75 micrograms/mg, especially for the carboxyl-modified magnetic microspheres. The carboxyl-modified magnetic microspheres can be used for the separation of VEGF nucleic acid by coupling with corresponding primer. Moreover, the immobilized enzyme was proportional to the amount of the carboxyl-modified magnetic microspheres. CONCLUSIONS: The surface functional magnetic polymer microspheres can be bound with active bio-substance, and have a wide application prospect in the fields of biology and medicine.

Adsorption↗

[Isolation and identification of a gene: attractin related to inhibiting erythroid differentiation in K562 cells].

Differential display PCR method was used to isolate four differential display fragments between the wild type K562 cell line and the variant type K562 cell line that expressed the human beta-globin gene. After sequencing, the most remarkable different fragment,named dd1,was selected for further study. The analysis of RT-PCR and Northern blot hybridization showed that dd1 was exactly the differentiation fragment between the two cell lines. The homology analysis indicated that dd1 was matched to Attractin (GeneBank registration No.AF106861). It might be an adhesion receptor related to inhibiting erythroid differentiation based on its structure.

English Abstract↗

Pharmacokinetics of traditional Chinese syndrome and recipe: a hypothesis and its verification (I).

AIM:To propose a hypothesis defining the absorption, distribution, metabolism and elimination of traditional Chinese recipe (TCR)component in blood of healthy subjects and patients, and estimate its correctness.METHODS:The pharmacokinetics (PK) of same dose of drug was studied in the animal model of traditional Chinese syndrome (S)and healthy animals. The classification, termi-nology, concept and significance of the hypothesis were set forth with evidence provided in the present study. The hypotheses consisted of traditional Chinese syndrome PK (S-PK) and traditional Chinese recipe PK (R-PK). Firstly, the observed tetramethylpyrazine (TMP) PK in healthy, chronically reserpinized rats (rat model of spleen deficiency syndrome, RMSDS) and RMSDS treated with Sijunzi decoction (SJZD) for confirmation were used to verify S-PK; secondly, the ferulic acid (FA) PK in healthy and high molecular weight dextran (HMWD)-induced rabbit model with blood stasis syndrome (RDBSS) was also used to verify S-PK; and lastly, TMP PK parameters in serum of healthy rats after orally taken Ligusticum wallichii (LW), LW and Salvia miltiorrhiza (LW&SM) decoctions were compared to verify R-PK.RESULTS:The apparent first-order absorption Ka,(13.61 plus minus 2.56)h(-1) ,area under the blood drug concentration-time curve AUC, (24.88 plus minus 9.76)&mgr;gcenter doth(-1)mL(-1) , maximum drug concentration C(max), (4.82 plus minus 1.23)&mgr;gcenter dotmL(-1) of serum TMP in RMSDS were increased markedly(P< 0.05) compared with those Ka = (5.41 plus minus1.91)h(-1), AUC = (5.20 plus minus 2.57)&mgr;gcenter doth(-1)center dotmL(-1), C(max) = (2.33 plus minus 1.77)&mgr;gcenter dotmL(-1) of healthy rats (HR). The apparent first-order rate constant for alpha and beta distribution phase alpha = (0.38 plus minus 0.09)h(-1), beta = (0.06 plus minus 0.03)h(-1) , the apparent first-order intercompartmental transfer rate constants K10 = (0.24 plus minus 0.07)h(-1), K(12) = (0.11 plus minus 0.02)h(-1), K(21) = (0.11 plus minus 0.02)h(-1) of serum TMP in RMSDS were decreased significantly (P <0.01) compared with those K(10) = (0.88 plus minus 0.20)h(-1), K(12) = (1.45 plus minus 0.47)h(-1), K(21) = (0.72 plus minus 0.22)h(-1) of HR. However, no apparent differences occurred between HR and RMSDS treated with SJZD. The serum FA concentration and its AUC (5.6690 plus minus 2.3541)&mgr;gcenter doth(-1)center dotmL(-1) in RMBSS were also higher than those AUC =(2.7566 plus minus0.8232)&mgr;gcenter doth(-1)center dotmL(-1) of healthy rabbits (P <0.05). The Ka (11.51 plus minus 2.82)h(-1), AUC (0.84 plus minus0.17)&mgr;gcenter doth(-1)center dotmL(-1) of LW & SM-derived TMP in serum were much lower (P <0.05) than those Ka = (19.58 plus minus 4.14)h(-1),AUC = (1.27 plus minus 0.26)&mgr;gcenter doth(-1)center dotmL(-1) of LW-derived TMP in serum after oral decoctions.CONCLUSION:The SDS and blood stasis syndrome state could affect significantly the pharmacokinetic parameters of drugs and the abnormal SDS pharmacokinetic parameters could be normalized by SJZD. The combination of Chinese medicine in TCR could reciprocally affect the pharmacokinetic parameters of other components absorbed into the systemic circulation. These results support the S and R-PK hypothesis.

Journal Article↗

Expression of single-chain Fv gene specific for gamma-seminoprotein by RTS and its biological activity identification.

Fabricating a single-chain variable fragment specific for human seminoprotein is very important in antibody-directed enzyme prodrug therapy and NMR imaging for prostate cancer. Here a single-chain Fv specific for gamma-seminoprotein was expressed by RTS. Its activity and the efficiency of entry into prostate cancer cells are investigated by immunoprecipitation and Western blotting and immunofluorescent staining, as well as entry of conjugated magnetic beads into cells. Results showed that ScFv peptides specific for gamma-seminoprotein were successfully prepared, which can bind with the prostate cells specifically and can bring magnetic beads into prostate cancer cells within 15 min, the amount of magnetic beads inside prostate cancer cells increased as the culture time prolonged. ScFv-conjugated magnetic beads did not enter into control cells. In conclusion, the ScFv peptide against human gamma-seminoprotein with biological activity was successfully fabricated, which can take magnetic beads to prostate cancer cells specifically and not to the control cells. This ScFv peptide against human gamma-seminoprotein should be useful in improving the detection and therapy of prostate cancer at early stages and NMR imaging.

Binding Sites↗