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Biomedical subjects

Feng Gao

Publications and source records attributed to Feng Gao.

At least 55 records · Page 3Linked to original sources
PubMed2006

Detection of known thalassemia point mutations by snapback single-strand conformation polymorphism: the feasibility analysis.

OBJECTIVES: To explore if snapback single-strand conformation polymorphism (snapback SSCP) can be applied to the detection of known thalassemia point mutations. DESIGN AND METHODS: We examined 13 types of known thalassemia point mutations by using snapback SSCP. RESULTS: These 13 different thalassemia point mutations could be identified by snapback SSCP. CONCLUSIONS: Snapback SSCP can be applied to the detection of known thalassemia point mutations. The advantages of snapback SSCP are (1) it is simple as compared to PCR-ASO; (2) snapback SSCP is specific and stable once the conditions of snapback SSCP are optimized; (3) samples can be checked at any time without the limit of half-life of radioactive isotope; and (4) since PCR products used in snapback SSCP can be checked by using 2% agarose gel before snapback SSCP, misdiagnoses caused by false positive or false negative PCR can be reduced significantly in snapback SSCP.

Base Sequence↗
PubMed2006

CD4+ T regulatory cell induction and function in transplant recipients after CD154 blockade is TLR4 independent.

Although the role of CD4(+) T regulatory cells (Treg) in transplantation tolerance has been established, putative mechanisms of Treg induction and function in vivo remain unclear. TLR4 signaling has been implicated in the regulation of CD4(+)CD25(+) Treg functions recently. In this study, we first examined the role of recipient TLR4 in the acquisition of operational CD4(+) Treg following CD154 blockade in a murine cardiac transplant model. Then, we determined whether TLR4 activation in allograft tolerant recipients would reverse alloimmune suppression mediated by CD4(+) Treg. We document that donor-specific immune tolerance was readily induced in TLR4-deficient recipients by a single dose of anti-CD154 mAb, similar to wild-type counterparts. The function and phenotype of CD4(+) Treg in both wild-type and TLR4 knockout long-term hosts was demonstrated by a series of depletion experiments examining their ability to suppress the rejection of secondary donor-type test skin grafts and to inhibit alloreactive CD8(+) T cell activation in vivo. Furthermore, TLR4 activation in tolerant recipients following exogenous LPS infusion in conjunction with donor-type skin graft challenge, failed to break Treg-mediated immune suppression. In conclusion, our data reveals a distinctive property of CD4(+) Treg in tolerant allograft recipients, whose induction and function are independent of TLR4 signaling.

Animals↗
PubMed2006

CXCR3+CD4+ T cells mediate innate immune function in the pathophysiology of liver ischemia/reperfusion injury.

Ischemia-reperfusion injury (IRI), an innate immune-dominated inflammatory response, develops in the absence of exogenous Ags. The recently highlighted role of T cells in IRI raises a question as to how T lymphocytes interact with the innate immune system and function with no Ag stimulation. This study dissected the mechanism of innate immune-induced T cell recruitment and activation in rat syngeneic orthotopic liver transplantation (OLT) model. Liver IRI was induced after cold storage (24-36 h) at 4 degrees C in University of Wisconsin solution. Gene products contributing to IRI were identified by cDNA microarray at 4-h posttransplant. IRI triggered increased intrahepatic expression of CXCL10, along with CXCL9 and 11. The significance of CXCR3 ligand induction was documented by the ability of neutralizing anti-CXCR3 Ab treatment to ameliorate hepatocellular damage and improve 14-day survival of 30-h cold-stored OLTs (95 vs 40% in controls; p < 0.01). Immunohistology analysis confirmed reduced CXCR3+ and CD4+ T cell infiltration in OLTs after treatment. Interestingly, anti-CXCR3 Ab did not suppress innate immune activation in the liver, as evidenced by increased levels of IL-1beta, IL-6, inducible NO synthase, and multiple neutrophil/monokine-targeted chemokine programs. In conclusion, this study demonstrates a novel mechanism of T cell recruitment and function in the absence of exogenous Ag stimulation. By documenting that the execution of innate immune function requires CXCR3+CD4+ T cells, it highlights the critical role of CXCR3 chemokine biology for the continuum of innate to adaptive immunity in the pathophysiology of liver IRI.

Amino Acid Sequence↗
PubMed2006

Effect of somatostatin analogue octreotide injected into the third cerebral ventricle on pentagastrin-induced gastric acid secretion in rats.

AIM: To investigate the effect of long-lasting somatostatin analogue octreotide (Oct) injected into the third cerebral ventricle (TCV) on gastric acid secretion in rats. METHODS: TCVs were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later acute gastric lumen perfusion was carried out and gastric acid was continuously washed with 37 degree Celsius saline by a perfusion pump. Gastric perfusion samples were collected every 10 min and titrated by 0.01 moL/L NaOH to neutral. On the basis of subcutaneous (sc) injection of pentagastrin (G-5, 160 microg/kg), Oct (0.025 microg, 0.05 microg, 0.1 microg, n=12 in each group) or vehicle (pyrogen-free physiological saline, n=10) was injected into the TCV. Before and after the TCV injection, 1 h total acid output (TAO) was determined and experimental data were expressed in change rate (%) of TAO. RESULTS: Oct (0.025, 0.05 and 0.1 microg) injected into the TCV resulted in change rate of 1.56% (P>0.05), 20.21% (P<0.01) and 37.82% of TAO (P<0.001), respectively. Moreover, comparison in change rate of TAO among these 3 doses showed P<0.05 between 0.025 microg and 0.05 microg, P<0.01 between 0.025 microg and 0.1 microg, and P<0.05 between 0.05 microg and 0.1 microg. However, sc injection of 0.05 microg Oct had no effect on G-5 stimulated gastric acid secretion. CONCLUSION: Octreotide injected into the third cerebral ventricle inhibits gastrin-induced gastric acid secretion in a dose-dependent manner.

Animals↗
PubMed2006

Characterization of HCoV-229E fusion core: implications for structure basis of coronavirus membrane fusion.

Human coronavirus 229E (HCoV-229E), a member of group I coronaviruses, has been identified as one of the major viral agents causing respiratory tract diseases in humans for nearly 40 years. However, the detailed molecular mechanism of the membrane fusion mediated by the spike (S) protein of HCoV-229E remains elusive. Here, we report, for the first time, a rationally designed fusion core of HCoV-229E (HR1-SGGRGG-HR2), which was in vitro produced in GST prokaryotic expression system. Multiple lines of experimental data including gel-filtration, chemical cross-linking, and circular diagram (CD) demonstrated that the HCoV-229E fusion core possesses the typical properties of the trimer of coiled-coil heterodimer (six alpha-helix bundle). 3D structure modeling presents its most-likely structure, similar to those of coronaviruses that have been well-documented. Collectively, HCoV-229E S protein belongs to the type I fusion protein, which is characterized by the existence of two heptad-repeat regions (HR1 and HR2), furthermore, the available knowledge concerning HCoV-229E fusion core may make it possible to design small molecule or polypeptide drugs targeting the membrane fusion, a crucial step of HCoV-229E infection.

Amino Acid Sequence↗
PubMed2006

Stress analysis in a layered aortic arch model under pulsatile blood flow.

BACKGROUND: Many cardiovascular diseases, such as aortic dissection, frequently occur on the aortic arch and fluid-structure interactions play an important role in the cardiovascular system. Mechanical stress is crucial in the functioning of the cardiovascular system; therefore, stress analysis is a useful tool for understanding vascular pathophysiology. The present study is concerned with the stress distribution in a layered aortic arch model with interaction between pulsatile flow and the wall of the blood vessel. METHODS: A three-dimensional (3D) layered aortic arch model was constructed based on the aortic wall structure and arch shape. The complex mechanical interaction between pulsatile blood flow and wall dynamics in the aortic arch model was simulated by means of computational loose coupling fluid-structure interaction analyses. RESULTS: The results showed the variations of mechanical stress along the outer wall of the arch during the cardiac cycle. Variations of circumferential stress are very similar to variations of pressure. Composite stress in the aortic wall plane is high at the ascending portion of the arch and along the top of the arch, and is higher in the media than in the intima and adventitia across the wall thickness. CONCLUSION: Our analysis indicates that circumferential stress in the aortic wall is directly associated with blood pressure, supporting the clinical importance of blood pressure control. High stress in the aortic wall could be a risk factor in aortic dissections. Our numerical layered aortic model may prove useful for biomechanical analyses and for studying the pathogeneses of aortic dissection.

Aorta, Thoracic↗
PubMed2006

Electrochemical properties of carbon nanotube (CNT) film electrodes prepared by controllable adsorption of CNTs onto an alkanethiol monolayer self-assembled on gold electrodes.

This paper describes electrochemical properties, such as electrode reactivity, electrode dimensions, and interfacial capacitance, of multiwalled carbon nanotube (MWNT) film electrodes prepared by controllable adsorption of the MWNTs onto the self-assembled monolayer (SAM) of n-octadecyl mercaptan (C18H37SH) deposited onto Au electrodes. The adsorption of the MWNTs onto the SAM-modified Au electrode substantially restores heterogeneous electron transfer between bare Au electrode and redox species in solution phase that is almost totally blocked by the SAM of C18H37SH, and as a result, the prepared MWNT/SAM-modified electrode possesses good electrode reactivity without a remarkable barrier to heterogeneous electron transfer. In addition, the surface coverage of the MWNTs is readily controlled by adjusting the immersion time for the adsorption of the MWNTs onto the SAM of C18H37SH, which essentially endows the prepared MWNT/SAM-modified electrodes with tunable electrode dimensions ranging from a nanoelectrode array to a macro-sized conventional electrode. On the other hand, the MWNT/SAM-modified electrode is found to possess a largely reduced interfacial capacitance, as compared with the MWNT film electrodes prepared with existing methods by directly confining the MWNTs onto electrode surface. This demonstration offers a new approach to fabrication of stable MWNT film electrodes with excellent electrochemical properties that are believed to be very attractive for electrochemical studies and electroanalytical applications.

Journal Article↗
PubMed2006

Probing lipid vesicles by bimolecular association and dissociation trajectories of single molecules.

Vesicles prepared by DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and SOPC (1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine) lipid molecules having sizes smaller than the diffraction-limited focused laser beam have been used to confine single molecules in the laser focus. The confinement of single molecules in a volume smaller than the focused laser beam leads to a Gaussian distribution of single molecule fluorescence intensity. The interactions of single Nile Red molecules with DMPC and SOPC lipid bilayers were studied by single molecule fluorescence confocal microscopy. Nile Red molecules were observed to associate with and dissociate from individual DMPC and SOPC vesicles adsorbed on a glass surface, generating on-and-off fluctuations in a fluorescence signal representing a very low noise two-state trajectory. Off-time statistics were used to investigate the mean radius of the vesicles and the size distribution functions. The means of the on-time distributions of Nile Red in DMPC and SOPC vesicles were significantly different. The association and dissociation reactions of single Nile Red molecules with a vesicle have been studied. Features of the bimolecular interaction between the probe Nile Red and the vesicle were evaluated from the uncorrelated mean on-time and vesicle radius distributions, and the linear Nile Red concentration dependence of the mean off-time. Nile Red is shown to be a useful probe of the structural fluctuations and heterogeneity of these membrane structures, and it is a useful model with which to directly study a diffusion-influenced reversible bimolecular reaction.

Dimyristoylphosphatidylcholine↗
PubMed2006

Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2.

BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS: We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study.

Adult↗
PubMed2006

A hybrid mixture discriminant analysis-random forest computational model for the prediction of volume of distribution of drugs in human.

A computational approach is described that can predict the VD(ss) of new compounds in humans, with an accuracy of within 2-fold of the actual value. A dataset of VD values for 384 drugs in humans was used to train a hybrid mixture discriminant analysis-random forest (MDA-RF) model using 31 computed descriptors. Descriptors included terms describing lipophilicity, ionization, molecular volume, and various molecular fragments. For a test set of 23 proprietary compounds not used in model construction, the geometric mean fold-error (GMFE) was 1.78-fold (+/-11.4%). The model was also tested using a leave-class out approach wherein subsets of drugs based on therapeutic class were removed from the training set of 384, the model was recast, and the VD(ss) values for each of the subsets were predicted. GMFE values ranged from 1.46 to 2.94-fold, depending on the subset. Finally, for an additional set of 74 compounds, VD(ss) predictions made using the computational model were compared to predictions made using previously described methods dependent on animal pharmacokinetic data. Computational VD(ss) predictions were, on average, 2.13-fold different from the VD(ss) predictions from animal data. The computational model described can predict human VD(ss) with an accuracy comparable to predictions requiring substantially greater effort and can be applied in place of animal experimentation.

Algorithms↗
PubMed2006

The in vitro inhibition of multidrug resistance by combined nanoparticulate titanium dioxide and UV irradition.

The appearance of drug-resistant (especially, multidrug-resistant (MDR)) tumor cells is a major obstacle to the success of chemotherapy; thus, the development of effective anti-MDR agents plays an important role in the tumor therapy. In this report, the considerable effect of nano-TiO2 and UV illumination on the drug resistance of target cancer cells has been explored, and the fresh evidence from the fluorescence spectroscopy and microscopy as well as electrochemical studies demonstrates the significant enhancement effect of nano-TiO2 to the drug uptake by drug-resistant leukemia cells. Besides, it is also observed that the combination of the nano-TiO2 and UV irradiation with the accompanying anticancer drug daunorubicin could provoke some considerable changes of the cell membrane of the target leukemia cells, which indicates that nano-TiO2 could not only increase the drug accumulation in target cancer cells, but also act as an effective anti-MDR agent to inhibit the relative drug resistance.

Biocompatible Materials↗
PubMed2006

Controlled bimolecular collisions allow sub-diffraction limited microscopy of lipid vesicles.

The concentration and vesicle size-controlled collisions of single molecules with target biological assemblies allow sub-diffraction limited optical images to be obtained that are not subject to the usual photobleaching problems with single molecule experiments. For example, single molecules of the probe Nile Red in aqueous solution emit a burst of fluorescence when they collide with a 50 nm hydrophobic vesicle situated on the surface in the laser focus. The bimolecular kinetics of the bursts is defined by their on- and off-time distribution functions which depend on the concentration and diffusion of the probe and the vesicle size. The mean burst frequency changes much more sharply than does the fluorescence intensity when a vesicle is raster scanned through the laser focus. This sharpness allows the spatial resolution of two objects to be improved and separations less than the diffraction limited resolution of the conventional optical microscope to be measured. The principle of this method of trajectory time distribution optical microscopy (TTDOM) could be used in a far field optical microscopic system with a resolution of several nanometers.

Computer Simulation↗
PubMed2006

Outcome of surgical management of the bladder in advanced colorectal cancer.

BACKGROUND: To evaluate morbidity, mortality, and long-term survival in patients undergoing partial or total cystectomy during en bloc resection for locally advanced colorectal cancer. METHODS: This study retrospectively evaluated the outcome of combined bladder resection for colorectal cancer in our department. RESULTS: Patients (n=33) with colorectal tumors adherent to the bladder were followed. Overall morbidity was 11/33 (33.3%). Histological staging demonstrated inflammatory adhesion in 54.5% (18/33) and invasion in 45.6% (15/33). Morbidity was significantly higher in those that had undergone total cystectomy than in those that had undergone partial cystectomy (4/5 vs 7/28, P=0.033). The local recurrence has no difference the between total cystectomy group and the partial cystectomy group (1/5 vs 8/28, P=1.000). Overall 5-year survival rate was 39.4% (13/33). Mean survival time was 46.6875 month. There was no difference in 5-year survival between patients with inflammatory adhesion vs those with tumorous infiltration between colorectal tumor and bladder (P=0.7389). CONCLUSION: Survival after surgery for colorectal cancer is not influenced by the need to excise part or all of the urinary bladder in case it is contiguous to a colorectal tumor. Experienced surgeons in urology and colon and rectal surgery should be left to decide on the surgical options to be employed.

Adult↗
PubMed2006

Discovery of EGFR selective 4,6-disubstituted pyrimidines from a combinatorial kinase-directed heterocycle library.

The epidermal growth factor receptor (EGFR) tyrosine kinase was one of the first receptor tyrosine kinases to be targeted for drug development by the pharmaceutical industry due to its ubiquitous overexpression in a variety of tumors. Despite the validation of several quinazoline-based scaffolds in the clinic, there is a dearth of alternative chemical structure classes that are capable of inhibiting EGFR kinase activity selectively. Here we describe the discovery of potent and highly selective 4,6-disubstituted pyrimidine inhibitors of enzymatic and cellular EGFR activity and provide an explanation for their exceptional degree of kinase selectivity.

Combinatorial Chemistry Techniques↗
PubMed2006

Fluoroimmunoassay for antigen based on fluorescence quenching signal of gold nanoparticles.

A unique, sensitive, and highly specific fluoroimmunoassay system for antigen detection using gold and magnetic nanoparticles has been developed. The assay is based on the fluorescence quenching of fluorescein isothiocyanate caused by gold nanoparticles coated with monoclonal antibody. To demonstrate its analytical capabilities, the magnetic nanoparticles were coated with anti-alpha-fetoprotein polyclonal antibodies, which specifically bound with alpha-fetoprotein. Gold nanoparticles coated with anti-alpha-fetoprotein monoclonal antibodies could sandwich the alpha-fetoprotein captured by the magnetic nanoparticle probes. The sandwich-type immunocomplex was formed on the surface of magnetic nanoparticles and could be separated by a magnetic field. The supernatant liquid, which contained the unbound gold nanoparticle probes, was used to quench the fluorescence, and the fluorescence intensity of fluorescein isothiocyanate at 516 nm was proportional to the alpha-fetoprotein concentration. The result showed that the limit of detection of alpha-fetoprotein was 0.17 nM. This new system can be extended to detect target molecules with matched antibodies and has broad potential applications in immunoassay and disease diagnosis.

Fluorescence↗
PubMed2006

Meta-analysis of short-term outcomes after laparoscopic resection for rectal cancer.

BACKGROUND: Laparoscopic resection (LR) has become increasingly popular for the management of rectal cancer. Despite a decade of experience, the safety and efficacy of LR for rectal cancer remains to be established. This report performs a meta-analysis to compare LR with conventional open resection (CR) in patients with rectal cancer. METHODS: Using a defined search strategy, studies directly comparing CR with LR for rectal cancer were identified. The data for patients with rectal cancer treated with both approaches were extracted and used in our meta-analysis. Open surgery and laparoscopic surgery were compared in terms of postoperative mortality, morbidity, complications, oncological clearance, operating time, and time before recovery to a normal diet. RESULTS: Compared with CR, LR is associated with lower morbidity rates [OR 0.63 (0.41, 1.96) P=0.03], longer operating times [weighted mean difference 1.59 (1.20, 1.98) P<0.00001], similar mortality rates, wound healing disorder rates, urinary disorder rates, cardiopulmony disease rates, all leakage rates, all abscess rates and a positive rate of margin. CONCLUSION: LR is associated with less postoperative morbidity, but longer operation time. A prospective randomized controlled trial is warranted to fully investigate these and other outcome measures.

Blood Loss, Surgical↗
PubMed2006

Long-term outcome of women who undergo panniculectomy at the time of gynecologic surgery.

OBJECTIVE: While panniculectomy has been shown to be a useful technique in obese women undergoing gynecologic surgery, the long-term outcome of these patients has been poorly described. The goal of this study was to determine the long-term outcomes and patient satisfaction of women who underwent panniculectomy at the time of pelvic surgery. METHODS: A retrospective review of patients who underwent panniculectomy at the time of pelvic surgery between 1996 and 2004 was performed. Postoperative complications and long-term trends in weight were evaluated. Patient satisfaction was assessed by telephone survey. RESULTS: Forty-two patients were identified. The mean EBL was 522 ml, the mean operating time was just over 4 h. Wound complications were noted in 36% of the subjects. Two weeks after the procedure, 86% of the women had a weight that was lower than their preoperative weight. Weight loss peaked 3 months postoperatively, 97% of the subjects had a net lower weight, with a mean loss of nearly 20 lb. Over the ensuing 2 years, weight loss gradually declined. After 2 years of follow-up, 62% of the women were below their preoperative body weights. The mean weight loss at 24 months was 7 lb. Overall patient satisfaction with the procedure was high. Eighty-six percent of the subjects responded that they would undergo the procedure again given their outcome. CONCLUSIONS: Panniculectomy is well tolerated and associated with a high rate of patient satisfaction. Panniculectomy is a valuable component of gynecologic surgery in morbidly obese women.

Abdomen↗