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Biomedical subjects

G Chen

Publications and source records attributed to G Chen.

At least 37 records · Page 2Linked to original sources

Comparison of two numerical approaches for bone remodelling.

This paper addresses the "checkerboard" phenomenon, which occurs in numerical simulation of bone remodelling. It attempts to answer the question: is an element-based approach suitable for bone remodelling? Two different numerical approaches, the element-based and the node-based finite element analyses, are implemented using ABAQUS. A comparison of the numerical results demonstrates that the checkerboard phenomenon occurs only in the element-based finite element analyses; the node-based approach eradicates the checkerboard phenomenon but requires much more computational time. This study shows that it is essential to enforce the continuity of bone density across the element boundaries. As the node-based approach requires much more computational time, the first-order Adams-Bashforth integration method is introduced to reduce computational cost. The comparisons with Euler's forward method demonstrate that the first-order Adams-Bashforth method indeed enhances accuracy and reduces computational cost. This study concludes that the node-based approach with the first-order Adams-Bashforth integration scheme is to be recommended for computational bone remodelling studies.

Algorithms↗

Stoichiometry driven impurity configurations in compound semiconductors.

Precise stoichiometry and departures therefrom in the composition of the tetrahedrally coordinated compound semiconductors allow impurity incorporation in more than one configuration. Ultrahigh resolution infrared spectroscopy of CdTe:O at low temperatures reveals a unique sharp doublet associated with the local vibrational modes of OTe in a (OTe-VCd) complex with nearest neighbor Cd vacancy VCd and a single sharp line attributed to the local vibrational mode of OTe in a perfect CdTe. The uniaxial (C3v) symmetry of (OTe-VCd) transforms to Td symmetry at T* approximately 300 K, acquired due to an increasing rate of dynamic switching of the "OTe-VCd" dangling bond in which the vacancy and its three next nearest neighbor Cd cations exchange positions as temperature (T) approaches T*; for T>or=T*, the doublet thus transforms into a single, triply degenerate line.

Journal Article↗

Superplastic carbon nanotubes.

The theoretical maximum tensile strain--that is, elongation--of a single-walled carbon nanotube is almost 20%, but in practice only 6% is achieved. Here we show that, at high temperatures, individual single-walled carbon nanotubes can undergo superplastic deformation, becoming nearly 280% longer and 15 times narrower before breaking. This superplastic deformation is the result of the nucleation and motion of kinks in the structure, and could prove useful in helping to strengthen and toughen ceramics and other nanocomposites at high temperatures.

Journal Article↗

The role of the amygdala and rostral anterior cingulate in encoding expected outcomes during learning.

Successful passive avoidance learning is thought to require the use of learned stimulus-reinforcement associations to guide decision making [Baxter, M.G., Murray, E.A., 2002. The amygdala and reward. Nature Reviews. Neuroscience 3, 563-573]. The current experiment investigated the neural correlates of successful passive avoidance learning in 19 healthy adults. Behaviorally, subjects showed a distinct pattern of performance: early indiscriminate responding to stimuli (pre-criterion performance), followed by relatively rapid learning before a plateau of successful performance (post-criterion performance). Neural responses to post-criterion correct responses were compared with neural responses to both incorrect responses and pre-criterion correct responses. Post-criterion correct responding was associated with increased activation in regions including rostral anterior cingulate, insula, caudate, hippocampal regions, and the amygdala.

Adult↗

Inhibition of telomerase enhances apoptosis induced by sodium butyrate via mitochondrial pathway.

Telomerase activation represents an early step in carcinogenesis. Increased telomerase activity in cervical cancer suggests a potential target for the development of novel therapeutic drugs. The aim of this study is to investigate the impact of telomerase activity on the biological features of HeLa cells and the possible mechanisms of enhanced apoptosis rate induced by sodium butyrate after telomerase inhibition. We introduced vectors encoding dominate negative (DN)-hTERT, wild-type (WT)-hTERT, or a control vector expressing only a drug-resistance marker into HeLa cells. Thus we assessed the biological effects of telomerase activity on telomere length, cell proliferation, chemosensitivity and radiosensitivity. In order to understand the mechanisms in which DN-hTERT enhances the apoptosis induced by sodium butyrate, we detected the release status of cytochrome c and apoptosis inducing factor (AIF) from mitochondria. Ectopic expression of DN-hTERT resulted in inhibition of telomerase activity, reduction of telomere length, decreased colony formation ability, and loss of tumorigenicity in nude mice. Moreover, DN-hTERT transfected HeLa cells with shortened telomeres were more susceptible to multiple chemotherapeutic agents and radiation. WT-hTERT transfected HeLa cells with longer telomeres exhibited resistance to radiation and chemotherapeutic agents. Our data demonstrate that elevated release level of cytochrome c and AIF from mitochondria might contribute to the enhanced apoptosis in DN-hTERT transfected HeLa cells after treatment with sodium butyrate. Inhibition of telomerase might serve as a promising adjunctive therapy combined with conventional therapy in cervical cancer.

Animals↗

Organogenesis of pancreatic anlagen allografted in rats.

AIMS: To study the possibility of revascularization, growth, and differentiation of embryonic pancreatic anlagen transplanted to adult hosts. While transplantations of pancreas and islets are the main methods to cure diabetes mellitus, the donor source is in shortage. So it's necessary to find a new source for transplantation. METHODS: The pancreas from embryonic day 14.5 (E14.5) and 15.5 (E15.5) Lewis rat embryos were implanted into either intraperitoneal or subrenal capsular site of healthy Lewis rats. at 3 weeks or 6 weeks after implantation, the pancreatic anlagen in the host rats were resected for size measurements, as well as histopathologic and immunohistochemical examinations. RESULTS: Three weeks after implantation into the renal-capsular site, the size of both E14.5 and E15.5 pancreatic anlagen had enlarged 10- to 15-fold with differentiation of acinar components upon histological examination. Moreover, increasing numbers of beta cells and islets stained positive for insulin, and newly generated vessels were observed around the tissues. Continued proliferation of the endocrine islets in E14.5 pancreatic anlagen grafts was observed after another 3 weeks, whereas further proliferation in the E15.5 pancreatic anlagen graft was not seen. Additionally fibrosis appeared in the exocrine component of both E14.5 and E15.5 pancreatic anlagen at this time point. When implanted into intraperitoneal site, enlarged E15.5 pancreatic anlagen with proliferatels beta cells were also observed after 3 weeks. However, both the size of the pancreatic anlagen and the proliferation of the beta cells were much less than that in the subrenal capsular site. CONCLUSIONS: The allografted E14.5 and E15.5 pancreatic anlagen revascularised and grew into tissues that were structurally similar to normal mature rats pancreatic tissue. Adequate embryonic age for the transplantation of pancreatic anlagen is 14.5 and 15.5 days old. Subrenal capsula is a more suitable site than the peritoneal cavity for implantation of pancreatic anlagen.

Animals↗

Prolonged cardiac allograft survival in presensitized rats after a high activity Yunnan-cobra venom factor therapy.

UNLABELLED: Complement-dependent antibody-mediated acute humoral rejection is the major obstacle of clinical transplantation across ABO incompatibility and human leukocyte antigen presensitization. We previously demonstrated that Yunnan-cobra venom factor (Y-CVF) could almost completely abrogate complement activity and successfully prevent hyperacute rejection in some xenotransplant models without any obvious toxicity. In this study we investigated whether depletion of complement by Y-CVF prevented acute humoral allograft rejection in presensitized rats thereby prolonging graft survival. METHODS: Presensitization was achieved in Lewis rats by sequential grafting of three full-thickness skin pieces from Brown Norway rats. Serum cytotoxic alloantibody titers were determined by a modified in vitro complement-dependent microcytotoxicity assay. After presensitization, each Lewis rat received a heterotopic Brown Norway cardiac allograft. Fifteen recipients were divided into two groups: (1) no treatment control (n = 7); (2) Y-CVF therapy group (86 u/kg, IV, day -1) (n = 8). After cessation of the heart beat, allograft rejection was confirmed by pathologic as well as IgG and C3 immunohistochemical examinations. RESULTS: The mean graft survival time was significantly prolonged to 99.50 +/- 38.72 hours among rats that received Y-CVF vs 12.71 +/- 13.94 hours in nontreated controls (P < .001). Upon pathological and immunohistochemical examination, acute humoral rejection was mainly exhibited in the control group, whereas acute cellular rejection was mainly displayed in the Y-CVF therapy group. CONCLUSIONS: Our study demonstrated that complement depletion by Y-CVF significantly inhibited acute humoral allograft rejection in presensitized rats. As a therapeutic immunointervention tool for complement, Y-CVF has shown potential efficacy across ABO incompatible and positive cross-match barriers.

Animals↗

Sertoli cells induce xenolymphocyte apoptosis in vitro.

BACKGROUND: Testicular Sertoli cells can protect pancreatic islet grafts from allo- and autoimmune destruction; however, the mechanisms underlying immune privilege of the testicle are not well understood, especially in xenotransplantation. The purpose of this study was to investigate whether rat Sertoli cells could induce mouse lymphocyte apoptosis in vitro. METHODS: Testis was isolated from 2- to 4-week-old Sprague Dawley (SD) rats. Sertoli cells were successfully prepared by digestion with collagenase type V, trypsin, and DNase I, and then identified by electron microscope. Viability and apoptosis of cultured cells were measured by flow cytometry. We examined the apoptosis rates of Balb/c mouse lymphocytes, which were cocultured with SD rat Sertoli cells by FACS. The expression of Fas ligand (Fasl), transforming growth factor (TGF)-beta1 and clusterin on Sertoli cells were detected by immunocytochemistry. RESULTS: In the cocultured system, Sertoli cells accounted for more than 93%. With our isolation method, the viability of Sertoli cells was more than 95% and the apoptosis rate was 10.87% +/- 3.87%. The lymphocyte apoptosis ratio was 15.52 +/- 0.17 (P < .01, compared with the control groups). SABC immunochemistry staining showed that the sertoli cells could express FasL, TGF-beta, and clusterin. CONCLUSIONS: In our coculture in vitro, rat Sertoli cells expressed FasL and TGF-beta1 as well as induced the apoptosis of mouse lymphocytes. These results indicated that the expression of FasL and TGF-beta1 on Sertoli cells might relate to immune privilege in xenotransplantation.

Animals↗

Induction of accommodation model by combined RNA interference targeting 1,3-galactosyltransferase gene and low-dose GS-IB4 lectin in vitro.

OBJECTIVE: This study sought to mimic the interaction of xenograft endothelial cells and human serum in vitro after successfully silencing the expression of porcine alpha1,3-galactosyltransferase (alpha1,3GT) gene by RNA interference (RNAi), and to investigate the possibility of inducing accommodation in vitro by stimulation of alpha-Gal-specific binding lectin, Griffonia simplicifolia isolectin B4 (GS-IB4) and RNAi. MATERIALS AND METHODS: Various alpha-Gal expression patterns on a pig endothelial cell immortalized line (PED) was achieved by serial doses of small interfering RNA (siRNA) targeting porcinc alpha1,3GT gene. alpha1,3GT-siRNA transfected PEDs were exposed to increasing doses of GS-IB4 lectin (0.5, 2, and 8 microg/mL) for 4 hours before incubation with normal human serum (NHS). Accommodation phenomenon of PEDs in NHS was observed by 51Cr release and antibody/complement binding assays. RESULTS: With combined RNAi and low-dose GS-IB4 stimulation, PEDs remarkably inhibited complement-mediated cytotoxicity, which showed a better protective effect than using RNAi alone. At a concentration of 2 mug/mL, GS-IB4 exhibited the maximum protective effect. The expression of E-selectin on alpha1,3GT-siRNA transfected PEDs did not differ from that on parental PEDs with heat-inactivated NHS (HINHS) stimulation. Combined with GS-IB4 stimulation, however, it inhibited expression of E-selectin, which was GS-IB4 dose dependent, resulting in mean fluorescence intensity values of 98.5, 42.0, and 36.3 at 0.5, 2, and 8 microg/mL. The mRNA expression of the protective gene HO-1 was significantly up-regulated after treatment with RNAi and low-dose of GS-IB4. CONCLUSIONS: Combined RNAi and low-dose GS-IB4 induced pig endothelial cell accommodation in vitro. The level of alpha-Gal expression played an important role in the induction of accommodation.

Animals↗

Real-time observation of tubule formation from amorphous carbon nanowires under high-bias Joule heating.

The tubule formation process from amorphous carbon nanowires under high-bias-caused Joule heating was observed in real time in a high-resolution transmission electron microscope. The crystallization of the amorphous carbon nanowires occurred in two distinct ways: the formation of tubular graphitic basal planes parallel to the nanowire axis on the surface and the formation of nano-onions in the interior of the nanowire. The tubule formation mechanism is a process of solid-state atom diffusion at high temperatures. Energetically, the tubule formation is caused by the exceptionally low surface energy of the (0002) plane of graphite. Higher input power to the amorphous nanowires generally leads to improved graphitization and, in turn, to increased conductance. The results suggest that nanotube formation in the arc-discharge growth process may involve the formation and crystallization of amorphous carbon.

Computer Systems↗

Raman scattering from high-frequency phonons in supported n-graphene layer films.

Results of room-temperature Raman scattering studies of ultrathin graphitic films supported on Si (100)/SiO2 substrates are reported. The results are significantly different from those known for graphite. Spectra were collected using 514.5 nm radiation on films containing from n = 1 to 20 graphene layers, as determined by atomic force microscopy. Both the first- and second-order Raman spectra show unique signatures of the number of layers in the film. The nGL film analogue of the Raman G-band in graphite exhibits a Lorentzian line shape whose center frequency shifts linearly relative to graphite as approximately 1/n (for n = 1 omegaG approximately 1587 cm-1). Three weak bands, identified with disorder-induced first-order scattering, are observed at approximately 1350, 1450, and 1500 cm-1. The approximately 1500 cm-1 band is weak but relatively sharp and exhibits an interesting n-dependence. In general, the intensity of these D-bands decreases dramatically with increasing n. Three second-order bands are also observed (approximately 2450, approximately 2700, and 3248 cm-1). They are analogues to those observed in graphite. However, the approximately 2700 cm-1 band exhibits an interesting and dramatic change of shape with n. Interestingly, for n < 5 this second-order band is more intense than the G-band.

Journal Article↗

Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model.

Ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. The present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23H1 expression through adeno-associated virus (AAV)-mediated gene transfer. A cell line of high metastatic potential, SW626-M4, was derived by in vivo selection and used to establish an ovarian cancer metastasis model in the mouse. Liver metastasis and animal survival time were measured after transfer of a recombinant adeno-associated viral vector expressing nm23H1 (AAV-nm23H1) into the aforementioned model. Intraperitoneal injection of AAV-nm23H1 into this orthotopic implantation model of ovarian cancer resulted in (1) expression of the exogenous gene in more than 95% of tumor cells in situ in nude mice; (2) a 60% reduction in the number of animals developing liver metastases; and (3) a 35-day prolongation of median survival time compared with the untreated host group. In conclusion, the results support the feasibility of induction of nm23H1 expression through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival time, and indicate that AAV vectors deserve attention in the design of future gene therapy approaches to achieving long-term expression of curative genes in vivo.

Adenocarcinoma↗

Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans.

OBJECTIVE: The role of the central melanocortin system in the development of obesity has been extensively studied. Single-nucleotide polymorphisms (SNPs) within several candidate genes have been associated with food intake and obesity-related phenotypes; however, few of these associations have been replicated. SNPs in the agouti-related protein (AGRP) gene coding (Ala67Thr, 199G/A) and promoter (-38C/T) have been reported to be associated with body mass index (BMI), fat mass (FM) and percent body fat, in populations of European and African descent. In this study, we evaluated the association between the functional AGRP -38C/T promoter SNP and weight-related traits, namely BMI, FM and fat-free mass (FFM), as well as diabetes status. DESIGN: An association study of the AGRP -38C/T SNP and indices of obesity and diabetes status. SUBJECTS: A well-characterized population of 538 West Africans from Ghana and Nigeria recruited in the AADM (Africa America Diabetes Mellitus) study (mean age 52 years, 41.3% males, 71% diabetic). MEASUREMENTS: Genotyping of the AGRP -38C/T SNP, BMI, FM, FFM and fasting plasma glucose. RESULTS: Women carrying two copies of the variant T allele had significantly lower BMI (OR=0.47; 95% CI, 0.25-0.87). Also, men with at least one copy of the variant T allele were over two times less likely to be diabetic than other men (OR=0.44; 95% CI, 0.22-0.89). CONCLUSION: Our results replicate previous findings and implicate the AGRP -38C/T SNP in the regulation of body weight in West Africans.

Agouti Signaling Protein↗

Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population.

Therapy with losartan compared to irbesartan was performed in a Chinese sample of hypertensive patients with elevated serum uric acid (SUA) levels. After 1 week of screening and a 2 week single-blinded placebo baseline period, patients were treated for 4 weeks with losartan 50 mg or irbesartan 150 mg. After 4 weeks, patients with SiDBP <90 mmHg and SiSBP <140 mmHg continued the same dose regimen for another 4 weeks. If blood pressure was not controlled after 4 weeks of treatment, the dose of either regimen was doubled to losartan 100 mg and irbesartan 300 mg. There were 351 patients randomized (176 to losartan and 175 to irbesartan), and of these, 325 patients completed the study (162 in the losartan group and 163 in the irbesartan group). At baseline, the median SUA level in the losartan group was 422 and 420 micromol/l in the irbesartan group. At 8 weeks of therapy, SUA decreased by 63 mumol/l in the losartan group compared to 12 mumol/l in the irbesartan group (P < 0.0001). Blood pressure declined comparably in both groups from 151/92 mmHg at baseline to 137/83 and 135/83 (losartan and irbesartan, respectively, NS). No severe AEs were found for either treatment group. Therapy with losartan decreased SUA levels significantly more than irbesartan in Chinese patients with hypertension and elevated SUA levels, demonstrating the unique uricosuric effect of this ARB in this ethnic group.

Angiotensin II Type 1 Receptor Blockers↗

Effects of two different hydroxyethyl starch solutions (HES200/0.5 vs. HES130/0.4) on the expression of platelet membrane glycoprotein.

BACKGROUND: There are various hydroxyethyl starch (HES) solutions with different degrees of hydroxylation and different molecular weights. HES200/0.5 solution is most commonly used. HES130/0.4 is a new HES solution and is the 'state-of-the-art' in volume substitution. However, the mechanism of the observed anticoagulation action of HES has not been fully delineated. The objective of this study was to further investigate the effect of HES200/0.5 and HES130/0.4 on platelet coagulation. METHODS: Sixty ASA I-II patients undergoing elective minor surgery were randomly allocated to receive an intravenous infusion (20 ml/kg) of lactated Ringer's solution (group L), HES200/0.5 (group H) or HES130/0.4 (group V) after the induction of anesthesia. The expression of CD42b, CD41/61 and CD62p in vivo was assessed on non-stimulated platelets and adenosine diphosphate (ADP) agonist-activated platelets using flow cytometry. RESULTS: Resting glycoprotein expression of the non-stimulated platelets was observed. HES200/0.5 and HES130/0.4 reduced the CD42b, CD41/61 and CD62p expression of ADP-agonist-activated platelets at 15 min after intravenous infusion. At 6 h after intravenous infusion, the trend of decreasing expression of activated CD42b, CD41/61 and CD62p was maintained in group H. However, CD42b, CD41/61 and CD62p expression returned to the pre-operative level in group V. CONCLUSION: This study showed that both HES200/0.5 and HES130/0.4 can inhibit platelet coagulation. Platelet dysfunction experienced a faster recovery after the infusion of HES130/0.4 than after HES200/0.5. Liquid resuscitation with HES130/0.4 may decrease the risk of hemorrhage in the operative period.

Adenosine Diphosphate↗

A synergistic effect between PG490-88 and tacrolimus prolongs renal allograft survival in monkeys.

This study was undertaken to determine if PG490-88 and tacrolimus (Tac) act synergistically to prevent renal allograft rejection in monkeys and to explore possible mechanisms of synergy between these agents. MHC-mismatched renal allografts were transplanted into cynomolgus monkeys after bilateral nephrectomy. Recipients were divided into the following groups: (i) no treatment; (ii) PG490-88 (0.03 mg/kg); (iii) Tac (1 mg/kg); (iv) PG490-88 (0.01 mg/kg) + Tac (1 mg/kg) and (v) PG490-88 (0.03 mg/kg) + Tac (1 mg/kg). Through synergy PG490-88 and Tac inhibited anti-CD3/PMA-induced T-cell proliferation and IFN-gamma expression in vitro. Tac monotherapy only marginally prolonged survival (27 +/- 3.2 days), while the combination of PG490-88 and Tac significantly prolonged graft survival to a median of 99 days (PG490-88 at 0.03 mg) and 38.5 days (PG490-88 at 0.01 mg/kg). Prolonged survival correlated with inhibited IgM production as well as reduced T-cell infiltration, IL-2 protein expression and NF-AT/NF-kappaB activity. We conclude that PG490-88 and a subtherapeutic dose of Tac significantly prolong renal allograft survival in monkeys through the synergistic inhibition of T-cell activation and a decrease in IFN-gamma production and NF-AT/NF-kappaB activity.

Animals↗

Interleukin-18 affects local cytokine expression but does not impact on the development of kidney allograft rejection.

Interleukin-18 is predominantly a macrophage-derived cytokine with a key role in inflammation and cell-mediated immunity. Having previously demonstrated IL-18 upregulation in a rat model of kidney rejection, here we examined IL-18 in a fully MHC-mismatched murine model of acute kidney rejection using IL-18-deficient recipients (IL-18-/-) and animals administered neutralizing IL-18 binding protein (IL-18BP). Gene expression of IL-18 and its receptor were significantly upregulated in allografts compared to isografts, as was the cellular infiltrate (T cells and macrophages) (p < 0.001). Allografts developed kidney dysfunction (p < 0.05) and tubulitis (p < 0.01) not observed in controls. There was a significant reduction in gene expression of IL-18 downstream pro-inflammatory molecules (iNOS, TNFalpha and IFNgamma) in IL-18-/- recipients (p < 0.01), and IL-18BP-treated animals. The CD4+ infiltrate and IL-4 mRNA expression was greater in the IL-18-/- recipients than wild-type (WT) allografts and IL-18BP-treated animals (p < 0.05), suggesting a Th2-bias which was supported by IFNgamma and IL-4 ELISPOT data and an increased eosinophil accumulation (p < 0.001). Neither IL-18 deficiency nor neutralization prevented renal dysfunction or tubulitis. This study demonstrates increased production of IL-18 in murine kidney allograft rejection and provides evidence that IL-18-induced pathways of inflammation are active. However, neither IL-18 deficiency nor neutralization was protective against the development of allograft rejection.

Animals↗

Patient self assessment of pregnancy status in the emergency department.

OBJECTIVES: Pregnancy tests are often performed routinely for female emergency department (ED) patients of reproductive age. One major reason is a perception that patients are unreliable in predicting their own pregnancy status. We hypothesised that patients could reliably predict that they were not pregnant. METHODS: The study used a prospective cohort design, in an urban academic ED, from January 19 to May 19, 2004. All patients for whom a pregnancy test was ordered were asked about their sexual history as well as two additional questions: "Do you think you might be pregnant?" and "Is there any chance you could be pregnant?" Patients with already documented pregnancies were excluded. RESULTS: A total of 474 patients had pregnancy tests performed that met inclusion criteria. Eleven (2.3%) tests were positive. Among patients who answered no to both questions (337), one test (0.3%) was positive (negative predictive value (NPV) 99.7%, likelihood ratio (LR) 0.13 (95% CI, 0.02 to 0.82)). The other historical factor with a high NPV (100%) was not being sexually active (LR not calculable). All pregnancies occurred in patients with gastrointestinal or genitourinary as the chief complaint: this comprised only 56% of the presentations for which tests were ordered. CONCLUSION: Sexual history and self assessment can be used as a highly effective predictor of a patient not being pregnant. Given the risks of missed pregnancy in the ED, and low monetary and time cost of pregnancy tests, frequent testing is still recommended in most instances.

Adolescent↗