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Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 109 records · Page 6Linked to original sources

Origins of endothelial and osteogenic cells in the subcutaneous collagen gel implant.

The interdependent relationship between vascular endothelial cells and osteoblasts during bone formation and fracture healing has been long appreciated. This paper reports a heterotopic implant model using FGF-2-expanded bone marrow stromal cells (BMSC) derived from Tie2eGFP (endothelial marker) and pOBCol3.6GFPcyan or topaz (early osteoblast marker) transgenic mice to appreciate the host/donor relationships of cells participating in the process of heterotopic bone formation. The study included various combinations of Tie2eGFP and pOBCol3.6GFPcyan and topaz transgenics as BMSC or whole bone marrow (WBM) donors and also as recipients. Rat tail collagen was used as a carrier of donor cells and implantation was done in lethally irradiated mice rescued with WBM injection. Development of ossicles in the implants was followed weekly during the 4- to 5-week long post-implantation period. By 4-5 weeks after total body irradiation (TBI) and implantation, a well-formed bone spicule had developed that was invested with bone marrow. Experiments showed absolute dominance of donor-derived cells in the formation of endothelial-lined vessels inside the implants as well as the marrow stromal-derived osteogenic cells. Host-derived fibroblasts and osteogenic cells were confined to the fibrous capsule surrounding the implant. In addition, cells lining the endosteal surface of newly formed marrow space carrying a pOBCol3.6GFP marker were observed that were contributed by WBM donor cells and the host. Thus, FGF-2-expanded BMSC appear to be a source of endothelial and osteogenic progenitor cells capable of eliciting heterotopic bone formation independent of cells from the host. This model should be useful for understanding the interactions between these two cell types that control osteogenic differentiation in vivo.

Animals↗

Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice.

BACKGROUND AND AIMS: Abdominal pain and discomfort are common symptoms in functional disorders and are attributed to visceral hypersensitivity. These symptoms fluctuate over time but the basis for this is unknown. Here we examine the impact of changes in gut flora and gut inflammatory cell activity on visceral sensitivity. METHODS: Visceral sensitivity to colorectal distension (CRD) was assessed at intervals in healthy mice for up to 12 weeks, and in mice before and after administration of dexamethasone or non-absorbable antibiotics with or without supplementation with Lactobacillus paracasei (NCC2461). Tissue was obtained for measurement of myeloperoxidase activity (MPO), histology, microbiota analysis, and substance P (SP) immunolabelling. RESULTS: Visceral hypersensitivity developed over time in healthy mice maintained without sterile precautions. This was accompanied by a small increase in MPO activity. Dexamethasone treatment normalised MPO and CRD responses. Antibiotic treatment perturbed gut flora, increased MPO and SP immunoreactivity in the colon, and produced visceral hypersensitivity. Administration of Lactobacillus paracasei in spent culture medium normalised visceral sensitivity and SP immunolabelling, but not intestinal microbiota counts. CONCLUSION: Perturbations in gut flora and in inflammatory cell activity alter sensory neurotransmitter content in the colon, and result in altered visceral perception. Changes in gut flora may be a basis for the variability of abdominal symptoms observed in functional gastrointestinal disorders and may be prevented by specific probiotic administration.

Abdominal Pain↗

Effect of cardiac lymph flow obstruction on cardiac collagen synthesis and interstitial fibrosis.

The effect of chronic cardiac lymphatic obstruction on the myocardial synthesis of collagen type I and III was investigated in a rabbit model. In the lymphatic obstruction group (n=16), plasma C-terminal propeptide type I procollagen (PICP) and N-terminal propeptide type III procollagen (PIIINP) were elevated at 7, 14 and 30 days after the operation (p<0.05). The elevated PICP and PIIINP returned to the pre-operation values 60 days after the operation. The myocardial expression of collagen type I and III mRNA were also enhanced in the lymphatic flow obstruction group. Plasma PICP, PIIINP and myocardial collagen type I and III mRNA remained unchanged in the control group (n=16). We concluded that chronic obstruction of cardiac lymph flow leads to enhanced myocardial collagen synthesis in rabbits. The enhanced collagen synthesis starts within seven days after lymphatic obstruction and subsides after 60 days.

Animals↗

A method for repositioning of stereotactic brain patients with the aid of real-time CT image guidance.

This note presents a method that recalculates the coordinates of the isocentre for patients undergoing stereotactic radiotherapy to the brain with a relocatable head frame based on a pre-treatment CT scan. The method was evaluated by comparing initial stereotactic coordinates of the isocentre with the recalculated coordinates for eight single-fraction patients. These patients had the Brown-Roberts-Wells (BRW) frame fixed to the outer table of the skull, and therefore the coordinates of any anatomical point should be identical between the initial scan and the pre-treatment scan. The differences between the two sets of coordinates were attributed to errors in the method. The results showed that the systematic errors in the recalculated coordinates were less than 0.05 mm, and they were not statistically significant. The random errors (one standard deviation) were from 0.35 mm (lateral) to 0.58 mm (vertical). The average value of the combined 3D difference was 0.75 mm.

Algorithms↗

CRF2 receptor activation prevents colorectal distension induced visceral pain and spinal ERK1/2 phosphorylation in rats.

BACKGROUND AND AIMS: Activation of corticotropin releasing factor 1 (CRF1) receptors is involved in stress related responses and visceral pain, while activation of CRF2 receptors dampens the endocrine and some behavioural stress responses. We hypothesised that CRF2 receptor activation may influence visceral pain induced by colorectal distension (CRD) in conscious rats, and assessed the possible sites and mechanisms of action. METHODS: Male Sprague-Dawley rats were exposed to CRDs (60 mm Hg, 10 minutes twice, with a 10 minute rest interval). Visceromotor responses (VMR) were measured by electromyography or visual observation. Spinal (L6-S1) extracellular signal regulated kinase 1/2 (ERK 1/2) activation following in vivo CRD and CRF2 receptor gene expression in the T13-S1 dorsal root ganglia (DRG) and spinal cord were determined. Inferior splanchnic afferent (ISA) activity to CRD (0.4 ml, 20 seconds) was assessed by electrophysiological recording in an in vitro ISA nerve-inferior mesenteric artery (intra-arterial)-colorectal preparation. RESULTS: In controls, VMR to the second CRD was mean 31 (SEM 4)% higher than that of the first (p<0.05). The selective CRF2 agonist, human urocortin 2 (hUcn 2, at 10 and 20 microg/kg), injected intravenous after the first distension, prevented sensitisation and reduced the second response by 8 (1)% and 30 (5)% (p<0.05) compared with the first response, respectively. RT-PCR detected CRF2 receptor gene expression in the DRG and spinal cord. CRD (60 mm Hg for 10 minutes) induced phosphorylation of ERK 1/2 in neurones of lumbosacral laminae I and IIo and the response was dampened by intravenous hUcn 2. CRD, in vitro, induced robust ISA spike activity that was dose dependently blunted by hUcn 2 (1-3 microg, intra-arterially). The CRF2 receptor antagonist, astressin2-B (200 microg/kg subcutaneously or 20 microg intra-arterially) blocked the hUcn 2 inhibitory effects in vivo and in vitro. CONCLUSIONS: Peripheral injection of hUcn 2 blunts CRD induced visceral pain, colonic afferent, and spinal L6-S1 ERK 1/2 activity through CRF2 receptor activation in rats.

Animals↗

Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly.

Structural deformity of the hippocampus is characteristic of individuals with very mild and mild forms of dementia of the Alzheimer type (DAT). The purpose of this study was to determine whether a similar deformity of the hippocampus can predict the onset of dementia in nondemented elders. Using high dimensional diffeomorphic transformations of a neuroanatomical template, hippocampal volumes and surfaces were defined in 49 nondemented elders; the hippocampal surface was subsequently partitioned into three zones (i.e., lateral, superior and inferior-medial), which were proximal to the underlying CA1 subfield, CA2-4 subfields plus dentate gyrus, and subiculum, respectively. Annual clinical assessments using the Clinical Dementia Rating scale (CDR), where CDR 0 indicates no dementia and CDR 0.5 indicates very mild dementia, were then performed for a mean of 4.9 years (range 0.9-7.1 years) to monitor subjects who converted from CDR 0 to CDR 0.5. Inward variation of the lateral zone and left hippocampal volume significantly predicted conversion to CDR 0.5 in separate Cox proportional hazards models. When hippocampal surface variation and volume were included in a single model, inward variation of the lateral zone of the left hippocampal surface was selected as the only significant predictor of conversion. The pattern of hippocampal surface deformation observed in nondemented subjects who later converted to CDR 0.5 was similar to the pattern of hippocampal surface deformation previously observed to discriminate subjects with very mild DAT and nondemented subjects. These results suggest that inward deformation of the left hippocampal surface in a zone corresponding to the CA1 subfield is an early predictor of the onset of DAT in nondemented elderly subjects.

Aged↗

Chemical ablation of the gallbladder: clinical application and long-term observations.

BACKGROUND: We investigated whether minicholecystostomy followed by chemical ablation of the gallbladder could be used as a alternative to cholecystectomy in patients at high risk for complications of surgery. METHODS: From January 1990 through January 2003, 34 patients at high risk underwent minicholecystostomy. Six weeks after the operation, microwave irradiation was provided to burn the mucosa of the cystic duct at locations at 3, 6, 9, and 12 o'clock around the orifice. Each location was treated eight times at 50 mA for 10 sec. Then chemical ablation of the gallbladder was performed by infusing 95% ethanol into the gallbladder cavity for 30 min. For each sclerosis course, the procedure was repeated every 4 h for a total of eight times. Approximately 2 weeks later, the drainage tube was removed from the gallbladder after cholecystography showed that no cavity other than the lumen of the tube remained in the gallbladder. RESULTS: Patients tolerated the procedure well and were followed with ultrasonography for 2-14 years (mean, 9). Twenty-nine patients had no complications or side effects, and five patients developed a 1.5- to 3- cm mucocele in the gallbladder. The long-term success rate of sclerotherapy was 85.3% (29/34). No recurrent cholecystitis, new stone or formation, canceration were encountered at the site of the gallbladder. CONCLUSIONS: Minicholecystostomy followed by chemical ablation of the gallbladder was a safe, effective, and simple procedure for treating high-risk patients with acute cholecystitis and/or cholelithiasis.

Aged↗

The effect of overhanging nucleotides on fluorescence properties of hybridising oligonucleotides labelled with Alexa-488 and FAM fluorophores.

In order to rationally select and design probes for real-time PCR, we have determined the influence of the overhang region of the complementary strand on the resulting fluorescence from a hybridising probe. A series of target oligonucleotides, each with a unique 3' overhang (4 bases), was hybridised to either 5' fluorescein (FAM)- or Alexa-488-labelled probes, and the changes in fluorescence properties were monitored. We found that the number of guanine bases in the overhang region of the target oligonucleotides was proportional to the amount of fluorescence quenching observed for both the FAM and Alexa-488 dyes. FAM appeared to be more sensitive to guanine-induced quenching with three and four guanine bases resulting in greater than a twofold decrease in the quantum yield of the fluorophore compared to the no-overhang target. In addition, we found that adenine bases caused fluorescence quenching of the Alexa-488-labelled probe, whereas the FAM-labelled probe appeared insensitive. The quenching data, generated with the steady-state fluorescence measurements, displayed a linear correlation with that obtained using a fluorescent thermal cycler, suggesting the applicability to real-time PCR measurements. Anisotropy data from the series of duplexes correlated with the fluorescence quantum yield, suggesting that quenching was accompanied by increased dye mobility.

Anisotropy↗

Dosimetric verification of IMRT treatment planning using Monte Carlo simulations for prostate cancer.

The purpose of this work is to investigate the accuracy of dose calculation of a commercial treatment planning system (Corvus, Normos Corp., Sewickley, PA). In this study, 30 prostate intensity-modulated radiotherapy (IMRT) treatment plans from the commercial treatment planning system were recalculated using the Monte Carlo method. Dose-volume histograms and isodose distributions were compared. Other quantities such as minimum dose to the target (D(min)), the dose received by 98% of the target volume (D98), dose at the isocentre (D(iso)), mean target dose (D(mean)) and the maximum critical structure dose (D(max)) were also evaluated based on our clinical criteria. For coplanar plans, the dose differences between Monte Carlo and the commercial treatment planning system with and without heterogeneity correction were not significant. The differences in the isocentre dose between the commercial treatment planning system and Monte Carlo simulations were less than 3% for all coplanar cases. The differences on D98 were less than 2% on average. The differences in the mean dose to the target between the commercial system and Monte Carlo results were within 3%. The differences in the maximum bladder dose were within 3% for most cases. The maximum dose differences for the rectum were less than 4% for all the cases. For non-coplanar plans, the difference in the minimum target dose between the treatment planning system and Monte Carlo calculations was up to 9% if the heterogeneity correction was not applied in Corvus. This was caused by the excessive attenuation of the non-coplanar beams by the femurs. When the heterogeneity correction was applied in Corvus, the differences were reduced significantly. These results suggest that heterogeneity correction should be used in dose calculation for prostate cancer with non-coplanar beam arrangements.

Computer Simulation↗

CFD simulation of aggregation and breakage processes in laminar Taylor-Couette flow.

An experimental and computational investigation of the effects of local fluid shear rate on the aggregation and breakage of approximately 10 microm latex spheres suspended in an aqueous solution undergoing laminar Taylor-Couette flow was carried out according to the following program. First, computational fluid dynamics (CFD) simulations were performed and the flow field predictions were validated with data from particle image velocimetry experiments. Subsequently, the quadrature method of moments (QMOM) was implemented into the CFD code to obtain predictions for mean particle size that account for the effects of local shear rate on the aggregation and breakage. These predictions were then compared with experimental data for latex sphere aggregates (using an in situ optical imaging method) and with predictions using spatial average shear rates. The mean particle size evolution predicted by CFD and QMOM using appropriate kinetic expressions that incorporate information concerning the particle morphology (fractal dimension) and the local fluid viscous effects on aggregation collision efficiency match well with the experimental data.

Biophysics↗

Co1-xFexS2: a tunable source of highly spin-polarized electrons.

In the emerging field of spin-electronics ideal ferromagnetic electron sources would not only possess a high degree of spin polarization, but would also offer control over the magnitude of this polarization. We demonstrate here that a simple scheme can be utilized to control both the magnitude and the sign of the spin polarization of ferromagnetic CoS2, which we probe with a variety of techniques. The position of the Fermi level is fine-tuned by solid solution alloying with the isostructural diamagnetic semiconductor FeS2, leading to tunable spin polarization of up to 85%.

Journal Article↗

Development of an integrated model for heat transfer and dynamic growth of Clostridium perfringens during the cooling of cooked boneless ham.

Numerous small meat processors in the United States have difficulties complying with the stabilization performance standards for preventing growth of Clostridium perfringens by 1 log10 cycle during cooling of ready-to-eat (RTE) products. These standards were established by the Food Safety and Inspection Service (FSIS) of the US Department of Agriculture in 1999. In recent years, several attempts have been made to develop predictive models for growth of C. perfringens within the range of cooling temperatures included in the FSIS standards. Those studies mainly focused on microbiological aspects, using hypothesized cooling rates. Conversely, studies dealing with heat transfer models to predict cooling rates in meat products do not address microbial growth. Integration of heat transfer relationships with C. perfringens growth relationships during cooling of meat products has been very limited. Therefore, a computer simulation scheme was developed to analyze heat transfer phenomena and temperature-dependent C. perfringens growth during cooling of cooked boneless cured ham. The temperature history of ham was predicted using a finite element heat diffusion model. Validation of heat transfer predictions used experimental data collected in commercial meat-processing facilities. For C. perfringens growth, a dynamic model was developed using Baranyi's nonautonomous differential equation. The bacterium's growth model was integrated into the computer program using predicted temperature histories as input values. For cooling cooked hams from 66.6 degrees C to 4.4 degrees C using forced air, the maximum deviation between predicted and experimental core temperature data was 2.54 degrees C. Predicted C. perfringens growth curves obtained from dynamic modeling showed good agreement with validated results for three different cooling scenarios. Mean absolute values of relative errors were below 6%, and deviations between predicted and experimental cell counts were within 0.37 log10 CFU/g. For a cooling process which was in exact compliance with the FSIS stabilization performance standards, a mean net growth of 1.37 log10 CFU/g was predicted. This study introduced the combination of engineering modeling and microbiological modeling as a useful quantitative tool for general food safety applications, such as risk assessment and hazard analysis and critical control points (HACCP) plans.

Animals↗

Phospholipase A2 activating protein (PLAA) is required for 1alpha,25(OH)2D3 signaling in growth plate chondrocytes.

Phospholipase A2 (PLA2) is pivotal in the rapid membrane-mediated actions of 1,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. Microarray analysis indicated that PLA2 activating protein (PLAA) mRNA is upregulated 6-fold before rat growth plate cells exhibit 1alpha,25(OH)2D3-dependent protein kinase C (PKC) increases, suggesting that it plays an important role in 1alpha,25(OH)2D3's mechanism of action. PLAA mRNA was confirmed in 1alpha,25(OH)2D3-responsive growth zone (prehypertrophic and upper hypertrophic cell zones) chondrocytes by RT-PCR and Northern blot in vitro and by in situ hybridization in vivo. PLAA protein was shown by Western blot and immunohistochemistry. PLAAs role in 1alpha,25(OH)2D3 signaling was evaluated in growth zone cell cultures using PLAA peptide. Arachidonic acid release was increased as was PLA2-specific activity in plasma membranes and matrix vesicles. PKCalpha, but not PKCbeta, PKCepsilon, or PKCzeta, was increased. PLAAs effect was comparable to that of 1alpha,25(OH)2D3 and was additive with 1alpha,25(OH)2D3. PLA2 inhibitors quinacrine and AACOCF3, and cyclooxygenase inhibitor indomethacin blocked the effect of PLAA peptide on PKC, indicating arachidonic acid and its metabolites were involved. This was confirmed using exogenous arachidonic acid. Prostaglandin acted via EP1 based on inhibition by SC19220 and not via EP2 since AH6809 had no effect. Like 1alpha,25(OH)2D3, PLAA peptide also increased activity of phospholipase C-specific activity via beta-1 and beta-3 isoforms, but not delta-1 or gamma-1; the effect of PLAA was via lysophospholipid but not via arachidonic acid. PLAA peptide decreased [3H]-thymidine incorporation to 50% of the decrease caused by 1alpha,25(OH)2D3. In contrast, PLAA peptide increased alkaline phosphatase-specific activity and proteoglycan production in a manner similar to 1alpha,25(OH)2D3. This indicates that PLAA is a specific activator of PLA2 in growth plate chondrocytes, and suggests that it mediates the membrane effect of 1alpha,25(OH)2D3, thereby modulating physiological response.

Animals↗

B-type natriuretic peptide in patients with clinical hyperthyroidism.

AIMS: To investigate the level and clinical significance of plasma B-type natriuretic peptide (BNP) in patients with hyperthyroidism. METHODS: Plasma BNP was measured in 32 healthy subjects and 67 patients with clinical hyperthyroidism. Left ventricular anatomy and function was assessed with echocardiography. RESULTS: The average BNP in hyperthyroid patients was higher than that in healthy subjects (186+/-140 vs 34+/-17 ng/l, p =0.001). The increase in BNP was mainly found in hyperthyroid patients who had clinical and echocardiographic evidence of left ventricular dysfunction (250+/-190 ng/l). The BNP level in patients with hyperthyroidism, but with normal left ventricular function, was similar to that of the controls (37+/-17 vs 34+/-17, ng/l, p>0.05). Multi-regression analysis showed that left atrial diameter and left ventricular ejection fraction were independently associated with the plasma levels of BNP. CONCLUSIONS: there is a significant elevation in plasma BNP in patients with hyperthyroidism; the increase is largely due to hyperthyroidism-induced left ventricular dysfunction. Measurements of plasma BNP may help to detect heart failure in patients with clinical hyperthyroidism.

Adult↗

TNF-alpha upregulates adenosine 2b (A2b) receptor expression and signaling in intestinal epithelial cells: a basis for A2bR overexpression in colitis.

Adenosine is an endogenous signaling molecule upregulated during inflammatory conditions. Acting through the A2b receptor (A2bR), the predominant adenosine receptor in human colonic epithelia, adenosine has been directly implicated in immune and inflammatory responses in the intestine. Little is known about expression and regulation of A2bR during inflammation. Tumor necrosis factor alpha (TNF-alpha) is highly upregulated during chronic and acute inflammatory diseases. This study examined the expression of A2bR during colitis and studied effects of TNF-alpha on A2bR expression, signaling and function. Results demonstrated that A2bR expression increases during active colitis. TNF-alpha pretreatment of intestinal epithelial cells increased A2bR messenger RNA and protein expression. TNF-alpha significantly increased adenosine-induced membrane recruitment of A2bR and cyclic adenosine monophosphate downstream signaling. Further, TNF-alpha potentiated adenosine-induced shortcircuit current and fibronectin secretion. In conclusion, we demonstrated that TNF-alpha is an important regulator of A2bR, and during inflammation, upregulation of TNF-alpha may potentiate adenosine-mediated responses.

Adenosine↗

Comparison of bone marrow cell growth on 2D and 3D alginate hydrogels.

Calcium cross-linked sodium alginate hydrogels have several advantageous features making them potentially suitable as tissue engineering scaffolds and this material has been previously used in many biomedical applications. 3D cell culture systems are often very different from 2D petri dish type cultures. in this study the effect of alginate hydrogel architecture was investigated by comparing rat bone marrow cell proliferation and differentiation on calcium cross linked sodium alginate discs and 1mm internal diameter tubes. It was found that bone marrow cell proliferation was diminished as the concentration of alginate in the 2D hydrogel substrates increased, yet proliferation was extensive on tubular alginate constructs with high alginate contents. Alginate gel thickness was found to be an important parameter in determining cell behaviour and the different geometries did not generate significant alterations in BMC differentiation profiles.

Absorbable Implants↗

Effects of lead on voltage-gated sodium channels in rat hippocampal CA1 neurons.

In this study, the effects of lead (Pb2+) on voltage-gated sodium channel currents (INa) were investigated in acutely dissociated rat hippocampal CA1 neurons using the conventional whole-cell patch-clamp technique. We found that Pb2+ reduced the amplitudes of INa in a concentration-dependent manner, and the effect could be washed out by extracellular application of 3 mM EGTA. The results also showed that at the concentration of 100 microM, Pb2+ decreased the activation threshold and the voltage at which the maximum INa current was evoked and caused negative shifts of INa steady-state activation curve, and enlarged INa tail-currents; Pb2+ induces a left shift of the steady-state inactivation curve, and delayed the recovery of INa from inactivation, and reduced the fraction of available sodium channels; Pb2+ delayed the activation of INa in a concentration- and voltage-dependent manner, and prolonged the time course of the fast inactivation of sodium channels; activity-dependent attenuation of INa was not altered by Pb2+. It was suggested that Pb2+ might exert its effects on sodium channels by binding a specific site on the extracellular side of sodium channels and dragging the IIS4 voltage sensor outwardly. The interaction of Pb2+ with voltage-dependent sodium channels may lead to change in electrical activity and contribute to worsen the neurotoxicological damage.

Animals↗