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Biomedical subjects

Wei Sun

Publications and source records attributed to Wei Sun.

At least 73 records · Page 4Linked to original sources

Biomechanical analysis of silicon microelectrode-induced strain in the brain.

The ability to successfully interface the brain to external electrical systems is important both for fundamental understanding of our nervous system and for the development of neuroprosthetics. Silicon microelectrode arrays offer great promise in realizing this potential. However, when they are implanted into the brain, recording sensitivity is lost due to inflammation and astroglial scarring around the electrode. The inflammation and astroglial scar are thought to result from acute injury during electrode insertion as well as chronic injury caused by micromotion around the implanted electrode. To evaluate the validity of this assumption, the finite element method (FEM) was employed to analyze the strain fields around a single Michigan Si microelectrode due to simulated micromotion. Micromotion was mimicked by applying a force to the electrode, fixing the boundaries of the brain region and applying appropriate symmetry conditions to nodes lying on symmetry planes. Characteristics of the deformation fields around the electrode including maximum electrode displacement, strain fields and relative displacement between the electrode and the adjacent tissue were examined for varying degrees of physical coupling between the brain and the electrode. Our analysis demonstrates that when physical coupling between the electrode and the brain increases, the micromotion-induced strain of tissue around the electrode decreases as does the relative slip between the electrode and the brain. These results support the use of neuro-integrative coatings on electrode arrays as a means to reduce the micromotion-induced injury response.

Biomechanical Phenomena↗

[Clinical research of correlation between osteonecrosis and steroid].

OBJECTIVE: To explore the correlation between the dosage of corticosteroid, time of onset and incidence of osteonecrosis (ON) in patients with SARS. METHODS: From July 2003 to January 2004, general survey carried out for ON in 551 patients with SARS. Five hundred and fifty-one patients except 12 were administrated by corticosteroid from 80 mg to 30 000 mg. The age of patients was (33 +/- 9) years old ranging from 19 to 59 years old. One hundred and thirty-one were male, and four hundred and twenty were female. MRI and X-ray film were taken in all patients including both hips, knees, shoulders, ankles and wrists. CT scan was taken in partial patients. Common classification system were used for staging of hip (ARCO), knee (Lotka) and shoulder (Cruess). Independent test, rank-sum test and multiple factor logistic regression analysis were used for statistical analysis. RESULTS: No osteonecrosis was detected in 12 patients without corticosteroid. Osteonecrosis was detected in 176 patients (32.7 percent) among 539 patients. There were ON of femoral head in 130 cases (210 hips), ON of knee in 98 cases (130 knees), ON of humeral head in 21 cases (36 shoulders), ON of talus and calcaneus in 16 cases (26 ankles), ON of scaphoid and lunate in 11 cases (17 wrists), ON of patella in 3 cases (4 patella), ON of ilium in 1 case and bone infarction (femur, tibia) in 18 cases. One hundred and nineteen cases (195 hips) with ONFH were in stage I (IA 45 hips, IB 77 hips, IC 73 hips). Eleven cases (15 hips) were in stage II. All osteonecrosis of the knee and humoral head was stage I. Thirty-four patients with ON had one joint affected, 45 patients had 2 joints, 93 patients had more than 3 joints. The dosage of corticosteroid was (5842 +/- 4988) mg in ON group and (2719 +/- 2571) mg in non-ON group (P < 0.0001). The duration of steroid was (38 +/- 17) d in ON group and (27 +/- 15) d in non-ON group (P < 0.01). The dosage of pulse treatment was (340 +/- 207) mg/d in ON group and (211 +/- 160) mg/d in non-ON group (P < 0.01). The duration of pulse treatment was (28 +/- 13) d in ON group and (18 +/- 11) d in non-ON group (P < 0.01). All patients with ON were detected within 6 months from administration. CONCLUSION: About one-third patients with SARS who were treated with a high dose of corticosteroid occurred osteonecrosis. ON is frequently multiple focuses. The actual time of onset of ON is early of steroid used. MRI is golden standard for early diagnosis of ON. The patients who were treated with a high dose of corticosteroid should be inspected initially by MRI.

Adrenal Cortex Hormones↗

Finite element implementation of a generalized Fung-elastic constitutive model for planar soft tissues.

Numerical simulations of the anisotropic mechanical properties of soft tissues and tissue-derived biomaterials using accurate constitutive models remain an important and challenging research area in biomechanics. While most constitutive modeling efforts have focused on the characterization of experimental data, only limited studies are available on the feasibility of utilizing those models in complex computational applications. An example is the widely utilized exponential constitutive model proposed by Fung. Although present in the biomechanics literature for several decades, implementation of this model into finite element (FE) simulations has been limited. A major reason for limited numerical implementations are problems associated with inherent numerical instability and convergence. To address this issue, we developed and applied two restrictions for a generalized Fung-elastic constitutive model necessary to achieve numerical stability. These are (1) convexity of the strain energy function, and (2) the condition number of material stiffness matrix set lower than a prescribed value. These constraints were implemented in the nonlinear regression used for constitutive model parameter estimation to the experimental biaxial mechanical data. We then implemented the generalized Fung-elastic model into a commercial FE code (ABAQUS, Pawtucket, RI, USA). Single element and multi-element planar biaxial test simulations were conducted to verify the accuracy and robustness of the implementation. Results indicated that numerical convergence and accurate FE implementation were consistently obtained. The present study thus presents an integrated framework for accurate and robust implementation of pseudo-elastic constitutive models for planar soft tissues. Moreover, since our approach is formulated within a general FE code, it can be straightforwardly adopted across multiple software platforms.

Anisotropy↗

Study of coordinative gene expression at the biological process level.

MOTIVATION: Cellular processes are not isolated groups of events. Nevertheless, in most microarray analyses, they tend to be treated as standalone units. To shed light on how various parts of the interlocked biological processes are coordinated at the transcription level, there is a need to study the between-unit expressional relationship directly. RESULTS: We approach this issue by constructing an index of correlation function to convey the global pattern of coexpression between genes from one process and genes from the entire genome. Processes with similar signatures are then identified and projected to a process-to-process association graph. This top-down method allows for detailed gene-level analysis between linked processes to follow up. Using the cell-cycle gene-expression profiles for Saccharomyces cerevisiae, we report well-organized networks of biological processes that would be difficult to find otherwise. Using another dataset, we report a sharply different network structure featuring cellular responses under environmental stress. SUPPLEMENTARY INFORMATION: http://kiefer.stat.ucla.edu/lap2/download/KL_supplement.pdf.

Algorithms↗

Studies on the interaction of protein with acid chrome blue K by electrochemical method and its analytical application.

An electrochemical investigation on the interaction of acid chrome blue K (ACBK) with protein on the mercury electrode with different electrochemical methods such as cyclic voltammetry and linear sweep voltammetry was reported in this paper. In pH 3.0 Britton-Robinson (B-R) buffer solution, ACBK has an irreversible voltammetric reductive peak at -0.23 V (vs. SCE). The addition of human serum albumin (HSA) into the ACBK solution resulted in the decrease of reductive peak currents without the change of the peak potential and no new peaks appeared on the cyclic voltammogram. In the absence and presence of HSA, the electrochemical parameters such as the formal potential E0, the electrode reaction standard rate constant k(s) and the charge transfer coefficient alpha of the interaction system were calculated and the results showed that there were no significant changes between each other. Thus, the interaction of ACBK with protein forms an electro-inactive supramolecular bio-complex, which induces the decrease of the free concentration of ACBK in the reaction solution, and the decrease of the reductive peak current of ACBK. The binding constant and the binding ratio are calculated as 1.29 x 10(8) and 1:2, respectively, and the interaction mechanism is discussed. Based on the binding reaction, this new electrochemical method is further applied to the determination of HSA with the linear range from 3.0-20.0 mg/L and the linear regression equation as deltaIp"(nA) = 10.08 + 19.90 C (mg/L). This method was further applied to determinate the content of protein in the healthy human serum samples with the results in good agreement with the traditional Coomassie brilliant blue G-250 spectrophotometric method.

Azo Compounds↗

Design and synthesis of N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5- methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine [Muraglitazar/BMS-298585], a novel peroxisome proliferator-activated receptor alpha/gamma dual agonist with efficacious glucose and lipid-lowering activities.

Muraglitazar/BMS-298585 (2) has been identified as a non-thiazolidinedione PPAR alpha/gamma dual agonist that shows potent activity in vitro at human PPARalpha (EC(50) = 320 nM) and PPARgamma(EC(50) = 110 nM). Compound 2 shows excellent efficacy for lowering glucose, insulin, triglycerides, and free fatty acids in genetically obese, severely diabetic db/db mice and has a favorable ADME profile. Compound 2 is currently in clinical development for the treatment of type 2 diabetes and dyslipidemia.

Adipocytes↗

CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling.

Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors.

Actinin↗

Cytologic features of renal medullary carcinoma.

BACKGROUND: Renal medullary carcinoma is a rare tumor that is most common in young black men with sickle cell disease or trait. Patients often present with advanced disease at the time of diagnosis, and their prognosis is poor, even with aggressive therapy. The clinical and pathologic features of renal medullary carcinoma have been described in several articles, but reports describing the cytologic features are rare. METHODS: In the current report, the authors describe the cytologic features of three cases of renal medullary carcinoma. The patients were young black men with sickle cell trait ages 20 years, 33 years, and 33 years. RESULTS: All three patients presented with hematuria, flank pain, and a renal mass. The cytologic specimens from all three patients showed primarily cohesive groups of cells with vacuolated cytoplasm that often displaced or indented the nuclei. The nuclei often had irregular membranes, coarse or vesicular chromatin, and prominent nucleoli. Both of the two patients who were tested with fluorescence in situ hybridization were negative for the bcr/abl rearrangement. CONCLUSIONS: Renal medullary carcinoma should be considered in the differential diagnosis of patients who present with hematuria or a renal mass, especially in young black men with sickle cell disease or trait. Cytologically, renal medullary carcinoma cells appear similar to the cells in high-grade carcinoma. Immunohistochemical studies can be helpful in distinguishing renal medullary carcinoma from other poorly differentiated kidney tumors, except for collecting duct carcinoma. The clinical findings are key to diagnosing renal medullary carcinoma.

Adult↗

Defining projections from the caudal pressor area of the caudal ventrolateral medulla.

We previously defined a functional area in the caudal medulla oblongata that elicits an increase in arterial pressure when stimulated (Sun and Panneton [2002] Am. J. Physiol. 283:R768-R778). In the present study, anterograde and retrograde tracing techniques were used to investigate the projections of this caudal pressor area (CPA) to the medulla and pons. Injections of biotinylated dextran amine into the CPA resulted in numerous labeled fibers with varicosities in the ipsilateral subnucleus reticularis dorsalis, commissural subnucleus of the nucleus tractus solitarii, lateral medulla, medial facial nucleus, A5 area, lateral vestibular nucleus, and internal lateral subnucleus of the parabrachial complex. Sparser projections were found ipsilaterally in the pressor and depressor areas of the medulla and the spinal trigeminal nucleus and contralaterally in the CPA. Injections of the retrograde tracer Fluoro-Gold into these areas labeled neurons in the CPA as well as the nearby medullary dorsal horn and reticular formation. However, we conclude that the CPA projects preferentially to the subnucleus reticularis dorsalis, commissural nucleus tractus solitarii, lateral medulla, A5 area, and internal lateral parabrachial nucleus. Weaker projections were seen to the CVLM and RVLM and to the contralateral CPA. The projection to the facial nucleus arises from nearby reticular neurons, whereas projections to the vestibular nucleus arise from the lateral reticular nucleus. Labeled neurons in the CPA consisted mostly of small bipolar and some triangular neurons. The projection to the CVLM, or to A5 area, may provide for the increase in arterial pressure with CPA stimulation. However, most of the projections described herein are to nuclei implicated in the processing of noxious information. This implies a unique role for the CPA in somatoautonomic regulation.

Animals↗

Human urine proteome analysis by three separation approaches.

The urinary proteome is known to be a valuable field of study related to organ functions. There have been several extensive urine proteome studies. However, the overlapping rate among different studies is relatively low. Whether the low overlapping rate was caused by different sample sources, preparation, separation and identification methods is unknown. Moreover, low molecular mass (<10 kDa) proteins have not been studied extensively. In this report, male and female pooled urine samples were collected from healthy volunteers. The urinary proteins were acetone precipitated, separated and identified by three approaches, 1-DE plus 1-D LC/MS/MS, direct 1-D LC/MS/MS and 2-D LC/MS/MS. 1-D tricine gels were used to separate low molecular mass proteins. The tandem mass spectra of positive identifications were quality controlled both by manual validation and using advanced mass spectrum scanner software. A total of 226 urinary proteins were identified; 171 proteins were identified by proteomics approach for the first time, including 4 male-specific proteins. Twelve low molecular mass proteins were identified. Most urinary proteins had a molecular mass between 30 and 60 kDa and a pI between 4 and 10. The apparent molecular masses of many proteins were different from theoretical ones, which indicated their post-translational modification and degradation. The effects of sample preparation, separation and identification methods on the overlapping rate of different experiments are discussed.

Adult↗

Phylogenetic relationships of sheep populations from coastal areas in East Asia.

Using the method of random sampling in typical colonies of the central area of the habitat and several electrophoresis techniques, the variations of 12 structural loci encoding blood protein of 60 Small-tailed Han sheep were examined and compared with those of four other sheep populations from coastal areas in East Asia to explore their phylogenetic relationships. Average heterozygosity of the five populations was: Kharkhorin sheep 0.3447, Ulaanbaatar sheep 0.3285, Small-tailed Han sheep 0.3157, Hu sheep 0.3884, and Cham Tribe sheep 0.2300. The earlier researchers' conclusion through documentary research, indicating that Small-tailed Han sheep and Hu sheep both evolved from Mongolian sheep, was further verified by the results of this study. Hu sheep, Small-tailed Han sheep, and Cham Tribe sheep were decreasingly affected by the bloodline of Mongolian sheep. A 1partial founder population, i.e., Mongolian sheep forming current Small-tailed Han sheep, possibly made a contribution to the bloodline of Cham Tribe sheep.

Animals↗

Identification of beta-lactamase inhibitory peptide using yeast two-hybrid system.

Random oligonucleotide fragments were designed and amplified by PCR and fused with the activating domain of pGAD424 to construct a random peptide library. The DNA fragment encoding beta-lactamase was fused with the binding domain of pGBT9(+2). Subsequently, using yeast two-hybrid system we found two positive clones encoding peptides P1 and P2 that have the ability to bind beta-lactamase in vivo. The genes encoding P1 and P2 were cloned into pGEX-4T-1. GST-peptide fusion proteins were expressed in Escherichia coli and isolated by glutathione-Sepharose 4B affinity chromatography. Finally, P1 and P2 were cleaved from the fusion protein with thrombin and purified by ultrafiltration. Inhibition assay of peptides with beta-lactamase in vitro indicated that only P1 has the ability to inhibit beta-lactamase.

Amino Acid Sequence↗

Synthesis, characterization and DNA-binding properties of a new cobalt(II) complex: Co(bbt)2Cl2.

A new bis(N-benzyl-benzotriazole)dichloro Co(II) complex (Co(bbt)(2)Cl(2)) was synthesized and the structure was characterized by X-ray crystallography, IR spectrum and elemental analysis. The electrochemical characterization of Co(bbt)(2)Cl(2) was measured in detail, and the interaction of this Co(II) complex with fish sperm DNA was studied by electrochemical techniques and ultraviolet-visible (UV-Vis) spectrophotometry. The cyclic voltammetry (CV) showed that Co(bbt)(2)Cl(2) had two reduction peaks and one oxidation peak on gold electrode. It was found that the currents of both the reduction peaks and the oxidation peak decreased significantly in the presence of DNA compared with those in the absence of DNA, which indicated that Co(bbt)(2)Cl(2) could interact with DNA. The binding of DNA with the complex was not only electrostatic binding but also intercalation.

Animals↗

Low-dose cholinesterase inhibitors do not induce delayed effects on cerebral blood flow and metabolism.

The acetylcholinesterase (AChE) inhibitors sarin and pyridostigmine bromide (PB) have been proposed as causes of neurobehavioral dysfunction in Persian Gulf War veterans. To test possible delayed effects of these agents, we exposed rats to low (subsymptomatic) levels of sarin (0.5 LD50 s.c. 3 times weekly) and/or PB (80 mg/L in drinking water) for 3 weeks. Controls received saline s.c. and tap water. At 2, 4 and 16 weeks after exposure, regional cerebral blood flow (rCBF) and glucose utilization (rCGU) were measured in conscious animals with the Iodo-14C-antipyrine and 14C-2 deoxyglucose methods, respectively. Two weeks after exposure, PB+sarin caused significant rCBF elevations, but no changes in rCGU, in neocortex, with lesser effects on allocortex. Four weeks after exposure, the same general pattern was found with sarin. Only a few changes were found at 16 weeks post-treatment. The predominant effects of sarin or PB+sarin on rCBF at earlier times after treatment are consistent with the well known direct cerebral vascular effect of cholinergic agonists. The lack of changes in rCBF and rCGU observed at 16 weeks after treatment does not support the hypothesis that repeat exposure to low-dose cholinesterase inhibitors can generate permanent alterations in cerebral activity.

Animals↗

Effects of physostigmine and human butyrylcholinesterase on acoustic startle reflex and prepulse inhibition in C57BL/6J mice.

The use of exogenously administered cholinesterases as bioscavengers of highly toxic organophosphorus nerve agents is a viable prophylactic against this threat. To use this strategy, cholinesterases must provide protection without disrupting behavior when administered alone. To assess behavioral safety, the acoustic startle reflex and prepulse inhibition (PPI) of C57BL/6J mice were investigated following administration of human plasma-derived butyrylcholinesterase (HuBChE). Two hours before testing, four groups of mice (n=10 per group) were pretreated with saline or HuBChE (2000 U, ip). Fifteen minutes before testing, subjects received either saline or the carbamate physostigmine (0.4 mg/kg, sc). Mice exposed to physostigmine exhibited a significant attenuation of the startle reflex, an increased time to peak startle amplitude, and significantly increased PPI. This effect was partially mitigated in mice pretreated with HuBChE. HuBChE alone did not change startle behavior or PPI significantly compared to saline controls. The circulatory time-course of butyrylcholinesterase was assessed in a separate group of mice and revealed levels approximately 600 times the physiological norm 2-4 h post administration. Thus, HuBChE does not appear to significantly alter startle or PPI behavior at a dose 30-fold higher than that estimated to be necessary for protection against 2LD50 of soman in humans.

Acoustic Stimulation↗

Analysis of tumor necrosis factor-alpha, interleukin-6, interleukin-1beta, soluble tumor necrosis factor receptors I and II, interleukin-6 soluble receptor, interleukin-1 soluble receptor type II, interleukin-1 receptor antagonist, and protein in the synovial fluid of patients with temporomandibular joint disorders.

OBJECTIVE: To measure the levels of various cytokines, cytokine receptors, and cytokine antagonists in the synovial fluid of patients with temporomandibular disorders (TMD) and to determine the correlations among these expression levels. STUDY DESIGN: Synovial fluid was obtained from 55 patients with TMD and from 5 asymptomatic healthy volunteers as controls. The concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta, soluble tumor necrosis factor receptors I and II (sTNFR-I and sTNFR-II), IL-6 soluble receptor (IL-6sR), IL-1 soluble receptor type II, and IL-1 receptor antagonist were determined by enzyme-linked immunosorbent assay. RESULTS: The concentrations of TNF-alpha, IL-6, IL-1beta, sTNFR-I, and sTNFR-II were significantly higher in the synovial fluid of patients than in controls (P < .05). TNF-alpha level was positively correlated with those of IL-6, sTNFR-I, and sTNFR-II. In particular, there was a highly significant positive correlation between sTNFR-I and sTNFR-II. CONCLUSION: TNF and sTNFRs in the synovial fluid of patients with TMD may be important in the pathogenesis of these disorders.

Adult↗

Levels of soluble cytokine factors in temporomandibular joint effusions seen on magnetic resonance images.

OBJECTIVE: To elucidate the correlations between joint effusion (JE) on T2-weighted magnetic resonance images (MRI) of the temporomandibular joint (TMJ) and the levels of various cytokine receptors, cytokine antagonists, and protein in the synovial fluid of patients with temporomandibular joint disorders (TMD). STUDY DESIGN: Fifty-five TMJs of 55 patients with TMD were scanned by MRI, and synovial fluid samples were obtained on the same day. The grade of JE was evaluated on a scale of 0 to 3: Grades 0 and 1 indicated absence, and grades 2 and 3 indicated the presence of JE. Correlations were evaluated between JE and the concentrations of soluble tumor necrosis factor receptors I and II (sTNFR-I and sTNFR-II, respectively), IL-6 soluble receptor (IL-6sR), IL-1 soluble receptor type II, and IL-1 receptor antagonist and protein in the synovial fluid of patients with TMD. RESULTS: The concentrations of sTNFR-I and protein in the group with JE (18 joints) were significantly higher than in the group without JE (37 joints). In addition, there were significant positive correlations between the grade of JE and the levels of sTNFR-I, sTNFR-II, and protein. CONCLUSIONS: sTNFRs and protein may play important roles in the pathogenesis of TMD. These mediators seem to influence the expression of JE, which may reflect synovial inflammation of the TMJ.

Adult↗