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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 271 records · Page 15Linked to original sources

In vitro complement activation favoring soluble C5b-9 complex formation alters myocellular sodium homeostasis.

BACKGROUND: Deranged Na(+) homeostasis in skeletal muscle is closely associated with excessive complement activation that is encountered during sepsis. Recent evidence suggests that soluble C5b-9 complexes (SC5b-9), which are readily detected in plasma during sepsis and have long been considered irrelevant nonmembrane binding end products of complement activation, may have numerous biologic effects. The purpose of this study, therefore, was to determine the effects of SC5b-9 on myocellular ion homeostasis and its mechanism(s) of action. METHODS: Hindlimb fast-twitch extensor digitorum longus (EDL) was freshly isolated from rats weighing 50 to 70 g and then incubated at 30 degrees C for 60 minutes in normal Krebs-Henseleit buffer (KHB, pH 7.4) containing 10% zymosan-activated rat serum (10 mg/mL at 37 degrees C for 60 minutes) as a source of SC5b-9. Zymosan particles were removed by centrifugation after activation to exclude any noncomplement direct effects. Heat-inactivated rat serum (56 degrees C for 30 minutes) was used as control. EDL muscle was also incubated with pertussis toxin (1 microg/mL), in Ca(2+)-free KHB, with thapsigargin (0.3 or 3 micromol/L), or with ouabain (0.01, 0.1 or 1 micromol/L) before and/or during incubation with 10% zymosan-activated or heat-inactivated rat serum. Intracellular Na(+) and K(+) contents ([Na(+)](i) or [K(+)](i)) of EDL muscle were determined by using flame photometry after washing in ice-cold Na(+)-free Tris-sucrose buffer. SC5b-9 in zymosan-activated human serum was determined by SC5b-9 enzyme-linked immunoassay. RESULTS: SC5b-9 in zymosan-activated human serum significantly increased by 400% as compared with nonactivated, normal human serum. Zymosan-activated rat serum markedly increased [Na+]i without affecting [K(+)](i) in fast-twitch EDL muscle, which was completely inhibited by pertussis toxin, removal of extracellular Ca(2+) or depletion of intracellular Ca(2+) with thapsigargin. The addition of ouabain (at micromolar concentrations) increased myocellular [Na(+)](i) and decreased myocellular [K(+)](i) in both the zymosan-activated and the heat-inactivated rat serum groups. The effects of ouabain on myocellular [Na(+)](i) and [K(+)](i) were equivalent in these 2 groups. Zymosan-activated and heat-inactivated rat serum had similar effects on myocellular [K(+)](i) in the presence or absence of pertussis toxin, removal of extracellular Ca(2+) or depletion of intracellular Ca(2+). CONCLUSIONS: Zymosan-activated rat serum (presumed SC5b-9 enriched) selectively alters Na(+) homeostasis in isolated fast-twitch skeletal muscle. The mechanisms for such effects may be linked to G-proteins, Ca(2+) flux and Na(+),K(+)-adenosine triphosphatase pump binding site blockade.

Animals↗

Preliminary results from an EIT breast imaging simulation system.

An electrical impedance tomography (EIT) simulation system for breast imaging has been developed using impedance data from a previous study and a finite-element model (FEM). This system has the functionality to construct various models of the breast, image the boundary voltages developed from any injection schema and provide parametric Cole-Cole modelling. Simulations indicate that breast carcinoma can be imaged and multi-frequency Cole-Cole dispersion data can be extracted. This is intended as the first stage towards providing an artificial intelligence based system capable of producing clinically relevant analytical data.

Algorithms↗

Resistance of [18f]-fluorodeoxyglucose-avid metastatic thyroid cancer lesions to treatment with high-dose radioactive iodine.

Radioactive iodine (131I) is an important therapeutic option for the treatment of metastatic thyroid carcinoma. Survival in patients with metastases that concentrate radioiodine is better than those whose metastatic lesions do not take up radioiodine. Survival is markedly reduced in patients who have metastatic lesions that concentrate 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET). In this retrospective study, we evaluated the ability of 131I to destroy FDG-avid metastatic lesions in thyroid cancer patients. Twenty-five patients with positive FDG-PET scans received at least one dose of 131I treatment before a second FDG-PET was performed. The average interval between the two PET scans was 12.9 months. The average interval between the 131I treatment and the follow-up FDG-PET was 10.1 months. We measured posttherapy changes in lesional volume, in standard uptake values (SUV) of FDG, and in serum thyroglobulin (Tg) levels. The total volume of FDG-avid metastases rose significantly (p = 0.036) from a mean of 159 mL to 235 mL after 131I therapy, the maximum SUV rose from 9.3 to 11.9, the median Tg at the time of the second PET scan was 132% of that at baseline. Statistical analyses demonstrated no significant changes in maximum SUV, or serum Tg levels after 131I in the FDG-PET-positive group. In a control group of FDG-PET-negative patients, the serum Tg decreased to 38% of baseline after 131I therapy (p < 0.001). We conclude that high-dose 131I therapy appears to have little or no effect on the viability of metastatic FDG-avid thyroid cancer lesions.

Adolescent↗

Dietary energy restriction inhibits ERK but not JNK or p38 activity in the epidermis of SENCAR mice.

Ongoing studies in our laboratory have demonstrated that dietary energy restriction (DER) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 transcription factor binding to DNA in the epidermis of SENCAR mice. To dissect the specific signal transduction pathways through which DER inhibits the AP-1:DNA binding, we analyzed the activities of three major MAP kinases that lead to the induction of AP-1. The changes in ERK1 and ERK2 protein expression and phosphorylation were further characterized by western blot analysis. Female SENCAR mice were pre-fed ad libitum (AL) or 40% DER diet for 8-10 weeks. The kinase activities in mouse epidermis were determined by immune complex kinase assays at 0.5, 1, 4, or 6 h following treatment with 3.2 nmol TPA to the shaved dorsal backs. ERK activity at 1 h post-TPA treatment was nearly 5-fold (P< 0.005) above basal levels in AL mice while the increase was abolished in DER mice. The TPA-induced ERK activity in AL mice was accompanied by increased phosphorylation of ERK1 and ERK2 (P< 0.05), which was abrogated in DER mice. In addition, DER mice exhibited reduced expression of total ERK1 and ERK2 and higher proportions of ERK1 and ERK2 phosphorylation in comparison with AL mice (P<0.05). JNK activity was decreased at 1 and 6 h but increased at 4 h (P<0.05) post-TPA treatment. TPA did not change p38 kinase activity at the time points tested. Neither JNK nor p38 activity was altered by DER. Taken together, our results indicated for the first time that DER blocked the TPA stimulation of ERK activity and suggested that the inhibition of TPA-induced AP-1 activity by DER is likely through inhibition of ERK but not JNK or p38 kinase pathway.

Animals↗

Inhibition of phorbol ester-induced AP-1-DNA binding, c-Jun protein and c-jun mRNA by dietary energy restriction is reversed by adrenalectomy in SENCAR mouse epidermis.

The aim of this study was to determine the effects of 40% dietary energy restriction (DER) relative to ad libitum feeding on AP-1-DNA binding and expression of c-Jun protein and c-jun mRNA in SENCAR mouse skin treated with acetone or 12-O-tetradecanoylphorbol 13-acetate (TPA). The role of the glucocorticoid hormone corticosterone (CCS) was investigated by adding CCS or vehicle control to the drinking water of adrenalectomized mice. AP-1-DNA binding, measured by electrophoretic mobility shift assay, showed that TPA treatment for 4 h increased AP-1-DNA binding by 2-fold over acetone controls (P < 0.05) and that DER reduced basal and TPA-induced AP-1-DNA binding in comparison with ad libitum fed groups in sham-operated mice (P < 0.05). TPA treatment increased c-Jun protein levels in control fed mice (4-fold) and in DER mice (2-fold) over basal levels 4 h post-treatment (P < 0.05). Analyzed over all groups, DER reduced c-Jun protein levels (P < 0.01) and this effect was reversed by adrenalectomy. TPA induction of c-jun mRNA was also reduced by DER compared with ad libitum fed mice (P < 0.05). Adrenalectomy and CCS supplementation demonstrated that the effects of DER on AP-1-DNA binding were mediated in part by CCS. Measurement of blood plasma CCS concentrations showed that: (i) DER increased CCS 5-fold over ad libitum fed mice in sham-operated animals (P < 0.05); (ii) adrenalectomy decreased CCS over sham-operated mice (P < 0.05); (iii) TPA treatment had no effect on CCS. Blood plasma IGF-I concentrations were unaffected by CCS modulation or TPA treatment but were decreased by DER compared with ad libitum fed mice (P < 0.05). Thus, dietary energy restriction may inhibit cancer mechanistically by reducing overall AP-1 transcription through a process that is mediated in part by glucocorticoid hormones.

Adrenalectomy↗

Ectopic expression of alpha1,6 fucosyltransferase in mice causes steatosis in the liver and kidney accompanied by a modification of lysosomal acid lipase.

The alpha1,6 fucosyltransferase (alpha1,6 FucT) catalyzes the transfer of a fucose from GDP-fucose to the innermost GlcNAc residue of N-linked glycans via an alpha1,6 linkage. alpha1,6 FucT was overexpressed in transgenic mice under the control of a combined cytomegalovirus and chicken beta-actin promoter. Histologically numerous small vacuoles, in which lipid droplets had accumulated, were observed in hepatocytes and proximal renal tubular cells. Electron microscopic studies showed that the lipid droplets were membrane-bound and apparently localized within the lysosomes. Cholesterol esters and triglycerides were significantly increased in liver and kidney of the transgenic mice. Liver lysosomal acid lipase (LAL) activity was significantly lower in the transgenic mice compared to the wild mice, whereas LAL protein level, which was detected immunochemically, was increased, indicating that the specific activity of LAL was much lower in the transgenic mice. In all of the transgenic and nontransgenic mice examined, the activity of liver LAL was negatively correlated with the level of alpha1,6 FucT activity. As evidenced by lectin and immunoblot analysis, LAL was found to be more fucosylated in the transgenic mice, suggesting that the aberrant fucosylation of LAL causes an accumulation of inactive LAL in the lysosomes. Such an accumulation of inactive LAL could be a likely cause for a steatosis in the lysosomes of the liver and kidney in the case of the alpha1,6 FucT transgenic mice.

Animals↗

Fast repair of the radical cations of dCMP and poly C by quercetin and rutin.

The effects of quercetin and rutin on the repair of the radical cations of dCMP and poly C were studied using the technique of pulse radiolysis. The radical cations of dCMP and poly C were formed by the reaction of dCMP and poly C with SO( 4)(-). After pulse irradiation of nitrogen-saturated aqueous solutions containing dCMP, 20 mM K(2)S(2)O(8), 200 mM t-BuOH and either rutin or quercetin, the initially formed radical cation of dCMP, detected spectrophotometrically, rapidly decayed with the concurrent formation of the phenoxyl radical of rutin or quercetin within 8-40 micros. The repair efficiencies of the tested compounds towards the poly C radical cation were also determined using the same procedure. The results indicate that dCMP and poly C radical cations can be rapidly repaired by quercetin and rutin. The rate constants of the repair reactions were determined to be 4.3-8.8x10(8) M/s and 1.5-3.6x10(8) M/s for dCMP and poly C radical cations, respectively. Together with findings from our previous studies, the present results demonstrate that non-enzymatic fast repair may be a universal form of repair involving phenolic antioxidants.

Antioxidants↗

Increased cell proliferation and associated expression of PDGFRbeta causing hypercellularity in patellar tendinosis.

OBJECTIVE: This study assessed cellularity in patellar tendinosis with respect to cell proliferation and the expression of platelet-derived growth factor receptor beta (PDGFRbeta). METHODS: Surgical samples were taken from 11 patients fulfilling criteria of patellar tendinosis and from 12 matched controls. Standard immunohistochemistry methods were used to detect expression of PDGFRbeta and proliferation cell nuclear antigen (PCNA). Results were analysed by computer-assisted microscopy. Tendon cells were isolated from nine tendinosis and eight control tissues for cell culture. RESULTS: Increased cellularity (P<0.001) was observed in tendinosis tissues compared with controls, and also a higher proliferative index (P:<0.001). Increased expression of PDGFRbeta was demonstrated (P<0.001). Cultured tendinosis cells showed a higher proliferation rate than controls (P<0.001). This was maintained when the cells were cultured under various conditions of serum supplementation (P<0.01). Tendinosis cells also showed a higher proliferation rate (P<0.01) in medium containing 10 ng/ml PDGF. CONCLUSION: Hypercellularity in patellar tendinosis is caused by increased cell proliferation and is associated with increased expression of PDGFRbeta.

Adolescent↗

Wy-14,643-induced hypomethylation of the c-myc gene in mouse liver.

The carcinogenic activity of Wy-14,643 in mouse liver appears to be nongenotoxic and could involve a decrease in DNA methylation. The mechanism for Wy-14,643-induced decrease in DNA methylation is proposed to involve increased cell proliferation followed by prevention of the methylation of the newly synthesized DNA. To investigate this mechanism, female B6C3F1 mice were administered daily by oral gavage 50 mg/kg Wy-14,643. Mice were sacrificed at 2, 5, 8, 24, 26, 29, 32, 36, 48, 72, and 96 h after the first dose. Some mice also received 450 mg/kg methionine by ip injection at 30 min after administering Wy-14,643. Hypomethylation of the c-myc gene first occurred at 48 h after the first dose of Wy-14,643. Cell proliferation determined by the Proliferating Cell Nuclear Antigen (PCNA)-Labeling Index started to increase at 36 h and peaked at 72h. Wy14,643 did not affect the liver concentration of either S-adenosyl methionine (SAM) or S-adenosyl homocysteine (SAH). Methionine prevented and reversed the hypomethylation of the c-myc gene induced by Wy-14,643. However, the increased levels of SAM and SAH returned to control levels prior to the prevention by methionine of Wy-14,643-induced hypomethylation. Furthermore, methionine did not prevent Wy-14,643-induced increase in the PCNA-Labeling Index. The activity of nuclear DNA methyltransferase (DNA MTase) was increased at 72 and 96 h after administering Wy14,643. Wy14,643 also increased the activity of DNA MTase when added in vitro to nuclear extracts. The results are consistent with Wy-14,643 decreasing the methylation of the c-myc gene by a mechanism that includes enhancement of cell proliferation followed by prevention of the methylation of the newly synthesized DNA. However, the results indicate that Wy-14,643 does not prevent methylation by decreasing either the availability of SAM or the activity of DNA MTase.

Administration, Oral↗

Intraocular lens power calculation after laser in situ keratomileusis for myopia and hyperopia: a standardized approach.

PURPOSE: (1) To determine the effect of myopic and hyperopic laser in situ keratomileusis (LASIK) on calculation of intraocular lens (IOL) power. (2) To determine a standard way to approach the IOL power determination after LASIK, and (3) To compare different suggested methods. METHODS: Biometric analysis and theoretical calculation of IOL powers for eyes undergoing LASIK for myopia and hyperopia were performed. RESULTS: Manual keratometry after LASIK for myopia resulted in underestimation of IOL power. Manual keratometry after hyperopic LASIK resulted in overestimation of IOL power. The amount of error was directly related to the amount of correction by LASIK. CONCLUSION: The pre-LASIK refraction can be used theoretically to determine an accurate IOL power.

Cataract Extraction↗

Role of short-term inhibition of factor Xa by FXV673 in arterial passivation: a study in a chronic model of thrombosis in conscious dogs.

Factor Xa (fXa) plays a pivotal role in the activation of the coagulation system during thrombosis, but, unlike GPIIb/IIIa receptor antagonists, the role of fXa inhibition in arterial passivation is not well defined. We compared the long-term antithrombotic efficacy of a direct fXa inhibitor, FXV673, and heparin after short-term infusion in conscious dogs. Dogs were instrumented surgically to induce carotid artery thrombosis by electrolytic injury. On day 1, dogs received a 3-h infusion of placebo (n = 10), FXV673 (100 microg/kg + 10 microg/kg/min, n = 7), or heparin (60 U/kg + 0.7 U/kg/min, n 7). Injury (100 microA) was initiated concomitantly for 1 h. The procedure was repeated on day 2 with injury of 200 microA for 3 h. Carotid artery blood flow (CBF) and coagulation parameters were monitored continuously for 3 h on days 1 and 2 and for 30 min on days 3, 4, and 5. On day 1 at 3 h, CBF in the placebo-treated group was 26% of baseline with 70% incidence of occlusion. None of the vessels occluded in the heparin and FXV673 groups; however, the CBF was significantly higher in the FXV673 group (92+/-8 ml/min versus 39+/-12 ml/min). Before injury on day 2, CBF recovered in all groups to 71-89% of baseline. After the second injury, all vessels in the placebo-treated group progressed to complete occlusion by 3 h. CBF was significantly higher in FXV673 group compared with heparin throughout the 3-h period. On days 3, 4, and 5 the placebo-treated vessels remained occluded, but the CBF in the heparin group was 33+/-20 ml/min, 55+/-11 ml/min and 68+/-12 ml/min, respectively, compared with 84+/-10 ml/min, 98+/-7 ml/min, and 99+/-10 ml/min in the FXV673 group. The arterial thrombus mass was significantly lower in FXV673 group (13+/-4 mg) compared with placebo (103+/-10 mg) and heparin (44+/-11 mg). In summary, these data demonstrate that short-term infusion of FXV673 was associated with long-term efficacy that was superior to standard heparin and underscore the role of direct fXa inhibition in arterial passivation.

Animals↗

Parental health beliefs and compliance with prophylactic penicillin administration in children with sickle cell disease.

PURPOSE: Prophylactic penicillin is effective in preventing severe invasive pneumococcal infection in children with sickle cell disease. In some families, compliance has been problematic. The aims of this study were to monitor compliance and to assess the efficacy of the Health Belief Model (HBM) in predicting compliance. METHODS: Fifty mothers of children with sickle cell disease, ages 6 to 60 months, participated in the study. On enrollment, mothers completed surveys assessing their health beliefs regarding sickle cell disease and infections. Compliance was assessed through self-reporting by the mothers and through review of local pharmacy records of penicillin refills. RESULTS: Sixty percent of the mothers reported that they were highly compliant with obtaining the prescribed 14-day refills. Pharmacy records indicated that only 12% actually adhered to this schedule. The self-reports were significantly related to compliance ratings; mothers who admitted less than optimal compliance averaged 42 days between refills, compared with 19 days for mothers who reported good compliance. Varying perceptions identified through the HBM accounted for approximately 30% of the variance in compliance rates. The perceived burdens of picking up the refills and remembering to administer the medication were the most significant factors. CONCLUSIONS: Educational efforts alone are not sufficient to ensure compliance with penicillin prophylaxis. Routinely monitoring compliance through pharmacy records, reviewing parental beliefs about sickle cell disease and infections, and exploring barriers to treatment will promote dialogue about the importance of strict compliance with this relatively simple yet life-saving prophylaxis.

Adult↗

Hormonal changes in the grains of rice subjected to water stress during grain filling.

Lodging-resistant rice (Oryza sativa) cultivars usually show slow grain filling when nitrogen is applied in large amounts. This study investigated the possibility that a hormonal change may mediate the effect of water deficit that enhances whole plant senescence and speeds up grain filling. Two rice cultivars showing high lodging resistance and slow grain filling were field grown and applied with either normal or high amount nitrogen (HN) at heading. Well-watered and water-stressed (WS) treatments were imposed 9 days post anthesis to maturity. Results showed that WS increased partitioning of fixed (14)CO(2) into grains, accelerated the grain filling rate but shortened the grain filling period, whereas the HN did the opposite way. Cytokinin (zeatin + zeatin riboside) and indole-3-acetic acid contents in the grains transiently increased at early filling stage and WS treatments hastened their declines at the late grain filling stage. Gibberellins (GAs; GA(1) + GA(4)) in the grains were also high at early grain filling but HN enhanced, whereas WS substantially reduced, its accumulation. Opposite to GAs, abscisic acid (ABA) in the grains was low at early grain filling but WS remarkably enhanced its accumulation. The peak values of ABA were significantly correlated with the maximum grain filling rates (r = 0.92**, P < 0.01) and the partitioning of fixed (14)C into grains (r = 0.95**, P < 0.01). Exogenously applied ABA on pot-grown HN rice showed similar results as those by WS. Results suggest that an altered hormonal balance in rice grains by water stress during grain filling, especially a decrease in GAs and an increase in ABA, enhances the remobilization of prestored carbon to the grains and accelerates the grain filling rate.

Abscisic Acid↗

Doppler ultrasound signal denoising based on wavelet frames.

A novel approach was proposed to denoise the Doppler ultrasound signal. Using this method, wavelet coefficients of the Doppler signal at multiple scales were first obtained using the discrete wavelet frame analysis. Then, a soft thresholding-based denoising algorithm was employed to deal with these coefficients to get the denoised signal. In the simulation experiments, the SNR improvements and the maximum frequency estimation precision were studied for the denoised signal. From the simulation and clinical studies, it was concluded that the performance of this discrete wavelet frame (DWF) approach is higher than that of the standard (critically sampled) wavelet transform (DWT) for the Doppler ultrasound signal denoising.

Algorithms↗

Effects of charged amino-acid mutation on the solution structure of cytochrome b(5) and binding between cytochrome b(5) and cytochrome c.

The solution structure of oxidized bovine microsomal cytochrome b(5) mutant (E48, E56/A, D60/A) has been determined through 1524 meaningful nuclear Overhauser effect constraints together with 190 pseudocontact shift constraints. The final family of 35 conformers has rmsd values with respect to the mean structure of 0.045+/-0.009 nm and 0.088+/-0.011 nm for backbone and heavy atoms, respectively. A characteristic of this mutant is that of having no significant changes in the whole folding and secondary structure compared with the X-ray and solution structures of wild-type cytochrome b(5). The binding of different surface mutants of cytochrome b(5) with cytochrome c shows that electrostatic interactions play an important role in maintaining the stability and specificity of the protein complex formed. The differences in association constants demonstrate the electrostatic contributions of cytochrome b(5) surface negatively charged residues, which were suggested to be involved in complex formation in the Northrup and Salemme models, have cumulative effect on the stability of cyt c-cyt b(5) complex, and the contribution of Glu48 is a little higher than that of Glu44. Moreover, our result suggests that the docking geometry proposed by Northrup, which is involved in the participation of Glu48, Glu56, Asp60, and heme propionate of cytochrome b(5), do occur in the association between cytochrome b(5) and cytochrome c.

Amino Acid Sequence↗

Modulation of fibrin cofactor activity in plasminogen activation.

Fibrin is a cofactor for the formation of plasmin from plasminogen as catalyzed by tissue plasminogen activator. Initial cleavages of fibrin by plasmin upregulates the cofactor activity of fibrin by exposing carboxyl terminal lysine residues. This effect is eliminated by a carboxypeptidase B-like enzyme generated from the precursor, thrombin activatable fibrinolysis inhibitor (TAFI) that is generated by thrombin during the formation of fibrin. Thus, TAFI and its activation to TAFIa create a link between the coagulation and fibrinolytic cascade, such that activation of the former suppresses the latter. Complete solubilization of fibrin results in a family of very large fibrin degradation products. These also have very substantial tissue plasminogen activator cofactor activity that is very highly downregulated by TAFIa.

Carboxypeptidase B2↗