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Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 1,441 records · Page 80Linked to original sources
PubMed1997

CONV--convolution for responses to a finite diameter photon beam incident on multi-layered tissues.

A convolution program (CONV) solving responses to a collimated finite diameter photon beam perpendicularly incident on a multi-layered tissue has been coded in ANSI Standard C, hence, the program can be executed on various computers. The program, employing an extended trapezoidal rule for integration, convolves the responses to an infinitely narrow photon beam computed by a companion program (MCML). Dynamic data allocation is used for CONV as well as MCML, therefore, the number of tissue layers and grid elements of the grid system can be varied at run time. The potential error due to not scoring the first photon-tissue interactions separately is illustrated. The program, including the source code, has been in the public domain since 1992 and can be downloaded from the web site at http:(/)/biomed.tamu.edu/-lw.

Computer Simulation↗
PubMed1997

Can superoxide dismutase prevent postburn dermal ischemia?

Decreasing progressive dermal ischemia after burning could theoretically limit the amount of skin necrosis. It is controversial whether the use of free radical scavengers could prevent the progressive dermal ischemia of the postburn stasis zone. We evaluated the effect of superoxide dismutase (SOD) on preventing postburn dermal ischemia in animal models by the India ink perfusion and skin transparent preparation techniques. The closely clipped backs of guinea-pigs were bathed in 75 degrees C water for 10 s. Within 5 min postburn, SOD-treated groups were administered SOD (10,000 u/kg) intra-peritoneally every 6 h. All animals were perfused with 70 per cent India ink via cervical artery cannula by 16 kPa constant pressure at 0, 8, 16, 24 h postburn, and the skin transparent preparations were made, while the level of malonyl dialdehyde (MDA) in skin tissue was assessed. The results showed that with prolongation of postburn time, the rate of filling of India ink in skin capillary plexuses decreased gradually (p < 0.01). MDA increased continuously, which was related to postburn dermal ischemia (r = 0.689, p < 0.01). Though the level of MDA decreased in SOD-treated groups, the India ink filling rates showed no significant difference between controls and experimental groups (p > 0.05). The results were also confirmed by observation of skin transparent preparations and TEM. This study suggests that superoxide dismutase fails to prevent progressive dermal ischemia after burning.

Animals↗
PubMed1997

Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: a model for a mechanism of carcinogenesis.

Arsenic is a potent human carcinogen to which there is significant worldwide exposure through natural contamination of food and drinking water sources. Because arsenic is detoxified via methylation using a methyltransferase (MTase) and S-adenosylmethionine (SAM) as the methyl donor, we hypothesized that a mechanism of carcinogenesis of arsenic could involve alterations of MTase/SAM-dependent DNA methylation of a tumor suppressor gene. We found that exposure of human lung adenocarcinoma A549 cells to sodium arsenite (0.08-2 microM) or sodium arsenate (30-300 microM), but not dimethylarsenic acid (2-2000 microM), produced significant dose-responsive hypermethylation within a 341-base pair fragment of the promoter of p53. This was determined by quantitative PCR/HpaII restriction site analysis to analyze methylation status of two CCGG sites. In experiments with arsenite, DNA sequencing using bisulfite to visualize 5-methylcytosine (5-MeC) over the entire promoter region confirmed data obtained by restriction analysis. Limited data using SssI methylase also suggested that over-methylation of CpG sequences may exist over the entire genome in response to arsenite exposure. We propose that alteration of DNA methylation by arsenic offers a plausible, unified hypothesis for the carcinogenic mechanism of action of arsenic, and we present a model for arsenic carcinogenesis that utilizes perturbations of DNA methylation as the basis for the carcinogenic effects of arsenic.

Adenocarcinoma↗
PubMed1997

Exponential heating in drug stability experiment and statistical evaluation of nonisothermal and isothermal prediction.

A new nonisothermal heating model (exponential heating model) for drug stability experiments, based on a theoretical study of simulated nonisothermal data, is presented. In the model, the heating rate dT/dt is increased by 2-4 times at every increase of 10 degrees C in temperature: dT/dt = a(T-T0)/10.(dT/dt)0 where a is the times by which the heating rate is increased at every increase of 10 degrees C. A computation method with optimization and Simpson integration for the experiment was also introduced. The estimates for the shelf-life and activation energy obtained by the exponential and other nonisothermal heating models were statistically evaluated and were compared with those obtained by the isothermal method under various conditions. The results indicated that under the same experimental conditions, the estimates obtained by the exponential heating model were significantly more accurate and precise than those obtained by the linear, reciprocal, and logarithmic heating models. The accuracy and precision of the estimates were independent of the shelf-life of drugs and experimental period. The estimates obtained by the isothermal method were somewhat more accurate and precise than those obtained by the exponential heating model. However, the experimental period needed by the isothermal method was about five times longer than that needed by the exponential heating model. The results also showed that in each of the heating models, the estimates are more accurate and precise by increasing the extent of drug degradation, changing temperature range or sampling frequency, or by having the mean temperature closer to room temperature. To demonstrate its applicability, the exponential heating model was used to study the stability of vitamin C tablets and predict their shelf-life.

Drug Stability↗
PubMed1997

Pyridyloxobutyl adduct O6-[4-oxo-4-(3-pyridyl)butyl]guanine is present in 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone-treated DNA and is a substrate for O6-alkylguanine-DNA alkyltransferase.

The lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is activated to reactive metabolites that methylate or pyridyloxobutylate DNA. Previous studies demonstrated that pyridyloxobutylated DNA interferes with the repair of O6-methylguanine (O6-mG) by O6-alkylguanine-DNA alkyltransferase (AGT). The AGT reactivity of pyridyloxobutylated DNA was attributed to (pyridyloxobutyl)guanine adducts. One potential AGT substrate adduct, 2'-deoxy-O6-[4-oxo-4-(3-pyridyl)butyl]guanosine (O6-pobdG), was prepared. This adduct was stable at pH 7.0 for greater than 13 days and to neutral thermal hydrolysis conditions (pH 7.0, 100 degrees C, 30 min). Under mild acid hydrolysis conditions (0.1 N HCl, 80 degrees C), O6-pobdG was depurinated to yield O6-[4-oxo-4-(3-pyridyl)butyl]guanine (O6-pobG). O6-pobdG was hydrolyzed to 4-hydroxy-1-(3-pyridyl)-1-butanone and guanine under strong acid hydrolysis conditions (0.8 N HCl, 80 degrees C). O6-pobG was detected in 0.1 N HCl hydrolysates of DNA alkylated with the model pyridyloxobutylating agent 4-(acetoxymethylnitrosamino)-1-(3-[5-3H]pyridyl)-1-butanone ([5-3H]NNKOAc). When [5-3H]NNKOAc-treated DNA was incubated with either rat liver or recombinant human AGT, O6-pobG was removed, presumably a result of transfer of the pyridyloxobutyl group from the O6-position of guanine to AGT's active site.

Animals↗
PubMed1997

Cellular delivery of oligonucleotides by synthetic import peptide carrier.

PURPOSE: Inefficient cellular uptake and endosomal entrapment are among the obstacles impeding the therapeutic use of oligonucleotides (ONs). The objectives of this study are to investigate the feasibility of utilizing a synthetic import peptide as a drug carrier for cytoplasmic delivery of ONs and to study its transport mechanisms. METHODS: A molecular conjugate consisting of a signal import peptide (IP) derived from Kaposi fibroblast growth factor (K-FGF) and a polycationic ON linker, polylysine (PL), was synthesized and complexed with 5' fluorescently-labeled ON. Complex formation was verified by spectral shift assay and cellular uptake of the ON complex was studied fluorometrically. Microscopic studies were performed to visualize the intracellular distribution of the ON. RESULTS: Cells treated with the ON:IP-PL complex exhibited a dose-dependent increase in ON uptake over free ON-treated controls. The uptake of the complex was shown to occur via an energy-independent, non-endocytic, process since metabolic and endocytic inhibitors and low temperature did not prevent the uptake. Microscopic studies revealed a non-punctate fluorescence pattern, consistent with the non-endocytic transport process. Intense nuclear fluorescence was observed in cells treated with the complex but not with free ON, suggesting enhanced cytoplasmic delivery and nuclear accumulation of the ON by the conjugate. Efficient complex uptake was shown to require both the ON-binding moiety PL and the IP moiety. The delivery system was found to be non-toxic at the concentrations used. CONCLUSIONS: The peptide carrier was effective in promoting the cellular uptake of ON. The mechanism by which the peptide facilitates ON uptake appears to involve a direct translocation of ON via a non-endocytic process. The peptide carrier has the potential to overcome the problem of ON endosomal entrapment and degradation.

Animals↗
PubMed1997

Intestinal transit is more potently inhibited by fat in the distal (ileal brake) than in the proximal (jejunal brake) gut.

Fat in the proximal and distal gut inhibits intestinal transit as the jejunal brake and the ileal brake. It is unknown, however, whether the intestinal transit response to fat in the proximal vs distal gut is different. Since surgical removal of the distal small intestine induced faster transit and greater steatorrhea than removal of the proximal small intestine, we hypothesized that the ileal brake inhibited intestinal transit more potently than the jejunal brake. In six dogs equipped with duodenal (10 cm from pylorus) and midintestinal (160 cm from pylorus) fistulas, we compared intestinal transit across an isolated 150-cm test segment (between fistulas), while 0 (buffer), 15, 30, or 60 mM oleate was delivered into either the proximal (between fistulas) or the distal (beyond the midintestinal fistula) half of the gut. The half of the gut not receiving oleate was perfused with buffer. Buffer perfused into both the proximal and the distal half of the gut served as the control. A meal was administered and diverted completely out of the duodenal fistula so that the studies were all done in the fed state. Intestinal transit was measured by counting for the recovery of a radioactive marker from the temporarily diverted output of the midintestinal fistula. We found that (1) intestinal transit was inhibited more potently by oleate in the distal than in the proximal half of the gut (region effect; P < 0.01), (2) oleate inhibited intestinal transit in a load-dependent fashion (dose effect; P < 0.05), and (3) load-dependent inhibition of intestinal transit by oleate depended on the region of exposure (interaction between load and region; P < 0.01). We conclude that intestinal transit is more potently inhibited by fat-induced ileal than jejunal brake.

Animals↗
PubMed1997

Glucose metabolism in pig outer retina in light and darkness.

Glucose metabolism in the outer retina of pigs was studied in the light and in the dark in pentobarbital anaesthetized pigs. Blood was collected from a vortex vein and an artery, and the arteriovenous concentration differences of lactate, glucose and oxygen were determined in light-adapted eyes. Local blood flows were simultaneously determined using the microsphere method. In a second group of experiments, the flow from a vortex vein and arteriovenous concentration differences were measured in both darkness and light. In light, the mean net lactate formation and oxygen and glucose consumption in the outer retina were about 0.137, 0.150 and0.115 mumol min-1, respectively. In eyes previously dark-adapted, constant light caused a 63% reduction in lactate formation, whilst oxygen and glucose consumptions were reduced by 40 and 44%, respectively. The results indicate that in both darkness and constant light, most of the glucose consumed by the outer retina is used in lactate formation, and that less than 20% is oxidized. Energy production through glycolysis and glucose oxidation is approx. 42% lower in constant light than in darkness.

Adaptation, Ocular↗
PubMed1997

Glucose metabolism of the inner retina in pigs in darkness and light.

In the pig eye, oxygen and glucose consumption in the outer retina are reduced in light compared to the consumption in the dark and most of the glucose consumed is metabolized to lactate both in light and in the dark. In the present study, in order to characterize the metabolism of glucose in the inner retina. Blood was collected from an artery and from a plexus on the optic nerve draining blood from the retina. Arteriovenous concentration differences for glucose, lactate and oxygen were determined. Observations were made in dark-adapted eyes and then after light adaptation. The consumption of oxygen and glucose and the lactate formation in the inner retina were calculated on the basis of these observations and recent data for retinal blood flow. In dark-adapted eyes, approx. 69% of the glucose was oxidized and approx. 20% was used in lactate formation. After 5-10 min of exposure to constant light, the levels of oxygen consumption and lactate formation were no different from those in darkness. The results indicate that lactate formation is a normal property of the pig inner retina, but that it is much less pronounced than in the outer part. The metabolism of the inner retina in constant light is similar to that in darkness. A comparison with data for the outer retina indicates that oxygen consumption in the inner retina in constant light is approx. 47% of that in the whole retina, while for glucose consumption and lactate production, the corresponding figures are approx. 12 and 8%, respectively.

Animals↗
PubMed1997

Dysfunction of guinea-pig pulmonary surfactant and type II pneumocytes after repetitive challenge with aerosolized ovalbumin.

BACKGROUND: Asthma symptoms may partially be caused by a surfactant dysfunction. The inflammatory reaction, so characteristic of asthma, involves a protein invasion of airways which harmfully affects the surfactant function. However, mild asthma attacks might also impede the surfactant synthesis in alveolar type II cells. OBJECTIVE: The present study evaluates the hypothesis that type II pneumocyte metabolic function might be disturbed in a model of mild asthma. METHODS: Immunized, as well as not immunized control guinea-pigs, were challenged three times at two-day intervals with 0.04% ovalbumin aerosol. Bronchoalveolar lavage (BAL) was performed one day after the last challenge and the fluid was evaluated for surface activity, and content of phospholipids and proteins. Alveolar type II cells were isolated and their ability to incorporate a 3H labeled surfactant precursor was evaluated. RESULTS: BAL fluid from immunized and challenged animals showed less surface activity (P < 0.01) when compared with BAL fluid from controls, not immunized but challenged. Most likely the reduced surface activity was caused by a 74% increase in the protein concentration (P < 0.05). Isolated type II cells from immunized and challenged animals had 33% less phospholipids than cells from controls (P < 0.05), and phosphatidylcholine synthesis was reduced 35% (P < 0.05). CONCLUSION: These results suggest that the synthesis, intra-cellular storage, and biophysical activity of surfactant are decreased in an intermittent and mild form of asthma.

Allergens↗
PubMed1997

Evaluation of the quality of HLA antibodies in placental blood.

Two groups of blood samples, placental blood and female donor blood, were shown to have a frequency of 16.4 and 1.5% of anti-human leucocyte antigen (HLA) antibodies respectively. The specificities and qualities of these antibodies were further characterized by their relative coefficient (r) values and strength indices (SIs). Most had an r value of approximately one, but their SIs varied from 41 to 100%. Among these two groups, nine samples gave very strong and definite results (r = 1 and SI = 100%). Data analysis revealed that the qualities of the two groups were comparable. However, the antibody positive rate was higher in placental blood samples than that in donor blood samples.

Antibodies↗
PubMed1997

Altered mu-opiate receptor-G protein signal transduction following chronic morphine exposure.

This laboratory has demonstrated that the longitudinal muscle/myenteric plexus (LMMP) preparation manifests pleiotropic responses to opioid agonists. For example, the mu-selective opiate receptor agonist sufentanil can produce a naloxone-reversible increase or decrease in the electrically stimulated formation of cyclic AMP, depending on its concentration. The present study demonstrates that the sufentanil facilitation and inhibition of stimulated cyclic AMP formation are mediated via Gs- and Gi-like G proteins, respectively. Inactivation of Gi (via pertussis toxin) not only abolishes sufentanil inhibition of cyclic AMP formation but also unmasks a facilitory effect. The latter response is eliminated following treatment with cholera toxin. In tolerant/dependent LMMP tissue, previously inhibitory concentrations of sufentanil produce a facilitation of cyclic AMP formation. However, this unmasked facilitory effect is resistant to cholera toxin. Thus, although inactivation of the inhibitory signal transduction pathway (via pertussis toxin) is sufficient to unmask excitatory sufentanil effects in opiate naive preparations, this mechanism cannot explain the reversal of sufentanil inhibition to facilitation that is observed in tolerant/dependent tissue. Instead, the chronic morphine-induced emergence of a mu-opiate receptor-coupled facilitory pathway that is either not expressed or not fully manifest in opiate naive LMMP tissue is suggested.

Animals↗
PubMed1997

Heparins, low-molecular-weight heparins, and other glycosaminoglycans analyzed by agarose gel electrophoresis and azure A-silver staining.

A sensitive, nonradioactive azure A-silver staining method combining agarose gel electrophoresis was established and evaluated. Unfractionated heparins (UFHs), low-molecular-weight heparins (LMWHs), heparan sulfate (HS), chondroitin sulfate A (CSA), dermatan sulfate (DS), keratan sulfate (KS), and hyaluronic acid (HA) were analyzed. The detection limit of the method was 0.5 ng for heparin, LMWH, HA, CSA, and DS, 2 ng for KS, and 6 ng for HA in the 2-microliter sample volume. Dilution curves demonstrated linear correlation between the logarithm of the concentration of glycosaminoglycans (GAGs) and their optical absorbance at 548 nm. The linear ranges were 1 to 500 ng/microliter for heparins, LMWHs, HS, DS, and CSA, 3 to 500 ng/microliter for KS, and 8 to 500 ng/microliter for HA. GAGs have their characteristic migration patterns and their Rf value decreased from CSA to KS, DS, HS, heparin, and HA. The differences were described for heparins and LMWHs. LMWHs migrated faster and displayed broader bands than unfractionated heparins. It was also observed that some unfractionated heparins contained low sulfated GAGs as contamination, which seemed to be DS as judged by their migration patterns.

Azure Stains↗
PubMed1997

High-level expression of cecropin CMIV in E. coli from a fusion construct containing the human tumor necrosis factor.

Cecropin CMIV gene was fused to the 3'-terminus of the mutated tumor necrosis factor (TNFb) gene and the fusion gene was directly under the control of an inducible T7 promoter in pET-11d. This fusion gene was overexpressed in Escherichia coli with an expression level of approximate 40%-50% of total cellular proteins, and was produced mainly in the form of inclusion body. Peptide with antibacterial activity was obtained by cleaving the fusion protein with CNBr.

Escherichia coli↗
PubMed1997

Characterization of a soluble IL-6 receptor alpha mutant C277D/H280I expressed in E.coli.

The pleiotropic cytokine interleukin-6(IL-6) triggers the formation of a high affinity receptor complex constituted by the ligand-binding subunit IL-6 receptor alpha (IL-6R alpha) and the signal transducer gp130. To construct the antagonist of IL-6, a DNA segment encoding the soluble human IL-6R alpha (shIL-6R alpha) mutant with two substitutions C277D/H280I was generated by overlap extension polymerase chain reaction. The DNA segment was then subcloned into vector pET-3b and expressed in E.coli at a high level. The refolded and purified recombinant protein, which was designated as DM650, exhibited an increased IL-6-binding capability by 8-fold. DM650 antagonized IL-6 perfectly, resulting in the growth-inhibition of human myeloma AF-10 cells. DNA fragmentation assay proved that the growth of AF-10 cells was inhibited through the induction of apoptosis suppressed by IL-6.

Antigens, CD↗
PubMed1997

Fast Fourier transform analysis of dynamic data: sine wave stress-strain analysis of biological tissue.

We propose an improvement to the dynamic oscillation method using as an example the measurement of the tensile stiffness of the rabbit tracheal mucosal membrane. A sine wave oscillation technique was used to study the tissue mechanical properties. A mathematical model was developed using fast Fourier analysis. After mathematically eliminating the machine response, this analysis reveals the tissue frequency response over a wide range of frequencies. This study addresses the advantages of using Fourier analysis to interpret dynamic properties of biological tissue and provides a complete description of how to obtain the pure tissue response.

Animals↗
PubMed1997

Primary structure and functional expression of heavy- and light-chain variable region genes of a monoclonal antibody specific for human fibrin.

The immunoglobulin heavy- and light-chain variable region (VH and VK) genes were isolated from 8E5 hybridoma cells, which secreted monoclonal antibody against human fibrin by RT-PCR. An expression vector pOPE51-8E5 was constructed for the recombinant VH-VK scFv expression. The primary sequence of the variable regions was determined. Expression product was found in the periplasmic space and inclusion bodies by SDS-PAGE and immunoblotting. It was a 30 KDa single chain fragment (scFv) with the antigen-binding specificity of the parental monoclonal antibody. A light chain shuffling with an unspecific VL did not result in a loss of fibrin binding specificity.

Amino Acid Sequence↗