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Biomedical subjects

G Wang

Publications and source records attributed to G Wang.

At least 541 records · Page 30Linked to original sources

Force generation and phosphate release steps in skinned rabbit soleus slow-twitch muscle fibers.

The force-generation and phosphate-release steps of the cross-bridge cycle in rabbit soleus slow-twitch muscle fibers (STF) were investigated using sinusoidal analysis, and the results were compared with those of rabbit psoas fast-twitch fibers (FTF). Single fiber preparations were activated at pCa 4.40 and ionic strength 180 mM at 20 degrees C. The effects of inorganic phosphate (Pi) concentrations on three exponential processes, B, C, and D, were studied. Results are consistent with the following cross-bridge scheme: [formula: see text] where A is actin, M is myosin, D is MgADP, and P is inorganic phosphate. The values determined are k4 = 5.7 +/- 0.5 s-1 (rate constant of isomerization step, N = 9, mean +/- SE), k-4 = 4.5 +/- 0.5 s-1 (rate constant of reverse isomerization), K4 = 1.37 +/- 0.13 (equilibrium constant of the isomerization), and K5 = 0.18 +/- 0.01 mM-1 (Pi association constant). The isomerization step (k4) in soleus STF is 20 times slower, and its reversal (k-4) is 20 times slower than psoas fibers. Consequently, the equilibrium constant of the isomerization step (K4) is the same in these two types of fibers. The Pi association constant (K5) is slightly higher in STF than in FTF, indicating that Pi binds to cross-bridges slightly more tightly in STF than FTF. By correlating the cross-bridge distribution with isometric tension, it was confirmed that force is generated during the isomerization (step 4) of the AMDP state and before Pi release in soleus STF.

Actins↗

Influence of two apo A4 polymorphisms at codons 347 and 360 on non-fasting plasma lipoprotein-lipids and apolipoproteins in Asian Indians.

Apolipoprotein A-IV (apo A-IV, protein; apo A4, gene) is a major constituent of triglyceride-rich and high-density lipoprotein particles and may, therefore, play an important role in lipid metabolism. We studied the distribution of two apo A4 polymorphisms at codons 347 (alleles A and T) and 360 (alleles 1 and 2) in relation to plasma lipoprotein-lipid and apolipoprotein levels in 176 non-fasting male blood donors from New Delhi, Northern India. The frequencies of the T allele at codon 347 and the 2 allele at codon 360 were 0.12 and 0.03 respectively. Carriers of the T allele (AT and TT genotypes) had significantly lower plasma total cholesterol (P = 0.04) and low density lipoprotein (LDL)-cholesterol (P = 0.02) levels than individuals homozygous for the A allele (AA genotype). The codon 347 polymorphism explained 2.2 and 2.6% of the phenotypic variation in total cholesterol and LDL-cholesterol, respectively. The 2 allele at codon 360 was associated with marginally reduced plasma LDL-cholesterol (P = 0.09) and increased triglyceride (P = 0.05) levels compared to the 1 allele. To further elucidate the combined effects of the two polymorphism we constructed two-site haplotypes. The haplotype data showed a stronger influence and explained 3.0 and 5.2% of the phenotypic variation in total cholesterol and LDL-cholesterol, respectively. The two uncommon haplotypes, T1 and A2, were associated with 24.2 and 23.5 mg/dl lower total cholesterol and 22.5 and 42.0 mg/dl lower LDL-cholesterol levels, respectively. The accentuated effect of apo A4 polymorphisms on non-fasting plasma cholesterol suggest that apo A-IV may play an important role in regulating the postprandial metabolism of lipoproteins.

Adolescent↗

Some observations on pharmacoepidemiology in Europe.

The need for pharmacoepidemiology, defined as the study of the use of and the effects of drugs in large numbers of people, will increase exponentially in the next decade both in developed and in developing countries. Within Europe, a common market of over 350 million consumers, regulations and guidelines related to drug use were formulated, especially with respect to post-marketing surveillance and the detection, interpretation and management of rare but serious drug related adverse events. The activities of international organizations like the World Health Organization in this context are briefly addressed. In the European Union a choice has been made by the regulatory authorities for spontaneous reporting systems as a minimal requirement for post marketing surveillance in all member states. The French pharmacovigilance system has to some extend functioned as a blueprint for a common European post marketing surveillance system. Therefore the organization of this French system is explained in some detail. Also in this context the need for drug utilization studies to get quantitative information about drug use is stressed. For the creation of the databases needed for case control and cohort studies a variety of approaches is used in different countries, all with their own advantages and shortcomings. Some examples from England and the Netherlands are given. The efforts of the European Commission and various scientific organizations aiming to promote the harmonization of pharmacovigilance actions in Europe are discussed. Finally, some guidelines for good pharmacovigilance practice are suggested.

Databases as Topic↗

1H MAS and 1H[23Na] double resonance NMR studies on the modification of surface hydroxyl groups of gamma-alumina by sodium.

The modification of surface hydroxyl groups with sodium in a series of Na2CO3-gamma-Al2O3 catalysts was investigated as a function of both the Na2CO3 loading and the calcination temperature by means of 1H magic angle spinning (MAS) and 1H(23Na) spin-echo double resonance NMR techniques. The 1H NMR experiments revealed that sodium ions are homogeneously distributed over the alumina surface and closely coordinated with the surface hydroxyl groups. In the catalysts calcined at 250 degrees C, the acidic hydroxyl groups (with a chemical shift of 2.0 ppm) are preferentially associated with sodium ions at low Na2CO3 coverages (5 and 10%), while both the acidic and the basic (0 ppm) hydroxyl groups are accessible for sodium ions at high coverages (15 and 20%). The coordination causes a low-field shift of about 2 ppm in the 1H MAS spectra, and a broad signal at 4.5 ppm appears. It is interesting that the 4.5 ppm signal is completely suppressed in the 1H(23Na) MAS experiments, providing direct evidence that a strong interaction exists between adsorbed sodium ions and the surface hydroxyl groups. Increasing the calcination temperature to 450 degrees C results in preferential removal of the acidic hydroxyl groups, and only the most basic hydroxyl groups remain when the calcination temperature is raised to 600 degrees C. This is attributed to the formation of the coordinated species. [formula: see text] which enhances the acidity of the surface hydroxyl groups and prompts their dehydroxylation, especially at high calcination temperature. Correlation of the 1H MAS NMR results and catalytic activity measurements indicates that the basic hydroxyl groups are essential for the carbonyl sulfide hydrolysis reaction.

Aluminum Oxide↗

Spiral computed tomographic colonography: determination of the central axis and digital unraveling of the colon.

RATIONALE AND OBJECTIVES: The authors developed and tested automated and semiautomated bowel-lumen tracking and colon-unraveling techniques for determining the central axis of the bowel. METHODS: A computer-simulated gastrointestinal tract phantom was used to test the accuracy of an automated algorithm for central axis determination and bowel unraveling. Variations in cross-sectional features between straight and unraveled formats were compared in a canine bowel segment in vitro and a human colon in vivo by using spiral computed tomography. Three readers each performed three semiautomated evaluations. RESULTS: Accuracy of the automated algorithm was confirmed by the high degree of correlation in the cross-sectional feature measurements (length error, < 1%). For the canine colon segment, accuracy of the semiautomated algorithm was confirmed by comparison with the automated tracing. For the human colon, readings were reproducible with 3.3% (+/- 1.9 standard deviation) mean variation in length. CONCLUSION: An automated algorithm for central axis deterioration and unraveling the colon has been validated in a gastrointestinal tract phantom. A semiautomated algorithm has been shown to be reproducible and time-efficient.

Algorithms↗

Three-dimensional dental imaging by spiral CT. A progress report.

OBJECTIVE: To demonstrate the feasibility of using spiral computed tomographic data for three-dimensional image acquisition, display, and segmentation of dental structures and lesions and to demonstrate the feasibility of metal artifact suppression. STUDY DESIGN: Isolated extracted teeth, a dry mandible, cadaver mandible, and cadaver head were scanned and reconstructed using spiral computed tomography data. Algorithms for metal artifact reduction including extended attenuation range and interpolation of missing projections were applied. Volumetric rendering was performed to synthesize images comparable to conventional intraoral dental radiographs. Serial examinations were obtained by spiral computed tomographic tomography, registered by surface matching, and interval change determined by three-dimensional subtraction. RESULTS: Metal artifact reduction was successful in markedly reducing the streaks and star patterns that usually accompany metallic restorations and intraoral appliances. Voxel sum images were comparable to dental radiographs. Image segmentation could successfully isolate dental structures, and simulated lesions could be detected through three-dimensional subtraction. CONCLUSION: The results demonstrate the feasibility of spiral volumetric computed tomography for quantitative study of oral hard tissues in the presence of metal restorations.

Algorithms↗

Tissue-specific activation of the osmotin gene by ABA, C2H4 and NaCl involves the same promoter region.

The gene encoding the antifungal protein osmotin is induced by several hormonal and environmental signals. In this study, tissue-specific and inducer-mediated expression of the reporter gene beta-glucuronidase (uidA) fused to different fragment lengths of the osmotin promoter was evaluated in transgenic tobacco (Nicotiana tabacum). The region of the promoter between -248 to -108 (Fragment A) was found to be essential and sufficient for inducer (abscisic acid (ABA), C2H4 and NaCl)-mediated expression of the reporter gene. Expression of the reporter gene was developmentally regulated and increased with maturity of leaves, stem and flowers. Expression also was tissue-specific being most highly expressed in epidermis and vascular parenchyma of the stem. The regulators ABA, C2H4 and NaCl exhibited tissue-specific induction of this promoter. The promoter was specifically responsive to C2H4 in flowers at virtually all stages of development, but not responsive in these tissues to ABA or NaCl. Conversely, ABA and NaCl were able to induce reporter gene activity using promoter Fragment A in specific tissues of root where C2H4 was unable to induce activity. Further dissection of the promoter Fragment A into fragments containing either the conserved GCC element (PR); PR/AT; or G/AT sequences, and subsequent testing of these fragments fused to GUS in transgenic plants was performed. These experiments revealed that the promoter fragment containing PR element alone, although required, was barely able to allow responsiveness to C2H4. However, significant C2H4-induced activity was obtained with a promoter fragment containing the AT and PR elements together.

Abscisic Acid↗

Replication of M13 single-stranded DNA bearing a site-specific ethenocytosine lesion by Escherichia coil cell extracts.

Previous investigation on the mutagenic effects of 3, N4-Ethenocytosine (epsilon C), a nonpairing DNA lesion, revealed the existence of a novel SOS-independent inducible mutagenic mechanism in E. coli termed UVM for UV modulation of mutagenesis. To investigate whether UVM is mediated by an alteration of DNA replication, we have set up an in vitro replication system in which phage M13 viral single-stranded DNA bearing a single site-specific (epsilon C) residue is replicated by soluble protein extracts from E. coli cells. Replication products were analyzed by agarose gel electrophoresis and the frequency of translesion synthesis was determined by restriction endonuclease analyses. Our data indicate that DNA replication is strongly inhibited by epsilon C, but that translesion DNA synthesis does occur in about 14% of the replicated DNA molecules. These results are very similar to those observed previously in vivo, and suggest that this experimental system may be suitable for evaluating alterations in DNA replication in UVM-induced cells.

Bacteriophage M13↗

Voltage dependent calcium and potassium currents in Y-1 adrenocortical cells are unresponsive to ACTH.

In this report we use both whole cell and perforated patch clamp recording techniques to characterize calcium and potassium channels in Y-1 adrenocortical cells in order to assess their responsiveness to ACTH. Both transient and long-lasting components of an inward calcium current were identified which were similar to T and L-type Ca2+ currents. With Ba2+ as the charge carrier, the transient current activated at voltages more hyperpolarized than -50 mV with V1/2 for activation at -78.1 mV, and for steady state inactivation at -52.3 mV. The L-type current activated at -20 mV, with a V1/2 for activation at -29.9 mV and steady state inactivation at -44.2 mV. Under perforated patch conditions the response was shifted to more depolarized voltages. Both currents were responsive to agents which usually affect T- or L-type Ca2+ currents. The transient current was completely blocked by 50 microM lanthanum or 200 microM nickel and partially blocked by 300 mM amiloride. Cadmium (100 microM) and nifedipine (300 nM) completely blocked the long-lasting current while omega-conotoxin GVIA (1992 nM) inhibited the current by only 20-25%. The agonist, Bay K 8644 was stimulatory at 50 nM. Both transient and sustained outward potassium currents similar to A-type and delayed rectifier currents, respectively, were present. The transient current demonstrated fast activation at voltages more positive than -10 mV, inactivation with continued depolarization and steady state inactivation at V1/2 = -50 mV. The sustained current activated rapidly and had minimal inactivation with continued depolarization. The transient current was blocked by 5 mM 4AP and the sustained by 25 mM TEA. While Y-1 cells contain both calcium and potassium currents similar to those found in other adrenocortical cells, none of the currents were affected by ACTH or AII, secretagogues which stimulate steroidogenesis. These data, combined with the inability of both Ca2+ and K+ channel blockers to alter ACTH-induced steroidogenesis as reported earlier, suggests that neither calcium nor potassium currents are responsive to ACTH in Y-1 cells.

Adrenal Cortex↗

Effects of nitric oxide on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats.

We performed this study to evaluate the effects of changing the level of nitric oxide (NO) on disruption of the blood-brain barrier (BBB) by hyperosmolar mannitol. Under isoflurane anesthesia, control rats (control group, n = 6) were given infusions with 25% mannitol into the internal carotid artery before measuring the transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB). In the CAS group (n = 6), [3-(cis-2,6-dimethyl piperidino)-sydnonimine] (CAS 754), a NO donor, was injected to decrease the mean arterial pressure (MAP) to 55 mm Hg and in the L-NAME group (n = 6), NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, was injected before administering mannitol. In additional control animals (control + P group, n = 6) and additional CAS 754-treated animals (CAS + P group, n = 6), phenylephrine was infused to keep MAP at 130 mm Hg during the experimental period. In the control group, with mannitol injection, the Ki of the ipsilateral cortex (IC) where mannitol was injected increased to 4.3 times that of the contralateral cortex (CC) (17.2 +/- 2.9 vs 4.0 +/- 2.6 microliters.g-1.min.1). Without blood pressure control, the Ki of the IC of the CAS group (7.0 +/- 4.5) was lower and that of the L-NAME group (26.2 +/- 12.7) was higher than that of the control animals. At the same MAP, the Ki of the IC of the CAS + P group (9.6 +/- 3.1) was significantly lower than that of the control + P group (21.3 +/- 14.5) or that of the L-NAME group. There was no significant difference in the Ki of the IC between the control + P and the L-NAME groups. In conclusion, L-NAME worsened BBB disruption induced by hyperosmolar solution, which may be due to the pressure effect of L-NAME. CAS 754 was effective in attenuating disruption of the BBB caused by hyperosmolar mannitol. This effect is apparently not due to decreased MAP.

Aminobutyrates↗

Modified transverse locking nail fixation of proximal femoral fractures.

It was hypothesized that transverse locking screws of intramedullary nails, seated above the lesser trochanter, provide equal strength to that of reconstruction nails, and that screws placed through the medial cortex of the femoral neck do not have adverse biomechanical effects during physiologic loading. Synthetic femurs (n = 10) and paired anatomic specimen femurs (n = 14) were tested intact and with an intramedullary device in place. Intact specimens were loaded nondestructively, then a segmental subtrochanteric defect was created and either a high seated transverse locking nail or a reconstruction nail was inserted and statistically locked. Axial and torsional stiffness were determined followed by axial failure testing. Mechanical parameters evaluated were stiffness, displacement, and energy. The implanted specimens did not show any statistically significant difference between transverse or reconstruction screw constructs with any of the measured parameters (stiffness, displacement, and energy). Failure tests in implanted specimens also did not show any statistically significant difference in yield load, yield displacement, or energy to failure between implant constructs. All anatomic specimens failed, with fractures of the proximal fragment involving medial and lateral cortices. Synthetic specimens did not fracture but showed failure with implant deformation at the level of the skeletal defect. The use of high seated transverse locking nails for complex proximal femoral fractures is a viable option and has comparable in vitro mechanical performance with reconstruction nails. Although not shown to be a problem in the present study, clinical evaluation of screws through the medial femoral neck cortex is required.

Bone Nails↗

Genetic and phenotypic analysis of Borrelia valaisiana sp. nov. (Borrelia genomic groups VS116 and M19).

To clarify the taxonomic status of two recently described Borrelia genomic groups, groups VS116 and M19, three group VS116 strains and eight group M19 strains isolated from Ixodes ricinus ticks in Switzerland, The Netherlands, and the United Kingdom were characterized. PCR-restriction fragment length polymorphism (RFLP) analysis of the 5S-23S intergenic spacer amplicon, rRNA gene restriction analysis, 16S rRNA gene sequence analysis, randomly amplified polymorphic DNA (RAPD) fingerprinting, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and immunoblotting with monoclonal antibodies were used for genetic and phenotypic analysis. The PCR-RFLP and RAPD patterns of three group VS116 strains and eight group M19 strains were identical but differed from those of Borrelia burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii, and Borrelia japonica. DNAs from all group VS116 and M19 strains yielded three fragments (6.9, 3.2, and 1.4 kb) and four fragments (2.1, 1.2, 0.8, and 0.6 kb) after digestion with EcoRV and HindIII, respectively, hybridizing with an Escherichia coli 16S + 23S cDNA probe. The SDS-PAGE protein profiles of group VS116 and M19 strains were heterogeneous. Phylogenetic analysis of the partial 16S rRNA gene sequences showed that group VS116 and M19 spirochetes were members of a Borrelia species distinct from previously characterized members of the genus Borrelia. Based on our present study and data from previous DNA-DNA hybridizations, a new Borrelia species, Borrelia valaisiana sp.nov., in the B. burgdorferi complex, is proposed. Strain VS116 is the type strain of this new species.

Bacterial Proteins↗

Low-contrast resolution in volumetric x-ray CT--analytical comparison between conventional and spiral CT.

Spiral/helical computed tomography (CT) was introduced to scan an anatomical volume in a single breath-hold for better temporal resolution as compared to conventional CT. Recently, it was established that given an x-ray dose, spiral CT also allows better longitudinal high-contrast resolution due to retrospective reconstruction. In spiral CT, full scan with interpolation (FI) and half-scan with interpolation (HI) are limited by the degraded slice sensitivity profile and increased image noise, respectively. We combined these two interpolation methods for a desirable balance. This new interpolation method, FI + HI, was shown to produce 4% lower image noise standard deviation than conventional CT, without loss of longitudinal bandwidth according to one-tenth-cutoff and mean-square-root measures. The analytic model of image noise was validated in a water phantom experiment. Our findings suggest the superiority of spiral CT over conventional CT in terms of both low-contrast resolution and high-contrast resolution.

Biophysical Phenomena↗

Optimal pitch in spiral computed tomography.

The focus of this paper is to analytically optimize spiral/helical computed tomography (CT) protocols based on a simplified imaging model. Spiral CT was approximately modeled as follows: Using the half-scan raw data interpolation method, the variance of the spiral CT slice sensitivity profile is equal to the sum of squared detector collimation divided by 12 and squared table increment divided by 24. Image noise variance is inversely proportional to tube current and detector collimation. The maximum continuous scanning time is inversely proportional to tube current. Slice thickness, image noise, and signal-to-noise ratio were, respectively, optimized for a given scanning coverage, consistently resulting in pitch of square root of 2. To avoid longitudinal aliasing, at least 2-3 transverse slices should be reconstructed per collimation. When the simplified spiral CT model is valid and a scanning range specified, 1.4 pitch is required for optimal image quality. The method can be applied to more accurate spiral CT models.

Biophysical Phenomena↗

Depiction of pulmonary emboli with spiral CT: optimization of display window settings in a porcine model.

PURPOSE: To determine optimal spiral computed tomographic (CT) image display for depiction of pulmonary emboli (PE). MATERIALS AND METHODS: Autologous PE detected in 10 pigs with contrast material-enhanced spiral CT were displayed with six display window settings (standard mediastinal window and five modified windows referenced to attenuation values in pulmonary artery [PA] branches). The thrombus gray level and gray level contrast and separability of PE versus those of the local PA branch were computed for each window setting; results were compared with repeated measured analysis of variance. RESULTS: Of 114 PE detected pathologically, 28 were visible with spiral CT. Two of the 28 PE were not detectable with standard mediastinal windows. Statistically significantly improved gray level contrast and separability were noted with modified windows referenced to the second-order PA branch and the local PA branch than with the standard mediastinal and other modified window settings (P < .05). However, thrombus gray level was statistically significantly higher with the standard mediastinal window (P < .05). CONCLUSION: PE are best depicted as filling defects when displayed with a modified window referenced to the right or left main PA attenuation. Standard mediastinal windows are useful for identifying vessels that are occluded completely with PE.

Acute Disease↗

Visualization of colorectal polyps with spiral CT colography: evaluation of processing parameters with perspective volume rendering.

PURPOSE: To evaluate two key processing steps for detection of colon polyps with spiral computed tomographic (CT) colography with perspective volume rendering (PVR): image reconstruction and opacity assignment of the attenuation data. MATERIALS AND METHODS: Spiral CT was performed in 10 patients with known polyps confirmed at colonoscopy, and detailed quantitative analyses were performed of data obtained in four. First, anatomic fidelity of three-dimensional (3D) images generated from two-dimensional (2D) source images with equal voxel dimensions (87%-90% overlap) was compared with 3D images generated from 2D source images with unequal voxel dimensions (0%-80% overlap). Next, the relative dimensions of colorectal polyps to adjacent structures were evaluated for various opacity threshold settings. Then, step and sigmoidal opacity functions were compared with respect to image smoothness and edge sharpness. RESULTS: PVR images generated after interpolation of image data reconstructed with at least 60% overlap were equivalent in image quality to PVR images generated from source images with equal voxel dimensions. Relative polyp-to-haustral fold dimensions demonstrated substantial distortions with opacity thresholds below -700 HU. The 3D PVR images generated with the sigmoidal opacity function were significantly smoother than those generated with the step opacity function (paired t test, P < .02), with small differences noted in edge sharpness. CONCLUSION: Use of highly overlapping source images (87%-90%) was not necessary to generate 3D PVR images of colorectal polyps. Image artifacts were suppressed with use of an appropriate opacity threshold and a sigmoidal opacity function without substantial loss in edge sharpness.

Artifacts↗

Interferon-gamma regulation of Clara cell gene expression: in vivo and in vitro.

This report demonstrates that Clara cell 10-kDa protein (CC10) mRNA levels are regulated by interferon-gamma (IFN-gamma). An analysis of total lung RNA from mice given IFN-gamma intratracheally showed increased levels of CC10 mRNA compared to control animals but no significant increases in surfactant proteins B and C. These results were confirmed in a Clara cell line, mtCC1-2, generated from the lungs of a transgenic mouse expressing the SV40 large T antigen under the control of a Clara cell-specific promoter. Significant increases in mtCC1-2 CC10 mRNA levels were observed in a time- and a dose-dependent manner. The expression of transacting factors hepatocyte nuclear factors 3 alpha and 3 beta (HNF-3 alpha and HNF-3 beta) were also analyzed, and a transient increase in the expression of HNF-3 beta but not HNF-3 alpha was detected. Deoxyribonuclease I footprint analysis identified a signal transducer and activator of transcription (STAT) binding site (at nucleotides -293 to -284 of CC10) adjacent to two thyroid transcription factor-1 (TTF-1) binding sites, suggesting a potential interaction between STAT1 and TTF-1. This report reinforces the hypothesis that CC10 functions as an anti-inflammatory protein and that increases in CC10 protein may provide additional protection from inflammation and disease in the lung.

Animals↗