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Biomedical subjects

C Wu

Publications and source records attributed to C Wu.

At least 307 records · Page 17Linked to original sources
PubMed1998

Ultrasound characterization of bone demineralization.

Quantitative ultrasound (QUS) assessment of bone may permit an assessment of bone properties currently not available by bone densitometry techniques. To explore the effects of the quantity of bone mineral on acoustic parameters, we carried out an in vitro study of the impact of demineralization on attenuation of ultrasound in trabecular bone. Ten fresh cubes of trabecular bone obtained from bovine distal femurs were progressively demineralized using formic acid solution. The progression of demineralization was controlled by monitoring the specimen bone mineral density (BMD) using dual x-ray absorptiometry (DXA). At five stages of demineralization-0% (baseline), 25%, 50%, 75%, and 100% (all mineral removed)-the US properties of the specimens were assessed (Walker Sonix UBA 575+). The US parameters investigated were broadband ultrasound attenuation (BUA) and ultrasound attenuation in bone (UAB). Both DXA and QUS measurements were made along the three orthogonal axes of each cube. Our results demonstrated significant variability in both BUA and UAB along the three principle axes of the cubes whereas BMD did not differ in the different directions. A strong but nonlinear correlation was found between BMD and US attenuation. A reduction in BMD to 50% of the baseline values resulted in BUA (UAB) reduction to 25% and 19%, respectively. A random effect model analysis supported a multiplicative relationship between BMD and the US parameters. US attenuation is a sensitive indicator of bone mineral changes with nonlinear dependence on bone mineral loss. Bone collagen structure reinforced by hydroxyapatite crystal accounts for fundamental US characteristics. Ultrasound attenuation associated with trabecular orientation is basically dominated by the mineral spread in a collagen framework.

Absorptiometry, Photon↗
PubMed1998

Expression of the integrin-linked kinase (ILK) in mouse skin: loss of expression in suprabasal layers of the epidermis and up-regulation by erbB-2.

Integrin-linked kinase (ILK) is a newly identified serine/threonine protein kinase implicated in integrin signaling. To investigate the functions of ILK in vivo, we have analyzed the expression and regulation of ILK in the skin, in which proper control of cell-extracellular matrix interactions and cell proliferation is essential for its normal development and homeostasis. We report here that ILK is abundantly expressed throughout the extracellular matrix-rich dermis. ILK mRNA was also detected in the hair follicles and the basal cells of the interfollicular epidermis. However, ILK expression is lost in the suprabasal layers of keratinocytes that are undergoing terminal differentiation. PINCH, an ILK-binding protein, exhibited a similar expression pattern in the skin. Recent studies have indicated that erbB-2, a member of the epidermal growth factor receptor family, plays a pivotal role in epidermal growth, differentiation, and hair follicle morphogenesis. Using a transgenic mouse system in which an activated erbB-2 is overexpressed in the epidermis, we show that ILK expression is regulated by erbB-2. The in vivo expression and regulation patterns of ILK, together with its biochemical activities, suggest an important role of ILK in coordinating the integrin signaling pathways and the growth factor signaling pathways in the development of the skin and the pathogenesis of skin diseases.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Direct myocardial effects of OPC-18790 in human heart failure: beneficial effects on contractile and diastolic function demonstrated by intracoronary infusion with pressure-volume analysis.

OBJECTIVES: We sought to determine the precise myocardial effects of OPC-18790 as demonstrated by intracoronary administration. BACKGROUND: Although previous studies have determined the cardiovascular effects of a novel intravenous inotrope, OPC-18790, the observed benefits on contractile and diastolic function may have been confounded by the marked changes in peripheral loading associated with this drug when given intravenously. METHODS: Eight heart failure patients received intracoronary OPC-18790 at 31.25 microg/min for 20 min, and then at 62.5 microg/min for another 20 min. Hemodynamic variables and pressure-volume indexes using the conductance catheter method were determined at baseline and then after the two doses. RESULTS: There were no significant effects on heart rate, cardiac output or loading conditions, including afterload as determined by systemic vascular resistance and arterial elastance (Ea) and preload as determined by end-diastolic volume (EDV). There were significant increases in end-systolic elastance (Ees) from 0.74+/-0.11 to 0.90+/-0.16 mm Hg/ml at 31.25 microg/min and to 137+/-0.33 mm Hg/ml at 62.5 microg/min (p < 0.05 by analysis of variance [ANOVA]). Diastolic function improved, as determined by the time constant for isovolumetric relaxation tau, which decreased significantly from baseline to 31.25 microg/min (94+/-9 to 79+/-9 ms, p < 0.05), and did not shorten further at 62.5 microg/min (78+/-8 ms, p=NS). There were significant decreases in right atrial pressure (9+/-1 to 7+/-1 mm Hg, p < 0.01 by ANOVA) and mean pulmonary artery wedge pressure (21+/-3 to 16+/-2 mm Hg, p < 0.05 by ANOVA). This fall in filling pressures was not accompanied by any change in EDV. Inspection of the diastolic portion of the pressure-volume curve confirmed a downward shift consistent with pericardial release in five of the eight patients. CONCLUSIONS: Intracoronary administration of OPC-18790 demonstrates that the direct myocardial effects of this agent include a modest increase in inotropy and improvement in diastolic function, both of which occur without increases in heart rate, indicating that this agent may be beneficial for the intravenous treatment of congestive heart failure.

Aged↗
PubMed1998

The discovery and structure-activity relationships of nonpeptide, low molecular weight antagonists selective for the endothelin ET(B) receptor.

The systematic modification of the ETA selective N-(5-isoxazolyl)benzene-sulfonamide endothelin antagonists to give ETB selective antagonists is reported. The reversal in selectivity was brought about by substitution of the 4-position with aryl and substituted aryl groups. Of all the aromatic substituents studied, the para-tolyl group gave rise to the most active and selective ETB antagonist. Larger substituents caused a decrease in both ETB activity and selectivity. A similar trend was observed by substitution at the 5-position of the N-(5-isoxazolyl)-2-thiophenesulfonamide ETA receptor antagonists. The para-tolyl group was again found to be optimal for the ETB activity and selectivity. The structural features that were found to be favorable for binding to the ETB receptor, that is, the presence of a linear, conjugated pi-system of definite shape and size, have been successfully incorporated into the design of ETB selective polycyclic aromatic sulfonamides antagonists.

Animals↗
PubMed1998

Direct sensing of heat and oxidation by Drosophila heat shock transcription factor.

The heat shock transcription factor HSF activates expression of its target genes in response to elevated temperatures and chemical or physiological stress. A key step in the activation process involves the formation of HSF homotrimers, leading to high-affinity DNA binding. The mechanism by which HSF trimerization and DNA binding is regulated by stress signals has remained elusive. Here, we report that trimerization and DNA binding of purified Drosophila HSF can be directly and reversibly induced in vitro by heat shock temperatures in the physiological range and by an oxidant, hydrogen peroxide. Other inducers of the heat shock response, including salicylate, dinitrophenol, ethanol, and arsenite, have no effect on HSF trimerization in vitro, indicating that these inducers act by indirect mechanisms.

Adaptation, Physiological↗
PubMed1998

Micromechanical devices for intravascular drug delivery.

Microfabrication technology, more commonly applied to the manufacture of integrated circuits, can be used to build devices useful for mechanical delivery of drugs and genes. Microprobes fabricated using silicon micromachining have been used to deliver DNA into cells as an alternative to bombardment and microinjection. This idea can be extended to intravascular stents with integrated microprobes capable of piercing compressed plaque and delivering anti-restenosis therapies into coronary arteries. Preliminary experiments using filleted rabbit arteries have demonstrated transection of the internal elastic lamina. New nonplanar microfabrication technologies are necessary for creating practical devices with cylindrical symmetry; a promising possibility is to use microfabricated structures of anodic metal oxides.

Animals↗
PubMed1998

Concepts of human differences: a comparison of American, Japanese, and Chinese children and adolescents.

Concepts of human differences were studied among 5th and 11th graders in the United States (n = 175), Japan (n = 256), and the People's Republic of China (n = 160). Relative to their peers in the other 2 cultures, more American students noted differences in appearance and attractiveness and material resources; more Japanese students noted various physical features, and more Chinese students noted specific behaviors. On the whole, Japanese responses resembled those of the American students more closely than those of the Chinese students. With increasing age, American students reported a larger number, whereas Asian students tended to report a smaller number of distinct categories of human differences. Results are discussed in terms of cultural construals of self and theories of cognitive development.

Adolescent↗
PubMed1998

Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy.

Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new polymorphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein 'dysferlin'. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset).

Adult↗
PubMed1998

Feasibility study of the spectroscopic measurement of oxyhemoglobin using whole blood without pre-treatment.

A feasibility study was carried out to evaluate a chemometrics-enhanced measurement of oxyhemoglobin concentration in whole blood without pre-treatment by lysing cellular components in the sample. Conventional in vitro multi-wavelength CO oximeters pre-process blood by sonication or detergent dilution to lyse blood cells to reduce light scattering. Two limitations result: (1) residual cell membrane fragments can seed surface biofouling and (2) dilution errors can occur. A full wavelength method using multivariate analysis in chemometrics was applied to correct the light scattering effect in the measurement of oxyhemoglobin concentration. Whole blood specimens were adjusted to different oxyhemoglobin concentrations with gas mixtures (N2, CO2 and O2). An Ocean Optics miniaturized spectrophotometer with a 100 microns pathlength optical cell was used for transmission measurements from 500 to 700 nm. Original spectra were smoothed and a second derivative transformation was performed to eliminate the baseline shift and slope changes from light scattering. Indirect calibration was applied to the second derivative spectra. Two-factor cross-validation by principle components regression on two sets of data showed r2 = 0.985 and 0.946 between predicted oxyhemoglobin concentration and those measured by an AVL 912 CO oximeter with RSD = 3.85 and 6.83%, respectively. Error analysis gave s = 2.36 x 10(-5) (RSD = 0.23%) on derivative absorbance for the spectrophotometer measurement alone. Specimen settling and specimen sampling gave imprecision on derivative absorbance of s = 6.17 x 10(-4) (RSD = 4.4%) and s = 4.52 x 10(-4) (RSD = 1.4%), respectively.

Feasibility Studies↗
PubMed1998

Designs of reference families for the construction of genetic linkage maps.

The reference family panel is the foundation of a gene mapping program because it affects the cost and quality of the genetic linkage maps, and should be designed to yield reliable linkage detection and locus ordering at minimal gene mapping cost. A map cost function was defined as the number of genotypes required per marker per unit of genome coverage and was used to obtain optimal designs with respect to linkage detection. An ordering reliability function was defined as the likelihood ratio of the most likely order to the second most likely order of genetic markers and was used to find optimal designs with respect to locus ordering. Optimum levels of recombination frequency were found to be in the neighborhood of 0.11-0.15 for linkage detection and were in the region of 0.05-0.20 for locus ordering. Therefore, recombination frequencies optimal for linkage detection are also optimal for locus ordering. Based on the optimal detection levels, sample size (number of offspring) and map cost requirements were derived for six representative designs, assuming gender-specific linkage maps and two alleles with equal frequency for each marker. The sample size required for linkage detection ranged from 168 to 432 offspring for full-sib designs and ranged from 350 to 600 offspring for half-sib designs depending on the family size and the target LOD score, with corresponding minimal map costs of 10-20 genotypes per marker per centiMorgan map coverage. Locus ordering generally requires more genotypes than linkage detection. For full-sib designs, meioses from both genders should be used for locus ordering even when the maps are gender-specific. For half-sib designs, additional families may be needed for locus ordering. Sample size for ordering closely linked loci as required by positional cloning were provided. Effects of family size, grandparents, and marker polymorphism on design efficiency were analyzed.

Chromosome Mapping↗
PubMed1998

Increased inducible activation of NF-kappaB and responsive genes in astrocytes deficient in the protein tyrosine phosphatase SHP-1.

The protein tyrosine phosphatase SHP-1 is critical for controlling cytokine signaling through the Jak-Stat pathway and, consequently, for controlling inflammatory cellular immune responses dependent on these cytokines. However, the role of SHP-1 in regulating proinflammatory signaling may be incompletely understood, and it may control other distinct inflammatory agents. The present study analyzed the ability of tumor necrosis factor-alpha (TNF-alpha), double-stranded RNA, and interferon-gamma (IFN-gamma) to induce the transcription factor NF-kappaB in astrocytes expressing or lacking SHP-1. On exposure to the inducers, NF-kappaB was markedly increased in astrocytes obtained from motheaten mice lacking SHP-1 compared with normal littermate cells expressing SHP-1, consisted of p50 and p65 subunits, and was induced in a protein synthesis-independent manner. The increased nuclear NF-kappaB expression coincided with elevated loss of the cytoplasmic inhibitor IkappaB alpha in motheaten mouse cells. Enhanced NF-kappaB expression in motheaten mouse cells correlated with increased expression of genes with functional kappaB sites, including IFN regulatory factor-1 (IRF-1) and inducible nitric oxide synthase (iNOS) genes. MHC class I molecules were also increased in motheaten cells, consistent with the increased expression of IRF-1. Together, the data indicate an increased sensitivity of cells lacking SHP-1 to various inducers of NF-kappaB. Therefore, the regulation of not only Stats but also of NF-kappaB by SHP-1 may be important in controlling events promoted by proinflammatory agents in vivo that are especially apparent in multiple tissues of motheaten mice. This study suggests an additional role for SHP-1 in controlling specific and nonspecific immune responses where induction of NF-kappaB is involved.

Animals↗
PubMed1998

Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways.

Many of the protein-protein interactions that are essential for eukaryotic intracellular signal transduction are mediated by protein binding modules including SH2, SH3, and LIM domains. Nck is a SH3- and SH2-containing adaptor protein implicated in coordinating various signaling pathways, including those of growth factor receptors and cell adhesion receptors. We report here the identification, cloning, and characterization of a widely expressed, Nck-related adaptor protein termed Nck-2. Nck-2 comprises primarily three N-terminal SH3 domains and one C-terminal SH2 domain. We show that Nck-2 interacts with PINCH, a LIM-only protein implicated in integrin-linked kinase signaling. The PINCH-Nck-2 interaction is mediated by the fourth LIM domain of PINCH and the third SH3 domain of Nck-2. Furthermore, we show that Nck-2 is capable of recognizing several key components of growth factor receptor kinase-signaling pathways including EGF receptors, PDGF receptor-beta, and IRS-1. The association of Nck-2 with EGF receptors was regulated by EGF stimulation and involved largely the SH2 domain of Nck-2, although the SH3 domains of Nck-2 also contributed to the complex formation. The association of Nck-2 with PDGF receptor-beta was dependent on PDGF activation and was mediated solely by the SH2 domain of Nck-2. Additionally, we have detected a stable association between Nck-2 and IRS-1 that was mediated primarily via the second and third SH3 domain of Nck-2. Thus, Nck-2 associates with PINCH and components of different growth factor receptor-signaling pathways via distinct mechanisms. Finally, we provide evidence indicating that a fraction of the Nck-2 and/or Nck-1 proteins are associated with the cytoskeleton. These results identify a novel Nck-related SH2- and SH3-domain-containing protein and suggest that it may function as an adaptor protein connecting the growth factor receptor-signaling pathways with the integrin-signaling pathways.

3T3 Cells↗
PubMed1998

Effects of dietary vitamin E supplementation on lipid oxidation and volatiles content of irradiated, cooked turkey meat patties with different packaging.

A study was conducted to determine the effects of dietary vitamin E supplementation on the storage stability and volatiles production in irradiated cooked turkey meat. Turkeys, raised with diets containing 25, 50, 75, or 100 IU of dl-alpha-tocopheryl acetate (TA)/kg diet from 1 to 105 d of age, were fed with diets containing 25, 200, 400, or 600 IU of TA/kg diet from 105 to 122 d of age. Breast and leg meat patties were prepared, irradiated at 0 or 2.5 kGy dose, cooked to an internal temperature of 78 C, and stored in either vacuum or aerobic packaging. Thiobarbituric acid reactive substance (TBARS) values gradually decreased as the dietary TA increased and > 200 IU TA/kg diet treatments were helpful in maintaining low TBARS values in irradiated breast and leg meat patties during the 7-d storage period. With vacuum-packaging, irradiated cooked breast patties developed more oxidation than nonirradiated patties but the prooxidant effect of irradiation in cooked leg meat patties was not consistent. In aerobic-packaged cooked meat, irradiated patties had lower TBARS than nonirradiated patties in both breast and leg meat stored in oxygen permeable bags for 7 d. Propanal, pentanal, hexanal, 1-pentanol, and total volatiles were highly correlated with the TBARS values of meat. However, hexanal represented the lipid oxidation status of cooked meat better than any other volatiles component. The amount of hexanal and total volatiles in cooked breast and leg meat shows decreasing trends as dietary TA increased. In vacuum packaging, irradiated breast and leg meat had higher hexanal and total volatiles content than nonirradiated meat at both 0 and 7 d of storage. In aerobic packaging, the amount of hexanal and total volatiles greatly increased in both irradiated and nonirradiated meat patties during the 7-d storage periods. The results illustrated that the antioxidant effect of TA was not strong enough to control lipid oxidation and off-odor generation in cooked meat stored under aerobic conditions because the progress of lipid oxidation in cooked meat under aerobic condition is very rapid. However, the combination of dietary TA and vacuum packaging of cooked meat immediately after cooking could be a good strategy to minimize oxidation and volatiles production in cooked meat.

Animal Feed↗
PubMed1998

Dysprosium-DOTA-PAMAM dendrimers as macromolecular T2 contrast agents. Preparation and relaxometry.

RATIONALE AND OBJECTIVES: The authors have investigated dysprosium [Dy]-DOTA-PAMAM, generation 5 (G = 5) dendrimers as a possible new class of macromolecular T2 contrast agents. The use of DOTA provides a metal complex with greater stability than can be achieved using DTPA as ligand, an important factor in the design of blood pool agents with long half-lives. METHODS: Generation 5 ammonia-core PAMAM dendrimers were linked to the bifunctional ligand p-SCN-Bz-DOTA. After determination of the number of conjugated DOTA molecules by 1H nuclear magnetic resonance, Dy3+ was titrated at a 90% molar ratio. For comparison, single ionic chelates of Dy-DTPA and Dy-DOTA also were prepared. Using a variable field relaxometer, T1 and T2 relaxation times were measured at 13 different field strengths from 0.05 to 1.5 T and temperatures of 3, 10, 20 and 37 degrees C. RESULTS: The synthesis resulted in a preparation with 76 DOTA and 68 Dy3+ ions per dendrimer molecule. The T1 relaxivity values for Dy-DTPA, Dy-DOTA, and the Dy-DOTA-based dendrimer all were independent of field strength, with values between 0.12 and 0.20 mM-1 sec-1. At lower fields (0.05-0.1 T), 1/T2 was identical to 1/T1. At higher fields, however, 1/T2 increased quadratically with field strength, with a strong dependence on temperature. The field-dependent component of 1/T2 was up to three times higher for the Dy-DOTA-based dendrimer compared with the single chelate molecules, with coefficients of 0.37 to 0.03 sec-1/Tesla2 for T = 3 to 37 degrees C. CONCLUSIONS: The results are interpreted with the "inner sphere" theory of susceptibility effects (Curie spin relaxation). The large temperature dependence suggests that the dominant mechanism of relaxation is the contact interaction effect, with the proton residence time as the primary time constant. This largely unexplored relaxation mechanism has the potential to create a new class of T2-selective contrast agents.

Contrast Media↗
PubMed1998

Pseudomonas aeruginosa invasion and cytotoxicity are independent events, both of which involve protein tyrosine kinase activity.

Pseudomonas aeruginosa clinical isolates exhibit invasive or cytotoxic phenotypes. Cytotoxic strains acquire some of the characteristics of invasive strains when a regulatory gene, exsA, that controls the expression of several extracellular proteins, is inactivated. exsA mutants are not cytotoxic and can be detected within epithelial cells by gentamicin survival assays. The purpose of this study was to determine whether epithelial cell invasion precedes and/or is essential for cytotoxicity. This was tested by measuring invasion (gentamicin survival) and cytotoxicity (trypan blue staining) of PA103 mutants deficient in specific exsA-regulated proteins and by testing the effect of drugs that inhibit invasion for their effect on cytotoxicity. A transposon mutant in the exsA-regulated extracellular factor exoU was neither cytotoxic nor invasive. Furthermore, several of the drugs that inhibited invasion did not prevent cytotoxicity. These results show that invasion and cytotoxicity are mutually exclusive events, inversely regulated by an exsA-encoded invasion inhibitor(s). Both involve host cell protein tyrosine kinase (PTK) activity, but they differ in that invasion requires Src family tyrosine kinases and calcium-calmodulin activity. PTK inhibitor drugs such as genistein may have therapeutic potential through their ability to block both invasive and cytotoxicity pathways via an action on the host cell.

Animals↗