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Biomedical subjects

J C Chow

Publications and source records attributed to J C Chow.

At least 19 recordsLinked to original sources
PubMed2002

Ectopic XIST transcripts in human somatic cells show variable expression and localization.

XIST encodes a functional RNA that is expressed exclusively from the inactive X in female mammals and is required for the silencing of most of the genes on the chromosome. XIST transcripts remain in the nucleus, and their specific localization to the inactive X is important for silencing; however, it is not known how these transcripts localize to the inactive X chromosome. Expression of mouse and human XIST from ectopic sites has suggested that localization to the chromosome from which the gene is expressed may be dependent upon either the copy number of the integrated constructs or the level of ectopic XIST expression. To further examine the behavior of XIST transgenes when expressed from ectopic sites, we introduced an XIST-containing PAC into the human male somatic cell line HT-1080. In five different transformant clones, the degree of localization and associated DNA condensation of the surrounding chromatin varied within nuclei of the same clone, as well as among different clones. Comparing the number of integrated transgenes and the levels of XIST expression revealed that neither factor was sufficient for a tight localization of the XIST signal. Therefore, the extent of expression and localization of XIST transcripts from ectopic transgenes is likely dependent upon many interacting factors, including the number of integrated transgenes, the level of XIST expression, and the site of integration.

Gene Expression↗
PubMed2001

Source characterization of major emission sources in the imperial and Mexicali Valleys along the US/Mexico border.

Chemical profiles for particle emissions are needed for source apportionment studies using the chemical mass balance (CMB) receptor model. Source measurements of geological sources, motor vehicle exhaust, vegetative burning (e.g. asparagus, field burning, charbroil cooking), and industrial sources (e.g. oil-fueled glass plant, manure-fueled power plants) were acquired as part of the Imperial/Mexicali Valley Cross Border PM10 Transport Study in 1992. Six different source sampling techniques (i.e. hot- and diluted-exhaust sampling, ground-based source sampling, particle sweeping/grab sampling, vacuum sampling, and laboratory resuspension sampling) were applied to acquire filter samples of PM 2.5 and PM10 (particulate matter with aerodynamic diameters < 2.5 and 10 microm, respectively). Filter samples were analyzed for mass by gravimetry, elements (Na to U) by X-ray fluorescence, anions (Cl(-), NO3(-), SO4(=)) by ion chromatography, ammonium (NH4(+)) by automated colorimetry, soluble sodium (Na+) and potassium (K+) by atomic absorption spectrophotometry, and organic and elemental carbon (OC, EC) by thermal/optical reflectance. Concentration data were acquired for a total of approximately 50 chemical species. Elevated abundances of crustal components (Al, Si, K, Ca, Fe) from geological material, carbon (OC, EC) and trace elements (Br, Pb) from vehicle exhausts, carbon (OC, EC) and ions (K(+), Cl(-)) from vegetative burning, ions (SO4(=), NH4(+), Na(+), K(+), Cl(-)) and elements (Cl, Se) from a manure-fueled power plants, and sulfur and trace elements (Na(+), Pb, Se, Ni, V) from an oil-fueled glass plant were found in the resulting source profiles. Abundances of crustal species (e.g. Al, Si, Ca) in the Imperial/Mexicali Valley geological profiles are more than twice those found in central and southern California. Abundances of lead in motor vehicle exhausts indicate different vehicle fleets in border cities. Emission profiles from field burning and charbroil cooking specific to the border area show that a majority (>60%) of emissions are comprised of carbon, with high organic to total carbon ratios (0.93 to 0.97). Abundances of sulfate and ammonium account for nearly 60% of the manure-fueled power plant's emissions. Elevated levels of metals (Na(+), Pb, Cd, Se) and byproducts of petroleum combustion (S, Ni, V) were found in the oil-fueled glass plant's emissions.

Air Movements↗
PubMed2001

Zones of representation for PM10 measurements along the US/Mexico border.

The 'Imperial/Mexicali Valley Cross-Border PM10 Transport Study' acquired a database of meteorological and air quality measurements to determine source contributions to elevated PM10 concentrations and to estimate transport of PM10 between the US and Mexico. The study was conducted from 13 March 1992 to 29 August 1993, in a 80-km long by 20-km wide area spanning the US/Mexico border approximately 200 km inland from the coast of the Pacific Ocean, with monitoring sites located in the Imperial Valley on the US side and in the Mexicali Valley on the Mexico side. Measurements of PM 10 (particles with aerodynamic diameters less than 10 microm) mass, elements, water-soluble cations (i.e. sodium, potassium, ammonium) and anions (i.e. chloride, nitrate, sulfate), organic and elemental carbon and particle light absorption were acquired at two base sites on an every-sixth-day schedule supplemented by daily monitoring during winter and 4 times per day monitoring during intensive periods. Measurements were also taken at as many as 30 neighborhood (satellite) sites during week-long intensive monitoring periods in spring, summer and winter. This paper examines the zones of representation of long-term PM10 monitors by comparing their measurements with those from a spatially dense network of satellite sites. PM10 concentrations at the Mexicali site were consistently 30 to 50% higher than those observed at the Calexico site, even though the two sites were only 12 km apart. Distinct diurnal variations were found, with 6-h average PM10 concentrations often varying by a factor of 2 throughout the day - lowest during afternoon (12.00-18.00 h PST) and highest during night time (18.00-24.00 h PST). On average, crustal material accounted for 32-35% of annual-average PM10, carbonaceous aerosol for 20-30%, and ionic species for 8-10%. Levels of trace elements and sea salt were in the range of 1-4% of PM10. Significant concentration variations were found within the study area. PM10 concentrations in Mexico were double those in the US, decreasing with increasing northerly distance.

Air Movements↗
PubMed2001

Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling.

Somatic cell mutagenesis is a powerful tool for characterizing receptor systems. We reported previously two complementation groups of mutant cell lines derived from CD14-transfected Chinese hamster ovary--K1 fibroblasts defective in responses to bacterial endotoxin. Both classes of mutants expressed a normal gene product for Toll-like receptor (TLR)4, and fully responded to stimulation by tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 beta. We identified the lesion in one of the complementation groups in the gene for MD-2, a putative TLR4 coreceptor. The nonresponder phenotype of this mutant was reversed by transfection with MD-2. Cloning of MD-2 from the nonresponder cell line revealed a point mutation in a highly conserved region resulting in a C95Y amino acid exchange. Both forms of MD-2 colocalized with TLR4 on the cell surface after transfection, but only the wild-type cDNA reverted the lipopolysaccharide (LPS) nonresponder phenotype. Furthermore, soluble MD-2, but not soluble MD-2(C95Y), functioned to enable LPS responses in cells that expressed TLR4. Thus, MD-2 is a required component of the LPS signaling complex and can function as a soluble receptor for cells that do not otherwise express it. We hypothesize that MD-2 conformationally affects the extracellular domain of TLR4, perhaps resulting in a change in affinity for LPS or functioning as a portion of the true ligand for TLR4.

Animals↗
PubMed2001

The extra domain A of fibronectin activates Toll-like receptor 4.

Cellular fibronectin, which contains an alternatively spliced exon encoding type III repeat extra domain A (EDA), is produced in response to tissue injury. Fragments of fibronectin have been implicated in physiological and pathological processes, especially tissue remodeling associated with inflammation. Because EDA-containing fibronectin fragments produce cellular responses similar to those provoked by bacterial lipopolysaccharide (LPS), we examined the ability of recombinant EDA to activate Toll-like receptor 4 (TLR4), the signaling receptor stimulated by LPS. We found that recombinant EDA, but not other recombinant fibronectin domains, activates human TLR4 expressed in a cell type (HEK 293 cells) that normally lacks this Toll-like receptor. EDA stimulation of TLR4 was dependent upon co-expression of MD-2, a TLR4 accessory protein. Unlike LPS, the activity of EDA was heat-sensitive and persisted in the presence of the LPS-binding antibiotic polymyxin B and a potent LPS antagonist, E5564, which completely suppressed LPS activation of TLR4. These observations provided a mechanism by which EDA-containing fibronectin fragments promote expression of genes involved in the inflammatory response.

Animals↗
PubMed2001

A confirmatory factor analysis of the BASIS-32 in racial and ethnic samples.

The present study performed confirmatory factor analysis across major racial and ethnic groups of the BASIS-32, a measure of functional status of persons receiving mental health treatment and suitable for routine assessment mental health care. The purpose was to perform a preliminary investigation of cross-cultural equivalence in a county-level mental health program in a major metropolitan area. The results indicated a factor structure similar to that reported in the literature, and they suggested acceptable levels of agreement in structure between racial and ethnic minority groups and whites. The study revealed little reason to believe that the BASIS-32 varied in underlying structure across racial and ethnic boundaries, although further research is indicated.

Adult↗
PubMed2001

PM2.5 chemical source profiles for vehicle exhaust, vegetative burning, geological material, and coal burning in Northwestern Colorado during 1995.

PM2.5 (particles with aerodynamic diameters less than 2.5 microm) chemical source profiles applicable to speciated emissions inventories and receptor model source apportionment are reported for geological material, motor vehicle exhaust, residential coal (RCC) and wood combustion (RWC), forest fires, geothermal hot springs; and coal-fired power generation units from northwestern Colorado during 1995. Fuels and combustion conditions are similar to those of other communities of the inland western US. Coal-fired power station profiles differed substantially between different units using similar coals, with the major difference being lack of selenium in emissions from the only unit that was equipped with a dry limestone sulfur dioxide (SO2) scrubber. SO2 abundances relative to fine particle mass emissions in power plant emissions were seven to nine times higher than hydrogen sulfide (H2S) abundances from geothermal springs, and one to two orders of magnitude higher than SO2 abundances in RCC emissions, implying that the SO2 abundance is an important marker for primary particle contributions of non-aged coal-fired power station contributions. The sum of organic and elemental carbon ranged from 1% to 10% of fine particle mass in coal-fired power plant emissions, from 5% to 10% in geological material, >50% in forest fire emissions, >60% in RWC emissions, and >95% in RCC and vehicle exhaust emissions. Water-soluble potassium (K+) was most abundant in vegetative burning profiles. K+/K ratios ranged from 0.1 in geological material profiles to 0.9 in vegetative burning emissions, confirming previous observations that soluble potassium is a good marker for vegetative burning.

Air Pollutants↗
PubMed2001

Sources of PM10 and sulfate aerosol at McMurdo Station, Antarctica.

Source contributions to PM10 and sulfate aerosol at McMurdo Station, Antarctica during the austral summers of 1995-1996 and 1996-1997 were estimated using Chemical Mass Balance (CMB) receptor modeling. The average PM10 (particles with aerodynamic diameters less than 10 microm) concentration at Hut Point, located less than 1 km downwind of downtown McMurdo, was 3.4 microg/m3. Emissions profiles were determined for potentially important aerosol source types in McMurdo: exposed soil, power generation, space heating, and surface vehicles. Soil dust, sea salt, combustion emissions, sulfates, marine biogenic emissions as methanesulfonate, and nitrates contributed 57%, 15%, 14%, 10%, 3%, and 1%, respectively, of average estimated PM10 at Hut Point (3.2 microg/m3). Soil dust, sea salt, and combustion sources contributed 12%, 8%, and 20%, respectively, of the average PM10 sulfate concentration of 0.46 microg/m3. Marine biogenic sources contributed 0.17 microg/m3 (37%). The remaining sulfate is thought to have come from emissions from Mt. Erebus or hemispheric pollution sources.

Aerosols↗
PubMed2001

PM2.5 and PM10 concentrations from the Qalabotjha low-smoke fuels macro-scale experiment in South Africa.

This article presents results from the particulate monitoring campaign conducted at Qalabotjha in South Africa during the winter of 1997. Combustion of D-grade domestic coal and low-smoke fuels were compared in a residential neighborhood to evaluate the extent of air quality improvement by switching household cooking and heating fuels. Comparisons are drawn between the gravimetric results from the two types of filter substrates (Teflon-membrane and quartz-fiber) as well as between the integrated and continuous samplers. It is demonstrated that the quartz-fiber filters reported 5 to 10% greater particulate mass than the Teflon-membrane filters, mainly due to the adsorption of organic gases onto the quartz-fiber filters. Due to heating of sampling stream to 50 degrees C in the TEOM continuous sampler and the high volatile content of the samples, approximately 15% of the particulate mass was lost during sampling. The USEPA 24-hr PM2.5 and PM10 National Ambient Air Quality Standards (NAAQS) of 65 microg m(-3) and 150 microg m(-3), respectively, were exceeded on several occasions during the 30-day field campaign. Average PM concentrations are highest when D-grade domestic coal was used, and lowest between day 11 and day 20 of the experiment when a majority of the low-smoke fuels were phased in. Source impacts from residential coal combustion are also found to be influenced by changes in meteorology, especially wind velocity. PM2.5 and PM10 mass, elements, water-soluble cations (sodium, potassium, and ammonium), anions (chloride, nitrate, and sulfate), as well as organic and elemental carbon were measured on 15 selected days during the field campaign. PM2.5 constituted more than 85% of PM10 at three Qalabotjha residential sites, and more than 70% of PM10 at the gradient site in the adjacent community of Villiers. Carbonaceous aerosol is by far the most abundant component, accounting for more than half of PM mass at the three Qalabotjha sites, and for more than a third of PM mass at the gradient site. Secondary aerosols such as sulfate, nitrate, and ammonium are also significant, constituting 8 to 12% of PM mass at the three Qalabotjha sites and 15 to 20% at the Villiers gradient site.

Aerosols↗
PubMed2001

Arthroscopic osteochondral transplantation: Histologic results.

PURPOSE: Localized, full-thickness articular cartilage defects of the femoral condyle are challenging. This report presents the histology of clinical cases obtained at intervals from 2 to 12 months after arthroscopic osteochondral transplantation. TYPE OF STUDY: Longitudinal cohort study. METHODS: Patients found at arthroscopy to have full-thickness femoral condyle defects between 1 and 3.5 cm in diameter underwent arthroscopic osteochondral transplantation. Exclusion criteria were associated tibial defects, patellar defects, or generalized arthritic change. The grafts taken from the superior and lateral intercondylar femoral notch were press-fit into holes drilled into the defect starting adjacent to the articular cartilage margin. Cancellous bone bridges were maintained between grafts. At various time intervals from 2 to 12 months after the osteochondral transplantation, arthroscopic biopsy specimens of the recipient sites were obtained. RESULTS: Ten patients (5 male, 5 female) enrolled at 2 centers were evaluated arthroscopically at various intervals up to 13 months after osteochondral transplantation. The average patient age was 40 years (range, 17 to 65 years). One to 3 plugs had been harvested and inserted. Seven patients underwent biopsy at intervals ranging up to 12 months postoperatively. All showed maintenance of the integrity of the grafts with living chondrocytes and osteocytes. Donor sites filled without grafting and were covered with fibrocartilagenous scar. No complications occurred in this group. CONCLUSIONS: These histologic results suggest that arthroscopic osteochondral transplantation is a viable alternative for treating full-thickness chondral defects, with the grafts retaining their integrity and living chondrocytes and osteocytes observed in the grafts for up to 12 months after implantation.

Adolescent↗
PubMed2001

Black carbon aerosol at McMurdo Station, Antarctica.

Aerosol light absorption as black carbon (BC) was measured from November 19, 1995, to February 6, 1996, at a location 0.65 km downwind of the center of McMurdo Station on the Antarctic coast. The results show a bimodal frequency distribution of BC concentrations. Approximately 65% of the measurements were found in a mode at a low range of concentrations centered at approximately 20 ng/m3. These concentrations are higher than those found at other remote Antarctic locations and probably represent contamination from the station. The remaining measurements were in a high-concentration mode (BC approximately 300 ng/m3), indicating direct impact of local emissions from combustion activities at the station. High values of BC were associated with winds from the direction of the station, and the BC flux showed a clear directionality. Maximum BC concentrations occurred between 7:00 and 11:00 a.m. The "polluted" mode accounted for more than 80% of the BC frequency-weighted impact at this location.

Aerosols↗
PubMed2001

Estimating middle-, neighborhood-, and urban-scale contributions to elemental carbon in Mexico City with a rapid response aethalometer.

A successive moving average subtraction method is developed and applied to black carbon measured over 5-min intervals at a downtown location near many small emitters and at a suburban residential site within the urban plume but distant from specific emitters. Short-duration pulses assumed to originate from nearby sources are subtracted from the concentrations at each site and are summed to estimate middle-scale (approximately 0.1-1 km) contributions. The difference of the remaining baselines at the urban and suburban monitors is interpreted as the contribution to the downtown monitor from source emissions mixed over a neighborhood scale (1-5 km). The baseline at the suburban site is interpreted as the contribution of the mixture of black carbon sources for the entire city. When applied to a 24-day period from February and March 1997 in Mexico City, the analysis showed that 65% of the 24-hr black carbon was part of the urban mixture, 23% originated in the neighborhood surrounding the monitor, and only 12% was contributed from nearby sources. These analyses indicate that a fixed-site monitor can reasonably represent exposures in its surrounding neighborhood even when many local sources, such as exhaust from diesel buses and trucks, affect the monitor.

Air Pollutants↗
PubMed2001

Sustained endotoxemia leads to marked down-regulation of early steps in the insulin-signaling cascade.

OBJECTIVES: To determine the effects of sustained, 3-day endotoxin infusion on early steps of the insulin-signaling pathway in rat liver and skeletal muscle in vivo; to examine insulin signaling in well-established acute endotoxin models of insulin resistance. DESIGN: Prospective, controlled animal study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats: 24 in the 3-day endotoxin study, 22 in each acute endotoxin study. INTERVENTIONS: In prolonged endotoxemia studies, endotoxin (1 mg.kg-1.24 hrs-1) was administered via jugular venous catheter for 74 hrs. Insulin was then injected, and liver and skeletal muscle were removed after 5 mins. In acute endotoxemia studies, an endotoxin bolus (1 mg/kg) was administered, and insulin-signaling responses were studied after 4 hrs. MEASUREMENTS AND MAIN RESULTS: In liver of rats with sustained endotoxemia, there were significant decreases in insulin-stimulated tyrosine phosphorylation of insulin receptors (74%), insulin receptor substrate (IRS)-1 (74%), and IRS2 (53%); binding of the p85 subunit of phosphatidylinositide 3-kinase to IRS1 (80%); and IRS1-precipitable phosphatidylinositide 3-kinase activity (>90%). These findings were associated with significant reductions in abundance of insulin receptors (37%), IRS1 (60%), and IRS2 (23%). Signaling in skeletal muscle was similarly affected, with reduced IRS1 phosphorylation (49%), IRS1 abundance (50%), and binding of p85 to IRS1 (57%). Insulin signaling 4 hrs after endotoxin administration was not different from controls. CONCLUSIONS: Prolonged endotoxemia is associated with marked deficits in early steps of the insulin-signaling pathway, which are at least partly explained by reduced abundance of the insulin receptor and IRS proteins. Signaling defects were not evident 4 hrs after endotoxin administration under conditions of adequate nutrition, indicating that insulin resistance develops gradually, may require concomitant malnutrition, and is not reversed by the development of endotoxin tolerance.

Analysis of Variance↗
PubMed2000

A novel synthetic acyclic lipid A-like agonist activates cells via the lipopolysaccharide/toll-like receptor 4 signaling pathway.

ER-112022 is a novel acyclic synthetic lipid A analog that contains six symmetrically organized fatty acids on a noncarbohydrate backbone. Chinese hamster ovary (CHO)-K1 fibroblasts and U373 human astrocytoma cells do not respond to lipopolysaccharide (LPS) in the absence of CD14. In contrast, exposure to ER-112022 effectively induced activation of CHO and U373 cells under serum-free conditions. Expression of CD14 was not necessary for cells to respond to ER-112022, although the presence of soluble CD14 enhanced the sensitivity of the response. Several lines of evidence suggested that ER-112022 stimulates cells via the LPS signal transduction pathway. First, the diglucosamine-based LPS antagonists E5564 and E5531 blocked ER-112022-induced stimulation of CHO-K1, U373, and RAW264.7 cells. Second, ER-112022 was unable to activate C3H/HeJ mouse peritoneal macrophages, containing a mutation in Toll-like receptor (TLR) 4, as well as HEK293 cells, an epithelial cell line that does not express TLR4. Third, ER-112022 activated NF-kappaB in HEK293 cells transfected with TLR4/MD-2. Finally, tumor necrosis factor release from primary human monocytes exposed to ER-112022 was blocked by TLR4 antibodies but not by TLR2 antibodies. Our results suggest that ER-112022 and the family of lipid A-like LPS antagonists can functionally associate with TLR4 in the absence of CD14. Synthetic molecules like ER-112022 may prove to be valuable tools to characterize elements in the LPS receptor complex, as well as to activate or inhibit the TLR4 signaling pathway for therapeutic purposes.

Animals↗
PubMed2000

Cellular events mediated by lipopolysaccharide-stimulated toll-like receptor 4. MD-2 is required for activation of mitogen-activated protein kinases and Elk-1.

Lipopolysaccharide (LPS) stimulates multiple signaling events, including nuclear factor-kappaB (NF-kappaB) activity and the mitogen-activated protein (MAP) kinases, ERK, JNK, and p38 in LPS-responsive cells, resulting in transcriptional activation and cytokine generation. LPS-induced signaling via toll-like receptor 4 (TLR4) results in the activation of the transcription factor NF-kappaB. Since LPS activates other signaling cascades in responsive cells, the objective of this study was to determine whether such events are mediated by TLR4 in response to LPS. We generated human embryonic kidney cells (HEK293) that stably express TLR4 (HEK-TLR4) and examined their responsiveness to LPS by measuring NF-kappaB activity and production of interleukin-8 (IL-8). A trans-reporting system was used to measure the activity of Elk-1, an ETS-domain transcription factor targeted by MAP kinase pathways. LPS stimulated NF-kappaB reporter activity and IL-8 production but not Elk-1 activity in HEK-TLR4 cells. When MD-2, a protein associated with the extracellular domain of TLR4, was expressed in these cells, there was a marked increase in Elk-1 activity as well as ERK, JNK, and p38 MAP kinase phosphorylation in response to LPS. TLR4-mediated NF-kappaB reporter activity and IL-8 production was enhanced by the expression of MD-2. This study demonstrates that expression of both TLR4 and MD-2 is required for LPS to activate or augment the MAP kinase pathways, Elk-1 stimulation, and IL-8 generation.

Antigens, Surface↗