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Biomedical subjects

J C Chow

Publications and source records attributed to J C Chow.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Air quality measurements from the Fresno Supersite.

The Fresno Supersite intends to 1) evaluate non-routine monitoring methods, establishing their comparability with existing methods and their applicability to air quality planning, exposure assessment, and health effects studies; 2) provide a better understanding of aerosol characteristics, behavior, and sources to assist regulatory agencies in developing standards and strategies that protect public health; and 3) support studies that evaluate relationships between aerosol properties, co-factors, and observed health end-points. Supersite observables include in-situ, continuous, short-duration measurements of 1) PM2.5, PM10, and coarse (PM10 minus PM2.5) mass; 2) PM2.5 SO4(-2), NO3-, carbon, light absorption, and light extinction; 3) numbers of particles in discrete size bins ranging from 0.01 to approximately 10 microns; 4) criteria pollutant gases (O3, CO, NOx); 5) reactive gases (NO2, NOy, HNO3, peroxyacetyl nitrate [PAN], NH3); and 6) single particle characterization by time-of-flight mass spectrometry. Field sampling and laboratory analysis are applied for gaseous and particulate organic compounds (light hydrocarbons, heavy hydrocarbons, carbonyls, polycyclic aromatic hydrocarbons [PAH], and other semi-volatiles), and PM2.5 mass, elements, ions, and carbon. Observables common to other Supersites are 1) daily PM2.5 24-hr average mass with Federal Reference Method (FRM) samplers; 2) continuous hourly and 5-min average PM2.5 and PM10 mass with beta attenuation monitors (BAM) and tapered element oscillating microbalances (TEOM); 3) PM2.5 chemical speciation with a U.S. Environmental Protection Agency (EPA) speciation monitor and protocol; 4) coarse particle mass by dichotomous sampler and difference between PM10 and PM2.5 BAM and TEOM measurements; 5) coarse particle chemical composition; and 6) high sensitivity and time resolution scalar and vector wind speed, wind direction, temperature, relative humidity, barometric pressure, and solar radiation. The Fresno Supersite is coordinated with health and toxicological studies that will use these data in establishing relationships with asthma, other respiratory disease, and cardiovascular changes in human and animal subjects.

Aerosols↗
PubMed2000

Aqueous humor nitric oxide levels differ in patients with different types of glaucoma.

Nitric oxide (NO) has effects on the regulation of aqueous humor dynamics, but the exact mechanism is not yet established. To investigate the possible roles of NO in glaucoma, we determined NO levels in aqueous humor and plasma in glaucoma patients and a control group, cataract patients. The study is an open trial with purposed sampling. One hundred fifty-two patients, including 87 glaucoma patients and 65 cataract patients from two medical centers, were recruited. NO levels in the samples were measured by a chemiluminescence assay. We found that, although the mean aqueous humor NO level (mean +/- SEM) was higher in the glaucoma patients than in the cataract patients (39.7 +/- 1.5 microM vs. 35.5 +/- 1.3 microM, p < 0.05), NO levels varied significantly in different types of glaucoma. The juvenile glaucoma patients had the lowest mean NO level (8.4 +/- 0.9 microM), while the acute angle-closure glaucoma and neovascular glaucoma patients had the highest mean NO levels (64.8 +/- 7.6 microM, 67.3 +/- 8.2 microM). In comparison, the mean plasma NO level in the glaucoma patients was not statistically different from that in the cataract patients (14.1 +/- 1.2 microM vs. 13.9 +/- 1.1 microM, p = 0.91). Our data may provide information for applying NO-mimicking nitrovasodilators in the treatment of glaucoma.

Aged↗
PubMed2000

Examination of chlorpromazine and other amphipathic drugs on the activity of lipopolysaccharide antagonists, E5564 and E5531.

The synthetic antagonists of lipopolysaccharide (LPS), E5531 and E5564, are analogs of the lipid A portion of LPS that not only lack agonistic activity but also inhibit the biological effects of LPS both in vitro and in vivo. The effects of LPS and these synthetic antagonists have been localized to the recently described Toll-like receptor 4 (TLR4). A recent report indicated that the naturally occurring LPS antagonist Rhodobacter sphaeroides LPS loses its antagonist properties and gains pro-inflammatory qualities in the presence of chlorpromazine and other amphipathic drugs. To determine whether these reported actions occur with our chemically defined LPS antagonists, we examined the effects of chlorpromazine, fluphenazine, trifluoperazine, and lidocaine on the antagonism elicited by RsLPS and E5531 in U373 cells, which produce IL-6 in response to LPS. We also tested the effects of these amphipathic molecules on the LPS-neutralizing activity of RsLPS and E5564 on LPS-induced TNF-alpha release in human whole blood. The results indicate that neither chlorpromazine, fluphenazine, trifluoperazine nor lidocaine alter the activity of E5531 or E5564 in an in vitro cell system or human whole blood. Furthermore, chlorpromazine did not affect the antagonistic activity of RsLPS or E5564 on IL-6 generation by peripheral blood mononuclear cells. Thus, based on these data, our purified synthetic LPS-antagonists do not appear to lose their antagonistic properties and/or become agonists in the presence of amphipathic agents or drugs.

Adolescent↗
PubMed1999

Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction.

TLR4 is a member of the recently identified Toll-like receptor family of proteins and has been putatively identified as Lps, the gene necessary for potent responses to lipopolysaccharide in mammals. In order to determine whether TLR4 is involved in lipopolysaccharide-induced activation of the nuclear factor-kappaB (NF-kappaB) pathway, HEK 293 cells were transiently transfected with human TLR4 cDNA and an NF-kappaB-dependent luciferase reporter plasmid followed by stimulation with lipopolysaccharide/CD14 complexes. The results demonstrate that lipopolysaccharide stimulates NF-kappaB-mediated gene expression in cells transfected with the TLR4 gene in a dose- and time-dependent fashion. Furthermore, E5531, a lipopolysaccharide antagonist, blocked TLR4-mediated transgene activation in a dose-dependent manner (IC50 approximately 30 nM). These data demonstrate that TLR4 is involved in lipopolysaccharide signaling and serves as a cell-surface co-receptor for CD14, leading to lipopolysaccharide-mediated NF-kappaB activation and subsequent cellular events.

Animals↗
PubMed1999

Endoscopic release of the carpal ligament for carpal tunnel syndrome: long-term results using the Chow technique.

This report presents the author's experience with the Chow method for endoscopic release of the carpal ligament for carpal tunnel syndrome, with a minimum follow-up of 5 years. The report includes 116 cases (wrists) of 84 patients. The success rate for these cases is 93.3% and the recurrence rate is 0.96%. One temporary ulnar neuropraxia was reported in this group with spontaneous recovery. There were no permanent nerve injuries. Results of 5-year follow-up nerve conduction velocity tests are also included. This report shows that endoscopic release of the carpal ligament for carpal tunnel syndrome, using the Chow method, is a reliable alternative to the open procedure and has produced good, long-term, results.

Adult↗
PubMed1999

Use of public mental health services by Russian refugees.

OBJECTIVES: This study identifies the demographic characteristics and patterns of mental health service use among Russian refugees in New York State. METHODS: Data from a 1995 statewide survey of characteristics of patients served by the New York State mental health system were analyzed using chi square statistics and logistic regression. RESULTS: The demographic characteristics and service-use patterns of Russian refugees are different from those of non-Russian refugees and non-refugees. Russian refugees who used mental health services were likely to be older women with major depression who were enrolled in Medicaid and who were using those services for the first time. Relying heavily on themselves, family members, or friends as referral sources, they tended to use exclusively individual, outpatient services at voluntary, nonprofit agencies. CONCLUSIONS: Existing services systems must recognize the presence of Russian refugees. To improve access and service use, outreach efforts to the refugee community should be conducted, and services must be tailored to meet their mental health needs.

Adult↗
PubMed1998

Stabilization and localization of Xist RNA are controlled by separate mechanisms and are not sufficient for X inactivation.

These studies address whether XIST RNA is properly localized to the X chromosome in somatic cells where human XIST expression is reactivated, but fails to result in X inactivation (Tinker, A.V., and C.J. Brown. 1998. Nucl. Acids Res. 26:2935-2940). Despite a nuclear RNA accumulation of normal abundance and stability, XIST RNA does not localize in reactivants or in naturally inactive human X chromosomes in mouse/ human hybrid cells. The XIST transcripts are fully stabilized despite their inability to localize, and hence XIST RNA localization can be uncoupled from stabilization, indicating that these are separate steps controlled by distinct mechanisms. Mouse Xist RNA tightly localized to an active X chromosome, demonstrating for the first time that the active X chromosome in somatic cells is competent to associate with Xist RNA. These results imply that species-specific factors, present even in mature, somatic cells that do not normally express Xist, are necessary for localization. When Xist RNA is properly localized to an active mouse X chromosome, X inactivation does not result. Therefore, there is not a strict correlation between Xist localization and chromatin inactivation. Moreover, expression, stabilization, and localization of Xist RNA are not sufficient for X inactivation. We hypothesize that chromosomal association of XIST RNA may initiate subsequent developmental events required to enact transcriptional silencing.

Animals↗
PubMed1998

Insulin-like growth factor-I receptor internalization regulates signaling via the Shc/mitogen-activated protein kinase pathway, but not the insulin receptor substrate-1 pathway.

Insulin-like growth factor-I (IGF-I) receptors activate divergent signaling pathways by phosphorylating multiple cellular proteins, including insulin receptor substrate-1 (IRS-1) and the Shc proteins. Following hormone binding, IGF-I receptors cluster into clathrin-coated pits and are internalized via an endocytotic mechanism. This study investigates the relationship between IGF-I receptor internalization and signaling via IRS-1 and Shc. A mutation in the C terminus of the IGF-I receptor decreased both the rate of receptor internalization and IGF-I-stimulated Shc phosphorylation by more than 50%, but did not affect IRS-1 phosphorylation. Low temperature (15 degrees C) decreased IGF-I receptor internalization and completely inhibited Shc phosphorylation. Although receptor and IRS-1 phosphorylation were decreased in accordance with delayed binding kinetics at 15 degrees C, the ratio of IRS-1 to receptor phosphorylation was increased more than 2-fold. Dansylcadaverine decreased receptor internalization and Shc phosphorylation, but did not change receptor or IRS-1 phosphorylation. Consistent with these findings, dansylcadaverine inhibited IGF-I-stimulated Shc-Grb2 association, mitogen-activated protein kinase phosphorylation, and p90 ribosomal S6 kinase activation, but did not affect the association of phosphatidylinositide 3-kinase with IRS-1 or activation of p70 S6 kinase. These data support the concept that Shc/mitogen-activated protein kinase pathway activation requires IGF-I receptor internalization, whereas the IRS-1 pathway is activated by both cell surface and endosomal receptors.

Animals↗
PubMed1998

Effects of dietary protein and tumor necrosis factor on components of the insulin-like growth factor-I pathway in the colon and small intestine in protein-depleted rats.

Intestinal cell growth is markedly affected by nutrient intake and the presence of cytokines. Since insulin-like growth factor-I (IGF-I) is an important hormone regulator of intestinal proliferation, this study examined the effects of dietary protein content and tumor necrosis factor (TNF) on mRNA levels of IGF-I, IGF-I receptor, IGF binding protein-3 (IGFBP-3), and IGFBP-4 and on the histology of the colon, jejunum, and ileum in protein-malnourished rats. After 2 weeks of feeding a 2% casein diet, rats continued on the 2% casein diet or were refed with a 20% casein diet and received daily intraperitoneal injections of either TNF (50 microg/kg) or saline for 4 days. The abundance of mRNA in the intestine was determined by RNA dot-blot analysis, and morphology measurements were performed by light microscopy. Simultaneous refeeding with the 20% casein diet and administration of TNF led to a modest increase in IGF-I and IGFBP-4 mRNA abundance in the colon. However, in the jejunum and ileum, refeeding had no effect but TNF caused a decrease in IGF-I and IGFBP-3 mRNA levels in malnourished rats. Refeeding with the 20% casein diet resulted in relatively modest histologic changes, which were greater in the colon versus the small intestine. The decreased magnitude of histologic changes in the order of the colon, ileum, and jejunum may reflect a response to a gradient of amino acid availability from intraluminal nutrients. These data demonstrate that TNF has distinct effects on colon and small intestine mRNA, but these mild changes had only a slight impact in the colon and did not translate into identifiable histologic changes in the small intestine. Combined protein restriction and TNF administration had only a modest effect on intestinal mRNA levels and mucosal histology.

Animals↗
PubMed1998

Particulate emission rates for unpaved shoulders along a paved road.

This paper reports the first empirical estimate of particle emissions from unpaved shoulders along paved roads. Its objectives are to develop and demonstrate an emission rate measurement methodology that can be applied in different areas; identify the mechanisms that suspend dust from unpaved shoulders and the observables related to this suspension process; and quantify PM10 mass emissions in the form of an emission rate. To achieve these objectives, fast-response observations from nephelometers and a sonic anemometer were used to characterize short-lived dust plumes generated by passing vehicles. In addition, detailed soil surface measurements determined the mechanical properties of the shoulder surfaces. Large traffic-induced turbulence events that led to significant dust entrainment were almost exclusively caused by "large" vehicles such as trucks, semis, and vehicles pulling trailers, all traveling 50-65 mph. PM10 emission rates for these large, fast-traveling vehicles were determined to be 8 +/- 4 grams per vehicle kilometer traveled under dry conditions. Emissions due to smaller vehicles such as cars, vans, and sport utility vehicles were negligible for normal on-road driving. These results indicate that the majority of PM10 emissions from unpaved shoulders is caused by relatively few vehicles.

Air Movements↗
PubMed1998

Leptin signaling in the hypothalamus of normal rats in vivo.

Leptin has been shown to activate multiple signaling molecules in cultured cells, including Janus kinase-2, STAT (signal transducer and activator of transcription) proteins, and mitogen-activated protein kinase, and to stimulate the DNA-binding activity of STAT3 in mouse hypothalamus. In this study, the activation of candidate leptin signaling molecules in the hypothalamus of normal rats in vivo was investigated. Fasted male Sprague-Dawley rats were injected iv with recombinant murine leptin or vehicle. Plasma leptin concentrations were determined at defined time points, and the phosphorylation of signaling proteins was assessed in hypothalamic lysates. There was a marked increase in plasma leptin concentration at 2 min and a gradual decline by 45 min after leptin injection. Immunoblotting analysis of hypothalamic lysates with a phosphospecific STAT3 antibody demonstrated a time-dependent stimulation of STAT3 tyrosine phosphorylation. STAT3 phosphorylation was first evident at 5 min and was maximal at 30 min after leptin injection. By contrast, leptin did not increase the phosphorylation of Janus kinase proteins, mitogen-activated protein kinase, or STAT1 and -5 despite abundant expression of these signaling molecules in the hypothalamus. These results differ from findings in cultured cells and in vitro systems. It remains unclear how signaling is propagated downstream from the leptin receptor to STAT3, but this may involve novel signaling intermediates.

Animals↗
PubMed1998

Intestinal adaptation after extensive small bowel resection: differential changes in growth and insulin-like growth factor system messenger ribonucleic acids in jejunum and ileum.

The distal small bowel exhibits greater adaptive growth than proximal segments after partial small intestine resection. To explore this process, we evaluated adaptive cellularity, intestinal insulin-like growth factor (IGF) system messenger RNA (mRNA) transcripts, and effects of recombinant IGF-I treatment in jejunum and ileum of adult rats. Gastrostomy-fed animals underwent 80% jejuno-ileal resection or intestinal transection and reanastomosis without resection, followed by infusion of human recombinant IGF-I (2.4 mg/kgXday) or vehicle. After 7 days, resected rats demonstrated modest adaptive growth in jejunum and marked cell proliferation in ileum. Resection increased IGF-I mRNA in both jejunum (183%) and ileum (249%) and up-regulated IGFBP-4 mRNA levels in both tissues. IGFBP-3 mRNA fell significantly in ileum after resection. IGF-I infusion modestly increased ileal cellularity after resection, but had no effect in jejunum. IGF-I markedly increased IGFBP-3 mRNA levels in jejunum after both transection and resection. These data confirm that bowel resection induces greater adaptive growth in ileum than jejunum. IGF-I administration modestly increases ileal, but not jejunal, growth after resection. Increased levels of intestinal IGF-I and IGFBP-4 mRNA suggest roles for IGF-I and IGFBP-4 in mediating small bowel adaptation. Higher levels of jejunal IGFBP-3 mRNA may be related to limited jejunal vs. ileal growth after extensive jejuno-ileal resection.

Adaptation, Physiological↗
PubMed1997

The adapter protein Grb10 associates preferentially with the insulin receptor as compared with the IGF-I receptor in mouse fibroblasts.

To identify receptor-associated proteins that may contribute to the specificity of insulin and IGF-I signaling responses, a mouse embryo library was screened using the yeast two-hybrid system. Multiple receptor-interactive clones encoding the SH2 domain of the adapter protein Grb10 were isolated. Subsequent cloning of the full-length Grb10 sequence from a mouse fat cDNA library defined a previously unknown Grb10 variant, that appears to be the predominant isoform in mouse tissues. Receptor-deficient R- cells (fibroblasts from mice with homologous disruption of the IGF-I receptor gene) and transfected R- cells expressing either insulin receptors (R-IR cells) or IGF-I receptors (R+ cells) were used to investigate the specificity of Grb10 interaction with the two related receptors. Hormone-activated insulin receptors in R-IR cells coprecipitated with three species, all recognized as Grb10 isoforms by specific Grb10 antibody. Under the same conditions, Grb10 was essentially undetectable in IGF-I receptor immunoprecipitates from stimulated R+ cells. Grb10 association with insulin receptors was maximal at 10 nM insulin stimulation and sustained from 5-10 min after hormone stimulation in R-IR cells. In conclusion, Grb10 interacts preferentially with insulin vs. IGF-I receptors in intact cells and, thus, may have a role in mediating insulin receptor-specific cellular responses.

Animals↗
PubMed1997

Tissue-specific effects of chronic dietary protein restriction and gastrostomy on the insulin-like growth factor-I pathway in the liver and colon of adult rats.

Dietary protein restriction decreases plasma concentrations of insulin-like growth factor-I (IGF-I) and reduces IGF-I mRNA levels in the liver. In addition to the actions of systemic IGF-I, locally produced IGF-I is thought to mediate autocrine and paracrine growth effects in the colon. The objectives of the present study were to investigate the IGF-I pathway in the colon and liver of adult rats under conditions of dietary protein restriction, surgical stress, and dietary protein repletion. Two groups of rats were placed on either a 20% or 2% casein diet for 19 days. Two additional groups of rats underwent gastrostomy after a 2% casein diet for 2 weeks, and then were either kept on the 2% casein diet or changed to a 20% casein diet until day 19. Dietary protein restriction reduced plasma concentrations of IGF-I and IGF-binding proteins (IGFBPs) and hepatic IGF-I mRNA content, while increasing colonic IGF-I receptor mRNA. Gastrostomy in protein-depleted animals had no effect on hepatic IGF-I mRNA, but led to a marked increase in colonic IGF-I mRNA levels. Dietary protein repletion resulted in a decrease in colonic IGF-I receptor mRNA. The distinct effects of dietary protein depletion and operative stress on the IGF pathway in the colon as compared with the liver may serve to maintain the level of IGF-I signaling in the colon by autocrine or paracrine mechanisms under these conditions.

Animals↗
PubMed1997

The use of routine wrist radiography in the evaluation of patients with carpal tunnel syndrome.

The objective of this study was to evaluate the use of routine wrist radiography in the evaluation of patients with carpal tunnel syndrome (CTS). In the setting of a community-based hand surgery practice, we performed a retrospective review of charts and radiographs for 300 consecutive patients (447 wrists) meeting clinical and electrophysiologic criteria for CTS. Data on all patients included information obtained by the use of medical history questionnaires, physical examinations, nerve conduction studies, and radiographs of the wrist. Abnormalities were noted in 146 of 447 wrist radiographs (33%). Eighty-three (18.6%) had abnormalities that might have been implicated in the development of CTS, although these findings would not alter management. For only 2 of 447 wrists (0.4% of wrists; 0.6% of patients) were there radiographic findings of therapeutic significance. Radiographic charges were calculated to be $5,869 to $20,115 for each finding of therapeutic significance. We conclude that wrist radiographs should not be performed routinely in patients with CTS, owing to the low yield of useful information.

Adolescent↗