PubMed Health⌕ Search

Biomedical subjects

K Page

Publications and source records attributed to K Page.

At least 19 recordsLinked to original sources
PubMed2006

Mechanism and function of heat shock-dependent IkappaBalpha expression.

OBJECTIVE: Heat shock is known to inhibit activation of the NF-kappa B pathway. One potential mechanism of this effect is de novo expression of the intracellular NF-kappaB inhibitor, Ikappa Balpha. Herein we sought to elucidate the mechanisms by which heat shock induces Ikappa Balpha gene expression and the functional consequences of heat shock-mediated Ikappa Balpha gene expression in A549 cells. METHODS: Nuclear run-on assays demonstrated that heat shock had a small effect on transcription of the Ikappa Balpha gene relative to the level of steady state Ikappa Balpha mRNA that is seen following heat shock. Accordingly, we determined the effect of heat shock on Ikappa Balpha mRNA stability by treating cells with actinomycin D to induce transcriptional arrest. RESULTS: The half-life of IkappaBalpha mRNA was 36 +/- 7.2 min in control cells and 101 +/- 3.7 min in cells subjected to heat shock. These data were consistent with heat shock-mediated increased stability of Ikappa Balpha mRNA. Heat shock induced activation of p38 MAP kinase and inhibition of p38 MAP kinase substantially reduced heat shock-dependent expression of Ikappa Balpha mRNA. After a 4 h recovery period from heat shock, there was inhibition of tumor necrosis factor-alpha-mediated NF-kappaB activation. The introduction of an Ikappa Balpha anti-sense oligonucleotide reversed this inhibitory effect of heat shock. CONCLUSIONS: We conclude that heat shock increases IkappaBalpha gene expression primarily by increasing Ikappa Balpha mRNA stability and this effect is partially dependent on p38 MAP kinase. The functional consequence of heat shock-mediated Ikappa Balpha gene expression is inhibition of NF-kappaB activation.

Cell Line↗
PubMed2006

German cockroach proteases regulate matrix metalloproteinase-9 in human bronchial epithelial cells.

BACKGROUND: Matrix metalloproteinases (MMPs) digest extracellular matrix proteins and may play a role in the pathogenesis of bronchial asthma. MMP-9 levels are increased in the bronchoalveolar lavage fluid and sputum of asthmatics compared with that of controls. As exposure to cockroaches is an environmental risk factor for asthma, we sought to investigate the role of German cockroach fecal remnants (frass) on MMP-9 expression. METHODS: Human bronchial epithelial cells (16HBE14o-) and primary normal human bronchial epithelial cells were treated with cockroach frass in the absence or presence of tumor necrosis factor (TNF)alpha. MMP-9 mRNA, protein levels and pro-MMP-9 activity were determined using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and zymogram assays. Pretreatment of frass with aprotinin abolished protease activity. PD98059, a chemical inhibitor of extracellular signal regulated kinase (ERK), and SLIGKV, an activator of protease-activated receptor (PAR)-2 were also used. AP-1DNA binding was determined by electrophoretic mobility shift assay (EMSA) and ERK phosphorylation by Western blot analysis. RESULTS: Cockroach frass augmented TNFalpha-mediated MMP-9 mRNA and protein expression by a mechanism dependent on active serine proteases within frass and not on endogenous endotoxin. Frass increased ERK phosphorylation, and chemical inhibition of ERK attenuated cockroaches' effects on MMP-9. Serine proteases are known to activate the PAR-2 receptor. We found that selective activation of PAR-2 using the peptide SLIGKV augmented TNFalpha-induced MMP-9 protein levels and increased ERK phosphorylation. Frass and SLIGKV each increased AP-1 translocation and DNA binding. CONCLUSIONS: These data suggest that German cockroach frass contains active serine proteases which augment TNFalpha-induced MMP-9 expression by a mechanism involving PAR-2, ERK and AP-1.

Animals↗
PubMed2005

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Journal Article↗
PubMed2004

A paralleling device and ethylene vinyl acetate baffles for use with mandibular distraction osteogenesis: technical note.

A novel method for planning the placement of intra-oral lengthening devices using a paralleling device is described and illustrated with a case report. Simple radiographic measurements and study models are all that is required to construct a simple acrylic splint with guides, which allows accurate positioning of the distractors at surgery. The construction of ethylene vinyl acetate (EVA) baffles to prevent trauma to the labial mucosa from the intra-oral link arms is a technique that enhances patient comfort during distraction of the mandible. The case report demonstrates the application of the surgical planning technique and the use of EVA baffles for a patient with an overjet of 21.5 mm.

Acrylic Resins↗
PubMed2004

Increasing hCG concentrations during storage at (+)4 degrees C with the Bayer Centaur Total hCG method.

BACKGROUND: The interpretation of changes in serum human chorionic gonadotropin (hCG) concentrations in early pregnancy requires a knowledge of the day-to-day imprecision of the method at the concentrations measured. We therefore attempted to determine the analytical imprecision of our total hCG method over a 4-week period at concentrations up to 20,000 IU/L. METHODS: Serum specimens with hCG concentrations between 100 and 20,000 IU/L were collected during early pregnancy and analysed using the Bayer Centaur Total hCG method at weekly intervals after storage at (+)4 degrees C and (-)20 degrees C. RESULTS: The reproducibility of hCG results over a 4-week period in refrigerated specimens with an initial hCG concentration below 1000 IU/L was poor (mean coefficient of variation = 17.4%) and there was an apparent increase in serum hCG concentrations of up to 68%. Similar changes occurred in some specimens stored at (-)20 degrees C. Further experiments confirmed that significant increases can occur during the first week following specimen collection. CONCLUSIONS: Total hCG concentrations in serum specimens collected during early pregnancy increase significantly during storage when measured by the Bayer Centaur Total hCG method, possibly due to a conformational change in hyperglycosylated hCG. When this method is used for monitoring early pregnancy, specimens should ideally be analysed on the day of collection.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed2003

German cockroach extract increases bronchial epithelial cell interleukin-8 expression.

BACKGROUND: Cockroach exposure has been recognized as a common trigger for asthma. While dust mite and Aspergillus fumigatus aeroallergens have been noted to have direct effects on airway epithelium, direct effects of cockroach proteins have not been determined. OBJECTIVE: The purpose of this study was to investigate whether cockroach extract has a direct pro-inflammatory effect on airway epithelium. METHODS: We examined the effect of crude German cockroach (Blattella germanica) extract on IL-8 expression in a human bronchial epithelial cell line (16HBE14o-cells) and primary human bronchial epithelial cells. Transcription from the IL-8 promoter and protein abundance were determined by reporter assay and enzyme-linked immunosorbent assay (ELISA), respectively. Endotoxin levels in the crude cockroach extracts were determined using the Limulus Amebocyte Lysate assay. Protease activity was assessed using Azocoll as a substrate. RESULTS: We found that crude cockroach extract induced a synergistic increase in TNF-alpha-induced transcription from the IL-8 promoter. The synergistic effect was observed with as little as 0.3 micro g/mL of crude cockroach extract, while larger concentrations (30 micro g/mL) approximately doubled TNF-alpha-induced IL-8 promoter activity. Similar effects of cockroach extract on IL-8 protein abundance were observed in both 16HBE14o- and primary human bronchial epithelial cells. Addition of endotoxin at concentrations found in the cockroach extract had no effect on TNF-alpha-mediated IL-8 expression. The serine protease inhibitors aprotinin and phenylmethylsulphonyl fluoride abolished cockroach-induced synergy, while the cysteine protease inhibitors E64 and leupeptin had little effect. Measurement of protease activity using Azocoll as a substrate confirmed the presence of protease activity in cockroach extracts. Addition of recombinant Bla g 2, Bla g 3 and Bla g 5 had no effect on TNF-alpha-induced IL-8 promoter activation. Finally, cockroach extract also increased TNF-alpha-induced transcription from the IL-6 promoter. CONCLUSIONS: German cockroach extract contains novel serine protease activity which has a direct pro-inflammatory effect on airway epithelial cells

Allergens↗
PubMed2003

Clinical validation of a proANP 31-67 fragment ELISA in the diagnosis of heart failure in the dog.

Atrial natriuretic peptide (ANP) is a polypeptide hormone found in increased concentrations in the plasma of dogs with heart failure. However, problems arise in using ANP as a diagnostic marker for heart failure because of its short half-life in plasma, proteolysis post-collection and the necessity for a radioimmunoassay. The diagnostic utility of a proANP 31-67 ELISA for the detection of heart failure in dogs was evaluated using plasma collected from 31 dogs with clinical and radiographic signs of heart failure and control samples from 40 dogs considered to be free of cardiac disease. Log proANP 31-67 levels were significantly higher in the heart failure group (P < 0.001). In this population of dogs, using a cut-off value of 1,750 fmol/ml, the sensitivity and specificity of the assay were 83.9 per cent and 97.5 per cent, respectively. Using a cut-off of 1,350 fmol/ml, the sensitivity and specificity were 93.5 per cent and 72.5 per cent, respectively. It is concluded that a proANP 31-67 fragment ELISA should prove to be a useful diagnostic aid in naturally occurring canine heart failure.

Animals↗
PubMed2002

The effect of maternal smoking and ethanol on fatty acid transport by the human placenta.

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentas from non-smokers (n 5), smokers (>ten cigarettes/d; n 5) and after addition of ethanol at 2 mg/ml (n 4). The maternal side was of the placenta was perfused ex vivo for 90 min with a physiological mixture of fatty acids and fatty acid:human albumin ratio. There was no effect of smoking on the transfer of linoleic (LA, 18: 2 n-6), alpha-linolenic (alphaLN, 18: 3 n-3), arachidonic (AA, 20: 4 n-6) or docosahexaenoic acid (DHA, 22: 6 n-3), expressed per perfused area (calculated from H2(18)O exchange). However, the presence of ethanol in the perfusate at a concentration of 2 mg/ml significantly reduced (P<0.01) the absolute rate of transfer of the two n-3 polyunsaturated fatty acids, alphaLN and DHA. This specific effect of ethanol on alphaLN and DHA also resulted in an altered selectivity for transfer of individual fatty acids. In the non-smoking control group the placenta selectively transferred polyunsaturated fatty acids to the fetus in the order DHA > AA > alphaLN > LA. The order of selectivity was unaltered in placentas from smokers, but the addition of ethanol to the perfusion medium altered the order of selectivity to AA > alphaLN > LA > DHA. The presence of ethanol in the perfusate was also associated with a significant reduction (P<0.05) in the clearance of H2(18)O. These results suggest that the presence of ethanol at a concentration of 2mg/ml may reduce the availability of polyunsaturated fatty acids to the developing fetus.

Arachidonic Acid↗
PubMed2002

Optical dating of palaeochannel deposits in the Riverine Plain, southeastern Australia: testing the reliability of existing thermoluminescence dates.

We present the first quartz optically stimulated luminescence (OSL) ages for palaeochannel sediments from the Riverine Plain in southeastern Australia. For young fluvial sediments, we agree with the notion that analysis of the leading edge of a dose distribution curve provides an objective method for determining the OSL age. For a modern flood deposit (less than 200 years old), the OSL ages estimated using the leading edge method (250 +/- 50 years) and by using the lowest 5% of the measured dose in single aliquots (230 +/- 50 years) agree within experimental errors. For older sediments, we suggest that the mean estimate of the dose distribution is likely to provide a reliable estimate of the OSL age. The luminescence ages suggest that the Coleambally and Kerarbury palaeochannel systems were active between 105 and 80 ky and 55 and 35 thousand years ago; the Yanco palaeochannel system could have been active as recently as 9000 years ago.

Australia↗
PubMed2001

The virulence for gnotobiotic pigs of live attenuated vaccine strains of Salmonella enterica serovars Typhimurium and Enteritidis.

Gnotobiotic pigs were inoculated orally with wild-type or defined aroA or cya crp vaccine strains of Salmonella enterica serovars Typhimurium and S. Enteritidis. The parental strains were virulent, inducing severe diarrhoea, dehydration and systemic disease. The cya crp mutant was also highly virulent whereas the aroA strains were attenuated.

Adenylyl Cyclases↗
PubMed2001

The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy.

RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNFalpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies.

Administration, Oral↗
PubMed2001

p38 MAP kinase negatively regulates cyclin D1 expression in airway smooth muscle cells.

We have demonstrated that platelet-derived growth factor (PDGF) stimulates p38 mitogen-activated protein (MAP) kinase activation in bovine tracheal myocytes, suggesting that p38 is involved in growth regulation. We therefore examined whether p38 regulates expression of cyclin D1, a G(1) cyclin required for cell cycle traversal. The chemical p38 inhibitors SB-202190 and SB-203580 each increased basal and PDGF-induced cyclin D1 promoter activity and protein abundance. Overexpression of a dominant negative allele of MAP kinase kinase-3 (MKK3), an upstream activator of p38alpha, had similar effects. Conversely, active MKK3 and MKK6, both of which increase p38alpha activity, each decreased transcription from the cyclin D1 promoter. Together, these data demonstrate that p38 negatively regulates cyclin D1 expression. We tested whether p38 regulates cyclin D1 expression via inhibition of extracellular signal-regulated kinase (ERK) activation. Chemical inhibitors of p38 induced modest ERK phosphorylation and activation. However, dominant negative MKK3 was insufficient to activate ERK, and active MKK3 and MKK6 did not attenuate platelet-derived growth factor-mediated ERK activation. These data are consistent with the notion that p38alpha negatively regulates cyclin D1 expression via an ERK-independent pathway.

Animals↗
PubMed2001

Cdc42, but not RhoA, regulates cyclin D1 expression in bovine tracheal myocytes.

We previously demonstrated that Rac1 increased cyclin D1 promoter activity in an extracellular signal-regulated kinase (ERK)-independent, antioxidant-sensitive manner. Here, we examined the regulation of cyclin D1 expression by Cdc42 and RhoA. Overexpression of active Cdc42, but not of RhoA, induced transcription from the cyclin D1 promoter. Furthermore, dominant negative Cdc42, but not RhoA, attenuated platelet-derived growth factor-mediated activation of the cyclin D1 promoter. Overexpression of active Cdc42 increased cyclin D1 protein abundance in COS cells. Cdc42-induced cyclin D1 promoter activation was independent of ERK as evidenced by insensitivity to PD-98059, an inhibitor of mitogen-activated protein kinase/ERK kinase (MEK). Furthermore, Cdc42 was neither sufficient nor required for activation of ERK. Similar to Rac1-induced cyclin D1 expression, pretreatment with the antioxidants catalase and ebselen inhibited Cdc42-mediated transcription from the cyclin D1 promoter. Finally, like Rac1, active Cdc42 induced transactivation of the cyclin D1 promoter cAMP response element binding protein/activating transcription factor-2 binding site. Together, these data suggest that in airway smooth muscle cells, Cdc42 and Rac1 share a common signaling pathway to cyclin D1 promoter activation.

Animals↗
PubMed2001

Association between schizophrenia and social inequality at birth: case-control study.

BACKGROUND: The association between social inequality at birth and subsequent risk of schizophrenia is uncertain. AIMS: To investigate the relationship between adult-onset schizophrenia and two indicators of social inequality at birth: social class and area of residence. METHOD: A matched case-control design was used with data from birth certificates of first-episode cases and age- and gender-matched controls. RESULTS: Risk increased with increasing levels of deprivation at birth. Subjects whose fathers were social class IV-V or who were born in deprived areas were at increased risk of schizophrenia (odds ratio=2.1; 95% Cl=0.8-5.5). Risk was greater in those with both of these indicators (odds ratio=8.1; 95% Cl=2.7-23.9). There was some evidence that associations were stronger in older subjects. Exclusion of African-Caribbeans or cases with positive family history somewhat attenuated the association. CONCLUSIONS: Indicators of social inequality at birth are associated with increased risk of adult-onset schizophrenia, suggesting that environmental factors are important determinants of schizophrenic disorders.

Age Factors↗
PubMed2001

The distribution of Biomphalaria spp. in different habitats in relation to physical, biological, water contact and cognitive factors in a rural area in Minas Gerais, Brazil.

A total of 256 sites in 11 habitats were surveyed for Biomphalaria in Melquiades rural area (State of Minas Gerais) in August and November 1999 and in March 2000. Of the 1,780 Biomphalaria collected, 1,721 (96.7%) were B. glabrata and 59 (3.3%) B. straminea. Snails were found in all habitats except in wells, with the largest mean numbers in tanks, seepage ponds and canals, and the smallest numbers in springs, rice fields and fishponds. People's knowledge of the occurrence of Biomphalaria at the collection sites and the presence of Biomphalaria ova were strongly correlated with the occurrence of snails, and distance between houses and collection sites, as well as water velocity were inversely correlated with Biomphalaria occurrence (p < 0.001). The strongest predictor o f Biomphalaria occurrence was the presence of tilapia fish in fishponds. Fourteen Biomphalaria (0.8% of all snails) found at 6 sites were infected with Schistosoma mansoni. Suggestions are made for the utilization of local people's knowledge in snail surveys and further studies are recommended on the possible use of tilapia for biological control of Biomphalaria in fishponds, as well as modeling of S. mansoni transmission and reinfection.

Animals↗
PubMed2000

Mitogen-activated signaling and cell cycle regulation in airway smooth muscle.

Increased airway smooth muscle mass has been demonstrated in patients with bronchopulmonary dysplasia and asthma. These data highlight the need for a precise understanding of the events involved in airway smooth muscle mitogenesis. To that end, investigators have developed cell culture systems adopting tracheal and bronchial myocytes from different species. A growing body of literature suggests that common signal transduction pathways regulate airway smooth muscle cell cycle entry across species lines. This review summarizes what is known about mitogen-activated signal transduction in airway smooth muscle cells. The extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI 3-kinase) pathways appear to be major positive regulators of airway smooth muscle proliferation. It is also conceivable that growth factor stimulation of airway smooth muscle simultaneously elicits signaling through negative regulatory pathways such as the p38 mitogen-activated protein (MAP) kinase pathway, perhaps as a safeguard against excessive growth.

Animals↗
PubMed2000

Inhibition of colonisation of the alimentary tract in young chickens with Campylobacter jejuni by pre-colonisation with strains of C. jejuni.

Strains of Campylobacter jejuni, isolated from human gastro-intestinal infection and inoculated orally into 1-day-old chicks, colonised the alimentary tract (caecum) well. There was evidence of invasion from the intestine to the spleen. Oral inoculation with some but not all strains of C. jejuni 24 h earlier (within 12 h of hatching) prevented establishment by challenge strains administered orally 1 day later. One strain which was less able to colonise the gut was less inhibitory than other strains. Precolonisation of newly hatched chicks with a strain of Salmonella typhimurium had no inhibitory effect on establishment by the challenge strain of C. jejuni and may even have exacerbated it. Inhibition of multiplication of a nalidixic acid-resistant mutant of a C. jejuni strain was prevented when it was added to a stationary-phase broth culture of the antibiotic-sensitive parent strain and the mixed culture re-incubated.

Animals↗