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Biomedical subjects

Michael Norman

Publications and source records attributed to Michael Norman.

8 recordsLinked to original sources
PubMed2006

Spatial & temporal variations of PM10 and particle number concentrations in urban air.

The size of particles in urban air varies over four orders of magnitude (from 0.001 microm to 10 microm in diameter). In many cities only particle mass concentrations (PM10, i.e. particles <10 microm diameter) is measured. In this paper we analyze how differences in emissions, background concentrations and meteorology affect the temporal and spatial distribution of PM10 and total particle number concentrations (PNC) based on measurements and dispersion modeling in Stockholm, Sweden. PNC at densely trafficked kerbside locations are dominated by ultrafine particles (<0.1 microm diameter) due to vehicle exhaust emissions as verified by high correlation with NOx. But PNC contribute only marginally to PM10, due to the small size of exhaust particles. Instead wear of the road surface is an important factor for the highest PM10 concentrations observed. In Stockholm, road wear increases drastically due to the use of studded tires and traction sand on streets during winter; up to 90% of the locally emitted PM10 may be due to road abrasion. PM10 emissions and concentrations, but not PNC, at kerbside are controlled by road moisture. Annual mean urban background PM10 levels are relatively uniformly distributed over the city, due to the importance of long range transport. For PNC local sources often dominate the concentrations resulting in large temporal and spatial gradients in the concentrations. Despite these differences in the origin of PM10 and PNC, the spatial gradients of annual mean concentrations due to local sources are of equal magnitude due to the common source, namely traffic. Thus, people in different areas experiencing a factor of 2 different annual PM10 exposure due to local sources will also experience a factor of 2 different exposure in terms of PNC. This implies that health impact studies based solely on spatial differences in annual exposure to PM10 may not separate differences in health effects due to ultrafine and coarse particles. On the other hand, health effect assessments based on time series exposure analysis of PM10 and PNC, should be able to observe differences in health effects of ultrafine particles versus coarse particles.

Environmental Exposure↗
PubMed2005

Prolactin-induced activation of STAT5 within the hypothalamic arcuate nucleus.

Prolactin signalling within hypothalamic areas associated with the control of fertility was examined in male and lactating female rats. Following exogenous prolactin treatment, phosphorylation of STAT5 (signal transducer and activator of transcription) within the arcuate nucleus was measured using a highly sensitive immunoblotting strategy. A significant increase in phosphorylated STAT5 was detected in the arcuate nucleus of female rats compared with same-sex controls. No such effect was apparent in the males. Phosphorylation of STAT5 was not observed in the liver of either males or females. These results show that prolactin-induced intracellular signalling within the hypothalamus involves activation of the Janus tyrosine kinase/signal transducer and activator of transcription pathway, and that this signalling mechanism can be readily triggered in lactating females where prolactin receptors are known to be upregulated and fertility impaired.

Animals↗
PubMed2004

Protein-DNA array-based identification of transcription factor activities regulated by interaction with the glucocorticoid receptor.

The glucocorticoid receptor (GR) regulates gene expression by binding specific sequence elements within the promoters of target genes or by cross-talk with other transcription factors (TFs). For some TFs, interaction with the GR results in alteration of DNA binding and transcriptional regulation. We used a protein-DNA array, a system that facilitates simultaneous profiling of the activities of multiple transcription factors, to systematically examine the potential cross-talk of GRalpha with 149 TFs. Using this array, we identified several TFs, including IRF, E47, and COUP-TF, whose DNA binding activities were modulated by GRalpha. We then confirmed these results with in vitro electrophoretic mobility shift assays and in vivo reporter assays. In this study, IRF and E47 were identified as participants in GRalpha cross-talk for the first time. This new finding expands our understanding of the functional role of GRalpha in the context of gene expression regulation.

Actins↗
PubMed2003

Use of an array technology for profiling and comparing transcription factors activated by TNFalpha and PMA in HeLa cells.

Multiple signal transduction pathways are generally triggered simultaneously by a single extracellular stimulus. As a result, multiple transcription factors (TFs) can be activated downstream to mediate the inducible expression of target genes. Profiling the activation of all TFs will aid in the dissection of the numerous pathways of signal transduction. Tumor necrosis factor alpha (TNFalpha) and phorbol 12-myristate 13-acetate (PMA) mediate many biological functions, including cell proliferation and apoptosis, by stimulating signaling pathways. Two TFs, nuclear factor kappaB (NFkappaB) and activating factor 1 (AP1), have been identified as targets of both TNFalpha and PMA activation. Here, we describe the use of a protein/DNA array system to identify additional TFs activated by TNFalpha and PMA in HeLa cells. From a total of 150 targeted TFs, six-CREB, E2F, CETP/CRE, c-Rel, MSP1, and Pax6-were identified whose activities, like NFkappaB and AP1, were regulated by both TNFalpha- and PMA-induced pathways. Interestingly, the TF E47 was shown to be specifically activated by TNFalpha but was not affected by treatment with PMA. In addition, GATA, NF-E1, and ISRE were shown to be specifically activated by PMA but not TNFalpha. These findings suggest that TNFalpha and PMA both stimulate unique signaling pathways while mediating transcriptional activation through common pathways.

DNA Fingerprinting↗
PubMed2002

Glucocorticoid resistance - what is known?

It has become apparent in recent years that the glucocorticoid receptor is not a simple on/off switch, but instead orchestrates subtle and complex interactions between large numbers of proteins. This more sophisticated understanding awaits a unifying concept that will explain mechanisms of glucocorticoid resistance and allow new approaches to enhancing sensitivity.

Drug Resistance↗
PubMed2002

Sulfonylurea receptor knockout causes glucose intolerance in mice that is not alleviated by concomitant somatostatin subtype receptor 5 knockout.

OBJECTIVE: To examine the long-term effects of Sur KO, SSTR5 KO, and double Sur/SSTR5 KO on insulin secretion and glucose regulation. SUMMARY BACKGROUND DATA: The sulfonylurea receptor (Sur) and somatostatin receptor type 5 (SSTR5) play an integral role in the regulatory pathways of the endocrine pancreas. Sur knockout (KO) and SSTR5 KO mice were generated in the authors' laboratories and crossbred to generate Sur/SSTR5 KO mice. All mice were genotyped by Southern blotting and polymerase chain reaction analysis. METHODS: One-year-old Sur KO, Sur/SSTR5 KO, SSTR5 KO, and age-matched wild-type control mice underwent single-pass perfusion of isolated pancreata with low and high glucose concentration (n = 4-6/group). Another group of mice also underwent intraperitoneal glucose tolerance tests with 1.2 g glucose/kg body weight (n = 4/group per time point). RESULTS: Sur1 KO and Sur/SSTR5 KO mice had profoundly decreased insulin secretion in vitro, whereas SSTR5 KO had increased insulin secretion compared with wild-type mice. Sur1 KO and Sur/SSTR5 mice had increased glucose response in vivo compared with wild-type mice. Sur1 KO and Sur/SSTR5 KO mice exhibit glucose intolerance and SSTR5 KO mice show increased insulin response in vitro. CONCLUSIONS: Sur1 KO causes glucose intolerance and SSTR5 KO causes increased insulin secretion. However, Sur/SSTR5 double ablation does not alleviate the diabetic state of the Sur1 KO.

ATP-Binding Cassette Transporters↗