Browsing by Author "Kendall, Michaela"

Now showing 1 - 9 of 9

Airborne particulate matter (PM2.5 and PM10) and associated metals in urban Turkey
(Springer, 2011-12) Kendall, Michaela; Pala, Kayıhan; Uçaklı, Sumru; Güçer, Şeref; Uludağ Üniversitesi/Tıp Fakültesi/Halk Sağlığı Bilimleri Bölümü.; Uludağ Üniversitesi/Mühendislik Fakültesi/Çevre Mühendisliği Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Anabilim Dalı.; 0000-0002-0983-4904; 0000-0003-0610-2019; F-7816-2013; 6603159416; 36867786400; 36849130600
Airborne particulate matter (PM) and associated metals were measured in a district of an industrial city in Western Turkey. We compared PM concentrations in Bursa, Turkey (Nilufer district) with international air quality standards. Turkish legislature adopted the EC Air Quality Framework in 2008, and compliance is required in the medium term. State-of-the-art reference methods were used for all measurements. A Partisol sampler measured urban background PM2.5 and PM10 between May 2007 and April 2008, and PM2.5 samples were later analysed for selected metals using ICP-MS. Average PM2.5 and PM10 mass concentrations over the year were 53 and 83 mu g/m(3), respectively. The annual mean PM2.5:PM10 ratio in Bursa was 0.64. PM2.5 and PM10 were highly correlated at the site (R=0.91 overall), especially in winter. In the cold seasons, the coarse and fine fractions were strongly correlated R=0.67 (p<0.1), while in the warm seasons, they were not (R=0.01). Sampler results correlated well with a nearby Government sampler. Current PM10 and PM2.5 levels in Bursa breach current and prospective EU air quality standards, with significant implications in public health.
A deletion including exon 2 of the TSHR gene is associated with thyroid dysgenesis and severe congenital hypothyroidism
(Walter De Gruyter Gmbh, 2014-07) Cangül, Hakan; Schoenmakers, Nadia A.; Saǧlam, Yaman; Kendall, Michaela; Timothy Barrett, Timothy; Chatterjee, Krish; Mäher, Eamonn Richard; Saǧlam, Halil; Doğanlar, Durmuş; Eren, Erdal; Tarım, Ömer Faruk; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Endokrinoloji Anabilim Dalı.; 0000-0003-0710-5422; 0000-0002-1684-1053; C-7392-2019; AAH-1155-2021; 35612700100; 56363214600; 36113153400; 6701427186
Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and 2% of cases have a familial origin. Our aim in this study was to determine the genetic alterations in two siblings with CH coming from a consanguineous family. As CH is often inherited in an autosomal recessive manner in consanguineous/multi case-families, we first performed genetic linkage studies to all known causative CH loci followed by conventional sequencing of the linked gene. The family showed potential linkage to the TSHR locus and our attempts to amplify and sequence exon 2 of the TSHR gene continuously failed. Subsequent RT-PCR analysis using mRNA and corresponding cDNA showed a large deletion including the exon 2 of the gene. The deletion was homozygous in affected cases whilst heterozygous in carrier parents. Here we conclude that CH in both siblings of this study originates from a large deletion including the exon 2 of the TSHR gene. This study demonstrates that full sequence analysis in a candidate CH gene might not always be enough to detect genetic alterations, and additional analyses such as RT-PCR and MLPA might be necessary to describe putative genetic causes of the disease in some cases. It also underlines the importance of detailed molecular genetic studies in the definitive diagnosis and classification of CH.
An essential splice site mutation (c.317+1G > A) in the TSHR gene leads to severe thyroid dysgenesis
(Walter De Gruyter Gmbh, 2014-09) Cangül, Hakan; Sağlam, Yaman; Kendall, Michaela; Mäher, Eamonn Richard; Barrett, Timothy; Sağlam, Halil; Eren, Erdal; Doǧan, Durmuş; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Endokrinoloji Anabilim Dalı.; 0000-0002-1684-1053; 0000-0003-0710-5422; AAM-1734-2020; C-7392-2019; 35612700100; 36113153400; 24467663400
Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and 2% of cases have familial origin. Our aim in this study was to determine the genetic alterations in two siblings with CH coming from a consanguineous family. Because CH is often inherited in autosomal recessive manner in consanguineous/multi-case-families, we first performed genetic linkage studies to all known causative CH loci followed by conventional sequencing of the linked gene. The family showed potential linkage to the TSHR locus, and we detected an essential splice site mutation (c.317+1G>A) in both siblings. RT-PCR analysis confirmed the functionality of the mutation. The mutation was homozygous in the cases whereas heterozygous in carrier parents and an unaffected sibling. Here we conclude that thyroid agenesis in both siblings in this study originates from c.317+1G>A splice site mutation in the TSHR gene, and this study underlines the importance of detailed molecular genetic studies in the definitive diagnosis and classification of CH.
Fine airborne urban particles (PM2.5) sequester lung surfactant and amino acids from human lung lavage
(American Physiological Society, 2007-07-06) Kendall, Michaela; Uludağ Üniversitesi/Tıp Fakültesi/Halk Sağlığı Anabilim Dalı.; 7201638493
Components of surfactant act as opsonins and enhance phagocytosis of bacteria; whether this process occurs with atmospheric fine particles has not been shown. We have studied the interactions of fine particles ( urban PM2.5) and surfactant removed from normal human lungs by lavage, using a surface analysis technique. The aim was to identify which of the chemical components of brochoalveolar lavage ( BAL) deposit on the surfaces of urban PM2.5. Deposition of surfactant components on urban PM2.5 surfaces was reported in previous studies, but molecular identification and relative quantification was not possible using simple data analysis. In this study, we were able to identify adsorbed components by applying an appropriate statistical technique, factor analysis. In this study, the most strongly associated mass fragment on PM2.5 surfaces exposed to BAL ( and undetected on both untreated samples and saline controls) was di-palmitoyl-phosphatidylcholine, a component of lung surfactant. Amino acids were also strongly associated with BAL-exposed PM2.5 surfaces and not other sample types. Thirteen mass fragments were identified, diagnostic of the amino acids alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, serine, and valine. This study provides evidence that lung surfactant and amino acids related to opsonin proteins adsorb to nonbiological particle surfaces exposed to human lung lining fluid. Disruption of normal surfactant function, both physical and immunological, is possible but unproven. Further work on this PM-opsonin interaction is recommended.
Heavy metal content of plant species along nilufer stream in industrialized Bursa city, Turkey
(Springer, 2008-11) Çelik, Cengiz; Güleryüz, Gürcan; Arslan, Hülya; Güçer, Şeref; Kendall, Michaela; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü.; 6603334913; 7006712783; 36849130600
In this study, heavy metal content (Cr, Cu, Mn, Ni, Zn) was determined in sediments and different organs of Rumex obtusifolius L. and Polygonum lapathifolium L. (Polygonaceae), Urtica dioica L. (Urticaceae) and Xanthium strumarium L. (Asteraceae) species. These species grow ubiquitously and vigorously on the periodic flooding areas of Nilufer stream which have been polluted by different local industrial activities. Below and above-ground parts of plant samples and their sediments were analyzed by ICP-MS for their elemental contents. In general, the variations in the heavy metal content in sediments are reflected in heavy metal status of plant organs. However, this variation depends on plant species and heavy metals. R. obtusifolius, U. dioica and X. strumarium species have elevated levels of Cr, Cu, Ni, and Zn whereas Mn was observed only in P. lapathifolium. The contribution of different organs to the accumulation capacity of the total phytomass is specific to species.
Locus heterogeneity and novel TSHR mutations in consanguineous families with congenital non-goitrous hypothyroidism
(BMJ Publing Group, 2010-09) Cangül, Hakan; Aycan, Zehra; Morgan, Neil; Forman, Julia; Çetinkaya, Semra; Baş, Veysel; Demir, Korcan; Yuca, Sevil Arı; Kirby, Gail; Pasha, Shanaz; Kendall, Michaela; Hoegler, Wolfgang; Barret, T. G.; Maher, E. R.; Sağlam, Halil; Yakut, Tahsin; Gülten, Tuna; Karkucak, Mutlu; Eren, Erdal; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; 0000-0003-0710-5422; 0000-0002-1684-1053; C-7392-2019; AAM-1734-2020
Molecular adsorption at particle surfaces: A PM toxicity mediation mechanism
(Taylor & Francis, 2004) Brown, Leslie; Trought, Katherine; Kendall, Michaela; Uludağ Üniversitesi/Tıp Fakültesi/Halk Sağlığı Anabilim Dalı.
Fine atmospheric particles depositing in the lung present a large adsorbent surface for the adsorption of bronchoalveolar lining fluid (BALF) components, including lung surfactant and its associated proteins. Such adsorption at invading particle surfaces is known to be important in biological particle clearance, and the immunological and toxicological fate of these particles. In the experiments conducted here, it was hypothesized that this is also true for particles of nonbiological origin, and that fine particles with large surface areas would selectively adsorb the opsonizing components of BALF. This work quantifies the adsorption rates (adsorption of compound per unit surface area) of isolated BALF components. Elemental carbon (EC) is a ubiquitous component of fine urban particulate matter (PM2.5), and particular forms of EC are extremely surface active (e.g., activated carbon). EC originates largely from fossil fuel combustion, and vehicles in particular contribute a significant proportion Of PM2.5 EC mass in urban areas. Since the size distribution of EC is submicrometer, industrially produced carbon blacks in the 25-100 nm size range can be used as a surrogate for urban EC, in terms of surface area and chemistry. Three types of carbon black (CB) particles were used. Two were identical in size (25 nm) but different in surface treatment; R330, a CB with a nonoxidized surface, and R400, a CB produced with an oxidized surface. The third particle type, M120, was 75 mn, different in size from R330 and R400, but similar to R330 in surface chemistry, that is, nonoxidized. Particles were first washed and resuspended in phosphate-buffered-saline (PBS, pH 7.0) three times to remove surfactant coatings added during their manufacture. Colloidal suspensions of M120, R330, and R400 particles with decreasing surface areas were then generated and separated into reaction vials. BALF proteins were added spanning physiological concentrations while the dominant phospholipid in surfactant was added at a fixed concentration lower than physiological lung lavage concentrations to ensure the lipid remained in suspension during experimentation ex situ. For dipalmitoylphosphatidylcholine (DPPC) combinations with particles, visible particle agglomeration occurred within 1 h. Marked changes in the size distribution of the immersed particles were observed, compared to a phosphate buffer control. Differences in particle agglomeration and particle settling were observed between M120, R330, and R400. Reduction of DPPC occurred in a surface- and size-dependent manner. This indicates that surface adsorption was responsible for the observed agglomeration and the gross reductions in phospholipid concentrations. Combination of particles with fibrinogen and albumin revealed little agglomeration/precipitation at the protein concentrations chosen. However, surfactant protein (SP-D) was completely eliminated from suspension upon combination with all three-particle types. This reaction between SP-D particles was therefore concluded to be independent of surface chemistry. Further investigation as to whether this is size- or surface-area-dependent is recommended. The biological implication is that molecular adsorption at nonbiological particulate matter (PM) surfaces in BALF may mediate the toxicity of PM via one or both of these mechanisms, as in the case of biological particles.
Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism
(Wiley, 2010-11) Morgan, Neil V.; Forman, Julia R.; Aycan, Zehra; Böber, Ece; Cesur, Yaşar; Kirby, Gail A.; Pasha, Shanaz S.; Çetinkaya, Semra Çağlar; Baş, Veysel Nihat; Demir, Korcan; Yuca, Sevil Arı; Meyer, Esther; Högler, Wolfgang; Timothy Barrett, Timothy; Mäher, Eamonn Richard; Cangül, Hakan; Sağlam, Halil; Yakut, Tahsin; Gülten, Tuna; Tarım, Ömer Faruk; Karkucak, Mutlu; Eren, Erdal; Kendall, Michaela; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Halk Sağlığı Anabilim Dalı.; 0000-0003-0710-5422; 0000-0002-1684-1053; C-7392-2019; AAM-1734-2020; 8911611600; 35612700100; 6602802424; 6505944216; 6701427186; 35388323500; 36113153400; 8062516400
Objective Nonsyndromic autosomal recessively inherited non-goitrous congenital hypothyroidism (CHNG) can be caused by mutations in TSHR, PAX8, TSHB and NKX2-5. We aimed to investigate mutational frequencies of these genes and genotype/phenotype correlations in consanguineous families with CHNG. Design Because consanguinity in individuals with a presumptive genetic condition is often an indicator of an autosomal recessive inheritance and allows firmer correlations to be established between genotype and phenotype, we planned to execute our study in consanguineous families. Patients Hundred and thirty-nine children with CHNG phenotype born to consanguineous families. Measurements First, we investigated cases for evidence of linkage to the four known CHNG genes by microsatellite marker analysis. Mutation analysis by direct sequencing was then performed in those cases in whom linkage to the relevant candidate gene could not be excluded. In addition, in silico analysis of the predicted structural effects of TSHR mutations was performed and related to the mutation-specific disease phenotype. Results Homozygous germline TSHR mutations were detected in six families (5%), but no mutations were detected in PAX8, TSHB and NKX2-5. Four of TSHR mutations had not previously been described. Genotype-phenotype correlations were established and found to be related to the predicted structural effects of the mutations. Conclusions Known causative genes account for the development of CHNG only in a minority of cases, and our cohort should provide a powerful resource to identify novel causative genes and to delineate the extent of locus heterogeneity in autosomal recessively inherited CHNG.
Personal exposures to traffic-related particle pollution among children with asthma in the South Bronx, NY
(Springernature, 2010-07) Spira Cohen, Ariel; Chen, Lung Chi; Sheesley, Rebecca J.; Thurston, George D.; Kendall, Michaela; Uludağ Üniversitesi/Tıp Fakültesi/Halk Sağlığı Anabilim Dalı.; 7201638493
Personal exposures to fine particulate matter air pollution (PM(2.5)), and to its traffic-related fraction, were investigated in a group of urban children with asthma. The relationships of personal and outdoor school-site measurements of PM(2.5) and elemental carbon (EC) were characterized for a total of 40 fifth-grade children. These students, from four South Bronx, NY schools, each carried air pollution monitoring equipment with them for 24 h per day for similar to 1 month. Daily EC concentrations were estimated using locally calibrated reflectance of the PM(2.5) samples. Personal EC concentration was more closely related to outdoor school-site EC (median subject-specific: r=0.64) than was personal PM(2.5) to school-site PM(2.5) concentration (median subject-specific: r=0.33). Regression models also showed a stronger, more robust association of school site with personal measurements for EC than those for PM(2.5). High traffic pollution exposure was found to coincide with the weekday early morning rush hour, with higher personal exposures for participants living closer to a highway (<500 ft). A significant linear relationship of home distance from a highway with personal EC pollution exposure was also found (up to 1000 ft). This supports the assumptions by previous epidemiological studies using distance from a highway as an index of traffic PM exposure. These results are also consistent with the assumption that traffic, and especially smoke emitted from diesel vehicles, is a significant contributor to personal PM exposure levels in children living in urban areas such as the South Bronx, NY. Journal of Exposure Science and Environmental Epidemiology (2010) 20, 446-456; doi: 10.1038/jes.2009.34;published online 28 October 2009