ORCID Profile
0000-0003-1788-9347
Current Organisations
Hacettepe University
,
University of California, Irvine
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Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JAUT.2015.06.002
Abstract: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease. We performed an international survey, of clinicians treating C1q deficient patients. A high response rate of >70% of the contacted clinicians yielded information on 45 patients with C1q deficiency of which 25 are published. Follow-up data of 45 patients from 31 families was obtained for a median of 11 years after diagnosis. Of these patients 36 (80%) suffer from SLE, of which 16 suffer from SLE and infections, 5 (11%) suffer from infections only and 4 (9%) have no symptoms. In total 9 (20%) of the C1q deficient in iduals had died. All except for one died before the age of 20 years. Estimated survival times suggest 20% case-fatality before the age of 20, and at least 50% of patients are expected to reach their middle ages. Here we report the largest phenotypic data set on C1q deficiency to date, revealing high variance with high mortality but also a subset of patients with an excellent prognosis. Management of C1q deficiency requires a personalized approach.
Publisher: Public Library of Science (PLoS)
Date: 14-09-2015
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 09-2014
Publisher: Rockefeller University Press
Date: 25-02-2019
DOI: 10.1084/JEM.20181812
Abstract: Salmonella species are among the world’s most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Salmonella Paratyphi and S. Typhi, we focused on lipids that are enriched in S. Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6′-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformed clsB homology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced by S. Typhi, lower amounts by other pathogens, and variable amounts by Escherichia coli strains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6′-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species.
Publisher: American Association for Cancer Research (AACR)
Date: 2006
DOI: 10.1158/1541-7786.MCR-04-0187
Abstract: Microarrays have been used extensively to identify differential gene expression at the level of transcriptional control in oncogenesis. However, increasing evidence indicates that changes in translational control are critical to oncogenic transformation. This study identifies mRNA transcripts that are differentially regulated, primarily at the level of translation, in the immortalized human embryonic prostate epithelial cell line 267B1 and the v-Ki-ras–transformed counterpart by comparing total mRNA to polysome-bound mRNA by using Affymetrix oligonucleotide microarrays. Among the transcripts that were identified were those encoding proteins involved in DNA replication, cell cycle control, cell-to-cell interactions, electron transport, G protein signaling, and translation. Many of these proteins are known to contribute to oncogenesis or have the potential to contribute to oncogenesis. Differential expression of RNA-binding proteins and the presence of highly conserved motifs in the 5′ and 3′ untranslated regions of the mRNAs are consistent with multiple pathways and mechanisms governing the changes in translational control. Although Alu sequences were found to be associated with increased translation in transformed cells, an evolutionarily conserved motif was identified in the 3′ untranslated regions of ephrinB1, calreticulin, integrinα3, and mucin3B that was associated with decreased polysome association in 267B1/Ki-ras. (Mol Cancer Res 2006 (1):47–60)
Publisher: American Society for Microbiology
Date: 12-2016
DOI: 10.1128/IAI.00734-16
Abstract: Intestinal epithelial cells provide an important colonization niche for Salmonella enterica serovar Typhimurium during gastrointestinal infections. In infected epithelial cells, a subpopulation of S . Typhimurium bacteria damage their internalization vacuole, leading to escape from the Salmonella -containing vacuole (SCV) and extensive proliferation in the cytosol. Little is known about the bacterial determinants of nascent SCV lysis and subsequent survival and replication of Salmonella in the cytosol. To pinpoint S . Typhimurium virulence factors responsible for these steps in the intracellular infectious cycle, we screened a S . Typhimurium multigene deletion library in Caco-2 C2Bbe1 and HeLa epithelial cells for mutants that had an altered proportion of cytosolic bacteria compared to the wild type. We used a gentamicin protection assay in combination with a chloroquine resistance assay to quantify total and cytosolic bacteria, respectively, for each strain. Mutants of three S . Typhimurium genes, STM1461 ( ydgT ), STM2829 ( recA ), and STM3952 ( corA ), had reduced cytosolic proliferation compared to wild-type bacteria, and one gene, STM2120 ( asmA ), displayed increased cytosolic replication. None of the mutants were affected for lysis of the nascent SCV or vacuolar replication in epithelial cells, indicating that these genes are specifically required for survival and proliferation of S . Typhimurium in the epithelial cell cytosol. These are the first genes identified to contribute to this step of the S . Typhimurium infectious cycle.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2017
DOI: 10.1038/NG.3933
Location: United States of America
No related grants have been discovered for Michael McClelland.