Browsing by Author "Moolman-Smook H."
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- Item5-HT2A: Its role in frontally mediated executive function and related psychopathology(2007) Stein D.J.; Hemmings, Sian M. J.; Moolman-Smook H.; Audenaert K.Serotonin (5-HT)2A receptors are widely distributed, with high levels in the frontal cortex, where postsynaptic activation may increase activity in pyramidal glutamatergic neurons and mediate various executive functions. More specifically, reciprocal cortical-raphe pathways may allow the ventral prefrontal cortex to inhibit stress-induced neural activity in the brainstem when stressors are perceived as controllable. However, early adversity and negative attitudes may be associated with higher frontal 5-HT2A receptor levels and greater risk for stress-induced psychopathology, and certain 5-HT2A gene variants have been associated with increased risk for impulsive behavior. Conversely, many antidepressants result in decreased levels of 5-HT2A receptor levels, and blockade of 5-HT2A receptors has proven useful in the treatment of a number of psychiatric disorders.
- ItemDopamine transporter binding in social anxiety disorder: The effect of treatment with escitalopram(2012) Warwick, James M.; Carey P.D.; Cassimjee N.; Lochner C.; Hemmings, Sian M. J.; Moolman-Smook H.; Beetge E.; Dupont P.; Stein D.J.Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using 123I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects' Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration. © Springer Science+Business Media, LLC 2012.
- ItemFluorometric assay for testing rifampin susceptibility of Mycobacterium tuberculosis complex(2008) Hoek K.G.P.; Gey Van Pittius N.C.; Moolman-Smook H.; Carelse-Tofa K.; Jordaan A.; Van Der Spuy G.D.; Streicher E.; Victor T.C.; Van Helden P.D.; Warren R.M.The emergence and transmission of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have raised concern about diagnostic delay associated with culture-based drug susceptibility testing methods. The association between rifampin resistance and MDR-TB or XDR-TB makes it an important genetic marker for genotypic drug susceptibility testing. In this article, we describe the analysis of the physical properties of the rifampin resistance-determining region (RRDR) in the rpoB gene by high-resolution thermal melt analysis as a method for detecting rifampin resistance in Mycobacterium tuberculosis complex. The RRDR from the M. tuberculosis complex was amplified by PCR from DNA templates extracted from sputum cultures of M. tuberculosis or the laboratory strain (H37Rv) in the presence of a fluorescent DNA binding dye. Subsequent mixing of the amplification products from the respective sputum cultures and the laboratory strain and thermocycling allowed the formation of DNA duplexes. The thermal denaturation properties of these DNA duplexes were determined by measuring the derivative of the intensity of fluorescence at different temperatures. Analysis of DNA extracted from 153 sputum cultures showed a sensitivity of 98% and a specificity of 100% for the detection of rifampin resistance compared to the "gold standard" culture-based phenotyping method. No statistical difference was detected in the performance of the method when applied to crude DNA from 134 boiled cultures. This method, named "FAST-Rif" ("fluorometric assay for susceptibility iesting of rifampin"), allowed the rapid, reliable, and easy detection of genotypic rifampin resistance as a marker for MDR-TB and XDR-TB. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
- ItemNovel mutations identified within the 3′ region of the PKD1 gene in South African polycystic kidney disease patients(2006) Chauke G.; Bardien S.; Moolman-Smook H.; Freeman V.; Makubalo Z.; Brink P.; Corfield V.Autosomal dominant polycystic kidney disease (ADPKD), a common, potentially lethal, inherited disorder, can arise from mutations in the polycystln-1 and polycystin-2 encoding genes (PKD1 and PKD2, respectively). To date, more than 260 PKD1 mutations have been reported in American, European and Asian populations. No information, however, is available on the molecular aetiology of ADPKD in South Africa. Since polycystic kidney disease (PKD) occurs in this country, the aim of this study was to investigate whether disease-causing mutations in PKD1 exist in a South African cohort of PKD patients. Thirty-two PKD-affected index cases (probands) were recruited from Tygerberg Hospital, Western Cape, for mutation screening of PKD1 exons 34 to 46. We identified three novel, putative disease-causing substitutions (V3682L, R3832P, and R4149L) and one previously reported substitution (R4227P) in four of the probands. Additionally, using genetic linkage analysis, the disease phenotype was strongly linked to the PKD1 locus in two multi-generation ADPKD pedigrees and, less clearly, in a third. The identification of novel, disease-causing mutations in PKD1 will help to identify functionally important domains, thereby furthering an understanding of the role of this membrane-bound protein in the healthy and the polycystic kidney.