Biomedical subjects

Lize van der Merwe

Publications and source records attributed to Lize van der Merwe.

9 recordsLinked to original sources

PubMed2007

Genotype and childhood sexual trauma moderate neurocognitive performance: a possible role for brain-derived neurotrophic factor and apolipoprotein E variants.

BACKGROUND: Limited success in the identification of genetic variants underpinning psychiatric illness has prompted attempts to elucidate gene-environment interactions and illness-associated endophenotypes. Here we measured childhood sexual abuse, a potential environmental risk factor, and verbal and visual recall and recognition memory, a possible illness-associated endophenotype in a cohort of bipolar disorder (BPD) subjects and their relatives. We predicted that memory would be affected by sexual trauma and that a number of functional polymorphisms previously implicated in BPD and cognition would moderate the effect of psychological trauma on memory. METHODS: A cohort of 350 individuals from 47 BPD families was recruited, tested with a neuropsychological battery, and given the Childhood Trauma Questionnaire (CTQ). Eleven different genetic variants previously found to be relevant to BPD or memory dysfunction were typed. RESULTS: As predicted, scores on the sexual abuse scale of the CTQ were negatively associated with memory performance. Furthermore, the low-activity Met allele of the brain-derived neurotrophic factor (BDNF) gene and the epsilon4 allele of the apolipoprotein E gene interacted with sexual abuse scores to result in reduced memory test performance. CONCLUSIONS: Apolipoprotein E and BDNF exert a neurotrophic effect in response to cellular injury. Their possible moderation of the association between sexual abuse and memory performance might indicate that there is some degree of overlap in the pathophysiological mechanisms by which psychological and physical trauma impact brain function. The finding of an environmental effect on memory performance and a gene-environment interaction on this hypothetical endophenotype of BPD illustrates the difficulty of identifying genetically and phenotypically simple intermediate traits for molecular genetic studies.

Adolescent↗

PubMed2006

GSTM1 and GSTT1 polymorphisms as modifiers of age at diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) in a homogeneous cohort of individuals carrying a single predisposing mutation.

The variability in phenotype that occurs for so-called 'single-gene disorders' may be because of germline alterations in numerous primary and "modifier" genes. Within HNPCC families harbouring the same primary predisposing mutation, differences exist in the site of cancer, age of onset of disease symptoms and, consequently, survival until diagnosis of disease. The current study investigated a cohort of 129 individuals, from 13 different families, who harbour the identical nonsense mutation (C1528T) in the hMLH1 gene, predisposing them primarily to Lynch I syndrome. This cohort was screened for previously described polymorphisms in the glutathione-S-transferase genes, viz. GSTT1 and GSTM1. Male null carriers for both GSTT1 and GSTM1 were approximately three times more at risk of developing cancer at an earlier age when compared to non-null males. This work, particularly because of the relatively large "homogeneous" primary mutation cohort, provides evidence that genotypic changes distinct from the primary 'HNPCC-causing' mutation, influence the survival period until diagnosis of disease. It provides an impetus for expanding the study to include a wider range of candidate modifier genes. Such work may potentially lead to the development of individualised interval screening regimens for individuals with varying modifier genotypes--an attractive option in a resource-poor country.

Adolescent↗

PubMed2006

Mycotoxin contamination of dietary and medicinal wild plants in the Eastern Cape Province of South Africa.

Nineteen dietary and 30 medicinal wild plants used by residents of the Eastern Cape Province of South Africa were investigated for the presence of fumonisin B1 and aflatoxin B1. The plants were extracted in water, and cleanup was undertaken on immunoaffinity cartridges; analysis was by HPLC using fluorescence detection. None of the plant extracts contained detectable levels of aflatoxin B1; however, eight plants, four dietary and four medicinal, were positive for fumonisin B1 at levels ranging from 34 to 524 microg/kg and from 8 to 1553 microg/kg, respectively. The presence of fumonisin B1 was confirmed by LC-MS/MS using positive ion electrospray ionization. Fumonisin B1 provided characteristic fragment ions at m/z 704, 686, 546, 528, 370, and 352 corresponding to sequential loss of H2O and tricarboxylic acid moieties from the alkyl backbone. These results indicate that exposure to fumonisin B1 is much more widespread than initially thought and is the first report of mycotoxin contamination in South African medicinal and dietary wild plants.

Aflatoxin B1↗

PubMed2006

Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in worm/HIV co-infection analyses.

BACKGROUND: Ascariasis and HIV/AIDS are often co-endemic under conditions of poverty in South Africa; and discordant immune responses to the respective infections could theoretically be affecting the epidemic of HIV/AIDS in various ways. It is well-known that sensitisation to helminthic antigens can aggravate or ameliorate several non-helminthic diseases and impair immunisation against cholera, tetanus and tuberculosis. The human genotype can influence immune responses to Ascaris strongly. With these factors in mind, we have started to document the extent of long-term exposure to Ascaris and other helminths in a community where HIV/AIDS is highly prevalent. In more advanced studies, objectives are to analyse relevant immunological variables (e.g. cytokine activity and immunoglobulin levels). We postulate that when Ascaris is hyperendemic, analysis of possible consequences of co-infection by HIV cannot be based primarily on excretion vs non-excretion of eggs. METHODS: Recall of worms seen in faeces was documented in relation to the age of adult volunteers who were either seropositive (n = 170) or seronegative (n = 65) for HIV. Reasons for HIV testing, deworming treatments used or not used, date and place of birth, and duration of residence in Cape Town, were recorded. Confidence intervals were calculated both for group percentages and the inter-group differences, and were used to make statistical comparisons. RESULTS: In both groups, more than 70% of participants were aware of having passed worms, often both when a child and as an adult. Most of the descriptions fitted Ascaris. Evidence for significantly prolonged exposure to helminthic infection in HIV-positives was supported by more recall of deworming treatment in this group (p < 0.05). Over 90% of the participants had moved to the city from rural areas. CONCLUSION: There was a long-term history of ascariasis (and probably other helminthic infections) in both of the groups that were studied. In women in the same community, and in children living where housing and sanitation are better, Ascaris sero-prevalence exceeded egg-prevalence by two- and three-fold, respectively. For ongoing and future analyses of possible consequences of co-infection by Ascaris (and/or other helminths) and HIV/AIDS (and/or other bystander conditions), comparisons must be based mainly on disease-related immunological variables. Especially in adults, comparisons cannot be based only on the presence or absence of eggs in excreta.

Adult↗

PubMed2006

Maternal and early life influences on calcaneal ultrasound parameters and metacarpal morphometry in 7- to 9-year-old children.

We investigated the relationship between maternal and early life influences, calcaneal ultrasound parameters, and metacarpal morphometry in 7- to 9-year-old children (n = 109) of mixed ancestral origin from a working class community. Their mothers had participated in a nutrition and pregnancy study at the time of the birth. Demographic and maternal data were collected. Anthropometry was assessed. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the children and a subsample of the mothers (n = 94), using calcaneal ultrasound. Hand radiographs were used to measure metacarpal morphometry. There was no relationship between the ultrasound parameters, birthweight, current weight, or height. The ponderal index was correlated with BUA (r = 0.25; P = 0.036). BUA was lower in children whose mothers smoked during pregnancy compared to children whose mothers did not smoke (P = 0.054). Children whose mothers consumed alcohol during pregnancy had a lower Barnett-Nordin metacarpal index compared to children whose mothers did not consume alcohol (P < 0.05), after covarying for sex, age, gestational age, weight, and height of the child. Children's BUA was negatively correlated with housing density (r = -0.23; P = 0.021). In this study, we found an association between maternal and early life influences on calcaneal ultrasound parameters and metacarpal morphometry in prepubertal children, an association that was also influenced by sociodemographic and environmental factors.

Birth Weight↗

PubMed2005

Glucocorticoid administration and brief occlusion of the main pancreatic duct are likely to increase islet mass by a similar mechanism.

OBJECTIVES: Both glucocorticoid (GC) administration and brief occlusion of the main pancreatic duct result in an increase in total islet mass. Consequently, it was questioned whether these 2 stimuli would produce similar islet growth, indicating commonality in the mechanism of expansion. To test this, we assessed the effects on morphology after single and dual stimulation of the pancreas. METHODS: Rat pancreata were harvested 56 days after (1) brief occlusion of the main pancreatic duct, (2) daily GC administration, (3) GC administration and brief occlusion, or (4) sham operation without GC administration or occlusion. The pancreata were weighed, fixed, wax embedded, and sectioned for morphologic analysis. The endocrine to exocrine ratio, endocrine mass, and the contribution that small, medium, and large islets made to increased pancreatic endocrine mass were assessed. Blood was taken immediately before termination, after overnight fasting, for analysis of serum glucose, amylase, and insulin. RESULTS: GC treatment resulted in increased total pancreatic mass and exocrine mass, which were dissimilar to increases elicited by brief occlusion. However, there was no significant difference in the increase in the total endocrine mass or the increased mass of small, medium, or large islets between the GC, occluded, and dually stimulated pancreata. There were also no significant differences in the mean number of cells per islet between these groups. GC administration increased both circulating glucose and insulin in both occluded and nonoccluded groups, whereas occlusion alone had no effect on these parameters. CONCLUSIONS: Glucocorticoid administration and brief occlusion of the main pancreatic duct result in a similar expansion of islet mass. This is reflected in nonsignificant increases in endocrine mass/body weight and the percentage contribution of small, medium, and large islets to this increase. The majority of additional islet mass is from the expansion of the large islet population, although extra large islets are not found after either pancreatic treatment. The effects of GC treatment and occlusion are not additive, indicating that there is commonality in the mechanism of expansion. Because occlusion does not result in elevated glucose or insulin levels and gives rise to increased islet mass equivalent to GC administration and dual stimulation, it is unlikely that the increased islet mass after GC treatment is caused by the accompanying hyperinsulinemia as previously hypothesized.

Amylases↗

PubMed2005

A novel energy expenditure prediction equation for intermittent physical activity.

PURPOSE: This study was designed to characterize the relative contributions of the current heart rate (HR) and HR in the previous minute to predict energy expenditure (EE) and to model these and other determinants to predict EE during intermittent activity. METHODS: Regularly exercising subjects (N=65, 36+/-9 yr, body mass index (BMI), 23.9+/- 2.5 kg.m) were tested. Body composition and maximal oxygen uptake (& OV0312;O2) were measured. On a separate day, subjects completed 12 x 4-min workloads, separated by 4 x 1-min rest periods, during which HR and & OV0312;O2 were continuously monitored. Using the intermittent activity calibration data, an EE model was developed. For validation, the final model was used to predict EE in a separate sample (N=17), who completed a gym training exercise session. Using the HR data, EE data were estimated using (a) the new model and were compared with (b) a previous model developed using a continuous incremental calibration test. RESULTS: The following variables contributed significantly to the estimation of EE during intermittent activity: age, gender, & OV0312;O2 max, current minute's HR, previous minute's HR, and an interaction variable consisting of previous minute's HR and & OV0312;O2 max. The final model yielded an R of 82% for the comparison of predicted and measured EE. When this model was applied to an independent sample for validation (N=17), improvements in EE prediction, when compared to the existing model (b), were most apparent during free-living non-continuous exercise. CONCLUSION: It is possible to improve the accuracy of predicting EE from HR, by incorporating both & OV0312;O2 max and the previous minute's HR in the prediction model.

Adult↗

PubMed2004

Islet neogenesis is stimulated by brief occlusion of the main pancreatic duct.

OBJECTIVE: Current models of islet neogenesis either cause substantial pancreatic damage or continuously stimulate the pancreas, making these models unsuitable for the study of early events that occur in the neogenic process. We aimed to develop a method where the initial events that culminate in increased pancreatic endocrine mass can be studied. DESIGN AND METHODS: Ten 12-week-old female Wistar rats were subjected to a midline laparotomy, the pancreas was isolated and the main pancreatic duct was occluded for 60 seconds. The pancreas was released and carefully relocated within the abdomen. Ten age-, strain- and sex-matched control rats were subjected to a sham operation. The animals were killed 56 days post occlusion, and the pancreata excised and fixed for histological analysis. Body, pancreatic and hepatic weights were noted at termination and serum was taken for analysis. The endocrine-to-exocrine ratio was calculated and the number of endocrine cells in each islet from the sectioned pancreata was counted. RESULTS: Occlusion of the main pancreatic duct for 60 seconds results in an increase in endocrine mass by 80% 56 days post occlusion. This constitutes an increase in endocrine units (1-6 cells), and in small (7-30 cells), medium (31-60 cells) and large (> 60 cells) islets by 85%, 96%, 95% and 71% respectively. CONCLUSION: Brief occlusion of the main pancreatic duct results in an increase in pancreatic endocrine mass. An increase in endocrine units and small islets is indicative of islet neogenesis. Therefore, owing to the briefness of the stimulation, this model can therefore be used to study the initial events that occur during the neogenic process.

Animals↗

PubMed2002

Estimating the conditional false-positive rate for semi-latent data.

When comparing tests for a disease, it is necessary to know whether individuals are diseased or nondiseased. In practice, the confirmatory (gold standard) procedure is often limited to individuals with positive test results, because the confirmatory procedure is not applied to individuals with negative test results. We present a model for estimating the sensitivity and specificity when two tests are compared and the gold standard classification is unavailable (semi-latent) for those individuals with negative results on both tests. The model does not assume independent error rates, and estimates of specificity conditional on a false-positive result for another test are derived. We use a Bayes approach for estimating the distributions of the performance parameters.

Bayes Theorem↗