Browsing by Author "van der Merwe, Elizabeth"

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    Deletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzyme
    (Elsevier, 2004) Chubb, Anthony J; Schwager, Sylva L U; van der Merwe, Elizabeth; Ehlers, Mario R W; Sturrock, Edward D
    Ectodomain shedding generates soluble isoforms of cell-surface proteins, including angiotensin-converting enzyme (ACE). Increasing evidence suggests that the juxtamembrane stalk of ACE, where proteolytic cleavage-release occurs, is not the major site of sheddase recognition. The role of the cytoplasmic domain has not been completely defined. We deleted the cytoplasmic domain of human testis ACE and found that this truncation mutant (ACE-ΔCYT) was shed constitutively from the surface of transfected CHO-K1 cells. Phorbol ester treatment produced only a slight increase in shedding of ACE-ΔCYT, unlike the marked stimulation seen with wild-type ACE. However, for both wild-type ACE and ACE-ΔCYT, shedding was inhibited by the peptide hydroxamate TAPI and the major cleavage site was identical, indicating the involvement of similar or identical sheddases. Cytochalasin D markedly increased the basal shedding of wild-type ACE but had little effect on the shedding of ACE-ΔCYT. These data suggest that the cytoplasmic domain of ACE interacts with the actin cytoskeleton and that this interaction is a negative regulator of ectodomain shedding.
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    Risk factors and outcomes of acute kidney injury in South African critically ill adults: a prospective cohort study
    (2019-12-10) Aylward, Ryan E; van der Merwe, Elizabeth; Pazi, Sisa; van Niekerk, Minette; Ensor, Jason; Baker, Debbie; Freercks, Robert J
    Abstract Background There is a marked paucity of data concerning AKI in Sub-Saharan Africa, where there is a substantial burden of trauma and HIV. Methods Prospective data was collected on all patients admitted to a multi-disciplinary ICU in South Africa during 2017. Development of AKI (before or during ICU admission) was recorded and renal recovery 90 days after ICU discharge was determined. Results Of 849 admissions, the mean age was 42.5 years and mean SAPS 3 score was 48.1. Comorbidities included hypertension (30.5%), HIV (32.6%), diabetes (13.3%), CKD (7.8%) and active tuberculosis (6.2%). The most common reason for admission was trauma (26%). AKI developed in 497 (58.5%). Male gender, illness severity, length of stay, vasopressor drugs and sepsis were independently associated with AKI. AKI was associated with a higher in-hospital mortality rate of 31.8% vs 7.23% in those without AKI. Age, active tuberculosis, higher SAPS 3 score, mechanical ventilation, vasopressor support and sepsis were associated with an increased adjusted odds ratio for death. HIV was not independently associated with AKI or hospital mortality. CKD developed in 14 of 110 (12.7%) patients with stage 3 AKI; none were dialysis-dependent. Conclusions In this large prospective multidisciplinary ICU cohort of younger patients, AKI was common, often associated with trauma in addition to traditional risk factors and was associated with good functional renal recovery at 90 days in most survivors. Although the HIV prevalence was high and associated with higher mortality, this was related to the severity of illness and not to HIV status per se.
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    Variations in arterial supply via the external and internal carotid arteries to the bony orbit and eyeball in full-term fetuses, infants, children, adolescents, and adults – a South African perspective
    (2022) Mpolokeng, Kentse Sana; Louw, Graham J; van der Merwe, Elizabeth
    The anatomy of the orbital region is of great importance for many highly specialised clinical disciplines such as ophthalmology, maxillofacial surgery, and neurosurgery. The main source of arterial blood supply to the orbital region is by the ophthalmic artery, a branch of the internal carotid artery, and to a lesser extent by the anastomotic patterns which are formed through the external carotid artery. A range of arterial variations which may be developmental in origin, or which may develop due to pathologies later in life, may affect the ophthalmic artery in terms of its origin, course, and branching. If clinicians are not aware of the variations occurring in this region, the eye of the patient may be at risk of injury during invasive procedures, which may lead to partial or complete visual loss. Up until the present time, there have been only a few cadaveric studies that revealed some of the variant patterns and the overall frequencies of the recorded anastomotic patterns for the orbital blood supply. Whilst the anatomical variations are known, the frequencies of variations in the population are not. Furthermore, no published data exists regarding the variations in the orbital blood supply in a South African population. Therefore, the aim of this study was to investigate the orbital vascular supply within the South Africans of different age groups, to document and describe any variations in anastomotic patterns and record their frequencies. The current study was conducted through dissections of bodies in the Department of Human Biology, University of Cape Town, and patients' angiograms from Groote Schuur Hospital. The angiograms included data obtained from other hospitals within the Cape Town area and were reviewed retrospectively. The dissection sample included six full term fetuses and 63 adults, and the angiograms accounted for 870 individuals. The ophthalmic artery was studied from the point of origin from the internal carotid artery and its course in relation to the optic nerve, and both sides were compared to note any similarities or differences. Statistical analyses were performed to record the frequencies of the patterns of variations and to note whether there were any associations between sex, age, sidedness, and these variations. The results revealed statistically significant associations between age and sex for the patterns of variation. Several variations were noted in the current study. Among the novel findings were those in the origin of the ophthalmic artery from the internal carotid artery, whereby a lateral and inferior origin were recorded in both samples (dissected bodies and angiograms). In addition, it was noted that the ophthalmic artery may take origin from the A2 segment of the anterior cerebral artery, which is also a novel finding. This study, therefore, adds significantly to the current body of knowledge regarding the patterns of arterial supply to the ophthalmic region in a South African sample.