Browsing by Author "Wainwright, Helen"
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- ItemOpen AccessCD146 expression in early and late onset pre-eclampsia : is there a difference?(2014) Schubert, Pawel Tomasz; Wainwright, Helen; Wright, Colleen AObjective: To investigate the difference in expression of CD146 immunohistochemical staining on intermediate trophoblast in early and late onset pre-eclampsia placentas as well as comparing this expression to gestational age matched control placentas. Study Design: Retrospective case series of 100 placentas: 25 early onset and 25 late onset pre-eclampsia placentas as well as 25 early and 25 late gestational age matched control placentas. Placentas were obtained from patients delivering in Tygerberg Hospital. Methods: Placentas were routinely fixed and processed. 2 sections of one preselected block from each case was cut and stained with CD146 and MNF116 immunohistochemical stain. The expression of the staining would be performed by means of analytical and image analysing software. Results: The study failed to demonstrate differences in CD146 expression by the intermediate trophoblast in the pre-eclampsia and control placentas. The analytical approach was deemed to be subjective and the image analysing software had too much background staining and inaccurate identification of the intermediate trophoblast in order to produce reproducible consistent results. Conclusion: Dual staining, using immunofluorescent staining of CD146 and MNF116 on smaller biopsies of the decidua are thought to be able to produce much better material for image analyses software.
- ItemOpen AccessCharacterisation of innate fungal recognition in the lung(Public Library of Science, 2012) Faro-Trindade, Inês; Willment, Janet A; Kerrigan, Ann M; Redelinghuys, Pierre; Hadebe, Sabelo; Reid, Delyth M; Srinivasan, Naren; Wainwright, Helen; Lang, Dirk M; Steele, ChadThe innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (PRR), such as Dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. In the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. Here we have explored pulmonary innate recognition of a variety of fungal particles, including zymosan, Candida albicans and Aspergillus fumigatus , and demonstrate that opsonisation with surfactant components can limit inflammation by reducing host-cell fungal interactions. However, we found that this opsonisation does not contribute directly to innate fungal recognition and that this process is mediated through non-opsonic PRRs, including Dectin-1. Moreover, we found that pulmonary inflammatory responses to resting Aspergillus conidia were initiated by these PRRs in acidified phagolysosomes, following the uptake of fungal particles by leukocytes. Our data therefore provides crucial new insights into the mechanisms by which surfactant can maintain pulmonary function in the face of microbial challenge, and defines the phagolysosome as a novel intracellular compartment involved in the innate sensing of extracellular pathogens in the lung.
- ItemOpen AccessHIV associated Lymphocytic Interstitial Pneumonia: a clinical, histological and radiographic study from an HIV endemic resource-poor setting(BioMed Central, 2015-04-22) van Zyl-Smit, Richard N; Naidoo, Jashira; Wainwright, Helen; Said-Hartley, Quanita; Davids, Malika; Goodman, Hillel; Rogers, Sean; Dheda, KeertanBackground: There is a paucity of clinical and histopathological data about HIV-associated lymphocytic interstitial pneumonitis (LIP) in adults from HIV endemic settings. The role of Ebstein-Barr virus (EBV) in the pathogenesis remains unclear. Methods: We reviewed the clinical, radiographic and histopathological features of suspected adult LIP cases at the Groote Schuur Hospital, Cape Town South Africa, over a 6 year period. Archived tissue sections were stained for CD3, CD4, CD8, CD20 and LMP-1 antigen (an EBV marker). Results: 42 cases of suspected LIP(100% HIV-infected) were identified. 75% of patients were empirically treated for TB prior to being referred to the chest service for further investigation. Tissue samples were obtained using trans-bronchial biopsy. 13/42 were classified as definite LIP (lymphocytic infiltrate with no alternative diagnosis), 19/42 probable LIP (lymphocytic infiltrate but evidence of anthracosis or fibrosis) and 10 as non-LIP (alternative histological diagnosis). Those with definite LIP were predominantly young females (85%) with a median CD4 count of 194 (IQR 119–359). Clinical or radiological features had poor predictive value for LIP. Histologically, the lymphocytic infiltrate comprised mainly B cells and CD8 T cells. The frequency of positive EBV LMP-1 antigen staining was similar in definite and non- LIP patients [(2/13 (15%) vs. 3/10 (30%); p = 0.52]. Conclusions: In a HIV endemic setting adult HIV-associated LIP occurs predominantly in young women. The diagnosis can often be made on transbronchial biopsy and is characterized by a predominant CD8 T cell infiltrate. No association with EBV antigen was found.
- ItemOpen AccessAn immunohistochemical assessment of endomyocardial biopsy specimens from the South African arrhythmogenic right ventricular cardiomyopathy registry(2014) Morse, Nicole; Wainwright, Helen; Mayosi, BonganiArrhythmogenic right ventricular cardiomyopathy / dysplasia (ARVC/D) is a genetic disease causing fibro-fatty replacement of the right ventricular myocardium, resulting in cardiac arrhythmias and sudden death. Part of the diagnostic work up for these patients includes a biopsy of the endocardium which has historically been difficult to interpret and of limited value in the early stages of disease. This study will focus on novel immunohistochemical stains of the cardiac desmosomes. These will be used to try to aid in the early diagnosis of ARVC.
- ItemOpen AccessInduction of ER stress in macrophages of tuberculosis granulomas(Public Library of Science, 2010) Seimon, Tracie A; Kim, Mi-Jeong; Blumenthal, Antje; Koo, Jovanka; Ehrt, Sabine; Wainwright, Helen; Bekker, Linda-Gail; Kaplan, Gilla; Nathan, Carl; Tabas, IraBACKGROUND: The endoplasmic reticulum (ER) stress pathway known as the Unfolded Protein Response (UPR) is an adaptive survival pathway that protects cells from the buildup of misfolded proteins, but under certain circumstances it can lead to apoptosis. ER stress has been causally associated with macrophage apoptosis in advanced atherosclerosis of mice and humans. Because atherosclerosis shares certain features with tuberculosis (TB) with regard to lesional macrophage accumulation, foam cell formation, and apoptosis, we investigated if the ER stress pathway is activated during TB infection. Principal FINDINGS: Here we show that ER stress markers such as C/EBP homologous protein (CHOP; also known as GADD153), phosphorylated inositol-requiring enzyme 1 alpha (Ire1α) and eukaryotic initiation factor 2 alpha (eIF2α), and activating transcription factor 3 (ATF3) are expressed in macrophage-rich areas of granulomas in lungs of mice infected with virulent Mycobacterium tuberculosis (Mtb) . These areas were also positive for numerous apoptotic cells as assayed by TUNEL. Microarray analysis of human caseous TB granulomas isolated by laser capture microdissection reveal that 73% of genes involved in the UPR are upregulated at the mRNA transcript level. The expression of two ER stress markers, ATF3 and CHOP, were also increased in macrophages of human TB granulomas when assayed by immunohistochemistry. CHOP has been causally associated with ER stress-induced macrophage apoptosis. We found that apoptosis was more abundant in granulomas as compared to non-granulomatous tissue isolated from patients with pulmonary TB, and apoptosis correlated with CHOP expression in areas surrounding the centralized areas of caseation. CONCLUSIONS: In summary, ER stress is induced in macrophages of TB granulomas in areas where apoptotic cells accumulate in mice and humans. Although macrophage apoptosis is generally thought to be beneficial in initially protecting the host from Mtb infection, death of infected macrophages in advanced granulomas might favor dissemination of the bacteria. Therefore future work is needed to determine if ER-stress is causative for apoptosis and plays a role in the host response to infection.
- ItemOpen AccessA semiquantitative and qualitative histopathologic assessment of the effect of type II intrauterine growth retardation on the structure of the carotid bodies in fetuses and neonates(1996) Laing, David; Wainwright, HelenThe major physiological function of the carotid body is to respond to a low partial pressure of oxygen in the systemic arterial blood. The structure and functions of the adult carotid body have been extensively investigated over the past fifteen years. However, the carotid body in children has been relatively neglected with only a handful of studies being performed. To date, no study has been undertaken to investigate the effects of intrauterine hypoxia on the carotid body of foetuses. Clinically, intrauterine growth retardation has been ascribed, amongst other causes, to placental insufficiency that results in chronic hypoxia in the fetus. Intrauterine growth retardation can be divided into two types: - Type I (symmetrical) and type II (asymmetrical). In Type II intrauterine growth retardation, growth retardation does not become clinically evident until the third trimester. There is relative brain sparing with a greater deprivation in the size of abdominal organs, such as the liver and the kidneys. Previous studies have shown that there is no correlation between volume of the carotid body and hypoxia in children. However, Heath et al. made the observation that there are three variants of chief cells (progenitor, light and dark) within the carotid body and that an increase in the relative percentage of the dark subtype is an indicator of hypoxia. Using this observation, the present study set out to test two hypotheses: Firstly, whether the carotid body is functional in utero; and secondly whether there are any objective morphological changes in the carotid bodies of fetuses that have been subjected to intrauterine growth retardation. The carotid bodies from 72 fetuses with a gestational age between thirty and forty weeks were removed from the archived autopsy material, and differential cell counts were performed of the various cells present within the carotid bodies, using haematoxylin and eosin stained sections of the carotid bodies. The cases were assigned to three groups: - I) cases that had clinical and pathological evidence of intrauterine growth retardation, 2) negative controls and 3) positive controls. The three main groups were categorised as follows: -: (1) Intrauterine growth retardation (all cases with a weight for gestational age that is below the tenth centile and a brain to liver ratio of greater than four.) (2) Negative controls (all cases in whom there is a normal weight for age, a brain to liver ratio of less than three and no histological evidence of an episode of significant hypoxia before death). (3) Positive controls (all cases in whom there was clinically significant hypoxia present before death). The groups comprised of: 20 hypoxic positive controls, 15 negative controls, and 16 test cases which had suffered from intrauterine growth retardation. The remaining 21 cases were 7 dysmorphic infants, 3 congenital infection cases (congenital syphilis) and 11 cases that fitted the negative control criteria but had suffered significant hypoxia, thus excluding them from that category. The results showed that no significant difference was present in the percentage of sustentacular cells between any of the three groups. The results of the percentage of dark chief cells were as follows: l) mean percentage of dark chief cells in the intrauterine growth retardation group was 21.1 ±10.9%. 2) mean percentage of dark chief cells in the negative controls was 12.3 ±7.3%. 3) mean percentage of dark chief cells in the positive controls was 21.2 ±9.8%. A significant difference was present between the intrauterine growth retardation cases and the negative controls p=0.013, and between the positive and negative controls p=0.006. The dark chief cell count in the intrauterine growth retardation group showed no significant difference from the positive controls. No age-related difference appeared to be present in any of the groups. The conclusions reached are: a) Clinical hypoxia correlates with morphological changes in the carotid body, manifesting as an increase in the percentage of dark chief cells. b) intrauterine growth retardation cases show similar morphological changes in the carotid body to cases that have suffered from clinical hypoxia. c) therefore, by deduction intrauterine growth retardation fetuses have probably also been exposed to significant hypoxia while in utero. d) the fact that morphological changes in response to hypoxia are occurring in the carotid bodies of fetuses is an indication that the carotid body may be functional in utero. The results of the study indicate that a dark chief cell percentage of greater than 20% indicates that the fetus has been subjected to significant hypoxia, while a percentage of less than 10% indicates that it has not. A percentage of between 10 and 20% is unhelpful in determining whether hypoxia has taken place. The results of this study indicate that histological examination of the carotid bodies in neonates suspected of intrauterine growth retardation could be a useful additional means of assessment.
- ItemOpen AccessUnnatural causes of death in South African children under 14 years in 2001 : an intercity comparison(2003) Van der Heyde, Yolande; Wainwright, Helen; van As, Arjan Bastiaan (Sebastian)Includes bibliographical references.