Browsing by Author "Schoeman, Johan"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Open Access
    Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function
    (2017) Hemingway, Cheryl; Berk, Maurice; Anderson, Suzanne T; Wright, Victoria J; Hamilton, Shea; Eleftherohorinou, Hariklia; Goldgof, Greg M; Hickman, Katy; Kampmann, Beate; Schoeman, Johan; Eley, Brian; Beatty, David; Pienaar, Sandra; Nicol, Mark P; Griffiths, Michael J; Waddell, Simon J; Newton, Sandra M; Coin, Lachlan J; Relman, David A; Montana, Giovanni; Levin, Michael
    The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies.
  • Thumbnail Image
    Item
    Open Access
    Skeletal muscle composition in various breeds of domestic dogs: (A comparative study)
    (2019) van Boom, Kathryn; Kohn, Tertius; Schoeman, Johan
    The rising rate of insulin resistance and type 2 diabetes in humans over the past two decades have been linked to increasing rates of obesity, aging and urbanisation. A similar pattern is occurring in domestic animals, specifically cats and dogs. Skeletal muscle is a vital organ in the regulation of blood glucose. Its composition in terms of muscle fibre type, metabolism and contractility can differ substantially between species, but is poorly studied in the domestic dog, in particular the various breeds. It was hypothesised that insulin resistance and type 2 diabetes may be associated with muscle fibre type, in particular, muscle with a low type I fibre content being a predisposing factor. Therefore, the aims of this study were to investigate the skeletal muscle fibre composition and metabolic profile in the Triceps brachii (TB) and Vastus lateralis (VL) of 16 breeds of domestic dogs (Canis lupus familiaris). A secondary aim was to correlate the skeletal muscle composition with breeds reported as having a high incidence of diabetes. Skeletal muscle samples were collected post mortem from the TB and VL of 38 dogs from different breeds, age and sex, and analysed for fibre type composition, fibre size, oxidative and glycolytic metabolic capacity (citrate synthase (CS), 3-hydroxyacetyl co A dehydrogenase (3-HAD), creatine kinase (CK) and lactate dehydrogenase (LDH) enzyme activities). There was no significant difference between the TB and VL in any of the measurements. Type IIA was the predominant fibre type for both muscle groups (TB: 43%; VL: 44%) followed by type I (TB: 33%; VL: 38%) and type IIX (TB: 24%; VL: 18%). The cross sectional area (CSA) of the fibres were all smaller compared to humans and other wild animals. Surprisingly, there was no difference in the CSA between the fibres types and muscle groups: Type I: TB: 1740 µm2 ; VL: 1712 µm2 , Type IIA: TB: 1690 µm2 ; VL: 1720 µm2 , Type IIX TB: 1726 µm2 ; VL: 1791 µm2 ). Metabolically, the muscle of the dog displayed a high oxidative capacity with high activities (all activities in µmol/min/g protein) for CS (TB: 61; VL: 49) and 3-HAD (TB: 53; VL: 46). Lower CK (TB: 6115; VL: 6279) and higher LDH (TB: 1550; VL: 1478) activities than humans indicated a lower and higher flux through the high energy phosphate and glycolytic pathway, respectively. These results indicate that the dog has a predominance of type IIA fibres along with a higher oxidative capacity. There appears to be no pattern in fibre type profile that could be associated with a predisposition of a specific breed to insulin resistance and diabetes, although many of the breeds with a known risk did not form part of the study sample. This is the first study to characterise the skeletal muscle composition of a large population of dogs (16 breeds), but the association of breed to diabetes was not found. Future studies should include younger and more animals, as well as a diabetic population of dogs.