ORCID Profile
0000-0002-5836-8831
Current Organisations
University of Wollongong
,
University of Wollongong School of Medicine
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Publisher: Informa UK Limited
Date: 30-11-2016
Publisher: Springer Science and Business Media LLC
Date: 28-06-2023
Publisher: Wiley
Date: 02-07-2018
DOI: 10.1111/APT.14866
Abstract: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect. STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined. STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ. Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-06-2020
DOI: 10.2215/CJN.13611119
Abstract: The published tissue adequacy requirement of kidney medulla for BK virus allograft nephropathy diagnosis lacks systematic verification and competes against potential increased procedural risks from deeper s ling. We evaluated whether the presence of kidney medulla improved the diagnostic rate of BK nephropathy in 2244 consecutive biopsy s les from 856 kidney transplants with detailed histologic and virologic results. Medulla was present in 821 s les (37%) and correlated with maximal core length ( r =0.35 P .001). BK virus allograft nephropathy occurred in 74 (3% overall) but increased to 5% (42 of 821) with medulla compared with 2% (32 of 1423) for cortical s les ( P .001). Biopsy medulla was associated with infection after comprehensive multivariable adjustment of confounders, including core length, glomerular number, and number of cores (adjusted odds ratio, 1.81 95% confidence interval, 1.02 to 3.21 P =0.04). In viremic cases ( n =275), medulla was associated with BK virus nephropathy diagnosis (39% versus 19% for cortex P .001) and tissue polyomavirus load (Banff polyomavirus score 0.64±0.96 versus 0.33±1.00 P =0.006). Biopsy medulla was associated with BK virus allograft nephropathy using generalized estimating equation (odds ratio, 2.04 95% confidence interval, 1.05 to 3.96 n =275) and propensity matched score comparison (odds ratio, 2.24 95% confidence interval, 1.11 to 4.54 P =0.03 for 156 balanced pairs). Morphometric evaluation of Simian virus 40 large T immunohistochemistry found maximal infected tubules within the inner cortex and medullary regions ( P .001 versus outer cortex). Active BK virus replication concentrated around the corticomedullary junction can explain the higher detection rates for BK virus allograft nephropathy with deep s ling. The current adequacy requirement specifying targeting medulla can be justified to minimize a missed diagnosis from unders ling.
Publisher: Elsevier BV
Date: 2007
Abstract: Major earthquakes may provoke a substantial number of crush casualties complicated by acute kidney injury (AKI). After the 1988 Armenian earthquake, the International Society of Nephrology (ISN) established the Renal Disaster Relief Task Force (RDRTF) to organize renal care in large disasters this approach proved to be useful in several recent disasters. This paper depicts the organizational aspects of the rescue intervention during the Kashmir earthquake, in 2005. Specific problems were fierce geographic circumstances, lack of pre-registered local keymen, transportation problems, and inexperience of local teams to cope with problems related to mass disasters. Once treatment was installed, global outcomes were favorable. It is concluded that well-organized international help in renal disasters can be effective in saving many lives, but still necessitates conceptual adaptations owing to specific local circumstances.
Publisher: International Scientific Information, Inc.
Date: 02-09-2022
DOI: 10.12659/AOT.937688
No related grants have been discovered for Asrar Khan.