ORCID Profile
0000-0003-2076-2478
Current Organisations
Nepean Hospital
,
University of Sydney
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Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
Publisher: Springer Science and Business Media LLC
Date: 08-2007
DOI: 10.1038/NRD2194
Abstract: Embryonic stem cells (ESCs) will become a source of models for a wide range of adult differentiated cells, providing that reliable protocols for directed differentiation can be established. Stem-cell technology has the potential to revolutionize drug discovery, making models available for primary screens, secondary pharmacology, safety pharmacology, metabolic profiling and toxicity evaluation. Models of differentiated cells that are derived from mouse ESCs are already in use in drug discovery, and are beginning to find uses in high-throughput screens. Before analogous human models can be obtained in adequate numbers, reliable methods for the expansion of human ESC cultures will be needed. For applications in drug discovery, involving either species, protocols for directed differentiation will need to be robust and affordable. Here, we explore current challenges and future opportunities in relation to the use of stem-cell technology in drug discovery, and address the use of both mouse and human models.
Publisher: Wiley
Date: 04-2021
DOI: 10.1111/JPC.1_15466
Publisher: Wiley
Date: 12-2009
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.VASCN.2009.11.001
Abstract: The use of antibodies to proliferating cell nuclear antigen (PCNA) for the immunohistochemical detection of proliferating cells has been limited in frozen tissue sections because of its temperature dependence and instability in formaldehyde. In this study various protocols for the immunohistochemical staining of PCNA in frozen mouse prostate tissue sections were tested in order to identify optimal conditions. Fresh prostate tissues from 8 week old mice were frozen in liquid nitrogen or fixed with formaldehyde or paraformaldehyde before freezing with liquid nitrogen. Frozen tissues were then cut in a cryostat and unfixed sections were fixed by dipping slides with sections into fixative. Slide-mounted tissue sections were permeabilized with Triton X-100 before incubating overnight in primary antibody to PCNA diluted to different concentrations in different diluting media at room temperature or 4 degrees C. Secondary antibody was applied in the same medium as the primary. 19 different experimental protocols were examined. Only one protocol showed strong positive immunostaining for PCNA. PCNA-immunopositive cells were observed in greater abundance in the stromal layer. Paraformaldehyde fixation with Triton X-100 permeabilization without any blocking protocol produced the strongest nuclear PCNA immunolabeling probably when cells are in S-phase of mitosis which indicates the feasibility of PCNA immunoflourescence staining on frozen tissues.
Publisher: Wiley
Date: 04-2007
DOI: 10.1111/J.1460-9568.2007.05489.X
Abstract: The possibility exists that directed differentiation of mouse embryonic stem (mES) cells is capable of yielding enriched populations of dopaminergic neurons, but at present there is little understanding of the pharmacological properties of these cells or whether such cells represent a pharmacologically, phenotypically similar population. In this study we used a simple culture protocol to generate dopaminergic neurons and offer a preliminary pharmacological investigation of these cells using Ca2+ imaging and [3H]-dopamine release studies. In fluo-4 AM loaded cells, 13-17 days postplating, and after the addition of tetrodotoxin some of the population of mouse embryonic stem cell-derived neurons responded to adenosine triphosphate (ATP), noradrenaline (NA), acetylcholine (ACh) and L-glutamate (L-glut) with elevations of Ca2+ influx. Within the microtubule-associated protein and tyrosine hydroxylase (TH)-positive cell population adenosine triphosphate, noradrenaline, acetylcholine and L-glutamate elicited positive elevations of Ca2+ in 74, 66, 58 and 67% of the population cells could be further sub ided into three major pharmacologically distinct populations based on the combinations of agonist they responded to. Acetylcholine (30 microM) and noradrenaline (30 microM) were the only agonists to elicit significant tritium overflow from [3H]-dopamine loaded cells. The acetylcholine effect was blocked by atropine (1 microM) and tetrodotoxin (1 microM) and elevated by haloperidol (100 nM). The noradrenaline effects were reduced by cocaine (10 microM), but not by tetrodotoxin (100 nM). These data indicate that the dopaminergic neurons derived from mouse embryonic stem cells represent a heterogeneous population possessing combinations of purinergic, adrenergic, cholinergic and glutamatergic receptors located on the cell soma.
Publisher: Wiley
Date: 03-04-2023
DOI: 10.1111/JPC.16392
Abstract: To determine characteristics and risk factors for non‐urgent presentations (NUPs) (triage categories 4 and 5) in neonates to a Western Sydney metropolitan mixed adult emergency department (ED) and the effect of COVID‐19 on presentations and admissions. A retrospective medical record study examined neonates (age weeks) presenting to the ED between October 2019 and September 2020 and assessed risk factors for NUPs including the impact of COVID‐19. Regression analysis was used to determine which risk factors were significant for NUPs to ED and whether there were any significant differences in urgency of presentations and admissions during the post‐COVID‐19 time (on/after 11th March 2020). From 277 presentations, 114 (41%) were non‐urgent. After regression analysis, being a mother born overseas (odds ratio 2.15, 95% confidence interval 1.13–4.12, P = 0.02) was a significant risk factor and maternal age (odds ratio 0.98, 95% confidence interval 0.96–0.1.00, P = 0.02) was a significant protective factor for NUPs in the neonatal period. There were 54 (47%) NUPs pre‐COVID‐19 and 60 (53%) NUPs post‐COVID ( P = 0.70). There were similar presenting complaints and diagnoses compared to the literature. Mothers born overseas and younger maternal age were found to be significant risk factors for NUPs in the neonatal period. There was no apparent impact on presentations and admissions to ED during the COVID‐19 period. Further studies are warranted to further evaluate risk factors for NUPs in the neonatal period and further elucidate the impact of COVID‐19 on presentations and admissions, specifically in later waves of the virus.
Publisher: American Medical Association (AMA)
Date: 10-2017
Publisher: Wiley
Date: 03-07-2023
Abstract: This structured survey sought to identify barriers to recognising and reporting potential child abuse by medical officers and nursing staff in the EDs of three Western Sydney hospitals. These include a large metropolitan teaching hospital, a small metropolitan hospital and a rural hospital. A mixed approach of qualitative and quantitative study methodology was used to survey potential participants. The electronic survey was distributed to participants to assess knowledge and experiences with identifying child abuse presenting to the ED over a 6‐month period. A descriptive analysis of the data was performed. A total of 121 responses were received from 340 potential participants, giving a participation rate of 35%. The majority of the respondents were senior medical officers (38/110, 34%) or registered nurses (35/110, 32%). The study participants perceived the lack of time as the most significant barrier to reporting child abuse (85/101, 84%). This was followed by a lack of education (35/101, 34%), resources (33/101, 32%) and support (30/101, 29%). The combination of hospital, departmental and in idual staff issues such as time limitations, lack of resources, education and support are potential barriers to reporting suspected child abuse. We recommend tailored teaching sessions, improved reporting procedures and increased support from senior staff to overcome these barriers.
Publisher: Wiley
Date: 09-01-2008
Publisher: American Medical Association (AMA)
Date: 12-2017
Publisher: American Medical Association (AMA)
Date: 02-2018
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/JPC.13596
Publisher: Wiley
Date: 2007
DOI: 10.1002/PROS.20504
Publisher: Elsevier BV
Date: 02-2007
No related grants have been discovered for Sowmya Gandham.