ORCID Profile
0000-0002-5678-5965
Current Organisation
University of Helsinki
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Publisher: Oxford University Press (OUP)
Date: 09-2004
Publisher: The Company of Biologists
Date: 15-09-2006
DOI: 10.1242/JCS.03105
Abstract: Oocytes regulate follicle growth by secreting paracrine growth factors that act on neighbouring granulosa cells (GCs). Those factors identified to date are mainly members of the transforming growth factor-β (TGFβ) superfamily, but little is known about which specific receptor/signalling system(s) they employ. This study was conducted to determine the requisite pathways utilised by oocytes to promote GC proliferation. We used an established oocyte-secreted mitogen bioassay, where denuded mouse oocytes are co-cultured with mural GCs. Oocytes, growth differentiation factor-9 (GDF9), TGFβ1 and activin-A all promoted GC DNA synthesis, but bone-morphogenetic protein 6 (BMP6) did not. Subsequently, we tested the capacity of various TGFβ superfamily receptor ectodomains (ECD) to neutralise oocyte- or specific growth factor-stimulated GC proliferation. The BMP type-II receptor (BMPR-II) ECD antagonised oocyte and GDF9 bioactivity dose-dependently, but had no or minimal effect on TGFβ1 and activin-A bioactivity, demonstrating its specificity. The TGFβR-II, activinR-IIA and activinR-IIB ECDs all failed to neutralise oocyte- or GDF9-stimulated GC DNA synthesis, whereas they did antagonise the activity of their respective native ligands. An activin receptor-like kinase (ALK) 4/5/7 inhibitor, SB431542, also antagonised both oocyte and GDF9 bioactivity in a dose-dependent manner. Consistent with these findings, oocytes, GDF9 and TGFβ1 all activated SMAD2/3 reporter constructs in transfected GC, and led to phosphorylation of SMAD2 proteins in treated cells. Surprisingly, oocytes did not activate the SMAD1/5/8 pathway in transfected GCs although exogenous BMP6 did. This study indicates that oocyte paracrine factors primarily utilise a similar signalling pathway first identified for GDF9 that employs an unusual combination of TGFβ superfamily receptors, the BMPR-II and a SMAD2/3 stimulatory ALK (4, 5 or 7), for transmitting their mitogenic actions in GC. This cell-signalling pathway may also have relevance in the hypothalamic-pituitary axis and in germ-somatic cell interactions in the testis.
Publisher: BMJ
Date: 31-12-2021
DOI: 10.1136/BMJSPCARE-2021-003087
Abstract: It is essential that the physical environments in which inpatient palliative care is provided support the needs of patients and the facilitate the multidimensional delivery of palliative care. This review aims to identify the features and characteristics of inpatient palliative care environments that enhance or detract from the patient experience and identify opportunities for progress within this field. Three databases were searched: MEDLINE (1946–2020), PsycINFO (1806–2020) and CINAHL (1937–2020). Articles were screened by title and abstract with included studies read in full for data extraction. Data synthesis involved thematic analysis informed by the findings of the included literature. Inclusion criteria were studies with empirical methodology examining adult palliative care in the hospital, hospice or nursing home environment. Studies that examined palliative care delivered within the emergency department, ICU or within the home were excluded, as were those related to paediatric palliative care. Four main themes were identified: the provision of privacy, facilitating interactions with family, facilitating comfort through homeliness and connections to nature. The board acceptance of single rooms as the preeminent design solution for supporting privacy, dignity and family interaction, alongside current conceptions of homeliness that typically focus on matters of interior design, are limiting possibilities for further design innovation within palliative care settings. Research that investigates a broader set of design strategies through which the built environment can support care, alongside enhanced interdisciplinary collaboration, could positively contribute to patient and family experiences of inpatient palliative care.
No related grants have been discovered for Kevin Wong.