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Notes: We have previously shown that the MC1R is a key determinant of pigmentary phenotype in man. A range of common and uncommon alleles show diminished function leading to a change in the relative amounts of eumelanin and pheomelanin. As expected, these particular allelic variants are associated with both non-melanoma and melanoma skin cancer and other pigmentary phenotypic characteristics such as freckling. We have recently shown that even against very different genetic backgrounds, the MC1R variants show a phenotypic effect [J Invest Dermatol 2003: 121 (1): 207]. We will present data to explain how the human pigmentary phenotypes can be quantified more appropriately, in terms of both hair melanins and cutaneous response to ultraviolet radiation (submitted and in press). Our results, we would argue, are relevant to those interested in melanocortin signalling in skin and to studies of the genetics of human skin colour and evolution of skin colour.

Notes: 1. The aim of the present study was to investigate whether pre-eclampisa, a state of placental hypoxia, is associated with placental abnormalities in the amount, distribution and expression of enothelial nitric oxide synthase (eNOS).2. Localization and intensity of eNOS was determined by immunohistochemistry using an antibody specific for eNOS. The amount of eNOS mRNA expression was determined by reverse transcription–polymerase chain reaction (RT-PCR) and the densitometry of gel bands was expressed as a ratio of the band density of the housekeeping gene β2-microglobulin.3. Endothelial NOS staining was localized to syncytiotrophoblast cells within the villi and decidual trophoblast cells. It was not present in the endothelium of terminal villous vessels. There was no significant difference in eNOS villous or decidual staining intensity between normal pregnancy (NP; n = 12), pre-eclampsia (n = 14), or gestational hypertension (GH; n = 4). Staining for eNOS was not significantly different in the decidua compared with the villi in NP, GH or pre-eclampsia. Within the decidua, the depth of eNOS staining was similar in NP, pre-eclampisa and GH.4. There was no significant difference in eNOS mRNA expression between NP (0.70 ± 0.11), pre-eclampsia (0.5 ± 0.07) or GH (0.69 ± 0.26).5. These findings suggest that the amount of eNOS in the placenta is not deficient in pre-eclampsia, excluding a possible pathogenic role for eNOS in this disease. Furthermore, placental hypoxia, which is associated with pre-eclampsia, did not induce an upregulation of eNOS

Notes: 1. Pre-eclampsia is a human disease of pregnancy characterized by high blood pressure, proteinuria and end-organ damage, if severe. Pre-eclampsia is thought to be related to changes in early placental development, with the formation of a shallower than normal placental bed.2. Transforming growth factor (TGF)-β1 is a multifunctional fibrogenic growth factor involved in immune regulation that is elevated in some populations with a high risk of hypertensive end-organ disease related to increases in endothelin release. Transforming growth factor-β1 is also an important factor in placental implantation. Alterations in TGF-β1 may be related to abnormal placental development in early pregnancy and, thus, are a candidate for the development of hypertension in pre-eclampsia.3. The aim of the present study was to examine the placental distribution and serum concentration of TGF-β1 in patients with pre-eclampsia compared with normal pregnancy.4. Patients with pre-eclampsia (n = 12) were compared with patients with normal pregnancy (n = 14). Transforming growth factor-β1 was determined by TGF-β1 Max ELISA (Promega, Madsion, WI, USA) after serum dilution (1/150) and acid activation. Placental distribution was determined by immunostaining with TGF-β1 (Santa Cruz, Santa Cruz, CA, USA; 20 ng/mL) and the villi and decidual trophoblast were scored for intensity and extent of staining.5. Patients with pre-eclampsia had a mean gestational age of 36 weeks, whereas those with a normal pregnancy had a mean gestational age of 39.0 ± 0.4 weeks. There was no difference in TGF-β1 concentration between the two groups (mean (±SEM) 27.1 ± 1.0 vs 26.4 ± 0.7 pg/mL for normal pregnancy and pre-eclampsia, respectively; P = 0.73, Mann–Whitney U-test). There was no correlation between systolic or diastolic blood pressure and TGF-β1 concentration (regression analysis P = 0.4 and 0.2). Immunostaining was absent in the villous trophoblast cells and endovascular and extravillous trophoblast of term placentas.6. Although TGF-β1 is present in trophoblast cells in early pregnancy during placental development, TGF-β1 concentrations were not increased in the placenta at term in pre-eclampsia and there was no correlation between blood pressure and serum TGF-β1, suggesting that TGF-β1 does not play a role in the development of late gestation pre-eclampsia and hypertension.