1 Pharmacological characterization of different lysophosphatidylcholines was performed based on their effect on the Ca2+ sensitivity of contraction in α-toxin-permeabilized rat mesenteric arteries. Furthermore, the effect of noradrenaline on [3H]-myristate-labelled lysophosphatidylcholine levels was assessed, to investigate whether lysophosphatidylcholines could be second messengers. 2 Palmitoyl or myristoyl L-α-lysophosphatidylcholine increased the sensitivity to Ca2+, whereas lysophosphatidylcholines containing other fatty acids had less or no effect. 3 L-α-phosphatidylcholine, L-α-glycerophosphorylcholine, palmitic acid, myristic acid and choline, potential metabolites of lysophosphatidylcholines, did not affect contractions. 4 Noradrenaline (GTP was required) and GTPγS increased the sensitivity to Ca2+, and GDP-β-S inhibited the effect of noradrenaline. Lysophosphatidylcholines, however, had no requirement for GTP and caused sensitization in the presence of GDP-β-S. 5 Calphostin C, a relatively specific protein kinase C inhibitor, did not affect contraction induced by Ca2+, but abolished the sensitizing effect of lysophosphatidylcholine. 6 Noradrenaline caused no measurable changes in the levels of [3H]-myristate-labelled phosphatidylcholine and lysophosphatidylcholine at 30 s and 5 min stimulation. 7 These results suggest that lysophosphatidylcholines can increase Ca2+ sensitivity through a G-protein-independent, but a protein kinase C-dependent mechanism. However, the role for lysophosphatidylcholines as messengers causing Ca2+ sensitization during stimulation with noradrenaline remains uncertain because no increase in [3H]-myristate labelled lysophosphatidylcholine could be measured during noradrenaline stimulation.
The purpose of this study was to measure differences in oxygenation between the left and right sides of the fetal liver during varying oxygenation levels.Eight ewes carrying singleton fetuses at gestational age 125 days (term, 145 days) were included in the study. Under anesthesia the ewes were ventilated with gas containing different levels of oxygen, thereby subjecting the fetuses to hyperoxia (mean ± SD maternal arterial partial pressure of oxygen (pO2), 23.2 ± 8.2 kPa) and hypoxia (mean maternal arterial pO2, 7.1 ± 0.5 kPa). Changes in oxygenation within the fetal liver were assessed by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI).During hyperoxia there was no difference between the BOLD signal in the left and right sides of the fetal liver; mean change in BOLD (ΔBOLD)(hyperox), -0.9 ± 3.7%. During hypoxia, however, the decrease in the BOLD signal was more pronounced in the right side as compared with the left side, thereby creating a significant increase in the left-right difference in the BOLD signal; mean ΔBOLD(hypox), 5.2 ± 2.2% (P = 0.002, paired t-test). The left-right difference was directly proportional to the degree of hypoxia (R2 = 0.86, P = 0.007).To our knowledge, this is the first study demonstrating differences in oxygenation between the left and right sides of the fetal liver during hypoxia, a difference that can be explained by increased ductus venosus shunting. Thus, the BOLD MRI technique is a promising non-invasive tool that might be useful for the future monitoring of the human fetus.
The aim was to characterize the variation in the cellular in vitro radiosensitivities in squamous cell carcinomas of the head and neck, and to test for a possible correlation between different measures of radiosensitivity and the clinical and histopathological data. Cellular in vitro radiosensitivities were assessed in tumour biopsies from 71 patients using the modified Courtenay–Mills soft agar clonogenic assay combined with an immunocytochemical analysis. Radiosensitivity was quantified as the surviving fraction after a radiation dose of 2 Gy irrespective of cell type (overall SF2), or based on identification of cell type (tumour cell SF2, fibroblast SF2). Sixty-three biopsies were from primary tumours, and eight were from recurrences. Overall plating efficiency ranged from 0.005 to 1.60% with a median of 0.052%. The majority of the colonies obtained from the biopsies were fibroblast marker-positive; the proportion of tumour marker-positive colonies ranged from 1 to 88% with a median of 15%. The median overall SF2 was 0.47 (range 0.24–0.96), the median tumour cell SF2 was 0.50 (range 0.11–1.0) and the median fibroblast SF2 was 0.49 (range 0.24–1.0). Comparing data from independent experiments, the overall SF2 was significantly correlated with the SF2 of fibroblasts (2P = 0.006) but not with the tumour cell SF2. The tumour cell and fibroblast radiosensitivities measured in the same individuals were not correlated (r = 0.06, 95% CI [–0.19, 0.30]). This finding seems to preclude a strong correlation between the radiosensitivity of tumour cells and fibroblasts. Concerning the clinical characteristics, neither of the measures of tumour radiosensitivity was correlated with T- and N-category, stage, tumour size, sex and age. However, the tumour cell radiosensitivity decreased with increasing grade of histopathological differentiation (2P = 0.012). The same tendency was found in two independent analyses of the same patient material. This correlation was not significant in case of the overall SF2 or the fibroblast SF2.
Foetal MRI has become an established image modality in the prenatal diagnosis of CNS anomalies, but image quality can be severely affected by foetal movements. The objective was to overcome these inherent motion problems by applying interactive real-time MRI and to evaluate the diagnostic usefulness of the applied real-time MRI sequence in relation to standard protocols.Ten healthy foetuses (gestation week 21·3 ± 0·5) were scanned using a system, which allowed visual feedback and interactive slice positioning in real time. The data were compared to a control group of 14 healthy foetuses (gestation week 21·0 ± 0·8) who had previously been scanned using standard MRI. Comparisons were carried out by two radiologists with regard to cerebral anthropometric sizes, presence of important brain structures, degree of movement, clinical image value, image quality and ability to obtain correct slice planes.Two out of eight anthropometric sizes were statistically different between the two groups. Representation of cerebral structures was found in 70-100% in the real-time group. No statistically differences were found in clinical image value and image quality. The mean ability to obtain optimal slice planes was higher in the real-time group, but it was not significant.Imaging of the foetal brain using the proposed interactive real-time MRI system is a promising alternative to traditional foetal MRI for anthropometrics or as a supplement for the representation of foetal brain structures in cases in which foetal motion causes challenges in relation to obtaining optimal slice planes using conventional MRI techniques.
Children with major congenital heart defects are risking impaired cerebral growth, delayed cerebral maturation, and neurodevelopmental disorders. We aimed to compare the cerebral tissue oxygenation of fetuses with major heart defects to that of fetuses without heart defects as estimated by the magnetic resonance imaging modality T2*. T2* is low in areas with high concentrations of deoxyhemoglobin.At gestational age mean 32 weeks (early) and mean 37 weeks (late), we compared the fetal cerebral T2* in 28 fetuses without heart defects to that of 15 fetuses with major heart defects: transposition of the great arteries (n=7), coarctation of the aorta/hypoplastic aortic arch (n=5), tetralogy of Fallot (n=1), hypoplastic right heart (n=1), and common arterial trunk (n=1). The women were scanned with a 1.5 T Philips scanner using a breath-hold multiecho gradient echo sequence. Among fetuses without heart defects, the mean T2* value was 157 ms (95% confidence interval [CI], 152-163) early and 125 ms (95% CI, 120-130) late. These figures were significantly lower (mean 14 ms; 95% CI, 6-22; P<0.001) among fetuses with heart defects 143 ms (95% CI, 136-150) early and 111 ms (95% CI, 104-118) late.Our findings indicate that fetal cerebral T2* is measurable and that fetal cerebral tissue oxygenation measured by T2* is lower in fetuses with heart defects compared with fetuses without heart defects. This corroborates the hypothesis that tissue hypoxia may be a potential pathogenic factor that possibly affects brain development in fetuses with heart defects.
