p38alpha antagonizes p38gamma activity through c-Jun-dependent ubiquitin-proteasome pathways in regulating Ras transformation and stress response

p38 MAPK family consists of four isoform proteins (alpha, beta, gamma, and delta) that are activated by the same stimuli, but the information about how these proteins act together to yield a biological response is missing. Here we show a feed-forward mechanism by which p38alpha may regulate Ras transformation and stress response through depleting its family member p38gamma protein via c-Jun-dependent ubiquitin-proteasome pathways. Analyses of MAPK kinase 6 (MKK6)-p38 fusion proteins showed that constitutively active p38alpha (MKK6-p38alpha) and p38gamma (MKK6-p38gamma) stimulates and inhibits c-Jun phosphorylation respectively, leading to a distinct AP-1 regulation. Depending on cell type and/or stimuli, p38alpha phosphorylation results in either Ras-transformation inhibition or a cell-death escalation that invariably couples with a decrease in p38gamma protein expression. p38gamma, on the other hand, increases Ras-dependent growth or inhibits stress induced cell-death independent of phosphorylation. In cells expressing both proteins, p38alpha phosphorylation decreases p38gamma protein expression, whereas its inhibition increases cellular p38gamma concentrations, indicating an active role of p38alpha phosphorylation in negatively regulating p38gamma protein expression. Mechanistic analyses show that p38alpha requires c-Jun activation to deplete p38gamma proteins by ubiquitin-proteasome pathways. These results suggest that p38alpha may, upon phosphorylation, act as a gatekeeper of the p38 MAPK family to yield a coordinative biological response through disrupting its antagonistic p38gamma family protein.     

Electron-microscopic immunolabelling of vasoactive substances in human umbilical endothelial cells and their actions in early and late pregnancy

Human umbilical vessels are devoid of nerves and therefore endothelial cells may play an important role in the control of feto-placental blood flow. The pharmacological effects of 5-hydroxytryptamine, histamine and endothelin were examined in umbilical arteries and veins from legal terminations (gestational age 8–17 weeks, n=12) and normal term vaginal deliveries (gestational age 38–41, n=12). Immunocytochemistry of human unbilical vessels indicated that 5-hydroxytryptamine, histamine and endothelin were localised in subpopulations of endothelial cells of both artery and vein in late, but not early, pregnancy. 5-Hydroxytryptamine (10 nM–30 μM) caused sustained concentration-dependent contractions in all vessels from early and late pregnancy. Histamine (0.1 μM–30 mM) also caused sustained contractions in all vessels from late pregnancy but only 27% of arteries and 41% of veins from early pregnancy responded. Endothelin (10 pM–30 nM) caused slow long-lasting contractions in all vessels from early and late pregnancy. Atrial natriuretic peptide and neuropeptide Y did not alter vascular tone. The endothelium may thus play an autocrine/paracrine role, by synthesizing and releasing the above reactive substances in late pregnancy to influence feto-placental blood flow. Received: 23 May 1995 / Accepted: 13 October 1995     

Dermatoglyphic variation and weight and length at birth

Relationships between dermatoglyphic variables, including finger ridge counts and finger, palmar, and plantar pattern intensities, and weight and length at birth, were tested in a sample of 184 boys and 202 girls from Warsaw schools. No convincing evidence for such relationships has been obtained from the results of correlations and one-way analysis of variance, although there are indications that some palmar traits may be related to length at birth in females. The data agree with the common belief that birth weight and birth length are mainly determined by influences operating in later stages of pregnancy, that is, after the 20th gestational week.     

Bivariate and multivariate analysis of the skin ridge pattern intensities

Bivariate correlations and multivariate (factor) analysis of pattern intensities on individual fingers and all specified areas of palms and soles were performed in a large sample of 834 individuals from two rural districts of Poland, and in a sample of 383 school children from the city of Warsaw, with males and females considered separately. Eleven factors were extracted in all samples, including two for finger pattern intensities, and the remaining nine for palmar or sole individual areas, or some of their combinations. Patterns of intercorrelation between variables and the factor structure matrices were essentially similar in all subsamples, but several factors differed in the amount of variance they contributed to individual variables, or the factors occupied somewhat different positions when ranked in respect of the contribution to the total variance. Orthogonal and oblique rotation were applied to the data, but only the results of the latter were tabulated and fully discussed. In contrast with finger patterns, separate and independent factors have mainly been extracted for individual pattern intensities on palms or soles. Nevertheless the obtained factor solution on the whole is not incompatible with the concept of developmental induction fields. It is postulated that the factor structure may be susceptible to natural selection acting through functional preferences in man, and that epistatic interaction may account for some common factors.     

Perivascular nerves and vascular endothelium: recent advances

Within the last few years, advances have been made regarding perivascular nerves and the endothelium of the vascular system, both potentially important in the understanding of the mechanisms of local control of blood flow. Endothelin-1 (ET-1) has been identified in rat cerebrovascular nerves, neuropeptide Y (NPY) has been demonstrated in umbilical endothelium, the arginine-vasopressin (VP) system has been discovered in the heart (including coronary endothelium), and P2X receptors have been observed in vascular endothelial cells. After a brief introduction to vascular biology, this review will focus on the above-mentioned new data.     

Human saphenous vein and coronary bypass surgery: ultrastructural aspects of conventional and "no-touch" vein graft preparations

Coronary artery bypass graft surgery (CABG) is routinely used to restore blood flow to diseased cardiac muscle due to coronary artery disease. The patency of conventional grafts decreases with time, which is due to thrombosis and formation of neointima. A primary cause of graft failure is the mechanical damage inflicted to the graft during harvesting, including removal of surrounding tissue accompanied by high pressure saline distension to overcome vasospasm (both causing considerable mechanical trauma). The aim of this study was to compare the ultrastructural features of human saphenous vein (SV) grafts harvested conventionally and grafts prepared using an atraumatic 'no-touch' harvesting technique introduced by Souza (1996). The results of this study showed a better preservation of the lumenal endothelium and medial vascular smooth muscle (SM) in 'no-touch' versus conventional grafts. A 'fast' (within 30 min) response of SM cells to conventional harvesting was noted where features of both SM cell division and apoptosis were observed. It is concluded that the 'preserved' nature of the 'no-touch' aortocoronary SV grafts renders them less susceptible to thrombotic and atherosclerotic factors than grafts harvested conventionally. These features are suggested to contribute to the improved early patency rate described using the no-touch technique of SV harvesting.     

Ultrastructural investigation of nitric oxide synthase-immunoreactive nerves associated with coronary blood vessels of rat and guinea-pig

Ultrastructural investigation of nitrix oxide synthase-immunoreactive nerves closely associated with blood vessels in rat and guinea-pig hearts revealed many labelled nerve fibres in the walls of the main branches of the coronary arteries, and in arterioles, capillaries and post-capillary venules. The number of nitric oxide synthase-containing nerve fibres associated with different vessels, even those of the same calibre, varied. Terminal regions of nitric oxide synthase-immunoreactive fibres were observed in the endocardium and myocardium. Nitric oxide synthase-labelled fibres displayed electrondense immunoproduct in both varicose and intervaricose regions. Immunoreactive axonal varicosities contained both small and large synaptic vesicles. The characteristics of the nitric oxide synthase-immunoreactive nerve fibres observed in the heart and the possibility that these fibres represent the processes of intracardiac neurones and/or sensory neurones of extrinsic origin are discussed.