High density lipoprotein receptors, binding proteins, and ligands

Several HDL binding proteins, quite disparate in structure, have recently been cloned and their role in HDL metabolism is currently being assessed. High density lipoprotein binding protein, HBP (vigilin), which lacks a transmembrane domain is responsive to cell cholesterol levels, but its physiological significance remains unknown. On the other hand much is known about SR-B1, a member of the class B scavenger receptors. The level of SR-B1 expression correlates with both the selective transfer of cholesteryl ester into cells and cholesterol efflux from cells, the transfers probably mediated after docking of HDL at the cell surface. SR-B1 exhibits broad ligand specificity and, in animal models, appears to be regulated by the action of pituitary hormones that stimulate steroidogenesis, suggesting an important role for steroid hormone production in supplying precursor cholesterol. Another candidate HDL receptor, HB2, one of a pair of liver HDL binding proteins, shows high sequence homology with adhesion molecules, particularly activated leukocyte-cell adhesion molecule (ALCAM). When HB2 is overexpressed in cells, HDL binding increases. After PMA-induced differentiation of monocytes into macrophages, HB2 mRNA is strikingly elevated, which correlates with increased binding of HDL, but is down-regulated by cholesterol loading of macrophages. The ligand specificity of the HDL receptors, confounded by nonspecific lipid interactions, remains controversial. Their affinity for apoA-I versus apoA-I/A-II-rich HDL particles has clinical implications; both specific sequences in apoA-I and amphipathic alpha-helices may determine binding events. Post-receptor-mediated signalling events may regulate cell functions which, although not primarily related to lipid transport, nevertheless protect against coronary artery disease. Growing evidence for the involvement of lipid-poor apoA-I as a mediator of such pathways is also discussed.     

Using 2-step PCR and restriction endonuclease digestion to detect K-ras mutation in paraffin-embedded tissues: is it reliable?

BACKGROUND: Among the myocutaneous island flaps applied for reconstruction of large soft-tissue defects after ablative surgery for malignomas, the pectoralis major flap is the one most frequently used. In comparison, the sternocleidomastoid myocutaneous island flap is not as popular. METHODS: We report on our experiences with the superiorly based sternocleidomastoid myocutaneous (SCM) island flap (cutaneous island of 6-8 cm in diameter) in seven consecutive cases after resection of malignomas of the oral cavity and the pharynx. The vascularization from the occipital artery is additionally supplied by preserving the platysma during preparation of the SCM flap. RESULTS: Only one total cutaneous necrosis was observed in a patient who had received prior radiation. In the other 6 cases no major complications (necrosis or fistula) occurred. CONCLUSION: When the preservation of the sternocleidoid muscle does not compromise oncologic principles as in cases with limited lymphe node involvement (N0-N1), the SCM flap appears to be a useful and simple technique, particularly in female patients compared with the pectoralis major flap, in addition to others.     

Abnormal thymocyte subset distribution and differential reduction of CD4+ and CD8+ T cell subsets during peripheral maturation in diabetes-prone BioBreeding rats

In this study we quantified CD8+ and CD4+ T cells in T lymphocytopenic BB rats as compared with control rats at given stages along the maturational pathway from immature thymocytes to mature peripheral T cells. Our results show that BB rats exhibit abnormal thymocyte subset distribution. Numbers of mature TCRhigh/CD4-8+ thymocytes, and also their TCRhigh/CD4+8+ precursors were decreased, as were levels of CD8 expression on all thymocyte subsets investigated. By analogy with mouse thymocyte development, these findings suggest a decreased efficiency for positive selection of CD8 precursors in BB rats. Furthermore, as related to the number of available mature TCRhigh single positive thymocytes, numbers of CD4+ and CD8+ T cells most recently migrated from the thymus were severely decreased in BB blood, indicating either reduced thymic output or rapid cell death after migration. Subsequently, in peripheral blood and cervical lymph nodes, a 95% decrease of CD8+ and a 50 to 80% decrease of CD4+ T cells were demonstrated upon maturation from recent thymic migrants to mature peripheral T cells, leaving the BB rat with a severely reduced T cell population, consisting of CD4+ T cells and a minute population of CD8+ T cells. The vast majority of the latter was found to have an immature peripheral phenotype. Possible consequences of our findings for the generation of autoreactive CD8+ T cells are discussed.     

Acetabular growth potential in congenital dislocation of the hip and some factors upon which it may depend

The factors which determine the rate and amount of acetabular growth in congenital dislocation of the hip are ill-understood. A prospective radiological study has been devised in order to assess the influence of the age of congruity, femoral anteversion and neck/shaft angles on acetabular growth. To be included, the children must have reached at least 8 years of age. Those with associated congenital abnormalities and subluxation were excluded, as were those who had operations for acetabular reconstruction. Seventy-four hips were suitable for analysis, and the age range at follow-up was from 8 to 17 years. The acetabular angle was used as an index of acetabular growth. Measurement of this angle, and the anteversion and neck/shaft angles were made before, and each year after reduction of the hip. Congruity was assessed from a radiograph with the legs in the functional position. A satisfactory acetabulum was obtained in 44 hips and the mean age of congruity was 33 months; the acetabulum was unsatisfactory in 30 hips, with a mean age of congruity of 48 months. Four years is the critical age, for if congruity is obtained later, the risk of producing a moderate or severely dysplastic acetabulum is more than doubled. If congruity is obtained under four years of age, growth of the acetabulum with continue in most patients up to 8 and in some to 11 YEARS OF age; the resulting acetabulum was normal or mildly dysplastic. Fifty-nine per cent of the satisfactory hips at follow-up had a normal anteversion angle, and 6 per cent a normal neck/shaft angle. Correction of these angles by themselves, seems not to be a major importance for promoting acetabular growth.