Excitatory amino acid stimulation of the survival of rat cerebellar granule cells in culture is associated with an increase in SMN, the spinal muscular atrophy disease gene product.

Excitatory amino acids which promote the survival of cerebellar granule cells in culture, also promote the expression of the survival of motor neuron (SMN) protein. Immunolocalization studies using SMN monoclonal antibody showed that SMN is decreased in cultures grown in low K+ or chemically defined medium with respect to cultures grown in high K+ medium and that an increase of SMN can be induced by treatment of low K+ cultures with glutamate or N-methyl-D-aspartate.

SMN protein analysis in fibroblast, amniocyte and CVS cultures from spinal muscular atrophy patients and its relevance for diagnosis.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by the homozygous absence of the telomeric copy of the survival motor neuron (SMNt) gene, due to deletion, gene conversion or point mutation. SMNt and its homologous centromeric copy (SMNc) encode the SMN protein, which is diffusely present in the cytoplasm and in dot-like structures, called gems, in the nucleus. We have studied the SMN protein in different cell cultures, including fibroblasts, amniocytes and CVS cells from SMA individuals and controls. By immunofluorescence analysis we found a marked reduction in the number of gems in fibroblasts, amniocytes and chorionic villus cells of all SMA patients and foetuses, independent of the type of the genetic defect. We also show that immunolocalisation of the SMN protein may be a useful tool for the characterisation of particular patients of uncertain molecular diagnosis.

Fluid shear stress increases the release of platelet derived growth factor BB (PDGF BB) by aortic endothelial cells.

OBJECTIVES: The aim of this study was to determine the correlation between shear stress and the release of Platelet Derived Growth Factor (PDGF BB) by aortic endothelial cells. DESIGN AND SETTING: Laboratory in vitro study. MATERIALS: Bovine aortic endothelial cells were seeded in fibronectin-coated cylinders at 1.0 x 10(6) cells/tube and allowed to reach confluence and to adhere for 48 hours. The experimental groups were subjected to nonpulsatile, laminar flow of 50, 100, 150 ml/min in polystyrene cylinders (i.d. 10 mm) of a closed circulatory loop giving a shear stress on the endothelial cells of 3, 6, 9 dyn/cm2. The control group was subjected to similar incubation conditions without flow. OUTCOME MEASURES: The release of PDGF BB by endothelial cells was measured by ELISA and Western Blot Analysis. RESULTS: Shear stress increased significantly (p < 0.01) the release of PDGF BB by endothelial cells. CONCLUSIONS: PDGF BB release by endothelial cells may be one of the mechanisms linking hemodynamic forces and adaptation of blood vessels wall.

Growth factor production after polytetrafluoroethylene and vein arterial grafting: an experimental study.

PURPOSE: Occlusion caused by myointimal hyperplasia appears to be the main reason of late failure of polytetrafluoroethylene (PTFE) arterial bypass grafts. Evidence exists that growth factors are involved in the genesis of myointimal hyperplasia. The aim of this study was to assess the release of platelet-derived growth factor (PDGF) and basic fibroblastic growth factor (bFGF) by PTFE arterial grafts. METHODS: In 15 inbred Lewis rats a 1 cm long segment of PTFE was interposed at the level of the abdominal aorta. In a control of another 15 Lewis rats in a vein graft was implanted at the level of the abdominal aorta. Animals were killed four weeks after implantation and the tissue was studied in organ culture for release of PDGF AA, PDGF BB, and bFGF. RESULTS: PTFE grafts released a greater quantity of PDGF AA than did control vein grafts (28 +/- 4 ng/cm2/72 hr vs 7 +/- 2 ng/cm2/72 hr). Similarly, PTFE grafts released a greater quantity of bFGF than did arterial vein grafts (308 +/- 22 ng/cm(2)/72hr vs 204 +/- 20 ng/cm2/72 hr). CONCLUSIONS: We conclude that PTFE arterial grafts released a high quantity of growth factor, which could explain, in part, the occurrence of distal anastomotic myointimal hyperplasia.

The degree of porosity influences the release of growth factors by healing polytetrafluoroethylene (PTFE) grafts.

OBJECTIVES: The aim of this study was to determine the influence of the degree of porosity on the release of growth factors (PDGF AA, PDGF BB, bFGF) by healing PTFE grafts. DESIGN AND SETTING: Laboratory animal study. MATERIALS: 1 cm long segments of non-reinforced PTFE grafts (30 microns fibril length, 2 mm internal diameter, 0.39 mm thick) were placed as an abdominal aortic interposition in Lewis rats. Fifteen grafts served as control (Group A; porous grafts); in eight rats (Group B; non porous grafts) the PTFE graft was completely wrapped by a non-porous plastic envelope. Animals were killed 4 weeks after surgery. OUTCOME MEASURES: The release of PDGF AA, PDGF BB and bFGF was assessed by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: The release of PDGF AA, PDGF BB and bFGF was statistically higher in porous grafts. The only histological difference between the two groups was that porous PTFE grafts were invaded by many tufts of capillaries from the surrounding tissue, whereas this phenomenon was absent in non porous PTFE grafts. CONCLUSIONS: The degree of porosity influences the release of growth factors by healing PTFE grafts. This fact may have implication in the endothelisation of PTFE grafts and in myointimal hyperplasia formation as well.

bFGF release is dependent on flow conditions in experimental vein grafts.

OBJECTIVES: Basic Fibroblastic Growth Factor (bFGF) is a powerful mitogen for smooth muscle cells and has been implicated in the genesis of Myointimal hyperplasia. The aim of this study was to determine the release of bFGF by veins in different haemodynamic conditions. DESIGN AND SETTING: Laboratory animal study. MATERIALS: In 39 Lewis rats, a 1 cm long segment of inferior vena cava was inserted at the level of the abdominal aorta. The segments of inferior vena cava were obtained from syngenic Lewis rats. Arterial Vein Grafts (AVG) were harvested after 4 weeks (AVG 4) and 12 weeks (AVG 12). In 16 animals the arterial vein grafts were explanted 4 weeks after the initial operation and reimplanted (Reimplanted Vein Grafts: RVG) in syngenic Lewis rats as venous-venous bypass grafts at the level of the left iliac vein and harvested after 2 weeks (RVG 2) and 8 weeks (AVG 8). OUTCOME MEASURES: The tissue was studied in organ culture in a serum-free system for (1) release of bFGF (immunoassay) and (2) mitogenic activity of the conditioned media. Scanning electron and light microscopy studies were also performed. RESULTS: bFGF release by veins increased significantly (p < 0.01) when veins were inserted in the arterial circulation, and decreased significantly (p < 0.01) when grafts were reimplanted in the venous system. bFGF release (ng/cm2): [Formula: see text] CONCLUSION: Vein inserted in the arterial circulation release a higher quantity of bFGF. This could explain in part, the formation of myointimal hyperplasia in arterial vein graft.

Sweet's syndrome: association with accelerated phase of chronic myeloid leukemia.

The authors describe a case of Sweet's syndrome in a woman affected with chronic myeloid leukemia. They emphasize the association of the syndrome with a progression of the disease and the complete disappearance of it for 3 years until the present time after allogeneic bone marrow transplantation.