Effects of epidermal growth factor and dibutyryl cyclic adenosine monophosphate on the migration pattern of astrocytes grafted into adult rat brain.

OBJECTIVE: Neonatal rat astrocytes transplanted into host brains migrate in specific patterns, which are determined by the developmental stage of the host brain and the region of implantation. We hypothesized that the differentiation state of the implanted astrocytes could also affect astrocyte migration. METHODS: Astrocytes derived from neonatal rats (1-4 d) were placed in culture and exposed to growth- or differentiation-promoting agents (e.g., epidermal growth factor or dibutyryl cyclic adenosine monophosphate). Treated cells were then injected into different regions of the adult rat brain. At 3, 6, and 9 days after implantation, the extent and pattern of astrocyte migration after injection into the cortex, hippocampus, and corpus callosum were assessed. RESULTS: Astrocytes pretreated with either factor did not migrate during the first 3 days after implantation into the host cortex and hippocampus, whereas untreated cells migrated extensively by Day 3. After 9 days, implanted cells that had been pretreated with dibutyryl cyclic adenosine monophosphate began to demonstrate migratory activity, whereas those exposed to epidermal growth factor remained at the site of implantation. These findings corresponded to the effects of these agents in culture. On the other hand, cells implanted into the corpus callosum migrated in spite of pretreatment. CONCLUSION: Epidermal growth factor and dibutyryl cyclic adenosine monophosphate each altered the cells in culture such that they were inhibited from migrating after transplantation into the host cortex and hippocampus. This finding suggests that the activation of either growth or differentiation cascades partially inhibits the migratory ability in these cells either through effects on their internal migratory potentials or their responsiveness to external migratory signals. In contrast, cells implanted into the corpus callosum migrated in spite of pretreatment, suggesting that this structure may present migratory cues sufficient to override the effects of treatment.     

Pediatric anesthesia in France. Which patients? What reasons?

The population undergoing anaesthesia and the reasons for such a procedure were studied in children (under 15 years of age), through data collected in an INSERM national survey on anaesthesia. This survey was representative of the whole anaesthetic activity performed yearly in France. 750,000 anaesthesias are performed each year in paediatrics, giving an annual rate of 6.4 anaesthesias per 100 children. The highest rate was observed at the age of 4 years, and the higher percentage of boys exists at any age. The main fields of intervention are ENT surgery (30.9%), digestive surgery (25.2%), orthopedic and trauma surgery (12,2%) and surgery on male genitalia (8.9%). The most common procedure is appendectomy which accounts for one fifth of all procedures in children (153,000 each year).     

An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study Ann Oncol 2002; 13: 1264-1274

The authors wish     

Metabolism of rabbit angiostatin glycoforms I and II in rabbits: angiostatin-I leaves the intravascular space faster and appears to have greater anti-angiogenic activity than angiostatin-II

Plasminogen (PLG) exists in the circulation as two glycoforms, I and II. Angiostatin (AST) is a polypeptide that has been cleaved from the kringle region of PLG and has strong anti-angiogenic properties. AST-I and AST-II, which consisted only of kringles 1 through 3, were prepared by the action of urokinase on purified rabbit PLG-I and PLG-II, respectively, in the presence of N-acetyl cysteine, followed by affinity chromatography on lysine-Sepharose. Purified AST-I and AST-II were tested for functional activity with a chick chorioallantoic membrane (CAM) model; when similar amounts were applied to a 6-day CAM, AST-I was substantially more effective than AST-II in decreasing vascular supply to the CAM over a 72-hour period; this activity correlated with a loss of capillaries, probably through apoptosis of endothelial cells. Radiolabeled AST-I and AST-II (iodine 125 and iodine 131) were co-injected intravenously into healthy rabbits to determine their clearances from plasma measured over 3 days. Over a dose range of 0.08 to 2.7 microg/kg, the fractional catabolic rate within the intravascular space (j(3)) indicated that AST-I was cleared 3-fold to 4-fold more rapidly than AST-II (P < .001). The catabolic half-life of AST-I (2.01 +/- 0.19 days) was significantly less than that of AST-II (2.62 +/- 0.20 days). The faster clearance of AST-I from the intravascular space was matched by its more rapid passage than AST-II to the extravascular space of various organs over 60 minutes in vivo. This property of AST-I as compared with AST-II may partially explain its greater anti-angiogenic potential. From the plasma concentrations of PLG-I and PLG-II and their relative behaviors toward rabbit VX-2 lung tumors in vivo, we predict that substantially greater quantities of AST-II than AST-I may be released into the extravascular space of tumors.     

Enhanced binding of fibrinogen by the subendothelium after treatment of the rabbit aorta with thrombin

Damage to the endothelial surface of an artery invokes a hemostatic response that causes platelet deposition and activation of the coagulation and fibrinolytic pathways on the exposed subendothelial surface. Plasma fibrinogen is rapidly adsorbed at the site of injury. To gain insight into fibrinogen uptake, undamaged and de-endothelialized rabbit thoracic aortas were pretreated with various concentrations of thrombin and then incubated with fibrinogen labeled with iodine 125 in vitro. Uptake of fibrinogen by the subendothelium was not affected by low thrombin concentrations (less than 10 nmol/L), probably because of the antithrombin capacity of the vessel wall to inactivate any thrombin adsorbed. Over the thrombin concentration range of 10 to 90 nmol/L. fibrinogen binding increased linearly as binding of thrombin labeled with iodine 131 increased. In contrast, treatment of the subendothelium with enzymatically inactive thrombin did not enhance fibrinogen binding. Fibrinogen binding was inhibited by exposing the thrombin-treated subendothelium to hirudin or phenylalanyl-prolyl-arginyl-chloromethyl ketone. High thrombin concentrations (greater than 100 nmol/L) caused either a steadily decreasing uptake of fibrinogen with low fibrinogen concentrations or fibrin coagulation on the subendothelial surface from a high fibrinogen concentration. Glycyl-prolyl-arginyl-proline (0.1 mg/ml), a selective inhibitor of fibrin polymerization, inhibited 72% to 78% of fibrinogen uptake by the thrombin-treated subendothelium. Fibrinogen uptake was Ca2(+)-dependent, but ethylenediaminetetraacetic acid (10 mmol/L) did not displace subendothelium-bound fibrinogen. Plasmin effectively removed at least 75% of bound fibrinogen, indicating an extracellular location for the protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

Staff Stress and Morale in Community‐Based Settings for People with Intellectual Disabilities and Challenging Behaviour: A Brief Report

Background There are no studies that have compared outcomes for staff in different types of supported accommodation for people with intellectual disabilities and challenging behaviour. This study looked at stress, morale and intended job turnover in staff in two types of community‐based residential supports: non‐congregate settings where the minority of residents have challenging behaviour; and congregate settings where the majority of residents have challenging behaviour. Materials and methods A self‐completion survey questionnaire was used to collect information on the basic characteristics of staff, levels of staff stress, job satisfaction and propensity to leave their employment. Results One hundred and fifty‐seven questionnaires were returned from staff, the majority of whom were on fixed‐term contracts. Congregate settings were not associated with higher levels of stress as might be assumed. Overall, over a quarter of staff reached criterion on the General Health Questionnaire‐12 for experiencing emotional distress, and over a third were likely to actively seek new employment in the next year. The greatest perceived sources of stress were lack of resources and lack of staff support. The lowest level of satisfaction was with the rate of pay. Those in non‐congregate settings reported greater perceived stress because of lack of procedures to deal with challenging behaviour. Conclusions High levels of intended staff turnover may be more due to job insecurity and lack of support than service user challenging behaviour. Employers seeking to reduce turnover should pay attention to basic pay and conditions, as well as staff training in appropriate methods for dealing with challenging behaviour.     

CD8(+) T-cell selection, function, and death in the primary immune response in vivo

The primary immune response to Epstein Barr virus (EBV) is characterized by striking proliferation of EBV-specific CD8(+) T cells. In this study we have investigated the clonal composition and functional properties of the cells mediating this primary response and have analyzed the mechanisms that control the downregulation of the primary response and the selection of memory cells. We show that massively expanded T-cell clones often dominate the primary antigen-specific T-cell response. Despite the enormous extent of expansion, the virus-specific T cells express high levels of intracellular perforin and are potently cytotoxic. They are, however, functionally heterogeneous in their ability to secrete proinflammatory cytokines, with subpopulations of the antigen-specific T cells being hyporesponsive. The primary response is closely regulated, and the majority of cells are programmed to die via a cytokine-rescuable pathway, leaving only small populations of memory T cells surviving. Comparison of the clonal composition of primary and memory responses in vivo shows that the clones that dominate the primary response are relatively heavily culled during the downregulation of the primary response and the establishment of T-cell memory.     

α- andβ-mannosidoses

Summary Clinical, pathological and biochemical findings in the mannosidoses are described. Family studies showed granulocyte-rich white cell fractions to be the tissue of choice for carrier detection in-mannosidosis. Metabolic labelling studies using [³H] mannose demonstrated accumulation of Man1-4GlcNAc in cultured skin fibroblasts from a patient with this condition. Alternative methods of egress from lysosomes were suggested for this compound by its secretion into culture medium and apparent reduction of storage with time in cultures.-mannosidase deficient goats are not thought to be a true animal model of the human condition, as although they showed a similar enzyme deficiency, the clinical presentation is much more severe and the major storage material (Man1-4GlcNAc1-4GlcNAc) is different.