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The aberrant transcription factor EWS FLI1 drives Ewing sarcoma but its molecular function is not completely understood. We find that EWS FLI1 reprograms gene regulatory circuits in Ewing sarcoma by directly inducing or repressing enhancers. At GGAA repeat elements which lack evolutionary conservation and regulatory potential in other cell types EWS FLI1 multimers induce chromatin opening and create de novo enhancers that physically interact with target promoters. Conversely EWS FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild type ETS transcription factors. These divergent chromatin remodeling patterns repress tumor suppressors and mesenchymal lineage regulators while activating oncogenes and potential therapeutic targets such as the kinase VRK1. Our findings demonstrate how EWS FLI1 establishes an oncogenic regulatory program governing both tumor survival and differentiation.

Angiography under experimental conditions shows that Urografin has a vasodilator action of the order of 8% upon the basal cerebral arteries of the baboon. This action is not seen within the first 4 sec of the angiogram and the dilator effect of a single injection has passed off completely 15 min later. Three successive injections within 7 min show little evidence of cumulative vasodilatation. The vasodilator action of three successive angiograms has disappeared 22 to 29 min later. Because of wide variations in the degree of vasodilatation shown by individual baboons it may be necessary to use each baboon as its own control in subsequent work.

The relationship between length of history of raised intracranial pressure and the presence of suture diastasis and changes in the sella turcica has been studied. At least six weeks of high pressure usually precedes any sign of alteration in the sella turcica; but sella changes may be found in children of any age after illness of that duration. Suture diastasis may occur very much more rapidly in young children, but after the age of ten, it is usually evidence of a long-standing condition. Suture diastasis and osteoporosis are often seen together in childhood. Erosion of the sella turcica, when seen in young children without suture diastasis, is usually an indication of a tumour in the region of the sella.

(1) The extent and severity of visual field loss has been compared in a series of 14 patients with occlusions of the posterior cerebral artery or its branches, all verified angiographically. Atheroma, embolism, and migraine were the commonest types of underlying vascular disease. (2) Occlusion of the main trunk of the artery was associated with severe and permanent field loss usually with some sparing of the central area and, in one case, of some field adjacent to the vertical meridian. It is suggested that this is due to collateral blood flow reaching the margins of the posterior cerebral territory from the adjacent middle cerebral territory via pial anastomoses. (3) Single or multiple occlusions of the main branches of the posterior cerebral artery gave variable amounts of field loss with considerable recovery in some cases. Collateral blood flow from the middle cerebral territory and from other branches of the posterior cerebral artery was demonstrated and the variation may be due to the size and number of pial anastomoses and to systemic factors such as blood pressure and vascular reactivity. (4) Occlusion of smaller branches of the calcarine artery produced localized zones of capillary underperfusion near the posterior cerebral pole. These corresponded to scotomatous paracentral defects in the visual field which were often permanent and showed no central sparing. The potential capacity of the collateral system may be limited by occlusion of intracerebral arteries or by involvement of segments of the pial arteries in the disease process.

This study was designed to determine in six-week old specific pathogen free pigs, the effect of previous experimental exposure to Mycoplasma hyopneumoniae and transmissible gastroenteritis virus on a challenge infection with Actinobacillus pleuropneumoniae. Pigs exposed simultaneously to M. hyopneumoniae and transmissible gastroenteritis virus appeared more resistant to challenge (one week later) with A. pleuropneumoniae. Four pigs out of a group of ten died following the challenge infection, compared to all ten pigs in the control group not submitted to previous infections. Clinical signs and lesions were also less severe in the previously infected group than in the control group. Pigs submitted to a single previous infection with M. hyopneumoniae only appeared to be less resistant to the challenge infection than pigs submitted to the dual previous infection with M. hyopneumoniae and the transmissible gastroenteritis virus. A correlation was found between the resistance of pigs to the challenge infection and their serum gammaglobulin levels.

Quantitative determinations of IgG1 and IgG2, in one group of colostrum-fed and one group of colostrum-deprived neonatal goats revealed that the occurrence of the IgG1 subclass preceeded that of the IgG2 in both cases. In the colostrum-fed animals the IgG2 appeared, on an average, in the fourth week of life whereas in the colostrum-deprived animals the IgG2 was detected as early as three weeks after birth. At the age of twelve weeks the mean concentrations for IgG, and IgG2 were higher in the animals deprived of colostrum. The immune response to human gamma globulin was studied in colostrum-fed and colostrum-deprived neonatal goats which were immunized at birth and again after four and eight weeks. Following the first two antigen administrations a significantly higher response was obtained in the colostrum-fed neonates. However, the third injection determined a similar response in both groups. A marked suppressive effect on the immune response was observed in colostrum-fed neonatal goats when specific antibodies were present in the colostrum after preimmunization of the mothers with human gamma globulin.

Experimental and clinical findings are presented to show that the magnitude of displacement of cerebro-spinal fluid from the basal cisterns during systole is an adequate force to cause hydromyelia in the presence of a Chiari malformation. The abnormal mechanism is discussed in detail and involves obstruction of the foramen magnum by the cone of depressed cerebellum adherent to the spinal cord, systolic deflection of the cerebro-spinal fluid from the basal cisterns into the 4th ventricle, and a milking action of the adherent cerebellum on the brainstem. These factors force cerebro-spinal fluid into the central canal of the spinal cord, tending to form a syrinx. Changes in epidural pressure associated with coughing and straining may cause extension of such a syrinx once it has formed.

✓ Oxyhemoglobin was injected intracisternally into three baboons, and methemoglobin into one baboon, in an attempt to mimic the prolonged cerebral arterial spasm sometimes seen after subarachnoid hemorrhage due to aneurysm rupture. Cerebral angiography was performed for up to 7 days after injection of hemoglobin, and the degree of vasospasm was estimated from the angiograms. Oxyhemoglobin caused slight arterial narrowing, which lasted for 3 days. Methemoglobin had no significant effects. Motor neurological deficits and histopathological signs, characteristic of prolonged cerebral vasospasm, were not observed. It was concluded that hemoglobin alone is not capable of causing the cerebral vasospasm syndrome in these experimental animals.

Thirty-four cases of congenital deafness have been radiologically examined by plain radiographs and linear tomography (with a high definition technique). The results are set out and the techniques described so that other workers may assess the value of such fairly simple methods against the currently fashionable “polytomography”. It is suggested that linear tomography is a satisfactory technique for the demonstration of even minute anatomy.