High prevalence of oncogenic MYD88 and CD79B mutations in diffuse large B-cell lymphomas presenting at immune-privileged sites.

Activating mutations in CD79 and MYD88 have recently been found in a subset of diffuse large B-cell lymphoma (DLBCL), identifying B-cell receptor and MYD88 signalling as potential therapeutic targets for personalized treatment. Here, we report the prevalence of CD79B and MYD88 mutations and their relation to established clinical, phenotypic and molecular parameters in a large panel of DLBCLs. We show that these mutations often coexist and demonstrate that their presence is almost mutually exclusive with translocations of BCL2, BCL6 and cMYC, or Epstein-Bar virus infection. Intriguingly, MYD88 mutations were by far most prevalent in immune-privileged site-associated DLBCL (IP-DLBCL), presenting in central nervous system (75%) or testis (71%) and relatively uncommon in nodal (17%) and gastrointestinal tract lymphomas (11%). Our results suggest that MYD88 and CD79B mutations are important drivers of IP-DLBCLs and endow lymphoma-initiating cells with tissue-specific homing properties or a growth advantage in these barrier-protected tissues.

The fate of the free fat graft. A prospective clinical study using CT scanning.

In a prospective clinical study, the fate of free fat grafts used in lumbar decompressive surgery to prevent epidural fibrosis was evaluated. The size of the fat graft was measured at operation and 2 years later by CT scanning. Of 26 consecutive patients, data were available from 21. In 15 patients the fat graft was unchanged, in three patients the fat graft contained fibrous bands, and in another three patients the fat graft was completely replaced by scar tissue. Blood loss at operation, the extent of surgical dissection, and thickness of the fat graft are important prognostic factors relating to the survival of the free fat graft.

Plasma renin activity and plasma catecholamines in intact and splenectomized running and swimming beagle dogs.

The influence of splenectomy in the dog on plasma catecholamine levels and plasma renin activity during treadmill running and swimming was investigated. Plasma catecholamines were measured by a radioenzymatic assay and plasma renin activity by a radioimmunoassay. Exercise consistently increased plasma catecholamine levels before and after splenectomy (range of increase:3--38 pmol X ml-1). Swimming, however, was a stronger stimulus than running. No change in the ratio between noradrenaline and adrenaline was found. In intact dogs exercise results in a marked increase in hematocrit due to splenic contraction (range of increase 3--8 volume %), while renal blood flow and plasma renin activity remain virtually constant. In splenectomized dogs, exercise has been reported to induce a decrease in renal blood flow. In contrast to this known effect on renal blood flow, splenectomy did not affect plasma renin activity in treadmill running dogs. In swimming dogs, however, plasma renin activity was increased after splenectomy (range of increase 3.3--6.9 ng X Ang I X ml-1 X h-1). Possibly, a threshold in sympathetic tone is required to increase renin release in the dog.

Renal hemodynamics and proteinuria in running and swimming beagle dogs.

In beagle dogs swimming, in contrast to treadmill running, was found to cause an increase in urine flow and urinary protein excretion. Renal blood flow measured by electromagnetic flow probes decreased by 13.0 +/- 4.9% when the treadmill gradient was 15% and arterial pressure was elevated by 11.6 +/- 4.9%. Immersion resulted in an immediate decrease in renal blood flow of 8.8 +/- 5.1% and a 24.6 +/- 6.9% increase in arterial pressure. Acid-base status indicated a respiratory alkalosis in all running experiments, no net change in five swimming experiments in which hyperventilation occurred, but a metabolic acidosis in eight swimming experiments without hyperventilation. During running there was a threefold increase in oxygen consumption. We conclude that swimming possibly induces more sympathetic nervous activity than treadmill running in dogs, while an alkalosis is consistently present during running, but acid-base response is variable during swimming.

Splenic storage volume in the unanesthetized resting beagle.

Determination of the dog's splenic storage volume without surgical procedures requires measurement of both circulating and total red cell volumes. The estimation of circulating red cell volume by radioisotope techniques is impeded by the rapid uptake of tagged cells in the spleen. The circulating cell volume might be calculated from plasma volume and large vessel hematocrit, provided that the latter is corrected for the unequal distribution of red cells in the circulatory system. However, the correction factor can only be estimated in the splenectomized dog. We describe here a method to determine the factor in the intact dog, "physiologically splenectomized" by the severe exercise. The values obtained by this method slightly exceed those in the resting dog, as shown by studies in splenectomized exercising beagles in which splenic function was simulated by infusion of packed cells. The method was tested in beagles exercised by swimming and treadmill running and it was concluded that in the unanesthetized resting beagle about one-third of all erythrocytes is stored in the spleen. Labeled cells are equilibrated with about one-half of the splenic storage volume within 10 min after their injection. During maximal exertion the mean increase in large vessel hematocrit was 38.6 +/- 3.3%, the mean decrease in plasma volume 13.6 +/- 1.7% and the mean increase in plasma osmolarity 2.8 +/- 0.9% (percentages of control values).