Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels.

Acute graft-versus-host disease (GvHD) limits the applicability of allogeneic hematopoietic cell transplantation for the treatment of leukemia. GvHD occurs as a consequence of multiple activating events in antigen-presenting cells (APCs) and T cells (Tcs). Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase involved in multiple signaling events of immune cells. Therefore, we hypothesized that Syk may be a promising target to inhibit GvHD, which involves activation of different immune cell populations. In vivo expansion of luciferase(+) donor Tcs in mice developing GvHD was reduced by treatment with the Syk inhibitor Fostamatinib, which led to increased survival and reduced histologically confirmed GvHD severity. Importantly, in vivo and in vitro cytotoxicity against leukemia target cells and anti-murine cytomegalovirus immune responses were not impacted by Fostamatinib. In APCs Syk inhibition reduced the expression of costimulatory molecules and disrupted cytoskeletal organization with consecutive APC migratory defects in vitro and in vivo while phagocytic activity remained intact. On the basis of these immunomodulatory effects on different cell populations, we conclude that Syk targeting in alloantigen-activated Tcs and APCs with pharmacologic inhibitors, already applied successfully in anti-lymphoma therapy, has clinical potential to reduce GvHD, especially as anti-leukemia and anti-viral immunity were preserved.

Influence of the type of undertrousers and physical activity on scrotal temperature.

BACKGROUND: Testicular temperature correlates highly with scrotal temperature. The aim of this study was to evaluate the influence of the type of undertrousers on scrotal temperature during standardized periods of sitting and walking. METHODS: Fifty volunteers without a history of infertility and normal andrological examination were included for scrotal temperature evaluation. Temperatures were measured every minute with a portable data recorder connected with two thermistor temperature sensors, which were attached on either side of the scrotum. Ambient temperature in the study room was adjusted to 20 degrees C throughout the whole experiment. All volunteers started the experiment at the same time of day. Clothing of the volunteers consisted of standardized cotton wool trousers and shirts fitting to body size. Each volunteer performed six periods of 45 min, either walking on a treadmill (3.0 km/h) or sitting, and wearing in a standardized and randomized manner either tight, loose fitting or no undertrousers respectively. RESULTS: The following interactions were demonstrated by means of multivariate analysis of variance for repeated measurements: scrotal temperatures were significantly higher for tight versus loose fitting versus absent undertrousers. Furthermore, significantly lower scrotal temperatures were identified for walking versus sitting as well as for the right versus the left scrotal side. CONCLUSIONS: The present study suggests that wearing tight fitting undertrousers is associated with higher scrotal and consequently testicular temperatures than wearing loose fitting undertrousers or none.

Computer program for iterative evaluation of fractional turnover rates by exponential regression: application to the turnover of VLDL-triglycerides in blood.

A microcomputer program ('EXREG') in GW BASIC was developed for fitting experimental data of A(T) to the equation A = A0 + A1.exp(-K.T) by exponential regression. In an iterative procedure K-values are tested to yield the maximum coefficient of determination. The accuracy of K is further improved in consecutive steps. The program is used to obtain the fractional turnover rate K of radiolabelled very low density lipoprotein (VLDL)-triglycerides in patients suffering from disturbances of lipid metabolism. A is the radioactivity of VLDL-triglycerides which is measured after isolation from blood. Seventeen consecutive blood samples are taken within a period of 24 h after injection of radioactive glycerol. T is the time after injection. The production rate of VLDL-triglycerides is calculated using K, the VLDL-triglyceride concentration, the body weight and height.