Phosphatidylinositol 3-kinase-gamma activates Bruton's tyrosine kinase in concert with Src family kinases

Bruton's tyrosine kinase (Btk) is essential for normal B lymphocyte development and function. The activity of Btk is partially regulated by transphosphorylation within its kinase domain by Src family kinases at residue Tyr-551 and subsequent autophosphorylation at Tyr-223. Activation correlates with Btk association with cellular membranes. Based on specific loss of function mutations, the Btk pleckstrin homology (PH) domain plays an essential role in this activation process. The Btk PH domain can bind in vitro to several lipid end products of the phosphatidylinositol 3-kinase (PI 3-kinase) family including phosphatidylinositol 3,4,5-trisphosphate. Activation of Btk as monitored by elevation of phosphotyrosine content and a cellular transformation response was dramatically enhanced by coexpressing a weakly activated allele of Src (E378G) and the two subunits of PI 3-kinase-gamma. This activation correlates with new sites of phosphorylation on Btk identified by two-dimensional phosphopeptide mapping. Activation of Btk was dependent on the catalytic activity of all three enzymes and an intact Btk PH domain and Src transphosphorylation site. These combined data define Btk as a downstream target of PI 3-kinase-gamma and Src family kinases.     

Homeless youth and their exposure to and involvement in violence while living on the streets

Sick building syndrome is the term given to a heterogeneous constellation of symptoms that affects workers in modern mechanically ventilated office buildings. Although the cause is unknown, there is evidence that the local environment of the work station is an important determinant of symptoms. In this study, investigators examined the effect of a new, individually controlled ventilation system on workers' symptoms. Investigators studied two groups of workers in one mechanically ventilated office building: (1) a control group at whose worksite no intervention was made and (2) an intervention group. The intervention consisted of installation of a device that allowed each worker control over the ventilation supplied to his or her worksite. Just before, and 4 and 16 mo after installation of this device, workers completed self-administered questionnaires regarding occurrence of symptoms. The new ventilation system resulted in higher air velocities, more variable temperatures, and higher concentrations of airborne dust and fungal spores. Four months after installation, workers with the new ventilation system reported fewer symptoms that were (a) work-related (p < .05) and that were work-related and frequent (p < .05); in addition, they reported fewer symptoms that reduced their capacity to work (p < .01). Sixteen months after installation, workers with the new device reported fewer symptoms than at baseline (although not as significantly), and they indicated that the indoor air quality improved their productivity by 11%, compared with a 4% reduction of productivity among the control group of workers (p < .001). Investigators concluded that the new ventilation system, which provided the workers with individual control over ventilation, was associated with important and sustained reduction in symptoms.     

Mild traumatic brain injury--the Fife perspective

Excretion was studied of catecholamines and diphenilamine (DOPA) in 310 patients with carcinoma of the stomach and large intestine and 43 patients with non-malignant diseases. The oncological patients showed decrease in activity of the mediator link of the sympathoadrenal system (SAS) as well as its reserves but there was no association with sex, age, location or histological structure. Three types of SAS functioning were identified, such as compensation, overstrain and emaciation. Surgical intervention led to activation of the hormonal link and exhaustion of the system's reserves. Two kinds of sympathoadrenal response to stress were described--adequate and inadequate. In the former type, phases of stress remain as they are, unchanged, as are time periods of formation thereof, while under the latter one time periods of the phases formation or formation thereof get disordered.     

Secobarbital in humans discriminating triazolam under two-response and novel-response procedures

The percentage of long-term survivors after intensive chemotherapy and the outcome of MDS patients who achieve partial remission (PR) with intensive chemotherapy (IC) are not known. Between 1981 and 1996 we treated 99 patients with de novo MDS who had high-risk MDS or progression to AML, with IC. 41 (41%) achieved CR, 16 (16%) achieved partial remission (PR), 26 (26%) had failure, and 16 (16%) died in aplasia. Eight of the patients who achieved CR were autografted, three were allografted and the remaining cases received moderate consolidation chemotherapy. After IC, the 16 PR patients fulfilled the criteria for RA in 15 cases and CMML in one case. Median PR duration was 17 months, and three PR were > 3 years (39, 50+, 82+ months). Median actuarial survival of patients who achieved PR and CR was 18 months and 20 months from the onset of IC, respectively (difference not significant). Of the 71 patients treated before 1993, with sufficient follow-up, 10 (14%) had survived > 4 years (long-term survivors). Four of them were alive in first CR after 49+ to 110+ months and probably cured, two were alive in PR after 50+ and 82+ months and four had died after 49-78 months. Long-term survivors were characterized by a significantly higher incidence of RAEB-T at diagnosis, and with normal or favourable cytogenetic findings. In patients with RAEB-T at diagnosis included before 1993, 8/23 (35%) cases who had no unfavourable karyotype had survived > 4 years. Our findings suggest that MDS patients who achieve PR with IC, and not only those who achieve CR, can benefit from this type of treatment. The percentage of long-term survivors remains low, however, and is almost restricted to patients with RAEB-T at diagnosis and no unfavourable karyotype.     

The quantitative analysis of coal processing solvents by combined g.c.-m.s.

The application of combined g.c.-m.s. with automated data processing to the rapid analysis of coal solvents has been described. An analytical method, using commercially available data processing routines, has been developed for the automatic quantitative analysis of specific aromatic and hydroaromatic compounds in coal processing solvents. To demonstrate the use of this technique, raw anthracene oil was hydrogenated under different conditions and the resulting hydrogenated anthracene oils were analysed. The results showed correlations between the hydrogen content and the absolute concentrations of specific compounds in the samples.     

Physiological effects of whole cottonseed in the diet of lactating dairy cows

With 32 lactating Holstein cows we evaluated physiological effects of gossypol and cyclopropenoid fatty acids in diets containing 18.5% whole cottonseed (dry matter) based on corn, corn silage, and soybean meal. All cows consumed a control diet for the first 2 wk of lactation and then were assigned to either control or whole cottonseed diet for the remainder of their lactation. Milk production, milk fat and protein percentages, and daily dry matter intake were measured. Dry matter intakes were less for cows consuming the whole cottonseed diet, but net energy intake was similar for all diets. Milk fat from cows consuming whole cottonseed contained detectable concentrations of cyclopropene fatty acids. Total lipid in plasma, total serum cholesterol, serum gossypol, and apparent liver gossypol concentrations were greater in cows fed whole cottonseed. Gossypol and cyclopropenoid fatty acids appeared to be absorbed from the gut of cows fed whole cottonseed. Small amounts of gossypol in serum and liver tissue and small amounts of cyclopropene fatty acids in adipose tissue lipids and milk fat indicate a need to elucidate the significance of these physiologically active compounds in the human diet and their biological effects on lactating dairy cows.