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.     

Growth & development. Turner syndrome

This article examines the prediction of risk and dangerousness and identifies aspects relevant to a risk assessment by mental health professionals, in particular nurses.     

Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival

We report the electrophysiologic findings of myoclonus in a patient with Huntington's disease (HD). This patient was studied postoperatively after a bilateral fetal cell transplant in his striatum. Incomplete transient improvement was seen in the myoclonus, followed by gradual deterioration. The myoclonus itself had a cortical correlate and was associated with an enlarged somatosensory evoked potential (SEP), consistent with the presence of cortical reflex myoclonus. An enlarged SEP has not been previously reported in myoclonus associated with HD. The postulated mechanisms for myoclonus, when it occurs in HD, have differed in the literature. The reason for the transient improvement of the myoclonus following transplantation is unclear, but this case raises the possibility that basal ganglia circuits may modulate cortical myoclonic activity.     

Meckel''s diverticulum presenting as gastric outlet obstruction: case report

We report a case of gastric outlet obstruction simulating gastric antral neoplasm resulting from a perforated Meckel's diverticulum. Presentation of this nature has not been previously reported.     

Evidence of visual processing negativity with attention to orientation and color in central space

The aim of this study was to determine whether the visual frontal processing negativity reported in our earlier paper (Karayanidis, F. and Michie, P.T. Electroenceph. clin. Neurophysiol., 1996, 99: 38-56) is related to selection of spatial location, or occurs regardless of the stimulus features used to define the target. Subjects were instructed to respond to infrequent target stimuli of a particular combination of orientation, color and size. All stimuli were presented at central fixation. Posteriorly, orientation selection enhanced P125 amplitude over the right hemisphere but neither orientation nor color selection had an effect on N190. Posterior selection negativities emerged for orientation, color and their conjunction. At anterior sites, widespread effects of orientation and color processing were evident. The effect of location selection on the anterior N1 seen in our previous study was not evident with orientation selection. Instead, selection of orientation, color and their conjunction resulted in P145-250 frontally. Two later anterior negativities emerged. The early negativity (vPNe) was affected independently by orientation and color selection while the late negativity (vPNl) was affected only by selection of feature conjunction. Thus, the present results show that, like its auditory counterpart, the visual processing negativity occurs with a variety of stimulus classification features and is not exclusively related to spatial selection.     

Expression of smooth-muscle actin in cultured cells from human plasmacytoid myoepithelioma

BACKGROUND: Endoscopic sclerotherapy (ST), widely used as treatment of bleeding esophageal varices, might cause motility disturbances of the esophagus as well as mucosal damage. We performed this study to evaluate the long-term effects of repeated sclerotherapy on esophageal motility and mucosa. METHODS: Ten patients with liver cirrhosis and bleeding esophageal varices treated with repeated ST were evaluated after the last ST, median 52 months, by esophageal manometry and gastroscopy where forceps biopsies were taken. RESULTS: We found a significant difference in the distal esophageal sphincter intraabdominal length. The distal esophageal sphincter pressure was somewhat lower in the ST group although the difference did not reach statistical significance. There was infiltration of neutrophil leukocytes in biopsies from four patients and normal findings in the rest. CONCLUSIONS: Long-term follow-up evaluation showed statistically longer distal esophageal intraabdominal length in the ST group. No mucosal alterations were found at the histopathological investigation.     

Differential responses in anterior pituitary luteinizing hormone (LH) content and LH beta- and alpha-subunit mRNA, and plasma concentrations of LH and testosterone, in bulls treated with the LH-releasing hormone agonist deslorelin

Tooth loss diminishes oral function and quality of life, and national health targets aim to reduce population levels of tooth loss. OBJECTIVES: The purpose of this study was to determine tooth loss incidence and predictors of tooth loss among older adults in South Australia. METHODS: Data were obtained from a cohort study of a stratified random sample of community-dwelling dentate people aged 60+ years. Interviews and oral examinations were conducted among 911 individuals at baseline and among 693 of them (76.1%) 2 years later. Incidence rates and relative risks were calculated for population subgroups and multivariate logistic regression was used to construct risk prediction models. A method was developed to calculate 95% confidence intervals (95% CI) for relative risks (RR) from logistic regression models using a Taylor series approximation. RESULTS: Some 19.5% (95% CI = 15.4-23.6%) of people lost one or more teeth during the 2 years. Men, people with a recent extraction, people who brushed their teeth infrequently, smokers and people born outside Australia had significantly (P < 0.05) greater risk of tooth loss. Baseline clinical predictors of tooth loss included more missing teeth, retained roots, decayed root surfaces, periodontal pockets and periodontal recession. In a multivariate model that controlled for baseline clinical predictors, former smokers (RR = 2.55, 95% CI = 1.48-4.40) and current smokers (RR = 2.06, 95% CI = 0.92-4.62) had similarly elevated risks of tooth loss compared with non-smokers. CONCLUSIONS: The findings from this population suggest that a history of smoking contributes to tooth loss through mechanisms in addition to clinical disease processes alone.