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Brutons's tyrosine kinase (Btk) is a non-receptor protein tyrosine kinase (nrPTK) essential for the development of B lymphocytes in humans and mice. Like Src and Abl PTKs, Btk contains a conserved cassette formed by SH3, SH2 and protein kinase domains, but differs from them by the presence of an N-terminal PH domain and the Tec homology region. The domain structure of Btk was analysed using X-ray synchrotron radiation scattering in solution. Low resolution shapes of the full-length protein and several deletion mutants determined ab initio from the scattering data indicated a linear arrangement of domains. This arrangement was further confirmed by rigid body modelling using known high resolution structures of individual domains. The final model of Btk displays an extended conformation with no, or little, inter-domain interactions. In agreement with these results, deletion of non-catalytic domains failed to enhance the activity of Btk. Taken together, our results indicate that, contrary to Src and Abl, Btk might not require an assembled conformation for the regulation of its activity. [ABSTRACT FROM AUTHOR]

Until now, transthoracic echocardiography (TTE) has had the capability to visualize only the proximal portions of the main coronary arteries. However, we noticed that transthoracic color Doppler echocardiography has marked potential to visualize flow in the coronary arteries. In clinical cases we tested whether this method is useful for visualizing stenoses and flow even in peripheral branches of the coronaries. This article presents two illustrative clinical cases. In our experience, transthoracic color Doppler echocardiography is very suitable for clinical use.

Perchloric acid soluble protein purified from the cytosol fraction of rat liver has been crystallized in a form suitable for high-resolution X-ray diffraction studies. Octahedral crystals reaching 0.5 mm in cross-sectional diameter were produced by the hanging-drop method using polyethylene glycol (Mr = 8 kDa) as precipitant. These crystals diffract to 2.44 A on an in-house X-ray source and to 1.8 A using a bending-magnet beamline at ESRF Grenoble. The crystals belong to the cubic space group P213 with a = 89.90 A and two molecules per asymmetric unit, as indicated from a Vm value of 2.12 A3 Da-1 and self-rotation function computation. Screening for heavy-atom derivatives identified a platinum compound and xenon that bind to the protein.

The purpose of this study was to test whether the systolic myocardial wall motion abnormalities at the early stages of ischemia are applicable to the diagnosis of coronary artery disease. Forty-four patients with suspected coronary artery disease were studied with the use of low-level exercise echocardiography. Exercise was stopped at the onset of first cardiac symptoms, and no patient exceeded 70% of the age-predicted maximal heart rate level. Forty patients had significant stenosis in at least one coronary artery on coronary angiography. Ten control subjects with a low probability of ischemic heart disease also were studied with exercise echocardiography. The first ischemic wall motion abnormality in systole, defined as delayed onset of the contraction (a regional delay of at least 100 milliseconds in a frame-by-frame analysis of echocardiograms) without any reduction in systolic movement, was regarded separately from hypokinesis (systolic wall motion excursion of less than 5 mm). When the delayed onset of the contraction also was taken into account, 37 of the 40 patients with coronary artery disease had an ischemic response after exercise. The sensitivity of the test thus was 93%. The reduction in systolic wall movement was detected in only 18 of these patients at the exercise level attained (70% or less of age-predicted maximal heart rate). There were two false-positive echocardiograms, but when the control group also was considered, the specificity of the test remained high at 86%. The sensitivity of exercise echocardiography can be increased by paying attention to the delayed onset of the systolic contraction, which occurs at the early stages of ischemia.

The effects on plasma lipids and apoproteins A-I and B of oral administration of doxazosin and atenolol over a 20-week period were studied in 42 patients with mild to moderate essential hypertension. Total plasma cholesterol decreased by 8.9% (P less than 0.01) and LDL cholesterol by 16.9% (P less than 0.01) after 20 weeks' treatment with doxazosin. Total HDL cholesterol and HDL2 cholesterol concentrations increased slightly during doxazosin treatment and the increase in HDL2 level at 4 weeks was statistically significant (P less than 0.05). At 20 weeks, the levels of total HDL cholesterol and HDL2 were significantly (P less than 0.05) lower with atenolol than with doxazosin. The ratio HDL/total cholesterol increased during doxazosin treatment (P less than 0.05 at 4, 12 and 20 weeks). The HDL/total cholesterol ratio was significantly higher after 20 weeks with doxazosin than with atenolol (P less than 0.05). The levels of VLDL cholesterol and triglycerides increased significantly (P less than 0.01) during atenolol treatment. The concentrations of apoproteins A-I and B did not change significantly during treatment with doxazosin or with atenolol but at 20 weeks the ratio of apo A-I to apo B was significantly (P less than 0.05) lower with atenolol than with doxazosin. On the basis of these results, doxazosin would seem to have significant favourable effects on the serum lipid profile.