RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes

The related adhesion focal tyrosine kinase (RAFTK), a recently discovered member of the focal adhesion kinase family, has previously been reported to participate in signal transduction in neuronal cells, megakaryocytes, and B lymphocytes. We have found that RAFTK is constitutively expressed in human T cells and is rapidly phosphorylated upon the activation of the T cell receptor (TCR). This activation also results in an increase in the autophosphorylation and kinase activity of RAFTK. After its stimulation, there was an increase in the association of the src cytoplasmic tyrosine kinase Fyn and the adapter protein Grb2. This association was mediated through the SH2 domains of Fyn and Grb2. RAFTK also co-immunoprecipitates with the SH2 domain of Lck and with the cytoskeletal protein paxillin through its COOH-terminal proline-rich domain. The tyrosine phosphorylation of RAFTK after T cell receptor-mediated stimulation was reduced by the pretreatment of cells with cytochalasin D, suggesting the role of the cytoskeleton in this process. These observations indicate that RAFTK participates in T cell receptor signaling and may act to link signals from the cell surface to the cytoskeleton and thereby affect the host immune response.     

Successful weight loss in a self-taught, self-administered program

There is little evidence concerning the effectiveness of self-help materials for weight control. The purpose of this research was to evaluate a self-help weight-loss program. Obese (body fat > or = 25.0%, range = 25.0-48.6%, mean +/- SEM = 36.5 +/- 1.3%) men (n = 14) and women (n = 21) were given a workbook detailing a behavior modification approach to weight loss that emphasizes self-monitoring of diet and exercise behaviors, and then sent home for 6 months to learn how to lose weight on their own. A group of 9 controls (CONT) who did not get a workbook were used for comparison. ANOVA showed that the experimental group (EXP) lost 8.1 +/- 0.9 (mean +/- SEM) kg body weight, 6.4 +/- 0.8 kg fat, and 3.9 +/- 0.6% body fat; all significant over time (p < 0.001) and different from the CONT (p < 0.0001) who showed no change in these variables. The EXP also reduced their fat intake (% of joules) from 36.1 +/- 1.0% to 27.9 +/- 1.3% (p < 0.0001), increased their carbohydrate intake from 45.7 +/- 1.2% to 50.0 +/- 1.7% (p < 0.007) and their protein intake from 16.3 +/- 0.05% to 20.7 +/- 0.7% (0 < 0.03), all of which were significantly different (p < 0.03) than the CONT who did not change. Dietary fiber increased in the EXP from 19.8 +/- 1.4 to 27.3 +/- 2.2 g/d (p < 0.001) even with a significant reduction in energy intake (11.3 +/- 0.6 vs. 8.9 +/- 0.5 Mj/d; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors related to rehospitalization within thirty days of discharge after coronary artery bypass grafting

BACKGROUND: Early rehospitalization after coronary artery bypass grafting (CABG) is an expensive and frequently adverse outcome. Rehospitalization rates after various surgical procedures have been used as an indicator of quality of care. Determining the extent to which rehospitalization rates reflect patient case mix and severity of illness rather than quality of care requires detailed information regarding the patients, the care they received, and the reasons for their rehospitalization. METHODS: We conducted a nested case control study comparing 110 CABG patients who were rehospitalized within 30 days after discharge with 224 control patients. Control patients were randomly selected from patients undergoing CABG during the same time frame as the cases and were matched on age, gender, and priority of surgery. A detailed chart review provided information regarding treatment in the postsurgical period, in addition to the preoperative information collected on all CABG patients as part of an ongoing regional prospective study. RESULTS: The overall rehospitalization rate was 13.8%. The most common reasons for rehospitalization included: wound infection (19%), atrial fibrillation (13%), pleural effusion (11%), and thromboembolic event (10%). Preoperative severity of illness and comorbidity accounted for 24% of the total variance. After adjustment for these factors, discharge hematocrit less than 30% (OR = 2.01, p = 0.018) and several discharge medications including: antiarrhythmics (OR = 3.26, p = 0.047), diuretics (OR = 2.18, p = 0.055), beta blockers (OR = 0.44, p = 0.036), and long length of stay (more than 7 days; OR = 2.09, p = 0.029) were the most important predictors of rehospitalization risk. CONCLUSIONS: Although the reasons for rehospitalization after CABG are heterogeneous and related to patient severity of illness as well as comorbid status, several of the most common are potentially preventable and related to quality of care. Rehospitalization was not related to early discharge.     

Comparative studies on mammalian Hoxc8 early enhancer sequence reveal a baleen whale-specific deletion of a cis-acting element

Variations in regulatory regions of developmental control genes have been implicated in the divergence of axial morphologies. To find potentially significant changes in cis-regulatory regions, we compared nucleotide sequences and activities of mammalian Hoxc8 early enhancers. The nucleotide sequence of the early enhancer region is extremely conserved among mammalian clades, with five previously described cis-acting elements, A-E, being invariant. However, a 4-bp deletion within element C of the Hoxc8 early enhancer sequence is observed in baleen whales. When assayed in transgenic mouse embryos, a baleen whale enhancer (unlike other mammalian enhancers) directs expression of the reporter gene to more posterior regions of the neural tube but fails to direct expression to posterior mesoderm. We suggest that regulation of Hoxc8 in baleen whales differs from other mammalian species and may be associated with variation in axial morphology.     

Pulmonary carcinogenicity of relatively low doses of beta-particle radiation from inhaled 144CeO2 in rats

This study was conducted to examine the carcinogenic effects of inhaled beta-particle-emitting radionuclides, particularly in lower dose regions in which there were substantial uncertainties associated with available information. A total of 2751 F344/N rats (1358 males and 1393 females) approximately 12 weeks of age at exposure were used. Of these, 1059 rats were exposed to aerosols of 144CeO2 to achieve mean desired initial lung burdens (ILBs) of 18 kBq (low level), 247 rats to achieve mean ILBs of 60 kBq (medium level) and 381 rats to achieve mean ILBs of 180 kBq (high level). Control rats (total of 1064) were exposed to aerosols of stable CeO2. Based on the 95% confidence intervals of the median survival times and the cumulative survival curves, there were no significant differences in the survival of groups of female and male exposed rats relative to controls. The mean lifetime beta-particle doses to the lungs of the rats in the four groups were: low level, 3.6 +/- 1.3 (+/-SD) Gy; medium level, 12 +/- 4.5 Gy; and high level, 37 +/- 5.9 Gy. The crude incidence of lung neoplasms increased linearly with increasing doses to the lungs (controls, 0.57%; low level, 2.0%; medium level, 6.1%; and high level, 19%). The estimated linear risk coefficients for lung neoplasms per unit of dose to the lung were not significantly different for the three dose levels studied. The risk coefficient at the lower level was 39 +/- 14 (+/-SE) excess lung neoplasms per 10(4) rat Gy; at the medium level the risk was 47 +/- 12; and at the higher level the risk was 50 +/- 9.0. The relationship of beta-particle dose to the lung and the crude incidence of lung neoplasms was described adequately by a linear function. We concluded that the risk of lung neoplasms in rats per unit of radiation dose did not increase with decreasing mean beta-particle dose to the lung over the range of 3.6 to 37 Gy. The weighted average of these three values was 47 +/- 6.4 (+/-SE) excess lung neoplasms per 10(4) rat Gy. To extend the risk coefficients for lung neoplasms to lower doses by experimentation will require much larger numbers of rats than used in this study.     

The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study

1. We have studied the effects of muscarinic cholinoceptor agonists and subtype-preferring antagonists on the isometric contraction of smooth muscle strips from dog prostate. 2. Acetylcholine and carbachol induced contraction of prostate strips from the peripheral zone, ('the capsule'). Bethanechol contracted the tissue but not at lower doses. McN-A-343 and oxotremorine-M showed the same effects. 3. Blocking alpha- and beta-adrenoceptors with phentolamine and propranolol, respectively, did not modify carbachol-induced contractions. 4. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M) did not affect the contractile response evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic receptor antagonist, atropine (10(-11)-10(-9) M), inhibited it in a competitive manner. 5. The muscarinic M1 (pirenzepine), M2 [AF-DX 116, himbacine (M2/M4) and methoctramine], M3 (HHSID and f-F-HHSID), and putative M4 (tropicamide) antagonists reduced significantly the carbachol-induced contractions. The pIC50 values were: atropine (10.01) > himbacine (8.3) > methoctramine (7.85) > AF-DX 116 (7.60) > HHSID (7.21) > p-F-HHSID (7.10) > pirenzepine (7.30) > tropicamide (7.00). 6. The antagonist profile indicates that an predominant M2 receptor subtype could mediate the muscarinic contraction in the canine prostate.     

Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura: report of seven patients and a meta-analysis

We present the results of a meta-analysis using clinical data obtained from seven of our patients and 24 previously reported patients with idiopathic thrombocytopenic purpura complicated by intracranial hemorrhage. Twenty-four had an intracerebral hemorrhage (ICH) and seven had a subdural hematoma (SDH). Mean age of the patients with ICH was significantly younger than those with SDH. The mortality rate of ICH associated with ITP was similar to that of spontaneous ICH. All seven patients with SDH improved without sequelae.