CNS neuronal focal adhesion kinase forms clusters that co-localize with vinculin

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that appears to play a central role in integrin-mediated signal transduction in non-neuronal cells, linking the extracellular matrix to the actin-based cytoskeleton at focal adhesion contacts. Biochemical analysis has revealed the presence of FAK immunoreactivity in cells of neuronal lineage (Zhang et al., 1994) and in the CNS (Burgaya et al. 1995; Grant et al., 1995). In the current work, we have examined the immunodistribution of FAK in nerve cell cultures and tissue sections from the rat CNS. Cultures of B103 CNS neuroblastoma cells and primary cultures of hippocampal neurons both showed abundant FAK immunoreactivity in nerve cell bodies. Immunoreactivity also extended into neurites and growth cones. The most striking feature of FAK distribution was the presence of short, punctate clusters of high FAK concentration. These FAK clusters were maintained in triton-extracted cell ghosts, indicating association with the cytoskeleton. Double-label confocal imaging showed that clusters of FAK coincided with clusters of vinculin, another actin-associated signal transduction molecule implicated in control of growth cone motility. Data from hippocampal sections verified the presence of FAK in adult neurons where it was enriched in somato-dendritic domains and showed a non-uniform distribution. Quantitative FAK immunoprecipitation to compare adult with embryonic brain showed a 7-fold developmental down-regulation of FAK and a 21-fold down-regulation of FAK TyrP. The data suggest that neuronal FAK may participate in signal transduction complexes relevant to neuronal morphogenesis and plasticity.     

Clinical outcome in diffuse large B-cell lymphoma is dependent on the relationship between different cell-cycle regulator proteins

PURPOSE: The goal of this work was to perform a comprehensive exploration of the relationship between the clinical outcome of diffuse large B-cell lymphoma (DLBCL) and the expression of a panel of tumor suppressor and oncogenic proteins, which includes some cell-cycle regulator proteins involved in the p53 pathway. PATIENTS AND METHODS: To this end, we collected the clinical data of 141 patients with DLBCL and immunohistochemically analyzed diagnostic tumoral tissue from each patient for the presence of Ki67 (MIB1, Immuno-tech, Marseille, France), bcl2, p53, p21/WAF1, MDM2, and retinoblastoma (Rb) proteins. RESULTS: The results show that several proteins are associated with some of the clinical traits analyzed. Multivariate analysis showed that an extended overall survival (OS) time was associated with low growth fraction, high Rb protein, and low MDM2 expression, as well as with known clinical parameters. The probability of inducing a complete remission (CR) was only associated with clinical parameters, although univariate study showed that a low growth fraction was associated with a higher probability of inducing a CR. Univariate study of disease-free survival (DFS) showed that tumors with high bcl2 expression and nodal origin have a shorter DFS time, although multivariate study only confirmed the adverse effect of bcl2 expression. CONCLUSION: Taking all these results into consideration, it seems that although the overall outcome for patients with DLBCL is decided by a combination of different clinical and biologic variables, the expression of some of these cell-cycle regulator proteins appears to be specifically associated with the different clinical features of tumors.     

Transforaminal and posterior decompressions of the lumbar spine. A comparative study of stability and intervertebral foramen area

STUDY DESIGN: Ten fresh, cadaveric, two-vertebrae, functional spinal units were used to study the pathoanatomy, intervertebral foraminal area, and flexibility changes after posterior and transforaminal decompression. OBJECTIVES: To determine the feasibility of an endoscopic transforaminal approach as an alternative to conventional approaches, to establish the adequacy of transforaminal decompression without destabilizing the spine, and to study the structural changes in the spine after decompressions. SUMMARY OF THE BACKGROUND DATA: Posterior decompression entails major dissection and excision of bone and ligaments to access the spinal canal. Posterior decompression may be complicated by acute or chronic spinal instability, and the adequacy of lateral decompression is highly subjective. METHODS: The functional spinal units were mounted in quick-setting epoxy blocks. Pre- and postoperative computed tomography scans were taken to study changes in the foraminal area. Pre- and postoperative flexibility and anatomic studies were performed to compare the results. RESULTS: A 45.5% increase in the intervertebral foraminal area was possible, there was no flexibility change, and minimal anatomic damage to the spine was noted after transforaminal decompression. A 34.2% increase in the intervertebral foraminal area and a significant increase in extension and axial rotation flexibility were noted after the posterior decompression. CONCLUSION: Transforaminal decompression produced a significantly larger increase in the intervertebral foraminal area than posterior decompression, without increasing the range of motion or neutral zone in any direction. Because there was no violation of the anatomic integrity of the spine in the transforaminal approach, the risk of surgically induced instability was minimized. Endoscopic transforaminal decompression is a feasible alternative to current approaches.     

Report of the WHO working group on the assessment of health risks for human infants from exposure to PCDDs, PCDFs and PCBs

On Nov. 20-22, 1995, a World Health Organization working group consisting of 12 scientific representatives from 6 different countries met to reassess the health risks to infants associated with perinatal exposure to polyhalogenated aromatic hydrocarbons (PHAHs). Following a review of previous WHO/EURO consultations, as part of their comprehensive programme on PCDDs, PCDFs and PCBs, current exposure information and recent experimental and epidemiologic data were discussed. Exposure assessments within the past decade have revealed that in the case of breast milk samples concentrations of PCDDs/DFs and PCBs have shown a continual decline, in certain countries by up to 50%. New experimental data has revealed that a variety of structural, functional and behaviourial alterations can be induced in rodent species following exposure to PHAHs while a Dutch collaborative PCB/dioxin study has illustrated subtle clinical, endocrine and mental/psychomotor development effects can occur in breast fed infants. The provisional conclusions of the working group were: 1) current evidence does not warrant altering the previous WHO recommendation for promotion/support of breast feeding and 2) based on new clinical data which supports the biological plausibility of certain observed experimental observations, continued and enhanced effort should be directed towards identifying and controlling sources of environmental input for these contaminants.     

Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy

Atrial and brain natriuretic peptides (ANP and BNP) are produced by the heart, and their plasma concentrations are increased in human chronic congestive heart failure. Although separate studies have suggested that circulating levels of the biologically active C-terminal ANP, the biologically inactive N-terminal ANP, and BNP may have diagnostic utility in the detection of left ventricular systolic dysfunction or left ventricular hypertrophy, no studies have directly assessed the relative value of these peptides prospectively. We therefore designed this study to compare the relative ability of the different natriuretic peptides to detect abnormal left ventricular systolic and diastolic function and left ventricular hypertrophy. Using a prospective study design, we investigated 94 patients referred for cardiac catheterization and 15 age-matched normal subjects. The diagnostic abilities of elevated plasma C-terminal ANP, N-terminal ANP-(1-30), and BNP concentrations to identify systolic dysfunction (ejection fraction < 45%), diastolic dysfunction (time constant of left ventricular relaxation > 55 milliseconds, left ventricular end-diastolic pressure > 18 mm Hg), and left ventricular hypertrophy (left ventricular mass index > 120 g/m2) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean + 3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m2. The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-terminal ANP or N-terminal ANP-(1-30) has potential utility for the detection of altered left ventricular structure and function in a patient population at risk for cardiovascular disease.     

Effects of dialogue and therapeutic touch on preoperative and postoperative experiences of breast cancer surgery: an exploratory study

PURPOSE/OBJECTIVES: To obtain preliminary data and determine the feasibility of a large-scale experimental study to test the efficacy of the Rogerian Science of Unitary Human Beings-based intervention of dialogue and therapeutic touch (TT) on pre- and postoperative anxiety and mood and postoperative pain from breast cancer surgery. DESIGN: Experimental. SETTING: Mid-Atlantic region; ambulatory. SAMPLE: 29 Caucasian and 2 African American English-speaking women with positive breast cancer biopsy (experimental, n = 14; control, n = 17), ranging in age from 31-84 years old (F = 55.6). METHODS: Treatments administered in subjects' homes within seven days prior to surgery and 24 hours after hospital discharge. Experimental treatment consisted of 10 minutes of TT and 20 minutes of dialogue. Control treatment consisted of 10 minutes of quiet time and 20 minutes of dialogue. Data (Spielberger State-Trait Anxiety Inventory. Affects Balance Scale, and Visual Analog Scale-Pain) were collected at the conclusion of each home visit. MAIN RESEARCH VARIABLES: Anxiety, mood, and pain. FINDINGS: The experimental group had lower preoperative state anxiety than the control groups (p = 0.008). No difference was found for preoperative mood. No differences were found for any postoperative measure. CONCLUSIONS: A large-scale study of dialogue and TT would require changes in design and recruitment strategies. IMPLICATIONS FOR NURSING PRACTICE: Nurses may provide more comprehensive care by incorporating dialogue and TT or quiet time into their pre- and postoperative care. Additional research, however, is recommended to determine the differential effects of dialogue, TT, and quiet time on women's experiences with breast cancer prior to incorporating these noninvasive modalities into clinical practice.