A myosin III from Limulus eyes is a clock-regulated phosphoprotein

The lateral eyes of the horseshoe crab Limulus polyphemus undergo dramatic daily changes in structure and function that lead to enhanced retinal sensitivity and responsiveness to light at night. These changes are controlled by a circadian neural input that alters photoreceptor and pigment cell shape, pigment migration, and phototransduction. Clock input to the eyes also regulates photomechanical movements within photoreceptors, including membrane shedding. The biochemical mechanisms underlying these diverse effects of the clock on the retina are unknown, but a major biochemical consequence of activating clock input to the eyes is a rise in the concentration of cAMP in photoreceptors and the phosphorylation of a 122 kDa visual system-specific protein. We have cloned and sequenced cDNA encoding the clock-regulated 122 kDa phosphoprotein and show here that it is a new member of the myosin III family. We report that Limulus myosin III is similar to other unconventional myosins in that it binds to calmodulin in the absence of Ca2+; it is novel in that it is phosphorylated within its myosin globular head, probably by cAMP-dependent protein kinase. The protein is present throughout the photoreceptor, including the region occupied by the photosensitive rhabdom. We propose that the phosphorylation of Limulus myosin III is involved in one or more of the structural and functional changes that occur in Limulus eyes in response to clock input.     

Memory association and personality as predictors of alcohol use: mediation and moderator effects

We investigated the nature of the effects of memory associations on alcohol use and abuse. First, we determined if effects of memory associations on drinking problems are mediated entirely through the frequency of alcohol consumption or, alternatively, if such effects are more direct. Second, personality traits were assessed to evaluate whether they were confounded with memory association in their effects or whether they might moderate the effects of memory associations on alcohol use and abuse. The results showed that memory association measures directly and independently predicted alcohol consumption; these measures indirectly predicted problems from drinking, including drunk driving. None of the assessed personality variables moderated the predictive effects of memory association. The results are consistent with the view that memory associations influence behavior through cognitive processes that are not affected by personality traits or by cognitions emanating from such traits.     

Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.     

beta-Amyloid precursor protein isoforms show correlations with neurones but not with glia of demented subjects

Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of beta-amyloid precursor protein (APP) of high apparent molecular mass (> or = 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity.     

Optimization of stirrer designs in a reverberation chamber

This paper describes an investigation into the key factors which contribute to an effective mode stirrer. The work concentrates on the lower frequency range, since all stirrers have poorer performance at low frequencies. The stirrer's shapes and sizes have been investigated, together with an optimization of the finer details in the stirrer's shape. The modeling of the mode stirred chamber has been performed using the transmission-line matrix (TLM) method. Software has been developed which, for each position of the rotating stirrer, builds the shape of the stirrer using thin, perfectly conducting boundaries. Results indicate that the design of the stirrer's basic shape has a small but significant impact on its performance. A genetic algorithm has been used to optimize certain parameters in the shape of the stirrer, and a fitness factor based on a free space model of the stirrer has been used. The free space model runs 1500 times faster than the model in the chamber. The optimization is shown to improve the stirrer's performance in three different sizes of chamber. Computer modeling has been verified by measurements performed in the chamber at the University of York.     

Social support in families of children with chronic conditions: supportive and nonsupportive behaviors

We questioned parents of 182 young children with a variety of chronic health conditions concerning the amount of emotional, informational, and tangible social support they received from the family, community, and service providers. We also asked parents to describe nonsupportive or hurtful behaviors received from family or community members. Both mothers and fathers reported that family members provided the most emotional and tangible social support and service providers the most informational support. The amount of perceived support from all sources increased over time, but 78% of mothers and 60% of fathers reported at least one instance of nonsupport from these same sources, primarily from extended family members and health professionals. We encourage health professionals to show respect and to provide timely, accurate information in a sensitive manner to parents whose child has a chronic health condition and to assist parents in handling nonsupportive behaviors from family and friends.     

Low- and high-density lipoproteins as mitogenic factors for vascular smooth muscle cells: individual, additive and synergistic effects

The mitogenic activities of low (LDL)- and high (HDL)-density lipoproteins have been examined in cultures of human vascular smooth muscle cells (VSMC). LDL and HDL3 dose-dependently (EC50 values approximately 50 micrograms/ml) stimulated DNA and protein synthesis ([3H]-thymidine and [3H]-leucine incorporation, respectively) in the absence of exogenously added mitogens. The synthetic responses of VSMC to combinations of LDL and HDL3 were additive, indicating that each lipoprotein mediates discrete effects. LDL or HDL3 promoted VSMC proliferation under strict mitogen-free conditions, but this growth response was not sustained. VSMC exposed to combinations of lipoproteins (either LDL or HDL3) and growth factors (either PDGF-BB, EGF, bFGF or IGF) exhibited synergistic DNA synthesis responses. In the combined presence of PDGF-BB and either LDL or HDL3, VSMC proliferation was sustained. Anionized lipoprotein preparations (oxidized, acetylated, carbamylated or malonimylated) also stimulated DNA and protein synthesis. Since the antioxidant beta-hydroxylated toluene did not block the effect of native LDL on DNA synthesis, and fucoidin, a specific competitor for the 'scavenger' receptor, did not inhibit oxidized LDL-induced DNA synthesis, activation of mitogenic signals by lipoproteins does not depend on lipid peroxidation. Rather, the apparent intrinsic mitogenic potential of lipoproteins may depend upon their direct activation of replication-coupled signal transduction systems.     

Attitudes of Dublin accident and emergency department doctors and nurses towards the services offered by local general practitioners

We report a case of a depressed patient who received a full course of electroconvulsive therapy (ECT) 2 weeks post four-vessel coronary artery bypass graft surgery (CABG). ECT was well tolerated, and a full remission was induced. In spite of the lack of information in the literature concerning guidelines for administering ECT to a patient with recent postoperative status, we were encouraged by this patient's response. This case suggests that ECT may be considered a viable treatment option for refractory depression associated with severe medical comorbidity and recent post-operative status such as in CABG.