Protein kinase A activators inhibit agonist induced prostaglandin production in human amnion

Prostaglandin (PG) production by human amnion has been postulated to have a role in the onset of labor. Previous work by ourselves and others has demonstrated that oxytocin, phorbol esters and epidermal growth factor (EGF) increase PGE2 production in human amnion cells by activation of the Phospholipase C/Protein Kinase C (PKC) cascade system. The present study was undertaken to determine the effect of prior activation of the Adenylate Cyclase cascade system upon subsequent stimulation of PGE2 production by oxytocin, phorbol 12-myristate-13-acetate (PMA) or EGF in amnion cells and membrane discs. Isoproterenol, forskolin and dibutyryl cyclic adenosine monophosphate (dbcAMP) were utilized to activate the Adenylate Cyclase system at the receptor, enzyme and second messenger level. In control amnion cells, oxytocin, PMA and EGF each provoked dose dependent increases in PGE2 production. In cells preincubated with dbcAMP, forskolin or isoproterenol, agonist stimulated PGE2 production was markedly (50-90%) inhibited (p < 0.01). Inhibition was dose dependent upon preincubator concentrations. Maximal inhibition by adenylate cyclase activators occurred with 2-4 h of preincubation. In membrane discs, forskolin preincubation also inhibited oxytocin, PMA and EGF stimulation of PGE2 production. Activation of the Adenylate Cyclase system in human amnion cells or membrane discs inhibits the subsequent action of potent stimulators of PGE2 production in human amnion.     

Optimisation of antibiotic therapy in cystic fibrosis patients. Pharmacokinetic considerations

Antibiotic therapy plays a central role in the medical management of patients with cystic fibrosis. While totally convincing efficacy data are lacking, antibiotics probably have a pronounced beneficial effect on both morbidity and mortality. Much has been learned in the past 20 years about antibiotic use in this population. At the same time, new antimicrobial agents with the potential to treat this condition have become available for use. The pharmacokinetics of a number of antibiotic classes, including beta-lactams, aminoglycosides and quinolones, are altered in this patient population. Increased total body clearance is a common occurrence but is not always changed enough to warrant altered dosages. Nonetheless, in light of altered pharmacokinetics in the cystic fibrosis population, appropriate dosage and monitoring parameters for a number of antibiotics have been determined.     

Multifocal primary neuroblastoma

The purpose of this study is to present three patients with multifocal primary neuroblastoma, to review the literature, and describe the radiographic findings. SUBJECTS AND METHODS: Three children with multifocal neuroblastoma have been identified. The case histories and imaging findings in these patients are reviewed. RESULTS: Two children had synchronous and one child had metachronous multifocal primary neuroblastoma. The primary tumors were both in the abdomen in one patient, both in the chest in another patient, and in the chest and abdomen in the third patient. Evidence for multifocal origin of these tumors, rather than metastatic spread, is presented. CONCLUSION: Multifocal primary neuroblastomas can occur. The tumors maybe synchronous or metachronous. Awareness of this disorder may prevent errors in diagnosis and staging. Although not identified in our patients there is a strong familial incidence of neuroblastomas in those patients with multifocal tumors.     

Muscle-ligament interactions at the knee during walking.

A two-dimensional mathematical model of the knee is used with gait analysis to calculate muscle, cruciate ligament and tibio-femoral contact forces developed at the knee during normal level walking. Ten normal adult subjects--four females and six males--participated. The knee model is based upon a four-bar linkage comprising the femur, tibia and two cruciate ligaments. It takes account of the rolling and sliding of the femur on the tibia during flexion/extension and the changes in direction of the ligaments and muscle tendons. We considered forces transmitted by six elements: quadriceps, hamstrings, gastrocnemius, anterior and posterior cruciate ligaments, and tibio-femoral contact. The equations of mechanics can be used to determine the absolute values of only three of the knee forces simultaneously, so that twenty limiting solutions of three of the six forces were considered. A limiting solution was rejected if any of the three forces were negative, corresponding to compressive muscle or ligament forces, or tensile contact forces. These constraints always reduced and at times removed the redundancy of the knee structures. The high incidence of predicted single muscle activity, supported by electromyography, suggested that the ligaments play a significant role in load transmission during gait. The temporal patterns of muscle and ligament activity and ligament force magnitudes were sensitive to the choice of model parameters. The analysis showed that each of four possible minimum principles of muscle selection--minimal muscle force, muscle stress, ligament force and contact force--was unlikely to be valid throughout the walking cycle.     

Motion Planning for Redundant Manipulators Using a Floating Point Genetic Algorithm

This paper deals with the trajectory planning problem for redundant manipulators. A genetic algorithm (GA) using a floating point representation is proposed to search for the optimal end-effector trajectory for a redundant manipulator. An evaluation function is defined based on multiple criteria, including the total displacement of the end-effector, the total angular displacement of all the joints, as well as the uniformity of Cartesian and joint space velocities. These criteria result in minimized, smooth end-effector motions. Simulations are carried out for path planning in free space and in a workspace with obstacles. Results demonstrate the effectiveness and capability of the proposed method in generating optimized collision-free trajectories.     

Transient Response and Fixed Pattern Noise in Logarithmic CMOS Image Sensors

Logarithmic CMOS image sensors are appealing for their high-contrast and high-speed response but they require postprocessing to achieve high-quality images. Previously published work has explained the fixed pattern noise (FPN) in these image sensors using a steady-state analysis. This paper explains how the transient response of the readout circuit may also contribute to FPN. Thus, the performance of these CMOS cameras may be optimized with a proper understanding of the transient response, which is explained here through modeling and simulation with some experimental validation. In particular, the gain variation of a logarithmic camera is shown to be caused primarily by premature digitization. As logarithmic and linear active pixel sensors use similar circuits, some results in this paper, e.g., an analysis of readout capacitance, apply equally to the latter.     

基于PSOS的TM1300应用系统中的BSP研究

通过在应用软件与板级支持包BSP之间加一层库函数的方法较好地解决了应用程序与板级支持包函数间的通信问题，减少了板级支持包函数的维护复杂度，从而为嵌入式系统板级支持包的实现提供了一个有价值的思路。     

The role in cell binding of a beta-bend within the triple helical region in collagen alpha 1 (I) chain: structural and biological evidence for conformational tautomerism on fiber surface

Dystrophin is a plasma membrane-associated cytoskeletal protein of the spectrin superfamily. The dystrophin cytoskeleton has been first characterized in muscle. Muscular 427 kDa dystrophin binds to subplasmalemmal actin filaments via its amino-terminal domain. The carboxy-terminus of dystrophin binds to a plasma membrane anchor, beta-dystroglycan, which is associated on the external side with the extracellular matrix receptor, alpha-dystroglycan, that binds to the basal lamina proteins laminin-1, laminin-2, and agrin. In the muscle, the dystroglycan complex is associated with the sarcoglycan complex that consists of several glycosylated, integral membrane proteins. The absence or functional deficiency of the dystrophin cytoskeleton is the cause of several types of muscular dystrophies including the lethal Duchenne muscular dystrophy (DMD), one of the most severe and most common genetic disorders of man. The dystrophin complex is believed to stabilize the plasma membrane during cycles of contraction and relaxation. Muscular dystrophin and several types of dystrophin variants are also present in extramuscular tissues, e.g. in distinct regions of the central nervous systems including the retina. Absence of dystrophin from these sites is believed to be responsible for some extramuscular symptoms of DMD, e.g. mental retardation and disturbances in retinal electrophysiology (reduced b-wave in electroretinograms). The reduced b-wave in electroretinograms indicated a disturbance of neurotransmission between photoreceptors and ON-bipolar cells. At least two different dystrophin variants are present in photoreceptor synaptic complexes. One of these dystrophins (Dp260) is virtually exclusively expressed in the retina. In the neuroretina, dystrophin is found in significant amounts in the invaginated photoreceptor synaptic complexes. At this location dystrophin colocalizes with dystroglycan. Agrin, an extracellular ligand of alpha-dystroglycan, is also present at this location whereas the proteins of the sarcoglycan complex appear to be absent in photoreceptor synaptic complexes. Dystrophin and dystroglycan are located distal from the ribbon-containing active synaptic zones where both proteins are restricted to the photoreceptor plasma membrane bordering on the lateral sides of the synaptic invagination. In addition, some neuronal profiles of the postsynaptic complex also contain dystrophin and beta-dystroglycan. These profiles appear to belong at least in part to projections of the photoreceptor terminals into the postsynaptic dendritic complex. In view of the abnormal neurotransmission between photoreceptors and ON-bipolar cells in DMD patients the dystrophin/beta-dystroglycan-containing projections of photoreceptor presynaptic terminals into the postsynaptic dendritic plexus might somehow modify the ON-bipolar pathway. Another retinal site associated with dystrophin/beta-dystropglycan is the plasma membrane of Müller cells where dystrophin/beta-dystroglycan appear to be present at particular high concentrations. At this location the dystrophin/dystroglycan complex may play a role in the attachment of the retina to the vitreous, and, under pathological conditions, in traction-induced retinal detachment.     

A comparison of placebo response with major depressive disorder in patients recruited through newspaper advertising versus consultation referrals

Recent evidence indicates few differences between patients recruited through advertising and by consultation referral, and there is some suggestion that those recruited through advertising are more representative of the target community population. However little has been reported on differences in placebo response and compliance in these two patient groups. We conducted a retrospective chart review of 49 patients with major depressive disorder (MDD), recruited through advertising or consultation, randomized to placebo in five clinical trials. Variables included demographics, clinical history, efficacy, compliance, and completion data. Homogeneity was demonstrated for most variables. Differences in placebo groups included significantly lower Hamilton Rating Scale for Depression (HAM-D) scores for the advertisement group throughout the trials. Advertisement patients were also more likely to be early placebo responders and in remission at Days 14 and 28. No differences were found in completion rates or reasons for early termination. Compliance was excellent for both groups. Early placebo response of the advertisement group reinforces the need for trials of at least 8 weeks. In addition, consultation patients may have a more severe illness and be treatment resistant, suggesting they are less generalizable to community practice populations.