Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspartate shuttle

The flux through different segments of the tricarboxylic acid cycle was measured in rat brain synaptosomes with gas chromatography-mass spectrometry using either deuterated glutamine or [13C]aspartate. The flux between 2-oxoglutarate and oxaloacetate was estimated to be 3.14 and 4.97 nmol/min/mg protein with and without glucose, respectively. These values were 3-5-fold faster than the flux between oxaloacetate and 2-oxoglutarate (0.92 nmol/min per mg protein) measured in the presence of glucose. The pattern of intermediates labeling suggests that the overall rate-controlling reaction involves either citrate synthase or pyruvate dehydrogenase but not 2-oxoglutarate or isocitrate dehydrogenase. The enrichment in [3,3,4,4-2H4]glutamate from [2,3,3,4,4-2H5]glutamine was as rapid as in [2,3,3,4,4-2H5]glutamate, which indicates that the aspartate aminotransferase reaction is severalfold faster than the flux through the tricarboxylic acid cycle. [13C]Aspartate was rapidly converted to [13C]malate, suggesting that in intact synaptosomes aspartate entry into the mitochondrion is very slow. The finding that aspartate is taken up by mitochondria as malate, along with the observed high enrichment in [3-2H]malate (from [2,3,3,4,4-2H5]glutamine), is consistent with the substantial synaptosomal activity of the malate/aspartate shuttle.     

Responsiveness of self-reported and objective measures of disease severity in carpal tunnel syndrome

Responsiveness, the ability to detect meaningful clinical change, is a critical attribute of instruments used to evaluate outcomes of treatments. The authors hypothesized that self-administered symptom severity and functional status questionnaires are more responsive to clinical improvement after carpal tunnel release than traditional physical examination measures of strength and sensibility. Data were obtained from a randomized clinical trial of endoscopic versus open carpal tunnel release conducted in four university medical centers. Patients were evaluated before surgery and 3 months after surgery. Seventy-four patients indicating that they were more than 80% satisfied with the results of surgery were assumed to have clinically meaningful improvement and were the focus of the analysis. Evaluations included questionnaires assessing symptom severity, functional status, and activities of daily living as well as measurement of grip, pinch, and abductor pollicus brevis strength, and 2-point discrimination and Semmes-Weinstein pressure sensibility. Responsiveness was calculated with the standardized response mean (mean change/standard deviation of change) as well as the effect size (mean change/standard deviation of baseline values). The symptom severity scale was four times as responsive, and the functional status and activities of daily living scales were twice as responsive, as the measures of strength and sensibility. Self-administered symptom severity and functional status scales are much more responsive to clinical improvement than measures of neuromuscular impairment and should severe as primary outcomes in clinical studies of therapy for carpal tunnel syndrome.     

Treatment of radiation-induced nervous system injury with heparin and warfarin

When radiation is used to treat nervous system cancer, exposure of adjacent normal nervous system tissue is unavoidable, and radiation-induced injury may occur. Acute injury is usually mild and transient, but late forms of radiation-induced nervous system injury are usually progressive and debilitating. Treatment with corticosteroids, surgery, and antioxidants is often ineffective. We treated 11 patients with late radiation-induced nervous system injuries (eight with cerebral radionecrosis, one with a myelopathy, and two with plexopathies, all unresponsive to dexamethasone and prednisone) with full anticoagulation. Some recovery of function occurred in five of the eight patients with cerebral radionecrosis, and all the patients with myelopathy or plexopathy. Anticoagulation was continued for 3 to 6 months. In one patient with cerebral radionecrosis, symptoms recurred after discontinuation of anticoagulation and disappeared again after reinstitution of treatment. We hypothesize that anticoagulation may arrest and reverse small-vessel endothelial injury--the fundamental lesion of radiation necrosis--and produce clinical improvement in some patients.     

Tuning of MST neurons to spiral motions

Cells in the dorsal division of the medial superior temporal area (MSTd) have large receptive fields and respond to expansion/contraction, rotation, and translation motions. These same motions are generated as we move through the environment, leading investigators to suggest that area MSTd analyzes the optical flow. One influential idea suggests that navigation is achieved by decomposing the optical flow into the separate and discrete channels mentioned above, that is, expansion/contraction, rotation, and translation. We directly tested whether MSTd neurons perform such a decomposition by examining whether there are cells that are preferentially tuned to intermediate spiral motions, which combine both expansion/contraction and rotation components. The finding that many cells in MSTd are preferentially selective for spiral motions indicates that this simple three-channel decomposition hypothesis for MSTd does not appear to be correct. Instead, there is a continuum of patterns to which MSTd cells are selective. In addition, we find that MSTd cells maintain their selectivity when stimuli are moved to different locations in their large receptive fields. This position invariance indicates that MSTd cells selective for expansion cannot give precise information about the retinal location of the focus of expansion. Thus, individual MSTd neurons cannot code, in a precise fashion, the direction of heading by using the location of the focus of expansion. The only way this navigational information could be accurately derived from MSTd is through the use of a coarse, population encoding. Positional invariance and selectivity for a wide array of stimuli suggest that MSTd neurons encode patterns of motion per se, regardless of whether these motions are generated by moving objects or by motion induced by observer locomotion.     

A comparison of category and letter fluency in Alzheimer's disease and Huntington's disease.

44 patients with dementia of the Alzheimer type (DAT), 44 elderly normal control (ENC) Ss demographically matched to the DAT group, 42 patients with Huntington's disease (HD), and 42 middle-aged normal control (MNC) Ss demographically matched to the HD group were administered letter and category fluency tasks. DAT patients showed an overproportional impairment on category than on letter fluency tasks, whereas HD patients were equally impaired. Analyses based on receiver operating characteristic curves revealed that category fluency correctly classified significantly more DAT and ENC Ss than did letter fluency, whereas the 2 fluency tasks did not differ in this respect for HD and MNC Ss. Results suggest that HD patients' failures on fluency tasks are caused by impaired initiation/retrieval capacities. In contrast, DAT patients' greater category than letter fluency deficits are primarily due to a breakdown in the structure of semantic knowledge. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Semantic homophone priming in patients with dementia of the Alzheimer's type.

To examine the role of semantic processes in the verbal priming deficits of patients with dementia of the Alzheimer type (DAT), 15 DAT patients, 8 amnesic patients, and 12 controls were administered a homophone spelling bias task. Ss' spellings were biased against their previously preferred homophone spellings by presenting the homophones aurally in a semantically related context. The results showed that DAT patients were not significantly different from controls or amnesic patients on the immediate priming measure. However, both patient groups' semantic priming effects decayed more rapidly and their recognition performance was significantly impaired in relation to those for control Ss. These results suggest that DAT patients can perform normally on some semantic priming tasks if the task demands are within the capacity of the patients' remaining intact semantic structure and if the delay between presentations is brief. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spectral Representation of High‐Frequency Space Shuttle Data

High frequency Space Shuttle liftoff data are treated by autoregressive (AR) and autoregressive‐moving‐average (ARMA) digital algorithms. These algorithms provide useful information on the spectral densities of the data. Further, they yield spectral models, which lend themselves to incorporation into the concept of the random response spectrum. This concept yields a reasonably smooth power spectrum for the design of structural and mechanical systems when the available data bank is limited. Due to the nonstationarity of the liftoff event, the pertinent data are split into three slices. Each of the slices is associated with a rather distinguishable phase of the liftoff event, in which stationarity can be expected. The presented results are preliminary in nature; they aim to call attention to the availability of the discussed concepts and to the need to augment the Space Shuttle data bank as more flights are completed.     

Psychology and psychiatric survivors.

Comments on the G. B. Smith et al (see record 1993-46150-001) presentation of 8 models and roles for psychologists in the treatment, management, and prevention of chronic mental illness. Smith et al describe the models, but fail to critically analyze them or to provide a synthesis of viewpoints. A new paradigm is suggested in which psychology's agenda is to understand the oppressive nature of psychiatric survivors' daily living conditions and experiences and to collaborate with survivors in developing empowering interventions. Three themes of an empowerment perspective are outlined. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Small cardioactive peptide B increases the responsiveness of the neural system underlying prey capture reactions in the pteropod mollusc, Clione limacina

Effects of small cardioactive peptide B (SCPB) on cerebral neurons which underlie prey capture in the carnivorous pteropod mollusc, Clione limacina, were investigated. SCPB in concentrations of 10 microM and higher produced direct activation of cerebral ganglion neurons underlying extrusion of buccal cones used in prey capture. SCPB in lower concentrations, between 1 and 5 microM, did not have a noticeable effect on the membrane potentials of these neurons; however, it significantly increased their responsiveness to sensory inputs from the tactile stimulation of the head, and their ability to generate afterdischarge activity. SCPB immunoreactivity was observed in cell bodies in buccal, cerebral, pedal, and intestinal ganglia, as well as in the anterior esophagus and in buccal cones where fibers stained intensely. These electrophysiological and immunohistochemical data suggest that SCPB may have a physiological role in feeding arousal in Clione.     

Genetically engineered antibodies for diagnostic pathology

Antibody genes can be cloned, genetically manipulated, and expressed in both homologous and heterologous expression systems to produce viable antigen-binding proteins complete with natural effector functions. Manipulation of antibody genes permits the expression of fusion proteins or truncated proteins that retain antigen-binding activity. The new antibody technologies are becoming increasingly sophisticated, permitting the alteration of antigen-binding responses, the transfer of antigen specificity between antibodies, and the expression of minimal-size antigen-binding protein domains. These new molecules have been made mostly for studies on function or to provide molecules suited for in vivo diagnosis and therapy; very few have been specifically designed for, or used for, diagnostic histopathology. We describe here the adaptation of small antibody derivatives for use in immunohistochemistry. Molecules suitable for this purpose need only to possess specific antigen-binding ability and some means of detection of antigen-bound material. Detection could be by recognition of a genetically fused flag or tag epitope, by the fusion of an enzyme whose activity can be assayed, or by fusion with a protein that can interact with pre-existing histopathological reagents.