Dynamic cortical networks of verbal and spatial working memory: effects of memory load and task practice

Working memory (WM), the ability to briefly retain and manipulate information in mind, is central to intelligent behavior. Here we take advantage of the high temporal resolution of electrophysiological measures to obtain a millisecond timescale view of the activity induced in distributed cortical networks by tasks that impose significant WM demands. We examined how these networks are affected by the type and amount of information to be remembered, and by the amount of task practice. Evoked potentials (EPs) were obtained from eight subjects performing spatial and verbal versions of a visual n-back WM task (n = 1, 2, 3) on each of three testing days. In well-trained subjects, WM tasks elicited transient responses reflecting different subcomponents of task processing, including transient (lasting 0.02-0.3 s) task-sensitive and load-sensitive EPs, as well as sustained responses (lasting 1-1.5 s), including the prestimulus Contingent Negative Variation (CNV), and post-stimulus frontal and parietal Slow Waves. The transient responses, with the exception of the P300, differed between the verbal and spatial task versions, and between trials with different response requirements. The P300 and the Slow Waves were not affected by task version but were affected by increased WM load. These results suggest that WM emerges from the formation of a dynamic cortical network linking task-specific processes with non-specific, capacity-limited, higher-order attentional processes. Practice effects on the EPs suggested that practice led to the development of a more effective cognitive strategy for dealing with lower-order aspects of task processing, but did not diminish demands made on higher order processes. Thus a simple WM task is shown to be composed of numerous elementary subsecond neural processes whose characteristics vary with type and amount of information being remembered, and amount of practice.     

Endopeptidase 24.11 inhibition does not modify uterotonic effects of endothelins in rat uterus

We investigated effects of the endopeptidase 24.11 inhibitor, SCH 39370, on uterotonic effects of endothelins (ETs) and sarafotoxin S6b. Responses of uteri from non-pregnant rats were inhibited by the ETA receptor antagonist, BQ123 (1 microM) but not the ETB receptor antagonist, BQ 788 (1 microM). ET-1, sarafotoxin S6b and ET-2 were more potent than ET-3 in tissues from non-pregnant and pregnant rats. SCH 39370 (10 microM) did not affect uterotonic responses to these peptides in either group, but inhibited those of big ET-1 in non-pregnant rat tissues, indicating inhibition of conversion of big ET-1 to ET-1. These data indicate that endopeptidase 24.11 does not inactivate the endothelin peptides in the rat uterus.     

Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.     

Identifying adolescent runaways: the predictive utility of the personality inventory for children

This study investigated whether runaway behavior could be related to six problematic areas. Selected scales of the Personality Inventory for Children, representative of the six areas, were hypothesized to discriminate between an adolescent runaway group and a control group. Four scales correctly classified 95.1% of the runaway subjects and 100% of the control subjects with a total correct classification rate of 97.52%. It was further hypothesized that the runaway group was not significantly different from a known clinical group with moderate to severe psychopathology. Results indicated that the runaway group was not significantly different except on one scale, Delinquency (DLQ). On the DLQ scale the runaway group had a significantly higher mean score than the clinical group. Application and recommendations are presented.     

Aortic perforation during lumbar laminectomy

A method to determine the optimal replacement time for dye affinity adsorbents used in protein purification processes that are subjected to severe regeneration conditions has been developed. To demonstrate the utility of the method, an experimental fixed-bed decay model was employed to determine the optimum number of cycles for the adsorbent replacement. This number is a function of the column regeneration frequency and of the capital and operation costs. The implications of the results on the design and operation of dye-ligand chromatographic processes are discussed.     

Inactivation of aconitase and oxoglutarate dehydrogenase in skeletal muscle in vitro by superoxide anions and/or nitric oxide

Strips of rat soleus muscle were incubated in media containing a superoxide generating system and/or the nitric oxide donor sodium nitroprusside (SNP) before the maximal catalytic activities of aconitase, citrate synthase, and oxoglutarate dehydrogenase were measured. The maximal activities of aconitase and oxoglutarate dehydrogenase were both decreased by 25-30% by superoxide anions; however, only the maximal activity of aconitase was decreased, by approximately 50%, by incubation of muscles with SNP. Furthermore, when both superoxide and NO were present in the medium, aconitase activity was decreased by 70%. The maximal activity of citrate synthase was not affected by any of the treatments. This is the first time that superoxide anions or NO has been shown to inactivate aconitase and oxoglutarate dehydrogenase in skeletal muscle. It is suggested that these effects may be responsible for some alterations in skeletal muscle metabolism, and these possibilities are discussed.