Firing characteristics of deep layer neurons in prefrontal cortex in rats performing spatial working memory tasks

Single cells were recorded with 'tetrodes' in regions of the rat medial prefrontal cortex, including those which are targets of hippocampal afferents, while rats were performing three different behavioral tasks: (i) an eight-arm radial maze, spatial working memory task, (ii) a figure-eight track, delayed spatial alternation task, and (iii) a random food search task in a square chamber. Among 187 recorded units, very few exhibited any evidence of place-specific firing on any of the behavioral tasks, except to the extent that different spatial locations were related to distinct phases of the task. Furthermore, no prefrontal unit showed unambiguous spatially dependent delay activity that might mediate working memory for spatial locations. Rather, the cells exhibited diverse correlates that were generally associated with the behavioral requirements of performing the task. This included firing related to intertrial intervals, onset or end of trials, selection of specific arms on the eight-arm radial maze, delay periods, approach to or departure from goals, and selection of paths on the figure-eight track. Although a small number of cells showed similar behavioral correlates across tasks, the majority of cells showed no consistent correlate when recorded across multiple tasks. Furthermore, some units did not exhibit altered firing patterns in any of the three tasks, while others showed changes in firing that were not consistently related to specific behaviors or task components. These results are in agreement with previous lesion and behavioral studies in rats that suggest a prefrontal cortical role in encoding 'rules' (i.e. structural features) or behavioral sequences within a task but not in encoding allocentric spatial information. Given that the hippocampal projection to this cortical region is capable of undergoing LTP, our data lead to the hypothesis that the role of this projection is not to impose spatial representations upon prefrontal activity, but to provide a mechanism for learning the spatial context in which particular behaviors are appropriate.     

Metabolism and pharmacokinetics of 1-(2''-trimethylacetoxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP117) in the rat

A modified endoscopic technique for anterior cruciate ligament (ACL) reconstruction using an autologous patellar tendon graft is described using the early results for 120 patients. A special technique using an oscillating hollow saw allows for the rapid and standardized harvest of cylindrical bone plugs, ensuring safe and adequate femoral press-fit fixation. The complications encountered included one fracture of a bone back on plugging in as well as two cases with revision procedures for interference screw fixation due to insufficient femoral anchorage. Within the framework of a prospective study, all 120 patients underwent a control arthroscopy after the first postoperative year showing viable and mechanically stable grafts in 64 (53.3%) of the patients. In 44 patients (36.7%), viable though somewhat lax grafts were found, whereas the remaining 12 patients (10%) only showed insufficient tissue residues. All of these cases were the result of a ventral misplacement of the femoral insertion site representing the primary complication of transtibial technique. The results of the control arthroscopies showed a highly significant correlation with the clinical results for the IKDC score obtained in a follow-up after an average 29 (18 to 36) months. The results for stability according to the IKDC rating scale showed a normal or near-normal knee function in 76.7%. With regard to the subjective results in the IKDC rating scale, 83.3% of the patients (n = 100) assessed their knee function as normal or almost normal. The location and positioning of the femoral and tibial tunnel were evaluated in an exact radiographic evaluation showing an "ideal position" of the graft in only 94 cases (78.3%). Statistically, a significant correlation of stability with the femoral fixation site could be shown.     

Calcineurin-immunosuppressor complexes

Crystal structures of the Ser/Thr phosphatase calcineurin (protein phosphatase 2B) have recently been solved by X-ray crystallography, both in the free-protein state, and complexed with the immunophilin/immunosuppressant FKBP12/FK506. Core elements of the calcineurin phosphatase have been found to be similar to the corresponding elements of Ser/Thr phosphatase 1 and purple acid phosphatase. The structures provide a basis for understanding calcineurin inhibition by a ternary complex of immunophilin and immunosuppressant proteins.     

Pathology of diseases in wild desert tortoises from California

Twenty-four ill or dead desert tortoises (Gopherus agassizii) were received between March 1992 and July 1995 for necropsies from the Mojave and Colorado deserts of California (USA). Diseases observed in these animals included cutaneous dyskeratosis (n = 7); shell necrosis (n = 2); respiratory diseases (n = 7); urolithiasis (n = 3); and trauma (n = 5). In tortoises with cutaneous dyskeratosis the horn layer of shell was disrupted by multiple crevices and fissures and, in the most severe lesions, dermal bone showed osteoclastic resorption, remodeling, and osteopenia. In tortoises with shell necrosis, multiple foci of necrotic cell debris and heterophilic inflammation within the epidermal horn layer were subtended by necrotic dermal bone colonized by bacteria and fungi. Of the seven tortoises with respiratory disease, five were diagnosed with mycoplasmosis. The diagnosis of mycoplasmosis was based on the presence of chronic proliferative rhinitis and positive serologic tests and/or isolation of Mycoplasma sp. Chronic fungal pneumonia was diagnosed in one tortoise with respiratory disease. In the three tortoises with urolithiasis, two were discovered dead, and the live tortoise had renal and articular gout. Traumatic injuries consisted of one tortoise entombed within its burrow, one tortoise burned in a brush fire, two tortoises struck by moving vehicles, and one tortoise attacked by a predator. While the primary cause of illness could be attributed to one or two major disease processes, lesions were often found in multiple organ systems, and a variety of etiologies were responsible for morbidity and mortality.     

Thrombin receptor (PAR-1) antagonists. Heterocycle-based peptidomimetics of the SFLLR agonist motif

Phorbol ester treatment of MCF-7 cells led to the tyrosine phosphorylation and activation of PKC delta. However, through Western blot analysis and in vitro immunecomplex kinase assays, we detected a differential localization of tyrosine-phosphorylated PKC delta and catalytically active PKC delta. Catalytically active PKC delta was concentrated in Triton X-100 solubilized-membrane fractions while tyrosine-phosphorylated PKC delta was localized to the cytosol fraction. Phorbol ester treatment of MCF-7 cells stimulated both the time-dependent in vivo association of Src with PKC delta, evidenced in Src immunoprecipitates by the co-immunoprecipitation of PKC delta, and activation of Src, evidenced in Src immunoprecipitates as an increase in reactivity with a Src antibody (clone 28) reactive only with active Src (dephosphorylated on residue 530) and in Src and PKC delta immunoprecipitates by an increase in Src kinase activity. While our data are consistent with reports in the literature showing the activator/stimulus-dependent tyrosine phosphorylation of PKC delta, our data show that the tyrosine phosphorylation of PKC delta is not essential for kinase activity. These results are the first to demonstrate an in vivo association between PKC delta and active Src in the absence of over-expression of either PKC delta or Src, and support the association of Src and PKC delta towards a physiological function.