Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging

BACKGROUND: Functional neuroimaging experiments have implicated prefrontal cortex (PFC) in memory processes. Several studies of schizophrenic patients have shown failure of activation in the dorsolateral region of PFC (DLPFC). We used a graded memory challenge to characterize functional neuroanatomical differences between schizophrenic and control subjects. The graded manipulation of task demands enabled us to assess group differences in the context of normal and abnormal psychological task performance. METHODS: Memory-related activity was assessed using positron emission tomography in schizophrenic patients and age-matched controls during performance of a graded memory task. Subjects underwent scanning while learning and recalling word lists of variable length. RESULTS: We used a model that assessed linear and nonlinear effects of memory load. Nonlinear group differences in DLPFC activation were observed. Controls showed a steepening slope of DLPFC increase as task demands increased. By contrast, schizophrenic subjects showed initial DLPFC increases that fell away with increasing memory load. The DLPFC response in schizophrenic subjects was closely related to measured task performance. In addition, schizophrenic subjects failed to show task-related decreases in activity in the left superior temporal and inferior parietal gyrus. CONCLUSIONS: Patients with schizophrenia showed a failure in DLPFC activation only in the face of diminished performance measures, suggesting that a full characterization of task-related changes in DLPFC activation must consider performance levels. However, striking failures of deactivation in superior temporal and inferior parietal regions were independent of task performance, possibly reflecting a core abnormality of the condition.     

Absence of normal activation of the left anterior fusiform gyrus during naming in left temporal lobe epilepsy

Patients with left temporal lobe epilepsy (TLE) often have impaired naming. We studied 13 patients with left TLE and 10 healthy control subjects with [(15)O]H2O PET during visual confrontation naming. Statistical mapping detected multiple regions of significant cerebral blood flow increases within individuals. The left fusiform gyrus was activated in nine healthy subjects, but only in two patients with TLE (a significant difference, p < 0.001). Other activation sites were more variable in healthy subjects and those with TLE. Impaired naming ability may be associated with a lack of increased cerebral blood flow in the left fusiform gyrus in TLE.     

Structure-based design of cathepsin K inhibitors containing a benzyloxy-substituted benzoyl peptidomimetic

Peptidomimetic cathepsin K inhibitors have been designed using binding models which were based on the X-ray crystal structure of an amino acid-based, active site-spanning inhibitor complexed with cathepsin K. These inhibitors, which contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained good inhibitory potency relative to the amino acid-based inhibitor, and the binding models were found to be very predictive of relative inhibitor potency. The binding mode of one of the inhibitors was confirmed by X-ray crystallography, and the crystallographically determined structure is in close qualitative agreement with the initial binding model. These results strengthen the validity of a strategy involving iterative cycles of structure-based design, inhibitor synthesis and evaluation, and crystallographic structure determination for the discovery of peptidomimetic inhibitors.     

Electron-beam CT-angiography in abdominal aortic aneurysms. Initial results

PURPOSE: To evaluate the suitability of ultrafast electron-beam tomography (EBT) for the investigation of abdominal aortic aneurysms using CTA. METHODS: Thirty-one patients with suspected abdominal aortic aneurysm were investigated with EBT using an Evolution XP scanner (Siemens, Erlangen) with the newest software version 12.34 with continuous volume scanning of 140 images in 17 s. Collimation was 3 mm, table increment 4 mm with overlapping image reconstruction every 2 mm, exposure time 200 ms (124 mAs), resulting in a scan-range of 28 cm. A quantity of 80 ml contrast material was administered (flow 4 ml/s). Visualization of the abdominal aorta and its branches was performed with MIPs and shaded surface display. Evaluation of image quality was based on a four-step classification scale (1 = good, 4 = insufficient) for the demonstration of the abdominal aorta and the visceral, renal and iliac arteries. RESULTS: All EBT examinations demonstrated high and homogeneous density values along the whole vessel course with a mean density value of 258.7 +/- 47.3 HU for the abdominal aorta and the iliac arteries. Quality evaluation for the vessel demonstration showed mean values between 1.22 and 1.57 for the abdominal aorta and the visceral, renal and iliac arteries. CONCLUSIONS: EBT with 140 slices and slice reconstruction every 2 mm offers a high z-axis resolution resulting in high-quality CT angiographies of the whole abdominal aorta and its branches.     

Intramedullary versus extramedullary fixation of subtrochanteric fractures. A biomechanical study

We compared two different subtrochanteric fracture fixation techniques, an intramedullary hip screw system (IMHS) and an extramedullary, dual sliding screw-plate system (MSP), to determine relative fixation stability. 6 matched pairs of osteosynthesized osteopenic cadaver femurs were axially loaded to 1000 N with concurrent, simulated abductor forces of 0%, 50%, or 86% of the applied head force. The initial loading sequence was made with uniaxial dynamization--the lag screw of the MSP locked and distal locking of the IMHS nail. Femoral head displacement and medial femoral strain were measured for intact femur controls, after fixation of a 2-part reverse oblique subtrochanteric fracture and finally a 3-part reverse oblique subtrochanteric fracture with a lateral wedge defect. The samples were then loaded at 750 N for 10(4) cycles with both devices uniaxially locked, followed by 10(4) cycles with both devices fully biaxially dynamized (unlocked). For the 2-part subtrochanteric fracture pattern, both devices exhibited similar inferior displacements of the femoral head (average 2.0 mm) and medial femoral strain (approximately 70% of intact). Increasing abductor forces decreased medial compressive strain but did not significantly affect head displacement. For the 3-part fracture model, the MSP demonstrated significantly less inferior displacement of the head (1.6 mm vs. 2.1 mm) and both devices demonstrated significantly decreased medial strain. After cycling, head displacement increased approximately 50% in both devices and medial strain increased slightly. After unlocking and cycling, the MSP group showed significant lateral displacement of the proximal fragment. The IMHS and MSP devices provide similar stability for fixation of 2-part and 3-part reverse oblique subtrochanteric fractures. In a biaxially dynamized, 3-part reverse oblique fracture, displacement of the proximal fragment can occur with the MSP.     

Neutrophil accumulation is reduced during partial liquid ventilation

OBJECTIVE: This study evaluates the ability of perflubron to inhibit pulmonary neutrophil accumulation during partial liquid ventilation (PLV) in the setting of acute lung injury. DESIGN: Randomized, controlled, nonblinded study. SETTING: Research laboratory at a university. SUBJECTS: Male, Sprague-Dawley rats (n = 120, 506 +/- 42 g). INTERVENTIONS: Animals were divided into eight groups (n = 15 in each group, of which n = 12 for myeloperoxidase content and n = 3 for histologic neutrophil counting): a) GV-CVF group, animals received gas ventilation (GV) with the induction of lung injury using cobra venom factor (CVF); b) PLV-CVF group, animals received partial liquid ventilation before the induction of lung injury; c) PEEP-CVF group, animals received positive end-expiratory pressure (PEEP) before the administration of cobra venom factor; d) CVF-PLV group, animals received partial liquid ventilation after cobra venom factor; e) CVF-PEEP group, animals received PEEP after cobra venom factor; f) PLV only group, animals received partial liquid ventilation only; g) GV only group, animals received gas ventilation only; and h) NVSBA group, nonventilated spontaneous breathing animals. MEASUREMENTS AND MAIN RESULTS: After the experimental period, total lung myeloperoxidase content was significantly decreased in the PLV-CVF (0.29 +/- 0.08, p = .02) and PEEP-CVF (0.34 +/- 0.04, p = .01) groups when compared with the GV-CVF group (0.62 +/- 0.07). When compared with the GV-CVF group, a trend toward a reduction in myeloperoxidase was observed in the CVF-PLV (0.42 +/- 0.05, p = .07) and the CVF-PEEP (0.39 +/- 0.06, p = .07) groups. When compared with the cobra venom factor only group (GV-CVF 47 +/- 2 neutrophils/high-power field), reductions in neutrophil count were observed in all groups (neutrophils/high-power field): PLV-CVF (20 +/- 2, p = .009); PEEP-CVF (24 +/- 1, p = .01); CVF-PLV (30 +/- 2, p = .03); and CVF-PEEP (37 +/- 1, p = .04). CONCLUSION: These data suggest that both partial liquid ventilation and PEEP result in a reduction in neutrophil accumulation in the setting of acute lung injury.     

Influence of communication during the distant phase of the 1996 republican presidential primary campaign

This study examines the influence of five communication modalities on voters' perceptions of candidates during what Popkin terms 'the distant phase' of the presidential primary campaign. During the final week of the New Hampshire primary campaign, researchers surveyed 315 prospective votes in four states whose primaries followed New Hampshire's by 1, 2, 4, and 5 weeks. The results revealed that political talk radio exerted the greatest influence on voters' perceptions of Bob Dole and considerable impact on perceptions of Steve Forbes. In addition, prospective voters' conversations with other people, television news, and candidate spots (only for Forbes) exerted modest influence on voters' perceptions of Republican candidates.     

Tissue reactions induced by Schistosoma mansoni in Biomphalaria glabrata

In Biomphalaria glabrata with a strong natural resistance, Schistosoma mansoni sporocysts are rapidly encapsulated by granulocytes and killed, mainly by the strong phagocytic activity of the cells. Irradiated Echinostoma paraensei sporocysts seem able to suppress the function of the granulocytes. Tissue reactions in snails with self-cure demonstrate: involvement of two types of cells, granulocytes and hyalinocyte-like cells; formation of amoeba-fibrous capsules; limited tendency of granulocytes to become attracted to the parasites; a slow process of parasite destruction; and a possible involvement of humoral factors. It seems that there is partial suppression of the granulocyte function in smails with self-cure.     

Synthesis and turnover of the regularly arranged surface protein of Acinetobacter sp. relative to the other components of the cell envelope

The formation of the components of the cell envelope of Acinetobacter sp. 199A was investigated by measuring the incorporation of [3H]leucine into protein, [14C]galactose into lipopolysaccharide, 32P into phospholipid, and [3H]diaminopimelic acid into peptidoglycan. Whereas the lipopolysaccharide and intrinsic protein of the outer membrane were stable, some of the regularly arranged surface protein, the alpha-protein, was lost into the growth medium. Only newly synthesized alpha-protein was lost. The peptidoglycan of the murein layer was also labile. Selective inhibition of the formation of individual components of the cell envelope with penicillin, chloramphenicol, and bacitracin showed that incorporation of protein into the outer membrane required the simultaneous formation of complete lipopolysaccharide. The converse was not true: protein synthesis was not required for lipopolysaccharide incorporation. Formation of the outer membrane and the murein layer proceeded independently.