Golgi structure in three dimensions: functional insights from the normal rat kidney cell. (41/18387)

Three-dimensional reconstructions of portions of the Golgi complex from cryofixed, freeze-substituted normal rat kidney cells have been made by dual-axis, high-voltage EM tomography at approximately 7-nm resolution. The reconstruction shown here ( approximately 1 x 1 x 4 microm3) contains two stacks of seven cisternae separated by a noncompact region across which bridges connect some cisternae at equivalent levels, but none at nonequivalent levels. The rest of the noncompact region is filled with both vesicles and polymorphic membranous elements. All cisternae are fenestrated and display coated buds. They all have about the same surface area, but they differ in volume by as much as 50%. The trans-most cisterna produces exclusively clathrin-coated buds, whereas the others display only nonclathrin coated buds. This finding challenges traditional views of where sorting occurs within the Golgi complex. Tubules with budding profiles extend from the margins of both cis and trans cisternae. They pass beyond neighboring cisternae, suggesting that these tubules contribute to traffic to and/or from the Golgi. Vesicle-filled "wells" open to both the cis and lateral sides of the stacks. The stacks of cisternae are positioned between two types of ER, cis and trans. The cis ER lies adjacent to the ER-Golgi intermediate compartment, which consists of discrete polymorphic membranous elements layered in front of the cis-most Golgi cisterna. The extensive trans ER forms close contacts with the two trans-most cisternae; this apposition may permit direct transfer of lipids between ER and Golgi membranes. Within 0.2 microm of the cisternae studied, there are 394 vesicles (8 clathrin coated, 190 nonclathrin coated, and 196 noncoated), indicating considerable vesicular traffic in this Golgi region. Our data place structural constraints on models of trafficking to, through, and from the Golgi complex.  (+info)

Effects of atypical antipsychotic drug treatment on amphetamine-induced striatal dopamine release in patients with psychotic disorders. (42/18387)

Clozapine, risperidone, and other new "atypical" antipsychotic agents are distinguished from traditional neuroleptic drugs by having clinical efficacy with either no or low levels of extrapyramidal symptoms (EPS). Preclinical models have focused on striatal dopamine systems to account for their atypical profile. In this study, we examined the effects of clozapine and risperidone on amphetamine-induced striatal dopamine release in patients with psychotic disorders. A novel 11C-raclopride/PET paradigm was used to derive estimates of amphetamine-induced changes in striatal synaptic dopamine concentrations and patients were scanned while antipsychotic drug-free and during chronic treatment with either clozapine or risperidone. We found that amphetamine produced significant reductions in striatal 11C-raclopride binding during the drug-free and antipsychotic drug treatment phases of the study which reflects enhanced dopamine release in both conditions. There were no significant differences in % 11C-raclopride changes between the two conditions indicating that these atypical agents do not effect amphetamine-related striatal dopamine release. The implications for these data for antipsychotic drug action are discussed.  (+info)

Assessment of regional and global left ventricular function by reinjection T1-201 and rest Tc-99m sestamibi ECG-gated SPECT: comparison with three-dimensional magnetic resonance imaging. (43/18387)

OBJECTIVES: The purpose of this study was to test the ability of reinjection thallium-201 and rest technetium-99m sestamibi ECG (electrocardiographic)-gated SPECT (i.e., reinjection-g-SPECT [single-photon emission computed tomography] and MIBI-g-SPECT) to determine regional and global functional parameters. BACKGROUND: The ECG-gated perfusion SPECT was reported to provide accurate left ventricular ejection fraction (LVEF) using an automated algorithm. We hypothesized that other various functional data may be obtained using reinjection-g-SPECT and MIBI-g-SPECT. METHODS: Reinjection-g-SPECT, MIBI-g-SPECT, and three-dimensional magnetic resonance imaging (3DMRI) were conducted in 20 patients with coronary artery disease. Regional wall motion (RWM) and wall thickening (RWT) were analyzed using semiquantitative visual scoring by each g-SPECT and 3DMRI. The left ventricular end-systolic and end-diastolic volumes (EDV, ESV) and LVEF estimated by reinjection- and MIBI-g-SPECT were compared with the results of 3DMRI. RESULTS: A high degree of agreement in RWM and RWT assessment was observed between each g-SPECT and 3DMRI (kappa >.70, p < .001). The LVEF values by reinjection- and MIBI-g-SPECT correlated and agreed well with those by 3DMRI (reinjection: r = .92, SEE = 5.9%, SD of differences = 5.7%; sestamibi: r = .94, SEE = 4.4%, SD of differences = 5.1%). The same also pertained to EDV (reinjection: r = .85, SEE = 18.7 ml, SD of differences = 18.4 ml; sestamibi: r = .92, SEE = 13.1 ml, SD of differences = 13.0 ml) and ESV (reinjection: r = .94, SEE = 10.3 ml, SD of differences = 10.3 ml; sestamibi: r = .97, SEE = 6.7 ml [p < .05 vs. reinjection by F test], SD of differences = 6.6 ml [p < .05 vs. reinjection by F test]). CONCLUSIONS: Reinjection- and MIBI-g-SPECT provide clinically satisfactory various functional data. These functional data in combination with the perfusion information will improve diagnostic and prognostic accuracy without an increase in cost or the radiation dose to the patients.  (+info)

Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson's disease. (44/18387)

The purpose of this study was to examine the relationship between lesion location and clinical outcome following globus pallidus internus (GPi) pallidotomy for advanced Parkinson's disease. Thirty-three patients were prospectively studied with extensive neurological examinations before and at 6 and 12 months following microelectrode-guided pallidotomy. Lesion location was characterized using volumetric MRI. The position of lesions within the posteroventral region of the GPi was measured, from anteromedial to posterolateral along an axis parallel to the internal capsule. To relate lesion position to clinical outcome, hierarchical multiple regression analysis was used. The variance in outcome measures that was related to preoperative scores and lesion volume was first calculated, and then the remaining variance attributable to lesion location was determined. Lesion location along the anteromedial-to-posterolateral axis within the GPi influenced the variance in total score on the Unified Parkinson's Disease Rating Scale in the postoperative 'off' period, and in 'on' period dyskinesia scores. Within the posteroventral GPi, anteromedial lesions were associated with greater improvement in 'off' period contralateral rigidity and 'on' period dyskinesia, whereas more centrally located lesions correlated with better postoperative scores of contralateral akinesia and postural instability/gait disturbance. Improvement in contralateral tremor was weakly related to lesion location, being greater with posterolateral lesions. We conclude that improvement in specific motor signs in Parkinson's disease following pallidotomy is related to lesion position within the posteroventral GPi. These findings are consistent with the known segregated but parallel organization of specific motor circuits in the basal ganglia, and may explain the variability in clinical outcome after pallidotomy and therefore have important therapeutic implications.  (+info)

A PET study of sequential finger movements of varying length in patients with Parkinson's disease. (45/18387)

To study the difficulty that patients with Parkinson's disease have in performing long sequential movements, we used H2(15)O PET to assess the regional cerebral blood flow (rCBF) associated with the performance of simple repetitive movements, well-learned sequential finger movements of varying length and self-selected movements. Sequential finger movements in the Parkinson's disease patients were associated with an activation pattern similar to that found in normal subjects, but Parkinson's disease patients showed relative overactivity in the precuneus, premotor and parietal cortices. Increasing the complexity of movements resulted in increased rCBF in the premotor and parietal cortices of normal subjects; the Parkinson's disease patients showed greater increases in these same regions and had additional significant increases in the anterior supplementary motor area (SMA)/cingulate. Performance of self-selected movements induced significant activation of the anterior SMA/cingulate in normal subjects but not in Parkinson's disease patients. We conclude that in Parkinson's disease patients more cortical areas are recruited to perform sequential finger movements; this may be the result of increasing corticocortical activity to compensate for striatal dysfunction.  (+info)

The neural consequences of conflict between intention and the senses. (46/18387)

Normal sensorimotor states involve integration of intention, action and sensory feedback. An example is the congruence between motor intention and sensory experience (both proprioceptive and visual) when we move a limb through space. Such goal-directed action necessitates a mechanism that monitors sensorimotor inputs to ensure that motor outputs are congruent with current intentions. Monitoring in this sense is usually implicit and automatic but becomes conscious whenever there is a mismatch between expected and realized sensorimotor states. To investigate how the latter type of monitoring is achieved we conducted three fully factorial functional neuroimaging experiments using PET measures of relative regional cerebral blood flow with healthy volunteers. In the first experiment subjects were asked to perform Luria's bimanual co-ordination task which involves either in-phase (conditions 1 and 3) or out-of-phase (conditions 2 and 4) bimanual movements (factor one), while looking towards their left hand. In half of the conditions (conditions 3 and 4) a mirror was used that altered visual feedback (factor two) by replacing their left hand with the mirror image of their right hand. Hence (in the critical condition 4) subjects saw in-phase movements despite performing out-of-phase movements. This mismatch between intention, proprioception and visual feedback engendered cognitive conflict. The main effect of out-of-phase movements was associated with increased neural activity in posterior parietal cortex (PPC) bilaterally [Brodmann area (BA) 40, extending into BA 7] and dorsolateral prefrontal cortex (DLPFC) bilaterally (BA 9/46). The main effect of the mirror showed increased neural activity in right DLPFC (BA 9/ 46) and right superior PPC (BA 7) only. Analysis of the critical interaction revealed that the mismatch condition led to a specific activation in the right DLPFC alone (BA 9/46). Study 2, using an identical experimental set-up but manipulating visual feedback from the right hand (instead of the left), subsequently demonstrated that this right DLPFC activation was independent of the hand attended. Finally, study 3 removed the motor intentional component by moving the subjects' hand passively, thus engendering a mismatch between proprioception and vision only. Activation in the right lateral prefrontal cortex was now more ventral than in studies 1 or 2 (BA 44/45). A direct comparison of studies 1 and 3 (which both manipulated visual feedback from the left hand) confirmed that a ventral right lateral prefrontal region is primarily activated by discrepancies between signals from sensory systems, while a more dorsal area in right lateral prefrontal cortex is activated when actions must be maintained in the face of a conflict between intention and sensory outcome.  (+info)

Evaluation of cerebral aneurysms with high-resolution MR angiography using a section-interpolation technique: correlation with digital subtraction angiography. (47/18387)

BACKGROUND AND PURPOSE: The objective was to evaluate the results of high-resolution, fast-speed, section-interpolation MR angiography and digital subtraction angiography (DSA), thereby examining the potential use of a primary noninvasive screening test for intracranial aneurysms. METHODS: The images were obtained in 39 cerebral aneurysmal lesions from 30 patients with a time-of-flight MR angiographic technique using a 1.5-T superconducting MR system. The total image volume was divided into four slabs, with 48 partitions each. To save time, only 24 phase-encoded steps were measured and interpolated to 48. The parameters used included 30/6.4 (TR/TE), a flip angle of 25 degrees , a 160x512 matrix, a field of view of 150x200, 7 minutes 42 seconds of scan time, an effective thickness of 0.7 mm, and an entire thickness of 102.2 mm. Maximum intensity projection was used for the image analysis, and a multiplanar reconstruction technique was used for patients with intracranial aneurysms. RESULTS: Among 39 intracranial aneurysmal lesions in 30 patients, 21 were ruptured and 18 were unruptured. Twelve lesions were less than 2 mm in size, 12 were 3 to 5 mm, 12 were 6 to 9 mm, and three were larger than 10 mm. At initial examinations, 38 of 39 aneurysmal lesions were detected by both MR angiography and DSA, with 97% sensitivity. In confirming aneurysms in neck and parent vessels, multiplanar reconstruction was successful in detecting all 39 aneurysms, whereas MR angiography was successful in detecting 27 (69%) and DSA was successful in detecting 32 (82%) of the lesions. CONCLUSION: High-resolution MR angiography with a section-interpolation technique showed equal results to those of DSA for the detection of intracranial aneurysms and may be used as a primary noninvasive screening test. In the evaluation of aneurysms in neck and parent vessels, the concurrent use of MR angiography and multiplanar reconstruction was far superior to the use of either MR angiography or DSA alone.  (+info)

Cerebral veins: comparative study of CT venography with intraarterial digital subtraction angiography. (48/18387)

BACKGROUND AND PURPOSE: Our objective was to compare the reliability of CT venography with intraarterial digital subtraction angiography (DSA) in imaging cerebral venous anatomy and pathology. METHODS: In 25 consecutive patients, 426 venous structures were determined as present, partially present, or absent by three observers evaluating CT multiplanar reformatted (MPR) and maximum intensity projection (MIP) images. These results were compared with the results from intraarterial DSA and, in a second step, with the results of an intraobserver consensus. In addition, pathologic conditions were described. RESULTS: Using DSA as the standard of reference, MPR images had an overall sensitivity of 95% (specificity, 19%) and MIP images a sensitivity of 80% (specificity, 44%) in depicting the cerebral venous anatomy. On the basis of an intraobserver consensus including DSA, MPR, and MIP images (415 vessels present), the sensitivity/specificity was 95%/91% for MPR, 90%/100% for DSA, and 79%/91% for MIP images. MPR images were superior to DSA images in showing the cavernous sinus, the inferior sagittal sinus, and the basal vein of Rosenthal. Venous occlusive diseases were correctly recognized on both MPR and MIP images. Only DSA images provided reliable information of invasion of a sinus by an adjacent meningioma. CONCLUSION: CT venography proved to be a reliable method to depict the cerebral venous structures. MPR images were superior to MIP images.  (+info)