Neocortical Grafts Placed in the Infarcted Brain of Adult Rats: Few or No Efferent Fibers Grow from Transplant to Host

The present stud y examines the capacity of fetal neocortical grafts placed in a brain infarct to exchange axonal projections with the host brain. Five to 7 days after a middle cerebral artery occlusion in adult spontaneously hypertensive rats, dissociated neocortical primordium from fetuses of gestational age 15-16 days was implanted into the infarcted area. Four to 11 months later, the neural tracers Phaseolus vulgaris-leucoagglutinin and Fluoro-Gold were injected in the grafts and host neocortex. An extensive axonal network was present in the transplants but only one of eight rats with appropriate placed injections displayed efferent connections from transplant to host. The sparse axonal outgrowth indicates major limitations for fetal rat cortical grafts to form connections with host neural circuitries after an ischemic insult.     

Intravesical bacillus Calmette-Guèrin therapy: experience with a reduced dwell-time in patients with pronounced side-effects

OBJECTIVE: To report the side-effects after a reduction in the dwell-time in patients who had pronounced symptoms after intravesical bacillus Calmette-Guèrin (BCG) treatment, as side-effects such as fever, haematuria, and frequency are common and sometimes severe after BCG treatment in patients with bladder cancer. PATIENTS AND METHODS: The dwell-time was reduced to < or = 30 min in 51 patients who had pronounced side-effects after the preceding BCG instillation. All patients self-reported side-effects after each instillation in a questionnaire. RESULTS: After reducing the BCG dwell-time, fever, chills, dysuria and the overall time-to-recovery were significantly reduced but frequency and haematuria were not influenced. Patients with carcinoma in situ had significantly less dysuria than patients with papillary tumours. There was no difference in the treatment results between patients who had a normal dwell-time and a reduced dwell-time, determined at the first and second follow-up cystoscopy. CONCLUSION: Reducing the BCG dwell-time to < or = 30 min could be an alternative to a dose reduction in patients who experience pronounced side-effects after BCG instillations. The long-term outcome after reducing dwell-time and after dose reduction has not been studied and warrants further investigation.     

Platelet-derived growth factor (PDGF-BB) and brain-derived neurotrophic factor (BDNF) induce striatal neurogenesis in adult rats with 6-hydroxydopamine lesions

The effects of i.c.v. infused platelet-derived growth factor and brain-derived neurotrophic factor on cell genesis, as assessed with bromodeoxyuridine (BrdU) incorporation, were studied in adult rats with unilateral 6-hydroxydopamine lesions. Both growth factors increased the numbers of newly formed cells in the striatum and substantia nigra to an equal extent following 10 days of treatment. At 3 weeks after termination of growth factor treatment, immunostaining of BrdU-labeled cells with the neuronal marker NeuN revealed a significant increase in newly generated neurons in the striatum. In correspondence, many doublecortin-labeled neuroblasts were also observed in the denervated striatum following growth factor treatment. Further evaluation suggested that a subset of these new neurons expresses the early marker for striatal neurons Pbx. However, no BrdU-positive cells were co-labeled with DARPP-32, a protein expressed by mature striatal projection neurons. Both in the striatum and in the substantia nigra there were no indications of any newly born cells differentiating into dopaminergic neurons following growth factor treatment, such that BrdU-labeled cells never co-expressed tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. In conclusion, our results suggest that administration of these growth factors is capable of recruiting new neurons into the striatum of hemiparkinsonian rats.     

Intratumor versus intertumor heterogeneity in gene expression profiles of soft-tissue sarcomas

Soft-tissue sarcomas (STSs) constitute more than 30 histologic entities. In addition, within each entity, tumors are often heterogeneous in macroscopic features, genetic alterations, microscopic appearance, and clinical course. Therefore, there has been concern about whether a single tumor sample can provide a gene expression profile representative of the entire tumor. We used 27-k cDNA microarray slides to assess the importance of intratumor versus intertumor heterogeneity of the gene expression profiles of 2 morphologically heterogeneous STSs. Multiple pieces of tumor (8 and 10 pieces) were obtained from a myxoid variant of malignant fibrous histiocytoma (MFH) and a leiomyosarcoma (LMS), respectively, and the expression patterns were compared with single tumor samples from 20 MFHs and 16 LMSs. Hierarchical clustering analysis of the expression profiles showed that samples from the same tumor clustered together. The average intratumor distance was considerably shorter than the average intertumor distance in both LMS and MFH. In addition, tumor subclusters that distinguished different macroscopic parts of the tumor could be discerned. We concluded that intratumor variability exists but that accurate gene expression profiling also could be obtained using single samples from a large STS.     

The voices of wrath: brain responses to angry prosody in meaningless speech

We report two functional magnetic resonance imaging experiments showing enhanced responses in human middle superior temporal sulcus for angry relative to neutral prosody. This emotional enhancement was voice specific, unrelated to isolated acoustic amplitude or frequency cues in angry prosody, and distinct from any concomitant task-related attentional modulation. Attention and emotion seem to have separate effects on stimulus processing, reflecting a fundamental principle of human brain organization shared by voice and face perception.     

Enhanced extrastriate visual response to bandpass spatial frequency filtered fearful faces: time course and topographic evoked-potentials mapping

We compared electrical brain responses to fearful vs. neutral facial expressions in healthy volunteers while they performed an orthogonal gender decision task. Face stimuli either had a broadband spatial-frequency content, or were filtered to create either low spatial-frequency (LSF) or high spatial-frequency (HSF) faces, always overlapped with their complementary SF content in upside-down orientation to preserve the total stimulus energy. We tested the hypothesis that the coarse LSF content of faces might be responsible for an early modulation of event-related potentials (ERPs) to fearful expressions. Consistent with previous findings, we show that broadband images of fearful faces, relative to neutral faces, elicit a higher global field power of approximately 130 ms poststimulus onset, corresponding to an increased P1 component over lateral occipital electrodes, with neural sources located within the extrastriate visual cortex. Bandpass filtering of faces strongly affected the latency and amplitude of ERPs, with a suppression of the normal N170 response for both LSF and HSF faces, irrespective of expression. Critically, we found that LSF information from fearful faces, unlike HSF information, produced a right-lateralized enhancement of the lateral occipital P1, without any change in the scalp topography, relative to unfiltered (broadband) fearful faces. These results demonstrate that an early P1 response to fear expression depends on a visual pathway preferentially tuned to coarse-magnocellular inputs, and can persist unchanged even when the N170 generators are disrupted by SF filtering.     

Correlated dynamics of consecutive residues reveal transient and cooperative unfolding of secondary structure in proteins

Nuclear spin relaxation is a powerful method for studying molecular dynamics at atomic resolution. Recent methods development in biomolecular NMR spectroscopy has enabled detailed investigations of molecular dynamics that are critical for biological function, with prominent examples addressing allostery, enzyme catalysis, and protein folding. Dynamic processes with similar correlation times are often detected in multiple locations of the molecule, raising the question of whether the underlying motions are correlated (corresponding to concerted fluctuations involving many atoms distributed across extended regions of the molecule) or uncorrelated (corresponding to independent fluctuations involving few atoms in localized regions). Here, we have used (13)C(alpha)(i - 1)/(13)C(alpha)(i) differential multiple-quantum spin relaxation to provide direct evidence for correlated dynamics of consecutive amino acid residues in the protein sequence. By monitoring overlapping pairs of residues (i - 1 and i, i and i + 1, etc.), we identified correlated motions that extend through continuous segments of the sequence. We detected significant correlated conformational transitions in the native state of the E140Q mutant of the calmodulin C-terminal domain. Previous work has shown that this domain exchanges between two major conformational states that resemble the functionally relevant open and closed states of the WT protein, with a mean correlation time of approximately 20 micros. The present results reveal that an entire alpha-helix undergoes partial unraveling in a transient and cooperative manner.     

Priming of color and position during visual search in unilateral spatial neglect

We examined priming of visual search by repeated target location or color in two patients with left visual neglect and extinction, following strokes centered on the right inferior parietal lobe. Both patients, like the healthy controls we tested, showed intact priming, with performance speeded when either the location or color of a singleton target was repeated over successive trials in a standard search condition (Experiment 1). This was observed both from and to targets on the contralesional (left) side. Moreover, priming of search was still observed even when a return of fixation back to display-center was required between successive trials (Experiment 2). When briefer displays were used (Experiment 3), the patients often failed to detect left targets. This situation revealed an important dissociation: Whereas location priming only arose from preceding left targets that had been consciously detected, color priming (possibly arising within the intact ventral stream) did not depend on awareness of the preceding target. There was considerable color priming from missed targets. These findings demonstrate relatively intact priming of visual search by color and location in patients with right parietal damage, and also reveal that location priming may differ from color priming in requiring awareness.     

Portraits or people? Distinct representations of face identity in the human visual cortex

Humans can identify individual faces under different viewpoints, even after a single encounter. We determined brain regions responsible for processing face identity across view changes after variable delays with several intervening stimuli, using event-related functional magnetic resonance imaging during a long-term repetition priming paradigm. Unfamiliar faces were presented sequentially either in a frontal or three-quarter view. Each face identity was repeated once after an unpredictable lag, with either the same or another viewpoint. Behavioral data showed significant priming in response time, irrespective of view changes. Brain imaging results revealed a reduced response in the lateral occipital and fusiform cortex with face repetition. Bilateral face-selective fusiform areas showed view-sensitive repetition effects, generalizing only from three-quarter to front-views. More medial regions in the left (but not in the right) fusiform showed repetition effects across all types of viewpoint changes. These results reveal that distinct regions within the fusiform cortex hold view-sensitive or view-invariant traces of novel faces, and that face identity is represented in a view-sensitive manner in the functionally defined face-selective areas of both hemispheres. In addition, our finding of a better generalization after exposure to a 3/4-view than to a front-view demonstrates for the first time a neural substrate in the fusiform cortex for the common recognition advantage of three-quarter faces. This pattern provides new insights into the nature of face representation in the human visual system.