Differential expression of neuronal calcium sensor-1 in the developing chick retina

Neuronal calcium sensor-1 (NCS-1) is a Ca(2+) binding protein that has been implicated in the regulation of neurotransmission and synaptogenesis. In this study we investigated the developmental expression and localization of NCS-1 in the chick retina. Single- and double-labeling experiments with three-dimensional reconstruction as well as ultrastructural data of the distribution of NCS-1 suggest that this protein is also involved in axonal process outgrowth. We found an early expression of NCS-1 in ganglion cells and their axons, in amacrine, and in horizontal cells, whereas photoreceptors were immunonegative at embryonic stages. In the early posthatching days we found strong immunostaining for NCS-1 in horizontal cells and their processes in the outer plexiform layer. In contrast, synaptic vesicle protein 2 (SV2) was prominent only in photoreceptor synaptic terminals. Ultrastructural analysis confirmed that NCS-1 was localized postsynaptically in horizontal cell processes, whereas presynaptic terminals were immunonegative. However, at late posthatching days we observed that photoreceptor ribbon synapses (from rods and/or cones) also expressed NCS-1. Thus the results support the notion that NCS-1 is involved in neuronal process outgrowth and is localized in pre- and postsynaptic compartments including mature photoreceptor synapses.     

Odorant responses of Xenopus laevis tadpole olfactory neurons: a comparison between preparations

We used a slice preparation of the olfactory epithelium of Xenopus laevis tadpoles to record odorant responses of olfactory receptor neurons (ORNs) and compared these to odorant responses recorded in isolated ORNs. The maximum recording time in the slice was considerably longer than in isolated ORNs, which is essential when many odorants are to be tested. No odorant-induced responses could be obtained from isolated ORNs recorded in the on-cell mode, while recordings in the slice (on-cell and whole-cell) as well as previously reported perforated-patch recordings in isolated ORNs of the same species () were successful, though qualitatively different. In the slice preparation, amino acids as well as an extract from Spirulina algae always induced excitatory responses, while, in a previous study on isolated ORNs, responses were either excitatory or inhibitory. The results of this study show that ORNs obtained using different preparation techniques can give markedly different responses upon the application of odorants. Our experiments indicate that the slice preparation combined with the on-cell configuration of the patch-clamp technique is the method of choice for testing many odorants on individual ORNs.     

Neurobiology of primate audio-vocal behavior

Audio-vocal behavior is an outstanding means of social communication among nonhuman primates and man. Neurobiological studies of this behavior contribute to a better understanding of communication processes in general and of the cerebral prerequisits for the evolution of language and speech in particular. In the first part of the review the cerebral system which generates, selects and controls species-specific vocal behavior is described in anatomical and physiological terms. Its structures and functions are organized in a hierarchical manner whereby the pericingular cortex and the periaqueductal gray are nodal areas in the system. In the second part auditory decoding mechanisms of vocal signals are discussed in terms of cortical ablation studies and response characteristics of single neurons along the auditory pathway. There are marked differences in the processing of natural calls at the collicular, medial geniculate and cortical levels. The cortex makes a necessary contribution to the decoding of complex sounds. References to the problem of lateralization of auditory function in non-human primates are made. A keystone for the understanding of communication processes in general lies in the question of how the signal producing motor system and the signal receiving decoding system is centrally tied together. One way to investigate such processes is to compare single unit responses along the auditory pathway during an animal's own phonation and during the playback of that vocalization. The results provide evidence for an internal feed-forward mechanism during phonation which influences parts of the auditory system.     

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease

Purpose The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation.Methods The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6±1.8 months after atorvastatin therapy, ¹³N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine 2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF.Results LDL cholesterol decreased after atorvastatin therapy from 186±43 mg/dl to 101±26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy.Conclusion The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET.P. Wielepp and D. Baller contributed equally to the study     

The first missense alteration in the MCPH1 gene causes autosomal recessive microcephaly with an extremely mild cellular and clinical phenotype

Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by mental retardation and congenital microcephaly with a head circumference at least 4 SD below age and sex means, in the absence of other significant malformations or neurological deficits. Truncating alterations in the MCPH1 gene have previously been shown to exhibit a distinct cellular phenotype, with a high proportion of prophase-like cells (>10%) due to premature chromosome condensation in early G2- and delayed decondensation in early G1-phase of the cell cycle. We report here the first patient with a homozygous substitution of a highly conserved threonine residue by an arginine (c.80C>G, Thr27Arg) localized in the N-terminal BRCT domain of MCPH1. The cellular and clinical phenotype of this patient is much less pronounced than that of previously described patients with truncating alterations in the MCPH1 gene. Firstly, the fraction of prophase-like cells accounts for just 3-4% of the cell population. Secondly, clinically, he has only a very mild mental retardation with predominantly delayed motor skills but normal verbal IQ attainment. Additionally, head circumference was less severely affected, being -2.4 SD at birth and -3 SD at the age of six years. This justifies reconsideration and widening of the clinical phenotype definition of MCPH1.     

Global and regional myocardial oxygen consumption and blood flow in severe cardiomyopathy with left bundle branch block

OBJECTIVE: In patients with dilated cardiomyopathy (DCM), left bundle branch block (LBBB) is a common finding. The characteristic feature is an asynchronous septal wall motion and most frequently a delay of the lateral and/or posterior wall segments. With the onset of cardiac resynchronization therapy, there is a focus on the specific pathophysiology of a LBBB. However, quantitative data on regional myocardial oxygen consumption (MVO(2)) and blood flow (MBF) are missing. METHODS: We studied 31 patients with severe DCM and LBBB (ejection fraction 22.1+/-7.1%) and 14 patients with mild to moderate DCM without LBBB (ejection fraction 46.7+/-7.9%). Global and regional MVO(2) as well as MBF were determined from a dynamic (11)C-acetate positron emission tomography (PET) study. RESULTS: Global MVO(2) and MBF were lower in the DCM group with LBBB than in the control group (P<0.05). Regionally, the LBBB group revealed a higher (P<0.05) MVO(2) and MBF in the lateral wall than in the other walls. The control group did not show significant differences between the myocardial walls and demonstrated a smaller variability of the parameters. CONCLUSION: DCM patients with LBBB exhibit a more heterogeneous distribution of MVO(2) and MBF among the myocardial walls than DCM patients without LBBB. Due to the LBBB associated electromechanical alterations, the highest regional values of MVO(2) and MBF are found in the lateral wall.     

Suppression of kindled seizures by paracrine adenosine release from stem cell-derived brain implants

PURPOSE: Stem cells and their derivatives have emerged as a promising tool for cell-based drug delivery because of (a) their unique ability to differentiate into various somatic cell types, (b) the virtually unlimited donor source for transplantation, and (c) the advantage of being amenable to a wide spectrum of genetic manipulations. Previously, adenosine-releasing embryonic stem (ES) cells have been generated by disruption of both alleles of adenosine kinase (Adk-/-). Lack of ADK did not compromise the cells' differentiation potential into embryoid bodies or glial precursor cells. The aim of the present study was to investigate the potential of differentiated Adk-/- ES cell progeny for seizure suppression by paracrine adenosine release. METHODS: To isolate paracrine effects of stem cell-derived implants from effects caused by network integration, ES cell-derived embryoid bodies and glial precursor cells were encapsulated into semipermeable polymer membranes and grafted into the lateral brain ventricles of kindled rats. RESULTS: While seizure activity in kindled rats with wild-type Adk+/+ implants remained unaltered, rats with adenosine-releasing Adk-/- ES cell-derived implants displayed transient protection from convulsive seizures and a profound reduction of afterdischarge activity in EEG recordings. Long-term seizure suppression was precluded by limited viability of the encapsulated cells. CONCLUSIONS: We thereby provide a proof-of-principle that Adk-/- ES cell-derived brain implants can suppress seizure activity by a paracrine mode of action. Adk-deficient stem cells therefore represent a potential tool for the treatment of epileptic disorders.     

Fanconi anemia in a neonate with pancytopenia

We report the case of a newborn infant with Fanconi anemia with congenital thrombocytopenia and development of pancytopenia during the neonatal period. The boy showed no malformations characteristic for Fanconi anemia.     

Anterolateral thigh flap technique in hand and upper extremity reconstruction

The anterolateral thigh flap is an extremely versatile flap first described in 1984. The flap is based on either a septocutaneous or musculocutaneous perforator of the descending branch of the lateral circumflex femoral system. It can be designed as a skin and subcutaneous flap, fasciocutaneous, or musculocutaneous flap. Furthermore, it can be harvested as a sensate flap by taking the lateral cutaneous nerve of the thigh. Technique for harvesting the flap is described in detail. Complications include flap failure and donor site morbidity. Due to its versatility, the anterolateral thigh flap is particularly useful for upper extremity reconstruction.