Kinetics of chemically mediated neurodegeneration/neuroregeneration of mouse olfactory epithelium: monitoring by hyperlayer sedimentation field flow fractionation.

The increase in the incidence of neurodegenerative diseases linked to aging or injury needs to be addressed in research into neuroprotective or neuroregenerative therapies, and requires the development of specific biological models. To achieve this goal we propose (1) the use of the mouse olfactory epithelium as a biological support which specifically exhibits a regenerative or a self-renewing capacity and during the lifetime necessitates the presence of neural stem cells, and (2) the use of an intraperitoneal injection of 2,6-dichlorobenzonitrile (diclobenil) as a chemical inducer of neurodegeneration in olfactory epithelium by selectively killing mature cells. We developed a biological model to follow the processes of neurodegeneration (chemically induced) and neuroregeneration (self-renewal of olfactory epithelium). The purpose of this study was to develop a method to monitor quickly neurodegeneration/neuroregeneration processes in order to further screen protective and regenerative therapies. For this purpose, we used the sedimentation field flow fractionation elution of olfactory epithelium. We obtained specific elution profiles and retention parameters allowing the monitoring of the induction and kinetics of biological processes. The use of insulin-like growth factor 1α as a neuroprotective agent in an innovative nebulization protocol showed sedimentation field flow fractionation to be a simple, fast and low-cost method to monitor such a biological event on the scale of an entire organism.

Oncogramme, a new promising method for individualized breast tumour response testing for cancer treatment.

BACKGROUND: Breast cancer is the most widely spread cancer in the world, attracting much research and individualized tumour response testing (ITRT) methods are now used to individualize patient chemotherapeutic administrations. A new ITRT method was developed with optimized processing. MATERIALS AND METHODS: Breast tumour fragments were separated and the cells seeded in a foetal calf serum-free defined medium. After various chemotherapeutic treatments, cytotoxicity was determined by cell death detection with calcein acetoxymethyl and ethidium homodimer labelling. RESULTS: The culture medium allowed breast tumour cell proliferation in culture, while preventing fibroblastic cell survival. Moreover, the cell death analysis gave rise to a chemoresistance profile called an Oncogramme, with statistically significant values. CONCLUSION: The Oncogramme is a new ITRT method which can predict patient cell sensitivities to chemotherapeutics and should be validated by a new phase I clinical trial.

Neural stem cell separation from the embryonic avian olfactory epithelium by sedimentation field-flow fractionation.

The aim of the present study was to isolate neural stem cells from a complex tissue: the avian olfactory epithelium; by using sedimentation field flow fractionation (SdFFF). By using "Hyperlayer" elution mode, fraction collection and cell characterization methods, results shows that SdFFF could be a useful cell sorter to isolate an enriched, viable and sterile immature neural cell fraction from which the reconstitution of a complete epithelium was possible. In culture, SdFFF eluted cells first led to a "pseudoplacodal" epithelioid cell type from which derived "floating cells". These cells were then able to generate neurosphere-like structures which were composed of cell having many features of immature cells: undifferentiated, self-renewable and multipotentiality. Such a population might be used as a model to improve our understanding of the mechanisms of olfactory neoneurogenesis.

Modulation of Fas-induced apoptosis by p75 neurotrophin receptor in a human neuroblastoma cell line.

Fas and p75 neurotrophin receptors (p75(NTR)) are death receptors that alone induce apoptosis of SH-SY5Y neuroblastoma cell line respectively by Fas ligand or brain-derived neurotrophic factor (BDNF, a p75(NTR) ligand). We report on the modulation of Fas-mediated apoptosis by concomitant p75(NTR) activation. The exposure to both ligands suppressed the apoptotic effect. A co-localisation of Fas and p75(NTR) receptors was evidenced by co-capping and immunoprecipitation assays. Moreover, a caspase-8 inhibitor suppressed the protective effect of the concomitant BDNF and Fas ligand stimulation, suggesting that p75(NTR) and Fas receptors could share common signalling pathways.

The incidence of sacroiliac joint disease in patients with low-back pain.

PURPOSE: The clinical presentation of intervertebral disc, facet joint, nerve root, and sacroiliac (SI) joint diseases are often indistinguishable. SI joint arthritis likely accounts for a significant proportion of what is called "low-back pain" or "sciatica." Our goal was to determine the incidence of SI joint arthritis in patients with this presentation. METHODS: Computed tomographic (CT) scans of the lumbosacral spine (LSS) of patients referred with low-back pain, sciatica, spinal stenosis or disc pathology were gathered over a 3-month period. Scans were retrospectively reviewed by 2 independent readers for SI joint arthritis. When there was disagreement, the 2 readers reviewed the case and reached a concensus opinion. SI joint arthritis was considered to be present if subchondral sclerosis, osteophytosis, or cartilage loss was noted on the CT scan. RESULTS: The SI joint(s) were visualized by both readers on 64 LSS CT scans performed in 29 women and 35 men, mean age 52 years. By the aforementioned criteria, 16 SI joints (25%) were considered normal by both readers. In 48 cases (75%), there was evidence of osteoarthritis. The diagnosis of osteoarthritis was made by concensus opinion in 8 of these 48 cases (16%). CONCLUSION: There is a relatively high incidence of SI joint arthritis in patients undergoing evaluation for "low-back pain" or "sciatica." Hence, SI joint arthritis should be considered a possible diagnosis in these patients.

Diagnosis of the acute os peroneum fracture.

Acute fracture of the os peroneum is a relatively uncommon injury. However physicians must be cognizant of its occurrence and include it in their differential diagnosis of acute ankle trauma. A careful clinical evaluation as well as awareness of its radiographic appearance and of the possibility for injury to other surrounding structures is important in the appropriate diagnosis and management of this fracture. We present the case of a patient who sustained an os peroneum fracture and review the relevant literature.

Behavioral effects of chronic imipramine treatment in genetically nervous pointer dogs.

The genetically nervous pointer dog has been proposed as a model for human anxiety disorders. In a double-blind placebo-controlled study, seventeen nervous pointer dogs were treated for four weeks with imipramine hydrochloride (10 mg/kg), a potent antipanic agent in humans. Although three of the dogs demonstrated marked improvement to imipramine but not placebo treatment after short-term administration, chronic imipramine failed to modify the aberrant behavior in any of the dogs. These findings are discussed in the context of the nervous pointer dog as a model for human anxiety disorders.

Intensity, color, and pattern discrimination deficits after lesions of the core and belt regions of the ectostriatum.

Pigeons were trained to discriminate visual stimuli that differed in intensity, color, or pattern, after which lesions were made in the ectostriatum, either the core region (EC), the belt region (EB), or both (EC + EB). Control lesions were made in the lateral neostriatum. After surgery, the birds were again trained to discriminate the stimuli. On the basis of a quantitative analysis of the lesion reconstructions, each pigeon was assigned to one of five groups: EC, EB, moderate (EC + EB), slight (EC + EB), or control. Postoperative savings scores, based on the number of preoperative and postoperative sessions required to discriminate the stimuli, were calculated. An analysis of variance indicated a significant effect of lesion location on the extent of postoperative savings or loss. Only the moderate (EC + EB) group was significantly different from the neostriatum controls. A multiple regression analysis of performance on the individual discrimination tasks indicated that the extent of damage to EC predicted the initial performance deficit on the intensity and one of the two pattern discrimination tasks (vertical versus horizontal bar). The color discrimination deficit, which was modest in extent and of short duration, was predicted only by the damage to (EC + EB) that was at least moderate in extent (20-40% of the volume of (EC + EB].

Head orientation in pigeons: postural, locomotor and visual determinants.

We have determined the pigeon's head orientation for two postures and two locomotor activities that do not involve a specific visual stimulus. Using a high-speed cine camera, we filmed four pigeons (Columba livia) while (1) flying, (2) walking, (3) perching and (4) standing on a flat surface. Under these conditions, the head orientation is relatively constant, allowing us to estimate the normal horizon of the visual field and thus the horizontal meridian of the retina. Measurements of the lateral semicircular canal showed that the canal is tilted slightly up with respect to the horizon in the head orientation determined by the film analysis. In contrast to their relatively stable head posture during locomotion, the pigeons consistently altered their head orientation when presented with seed targets, apparently to fixate each seed with a small portion of the visual field around the bill tip.

Intensity difference thresholds after lesions of ectostriatum in pigeons.

Seven pigeons were trained to perform in a psychophysical procedure to determine the smallest difference in luminous intensity (intensity difference threshold) that they could discriminate. When their performance stabilized, lesions were made in the ectostriatum in 4 birds and in the neostriatum in the remaining 3 birds. After surgery, the pigeons with ectostriatum lesions showed markedly elevated thresholds. The neostriatum control cases showed only trivial threshold changes as a consequence of the surgery. A psychophysical scaling analysis showed that the ectostriatum-lesioned pigeons had lost from 50% to 83% of their preoperative capacity to discriminate differences in the intensity of visual stimuli. A multiple-regression analysis based on quantitative reconstructions of the lesions revealed that only damage to the core region of the ectostriatum contributed to the postoperative threshold changes.

Size-threshold changes after lesions of the visual telencephalon in pigeons.

Fifteen pigeons were tested in a psychophysical procedure that determined the limits of their ability to detect differences in the sizes of stimuli. The results indicated that intact pigeons can reliably discriminate an annulus 3.0 mm in diameter from one that is 3.9 mm in diameter. In the first experiment, pigeons with lesions of the ectostriatum that spared the medial 15% were unimpaired in their size-discrimination ability. Those cases in which the lesions involved both the medial and lateral regions of the ectostriatum were greatly impaired. In a second experiment, these findings were replicated. In some cases, the electrode trajectory was varied to rule out possible effects from non-ectostriatal structures. In addition, the second study indicated that destruction of the medial ectostriatum with the lateral regions intact had no measurable effect on size-difference thresholds. The medial region of ectostriatum is part of the termination field of a second tectofugal pathway to the telencephalon. This pathway passes from the optic tectum to nucleus dorsolateralis posterior thalami and then to the neostriatum intermedium, including the medial ectostriatum. An examination of the data of the present experiment and those of other behavioral studies of the ectostriatum suggest that the medial ectostriatum may be involved in the processing of visual information with low spatial-frequency components and the lateral ectostriatum may be processing information about the high-frequency composition of stimuli.

Interocular transfer in parallel visual pathways in pigeons.

Pigeons were trained to perform intensity, color and pattern tasks monocularly. After their training was completed, a unilateral electrolytic lesion was made either in the nucleus rotundus or in the nucleus opticus principalis thalami (OPT). The lesion was made in the trained hemisphere (contralateral to the trained eye) in half of the subjects and in the untrained hemisphere in the other half. After a 7-day recovery period the birds were retrained on the same tasks with the previously untrained eye. A rotundal lesion, on either side, resulted in the loss of interocular transfer of discrimination, whereas neither contralateral nor ipsilateral OPT lesions affected discrimination. These results suggest that the tectofugal visual pathway plays a crucial role in the interhemispheric transfer of visual information in pigeons.

Normative data for pigeon vision.

Normative data are reported for the visual acuity, luminance-difference threshold and size-difference threshold of pigeons (Columba livia). The mean visual acuity was 12.66 c/deg or 2.53 min (N = 54), the mean log luminance-difference threshold was 0.11 (N = 105) and the mean size-difference threshold was 0.94 mm (N = 20).

Near-field acuity changes after visual system lesions in pigeons. II. Telencephalon.

Pigeons were trained to perform in a psychophysical task that measured their minimum-separable visual acuity. After their performance stabilized, lesions were made in telencephalic components of the visual system. In one group, lesions were made in the ectostriatum, which is the telencephalic target of the tectofugal visual pathway. These cases showed severe to moderate losses of acuity. The magnitude of the loss was correlated with the extent of ectostriatal damage. In another group, lesions were made in the visual Wulst, a portion of which receives the ascending fibers of the thalamofugal visual pathway. Within this group, only lesions that were large and included all components of the visual Wulst were effective in decreasing visual acuity to a moderate degree. A partial correlation analysis indicated that the components of the visual Wulst that were responsible for the acuity changes were the accessory hyperstriatum and the hyperstriatum ventrale. However, lesions that were generally confined to these regions alone were ineffective. Also ineffective were lesions of the granular components of the visual Wulst, which receive the ascending thalamofugal fibers. The results raise questions about the presumed roles of the tectofugal pathway as a background-vision mechanism and the thalamofugal pathway as a fine-detail vision mechanism.

Two eyes are better than one: superior binocular discrimination learning in pigeons.

Four groups of pigeons each were trained to perform four visual-discrimination tasks of varying difficulty. Two groups received the training binocularly and the other two monocularly. Two types of stimulus displays were used. In one display the two pecking keys were mounted in a horizontal arrangement, whereas, in the other display, the two keys were mounted in a vertical arrangement. In both displays binocular learning was more rapid than monocular learning. This difference increased with problem difficulty. Moreover, training with the horizontal key arrangement resulted in more rapid learning with either viewing condition. These results suggest that the inferiority of monocular learning was not caused by restriction of the visual field along the horizontal plane, and the failure to detect monocular-binocular differences in learning in previous reports may have resulted from inadequate task difficulty. Finally, the results suggest that monocularly-viewing birds should not be regarded as "natural split-brain" preparations.