Tissue Engineering of Peripheral Nerves: A Comparison of Venous and Acellular Muscle Grafts with Cultured Schwann Cells.
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Biomedical subjects
Publications and source records attributed to Gerald Wolf.
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PURPOSE: Nerve allografts are highly antigenic and, thus, require the continuous use of immunosuppressive drugs. FK 506 was found to pre-vent rejection successfully. However, clinically neurotoxic complications have been noted in the central and peripheral nervous system although an increased rate of axonal regeneration has also been shown after nerve crush experiments. To investigate whether a possible regeneration pro-moting potency of FK 506 is determined via an influence on Schwann cells, Schwann cells were cultured from the sciatic nerve of the rat. METHODS: The effect of 100 micro M FK 506 administered daily on these cultures was assessed microscopically over a period of seven days and compared to an untreated control group of cultures. Additionally, the changes in intracellular calcium were recorded using a laser scanning microscope. In vivo regeneration of autologous rat sciatic nerve grafts was assessed clinically, histologically and morphometrically after two and six weeks. The animals received a daily administration of 0.6 mg FK 506/kg body weight, the control received saline. RESULTS: In vitro FK 506 increased the Schwann cell number in culture significantly compared to non treated cultures, while the fibrocyte population was decreased. FK 506 caused a transient increase of intracellular calcium levels in cultured cells. In vivo, a significantly higher axon count was observed in the FK 506 treated grafts after two weeks regeneration compared with controls. Good regeneration was noted in all grafts after six weeks regeneration. CONCLUSIONS: The increased axon counts and decreased myelin debris in the FK 506 grafts after two weeks indicate an accelerated Wallerian degeneration and increased axon sprouting into the graft initially. The inhibition of calcineurin activity is not the mediator of the neurotrophic effect. FK 506 promotes axonal regeneration through binding to FKBP-12. The increase of intracellular calcium may induce Schwann cell pro-liferation via calmodulin. The therapeutic relevance for autologous nerve grafting, however, has to be defined in further studies.
Experiments on photic damage to the retinas of rats with hereditary retinal dystrophy and some tentative clinical evidence on human patients suggest that, in human retinitis pigmentosa, one could try to protect the retina and especially the rods from bright light in an attempt to delay the retinal degeneration and to prolong the period of useful vision. Several theoretical criteria have been proposed for protection of RP patients from possible photic retinal damage. Observing these criteria, Adrian developed a brownish ophthalmic filter which absorbs the short wavelengths preferentially, thus protecting the rods primarily. Whether or not use of these filters will be efficacious has yet to be determined and will require careful experimentation and the accumulation of clinical experience. Several brown ophthalmic filters also have been tested against the criteria for a protective device. The NoIR Amber 7% plastic glasses satisfy these criteria quite well and thus can be considered as a substitute for the Adrian lens. The characteristics of the two types of filters are compared. Experience with different methods of protection may show whether it is better to attempt to delay degeneration of both retinas simultaneously by decreasing their illuminations with filters or to exclude light completely from one eye in an attempt to preserve it while the other eye degenerates in the usual course of the disease. In any event, given the present state of knowledge, it seems to be appropriate, especially in the early stages of the disease, to suggest that RP patients protect their retinas from excessive light.
OBJECTIVE: The aim was to evaluate the clinical and therapeutic value of digital image fusion of 2-[18]-fluoro-2-deoxy-D-glucose (F18-FDG) positron emission tomography (PET) and computed tomography (CT) in patients suffering from an oral maxillofacial carcinoma. METHODS: Seventeen patients (11 male, 6 female; age range: 45-89 years) suffering from an oral maxillofacial carcinoma underwent CT and F18-FDG-PET (333-370 MBq). The data of the 2 imaging modalities were fused on an image workstation. This image fusion was then visualized in the axial, coronal, and sagittal planes. RESULTS: PET showed a high pathologic FDG uptake in the tumor in 17 of 17 patients. CT detected the tumor in 12 of 17 patients. The image fusion of FDG-PET and CT showed the tumor in 17 of 17 patients. The final diagnosis was carcinoma of the mandible in 9 of 17 patients, carcinoma of the mouth floor in 3 of 17 patients, carcinoma of the tongue in 3 of 17 patients, carcinoma of the roof of the mouth in 1 of 17 patients, and carcinoma of the parotis gland in 1 of 17 patients. CONCLUSIONS: Preoperative image fusion of FDG-PET and CT data sets in oral maxillofacial carcinoma is possible in the clinical routine. Combined morphologic (CT) and functional (PET) imaging improves tumor localization even if the tumor is hardly visible on CT because of the artefacts of dental metallic implants (3/17 patients) or because of the small size of the tumor (2/17 patients). Image fusion is helpful for planning possible surgery (visual models) or radiotherapy (exact region of interest).
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Olfactory recognition memory was tested in adult male mice using a social discrimination task. The testing was conducted to begin to characterize the role of protein synthesis and the specific brain regions associated with activity in this task. Long-term olfactory recognition memory was blocked when the protein synthesis inhibitor anisomycin was injected 20 min before, immediately after, or 6 h after sampling. No effect was observed when anisomycin was administered 3 h or 18 h after sampling. Immunohistochemical analysis of Fos expression revealed that sampling-like exposure to a juvenile increased the activity of a subset of cells in the accessory olfactory bulb and the brain areas that are associated with it. Additionally, increased Fos expression was measured in the main olfactory bulb and the piriform cortex, whereas no signs of activation were seen in the cortical nucleus of the amygdala, all components of the main olfactory system. No increases in Fos immunoreactivity were observed after 4 h. Our data suggest that long-lasting olfactory recognition memory requires two stages of protein synthesis. The first stage takes place within 1-2 h and the second stage between 6-7 h after sampling. The first but not the second stage is paralleled by an increase in the number of Fos-immunoreactive cells in brain areas associated with both the main and accessory olfactory systems. It therefore appears that the role of the second stage of protein synthesis in recognition memory depends on the integrity of the first stage of protein synthesis.