Biomedical subjects
Publications and source records attributed to A Brandis.
The subject of the paper is study of optical absorption of sensitizers in biological tissue. The study shows that absorbance can be used as a tool that allows studying biodistribution of sensitizers and their interaction with tissue in vivo. The article presents a simple technique of determining biological tissue absorption in vivo, and discusses the results of experimental animal studies of some sensitizers.
HYPOTHESIS: Transforming growth factor-beta1, glial cell line-derived neurotrophic factor, and their receptors are expressed in vestibular schwannoma, and the expression data correlate with the proliferation activity (Ki-67 labeling index) and the clinical growth rate of vestibular schwannoma tissue. BACKGROUND: Glial cell line-derived neurotrophic factor is a potent growth factor for the central and peripheral nervous system. Recent results demonstrate that glial cell line-derived neurotrophic factor requires transforming growth factor-beta to exert its trophic effect on neural tissue. A functional role, including that in Schwann cell proliferation, is discussed for both transforming growth factor-beta1 and glial cell line-derived neurotrophic factor. METHODS: Immunohistochemical analysis for transforming growth factor-beta1 and glial cell line-derived neurotrophic factor and their receptors TbetaR II, GFRalpha-1, and Ret was performed on formalin-fixed, paraffin-embedded archival surgical specimens. The Ki-67 labeling index (mean Ki-67 labeling index and highest Ki-67 labeling index for Antoni Type A and Type B regions) and the clinical growth rate of vestibular schwannoma were determined and correlated with the expression patterns of the examined neurotrophic factors and their receptors. RESULTS: Results demonstrate co-expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor with higher levels in Antoni Type A than in Antoni Type B regions. Ninety-five percent of vestibular schwannomas exhibited transforming growth factor-beta1 immunoreactivity, and glial cell line-derived neurotrophic factor expression was found in 100% of vestibular schwannoma specimens. Fifty percent of vestibular schwannoma displayed TbetaR II immunostaining, 100% showed positive reactions for GFRalpha-1, and 86% showed positive reactions for Ret. Statistical analysis revealed no significant correlation in neurotrophin expression related to sex, age, tumor size, clinical growth rate, or Ki-67-labeling indices. CONCLUSIONS: Expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor may suggest a biological role for both growth factors in vestibular schwannomas. Trophic transforming growth factor-beta/glial cell line-derived neurotrophic factor synergism seems possible and is underscored by co-expression of both neurotrophic factors and their receptors.
The cochlear nerve of adult Lewis rats was following microsurgical exposure in the cerebellopontine angle (CPA). The lesions completely interrupted the auditory nerve axons at the lesion site producing ipsilateral deafness in all animals. The rats were then treated with a recombinant Fab fragment of the antibody IN-1 against nerve growth inhibitory proteins for one to two weeks. An age-matched control group of rats was treated with unspecific mouse IgG antibody. Because the cochlear nerve lesions resulted in significant neuronal apoptosis of spiral ganglion cells, neurotrophin-3 (NT-3) was applied to the lesion site immediately post-injury in some rats. Electrophysiological studies were carried out by recording the brainstem auditory evoked potentials (BAEP) before and immediately after the lesion, and at regular intervals up to 2 months after injury. Cochlear nerve fibres were anterogradely traced by horseradish peroxidase (HRP) or biotinylated dextran amine (BDA) injected into the spiral ganglion. The results achieved in this study were consistent with the following conclusions: 1) transection of the adult rat cochlear nerve at the CPA results in functional deafness, disappearance of BAEP, apoptosis of parent axotomized neurons of the spiral ganglion, and interruption of labelled axons close to the lesion site; 2) NT-3 is able to partially rescue axotomized neurons of the spiral ganglion; 3) injured cochlear nerve fibres show a limited spontaneous sprouting and regrowth response which does not lead to BAEP recovery; 4) intrathecal treatment with IN-1 directed against myelin-associated neurite growth inhibitory proteins promotes significant elongation of the injured fibres; and 5) the regenerating fibres seem to navigate to correct targets, and be able to establish synaptic connections for functional recovery as depicted by BAEP examinations.
Partial lesions of the nigrostriatal dopamine system can be induced reliably by the intrastriatal injection of 6-hydroxydopamine (6-OHDA) and are considered to be analogous to the early stages of human Parkinson's disease. Previous studies have established a clear correlation between different doses and placements of the 6-OHDA toxin and the degree of neurodegenerative changes and behavioral impairments. In the present study, the influence of the interdependence between the two nigrostriatal systems in both hemispheres on the effects on sensorimotor behavioral performances after terminal 6-OHDA lesions was investigated. The behavioral effects were correlated to the extent of nigral dopamine neuron cell and striatal tyrosine-hydroxylase (TH)-positive fiber loss. Sprague-Dawley rats receiving unilateral intrastriatal 6-OHDA injections (4 x 5 microg) exhibited a 30-70% reduction in striatal TH-positive fiber density along an anterior-posterior gradient, an 80% loss of nigral dopamine neurons and a mild degree of behavioral impairments as revealed by amphetamine-induced rotational asymmetry, and a reduced performance in the stepping and postural balance tests. When the same amount of toxin was injected twice into both hemispheres (2 x 4 x 5 microg), additional behavioral deficits were observed, consisting of a significant, but temporary, weight loss, a stable reduction in general locomotor activity and explorational behavior, and a long-term deficit in skilled forelimb use. This is interesting in light of the morphological findings, in which uni- and bilaterally lesioned animals did not differ significantly in the extent of TH-immunoreactive fiber and dopamine neuron loss within the nigrostriatal system in each lesioned hemisphere. These results indicate that the interdependent regulation of the two nigrostriatal systems may provide some compensatory support for the function and behavioral performance of the lesioned side via the normal unlesioned side, which is lost in animals with bilateral lesions of the nigrostriatal system. Therefore, this model of uni- and bilateral partial lesions of the nigrostriatal system, as characterized in the present study, may foster further exploration of compensatory functional mechanisms active in the early stages of Parkinson's disease and promote development of novel neuroprotective and restorative strategies.
Primary angiitis of the CNS (PACNS) is a rare inflammatory disease affecting middle-aged patients. The angiitis is focal and segmental in distribution, involving small and medium-sized leptomeningeal and intracranial vessels. The most frequent presenting symptoms are headaches, focal neurologic deficits, and confusion. In addition, aphasia, neuropsychological deficits, and seizures may occur. The paper presents a review of the literature. In addition, a typical case of PACNS is presented. This case demonstrates that diagnosis of PACNS is difficult and brain biopsy is essential to confirm it.
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The development of artificial microstructures suited for interfacing of peripheral nerves is not only relevant for basic neurophysiological research but also for future prosthetic approaches. Aim of the present study was to provide a detailed analysis of axonal sprouting and reactive tissue changes after implantation of a flexible sieve electrode to the proximal stump of the adult rat sciatic nerve. We report here that massive neurite growth after implantation, steadily increasing over a period of 11 months, was observed. Parallel to this increase was the expression of myelin markers like Po, whereas non-myelin-forming Schwann cells did not change. Compared to five weeks post-implantation. where both Schwann-cell phenotypes were intermingled with each other, non-myelin-forming Schwann cells occupied a peripheral position in each microfascicle after 11 months. After an initial increase, hematogenous macrophages were down-regulated in number but maintained close contact with the implant. However, at no time were signs of its degradation observed. It is concluded that the introduced flexible polyimide electrode is suitable for contacting peripheral nerves since it permits substantial neurite growth and offers excellent long-term stability.
Primary CNS lymphomas are detected with increasing frequency in immunocompetent and immunodeficient persons. Primary involvement of the spinal roots has only rarely been reported. The unusual history is described of a patient with a primary spinal Burkitt's lymphoma initially presenting as an S1 syndrome showing lymphocytic pleocytosis in the CSF, leading to the misdiagnosis of meningoradiculitis. Repeated spinal MRI disclosed a spinal mass lesion and histological and immunohistological examination of the tumour confirmed the diagnosis of spinal Burkitt's lymphoma.
Meningeal melanocytomas are uncommon lesions. They are generally considered to be benign tumors that derive from leptomeningeal melanocytes. A rare case of a metastatic spinal meningeal melanocytoma is presented. All relevant cases reported in literature since 1972, when the term "meningeal melanocytoma" was first used, were reviewed. Rates of tumor recurrence from 1 to 5 years were calculated for this rare lesion, based on published data and on additional information obtained from personal contact with most of the authors. Recurrency rates of 47 patients suitable for evaluation were correlated with the different therapeutic approaches. Complete tumor resection alone and incomplete resection alone followed by irradiation appeared to be superior to incomplete resection alone in terms of disease-free survival. Statistical significance was achieved for complete tumor resection at follow up between I and 4 years (range p = 0.010-0.050) and for incomplete resection combined with radiotherapy after 2 years (p = 0.034). Complete tumor resection should be considered the best therapeutic option, followed by incomplete resection combined with postoperative radiotherapy.
Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathy with almost benign course. Its clinical features include ptosis, dysphagia, and proximal limb muscle weakness. The OPMD gene has been localized to chromosome 14, causing expansions of GCG triplets. Scattered families with OPMD belonging to different ethnic groups have been described worldwide. We describe one from northern Germany. In genetic diagnosis, expansion of GCG triplets to 11 was observed, which proved that myopathy, which is very rare in Germany.
The unusual and rare case of a 6-year-old boy is reported who presented with an arachnoid cyst located in the cerebellopontine angle incorporating an ectopic piece of choroid plexus tissue. A microneurosurgical cyst wall resection was performed and the plexus tissue identified and removed. The rare occurrence of ectopic choroid plexus tissue within cysts of the CNS is discussed.
The chief relevance of telemedicine lies in its capability to link medical practitioners and remote hospitals to larger or specialized facilities in a very fast electronic manner. This may become even more important due to current increase in subspecialization and demand for more precise diagnosis and consultation in difficult cases. A network attaching small clinics or laboratories to larger and more specialized units, and to highly specialized referral centers may improve the professional standard of health care services and education. For a wider use, a technological standardization will be required, since the existence of several types of computer and numerous image manipulation programs, have resulted in a proliferation of file formats. However, every potential user or client of telemedicine should keep in mind, that standardization also includes legal and ethical issues such as patient confidentiality and malpractice avoidance. The adoption of workable guidelines and protocols is required. Telepathology in general and teleneuropathology in particular is the practice of pathology at a distance, viewing digitized images of histological slides on a video monitor rather than directly through a light microscope. For the transmission of the digitized images from a telemicroscope to the remote diagnostic video monitor, different technologies such as ordinary telephone lines, broadband telecommunications channels, and the Internet can be used. The transmitted images may serve for primary neuropathological diagnosis, teleconsultation, quality assurance, proficiency testing, and distance learning. Static-imaging and dynamic-imaging are the two major competing technologies of telemicroscopy. Static-imaging systems appear to have levels of diagnostic accuracy which are not satisfactory for diagnostic neuropathology. On the contrary, high levels of diagnostic accuracy can be achieved using dynamic-imaging systems with the transmission of live video images in real time and by using a robotized telemicroscope with the possibility to examine the entire histological specimen under control of the remote teleneuropathologist.
Chordoid glioma of the third ventricle was recently reported as a novel tumor entity of the central nervous system with characteristic clinical and histopathological features (Brat et al., J Neuropathol Exp Neurol 57: 283-290, 1998). Here, we report on a histopathological, immunohistochemical and molecular genetic analysis of five cases of this rare neoplasm. All tumors were immunohistochemically investigated for the expression of various differentiation antigens, the proliferation marker Ki-67, and a panel of selected proto-oncogene and tumor suppressor gene products. These studies revealed a strong expression of GFAP, vimentin, and CD34. In addition, most tumors contained small fractions of neoplastic cells immunoreactive for epithelial membrane antigen, S-100 protein, or cytokeratins. The percentage of Ki-67 positive cells was generally low (<5%). All tumors showed immunoreactivity for the epidermal growth factor receptor and schwannomin/merlin. There was no nuclear accumulation of the p53, p21 (Waf-1) and Mdm2 proteins. To examine genomic alterations associated with the development of chordoid gliomas, we screened 4 tumors by comparative genomic hybridization (CGH) analysis. No chromosomal imbalances were detected. More focussed molecular genetic analyses revealed neither aberrations of the TP53 and CDKN2A tumor suppressor genes nor amplification of the EGFR, CDK4, and MDM2 proto-oncogenes. Our data strongly support the hypothesis that chordoid glioma of the third ventricle constitutes a novel tumor entity characterized by distinct morphological and immunohistochemical features, as well as a lack of chromosomal and genetic alterations commonly found in other types of gliomas or in meningiomas.
The combination of new and rapidly developing interactive multimedia computers and applications with electronic networks will require a restructuring of our traditional approach to strategic planning and organizational structure. Worldwide telecommunication networks (using satellites, cable) are now facilitating the global pooling of healthcare information and medical knowledge independent of location. The development of multimedia information and communication systems demands cooperative working teams of authors, who are able to master several areas of medical knowledge as well as the presentation of these in different multimedia forms. The assemblage of telematics and services offers a base for multimedia applications, for example teleteaching, telelearning, telepublishing, teleconsulting, teleconferencing, telemedicine etc. The expansion of the internet will also lead to the formation of interdisciplinary "Global Education Networks". The theory and practice of education are undergoing dramatic changes. Lifelong learning and adaptation of medical practice to new knowledge and new techniques will be even more important in the future.
Neural transplantation, as a therapeutic approach to Parkinson's disease, still requires allogeneic graft material and raises questions of immunosuppression and graft rejection. The present study investigated the time course of major histocompatibility complex (MHC) expression and astrocytic response in allogeneic dopaminergic grafts, comparing two different grafting protocols. Adult 6-hydroxydopamine-lesioned Lewis 1.W rats received intrastriatal cell suspension grafts from the ventral mesencephalon of DA rat fetuses, either as single 1-microliter macrograft via metal cannula or as four micrografts of 250 nl/deposit via a glass capillary. No immunosuppression was administered. Immunohistochemistry was performed at 1, 3, 6, and 12 weeks after grafting, using antibodies against donor- and host-specific MHC class I and II antigen, glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). Most animals showed good allograft survival up to 12 weeks after transplantation with no signs of rejection. Reinnervation of the lesioned striatum by TH-positive neurites was observed from 3-6 weeks on. Expression of donor-specific MHC class I was comparably low in both allogeneic grafting groups, while host MHC class I and II reaction as well as astrocytic response tended to be higher in the macrografted animals. Donor MHC class II was not observed at any time point. It is concluded that intraparenchymal allografts of fetal mesencephalic cell suspensions can survive well in the rat Parkinson model without immunosuppression for at least 12 weeks, and that the expression of moderate amounts of donor-specific MHC class I antigen does not suffice to initiate a rejection process. In addition, the microtransplantation approach may reduce the level of trauma and subsequent MHC and GFAP expression and may, thereby, minimize the risk of graft rejection.
An encapsulated mass of brain tissue was found in the retroperitoneum of a fetus of gestational week 15 and a boy of age 3 years. The masses possessed fibrous tissue that bound them to the spine and intraspinal connective tissue, respectively, but there was no evidence of direct continuity of the ectopic brain tissue with the normal central nervous system. There was no dysraphism. In our fetal case, possible Foix-Alajouanine anomaly was additionally found. The ectopic neural tissue in the retroperitoneal region may be termed "abdominal brain." In the literature, an identical state has been described in the head (paracranial region) but there are no other records of the paraspinal region. Despite the different locations of the masses (head/paracranial or retroperitoneum/paraspinal), these ectopic brain masses should belong to the same disorder spectrum of the paraneuraxial neural ectopia, a new concept.
Single unit activity of substantia nigra pars reticulata (SNR) neurons was recorded bilaterally in rats subjected to unilateral 6-hydroxydopamine lesions of the ascending mesostriatal dopaminergic pathway, resulting in an almost complete loss of dopaminergic neurons in the ipsilateral SN pars compacta. Firing rate and firing pattern of SNR neurons in lesioned rats were compared with respective data from sham-lesioned rats and naive controls. In lesioned rats, the mean firing rate of SNR neurons at the lesioned side was significantly reduced and there was an increase in the occurrence of bursting activity. In contrast, firing rate in the contralateral SNR was significantly increased without change in the frequency of bursting neurons. This asymmetrical change in spontaneous firing characteristics of SNR neurons following the lesion could be involved in the complex behavioral changes seen in this model of Parkinson's disease.
A benign small cell tumor of the cerebellum of an infant boy is reported. The tumor exhibited cytological features strongly resembling those of central neurocytoma but in a pattern as usually seen in cerebellar nodular neuroblastoma or in desmoplastic medulloblastoma. It is suggested to call this tumor cerebellar neurocytoma, distinguishable from medulloblastoma or cerebellar neuroblastoma as most important differential diagnoses.