Biomedical subjects

T Moos

Publications and source records attributed to T Moos.

28 records · Page 2Linked to original sources

PubMed1996

Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and non-neoplastic cell lines. The purpose of the present study was to determine by immunohistochemistry: the presence/distribution of nerve growth factor receptor (NGFr), cellular proliferation expressed by Ki-67, and intratumoral vascularization visualized by the endothelial marker CD 31, in a series of 61 human vestibular schwannoma heterotransplants in athymic nude mice. The immunohistochemical results were correlated to the observed macroscopic growth in 22 heterotransplants (36%) with obvious macroscopic growth, versus 39 heterotransplants (64%), that were stationary or regressed. The positive immunoreactivity to NGFr, number of Ki-67 positive nuclei and number of intratumoral vessels were significantly higher in the 22 (36%) growing heterotransplants than in the 39 heterotransplants (64%), which were stationary or regressed (p < 0.00005, p = 0.046, p < 0.00001). NGFr was statistically related to the vascularity of the heterotransplants expressed by CD 31 (p<0.00001). No significant relation was observed between NGFr and the proliferation, as estimated by Ki-67. The results revealed that the macroscopic growth of VS in athymic nude mice was associated with strong positive expression of NGFr, high cellular proliferation expressed by Ki-67 and vivid neovascularization expressed by CD 31. The possible clinical applicability of the achieved results is discussed.

Animals↗

PubMed1995

Developmental profile of non-heme iron distribution in the rat brain during ontogenesis.

The entry of iron from blood into the developing rat brain was studied by means of non-heme iron-histochemistry. The content of non-heme iron in the endothelial cells was manifest already from E14, declined from P3 to P5, and was almost absent on P10-P15. The choroid plexus epithelial cells of either ventricle was non-heme iron-containing from E14. Non-heme iron-containing macrophages situated in the stroma of the choroid plexus were also observed from E14. From E19, the macrophage-like cells tended to invade into (a) regions with transitory structures like the intermediate zone of the cerebral hemisphere, (b) developing axonal tracts like corpus callosum and internal capsule, and (c) deep layers of the tectum, a region with an extensive degree of naturally occurring cell death. The amoeboid macrophage-like cells observed in the brain parenchyma gradually acquired prolonged extensions and apparently differentiated into ramified microglia-like cells, which later lost their non-heme iron-content. Thus, at P70, non-heme iron-positive microglia-like cells were hardly seen reflecting the transitory event of non-heme iron in microglia-like cells. At P200, non-heme iron-containing microglia cells and oligodendrocytes appeared in manifestly higher number than at P70, a phenomenon probably related to aging. These results delineate for the first time the appearance of iron in the developing brain. The results are of relevance for understanding the potential of iron-deficiency for harming the developing central nervous system, generally by decreased transport of iron through brain capillaries and choroid plexus, and specifically by an impaired modulation of the developing brain parenchyma by iron-containing macrophages.

Aging↗

PubMed1995

Age-dependent uptake and retrograde axonal transport of exogenous albumin and transferrin in rat motor neurons.

This study presents evidence for retrograde axonal transport of exogenous albumin and transferrin in adult brainstem motor neurons, whereas plasma proteins are not transported in neonatal motor neurons. The plasma protein uptake in motor neurons was dose-dependent, suggesting a nonspecific (fluid-phase) uptake mechanism. Further evidence for nonspecific uptake of exogenous transferrin in the motor neuron was found in the presence of transferrin receptor only on the soma and not on the axon terminal. The immunoreaction product of the exogenous plasma proteins was localized as perinuclear granules in association with the lysosomal system, as verified by staining for the lysosomal marker cathepsin D and by ultrastructural examinations. The results suggest that albumin and transferrin derived from hepatic synthesis gain access to motor neurons nonspecifically by retrograde axonal transport, whereas transferrin derived from intracerebral synthesis specifically gains access to motor neurons due to receptor-mediated uptake at the soma of the neuron. The lack of plasma proteins in developing motor neurons suggests that retrograde axonal transport of plasma proteins has no significance for developing axons. Plasma proteins have a potential for transporting toxic metals to motor neurons. Intraneuronal uptake of aluminum-transferrin either by nonspecific uptake in axon terminals or by receptor-mediated uptake at the soma may have a role in the pathogenesis of the motor neuron disease amyotrophic lateral sclerosis.

Aging↗

PubMed1995

Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes.

Exposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal-binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is expressed only in diminutive amounts in astrocytes of the neonatal rat brain, which could imply that neonatal rats are devoid of the capacity to detoxify free metals released from a brain wound. In order to examine the influence of a brain injury on the expression of metallothionein in the neonatal brain, PO rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood-brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP and vimentin, was observed surrounding the neocortical lesion site. Astrocytes and pial cells situated adjacent to the area of injury also became positively stained for metallothionein. At 3-6 days post-lesion, the highest level of reactive astrocytes expressing metallothionein was observed. Neo-Timm staining revealed that histochemically reactive zinc had disappeared from the lesion site. Extracellular albumin and metallothionein-positive astrocytes were absent approximately 2 weeks after the lesion, whereas reactive astrocytosis was still observed. These results show that a lesion of the neonatal rat brain induces a transient expression of metallothionein in reactive astrocytes, probably as a response to metals released from the site of the brain injury.

Animals↗

PubMed1995

Increased accumulation of transferrin by motor neurons of the mouse mutant progressive motor neuronopathy (pmn/pmn).

It has been suggested that iron-carrying transferrin exerts growth-factor-like influences on motor neurons. I have evaluated the distribution of proteins related to the intracerebral iron-homeostasis in the mouse mutant progressive motor neuronopathy (pmn/pmn); an autosomal recessive mutant with progressive caudo-cranial motor neuron degeneration. A higher immunoreactivity of transferrin and transferrin receptor in motor neurons of the pmn/pmn mutant compared to that in normal mice was demonstrated. Ferritin was not observed in motor neurons of the pmn/pmn mutant. Transferrin receptors were absent from axons and neuromuscular junctions, indicating that entry of blood-borne, liver-derived transferrin ('liver transferrin') into motor neurons due to uptake and subsequent retrograde axonal transport was unspecific. Due to the selective presence of transferrin receptors on neuronal somata, a more likely mode of entry of transferrin into the motor neurons was by receptor-mediated uptake of brain-derived transferrin ('brain transferrin') at the soma. This study provides data on transferrin accumulation and transferrin receptor expression in diseased motor neurons and adds further insights into influences of proteins related to iron-homeostasis in the diseased PNS.

Animals↗

PubMed1993

GAP43 identifies developing muscle cells in human embryos.

GAP43 has long been regarded as a neurone specific molecule present intraneuronally in both the central and peripheral nervous system, especially during development and regeneration. GAP43 has, however, recently been demonstrated in developing muscle cells of the chicken. In the prsent investigation, we have used immunohistochemistry to investigate whether GAP43 is also expressed in developing human muscle cell. Using specific monoclonal antibodies as markers for developing muscle cells (desmin) and axon terminals (synaptophysin), our results show that GAP43 is expressed in aneural, human embryonic muscle cells.

Antibodies, Monoclonal↗

PubMed1993

A sensitive post-DAB enhancement technique for demonstration of iron in the central nervous system.

A technique is described for enhancing the reaction product of the staining reaction for iron in paraffin-embedded tissue from central nervous system (CNS). After amplification of the Prussian Blue staining reaction with 3,3'-diaminobenzidine (DAB), the reaction product was further intensified using a stepwise treatment with silver methenamine, gold chloride and uranyl nitrate (post-DAB treatment). Following the Prussian Blue-DAB staining reaction, iron was seen only in glial cells and choroid plexus epithelial cells, whereas the post-DAB treatment revealed that neurons and endothelial cells of the brain capillaries were also positively stained. The post-DAB treatment resulted additionally in an increased intensity of the reaction product within choroid plexus epithelial cells compared to that obtained in sections subjected only to the Prussian Blue-DAB reaction. The reliability of the method was evaluated using liver sections as positive controls. Furthermore the higher sensitivity of the method was assessed using nitrocellulose filters containing serially diluted iron-saturated transferrin. The post-DAB method is simple and can easily be applied to formalin- or glutaraldehyde fixed, paraffin-embedded nervous and non-nervous tissue.

3,3'-Diaminobenzidine↗

PubMed1993

Simultaneous application of Timm's sulphide silver method and immunofluorescence histochemistry.

This study presents a method for simultaneous detection of metal ions of zinc and copper and proteins in single brain sections. Rat were transcardially perfused with sodium sulphide and subsequently fixed with formalin. Zinc and copper were demonstrated by Timm's sulphide silver staining method using physical development (autometallography). The glial cells markers glial fibrillary acidic protein and vimentin, and serum albumin having a capacity for binding of zinc and copper were detected by immunofluorescence histochemistry. The sections were examined for the presence of both metals and proteins in a microscope equipped for both light and epifluorescence microscopy. The reaction product of the autometallographic reaction did not interfere with immunofluorescence histochemistry, and vise versa. The method can be used for co-localization of zinc and copper with specific cell-marker proteins. Furthermore, the method can be used for simultaneous intracellular visualization of these metals and their respective metal-binding proteins.

Animals↗

PubMed1993

Cerebrovascular permeability to azo dyes and plasma proteins in rodents of different ages.

The often quoted investigation by Behnsen [4] provides some evidence for an increased permeability of the neonatal mouse blood-brain barrier (BBB) to trypan blue compared to the adult. Trypan blue, which circulates in plasma mainly bound to albumin, is commonly used as a macromolecular tracer, although Behnsen probably injected dyes in amounts exceeding the dye-binding capacity of plasma proteins. The cerebrovascular permeability in neonatal and adult mice and rats was investigated using the visual tracers trypan blue and Evans blue and immunocytochemical staining for endogenous plasma proteins. By administering different concentrations of the dyes, the permeability of the BBB was assessed. The presence of the dyes in plasma as either dye-protein complexes or as free dye was measured by a plasma protein binding assay. When dyes occurred in plasma as macromolecular dye-protein complexes, dyes and plasma proteins were restricted to CNS regions normally devoid of a BBB in both neonates and adults. When unbound (free) dyes occurred in plasma, dyes were observed intraneuronally in regions without projections beyond the BBB in both neonates and adults corresponding to that observed by Behnsen; intraneuronal accumulation of plasma proteins also occurred in regions with projections confined to the BBB but only in neonates. It is concluded that the BBB to macromolecular tracers is fully developed at birth in mouse and rats. However, when free dye is present in plasma, there is a differential permeability to plasma proteins between neonates and adults.

Aging↗

PubMed1991

Immunocytochemical evidence for retrograde axonal transport of exogenous albumin in adult rat brain stem motor neurons.

Serum albumin is present in cranial nerve motor neurons in the brain. This is suggested to be due to uptake into peripheral axon terminals with subsequent retrograde axonal transport to the perikarya of the motor nuclei. Indirect evidence for uptake and retrograde axonal transport of albumin in a cranial nerve has been presented previously e.g. by demonstration of fluorescence of the albumin-bound dye Evans blue in the neurons of the hypoglossal nucleus subsequent to injection in the tongue. In this study we present direct evidence for retrograde axonal transport of albumin. Human albumin was injected into the tongue of adult rats, and immunocytochemically detected with an antibody, which selectively reacted with human albumin. In brains processed 24 hours or later after injection, a positive reaction was seen in the neurons of the hypoglossal nucleus. The immunoreaction product was localized as perinuclear granules in an otherwise unstained perikaryon probably associated with the endosomal-lysosomal system. Thus, albumin present in hypoglossal motor neurons appears to originate from uptake in peripheral axon terminals. Judging from the early appearance after injection, this transport probably occurs by a fast component of retrograde axonal transport.

Animals↗