Search PubMed⌕ Search

Biomedical subjects

N Ulfig

Publications and source records attributed to N Ulfig.

At least 37 records · Page 2Linked to original sources

Alterations in the organization of the isocortical layer I in trisomy 22.

The isocortical layer I of human fetal brains obtained from different cases of chromosomal abnormalities (trisomy 18, 21, 22) and controls without pathological disturbances were investigated histologically and immunohistochemically by using the antibodies SMI 311, SMI 35 and SMI 81 (SNAP 25) as well as antibodies against GAP 43 and calretinin. In cases of trisomy 22 the Cajal-Retzius cells in Nissl-sections and in SMI 311-immunopreparations do not reveal any alterations regarding their location or morphology. However, the axonal plexus, selectively labelled with SMI 35, normally located in layer Ib, is malpositioned in Ia. Likewise, SNAP 25- and GAP 43-immunoreactive structures, which were taken as signs of synaptogenesis, are displaced and appear in Ia instead of Ib. Cases of trisomy 18 and 21 show no changes within the organization of layer I. In trisomy 22 the isocortical layer I reveals malpositioned axonal plexus and a corresponding displacement of synaptic proteins. The possible significance of this alteration in the developmental process of the isocortex is discussed.

Brain↗

Immunolabelling of spliceosomes in sections and cultured astrocytes of human fetal brain tissue.

In the cell nucleus first large pre-mRNAs are synthesized which contain protein coding as well as non-coding sequences. The latter are removed in a process called splicing which takes place in nuclear spliceosomes. These spliceosomes consist among others of protein factors, such as the splicing factor SC35 being abundant in speckled regions of the cell nucleus. This study aims at determining immunostaining patterns using anti-SC35 in sections of the human fetal prosencephalon and cultured human astrocytes. Within the allocortical entorhinal region of the fifth gestational month the number, size and distribution of SC35-positive speckles varies considerably among the laminae which can, thus, clearly be delineated. The immature isocortical plate, however, does not display a laminar arrangement at this developmental stage. Differential immunostaining patterns can be seen in subcortical areas. Cultured human astrocytes reveal numerous speckles occupying a large portion of the nucleoplasm. On account of the SC35-immunostaining patterns no distinction of subpopulations of astrocytes is possible. The results demonstrate that SC35-immunoreactive speckles show lamina and area-specific characteristics of human fetal brain sections. Conspicuous differences in number, size and distribution of speckles are visible in different cytoarchitectonic structures; thus, architectonic borders stand out clearly in SC35-immunopreparations. The occurrence of area-specific immunolabelling of nuclear speckle domains reflects neuronal differentiation at the pre-translational level. It may be assumed that a distinct set of proteins, generated by a definite nerve cell type, can be correlated with a distinct morphology of spliceosomes. The in vitro finding indicates that anti-SC35 may well be used as a tool to study possible alterations of the speckles after, for instance, application of growth factors.

Astrocytes↗

Distribution patterns of vimentin-immunoreactive structures in the human prosencephalon during the second half of gestation.

Neuronal migration is guided by long radially oriented glial fibres. During late stages of development radial glial cells are transformed into astrocytes. A predominant intermediate filament protein within radial glial cells and immature astrocytes is vimentin. In this study fetal brain sections were used to demonstrate the transient features of vimentin-positive radial glia. In the lower half of the cerebral wall of the 6th gestational month bundles, curvature, and crossing of vimentin-positive fibres are regularly seen. Moreover, fibres terminating on vessels are observed. In the upper half fibres are radially oriented; when ascending towards the pial surface the number and diameter of fibres appears conspicuously decreased. Radially aligned fibres display numerous varicosities. In the 8th month the bulk of vimentin-positive fibres is encountered next to the ganglionic eminence and below isocortical cerebral fissures. The dentate gyrus is conspicuous due to its high amount of immunolabelled fibres. Furthermore, densely packed fibres are visible within the internal and external capsule and in the vicinity of the anterior commissure. Radial glial somata are found in the proliferative areas as well as in the adjacent white matter. In the latter location bipolar, monopolar and stellate vimentin-positive cells are present. The results demonstrate an area-specific distribution pattern of vimentin-positive structures which can be correlated with migrational events. Areas maturing late in development for instance, reveal dense immunolabelling in the 8th month. The orientation and position of radial fibres point to an additional developmental role of these fibres, i.e. their involvement in the guidance of growing axons. Moreover, the arrangement and morphology of vimentin-positive fibres, such as retraction of fibres or occurrence of varicosities, are indicative of degenerative events. Accordingly, a transformation of radial glial somata, their displacement towards the white matter and finally the growth of stellate processes can clearly be demonstrated.

Astrocytes↗

Interleukin-6 receptor is highly expressed in the ganglionic eminence of the human fetal brain.

The expression of interleukin-6 receptor (IL-6R) has been investigated immunohistochemically in seven fetal brains with special reference to the ganglionic eminence (GE), a part of the telencephalic proliferative zone. Between the 22nd and 28th gestational week the GE stands out conspicuously due to its very high amount of intensely IL-6R-immunostained cells. Adjacent brain areas exhibit only very weak immunoreactivity. Between the 32nd and 36th week a moderate IL-6R immunolabelling is seen in the remnants of the GE. IL-6 may activate the immature IL-6R-positive cells to secrete a protease which is likely to be involved in GE involution and, perhaps, in the development of hemorrhage frequently occurring in the GE of premature infants.

Antibodies, Monoclonal↗

Antibiotics: treatment of preterm labor.

Our intention is to review recent data and provide recommendations for the use of antibiotics in cases of preterm labor or preterm premature rupture of the membranes (pPROM). Various studies assessing antibiotics as treatment for preterm labor demonstrate neonatal or maternal benefits only in certain circumstances. Antibiotic treatment should be given to patients with bacterial vaginosis and Trichomonas vaginalis. Currently, antibiotics should not be applied routinely to prolong pregnancy in women with preterm labor and intact membranes. However, antibiotic therapy should be given to patients with pPROM to prolong pregnancies at 24 to 32 weeks' gestation. Our management of pPROM up to 32 weeks' gestation includes use of corticosteroids, antibiotic (extended spectrum penicillins) and tocolytic treatment for preterm labor and pregnancy prolongation. We consider expectant management previous to evidence of intrauterine infection. In women with pPROM at 32 to 34 weeks we found it beneficial to deliver 24 hours after administration of corticosteroids or, in cases of intrauterine infection, immediately. Finally, we report on our research work regarding fetal brain development in preterm birth. Further studies will be necessary to clarify the role of the interleukin-6/interleukin-6 receptor pathway in the development of intracerebral hemorrhage frequently occuring in premature infants.

Adrenal Cortex Hormones↗

Distribution of GAP-43-immunoreactive structures in the human fetal amygdala.

The growth-associated protein GAP-43 is a developmentally regulated protein which is involved in the formation of neuronal contacts. In immunohistochemical studies, GAP-43 is detected within axons during their elongation; thus a fibrous immunoreactivity is visible. After axonal growth is completed there is a shift from a fibrous to a punctate immunoreactivity. The latter has been shown to correlate with synaptogenesis. In the amygdala of the 5th gestational month, a fibrous GAP-43-immunoreactivity is seen in the basolateral nuclei, whereas the corticomedial nuclei exclusively show a punctate immunoreactivity. In the 7th month, all amygdaloid nuclei display immunoreactive puncta, but no fibers. In the 9th month GAP-43-immunoreactivity is no longer visible within the amygdala. The results demonstrate the differential distribution of GAP-43-immunoreactive structures in the amygdaloid nuclei. The nuclear specific immunostaining and its changes may indicate the sequential appearance of the monoaminergic innervation of the amygdala, as GAP-43 is known to occur in monoaminergic systems. Nuclei involved in high levels of the cortical processing hierarchy such as the lateral or basal nucleus display a late occurrence of GAP-43-immunoreactivity. In general, anti-GAP-43 has been shown to be an appropriate tool to investigate axonal growth and synaptogenesis in the developing human brain.

Aged↗

Lectin staining in the basal nucleus (Meynert) and the hypothalamic tuberomamillary nucleus of the developing human prosencephalon.

Previous studies have demonstrated that extracellular matrix glycoconjugates, shown by lectin-histochemistry with Vicia villosa agglutinin (VVA) and peanut agglutinin (PNA) as so-called perineuronal nets, play an important role in brain maturation. Concanavalin A (ConA) binding to neuronal surface glycoconjugates may be a marker of synaptic junctions. The present study was done to demonstrate the binding sites of these lectins in two functionally related nuclei of the prosencephalon, the basal nucleus (Meynert) and the hypothalamic tuberomamillary nucleus. Fetal brains of 16-36 weeks of gestation were examined by using VVA, PNA, and ConA to determine appearance and distribution patterns of specific lectin-binding sites on glycoconjugates during fetal brain development. The basal nucleus and the tuberomamillary nucleus showed a characteristic "cellular staining" that may have been due to cytoplasmatic labeling, surface labeling, or both. Lectin-staining occurred much earlier in the basal nucleus than in the tuberomamillary nucleus. Although all three lectins were bound to neurons of the basal nucleus, only ConA-positive neurons were observed in the tuberomamillary nucleus. In conclusion, lectin-labeled cells most probably represent projection neurons that are GABAergic (tuberomamillary nucleus) or cholinergic (basal nucleus). Labeling with the three lectins demonstrated nuclear-specific staining patterns that occur early in fetal development and gradually increase. Binding sites for lectins characterizing perineuronal nets (VVA, PNA) occurred only in the basal nucleus, whereas binding sites for ConA on neuronal-surface glycoconjugates, which seem to play a role in early synaptogenesis, were present in the basal and the tuberomamillary nucleus. The basal nucleus, however, expressed ConA binding sites distinctly earlier, probably indicating early arriving afferents.

Cell Nucleus↗

Monoclonal antibodies SMI 311 and SMI 312 as tools to investigate the maturation of nerve cells and axonal patterns in human fetal brain.

Neurofilaments, which are exclusively found in nerve cells, are one of the earliest recognizable features of the maturing nervous system. The differential distribution of neurofilament proteins in varying degrees of phosphorylation within a neuron provides the possibility of selectively demonstrating either somata and dendrites or axons. Non-phosphorylated neurofilaments typical of somata and dendrites can be visualized with the aid of monoclonal antibody SMI 311, whereas antibody SMI 312 is directed against highly phosphorylated axonal epitopes of neurofilaments. The maturation of neuronal types, the development of area-specific axonal networks, and the gradients of maturation can thus be demonstrated. Optimal immunostaining with SMI 311 and SMI 312 is achieved when specimens are fixed in a mixture of paraformaldehyde and picric acid for up to 3 days and sections are incubated free-floating. Neurons, with their dendritic domains immunostained by SMI 311 in a Golgi-like manner, can be completely visualized in relatively thick sections. The limitations of Golgi-preparations, such as glia-labeling, artifacts, and the staining of only a small non-representative percentage of existing neurons, are not apparent in SMI preparations, which additionally provide the possibility of selectively staining axonal networks. The results achieved in normal fetal brain provide the basis for studies of developmental disturbances.

Abortion, Induced↗

Alterations in myelin formation in fetal brains of twins.

Insufficient nutrition is known to lead to disturbances in postnatal myelin formation. This study aims to demonstrate that early myelination is altered in human twin pregnancies. Five brains of twins with a symmetric blood supply and three brains of twins with chronic fetal-fetal transfusion syndrome (one hypervolemic acceptor and two hypoxemic donors) were investigated and compared with six brains of singletons. The globus pallidus, where myelination normally starts within the prosencephalon, was studied immunohistochemically using antibodies against myelin basic protein (MBP) and with the aid of electron microscopy. In twins and donors, MBP-immunostained somata of myelin-forming oligodendrocytes were packed densely within the globus pallidus, whereas in singletons and acceptors an intense fibrous immunoreactivity was observed. Electron micrographs revealed noncompacted myelin in twins, whereas in singletons the multilaminar structure of compact myelin was observed. The results demonstrate a distinct qualitative alteration in myelination because of nutritional insufficiency during pregnancy. The lack of MBP-positive fibers (i.e., compact myelin sheaths) may be correlated to impaired maturation of oligodendroglia. The alterations described here may reflect a delayed incorporation of MBP into the processes so that the formation of compact myelin is retarded.

Brain↗

Transient features of the thalamic reticular nucleus in the human foetal brain.

The architectonic organization and neuronal types of the human foetal reticular nucleus (RN)--with special reference to transient characteristics--have been investigated using antisera against calretinin, parvalbumin and neurofilament epitopes of somata and dendrites (SMI 311). The RN consists of four subdivisions (clearly distinguishable in the 6/7th gestational month): The main portion appears as a prominent structure on account of its extension and high packing density of neurons which coexpress calretinin and parvalbumin. These two calcium-binding proteins are also expressed by the perireticular nucleus forming a conspicuous grey within the internal capsule. Perireticular cells form clusters which are in continuity with the main portion, globus pallidus, ganglionic eminence and pregeniculate nucleus. In double-labellings, a medial subnucleus stands out distinctly as it only expresses calretinin. SMI 311-immunopreparations show neurons revealing a high degree of diversification and elaborated dendritic trees. Several transient characteristics become obvious: the perireticular nucleus, not visible in the adult, represents a distinct entity in the human foetal brain. The main portion and the pregeniculate nucleus appearing as prominent greys are dramatically reduced in size later on. The percentage of RN-neurons expressing calretinin, the diversity of neuronal types and elaborated dendritic trees are reduced. The transient features can be correlated with the RN's putative functional roles in development: early RN-afferents to the dorsal thalamus may represent pioneer fibres providing guiding cues for outgrowing axons from or into the thalamus. Moreover, the RN may serve as an intermediate target for growing axons which are sorted and directed towards different final targets.

Antibodies, Monoclonal↗

Transient architectonic features in the basolateral amygdala of the human fetal brain.

The architectonical differentiation in the basolateral nuclei of the human fetal amygdala - with special reference to transient structures - was studied using series of relatively thick Nissl-stained sections. These architectonic features were correlated with the process of migration. Radial glial fibers providing the scaffold of migratory routes can reliably be marked with the aid of antivimentin. In the 5th gestational month a transient feature is conspicuous in the inferior portions of the basolateral nuclei bordering upon the ganglionic eminence (proliferative zone): columnar cell clusters, separated by cell-sparse septa, extend from the poliferative zone to the nuclei. The width of the cell columns vary considerably between the different nuclei. In vimentin immunopreparations fibers are found inside these cell columns. So they most probably reflect clustered migratory streams. Two months later, instead of this merging area between the ganglionic eminence and the amygdaloid nuclei a cell-free capsule envelopes the nuclei and clearly separates them from the ganglionic eminence. Changes in cytoarchitectonics are accompanied by a distinct rearrangement of radial glial fibers. A basket-like arrangement of the vimentin-immunoreactive fibers around the cell columns inside the cell sparse septa is found. Towards the end of pregnancy radial glial fibers gradually vanish. A comparison of Nissl and vimentin preparations reveals that transient architectonic characteristics as visible in relatively thick Nissl sections may be correlated with migrational routes.

Amygdala↗

Vasopressinergic neurons in the magnocellular nuclei of the human basal forebrain.

Vasopressinergic structures were examined within the magnocellular nuclei of the human basal forebrain. Vasopressinergic neurons were found in all parts of the diagonal band nucleus, and less frequently in the anteromedial subnucleus of the basal nucleus (Meynert). They belong to the group of large multipolar neurons, previously defined as type I neurons, characterized by fine lipofuscin granules widely spread within the soma. Species differences exist in the topographic arrangement of vasopressinergic structures.

Adult↗

Glutamic-acid-decarboxylase-and parvalbumin-like-immunoreactive structures in the olfactory bulb of the human adult.

This study examines the distribution and morphological characteristics of glutamic-acid-decarboxylase-like (GAD)- and parvalbumin-like (PA)-immunoreactive structures in the olfactory bulb of the human adult. GAD-immunoreactive somata occurred in the glomerular layer, the external granule cell layer, the more superficial portion of the external plexiform layer, and the internal granule cell layer. The cells were small- to medium-sized. Demonstration of lipofuscin pigment revealed the presence of unpigmented as well as pigmented neurons, thus suggesting the existence of two subpopulations of GAD-positive neurons. GAD-immunoreactive puncta and/or fibers were mainly seen in the periglomerular region and the internal granule cell layer. All other layers of the bulb, as well as the intrabulbar portion of the anterior olfactory nucleus, displayed considerably less of these puncta and/or fibers. The olfactory nerve layer remained practically clear of immunoreactive material. PA-immunoreactive somata occurred in the glomerular layer and both the external and internal granule cell layer. Only a small number of immunoreactive nerve cells were encountered within the white matter or the olfactory tract. Most PA-positive neurons displayed characteristics of short axon cells whereas a few others resembled van Gehuchten cells. All of the PA-immunoreactive neurons were devoid of lipofuscin pigment. Immunoreactive puncta and fibers were present in all layers though predominating in the periglomerular region, the olfactory nerve layer, and the internal granule cell layer. The intrabulbar portions of the anterior olfactory nucleus did not show any immunoreactive structures.

Adult↗

Plastination of stained sections of the human brain.

A method is described which combines staining of human brain tissue with subsequent plastination of the sections. Staining of 1-4 mm thick frozen sections with astra blue or aldehydefuchsin provides a sharp contrast between white and grey matter. The plastination results in sections which are durable and convenient to handle. These preparations may be used for teaching purposes in neuroanatomy and neuropathology.

Brain↗

Combined staining of acidophilic inclusion bodies and lipofuscin granules.

Gomori's trichrome solution is shown to stain intracytoplasmic acidophilic granules that occur in some neuronal types of the human brain. Since nerve cells in the adult human brain can be classified on account of their characteristic pattern of lipofuscin pigmentation, a combined staining method is described for the demonstration of both lipofuscin granules and intracytoplasmic acidophilic granules. Paraffin sections are stained with aldehyde fuchsin and Gomori's trichrome solution. In this manner, the red acidophilic granules are in sharp contrast to the lipofuscin deposits stained in a bluish shade. Due to this staining procedure it is now possible to classify neurons revealing acidophilic granules as well as to determine their exact topographical localization.

Azo Compounds↗

Altered lipofuscin pigmentation in the basal nucleus (Meynert) in Parkinson's disease.

The basal nucleus (Meynert) and the horizontal limb nucleus of the diagonal band are composed of 3 types of neurons that can be differentiated with the use of Nissl preparations counterstained for the demonstration of lipofuscin pigment. The pattern of pigmentation of these neurons has been investigated in parkinsonian cases and compared with controls. In the parkinsonian cases the number of large multipolar neurons showing pigment granules in a dendritic stem is significantly higher than in controls. Moreover, the degree of pigment penetration is more pronounced in parkinsonian cases. The results show that staining of lipofuscin granules offers an approach to detecting further details of the changes in the basal nucleus in Parkinson's disease.

Aged↗