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Biomedical subjects

M Bundgaard

Publications and source records attributed to M Bundgaard.

At least 19 recordsLinked to original sources

Fine structure of the blood-brain interface in the cuttlefish Sepia officinalis (Mollusca, Cephalopoda).

The blood-brain interface was studied in a cephalopod mollusc, the cuttlefish Sepia officinalis, by thin-section electron microscopy. Layers lining blood vessels in the optic and vertical lobes of the brain, counting from lumen outwards, include a layer of endothelial cells and associated basal lamina, a layer of pericytes and a second basal lamina, and perivascular glial cells. The distinction between endothelial cells and pericytes breaks down in small vessels. In the smallest microvessels, equivalent to capillaries, and in venous channels, and endothelial and pericyte layers are discontinuous, but a layer of glial cells is always interposed between blood and neural tissue, except where neurosecretory endings reach the second basal lamina. In microvessels in which cell membranes of the entire perivascular glial sheath could be followed, the glial layer was apparently 'seamless', not interrupted by an intercellular cleft, in ca 90% (27/30) of the profiles. Where a cleft did occur, it showed an elongated overlap zone between adjacent cells. The walls of venous channels are formed by lamellae of overlapping glial processes. In arterial vessels, the pericyte layer is thicker and more complete, with characteristic sinuous intercellular clefts. Arterioles are defined as vessels containing 'myofilaments' within pericytes, and arteries those in which the region of the second basal lamina is additionally expanded into a wide collagenous zone containing fibroblast-like cells and cell processes enclosing myofilaments. The 'glio-vascular channels' observed in Octopus brain are not a prominent feature of Sepia optic and vertical lobe. The organization of cell layers at the Sepia blood-brain interface suggests that it is designed to restrict permeability between blood and brain.

Animals

Electron-dense tracer evidence for a blood-brain barrier in the cuttlefish Sepia officinalis.

Electron-dense tracers were used to study the permeability of the blood-brain interface in a cephalopod mollusc, the cuttlefish Sepia officinalis. Gel filtration established that horseradish peroxidase is a suitable tracer for in vivo injection, but microperoxidase is not, being subject to binding by plasma proteins. Perfusion-fixed brain vertical and optic lobes showed no endogenous peroxidatic activity. Horseradish peroxidase was injected intravenously, and allowed to circulate for 10-35 min before tissue fixation by immersion or perfusion. Horseradish peroxidase reaction product was undetectable in the bulk of the brain parenchyma. In microvessels, venous vessels and at the brain surface, horseradish peroxidase penetrated the layers of endothelial and pericyte cells, being stopped by the layer of perivascular glia. In arterial vessels, tracer restriction occurred at the level of the pericytes. In the region of tracer blockade, a gradient of tracer could be traced in the intercellular cleft, from high at the luminal end to undetectable at the tissue end. The clefts of the restricting zone were generally wide (15-20 nm), with faint periodicities or linking structures spanning the cleft, and contained a fibrillar extracellular material. Perfusion of lanthanum chloride in saline for 15 min, followed by precipitation of lanthanum phosphate during fixation, resulted in lanthanum tracer distribution similar to that of horseradish peroxidase. Horseradish peroxidase was seen filling extracellular spaces within the neuropile when the blood-brain barrier was breached by a stab wound, indicating that the interstitium itself does not restrict tracer diffusion. It is concluded that Sepia has a blood-brain barrier tight to horseradish peroxidase and ionic lanthanum. The restricting junction is not a typical zonula occludens or septate junction, but appears to reduce tracer penetration by a filtering mechanism within the extracellular cleft. The barrier is formed by perivascular glial cell processes in the microvessels and venous vessels, but by pericytes in arterial vessels. This organization suggests that a glial blood-brain barrier may be the primitive condition, and a barrier associated with vascular elements (endothelium/pericyte) a later development.

Animals

A fibre matrix model for the restricting junction of the blood-brain barrier in a cephalopod mollusc: implications for capillary and epithelial permeability.

A model is proposed for the novel restricting junction forming the blood-brain barrier in a cephalopod mollusc, the cuttlefish Sepia officinalis. The model is based on electron-microscopic findings, from both thin-section and freeze-fracture material, the distribution of electron-dense tracers, and radioisotopic measurements of permeability using small non-electrolytes. Biochemical properties of Sepia plasma proteins are also considered. It is proposed that an effective blood-brain barrier is achieved by a combination of mechanisms. As much as 90% of the Sepia brain microvessel wall is covered by a 'seamless' glial sheath, without intercellular clefts, limiting the number of potential leakage sites. The remaining clefts follow a tortuous course increasing the diffusion path to the neuropile. Entry into the clefts is reduced by a restricting junctional region at the luminal end, characterized by delicate striations spanning the cleft, and forming an effective barrier to both horseradish peroxidase and ionic lanthanum. This is a novel junctional type, different from previously-described vertebrate and invertebrate occluding junctions. It is proposed that the junction acts as a fine-mesh molecular filter, with condensed extracellular material in the cleft, cross-linked and consolidated by bound plasma protein. Cephalopod haemocyanin or its subcomponents are considered likely candidates for the bound protein. The model predicts that blood-brain barrier permeability should be sensitive to the charge structure of the extracellular matrix and the presence of protein, and is analogous to the 'fibre matrix' model of vertebrate capillary permeability. The Sepia blood-brain barrier also highlights the different strategies available for constructing a restricting cell layer, and suggests a possible evolutionary pattern underlying the present range of junctional mechanisms in vertebrate and invertebrate epithelia.

Animals

Chloride-selective channels of large conductance in bovine aortic endothelial cells.

Single-channel currents of an anionic channel in the plasma membrane of cultured bovine aortic endothelial cells have been recorded with the patch-clamp technique. The channel is selective for chloride over cations, and has an average single channel conductance of 382 picosiemens in symmetric 140 millimoles of chloride. In addition to the main conductance state it shows well-defined subconductance states of about 50, 100, 150 and 200 picosiemens. The channel is very active at membrane potentials close to 0 mV, but steps to either positive or negative membrane potentials above +/- 20 millivolt lead to a rapid inactivation of the channel. Changes in the concentrations of free calcium or adenosine tri-phosphate on the cytosolic surface do not influence channel activity. The chloride channel rarely opens at resting membrane potential, but it may help repolarize endothelial cells following depolarizing stimuli.

Animals

Barrier membranes at the outer surface of the brain of an elasmobranch, Raja erinacea.

This report gives the results of the first electron-microscopic examination of the cell layers covering the outer brain surface and the inner surface of the cartilaginous skull in the skate, Raja erinacea. The perivascular glial blood-brain barrier--a characteristic of elasmobranchs--extends to the outer surface of the brain. This outer barrier layer is surrounded, in turn, by a subarachnoid compartment (depth: 30-40 microns), containing loose connective tissue and blood vessels; by an arachnoid-like epithelium (10-15 cell layers), impermeable to horseradish peroxidase; and, by perimeningeal fluid, a fluid with a slow turnover rate and a protein composition different from plasma. The inside of the skull, facing the perimeningeal fluid, is covered by a multilayered (10-15 layers) cuboidal epithelium, also impermeable to horseradish peroxidase. Closely apposed cells in the luminal layer of this epithelium have apical microvilli and numerous vesicular profiles, containing material of moderate electron density. These observations may explain, in terms of structure, the regulated protein content of perimeningeal fluid and the restricted exchange of solutes between brain and perimeningeal fluid in elasmobranchs.

Animals

The three-dimensional organization of smooth endoplasmic reticulum in capillary endothelia: its possible role in regulation of free cytosolic calcium.

A rise in cytosolic free Ca in capillary endothelia leads to increased permeability. It has been proposed that this Ca(2+)-regulated modulation of junctional permeability of vascular endothelia involves structural elements comparable to those involved in stimulus-contraction coupling in smooth muscle. To explore this analogy the three-dimensional organization of smooth-surfaced cisternae, vesicular membrane profiles, and tight junctions was examined in endothelia of diaphragm and heart capillaries of the rat. Three-dimensional reconstructions, based on consecutive sections of the capillaries, have demonstrated a population of small, irregular membrane profiles, occurring in individual thin sections of the endothelial cytoplasm. These profiles represent an elaborate system of smooth-surfaced cisternae, structurally similar to the sarcoplasmic reticulum (SR) of smooth muscle cells. Slender processes from the cisternae are often situated in parallel to the tight junctions at a distance of about 100 nm. The great majority of the characteristic circular membrane profiles represents caveolae and racemose invaginations of the endothelial plasma membrane, often in close relation to the cisternae. It is hypothesized that the endothelial cisternae and invaginations of the cell membrane are involved in regulation of free cytosolic calcium in the same way as the SR and caveolae in smooth muscle cells. The junction-related cisternal processes may play a role in the Ca(2+)-regulated modulation of junctional permeability.

Animals

Postsurgical change of mandibular position in patients following Le Fort I osteotomy.

Mandibular displacement during and following maxillary osteotomy was observed. Cephalometric data obtained from radiographs produced before, immediately after, and at a minimum of 6 months after were analyzed. The displacement of the maxilla and of the mandible during and after surgery was studied, and the predictive value of maxillary displacement on the changes occurring in the mandibular region was evaluated by a stepwise regression analysis. The results indicated that as the maxilla was displaced superiorly, the mandible also displaced anterosuperiorly without significant relapse. The rotation and the vertical displacement of the maxilla during the Le Fort I osteotomy accounted for two thirds of the total mandibular change. Vertical displacement of the maxilla and mandible were significantly correlated, indicating that mandibular displacement and rotation can be predicted from maxillary displacement.

Adult

Combined orthodontic-surgical treatment of alveolar clefts.

After more than four years of postoperative follow-up, 224 patients receiving secondary bone grafting of alveolar clefts were examined. Patients were classified into three groups according to age and eruption stage of the cleft side canine tooth at surgery. Each group was then subdivided according to the diagnoses cleft lip alveolar process only, unilateral cleft lip and palate, and bilateral cleft lip and palate. The treatment results were evaluated with respect to bone level in the cleft area, gingival and periodontal condition, orthodontic treatment result, growth of the jaws after surgery, and complications. The best results were achieved when the bone grafting was performed before eruption of the cleft side canine. In half of these patients orthodontic treatment could be finished with a closed dental arch without the need for prosthodontic treatment. The sagittal growth of the jaws was unaffected by the bone grafting, whereas the anterior height of the maxilla was reduced apparently without any clinical significance.

Adolescent

Functional implications of structural differences between consecutive segments of microvascular endothelium.

Structural and functional data which can be ascribed to consecutive segments of the microvascular bed are reviewed and tentatively correlated. Compared to the knowledge of endothelial cells in general, little is known about segmental variations of the microvascular endothelium. The gradient in microvascular permeability has been quantified by single capillary techniques. The results conform to structural data on endothelial tight junctions which indicate that pathways through the junctions occur with increasing frequency towards the venous end of the microvascular bed. A number of compounds mediate gap formation in venular endothelium presumably via endothelial surface-receptors. It has been demonstrated that receptors to histamine are preferentially located at the luminal surface of venular endothelium. Immunocytochemical localization of metabolic activities of microvascular endothelium in situ has started; thus it has been shown that specific antibodies to xanthine oxidase bind only to endothelium of true capillaries.

Animals

Long-term results after secondary bone grafting of alveolar clefts.

The aim of this study was longitudinally to evaluate the treatment results after secondary bone grafting in 224 cleft patients with an observation period of more than four years. The patients were divided into three groups according to age and eruption stage of the canine at the time of surgery. Group A included 94 patients with a mean age of 10 years, operated before eruption of the canine; group B included 72 patients with a mean age of 13.1 years operated after eruption of the canine; and group C included 58 patients operated after the age of 16 years (mean age, 20.4 years). The evaluation of the treatment results included longitudinal comparison of marginal bone level, periodontal status on cleft-related teeth, dental status in the bone grafted region, esthetical and functional properties of the reconstructed alveolar process, as well as the influence on growth of the maxilla. The marginal bone level was found to be significantly higher among unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) patients in the youngest groups as compared to the other groups. The number of UCLP and BCLP patients who could be treated without bridgework was significantly higher in the youngest age group than in the other groups, as were the esthetic and functional properties of the reconstructed alveolar process. External root resorption occurred in 17 patients in groups B and C. No influence of the procedure on sagittal growth of the maxilla could be demonstrated, whereas the anterior facial height was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The effect of treatment with functional appliance on a pathologic growth pattern of the condyle.

Hemifacial microsomia causes asymmetry of the face frequently known to progress throughout the postnatal development if not submitted to any kind of treatment. According to the theoretic basis for treatment of hemifacial microsomia as presented by Harvold and associates, generation of the right muscle-bone interaction constitutes the necessary precondition for the bone apposition that produces facial symmetry. This theory was the basis for the treatment of three patients with abnormal condyles, one suffering from hemifacial microsomia, one patient with a unilateral condylar fracture followed by displacement and secondary resorption of the condyle, and one patient with bilateral loss of condylar cartilage as a result of trauma. The patients were treated with an activator a.m. Harvold, and the treatment results analyzed radiographically and clinically. The results demonstrated clearly that generation of an altered muscle balance is possible even though hemifacial microsomia patients suffer from absence of normal muscles--that is, normal functional matrix as well as absence of normal condyle--and that bone apposition required for establishment of symmetry can be achieved if the right microenvironment is established. It was, however, also obvious that treatment should be initiated as early as possible because the treatment result was dependent on both the timing and the cooperation of the patient.

Activator Appliances

Brain vascular volume, electrolytes and blood-brain interface in the cuttlefish Sepia officinalis (Cephalopoda).

Cephalopod molluscs have complex brains and behaviour, yet little is known about the permeability of their blood-brain interface. This paper presents studies on the brain fluid and electrolyte compartments of the cuttlefish Sepia, as a preliminary to characterization of the permeability of the blood-brain interface in this group. Sepia is shown to be a satisfactory experimental animal, and techniques are described for anaesthesia, cannulation, and tissue and fluid analysis. Our ionic analyses of body fluids are in general agreement with those of earlier workers. Analysis of brain tissue suggests that the extracellular space is 17-20 ml 100 g tissue-1 (i.e. 17-20%). Two large molecular weight tracers, 125I-human serum albumin (HSA) and Blue dextran, give consistent values for the brain vascular volume of 3.5-5.5%, slightly higher than in vertebrates. The HSA results further confirm that the Sepia blood-brain interface is relatively tight to proteins. Finally, we have shown that the fluid surrounding the brain, pericerebral fluid (PCF), is in relatively free communication with plasma.

Animals