Tibor Kerényi

Sterically Inhomogenous Viscoelastic Behavior of Human Saccular Cerebral Aneurysms

To clarify the mechanism leading to the development and rupture of intracranial aneurysms, tensile strength and viscoelastic parameters of 22 human saccular aneurysms were investigated. Meridional and circumferential strips from the thin and the thick part of the aneurysm sack and 18 control strips from the basilar artery of 8 patients with pathologies not affecting the cerebral arterial system were studied. The length of the strips was increased in 200-µm steps, while distending force was recorded. Tensile strength and viscoelastic parameters were computed. In both directions, tensile strength of thick strips was significantly lower than that of controls. In the meridional direction, tensile strength of thin strips was significantly larger than that of thick ones (14.5 ± 4.1 × 106 vs. 7.5 ± 2.0 × 106 dyn/cm2, p < 0.05). In the circumferential direction, thin strips tore at lower strain values than thick ones (29 ± 4 vs. 55 ± 16%, p < 0.05). Viscoelastic parameters changed in parallel. In circumferential direction, values of thick and thin strips were significantly lower than those of controls. In the meridional direction, values of thin strips were significantly higher than those of the thick ones. These observations show that characteristic mechanical deterioration and steric inhomogeneities accompany the loss of smooth muscle cells and the derangement of connective tissue elements in the wall of intracranial aneurysms, which may explain certain steps in their initiation, enlargement and rupture.

Biomechanical properties of normal and fibrosclerotic human cerebral arteries

Quasi-static passive mechanical properties of histologically fibrosclerotic and normal groups of human anterior cerebral arteries (ACA) and internal carotid arteries (ICA) were studied in vivo. Cylindrical arterial segments were subjected to slow, cyclic inflation by air in the range of 5-250 mm Hg intraluminal pressure at axial isometry. To characterize mechanical properties, incremental elastic modulus, incremental distensibility and strain energy density were computed from the continuously recorded pressure-external diameter curves. Compared to normal arteries, at identical intraluminal pressures, the elastic modulus of fibrosclerotic arteries was found to be 34-45% lower in ACA and 40-56% lower in ICA, and the radius to wall thickness ratio was 25-30% smaller in ACA and 37-38% smaller in ICA. Distensibility of fibrosclerotic arteries was not smaller than that of the normal vessels. There were no significant differences in internal radius and in strain energy density between the fibrosclerotic and normal groups. Results of mathematical modelling suggests that the observed decrease in the elastic modulus of fibrosclerotic arteries was accompanied by different types of structural reorganization in the case of ACA and ICA. It is supposed that changes in mechanical properties of the passive wall elements have a compensatory character to restore some hemodynamically important properties of fibrosclerotic arteries, namely tangential stress, incremental distensibility or characteristic impedance.

Tenascin expression and angiogenesis in breast cancers.

The expression and the distribution of tenascin as well as the extent of blood vessel formation (angiogenesis) were investigated in 70 invasive human breast carcinomas. Formalin-fixed, paraffin-embedded specimens were stained with monoclonal antibody against tenascin-C (DAKO and Biogenex). Anti-CD31 antibody (Biogenex), an acknowledged marker of stromal angiogenesis, was used to detect endothelial cells. Tenascin immunostaining was positive in the tumours around the persisting normal ducts, around tumour-cell nests, in the neostroma, in some tumour cells, and it was found in or around vascular channels. Tumour vascularity was assessed by quantitative vascular grading (Chalkley point count) and was related to the localization and intensity of tenascin immunoreactivity. 19 tumours (27.1%) were scored as low, 35 (50%) as medium, and 16 (22.9%) as having a high vascular grade. The positive correlation between the vascular grade and the tenascin immunopositivity in tumour stroma was observed. Our results suggest that tenascin expression may be associated with endothelial cell activation and may play an important role in tumour angiogenesis.

Fibrin formations in vascular fibrinoid change in experimental hypertension: An electron microscopic study

Abstract Fibrin formations in the small arteries with fibrinoid degeneration in albino rats with experimentally produced malignant hypertension by bilateral compression of renal corteces were examined. In the initial phase, the vessels wall showed generally loose fibrillar fibrin formations. In sites of the longitudinal sections of these structures, transverse striation of 200–220 A or 160–170 A periodicity was discerned. In preparations from the later phase, the occurrence of dense sharply defined crystal-like fibrin increased. The appearance of these formations was partly that of bundles with sharp straight contours and partly that of polygonal clumps. In the majority of bundles characteristic transverse striation, while in the polygonal formations a 90–115 A periodicity linear structure was demonstrable. In part of the polygonal crystal-like fibrin formations, striation of broad periodicity (600–1500 A) was often detectable, superimposed on the basic structure. Fibrin crystal bodies of broad periodicitystriation accumulated in the subendothelial fibrinoid, localized between the endothelial cells and the lamina elastica interna. It is proposed that the polygonal structures with 90–116 A periodicity represent transverse sections of highly organized crystal-like fibrin bundles. In these structures, striation of broad periodicity may be the result either of summation phenomena at certain planes of sectioning or that of the pulsation effect of the functioning vessel. This does not exclude, however, the possibility of incorporation of other plasma components into the fibrin crystal structure.

Connective tissue proteins on the injured endothelium of the rat aorta

Type V collagen (TVC), fibronectin (FN), and laminin (LAM) were detected on the endothelial surface of mechanically injured rat aortas with the help of monospecific antisera and protein A - gold conjugates, carbon film surface replicas, and conventional embedding techniques. Deendothelialized tracks were produced in the thoracic aorta, and the presence of the connective tissue proteins on the luminal surface of the endothelium was studied. The changes in the distribution of the proteins during repair of the endothelial surface was followed for up to 6 days after injury. From 1 to 3 days after injury small numbers of gold particles, indicating the presence of TVC, were found between the adherent platelets on the freshly deendothelialized subendothelial matrix and in higher amounts on cell debris and collagen fibers. On the sixth day after injury, however, the amount of TVC between the sparsely distributed platelets on the deendothelialized areas was significantly higher than it was previously. FN and LAM were readily detectable on the subendothelial matrix and on the damaged marginal endothelial cells. These proteins were especially obvious on both margins of the tracks even from the first day after treatment. FN was found also in connection with fibrin precipitations as well as on the surface of some platelets and monocytes. The amount of FN and LAM present on the damaged area decreased slightly up to the sixth day. Monocytes and leukocytes adhered mostly at the margin of the wound area in the vicinity of the lesions on the endothelium. FN and LAM were often detectable under and around these adherent cells. Little of the connective tissue proteins was found on the uninjured and on the regenerated endothelial cells. The results showed subtle transitory changes in the surface pattern of the subendothelial connective tissue matrix of the injured intima. The adhesion of blood-borne cells may have been induced by FN and LAM on the endothelial surface near the lesions, and later partly prevented by increasing amounts of TVC on the surface.

Alteration of DNA Template Activity in Artery Wall Cells Induced by Risk Factors

The nucleus of all eucaryotic cells contains most of the genetic information essential to maintain the variety of functions in a diversity of specialized cell populations. From general concepts of molecular biology (Goodenough and Levine, 1974) it has been known for some time that 1. the nuclei of all specialized cells continue to carry all the genetic information present in the zygote nucleus 2. the availability of the genetic information for transcription is restricted 3. cells are able to modulate gene expression in response to extracellular factors.

Fibrin deposition in smooth muscle cells of muscular type small arteries under temporary conditions of hypoxia

Abstract Rat mesenteric arteries subjected to acute hypoxia by ligation for 2 hours and subsequently recirculated, developed severe lesions up to the level of muscle cell necrosis. Cells showing the early phase of necrosis under the light microscope were seen to enclose cytoplasmic fibrin bundles on electron microscopic examination. In addition to the intracellular fibrin deposition, colloidal iron administered intravenously prior to extermination indicated a severe permeability disturbance of the cytoplasmic membrane and the destruction of most cell organelles signified an irreversible cell damage. The intracellular presence of a considerable amount of fibrin can account for the fibrin-specific polarization optical and staining reactions observed earlier in the initial phase of vascular smooth muscle cell necrosis.

STUDY OF INFLAMMATORY RESPONSES TO CROCIDOLITE AND BASALT WOOL IN THE RAT LUNG

The subacute effects of crocidolite and basalt wool dusts were studied by means of biochemical, morphological, and histological methods 1 and 3 mo after intrabronchial instillation. The cell count, protein and phospholipid contents, and lactate dehydrogenase (LDH) activity were determined in the bronchoalveolar lavage (BAL). Both types of fibers induced a prolonged inflammatory reaction in the lung. All the parameters studied in the experimental groups were more markedly elevated after 3 mo. Relative to the control, the protein and LDH values were increased three- to fivefold, the phospholipid content twofold, and the number of free cells in the BAL exceeded the control level up to ninefold. The inflammatory responses to crocidolite and basalt wool in the lung did not differ significantly. In spite of this, basalt wool is recommended as an asbestos substitute, as the use of this man-made fiber may result in a significantly lower release of dust than that from crocidolite.

Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation.

The evaluation of the toxicity of mineral fibres has been tried to achieve in experimental animal models. However, the appearance of fibres in the pleural space could not be explained satisfactorily. Histomorphological examinations showed that intratracheal instillation of asbestos fibres leads to parabronchial and intraalveolar granulomatous tissue reactions and bronchial epithelial regenerations. For further elucidation of the pathogenesis of lung cancer and of mesothelioma the localisation and transport of inhaled fibres is of high interest. Thus, a three dimensional visualization of the structure of rat lungs before and after intratracheal instillation of UICC crocidolite fibres was performed by plastic casts to follow the way of asbestos fibres in the lung tissues and the pleura. The casts allowed to demonstrate airway structures with imprints of epithelial cells and blood vessels of normal and treated animals by scanning electron microscopy. Instilled asbestos fibres transformed bronchial structures and resulted in cystic deformations of the pleural surface. The penetration of single fibres through bronchial trunks and the visceral pleura could be shown for the first time in a three-dimensional topography of the affected tissue. Now, there is support for similar results of histomorphological examinations indicating the possibility that asbestos fibres could penetrate the pleura and migrate into the pleural space. The question if the migration of fibres is a mechanical movement or an active transport is still under discussion.

Presence of connective tissue proteins on the endothelium of the rat aorta

The microdistribution of type V collagen, fibronectin, and laminin on the luminal surface of perfusion-fixed normal rat aortic endothelium has been studied by an immunoelectron microscopic method using monospecific antibodies and a protein A-gold complex. Gold particles indicating the presence of these biologically active connective tissue proteins were localized in groups on and in the vicinity of the interendothelial border. They were also found on the small flaps of cell junctions as well as on certain cell projections and scattered on the cell surface. Correlative transmission electron-microscopic examinations proved the specificity of these localizations. The endothelial cells of the aorta differed markedly in the amount of scattered connective tissue proteins on their surface, suggesting that there are several types of aortic endothelial cells with distinct functional differences. The findings provide evidence that connective tissue proteins may contribute to the surface pattern of the normal endothelium, especially on cell borders. It is likely that these proteins influence functions such as the permeability and chemotactic activity of the endothelium pertinent to the development of vascular disease.