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Biomedical subjects

C Mittermayer

Publications and source records attributed to C Mittermayer.

At least 19 recordsLinked to original sources

Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha.

The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.

Acanthosis Nigricans

In vitro and in vivo evaluation of a hydrophilized silicone intraocular lens.

The surface of a silicone-disc intraocular lens (IOL) was hydrophilized by plasma etching (oxygen plasma) and compared to an untreated but otherwise identical IOL. Various methods of surface analysis were used to characterize the modification (e.g., X-ray photoelectron spectroscopy, contact angle estimation). A cytotoxic effect of the modified surface was excluded by cell culture experiments evaluating cell spreading, cell morphology, DNA and protein synthesis. In vivo experiments on rabbits indicated that the postoperative foreign-body reaction was not significantly affected by the hydrophilization of the IOL surface. Throughout the entire follow-up (12 weeks) we found less induced posterior synechias in the eyes with hydrophilized lenses than in those with untreated lenses (P = .009). While the IOL dislocations out of the capsular bag and the posterior capsular opacification rate did not differ significantly between the two groups of eyes, we did see special patterns of posterior capsular opacification on the posterior capsules of eyes with the hydrophilized IOL.

Animals

Collecting duct carcinoma: cytogenetic characterization.

Most renal cell carcinomas are assigned to either the papillary or clear cell, non-papillary type by morphological and cytogenetic criteria. In rare cases, papillary carcinomas of the kidney have been classified as collecting duct carcinoma because of their medullary localization and the associated hyperplastic and dysplastic epithelial lesions of collecting ducts in the vicinity of the tumour. In this first report on the cytogenetics of collecting duct carcinoma, we describe unique and consistent chromosomal aberrations in three cases. Each of the three tumours showed monosomies for chromosomes 1, 6, 14, 15, and 22. This suggests that collecting duct carcinoma is the third type of kidney tumour whose definition is based on morphological as well as on cytogenetic criteria. It appears to be cytogenetically different from the cortical papillary kidney tumour which exhibits trisomy 17 and tri- or tetrasomy 7, and from the non-papillary renal cell carcinoma which characteristically presents deletion of the short arm of chromosome 3.

Adult

Interaction of human malignant melanoma (ST-ML-12) tumor spheroids with endothelial cell monolayers. Damage to endothelium by oxygen-derived free radicals.

Clinical and experimental observations suggest that tumor-induced endothelial cell injury may be one of several initial events in the establishment of tumor metastases. To test this hypothesis, the authors have analyzed the interaction of malignant melanoma (ST-ML-12) multicenter tumor spheroids with endothelial cell monolayers in a three-dimensional coculture system. After 1.5 hours of interaction, the authors observed a toxic effect on endothelial cells in the perispheroid region. The latter was demonstrated by testing membrane integrity with the fluorescent probes acridine orange/ethidium bromide and resulted in sensitivity to shear stress of the damaged cells. The endothelium then underwent a regenerative cycle to replace the denuded halo. Addition of the oxygen radical-scavenging enzyme superoxide dismutase to the culture medium prevented this endothelial cell damage in a dose-dependent manner for up to 12 hours. By contrast, catalase, deferoxamine mesylate, allopurinol, and the proteinase inhibitors soybean trypsin inhibitor and aprotinin were not protective under the same conditions. The endothelial damage was dependent on the attachment of the spheroids. Medium conditioned by ST-ML-12-spheroids proved to be ineffective. A similar, but less prominent, deleterious effect was seen when human peritoneal mesothelial cells were used in place of the human umbilical vein endothelial cells. Spheroids of the uroepithelial cell line HU-609 were used as control. No toxicity was observed in these cocultures. Melanin biosynthesis is associated with the production of oxygen-derived free radicals. The results suggest a possible implication of these free radicals in metastasis formation of malignant melanoma.

Cell Communication

Plasma-induced surface modifications on silicone intraocular lenses: chemical analysis and in vitro characterization.

In contrast to the high standard of intraocular lens implantation today, lens fixation and the occurrence of secondary opacifications are still not satisfactory. We are working on an implant that builds a stable connection to the surrounding lens-capsule. Disc-shaped lenses made of poly(dimethylsiloxane) were treated with different kinds of plasma to bring functional groups to the surface. This allows further macromolecular coating. The results of the surface modifications were characterized by electron spectroscopy for chemical analysis, scanning electron microscopy, Fourier transform infrared spectroscopy and cell culture experiments. O2 plasma induces a rapid increase of functional groups on the lens surface. CO2 plasma has to be used for longer treatment periods to achieve the same increase, but as SEM shows, did not lead to surface damage up to periods of 300 s. Using O2 plasma for longer than 60 s, a crack formation occurred. Therefore, CO2 plasma may be a more effective and sensitive tool in grafting functional groups to the surface.

Biocompatible Materials

Hemodynamic variables and plasma levels of PGI2, TXA2 and IL-6 in a porcine model of recurrent endotoxemia.

The pulmonary and systemic hemodynamic effects of recurrent endotoxemia were studied in pigs over a 48-hr period. Six pigs of the test group were given 0.5 micrograms/kg of an E. coli endotoxin (WO111: B4) over 60 min at the beginning and in the middle (22 hr) of the experiment. Three pigs given the same amount of physiological saline solution served as controls. The hemodynamic response to the first LPS injection was characterized by severe pulmonary hypertension, a significant increase in systemic vascular resistance, and a marked decrease in cardiac output. Circulating TxB2 levels were higher than those of 6-keto-PGF1 alpha levels, so that the first response to LPS is influenced by the vasoconstrictive actions of TxA2. With the second LPS application, the pulmonary response was attenuated, although a significant increase of pulmonary artery pressure and pulmonary vascular resistance occurred. Once again systemic vascular resistance rose and cardiac output decreased, but this time plasma levels of 6-keto-PGF1 alpha were greater than those of TxB2. Toward the end of the experiment, we noted the progressive onset of a hyperdynamic and hypotensive state. Systemic vascular resistant index decreased to 50% of the baseline value. IL-6, a cytokine of systemic importance during the course of septic shock, markedly and significantly peaked after each LPS injection. Circulating plasma levels in response to recurrent endotoxemia are described.

Animals

[Experience with hydrophilic silicone disc intraocular lenses].

When oxygen plasma was used for plasma etching it was possible to hydrophilize the surface of silicone intraocular lenses (IOLs) without changing the chemical composition or the properties of deeper layers of the polymer. The modification was characterized by surface analysis. (Electron spectroscopy = XPS, contact angle estimations) and by scanning electron microscope. A cytotoxic influence of the modified surface could be excluded by cell culture experiments in which we evaluated cell spreading, cell morphology, DNA synthesis and protein synthesis. In vivo experiments on rabbits showed that the postoperative foreign body reaction was not significantly influenced by the hydrophilization of the IOL surface. Over the entire follow-up period (12 weeks), there was a reduced tendency to induce posterior synechiae in the group with hydrophilized lenses (P = 0.009). The number of dislocations and the incidence of posterior opacification did not differ significantly; on the other hand there were indications of improved adhesion to the posterior lens capsule of the hydrophilized IOL.

Animals

Sclerosis of the internal anal sphincter--a process of aging.

Functional and organic alterations such as sclerosis of the internal anal sphincter muscle are often discussed as a cause of proctologic diseases. Systematic histopathologic examinations of this muscle are rare, although the internal anal sphincter is of primary significance for the continence of the anal canal and its functional efficiency. The authors believe that the degree of formation of connective tissue in this unstriated muscle depends on the age of the examined specimen. The authors can demonstrate that sclerosis is a physiologic process of aging.

Aging

In vitro studies on the expansion of endothelial cell monolayers on components of the basement membrane.

The purpose of the present study was to observe the expansion of a monolayer of endothelial cells over specific components of the basement membrane. This was performed in vitro in a monolayer expansion assay over 5 days. The control surface was uncoated glass in the form of coverslips. Test substances were coated at a concentration of 10 micrograms/ml. The highest expansion was obtained with a high molecular weight fragment mixture of collagen type IV (IV-F, consisting of 75, 120 and 140 KD fragments), followed by fibronectin. Collagens type I, III and IV tetramer gave similar results, less than fibronectin or collagen type IV-F, although all of the above basement membrane coatings promoted expansion significantly above that of the control (P less than 0.01). The poorest expansion was obtained with laminin, which was significantly less than the control. The pentapeptide GRGDS, related to the fibronectin cell binding region, gave expansion significantly below that of the intact fibronectin molecule, as did the intact collagen type IV molecule compared with type IV-F (P less than 0.025). This indicates that sequences of the fibronectin molecule other than the cell binding sequence may be involved in promoting endothelial cell expansion. In addition, the integrity of the collagen type IV molecule does not appear necessary for this effect. On the contrary, the higher movement on IV-F may represent an inherent repair mechanism in damaged endothelium. Autoradiographic studies show that endothelial cell proliferation at the expanding front is involved in the migration assay.

Amino Acid Sequence

Differential expansion of human endothelial monolayers on basement membrane and interstitial collagens, laminin and fibronectin in vitro.

In this study the ability of a human endothelial cell monolayer to expand over specific components of the basement membrane and extracellular matrix was investigated over a 5-day period. The method was intended as a model to study the mechanisms of endothelial regeneration. All components were coated onto sterile coverslips at a concentration of 10 micrograms/ml. The highest expansion was obtained on fibronectin, laminin and collagen type III, all three being statistically significantly greater than on the uncoated control surface (0.002 greater than p greater than 0.0001). Collagens types I and IV and a high molecular weight fragment mixture of type IV (IV-F, consisting of 75, 120 and 140 kD fragments) elicited approximately similar expansion rates, significantly higher than the control (0.02 greater than p greater than 0.003), although significantly lower (approximately 15%) than collagen type III, fibronectin and laminin (p less than 0.001). The high monolayer expansion on collagen type III is surprising, as it is a relatively minor biosynthetic product of the endothelial cell. It could, however, be of significance in wound healing, in which endothelial cells come into contact with this interstitial collagen. In addition, the similar results obtained with collagens IV and IV-F indicate that expansion of the endothelial monolayer is not dependent on the integrity of the tetrameric structure of type-IV collagen.

Basement Membrane

[Comparative studies on collagen expression of chondrocytes in monolayer and spheroid culture].

Dedifferentiation of cells is well known in cell culture biology. This phenomenon is examined in comparative studies on collagen expression of chondrocytes in monolayer and spheroid culture. Immunohistochemical studies were carried out by the indirect peroxidase technique. In the differentiated state a positive reaction for collagen type II was found. This was lost as dedifferentiation took place, in which case positivity for collagen types I, III, and V increased.

Cartilage

[Animal experiment studies of the biocompatibility of colored and plain lens haptics of polymethylmethacrylate].

In spite of the great clinical success of cataract surgery and intraocular lens implantation, adverse reactions still occur. In 2-3% of all cases, there is acute or chronic inflammation. One reason might be that the biocompatibility of the lens material is insufficient. This study evaluates the biocompatibility of dyed and undyed transparent PMMA lens haptics. The haptics were implanted subcutaneously in mobile and immobile mice tissue. After different implantation periods varying from 1 week to 6 months, the haptics were removed and evaluated histologically. The undyed PMMA lens haptics showed no adverse reactions. The dyed PMMA lens haptics showed a strong inflammatory response caused by diffusion of the dye into the surrounding tissue.

Animals

[Immunohistochemical studies of the human lens capsule].

In this study we made an attempt to localize components of the human lens capsule using immunohistochemical methods. Type IV collagen could be shown in all parts of the capsule in equal distribution. It could be found over the whole thickness of the lens capsule. By comparison, laminin could be detected only at the inner layer of the capsule. There was no difference concerning the contribution of these components between the anterior and the posterior capsule. No specific staining of collagen types I and III or of fibronectin could be found.

Collagen

Topography of the inferior rectal artery: a possible cause of chronic, primary anal fissure.

The authors believed that it might be possible to explain the local frequency of the anal fissure at the posterior commissure by an anatomic relationship, and examined the blood supply of the anus. The inferior rectal artery is demonstrated by postmortem angiography and by manual preparations (N = 41) and histologic study after angiography of the vessels (N = 10). The blood supply at the different sites of the anal canal are demonstrated by a morphometric study (N = 20). The inferior rectal artery presents two variants in the postmortem angiographies, type 1 (85.4 percent) and type 2 (14.6 percent). In type 1, the posterior commissure is less perfused than the other sections of the anal canal. In addition, the blood supply may be more compromised by contusion of the vessels passing vertically through the muscle fibers of the sphincter ani internus muscle during increased sphincter tone. The role of topography in the pathogenesis of the primary anal fissure is illustrated in a model.

Anal Canal