Search PubMed⌕ Search

Biomedical subjects

K Heimann

Publications and source records attributed to K Heimann.

At least 163 records · Page 9Linked to original sources

[Lactoferrin and transferrin--iron-binding proteins in physiological and pathological vitreous bodies].

Having demonstrated transferrin (TF) and the TF receptor in periretinal membranes, we now present results of quantitative studies of TF and lactoferrin (LF), another protein with iron-binding properties. Normal human vitreous contains 74 +/- 7 mg/l TF, but less than 50 micrograms/l LF (ELISA). The TF levels determined in vitreous aspirates from patients with proliferative intraocular diseases [traumatic proliferative vitreoretinopathy (PVR), idiopathic PVR, and proliferative diabetic retinopathy (PDR)] were higher. A statistically significant difference between the levels in the vitreous in the three types of proliferative intraocular disease and in physiological vitreous was not observed. In contrary to TF, LF could not be labeled in surgically obtained membrane specimens using immunochemistry. Apparently LF does not have the same importance for cell proliferation in proliferative intraocular diseases as is suggested for TF.

Enzyme-Linked Immunosorbent Assay↗

[Quantitative determination of 5 vitreal proteins in the normal vitreous body and proliferative retinal diseases].

While progress in vitreoretinal surgery has been very rapid in recent years, our understanding of the biochemistry of normal and pathological vitreous is still limited. Therefore, we developed non-competitive ELISA techniques for the quantification of five vitreal proteins which, together with vitreal collagen (300 mg/l), account for more than 70% of the total vitreal protein. Physiological levels of the individual proteins were determined as follows: albumin 293 +/- 18 mg/l, IgG 34 +/- 3 mg/l, transferrin 74 +/- 7 mg/l, alpha 1-antitrypsin 14 +/- 3 mg/l, alpha 1-acid glycoprotein 4 +/- 0.7 mg/l. Mean values for these proteins were also obtained in vitreous aspirates from patients with traumatic proliferative vitreoretinopathy (PVR) (n = 10), idiopathic PVR (n = 10) and proliferative diabetic retinopathy (PDR) (n = 15). Significant differences were found for total vitreal protein and alpha 1-antitrypsin between the control groups and the three vitreoretinal disorders, between the PDR and control group for transferrin, and between both types of PVR and controls for alpha 1-acid glycoprotein. Given the high plasma levels of the individual proteins quantified in this study and the uniform rise in total vitreal protein, a disturbancee of blood-retinal and blood-vitreal barriers seems to be an essential features of proliferative intraocular disorders. No disease-specific change in the protein pattern could be detected for the three disorders examined.

Blood Proteins↗

A fluorescein angiographic study on patients with proliferative vitreoretinopathy treated by vitrectomy and intraocular daunomycin.

Fluorescein angiographic findings in patients with proliferative vitreoretinopathy treated by victrectomy, silicone oil tamponade and intraocular daunomycin are compared to findings in patients who received the same treatment but no intraocular drug. A difference between drug treated and untreated eyes was not discovered. We observed, however, a delayed arteriovenous passage time, cystoid macular edema, ectopia of the foveolar region and late hyperfluorescence of the optic disk; these findings might partly explain the visual results. Reduction of redetachment and thus prevention of reoperations by treatment with antiproliferative drugs may decrease the rate of cystoid macular edema and thus improve the functional results of surgical treatment.

Adult↗

Pars plana vitrectomy and silicone oil injection in proliferative diabetic retinopathy.

A retrospective study is reported on 106 eyes with proliferative diabetic retinopathy, treated by vitrectomy and silicone oil injection. Indications were traction detachment in 91 eyes and nonclearing rebleeding in 15 eyes; 31 eyes had previously had vitrectomy. Anatomical success was obtained at the end surgery in 91 eyes, and after a minimum follow-up of 6 months in 68 eyes (64%). Functional results were as follows: satisfactory visual acuity (0.5-0.05) in 23 eyes (22%), ambulatory vision (0.03-CF) in 14 eyes (13%), HM-LP in 54 eyes (51%), and NLP in 15 eyes (14%). The functional results are limited by recurrent detachments due to characteristic reproliferations under the silicone bubble or by ischemic diabetic angiopathy in the attached retina. A positive effect of silicone oil is demonstrated in the reduction of preexisting or postoperatively new iris neovascularization and in preventing postoperative rebleeding.

Adult↗

Transferrin and transferrin receptor expression in intraocular proliferative disease. APAAP-immunolabeling of retinal membranes and ELISA for vitreal transferrin.

Transferrin (TF) is the major transport protein involved in human iron metabolism. The expression of the cell-surface TF receptor is associated with cellular proliferation, the dominant feature of proliferative vitreoretinal disorders with traction retinal detachment. A total of 14 retinal membranes from patients with different clinical diagnoses contained immunoreactive TF. Expression of the cell-surface TF receptor was confirmed by a monoclonal anti-human TF-receptor antibody label in 11 of the 14 specimens. We developed a noncompetitive enzyme-linked immunosorbent assay (ELISA) for TF and found it to be a significant component of vitreal protein, with a level of 65.7 +/- 33.9 mg/l. Vitreal TF as a major iron acceptor probably has a protective function, but its interaction with macrophages and its growth-promoting activity may subsequently stimulate the proliferation of fibroblasts and retinal pigment epithelial cells.

Antibodies, Monoclonal↗

[Problems in pneumatic retinopexy].

Fifty-four phakic eyes with selected rhegmatogenous retinal detachment (one retinal tear or a circumscribed group of tears in the upper two-thirds of the fundus, no sign of PVR) were treated by pneumatic retinopexy (transconjunctival cryopexy, intraocular gas injection with appropriate postoperative head positioning). After postoperative follow-up of six months or more primary reattachment of the retina was found in 27 patients (50%). In 12 eyes (22%) there was insufficient relief of traction, so that the detachment persisted (seven eyes) or recurred (five eyes). New retinal tears developed in 12 eyes (22%) between three days and six months postoperatively. This was probably due to interaction of the gas bubble with the vitreous base, an incompletely detached posterior vitreous border, or intravitreal condensations. Three eyes (6%) developed PVR. Other complications were vitreous hemorrhage (one eye) and subretinal gas bubble (one eye). The higher rate of complications, including the development of new tears, as compared to episcleral buckling procedures is discussed. In the authors's view appropriate experience on the part of the retinal surgeon and a level of intraoperative asepsis adequate for intraocular procedures are of major importance.

Adolescent↗

[Immunohistology of proliferative vitreoretinopathy following giant tear detachment].

A patient with multiple bilateral retinal holes and a history of several prior surgical interventions was treated by pars plana vitrectomy for total traction retinal detachment in the right eye. The preretinal membrane specimen obtained surgically was analyzed using an immunological label for macrophages, vimentin, cytokeratin, fibronectin, fibrinogen, transferrin, the transferrin receptor, blood coagulation factor XIII-A and XIII-S, and haptoglobin. The results of the study suggest that factor XIII and fibronectin play an important role in idiopathic PVR. Proliferating cells of fibroblastic appearance invade a preretinal exudate and restructure the injured vitreoretinal tissue, forming a contracted scar. Macrophages, known to be characteristic of early posttraumatic PVR development, were not present in this case of PVR, where traction retinal detachment was presumably induced by the formation of multiple retinal holes.

Eye Proteins↗

[Keratopathy following vitrectomy with silicone oil injection].

We present a retrospective study on keratopathy following vitrectomy and injection of SF96 silicone oil (viscosity 1000 centipoise, n = 232 eyes) and the purified OP 1000 silicone oil (viscosity 1000 centipoise, n = 129 eyes). In cases with aniridia, with closed inferior basal iridectomy (IBI) or without IBI, keratopathy was found in 74 of the 166 eyes (45%) injected with silicone SF96 and in 14 of the 30 eyes (47%) injected with silicone OP 1000. An intact IBI reduced the incidence of keratopathy to 0% (SF96, 0/45 eyes) or 6% (OP1000, 5/88 eyes) when the anterior chamber was free of silicone. When silicone oil was in contact with the corneal endothelium (due to periretinal reproliferation, hypotony, overfilling or droplet formation), there was corneal decompensation in 66% (SF96, 14/21 eyes) or 55% (OP1000, 6/11 eyes). The keratopathy presents as calcified band keratopathy or diffuse bullous corneal edema as in "endothelial decompensation." These variations in keratopathy are in agreement with the following basic diagnoses: 77% (43/56 eyes) of trauma patients (n = 130) develop calcified band keratopathy, and 47% (24/51 eyes) of patients with idiopathic proliferative vitreoretinopathy (n = 182) present with diffuse bullous corneal edema.

Cornea↗

[Immunohistochemical findings in proliferative retinal diseases--on the significance of fibronectin, macrophages and transferrin].

Surgically excised vitreoretinal membranes of different etiology were analyzed immunochemically using the APAAP stain. We investigated the presence of macrophages, lymphocytes, proliferating cell antigen, fibronectin, vimentin, cytokeratin, transferrin (TF), and the TF receptor. Fibronectin and vimentin were observed both in idiopathic and traumatic proliferative vitreoretinopathy (PVR); however, abundant macrophages were a typical feature only of traumatic PVR. A Coats' disease specimen contained fibronectin, vimentin, TF, and macrophages. Staining for proliferating cell antigen, lymphocytes, and cytokeratin was negative in all specimens. TF was detected in all membranes, and it was possible to label the receptor in 11 of 14 patients. TF quantities in native human vitreous were measured to be 65.7 mg/l by ELISA. TF is an essential growth factor for cultured cells, and current evidence suggests that TF may be involved in the pathogenesis of proliferative intraocular disease.

Cicatrix↗

Immunochemical analysis of periretinal membranes. Review and outlook.

The progressive immobilization of retinal detachment through periretinal membrane formation is a major cause of blindness and difficult to treat. Initial morphological studies have revealed several features of the natural history, but immunochemistry yielded the most important results. Among the antigens detected in periretinal membranes are GFAP, keratin, vimentin, actin, fibronectin, collagen, and macrophage antigen. Immunochemical findings, however, have to be carefully interpreted and several pitfalls have to be avoided. The significance of new interesting factors in proliferative intraocular disease, e.g. platelet-derived growth factor, transforming growth factor-beta, or the recently described integrins, is most likely to be determined by detailed immunochemical studies on surgically obtained human specimens.

Actins↗

[In vitro changes in the lens epithelium and corneal endothelium caused by the cytostatic drug daunomycin].

We evaluated the effects of the antiproliferative drug daunomycin on the viability and proliferation of cultured porcine lens epithelial cells. After a single short-term application, daunomycin penetrates the lens epithelial cells within 5 min. At a concentration of 2.5-7.5 mg/l, daunomycin has a low level of acute cytotoxicity and significantly suppresses the mitotic activity of the epithelial cells in culture. The daunomycin-induced endothelial lesions in freshly excised pig corneas were quantified with the Janus green photometry technique (n = 30) and studied with scanning electron microscopy (n = 9) in comparison to Ringer solution, which served as the control (n = 39). Whether the endothelial lesions were exposed to daunomycin or Ringer solution for 10 or 30 min seemed to make no significant difference. In addition, daunomycin did not seem to induce any morphological changes in the endothelial surface. These in vitro results confirm our clinical experience that daunomycin is apparently not harmful to the adult human corneal endothelium. Our results indicate that short-term endocapsular application of daunomycin during extracapsular cataract extraction, with or without IOL implantation, may prevent and/or delay the formation of capsular opacification.

Animals↗

[Isoelectric focusing and electroblotting of human vitreous body proteins].

Due to its high resolution and reproducibility, isoelectric focusing with a highly sensitive silver stain, in combination with electroblotting and immunodetection, may be a valuable technique to provide detailed mapping of the protein pattern of the human vitreous. By means of this technique, the presence of albumin, alpha 1-antitrypsin, alpha 1-acid glycoprotein, and transferrin in the normal human vitreous was established. Our results indicate that the differences between vitreous protein und serum protein are more of a quantitative than a qualitative nature. Preliminary studies on pathological vitreous samples obtained during vitrectomy indicate that a substantial amount of the intravitreal protein in PVR as well as in proliferative diabetic retinopathy is plasma-derived. The vitreous from eyes with a macular pucker shows a pattern of protein bands that is reminiscent of normal vitreous.

Eye Proteins↗

Immunochemical studies of epiretinal membranes using APAAP complexes: evidence for macrophage involvement in traumatic proliferative vitreoretinopathy.

Proliferative vitreoretinopathy is characterized by cellular proliferations in the periretinal space resulting in traction retinal detachment. Numerous cellular elements and connective tissue components have been identified by morphologic criteria as well as immunochemical techniques. In this study, we used the recently introduced APAAP (alkaline phosphatase - anti-alkaline phosphatase) immunostaining procedure to identify macrophages, T-lymphocytes, the structural proteins fibronectin, vimentin, and cytokeratin, and a proliferating cell antigen, in eleven human epiretinal membranes obtained during vitreoretinal surgery. Our results confirm that the pathologic processes in PVR are not immunologically mediated, but reveal the features of physiologic wound healing and scar formation. Posttraumatic PVR seems to be characterized by a severe initial inflammatory reaction as evidenced by the presence of numerous macrophages, whereas idiopathic PVR, as a complication of retinal detachment, may be caused by different mechanisms in the early pathogenesis.

Alkaline Phosphatase↗

Evaluation of daunomycin toxicity on lens epithelium in vitro.

Posterior capsule opacification is the major complication of extracapsular cataract extraction (ECCE). Lens epithelial cells derived from the periphery of the lens are thought to migrate posteriorly and contribute significantly to the postoperative proliferations at the posterior pole. We have evaluated the effects of the antiproliferative drug daunomycin on cultured porcine lens epithelial cell viability and proliferation. We observed that the mitotic activity of the cells is suppressed by a single short time treatment with daunomycin at a concentration as low as 2.5 mg/l. Long term effects on the reproductive capacity of the lens epithelial cells may not be as pronounced as the inhibition of other cells examined before e.g. retinal pigment epithelium and fibroblasts. Our results indicate that daunomycin may be useful for the pharmacologic prevention of postoperative proliferations in patients treated by ECCE.

Animals↗

Fibronectin quantification in plasma and vitreous by a noncompetitive ELISA technique.

Fibronectin, a high-molecular glycoprotein of the extracellular matrix and plasma, has provoked increasing interest in ophthalmology because of its possibly important role in the pathogenesis of proliferative vitreoretinopathy (PVR). A quantitative determination of fibronectin in vitreous aspirates is necessary for the evaluation of this glycoprotein in PVR. A noncompetitive enzyme-linked immunosorbent assay (ELISA) was developed for the quantification of immunoreactive fibronectin in human plasma samples and vitreous aspirates. Here, procedures to establish an ELISA for the clinical laboratory routine are discussed and possible pitfalls during the assay standardization are described.

Enzyme-Linked Immunosorbent Assay↗

Demonstration of mononuclear phagocytes in a human epiretinal membrane using a monoclonal anti-human macrophage antibody.

Proliferative vitreoretinopathy (PVR), the major complication of rhegmatogenous retinal detachment and posterior segment ocular trauma, is a multistage disease process eventually resulting in traction retinal detachment. The migration of macrophages to a site of disrupted barriers between the vitreous, retina, and choroidea, respectively, is considered to be an important step in the early pathogenesis of PVR. In this study, we demonstrate the presence of numerous mononuclear phagocytes in a human PVR membrane by an APAAP (alkaline phosphatase-anti-alkaline phosphatase) immunostain using a monoclonal mouse anti-human macrophage antibody. This finding correlates with a highly positive fibronectin immunostain in the same specimen. Our results warrant further investigation of the involvement of mononuclear phagocytes in vitreoretinal proliferative disorders.

Antibodies, Monoclonal↗

The significance of fibronectin in vitreoretinal pathology. A critical evaluation.

Proliferative vitreoretinopathy (PVR) is characterized by cellular proliferation and the formation of intravitreal and periretinal membranes predisposing to traction retinal detachment. Recently, fibronectin, a high-molecular glycoprotein, has been attributed an important role in the pathogenesis of PVR. In order to evaluate the significance of fibronectin as a diagnostic order prognostic marker for PVR, we determined levels of immunoreactive fibronectin in 59 human vitreous specimens by a noncompetitive ELISA technique. Before this study, fibronectin levels in the vitreous had not been investigated taking both protein and iron levels into consideration. The vitreous was obtained during vitrectomies performed for a broad spectrum of vitreoretinal disorders. Our measurements suggest that the amount of intravitreal fibronectin may be correlated with the severity of a manifested disorder rather than being diagnostic for PVR. As long as plasma-derived fibronectin cannot be differentiated from other tissue fibronectins, however, the concentration of this glycoprotein is not a reliable indicator of intraocular proliferative activity. The values for all three parameters--fibronectin, protein, and iron--were significantly higher in revitrectomy samples compared to patients undergoing a first vitrectomy. A somewhat surprising result was a high level of fibronectin in the vitreous of two patients with macular pucker.

Enzyme-Linked Immunosorbent Assay↗

[Traction detachment in Coats disease].

Immunocytochemical examination of a subretinal membrane removed during vitrectomy from a patient suffering from Coats' disease revealed macrophages, fibronectin, and vimentin. Vimentin is considered to be a marker of mesenchymal cells. Fibronectin may represent a guide rail and scaffold for the cellular organization of subretinal exudates.

Fibronectins↗