Search PubMed⌕ Search

Biomedical subjects

U Pleyer

Publications and source records attributed to U Pleyer.

At least 55 records · Page 3Linked to original sources
PubMed2001

Macrophage depletion prevents leukocyte adhesion and disease induction in experimental melanin-protein induced uveitis.

The purpose was to study the effects of macrophage depletion with liposomal dichloromethylene-diphosphonate (Cl(2)MDP-lip) on inflammation and leukocyte-endothelium interaction in experimental melanin-protein induced uveitis (EMIU). Lewis rats (n = 48) were immunized with melanin-associated protein in complete Freund's adjuvant and pertussis toxin. Control groups received adjuvants without the antigen (n = 12) or no injection (n = 6). Animals received treatment with either CL(2)MDP-lip or empty liposomes (empty-lip) on day -2, 1, 4, 6 and 8. Leukocytes were stained with rhodamine 6G i.v. and intravital fluorescence microscopy (IVM) was performed on day 4, 6, 8 and 10 to quantify leukocyte rolling and arrest. After IVM, the cell count and protein concentration were determined in aqueous humor and plasma levels of TNF-alpha and IFN-gamma were measured by ELISA. In EMIU, leukocyte rolling increased on day 4 (10.0 +/- 1.2 cells min(-1)vs baseline of 5.7 +/- 0.7 cells min(-1), mean +/- S.E.(M.)) and peaked on day 8 (40.8 +/- 4.2 cells min(-1);P < or = 0.05). Leukocyte arrest was increased on day 8 (175.4 +/- 18.2 cells mm(-2)vs baseline of 59.7 +/- 7.1 cells mm(-2);P < or = 0.05) and day 10 (371.7 +/- 30.7 cells mm(-2)). CL(2)MDP-lip prevented leukocyte rolling (day 10: 16.6 +/- 1.8 cells min(-1)vs 30.7 +/- 2.9 cells min(-1); CL(2)MDP-lip vs untreated EMIU;P < or = 0.05) and arrest (day 8: 88.3 +/- 13 cells mm(-2); day 10: 128.5 +/- 12.9 cells mm(-2);P < or = 0.05). Empty-lip had no effect on leukocyte rolling (day 10: 34.8 +/- 4.2 cells min(-1)) or arrest (day 8: 159.3 +/- 12.9 cells mm(-2), day 10: 421.2 +/- 41.6 cells mm(-2)). CL(2)MDP-lip completely suppressed leukocyte emigration (11 +/- 2 cells microl(-1)vs 100 +/- 29 cells microl(-1); CL(2)MDP-lip vs empty-lip;P < or = 0.05) and protein extravasation into aqueous humor (2.7 +/- 0.3 mg ml(-1)vs 14.2 +/- 2.1 mg ml(-1); CL(2)MDP-lip vs empty-lip;P < or = 0.05), abrogated the TNF-alpha response (32.5 +/- 2.7 pg ml(-1)vs 954.9 +/- 216.3 pg ml(-1); CL(2)MDP-lip vs untreated EMIU;P < or = 0.05) and caused an attenuated and delayed elevation of IFN-gamma. CL(2)MDP-lip prevented the inflammatory reaction of EMIU and inhibited the increase of leukocyte-endothelium interaction in iris vessels. Our findings emphasize the pivotal role macrophages play in the initiation of autoimmune disease.

Analysis of Variance↗
PubMed2001

Modulation of leukocyte-endothelium interaction by nitric oxide synthase inhibitors: effects on leukocyte adhesion in endotoxin-induced uveitis.

OBJECTIVE AND DESIGN: To examine the effects of the nitric oxide synthase (NOS) inhibitors aminoguanidine (AG) and L-NAME on leukocyte adhesion in endotoxin-induced uveitis (EIU). MATERIAL: Uveitis was induced in Lewis rats (n = 124) by LPS injection (Salmonella typhimurium). TREATMENT: Rats either (1) did not receive any LPS or other treatments (controls), received (2) only subcutaneous saline injections with LPS administration, (3) a single s.c. dose of AG (100 mg/kg body weight) at the time of LPS administration, (4) a single s.c. injection of AG 8 h after LPS injection, (5) s.c. injections of AG at the time of LPS administration and 8 h after LPS injection or (6) received a single dose of L-NAME (75 mg/kg body weight) at the time of LPS administration. METHODS: Intravital microscopy (IVM) of iris vessels was performed at 2, 4, 8, 16, 24 and 48 h after endotoxin injection. Aqueous humor analysis for protein concentration and cell count was performed after IVM. RESULTS: At 2 h after the induction of uveitis, significantly more rolling leukocytes were detected in the AG and L-NAME-treated group than in untreated EIU (4.8 +/- 0.31 and 9.83 +/- 0.64 vs. 2.85 +/- 0.37%, mean +/- SEM, p < 0.01). However, at 16 h the percentage of rolling leukocytes was significantly reduced in all groups which had received AG (LPS: 8.08 +/- 0.37%; LPS/AG 0 h: 3.78 +/- 0.25%; LPS/AG 8 h: 5.34 +/- 0.3%; LPS/AG 0+8h: 3.86 +/- 0.31%). L-NAME enhanced leukocyte rolling even at 24 h after LPS (12.38 +/- 0.64%). Early treatment of EIU with AG significantly reduced the number of sticking leukocytes at 4, 8 and 24 h (306 +/- 13 vs. 571 +/- 41, 228 +/- 12 vs. 345 +/- 19 and 240 +/- 14 vs. 469 +/- 23 cells/mm2, respectively). L-NAME inhibited LPS-induced sticking of leukocytes at all observed time points and this effect was most pronounced at 24 h (147 +/- 10 vs. 469 +/- 23 cells/mm2). CONCLUSIONS: In EIU, administration of AG or L-NAME causes enhanced leukocyte rolling in the early inflammatory response. However, firm adhesion of leukocytes to the vascular endothelium decreases and this effect prevails, ameliorating leukocyte infiltration.

Animals↗
PubMed2001

[In vitro bovine and human lens epithelial cell culture studies on inhibition of posterior capsule opacification using a cyclic RGD peptide].

BACKGROUND: RGD peptides competitively inihibit adhesion molecules of the lens epithelial cells (LEC). The purpose of our study was to investigate whether this peptide is capable of detaching adherent cells and preventing posterior capsule opacification (PCO). METHODS: Cultures of bovine and human LECs on culture dishes and discs of bovine anterior lens capsules were used. The inhibition of adhesion and the detachment of confluent LEC layers by the cyclic RGD peptide cRGDdFV were studied (incubation time was 3 days and 1 h and concentrations of 10(-4) and 10(-3) M were used). RESULTS: A dose-dependent inhibition of adhesion (48% and 42%, respectively) was obtained. There was a significant difference between the control peptide group and cRGDdFV (p < 0.0001). Cell detachment from lens capsules was not achieved but complete detachment from the culture dish occurred after 37 min. CONCLUSIONS: Short-term incubation of LECs by cRGDdFV did not lead to a sufficient inhibition of adhesion in vitro. A detachment of adherent LECs by cRGDdFV was not achieved.

Adhesiveness↗
PubMed2001

[Analysis of the aqueous humor in keratoplasty patients with keratitis. Initial results].

OBJECTIVE: Herpetic keratitis is a common indication for corneal transplantation. In this patient group especially, there is a relatively high risk of graft failure, partly because of viral recurrence. It can be difficult to clinically distinguish stromal herpetic recurrence from early endothelial allograft rejection. Also a perioperative observation of viral activity seems advisable because of therapeutic consequences. For these reasons we use aqueous humor analysis in certain corneal transplant patients to determine intraocular antibody production. The aim of this study was to evaluate the diagnostic value of such an analysis of aqueous humor. MATERIAL AND METHODS: A total of 28 samples of aqueous humor were obtained from 24 eyes and all samples were tested for antibodies against herpes simplex virus (HSV), most samples (26/28) were tested for antibodies against varizella zoster virus (VZV) and some samples (6/28) for antibodies against cytomegalovirus. We used a modified micro-ELISA technique to detect intraocular IgG production. RESULTS: In 14 samples (50%) we found antibodies against HSV, in 7 samples (25%) against HSV and VZV, in 1 sample (3.6%) against VZV and 6 samples (21.4%) were negative for all antibodies tested. CONCLUSION: The results of aqueous humor analysis led to a specific local or systemic antiviral therapy perioperatively or in the case of postoperative recurrence of herpetic keratitis in most patients. Some patients could be spared long-term treatment with antiviral agents because of negative results in the aqueous humor analysis.

Adult↗
PubMed2001

[Gene therapy in ophthalmology. Review of options and trends in corneal diseases].

BACKGROUND: Gene therapy has gained increasing attention and a number of ongoing clinical trials have been initiated. This article provides current perspectives and limitations on gene therapy in ophthalmology. Since a number of comprehensive studies on gene therapy for retinal diseases already exist, we focus attention to the treatment of anterior segment disorders of the eye. MATERIAL AND METHODS: We undertook a reference search (DIMDI, PubMed) of articles published between (1989-2000) using the key words cornea, conjunctiva, eye, gene therapy, and keratoplasty. The search was restricted to publications in English, French and German. In addition, we incorporated some results of our recent experiments on cytokine gene transfer to the cornea. RESULTS: Attention to gene therapy in ophthalmology is currently focused on retina and choroidea (40 articles) however, an increasing number of publications includes the cornea (12 articles). The majority of these contributions deals with improvements in the design of gene therapy vectors in particular for targeted application. CONCLUSIONS: Gene therapy to the cornea may offer interesting new venues. Currently, insufficient gene transfer technologies and safety concerns prevent the broad application in humans. However, a broad spectrum of applications can be supposed.

Corneal Diseases↗
PubMed2001

[Transplantation of autologous oral mucosa in the treatment of a symblepharon in Wegener's disease--a case report].

BACKGROUND: Wegener's disease, an immune vasculitis, is characterized by granulomata and vasculitis of small and large vessels. Ocular manifestations are observed in approximately half of all cases. PATIENT: We report on a 58-year-old male with severe generalized Wegener's disease which was first diagnosed in 1986. The involvement of the central nervous system became clinically manifest by a stroke, of the kidneys by incipient renal insufficiency, and of the larynx by recurrent subglottic stenosis of the trachea. The first ocular involvement, a conjunctivitis, was observed in 1988. Despite systemic immuno-suppressive therapy, local conservative therapy and repeated surgical procedures, his vision decreased bilaterally from 60/60 to hand movement (OD) and light perception only (OS) during the following years because of a massive bilateral symblepharon. Transplantation of autologous oral mucosa to the conjunctiva led to a persistent increase of vision and a good cosmetic result. CONCLUSIONS: We conclude that in patients with Wegener's disease, who have developed a symblepharon despite intensive therapy, the transplantation of oral mucosa can produce a sufficient functional and cosmetic result.

Conjunctival Diseases↗
PubMed2001

Detection of Borrelia burgdorferi DNA in urine of patients with ocular Lyme borreliosis.

AIM: To evaluate the diagnostic value of the polymerase chain reaction (PCR) to detect Borrelia burgdorferi DNA in patients with ocular Lyme borreliosis. METHODS: Of 256 consecutive uveitis patients six selected individuals with clinical evidence for Lyme borreliosis and 30 patients with non-Lyme uveitis were enrolled. Lyme serology was performed by ELISA and western blotting. Urine samples were examined by an optimised nested polymerase chain reaction (PCR) protocol. RESULTS: Only four of six uveitis patients suspected for Lyme borreliosis were ELISA positive, while all six subjects showed a positive western blot. B burgdorferi PCR was positive in all of these six patients. Whereas two of the 30 controls had a positive Lyme serology, B burgdorferi DNA was not detectable by PCR in any sample from these patients. CONCLUSIONS: PCR for the detection of B burgdorferi DNA in urine of uveitis patients is a valuable tool to support the diagnosis of ocular Lyme borreliosis. Moreover, these patients often show a weak humoral immune response which may more sensitively be detected by immunoblotting.

Adult↗
PubMed2000

The role of endogenous growth factors to support corneal endothelial migration after wounding in vitro.

Previous studies have shown that corneal endothelial cells contain mRNA and protein of various growth factors. However, the role of these endogenous growth factors in corneal endothelial wound healing is not fully elucidated. In the present study, we investigated the role of endogenous factors and several growth factor inhibitors on migration of corneal endothelial cells in an in vitro model of wound healing. Bovine corneal endothelial cells (BCEC) were grown to confluency and experiments performed at passage 2 under serum reduced [2% fetal calf serum (FCS)] conditions. A central circular 'wound' (5 mm diameter) was made with an especially designed trephine. In different experiments, cells were incubated over different time periods (1-72 hr) either with the cellular debris produced by the wounding procedure or with previously prepared endothelial cell lysates (protein content 50-500 microg ml(-1)). Additionally, purified bovine polyclonal anti-BFGF antibodies (Ab) (4.5-27 microg ml(-1)), suramin (0.5 m M) or anti-FGF receptor-Ab (1 microg ml(-1)) were added to both experimental approaches, respectively. Migration was quantitated by counting the cells inside the denuded area in four different sections from the wound edge after 5 days. Cellular migration of cells adjacent to the wound was significantly stimulated by factors released during wounding or by endothelial cell lysates at protein concentrations >100 microg ml(-1). This increase in migrating cells was partially inhibited when the anti-bFGF antibody was incubated with the cell debris or the lysates. The addition of suramin at 0.5 m M almost completely blocked the migration activity. Incubation of the anti-FGF-receptor antibody prior to and >5 hr after wounding significantly reduced migration to nearly 50% of the rate in control cultures (P<0.001). In the present study, we demonstrate that intracellular growth factors released from corneal endothelial cells enhance the migration of surviving cells in vitro. The strong inhibitory effect of suramin indicates a major role of heparin-binding growth factors for cellular migration. bFGF and the regulation of bFGF-receptor expression on cells at the wound margin seem to be of crucial importance for the wound healing process.

Analysis of Variance↗
PubMed2000

Survival of corneal allografts following adenovirus-mediated gene transfer of interleukin-4.

BACKGROUND: Genetic manipulation of the donor cornea ex vivo prior to transplantation may allow modulation of the allogeneic immune response following penetrating keratopasty. In this study we investigated the effect of adenovirus-mediated gene transfer of the Th2 cytokine interleukin-4 (IL-4) to rat corneas in an experimental keratoplasty model. METHODS: Ex vivo manipulation of Wistar-Furth rat corneas was performed using E1/E3-deleted adenoviral vectors transferring the gene for rat IL-4 (AdrIL-4) under control of the CMV promoter. Following transfection with AdrIL-4 (2 x 10(8) pfu) in DMEM/2% FCS for 3 h, donor corneas were transplanted in MHC class I/II-incompatible Lewis rats. Fifty-two Lewis rats were randomly assigned to receive either nontransfected grafts (n=32), AdrIL-4-transfected grafts (n=8), or syngeneic grafts (n=12). RESULTS: The rejection rate of AdrIL-4-transfected grafts (85.7%) could not be reduced as compared to controls (62.9%). In addition, the mean survival time of AdrIL-4-transfected grafts (12.6+/-4.5 days) did not differ (P>0.05) from that for untreated transplants (14.1+/-3.8 days). CONCLUSIONS: Our results indicate that overexpression of IL-4 is not sufficient to reduce the rejection rate of corneal allografts in an experimental keratoplasty model. Further investigations are necessary to identify the reasons for failure and establish more efficient modulatory approaches.

Adenoviruses, Human↗
PubMed2000

Inhibition of corneal neovascularization by alpha(v)-integrin antagonists in the rat.

BACKGROUND: The proliferation of vascular endothelial cells and ultimately angiogenesis is inhibited by blocking integrin-mediated cell-matrix interaction. To asses the therapeutic potential of alpha(v)-integrin antagonists LM609 and cRGDfV in neovascularization of the anterior segment, their inhibitory effect on angiogenesis was studied in two rat models for corneal neovascularization. METHODS: Corneal neovascularization was induced in Wistar rats (n=51) either by silver nitrate burns or intrastromal implantation of polymer pellets containing 400 ng of fibroblast growth factor (bFGF). Animals were treated with subcutaneous injections of a cyclic alpha(v)-integrin antagonist (cRGDfV, 15 mg/kg body wt) or saline twice daily. Additional animals received intrastromal implants containing 400 ng bFGF together with either Lm609 (mAb, anti-alpha(v)beta(3)) or control antibody. Four days later, the animals were killed and the percentage of the surface area covered with vessels determined using digital image analysis. RESULTS: Systemic treatment with cRGDfV resulted in a significant reduction of corneal vessel growth in animals with bFGF-induced corneal vascularization. In corneas with silver nitrate burns, systemic cRGDfV treatment showed no significant reduction of vascularization compared with controls. Pellets containing bFGF and LM609 mAb induced significantly less neovascularization than pellets containing bFGF and control mAb. CONCLUSION: Our results suggest that in the rat cornea, alpha(v)beta(3) ligation does inhibit bFGF-induced neovascularization. A chemical burn of the cornea induces angiogenisis which is not inhibited by blocking alpha(v)-integrins. This suggests an angiogenic pathway independent of alpha(v)-integrins.

Animals↗
PubMed2000

Intraocular antibody production in intraocular inflammation.

BACKGROUND: The production of intraocular antibodies is considered a specific marker for active infectious uveitis. The aim of our study was to evaluate the diagnostic value of aqueous humor analysis in consecutive patients referred to a tertiary clinical center. METHODS: We analyzed 91 paired aqueous humor/serum samples from 89 patients with intraocular inflammation. In 71 patients aqueous humor analysis was used as a positive or negative confirmation of the suspected cause, whereas in 18 patients the clinical diagnosis was completely uncertain. A modified micro-ELISA technique was used to detect intraocular IgG production against Toxoplasma gondii, varicella zoster virus, herpes simplex virus and cytomegalovirus. Statistical analysis was performed using the "Cohen's kappa" test. RESULTS: Specific intra-ocular antibody production could be detected in 12 (66.7%) of 18 patients with uncertain diagnosis. Subsequently initiated therapy led to clinical improvement in 10 patients, whereas 2 patients remained unchanged. In 2 (2.8%) of 71 patients aqueous humor analysis led to revision of the initially suspected etiology and to a change of therapy. Statistical analysis showed a significant accordance of diagnosis and aqueous humor analysis (P<0.01). CONCLUSION: In patients with infectious uveitis, analysis of intraocular synthesis of specific antibodies is a valuable tool to establish the etiology rapidly and allows initiation of targeted antimicrobial treatment.

Antibodies, Protozoan↗
PubMed2000

Corneal endothelial toxicity of different lidocaine concentrations.

PURPOSE: To examine the potential damaging effect on the corneal endothelium of unpreserved lidocaine in concentrations of 1%, 5%, and 10%. SETTINGS: Department of Ophthalmology, Charité Medical Faculty, Humboldt University, Berlin, Germany. METHODS: Experimental porcine corneas (n = 18) were exposed to 100 microL of unpreserved lidocaine hydrochloride at concentrations of 1%, 5%, and 10% for 60 minutes. Additional corneas (n = 6) were treated with lidocaine hydrochloride 1% for 30 minutes to simulate clinical conditions. Balanced salt solution (BSS((R))) served as a control to evaluate corneal endothelial cell damage using Janus Green photometry. Morphology, damage pattern, and changes in the ultrastructural appearance of corneal endothelial cells were examined by light and scanning electron microscopy. RESULTS: Lidocaine 1% used for 30 or 60 minutes did not cause significantly more corneal endothelial damage (mean 3.00% +/- 0.76% [SD] and 3.26% +/- 1.00%, respectively) than in the control group (mean 3.32% +/- 0. 86%) (P >.01). Significant corneal endothelial cell loss was observed with lidocaine 5% (mean 10.7% +/- 6.4%) (P <.001) and lidocaine 10% (42.3% +/- 17.0%) (P <.001). CONCLUSION: Experimental exposure of corneal endothelial cells to higher concentrations of lidocaine resulted in significant cell loss, indicating that the 1% concentration only should be used clinically.

Anesthesia, Local↗
PubMed2000

Detection of tumor necrosis factor alpha and interleukin 1 alpha gene expression in human lens epithelial cells.

PURPOSE: To analyze the gene expression of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) in human lens epithelial cells (LECs) by in situ RNA hybridization. SETTING: Department of Ophthalmology and Laboratory for Molecular Biology, Charité, Humboldt University, Berlin, Germany. METHODS: Anterior lens capsules with attached LECs were collected in RNase-free conditions from 10 consecutive patients during cataract surgery. Samples were then systematically analyzed by an in situ RNA-hybridization technique using specific gene probes for IL-1 alpha and TNF alpha, which were previously labeled with digoxigenin (DIG). RESULTS: The LECs tested positive for DIG-labeled gene probes in the described conditions. One (10%) patient showed a clearly detectable IL-1 alpha gene expression, and 7 (70%) showed a widely positive reaction for TNF alpha mRNA. CONCLUSION: The TNF alpha gene expression in LECs was more extended than that of IL-1 alpha in lens capsule samples from cataract surgery. Active synthesis of TNF alpha and IL-1 alpha may have consequences for postoperative inflammation and LEC proliferation.

Aged↗
PubMed2000

[Acute retinal necrosis syndrome: analysis, therapy and long-term follow up of 14 eyes].

PURPOSE: Acute retinal necrosis syndrome (ARN) might be complicated by retinal detachment, vasculopathy and optic neuropathy and has a poor prognosis despite intensive medical and surgical therapy. PATIENTS AND METHODS: A series of 10 consecutive patients (14 eyes) with ARN were followed for 36 months (average of 20 months +/- 10). We present the results of the clinical evaluation for diagnostic and therapeutic modalities. RESULTS: Viral etiology was confirmed in 9 of 10 aqueous-humor samples. Intraocular antibody synthesis against Varicella-Zoster Virus was found in 7, against Herpes-Simplex Virus in 5 and against Cytomegalovirus in 2 samples. Three eyes had a mild clinical course with a visual acuity of 0.6 or better. Vitrectomy and silicone-oil tamponade preserved visual acuity from 0.3 to 0.1. ARN lead to blindness in 5 eyes due to vasculopathy, optic neuropathy or retinal detachment. An arterial branch occlusion was successfully overcome with i.v. heparin treatment in one patient. CONCLUSION: Aqueous-humor analysis supports clinical diagnosis. Early vitrectomy and silicone oil tamponade stabilizes retinal structure and preserves visual acuity. Occlusive vasculopathy and optic neuropathy are the main causes leading to blindness.

Acyclovir↗