Search PubMed⌕ Search

Biomedical subjects

E Wandel

Publications and source records attributed to E Wandel.

At least 19 recordsLinked to original sources
PubMed2000

Fibroblasts surrounding melanoma express elevated levels of matrix metalloproteinase-1 (MMP-1) and intercellular adhesion molecule-1 (ICAM-1) in vitro.

Tumour growth and metastasis involve the degradation of extracellular matrix components by matrix degrading enzymes produced by tumour cells and stromal fibroblasts. In this study, fibroblasts were obtained from biopsies on the border (TB) and 1 cm distant from the melanoma (TD) and cultured separately. Similar studies were performed with fibroblasts surrounding melanocytic nevi as control. The expression of matrix metalloproteinase-1 (MMP-1) mRNA and tissue matrix metalloproteinase inhibitor 1 (TIMP-1) were studied by Northern blot analysis. The activation antigen intercellular adhesion molecule-1 (ICAM-1) in TB-and TD-fibroblasts was investigated by flow cytometry. In melanoma, TB-fibroblasts showed an increased expression of MMP-1 mRNA mainly in fibroblasts obtained from tumours with extended invasive growth demonstrated by Clark level whereas the expression of the major specific inhibitor TIMP-1 was unaltered. In contrast, fibroblasts surrounding benign melanocytic nevi did not express elevated levels of MMP-1. The upregulation of MMP-1 in TB-fibroblasts compared to TD-fibroblasts was maintained during cultivation. Furthermore, MMP-1 mRNA expression and MMP-1 total protein amount in normal fibroblasts were increased by melanoma cell conditioned medium. We demonstrated an increased expression of ICAM-1 in TB-fibroblasts compared to TD-fibroblasts in vitro depending on the amount of inflammatory infiltrate in situ. The differences of ICAM expression disappeared during continued cell culture. These results support the idea that fibroblasts surrounding melanoma are activated and are possibly involved in the degradation of matrix proteins surrounding the tumour.

Culture Media, Conditioned↗
PubMed2000

Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis.

BACKGROUND: Wegener's granulomatosis (WG) is characterized by systemic vasculitis with crescentic glomerulonephritis (CGN) and circulating autoantibodies directed against neutrophil cytoplasmic antigens (ANCA). Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid cells, has been identified as the target antigen for ANCA in WG. Since the kidneys are frequently involved in WG, we studied the in situ expression of PR-3 by renal parenchymal cells. METHODS: We assessed the expression of PR-3 in kidney biopsies of 15 patients with WG by immunohistochemistry (IHC) and in situ hybridization (ISH). Normal kidney tissue served as the control. RESULTS: We detected PR-3 mRNA and PR-3 protein in distal tubular epithelial cells (TECs) and glomerular epithelial cells (GECs) in normal kidney tissue and in CGN. Furthermore, a strong glomerular PR-3mRNA expression restricted to the site of cellular crescents was detected in patients with WG. The analysis of 144 glomeruli with cellular or sclerotic crescents revealed a positive correlation of glomerular PR-3mRNA expression with the percentage of cellular crescents per glomerulus. The capability of human TECs and GECs to synthesize PR-3 was confirmed by Northern blot and ISH on cultured cells. CONCLUSION: These data provide evidence that nonhematopoetic renal parenchymal cells express PR-3 and that glomerular expression of PR-3 is associated with crescent formation in WG. Our findings suggest that renal parenchymal cells may directly be involved in the pathogenesis of CGN in WG.

Adult↗
PubMed2000

Reduced secretion of proinflammatory cytokines of monosodium urate crystal-stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients?

BACKGROUND: In gouty arthritis, monosodium urate (MSU) crystals interact with monocytes and neutrophils to produce inflammatory reactions associated with acute synovitis. In patients with end-stage renal disease (ESRD), gouty arthritis is a rare condition despite often severe hyperuricaemia. We wondered whether differences in the secretion of proinflammatory cytokines by MSU crystal-stimulated monocytes might be one explanation for the low incidence of gouty arthritis in patients with ESRD compared with healthy controls. METHODS: Thirteen patients with ESRD on intermittent haemodialysis treatment, six patients with chronic renal failure not yet on dialysis, and 15 age- and sex-matched healthy controls were examined. Monocytes, purified from peripheral blood mononuclear cells (PBMC) by immunomagnetic bead separation, were incubated for 18 h in the presence of MSU crystals, Escherichia coli lipopolysaccharide (LPS) or medium alone. The supernatants were studied for the presence of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) using cytokine-specific enzyme-linked immunosorbent assays. RESULTS: Monocytes from patients with ESRD produced significantly lower amounts of IL-1beta, IL-6 and TNF-alpha after stimulation with MSU crystals or LPS than did monocytes from healthy subjects. Cytokine production was not significantly different between ESRD patients on haemodialysis and chronic renal failure patients not yet on dialysis. Artificial MSU crystals were stronger stimuli than tophus-derived 'natural' MSU crystals. CONCLUSION: We demonstrate that monocyte-associated immunosuppression in ESRD leads to reduced secretion of proinflammatory cytokines in response to stimuli such as MSU crystals. This may be one of the factors preventing many ESRD patients from the manifestation of acute gout despite often severe hyperuricaemia.

Adult↗
PubMed1998

Pain and pyuria.

Explore the source record for details and available documents.

Analgesics↗
PubMed1997

The use of computer-assisted video image analysis for the quantification of CD8+ T lymphocytes producing tumor necrosis factor alpha spots in response to peptide antigens.

Enzyme-linked immunospot (ELISPOT) analysis is a sensitive technique for the detection and quantification of single T lymphocytes forming cytokine spots after antigen contact in vitro. Herein computer-assisted video image analysis (CVIA) was applied to automatically determine the number and size of tumor necrosis factor alpha (TNF-alpha) spots formed by single blood-derived CD8+ T cells after contact with peptide-loaded target cells. With CVIA and TNF-alpha ELISPOT analysis we quantified CD8+ T cells responsive to HLA-A2.1-binding tyrosinase and influenza matrix peptides in healthy donors. We followed the course of the virus-specific T cell response in two HLA-A2-positive patients with reactivation of latent cytomegalovirus (CMV) infection during immunosuppressive therapy. The test proved sufficiently sensitive to detect in the blood of both patients a temporary expansion of CD8+ T lymphocytes reactive with a known immunogenic HLA-A2.1-binding peptide from glycoprotein B of CMV. Reactivity to peptide antigens was not only reflected by numeric increases of spot formation, but also by the appearance of larger spot areas, presumably formed by strongly peptide-reactive CD8+ T cells. We conclude that the combined use of the TNF-alpha ELISPOT assay and CVIA allows reliable monitoring of the T cell responsiveness to peptide antigens in peripheral blood.

Adult↗
PubMed1997

[Prospective observational study of surgical therapy of renal hyperparathyroidism].

A prospective long-term follow-up study in patients who had had surgical therapy for renal hyperparathyroidism was launched to investigate the results of surgical treatment and to evaluate possible correlations between preoperative laboratory values and the course of symptoms. From August 1987 to December 1995, 79 patients underwent surgery for renal hyperparathyroidism. It was the first neck exploration for 72 patients. Total parathyroidectomy with autotransplantation to a forearm was our preferred procedure (n = 67). The postoperative course of all patients is know. We carried out one to nine reexaminations (median 4) in 74 of 79 patients. The follow-up period ranged from 1 month to 5 years with a median of 18 months. After the operation transient hypocalcaemia occurred in 84.4% of patients. Postoperative hypocalcaemia correlated negatively with the preoperative levels of alkaline phosphatase and intact parathyroid hormone. Within the first month after surgery 60% of the preoperatively affected patients completely recovered from pruritus, whereas the skeletal syndrome took longer to disappear. One year after surgery 75% of the patients with pruritus and 79% of those with skeletal syndrome had became asymptomatic. After total parathyroidectomy with autotransplantation, patients with preoperatively elevated concentrations of alkaline phosphatase (> 200 U/I) experienced faster relief from joint pain than patients with preoperatively normal concentrations (P = 0.0297). To date 4.5% of the patients developed recurrent hyperparathyroidism after total parathyroidectomy with autotransplantation. Morbidity of surgery for renal hyperparathyroidism is influenced by patients' risk factors. Postoperative hypocalcaemia correlates negatively with the grade of renal osteopathy at the time of operation. Preoperative concentrations of alkaline phosphatase influence the rapidity of the relief from joint pain.

Adult↗
PubMed1997

[Surgical management of dysfunctions of dialysis fistulas].

Due to the superficial position of shunt vessels we do not use complicated equipment or diagnostic procedures in the morphological assessment of shunt insufficiency or shunt occlusion. Preoperatively, we merely conduct a clinical examination including inspection, pulse, palpation of the shunt veins and arteries with and without venous congestion, and shunt auscultation. Subsequently, we reoperate the shunt under local anesthesia, at which time the anastomosis is usually checked and repositioned. From January 1995 to May 1996, 539 shunt operations were performed in 371 patients, whereby 263 of these were reoperations. The reoperations were performed due to shunt occlusion (n = 144), shunt stenoses (n = 60), shunt aneurysms (n = 17), steal syndrome (n = 3), and rare complications such as hematoma, shunt infection, seroma, and other disturbances (n = 6) (32 patients were treated in other clinics after reoperation or the functional disturbance of the shunt was not recorded). Angiography was only conducted if the clinical examination did not provide enough information about the shunt problems, and so, preoperatively, only six angiographic examinations were conducted (stenosis, n = 3; aneurysm, n = 1; steal syndrome, n = 2). All reoperations, with only few exceptions (PTFE shunt), were conducted under local anesthesia. At reoperation, 184 new proximal shunts were made, 14 thrombectomies conducted, seven PTFE fistulas made, 13 shunts positioned on the opposite side, five shunts ligated, and eight various other operations performed (32 patients were given further treatment elsewhere or no treatment records were available). If during reoperation flow disturbances were suspected (arterial stenosis) or the blood was flowing towards center (proximal venous stenosis) angiography was performed intraoperatively to assess the condition of the vessels. The 4% rate of early occlusion using this procedure was very low. Only 21 patients had to have more than two reoperations. After 2 years 65% of the reoperated AV fistulas were still functional. Without further diagnostic procedures, we performed immediate, outpatient reoperation under local anesthesia, preferably positioning new proximal shunts so that dialysis could be conducted immediately using the existing dialysis shunt. Only if there were particularly complex functional shunt disturbances (steal syndrome, proximal venous flow disturbance, or arterial stenosis) did we employ other diagnostic procedures (angiography, DSA). With this approach the functional shunt disturbances could be eliminated quickly and effectively, which also minimized the cost and stress for the patient.

Adult↗
PubMed1995

[Tubulointerstitial nephritis-uveitis syndrome (TINU syndrome)].

For 10 weeks a 25-year-old man had been suffering from tiredness, fatigue, nausea and a 16 kg weight loss. Erythrocyte sedimentation rate (83/133 mm), serum C-reactive protein (5.5 mg/dl) and creatinine (5.05 mg/dl) were all elevated. He also had proteinuria (1120 mg daily), sterile leukocytosis and a creatinine clearance of 10 ml/min. Renal biopsy showed interstitial nephritis and bone marrow biopsy revealed non-caseous epithelioid-cell granulomas. 14 days after admission he developed acute iritis in the right eye. Other causes having been excluded, the diagnosis of tubulo-intestinal nephritis with uveitis (TINU syndrome) was made. The clinical symptoms and laboratory findings improved within a few days of the start of glucocorticoid treatment (initially, 100 mg prednisone daily, reduced to 5 mg within 30 days). The patient was discharged after 8 days in good general condition.

Acute Disease↗
PubMed1995

[Diagnosis of dysfunctions of replanted parathyroid gland tissue by bilateral analysis of intact parathyroid hormones in cubital vein blood. A prospective study].

AIM: In a prospective long-term follow-up study after operative therapy of hyperparathyroidism the value of bilateral determination of parathyroid hormone levels in cubital venous blood after total parathyroidectomy/autologous parathyroid gland reimplantation (musculus brachioradialis) for diagnosis of dysfunctioning grafted tissue is evaluated. PATIENTS AND MATERIAL: From August, 1, 1987 to March, 31, 1994 68 of 243 patients operated on for hyperparathyroidism underwent total parathyroidectomy. Autologous reimplantation of parathyroid gland was carried out simultaneously in 64 patients. Twice delayed reimplantation of cryopreserved tissue was carried out, and there was no reimplantation in two patients up to this day. Three patients were operated on for hyperfunctioning parathyroid autograft after former total parathyroidectomy/reimplantation. RESULTS: During follow-up 5 patients developed dysfunction of (reimplanted) parathyroid gland. Because of low or unprovable levels of intact parathormone the gradients of intact parathyroid hormone between grafted and nongrafted forearm were about 1:1 in postoperative hypoparathyroidism as well as in hypofunction of parathyroid gland. After successful replantation of cryopreserved parathyroid tissue gradients of intact parathyroid hormone increased (> 1:10). In hyperfunction of grafted parathyroid tissue hormone gradients were high (> 1:20 to 1:45,3) because of excessive high levels of intact parathormone in the cubital vein of the graft bearing arm. Successful reduction of parathyroid graft was followed by decrease of parathyroid hormone gradients. CONCLUSION: Regular follow-up of intact parathormone gradients together with intact parathyroid hormone levels and serumcalcium analysis allow the determination of parathyroid graft function. Also differentiation between graft dependent hyperparathyroidism and hyperfunctioning parathyroid tissue in the neck or mediastinum seems to be possible by bilateral determination of intact parathormone. Normal values or a normal range for intact parathyroid hormone gradients can not yet be defined.

Adult↗
PubMed1995

Dissection of the internal carotid artery after chiropractic manipulation of the neck.

A 29-year-old woman died from a right hemispheric infarction caused by dissection and subsequent thrombosis of the internal carotid artery after chiropractic manipulations of the neck. Pathologic study of several arteries of muscular and elastic type revealed a mediolytic arteriopathy with widespread mucoid degeneration and cystic transformation of the vessel wall caused by segmental degeneration of smooth muscle cells of the tunica media. We hypothesize that mediolytic arteriopathy was a predisposing factor for the dissection of the internal carotid artery after chiropractic manipulations in our patient.

Adult↗