[Spectroscopic investigation of the middle ear mucosa]. / Spektroskopische Untersuchung der Mittelohrschleimhaut.

BACKGROUND: The middle ear mucosa (MEM) plays a central role in the middle ear due to its function of providing regular ventilation. To date, assessment of the state of the MEM is only possible subjectively by the surgeon. An objective characterization of the state of the MEM is desirable. OBJECTIVE: The aim of this study was to enable objective characterization of the MEM and test infrared (IR) spectroscopy as a possible diagnostic tool for clinical use. MATERIALS AND METHODS: During middle ear surgery, 48 MEM samples were collected and divided into four groups according to clinical appearance: group I: normal MEM; group II: sclerotic MEM; group III: inflammatory thickened MEM; group IV: granulated MEM. After collection, samples were analyzed by IR spectroscopy to identify characteristic IR spectra. RESULTS: In the supervised analysis of the selected images, the biochemical differences representing the decisive factors for classification into groups I to IV were characterized. The differences in amide bands, carbohydrates, lipids, and proteins permit reliable separation of the clinical categories. CONCLUSION: Spectroscopic investigations enable objective characterization of the MEM. Conclusions regarding biochemical differences make it possible to weigh up treatment options. Routine use of IR spectroscopy in the operating theater requires histopathological comparison and an extended dataset with reference values of the individual groups.

From autoantibody research to standardized diagnostic assays in the management of human diseases - report of the 12th Dresden Symposium on Autoantibodies.

Testing for autoantibodies (AABs) is becoming more and more relevant, not only for diagnosing autoimmune diseases (AIDs) but also for the differentiation of defined AID subtypes with different clinical manifestations, course and prognosis as well as the very early diagnosis for adequate management in the context of personalized medicine. A major challenge to improve diagnostic accuracy is to harmonize or even standardize AAB analyses. This review presents the results of the 12th Dresden Symposium on Autoantibodies that focused on several aspects of improving autoimmune diagnostics. Topics that are addressed include the International Consensus on ANA Patterns (ICAP) and the International Autoantibody Standardization (IAS) initiatives, the optimization of diagnostic algorithms, the description and evaluation of novel disease-specific AABs as well as the development and introduction of novel assays into routine diagnostics. This review also highlights important developments of recent years, most notably the improvement in diagnosing and predicting the course of rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, and of autoimmune neurological, gastrointestinal and liver diseases; the potential diagnostic role of anti-DFS70 antibodies and tumor-associated AABs. Furthermore, some hot topics in autoimmunity regarding disease pathogenesis and management are described.

Expression patterns of CD44 and CD44 splice variants in patients with rheumatoid arthritis.

OBJECTIVES: It has been suggested that CD44 is involved in the pathogenesis of rheumatoid arthritis (RA). By alternative splicing, numerous CD44 isoforms can be generated which may play different roles the inflammatory process. We therefore studied the expression of various CD44 splicevariants in the circulation and synovial tissue of patients with RA and correlated expression with clinical features. METHODS: Expression of distinct CD44 splice variants was analysed by FACS in peripheral monocytes of 46 RA patients and 36 healthy controls. Expression of CD44 splice variants in synovial tissue of RA and OA patients was analysed by immunohistochemistry and the effects of blocking CD44v4 on RA-fibroblast like synoviocytes (FLS) were studied. RESULTS: On monocytes, the expression of CD44 and CD44v3 was significantly lower in patients with erosive disease than in those without radiographic progression (p<0.05 for CD44 and p<0.01 for CD44v3). CD44v6 on monocytes was significantly associated with the clinical disease activity index (r=0.34, p<0.05) and CRP-levels (r=0.37, p<0.02). Immunhistochemical analyses revealed that most variants were expressed to a significantly higher extent in RA than in OA synovial membranes. Particularly the variants CD44v4, CD44v6 and CD44v7-8 were highly expressed in the RA lining and also abundantly in the endothelium. Blocking CD44v4 in RA-FLS reduced the proliferation to 68±8% (p<0.02) when compared to control experiments and led to a reduction in IL-1ß mRNA expression (p<0.05). CONCLUSIONS: Expression of CD44 splice variants is generally increased in the synovial lining of RA patients when compared to OA. The inverse association of CD44v3 expression on monocytes with the development of erosive disease and the functional impacts of CD44v4 blockade in RA-FLS suggests a pathogenetic role of this splice variants which needs to be further investigated.

Inhibitors of p38 and ERK1/2 MAPkinase and hydrogen sulphide block constitutive and IL-1ß-induced IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2.

Mitogen-activated protein kinases (MAPKs) play a central role in inflammatory processes, and their blockage represents pharmacological approaches in the treatment of autoimmune diseases like rheumatoid arthritis (RA). Alternatively, H(2)S has long been used in sulphur bath therapy for patients suffering from different types of rheumatic disorders, but reports about the beneficial effects of this form of therapy are controversial, rare and of poor scientific quality. The human chondrocyte cell line C-28/I2 was treated with two different MAPK inhibitors (SB203580 and U0126) or with various concentrations of the H(2)S donor Natrium hydrogen sulphide (NaHS). Thereafter, the secretion of IL-6 and IL-8 was quantified by enzyme-linked immunosorbent assays (ELISAs). The impact of NaHS on the regulation of p38 and ERK1/2 MAPK was confirmed by Western blot experiments. Furthermore, IL-6 and IL-8 expression was quantified by real-time polymerase chain reaction (RT-PCR) and ELISAs from cells which were exposed to SB203580, U0126 and NaHS and stimulated by IL-1ß. The C-28/I2 cells constitutively expressed large quantities of IL-6 and IL-8. The data provided prove that in these cells, constitutive as well as IL-1ß-induced IL-6 and IL-8 expression was partially and transiently blocked by the treatment of cells with both MAPK inhibitors and NaHS. Presented data seem to be important in evaluating the beneficial functions of MAPK inhibitors and H(2)S in immune-pathophysiological processes.

El colgajo fasciocutáneo en cono / Use of a new cone shaped flap to cover skin defects: experience in 108 patients

Background: A new type of fasciocutaneous flap with the shape of an ice cream cone that is formed by locally rotated and V-Y advance flaps joined together, that can be used to cover complex defects, was developed. Previously, the irrigation of these flaps was ascertained in the legs of ten corpses. Aim: To report the results with the use of this type of ice cream cone shaped flap. Material and Methods: Retrospective analysis of 108 patients aged 20 to 52 years (99 males) in whom an ice cream cone shaped flap was used. Results: The defects covered were located in the leg in 27 percent, in the ankle in 10 percent, in the sole in 9 percent, in the heel in 8 percent and in other locations in the rest of patients. Eighty flaps (74 percent) had a good evolution, 11 (10 percent) had a major dehiscence, 13 (12 percent) had a minor dehiscence and 4 flaps (4 percent) had necrosis. Conclusions: This ice cream cone shaped flap is easy to use, safe and devoid of complications in most cases.

Se presenta un colgajo no descrito previamente en la literatura internacional ni nacional. El colgajo se denomina "en cono" por la forma final que se obtiene un barquillo de helado con su bocado. Consta de 2 colgajos acoplados: uno de rotación local y otro un avance en V-Y, ambos fasciocutáneos. Para comprobar su irrigación se practicó disección anatómica de las piernas de 10 cadáveres frescos inyectando azul de metileno y bario en la arteria poplítea. El resultado demostró un rico y amplio plexo tanto infra como supra fascial que irriga muy bien la piel de ambos colgajos a nivel de 1/3 distal de la pierna. Se realizó también un análisis geométrico del avance en V-Y para demostrar como los tejidos pueden avanzar y para determinar las dimensiones que debe tener este colgajo. Se operó 108 pacientes con lesiones en diferentes partes del organismo con complicaciones de un 3,7 por ciento. Los resultados permitieron determinar que el colgajo en cono es versátil, reproducible, sencillo y seguro de realizar. Es un colgajo que servirá para que los cirujanos plásticos resuelvan complejos problemas quirúrgicos en forma muy segura y a bajo costo.

Does damage cause inflammation? Revisiting the link between joint damage and inflammation.

Rheumatoid arthritis (RA) is characterised by both inflammation, as manifested by pain and swelling, and destruction of the joints. Unequivocal evidence indicates that disease activity, and thus the inflammatory response, is linked to joint damage. From this viewpoint we suggest that, vice versa, joint damage might be a cause of the active disease process, thus leading to a vicious cycle of events. The background to this notion stems from the known autoimmune response in RA, the potential of cartilage and bone breakdown products to elicit inflammation and notions that in joints that have undergone surgery with cartilage removal RA does not flare. However, the clinical evidence for this relationship is still to be provided as proof of the concept.

Characterisation of cellular and humoral autoimmune responses to histone H1 and core histones in human systemic lupus erythaematosus.

OBJECTIVE: To address key aspects of anti-histone autoimmunity in systemic lupus erythaematosus (SLE), we performed a detailed characterisation of cellular and humoral autoreactivity to histone H1 and the four core histones H2A, H2B, H3, H4 in patients with SLE and healthy controls. METHODS: Peripheral blood mononuclear cells of 41 patients with SLE and 28 healthy controls were exposed to individual histones and proliferation was measured by [(3)H]-thymidine incorporation. H1-reactive T cell clones were obtained by limiting dilution. Cytokines and total IgG in culture supernatants was measured by ELISA, and autoantibodies to histones were determined by ELISA and immunoblotting. RESULTS: Proliferative responses to H1 were more frequent and more pronounced in cell cultures from patients with SLE (p<0.002), while among the core histones only the response to H2A was increased in patient cultures (p<0.01). All histones elicited a Th1-like cytokine response in patients and controls (high interferon (IFN)gamma and tumour necrosis factor (TNF)alpha, no interleukin (IL)4) with H1 inducing the highest levels of TNFalpha. However, H1 stimulated production of IgG and anti-histone antibodies only in cell cultures derived from patients with SLE. H1-specific T cell clones from patients and controls showed a CD4+CD28+ phenotype and a Th1 cytokine profile. Anti-histone antibodies were detected in 51% of patients with SLE, were primarily directed to H1, H3 and H4, and predominantly of the IgG2 subtype. CONCLUSIONS: Histone H1 constitutes a major B cell and T cell autoantigen in SLE, triggering a proinflammatory Th1 response and driving autoantibody production. This suggests that histone H1 may be of considerable relevance for the pathogenesis of SLE.

Systemic lupus erythematosus patients exhibit functional deficiencies of endothelial progenitor cells.

OBJECTIVE: SLE is characterized by an increased cardiovascular risk. Since endothelial progenitor cells (EPCs) have been described to serve as a biomarker for the CV risk and are known to be depleted in various diseases, we were interested if SLE would also be associated with altered peripheral EPC levels or functional abnormalities of these cells. METHODS: EPCs were quantified in 31 female SLE patients with different disease activity and in age-matched healthy controls (HCs) by FACS analysis and by colony forming unit (CFU) assay. Furthermore, EPC adhesion and migration capacity were tested. RESULTS: EPC levels were similar in HC and SLE when assessed by FACS (0.045 +/- 0.006% vs 0.036 +/- 0.007% within the lymphocyte gate) and by the CFU assay (18 +/- 3 vs 15 +/- 2 colonies/well). No correlation with disease activity could be observed, but SLE patients treated with chloroquine exhibited significantly decreased EPC levels (0.058 +/- 0.005% without vs 0.024 +/- 0.008% with chloroquine, P < 0.05). Addition of chloroquine to in vitro cultures also led to a decreased colony formation in SLE and in HC. When testing the adhesion and migration capacity of EPC on human umbilical vein endothelial cells (HUVEC), cells from SLE patients had reduced adhesion (19.2 +/- 3.5% vs 36.6 +/- 5.2% EPC/high power field, P < 0.02) and migratory activity (56 +/- 6 cells/random microscopic field in SLE vs 121 +/- 28 in controls, P < 0.02). CONCLUSION: The data reveal that EPCs are significantly affected in SLE. While circulating EPC levels are in the range of HC, they exhibit functional deficiencies that may lead to impaired tissue availability.

A bio-electromechanical imaging technique with combined electrical impedance and ultrasound tomography.

Electrical impedance tomography (EIT) seeks to image the electrical conductivity of an object using electrical impedance measurement data at its periphery. Ultrasound reflection tomography (URT) is an imaging modality that is able to generate images of mechanical properties of the object in terms of acoustic impedance changes. Both URT and EIT have the potential to be used in various medical applications. In this paper we focus on breast tumour detection. Both URT and EIT belong to soft field tomography and suffer from the small amounts of available data and the inherently ill-posed nature of the inverse problems. These facts result in limited achievable reconstruction accuracy and resolution. A dual bio-electromechanical tomography system using ultrasound and electrical tomography is proposed in this paper to improve the detection of the small-size tumour. Data fusion techniques are implemented to combine the EIT/URT data. Based on simulations, we demonstrate the improvement of detection of small size anomalies and improved depth detection compared to single modality soft field tomography.

[Spontaneous vesicoacetabular cutaneous fistula after total hip replacement]. / Spontane vesikoazetabulo- kutane Fistel nach Implantation einer Hüftgelenktotalendoprothese.

Vesicoacetabular cutaneous fistula is a rare but severe complication after total hip replacement. Diagnosis is based on clinical symptoms as well as radiologic and endoscopic findings. Therapy, however, requires an interdisciplinary approach. Anuria was the leading symptom in this case. After verifying the diagnosis, the prosthesis was completely removed, the fistula was excised, and the bladder was closed in multiple layers using an omentum majus flap. The patient was mobilized early and is content to date with the situation.

Superselective embolization of arterial bleeding as a late complication 3 months after nephron sparing surgery for renal cell carcinoma.

To our knowledge, this is the first case of an arterial bleeding as a late complication 3 months after nephron sparing surgery of renal cell cancer, presumably originating from an arteriocalyceal fistula. Superselective embolization of the feeding arterial branch was chosen for treatment of the hemorrhage and proved successful. The high efficacy of superselective embolization as a minimally invasive procedure in this and other cases of bleeding Vessels should be the preferred method instead of open surgery.

Over-expression of anti-CD75 reactive proteins on distal and collecting renal tubular epithelial cells in calcium-oxalate stone-forming kidneys in Egypt.

OBJECTIVE: To assess the nature, distribution and expression pattern of CD75, a neuraminidase-sensitive lymphocyte cell surface differentiation antigen, in calcium oxalate (CaOx) stone disease, as cell-surface sialic acid might be involved CaOx crystal binding, and lectin-binding assays suggest that sialic acid in the alpha2,6 position is upregulated in stone-forming kidneys. MATERIALS AND METHODS: Human CaOx stone-forming and normal kidneys (13 each) and primary kidney epithelial cells (CAKI-1, three samples) were analysed. The protein pattern, distribution and expression of CD75 were analysed using Western blotting, immunohistology and semi-quantitative confocal laser scanning microscopy (cLSM). Production was investigated by alpha2,6-sialyltransferase specific reverse transcription-polymerase chain reaction. RESULTS: Western blotting showed one strong band at approximately 43 kDa that reacted with anti-CD75 when renal epithelial and CAKI-1 tumour cell extracts were analysed. However, in renal tissue extracts of CaOx stone formers there were additional bands at 120 and 205 kDa. Image processing after cLSM showed that anti-CD75 reactivity was significantly greater on E-cadherin-positive distal and collecting tubular cells from CaOx stone-forming kidneys, at a mean (sd) intensity of 87 (7), than on those from normal kidneys, at 41 (5) (P = 0.005). CONCLUSION: CD75 expression in human kidney was primarily on the luminal surface of distal tubules and collecting ducts. Whether increased epithelial CD75 expression in CaOx stone disease is a cause or result of the disease remains to be clarified.

TNFalpha mediates susceptibility to heat-induced apoptosis by protein phosphatase-mediated inhibition of the HSF1/hsp70 stress response.

TNFalpha uniquely combines proinflammatory features with a proapoptotic potential. Activation of HSF1 followed by induction of hsp70 is part of a stress response, which protects cells from apoptosis. Herein, the effects of TNFalpha on the hsp70 stress response were investigated. TNFalpha caused transient downregulation of HSF1 activation and hsp70 synthesis, leading to increased sensitivity to heat-induced apoptosis. Blockade of TNF-R1, but not TNF-R2, as well as inhibition of protein phosphatases PP1/PP2a and PP2b completely blocked this effect. In contrast, blockade of MAPK/SAPK-, NF-kappaB (NF-kappaB)-, and PKC- pathways as well as the caspase cascade did not prevent downregulation of HSF1/hsp70. These data demonstrate that TNFalpha transiently inhibits the hsp70 stress response via TNF-R1 and activation of protein phosphatases. The price of inhibition of an essential cellular stress response is increased sensitivity to apoptotic cell death.

[Gemcitabine/cisplatin vs. MVAC. 5 year survival outcome of the phase III study of chemotherapy of advanced urothelial carcinoma in Germany]. / Gemcitabin/Cisplatin vs. MVAC. 5-Jahres-Ergebnisse der Phase-III-Studie zur Chemotherapie des fortgeschrittenen Urothelkarzinoms in Deutschland.

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

Cell-surface matrix proteins and sialic acids in cell-crystal adhesion; the effect of crystal binding on the viability of human CAKI-1 renal epithelial cells.

OBJECTIVE: To investigate the role of sialic acids and cellular matrix proteins as crystal-binding molecules in human calcium-oxalate nephrolithiasis. MATERIALS AND METHODS: The well-defined human renal cancer cell line CAKI-1 was used a standard cell culture system. After enzymatic digestion of various cell surface molecules, the binding of alpha2,6 (Sambucus nigra, SN-) and alpha2,3 (Maackia amurensis, MA)-specific lectins to CAKI-1 cells was analysed. Simultaneously, the effect on adhesion and release of calcium oxalate monohydrate crystals was investigated (eight replicates). The effect of crystal adhesion on cell viability was assessed using Trypan blue exclusion (five replicates). RESULTS: Neuraminidase decreased MA-lectin binding of CAKI-1 cells by 39% (P < 0.05) but elevated SN-lectin binding by 812% (P < 0.05). Simultaneously, crystal binding to CAKI-1 cells was increased by 28% (P > 0.05). Pretreatment with collagenase type I, trypsin and dispase II reduced crystal-binding by 61-74% (P < 0.05) with no effect on sialic acid-specific lectin-binding. However, only collagenase type I and dispase (ratio 4 : 1) were also able to release crystals from their receptor-binding sites (P < 0.05). An increase in the number of cell surface-bound crystals correlated significantly with a decrease in cell viability (P < 0.05). CONCLUSIONS: alpha2,3-linked sialic acids protect cells from crystal-binding. Much greater SN-lectin binding associated with only moderately increased crystal binding argues against alpha2,6-linked sialic acids as a main target structure of crystals. In contrast, collagen type I, type IV and/or fibronectin seem to be potent crystal-binding molecules on human renal epithelial cells, with collagen type I involved in a potential second step of crystal-cell interaction.

Loss of CD38 correlates with simultaneous up-regulation of human leukocyte antigen-DR in benign prostatic glands, but not in fetal or androgen-ablated glands, and is strongly related to gland atrophy.

OBJECTIVE: To determine whether CD38 loss in benign and malignant prostatic disease is related to human leukocyte antigen (HLA)-DR up-regulation, by assessing the histopathology of the prostate and the effect of androgen deprivation. MATERIALS AND METHODS: Serial sections of frozen fetal (eight), infant (six), normal adult (10), benign hyperplastic (BPH, 24), and primary (10) and hormone-treated (11) carcinomatous human prostatic tissues were analysed by immunohistology for anti-CD38 and HLA-DR antigens. RESULTS: In BPH samples there was a significant correlation between CD38 loss (mean 21% of acini) and HLA-DR up-regulation (mean 20%; P < 0.001). Moreover, 76% of all CD38-negative acini in BPH had HLA-DR up-regulation in the same prostate epithelial cells, predominantly in atrophic and cystic glands, and in cells with retained secretions (74%). In contrast to the uniform expression in normal adult prostate, CD38 was negative or partly expressed in fetal acini (mean 19%) and almost completely negative in acini of the early infant period (mean 0.7%). In contrast to BPH, cancer cells did not selectively up-regulate HLA-DR when CD38 was lost. In patients with cancer treated by androgen deprivation, cancer cells were CD38-negative. CONCLUSIONS: The absence of CD38 and presence of HLA-DR expression in prostatic epithelium is consistent in BPH and tissue surrounding tumour, and strongly related to gland atrophy. This is particularly interesting as HLA-DR triggering can induce apoptosis of cells, whereas CD38 prevents it. A permissive role for androgens to maintain full CD38 expression in epithelial cells is suggested.

Ion beam treatment of titanium surfaces for enhancing deposition of hydroxyapatite from solution.

Surface coating with hydroxyapatite (HA) is a common way to improve the osseointegration of orthopaedic and dental titanium (Ti)-based materials. The main problems with current techniques are changes in composition during heating and poor adhesion to the surface. An alternative method is deposition of HA onto an activated surface out of a solution. The present work studies the surface treatment involving ion implantation of Na into Ti to induce a modification in chemistry and morphology, showing sodium titanate (Na(2)TiO(3)) incorporated within the surface layer with concentration, depth distribution, and morphology depending on the parameters of the ion implantation. Such ion-implanted Ti surfaces actively induce heterogeneous precipitation of HA from a simulated body fluid containing physiological concentrations of calcium and phosphate ions. This is compared with the activation by NaOH etching. The growth of bone forming cells on the pure Na implanted surface is oriented without an increased bone formation. Cell growth on the NaOH etched surface is reduced. After deposition of HA on both surfaces cell the growth pattern was improved.

Mucocele apendicular / Mucocele of the appendix

El mucocele apendicular es una patología de baja frecuencia, estimándose en alrededor de un 0,3 por ciento de las apendicectomías. Desde el punto de vista histológico puede clasificarse en: hiperplasia focal o difusa de la mucosa, cistoadenoma mucinoso y cistoadenocarcinoma mucinoso. El cuadro clínico no es característico y puede presentarse como apendicitis aguda, tumor cecal, masa abdominal, cuadro obstructivo, urinario, ginecológico, colección intraabdominal o hallazgo por imágenes. Se presentan 10 pacientes con diagnóstico histopatológico de mucocele apendicular. La forma de presentación correspondió a apendicitis aguda en 4 casos, tumor cecal en 4 y colección intraabdominal en los 2 restantes. El dolor abdominal en FID se presentó en 4 pacientes. A todos los pacientes se les extirpó el apéndice, agregándose hemicolectomía derecha en un caso y resección parcial de ciego en 2 casos. La ecotomografía abdominal y la tomografía computada fueron útiles en el diagnóstico. Se recomienda la manipulación cuidadosa del apéndice, durante su extirpación, cuando se sospecha el diagnóstico, para evitar la siembra peritoneal. Los pacientes deben continuar en control periódico para descartar la presencia de otras lesiones neoplásicas sincrónicas o metacrónicas, como los adenocarcinomas de colón

Increased bioactive TNF in human systemic lupus erythematosus: associations with cell death.

In systemic lupus erythematosus (SLE) serum TNF is increased and correlates with its soluble receptors and with disease activity. We therefore investigated (i) whether the TNF in SLE serum is bioactive, (ii) whether SLE cells react to TNF and (iii) whether there are associations with cell death, which is regarded as pathogenic in SLE. Sera from active SLE patients induced an increase in fibroblast CD54, which was abolished by blocking antibodies against TNF, suggesting TNF bioactivity. SLE lymphocytes had a similar surface expression of TNF-RI as healthy lymphocytes, their expression of TNF-RII was slightly increased. Recombinant TNF induced cell death in PBMC of SLE patients, suggesting functional receptors. Serum levels of sTNF-RII (as a surrogate marker for TNF activity) correlated with sTNF-RI and disease activity, as expected, and also correlated with the percentage of dying lymphocytes and with lymphocytic CD95. SLE sera contain increased amounts of biologically active TNF. Peripheral blood lymphocytes of SLE patients express functional TNF receptors. Finally, associations with cell death and CD95 receptors suggest that TNF may be pathogenic in SLE.