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Biomedical subjects

J Smolen

Publications and source records attributed to J Smolen.

At least 73 records · Page 4Linked to original sources
PubMed1995

Soluble receptors for tumor necrosis factor and interleukin-2 in serum and synovial fluid of patients with rheumatoid arthritis, reactive arthritis and osteoarthritis.

OBJECTIVE: To compare levels of soluble tumor necrosis factor receptor (TNF-R) and soluble interleukin 2 receptor (sIL-2R) in sera and synovial fluids (SF) of patients with rheumatoid arthritis (RA), reactive arthritis (ReA), and osteoarthritis (OA) in order to investigate the usefulness of soluble cytokine receptors for differentiation diagnosis and their involvement in the pathophysiology of rheumatic diseases. METHODS: Soluble TNF-R (55 kDa), sIL-2R, and TNF-alpha were measured by ELISA in sera and SF of patients with RA, ReA, and OA and correlated with serological and clinical disease activity variables. RESULTS: Serum TNF-R was significantly (p < 0.0001) elevated in RA (4.6 +/- 2.1 ng/ml, mean +/- SD) compared to ReA (2.5 +/- 0.6 ng/ml), OA (2.2 +/- 0.7 ng/ml), and healthy controls (2.0 +/- 0.4 ng/ml). In SF mean TNF-R levels were 21 +/- 9.3 ng/ml in RA, 12.5 +/- 5.1 ng/ml in ReA, and 8.7 +/- 3.7 ng/ml in OA (p < 0.0001 for RA vs ReA or OA; p < 0.02 for ReA vs OA). SF levels were significantly higher in rheumatoid factor (RF) positive than in RF negative patients with RA. In patients with RA, correlations were found between TNF-R and TNF-alpha in SF (r = 0.32, p < 0.01), and between TNF-R and early morning stiffness (r = 0.4, p < 0.003 in serum; r = 0.29, p < 0.05 in SF). However, there was no correlation with disease activity variables such as Ritchie index, erythrocyte sedimentation rate (ESR) or C-reactive protein. Serum levels of IL-2R were elevated in RA and ReA, but a significant difference was found only for RA versus OA and controls (p < 0.0005), whereas in SF significant differences existed between all 3 patient groups (RA/ReA: p < 0.004; RA/OA: p < 0.0001; ReA/OA: p < 0.0003); both in serum and SF, levels of RF positive patients with RA were higher than those of RF negative patients. In patients with RA, IL-2R correlated weakly with ESR (r = 0.24, p < 0.05), iron concentration (r = -0.35, p < 0.005), and CRP (r = 0.24, p < 0.05). CONCLUSION: In RA, in contrast to ReA and OA, TNF-R and IL-2R were not only elevated in the joint fluid but also in serum. This indicates general activation of the immune system in RA, but not in ReA and OA. Therefore the soluble receptors, especially TNF-R, might become useful diagnostic variables to distinguish RA from ReA and OA.

Adult↗
PubMed1994

[Radiographic changes of the calcaneus in the framework of chronic polyarthritis].

Plain films of the calcaneus of 768 patients with confirmed rheumatoid arthritis were examined retrospectively with reference to inflammatory rheumatic changes. 42 patients (5.5%) showed an erosion of the posterior upper calcaneal margin related to an Achilles bursitis. In three patients there were additional plantar erosions. The Achilles bursitis was bilateral in 50% of cases, particularly in patients in stages 2 and 3 according to Steinbrocker. In the majority of bilateral cases (62%) the size or shape of the lesions was asymmetrical. Our observations indicate that involvement of the os calcis is not uncommon in rheumatoid arthritis; routine examination of this bone would appear to be indicated even in patients without symptoms. Since the defect is unilateral in half the patients, unilateral occurrence of an erosive lesion cannot be regarded as a criterion for a bacterial-inflammatory bursitis. Contrary to the symmetrical involvement of joints in the hands in rheumatoid arthritis, defects in the calcaneus are often unilateral or asymmetrical.

Achilles Tendon↗
PubMed1994

[Rheumatoid arthritis of the craniocervical transition. Detection of inflammatory changes in contrast CT and MRI].

A total of 136 patients with rheumatoid arthritis underwent MRI with sagittal T1-weighted spin echo sequences before and after i.v. administration of Gd-DTPA and with a 15-min delay. In addition, T2-weighted gradient echo sequences were performed. Conventional radiographs, including tomography in sagittal and a.p. planes, were also taken of all patients; 51 were also examined by CT before and after i.v. administration of contrast medium and in addition with a 15-min delayed series. The signal intensities of MRI and the changes in density caused by contrast uptake on CT were examined visually and measured quantitatively. The inflammatory changes were classified in four phases by the MRI and CT findings and histological results. A correlation (p < 0.05) was found with the erythrocyte sedimentation rate. MRI was superior to CT in 10% of cases. A discrete effusion in the anterior junction was missed in 4 cases and a hypervascular pannus formation in 1 case by CT. The CT was superior to the other methods in detecting bony lesions and calcifications in the atlantödental region. The local activity of the inflammatory changes can be graded by classifying them with contrast-enhanced MRI and CT, which yield an exact result for better monitoring during therapy.

Adolescent↗
PubMed1994

Infection of human monocytes by Leishmania results in a defective oxidative burst.

The effect of infection by prototypes from the three major species of Leishmania on the oxidative burst of human mononuclear phagocytes in culture was examined. The presence of intracellular parasites of the three species, L.major, L.donovani and L.mexicana decreased hydrogen peroxide (H2O2) and superoxide anion (O2-) production. This was particularly apparent when infected cells were compared to control monocytes following treatment with IFN-gamma. Nitroblue tetrazolium (NBT) reduction by monocytes was also decreased in infected cells. This morphological analysis of infected monolayers clearly showed that infected monocytes were incapable of reducing the dye as compared to uninfected cells. Decrease in NBT positive cells and production of H2O2 and O2- was related to the degree of infection of the monocyte monolayers. These results suggest that the presence of intracellular Leishmania amastigotes in mononuclear phagocytes decreases the oxidative burst and may contribute to parasite survival. Failure of phagocytes from patients with chronic granulomatous disease to kill these intracellular parasites also emphasized the importance of the oxidative burst for this function. Nevertheless, the consistent increase in leishmaniacidal effect attained after IFN-gamma treatment of the monocyte monolayers indicates that other non-oxidative mechanisms induced by this cytokine are also important in the killing of these intracellular parasites.

Animals↗
PubMed1992

High incidence of asymptomatic urogenital infection in patients with uveitis anterior.

Acute anterior uveitis (AAU) may be associated with systemic infectious or inflammatory disease. We examined 92 patients with the first attack of acute anterior uveitis; all patients were free of any extraocular symptoms. A thorough clinical examination did not reveal any systemic underlying disease. In the course of microbiological examination, however, a high incidence of asymptomatic infection of the urethra and/or cervix with ureaplasma urealyticum, chlamydia trachomatis and mycoplasma hominis was found. Infections with ureaplasma were significantly more frequent in patients with AAU when compared with a sex- and age-matched control group. There was no statistically valid association of these infections with the HLA-B27 phenotype in the patients. The higher rate of urogenital infections in patients with AAU may reflect a higher rate of sexual promiscuity. Transmission of infectious agents seems to be one possible factor in the pathogenesis of AAU.

Acute Disease↗
PubMed1992

Phenotypic analysis of functionally associated molecules on peripheral blood and synovial fluid monocytes from arthritis patients.

Surface expression of 16 different membrane molecules was analyzed in peripheral blood and synovial fluid monocytes from patients with rheumatoid arthritis and reactive arthritis compared to controls. The most significant findings were modulated expression of function-associated FcRI, CR1, CR3, MHC class II and activation-associated CD31, M5, and M6 molecules in arthritis patients compared to controls. Of these molecules, only upregulated expression of MHC class II has previously been reported in synovial fluid monocytes of patients with rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1992

Evidence for the presence of activated CD4 T cells with naive phenotype in the peripheral blood of patients with rheumatoid arthritis.

We have investigated whether T cell activation in rheumatoid arthritis (RA) preferentially engages distinct T cell subpopulations in the peripheral blood (PB) and in the synovial fluid. We found that CD25 expression was enhanced among PB CD4 T cells of RA patients as compared with CD4 cells of patients with reactive arthritis, degenerative joint disease or of healthy controls. Within the CD4 T lymphocytes subset we found that the CD45RO- (naive) cells selectively in RA displayed higher levels of CD25 protein and of interferon-gamma mRNA expression when compared with the respective subset of all other investigated groups. These results show that in the PB of RA, but not in the PB of the other arthropathies or healthy controls, CD45RO-CD4 T lymphocytes exist which display well-defined signs of activation.

Aged↗
PubMed1992

Histamine modulates the interleukin-6-regulated acute phase protein synthesis in cultured murine hepatocytes.

Murine hepatocytes cultured in the presence of human recombinant interleukin-6 (IL-6) show increased synthesis of fibrinogen and complement component C3 by the addition of histamine. No similar effect was achieved when murine hepatocytes were treated with histamine alone or with histamine and interleukin-1 alpha together. Using histamine-1 (H1) and H2 receptor antagonists a prevalence of histamine H1 receptor in the enhancement of IL-6-induced effect is suggested.

Animals↗
PubMed1992

Dissimilar biosynthesis of interleukin-6 by different areas of synovial membrane of patients with rheumatoid arthritis and osteoarthritis.

In this study the IL-6 production was studied by synovial cells isolated from patients with either rheumatoid arthritis (RA) or osteoarthritis (OA). The kinetics of spontaneous IL-6 production differs in both groups. Furthermore, the induction of IL-6 by bacterial lipopolysaccharide (LPS) in synovial cell cultures of RA is much more rapid than in those of OA patients. On the other hand, more PGE2 was detected in culture supernatants from synovial adherent cells of OA than in those of RA patients. We also compared the IL-6 production and the amount of IL-6 mRNA in fragments derived from the areas of synovial tissue showing macroscopic signs of intensive inflammation (area A), with those from relatively intact (area B) synovial sites. In synovial fragments, but not in isolated adherent cells at area A the in vitro IL-6 production starts earlier in RA than in OA. In the area A, significantly more CD14+, CD43+ and HLA-DR+ cells were detected than in the other compartment less involved in local inflammatory events.

Antigens, CD↗
PubMed1991

Analysis of function-associated receptor molecules on peripheral blood and synovial fluid granulocytes from patients with rheumatoid and reactive arthritis.

In this study we report the expression pattern of 13 different function-associated surface molecules on synovial fluid and peripheral blood granulocytes from rheumatoid and reactive arthritis patients. We found increased expression of the complement receptors 1 (CD35) and 3 (CD11b) and of the activation-associated antigens CD67, CD24, and M5 on synovial fluid granulocytes from rheumatoid and/or reactive arthritis patients compared to autologous peripheral blood granulocytes. In addition, synovial fluid granulocytes expressed IgG Fc receptor 1 (CD64) and complement receptor 4 (CD11c), neither of which can be found on peripheral blood granulocytes. Peripheral blood granulocytes from rheumatoid and reactive arthritis patients expressed higher levels of leucocyte function-associated antigen 1 (CD11a) and of the membrane proteins CD31, CD24, M5, and M6 compared to peripheral blood granulocytes from healthy controls and patients with degenerative joint disease. No significant differences in the expression of any of the molecules studied could be observed between cells from rheumatoid and cells from reactive arthritis patients, suggesting a similar activation process for granulocytes in these two diseases.

Antigens, CD↗
PubMed1991

[Molecular biology in diagnosis and detection of deletion in Duchenne muscular dystrophy].

For the purpose of carrier identification and genetic counselling we investigated deletions of the Duchenne muscular dystrophy (DMD) gene in three families of patients with Duchenne muscular dystrophy. Using a limited number of probes of the DMD cDNA in Southern blots, we detected a deletion in only one patient. Additional methodology is necessary to warrant reliable identification of carriers and exact prenatal diagnosis.

Child↗
PubMed1990

Treatment of psoriatic arthritis by extracorporeal photochemotherapy.

Five patients with long-standing seronegative arthritis resistant to conventional therapy and who also had psoriasis of the skin were treated with photopheresis. This mode of treatment combines a lymphocyte-enrichment procedure with 8-methoxypsoralen-photochemotherapy. There was a marked in vitro effect on treated lymphocytes, with a reduction of viability, proliferation and mitogen response. There was a slight to moderate clinical improvement in four of the five patients with regard to the strength of grip, swelling, pain, morning stiffness, the dosage of non-steroidal anti-rheumatic drugs and the radiographical changes. The skin lesions did not respond to photopheresis. Short-term side-effects were minimal and consisted of a temporary sensitivity of the eyes to light and signs of circulatory dysregulation immediately after treatment. This experimental therapy has some measurable but not dramatic effect in improving psoriatic arthropathy.

Adult↗
PubMed1989

[Magnetic resonance tomography of the craniocervical junction in chronic polyarthritis].

Magnetic resonance imaging and conventional radiographs and tomograms were correlated in 61 patients with chronic polyarthritis. Radiographs of the occipito-cervical junction only demonstrated bone lesions, erosions were detected on conventional tomograms. MRI was adequate for demonstration of bone abnormalities and soft tissue lesion and was especially suitable for detection of complications at the cervical spinal cord.

Adult↗
PubMed1988

Adverse effect of low-dose prophylactic human recombinant leukocyte interferon-alpha treatment in renal transplant recipients. Cytomegalovirus infection prophylaxis leading to an increased incidence of irreversible rejections.

Since infections with Herpetoviridae after kidney transplantation still remain a major clinical problem, we conducted a double-blind, placebo-controlled trial using low-dose recombinant interferon-alpha-2C (rIFNa2C) prophylaxis in 50 renal graft recipients immunosuppressed with cyclosporine and methylprednisolone. Ten patients were excluded from further analysis because of graft loss due to surgical complications, side effects of rIFNa2C, and because of lack of compliance. There was a significant difference in graft loss due to irreversible rejections between the verum and the placebo group (6 vs. 0; P less than 0.05), whereas no difference was observed with regard to the occurrence of viral infections. We conclude, that low-dose rIFNa2C prophylaxis is harmful in renal allograft recipients treated with cyclosporine in view of the high incidence of irreversible transplant rejections without beneficial effects on the occurrence of viral infections.

Adult↗
PubMed1988

Decreased serum osteocalcin levels in phenprocoumon-treated patients.

Osteocalcin (OC) is a noncollagenous bone matrix protein containing gamma-carboxyglutamic acid, the synthesis of which is vitamin K dependent. Serum OC levels are generally believed to reflect the de novo synthesis of OC by osteoblasts and thus reflect bone formation. We measured serum OC levels by RIA in 48 patients receiving phenprocoumon anticoagulant treatment, which inhibits the posttranscriptional synthesis of gamma-carboxyglutamic acid, and in 22 matched normal subjects. The median serum OC level in the patients receiving phenprocoumon therapy was significantly lower than that in the normal subjects (P less than 0.0001). In 27 patients receiving anticoagulant therapy and in 21 normal subjects the proportion of noncarboxylated OC to total OC also was determined. The proportion of OC that was noncarboxylated was significantly higher in the patients receiving phenprocoumon therapy than in the normal subjects (P less than 0.0001). We conclude that OC carboxylation is impaired in patients receiving oral anticoagulant therapy. The decreased total OC levels in patients receiving phenprocoumon treatment might result from decreased bone formation, although these patients do not have symptoms of bone disease.

4-Hydroxycoumarins↗
PubMed1988

[Use of plasmapheresis in therapy of systemic lupus erythematosus: a controlled study].

The effectivity of a combination of various plasma exchange regimens in combination with immunosuppressive medication consisting of corticosteroids and cyclophosphamide was tested in patients with severe systemic lupus erythematosus (SLE) the symptoms of which were found to be refractory to conventional immunosuppressive treatment administered orally. The patients were then submitted in a controlled manner to the following treatment modalities: 1. consecutive plasmapheresis (plasma exchanges every 2 to 3 days during a period of 2 to 3 weeks) with a continuation of immunosuppressive therapy administered orally; 2. chronic intermittent treatment (once per week) with parallel immunosuppression; 3. 2 plasmaphereses followed by an i.v. cyclophosphamide bolus. Only the third approach resulted in a stable and persistent clinical and serological improvement of disease activity.

Adrenal Cortex Hormones↗