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W J Stevens

Publications and source records attributed to W J Stevens.

At least 55 records · Page 3Linked to original sources
PubMed1998

Evolution of lymphocyte transformation to wasp venom antigen during immunotherapy for wasp venom anaphylaxis.

BACKGROUND: Venom immunotherapy (VIT) has proven to be safe and effective in wasp venom anaphylaxis. However, there are no good parameters to indicate when to stop venom immunotherapy. OBJECTIVE: To evaluate the relationship of the lymphocyte transformation test (LTT) to history and specific IgE determination, and to address the time course of lymphocyte transformation responses to wasp (Vespula) venom during VIT and the possible utility of LTT to determine the duration of therapy. METHODS: Peripheral blood mononuclear cells (PBMCs) of 18 individuals with a history of wasp sting anaphylaxis and a positive serum-venom-specific IgE, were stimulated with wasp venom before immunotherapy, at the end of a 5-day semi-rush immunotherapy and at 24 months during venom immunotherapy. Results, expressed as stimulation index (SI), were compared with the SI in seven asymptomatic stung controls. RESULTS: In controls the median (minimum-maximum) of the SI were 2.39 (0.52-3.39) before therapy and 2.39 (1.12-6.02) when repeated after 24 months. For patients the median (minimum-maximum) of the SI were 10.13 (1.19-44.88) before immunotherapy (d0), 2.73 (0.67-12.03) at the end of the build-up immunotherapy (d5) and 4.21 (0.88-14.66) at the end of 24 months of maintenance therapy (m24). The proliferation responses in vespid-allergic patients were significantly higher than in stung controls (P = 0.006) but only 13/18 patients showed a positive LTT result before the start of immunotherapy (sensitivity of the LTT 72%). When the LTT was repeated after a 5 day build-up hyposensitization course the SI significantly dropped as compared to the pre-treatment levels (P = 0.002). The SI of the LTT was negative in eight out of 18 patients at 24 months and the median values were significantly lower than before therapy (P = 0.03). CONCLUSIONS: Although, in the absence of sting challenge data it is not possible to draw conclusions about the predictive value of the LTT, our data may suggest that abolition of the LTT during VIT might indicate clinical insensitivity. Further studies, comparing the results of sting challenges, with the results of lymphocyte transformation will be necessary in order to evaluate the role of LTT in stopping immunotherapy.

Adolescent↗
PubMed1998

Comparison between the in vitro cytokine production of mononuclear cells of young asthmatics with and without immunotherapy (IT)

BACKGROUND: The underlying mechanisms of immunotherapy (IT) are still unknown but may be related to modifications of cytokine production of T lymphocytes. OBJECTIVE: In this study we determined the in vitro allergen-induced production of IL-2, IL-4, IL-5, IL-12 and IFNgamma of peripheral blood mononuclear cells (PBMC) of eight young asthmatics, aged 15+/-2 years, receiving IT (IT group) and of eight comparable asthmatics, aged 13+/-3.5 years, who never received IT (non-IT group). METHODS: All patients suffered from perennial asthma and were allergic to house dust mite (HDM). They were selected if they showed a positive stimulation index (SI) of PBMC after in vitro incubation with HDM (i.e. SI > 2). Cells were incubated with and without HDM (10 microg/mL) during 24 h, 48 h and 7 days. Cytokines were determined in the supernatant at the three time points and are expressed as median values in pg/mL. RESULTS: In the IT group the secretion of IL-2 was lower compared with the non-IT group after 7 days incubation of PBMC with HDM (0 vs 33.2, P = 0.008). In both groups maximal secretion of IL-2 was observed after 48 h. In the non-IT group a high value of IL-2 persisted after 7 days, whereas in the IT group a significant decline of IL-2 occurred after 7 days. Although IL-4 secretion was low in all subjects, more patients of the non-IT group showed detectable IL-4 in the HDM cultures after 24 h and 48 h, although the difference was not statistically significant (P = 0.08 and P = 0.28, respectively). Furthermore, IL-4 secretion was lower in the HDM cultures after 24 h in the IT group (1.75 vs 4.1, P = 0.011) and 48 h (2.2 vs 4.1, P=0.035). IL-5 secretion was lower in the HDM cultures after 24h (12.4 vs 47.6, P = 0.035) and 48 h (26.8 vs 135, P = 0.046) in the IT group than in the non-IT group. After 7 days of incubation with HDM there was no difference between the groups. There was no difference between both groups in secretion of IFNgamma and IL-12. CONCLUSIONS: These results show a difference in vitro cytokine secretion of PBMC of asthmatics receiving IT compared with asthmatics who never received IT. PBMC of patients receiving IT secrete less IL-2 and IL-5 after in vitro incubation with HDM and show a tendency to secrete less IL-4. The efficacy of IT may be attributed to a modified cytokine secretion of PBMC.

Allergens↗
PubMed1998

Immunotherapy for allergic reactions.

In this review, hyposensitization or immunotherapy will be discussed. The earliest immunotherapy was applicated in allergic respiratory diseases such as asthma and rhinitis. The most important indication has become the treatment of hymenoptera allergy. Some less frequently indications are associated with drug allergy. Immunotherapy is most frequently indicated in IgE mediated diseases, but new applications for cell mediated reactions will be described. With the introduction of molecular biology in allergology new theoretical possibilities emerged: use of peptide antigens, recombinant allergens, anticytokines.... Unfortunately, these newer approaches did not (yet) cause a breakthrough. The cost of these products will be a major draw back, even when ethical problems for using them on a larger scale will have been solved.

Desensitization, Immunologic↗
PubMed1998

Influence of antirheumatic drugs on nitric oxide and interleukin 8 production in human articular chondrocytes.

OBJECTIVE: To determine whether antirheumatic drugs can inhibit chondrocyte nitric oxide and interleukin 8 (IL-8) production. METHODS: IL-1beta stimulated human chondrocytes were incubated with indomethacin, methotrexate, sulfasalazine, dexamethasone, and methylprednisolone. Nitric oxide was detected as nitrite; IL-8 was detected by a radioimmunoassay method. RESULTS: Nitric oxide production was partly (< or = 50%) inhibited and IL-8 almost completely suppressed (> 80%) by dexamethasone and methylprednisolone. Sulfasalazine in pharmacological concentration and indomethacin slightly increased IL-8. No effect of methotrexate on nitric oxide or IL-8 production was found. CONCLUSION: Dexamethasone and methylprednisolone are inhibitors of human chondrocyte nitric oxide production, although to a lesser extent than for IL-8 production. Indomethacin, sulfasalazine, and methotrexate had no major influence on these mediators.

Antirheumatic Agents↗
PubMed1997

Actin polymerisation in neutrophils of rheumatoid arthritis patients in relation to treatment with non-steroidal anti-inflammatory drugs.

There is evidence that neutrophil functions such as chemotaxis and oxygen radical formation are disturbed in rheumatoid arthritis (RA). Medication might also influence these functions. Cyclic formation and depolymerisation of actin microfilaments is crucial in cell motility, but this phenomenon has not been studied in RA. The aim of this study was to investigate basal and dynamic (formyl-methionyl-leucyl-phenylalanine (fMLP)-induced) neutrophil actin polymerisation in ten RA patients (a) during therapy with non-steroidal anti-inflammatory drugs (NSAIDS) and (b) after stopping NSAIDS> The results were compared with those of ten age-matched controls. Basal F-actin content in RA patients with NSAIDS was significantly lower than in RA patients without NSAIDS and controls: 35.5 (25.0-49.0), 50.5 (27.0-75.0) and 52.5 (32.0-85.0), respectively. Conversely, upon stimulation with fMLP, the actin polymerisation curve of RA patients with NSAIDS was higher than for RA patients without NSAIDS and controls. These results suggest that, in RA, the effects orf NSAIDS on neutrophil functions might be related to changes in the actin polymerisation-depolymerisation cycle.

Actins↗
PubMed1997

Latex-specific IgE, skin testing, and lymphocyte transformation to latex in latex allergy.

BACKGROUND: This study was designed to determine the discriminative value of latex-specific IgE tests, latex skin tests, and lymphocyte transformation tests (LTTs) to latex in 38 patients with latex allergy (12 nonatopic and 26 atopic) and 44 control subjects (24 nonatopic and 20 atopic). We also evaluated the recommended positive cutoff (i.e., 0.35 kU/L) of both in vitro latex-IgE tests. METHODS: Latex-specific IgE levels were determined by the Immuno-CAP (Upjohn-Pharmacia) and the ALaSTAT-RIA (Diagnostic Products Corp.) assays. Skin tests and LTFs were performed with a nonammoniated latex extract (DPC). Sensitivities and specificities were defined according to the 95th percentile value of nonatopic control subjects. For the in vitro IgE tests, sensitivity and specificity were also calculated by using the proposed positive threshold of 0.35 kU/L. Sensitivities and specificities of both cutoffs were compared. RESULTS: Compared with a clinical history of latex allergy and according to the 95th percentile value of nonatopic control subjects (0.44 kU/L), latex-specific IgE determined by the Immuno-CAP assay achieved a sensitivity of 97% and a specificity of 86%. For the ALaSTAT-RIA assay, with 0.54 kU/L as the 95th percentile threshold value in nonatopic control subjects, sensitivity was 100%, and specificity was 83%. According to the threshold value of 0.35 kU/L, a sensitivity of 97% and a specificity of 83% for the Immuno-CAP assay and a sensitivity of 100% and a specificity of 33% for the ALaSTAT-RIA assay were observed. The latex skin test reached a sensitivity of 97% and a specificity of 100%. The LTF to latex showed a sensitivity of 39% and a specificity of 95%. No relation between symptoms and latex-specific IgE tests, latex skin tests, or LTTs was found. CONCLUSIONS: Our results confirm that latex skin tests and latex-specific IgE assessments are sensitive and specific methods for establishing the diagnosis of latex allergy, although the specificity of the ALaSTAT-RIA assay was very low when interpreted according to the threshold of 0.35 kU/L. The LTT to nonammoniated latex is too insensitive for diagnosis of allergy to latex. This reemphasizes that in order to evaluate the sensitivity and specificity of diagnostic procedures, one should always include an appropriate control group.

Adolescent↗
PubMed1997

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease with special attention for IgA-class antibodies.

Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) of the IgG class have been reported in inflammatory bowel disease, mainly in ulcerative colitis. Since this disease affects the gastrointestinal tract, we determined whether IgA class ANCA were present in inflammatory bowel disease. We used an indirect immunofluorescence assay for IgG and IgA ANCA testing. Sera from 34 patients with Crohn's disease and 29 patients with ulcerative colitis were collected together with clinical and laboratory data. We found IgA class ANCA of a perinuclear type in 52% of patients with ulcerative colitis and in 9% of Crohn's disease patients. There was a significant association between the presence of IgA ANCA and the occurrence of blood in the feces in the ulcerative colitis group (P = 0.03). IgG ANCA was found in 56% of patients with ulcerative colitis and in 7% of patients with Crohn's disease. Because of partial overlap between IgG and IgA ANCA positivity, the sensitivity of ANCA testing in ulcerative colitis increased from 56% up to 78% by combining IgG and IgA assays. In conclusion, IgA ANCA occurs with a high prevalence in ulcerative colitis. Moreover there is a possible relationship between IgA ANCA and disease activity in ulcerative colitis.

Adult↗
PubMed1997

c-ANCA positivity in a Belgian patient with pulmonary paracoccidioidomycosis.

We present the case of a 69 yr old, white male, suffering from diffuse interstitial lung disease, finally diagnosed as paracoccidioidomycosis or South American blastomycosis. During the course of his disease, antineutrophil cytoplasmic antibodies (c-ANCAs) became positive, suggesting the possibility of a Wegener's granulomatosis. Transbronchial biopsies and a video-assisted thoracoscopic lung biopsy revealed only the pulmonary yeast infection, without other co-existing pathology. During treatment with itraconazole, the patient improved clinically and functionally, and c-ANCAs became negative. Serological monitoring confirmed the diagnosis. To our knowledge, this is the first report describing positive c-ANCAs in a patient with paracoccidioidomycosis. It re-emphasizes the fact that cautious interpretation of c-ANCAs in patients without convincing clinical signs or pathological evidence of a granulomatous vasculitis is absolutely necessary. In this era of increased mobility, a thorough medical history, including documentation of travel, remains an inexpensive tool in making a diagnosis and is still the cornerstone of good medical practice.

Aged↗
PubMed1997

Anticardiolipin, anti-beta(2)-glycoprotein I, antiprothrombin antibodies, and lupus anticoagulant in patients with systemic lupus erythematosus with a history of thrombosis.

OBJECTIVE: To determine the clinical importance of anticardiolipin (aCL), anti-beta(2)-glycoprotein I (a beta(2)-GPI), antiprothrombin (aPT), and lupus anticoagulant (LAC) antibodies in patients with systemic lupus erythematosis (SLE) with and without a history of thrombosis. METHODS: We studied 100 patients with SLE (32 with a history of thrombosis), 27 patients with a lupus-like disease (9 with a history of thrombosis), and 41 healthy volunteers, IgG and IgM aCL, antibodies to the protein cofactors (a beta(2)-GPI and aPT) were determined by ELISA. Eighty-six of 127 patients were also tested for LAC. RESULTS: IgG aCL and LAC were associated with thrombosis but sensitivity (63 and 61%) and specificity (66 and 66%, respectively) of these tests were low. IgG and IgM a beta(2)-GPI were, respectively, 85 and 86% specific for a thrombotic history, but sensitivity was very low (32 and 29%). High IgG aCL were associated with the presence of a beta(2)-GPI and were 85% specific for thrombosis. There was no significant association between IgG or IgM aPT and thrombosis. CONCLUSION: Only high levels of IgG aCL and presence of LAC and/or a beta(2)-GPI are relevant in defining a thrombotic subset of patients with SLE. Longitudinal prospective studies are needed to investigate the predictive value of the different antiphospholipid and protein cofactor antibodies.

Adult↗
PubMed1996

First-sphere and second-sphere electrostatic effects in the active site of a class mu gluthathione transferase.

The activation of the thiol of glutathione (GSH) bound in the active site of the class mu glutathione transferase M1-1 from rat involves a hydrogen-bonding network that includes a direct (first-sphere) interaction between the hydroxyl group of Y6 and the sulfur of GSH and second-sphere interactions involving a hydrogen bond between the main-chain amide N-H of L12 and the hydroxyl group of Y6 and an on-face hydrogen bond between the hydroxyl group of T13 and the pi-electron cloud of Y6 (i.e., T13-OH---pi-Y6-OH--- -SG). The functions of these hydrogen bonds have been examined with a combination of site-specific mutagenesis and X-ray crystallography. The hydroxyl group of Y6 has a normal pKa of about 10 even though it is shielded from solvent and is in a largely hydrophobic environment. The apparent pKa of GSH in the binary Y6F.GSH complex is increased by 1.6 log units, and the reactivity of the enzyme-bound nucleophile is reduced. The catalytic properties of the Y6L mutant are identical to those of Y6F, suggesting that the weakly polar on-edge interaction between the aromatic ring and sulfur has no influence on catalysis. The refined three-dimensional structure of the Y6F mutant in complex with GSH shows no major structural perturbation of the protein other than a change in the coordination environment of the sulfur. Removal of the second-sphere influence of the on-face hydrogen bond between the hydroxyl groups T13 as in the T13V and T13A mutants elevates the pKa of enzyme-bound GSH by about 0.7 pKa units. Crystal structures of these mutants show that structural changes in the active site are minor and suggest that the changes in pKa of E.GSH are due to the presence or absence of the on-face hydrogen bond. The T13S mutant has a completely different side-chain hydrogen-bonding geometry than T13 in the native enzyme and catalytic properties similar to the T13A and T13V mutants consistent with the absence of an on-face hydrogen bond. The gamma-methyl group of T13 is essential in enforcing the on-face hydrogen bond geometry and preventing the hydroxyl group from forming more favorable conventional hydrogen bonds.

Animals↗
PubMed1996

Relationship between interleukin-8 and neutrophil adhesion molecules in rheumatoid arthritis.

To evaluate the role of interleukin-8 (IL-8) on the activation of neutrophils in rheumatoid arthritis (RA), we measured IL-8 and the adhesion molecules, L-selectin (CD62L), CD1 1b and CD18, on neutrophils in paired peripheral blood and synovial fluid of RA patients. Synovial fluid IL-8 levels were significantly increased compared to peripheral blood. L-selectin was split off and CD1 1b and CD 18 were upregulated on neutrophils in the synovial fluid. A positive correlation occurred between the IL-8 concentration and CD18 or CD1 1b densities on neutrophils in the synovial fluid (r = 0.75, P < 0.005 and r = 0.60, P < 0.05, respectively). Peripheral blood neutrophils of the patients were desensitised with IL-8 in vivo, as shown by the significantly lower L-selectin shedding after in vitro IL-8 stimulation: 1.6 times decrease for patients vs 3.2 for controls (P < 0.05). In conclusion, these results add further evidence for the role of IL-8 in the activation of neutrophils in RA.

Adult↗
PubMed1996

Herpes zoster myelitis occurring during treatment for systemic lupus erythematosus.

A woman with systemic lupus erythematosus (SLE) presented with a zoster eruption. Transverse myelitis developed at the site of the dermatomal distribution of the rash. SLE and varicella zoster virus (VZV) can both cause myelitis, and are difficult to differentiate. The topographic association between the cutaneous and the neurological involvement suggesting VZV myelitis was confirmed by polymerase chain reaction (PCR) for VZV in the cerebrospinal fluid. This case illustrates the potential role of the selective amplification of VZV DNA in cerebrospinal fluid to diagnose central neurological complications associated with VZV. The value of magnetic resonance imaging of the spinal cord in the evaluation of patients with myelitis is emphasized.

DNA, Viral↗