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Biomedical subjects

M Meurer

Publications and source records attributed to M Meurer.

At least 109 records · Page 6Linked to original sources

[Toxic oil syndrome--an example of an exogenously-induced autoimmune disease].

In 1981 epidemic poisoning with adulterated cooking oil occurred in Spain, affecting more than 20,000 people. The condition caused has since become known as the toxic oil syndrome (TOS). About 10-15% of the patients with acute symptoms developed a chronic disease with scleroderma-like skin manifestations, polyneuropathy and myositis. While the acute phase of the TOS was characterized by eosinophilia and elevated IgE, the chronic stage involved humoral autoimmune phenomena, such as antinuclear and antinucleolar antibodies, in many cases. In women with the chronic phase of TOS there was a possible prevalence of HLA-DR3 and HLA-DR4. The recently characterized eosinophilia-myalgia syndrome (EMS), which is thought to have been induced by contaminated L-tryptophan preparations, is similar to the TOS in some particulars. Understanding of the toxicological, immunological and genetic pathways leading to these diseases might give us some insight into the pathogenesis of spontaneously occurring autoimmune diseases, such as systemic scleroderma.

Animals↗

Ultrastructural basis for antigen mapping using sodium chloride-separated skin.

In many cases of autoimmune blistering skin diseases indirect immunofluorescence with serum of patients on 1 M NaCl-separated skin represents a rapid diagnostic tool before the use of more complicated immunoelectron microscopy. The present study demonstrates that in skin samples from five adults, separated using 1 M NaCl, 0.15 M NaCl and 0.01 M phosphate buffered saline (PBS), the split formed within the lamina lucida at an identical ultrastructural level. The sub-basal dense plate (SDP) with a wreath of anchoring filaments remained on the epidermal side of the split adjacent to the hemidesmosomal part of the plasma membrane of basal keratinocytes. The base of the split blister was constituted from the lamina densa, with a remote possibility of some anchoring filaments attached. We demonstrate that antigens on the roof of the NaCl- or PBS-split blister may be associated, beside intracellular hemidesmosomal structures, with the SDP and basement membrane components between the SDP and the basal keratinocytes as well as with anchoring filaments attached to the SDP. The observations reported here allow a more precise mapping of antigen determinants in blistering skin diseases.

Animals↗

Chlamydia trachomatis induces an inflammatory response in the male genital tract and is associated with altered semen quality.

U. urealyticum with 15.8% and C. trachomatis antibodies with 15.4% were the most prevalent microbiological findings in 209 male infertility patients. The inflammatory marker granulocyte-elastase was significantly increased in men with C. trachomatis; these men also showed significantly decreased citric acid levels indicating inflammatory damage of the prostate induced by C. trachomatis.

Antibodies, Bacterial↗

Extracellular binding sites of IgA anti-jejunal antibodies on normal small bowel detected by indirect immunoelectronmicroscopy.

Patients with dermatitis herpetiformis (DH) have IgA deposition in the papillary dermis and in the lamina propria of the small bowel. In addition, most of DH patients' sera contain IgA class anti-reticulin antibodies, anti-endomysium antibodies (EMA), and anti-jejunal antibodies (JAB) during times of gluten intake. In previous studies, JAB and EMA seemed to be identical and related to the group of anti-reticulin antibodies. In the present study, pre-embedding en bloc immunoelectronmicroscopic methods were applied for analysis of the ultrastructural binding sites of JAB on monkey and rabbit small bowels. These substrates were incubated with sera from DH patients strongly positive for JAB. Simultaneous investigations with the PAP technique and with 5 nm gold-labeled protein A or second antibodies visualized the bound IgA identically: it was associated with collagen fibrils underlying the epithelial and cryptal basement membranes and with collagen fibrils around capillaries. Staining was also detected along the endomysial collagen fibrils of smooth muscle layers, around elastica and smooth muscle cells of blood vessel walls, and along collagen fibrils near smooth muscle cells in the lamina propria. Neither the peroxidase product nor gold deposition was detected directly on the fibers, but was associated with amorphous material surrounding collagen fibers of different diameters. The distribution of JAB-stained structures corresponded to the localization of reticulin network of the small bowel. Our data indicate that JAB recognize an antigen or antigens associated with an amorphous component of the reticulin-collagen structure of jejunum and may have identical binding sites, as anti-reticulin antibodies and EMA.

Animals↗

Herpes gestationis: ultrastructural identification of the extracellular antigenic sites in diseased skin using immunogold techniques.

Using a direct immunogold technique, we studied the level of immunological events in the skin basement membrane in a patient with herpes gestationis during blister formation. Within the lamina lucida, IgG and C3 were localized beneath the basement membrane of basal keratinocytes, 30-40 nm above the lamina densa. In many areas of blister formation sub-basal dense plates, but probably also the upper parts of the hemidesmosomes were separated from the roof of the blister. In the perilesional lamina lucida and in the blister, IgG and C3 containing amorphous grains, most probably immunocomplex aggregates, were detected. They covered the basement membrane of keratinocytes and left free a 30-40 nm band above the lamina densa. Our study indicates that in herpes gestationis the cleavage, accompanied by IgG, C3 and immunocomplex deposition, occurs at the level of the sub-basal dense plate. However, cleavage through upper hemidesmosomal structures can occur in parallel. These data further support the involvement of hemidesmosomes in the pathogenesis of the disease and therefore in its relationship to bullous pemphigoid.

Acute Disease↗

Blood rheology in lupus erythematosus.

Blood rheology is one of the determinants of perfusion and might therefore have an impact on the thromboembolic complications of lupus erythematosus. This study aimed at defining the flow properties of blood in patients with various types of lupus erythematosus. Results for 51 patients were compared with those for 20 controls matched for sex. The patients were divided into subgroups--chronic discoid, subacute cutaneous, and systemic lupus erythematosus--according to their clinical or laboratory characteristics. Blood and plasma viscosity, packed cell volume, red cell aggregation, and red cell deformability were used as parameters of blood rheology. Blood and plasma viscosity and red cell aggregation were significantly different in patients compared with controls, indicating reduced blood fluidity in lupus erythematosus. There were no marked sex differences. The rheological effects were greater in those with systemic lupus erythematosus than in those with chronic discoid or subacute cutaneous lupus erythematosus. The presence of a positive antinuclear antibody titre or methods of treatment (systemic steroids or retinoids) had no apparent effect on the parameters tested. It is suggested that a complex haemorheological deficit exists in lupus patients.

Acute Disease↗

[Isolated pemphigus vulgaris of the mouth mucosa--pemphigus test: diagnostic confirmation using direct immunofluorescence study of normal skin].

The diagnosis of oral pemphigus vulgaris (PV) without concomitant cutaneous manifestations is often complicated by difficulties in obtaining a biopsy specimen allowing histological examination and direct immunofluorescence (IF) microscopy. In this clinical study five of our patients with oral PV were investigated: biopsies were taken both from lesional oral mucous membranes and from unaffected gluteal skin for IF analysis. Identical IF results, with intercellular epidermal deposition of IgG in all and of C3 in two of the five cases, were obtained in lesional and nonlesional biopsies. Therefore, it is concluded that with current IF techniques examination of the normal skin is sufficient for the diagnosis of oral PV; thus, the often painful and difficult removal of biopsy specimens from within the affected oral cavity can be avoided. Further studies are needed to confirm the sensitivity of this method.

Adult↗

[Eosinophilia-myalgia syndrome and L-tryptophan intake].

We present the case of a 52-year-old woman who developed diffuse induration of the skin and severe edema of the subcutaneous tissue involving the extremities and the trunk, sparing hands, feet and face after 10 years of almost constant oral tryptophan medication. The skin manifestations were similar to those of eosinophilic fasciitis (Shulman syndrome). The patient complained of severe muscle pain and weakness. Laboratory studies revealed an elevated Westergren erythrocyte sedimentation rate and eosinophilia. There were no signs of internal organ involvement and no immunological parameters of progressive systemic scleroderma. Eosinophilia and myalgia resolved in response to intermittent systemic therapy with glucocorticosteroids, whereas the progressive scleroderma and the edema showed only slight improvement after the discontinuation of L-tryptophan.

Biopsy↗

Acquired epidermolysis bullosa with the clinical feature of Brunsting-Perry cicatricial bullous pemphigoid.

A 56-year-old woman with the typical clinical feature of cicatricial bullous pemphigoid of the Brunsting-Perry type was studied. Histologic examination of a lesion skin biopsy specimen demonstrated a subepidermal blister. Direct immunofluorescence microscopy revealed linear deposits of IgG, IgM, and C3 located on both the roof and the floor of the blister. Immunofluorescence antigen mapping using cryostat sections of a spontaneous blister and antisera against defined basement membrane components localized the bullous pemphigoid antigen and type IV collagen in the roof of the blister. This dermal type of blister formation was confirmed by electron microscopy, which showed the cleavage level below the lamina densa. In direct immunoelectron microscopy, granular deposits of C3 and IgG were found attached to and just beneath the lamina densa in a pattern identical to the distribution of anchoring fibrils. These findings are diagnostic of acquired epidermolysis bullosa, a blistering disease that has much more clinical heterogeneity than previously suggested.

Complement C3↗

Binding to human jejunum of serum IgA antibody from children with coeliac disease.

Jejunal histology and the presence of serum IgA antibodies (JAB) binding to human jejunum in vitro were studied in 139 children with severe malabsorptive symptoms. Among 33 children with confirmed coeliac disease (ESPGAN criteria), 13 (93%) of 14 sampled before starting on a gluten-free diet had JAB, none of 21 sampled had JAB while on a gluten-free diet of long duration, and 90% of 30 sampled during gluten challenge had JAB. 53 children had severe jejunal villous atrophy (probable coeliac disease): 71% of those younger than 2 years and 94% of those aged 2-18 years had JAB during gluten intake. JAB could not be detected in 53 disease control patients (normal jejunal histology) and in 3 coeliac disease patients with selective IgA deficiency. Simultaneous determination of antigliadin (AGA) and antiendomysium (EMA) levels, and gliadin and tissue absorption studies, showed that JAB and AGA are different, whereas JAB and EMA are probably identical. IgA JAB could be the target-organ-related autoantibodies in coeliac disease.

Adolescent↗

Immunogenetic associations of scleroderma-related antinuclear antibodies.

Patients selected for the presence of scleroderma-related antibodies (anti-DNA-topoisomerase I [anti-topo I; n = 43], anticentromere antibody [ACA; n = 63], or anti-Pm-Scl [n = 12]) were studied for class I and class II major histocompatibility complex antigens, as well as for Gm and Km allotypes. Anti-topo I was associated with HLA-DR5 (70% of patients versus 30.6% of controls; Pcorr = 0.0018, relative risk [RR] = 5.3). All patients with anti-Pm-Scl were positive for HLA-DR3 (versus 23.5% of controls; Pcorr less than 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr less than 0.001, RR = 27.3). Patients with ACA were frequently positive for HLA-DR1, DR4, or DRw8, with 73.7% demonstrating at least 1 of these alleles (versus 41.2% of controls; Pcorr = 0.0152, RR = 4.0). This group of ACA-positive patients who had DR1, DR4, and/or DRw8 consisted mainly of a subgroup of patients with rheumatoid arthritis. We conclude that different class II major histocompatibility complex antigens influence the formation of anti-topo I and anti-Pm-Scl. Important clinical differences between these patient groups and the immunogenetic heterogeneity support the notion of different antibody-defined scleroderma subsets.

Antibodies, Antinuclear↗

Clinical association of autoantibodies to fibrillarin with diffuse scleroderma and disseminated telangiectasia.

Circulating autoantibodies against a variety of nuclear and nucleolar antigens are characteristic serologic findings in systemic scleroderma. Some of these antibodies correlate with clinical subsets of the disease. We describe three patients with systemic scleroderma and high autoantibody titers against U3 ribonucleoprotein-associated fibrillarin, a recently identified 34 kD nucleolar protein. These patients showed a progressive course with multiple organ and diffuse skin involvement with disseminated telangiectasia.

Adult↗

Type III collagen aminopropeptide and laminin P1 levels in serum of patients with silicosis-associated and idiopathic systemic scleroderma.

A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin PI (Lam PI) fragment and the acid lysosomal beta-galactosidase (beta-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of beta-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam PI were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam PI and beta-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.

Aged↗