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At least 523 records · Page 29Linked to original sources
PubMed1990

Studies of cicatricial pemphigoid autoantibodies using direct immunoelectron microscopy and immunoblot analysis.

We studied 11 consecutive patients with classical cicatricial pemphigoid (CP) using direct immunoelectron microscopy (IEM) and Western immunoblotting analysis. Direct IEM performed in the skin or gingival mucosa revealed in all 11 CP patients that immunoglobulins and complement deposits were usually thick and discontinuous along the dermoepidermal junction, mostly localized on the lamina densa and occasionally in the lamina lucida. By direct IEM, the ultrastructural aspect in CP differs from the pattern observed in bullous pemphigoid (BP) and from that of chronic epidermolysis bullosa acquisita (EBA). Nine CP patients were studied by Western immunoblotting and, of these nine, only two had detectable anti-basement membrane zone (BMZ) antibodies by indirect immunofluorescence on salt-split skin. By immunoblotting performed on protein extracts of heat-separated epidermis, eight out of the nine CP sera specifically reacted with two protein bands of approximately 230-240 kD and 180 kD, similar to those recognized by BP sera in co-migration experiments. By immunoblotting on skin BMZ extracts, none of these nine CP sera recognized the 290-kD major polypeptide of EBA antigen. Taken together, these results suggest that, in CP, the target-antigen, as identified on immunoblots, is similar to BP antigen, but with an abnormal expression within the dermoepidermal junction of patients, which may in part explain the scarring course of the disease.

Adult↗
PubMed1989

Diagnosis of adult linear IgA dermatosis by immunoelectronmicroscopy in 16 patients with linear IgA deposits.

Homogeneous linear IgA deposits at the dermo-epidermal junction (DEJ) shown by direct immunofluorescence are characteristic of what is termed linear IgA bullous dermatosis. However, it is not yet certain that this disease constitutes an entity distinct from other subepidermal blistering diseases, especially when IgG deposits are also present. Sixty-one cases of subepidermal blistering disease in adults were therefore investigated by immunoelectron microscopy (IEM), and the 16 patients observed to have homogeneous linear IgA deposits were compared with the 45 who had no IgA but had IgG and/or C3. In 11 of the 16 patients with IgA (four of whom also had IgG), the deposits were linear and formed a mirror image pattern on each side of the lamina densa from which they were separated by a clear space. In contrast to this monomorphic IEM pattern, clinical and other laboratory findings were very heterogeneous, making exact clinical diagnosis difficult. Of the remaining five patients in this group of sixteen, three (all with both IgA and IgG) had bullous pemphigoid, epidermolysis bullosa acquisita, and cicatricial pemphigoid, respectively, on IEM and clinical investigation. In the remaining two patients (one with both IgA and IgG, and one with IgA only) the deposits were located in the lamina lucida, making precise classification impossible. None of the 45 patients with isolated IgG and/or C3 deposition displayed the mirror image pattern. We conclude that this IEM pattern may constitute a specific diagnostic criterion of linear IgA dermatosis.

Adult↗
PubMed1985

Lichen planus pemphigoides: an immuno-electron microscopic study.

We report a case of lichen planus pemphigoides. Immuno-electron localization of G-immunoglobulin and C3 showed that in the peribullous zone these were in the lamina lucida, as in typical bullous pemphigoid, but in the bulla itself they were along the floor, and not along the roof as in bullous pemphigoid. We conclude that bullous pemphigoid antigen and lichen planus pemphigoides antigen have different localizations.

Adult↗
PubMed1988

Cantharide acantholysis: endogenous protease activation leading to desmosomal plaque dissolution.

Using a method which allowed us to study the morphological consequences of the expression and the inhibition of proteases in living tissues, we demonstrated that the primary detectable cellular event in cantharide acantholysis is the dissolution of the dense plaque, leading to the detachment of tonofilaments from desmosomes. This process is inhibited by neutral serine protease inhibitors. This suggests that the desmosome-tonofilament complex, more precisely the desmosomal dense plaque, is the primary target of activated proteases during cantharide acantholysis, and can be disrupted by a specific epidermal protease-anti protease system. Cantharide acantholysis may be useful model for studying desmosomal turnover.

Acantholysis↗
PubMed1993

Serious childhood angiomas: unsuccessful alpha-2b interferon treatment. A report of four cases.

Over a 4-year period, we managed four children with alarming haemangiomas (two cases of Kasabach-Merritt syndrome and two life-threatening haemangiomas). Systemic steroid therapy was ineffective. Other treatments (radiotherapy, anti-platelet drugs) were also ineffective in the Kasabach-Merritt patients. On the basis of recent reports on the effects of interferon on endothelial cells, we used alpha-2 interferon therapy, but obtained no response.

Arm↗
PubMed1994

Cutaneous manifestations of methylmalonic and propionic acidaemia: a description based on 38 cases.

Methylmalonic and propionic acidaemias are rare metabolic disorders with an autosomal recessive mode of inheritance. A number of aminoacidopathies may have cutaneous manifestations, but these are usually absent in methylmalonic and propionic acidaemia. We have studied 38 children with propionic and methylmalonic acidaemia in the last 10 years at the Hôpital Necker-Enfants Malades. Thirteen had cutaneous manifestations: acute superficial scalded skin and superficial desquamation, bilateral and periorificial dermatitis, psoriasiform eruptions, and alopecia. The relative uniformity of these manifestations (scalded skin and desquamation after metabolic decompensation, chronic bilateral and periorificial dermatitis) suggests that methylmalonic and propionic acidaemias should be included in the category of aminoacidopathies with cutaneous manifestations. All these patients were suffering from severe forms of these diseases, with no residual enzyme activity, and they were all subjected to a very severe natural protein-restricted diet. These cutaneous manifestations may therefore either be part of a complex multideficiency syndrome, or be due to the enzyme deficiency itself.

Amino Acid Metabolism, Inborn Errors↗
PubMed2004

Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme.

OBJECTIVE: To validate the Eczema Area and Severity Index (EASI) by assessing its internal consistency, reliability and sensitivity to change and by correlating it to other efficacy parameters. DESIGN: Three short-term and two long-term double-blind, randomized, controlled trials, performed in 138 study centres in Europe, South Africa, Australia, New Zealand, and North and South America. PATIENTS AND METHODS: In total, 1550 paediatric patients with atopic dermatitis were studied. Pimecrolimus cream 1% was used twice daily to treat atopic dermatitis. The three short-term studies were placebo controlled. The two long-term studies evaluated the efficacy and safety of early intervention with pimecrolimus to prevent progression to disease flare requiring topical corticosteroid treatment, compared with reactive treatment with topical corticosteroids to treat flares of atopic dermatitis. MAIN OUTCOME MEASURES: Five parameters were measured: (i) the EASI (range of score 0-72); (ii) Investigators' Global Assessment (IGA), using a six-point (0-5) scale; (iii) patients' assessment, using a four-point (0-3) scale; (iv) severity of pruritus assessment, using a four-point (0-3) scale; and (v) a quality-of-life evaluation. RESULTS: The EASI score varied in parallel and in correlation with the IGA, pruritus and patients' assessment. All correlation coefficients were statistically different from 0 (P < 0.05). The EASI correlated well with each of its components, and all paired comparisons were within agreed limits. The EASI showed good sensitivity to changes in severity. CONCLUSION: In a large, multinational patient population with atopic dermatitis, the EASI showed good validity, reliability and sensitivity to change and correlated well with other measures of severity. It therefore qualifies as a valid method of assessment in clinical studies of atopic dermatitis.

Adolescent↗
PubMed2006

Absence of anti-BP180 antibodies in mothers of infants with bullous pemphigoid.

BACKGROUND: It is not clear whether bullous pemphigoid (BP) of infancy is linked to maternal transmission of pathogenic autoantibodies. Objectives To search for anti-BP180 antibodies in the sera of infants with BP and their mothers, using sensitive and specific methods. METHODS: Four infants (<6 months) with BP and their mothers were tested for anti-BP180 antibodies by indirect immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found anti-BP180 antibodies in the sera of the four infants with all methods. These antibodies reacted with the extracellular domain NC16A. In the serum of their mothers we found 180 and 160 kDa proteins, each in one case, but indirect immunofluorescence and ELISA were negative, suggesting the absence of anti-BP180 autoantibodies reacting with the extracellular domain NC16A. CONCLUSIONS: BP of infants is not due to maternofetal transmission of pathogenic autoantibodies. Other hypotheses for the pathophysiology of BP are discussed.

Adult↗
PubMed1993

Interleukin 4 prevents the induction of tissue factor mRNA in human monocytes in response to LPS or PMA stimulation.

Increased expression of tissue factor (TF) procoagulant activity by blood monocytes and tissue macrophages is implicated in a number of thrombotic disorders, as well as in fibrin deposition associated with inflammatory lesions and immunological diseases. We found that interleukin 4 (IL-4), a T lymphocyte-derived cytokine known to regulate a number of monocyte functions, inhibited the production of TF by monocytes in response to endotoxin and phorbol myristate acetate (PMA) in vitro. IL-4 had a concentration-dependent inhibitory effect on functional TF procoagulant activity (PCA) and reduced the binding of an anti-TF antibody, as assessed by flow cytometry analysis. Moreover, IL-4 reduced LPS- and PMA-induced TF mRNA levels. TF mRNA stability was not modified by IL-4 after the arrest of transcription by actinomycin D. We thus conclude that mRNA suppression is mediated by an effect occurring at the transcriptional level. Our results also show that the suppressive effect of IL-4 is independent of an increase in the intracellular concentration of cyclic AMP, another established inhibitor of TF production. Locally produced IL-4 might thus contribute to limiting the consequences of monocyte activation.

Blood Coagulation↗
PubMed1994

Disseminated cutaneous botryomycosis--an unexpected diagnosis after 20-years' duration.

A 35-year-old man presented with nodular suppurative lesions of the buttocks and the neck evolving over 20 years. A diagnosis of botryomycosis was established. Staphylococcus aureus, Acinetobacter baumanii and coagulase negative Staphylococcus were isolated from the biopsy specimen. Surgical excision was performed with success on the buttock.

Acinetobacter Infections↗
PubMed1979

Metabolic activity of human polymorphonuclear leucocytes: relation to ingestion rate.

The ingestion rate and oxygen-dependent metabolic activities of normal human polymorphonuclear leucocytes were measured with heat-killed Klebsiella as the particle. Since the experimental conditions were similar for each measurement, it was possible to make direct correlations between each oxygen-dependent reaction and (1) ingestion rate and (2) the other oxygen-dependent reactions. In the controls, oxygen-uptake was more reliably correlated (r = 0.960) with ingestion rates than with (in order of reliability) hydrogen peroxide produced (r = 0.860) and iodination (r = 0.858 and 0.813 for 100 and 20 micromol/l iodide respectively). Hydrogen peroxide production (r = 0.988), nitroblue tetrazolium reduction (r = 0.969) and cytochrome c reduction (r = 0.862) were more reliably correlated to oxygen-uptake than to ingestion rate, and iodination was better related to hydrogen peroxide production (r = 0.90 and 0.819 for 100 and 20 micromol/l iodide respectively) than to ingestion rate. From these findings it was possible to locate primary defects in abnormal polymorphonuclear leucocytes from individual patients with pyogenic infections, idiopathic refractory anaemia or idiopathic oesteomyelofibrosis with splenomegaly, even when several deficiencies existed.

Anemia↗
PubMed2006

Treatment of paediatric atopic dermatitis with pimecrolimus (Elidel, SDZ ASM 981): impact on quality of life and health-related quality of life.

AIM: To report on quality of life (QoL) and health-related quality of life (HRQL) impacts of pimecrolimus (Elidel, Novartis A.G., Basel, Switzerland, SDZ ASM 981) 1% cream in the long-term treatment of paediatric atopic dermatitis. METHODS: QoL and HRQL data are presented from two 12-month international clinical trials evaluating the efficacy and safety of pimecrolimus 1% cream. Both trials were randomized and double blinded and compared two treatment strategies, one involving the use of emollients, pimecrolimus and topical corticosteroids, the other is 'usual care' (emollients plus topical corticosteroids) with a vehicle cream to maintain study blinding. The first trial (the infant trial) involved patients between ages 3 months and 2 years, whereas the children trial included patients aged 2-17 years. In both trials, QoL of the affected child's parent was evaluated with the parent's index of quality of life in atopic dermatitis (PIQoL-AD). HRQL was assessed in the children trial only with the children's dermatology life quality index (CDLQI). QoL and HRQL assessments were conducted at baseline, 6 weeks, 6 months and 12 months. RESULTS: Generalized linear modelling of PIQoL-AD scores at each post-baseline visit showed a greater impact on parent's QoL for pimecrolimus compared with control at all time-points in both trials. HRQL scores showed a greater improvement from baseline for children in the pimecrolimus group compared with those in the control group at all time-points. CONCLUSIONS: The results show a beneficial impact of pimecrolimus on parents' QoL in paediatric atopic dermatitis, confirming findings from earlier shorter term trials. There was also a clear benefit to the HRQL of the children treated.

Administration, Cutaneous↗
PubMed1987

Prolonged beta blockade due to tertatolol: a comparative study with propranolol and atenolol.

Submaximal exercise heart rate was measured after oral administration of placebo, tertatolol 5 mg, propranolol 80 mg, and atenolol 100 mg to 12 subjects in a double-blind cross-over study. The peaks of beta-blocking activity, observed at 2 hr, were of similar extent for the 3 drugs. The duration of activity of tertatolol, a beta blocker with a short elimination half-life, extended up to 24 hr as did that of atenolol, but was longer than that of propranolol which reached only 18 hr. These results support once-daily administration of tertatolol in therapy.

Adult↗