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Biomedical subjects

U F Haustein

Publications and source records attributed to U F Haustein.

At least 55 records · Page 3Linked to original sources

Scleroderma-like lesions in insulin-dependent diabetes mellitus.

We report on two patients (one female 42 years, one male 47 years) suffering from insulin-dependent diabetes mellitus (IDDM) for more than 20 years. Both patients exhibited sclerodactyly and sclerosis of the hands and lower arms as well as swelling and slight contracture of the distal interphalangeal joints. Interestingly, internal organs were not involved and autoantibodies characteristic for scleroderma were missing. Poor utilization and excess of glucose seem to be responsible for the activation of fibroblasts to produce abundant matrix proteins in the skin. Significant therapeutic improvement of the glucose metabolism was able to improve joint contractures or at least to stop the progression of skin changes in our patients. These skin changes should not be misdiagnosed as systemic sclerosis.

Adult↗

[Progressive systemic scleroderma--prognosis determining involvement of internal organ systems].

Prognosis of systemic sclerosis (scleroderma, Ssc) is largely depending on involvement of internal organs. Abnormalities of the gastrointestinal tract are found most frequently (85%), especially decreased motility of the oesophagus, which has little impact on the longterm clinical course of Ssc. Pulmonary manifestations can be demonstrated in 40-90% of patients; one must distinguish between pulmonary hypertension or fibrotic lung disease. The heart is affected in 50% of cases. Patchy or diffuse myocardial fibrosis, as well as pericarditis and pericardial effusions can induce symptoms of arrhythmia or congestive heart failure. Renal involvement is associated with increased mortality and occurs in 45% of Ssc, producing proteinuria, hypertension, scleroderma renal crisis and renal failure. In conclusion, involvement of the lungs, heart and kidneys are determining factors for the longterm course of systemic sclerosis.

Heart Diseases↗

Serum levels of soluble Fas/APO-1 receptor are increased in systemic sclerosis.

It has been suggested that rheumatic diseases may result from a deficit in Fas-mediated T-cell apoptosis. Recent studies have demonstrated increased soluble Fas in sera from lupus erythematosus patients. We were interested to determine whether elevated soluble Fas levels are associated with systemic sclerosis. Soluble Fas levels were retrospectively assayed using a sandwich enzyme-linked immunosorbent assay in serum from 30 patients with systemic sclerosis and 15 normal controls. Hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients. Soluble Fas levels were analysed in subsets of patients with limited (lcSSc) versus diffuse cutaneous systemic sclerosis (dcSSc) and correlated with inflammatory activity. In systemic sclerosis soluble Fas serum levels (lcSSc, 2.19 +/- 0.71 ng/ml, dcSSc 2.53 +/- 1.37 ng/ml) were significantly higher than in normal controls (1.26 +/- 0.36 ng/ml). However, there were no significant differences in soluble Fas levels between lcSSc and dcSSc and poor correlation between soluble Fas levels and inflammatory activity status. Detection of elevated soluble Fas might serve as a clinical marker for immunological dysregulation in systemic sclerosis, but not for inflammatory disease activity.

Antibodies, Antinuclear↗

The monoclonal antibody AS02 recognizes a protein on human fibroblasts being highly homologous to Thy-1.

Recently, we described a novel fibroblast-restricted monoclonal antibody (mAb AS02) that recognizes a membrane-bound antigen. Characterization and isolation of the corresponding antigen showed that mAb AS02 recognized a protein on human fibroblasts that is highly homologous or identical to human Thy-1 antigen (CD90). Partial amino acid sequencing of the corresponding mAb AS02 antigen and comparison with known proteins revealed a 100% homology of the sequenced peptides to the human Thy-1 antigen. Cross-immunodepletion studies with mAb AS02 and an anti-Thy-1 antibody confirmed these results. Utilizing two-dimensional (2D) gel electrophoresis of fibroblast cell extracts and purified antigen, mAb AS02 and the anti-Thy-1-antibody recognized identical protein spots. Furthermore, we demonstrated many identical biochemical properties of the corresponding AS02 antigen and Thy-1 antigen, such as the molecular weight of the core protein and deglycosylation products and the detection of a GPI anchor. In functional assays, the attachment of fibroblasts to collagen I and fibronectin was increased after incubation of fibroblasts with mAb AS02. Therefore, the Thy-1 antigen appears to be involved in the regulation of the adherence of human dermal fibroblasts.

Amino Acid Sequence↗

Rhinocerebral zygomycosis following bone marrow transplantation in chronic myelogenous leukaemia. Report of a case and review of the literature.

We report on a man suffering from chronic myelogenous leukaemia treated by allogeneic bone marrow transplantation who, in the late post-transplantation phase, developed a hyperacute fatal invasive rhinocerebral zygomycosis. The origin of the ascending infection was the sinus sphenoidalis from which fungal hyphae spread to the central nervous system via the skull and the dura mater. The first symptoms of this severe infection were cerebral convulsions and a bilateral total amaurosis. The isolation of the pathogen from post mortem tissue was not successful. The present case is compared with previous reports of zygomycoses after bone marrow transplantation.

Adult↗

Conversion of psoriasis patients from the conventional formulation of cyclosporin A to a new microemulsion formulation: a randomized, open, multicentre assessment of safety and tolerability.

OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.

Adolescent↗

Cyclosporine A delays wound healing and apoptosis and suppresses activin beta-A expression in rats.

Cyclosporine A is a powerful immunosuppressive agent which is widely used for the prevention of allograft rejection and for the treatment of autoimmune diseases. Clinical and experimental data show that it may also act on connective tissue. We investigated the influence of cyclosporine A on granulation tissue formation and wound healing. Using an in vitro approach, we followed the time course of rat dermal fibroblasts during wound repair. Granulation fibroblasts were compared to dermal fibroblasts flow cytometrically and by mRNA analysis with respect to the expression of procollagen alpha1(I), integrin beta1, interleukin-6, transforming growth factor beta1, keratinocyte growth factor and activin betaA. The most pronounced effect in cyclosporine-treated rats was the strong down-regulation of activin beta expression. In cryo-sections of granulation tissue from the same rats, the distribution and expression intensity of intercellular adhesion molecule and its receptors were investigated by immunohistology. Clearly, a time course was detectable. Tissue from CsA-treated animals showed a delay of three days compared to untreated animals. Apoptosis was also delayed in CsA-treated rats by around three days. Furthermore, we investigated the effect of CsA on the expression of collagen alpha1(I), fibronectin and matrix metalloprotease 1 genes in dermal fibroblasts from untreated donors. No changes in the mRNA steady state levels of these genes were revealed after direct addition of different doses of CsA to fibroblast cultures. Our data suggest that CsA may interfere with the complicated net of interactions between connective tissue and the immune system by down-regulation of the inflammatory phase by modulation of cytokines and a subsequent delay of tissue repair.

Activins↗

Pathophysiology of scleroderma: an update.

OBJECTIVES: To review the pathophysiological background of systemic sclerosis in relation to the main components involved: microvascular system, immunological system and fibroblasts of the connective tissue. BACKGROUND: Although many particular aspects of the pathophysiology of systemic sclerosis have been investigated in recent years, the complexity of the pathogenesis and the important links between the components involved remain unclear. METHODS: Literature review. RESULTS AND CONCLUSION: Scleroderma is a connective tissue disorder resulting in a progressive fibrosis of skin and internal organs. The genetic background is not clear. The microvascular system is one of the first targets involved (damage of capillaries, enhanced expression of adhesion molecules interacting with lymphocytes, perivascular infiltrates as starting points for tissue fibrosis). The immune system is unbalanced (selection of T-cell subpopulations, elevated serum levels of several cytokines, occurrence of autoantigens to topoisomerase I, centromeric proteins and RNA polymerases). As far as autoimmunity is concerned the triggering autoantigen is still unknown. Development of connective tissue fibrosis is prominent (subpopulations of fibroblasts with disturbed regulation of collagen turnover by TGF-beta, CTGF and collagen receptors (alpha1beta1, alpha2beta1)). Investigation of pathophysiology of scleroderma is effected by monitoring the serum levels for soluble mediators, by cell culture studies of affected and non-affected fibroblasts and EC, by studying environmentally induced forms of scleroderma and by studies using animal models.

Animals↗

Squamous cell carcinoma of the skin--histopathological features and their significance for the clinical outcome.

BACKGROUND: Owing to the rising incidence of tumours, the question of reliable risk classification is becoming increasingly significant. OBJECTIVE: Participation in the multicentre carcinoma registry maintained by the Association of Operative and Oncological Dermatology of the German Dermatological Society requires, in addition to the parameters of clinical staging and grading already established by the International Union against Cancer, description of other histopathological criteria related to prognosis, with special attention to microstaging. METHODS: One hundred and eighty-four patients with squamous cell carcinoma of the skin were examined. The histological parameters, carcinoma type, Breslow index, invasion level, growth form, grading and mitotic index were recorded and classified, and clinical staging was performed. RESULTS: It was found that the clinical criterion of tumour diameter (T-category) determines the further course of the disease. The other parameters taken into account, namely pathohistological microstaging and grading, can increase the accuracy of prognosis evaluation, and in particular enable carcinomas of the T1-category to be classified as either high malignant or low malignant tumours. The desmoplastic squamous cell carcinoma subtype is a potential risk tumour. Endophytic tumours are more malignant in their development than exophytically-growing carcinomas, and the probability of recurrence and metastatic tumour spread further increases when ulceration can be detected by microscope. In order to distinguish metastatic and recurring carcinomas, in addition to determining the invasion levels after Clark, measuring the Breslow index proved to be an important criterion. Quoting the mitotic index augmented the grading system, which further improved the reliability of malignancy assessment. CONCLUSIONS: The TNM categories currently applied to squamous cell carcinomas of the skin must be supplemented by additional histological parameters which, according to our findings, permit more accurate classification of high and low malignant tumours.

Carcinoma, Squamous Cell↗

Silica induced scleroderma--clinical and experimental aspects.

Clinical and experimental data concerning silica induced systemic sclerosis (SSc) are discussed in comparison to current knowledge of the pathophysiology of idiopathic SSc. About 280 patients with SSc after longterm silica dust exposure, some with associated silicosis, have been reported; 111 of them were analyzed as the largest cohort in our department. Based on clinical and laboratory data, silica induced and idiopathic SSc show similar pathophysiology and similar markers of the disease including vascular involvement, immunological abnormalities, and dysregulation of extracellular matrix metabolism. Experimental studies show that silica dust is able to activate microvascular endothelial cells, mononuclear cells from peripheral blood, and dermal fibroblasts in vitro in a fashion in common with pathophysiological events known from idiopathic SSc.

Adult↗

[Bullous mastocytosis in a child].

We report a case of bullous mastocytosis in a 30-month-old girl, who developed disseminated pruritic urticarial and bullous lesions on the trunk accompanied by episodes of vomiting and generalized flushing. Her problems began at the age of 6 months. Her stool was repeatedly positive for occult blood. Histamine and 5-hydroxytryptamine were measured in the urine and serum; urine 5-hydroxytryptamine levels were elevated. In addition, trypsin and chymotrypsin levels were raised in the blister fluid. Metachromatic staining of the mast cells in a skin biopsy specimen confirmed the diagnosis. A combination of oral disodium cromoglycate and ketotifen produced a dramatic improvement of the cutaneous and gastrointestinal features.

Child, Preschool↗

[Longitudinal study of the excretion of 1-hydroxypyrene in urine after external treatment with coal tar].

In order to study the dermal uptake, time course, and urinary excretion of polycyclic aromatic hydrocarbons, the concentration of 1-hydroxypyrene in urine was determined by means of high performance liquid chromatography with fluorescence detection before, during, and after the topical treatment with coal tar in 19 patients suffering from prurigo simplex subacuta, microbial eczema, atopic dermatitis, eczematization after scabies, exanthematous lichen ruber, pityriasis lichenoides and cutaneous sarcoidosis. Beginning with a value of 6.04 +/- 2.06 micrograms 1-hydroxypyrene/g creatinine before treatment, the urinary excretion significantly increased during the therapy with coal tar (p < 0.0001 at 3rd, 5th, and 6th day of therapy). A maximum was reached at day 8 of topical treatment with a value of 584.35 +/- 191.96 micrograms 1-hydroxypyrene/g creatinine (p < 0.002). Already during treatment at day 10 there was a beginning decrease of 1-hydroxypyrene to 361.63 +/- 170.13 micrograms/g creatinine. After the end of treatment, the excretion further decreased reaching a value of 5.31 +/- 2.85 micrograms 1-hydroxypyrene/g creatinine at the 10th day after therapy. Skin carcinomas due to therapeutical use of coal tar occur extremely rarely and only after vergoten, non-controlled use. We suggest that the duration of exposure is the most important factor for the carcinogenic effect of coal tar.

Administration, Cutaneous↗

The fibroblast-specific MAb AS02: a novel tool for detection and elimination of human fibroblasts.

The unwelcome presence of fibroblasts in many cell cultures prevents the long term cultivation of various cell types and work with pure populations. Recently, we described a novel fibroblast-specific monoclonal antibody (MAb AS02) that recognises a membrane-bound antigen. We have now developed a method using the fibroblast-specific MAb AS02 immobilised on goat-anti-mouse-magnetic beads to separate contaminating fibroblasts. An endothelial cell line experimentally contaminated with 5%-50% fibroblasts was successfully purified. Additionally, an endothelial cell line with an initial fibroblast contamination of 1.5% was prepared. A proportion of each preparation was cultured with no separation step being performed, whereas the remainder was cultured after purification with MAb AS02 to exclude the presence of a minor number of fibroblasts (<0.1%). The proportion of fibroblasts increased up to 38% in the fifth passage of culture without elimination of the low initial fibroblast contamination, whereas in the fraction with the separation step, no fibroblasts were detectable by flow cytometry, even after the fifth passage. We also used the antibody to detect the presence of naturally contaminating fibroblasts in thyrocyte cultures. After cultivation of thyrocyte cultures over five passages, the number of fibroblasts increased dramatically up to 50%-80% of the whole population. Subsequently, we successfully applied the method for complete elimination of naturally contaminating fibroblasts from freshly isolated thyrocyte cultures from enzymatically digested thyroid glands. Thus, MAb AS02 is a fibroblast-specific marker that is a useful tool for the detection and elimination of contaminating fibroblasts. The specificity of MAb AS02 permits the universal application of this antibody for human cell cultures of interest.

Animals↗

Tinea corporis due to Trichophyton tonsurans Malmsten--report of a patient from Zaire.

Trichophyton tonsurans is an anthropophilic dermatophyte that is predominantly responsible in man for tinea capitis. Although this fungus has a world-wide distribution, most reports of the occurrence of Trichophyton tonsurans infections originate from the USA, Latin America and some European countries. A 31-year-old African woman, formerly a resident of Zaire, with tinea corporis caused by Trichophyton tonsurans infection is described here.

Administration, Oral↗

Combination of an island advancement flap and a composite graft for reconstruction of the nasolabial defect.

BACKGROUND: The alar region is one of the most difficult areas of the face to reconstruct. Up until now, various methods have been demonstrated for achieving the best possible results in terms of cosmetic appearance and function. This report deals with a combination of a random pattern flap and a free composite graft, carried out in two stages. OBJECTIVE: In order to reconstruct the alar region, an island advancement flap as well as a composite graft from the contralateral ear were used. METHODS: The defect in the cheek-upper lip region was closed using an island advancement flap. In a second operation 2 weeks later, the reconstruction of the alar region was attempted using a composite graft from the right ear. RESULTS: The reconstruction of the contour of the wing of the nose succeeded in a satisfactory manner. There are no functional restrictions on nose breathing. CONCLUSIONS: The combination of an island advancement flap with a composite graft from the ear for the reconstruction of the alar region is essentially a less invasive operation that can be carried out under local anaesthesia and that represents an addition to the previously stated methods.

Aged↗