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Summary: Spermatozoa were prepared by swim up technique in the same way as for in vitro fertilization of human eggs and incubated with antihuman fibronectin antibodies in the immunfluorescence technique. Fibronectin mediates adhesive interactions between cells. 69 p.c. of spermatozoa with a normal shape and only 17 p.c. of them exhibiting a pathological shape showed a positive fibronectin-fluorescent band on the equatorial segment, called equatorial fibronectin band (EFB). The cryopreservation of semen did not influence the EFB. The significance of EFB for the sperm-oocyte-binding is discussed in connection with the sperm morphology and epididymal function. Zusammenfassung: Das aquatoriale Fibronektinband menschlicher Spermatozoen -eine Erganzung bei der mannlichen Fertilitatsdiagnostik? Spermatozoen wurdem mit dem swim-up-Verfahren analog zur sper-miologischen Vorbereitung der in vitro Fertilisierung menschlicher Oozyten prapariert und mit Hilfe der Immunfluoreszenztechnik auf Fibronektin untersucht. Fibronektin spielt u.a. eine entscheidende Rolle bei Zell-zu-Zell-Interaktionen. 69% der normomorphen und nur 17% der pathomorphen Spermatozoen zeigten ein positives Fibronektin-Fluoreszenz-band im Bereich des Aquatorialsegments, genannt aquatoriales Fibronektinband (AFB). Die Sperma-Kryokonservierung beeinfluste nicht das AFB. Die Bedeutung des AFB fur die Spermien-Oozyten-Bindung wird im Zusammenhang mit der Spermienmorphologie und der Rolle des Nebenhodens diskutiert.

Background Local and systemic reactions can occur after bites of Argas reflexus (Argas), a soft tick parasitizing pigeons. Objective Risk assessment of IgE-mediated sensitizations and systemic reactions after Argas bites. Methods Case histories, skin prick tests (SPTs) with a whole-body extract of Argas containing major allergen Arg r 1, and common inhalants and specific IgE measurements were obtained from 148 subjects who had had Argas bites and 20 volunteers as a control group. Results Systemic reactions (urticaria, angioedema, dyspnea, cardiovascular dysregulation, unconsciousness) were reported in 12 of 148 (8%); 146 of 148 (99%) had local reactions. Atopy was found in 37 of 146 (25%) with local reactions and 3 of 12 (25%) with systemic reactions. SPT to Argas was positive in 24 of 148 (16%) with a high proportion of atopics 10 of 24 (42%); specific IgE to Argas was detectable in 12 of 135 (8% of 148) with moderate concordance to systemic reactions. No positive SPT or specific IgE results to Argas were obtained in the control group. Immunoblotting of 23 sera revealed an IgE-binding protein in 19 of 23 sera (82%) at 22 kd, indicating a major allergen of Argas. Conclusion Severe anaphylactic reactions were infrequently (approximately 8%) found after bites of the soft tick Argas reflexus. Atopy is a risk factor for skin sensitizations to Argas, but not for systemic reactions after bites by Argas. Using a whole-body extract of Argas, diagnosis through SPT and specific IgE is hampered by false-negative and irrelevant positive results, particularly in atopy.

Bisher ist nicht bekannt, wie sich durch Zufuhr aminosaurehaltiger Externa das „Feuchthaltekomplexsystem“ der Haut in vivo beeinflussen lasst. Untersucht wurde der Einfluss der topischen Zufuhr von Argininhydrochlorid auf den Harnstoffgehalt der Hornschicht der Epidermis, den transepidermalen Wasserverlust, die Hautfeuchtigkeit sowie den klinischen Hautzustand bei Patienten mit atopischem Ekzem sowie Altershaut. Die 4-wochige Behandlung von Patienten mit atopischem Ekzem bzw. Altershaut mit 2,5%iger Argininhydrochloridsalbe ergab einen signifikanten Harnstoffanstieg im Stratum corneum sowie einen kontinuierlichen Anstieg der Hautfeuchtigkeit. Das Harnstoffdefizit im Stratum corneum beim atopischen Ekzem sowie bei Altershaut konnte nicht nur durch den Moisturizer Harnstoff selbst, sondern auch durch dessen Precursor im Krebs-Henseleit-Harnstoff-Zyklus—Arginin—beseitigt und damit eine Besserung des klinischen Symptoms „trockene Haut“ erreicht werden.

Mycobacterium gordonae is a potentially pathogenic environmental mycobacterium occasionally causing skin infections in immunocompromised patients but only rarely affecting healthy patients. Methods: A 41-year-old engine driver of goods trains presented with a 2 year existing 7 x 7 cm, scaly erythematous and infiltrating skin lesion on his left shin which clinically resembled microbial eczema, granuloma anulare or necrobiosis lipoidica. Objectives: Histologic examination revealed a psoriasis-like, lichenoid plasmacellular infiltrate and spongiotic interface dermatitis. Ziehl-Neelsen staining and PAS reaction as well as alcian blue staining to detect mucin were negative. In microbiological culture M. gordonae was detected. Conclusion: The tumour was too extended to be excised. Therefore a combined therapy of doxycycline and trimethoprim /sulfamethoxazol was started, however, without any effect. Under clarithromycine (500 mg/d) and moxifloxacine [400 mg/d) the skin lesions showed regression after two months. Therefore an additional tuberculostatic therapy with rifampicin or isoniacid was not considered necessary.

Permethrin is used for the treatment of head-lice world-wide. Different formulations (creme, shampoo, solution) are used, in most cases with a 1% concentration of permethrin. As many trials showed this concentration to be perfectly effective, these formulations are considered to be the international state of the art. What had to checked was, if a 0.5% formulation of permethrine would be equally effective. In this multi-centred, open trial 67 patients with the diagnosis of pediculosis capitis were treated with a 0.5% permethrine-solution. 1 day after treatment 63 (94%) were free from living lice. After 8 days 61 (91 %) patients were free from lice. 66 of 67 (99%) considered the compliance to be good resp. very good. The 0.5% alcoholic solution has proved to be equally effective compared to the ordinary 1% solution of permethrine.

The expression of adhesion molecules on endothelial cells as well on tumor cells regulates and directs adhesion and transmigration of tumor cells through the endothelial cell barrier as one prerequisite to the formation of metastasis. Thy-1 is an inducible activation-associated cell-adhesion molecule on human dermal microvascular endothelial cells (HDMECs). In this study we investigated whether the Thy-1/Thy-1 ligand interaction may also play a role in adhesion of melanoma cells to endothelial cells. In situ, a strong Thy-1 expression on endothelial cells in melanoma and melanoma metastases was observed. In vitro, Thy-1 expression was stimulated by melanoma-cell-derived soluble factors, reflecting that Thy-1 expression in melanoma is not only due to a nonspecific inflammatory response. TNFalpha and bFGF were not responsible for this effect. In vitro and in situ a Thy-1 ligand was detected on melanoma cells. In cell-adhesion assays we showed the involvement of the Thy-1/Thy-1 ligand interaction in adhesion of melanoma cells to HDMECs. In summary, the data support that the study of the Thy-1/Thy-1 ligand interaction might give a more detailed insight into the regulation and direction of adhesion of melanoma cells to endothelial cells as one critical step in the formation of tumor metastasis.

Das seltene Multiple-Lentigines (LEOPARD)-Syndrom, ein komplexes Fehlbildungssyndrom mit Haut-, Herz-, Skelett- und anderen Auffalligkeiten wird anhand eines 36-jahrigen mannlichen Patienten und dessen 9-jahriger Tochter beschrieben. Atiopathogenetische Uberlegungen, Klinik und differenzialdiagnostische Aspekte werden diskutiert. Beim Auftreten multipler Lentigines sollte stets eine weiterfuhrende, insbesondere kardiale Diagnostik veranlasst werden.

ZusammenfassungZiel: Prüfung der Tumeszenzlokalanästhesie (TLA) als alternative Form einer nebenwirkungsarmen und schonenden Operationsmöglichkeit bei Varizen. Methoden: Von Dezember 1998 bis Februar 2002 wurden an 102 Patienten Varizenoperationen in TLA vorgenommen. Der anästhesierende Effekt der Gewebsdehnung wird mit der Wirkung des Lokalanästhetikums (Prilocain-Lösung mit Adrenalinzusatz, 0,1-0,4%) kombiniert. Ergebnisse: Es wurden 90 inguinale Crossektomien, 74 Strippings der Vena saphena magna, 91 Seitenastexhairesen und 49 Perforansligaturen durchgeführt. Postoperativ kam es zu einer Nachblutung, drei punktionswürdigen Seromen, einer Wundinfektion sowie einer Nahtdehiszenz. Es traten keine allergischen Reaktionen oder Thrombosen (91,1% der Patienten erhielten eine Thromboseprophylaxe mit niedermolekularem Heparin) auf. Die postoperative Versorgung erfolgte mittels Kompressionsverbänden, beziehungsweise Kompressionsstrümpfen (Klasse II) für 6-8 Wochen, Nachkontrolle über 4-6 Wochen. Schlussfolgerung: Varizenoperationen in Tumeszenzlokalanästhesie sind aufgrund der niedrigen Komplikations- und Nebenwirkungsrate eine gute Alternative und helfen aus gesundheitsökonomischer Sicht, Kosten einzusparen.

Classical HIV-negative Kaposi's sarcoma is primarily a skin disease of the lower extremities affecting predominantly elderly men of Mediterranean origin. We report a case of a 77 year old man with an extensive manifestation of disease, and we describe the clinical and epidemiological characteristics. Therapy of classical Kaposi's sarcoma is always palliative, however, there is slow progress of disease. We present ways of local and systemical treatment. History: A 77 year old patient being diagnosed for classical Kaposi's sarcoma in 1992. Previous treatment with Prospidine. Physical Examination: Extensive subcutanous-cutanous localized livid vascular tumors which predominantly infiltrate the lower extremities and lower trunk. Diagnostics: Paraclinic not remarkable. Human Herpes-Virus-8 is detectable both in tumor tissue and blood. Therapy/progress: Patient did not wish any treatment. Discussion: Etiology is still unclear. A strong association with HHV-8-infection has been established. There is no standard treatment for CKS, so various possibilities of topical and systemic treatment have been described. Side-effects and benefits of any treatment are to be evaluated for it's a slow growing tumor.

Clinical picture, potassium hydroxide preparation and fungal culture are the principal diagnostic tools of tinea capitis. In Germany, griseofulvin is the only approved antifungal agent for the treatment of tinea capitis in children. The modern ergosterole biosynthesis inhibitors (terbinafine, itraconazole, and fluconazole) are namely tested and allowed for antifungal therapy in adults. They are not yet admitted for the treatment of children with tinea capitis. Thus, far few randomized double blind controlled studies concerning the effectiveness of these agents for the systemic therapy of tinea capitis have been published. Almost all open studies showed that the modern antifungals terbinafine, itraconazole, and fluconazole are superior to griseofulvin because of shorter duration of therapy and higher rates of cure.

Wir beschreiben den Fall einer 43-jahrigen Patientin mit einer seit Kindheit bestehenden intermittierend schmerzhaften Livedo racemosa am Rucken, die im Krankheitsverlauf zu Ulzerationen fuhrte. Die umfangreichen Untersuchungen konnten keinen Hinweis auf eine zugrunde liegende Erkrankung erbringen, wobei initial und im Verlauf insbesondere kein Anhalt fur ein Sneddon-Syndrom bestand. Mittels konserativer und chirurgischer Masnahmen konnte zunachst eine Abheilung der Ulzerationen erreicht werden, diese rezidivierten jedoch in der Folgezeit. Eine zyklische Therapie mit Iloprost-Infusionen fuhrte im vorliegenden Fall zu einer langfristigen Abheilung der Ulzerationen und zum Sistieren der Schmerzsymptomatik. Eine derartige Behandlung ist bisher fur diese Erkrankung in der wissenschaftlichen Literatur noch nicht beschrieben.

Die histologischen Varianten des Plattenepithelkarzinoms (PE-CA) der Haut werden unter Berucksichtigung seltener sowie neu erwahnter Tumorsubtypen dargestellt. Neben dem am haufigsten auftretenden unterschiedlich differenzierten gewohnlichen PE-CA lassen sich mikroskopisch folgende Formen subsummieren: Bowen-PE-CA, akantholytisches PE-CA, klarzelliges PE-CA, spindelzelliges PE-CA, keratoakanthomahnliches PE-CA, desmoplastisches PE-CA, neurotropes PE-CA, verrukoses PE-CA, adenosquamoses Karzinom und basosquamoses Karzinom. Umstritten ist die phanotypische Zuordnung des lymphoepitheliomahnlichen Karzinoms zu den PE-CA der Haut, da regelmasig ein Bezug zur Epidermis fehlt und der Nachweis von glandularer und follikularer Differenzierung histogenetisch einen malignen Adnextumor vermuten lasst. Neben der Beschreibung von histologischen und zytomorphologischen Besonderheiten der einzelnen PE-CA-Subtypen werden bedeutende Unterschiede in Bezug auf Malignitat und klinischen Verlauf herausgestellt.

Mastocytosis is a heterogeneous group of disorders characterised by an abnormal growth and accumulation of mast cells in skin, bone marrow, gastrointestinal tract, liver, spleen, and lymph nodes. Symptoms occur due to the release of histamine, prostaglandin D2, heparin and other mediators derived from mast cells. The clinical feature covers a broad spectrum from single mastocytoma to malignant mastocytosis and mast cell leukaemia. We report on two cases with adult benign systemic mastocytosis to show the variety of symptoms. Diagnostics oriented according to symptoms and options on therapy are presented as well as differential diagnosis and associated haematological disorders. The importance of advice and regular follow-ups of patients with systemic mastocytosis is emphasised.

Malassezia furfur und andere, neu beschriebene Malassezia-Arten werden aus taxonomischer, epidemiologischer und mikrobiologischer Sicht dargestellt. Im Mittelpunkt steht die Vermittlung der pathogenetischen bzw. auch atiologischen Bedeutung des lipophilen Spross- oder Hefepilzes fur eine Reihe dermatologischer Erkrankungen, u. a. der Pityriasis versicolor, aber auch der Malassezia-Follikulitis und des seborrhoischen Ekzems. Die In-vitro-Empfindlichkeit von Malassezia gegenuber Antimykotika und antiseborrhoischen Wirkstoffen erhalt klinische Relevanz, wenn es um die vielfaltigen lokalen und systemischen Behandlungsmoglichkeiten der genannten Hautkrankheiten geht. Nicht zuletzt soll auch der neuerdings diskutierte Zusammenhang zwischen Malassezia und atopischem Ekzem anhand mikrobiologisch-immunologischer Mechanismen beleuchtet werden. Malassezia ist als auslosendes Agens mit einer Reihe v. a. dermatologischer Erkrankungen assoziiert. So gilt der lipophile Sprosspilz als Ursache der Pityriasis versicolor, der Pityrosporum- bzw. Malassezia-Follikulitis, daneben wurde eine Malassezia-Blepharitis beschrieben. Zunehmend treten systemische Infektionen durch Malassezia ausschlieslich bei unreifen Sauglingen und immunsupprimierten Patienten auf. Von Bedeutung ist Malassezia auch in Bezug auf die Pathogenese des seborrhoischen Ekzems und der Kopfschuppen. Aktuelle experimentelle Arbeiten lassen vermuten, dass Malassezia-Allergene als Trigger auch den Verlauf des atopischen Ekzems – zumindest der sog. “head-neck”-Form – beeinflussen.

A 19 year old woman presented with a 4 week history of scaly erythematous patches with pustules on the trunk and extremities. Additionally, a massive infection in the genital region was conspicuous. The mons pubis was swollen, indurated and very painful. The presence of follicular pustules and nodules with discharge led to the diagnosis of kerion celsi Trichophyton mentagrophytes var. asteroides was isolated as causative agent. Systemic treatment with itraconazole (Sempera®) was coupled with topical sertaconazolenitrat (Zalain® ). The lesions responded well. The source of human infections by zoophilic dermatophytes, e.g. Trichophyton mentagrophytes var. asteroides is rodents. Such infections typically involve the scalp and beard; kerion celsi of mons pubis area is a rarity.

Summary: Neutrophil granulocytes isolated from healthy volunteers were found to kill proteinase-producing Candida albicans strains more effectively than proteinase negative strains in vitro (p < 0.01).The proportion was one Candida cell to one, three or five granulocytes. Zusammenfassung: Durch neutrophile Granulozyten gesunder Probanden werden in vitro bei einem Verhaltnis von einer Candidazelle zu einem, drei oder funf Granulozyten Proteinase-positive Candida-albicans-Stamme besser abgetotet als Proteinase-negative Stamme (p < 0,01).

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.

Das Raynaud-Phanomen kommt bei 90–100% der Patienten mit progressiver Sklerodermie vor. Es beruht auf einer Dysregulation des Gefastonus im Gleichgewicht von vasokonstriktorischen und vasodilatatorischen Einflussen. Die fruhzeitige Schadigung des Gefasendothels und Aktivierung von Thrombozyten fuhren zur Freisetzung vasoaktiver Substanzen. Die strukturellen und funktionellen Veranderungen der perivaskularen Nervenfasern tragen zur Genese des Vasospasmus bei Sklerodermie bei. Neue Konzepte der gefaserweiternden Therapie, wie z.B. Infusionen mit Calcitonin gen-related Peptiden konnten fur die Verhinderung des Vasospasmus der peripheren Extremitaten und internen Organe bei der Sklerodermie nutzlich sein.

In 12 patients suffering from systemic sclerosis (SSc) the influence of autogenic training on the plasma level of the neuropeptides substance P and vasoactive intestinal peptide (VIP) was studied. Compared with healthy controls the SSc patients exhibited significantly elevated levels of substance P (mean±SD: 7.1±3.2 pmol/l vs 1.6±1.6 pmol/l). Apart from variations the VIP plasma concentration did not significantly differ from that in healthy controls (mean±SD: 10.7±7.1 pmol/l versus 12.0±5.3 pmol/l). Autogenic training did not bring about any significant changes in the plasma levels of neuropeptides.

In 12 patients with systemic sclerosis the influence of hypnosis and autogenic training on the acral blood circulation and the coping with the disease was investigated in a pilot study. In the first step significant increases in the skin temperature of the finger (mean +/- SD: 3.9 +/- 1.2 degrees C) could be found after relaxation hypnosis. In the second step six patients (study group) gained experience with autogenic training. The other six patients served as control group. In the study group, the skin temperature of the fingers (short-term effect) was significantly higher than in the control group (1.9 +/- 1.0 degrees C). Long-term effects of the autogenic training (mean acral rewarning time, duration and course of the Raynaud attacks, acral lesions of the hands, psychosomatic status of complaints, type of relation to the disease as precondition for coping with the disease) were not found within the relatively short follow-up period of 4 months. Two patients, however, reported that they could shorten the duration of Raynaud attacks by autogenic training. In our patients heterogenicity and an increased score of multiple psychosomatic complaints were registered at the outset. As far as the type of relation to the disease is concerned, the patients could be assessed as almost adapted. Hypnosis and autogenic training can be recommended as complementary therapy in systemic sclerosis.

Thirty strains of the lipophilic yeast Pityrosporum ovale were isolated from patients suffering from seborrhoeic dermatitis and dandruff and tested for susceptibility both to some classic antifungal agents and to several primarily non-antimycotic drugs. Minimal inhibitory concentrations (MIC) of altogether eleven agents were measured by the agar dilution technique. As expected, the tested imidazoles showed a good inhibition of growth of Pityrosporum. The most effective agents were ketoconazole (MIC 0.1 microgram/ml) and itraconazole (MIC 0.05 microgram/ml for some strains). MIC for fluconazole, clotrimazole and tioconazole were also low, indicating a good inhibition of Pityrosporum. In contrast, the range of MIC for bifonazole was moderate to high (for some strains 12.5-25 micrograms/ml). For zinc pyrithion a very good in vitro efficacy (MIC 0.78-1.56 micrograms/ml) was dedicated. The MIC for selenium disulphide was 1.56-3.13 micrograms/ml. The antipsoriatic drugs dithranol and liquor carbonis detergens also inhibited growth of all Pityrosporum ovale strains investigated but only at higher concentrations.

Cutaneous myelofibrosis with extramedullary hematopoiesis was detected in erythematous macules in the abdominal region of a 67-year-old woman. The infiltrates were composed of myeloic cells and CD-61-positive megacaryocytic series. Erythroid series were not found. During maintenance therapy with hydroxyurea, these eruptions developed eight months after electron beam radiation treatment. The skin lesions expanded to the proximal extremities but did not increase any more when the chronic myelogenous leukemia proceeded. Another electronic beam irradiation was considered, but the patient died from a blast crisis due to conversion into chronic myelogenous leukemia (CML).

Papular-purpuric gloves and socks syndrome (PPGSS) occurs mainly in young adults, but it should also be considered in the differential diagnosis of childhood exanthems. The case presented here is the youngest patient hitherto reported with PPGSS and supports the concept of a viral genesis.

A hypothesis is presented that microorganisms at very high concentration (>1010/ml) interfere with the sperm-egg interaction by masking the equatorial fibronectin band (EFB) of human sperm and thus impair the fertilization process.

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.

Bericht uber ein 21/2jahriges Kind mit bulloser Mastozytose seit dem 6. Lebensmonat. Disseminierte juckende urtikarielle und blasige Hauteruptionen am Stamm waren von Erbrechen und generalisiertem Flush begleitet. Im Stuhl fand sich wiederholt okkultes Blut. Histamin und 5-Hydroxytryptamin wurden im Urin und Serum bestimmt. Im Urin war Hydroxytryptamin vor der Therapie erhoht. Des weiteren fanden sich Anstiege von Trypsin und Chymotrypsin in der Blasenflussigkeit. Die metachromatische Farbung der Mastzellen bestatigte die Diagnose im histologischen Bild. Die kombinierte Behandlung mit oralem Dinatriumchromoglykat und Ketotifen fuhrte zu einer dramatischen Besserung der kutanen und gastrointestinalen Symptome.

Microvascular damage occurs in systemic sclerosis and is associated with increased serum levels of endothelial adhesion molecules and endothelium-associated cytokines, including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, endothelin-1 and vascular endothelial growth factor (VEGF). Iloprost, a prostacyclin analogue, induces clinical benefit in patients suffering from scleroderma-related Raynaud's phenomenon. This study was performed to investigate the effect of iloprost infusions on endothelium activation. Serum samples from 12 patients with systemic sclerosis were examined using specific enzyme-linked immunoassays. The serum levels of sICAM-1, sVCAM-1 and soluble E-selectin were initially elevated and significantly reduced after iloprost infusions. The serum concentrations of VEGF and endothelin-1 revealed decreased levels after therapy too. These results indicate that the well-known clinical benefit of iloprost infusions on Raynaud's phenomenon is serologically detectable by a reduction of serum levels of endothelium-associated adhesion molecules, cytokines and growth factors reflecting an improvement in endothelial function.

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 (

Cultured granulation fibroblasts grown from punch biopsies of the same lower arm area, obtained 3, 6, 9 and 14 days after wounding, were used as a human wound healing model in comparison to quiescent fibroblasts. We investigated the expression of key extracellular matrix components at the protein level by flow cytometry and mRNA steady state levels by Northern blotting of the different fibroblasts and compared these data to the ability to migrate towards a chemotactic signal. Procollagen alpha 1 (I), fibronectin and matrix metalloprotease-1 synthesis was strongly up-regulated at the mRNA steady state level on days 3 and 14. Tissue inhibitor of metalloprotease-1 mRNA is only 20% down-regulated between day 3 and 14. Chemotaxis towards conditioned medium reflects a net effect of several factors and is distinctly different from chemotaxis towards platelet-derived growth factor, which peaks at day 3. Compared to the protein level, the enhanced expression of the corresponding PDGF receptor beta chain mRNA is delayed by 3 to 6 days. PDGF receptor alpha shows no regulatory changes during the observation period. This data further supports the idea that functionally divergent subpopulations of fibroblasts exist during wound healing.

Expression of interleukin-2 (IL2) receptors was studied on peripheral blood lymphocytes (PBLs) in 25 patients with bullous pemphigoid. Analysis was carried out by flow cytometry. Without immunosuppressive therapy expression of IL2 receptors only on T cells (CD5) was significantly increased as shown by double staining (11.9% +/- 7.8% vs 2.1% +/- 1% in controls). After 2-3 weeks under immunosuppressive treatment with prednisolone and azathioprine, however, BP lymphocytes did not exhibit any IL2 receptors. PBLs of 18 BP patients showed an increase in IL2 production (1027.4 +/- 670.5 U/ml vs 270 +/- 100 U/ml in controls) during the acute stage of the disease after stimulation with phytohaemagglutinin (PHA)/phorbol myristate acetate (PMA). On the contrary, IL2 production of the same cells in five patients was only in the lowest range of control values after PHA stimulation without PMA (12.5 +/- 29.6 U/ml vs 40 +/- 20 U/ml in controls). Under treatment with immunosuppressants the IL2 production normalized after PHA/PMA stimulation and slightly decreased following PHA stimulation. From these results we conclude that a T-cell activation via activation antigens, as IL2 receptors, and the production of the specific ligand, IL2, may play a role in the pathogenesis of bullous pemphigoid, especially in the earliest stages, and serve as a marker of disease activity.

In polyacrylamide gel gradient electrophoresis, serum and blister fluid of patients with bullous pemphigoid showed a nearly identical protein distribution pattern except for one more concentrated fraction in the blister fluid. This fraction could be isolated by several gel chromatographic steps and then be characterized as a protein with a molecular weight of 240,000 (BFP 240,000) consisting of several subunits. Two of these subunits could be identified as C3 fragments and two other ones as basement membrane zone antigens (BMZ-Ag) by means of a modified Laurell technique. The molecular weight of the BFP 240,000 may be small enough to allow it to penetrate through the vessel wall into the blood circulation where, with the BMZ-antibodies (BMZ-Ag-BMZ-Ab-complexes can be formed. The occurrence of such immune complexes in the serum has been shown in a previous paper.

SUMMARY The activities of five lysosomal hydrolases were determined fluorometrically in the serum of patients with systemic sclerosis (PSS), systemic lupus erythematosus (SLE), dermatomyositis (DM), rheumatoid arthritis (RA), or Raynaud's disease (RD). In PSS the β-galactosidase activity was significantly increased compared with controls and the other connective tissue diseases. The β-N-acetyl-glucosaminidase was significantly increased in PSS, SLE and DM. In PSS both enzymes were more active in the early stage of the disease than later. These changes of enzyme pattern seem to be a relatively reliable marker for the differential diagnosis of PSS compared to other connective tissue diseases, especially for RD, in which the β-galactosidase activity was significantly decreased. Further work is required to determine whether these polysaccharide-degrading acid hydrolases play a role in the pathogenesis of PSS.

In 14 patients with progressive systemic sclerosis (PSS) the activities of acid lysosomal glycosidases (alpha-, beta-galactosidase, beta-glucosidase, beta-glucuronidase, and beta-N-acetyl-glucosaminidase) were determined fluorometrically in serum, leukocytes, and skin tissue. The beta-galactosidase was the only enzyme which exhibited a significantly elevated activity in PSS serum and skin but not leukocytes, as compared to the control. The activity patterns of the studied glycosidases in serum were similar to those found in skin, but differ from the distribution of glycosidase activities in leukocytes. In cultured dermal fibroblasts derived from PSS patients, an elevated intracellular activity of beta-galactosidase was detected. These results suggest that the increased beta-galactosidase activity in the serum originates from the skin fibroblasts.

SUMMARY No tree anti-basement membrane antibodies were found in the sera of four patients with bullous pemphigoid, and no free anti-DNA antibodies in the sera of two patients with systemic lupus erythematosus. The sera were treated with 3 mol/l urea and by gel chromatography to separate these antibodies from any circulating complexes, and antibodies to basement membrane were detected by immunofluorescence and to DNA by the Farr technique. The appropriate antibodies were found in all the sera, indicating that failure to detect antibodies by routine procedures may be due to binding of the antibodies to soluble antigens, forming complexes in the sera.

An Hand der in der Zeit von 1957–1967 in der Universitats-Hautklinik Jena behandelten, an Lichen sclerosus et atrophicus (LSA) erkrankten Patienten (17 Frauen, 9 Manner) wird uber die klinische Symptomatik sowie die Ergebnisse der Messung der sensitiven Chronaxie, der Bestimmung der antinuclearen Faktoren (ANF) und der oralen Belastung mit d,l-Tryptophan berichtet. Die Verlangerung der sensitiven Chronaxie im Hautherd des LSA deutet auf eine unspezifische Beteiligung der neurovegetativen Formationen hin, die an gewisse pathogenetische Parallelen mit der Sklerodermie denken last. Die in der gesunden Haut gefundenen Normalwerte erlauben eine sichere differentialdiagnostische Abgrenzung zur circumscripten Sklerodermie in klinisch aktiven Stadien. Die analog der circumscripten Sklerodermie nur leicht erhohte Frequenz der ANF unterstreicht unsere Konzeption uber die fehlende Beziehung des LSA zu immunologischen Krankheitsbildern. Die bei einzelnen Fallen von LSA nach Tryptophanbelastung erhohten Ausscheidungsquoten von Xanthurensaure und Kynurenin deuten auf einen vermehrten Vitamin B6-Bedarf, wie er bei vielen Hautkrankheiten beobachtet wird, hin, ohne das daraus auf eine echte Tryptophanstoffwechselstorung des LSA geschlossen werden konnte.

1. Die fibrinolytische Aktivitat ektodermaler und bindegewebiger Hauttumoren ging von den Blutgefasen aus. 2. Die Tumorzellen erwiesen sich als fibrinolytisch inaktiv mit Ausnahme von entdifferenzierten Melanomzellen, die eine starke Gewebsaktivatorwirkung besasen. 3. Tumoros veranderte Blutgefase in Gefasgeschwulsten zeigten eine deutlich erniedrigte, zum Teil fehlende Aktivitat. Daraus wird die Tendenz der Hamangiome zur Thrombosierung mit nachfolgender Spontanheilung abgeleitet.

Mit Hilfe der Fibrinschichtautographie nach Todd wurden die fibrinolytisch aktiven histologischen Strukturen bei verschiedenen Dermatosen topographisch ermittelt. 1. Bei den untersuchten Dermatosen dominierte die bereits bekannte, durch einen Gewebsaktivator hervorgerufene fibrinolytische Aktivitat der Venen, Venolen und Capillaren, seltener der Arterien mit einer Herd-Lysis-Zeit von 10–15 min. 2. Lymphgefase, Hautanhangsgebilde und entzundliche Infiltrate blieben fibrinolytisch stets inaktiv. 3. Lysehofe durch nicht verhornte, kernhaltige Mundschleimhautepithelien, die erst nach etwa 2 Std auftraten, bewiesen die schwachere fibrinolytische Aktivitat epidermalen Ursprungs. 4. Auch von spongiotischen Bezirken und exkoriierten Regionen des akutsubakuten Ekzems sowie parakeratotischen Zellen der Halbschleimhaut des inneren Vorhautblattes ging eine epidermale fibrinolytische Aktivitat aus. 5. Parakeratotische Schuppen entwickelten eine mittelstarke fibrinolytische Aktivitat nach 30–60 min, gleich welcher Dermatose sie entstammten. 6. Die bereits nach 15–30 min auftretende, stark erhohte fibrinolytische Aktivitat parakeratotischer, psoriatischer Schuppen weist auf die pathogenetische Sonderstellung der Psoriasis vulgaris mit exzessiv gesteigerter Epidermopoese hin. 7. Orthokeratotische Schuppen besasen keinen Gewebsaktivator. 8. Die Herd-Lysis-Zeit war bei keiner der untersuchten Dermatosen verkurzt. Mit entzundlichen Infiltraten im Corium einhergehende Dermatosen tendierten zur Verlangerung der Herd-Lysis-Zeit und damit zur Verminderung der fibrinolytischen Aktivitat.

Mit Hilfe der KSCN-Extraktionsmethode wurde der Gewebsaktivatorgehalt normaler, entzundlich und tumoros veranderter Haut untersucht. Auf Grund der Ergebnisse gehorte die Haut zu den Geweben mit mittelstarker fibrinolytischer Aktivitat. Parakeratotische Schuppen der Psoriasis vulgaris erwiesen sich im Gegensatz zu orthokeratotischen Schuppen der Ichthyosis congenita mit fehlendem fibrinolytischen Potential als stark aktiv, wahrend die Extrakte aus psoriatisch veranderter Haut Normalwerte aufwiesen. Die bei chronisch entzundlichen Dermatosen (chronisches Ekzem) erniedrigte Aktivitat wurde mit dem Fehlen von Gewebsaktivatoren in den Zellen des entzundlichen Infiltrates erklart. Daraus wurde die Unzweckmasigkeit einer antifibrinolytischen Therapie bei derartigen Dermatosen gefolgert. Die Erniedrigung der fibrinolytischen Aktivitat bei verschiedenen Hauttumoren (Fibrom, Keratoakanthom) und ihre Erhohung bei Plattenepithelcarcinomen wurde in Hinblick auf den Reifegrad der Tumorzellen sowie die in der Literatur referierten Wechselbeziehungen zwischen Tumor und umgebenden Stroma diskutiert. Viele Tumorarten (Naevuszellnaevus, Verruca seborrhoides, Basaliom) entwickelten jedoch eine normale Aktivitat. Subcutanes Fettgewebe zeigte eine deutlich herabgesetzte fibrinolytische Aktivitat. Offenbar kommt der lokalen Fibrinolyse bei den untersuchten Dermatosen und Hauttumoren keine entscheidende pathogenetische Bedeutung zu.

Bei allergischen Hautreaktionen ist das lymphozytare System mitbeteiligt. Beim Fruhtyp findet sich in den Lymphknoten eine Proliferation von B-Lymphozyten in den Keimzentren, beim Spattyp eine solche von T-Lymphozyten in den parakortikalen Zonen sowie ein Nachschub von Stammzellen aus dem Knochenmark zu den drainierenden Lymphknoten [4]. Bei der primaren Immunantwort ist die Proliferation von Lymphozyten starker ausgepragt als bei der sekundaren. Beide Lymphozytensubpopulationen beeinflussen sich gegenseitig, ihre Kooperation ist fur die Entwicklung einer normalen Immunantwort notwendig. In Zusammenhang mit dieser Lymphozytenproliferation und -kinetik interessierte die Frage, inwiefern die Anzahl der B- und T-Lymphozyten im peripheren Blut wahrend des Krankheitsverlaufes allergischer Hautreaktionen vom Fruh-und Spattyp verandert ist.