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Biomedical subjects

A A Hartmann

Publications and source records attributed to A A Hartmann.

At least 19 recordsLinked to original sources

The interleukin-2 receptor in lesions and serum of bullous pemphigoid.

The interleukin-2 receptor (IL-2R) is mainly expressed on activated T cells. Depending on its rate of synthesis, a portion is released from the cell surface as soluble IL-2R (sIL-2R). Since the role of mononuclear cells in the pathology of bullous pemphigoid (BP) is not well understood, we determined the sIL-2R in both blister fluid and serum of 15 BP patients with generalized disease before initiating systemic treatment. In addition, we obtained both lesional and perilesional skin biopsies and examined the mononuclear infiltrate with a panel of monoclonal antibodies. In BP blisters, sIL-2R levels were significantly increased (2070 +/- 350 U/ml), (+/- SEM) compared with serum samples taken at the time of blister puncture (1340 +/- 290 U/ml). In six patients with blisters due to second-degree burns or friction and in five suction blister volunteers, sIL-2R levels were normal in both blisters and serum. In BP, elevated serum levels decreased to normal during therapy, correlating with disease activity. The immunohistology showed that 30% of mononuclear cells in the dermal infiltrate of lesional skin expressed the IL-2R, whereas only 15% were positive in perilesional skin. IL-2R-positive cells are the most likely source of the shed receptor in BP blisters. Our results indicate the presence of activated T cells in lesions and peripheral blood of BP and thus underline the importance of cell-mediated immune mechanisms in the pathology of this disease.

Blister

Detection of human anti-annexin autoantibodies by enzyme immunoassays.

Annexins belong to a family of proteins characterized by calcium-dependent binding to the cytoskeleton and phospholipid surfaces. Basing on these properties annexins are discussed to be involved in the regulation of cytodynamic, anticoagulatory and antiinflammatory processes. Since autoantibodies against annexin I had been detected in patients suffering from inflammatory or autoimmune diseases, an impact on the pathophysiological outcome was assumed. Therefore we developed solid phase, enzyme-linked immunoassays for the quantitative determination of autoantibodies directed against six members of the annexin family. Some preliminary results obtained from sera of patients with malignant melanoma show a quite frequent presence of such autoantibodies. These data suggest that autoantibodies are generated against all annexins. Furthermore, in the individual patient autoantibodies of the IgG-type are monospecific, while about 1/4 of the IgM-type are directed against several annexins. These observations imply that for investigation of anti-annexin autoantibodies in inflammatory and autoimmune diseases as well as cancer all members of the annexin family have to be taken into consideration.

Autoantibodies

Circulating intercellular adhesion molecule-1 in melanoma patients: induction by interleukin-2 therapy.

Intercellular adhesion molecule-1 (ICAM-1, CD54), a molecule bound to the cell surface membrane, mediates various cell-cell interactions in inflammation and immunosurveillance. By means of a new specific enzyme-linked immunosorbent assay (ELISA) for soluble ICAM-1, free circulating ICAM-1 was measured in serum from five healthy volunteers, 10 melanoma patients at different stages of their disease, and eight patients receiving high-dose interleukin-2 (IL-2) for metastatic melanoma. No correlation between the concentration of circulating ICAM-1 and the tumor burden could be detected. In melanoma patients receiving high-dose IL-2, we observed an increase of circulating ICAM-1 of up to 200%, compared to the concentration prior to therapy, ranging between 4 and 13 ng/ml. The increase in circulating ICAM-1 was associated with the induction of tumor necrosis factor-alpha and interferon-gamma.

Cell Adhesion Molecules

[Shedding of soluble intercellular adhesion molecule 1 (ICAM-1) from melanoma cells and the effect on cellular cytotoxicity].

ICAM-1-mediated cell-cell adhesion is essential for various immunologic functions, including non-MHC-restricted cytotoxicity. Shedding of ICAM-1 occurred after stimulation of melanoma cells with TNF alpha and IFN gamma. Soluble forms of ICAM-1 inhibited the conjugate formation of NK clones with K562 and of LAK cells with melanoma cells. Furthermore, the non-MHC-restricted cytotoxicity mediated by NK clones or LAK cells could be abrogated by soluble ICAM-1.

Cell Adhesion

[Immune phenotyping of mononuclear infiltrate in bullous pemphigoid].

In bullous pemphigoid, autoantibodies alone are not capable of blister formation. In addition, they need complement and various inflammatory cells. The role of mononuclear cells, however, is poorly understood. Therefore, we studied the inflammatory infiltrate in 21 patients with bullous pemphigoid and 11 controls (normal skin, n = 5; eczematous skin, n = 6) using a panel of monoclonal antibodies. In bullous pemphigoid, 60% of the mononuclear infiltrate consists of CD3+ T-lymphocytes, while 25% represents monocytes/macrophages (MOMA); B-lymphocytes are absent. In the area of the basement zone (BMZ), which was studied separately, MOMA predominate. In 30% of bullous pemphigoid biopsies we found a close, almost linear attachment of MOMA to the BMZ. Along the BMZ, lymphocytes belong to the CD3+, CD4+ T-helper subset. CD8+ T-cytotoxic-suppressor cells, however, are rarely encountered there, and other cytotoxic lymphocytes are not found at all. All lymphocytes along the BMZ are memory cells. In small, early bullous pemphigoid lesions, MOMA are frequently the only effector cells. Eosinophilic granulocytes are rare in these lesions. Our findings suggest that mononuclear cells, and particularly MOMA, may be more important than believed hitherto in the inflammatory process resulting in separation of the BMZ.

Aged

Annexins I to VI: quantitative determination in different human cell types and in plasma after myocardial infarction.

Concentrations of annexins I to VI were quantitatively determined in extracts of placenta and different human cell types. They were detectable in all extracts studied, but lymphocytes/monocytes, endothelial cells and fibroblasts had very high annexin contents. The results indicate cell type specific annexin-repertoires. Annexins are intracellular proteins lacking signal sequences but which are detectable in trace amounts in plasma of healthy humans. The majority of plasma samples drawn from 14 patients suffering from myocardial infarction had elevated annexin III, IV and V concentrations. Shortly after infarction increased annexin levels were detected, reaching maximal values 24 to 48 h later. In the course of the following days annexin concentrations returned towards normal plasma levels.

Calcium-Binding Proteins

Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha. Functional consequences on cell-mediated cytotoxicity.

ICAM-1-mediated cell-cell adhesion is essential for various immunologic functions, including non-MHC-restricted cytotoxicity. The present study was designed to establish whether shedding of ICAM-1 from melanoma cells occurred and to characterize the effects of soluble ICAM-1 on some cell adhesion-dependent functions. The shed soluble ICAM-1 molecule was detected and quantified by a specific ELISA. Shedding of ICAM-1 could be induced by IFN-gamma and TNF-alpha alone, or more effectively, by a combination of the two cytokines together. The use of purified soluble ICAM-1 enabled us to test for the functional significance of the ICAM-1 shedding from tumor cells. Conjugate formation between the cloned NK cell line CNK6 and the erythromyeloid cell line K562, as well as between lymphokine-activated killer cells and the melanoma cell line M26, could be inhibited by purified soluble ICAM-1 and cell-free supernatants from melanoma cell cultures containing shed ICAM-1. Furthermore, the non-MHC-restricted cytotoxicity mediated by NK and lymphokine-activated killer cells could be abrogated either by purified soluble ICAM-1 or by melanoma cell culture supernatants containing shed ICAM-1. Thus, shedding of ICAM-1 may be one of the mechanisms by which neoplastic cells escape immunosurveillance.

Cell Adhesion

Intravenous single-dose ceftriaxone treatment of chancroid.

The antimicrobial susceptibility of Haemophilus ducreyi varies according to the geographic region. Increased resistance to trimethoprim and/or sulfamethoxazole led the Centers for Disease Control to recommend 250 mg ceftriaxone as a single intramuscular dose for chancroid. Intravenous or muscular routes of administration result in equivalent bioavailability. To avoid side effects such as syringe abscess and lidocaine intolerance, we prefer intravenous ceftriaxone therapy. The efficacy of this regimen is reported in 3 cases of chancroid. The intravenous administration of 1 g of ceftriaxone in chancroid seems to be as effective as administration by the intramuscular route, but it may lower the risk of syringe abscess, lidocaine intolerance and the emergence of resistant strains.

Adult

Vulvitis granulomatosa and anoperineitis granulomatosa.

We present the case of a 77-year-old female with a rare genital and anoperineal granulomatous cutaneous manifestation resembling cheilitis granulomatosa Miescher. The typical histological findings of epithelioid cell granulomas were localized in the vulva and anoperineal region; the latter manifestation has not yet been described. Based on our personal observations and a review of the literature, the clinical and histological features of vulvitis granulomatosa are described.

Aged

Sweet's syndrome associated with Salmonella typhimurium infection.

A 41-year-old woman presented with the typical clinical and pathohistological features of acute febrile neutrophilic dermatosis (AFND). The disease had been preceded by diarrhoea and vomiting for 2 weeks. Stool cultures proved positive for Salmonella typhimurium infection. Antibiotic therapy and tapering oral steroids led to a complete remission of skin lesions within 2 weeks. To our knowledge, this is the first report of Sweet's syndrome associated with salmonellosis.

Acute Disease

[The value of Gardnerella-vaginalis-culture in bacterial-vaginitis- score-confirmed bacterial vaginosis].

The relative value of a semiquantitative Gardnerella vaginalis culture for the diagnosis of bacterial vaginosis (BV) was studied in 113 women attending a STD clinic. The standard diagnosis of BV was based on the BV score, which is a 10-point grading system to evaluate gram-stained vaginal samples objectively and reproducibly. The sensitivity of G. vaginalis culture for the diagnosis of BV was 28%, while the specificity was 89%. The positive and the negative predictive values were 50% and 76% for G. vaginalis culture in our population. Our data suggest that G. vaginalis culture cannot be recommended for the routine diagnosis of BV. However, G. vaginalis culture will detect asymptomatic women with high vaginal colonization with G. vaginalis. Further studies are needed to find whether these women are at risk of developing BV.

Bacteriological Techniques

IgA pemphigus foliaceus: a case report.

An 84-year-old male with a 4-week history of vesiculobullous eruptions was diagnosed clinically and pathologically to suffer from pemphigus foliaceus. Amazingly, direct immunofluorescence demonstrated intercellular IgA deposits in the whole epidermis. The patient did not respond to a regimen of fluocortolone and azathioprine but rapidly improved under dapsone. The few reported dermatoses with intraepidermal IgA deposits do not form a homogeneous group. In the following, their spectrum will be outlined. It is important to distinguish these dermatoses from IgG pemphigus, since they require a different therapy.

Aged

Prevalence of Ureaplasma urealyticum in the urethra of men without urethritis in relation to clinical diagnosis.

Ureaplasma urealyticum is one of the microorganisms possibly causing nongonococcal urethritis. In a prospective study, 606 men without urethritis presented to an STD clinic in a rural West German region were investigated for the prevalence of U. urealyticum in the urethra. The overall isolation rate of the organism was 21.3%. Analyzing patients grouped by clinical diagnoses, the isolation rate of U. urealyticum was significantly higher in the genital warts group (25%) and in the partner's control group (35%) than in the group of patients suffering from fertility disorder (15.2%) or balanitis (14%). These findings stress the importance and the difficulty to select the appropriate controls in clinical studies concerning the role of U. urealyticum in the male urethra.

Adult

[Microbial ecosystems of the skin in antimicrobial therapy].

Healthy human skin provides wet, dry, and sebaceous habitats for well-adapted microbes living in a community and occupying three-dimensional spaces of the skin. These resident microbes of the skin are reduced either intentionally or unintentionally under systemic or topical antimicrobial therapy, e.g. in acne or tinea versicolor. As a result, quantitative or qualitative alterations of the microbial communities might ensue, including the selection of multiresistent variants in a habitat or a total change of the microbial community followed by the so-called gram-negative folliculitis. Skin disinfectants are antimicrobially effective within 30 to 60 seconds. Their long-term efficacy varies according to the specific substance. Moreover, the antimicrobial efficacy of skin disinfectants may vary to a considerable degree in the individual habitats of the human skin.

Anti-Bacterial Agents

The influence of various factors on the human resident skin flora.

Various factors, e.g. prolonged occlusion, skin disinfectants, systemic antimicrobials, can have an impact on the ecosystem of the normal human skin flora for a short time. These impacts are of clinical importance in the treatment of some skin diseases, where members of the normal human skin flora are involved in the pathogenesis of the disease, e.g. Propionibacterium acnes in acne vulgaris, Corynebacterium species in erythrasma, trichomycosis palmellina and pitted keratolysis, Pityrosporum orbiculare/ovale in Pityriasis versicolor, Pityrosporum folliculitis and others. Using the standardized forehead skin test, SFST, proposed by us, antibacterial short-term effects including the action degree profile, the action time profile, and the depth penetration profile of a topically applied antibacterial agent can be measured. Testing 60 v/v% isopropanol, 60 v/v% n-propanol, povidone iodine (aques solution), 3 w/v% salicylic acid in 50 v/v% isopropanol and 1 v/v% phenoli liquefacti in 50 v/v% isopropanol, salicylic acid showed equivalent reduction factors as 60 v/v% n-propanol immediately after the application. With the modified SFST, salicyclic acid tincture produced a 50-fold higher bacterial density reduction 12 hours after the fourth application and a 100-fold reduction 12 hours after the eighth application in comparison with 60 v/v% isopropanol. Salicylic acid, mainly used in dermatotherapy as a keratolytic agent, fulfills all these above mentioned requirements including a well antimicrobial efficacy. Since Salicyclic acid is also effective against yeast and dermatophytes, the substance has some advantages over other antimicrobials used in the dermatotherapy.

Bacteria