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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
PubMed1996

Gonadal function of young adults after therapy of malignancies during childhood or adolescence.

UNLABELLED: As the survival rate of children with malignancies has increased over past decades, the follow up of adult long-term survivors (LTS) of childhood cancer should focus on late effects of disease and treatment. Gonadal function was therefore studied in 54 LTS (aged 17-29 years; 33 male, 21 female) 2-18 years after treatment for malignancies during childhood or adolescence. To analyse the sensitivity of different diagnostic methods, tests of endocrine function (n = 52), spermiograms (n = 14), gynaecological status (n = 20) and ultrasonography of the gonads (n = 53) were compared with the results of equivalent tests in 23 age-matched normal controls (12 male, 11 female). There were no differences between male and female LTS concerning age at diagnosis, gonadal dose of irradiation (XRT) and doses of applied chemotherapeutic agents. Whereas male LTS had elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) before (P < 0.05; P < 0.001) and after (P < 0.01; P < 0.001) stimulation with gonadotropin releasing hormone, female LTS exhibited normal endocrine function. Accordingly, male patients exhibited lower testicular volumes than normal controls, as measured with a Prader orchidometer (P < 0.01) or by ultrasonography (P < 0.001). Gynaecological status and ultrasonography of the gonads were normal in female LTS and controls. Whereas all spermiograms of normal controls (n = 8) showed a normal sperm cell density (SCD), only 2 of 14 male LTS exhibited a normal SCD (P < 0.001). Azoospermic LTS (n = 9) had been treated more often with alkylating agents and had received higher (P < 0.05) gonadal doses of XRT. All male LTS with testicular volumes below the normal range (< 13 ml) and basal FSH levels above the normal range (> 10 IU/l) exhibited azoospermia, whereas LTS with normal values for testicular volume and basal FSH had a normal SCD. CONCLUSION: A sex-specific susceptibility for gonadal damage after treatment for malignancies might be responsible, in part, for the impaired gonadal function of male LTS. Therapy with alkylating agents and/or high gonadal doses of XRT were important risk factors for azoospermia. A simple method to estimate potential fertility in individual LTS is to measure testicular volume, using a Prader orchidometer, and basal FSH serum levels.

Adolescent↗
PubMed1993

MCP-1 mRNA expression in basal keratinocytes of psoriatic lesions.

In addition to hyperproliferation of keratinocytes, psoriasis is characterized by pronounced leukocytic infiltration. In contrast to the epidermal localization of neutrophils and T lymphocytes, macrophages are almost exclusively restricted to the dermal compartment. By immunohistologic analysis, these dermal macrophages were mainly encountered in the papillary dermis and arranged along the rete ridges in close proximity to proliferating keratinocytes. Monocyte chemoattractant protein (MCP-1) anti-sense RNA probes yielded abundant signals over the proliferating basal keratinocytes of the tips of the rete ridges, and, to a lesser extent, in cells in the papillae. Thus, the strongest MCP-1 message in psoriatic lesions is found above the dermal-epidermal junction and this may explain the characteristic sub-basal distribution of dermal macrophages. These results suggest that MCP-1 is important in regulating the interaction between proliferating keratinocytes and dermal macrophages in psoriasis pathogenesis.

Antigens, CD↗
PubMed1993

[Soluble interleukin 2 receptor as activity parameter in serum of systemic and discoid lupus erythematosus].

The evaluation of disease activity in systemic lupus erythematosus (SLE) is important for selection of the appropriate therapeutic regimen. In addition to the clinical picture, various laboratory parameters are taken into account. However, no validated criteria for the evaluation of the disease activity in SLE have yet been established. Recently, serum levels of soluble interleukin-2 receptor (sIL-2R) have been proposed as a potential parameter for disease activity in SLE. However, the studies reported on this subject so far have focused mainly on certain subsets of the disease, and the evaluation of the disease activity was based on a very limited number of parameters. In the present study, we determined serum levels of sIL-2R in 23 patients with SLE and 30 patients with discoid LE (DLE). Evaluation of disease activity in SLE was based on a comprehensive scale which considered numerous clinical signs and laboratory parameters. In SLE, serum levels of sIL-2R showed a better correlation with disease activity than all the other parameters investigated, including proteinuria, erythrocyte sedimentation rate, serum globulin concentration, titre of antibodies against double-stranded DNA, serum albumin concentration, serum complement levels and white blood cell count. For the first time, we report on elevated serum levels of sIL-2R in DLE, which also correlated with disease activity.

Adolescent↗
PubMed1993

[Pemphigus foliaceus caused by penicillamine].

We report the case of an 80-year-old woman who developed pemphigus foliaceus while taking penicillamine for rheumatoid arthritis. On the basis of this new case, we discuss fresh insights into the pathogenesis of drug-induced pemphigus. In addition, having reviewed the literature, we give a list of drugs that have been reported to induce this disease.

Aged↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗