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Biomedical subjects

S Erdmann

Publications and source records attributed to S Erdmann.

At least 19 recordsLinked to original sources
PubMed2002

Introduction: molecular and biomechanical basis of osteoarthritis.

Osteoarthritis has developed into the most common chronic disease in the highly industrialized nations. Moreover, because of the prevalence of the disease in the elderly, this trend occurs worldwide as a consequence of increasing longevity due to the overall improvement in living conditions and health status. In contrast, research on osteoarthritis is still financially marginalized within biomedical research, so that the molecular and biophysical bases for disease initiation and progression are largely unmapped. The following sequence of five reviews highlights a remarkable change in that body of knowledge taking place at the beginning of the World Health Organization (WHO) 'Bone and Joint Decade 2001-2010'. The data and ideas presented in these articles reflect to some extent the guidelines set up by the WHO and by the National Institutes of Health of the USA and therefore allow a glimpse into the directions that research in osteoarthritis will take in the future.

Humans↗
PubMed2002

Determination of interleukin-5 secretion from drug-specific activated ex vivo peripheral blood mononuclear cells as a test system for the in vitro detection of drug sensitization.

BACKGROUND: In vitro detection of drug sensitization is still limited. The lymphocyte transformation test, which determines drug-specific proliferation, is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction's clinical phenotype. Accumulation of eosinophils following IL-5 secretion from drug-specific stimulated T cells is a characteristic histological feature of drug-induced skin eruptions. OBJECTIVE: We determined whether in vitro drug-specific activation of ex vivo peripheral blood mononuclear cells from 10 patients with drug-induced maculopapular exanthems and three patients with severe skin reactions results in secretion of IL-5, IL-10 or IFN-gamma and assessed the sensitivity and specificity of drug-specific IL-5 secretion as a test system compared with the lymphocyte transformation test and patch tests. Furthermore, the subsets of CD4+ and CD8+ T cells involved in drug-specific proliferation, IL-5 secretion and mRNA expression were examined in three patients. METHODS: Drug-specific proliferation of peripheral blood mononuclear cells in the lymphocyte transformation test was investigated by 3H-thymidine uptake, and culture supernatants taken after 5 days were analysed for IL-5, IL-10 and IFN-gamma concentrations by ELISA technique. IL-5 mRNA expression was determined by RT-PCR. RESULTS: Drug-specific activation of peripheral blood mononuclear cells consistently resulted in IL-5 and to a lesser extent in IL-10 and IFN-gamma secretion. The sensitivities of the patch test, lymphocyte transformation test and assessment of drug-specific IL-5 secretion for the detection of drug sensitization were 55%, 75% and 92%, respectively. CONCLUSION: These data suggest a role for the determination of drug-specific IL-5 secretion by ex vivo peripheral blood mononuclear cells for the in vitro detection of drug-sensitization in drug-induced maculopapular exanthems.

Adult↗
PubMed2002

When should a substance be designated as sensitizing for the skin ('Sh') or for the airways ('Sa')?

In the List of MAK and BAT Values compounds are designated with 'Sa' ('sensitizing for the airways') or 'Sh' ('sensitizing for the skin') if, according to scientific evidence, they are allergens. Mainly based on suggestions by a WHO working group and based on our own experience, extended criteria have been elaborated by the working group 'skin and allergy' of the Commission of the Deutsche Forschungsgemeinschaft for the Investigation of Health Hazards of Chemical Compounds in the Work Area, which are presented in this article. They serve as guidelines for deciding which substances have to be labelled 'Sa' and 'Sh', respectively, for the prevention of sensitization and subsequent allergic diseases in workers. Although in some special cases their strict application may not be deemed necessary or possible, the proposed new criteria should be used to make the procedure of classification of substances: 1) more rational, 2) more consistent, 3) more comprehensible, and 4) more transparent. This paper informs readers working scientifically or administratively in this field and invites a critical discussion of the issue.

Allergens↗
PubMed2001

The novel ependymin related gene UCC1 is highly expressed in colorectal tumor cells.

Normal cells differ from malignant tumor cells in the transcription levels of many different genes. Two colorectal tumor cell lines were compared with a normal colorectal cell line by differential display reverse transcription PCR to screen for tumor cell specific differentially transcribed genes. By this strategy the upregulation of a novel gene was detected designated as 'upregulated in colorectal cancer gene-1' (UCC1). The UCC1 gene transcript level is increased in cultured tumor cells and in two out of three analyzed colorectal tumor tissue specimens compared to normal cultured cells and to corresponding normal tissue samples. Remarkably, the UCC1 protein shows significant sequence similarity to the highly divergent piscine glycoproteins termed ependymins which are synthesized by leptomeningeal fibroblasts and secreted into the cerebrospinal fluid.

Amino Acid Sequence↗
PubMed2001

Molecular features determining lymphocyte reactivity in allergic contact dermatitis to chloramphenicol and azidamphenicol.

BACKGROUND: We report on two cases of allergic contact dermatitis to chloramphenicol and azidamphenicol respectively, with in vivo and in vitro lymphocyte reactivity to both compounds. The molecular features determining lymphocyte reactivity were explored because chloramphenicol, azidamphenicol, and thiamphenicol exhibit almost identical chemical structures. METHODS: With chloramphenicol, azidamphenicol, and the chemically related thiamphenicol, we performed patch tests and lymphocyte transformation tests with both patients. Furthermore, the interleukin-5 and interferon-gamma concentrations in the cultures of peripheral blood mononuclear cells of one patient were determined. RESULTS: Patch tests showed delayed hypersensitivity reactions to chloramphenicol and azidamphenicol, but not to thiamphenicol. These results were confirmed by lymphocyte transformation tests with peripheral blood mononuclear cells of the patients, showing a proliferative T-cell response to azidamphenicol and chloramphenicol. Moreover, lymphocytes from one patient secreted large amounts of interleukin-5, but not of interferon-gamma upon coculture with azidamphenicol. CONCLUSIONS: Since lymphocyte reactivity was observed to chloramphenicol and azidamphenicol, but not to thiamphenicol, the epitope(s) recognized by the allergen-reactive T cells may be formed by the nitro-group of the benzene ring shared by chloramphenicol and azidamphenicol.

Aged↗
PubMed2001

In vitro drug allergy detection system incorporating human liver microsomes in chlorazepate-induced skin rash: drug-specific proliferation associated with interleukin-5 secretion.

BACKGROUND: Chlorazepate is a benzodiazepine often used for pre-operative anxiolysis. The central metabolite responsible for the pharmacological and probably for the adverse effects of most benzodiazepines, including chlorazepate, is N-desmethyldiazepam. We report a woman who developed a generalized exanthem 1 day after receiving chlorazepate and four other drugs related to anaesthesia for surgery of the larynx. Patch tests pointed to chlorazepate as the culprit drug for the skin rash. OBJECTIVES: The purpose of this study was to detect drug allergy to chlorazepate or a metabolite in vitro by means of the lymphocyte transformation test (LTT), and to determine the concentrations of the T-helper (Th) 2-type cytokine interleukin (IL)-5 and the Th1-type cytokine interferon (IFN) -gamma in the culture supernatants. METHODS: We performed an LTT with peripheral blood mononuclear cells from the patient and a control, employing human liver microsomes containing cytochrome P450 enzymes as a metabolizing system, in parallel cultures. IL-5 and IFN-gamma concentrations in the culture supernatants were assessed by enzyme-linked immunosorbent assay. RESULTS: In the LTT, no T-cell reactivity was observed to the parent compound chlorazepate, whereas coincubation of the drug with human liver microsomes yielded proliferative T-cell reactivity, which was associated with secretion of IL-5 but not of IFN-gamma. CONCLUSIONS: We conclude that addition of a metabolizing system may be advantageous for in vitro detection of T-cell reactivity to drug metabolites in the LTT.

Adult↗
PubMed2000

Seven genes that are differentially transcribed in colorectal tumor cell lines.

To identify genes which are differentially transcribed in colorectal tumor cells, we compared the two human tumor cell lines, SW480 and HCT116, with the cell line, NCM460, from normal colon epithelium as a control. Using the methods of differential display reverse transcription PCR and Northern blot hybridization, we detected the differential transcription of seven genes: cholecystokinin, reticulocalbin, Rab5 guanine nucleotide exchange factor Rabex5, caldesmon, differentiation related gene 1 (drg1), taxol resistant associated gene 3 (Trag-3) and the gene for the placental protein, diff33. The yet unidentified cDNA of the human Rabex5 gene and the 3' untranslated region of the human caldesmon gene were cloned.

Amino Acid Sequence↗
PubMed1999

Allergy, skin and environment.

The skin is very often the target organ of allergic reactions. This may be explained by many immunological competent cells in this organ such as the Langerhans cell, mast cells, lymphocytes, neutrophils and eosinophils. This is especially true for the antigen-presenting Langerhans cell. Therefore in many cases, the skin is a signalling organ for allergic reactions. Examples include food allergy which precipitates with signs and symptoms of skin diseases in about 45% and drug allergy to beta-lactam-antibiotics in about 90%. Also the skin serves as a test organ in allergic diseases of other organs such as rhinitis allergica or asthma. Examples include Reibtest, prick-, intracutaneous-, scratch- and patch test. Therefore it is no surprise, that allergic diseases of the skin are the most often diagnosed skin diseases such as urticaria, angioedema, vasculitis, contact dermatitis and atopic dermatitis. At these diseases, their diagnose and therapy and especially the promising progress in research with regard to these diseases which has been obtained during the last years will be focussed in this review.

Dermatitis↗
PubMed1999

Interdisciplinary clinical assessment of patients with illness attributed to environmental factors.

Patients with health problems attributed to environmental factors such as chemical pollutants and electromagnetic fields often do not present evidence of an environmental aetiology of their symptoms. It has been postulated, that their problems are due to disorders diagnosed by other medical disciplines, especially allergology and psychiatry. Our study was designed to subject these patients to a comprehensive diagnostic program involving several medical disciplines in order to achieve diagnoses appropriate to explain the patients' symptoms. Fifty patients consecutively referred to the department of environmental medicine in the university hospital of Aachen, Germany, were submitted to the following examinations: (i) environmental medicine (history, clinical examination, biological and/or ambient monitoring for environmental agents); (ii) allergological examination (history, clinical examination, skin tests); (iii) psychiatric examination (psychopathological examination, psychometric and neuropsychological testing). In addition, the patients were examined in other hospital departments according to the symptoms presented. The findings were discussed in case conferences attended by the physicians involved in order to achieve individual diagnoses. The numbers of patients to whom diagnoses were given by different medical disciplines are as follows: psychiatry (32 patients), dermatology (4), allergology (2), neurology (2), rheumatology (2), gynaecology (1), haematology (1). The most frequent mental disorders diagnosed by the psychiatrists were somatoform disorders (19), followed by schizophreniform and delusion disorders (7). In spite of extensive diagnostic efforts, patients with health problems attributed to the environment usually do not present sufficient evidence of an environmental aetiology of their symptoms. On the other hand the symptoms often meet the diagnostic criteria of other diseases, especially of mental disorders.

Adult↗
PubMed1998

Mapping of a carboxyl-terminal active site of parathyroid hormone by calcium-imaging.

We recently showed that the C-terminal fragment PTH (52-84) effectively increases intracellular free calcium ([Ca2+]i) in a subset of growth plate chondrocytes not activated by the N-terminal PTH fragment (1-34). Here we characterize the active site on C-terminal PTH (52-84) with respect to calcium (Ca2+)-signaling and the mechanism involved by using synthetic PTH-subfragments in digital CCD ratio-imaging experiments. Our results show amino acids 73-76 to be the core region for increasing [Ca2+]i. Ryanodine (1 microM), caffeine (10 mM), lithium (2 mM), or cyclopiazonic acid (2-5 microM), agents that interfere with intracellular Ca2+ release, all failed to block PTH (52-84) induced [Ca2+]i increases. Depletion of extracellular calcium ([Ca2+]o) blocked PTH (52-84) induced [Ca2+]i increases, indicating a transmembrane Ca2+ influx. In contrast to voltage-gated and Ca2+ release activated Ca2+ influx, PTH (52-84) evoked Ca2+ influx was not blocked by nickel (1 mM). We conclude that PTH amino acids 73-76 are essential for activation of a nickel-insensitive Ca2+ influx pathway in growth plate chondrocytes that is likely to be of relevance for matrix calcification, a key step in endochondral bone formation.

Binding Sites↗
PubMed1996

Differential effects of parathyroid hormone fragments on collagen gene expression in chondrocytes.

The effect of parathyroid hormone (PTH) in vivo after secretion by the parathyroid gland is mediated by bioactive fragments of the molecule. To elucidate their possible role in the regulation of cartilage matrix metabolism, the influence of the amino-terminal (NH2-terminal), the central, and the carboxyl-terminal (COOH-terminal) portion of the PTH on collagen gene expression was studied in a serum free cell culture system of fetal bovine and human chondrocytes. Expression of alpha1 (I), alpha1 (II), alpha1 (III), and alpha1 (X) mRNA was investigated by in situ hybridization and quantified by Northern blot analysis. NH2-terminal and mid-regional fragments containing a core sequence between amino acid residues 28-34 of PTH induced a significant rise in alpha1 (II) mRNA in proliferating chondrocytes. In addition, the COOH-terminal portion (aa 52-84) of the PTH molecule was shown to exert a stimulatory effect on alpha1 (II) and alpha1 (X) mRNA expression in chondrocytes from the hypertrophic zone of bovine epiphyseal cartilage. PTH peptides harboring either the functional domain in the central or COOH-terminal region of PTH can induce cAMP independent Ca2+ signaling in different subsets of chondrocytes as assessed by microfluorometry of Fura-2/AM loaded cells. These results support the hypothesis that different hormonal effects of PTH on cartilage matrix metabolism are exerted by distinct effector domains and depend on the differentiation stage of the target cell.

Animals↗