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Biomedical subjects

N Hunzelmann

Publications and source records attributed to N Hunzelmann.

At least 19 recordsLinked to original sources
PubMed2003

Enhanced frequency of a PTPRC (CD45) exon A mutation (77C-->G) in systemic sclerosis.

A point mutation in exon A (C to G transversion at position 77) of human PTPRC (CD45) has recently been associated with the development of multiple sclerosis (MS) for at least a subgroup of patients. In the present report, we studied the frequency of the 77C-->G transversion in two other autoimmune diseases namely systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The mutation was found with significantly enhanced frequency in patients suffering from SSc suggesting that PTPRC could play a role as susceptibility gene not only in MS but also in other autoimmune diseases. Further understanding of the mode of interaction of mutant PTPRC with other susceptibility genes may uncover mechanisms common in various autoimmune disorders.

Exons↗
PubMed2002

Vascular endothelial growth factor causally contributes to the angiogenic response upon ultraviolet B irradiation in vivo.

BACKGROUND: Ultraviolet (UV)-B irradiation has been shown to be an inducer of vascular endothelial growth factor (VEGF) in primary keratinocytes and epidermal cell lines in vitro. OBJECTIVES: To determine the expression pattern and the causal role of VEGF in the UVB-mediated angiogenic response in vivo in human skin and in a mouse model. METHODS: Skin biopsies or epidermal lysates thereof were studied for VEGF expression following UVB irradiation at a dose of 50 or 60 mJ cm-2, respectively, using immunostaining and a VEGF-specific highly sensitive sandwich enzyme-linked immunosorbent assay. The VEGF-dependent increase in vessels upon repetitive UVB irradiation was studied in skh-1 hairless mice using immunostaining for factor VIII-related antigen (FVIII RAG) in the presence and absence of intraperitoneally injected neutralizing VEGF antibodies. RESULTS: VEGF was found to be induced in the epidermis following UVB irradiation of human and mouse skin. Repetitive UVB irradiation of skh-1 hairless mice resulted in an increase in FVIII RAG positive vessels in the skin. UVB-induced angiogenic response could be partly abrogated by neutralizing antibodies against VEGF, while isotype-matched IgG control antibodies did not reveal any suppressive effect. CONCLUSIONS: Our results support previous in vitro data and show the in vivo relevance of VEGF as a paracrine inducer of cutaneous vessels after UVB irradiation.

Animals↗
PubMed2002

Detection and characterization of plasma cells in peripheral blood: correlation of IgE+ plasma cell frequency with IgE serum titre.

In atopic patients and patients with hyper-IgE syndrome (HIE) highly elevated IgE serum levels can be detected. Due to their very low frequency little is known about IgE-producing plasma cells (PC) in peripheral blood. We used CD138 MACS microbeads to enrich plasma cells from peripheral blood of normal donors, atopic patients and one HIE patient. CD138+ cells were mainly CD45+, CD44++, CD19dim, CD38++, CD27++, CD86+, HLA-DR+/++, CD71dim, VLA-4+, VLA-5-, CD28-, CD25-, CD69-, CLA-, CD20-, CD21- and CD22-. They show weak expression of surface Ig but high levels of intracellular Ig and they secrete Ig in culture. Thus CD138+ cells from peripheral blood show characteristics of early plasma cells. IgE+ CD138+ plasma cells could be detected in 19 of 24 normal donors with an average frequency of 0.06% IgE+ cells among CD138+ cells. Higher frequencies were detected in atopic patients, atopic patients with markedly elevated serum IgE levels and the hyper-IgE patient with an average of 0.32%, 7.21% and 6.54%, respectively. Additionally, using the recently developed cellular affinity matrix technology, we were able to detect IgE secreting plasma cells and thereby could demonstrate that most of the IgE secreting cells express CD138. The frequency of IgE+ CD138+ cells among PBMC correlated highly significantly with serum IgE titres (r = 0.8532***), indicating that IgE secreting CD138+ cells in peripheral blood are directly related to the plasma cell pool contributing to the IgE titre.

Antibody Affinity↗
PubMed2001

Rapid enrichment and detection of melanoma cells from peripheral blood mononuclear cells by a new assay combining immunomagnetic cell sorting and immunocytochemical staining.

Commonly used methods for detection of melanoma cells in blood, including RT-PCR and immunocytochemistry, display only a limited sensitivity and specificity. Reliable detection of less than one melanoma cell per ml of blood is hardly possible using these methods. To obtain greater sensitivity so that a single melanoma cell in up to 25 ml of blood can be detected (5 x 10(7) peripheral blood mononuclear cells, or PBMC), we developed a new assay for combined enrichment and immunocytochemical detection of disseminated melanoma cells from PBMC of patients with malignant melanomas. Melanoma cells are directly magnetically labeled using colloidal superparamagnetic microparticles approximately 60 nm in diameter conjugated to the anti-melanoma monoclonal antibody 9.2.27, with no reactivity to normal cells in blood. Magnetically labeled melanoma cells are enriched from PBMC by magnetic cell separation and detected by a new approach for immunocytochemical staining with monoclonal mouse anti-melanoma antibodies (anti-MelanA and HMB-45). The efficiency of this assay was demonstrated in a model system in which 5-500 tumor cells from the melanoma cell line SK-MEL-28 were seeded into PBMC samples from healthy donors containing 5 x 10(7) leukocytes. Mean recovery of the seeded tumor cells was 47.4 +/- 13.99% (n = 15). Applying the assay to 20-50 ml blood samples of patients with stage III-IV malignant melanomas, we were able to detect melanoma cells in two of eight patients (25%).

Antibodies, Monoclonal↗
PubMed2001

Different pattern of collagen cross-links in two sclerotic skin diseases: lipodermatosclerosis and circumscribed scleroderma.

Changes in the process of cross-linking of collagen molecules are associated with defects in the biomechanical stability of the extracellular matrix. Fibrosis of skin is characterized by an increase in pyridinolines, which are hydroxylysine aldehyde derived cross-links usually absent in healthy skin. In this study, we analyzed cross-links in lipodermatosclerosis and localized scleroderma to address the question whether all the mature cross-links currently characterized are increased in fibrosis in addition to the increase in pyridinolines. As psoralen plus ultraviolet A treatment leads to clinical improvement of fibrotic plaques in localized scleroderma we analyzed the cross-link content in lesional skin after bath psoralen plus ultraviolet A therapy. In skin from patients with localized scleroderma an increase in the total number of mature cross-links was found to be due to an increase in both pyridinolines and dehydro-histidinohydroxymerodesmosine. The concentration of histidinohydroxylysinonorleucine was unchanged. By contrast, the total number of mature cross-links was decreased in lipodermatosclerosis. This decrease was caused by a decrease of lysine aldehyde derived cross-links (dehydro-histidinohydroxymerodesmosine and histidinohydroxylysinonorleucine), whereas the concentration of pyridinolines increased. A decrease in the content of pyridinolines after bath psoralen plus ultraviolet A treatment was found in six out of nine patients with localized scleroderma, which might reflect a remodeling of the extracellular matrix. Our data provide evidence that sclerosis of skin is associated with either an increase in the number of cross-links per molecule of collagen or a change in the molecular nature of the cross-links formed.

Amino Acids↗
PubMed2001

Increased deposition of fibulin-2 in solar elastosis and its colocalization with elastic fibres.

BACKGROUND: Fibulin-2 is a 195-kDa protein belonging to a novel family of extracellular matrix proteins that might be involved in microfibril and elastic fibre organization. OBJECTIVES: To determine the localization of fibulin-2 in relation to elastic fibres in normal skin and in solar elastosis characterized by increased elastotic material in the papillary dermis. METHODS: The expression and synthesis of fibulin-2 was investigated by means of in situ hybridization, immunohistochemistry and Western blot analysis in normal and photoaged skin. RESULTS: Immunohistochemistry and elastic tissue staining revealed that fibulin-2 deposition mainly colocalized with microfibrils and elastin fibres, with a marked staining of elastotic material in solar elastosis. Western blot analysis demonstrated that in photoaged skin fibulin-2 showed the same electrophoretic mobility as in sun-protected skin. However, in actinic elastosis the amount of fibulin-2 was significantly higher. In addition, smaller degradation products were detectable, presumably reflecting increased proteinase activity in photodamaged skin. CONCLUSIONS: This study shows that deposition of fibulin-2 and elastin is highly co-ordinated, indicating that this protein plays an important role in elastic fibre and microfibril formation in normal and actinically damaged skin.

Aged↗
PubMed2001

Linear IgA bullous dermatosis induced by atorvastatin.

Linear IgA bullous dermatosis (LABD) is an autoimmune blistering skin disease characterized by circulating IgA antibodies binding the basement membrane zone. In most cases the origin is not clear, but in a minority of cases LABD is drug induced. We describe a patient in whom linear IgA disease developed shortly after beginning therapy with atorvastatin. In Western blotting analysis we detected IgA and IgG class antibodies targeting a 97-kd protein. To our knowledge this is the first reported case of atorvastatin-induced LABD.

Anticholesteremic Agents↗
PubMed2001

Anaphylactoid reactions after cisatracurium administration in six patients.

IMPLICATIONS: We report six cases of anaphylactoid reaction after the administration of the muscle relaxant cisatracurium. They include two first-time documented anaphylactoid reactions after a precurarising dose. These incidents challenge existing views of a substantially reduced anaphylactoid potential of cisatracurium relative to other muscle relaxants.

Adult↗
PubMed2001

Bullous pemphigoid in a patient treated with UVA-1 phototherapy for disseminated morphea.

Bullous pemphigoid is an autoimmune disease of the skin characterized by the production of antibodies directed at structures of the basement membrane zone (BMZ) leading to subepidermal blisters. Several causative triggers have been described in the literature, among them UV light. Here, we report on a 73-year-old Caucasian female with disseminated morphea who developed blisters on her extremities after receiving whole-body UVA-1 phototherapy. The initial differential diagnosis of a phototoxic versus photoallergic reaction was ruled out as the lesions continued to spread after discontinuation of phototherapy. Histological and direct immunofluorescence examination showing a subepidermal blister and linear IgG deposits along the BMZ along with detection of circulating anti-BMZ antibodies led to the diagnosis of bullous pemphigoid. Immunosuppressive therapy resulted in regression of all blisters. After ruling out other possible causes, such as neoplasias or drugs, we conclude that UVA-1 has to be regarded as the most likely trigger of the disease.

Aged↗
PubMed2000

[Cutaneous metastases from a leiomyosarcoma of the testicular tunica albuginea].

Cutaneous metastases from a leiomyosarcoma of the testicular tunica albuginea are very rare. Primary leiomyosarcomas in this site are uncommon and furthermore cutaneous metastases develop only in 1,4% of all malignant tumors of the internal organs [10]. A 71 year old patient with such a sarcoma underwent primary excision. Nine months later multiple, firm, nodules were identified as cutaneous metastases. Further staging revealed already extensive, diffuse pulmonary and bony metastases without contiguous or regional lymph node involvement.

Aged↗