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Biomedical subjects

K Neuber

Publications and source records attributed to K Neuber.

At least 19 recordsLinked to original sources
PubMed2006

Age-associated decrease of CD1d protein production in normal human skin.

BACKGROUND: CD1d belongs to a family of antigen-presenting molecules structurally related to the classical major histocompatibility complex class I proteins. OBJECTIVES: To examine the expression pattern of CD1d protein in normal human skin with ageing. METHODS: Twenty normal human skin biopsy specimens were obtained from 20 healthy individuals. The latter were divided into three age groups: children (5-20 years), adults (21-50 years) and the elderly (51-81 years). The intensity of CD1d protein production was examined in human skin using immunofluorescent and immunoalkalinephosphatase staining methods. RESULTS: In the epidermis, CD1d protein production was strong in the skin of the children and declined gradually with age, being moderate in adults and weak in the elderly. As compared with values in children, there was a statistically significant decrease (P<0.05) in CD1d protein production in the elderly. In the dermis, CD1d protein production was strong in the fibroblasts, sweat glands, sebaceous glands, blood vessels and hair follicles regardless of age. CONCLUSIONS: Our study reports a decreased CD1d protein production in normal human skin with ageing. The clinical ramifications of these observations mandate further investigations.

Adolescent↗
PubMed2006

Autoantibodies against CD28 are associated with atopic diseases.

The B7-1/B7-2-CD28/CTLA-4 pathway is crucial in regulating T cell activation and tolerance. Autoantibodies to surface molecules on lymphocytes have already been described in various immune conditions, such as autoimmune diseases, infections and blood transfusions. The objective of this study was to test sera from healthy individuals and from patients for association of CD28 autoantibodies with inflammatory and non-inflammatory diseases. First, CD28 was obtained by digestion of CD28-Ig fusion protein with trypsin. The cleavage products were separated by sodium dodecyl sulphate-page gel electrophoresis. Additionally, a CD28/GST fusion protein was expressed in Escherichia coli and was used to establish an enzyme-linked immunosorbent assay for detection of autoantibodies against CD28. Sera from healthy individuals (n = 72) and patients with different inflammatory and non-inflammatory skin diseases (n = 196) were tested for the presence of autoantibodies against CD28. Using mixed lymphocyte reaction (MLR), purified autoantibodies against CD28 were tested for their effects on CTLA-4-Ig-induced T cell anergy. In this study, for the first time, we describe the existence of autoantibodies against CD28 in humans which are associated with atopic diseases, e.g. allergic rhinitis and asthma. These antibodies stimulate T cells and overcome the CTLA-4-Ig-induced anergy of T cells in an MLR. The existence of autoantibodies against CD28, which may have a T cell-stimulating function, has been shown. The data indicate that autoantibodies against CD28 could be a new immunological mechanism in allergic inflammation. Additionally, autoantibodies against CD28 could be an important new marker to discriminate between atopic diseases and other inflammatory skin diseases.

Adult↗
PubMed2005

Comparison of standard phenotypic assays with a PCR method to discriminate Candida albicans and C. dubliniensis.

In 1995, Candida dubliniensis was described as a new species in the genus Candida. Its close relationship to C. albicans has proved problematic in the identification of C. dubliniensis in clinical specimens. The objective of this study was to determine if reproducible differentiation between both species can be obtained by phenotypic assays. Therefore, 100 strains from 86 patients with the ability to produce chlamydospores were examined with different methods including API ID 32 C, colour development on CHROMagar, chlamydospore formation on Staib agar, growth at different temperatures and germ tube formation at 39 degrees C. Additionally, polymerase chain reaction (PCR) was used as gold standard. Six of the investigated strains were C. dubliniensis. The results suggest that there is still no single phenotypic method satisfactory to distinguish between C. albicans and C. dubliniensis.

Agar↗
PubMed2004

Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study.

PURPOSE: To compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma. PATIENTS AND METHODS: Patients received either intravenous fotemustine 100 mg/m2 weekly for 3 weeks or DTIC 250 mg/m2/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m2 or DTIC 250 mg/m2 for 5 days). RESULTS: Two hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n=229; 15.2% v 6.8%; P=.043) and in full analysis set (n=221) (15.5% v 7.2%; P=.053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P=.059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P=.067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms. CONCLUSION: ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.

Adult↗
PubMed2003

[Cutaneous malignant melanoma of the head and neck with intermediate tumor thickness: the role of elective lymph node dissection for clinical stage I].

BACKGROUND: At present a tendency towards a more limited surgery in the treatment of clinical stage I and II melanoma exists. The controversy of elective lymph node dissections (ELND) in stage-I-melanoma with intermediate tumor thickness continues to be discussed. The sentinel lymph node biopsy may provide improved staging accuracy. METHODS: It was the aim of this study to examine whether extent of surgical treatment particularly the ELND in case of intermediate tumor thickness has prognostic significance. Metastatic pattern of these malignant melanoma were analyzed to form a basic for routine sentinel lymph node biopsy. RESULTS: No prognostic difference could be shown in clinical stage I melanoma with intermediate tumor thickness between "local excision" (no lymph node dissection) or "wait and see" (delayed lymph node dissection because of clinical suspicion) respectively and "local excision with elective neck dissection". The 5-year survival was 67 %, 67 % and 69 %. It ran to 53 % in case of therapeutical lymph node dissection as primary therapy. Occult nodal metastases occur in 15 % and "skip"-metastases in 6 %. CONCLUSIONS: No therapeutic value for ELND in clinical stage I malignant melanoma of the head and neck with intermediate tumor thickness could be shown. The low incidence of occult nodal metastases and "skip"-metastases represents the basic for sentinel lymph node biopsy.

Follow-Up Studies↗
PubMed2002

[Complicated antiphospholid antibody syndrome].

HISTORY AND CLINICAL FINDINGS: A 51-year-old female patient suffered from recurrent ischemic strokes and venous thromboembolism although treated with ASS and phenprocoumon, which mainly occurred after diagnosis and treatment of an invasive-ductal mamma carcinoma. The severely ill patient presented with right-sided hemiparesis and dysarthria, a swollen leg, a painful necrotic-ulcerative lesion at the left-lateral ankle and a systolic heart murmur. INVESTIGATIONS: Laboratory data revealed a haemoglobin of 8,4 g/dl, a leucocyte count of 3,1 x 10 (9)/l and a platelet count of 87 x 10 (9)/l. C-reactive protein, ESR and plasma fibrinogen were markedly increased. Levels of antinuclear, IgG-anticardiolipin and anti-doublestranded-DNA antibodies were excessively elevated. A test for lupus anticoagulant was strongly positive. Sonographic examinations showed deep vein thrombosis and significant mitral valve regurgitation. Suspected pulmonary embolism was demonstrated by CT scan. We diagnosed systemic lupus erythematosus with secondary antiphospholipid antibody syndrome (APAS). TREATMENT AND COURSE: Phenprocoumon was stopped and full-dose anticoagulation with low-molecular-weight heparin initiated. Additional immunosuppressive therapy consisted of cyclophosphamide, azathioprin and prednisone resulting in prevention of further thromboembolism and significant improvement of clinical symptoms. The observed severe interference of LA with the prothrombin time after cessation of phenprocoumon (INR 3,6; FII activity 81 %) suggested that the effect of oral anticoagulation had been overestimated in the past. CONCLUSION: APAS may present as an acute and life-threatening disorder. In this case interdisciplinary co-operation and a highly individualised treatment strategy are mandatory.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Combination chemotherapy with or without s.c. IL-2 and IFN-alpha: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM).

The purpose of this randomized trial was to evaluate the efficacy of combination chemoimmunotherapy compared with chemotherapy alone. A total of 124 patients were randomized to receive intravenous cisplatin (35 mg m(-2), days 1-3), carmustine (150 mg m(-2), day 1, cycles 1 and 3 only), dacarbacine (220 mg m(-2), days 1-3) and oral tamoxifen (20 mg m(-2), daily) in combination with (n=64) or without (n=60) sequential subcutaneous IL-2 and IFN-alpha. In those patients who received sequential immunotherapy, each cycle of chemotherapy was followed by outpatient s.c. IL-2 (10 x 10(6) IU m(-2), days 3-5, week 4; 5 x 10(6) IU m(-2), days 1, 3, 5, week 5) and s.c. IFN-alpha (5 x 10(6) IU m(-2), day 1, week 4; days 1, 3, 5, week 5). The overall response rate of patients treated with the combination of chemotherapy and IL-2/IFN-alpha was 34.3% with seven complete responses (10.9%) and 15 partial responses (23.4%). In patients treated with chemotherapy, only, the overall response rate was 29.9% with eight complete responses (13.3%) and 10 partial responses (16.6%). There was no significant difference in median progression free survival (0 months vs 4 months) and in median overall survival (12 months vs 13 months) for combined chemoimmunotherapy and for chemotherapy, respectively.

Administration, Oral↗
PubMed2001

Staphylococcus aureus enterotoxins induce histamine and leukotriene release in patients with atopic eczema.

BACKGROUND: Chronic skin colonization with Staphylococcus aureus is a characteristic feature of atopic eczema (AE), and about 60% of S. aureus strains isolated from the skin of patients with AE secrete enterotoxins. Furthermore, IgE antibodies to S. aureus enterotoxins have been identified in 78% of patients with AE. OBJECTIVES: To examine the S. aureus enterotoxin-induced histamine and leukotriene release of basophils from patients with AE. METHODS: Peripheral blood basophils from patients with AE were stimulated with the staphylococcal enterotoxins A, B, D, E and toxic shock syndrome toxin-1. Additionally, priming experiments were performed with interleukin (IL)-3, IL-8 and granulocyte/macrophage colony-stimulating factor followed by stimulation with S. aureus enterotoxins. RESULTS: In patients with AE, basophils secreted significantly higher amounts of histamine and leukotriene C4 (LTC4) than in healthy controls. The priming experiments showed additional histamine and LTC4 release in the group of AE patients. CONCLUSIONS: Histamine and leukotriene generation from atopic basophils stimulated with staphylococcal enterotoxins may indicate a role for these toxins as possible allergens in at least a subgroup of patients with AE.

Bacterial Toxins↗
PubMed2001

[Cutaneous malignant melanoma in the area of the head and neck with intermediate tumor thickness: does primary site have prognostic relevance?].

BACKGROUND: Tumor thickness and infiltration of malignant melanoma are the main prognostic factors for recurrence and survival. The sentinel lymph node biopsy may provide a step toward a more individual staging and therapy. It was the aim of this study to investigate the prognostic influence of the primary localization of head and neck melanoma subdivided into scalp, ear, neck, and face. To form a basis for routine sentinel lymph node biopsy in case of intermediate tumor thickness metastatic pattern of the different primary sites were analysed. METHOD: Survival rates depending on primary tumor site of 51 patients with cutaneous malignant melanoma of the head and neck were analysed. Metastatic pattern were evaluated with the help of clinical, intraoperative, pathohistologic data. RESULTS: Scalp and ear melanoma were found to be higher risk lesions with a 5-year survival rate of 28% and 59% respectively. Melanoma of the neck and face had a 5-year survival rate of 75% and 78% respectively. In two cases of ear melanoma lymph node metastases could be demonstrated in unusual sites by skipping the first draining basin. In three cases bilateral metastases could be shown histologically as opposed to clinical prediction. CONCLUSIONS: Localization of cutaneous malignant melanoma of the head and neck is a prognostic factor for survival. Because of the discordancy between clinical prediction and lymphatic drainage pattern sentinel lymph node biopsy improves accuracy of diagnostic and therapeutic procedures.

Follow-Up Studies↗
PubMed2000

Reduction of tumor burden and stabilization of disease by systemic therapy with anti-CD20 antibody (rituximab) in patients with primary cutaneous B-cell lymphoma.

BACKGROUND: Primary cutaneous B-cell lymphoma (CBCL) is characterized by restriction to the skin, a high incidence of recurrence after various treatment modalities, and a variable but mostly favorable prognosis. METHODS: Ten patients with long standing primary CBCL (3 with follicular CBCL, 5 with cutaneous, large B-cell lymphoma, 1 with diffuse large cell lymphoma, and 1 with extranodal large cell lymphoma) were treated by intravenous application of a chimeric antibody against the CD20 transmembrane antigen that is present on malignant and normal B-cells. In 6 of 10 patients, several treatment attempts either had failed or could not be used due to severe side effects or underlying disease. RESULTS: The treatment regimen resulted in two complete regressions, five partial responses, and one mixed response, and two patients did not respond to the treatment. No severe side effects occurred, except for slight pain in the nodules after infusion and an urticarial reaction at the tumor sites. A prolonged, complete disappearance of B-cells from the peripheral blood was observed. The immunoglobulin serum levels and inflammatory markers were unchanged. Histologic examination of biopsies from two regressing tumor nodes showed necrotic tumor cells and infiltration with CD8 positive cells. CONCLUSIONS: Intravenous therapy with the anti-CD20 antibody rituximab is a nontoxic and effective treatment for patients with primary cutaneous B-cell lymphoma.

Adult↗
PubMed2000

Effects of whole-body UVB irradiation on cytokine production by peripheral blood mononuclear cells from stage I melanoma patients.

Ultraviolet (UV) radiation causes significant impairment of immunological function in human skin. The immunosuppressive effects of UV radiation are thought to be due to local release of cytokines by human keratinocytes, leading to impaired function of epidermal antigen-presenting cells (APC) and failure to induce cutaneous delayed-type hypersensitivity (DTH) reactions. Recent studies have shown that individuals susceptible to UV-induced suppression of DTH may be more prone to develop skin cancer including malignant melanoma (MM). Since the causal relationship between UV radiation and the induction of MM still seems obscure, we investigated the immunological reactions of peripheral blood mononuclear cells (PBMC) to whole-body irradiation with UVB in 15 stage I melanoma patients as compared to PBMC from normal volunteers matched for age, gender and skin type. Whole-body irradiation was performed with 0.8 minimal erythema dosages on five consecutive days. Peripheral blood was obtained before and after the procedure. Overall, there were no major effects of UVB irradiation on peripheral lymphocyte subsets and proliferation of PBMC from patients or normal controls, but UVB irradiation led to a significant increase in PWM-stimulated production of IL-6, IL-2R and TNF by PBMC. These changes were independent of the individual UVB dosages administered and appeared in both groups similarly. UVB irradiation did not lead to significant changes on IL-1 and IL-2 expression by PBMC. Our results suggest that PBMC participate in the cytokine response to UV, even in the absence of inflammatory reactions, but that this participation is not specific to MM patients.

Adult↗
PubMed2000

Treatment of atopic eczema with oral mycophenolate mofetil.

BACKGROUND: Activated T and B lymphocytes are the predominant inflammatory cells in atopic eczema (AE) lesions. Mycophenolic acid, the active form of mycophenolate mofetil (MMF), blocks the proliferative responses of T and B lymphocytes. OBJECTIVES: In this pilot study, we examined the efficacy of MMF (CellCept(R), Hoffman La Roche, Grenzach-Wyhlen, Germany) in severe AE. METHODS: Ten patients with severe AE (severity index > 50) according to the Severity Scoring of Atopic Dermatitis (SCORAD) index were treated with oral MMF at an initial dose of 1 g daily during the first week and 2 g daily for a further 11 weeks. Laboratory examination including full blood count, lymphocyte subset analysis, serum immunoglobulins (IgE, IgG, IgM, IgA), total bilirubin, alkaline phosphatase, aminotransferases, lactate dehydrogenase and creatinine was performed every 2 weeks. Additionally, interleukin (IL)-10 and interferon (IFN)-gamma in serum were measured. RESULTS: None of the 10 patients who received MMF discontinued the trial because of lack of efficacy or adverse events. Compared with the baseline, the median scores for disease severity (SCORAD index) improved by 68% during treatment with MMF. The median serum IgE level decreased significantly, from 10,300 kU L-1 before treatment to 7830 kU L-1 after 12 weeks. MMF induced a significant increase in the T-helper (Th)-1-related cytokine IFN-gamma and a significant decrease in IL-10, mainly produced by Th2 cells. CONCLUSIONS: The present study demonstrates that oral MMF at a dose of 2 g daily is an effective, safe and well-tolerated immunosuppressive therapy for severe AE in adults.

Adult↗
PubMed1999

Indoor air pollution by lindane and DDT indicated by head hair samples of children.

The use of the pesticides DDT and lindane as wood preservatives causes indoor air contamination and subsequently exposure of the occupants of these rooms. As hair acts as a passive sampler for air contaminants, we tested pesticide concentrations in hair measured by the GC/MS technique. A comparison of the DDT and lindane concentrations in hair samples of 193 pre-school children from a rural area around Rostock with information concerning their home environments showed that this is a suitable method for screening purposes.

Air Pollution, Indoor↗
PubMed1999

[Painful ischemia of the extremities with T-cell lymphoma].

Two years after the diagnosis of Sézary syndrome, a 50-year old female patient experienced attacks of painful ischemia of both hands and feet, leading to acral necrosis. Another 59-year old patient presented with severe pain in his feet, secondary to ischemia. This was the first symptom of a T-cell-chronic lymphocytic leukemia. Similar cases have only occasionally been described. The relationship between acral ischemia and T-cell-lymphoma is not clear but is discussed in this article.

Chlorambucil↗
PubMed1999

Heterogeneity of chemosensitivity of metastatic cutaneous melanoma.

Advanced melanoma has a poor prognosis and chemotherapy provides little benefit for most patients. This may be related to heterogeneity of chemosensitivity as well as frequent constitutive resistance to individual cytotoxic drugs. We have therefore examined the heterogeneity of chemosensitivity in metastatic cutaneous melanoma specimens using an ex vivo ATP-based chemosensitivity assay (ATP-TCA). Melanoma deposits (n=55) in skin or lymph node were tested using the ATP-TCA, performed in three separate laboratories. Analysis of the data collected (based on an arbitrary sensitivity index < 300) shows considerable heterogeneity of chemosensitivity. The most active single cytotoxic agents in the assay were identified as cisplatin, treosulfan, paclitaxel, vinblastine, gemcitabine and mitoxantrone. There was also a limited direct inhibition of melanoma cell growth by interferon-alpha2b, although this agent is known to have a number of indirect biological antitumor effects. Exposure of tumor cells to combinations of drugs at the concentrations tested as single agents showed the most active combinations to be treosulfan+gemcitabine, cisplatin+paclitaxel and vinblastine+paclitaxel. There was considerable heterogeneity of chemosensitivity: some tumors responded well to one agent or combination, while others showed no response to this and instead responded to one of the alternatives tested. Occasional highly resistant tumors showed no response to any of the single agents or combinations tested. The degree of heterogeneity observed suggests that the ATP-TCA could be used to select patients who might benefit from specific chemotherapeutic agents alone or in combination. This provides the rationale for future randomized controlled trials of ATP-TCA-directed chemotherapy versus physician's choice to determine whether assay-directed chemotherapy can improve patient response and survival.

Adenosine Triphosphate↗
PubMed1999

Treosulfan is an effective alkylating cytostatic for malignant melanoma in vitro and in vivo.

The therapy of metastatic malignant melanoma is limited by poor responses and short overall survival. Thus it remains an important issue to identify and test potential new drugs in this disease. This study was performed to examine the effects of the bifunctional alkylating cytostatic treosulfan in vitro. Using an in vitro microplate ATP bioluminescence tumour chemosensitivity assay (ATP-TCA) five highly chemoresistant melanoma cell lines and melanoma cells freshly isolated from metastases surgically resected from stage IV melanoma patients (n = 10) were incubated with treosulfan. Three cell lines and eight of the 10 tested tumour cells isolated from melanoma metasteses showed tumour growth inhibition >50% after incubation with treosulfan. Therefore, 14 patients with rapidly progressing stage IV malignant melanoma who had been pretreated with at least one standard chemotherapy regimen received treosulfan. In this population of patients with highly refractory advanced melanoma, one complete remission (7.1%), two partial remissions (14.3%) and three cases of stable disease (21.4%) were observed. The median survival time for all the patients measured from the beginning of treosulfan treatment was 9 months, and the median overall survival was 17 months. Except for two patients who developed grade 3 leucopenia, only moderate side effects were observed. Therefore, we conclude that treosulfan was well tolerated in this small series of patients and seems to be a promising alkylating cytostatic for the treatment of metastatic melanoma. Further studies are warranted to test these findings.

Adenosine Triphosphate↗
PubMed1999

Expression of complement regulator proteins in primary and metastatic malignant melanoma.

The expression of complement regulatory antigens C3b/C4b receptor, (CD35) membrane cofactor protein (CD46), decay accelerating factor (CD55), and homologous restriction factor 20 (CD59) was determined immunohistochemically on ten primary malignant melanomas, 16 metastatic lesions, and ten melanocytic nevi. All of the melanocytic nevi and 9/10 primary melanomas showed both expression of CD46 and CD59. In one primary melanoma lacking CD46, expression of CD35 could be detected. In metastatic melanoma, 9/16 metastases were CD46+/CD59+, two were CD46-/CD59+, one CD46+/CD59-, and four CD46-/CD59-. Additionally, CD55 could be detected in two CD46+/CD59+ metastases, and CD35 in one. Expression or lack of complement regulatory antigens did not correlate with the expression of GD2, GD3, HMB-45 or S-100. In conclusion, some cases of metastatic melanoma show loss of normal expression of complement regulatory proteins. This might have implications on the immune response or the efficacy of immune therapy in malignant melanoma.

Adolescent↗