Search PubMed⌕ Search

Biomedical subjects

W Sterry

Publications and source records attributed to W Sterry.

At least 73 records · Page 4Linked to original sources
PubMed2002

[Skin diseases in organ transplant patients].

In Germany 3273 visceral organs were transplanted in the year 2000. Together with patients grafted abroad, it is estimated that between 70,000 and 100,000 organ transplant patients are currently living in Germany. With the provision of lifelong immunosuppression the survival-time of these patients can exceed more than 20 years. In the first year following transplantation special emphasis is given to the prevention of viral, bacterial and fungal infections. Regular dermatological screening can provide early diagnosis of even systemic infections. An increased incidence of skin cancer parallels the extended survival rates of grafted patients. Within the first 5 years of immunosuppression 40% of these patients develop pre-malignant skin tumors such as actinic keratoses, dysplastic nevi, squamous cell carcinomas and basal cell carcinomas. Squamous cell carcinomas show an aggressive biology and an uncommon clinical morphology. The increased incidence of cancer is now responsible for a mortality rate of 5-8% in grafted patients. Against a background of lifelong immunosuppression, other risk factors include sun exposure and infections with oncogenic viruses. The rapidly growing numbers of allograft recipients as well as the rising long term survival rates of these patients demand the provision of high quality interdisciplinary and dermatological care in this field.

Humans↗
PubMed2002

Cytokine therapy in dermatology.

Cytokines have been in the focus of scientific interest for some years now. Analysing their expression permitted a better understanding of the pathogenesis of various diseases, including in dermatology. Moreover, they are now far beyond the stage when they were of interest only to the pathophysiological research sector: some cytokine therapies are already being employed as part of the clinical practice. In fact, several cytokines are used for the treatment of malignant, inflammatory and infectious skin diseases. Their stage of development ranges from advanced, already approved and well established therapies (e.g. IFN-alpha and IL-2 for melanoma) to early explorative trials (e.g. IL-4 and IL-10 for psoriasis). Some of the new approaches currently under investigation will actually lead to registration of new drugs for dermatological treatment and to supplement existing therapeutic options. Beside this, the results of clinical trials with cytokines are significantly contributing to our understanding of the pathophysiology of diseases. They will give a better insight into which mechanisms play a greater or lesser part in their development and may generate momentum for still better targeted pharmacological approaches. Here we would like to give an overview about the current stage of cytokine therapy and the prospects for dermatological indications. The terminology and immunobiology of cytokines are also briefly discussed, since for a sensible interpretation of the relevant findings a basic knowledge of these biologically highly active messenger substances is essential.

Chronic Disease↗
PubMed2002

CD4+CD7- leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death.

In early stages of cutaneous T cell lymphoma (Sézary syndrome) both CD4+CD7- and CD4+CD7+ T cells clonally expand whereas in late stages of the disease CD7- cells are predominant in number, giving rise to the question whether CD7- T cells have a survival advantage in the skin. Galectin-1, a cell-bound lectin, was recently reported to trigger apoptosis in activated CD7+ T cells. Here, we demonstrate that in contrast to activated CD7(+) T cells, quiescent and activated CD69+ CD7- T cells from healthy donors and from Sézary patients are resistant to galectin-1-mediated cell death. CD7- T cells are apoptosis-resistant even during coculture with IFN-gamma-stimulated endothelial cells that constitutively express galectin-1 in high amounts. These data imply that resistance of CD7- T cells to galectin-1-induced apoptosis may contribute to the accumulation of CD7- Sézary T cells during progression of the disease.

Adjuvants, Immunologic↗
PubMed2002

Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion.

BACKGROUND: Imiquimod 5% cream has been investigated for non-surgical treatment of superficial and nodular basal cell carcinoma (BCC) tumours. OBJECTIVES: Two studies were conducted to examine the effect of occlusion at low dosing frequencies on the safety and efficacy of topical imiquimod 5% cream for the treatment of superficial and nodular BCC. PATIENTS AND METHODS: Both open-label studies were conducted in Europe. Patients diagnosed with BCC were enrolled into either the superficial (93 patients) or nodular (90 patients) study, depending on the histological confirmation of the patient's tumour subtype. Patients were randomized to one of four groups to apply imiquimod 5% cream 2 or 3 days per week either with or without occlusion. Six weeks following a 6-week treatment period, the entire target tumour area was excised and histologically examined for evidence of residual tumour. RESULTS: In both studies, the highest histologically complete response rate was seen in the 3 days per week with occlusion groups, with complete response rates of 87% and 65% for the superficial and nodular studies, respectively. Occlusion did not have a statistically significant effect on response rate at either dosing frequency. Response rates for superficial and nodular BCC tumours treated 3 days per week without occlusion were 76% and 50%, respectively. CONCLUSIONS: In the superficial study, the complete response rate of 87% in the 3 days per week with occlusion group was similar to that of daily and 5 days per week dosing without occlusion in a previous 12-week study and one study of daily dosing without occlusion for 6 weeks. All treatment groups had acceptable safety profiles in both studies. Occlusion did not have a statistically significant effect on efficacy for either superficial or nodular BCC tumours.

Administration, Cutaneous↗
PubMed2002

Cytokines: interleukin and interferon therapy in dermatology.

Cytokines are highly potent biologically active proteins that play an essential role in intercellular communication. They are vital to the mediation and regulation of inflammatory and specific immune reactions as well as to nonimmunological processes. Several cytokines are already used for the treatment of malignant, inflammatory and infectious skin diseases. This in particular includes certain interleukins (ILs) and interferons (IFNs). Whereas some cytokine therapies are already approved and well established, such as IFN-alpha and IL-2 (approved in the USA) for melanoma, others are in the early stages of development and are used in explorative trials (e.g. IL-4 and IL-10 in the treatment of psoriasis). It is likely that some of the new approaches currently under investigation will actually lead to both the registration of new drugs for dermatological treatment, and to supplementation of existing therapeutic options. The aim of this review is to give an overview on the current state of cytokine therapy in dermatology.

Antineoplastic Agents↗
PubMed2002

Vaccination therapy for cutaneous T-cell lymphoma.

Primary cutaneous T-cell lymphomas (CTCL) are defined as clonal proliferation of skin-infiltrating T lymphocytes. Despite their heterogeneity, CTCL are generally incurable, which has led to the development of various treatment strategies including vaccination. Here, the attempts to vaccinate against lymphoma will be reviewed with special emphasis on CTCL. Because an universal tumour antigen is not available so far, different targets - including whole tumour cells, idiotypes, cancer/testis antigens, proteins derived from tumour-associated mutations, and mimotopes - have been investigated for their applicability in CTCL vaccination. The antigenic information can be delivered in different ways. So far, tumour cells fused to dendritic cells, idiotypic proteins/peptides and DNA/RNA preparations have been applied in lymphoma. As most targets are weak immunogens, adjuvants and other helpers - including dendritic cells, immunogenic peptides and oligonucleotides, cytokines, and viral vectors - are required to enable proper presentation of the antigens and sufficient activation of the immune system. Although first data from CTCL patients prove the suitability of vaccination in CTCL therapy, the number of available antigens, carriers, adjuvants and application schemes creates a multitude of vaccine formulations; identification of the best-suited approach remains nearly impossible. Furthermore, the relationship between lymphoma and the host immune system is complex and incompletely understood. As a result, CTCL vaccination still requires a lot of research.

Adjuvants, Immunologic↗
PubMed2002

The future of vaccination as a treatment strategy in dermatological diseases.

Vaccination approaches are increasingly explored as means for both prevention and therapy of skin diseases. These development are boosted by the rapidly accumulating knowledge of the molecular and cellular bases of these disease and the antigens involved, on the one hand, and of the components and mechanisms of cellular and humoral immune responses, on the other. In a number of cases these newly developed vaccination strategies are already tested in clinical trials. Although most of them are still in very early stages of the development, it is foreseeable that vaccination will emerge as an important option for prevention and treatment of infectious skin diseases as well as of cancer, allergies and maybe, auto-immune disorders.

Antigens↗
PubMed2001

Efficacy of ultrasound B-scan compared with physical examination in follow-up of melanoma patients.

BACKGROUND: The value of ultrasound B-scan for routine follow-up of melanoma patients still is not generally accepted. Therefore, the authors compared the efficacy of physical examination (PE) with ultrasound B-scan (UBS) for detection of regional tumor recurrence in melanoma patients. The aim of the current study was to evaluate whether early detection of metastases improves relapse-free and overall survival. METHODS: For a period of 4 years, 829 consecutive melanoma patients were followed prospectively. Physical examination of 3011 patients and concomitant UBS of in-transit routes and regional lymph node basins were performed. Suspicious lesions were diagnosed by fine-needle aspiration cytology and pathology. RESULTS: During the study period, 242 (90.6%) of 267 patients with melanoma recurrences were first recognized by PE or UBS within the routine follow-up program. The sensitivities of both methods differed significantly (P = 0.001). Metastases were detected by PE in only 61 of 242 recurrences (25.2%, 95% confidence interval [CI]: 19.9-31.2%), whereas UBS revealed 240 recurrences (99.2%, 95% CI: 97.3-99.6%). The specificity was 98.4% (95% CI: 97.8-98.8%) and 98.3% (95% CI: 97.7-98.7%), respectively. Survival of 103 patients who presented with a first nodal melanoma recurrence was followed and analyzed by multiple Cox regression. Overall survival was affected by the diameter of the largest metastasis (P = 0.001) and the number of metastatic lesions (P = 0.012). CONCLUSION: The study found that ultrasound B-scan was highly effective in the early detection of regional melanoma metastases compared with physical examination. Earlier detection of such metastases seemed to result in improved overall survival.

Adolescent↗
PubMed2001

Identification of sample-specific sequences in mammalian cDNA and genomic DNA by the novel ligation-mediated subtraction (Limes).

The representational difference analysis (RDA) and other subtraction techniques are used to enrich sample-specific sequences by elimination of ubiquitous sequences existing in both the sample of interest (tester) and the subtraction partner (driver). While applying the RDA to genomic DNA of cutaneous lymphoma cells in order to identify tumor relevant alterations, we predominantly isolated repetitive sequences and artificial repeat-mediated fusion products of otherwise independent PCR fragments (PCR hybrids). Since these products severely interfered with the isolation of tester-specific fragments, we developed a considerably more robust and efficient approach, termed ligation-mediated subtraction (Limes). In first applications of Limes, genomic sequences and/or transcripts of genes involved in the regulation of transcription, such as transforming growth factor beta stimulated clone 22 related gene (TSC-22R), cell death and cytokine production (caspase-1) or antigen presentation (HLA class II sequences), were found to be completely absent in a cutaneous lymphoma line. On the assumption that mutations in tumor-relevant genes can affect their transcription pattern, a protocol was developed and successfully applied that allows the identification of such sequences. Due to these results, Limes may substitute/supplement other subtraction/comparison techniques such as RDA or DNA microarray techniques in a variety of different research fields.

Animals↗
PubMed2001

Mimotopes for tumor-specific T lymphocytes in human cancer determined with combinatorial peptide libraries.

Mimotopes of a tumor-associated T cell epitope were determined using randomized and combinatorial peptide libraries and a CD8(+) T cell clone specific for the cutaneous T cell lymphoma cell line MyLa. Antigen recognition by this clone was found to be HLA-B8 restricted. More than 80 % of HLA-matched patients with cutaneous T cell lymphoma had mimotope-specific CD8(+) T cells in their peripheral blood. Mimotope-specific T cells isolated and expanded from a patient lysed MyLa cells in in vitro assays thus demonstrating their cytolytic capacity and tumor specificity. Mimotope vaccination of a patient without detectable mimotope-specific T cells induced frequencies of these cells of up to 1.82 % of the peripheral blood CD8(+) T cells.

Amino Acid Sequence↗
PubMed2001

An approach to the sensitivity of temperature-gradient gel electrophoresis in the detection of clonally expanded T-cells in cutaneous T-cell lymphoma.

Detection of T-cell clonality by polymerase chain reaction (PCR) and high-resolution electrophoresis facilitates differentiation of early stages of cutaneous T-cell lymphoma (CTCL) from benign T-cell-rich dermatoses. However, data regarding the sensitivity of the various electrophoresis techniques differ remarkably. In the present study, the capacity of heteroduplex (HD)-loaded temperature-gradient gel electrophoresis (TGGE) to detect clonally expanded T-cells was assessed systematically and modifications to the procedure were defined. Using our standard protocol, HD-TGGE detected clonal T-cell receptor (TCR)-gamma PCR products, generated from the Jurkat cell line, down to a total of 2 ng/microL (14 ng) DNA. However, slowly migrating single strands of the clonal PCR product reduced the amount of the clonality indicating homoduplices. To overcome this single-strand formation, thus decreasing the detection limit, the urea concentration in the gel and the temperature ramp for the HD-formation were altered, as well as the temperature gradient in the gel. Application of the modified protocol resulted in a tenfold lower detection limit of 0.15 ng/microL (1.05 ng) DNA in the clonal band. The sensitivity of the adapted HD-TGGE was investigated by dilution experiments using the well established T-cell lines Jurkat, Molt-4, MyLa and SeAx. By these approaches clonal PCR products diluted in nonclonal PCR products were detectable down to concentrations of 5-10%. Comparably, in the case of mixtures of clonal in nonclonal DNA the detection limit reached 5-10% clonal DNA. However, by dilution of clonal cells in nonclonal peripheral blood mononuclear cells, which corresponds to in vivo conditions, a lower detection limit of approximately 1-5% was observed.

DNA, Neoplasm↗
PubMed2001

[Shiitake dermatitis: flagellate dermatitis after eating mushrooms].

The name of flagellate dermatitis originates from self-flagellating medieval people. This dermatitis is not rare as a drug eruption following bleomycin therapy. An identical skin eruption caused by the mushroom shiitake Lentinus edodes is more common but reported mostly from Japan. We saw a 67-year-old patient who presented with the typical linear scratch marks after a dinner in a Chinese restaurant. The basic mechanism is a toxic epidermal damage. Since it is not clear why the dermatitis does not occur frequently since Shiitake is the second most popular mushroom in the world, we discuss possible cofactors that may trigger the toxic reaction.

Administration, Oral↗
PubMed2001

[Anti-CD20 antibodies in primary cutaneous B-cell lymphoma. Initial results in dermatologic patients].

BACKGROUND AND OBJECTIVE: Primary cutaneous B cell lymphomas (pCBCL) are rare extra-cutaneous non-Hodgkin lymphomas which occur on the trunk as follicle center cell lymphoma or on the leg as large B cell lymphoma. The currently accepted therapy of pCBCL (excision and/or radiotherapy, systemic interleukin 2 and interferon alpha 2a, local injection of cisplatin or multiagent chemotherapy, i.e. CHOP) is insufficient for treatment of multifocal pCBCL and secondary extracutaneous involvement. For this reason, the new synthetic chimeric, monoclonal anti-CD20 antibody Rituximab is an alternative treatment for patients with pCBCL. PATIENTS/METHODS: Four patients with pCBCL localized to the trunk or head were treated with Rituximab (375 mg/kg weekly for 4-8 weeks, then maintenance therapy every 4 weeks for 6 months). RESULTS: All 4 patients showed a response (2/4 partial; 2/4 complete). Side effects were minimal. CONCLUSIONS: Rituximab is an alternative immunotherapeutic drug for the treatment of pCBCL. Our initial experience with this new modality are presented and discussed.

Aged↗
PubMed2001

[Keratosis lichenoides chronica following trauma. A case report and update of the last literature review].

Since the original description by M. Kaposi in 1895, 40 cases of keratosis lichenoides chronica have been published. Most have been reports of single cases. The clinical appearance is characterized by lichen planus-like papules, linear keratoses, and psoriasis-like plaques. While the etiology is still unknown, an association with a variety of diseases including hepatitis, tuberculosis, glomerulonephritis, and lymphoproliferative diseases has been reported. We present a new case which may have been triggered by trauma or carbamazepine.

Adolescent↗
PubMed2001

T cells engrafted with a recombinant anti-CD30 receptor target autologous CD30(+) cutaneous lymphoma cells.

T cells can be directed to antigen-specific, MHC-independent target cell lysis by grafting with a recombinant receptor with antibody-like specificity. Here, we asked whether T cells from the peripheral blood of a patient with cutaneous T cell lymphoma can be recruited for an immune response against autologous tumor cells. Lymphoma cells with a CD3(-) CD4(+) CD30(+) phenotype and clonal TCR-Vbeta7 rearrangement were isolated from a cutaneous lesion. The lymphoma lesion additionally harbored CD3(+) CD25(+) activated normal T cells despite ongoing tumor progression. Peripheral blood-derived T cells from the lymphoma patient were retrovirally engrafted with a recombinant anti-CD30-scFv-gamma receptor. Upon cocultivation with autologous CD30(+)lymphoma cells, grafted T cells increase IFN-gamma secretion and lyse specifically lymphoma cells with high efficiency, even at an effector to target cell ratio of as low as 1:20. Our data demonstrate that the recombinant anti-CD30-gamma receptor overcomes T cell tolerance for tumor cells and directs T cells specifically against autologous lymphoma cells.

Adult↗
PubMed2001

Effects of systemic interleukin-10 therapy on psoriatic skin lesions: histologic, immunohistologic, and molecular biology findings.

Interleukin-10 is an important anti-inflammatory and immunosuppressive cytokine with major impact on several immune reactions, including regulatory mechanisms in the skin. Recently, we performed a phase II trial in psoriatic patients receiving subcutaneously interleukin-10 over 7 wk. The clinical response suggested that interleukin-10 might represent a novel anti-psoriatic drug. In order to understand better the mode of action and to elucidate the effects of systemic interleukin-10 treatment on the skin immune system, skin punch biopsies from sites different from interleukin-10 injection were analyzed. Biopsies were obtained from the patients before, at the end, and 3 wk after interleukin-10 therapy. The results are reported here. Histologic examination showed a decrease of several parameters reflecting the psoriatic disease activity as acanthosis and extension of the horny layer. Immunohistologic examination demonstrated decreasing numbers of infiltrating T cells, dermal CD1a+ cells, and a diminished proliferation of epidermal cells. Using a novel, quantitative reverse transcriptase-polymerase chain reaction approach a significant shift within the cytokine pattern was found. Interleukin-10 therapy led to a decrease of cutaneous interleukin-8 and interleukin-10 mRNA expression. Whereas no significant changes of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma expression were found, interleukin-4 was strongly upregulated suggesting a shift from a type 1 towards a type 2 cytokine pattern. The changes within the local cytokine pattern seem to be disease-related, as an inverse course was found in a single interleukin-10 nonresponding patient. Our findings demonstrate considerable effects of systemic interleukin-10 application on the skin immune systems, which might contribute to the anti-psoriatic activity of interleukin-10.

Adult↗
PubMed2001

Primary cutaneous follicle center cell lymphomas and large B cell lymphomas of the leg descend from germinal center cells. A single cell polymerase chain reaction analysis.

Primary cutaneous B cell lymphomas are defined as non-Hodgkin lymphomas that occur in the skin without extracutaneous involvement for 6 mo after diagnosis. They are characterized by a less aggressive course and better prognosis than their nodal counterparts. According to the European Organization for Research and Treatment of Cancer classification, the major subentities of primary cutaneous B cell lymphoma are follicle center cell lymphomas, immunocytomas, and large B cell lymphomas of the leg, which differ considerably regarding their clinical behavior, the former two being indolent, the latter being of intermediate malignancy. In this study, we applied a single cell polymerase chain reaction approach to analyze immunoglobulin V(H)/V(L) genes in 532 individual B lymphocytes from histologic sections of four follicle center cell lymphomas localized on the head and trunk, and four large B cell lymphomas on the leg. We found: (i) in six of eight patients a clonal heavy chain, and in seven of eight patients a clonal light chain rearrangement, all being potentially productive; (ii) no bias in VH gene usage, in four of seven light chain rearrangements the V kappa germline gene IGVK3-20*1 was used; (iii) no biallelic rearrangements; (iv) all V(H)/V(L) genes are extensively mutated (mutation rate 5.4-16.3%); (v) intraclonal diversity in six of eight cases (three of each group); and (vi) low replacement vs silent mutation ratios in framework regions indicating preservation of antigen-receptor structure, as in normal B cells selected for antibody expression. Our data indicate a germinal center cell origin of primary cutaneous follicle center cell lymphomas and large B cell lymphomas independent of those belonging to one of these subentities.

Aged↗