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Biomedical subjects

G Burg

Publications and source records attributed to G Burg.

At least 127 records · Page 7Linked to original sources

Historical perspective on the use of retinoids in cutaneous T-cell lymphoma (CTCL).

Vitamin A and its analogues influence differentiation and proliferation and may also alter immune responses. Limited clinical efficacy of these compounds given alone or as part of a combination therapy has been shown in various types of cutaneous T-cell lymphoma (CTCL), including mycosis fungoides, Sézary syndrome, and prelymphomatous disorders such as parapsoriasis en plaques. Compounds used mostly in small, nonrandomized trials are isotretinoin (13-cis-retinoic acid), etretinate, acitretin, and all-trans-retinoic acid. Clinical responses have been found despite persistent residual disease with atypical lymphocytes in various compartments. The exact mechanism of action of retinoids in CTCL is unclear and depends on the presence of retinoid receptors on the tumor cells, which is variable in different forms of CTCL. Therapies combining retinoids with psoralen-ultraviolet A or with interferons may have a synergistic effect, which deserves confirmation through randomized trials in the future.

History, 20th Century↗

Inverse regulation of neuronal cellular adhesion molecule (NCAM) by IFN-gamma in melanoma cell cultures established from CNS lesions.

In advanced stages of malignant melanoma (MM), metastases to the CNS are frequently observed. Few results are available on trophic factors and immunological features involved in the process of invasion and adhesion of circulating metastatic cells into the CNS. A direct comparison of remote metastases found in different locations of the same patient might help to identify such properties. For this purpose, we screened a panel of MM cell cultures, which had been established from patients with surgically removed MM lesions of the CNS, for expression and regulation of immunorelevant molecules. The results were compared with standard controls and cultures established from non-CNS metastatic lesions of the same patients. No significant differences were observed for expression of HLA-I, HLA-II, ICAM-1 and the melanoma-associated antigens Mage-3, MelanA and tyrosinase. Constitutive expression of the neuronal cell adhesion molecule (NCAM) was found in all CNS-derived samples and in fewer than 50% of non-CNS derived cultures. IFN-gamma was found to have a weak up-regulating effect in all non-CNS-derived cultures, except normal melanocytes. However, in 6/7 CNS-derived cultures, pre-treatment with IFN-gamma reduced expression of NCAM to 28% to 77% of the level in untreated cultures. The presence and regulation of NCAM differs between MM cells derived from CNS metastases and non-CNS-derived melanocytic cells. Thus, NCAM might be a candidate immunoregulating molecule involved in the formation of CNS metastases of MM.

Antibodies, Monoclonal↗

[Dermatological aspects in prevention and treatment of the diabetic foot syndrome].

Diabetic neuropathy, osteoarthropathy, macro- and microangiopathy and susceptibility to infection are the major factors that contribute to the diabetic foot syndrome. Therefore, these patients benefit from a multidisciplinary treatment by the general practitioner, diabetologist, orthopaedic surgeon and shoemaker, angiologist and vascular surgeon. The role of the dermatologist is to recognize early diabetic foot lesions when the diabetic patient comes for a skin problem on his feet and more specifically to manage dermatologic aspects in diabetic foot patients. These should include recommendations for general skin care, examination and treatment for onychomycosis, patch testing in contact eczema or treatment of other dermatoses, such as plantar psoriasis. Therefore, dermatology has an important impact on the prevention of complications of the diabetic foot syndrome by keeping the skin intact and avoiding potential lesions of entry for bacterial soft tissue infection. The dermatologist must educate the diabetic patient to control his feet daily, to avoid foot-baths with hot water, to use hypoallergenic moisturizers for skin care. "Bathroom surgery" with sharp instruments for nail care or trimming of corns should be discouraged. Diabetics should wear wide, well-fitting shoes without sutures on the inner side. The inside of the shoes should always be checked for foreign bodies or irregular surfaces before they are put on. Diabetics should not walk barefoot. Callosities (calluses, corns) should be shown to the podologist or to the doctor. They are always a sign of increased mechanical stress and therefore, require an adjustment of footwear. Trimming of callosities can only aim at giving symptomatic relief and does not replace an appropriate correction of the mechanical stress. Semi-occlusive synthetic dressings have facilitated the treatment of non-infected chronic wounds. When probing of the bone is positive, however, osteomyelitis has to be assumed and empirical antibiotic therapy started. With the development of catheter-based interventional procedures and of cruro-pedal arterial bypasses the potiential of revascularization in diabetic foot with peripheral arterial occlusive disease has greatly improved. Retrograde intravenous antibiotic therapy under Bier's arterial arrest and the use of G-CSF improve the chance of healing bacterial soft tissue infection in a diabetic foot. In summary, optimization of prevention and treatment of the diabetic foot syndrome should allow for substantial reduction of amputations.

Diabetic Foot↗

[The atypical nevus: a risk situation?].

Many studies using different approaches and sets of data have concluded that there is a significantly increased risk of malignant melanoma in patients with atypical moles. For clinical identification, the features of ABCD's (Asymmetry, Border, Colour, Dimension) are used, the "ugly duckling" sign (the naevus that does not resemble its "brother naevi"), dermatoscopy and digital approaches. After excision, histologic criteria are used to identify naevi with architectural changes. It has recently been possible to identify allelic losses within known tumour suppressor genes in microdissected atypical moles, using microdissection and loss of heterozygosity analysis, thus providing additional evidence for the concept of the atypical mole as a precursor lesion of melanoma.

Humans↗

[Persistent erythema after total CO2 skin resurfacing].

Erythema after carbon dioxide laser resurfacing is one among other known side effects of the treatment. Postoperative erythema is considered to be an obligatory complication after resurfacing of facial rhytides or senile lentigines. Duration and intensity of the erythema is dependent on various factors, as shown in the following case report on a 77-year-old female patient. Detailed preoperative information is important in ensuring realistic expectations in regard to the postoperative results and averting liability claims.

Aged↗

Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma.

BACKGROUND: Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed-Sternberg cells originate from B cells. METHODS: We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell-rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed-Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced. RESULTS: In both patients, the Reed-Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed-Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type. CONCLUSIONS: In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B-cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed-Sternberg cells in classic Hodgkin's disease.

Aged↗

The sebaceous nevus: a nevus with deletions of the PTCH gene.

Sebaceous nevi (SN) are congenital malformations of the skin with the potential to develop into basal cell carcinoma (BCC). To date, the molecular basis for their carcinogenic potential remains unknown. The genetic defect in BCC is known and involves the human homologue of Drosophila patched (PTCH) on chromosome 9q22.3. The objective of this study was to test whether allelic deletion of the PTCH gene could already be detected in SN. Twenty-one paraffin-embedded SN were investigated in this study. Basaloid cells in conjunction with mature sebaceous glands as well as epidermal layer apart from SN were microdissected and subjected to single-step DNA extraction. We performed the analysis with polymorphic markers at 9q22.3 (D9S15, D9S252, D9S287, and D9S303). Of the 20 informative SN, 8 (40%) exhibited loss of heterozygosity at least at one locus. Here, we provide the first evidence of the involvement of the tumor suppressor gene PTCH in SN. Whether PTCH deletion in SN is associated with progression to BCC and/or other appendageal tumors should be addressed in future studies.

Basal Cell Carcinoma↗

[Erythroderma and alcohol abuse].

We report on 7 patients with chronic alcohol abuse and ichthyosiform erythroderma. Dry skin (i.e. xerosis cutis) was a striking common feature in all patients who did not present any signs of fluid depletion. Two patients had exclusively exsiccational dermatitis; three had atopic disposition and one nummular eczema of the legs. In another patient a drug allergy could be demonstrated. Xerosis cutis seems to be an important precipitating aetiologic factor for erythroderma, and may be a consequence of alcohol-induced diuresis. All patients recovered rapidly under topical treatment with emollients and low potency steroids. We propose that ichthyosiform erythroderma be added to the known skin diseases caused by chronic alcohol abuse.

Aged↗

Constitutive and interleukin-7/interleukin-15 stimulated DNA binding of Myc, Jun, and novel Myc-like proteins in cutaneous T-cell lymphoma cells.

Members of the Myc and Jun/Fos gene families have been found to be expressed in late stages of cutaneous T-cell lymphoma (CTCL) and may be responsible for the transition from low-grade to high-grade tumors. The composition of these complexes is an important parameter, as the different homo- and heterodimeric jun and myc complexes can have gene transcription activating or suppressing activities. We determined the composition of the jun and myc DNA-binding complexes in three CTCL cell lines and malignant cells of seven Sézary patients by electrophoretic mobility shift assays (EMSAs) and "supershift" assays in which specific antibodies against the different members of the tested gene families were included in the binding reactions. Complexes containing JunD were found in three cell lines and two patients. The three cell lines and one patient contained also c-Myc/Max heterodimers. Because c-Myc/Max heterodimers are strong gene transcription activators and are necessary for cell-cycle progression, they may play a role in the progression of CTCL. JunD may also promote cell-cycle progression and influence the expression of cell death survival genes. Interleukin-7 (IL-7) and IL-15, which have been identified as growth factors for CTCL cells, stimulated the DNA binding of JunD and two novel c-Myc recognition site (E-box) binding proteins, but not the DNA binding of c-Myc/Max heterodimers.

Adult↗

Tumor burden index as a prognostic tool for cutaneous T-cell lymphoma: a new concept.

OBJECTIVES: To introduce a prognostic tool for cutaneous T-cell lymphoma that takes into account the tumor burden and to compare the prognostic value of this tumor burden index (TBI) with that of other prognostic factors. DESIGN: Retrospective clinical and statistical study. PATIENTS: One hundred sixteen patients with cutaneous T-cell lymphoma. METHODS: A TBI was designed that takes into account the types, numbers, and severity of skin lesions with the use of the Cox proportional hazard model. RESULTS: Models of the TBI were developed to test the relative contributions of patches, plaques, and tumors to the total tumor burden and, hence, survival time. Weighting factors reflecting the severity of each skin lesion were tested and incorporated. The best prognostic correlation was a dichotomized index with the following formula: TBI = 1 + (patches x 2) + (plaques x 2) + (tumor x 1.3), where the patches factor equals 0 if 30% or less of the skin area is involved and 1 if greater than 30% of the skin area is involved and where the plaque or tumor factor equals 1 if plaques or tumors are present. Both the TBI and TNM provided predictive information. Discrimination of survival curves and significance of differences was better for TBI (P < .001) than for TNM (P = .009). Sex was also statistically related to survival (males had a better prognosis; P < .04), whereas neither age at first symptoms (P = .35) nor age at time of diagnosis (P = .36) was of prognostic value. CONCLUSIONS: The TBI offers a simple prognostic index for the evaluation of cutaneous T-cell lymphoma. It may become a valuable tool for designing therapeutic strategies for patients according to their specific survival expectancies. However, this model is preliminary and has to be validated on a larger number of patients.

Adolescent↗

Pityriasis rosea is not associated with human herpesvirus 7.

OBJECTIVE: To examine the proposed association between pityriasis rosea and human herpesvirus 7 (HHV-7). DESIGN: A retrospective cross-sectional survey. SETTING: University medical center in Switzerland. PATIENTS: Thirteen patients with pityriasis rosea and 14 persons with normal skin (control subjects). MAIN OUTCOME MEASURES: Detection of HHV-7-specific DNA sequences and antigen (85-kd phosphoprotein [pp85]) by nested polymerase chain reaction and immunohistochemical analysis, respectively. RESULTS: Human herpesvirus 7 DNA sequences and expression of the HHV-7-specific immunodominant pp85 antigen were found in 1 (8%) of 13 lesional skin biopsy specimens of pityriasis rosea. The prevalence of HHV-7 DNA sequences and antigens is even slightly lower in lesional skin of patients with pityriasis rosea than in clinically and morphologically normal skin of 14 control persons, in 2 of whom (14%) HHV-7 DNA sequences and antigens could be detected. CONCLUSION: The low detection rate of HHV-7 DNA sequences and antigens argues strongly against a causative role for HHV-7 in the pathogenesis of pityriasis rosea.

Adolescent↗

IL-12 directly up-regulates the expression of HLA class I, HLA class II and ICAM-1 on human melanoma cells: a mechanism for its antitumor activity?

IL-12 enhances cytolytic activity and proliferation of NK and T cells, and induces cytokines such as IFN-gamma. No direct effects on non-hematopoietic cells have been shown. This study investigates the effects of IL-12 on melanoma cells in vitro. We analyzed 15 melanoma cell cultures and 1 melanoma cell line. Out of 16 samples 13 expressed the beta chain of the IL-12 receptor (IL-12Rbeta). Preincubation with IL-12 increased the surface levels of human leukocyte antigen (HLA) class I, HLA class II and intercellular adhesion molecule (ICAM)-1 of those cultures with IL-12Rbeta expression. The effects of IL-12 on HLA class I could be blocked by an IL-12-neutralizing monoclonal antibody (mAb), but not by an mAb against IFN-gamma. Melanoma cells transduced with IL-12 expressed enhanced levels of HLA class I, HLA class II and ICAM-1 compared to controls. Co-incubation of the melanoma cells with allogeneic peripheral blood mononuclear cells (PBMC) resulted in enhanced proliferation and increased production of IL-2 and IFN-gamma after pretreatment with IL-12. IL-12 pretreatment increased the susceptibility of melanoma cells to lysis by prestimulated autologous PBMC. Since IL-12 induced immunocritical surface molecules on melanoma cells, it might be beneficial during immune interventions in melanoma patients.

Antibodies, Monoclonal↗

[Microdissection. Use in molecular oncologic dermatology].

Microdissection allows the procurement of selective cell populations or single cells of archival sections or frossen tissue. Most cutaneous tumors can not be cultivated or consist of heterogeneous cell populations. Thus, microdissection is an important pre-requisite for molecular genetic analyses of cutaneous neoplasms. This review describes the microdissection and its application in dermatologic oncology is demonstrated.

Cell Transformation, Neoplastic↗

Genotypic, phenotypic and functional analysis of CD4+CD7+ and CD4+CD7- T lymphocyte subsets in Sézary syndrome.

The expansion of CD4+CD7- T cells in the peripheral blood of Sézary syndrome (SS) is well known. It remains unclear whether this population contains the dominant T cell clone. Peripheral blood mononuclear cells (PBMC) of five SS patients were sorted by fluorescence-activated cell sorting into CD4+CD7- and CD4+CD7+ populations. These populations were analysed separately for clonality of the T cell receptor gamma chain (TCR-gamma) by PCR-DGGE. The cytokine profile of both populations was investigated by RT-PCR ELISA for IFN-gamma, IL-2, IL-4, IL-5, IL-10, IL-13 and IL-15. In three other patients with known Vbeta-usage, the dominant T cell clones were phenotypically characterized by double staining. PCR-DGGE of TCR-gamma demonstrated that all patients had a clonal population in their blood and that this population was present in CD4+CD7- and CD4+CD7+ populations. Concerning mRNA cytokine transcription, the two populations did not show any consistent differences. In three patients with identified clones (Vbeta 3.1, 5.3 and 6.7), double staining revealed positivity for CD2, CD3, CD4, CD5, CD45RO and CD7 in a significant proportion (at least 35%). We conclude that the CD4+CD7- population does not represent the dominant T cell clone in patients with SS. An increase in this population of PBMC in SS might account for deviations in the T cell functions of the patients.

Antigens, CD7↗

Measurement of 5-methoxypsoralen and 8-methoxypsoralen in saliva of PUVA patients as a noninvasive, clinically relevant alternative to monitoring in blood.

BACKGROUND: Monitoring of psoralen concentration and time-course in PUVA patients is vital for efficient PUVA therapy. Blood sampling is invasive and labour-intensive and thus unsuited for routine use and repeat measurements over the course of therapy. OBJECTIVE: Psoralen pharmacokinetics in saliva were investigated and validated as a noninvasive, simple and biologically relevant alternative to measurements in blood. METHODS: The time-course of psoralen concentration was measured in saliva and serum of volunteers and patients receiving PUVA or extracorporeal photopheresis therapy. The samples were analysed by high-performance liquid chromatography. Three commonly used oral psoralen preparations were tested: Psoraderm5 (5-methoxypsoralen; 5-MOP), Meladinine and Oxsoralen (both 8-methoxypsoralen; 8-MOP). RESULTS: The pharmacokinetic parameter Cmax in saliva averaged 10% (range 6-20%) of the serum values for 8-MOP, and < or = 4% for 5-MOP. These concentrations correspond to the therapeutically relevant, non-albumin-bound fraction of psoralen in serum that is available to diffuse into the tissues. The parameter tmax in saliva and serum coincided, indicating that psoralens diffuse rapidly between the two compartments. CONCLUSION: Monitoring of psoralens in saliva is a valuable, noninvasive alternative to measurements in serum, suitable for routine use. A series of five or six saliva samples is sufficient to determine tmax in a patient beginning photochemotherapy. To determine Cmax, three independent saliva measurements at t = tmax are recommended.

5-Methoxypsoralen↗

Eyebrow reconstruction with free skin and hair-bearing composite graft.

We describe a surgical reconstruction after micrographic surgery of a recurrent basal cell carcinoma of the middle third of the left eyebrow. After micrographic surgery there was a 46- x 26-mm defect in the middle part of the eyebrow. To perform a cosmetically satisfactory repair a combined nude and hair-bearing full-thickness skin graft was harvested from the contralateral postauricular temporoparietal region and placed in the defect with hair growth direction of the graft and the recipient bed in the same direction. By using a combined nude and hair-bearing full-thickness skin graft, larger eyebrow defects can be repaired with an optimal functional and aesthetic result.

Aged↗