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Biomedical subjects

G Burg

Publications and source records attributed to G Burg.

At least 55 records · Page 3Linked to original sources

[Manifestations of the "pretherapeutic phase" of malignant melanoma of the skin in Switzerland 1996-1998].

62 patients with a histologically confirmed diagnosis of cutaneous malignant melanoma were interviewed from 1996 to 1998. Lesions were found mostly on patients backs (30.6%) and they were noted most frequently because of a change in colour (darker) (50%) and increase in size (43.5%). The median time between first noticing the melanoma and visiting a physician was one month, but for 28% of the patients it was more than three months. The median time between a medical examination and surgical removal was shorter than one month, but for 22% of the patients it was more than three months. Patients with bleeding lesions sought medical help later (14 months). Misdiagnosis led to a six months delay in treatment and if no action was taken there was a 13 months delay.

Adult↗

Interleukin-7 and interleukin-15 regulate the expression of the bcl-2 and c-myb genes in cutaneous T-cell lymphoma cells.

Interleukin-7 (IL-7) and IL-15 have been recently identified as growth factors for cutaneous T-cell lymphoma (CTCL) cells, and they protect these cells from cell death. Using the CTCL cell line SeAx as a test system now shows that IL-7 and IL-15 are indeed necessary to maintain high levels of bcl-2. The up-regulation of bcl-2 was paralleled by increased DNA-binding activities of the transcription factors STAT2, STAT5, STAT6, and c-Myb to bcl-2 gene promoter-enhancer elements. Because STAT5 and c-Myb positively regulate bcl-2, IL-7 and IL-15 may mediate some of their effects on cell death survival gene expression through these 2 factors. Constitutive activities of the 3 STAT factors and c-Myb were found in the IL-7- and IL-15-independent CTCL cell lines HUT78 and MyLa 2059. The c-Myb protein was also present in CTCL cells of the skin lesions of all investigated patients. These results indicate that IL-7 and IL-15 may increase bcl-2 expression in CTCL cells by the activation of c-myb and STAT factors.

DNA-Binding Proteins↗

[Treatment of hyperfunctional facial lines with botulinum toxin].

Lines and wrinkles in the face are not only due to intrinsic and photoaging, but are also caused by lines of facial expression due to muscular action. Botulinum toxin A, which blocks the cholinergic transmission resulting in flaccid paralysis, is a powerful therapeutic tool in the treatment of frown lines, glabellar lines, crow-feet and platysma-bands. It has to be kept in mind, however, that the benefits of this treatment are transient and repeated injections are necessary. A treatment guide with injection sides and concentration of the toxin is presented in the context of the current literature.

Adult↗

TAP1 down-regulation in primary melanoma lesions: an independent marker of poor prognosis.

Melanoma tumor thickness is a major prognostic factor. Thin lesions, however, may metastasize, and sometimes thick tumors may not. To investigate the role of HLA class I-mediated antigen presentation, we correlated the expression of components of the antigen-processing machinery in primary melanoma lesions with their thickness and with the development of metastases. Seventeen formalin-fixed, paraffin-embedded primary melanomas thinner than 0.76 mm and 21 thicker than 1.50 mm were stained with anti-LMP2, -LMP7, -TAP1, -TAP2, -HLA class I and -beta2-microglobulin monoclonal antibodies. Twenty patients remained tumor-free in the follow-up period (10.5 +/- 1.8 years). Eighteen patients relapsed within a median period of 15.0 months following tumor excision. Expression of all markers in the tested lesions was down-regulated, the frequency ranging from about 40% for LMP and TAP subunits to about 70% for HLA class I antigens. Expression of all markers was not correlated with tumor thickness. Only TAP1 and TAP2 down-regulation was significantly (p = 0.026 and 0.042, respectively) correlated with the development of metastases. This correlation was independent of tumor thickness for TAP1. We suggest that TAP1 and probably TAP2 expression in primary lesions represents an independent prognostic marker in melanoma. Abnormalities in antigen presentation may account for the lack of absolute correlation between tumor thickness and prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Interferon resistance of cutaneous T-cell lymphoma-derived clonal T-helper 2 cells allows selective viral replication.

Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of lymphoproliferative disorders that are characterized by an accumulation of T-lymphocytes in the skin and occasionally in blood known as Sézary syndrome (SS). In most cases the dominant clone displays T-helper 2 cytokines. Because IFN-gamma is a natural inhibitor of T-helper 2 cells and IFN-alpha is frequently used in CTCL, the impact of IFNs on SS-derived purified clonal T-helper 2 cells was studied using anti-Vbeta antibodies. Moreover, IFNs are known to mediate virus resistance in normal cells. The isolated clonal CD4(+) cells, but not the nonclonal CD4(+) cells, appeared resistant to IFN-gamma and IFN-alpha stimulation in terms of human leukocyte antigen up-regulation and MxA induction caused in part by alterations in Stat-1 molecule mRNA and IFNgammaR1 mRNA transcription. The IFN resistance of the patient-derived clonal cells was then targeted by vesicular stomatitis virus infection after IFN-alpha priming, resulting in selective viral replication in clonal cells. In contrast, nonclonal cells of the same patient showed IFN-dependent MxA expression, which is a major mediator protein of viral protection. The IFN resistance of the dominant T-helper 2 cells might be important for lymphomagenesis. Interferon signaling deficiencies can be targeted for purging patients' cells in vitro. Furthermore, this approach may allow specific molecular interventions, resulting in the efficient treatment of CTCL and other IFN-resistant neoplasms such as lung cancer.

Clone Cells↗

Coexpression of CD40 and CD40 ligand in cutaneous T-cell lymphoma (mycosis fungoides).

Microarray analysis is a promising new approach for creating specific expression profiles of multiple genes simultaneously. We quantitatively analyzed differential gene expression patterns in mycosis fungoides-derived clonal T cells and autologous, identically cultured CD4+ lymphocytes using microarrays containing 588 cDNA segments from genes relevant to cell signaling, carcinogenesis, and apoptosis. Among other dissimilarities, neoplastic T cells showed coexpression of CD40 (Bp50) and CD40 ligand (gp39, CD154). These results could be corroborated by reverse transcription-PCR, immunohistochemistry, and two-color immunofluorescence staining. Our data suggest that in cutaneous T-cell lymphoma, CD40/CD40 ligand interactions might represent a paracrine loop that is crucial not only in preventing apoptosis or positively regulating growth but also in homing of neoplastic cells to the skin.

Adult↗

Spitz nevi display allelic deletions.

BACKGROUND: Spitz nevi are acquired benign melanocytic lesions that occur in childhood and adolescence. Histologically, they resemble malignant melanoma and were first termed benign juvenile melanoma. Several studies have attempted the difficult task of establishing diagnostic criteria to differentiate between Spitz nevi and malignant melanoma. OBJECTIVE: To elucidate sets of diagnostic criteria for differentiation between the 2 lesions. DESIGN: We aimed to search for allelic deletions in Spitz nevi and to evaluate whether loss of heterozygosity (LOH) or microsatellite instability (MSI) would be a valuable diagnostic tool to differentiate between Spitz nevi and malignant melanoma. SETTING: Two areas within each of 5 lesions were microdissected, and LOH and MSI were evaluated at chromosomes 6q (using polymorphic DNA marker D6S305), 9p21 (D9S171, IFNA, D9S265, and D9S270), 10q (D10S185), and 14q (D14S53). PATIENTS: Five Swiss patients with Spitz nevi. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Allelic deletions may serve as a diagnostic tool to distinguish Spitz nevi from melanoma. RESULTS: All lesions were informative, displaying LOH or MSI with at least one marker. No LOHs were found at 14q. At 6q, MSI was found in 2 dissected areas from the same lesion; the remaining lesions were noninformative. Loss of heterozygosity was found in 2 of 6 areas at D9S171, 2 of 6 at IFNA, 3 of 6 at D9S270, 3 of 4 at D9S265, and 1 of 4 at D10S185. Microsatellite instability was found in 1 of 4 areas at D9S265. CONCLUSIONS: With the markers used in our study, Spitz nevi display LOH and MSI similar to those in melanoma. Analysis of LOH or MSI is therefore not a suitable diagnostic tool in distinguishing Spitz nevi from melanoma.

Adolescent↗

Idiopathic localized unilateral hyperhidrosis: case report of successful treatment with botulinum toxin type A and review of the literature.

BACKGROUND: Localized unilateral hyperhidrosis (LUH) is a rare disorder of unknown origin. We describe a patient with LUH on the forearm, where a fracture was identified as a past injury. OBSERVATIONS: We treated the patient with botulinum toxin type A injections, and he was complaint free during the 6 months after treatment. In addition, the initially strong positive results of the iodine starch test (Minor sweat test) were negative in the affected region after treatment. CONCLUSIONS: This relatively new therapeutic modality already established for axillary, palmar, and plantar hyperhidrosis seems to be efficient in LUH. As the former therapeutic approaches are rather disappointing, and as botulinum toxin type A locally applied shows limited adverse effects, we think a trial of botulinum toxin type A is justified in cases of LUH, even as a first-line treatment. In addition, the literature considering localization and causes of LUH is reviewed.

Adult↗

[Multiple miliary osteomata cutis. Excision with "front lift" approach].

Multiple miliary osteomata of the skin commonly occur on the face and the upper trunk of young healthy women. The mechanism of bone formation is unknown. There is no adequate therapy, which reduces or reverses the growth of osteomatas. Those tumours which are cosmetically disturbing may be excised by a small incision through the skin. For the first time we report their removal via the subcutaneous "front-lift" approach.

Dermatologic Surgical Procedures↗

[Current pathogenetic aspects of Sézary syndrome and mycosis fungoides].

Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative skin disorders whose pathogenesis is poorly understood. Cytokines and chemokines are important factors which can modify the cutaneous microenvironment allowing the accumulation of lymphocytes. Most of these neoplasms seem to be T helper-2 cells. While interferon gamma is the natural inhibitor of clonal T-cell proliferations, interferon resistance has been recently found in these cells. This interferon resistance may be an Achilles heel that can be targeted by molecular therapeutic interventions.

Animals↗

[Successful therapy with tetracycline and nicotinamide in cicatricial pemphigoid].

We describe a case of cicatricial pemphigoid in a 92-year-old female with extensive mucocutaneous involvement. She developed extensive hemorrhagic blistering with severely bleeding lesions, that healed with scarring. The conjunctivae showed extensive synechia. The diagnosis was based on clinical and histopathological features as well as immunofluorescence findings and immunoblot analysis. There was no clinical response to topical corticosteroids. The patient was given tetracycline and nicotinamid and showed rapid improvement of the mucocutaneous lesions within a few weeks. The clinical features, differential diagnosis and various treatment modalities of cicatricial pemphigoid are briefly reviewed, whereby the use of tetracycline and nicotinamide is discussed as an alternative effective and safe therapy for this potentially incapacitating condition.

Aged↗

[Case report on therapy with granulocyte stimulating factor in diabetic foot].

Several pathogenetic factors such as peripheral neuropathy, vasculopathy and infection are responsible for the development of diabetic foot ulcerations. An important factor contributing to the high infection risk in diabetic patients is a defect in neutrophil granulocytes. Deficiencies in neutrophil chemotaxis, phagocytosis and respiratory burst activity with the decrease of the super- and peroxids are known to be associated with diabetes. Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophils from the bone marrow and improves neutrophil function. A 78-year old patient with non-insulin-dependent diabetes presented with ulcerations of both big toes and a malum perforans on the right sole. He also had generalized arteriosclerosis as well as a polyneuropathy with a dry foot and typical foot deformation as well as decreased in sensitivity. Intensive local care for 35 days led to no improvement of the ulcerations. Then G-CSF (Neupogen) was administered in a total dose of 165 million IU over 11 days; the daily dose varied between 15-30 million IU depending on the absolute leucocyte count. In addition 500 mg of oral ciprofloxacin (Ciproxin) was given b.i.d. This treatment led to a significant improvement of the lesions. Within 11 days cost analysis suggests G-CSF may be a cost-effective addition to antimicrobial therapy in diabetic foot infection.

Aged↗

[Drug reaction to terbinafine simulating an acute generalized exanthematous pustulosis].

Oral terbinafine (Lamisil) is a widely used and effective therapy of dermatophyte infections. A 20-year-old patient was treated with oral terbinafine for an inguinal-scrotal fungal infection and developed an acute generalized exanthematic pustulosis (AGEP) and fever. Histological examination of skin biopsy revealed subcorneal and spongiform pustules. The diagnosis of an AGEP induced by terbinafine was established based on the history, clinical manifestations, and laboratory findings. Clinical features, differential diagnosis, causative drugs, and the therapy of AGEP are discussed and the literature on cases of terbinafine-induced AGEP is reviewed.

Adult↗

[Granulomatous slack skin: partial remission following intralesional administration of interferon-alpha and PUVA].

Granulomatous slack skin (GSS) is a rare cutaneous T-cell lymphoma which typically runs a protracted and indolent course. On histopathological assessment lymphoid infiltrates with multinucleated giant cells in the dermis and subcutis with elastophagocytosis can be observed. Skin lesions are characterized by pendulous folds. We report on the successful response of the lesions to intralesional interferon alpha combined with PUVA.

Adult↗

Human leukocyte antigen G up-regulation in lung cancer associates with high-grade histology, human leukocyte antigen class I loss and interleukin-10 production.

Immune evasion in lung cancer results from both structural and functional alterations of human leukocyte antigen (HLA) class I molecules and the local release of immunosuppressive cytokines. Recent data suggest that HLA-G, a nonclassical class Ib molecule, is involved in immune evasion by tumor cells. We sought to determine whether HLA-G could contribute to immunescape in lung cancer. All of 19 tumor specimens examined demonstrated detectable membrane-bound (HLA-G1), as well as soluble (HLA-G5) isoform transcription. Nine of 34 (26%) tumors were positive by immunohistochemistry using monoclonal antibody (mAb) 4H84, recognizing all denatured HLA-G isoforms, of which six were positive using mAb 16G1, recognizing soluble HLA-G. HLA-G immunoreactivity correlated with high-grade histology, with HLA-G being preferentially expressed on large-cell carcinomas. In these patients, loss of classical HLA class I molecules was observed to associate with HLA-G protein up-regulation. Moreover, we found interleukin-10 expressed in 15 of 34 (44%) tumors, and in most of the HLA-G-positive cases (7 of 9), suggesting up-modulation of HLA-G by interleukin-10. It is conceivable that HLA-G expression in lung cancer might be one of the ways how the tumor down-regulates host immune response, in addition to interleukin-10 production and HLA class I loss.

Aged↗

Differential expression of cytotoxic molecules and killer cell inhibitory receptors in CD8+ and CD56+ cutaneous lymphomas.

Cutaneous lymphomas of the cytotoxic phenotype, including CD8+ and CD56+ lymphomas, have only recently been recognized. To characterize the phenotypic profile of these lymphomas, we investigated the expression of both cytotoxic molecules and killer cell inhibitory receptors by immunohistochemistry techniques. Frozen sections from four CD8+ and from three CD56+ cutaneous lymphomas were stained for the cytotoxicity markers including T-cell restricted intracellular antigen-1, perforin, granzyme B, and for expression of the inhibitory receptors including p58.1, p58.2, p70, p140, CD94, NKG2, and leukocyte immunoglobulin-like receptor (LIR-1). Apart from LIR-1, the CD8+ lymphomas in our series express p70 and p140 from the inhibitory receptors and only one or two of the cytotoxic proteins. The CD56+ lymphomas, on the other hand, express only LIR-1 of the set of inhibitory receptors and the whole panel of cytotoxic antigens. Various subtypes of cytotoxic cutaneous lymphomas (CD8+ and CD56+) differ in regard to their phenotypic and functional profile, which may explain differences in their biological behavior.

Adult↗

Tumor-infiltrating T cells in primary cutaneous B-cell lympho-proliferative disorders.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are considered to play an important role in the antitumoral immune response. The presence and percentage of CD8-positive tumor-infiltrating T cells have been shown to correlate with differentiation and prognosis in various neoplasms. The aim of this study was to determine the number of CD8-positive T cells in various primary cutaneous B-cell lymphoproliferative disorders and to evaluate its correlation with the histological type of tumor. METHODS: Fifty-three lesions were examined by immunohistochemistry with antibodies targeting CD3, CD4, CD8 and TIA-1. Thirty-two lesions had been diagnosed as primary cutaneous B-cell lymphomas (CBCL) and 21 as B-cell pseudolymphomas (B-PSL). CBCLs included 15 follicular lymphomas (FL), 6 marginal zone lymphomas (MZL), and 11 diffuse large B-cell lymphomas (LCL). The number of CD8-positive cytotoxic T cells was determined by computer-assisted morphometrical microscopy. RESULTS: No significant difference could be detected in the density of CD8-positive T cells in B-PSL (101/105 microm(2)), FL (110/105 microm(2)), and MZL (122/105 microm(2)). In contrast, the number of CD8-positive cells (55/105 microm(2)) in LCL was significantly lower (p<0.01) compared to B-PSL, FL and MZL. CONCLUSIONS: In summary the number of CD8-positive T cells in B-cell lymphoproliferative disorders differs in regard to tumor type and differentiation with lowest numbers in diffuse large B-cell lymphomas. However, due to an overlap of the number of TILs, this parameter cannot be employed as a diagnostic parameter for individual cases.

CD3 Complex↗