The Kummer tensor density in electrodynamics and in gravity

Guided by results in the premetric electrodynamics of local and linear media, we introduce on 4-dimensional spacetime the new abstract notion of a Kummer tensor density of rank four, ${\cal K}^{ijkl}$. This tensor density is, by definition, a cubic algebraic functional of a tensor density of rank four ${\cal T}^{ijkl}$, which is antisymmetric in its first two and its last two indices: ${\cal T}^{ijkl} = - {\cal T}^{jikl} = - {\cal T}^{ijlk}$. Thus, ${\cal K}\sim {\cal T}^3$, see Eq.(46). (i) If $\cal T$ is identified with the electromagnetic response tensor of local and linear media, the Kummer tensor density encompasses the generalized {\it Fresnel wave surfaces} for propagating light. In the reversible case, the wave surfaces turn out to be {\it Kummer surfaces} as defined in algebraic geometry (Bateman 1910). (ii) If $\cal T$ is identified with the {\it curvature} tensor $R^{ijkl}$ of a Riemann-Cartan spacetime, then ${\cal K}\sim R^3$ and, in the special case of general relativity, ${\cal K}$ reduces to the Kummer tensor of Zund (1969). This $\cal K$ is related to the {\it principal null directions} of the curvature. We discuss the properties of the general Kummer tensor density. In particular, we decompose $\cal K$ irreducibly under the 4-dimensional linear group $GL(4,R)$ and, subsequently, under the Lorentz group $SO(1,3)$.Comment: 54 pages, 6 figures, written in LaTex; improved version in accordance with the referee repor

In situ analysis of transforming growth factor-βs (TGF-β1, TGF-β2, TGF-β3and TGF-3 type II receptor expression in malignant melanoma

We have analysed, by in situ hybridization, mRNA expression of TGF-β1, TGF-β2, TGF-β3, and of TGF-β type II receptor in benign melanocytic naevi, primary melanomas, and in skin metastases of malignant melanomas. Our results show that melanoma progression correlates with overexpression of TGF-β. All skin metastases and most primary melanomas invasive to Clark's level IV-V revealed specific TGF-β2 mRNA and protein expression. However, expression of this cytokine was not observed in benign melanocytic lesions and was detected only in one of five early primary melanomas investigated. Some primary melanomas and skin metastases also revealed specific TGF-β1 mRNA signals although expression of this isoform was not found in benign naevi. TGF-β3 expression, which was only barely detectable in benign melanocytic lesions, was enhanced in some skin metastases. Interestingly, the epidermis overlaying melanomas revealed lower levels of TGF-β3 mRNA expression than epidermis of healthy skin or epidermis adjacent to benign naevi, thereby suggesting that paracrine mechanisms between tumour cells and keratinocytes may influence melanoma development. In primary melanomas TGF-β type II receptor mRNA signals were much more heterogeneously distributed when compared to benign melanocytic naevi, suggesting variable degrees of TGF-β resistance among melanoma cells within individual lesions. However, melanoma progression appeared not to be correlated with a complete loss of TGF-β type II receptor gene expression, since all skin metastases revealed clearly detectable although heterogeneous levels of TGF-β type II receptor mRNA expressio

Identification of human papillomavirus DNA in cutaneous lesions of Cowden syndrome

Background: Cowden syndrome (CS) or multiple hamartoma syndrome is a cancer-associated genodermatosis inherited in an autosomal dominant pattern. One of the diagnostic criteria is facial papules which are felt to be trichilemmomas, benign hair follicle tumors, which some consider to be induced by human papillomavirus (HPV). Objective: To search for HPV in skin tumors, especially trichilemmomas, from patients with CS. Methods: Skin lesions from patients with CS were classified histologically. Each tumor was then analyzed for HPV DNA by polymerase chain reaction with different primer sets; positive amplicons were typed by direct sequencing. Results: Twenty-nine biopsies from 7 patients with CS were investigated. Only 2 of 29 tumors clinically suspected of being trichilemmomas were confirmed histologically. In addition, 3 sclerotic fibromas, also typical of CS, were found, as well as 1 sebaceous hyperplasia. The other 23 lesions showed histological features of HPV-induced tumors in various stages of development. HPV DNA was found in 19 of 29 cutaneous lesions. Tumors without any histological signs of HPV induction were negative for HPV DNA. Two tumors which were histologically classified as common warts contained HPV types 27 and 28. All the 17 other HPV types belong to the group of epidermodysplasia-verruciformis-associated types. Conclusions: The majority of cutaneous lesions in CS contain HPV DNA. They may have a variety of histological patterns. Trichilemmomas are not clinically distinctive and can be difficult to identify in CS patients. Copyright (C) 2003 S. Karger AG, Basel

Giant ectopic liver, hepatocellular carcinoma and pachydermia-a rare genetic syndrome?

Ectopic liver is a very uncommon developmental anomaly that predisposes to the development of hepatocellular carcinoma. We describe the second documented case of a hepatocellular carcinoma developing in the primary liver of a patient with a rare and uncharacterized genetic symptom complex. Also present was the largest ectopic liver ever reported, measuring 12 cm in diameter which contained a solitary focus of metastatic hepatocellular carcinoma. The primary hepatocellular carcinoma is believed to have arisen in the native liver from a hepatic adenoma that was diagnosed 15 years earlier. The patient's uncharacterised condition featured prominent thick, yellow skin over the dorsum of the fingers, and was associated with follicular hyperkeratosis, abnormal plantar creases, digital clubbing, misshaped ears, a lingua plicata and an angioleiomyolipoma of the right kidney

MicroRNA expression differs in cutaneous squamous cell carcinomas and healthy skin of immunocompetent individuals

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, but the influence of microRNA (miRNA) expression has only been sporadically analysed. We hypothesized that miRNAs are differentially expressed in cSCC and hence influence its development. We therefore isolated total miRNA from well-differentiated cSCCs and from controls without SCC. Expression analyses of 12 miRNAs showed three significantly differentially expressed miRNAs. We identified a significant upregulation of the miR-21 and the miR-31, a proto-oncogene like miR-21. While the upregulated expression of miR-21 has been known for some time, the increased expression of miR-31 was never shown so clearly. Furthermore, we showed the upregulation of miRNA-205, which has never been described before. The miR-205 induces specific keratinocyte migration and could be a characteristic marker for cSCC. It has to be determined in following studies whether these upregulated expressions are specific for cSCC and if so, for which cSCC stages

Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome: study of a series of 91 patients.

BACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients. RESULTS: The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease. CONCLUSIONS: This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients

The phenotypic and genotypic spectra of ichthyosis with confetti plus novel genetic variation in the 3' end of KRT10: from disease to a syndrome

Ichthyosis with confetti (IWC) is a genodermatosis caused by dominant negative mutations in the gene encoding keratin 10 (KRT10). We investigated clinical and genetic details of a substantial number of patients with IWC in order to define major and minor criteria for diagnosis of this rare disorder.; Parallel clinical investigation of 6 patients with IWC revealed a novel spectrum of phenotypes. We found several features that qualify as major criteria for diagnosis, which are clearly and consistently associated with the condition. These included malformation of ears, hypoplasia of mammillae, and dorsal acral hypertrichosis. Genetic analysis of patients revealed several different frameshift mutations in intron 6 or exon 7 of KRT10. Analysis of this locus in 17 unrelated control individuals revealed 2 novel polymorphisms of KRT10.; We present for the first time to our knowledge the spectrum of clinical variability of IWC in 6 patients with confirmed mutations in KRT10. From this, we have extracted major and minor criteria to aid early and correct clinical diagnosis. Ectodermal malformations, present in all patients, suggest a novel classification of IWC as a syndrome. There is remarkable genetic variation at the IWC disease locus within control individuals from the general population

Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations

Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancer, mainly cutaneous squamous cell carcinoma (cSCC). Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC development, contain numerous single-nucleotide polymorphisms (SNPs).; To evaluate the effect of SNPs in both TMC/EVER genes on the different susceptibilities of RTRs to cSCC.; We determined the occurrence of cSCC in 105 RTRs who were transplanted at least 7 years previously and investigated the frequency of 26 SNPs within both TMC/EVER genes in severely affected (n = 16) as well as in nonaffected RTRs (n = 25).; Our data did not indicate a significant association between any SNP genotype and risk of cSCC development in RTRs.; To clarify the correlation between SNPs in both TMC genes and cSCC development in RTRs, integrated investigations of large cohorts including both RTRs and immunocompetent individuals with consideration of cSCC status, SNP genotype and human papillomavirus status might be necessary

Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations

Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancer, mainly cutaneous squamous cell carcinoma (cSCC). Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC development, contain numerous single-nucleotide polymorphisms (SNPs).; To evaluate the effect of SNPs in both TMC/EVER genes on the different susceptibilities of RTRs to cSCC.; We determined the occurrence of cSCC in 105 RTRs who were transplanted at least 7 years previously and investigated the frequency of 26 SNPs within both TMC/EVER genes in severely affected (n = 16) as well as in nonaffected RTRs (n = 25).; Our data did not indicate a significant association between any SNP genotype and risk of cSCC development in RTRs.; To clarify the correlation between SNPs in both TMC genes and cSCC development in RTRs, integrated investigations of large cohorts including both RTRs and immunocompetent individuals with consideration of cSCC status, SNP genotype and human papillomavirus status might be necessary