ABSTRACT: Primary cutaneous desmoplastic melanoma (DM) is a group of rare melanocytic tumors arising on severely sun-damaged skin, histologically characterized by the proliferation of spindled melanocytes in a prominent desmoplastic stroma, with a range of morphological presentations. In this article, we report a unique case of primary cutaneous DM composed of a nodular proliferation of highly pleomorphic spindled and epithelioid cells, pseudoglandular structures, clear cell change, and unusual collagen rosettes. Immunohistochemical analysis showed a strong and diffuse positivity for S-100 protein, SOX-10, nestin, p75 (nerve growth factor receptor), WT1, and p53. Molecular analysis detected a mutation in the NF1 gene [c.4084C > T, p.(Arg1362Ter)], 2 different pathogenic mutations in TP53 [c.742C > T, p.(Arg248Trp), AF:12%, COSM1640831 and c.528C > G, p.(Cys176Trp), AF:12%, COSM11114], and a mutation in GNAS [c.601C > T, p.(Arg201Cys), AF: 9%, COSM123397]. To the best of our knowledge, this is the first case reporting collagen rosettes and pseudoglandular features in primary cutaneous DM.
- MeSH
- chromograniny genetika MeSH
- imunohistochemie MeSH
- kolagen typu IV metabolismus MeSH
- lidé MeSH
- melanom genetika metabolismus patologie MeSH
- mutace MeSH
- nádorový supresorový protein p53 genetika MeSH
- nádory kůže genetika metabolismus patologie MeSH
- neurofibromin 1 genetika MeSH
- proteiny vázající GTP - alfa-podjednotky Gs genetika MeSH
- senioři nad 80 let MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
OBJECTIVE: Corticotropin (ACTH)-independent hypercortisolism due to bilateral adrenocortical hyperplasia (BAH) in infancy is an extremely rare condition that is often caused by McCune Albright syndrome (MAS). MAS is caused by an activating mutation of the GNAS gene which leads to increased cyclic (c) adenosine monophosphate (AMP) signaling. Most forms of BAH are linked to increased cAMP signaling. We report the case of an infant with MAS who had BAH. METHODS: Genomic DNA fragments from blood and adrenal tissue encompassing regions (exons 8 and 9) with the hot spot activating missense GNAS mutations were amplified by classical bidirectional Sanger sequencing. RESULTS: The infant was found to carry the most common GNAS mutation, in exon 8 (c.602G >A, p. R201H), only in her adrenocortical tissue, despite extensive skin and other findings. CONCLUSIONS: We conclude that infants with MAS, despite absence of the GNAS activating mutation in blood, may still have significant clinical findings, including ACTH-independent hypercortisolism. Molecular confirmation of the diagnosis should be sought at the tissue level in these patients.
- MeSH
- fibrózní dysplazie polyostotická genetika MeSH
- kojenec MeSH
- kongenitální adrenální hyperplazie genetika MeSH
- lidé MeSH
- proteiny vázající GTP - alfa-podjednotky Gs genetika MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
Albright hereditary osteodystrophy is a rare syndrome, in which cutaneous and superficial soft tissue lesions traditionally include osteomas and calcifications. We report 4 patients from 2 families affected with Albright hereditary osteodystrophy and demonstrate that the spectrum of these cutaneous and soft tissue lesions is broader than is usually defined in the literature. In addition to osteomas in the dermis and subcutis, including so-called plaque-like osteoma, we identified the following lesions: calcifying aponeurotic fibroma-like lesion, calcinosis circumscripta-like lesion, and unusual nevi with osteoid and/or peculiar intranuclear pseudoinclusions. One osteoma and the calcifying aponeurotic fibroma-like lesion were analyzed by HUMARA and proved to be clonal. In a family, a novel mutation in the GNAS gene was also identified.
- MeSH
- dítě MeSH
- dospělí MeSH
- fibrom diagnóza genetika patologie MeSH
- fibrózní dysplazie polyostotická diagnóza genetika patologie MeSH
- kalcinóza diagnóza genetika patologie MeSH
- lidé MeSH
- mutace genetika MeSH
- nádory kostí diagnóza genetika patologie MeSH
- nádory kůže diagnóza genetika patologie MeSH
- névus diagnóza genetika patologie MeSH
- osteom diagnóza genetika patologie MeSH
- předškolní dítě MeSH
- proteiny vázající GTP - alfa-podjednotky Gs genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Peptides eluted from peripheral blood cells of HLA-B*2705 healthy donor were analyzed by LC MALDI MS/MS and LC ESI FTMS techniques. The sequences of 92 peptide ligands identified from one healthy blood donor by LC MALDI-TOF MS/MS were compared with those previously published from in vitro long-term cell cultures available in SYFPEITHI database and splenocytes. It was found that 18 sequences confirmed within 1ppm mass error by LC ESI FTMS were already described and 3 of them matched with those previously reported from HLA-B*2705 splenocytes. Another 38 sequences validated within the same mass error were not found in SYFPEITHI database and are identified here for the first time. Finally, 36 sequences (5 sequences already published in SYFPEITHI database) were evaluated by LC MALDI-TOF MS/MS but no matches in the list of monoisotopic masses obtained from LC ESI FTMS were found.
- MeSH
- alkoholoxidoreduktasy MeSH
- ankylózující spondylitida genetika metabolismus MeSH
- autoimunita genetika MeSH
- databáze proteinů MeSH
- dospělí MeSH
- endopeptidasy metabolismus MeSH
- financování organizované MeSH
- genetická predispozice k nemoci MeSH
- histony genetika metabolismus MeSH
- HLA-B27 antigen analýza imunologie izolace a purifikace MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- interakční proteinové domény a motivy MeSH
- krevní buňky imunologie metabolismus MeSH
- lidé MeSH
- peptidové mapování MeSH
- peptidy analýza imunologie izolace a purifikace MeSH
- proteiny tepelného šoku HSC70 genetika imunologie krev MeSH
- proteiny vázající GTP - alfa-podjednotky Gs genetika imunologie krev MeSH
- sekvenční seřazení MeSH
- software MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
Muscarinic M(2) receptors preferentially couple with the G(i/o) class of G-proteins to inhibit cAMP synthesis. However, they can also stimulate net synthesis of cAMP and inositol phosphate (IP) accumulation. We investigated in intact Chinese hamster ovary (CHO) cells expressing human M(2) receptors (CHO-M(2) cells) whether direct interaction of M(2) receptors with G(s) and G(q/11) G-proteins is responsible for the latter effects. Suppression of the G(s)alpha subunit using RNA interference abolished stimulation of cAMP synthesis induced by 1 mM carbachol in both control and pertussis toxin-treated CHO-M(2) cells but had no effect on the inhibition of forskolin-stimulated cAMP synthesis. Carbachol stimulated accumulation of IP with an EC(50) of 79 microM. Removal of the G(q),G(11), or both alpha subunits reduced this response by 78, 54, and 92%, respectively, whereas suppression of the G(s)alpha subunit had no effect. Similar results obtained in CHO cells expressing M(1) receptors that preferentially couple with G(s) and G(q/11) G-proteins confirmed the efficiency of siRNA treatments. Stimulation of M(2) receptors in control and pertussis toxin-treated cells by a series of full agonists with respect to inhibition of adenylyl cyclase displayed different efficacies in stimulating IP accumulation. Carbachol, acetylcholine, and oxotremorine-M [N,N,N-trimethyl-4-(2-oxo-1-pyrolidinyl)-2-butyn-1-ammonium] behaved as full agonists, furmethide (N,N,N-trimethyl-2-furanmethammonium) and methylfurmethide [(5-methyl-2-furyl)methyltrimethylammonium] were partial agonists, and oxotremorine (1-[4-(1-pyrrolidinyl)-2-butynyl]-2-pyrrolidinone) had no effect. Our results provide direct evidence of M(2) receptor coupling with the alpha subunits of G(s) and G(q/11) G-proteins and demonstrate induction of multiple receptor conformational states dependent on both the concentration and the nature of the agonist used.
- MeSH
- AMP cyklický biosyntéza MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- financování organizované MeSH
- inositolfosfáty metabolismus MeSH
- křečci praví MeSH
- malá interferující RNA farmakologie MeSH
- proteiny vázající GTP - alfa-podjednotky Gq-G11 fyziologie MeSH
- proteiny vázající GTP - alfa-podjednotky Gs fyziologie MeSH
- receptor muskarinový M2 fyziologie MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- zvířata MeSH
- Klíčová slova
- psychoneuroimunomodulace,
- MeSH
- antidepresiva * farmakologie MeSH
- buněčná imunita účinky léků MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- nádorové buňky kultivované účinky léků MeSH
- neuroimunomodulace * účinky léků MeSH
- NKT buňky účinky léků MeSH
- potkani Wistar MeSH
- proteiny vázající GTP - alfa-podjednotky Gq-G11 analýza MeSH
- proteiny vázající GTP - alfa-podjednotky Gs analýza MeSH
- proteiny vázající GTP - alfa-podjednotky * analýza MeSH
- T-lymfocyty účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Clinical and experimental allergy, ISSN 0954-7894 ; Supplement Vol. 27. 2
56 s. : il. ; 30 cm
