Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bowenoid papulosis (BP) is an unusual dermatosis with variable clinical presentation: multiple, generally small, round, papules, isolated or confluent, with smooth or papillomatous surface, sometimes with desquamation. The colour is variable from rose, reddish-purple to brown. These papules are localized mostly on the genital mucosa or perigenital skin of young adults. The aetiopathogenesis of the disorder is not well defined, but it may be linked to human papillomavirus (HPV) infection. We report a case of BP with some particular aspects: (1) misdiagnosis of the disease for 2 years; (2) contemporaneous presence of different types of HPV.
Int J STD AIDS 2000 Dec
PMID:The presence of HPV types 6/11, 16/18, 31/33/51 in Bowenoid papulosis demonstrated by DNA in situ hybridization. 1113 19

Our objective was to evaluate the response to Trimovate cream in patients with Zoon's balanitis. Patients attending the penile dermatosis clinic between October 1996 and October 1999 with the clinical and histological features diagnostic of Zoon's balanitis were included in this study. They were treated with Trimovate cream for a varying length of time according to clinical response, having declined circumcision as first-line treatment. All cases had photographs taken before and after treatment. Ten cases of histologically-confirmed Zoon's balanitis were treated. Clinical resolution was observed in all cases, all of whom remain on long-term follow-up. In conclusion, topical Trimovate cream is an effective treatment for Zoon's balanitis.
Int J STD AIDS 2001 Feb
PMID:Plasma cell balanitis of Zoon: response to Trimovate cream. 1123 7

Keratolytic winter erythema is an autosomal dominant skin disorder characterised by erythema, hyperkeratosis, and peeling of the skin of the palms and soles, especially during winter. The keratolytic winter erythema locus has been mapped to human chromosome 8p22-p23. This chromosomal region has also been associated with frequent loss of heterozygosity in different types of cancer. To identify positional candidate genes for keratolytic winter erythema, a BAC contig located between the markers at D8S550 and D8S1695 was constructed and sequenced. It could be extended to D8S1759 by a partially sequenced BAC clone identified by database searches. In the 634 404 bp contig 13 new polymorphic microsatellite loci and 46 single nucleotide and insertion/deletion polymorphisms were identified. Twelve transcripts were identified between D8S550 and D8S1759 by exon trapping, cDNA selection, and sequence analyses. They were localised on the genomic sequence, their exon/intron structure was determined, and their expression analysed by RT-PCR. Only one of the transcripts corresponds to a known gene, encoding B-lymphocyte specific tyrosine kinase, BLK. A putative novel myotubularin-related protein gene (MTMR8), a potential human homologue of the mouse acyl-malonyl condensing enzyme gene (Amac1), and two transcripts showing similarities to the mouse L-threonine 3-dehydrogenase gene and the human SEC oncogene, respectively, were identified. The remaining seven transcripts did not show similarities to known genes. There were no potentially pathogenic mutations identified in any of these transcripts in keratolytic winter erythema patients.
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PMID:Physical and transcriptional map of the critical region for keratolytic winter erythema (KWE) on chromosome 8p22-p23 between D8S550 and D8S1759. 1189 52

Abnormal proliferation of keratinocytes in the skin appears crucial to the pathogenesis of psoriasis, but the underlying mechanisms remain unknown. Nitric oxide (NO), released from keratinocytes at high concentrations, is considered a key inhibitor of cellular proliferation and inducer of differentiation in vitro. Although high-output NO synthesis is suggested by the expression of inducible NO synthase (iNOS) mRNA and protein in psoriasis lesions, the pronounced hyperproliferation of psoriatic keratinocytes may indicate that iNOS activity is too low to effectively deliver anti-proliferative NO concentrations. Here we show that arginase 1 (ARG1), which substantially participates in the regulation of iNOS activity by competing for the common substrate L-arginine, is highly overexpressed in the hyperproliferative psoriatic epidermis and is co-expressed with iNOS. Expression of L-arginine transporter molecules is found to be normal. Treatment of primary cultured keratinocytes with Th1-cytokines, as present in a psoriatic environment, leads to de novo expression of iNOS but concomitantly a significant down-regulation of ARG1. Persistent ARG1 overexpression in psoriasis lesions, therefore, may represent a disease-associated deviation from normal expression patterns. Furthermore, the culturing of activated keratinocytes in the presence of an ARG inhibitor results in a twofold increase in nitrite accumulation providing evidence for an L-arginine substrate competition in human keratinocytes. High-output NO synthesis is indeed associated with a significant decrease in cellular proliferation as shown by down-regulation of Ki67 expression in cultured keratinocytes but also in short-term organ cultures of normal human skin. In summary, our data demonstrate for the first time a link between a human inflammatory skin disease, limited iNOS activity, and ARG1 overexpression. This link may have substantial implications for the pathophysiology of psoriasis and the development of new treatment strategies.
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PMID:Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation. 1463 38

Tight-skin (Tsk/+) mice develop a disease similar to human scleroderma, characterized by the spontaneous appearance of cutaneous hyperplasia, anti-nuclear antibodies, and emphysema. T helper (Th) 2 cells secreting interleukin (IL)-4 are known to play a critical role in the etiopathogenesis of this disease. Th2-mediated responses can be blocked by treatment with synthetic oligodeoxynucleotides (ODN) containing immunomodulatory CpG motifs. Thus, we examined whether CpG ODN might be of therapeutic benefit in Tsk/+ mice. Administering CpG ODN to Tsk/+ mice every 3 wk starting at 1 wk of age abrogated skin fibrosis. This reduction in skin thickness persisted even after the cessation of therapy, and was accompanied by increased serum levels of IL-12 and an increased ratio of T cells available to secrete interferon-gamma rather than IL-4. CpG ODN therapy also reduced autoantibody production, but did not inhibit the incidence of lung emphysema. Delaying the initiation of CpG ODN treatment until 6 wk of age failed to prevent skin disease. These results indicate that by preferentially promoting the development of a Th1-biased immune milieu in young Tsk/+ mice, CpG ODN can ameliorate Th2-driven scleroderma-like syndrome.
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PMID:CpG oligodeoxynucleotides prevent the development of scleroderma-like syndrome in tight-skin mice by stimulating a Th1 immune response. 1595 88

Psoriasis vulgaris is an autoimmune dermatosis characterized by type 1 T cell infiltration. Prolactin may be involved in the pathogenesis of psoriasis. CXC ligand 9 (CXCL9), CXCL10, and CXCL11 recruit type 1 T cells, and their production by keratinocytes is enhanced in psoriatic lesions. CXCL9, CXCL10, and CXCL11 production by keratinocytes depends on nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription (STAT)1 and that of CXCL11 depends on interferon (IFN)-regulatory factor (IRF)-1. We examined in vitro effects of prolactin on CXCL9, CXCL10, and CXCL11 production in human keratinocytes. Although prolactin alone was ineffective, it enhanced IFN-gamma-induced secretion and mRNA expression of CXCL9, CXCL10, and CXCL11 in parallel to the activation of STAT1, NF-kappaB, and IRF-1. Inhibitors of Janus kinase (JAK), p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities. Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK. Prolactin modestly or IFN-gamma greatly induced tyrosine phosphorylation of STAT1, and both were suppressed by JAK inhibitor. Prolactin modestly or IFN-gamma greatly induced serine phosphorylation of STAT1, which was suppressed by MEK or p38 MAPK inhibitor, respectively. Prolactin induced phosphorylation of inhibitory kappaBalpha and NF-kappaB p65, which was suppressed by MEK inhibitor. These results suggest that prolactin may enhance IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production in keratinocytes via activation of STAT1, NF-kappaB, and IRF-1 through JAK2 and MEK/ERK pathways. Prolactin may promote type 1 T cell infiltration into psoriatic lesions via these chemokines.
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PMID:Prolactin enhances interferon-gamma-induced production of CXC ligand 9 (CXCL9), CXCL10, and CXCL11 in human keratinocytes. 1725 1

A 24-year-old woman presented with genital warts which did not respond to treatment. Biopsy confirmed changes in keeping with a diagnosis of Darier's disease. The patient, however, had no other manifestations of Darier's disease, i.e. family history of skin disease, nail changes or other skin site involvement. We propose that this patient has a form of Darier's disease called genital papular acantholytic dyskeratosis.
Int J STD AIDS 2007 Dec
PMID:Papular acantholytic dyskeratosis presenting as genital warts. 1807 25

Our hospital (Shanghai Skin Diseases & STD Hospital) started to study 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in 1996. So far, we have treated 76 cases of skin cancer and pre-cancer using topical ALA-PDT. They included squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), mammary and extramammary Paget disease, actinic keratosis (AK) and erythroplasia of Queyrat. In this overview article, we would like to present several representative cases and discuss our experience.
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PMID:Treatment of skin cancer and pre-cancer using topical ALA-PDT--a single hospital experience. 1935 43

JAK3, a member of the Janus kinase family, is predominantly expressed in hemopoietic cells and binds specifically to the common gamma chain of a subfamily of cytokine receptors that includes IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Previous studies suggest that this tyrosine kinase plays key roles in mediating T cell functions, and inhibition of JAK3 has been shown to prevent graft rejection and decrease the severity of arthritis in rodent models. However, the functions of JAK3 in the development of skin immune responses and diseases such as psoriasis have not been determined. CD18 mutant PL/J mice develop spontaneous T cell-dependent psoriasiform skin disease with several similarities to human psoriasis. In this study, we treated mice with established skin disease with R348, a small molecule inhibitor of JAK3, and observed a marked attenuation of skin lesions following 6 wk of treatment. Histological analyses revealed major reductions of both epidermal and dermal lesion severity scores in R348-treated CD18-deficient PL/J mice compared with vehicle controls, which was associated with decreased CD4(+) T cell infiltration. In addition, systemic levels of IL-17, IL-22, IL-23, and TNF-alpha were significantly lower in mice receiving the compound, and T cells isolated from R348-treated mice also showed reduced phosphorylation of Stat5 after stimulation with IL-2. These findings suggest that small-molecule inhibitors of JAK3 may be useful in the treatment of inflammatory skin diseases such as psoriasis and strongly implicate JAK signaling events as important in the pathogenesis of this disease.
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PMID:JAK3 inhibition significantly attenuates psoriasiform skin inflammation in CD18 mutant PL/J mice. 1959 99

When no demonstrable cause is uncovered after excluding inflammatory dermatosis, infectious disease or a manifestation of anorectal disease, anogenital pruritus is often described as 'idiopathic'. Lumbosacral radiculopathy was described by Cohen et al. as one of the possible causes of 'idiopathic' anogenital pruritus. We report a case of a patient with chronic pruritus of the right scrotum that was relieved immediately post-ipsilateral inguinal hernia repair. This is, to the best of our knowledge, the first case of neuropathic scrotal pruritus secondary to direct nerve compression by an inguinal hernia. We propose that a proper examination for the presence of inguinal hernia be performed in the work-up for scrotal pruritus.
Int J STD AIDS 2010 Sep
PMID:A cured patient who came back for consultation: neuropathic scrotal pruritus relieved after ipsilateral inguinal hernia repair. 2109 42


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