Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of the 1418 patients with STDs, who attended the STD clinic between January 1996 to December 2000, 50 (3.4%) were children below 14 years of age. Boys (29) were more than girls (21). Syphilis was the most common STD found in these children (46.8%), followed by vulvo-vaginal candidiasis (19.2%), condylomata acuminata (10.6%), gonorrhoea (8.5%), herpes progenitalis (6.4%), chancroid (4.3%), perianal candidosis and perianal molluscum contagiosum (2.1 % each). Three children had more than one STD. A history of sexual abuse could be elicited in 30 children (60%), none of the children were positive of HIV. All children with symptoms pertaining to their genitourinary system should be evaluated thoroughtly for sexual abuse.
Indian J Dermatol Venereol Leprol
PMID:Pattern of childhood STDs in a major hospital of East Delhi. 1765 39

A study was undertaken from June 1999 to June 2000 with 4650 subjects, 2177 males and 2473 females, attending the STD clinic at Medical College, Calcutta. Study revealed 1.6% seropositivity. Highest prevalence of HIV seropositivity 5.2% was noted among young males upto 30 years of age. In females highest prevalence of HIV seropositivity was found among the age group of 31-40 years.
Indian J Dermatol Venereol Leprol
PMID:Sero-prevalence of HIV infections among STD clinic attenders at Medical College, Calcutta. 1765 64

Total 457 patients attending different STD clinics of Calcutta were studied for serological tests for STD. TPHA positivity was maximum (18.60%), followed by chlamydia infection (15.97%), VDRL reactivity (8.98%), HIV infection (6.35%), and HBs Ag (3.72%). Total 37.20% samples were positive for one or more infection. Out of these, one, two, three and four tests positivity was seen in 65.29%, 25.88%, 8.24% and 0.59% respectively. The age group which had maximum infection (20.13%) was 15-30 years.
Indian J Dermatol Venereol Leprol
PMID:Serological study for sexually transmitted diseases in patients attending STD clinics in Calcutta. 1765 67

The human antimicrobial peptide LL-37 plays an important role in host defense against infection. In addition to its antimicrobial action, other activities have been described in eukaryotic cells that may contribute to the healing response. In this study, we demonstrated that in vitro human cathelicidin activates migration of the human keratinocyte cell line HaCaT, involving phenotypic changes related to actin dynamics and associated to augmented tyrosine phosphorylation of proteins involved in focal adhesion complexes, such as focal adhesion kinase and paxillin. Other events involved in the LL-37 response were the induction of the Snail and Slug transcription factors, activation of matrix metalloproteinases and activation of the mitogen-activated protein kinase , and phosphoinositide 3-kinase/Akt signaling pathways. These signaling events could be mediated not only through the transactivation of EGFR but also through the induction of G-protein-coupled receptor FPRL-1 expression in these cells. Finally, by in vivo adenoviral transfer of the antimicrobial peptide to excisional wounds in ob/ob mice, we demonstrated that LL-37 significantly improved re-epithelialization and granulation tissue formation. The protective and regenerative activities of LL-37 support its therapeutic potential to promote wound healing.
J Invest Dermatol 2008 Jan
PMID:In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. 1807 31

The Shb adapter protein is an Src homology 2-domain containing signaling intermediate operating downstream of several tyrosine kinase receptors, including vascular endothelial growth factor receptor-2. Shb is multifunctional and apoptosis is one response that Shb regulates. Inhibition of angiogenesis can be used in cancer therapy, and one way to achieve this is by inducing endothelial cell apoptosis. The angiosarcoma cell line SVR is of endothelial origin and can be used as a tool for studying in vivo inhibition of angiogenesis, and we thus employed an Shb-knockdown strategy using an inducible lentiviral system to reduce Shb levels in SVR cells and to study their responses. Shb knockdown increases the susceptibility of SVR cells to the apoptotic agents, cisplatin and staurosporine. Simultaneously, Shb knockdown causes reduced focal adhesion kinase (FAK) activation, monitored as phosphorylation of the regulatory residues tyrosines 576/577. No detectable effects on Akt or extracellular signal-regulated kinase activity were noted. The altered FAK activity coincided with an elongated cell phenotype that was particularly noticeable in the presence of staurosporine. In order to relate the effects of Shb knockdown to in vivo tumorigenicity, cells were exposed to the angiogenesis inhibitor honokiol, and again the cells with reduced Shb content exhibited increased apoptosis. Tumor growth in vivo was strongly reduced in the Shb-knockdown cells upon honokiol treatment. It is concluded that Shb regulates apoptosis and cell shape in tumor endothelial cells via FAK, and that Shb is a potential target for inhibition of angiogenesis.
J Invest Dermatol 2008 Mar
PMID:Shb gene knockdown increases the susceptibility of SVR endothelial tumor cells to apoptotic stimuli in vitro and in vivo. 1791 55

The arrival of targeted therapeutics into the oncology clinic, while enthusiastically anticipated, introduced the oncologist to dermatologic events that can pose challenging management issues. The dermatologic effects of these targeted agents appear to be more frequent than those with cytotoxic therapy and are not uniform; that is, different agents have distinct dermatologic toxicities. Interestingly, dermatologic toxicity may correlate with antitumor activity with some of these targeted agents. The correlation of rash with response and survival in particular mandates the development of effective and appropriate management strategies. The nature and challenges of the dermatologic events observed to date with epidermal growth factor receptor inhibitors, multikinase inhibitors, proteosome inhibitors, BCR-ABL tyrosine kinase inhibitors, and immunomodulatory drugs will be addressed in this review.
Dermatol Clin 2008 Jan
PMID:Cutaneous reactions related to systemic immunomodulators and targeted therapeutics. 1802 75

An 8-year-old boy presented with eczematous skin lesions, recurrent otitis media and unexplained pyrexias. X-linked agammaglobulinaemia was diagnosed and treatment commenced with intravenous immunoglobulin replacement therapy. X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency syndrome associated with a deficiency of B lymphocytes, caused by a defect in the expression of Bruton's tyrosine kinase. It affects only boys and usually presents before the age of 2 years with recurrent bacterial sinopulmonary infections. IgG levels are usually <2 g/L (normal range 5.4-16.1) and IgM and IgA are usually undetectable. The commonest cutaneous features of XLA are pyogenic skin infections; however, eczema can occur with increased frequency. We report a child who presented with multiple discrete eczematous lesions who subsequently developed eczematous exacerbations several days after administration of intravenous immunoglobulin (IVIg) replacement therapy.
Clin Exp Dermatol 2008 Mar
PMID:Eczema and X-linked agammaglobulinaemia. 1807 88

Keloids are benign skin tumors characterized by collagen accumulation and hyperproliferation of fibroblasts. To find an effective therapy for keloids, we explored the pharmacological potential of (-)-epigallocatechin-3-gallate (EGCG), a widely investigated tumor-preventive agent. When applied to normal and keloid fibroblasts (KFs) in vitro, proliferation and migration of KFs were more strongly suppressed by EGCG than normal fibroblast proliferation and migration (IC(50): 54.4 microM (keloid fibroblast (KF)) versus 63.0 microM (NF)). The level of Smad2/3, signal transducer and activator of transcription-3 (STAT3), and p38 phosphorylation is more enhanced in KFs, and EGCG inhibited phosphorylation of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated protein kinase 1/2 (ERK1/2), and STAT3 (Tyr705 and Ser727). To evaluate the contribution of these pathways to keloid pathology, we treated KFs with specific inhibitors for PI3K, ERK1/2, or STAT3. Although a PI3K inhibitor significantly suppressed proliferation, PI3K and MEK/ERK inhibitors had a minor effect on migration and collagen production. However, a JAK2/STAT3 inhibitor and a STAT3 siRNA strongly suppressed proliferation, migration, and collagen production by KFs. We also found that treatment with EGCG suppressed growth and collagen production in the in vivo keloid model. This study demonstrates that EGCG suppresses the pathological characteristics of keloids through inhibition of the STAT3-signaling pathway. We propose that EGCG has potential in the treatment and prevention of keloids.
J Invest Dermatol 2008 Oct
PMID:Green tea polyphenol epigallocatechin-3-gallate suppresses collagen production and proliferation in keloid fibroblasts via inhibition of the STAT3-signaling pathway. 1846 84

Donovanosis is a slowly progressive, granulomatous ulcerative disease , caused by Klebsiella (Calymmatobacterium) granulomatis. The disease is known to persist for years together, leading to complications. A male patient aged 30 years with underlying HIV-2 infection presented to the department of STD with painful ulceration over the genital region of 5 months duration, with absence of penis. Tissue smear from the ulcer and histopathological examination revealed large histiocytes with intracellular Donovan bodies (Pund cell). A final diagnosis of donovanosis with auto-amputation of penis with HIV-2 infection was made. The old conventional medicines, viz. streptomycin, doxycycline and amoxycillin, were effective. Though HIV-2 infections are milder than HIV-1 infections in all aspects, donovanosis in this HIV-2 infected case presented with complications. However, since the CD4 count was 748 cells/cmm, the severity is attributed to the long standing nature and negligence by the patient, and not to possible immunodeficiency.
Indian J Dermatol Venereol Leprol
PMID:Donovanosis with auto-amputation of penis in a HIV-2 infected person. 1905 12

The vitamin D receptor (VDR) is a nuclear hormone receptor that controls transcription of target genes. It exerts its biological effects through transcriptional coactivators. Previously, we identified two distinct classes of VDR coactivators, VDR-interacting protein (DRIP) and steroid receptor coactivator (SRC) at different stages of keratinocyte differentiation. Here, we determined the functions of VDR and coactivators in lipid production and permeability barrier formation. Silencing of either VDR, SRC2, or SRC3 resulted in decreases in specific glucosylceramide (GlcCer) species but not other lipids such as cholesterol and free fatty acids. Their silencing also caused decreased transcription of fatty acid elongase and ceramide glucosyltransferase, which are critical for the synthesis of epidermis-unique GlcCer species, and defects in lamellar body formation associated with decreased expression of the lipid transporter ATP-binding cassette transporter protein 12. VDR null mice exhibit abnormal barrier function with altered lipid composition in vivo. These results demonstrate that VDR and coactivators SRC2 and SRC3, which are also involved in other nuclear receptors as well, are critical for epidermis-specific sphingolipid production and barrier formation. In contrast, DRIP silencing had no apparent effect on these processes indicating that the two classes of coactivators are differentially utilized.
J Invest Dermatol 2009 Jun
PMID:Vitamin D receptor and coactivators SRC2 and 3 regulate epidermis-specific sphingolipid production and permeability barrier formation. 1905 61


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