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)

Environmental signals from the extracellular matrix (ECM) are transmitted by cell surface receptors that connect to the actin cytoskeleton and to multiple intracellular signaling pathways. To dissect how the ECM regulates cell functions, we are using a three-dimensional (3D) fibrin-fibronectin matrix, resembling the wound provisional matrix. Fibroblasts adhere to fibronectin in this matrix via concomitant engagement of alpha 5 beta 1 integrin receptors and syndecan-4, a transmembrane proteoglycan. An adhesive phenotype is developed with actin stress fibers and activation of focal adhesion kinase (FAK) and Rho GTPase. Lack of syndecan-4 engagement, as occurs in the presence of the ECM protein tenascin-C, promotes a motile phenotype; FAK and Rho signaling are downregulated and filopodia are extended. Fibronectin matrices have distinct effects on two other receptors: alpha 4 beta 1 and beta v beta 3 integrins. Although alpha 4 beta 1 does not naturally support strong cell interactions with a fibrin-fibronectin matrix, binding is dramatically enhanced by proteolytic cleavage of fibronectin. Conversely, activity of alpha v beta 3 is stimulated by multimeric fibronectin fibrils showing that the organization of fibronectin differentially affects integrin functions. Thus, deposition of additional ECM components, expression of co-receptors for ECM, cleavage of adhesive proteins, and the architecture of the ECM microenvironment are different mechanisms for modulating cell responses to fibronectin matrix.
J Investig Dermatol Symp Proc 2006 Sep
PMID:Modulation of cell-fibronectin matrix interactions during tissue repair. 1706 13

It has long been known that the active metabolite of vitamin D, 1,25 dihydroxyvitamin D(3), stimulates differentiation and inhibits proliferation in epidermal keratinocytes through interaction with the vitamin D receptor (VDR). VDR functions through the coordinate binding of vitamin D response elements in the DNA and specific coactivator proteins which help to initiate transcription. It was recently observed that VDR binds to two major coactivator complexes, DRIP (VDR-interacting protein) and SRC (steroid receptor coactivator), during keratinocyte differentiation. To determine the role of VDR and its coactivators in mediating keratinocyte differentiation, we developed an adenoviral system to knock down, or in the case of VDR, overexpress these genes. In order to study all stages of keratinocyte development, we employed an advanced differentiated normal human keratinocyte culture system that produces a multilayer phenotype similar to that of normal skin. These studies have shown that VDR, DRIP, and SRC are all required for promotion of both early and late keratinocyte differentiation. Additionally, each individual differentiation marker that was assayed has a different specificity for the coactivators that regulate its expression.
J Invest Dermatol 2007 Apr
PMID:Regulation of human epidermal keratinocyte differentiation by the vitamin D receptor and its coactivators DRIP205, SRC2, and SRC3. 1736 57

Recently, a number of medications approved for nondermatologic use have proved useful against dermatologic diseases. This article reviews the dermatologic uses and effects of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops. Deferasirox--an oral iron chelator--could be an effective treatment against porphyria cutanea tarda, hemochromatosis, and pathogens such as mucor that thrive in iron rich environments. Bortezomib, a proteasome inhibitor and multiple myeloma treatment, may be effective against nodular amyloid and has been effectively used against squamous cell carcinoma; although trials demonstrate it is ineffective against metastatic melanoma. Bortezomib has many cutaneous side effects including erythematous plaques or nodules, a generalized morbilliform erythema with ulcerations and fever, purpuric eruptions, leukocytoclastic vasculitis, Sweet's syndrome, and folliculitis. Dasatinib is a multi-targeted tyrosine kinase inhibitor active in vitro against most cell lines containing BCR-ABL mutations that confer resistance to imatinib. Dasatinib is likely to be effective against dermatofibroma sarcoma protuberans and cutaneous acute lymphoblastic leukemia, and has caused panniculitis. Cyclosporine 0.05% ocular emulsion (eye drops) are approved to treat dry eyes including dry eyes caused by collagen vascular disease. Cyclosporine eye drops might also have utility in treating eye pathology of ocular rosacea, atopic keratoconjunctivitis, graft versus host disease, herpes keratitis, chronic sarcoidosis of the conjunctiva, conjunctival manifestations of actinic prurigo, keratitis of keratitis-ichthyosis deafness (KID) syndrome, and lichen planus-related kerato-conjunctivitis. This article speculates that cyclosporine eye drops would also be useful for any disease causing ectropion or eclabion of the eye as well as toxic epidermal necrolysis-related eye pathology (in particular corneal scarring).
J Drugs Dermatol 2007 Mar
PMID:A review of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops: possible uses and known side effects in cutaneous medicine. 1737 1

2013 patients with various sexually transmitted diseases were screened for HIV antibodies in voluntary counseling and testing centre (VCTC) attached to Microbiology Lab of Govt. Medical College, Amritsar from Jan. 1998 to Dec. 2001. Sixty-one (3.03%) were found to be positive for HIV. 44 were males and 17 were females. There was a constant rise in the percentage positivity in females from 14.3% in 1998 to 38.09% in 2002. There was also rise in the prevalence of HIV among the STD attenders (1.65% in 1998 to 5.13% in 2001).
Indian J Dermatol Venereol Leprol
PMID:HIV seropositivity among patients with sexually transmitted diseases. 1764 17

A retrospective descriptive study of 121 HIV patients in the Department was carried out. The male/female ratio was 2.3:1. The maximum number of patients were seen in age group 21-40 (77.68%). Skilled workers constituted the maximum (13.2%). Sexual route was the commonest mode of transmission (78.5%). Cutaneous manifestations were present in 57% of patients, oral condidiasis being the commonest (16.5%). Pulmonary tuberculosis was the commonest systemic manifestation (13.2%). 37 patients (30.57%) had other STD's, syphilis being the commonest (12.39%). 22 patients had AIDS defining conditions.
Indian J Dermatol Venereol Leprol
PMID:Clinico-epidemiological study of HIV patients in Trivandrum. 1764 47

A total of one hundred patients (75 males and 25 females) age ranged from 17-65 years with genital lesions attending the STD clinic of Bowring and LC Hospitals Bangalore constituted the study group. Based on clinical features, the study groups were classified as syphilis (39), chancroid (30), herpes genitalis (13), condylomato lato (9), LGV (7t condylomata acuminata (5), genital scabies (3), granuloma inguinole (2) and genital candidiasis (1). In 68% microbiological findings confirmed the clinical diagnosis. Of the 100 cases 13% and 2% were positive for HIV antibodies and HbsAg respectively.
Indian J Dermatol Venereol Leprol
PMID:Study of genital lesions. 1764 54

A study carried out among the 2230 STD patients during 1996-2000 shows the types, distribution and trends of the various STDs seen in our hospital. STDs contribute 3.30% of the total skin OPD cases. Males dominate with 89.3% of STD cases. Bolanoposthitis (22%) was the commonest STD, followed by gonorrhoea (11.8%) and nongonococcal urethritis (NGU) being 11.2%. Syphilis was seen in 6.2% of the cases. The prevalence of VDRL reactivity and HIV reactivity remains almost the some being 8.49% and 8.21% respectively. There is increased occurrence of various psychosexual disorders among the affected patients.
Indian J Dermatol Venereol Leprol
PMID:STD trends in regional institute of medical sciences, Manipur. 1764 64

A clinical and investigational study of 25 cases of Donovanosis was undertaken. The incidence was found to be 1.53% of all STD cases and 2.9% of GUD. M:F ratio was 2.12:1. Incidence was more in unmarried people. Fleshy exuberant type was seen in 88% of cases. Two patients (8%) had extragenital ulcers. Donovan bodies were found in 88%. Pseudo elephantiasis was seen in 8 patients. Biopsy was done in 8 cases and showed acanthosis, plasma cell infiltration and pseudo epitheliomatous hyperplasia. One patient developed squamous cell carcinoma of vulva.
Indian J Dermatol Venereol Leprol
PMID:A clinical and investigational study of donovanosis. 1764 66

A retrospective data analysis was carried out to find the trends in frequency and distribution of different STDs in North Eastern (NE) India during 1995-1999. The commonest STD was chancroid (25.7%) followed by condylomata acuminata (CA), nongonococcal urethritis (NGU), lymphogranuloma venereum (LGV), syphilis, gonorrhoea (GONO), herpes genitalis (HG), mixed infection (MI) and balanoposthitis (BP). Interestingly no case of donovanosis (Dono) was seen. HIV infection accounted for 9.62% of the total STD patients. A comparison of the present data with that reported a decade back (1986-1990) revealed a sharp decline in the incidence of syphilis, chancroid, GONO, whereas a conspicuous upward trend in CA and NGU. Factors responsible for these variations are analysed briefly.
Indian J Dermatol Venereol Leprol
PMID:Changing trends in sexually transmitted diseases in North Eastern India. 1765 79

A total of 4129 patients attended the STD clinic from 1996 to 1999. Of those 25.75% were STD cases. Male and female cases comprised 86% and 14% respectively. Majority were in the age group between 18 to 38 years. Chancroid was the commonest STD (37.7%). Other STDs in order were syphilis (30.66%), NGU (15.71%), gonorrhoea (7%), venereal wart (3.57%), candidiasis (2.53%), trichomonal vaginitis (1.6%), herpes genitalis (0.65%) and LGV (0.47%). No case of Donovanosis or HIV was detected. 13.7% of STD cases were reactive for VDRL test and 8% of the antenatal attendants were strongly VDRL test reactive. The urethral discharge on gram staining was positive for gonococcus, in 29%. 68% of the clinic attendants were given safer sex education and served condom.
Indian J Dermatol Venereol Leprol
PMID:A study on the present scenario of STD management in an urban clinic in Kolkata. 1765 84


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