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)

Multiple signal transduction events are triggered in the host cell during invasion by the protozoan parasite Trypanosoma cruzi. Here, we report the regulation of host cell phosphatydilinositol 3-kinase (PI3K) and protein kinase B (PKB/Akt) activities by T. cruzi during parasite-host cell interaction. Treatment of nonphagocytic cells (Vero, L(6)E(9), and NIH 3T3) and phagocytic cells (human and J774 murine macrophages) with the selective PI3K inhibitors Wortmannin and LY294002 significantly impaired parasite invasion in a dose-dependent fashion. A strong activation of PI3K and PKB/Akt activities in Vero cells was detected when these cells were incubated with trypomastigotes or their isolated membranes. Consistently, we were unable to detect activation of PI3K or PKB/Akt activities in host cells during epimastigote (noninfective) membrane-host cell interaction. Infection of transiently transfected cells containing an inactive mutant PKB showed a significant inhibition of invasion compared with the active mutant-transfected cells. T. cruzi PI3K-like activity was also required in host cell invasion since treatment of trypomastigotes with PI3K inhibitors prior to infection reduced parasite entry. Taken together, these results indicate that PI3K and PKB/Akt activation in parasites, as in host cells induced by T. cruzi, is an early invasion signal required for successful trypomastigote internalization.
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PMID:Trypanosoma cruzi: phosphatidylinositol 3-kinase and protein kinase B activation is associated with parasite invasion. 1126 78

The avian homologue of the interferon regulatory factor 4 (IRF-4) and a novel splice variant lacking exon 6, IRF-4DeltaE6, were isolated and characterized. Chicken IRF-4 is expressed in lymphoid organs, less in small intestine, and lungs. IRF-4DeltaE6 mRNA, though less abundant than full-length IRF-4, was detected in lymphoid tissues, with the highest levels observed in thymic cells. IRF-4 is highly expressed in v-Rel-transformed lymphocytes, and the expression of IRF-4 is increased in v-Rel- and c-Rel-transformed fibroblasts relative to control cells. The expression of IRF-4 from retrovirus vectors morphologically transformed primary fibroblasts, increased their saturation density, proliferation, and life span, and promoted their growth in soft agar. IRF-4 and v-Rel cooperated synergistically to transform fibroblasts. The expression of IRF-4 antisense RNA eliminated formation of soft agar colonies by v-Rel and reduced the proliferation of v-Rel-transformed cells. v-Rel-transformed fibroblasts produced interferon 1 (IFN1), which inhibits fibroblast proliferation. Infection of fibroblasts with retroviruses expressing v-Rel resulted in an increase in the mRNA levels of IFN1, the IFN receptor, STAT1, JAK1, and 2',5'-oligo(A) synthetase. The exogenous expression of IRF-4 in v-Rel-transformed fibroblasts decreased the production of IFN1 and suppressed the expression of several genes in the IFN transduction pathway. These results suggest that induction of IRF-4 expression by v-Rel likely facilitates transformation of fibroblasts by decreasing the induction of this antiproliferative pathway.
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PMID:Interferon regulatory factor 4 contributes to transformation of v-Rel-expressing fibroblasts. 1153 27

The chemokine stromal cell-derived factor (SDF)-1 and its receptor, CXCR4, play important roles in human immunodeficiency virus type 1 (HIV-1) pathophysiology, leukocyte trafficking, inflammation, hematopoiesis, embryogenesis, angiogenesis, and cancer metastasis. The effects of cytokines on the regulation of CXCR4 function were investigated in human primary monocytes-macrophages. The expression of functional CXCR4 on the cell surface was demonstrated by the detection of ligand-induced Ca(2+) mobilization, chemotaxis, and ligand-induced receptor endocytosis. Surface CXCR4 expression was down-regulated by cytokines interleukin-4 (IL-4), IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and up-regulated by IL-10 and transforming growth factor-beta 1. Down-regulation was mediated post-translationally, in the absence of protein degradation, through an endocytotic mechanism. In contrast to SDF-1 alpha-induced CXCR4 endocytosis, cytokine-induced endocytosis of this receptor was independent of actin filament polymerization. GM-CSF increased the expression of G protein-coupled receptor kinase 3 (GRK3), beta-arrestin-1, Pyk2, and focal adhesion kinase (FAK). Cytokine treatment also increased the total and tyrosine-specific phosphorylation of CXCR4 as well as the phosphorylation of FAK on tyrosine 397. It also induced the formation of GRK3.CXCR4 or FAK.CXCR4 complexes. Infection of macrophages by primary R5X4 and X4 isolates of HIV-1 was inhibited by IL-4, IL-13, and GM-CSF, an effect that was associated with down-regulation of surface CXCR4 expression. These data indicate that ligand-dependent and ligand-independent endocytoses of CXCR4 are mediated by different mechanisms. Cytokine-induced endocytosis of chemokine receptors may be of therapeutic value in HIV-1 infection, inflammation, tumor metastasis, and defective hematopoiesis.
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PMID:Role of tyrosine phosphorylation in ligand-independent sequestration of CXCR4 in human primary monocytes-macrophages. 1166 82

In the former West Germany, in specific venereal diseases legislation passed in 1953, only syphilis, gonorrhoea, ulcus molle, and lymphogranuloma venereum were defined as venereal diseases and subject to mandatory notification. The proportion of unreported cases was as high as 75% for syphilis and up to 90% for gonorrhoea. Epidemiological data for the past 10 years exist only on selected populations from research studies and are summarized in this article. In the former East Germany reporting of sexually transmitted infections (STIs) was mandatory and, due to the centralized organization, underreporting was considered to be low, although no specific studies have examined this. After the unification in 1990 of the two German states the West German laws were adopted in East Germany. Since 1982 - when the first AIDS case was reported in Germany - information on AIDS cases has voluntarily been collected at the national register at the AIDS Centre of the Robert Koch Institute in Berlin. The law governing the reporting of infectious diseases has recently been revised. Under the new Protection against Infection Act, which became effective on 1 January 2001, clinical diagnoses of STIs (with the exception of hepatitis B) are no longer notifiable diseases. Laboratory reporting of positive test results for Treponema pallidum has been introduced. With T. pallidum and HIV notifications, additional disaggregated data are collected. Since T. pallidum and HIV remain the only notifiable STIs, all other STIs have to be monitored through sentinel surveillance systems. These surveillance systems are currently being established. Under the new legislation, local health authorities have to provide adequate counselling and testing services for STIs, which may be provided free of charge if necessary.
Int J STD AIDS 2002 Apr
PMID:Sexually transmitted diseases in Germany. 1188 9

Infection with Human T-Cell Lymphotropic Virus type I (HTLV-I) have been associated with the development of the HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phylogenetic analyses of HTLV-I isolates have revealed that HTLV-I can be classified into three major groups: the Cosmopolitan, Central African and Melanesian. In the present study, we analyzed the tax, 5' ltr, gag, pol, and env sequences of proviruses of PBMC from ten HAM/TSP patients to investigate the phylogenetic characterization of HTLV-I in Chilean patients. HTLV-I provirus in PBMC from ten Chilean patients with HAM/TSP were amplified by PCR using primers of tax, 5' ltr, gag, pol, and env genes. Amplified products of the five genes were purified and nucleotide sequence was determined by the dideoxy termination procedure. DNA sequences were aligned with the CLUSTAL W program. The results of this study showed that the tax, 5' ltr, gag, pol, and env gene of the Chilean HTLV-I strains had a nucleotide homology ranged from 98.1 to 100%, 95 to 97%, 98.9 to 100%, 94 to 98%, and 94.2 to 98.5% respect to ATK-1 clone, respectively. According to molecular phylogeny with 5' ltr gene, the Chilean HTLV-I strains were grouped with each other suggesting one cluster included in Transcontinental subgroup.
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PMID:Genetic characterization and phylogeny of human T-cell lymphotropic virus type I from Chile. 1190 Aug 46

Interaction between the major fimbriae of Porphyromonas gingivalis and gingival epithelial cells is important for bacterial adhesion and invasion. In this study, we identified integrins as an epithelial cell cognate receptor for P. gingivalis fimbriae. Immunoprecipitation and direct binding assays revealed a physical association between recombinant fimbrillin and beta1 integrins. In vitro adhesion and invasion assays demonstrated inhibition of binding and invasion of P. gingivalis by beta1 integrin antibodies. In contrast, invasion of a fimbriae-deficient mutant of P. gingivalis was not affected by integrin antibodies. Infection of gingival epithelial cells with wild-type P. gingivalis induced tyrosine phosphorylation of the 68 kDa focal adhesion protein paxillin, whereas the fimbriae-deficient mutant failed to evoke similar changes. Interestingly, activation of paxillin was not accompanied by an increase in the phosphorylation of focal adhesion kinase (FAK). These results provide evidence that P. gingivalis fimbriae promote adhesion to gingival epithelial cells through interaction with beta1 integrins, and this association represents a key step in the induction of the invasive process and subsequent cell responses to P. gingivalis infection.
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PMID:Involvement of integrins in fimbriae-mediated binding and invasion by Porphyromonas gingivalis. 1202 58

This document addresses medical workforce needs for the speciality of Genitourinary Medicine (GUM) for the next 10 years. Data on current consultant numbers, working patterns and retirement are based on information from the Royal College of Physicians (RCP) Workforce Unit annual census undertaken on 30 September 2000. Information on specialist registrars is from the JCHMT. Senior house officers (SHO) data are from the RCP's General Professional Training department. Data on Non-Consultant Career Grade Doctors is from the Association of Genitourinary Medicine Survey. Data on incidence of Sexually Transmitted Infections (STIs) are from KC60 returns on STIs collected from GUM clinics by CDSC. There is considerable movement of doctors in GUM between countries in the UK both during progression from SpR to consultant and at consultant level. Data are therefore presented as amalgamated UK data and also by country. It is essential that workforce planning takes this lateral movement into consideration when undertaking calculations for future workforce requirements.
Int J STD AIDS 2002 Jul
PMID:Medical workforce speciality review for genitourinary medicine 2001/2002-England, wales, northern ireland and Scotland. 1217 70

The UK National Guidelines on Sexually Transmitted Infections recommend penile biopsy in patients with persistent balanitis and balanitis of uncertain aetiology. Many GUM clinics perform penile biopsy. However, few studies have looked at the usefulness and safety of penile biopsy in a GUM clinic setting. We assessed the spectrum of dermatological conditions seen in a penile dermatoses clinic and looked at the usefulness and safety of penile punch biopsy in a GUM clinic setting. We reviewed the case notes of patients who attended the penile dermatoses clinic at the GUM department, Royal Berkshire Hospital, Reading over a period of 18 months. A total of 87 patients were seen in the penile dermatoses clinic. Their ages ranged from 17 to 73 and 70 (80%) were uncircumcised. Twenty-four (28%) patients had biopsies and five (6%) declined. Forty-nine (56%) patients did not have a biopsy either because of a clinically apparent diagnosis (45) or lesions were close to the urethral meatus (4). Five were referred for circumcision and one was referred to a dermatologist. Three patients were lost to follow-up. Penile biopsy was performed to exclude malignancy in 17 (71%) cases and due to diagnostic uncertainty in seven (29%) cases. Histological diagnoses were consistent with initial clinical diagnoses in 17 (71%) cases. Four (17%) had minor complications following biopsy, two had wound dehiscence, one had bleeding and another had a wound infection. In conclusion, a wide spectrum of penile skin disorders were seen in the penile dermatoses clinic. The majority of patients had a clinically apparent diagnosis. The histological diagnosis was consistent with initial clinical diagnosis in most of the biopsied patients. The main indications for biopsy were to exclude malignancy and for diagnostic dilemma. Penile biopsy is a safe procedure with minimal complications.
Int J STD AIDS 2002 Aug
PMID:Efficacy and safety of penile biopsy in a GUM clinic setting. 1219 43

Many individuals infected with STDs have their infections/diseases misdiagnosed and mistreated by people who are not qualified to practice medicine. This paper looks at HIV infection and treatment behavior in India. All STD patients attending the private clinic of a senior dermatologist and venereologist in Varanasi during a 6-month period were interviewed. There were 54 men and 6 women of mean age 27.5 years in the range of 18-52. 40 of the men were younger than age 30 years, while most patients had contracted infection from prostitutes. A fair number of more casual contacts were also reported. Infections among males came from known prostitutes in 22 cases, girlfriends in 13, relatives in 10, and a neighbor in 9. 69% of the men were married, with 40.6% of these men living with their wives at the time of exposure. Viral STDs such as herpes genitalis were common. 20 of the men consulted a qualified venereologist after the first exposure to infection. Indigenous "gupt rog" specialists in sexual medicine attracted the second largest number of patients after first exposure. On subsequent visit, however, none of the men returned to a gupt rog specialist. Good compliance as in the case of primary syphilis, gonorrhea, and non-gonococcal urethritis was probably due to good symptomatic response. Poor compliance in the case of herpes genitalis was probably the result of recurrence and inconvenient treatment regimens.
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PMID:Sexual and treatment behaviour of STD patients. 1229 Jun 76

Joint meetings between the members of the US Family Planning Services Program and the STD Program of Region X (comprising Alaska, Idaho, Oregon, and Washington) from fall 1986 through spring 1987 led to the screening and treatment of patients with chlamydia. Samples from patients were sent to state health department laboratories in Idaho, Washington, and Oregon. A direct fluorescent antibody (DFA) slide technique was used to process the cervical smears. Clinic visit record (CVR) information and laboratory results were collected by a central data management company, and sent to CDC and Region X researchers. 6 clinics in 3 of the states collected 2 cervical samples from each of 3000 patients, 1 for smear (DFA slide) and 1 for tissue culture over a 4-month period. During the 1988-1990 period, 136 clinics in the region supplied patient information and test results on over 300,000 samples. Overall, positive rates for chlamydia in the region went from a high of 10.9% in the 1st quarter of 1988 to 6.8% in the last quarter of 1990, with an overall declining trend. This amounted to an almost 37% decrease within the region. When analyzed by state, the positivity rates and decreases were relatively similar: Alaska, 12.2% to 10.0% positivity (18% decrease); Idaho, 10.5% to 8.0% (24% decrease); Oregon, 8.9% to 6.9% (22% decrease); and Washington, 9.3% to 6.6% (29% decrease). In patients 17 years of age and younger, positive rates for chlamydia fell 19%, from 12.2% in 1988 to 9.9% in 1990. In women 18-19 years old and women 20-24 years old, the rates fell 24% and 31%, respectively. Larger decreases in chlamydia rates were found among women in the 25-29 year age group (31% reduction) and in those 30 years old and older (44% reduction). Infection rates decreased in all race/ethnic groups, except Asians. Approximately 2/3 of the women with positive chlamydia tests had no apparent symptoms of disease. Conversely, the presence of certain clinical indicators seemed to correlate with the probability of a positive test result.
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PMID:STDs and family planning clinics: a regional program for Chlamydia control that works. 1231 93


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