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)

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

In this article, Dr. P.N. Sehgal, former director of the National Institute of Communicable Diseases in Delhi, explains the steps that women need to take to protect themselves against AIDS and discusses some issues facing women who have already contracted the disease. Because of women's lack of status in the family and society, it is harder for them to ensure their safety. Women based at home often lack information on AIDS, and those women who are informed sometimes depend on their male partner for financial support, which means that they are forced to engage in unsafe sexual practices. Safer sexual practices can reduce the risk for women. Though varying in degree of safety, some safer practices include: monogamous relationships between uninfected partners; the use of condoms for all types of sexual intercourse; non-penetrative sex practices (hugging, kissing, masturbating); reducing the number of sexual partners; avoiding sex when either of the partners has open sores or any STD. Pregnant women should also receive information concerning AIDS, including: a baby born from an HIV-infected mother has a 20-40% of being infected; the risk of transmission is higher when the mother already shows signs of AIDS; and an infected baby may die within the first few years of life. the HIV transmission may occur prepartum or during birth itself, but the risk of transmission from breastfeeding is extremely low. Dr. Sehgal stresses the need for privacy and confidentiality when dealing with carriers of the disease or when carrying out HIV testing. Above all, the rights of HIV-infected people must be protected.
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PMID:Women and AIDS. 1228 4

A recently released Johns Hopkins University study of AIDS in India finds that India may have the world's highest rates of HIV transmission. The study findings were reported by Robert Bollinger, M.D., and numerous other authors in the December 1995 issue of the Journal of Infectious Diseases. Study findings show that 20% of patients at Pune City Sexually Transmitted Disease Clinics by 1993 had HIV infections. During 1993-95, 62 persons out of a total of 851 initially uninfected persons contracted AIDS, regardless of their having received STD treatment and AIDS awareness and prevention education. 85% of the 851 persons followed up were men, and about 60% of the women were prostitutes. The study estimated that the risk of HIV infection was over 10% per year among this population, which is one of the highest rates ever reported from such a risk group. The incidence of women's infections was higher (14.1% per year compared to 9.4% for men). Persons with recurrent genital ulcer disease (open sores) had a seven times higher risk than normal persons and a three times higher risk than persons with urethritis or cervicitis. Condom use during the previous three months of follow-up reduced risk by 56%. The concern about AIDS transmission is coupled with the concern about tuberculosis incidence. This research was funded by the Indian National AIDS Research Institute, Family Health International, and the Fogarty International Program. The World Health Organization estimates that India has over 1.5 million HIV infected persons.
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PMID:India faces major AIDS burden by end of decade. 1229 Nov 90

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

In Senegal, AIDS was 1st discovered in December 1986 going from 6 cases in 1987, to 181 in 1988, to 269 in 1989, and to 361 in June of 1990. Senegal has the HIV-2 virus, which has a longer incubation period than the HIV-1 virus and its incidence is becoming a growing problem. Unlike most other countries in Africa, Senegal did not institute an AIDS program with the World Health Organization; but signed a contract with Harvard, Tours and Lomoges Universities to undertake research on AIDS, sexually transmitted diseases, prostitution, tuberculosis, infectious diseases, cancer, and diseases of internal medicine. The project established: 1) an epidemiological surveillance system with prostitutes, patients with STD's, tuberculosis, cancer, problems of internal medicine and pregnant women; and 2) a diagnostic referral center for West Africa with a bacteriology-virology laboratory in le Dantec Hospital. This hospital has trained most West African biologists and produced the 1st epidemiological studies in West Africa. In 1986, after receiving the 1st results of an epidemiological survey on prostitutes and the incidence of STD's, the government created The National Multidisciplinary Committee for the Prevention of AIDS which includes a National Component made-up of an epidemiological, clinical, information and ethical/judicial and research groups; Regional Committees, an Executive Committee and a Mixed Committee for Follow-Up and Coordination. The Roles played by each of these committees interface at a National level to safeguard the fight against AIDS and STDs in Senegal.
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PMID:[AIDS in Senegal]. 1234 26

Current STD control efforts are largely confined to female sex workers (FSWs) registered with the local Social Hygiene Clinics. This study was conducted to compare the prevalence of gonococcal and chlamydial infections and its behavioral correlates among registered FSWs in two major urban centers. FSWs in Manila and Cebu City consented to undergo an STD physical examination and standardized interview to measure socioeconomic markers and STD-related practices. The questionnaire was pretested in a series of four focus groups in Manila and subsequently administered in Tagalog and Cebuano by trained interviewers. Infection with N. gonorrhea was determined by culture and infection with C. trachomatis was defined by antigen detection. From July through September 1994 similar numbers of women were recruited in Manila (n = 311) and Cebu City (n = 300). However, thanks to the abilities of an interviewer who was previously a FSW, Cebu City was more successful at recruiting unregistered FSWs (50%) than was Manila (18%). The gonorrhea prevalence was 5 times greater among unregistered FSWs (70/185 or 37.8%) than registered FSWs (29/403 or 7.2%) (p 0.05). Prevalence of chlamydial infection was 2 times greater among unregistered FSWs (30.5%) than among registered ones (14.6%) (p 0.05). Unregistered FSWs reported fewer years working as a FSW, more partners in the prior week, and less current use of contraceptives (p 0.05). Rates of antibiotic use in the last week and douching in the last 24 hours were similar between the two groups. This study shows that unregistered FSWs are at a higher risk for acquiring and transmitting STDs, including HIV infection, than registered FSWs. There is an urgent need to implement interventions to reach this vulnerable group of women.
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PMID:Comparison of STD prevalence and the behavioral correlates of STD among registered and unregistered female sex workers in Manila and Cebu City, Philippines. 1234 61


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