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)

Malignancy is the result of multistep transformational changes of normal somatic cells. In the case of respiratory epithelial malignancies this process lasts for several years. Many methods have been explored to mimic this process in an extracorporal model. In the present investigation we combined several of these methods. Organ cultures were prepared from tracheal specimens and were then consecutively treated with human papilloma virus, benzo(a)pyrene, methylnitronitrosoguanine and tetradecanoyl phorbol acetate. Identical numbers of organ cultures from the same specimen were maintained without exposure to carcinogens. After 6 weeks these cultures were further cultivated either in mixed cultures (MC) with autologous isotopic fibroblasts or under the kidney capsule of the nude mouse (SRC). These two methods were combined after a few months: MC cells were transplanted under the SRC or SRC transplants were explanted in cell culture. This long-term selection procedure revealed striking differences between control and treated organ cultures. Three-dimensional structures containing epithelial cells were isolated from both organ cultures but survived more than 3 months only from treated cultures. Only MC from treated organ cultures produced nodules under SRC. The incidence and morphology of the nodules in the SRC were directly related to carcinogen treatment, with more nodules with pronounced epithelial cell atypia obtained from treated organ cultures. MC and SRC showed the importance of a time factor for selecting cells with changed growth behavior--increased time increased the incidence of such cells.
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PMID:Induction of transformation of human respiratory epithelium in vitro. Preliminary investigation. 141 47

One hundred heterosexual women presenting at our clinic in 1979 with anogenital warts, were reviewed 10 years later. Median duration of warts following initial clinic attendance was 2 months (range 0-120 months). In 1979 cervical PAP smear results were available for 76 patients; cervical intraepithelial neoplasia (CIN) was seen in 15/76 (19.7%) women; 3 (4%) women had low grade CIN, 12 (15.7%) women had high grade CIN. Nineteen women had had treatment for CIN between 1979 and 1989, 7 laser ablation, 9 cone biopsy, 2 laser ablation and cone biopsy, and one woman laser ablation, cauterization and cone biopsy. At 10-year follow-up in 1989 4/100 women had anogenital warts, 12/100 women had cytological evidence of CIN (7 low grade, 5 high grade), and 37/100 women had CIN detected on colposcopic biopsy (31 low grade, 6 high grade). No women developed invasive cervical carcinoma during the study period. CIN lesions, detected in 1979, regressed without any treatment in 2 women. Colposcopic biopsy was 3.1 times more sensitive than single cervical PAP smear at detecting CIN (4.4 times as sensitive in detecting low grade CIN; 1.2 times as sensitive in detecting high grade CIN). In 1989 CIN was detected in 7/19 (36.8%) of women who had undergone cervical treatment between 1979 and 1989, and in 35/81 (43.2%) of women having no cervical treatment within this period (chi squared P greater than 0.5). These findings suggest that cervical laser ablative therapy and cone biopsy do not in the long term influence the natural history of cervical human papilloma virus-associated disease (CIN) in women with anogenital warts.(ABSTRACT TRUNCATED AT 250 WORDS)
Int J STD AIDS
PMID:Ten year follow-up study of women presenting to a genitourinary medicine clinic with anogenital warts. 154 64

Of the approximately 15 million HIV infections that have occurred since the epidemic began, over 10 million have been transmitted heterosexually. Although there have been studies to show that HIV-1 is relatively inefficiently transmitted heterosexually and substantially less readily transmitted than is herpes simplex 2 virus or human papilloma virus, studies in Kenya have identified 5 factors that facilitate heterosexual spread of HIV-1: 1) promiscuity, 2) other sexually transmitted diseases (ulcers, particularly chancroid), 3) cervical ectopia, 4) uncircumcised men, and 5) increased titers of HIV-1 secreted in the genital secretions of immunosuppressed patients. Poverty, illiteracy, discrimination and stigmatization, gender inequality, low respect for human rights, and political and civil unrest are also underlying determinants of HIV epidemiology. The World Health Organization Global Program on AIDS has mobilized resources to control AIDS, but culturally inappropriate interventions can be detrimental to slowing and stopping the spread of HIV-1. HIV prevention is difficult because of the stigmatization associated with it, the long incubation period negates awareness of cause and effect, and sexual behavior is poorly understood in all societies. Specific interventions comprise: 1) a defined mission with strong links to the national head of state and annual review of the program goals and strategies; 2) mass media and targeted educational campaigns to increase public awareness of AIDS and encourage behavior change; and 3) the synergism between HIV and other sexually transmitted diseases provides an opportunity for targeted interventions. Among specific interventions are: 1) Behavioral interventions for vulnerable groups. In Thailand condom promotion, prostitute and brothel registration, and education of those in male risk groups resulted in a 70% reduction in cases of STDs. 2) Improved clinical services for sexually transmitted infections. 3) Research to understand sexual health. 4) Integration of HIV- and STD-control programs. Physical and chemical barriers should be the major strategy of reduction and prevention of HIV transmission.
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PMID:Slowing heterosexual HIV transmission. 767 67

The purpose of this study was to demonstrate the prevalence of cervical human papilloma virus (HPV) infection correlated to reason for attending an STD clinic, presence of clinical signs of HPV infection, concomitant infection and abnormal cytology. Samples from the cervical canals of 588 consecutive women attending the STD clinic, Department of Dermato-Venereology, Sahlgrenska Hospital, Gothenburg, were taken with a Cytobrush for detection of HPV DNA with the dot blot/Southern-blot technique. Visible condylomata, i.e. filiform or papular condylomata, were registered. Acetic acid test and colposcopy were not routinely performed. Cytological examination was performed as well as isolation of Chlamydia trachomatis on Mc Coy's cells and culture on Sabouraud agar for Candida albicans. The prevalence of HPV DNA was 8% (48/588). In the group of 233 women attending because of concern about HPV infection, 94 (40%) had visible signs of HPV infection and 30 (13%) were positive for HPV DNA in the cervix. In 355 women attending for other reasons, such as discharge, pruritus or STD check-up, 4 (1%) had visible signs of HPV infection and 18 (5%) were HPV DNA positive. Of 98 women with visible signs of vulvar/vaginal HPV infection, 33 (34%) were HPV-positive in the cervix with a commercial Southern-blot test. Of 490 patients without visible signs of HPV infection, 15 (3%) were HPV-positive in the cervix. In the group of HPV-positive women a positive culture for Candida was demonstrated in 26% (11/43), Compared to 16% (79/504) of the HPV-negative women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human papilloma virus infection among women attending an STD clinic correlated to reason for attending, presence of clinical signs, concomitant infections and abnormal cytology. 774 43

Acetowhite lesions in the vulva disclosing koilocytosis have been related to infection by human papilloma virus (HPV). Because of the clinical resemblance of these lesions to oral hairy leukoplakia (OHL), and EBV-manifestation, 23 women with acetowhite koilocytotic lesions in the vulva were examined. The PCR-technique was used to detect EBV DNA as well as HPV DNA in 17% of 23 patients examined. In a control group of 19 patients EBV DNA was detected in 11% and HPV DNA in 42% of cell samples from normal vulvar mucosa. EBV DNA has not previously been demonstrated in the vulvar mucosa, and this virus might be related to subclinical acetowhite lesions.
Int J STD AIDS
PMID:Demonstration of Epstein-Barr virus DNA in acetowhite lesions of the vulva. 814 24

Twenty-one human immunodeficiency virus (HIV) seropositive patients were studied to determine the prevalence of cervical dysplasia, the distribution of human papilloma virus (HPV) subtypes, and the utility of cytologic diagnosis in this population. The patients ranged in age from 18 to 41 years. HIV infection was diagnosed in all patients by ELISA method and confirmed by Western blot. Patients were interviewed to document risk factors for HIV infection and cervical dysplasia. All were examined colposcopically and identifiable lesions were biopsied. In patients with normal colposcopic findings four quadrant biopsies were performed. Cervical and endocervical smears were obtained on all patients at the time of colposcopy and blood was collected for T-cell studies. Eighteen patients (86%) had abnormal cytologic findings. The Pap smear was able to identify 10 of 13 biopsy-proven epithelial abnormalities. In 14 patients there was sufficient tissue for HPV typing by in situ hybridization; the HPV subtypes identified were 6/11 (10 patients), 16/18 (9 patients), and 31/33/35 (9 patients). Dysplasia was present in 11/14 (79%) of the specimens submitted for subtyping. The absolute CD4 cell counts were 342 per mm3 for the dysplasia group and 281 per mm3 for the patients without dysplasia. Patients with dysplasia did not differ significantly from patients without dysplasia in regard to risk factors for cervical dysplasia, including history of STD, tobacco use, multiple sexual partners, age at first coitus, and parity. In addition, history of medication use and risk factors associated with HIV infection were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The correlation between HIV seropositivity, cervical dysplasia, and HPV subtypes 6/11, 16/18, 31/33/35. 831 33

Lectins or agglutinins are proteins with affinity for specific sugar residues. Peanut agglutinin (PNA) and the lectin from the edible mushroom (Agaricus bisporus, ABL) both bind to the disaccharide galactosyl beta-1,3-N-acetyl galactosamine alpha-. This is expressed in keratinocytes as an O-linked chain on CD44, a polymorphic membrane glycoprotein. Many lectins are mitogens and PNA is a mitogen for colonic epithelial cells. However, ABL reversibly inhibits proliferation of colonic cancer cell lines without cytotoxicity and thus has therapeutic potential in situations such as psoriasis where proliferation is increased. We have therefore investigated the effect of ABL on the growth of normal human cultured keratinocytes and a human papilloma virus (HPV)-transformed cell line. In a 5-day dose-response study, keratinocyte growth was greatly reduced by 1.0 microg/mL ABL and completely inhibited by 3.0 microg/mL ABL (ANOVA, P < 0.0001). Exposure to 1.0 microg/mL ABL for only 8 h gave the same growth inhibition as did continued exposure for 3 days. No cytotoxic or morphological changes were observed. An HPV-immortalized cell line was relatively resistant to ABL: in a 5-day dose-response study, exposure to 30 microg/mL was required to inhibit cell growth completely. Topical application of ABL 0.01% or 0.1% to normal human skin caused no change in skin erythema, blood flow or thickness compared with vehicle or baseline (n = 6). ABL 0. 1% in white soft paraffin was compared with vehicle in 11 psoriatic patients, using comparative contralateral plaques. Twice daily application for 2 weeks showed no significant difference from vehicle-treated sites, although the skin thickness of plaques fell from 5.3 +/- 0.4 (n = 11, mean +/- SEM) to 4.1 +/- 0.3 mm. In view of the in vitro results further studies are warranted, particularly if means can be found to improve the epidermal penetration of the relatively large ABL molecule (60 kDa).
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PMID:The antiproliferative effect of lectin from the edible mushroom (Agaricus bisporus) on human keratinocytes: preliminary studies on its use in psoriasis. 1021 68

The tumor suppressor PTEN is one of the most commonly inactivated genes in human cancer. Glioblastoma multiforme cells harboring mutant PTEN have abnormally high levels of 3' phosphoinositides and elevated protein kinase B activity. Expression of wild-type PTEN in glioma cells, containing endogenous mutant PTEN, reduces 3' phosphoinositides levels, inhibits PKB activity, and induces G1 cell cycle arrest. We investigated the mechanism of the PTEN-induced growth arrest in glioma cell lines. Expression of PTEN is associated with increased expression of p27Kip1, decreased expression of cyclins A and D3, inhibition of cdk2 activity, and dephosphorylation of pRb. Inactivation of p53, by the human papilloma virus E6 oncoprotein, does not prevent PTEN-induced G1 arrest, implying that p53 is not required for G1 arrest. In contrast, p27Kip1 antisense oligonucleotides abrogated the growth arrest induced by PTEN. Furthermore, blocking p27Kip1 expression prevented the PTEN-induced reduction of cyclin-dependent kinase 2 activity, indicating that p27Kip1 functions upstream of cyclin-dependent kinase 2 in the PTEN regulatory cascade. These results implicate p27Kip1 as a critical mediator of PTEN-induced G1 arrest.
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PMID:p27Kip1 is required for PTEN-induced G1 growth arrest. 1128 Jul 73

A cohort of 458 HIV-positive women under antiretroviral therapy has been followed at a reference hospital in Rio de Janeiro, Brazil. Most of them belong to impoverished social strata. Patients were screened for sexually transmitted infections (STIs) and gynaecologic conditions. Some STIs were found to be uncommon (e.g. chlamydial and gonococcal infections), while some conditions (bacterial vaginosis) and STIs, e.g. hepatitis B and human papilloma virus (HPV) infection, were found to be quite prevalent. The latter is of special concern, due to the high prevalence of HIV/HPV co-infection ( approximately 51%) and its association with severe immunodeficiency, in a context of unacceptable high levels of uterine cancer and uneven gynaecological care. HIV-positive women are in need of comprehensive health services, including high-quality, regular, gynaecologic care in order to diagnose and treat lower genital tract infections and prevent the evolution of HPV-related lesions. Reproductive counselling should be a part of this approach.
Int J STD AIDS 2006 Jul
PMID:Assessing sexually transmitted infections in a cohort of women living with HIV/AIDS, in Rio de Janeiro, Brazil. 1682 78

Bacterial vaginosis (BV) is a common disorder of the genital tract in women characterized by an alteration of the normal acidic lactobacilli-predominant vaginal ecosystem to a vaginal environment dominated by Gardnerella vaginalis, mycoplasma species and anaerobes, with an increase in pH. The present study evaluated whether BV is associated with reproductive complications in women. BV was screened with a Gram stain of vaginal smear and interpretation was done using the Nugent score. Wet mount and polymerase chain reaction were used to screen other infections. Among 510 enrolled women, 72 (14.1%) had BV. Statistical analysis between the BV negative and positive population revealed a significant association (P = 0.0001) with infertility. In pregnant women, the infection rate was low (P = 0.01). Multiple infections such as Candida, Chlamydia and human papilloma virus were observed in 4.2%, 15.3% and 8.3% of BV-infected women, respectively. Results suggest that BV infection is associated with infertility and its absence leads to pregnancy, emphasizing its screening and treatment.
Int J STD AIDS 2009 Nov
PMID:Bacterial vaginosis: a cause of infertility? 1983 94


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