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)

495 clients of 4 Manchester Family Planning Clinics, consulting for gynecological symptoms (194) or contraception (269), were examined to determine the prevalence of STD organisms and to rate signs, symptoms and laboratory findings for decisions about future screening. 38% of the family planning patients has symptoms of genital infection when asked. The 2 patients groups were combined, and signs and symptoms as well as laboratory results separated to establish criteria for lab screening. Among women with both signs and symptoms, 70% has positive laboratory findings. Trichomonas vaginalis, Candida albicans and bacterial vaginosis occurred in 22-26% of women with vaginal discharge. 72% of women with vaginal pH 4.5 has trichomonas and/or clue cells compared with 15% of those with normal pH. Cervicitis or cervical contact bleeding was associated with trichomonas. Candida, but not clue cells, was linked with vaginal inflammation. N. gonorrhoea was isolated from 12 women (2.4%), 10 of whom has symptoms. These results suggest that women with high pH could be given metronidazole before laboratory confirmation; that bacterial infection can be diagnosed by vaginal discharge, high pH and clue cells; that cervical swabs are more accurate than vaginal swabs for determining trichomonas; and that cervical smears for cytology are equally good for trichomonas; and that the high prevalence of gonococci justifies use of a culture medium that will also support growth of Candida.
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PMID:A prospective study of genital infections in a family-planning clinic. 1. Microbiological findings and their association with vaginal symptoms. 230 84

The most common pathogens involved in disseminated bacterial infection in people with acquired immunodeficiency syndrome (AIDS) are organisms of the Mycobacterium avium-intracellulare complex (MAC). Azithromycin and clarithromycin, a new azalide and macrolide, respectively, are among the most potent monotherapies for MAC bacteraemia, Although many bloodstream isolates demonstrate increased minimum inhibitory concentrations after 4 months of treatment. Current recommended prophylaxis, based on the results of two randomized, double-blind, prospective studies, is rifabutin 300 mg daily for people with AIDS with < 100 CD4 lymphocytes/mm3. In the beige mouse model, we have shown that both azithromycin and clarithromycin prevent MAC bacteraemia following repetitive oral challenge. Clinical trails are now underway to confirm these effects in man; comparative treatments include placebo, rifabutin and an azalide/macrolide plus rifabutin. While combinations might be more effective and reduce the emergence of resistance, the spectre of cytochrome P-450 drug interactions necessitates careful study before combination prophylactic approaches are accepted. Such interactions are associated with rifabutin and some macrolides, although azithromycin may be less problematic in this respect as it appears to have little potential to interact with other antimicrobial agents.
Int J STD AIDS 1996
PMID:Treatment and prophylaxis of Mycobacterium avium complex. 865 24

In order to describe the clinical features of HIV (non-AIDS), particularly injection drug use (IDU) related HIV, in patients attending the Regional Infectious Diseases Unit in Edinburgh, a prospective review utilizing the WHO staging system of the 680 HIV positive patients, 30% of whom were women and 68% were infected via IDU, was undertaken. Despite the fact that the majority of drug users and heterosexuals enrolled asymptomatic, by 1993, 71% of the patients had developed some HIV related clinical problem. The important clinical problems observed for the cohort were; minor skin problems, minor bacterial infections, major bacterial sepsis, oral thrush, oral hairy leucoplakia, significant weight loss of > 10%, HIV related thrombocytopenia and of course AIDS. Unlike previous reports from other areas, in Edinburgh drug users were not more likely than other risk groups to develop severe bacterial disease. Differences in morbidity and mortality rates by risk group but not by gender were noted but these may well be affected by the very different enrolment pattern observed in the various risk groups. The pre-AIDS mortality rates for drug users were remarkably similar to published rates from other centres.
Int J STD AIDS
PMID:Clinical features of early HIV in the Edinburgh City Hospital cohort. 873 35

The case records of consecutive patients admitted to a specialist HIV/AIDS inpatient unit between 1989 and 1993 with pyrexia of undetermined origin (PUO) were reviewed in order to determine the eventual diagnosis. Seventy-nine episodes occurred in 75 patients; 52 patients had a prior AIDS defining diagnosis. CD4+ lymphocyte counts ranged widely, 0-0.79 (median = 0.04) x 10(9)/l. Infections were found in 63 episodes (79%), including mycobacterial infection in 41 episodes (53%) and bacterial infection in 12 episodes (15%). Tumours were found in 6 episodes (8%), 5 of these were lymphoma. Factitious fever accounted for 2 episodes (3%) and connective-tissue disease for 1 episode (1%); no definite diagnosis was reached in 7 episodes (9%). PUO in HIV positive patients is commonly due to infection or tumour. Unexplained fever in this patient group should not be ascribed to HIV infection itself and should be vigorously investigated to find a cause.
Int J STD AIDS
PMID:Pyrexia of undetermined origin in patients with human immunodeficiency virus infection and AIDS. 879 78

This study set out to investigate whether plasma mannose-binding protein (MBP) deficiency caused by mutations in the MBP gene associates with pyogenic or opportunistic infections in HIV-infected patients. Plasma samples were selected randomly from 131 HIV-infected patients followed prospectively for a period not exceeding 12 months or until death. Plasma MBP concentrations were measured by an ELISA and genotyping was determined by amplification of exon 1 of the MBP gene by polymerase chain reaction (PCR) technology, followed by restriction enzyme analysis and Southern blotting using sequence-specific oligonucleotide probes. Neither MBP concentration nor genotype was found to associate with disease progression or opportunistic infection rate. There was an unexpected increased bacterial infection rate in patients with MBP levels greater than 100 ng/ml and wild type genotype. Thus, MBP does not appear to play a role in HIV infection. MBP is an acute phase reactant and this may explain the higher levels in those with more frequent pyogenic infections.
Int J STD AIDS 1998 Nov
PMID:Mannose-binding protein in HIV-seropositive patients does not contribute to disease progression or bacterial infections. 986 82

Human newborns are more susceptible than adults to bacterial infection. With gram-negative bacteria, this may be due to a diminished response of newborn leukocytes to lipopolysaccharide (LPS). Since protein tyrosine kinase inhibition abolishes LPS priming in adult cells, we hypothesized that protein tyrosine kinases may have a critical role in LPS priming of polymorphonuclear neutrophils (PMNs) and that newborn PMNs may have altered protein tyrosine kinase activities. In the present study, we investigated the role of src family protein tyrosine kinases in the LPS response of newborn PMNs compared to adult cells. In a respiratory assay, the LPS-primed increase in formylmethionylleucylphenylalanine (fMLP)-triggered O2- release by adult PMNs was greatly decreased by PP1 [4-amino-5-(4-methyphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine], a src kinase inhibitor, to the level of untreated newborn PMNs, in which LPS failed to prime. LPS activated the src-like kinases p59hck (HCK) and p58fgr (FGR) in both adult and newborn PMNs but increased the activation of p53/56lyn (LYN) only in adult cells. In newborn PMNs, LYN was highly phosphorylated independent of LPS. We evaluated subcellular fractions of PMNs and found that the phosphorylated form of LYN was mainly in the Triton-extractable, cytosolic fraction in adult PMNs, while in newborn cells it was located mainly in Triton-insoluble, granule- and membrane-associated fractions. In contrast, the phosphorylated mitogen-activated protein kinases ERK1/2 and p38 were mainly detected in the cytosol in both adult and newborn PMNs. These data indicate a role for LYN in the regulation of LPS priming. The trapping of phosphorylated LYN in the membrane-granule fraction in newborn PMNs may contribute to the deficiency of newborn cells in responding to LPS stimulation.
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PMID:Role of protein tyrosine kinase p53/56lyn in diminished lipopolysaccharide priming of formylmethionylleucyl- phenylalanine-induced superoxide production in human newborn neutrophils. 1550 76

The rapid turnover and exfoliation of mucosal epithelial cells provides an innate defence system against bacterial infection. Nevertheless, many pathogenic bacteria, including Shigella, are able to surmount exfoliation and colonize the epithelium efficiently. Here we show that the Shigella flexneri effector OspE (consisting of OspE1 and OspE2 proteins), which is highly conserved among enteropathogenic Escherichia coli, enterohaemorrhagic E. coli, Citrobacter rodentium and Salmonella strains, reinforces host cell adherence to the basement membrane by interacting with integrin-linked kinase (ILK). The number of focal adhesions was augmented along with membrane fraction ILK by ILK-OspE binding. The interaction between ILK and OspE increased cell surface levels of 1 integrin and suppressed phosphorylation of focal adhesion kinase and paxillin, which are required for rapid turnover of focal adhesion in cell motility. Nocodazole-washout-induced focal adhesion disassembly was blocked by expression of OspE. Polarized epithelial cells infected with a Shigella mutant lacking the ospE gene underwent more rapid cell detachment than cells infected with wild-type Shigella. Infection of guinea pig colons with Shigella corroborated the pivotal role of the OspE-ILK interaction in suppressing epithelial detachment, increasing bacterial cell-to-cell spreading, and promoting bacterial colonization. These results indicate that Shigella sustain their infectious foothold by using special tactics to prevent detachment of infected cells.
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PMID:Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment. 1948 19

Through acute enteric infection, Salmonella invades host enterocytes and reproduces intracellularly into specialized vacuolae. This involves changes in host cell signaling elicited by bacterial proteins delivered via type III secretion systems (TTSS). One of the two TTSSs of Salmonella enterica serovar Typhimurium encoded by the Salmonella pathogenicity island-1, triggers bacterial internalization. Among the effector proteins translocated by this TTSS, the GTPase modulator SopE/E2 and the phosphoinositide phosphatase SigD are known to play key roles in these processes. To better understand their contribution to re-programming host cell pathways, we used ZeptoMARK reverse-phase protein array technology, which allows printing 32-sample lysate arrays that can be analyzed with phospho-specific antibodies to evaluate the phosphorylation of signaling proteins. Lysates were obtained at different times after infection of HeLa cells with WT, TTSS-deficient, sopE/E2 and sigD single and double deletants, as well as different sigD Salmonella mutants. Our analysis detected activation of p38, JNK and ERK mitogen-activated protein kinases, mainly dependent on SopE/E2, as well as SigD-dependent phosphorylation of PKB/Akt and its targets GSK-3beta and FKHR/FoxO. This is the first time that reverse-phase protein array technology is used in the cellular microbiology field, demonstrating its value to screen for host signaling events through bacterial infection.
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PMID:Addressing the effects of Salmonella internalization in host cell signaling on a reverse-phase protein array. 1960 73

Microbes regulate a large panel of intracellular signalling events that can promote inflammation and/or enhance tumour progression. Indeed, it has been shown that infection of human intestinal cells with the Afa/Dr diffusely adhering E. coli C1845 strain induces expression of pro-angiogenic and pro-inflammatory genes. Here, we demonstrate that exposure of cryptic-like intestinal epithelial cells to C1845 bacteria induces HIF-1alpha protein levels. This effect depends on the binding of F1845 adhesin to the membrane-associated DAF receptor that initiates signalling cascades promoting translational mechanisms. Indeed, inhibition of MAPK and PI-3K decreases HIF-1alpha protein levels and blocks C1845-induced phosphorylation of the ribosomal S6 protein. Using RNA interference we show that bacteria-induced HIF-1alpha regulates the expression of IL-8, VEGF and Twist1, thereby pointing to a role for HIF-1 in angiogenesis and inflammation. In addition, infection correlates with a loss of E-cadherin and cytokeratin 18 and a rise in fibronectin, suggesting that bacteria may induce an epithelial to mesenchymal transition-like phenotype. Since HIF-1alpha silencing results in reversion of bacteria-induced EMT markers, we speculate that HIF-1alpha plays a key role linking bacterial infection to angiogenesis, inflammation and some aspects of cancer initiation.
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PMID:HIF-1alpha mediates the induction of IL-8 and VEGF expression on infection with Afa/Dr diffusely adhering E. coli and promotes EMT-like behaviour. 2003 80

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the gene coding for Bruton's tyrosine kinase (Btk). Most XLA patients have severely reduced or absent peripheral blood B cells and serum immunoglobulins, since the expression or function of Btk, critical for the maturation of B cell lineages at pro-B and pre-B cell stages, is deficient. Early and accurate diagnosis of XLA is important, since the affected patients suffer from severe and recurrent infections unless they receive intravenous immunoglobulin (IVIG) replacement therapy. However, the diagnosis of XLA is not always easy because some patients have detectable ( approximately 2%) B cells in the peripheral blood and have significant levels of serum immunoglobulins. In this study, we report on a patient who was diagnosed with XLA at the age of 10years. The diagnosis was delayed due to near-normal levels of serum immunoglobulins, although he presented with severe and recurrent bacterial infections since the age of 1year. He was demonstrated to have a novel non-invariant splice-site mutation in intron 10 (IVS10 -11C-->A) of the Btk gene, which was not detected by the standard PCR-based mutation analysis. This mutation resulted in no detectable Btk expression. This case suggests that patients suffering from severe or recurrent bacterial infection should be suspected to have XLA even though they may have significant levels of serum immunoglobulins. Furthermore, significant levels of serum immunoglobulins in XLA patients do not necessarily mean less severe phenotype.
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PMID:X-linked agammaglobulinemia in a 10-year-old boy with a novel non-invariant splice-site mutation in Btk gene. 2012 58


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