Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The type I IFNs represent a primordial, tightly regulated defense system against acute viral infection. IFN-alpha confers resistance to viral infection by activating a conserved signal transduction pathway that up-regulates direct antiviral effectors and induces immunomodulatory activities. Given the critical role of IFN-alpha in anti-human cytomegalovirus (HCMV) immunity and the profound ability of HCMV to escape the host immune response, we hypothesized that HCMV blocks IFN-alpha-stimulated responses by disrupting multiple levels of the IFN-alpha signal transduction pathway. We demonstrate that HCMV inhibits IFN-alpha-stimulated MHC class I, IFN regulatory factor-1, MxA and 2',5-oligoadenylate synthetase gene expression, transcription factor activation, and signaling in infected fibroblasts and endothelial cells by decreasing the expression of Janus kinase 1 and p48, two essential components of the IFN-alpha signal transduction pathway. This investigation is the first to report inhibition of type I IFN signaling by a herpesvirus. We propose that this novel immune escape mechanism is a major means by which HCMV is capable of escaping host immunity and establishing persistence.
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PMID:Human cytomegalovirus inhibits IFN-alpha-stimulated antiviral and immunoregulatory responses by blocking multiple levels of IFN-alpha signal transduction. 1022 53

Cytomegalovirus (CMV) infection is one of the most important opportunistic infections in AIDS. The most common manifestation of neurological CMV disease in HIV infection is retinitis followed by encephalitis, polyradiculopathy, and multifocal neuropathy. Untreated necrotizing retinitis proceeds to blindness but can readily be diagnosed by ophthalmological examination. CMV polyradiculopathy presents as subacute leg weakness, paraesthesia, and urinary retention. Untreated patients develop ascending paralysis and die within weeks. Multifocal neuropathy commonly affects the radial, ulnar, and peroneal nerves but cranial nerves may also be involved. Confusion, cranial nerve palsies, and hyperreflexia are signs of ventriculoencephalitis, whereas the presentation of diffuse micronodular encephalitis is often asymptomatic. The diagnostic approach relies on the detection of CMV DNA in the cerebrospinal fluid for polyradiculopathy, encephalitis, and neuropathy. Neuroimaging can exclude other causes of encephalitis and polyradiculopathy. Ganciclovir, foscarnet, and cidofovir monotherapy are current medical treatment options. Intraocular administration can be used for refractory retinitis, but additional systemic prophylaxis is required to suppress extraocular disease. Ganciclovir and foscarnet have improved the prognosis of multifocal neuropathy and polyradiculopathy, but response rates for encephalitis are low. However, despite therapy survival of central nervous CMV disease is still limited to months. Recently highly active antiretroviral therapy (HAART) has decreased the overall incidence of CMV disease in AIDS. Furthermore (HAART) has become a mainstay for CMV therapy by improving the patient's immunocompetence against CMV.
Int J STD AIDS 1999 Mar
PMID:Neurological manifestations of cytomegalovirus infection in the acquired immunodeficiency syndrome. 1034 Jan 95

This paper concerns the ophthalmic assessment of patients with acquired immunodeficiency syndrome (AIDS) for a number of eye conditions and in particular cytomegalovirus (CMV) retinitis. CMV has been the most common opportunistic infection associated with AIDS and the leading cause of blindness among AIDS patients. There have been early indications of a widespread fall in CMV prevalence internationally following the introduction of a new highly active antiretroviral triple (HAART) therapy. Our study sought to assess the position for Ireland. Our cohort was the entire population of stage IV AIDS patients attending the country's leading referral centre. The total number of patients examined was 167 and the period of examination was 1 May 1995 to 30 April 1997. HAART was introduced in March 1996, so the data permitted a 'before and after' comparison of various clinical findings. The incidence of new CMV cases was found to be 4 among the 102 patients examined in the first 12-month period and one among 107 patients examined in the second 12-month period. There were accompanying declines in HIV-related noninfectious retinal vasculopathy (HIVR), keratitis and other conditions. The findings are promising, but we argue that caution is needed in assessing long-term trends. In the paper we discuss a number of methodological issues in the collection and analysis of the clinical data and in the interpretation of results.
Int J STD AIDS 1999 Oct
PMID:Monitoring cytomegalovirus retinitis prevalence in an HIV-seropositive cohort: the assessment of improvements observed following the introduction of highly active antiretroviral triple therapy. 1058 31

A case of isolated necrotizing cytomegalovirus (CMV) oophoritis disclosed only by necropsy studies in a patient with AIDS, is described. This unusual case report is discussed with a review of the literature dealing with CMV involvement of genital organs in the immunocompromised host, and in patients with HIV infection and AIDS.
Int J STD AIDS 2000 Jun
PMID:Silent oophoritis due to cytomegalovirus in a patient with advanced HIV disease. 1087 16

We undertook a study to compare the safety of intravenous (i.v.) versus oral hydration to prevent nephrotoxicity associated with the use of foscarnet for induction therapy of cytomegalovirus (CMV) infection in HIV-infected persons. Patients, given foscarnet at a dose of 90 mg/kg every 12 h, were randomized to receive either i.v. or oral hydration. Thirty-seven patients were given i.v. hydration and 44 were given oral hydration. Median duration of therapy for both groups was 17 days. There was no difference between the 2 groups in either serious adverse events or rise of creatinine to > or = 2.0 mg/dl. However, serum creatinine, while generally remained within normal limits, increased more in patients who received oral hydration after 10 days of therapy (significant only by slope analysis, P < 0.05). Although i.v. hydration provided better protection against nephrotoxicity, oral hydration was relatively safe and convenient provided that creatinine clearance (CrCl) is monitored closely.
Int J STD AIDS 2000 Oct
PMID:Safety of oral versus intravenous hydration during induction therapy with intravenous foscarnet in AIDS patients with cytomegalovirus infections. 1105 34

Cytomegalovirus (CMV) colitis is a well recognized complication of advanced HIV disease and is only rarely diagnosed in patients with normal immune function. A case of CMV colitis occurring in early HIV infection is described. Although CMV infection is normally confined to patients with advanced HIV disease, it is possible that a number of contributing factors may have led to clinical disease in this patient. CMV colitis is an important diagnosis to consider in all patients who present with a diarrhoeal illness associated with systemic features, regardless of underlying immunosuppression.
Int J STD AIDS 2000 Nov
PMID:CMV colitis in early HIV infection. 1108 90

To assess the effect of highly active antiretroviral therapy (HAART) on cytomegalovirus (CMV) antigenaemia in AIDS patients, 70 patients with CD4+ cell counts < or = 50/mm3 and positive anti-(CMV) immunoglobulin G (IgG) were tested at 15-30 day intervals for CMV antigenaemia. We selected those patients who had been followed up for more than 3 months. Three patient profiles were defined: A, followed up before the introduction of HAART; B, followed up before and after the use of HAART; and C, followed up after the use of HAART. Thirty-nine patients were included, 12 in group A, 17 in group B, and 10 in group C. Group A patients presented a lower median CD4+ cell count compared with groups B and C patients (9, 122 and 127 cells/mm3, respectively), with the increase in the last 2 groups being related to the use of HAART (P<0.001). A lower proportion of positive antigenaemia was observed in group B after the introduction of HAART compared with the time before HAART (P=0.02). HAART caused an immunological improvement and was found to be associated with negativity of CMV antigenaemia.
Int J STD AIDS 2001 Apr
PMID:Effect of highly active antiretroviral therapy on cytomegalovirus antigenaemia in AIDS patients. 1131 74

Tumor necrosis factor (TNF)-alpha and lymphotoxin (LT) alpha/beta play multiple roles in the development and function of the immune system. This article focuses on three important aspects of the effects of these cytokines on the immune response and on autoimmunity. In several experimental systems (Jurkat T cells, murine T-cell hybridomas), TNF-alpha appears to cause a downregulation of signaling through the TCR, revealed by changes in calcium flux, activation of p21, p23 and ZAP70, and a decrease in nuclear activation of NF-kappaB. Previous and present results suggest that TNF-alpha interferes in some manner with signaling through the TCR, at a locus yet to be delineated. Transgenic expression of LTbetaR-Fc in nonobese diabetic (NOD) transgenic mice results in prevention of type 1 diabetes in NOD mice as long as the level of expression of the fusion protein (under the control of the cytomegalovirus promoter) remains above a level of 2-3 microg/ml. Once the expression levels of the fusion protein have dropped below this critical level, the diabetic process resumes and the animals become diabetic at 40-50 weeks of age, whereas nontransgenic littermates develop diabetes by 25-30 weeks of age. The paradoxical effects of neonatal TNF-alpha administration in NOD mice in increasing incidence of and hastening onset of type 1 diabetes, while neonatal anti-TNF administration completely prevents all signs of islet cell autoimmunity, are due partly to the low levels of CD4+CD25+ T cells in NOD mice. These low levels are reduced by a further 50% on neonatal administration of nontoxic levels of TNF-alpha. In contrast, neonatal administration of anti-TNF-alpha results in a dramatic increase in the levels of CD4+CD25+ regulatory T cells, to levels beyond those seen in wild-type untreated NOD mice. TNF-alpha and LTalpha/beta thus have pleomorphic regulatory effects on the development and expression of autoimmunity.
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PMID:Multiple roles for tumor necrosis factor-alpha and lymphotoxin alpha/beta in immunity and autoimmunity. 1211 Jan 33

Herpes simplex virus (HSV-2) and cytomegalovirus (CMV) infections produce brain damage in the newborn, and human papillomavirus (HPV) plays a role in cervical carcinogenesis. To assess the frequency of herpes virus and HPV in semen and its role in transmission, semen from 111 male partners of women with histologically-detected genital HPV infection was analysed for HSV, CMV and HPV infection. We used cell culture to detect HSV and CMV, and polymerase chain reaction (PCR) for HPV. Virological findings in the sperm were correlated to the presence or absence of HPV-associated genital lesions and to the viral type. Viral cultures yielded HSV-2 DNA in 9% and CMV DNA in 6.3% of cases. No correlation was established with a history of clinically apparent infection for HSV. HPV-DNA was detected in 23.4% of semen by PCR techniques: in 48% of subjects with urethral lesions, in 22% of patients with penile lesions, in 2% of patients without HPV-associated lesions. HPV-DNA type 16 was detected in 3.6% of cases. Patients with a positive HPV semen sample and penile or urethral lesions had the same HPV type detected in the two specimens. The study shows a high detection of clinically inapparent HSV and CMV, but does not confirm high HPV prevalence in semen from men without detectable lesions. Our study also suggests that the mechanism for semen contamination by HPV is the exfoliation of infected cells from urethral lesions during semen ejaculation, and probably, by abrasion from penile lesions. This could result in the contamination of semen used in assisted reproductive technology.
Int J STD AIDS 2002 Aug
PMID:Frequency of herpes simplex virus, cytomegalovirus and human papillomavirus DNA in semen. 1219 37

Antigens implicated in the graft-versus-leukemia (GVL) effect in chronic myeloid leukemia (CML) include WT1, PR1, and BCR-ABL. To detect very low frequencies of these antigen-specific CD8+ T cells, we used quantitative polymerase chain reaction (qPCR) to measure interferon-gamma (IFN-gamma) mRNA production by peptide-pulsed CD8+ T cells from HLA-A*0201+ healthy volunteers and from patients with CML before and after allogeneic stem cell transplantation (SCT). Parallel assays using cytomegalovirus (CMV) pp65 tetramers demonstrated the IFN-gamma copy number to be linearly related to the frequency of tetramer-binding T cells, sensitive to frequencies of 1 responding CD8+ T cell/100 000 CD8+ T cells. Responses to WT1 and PR1 but not BCR-ABL were detected in 10 of 18 healthy donors. Responses to WT1, PR1, or BCR-ABL were observed in 9 of 14 patients with CML before SCT and 5 of 6 after SCT, often to multiple epitopes. Responses were higher in patients with CML compared with healthy donors and highest after SCT. These antigen-specific CD8+ T cells comprised central memory (CD45RO+CD27+CD57-) and effector memory (CD45RO-CD27-CD57+) T cells. In conclusion, leukemia-reactive CD8+ T cells derive from memory T cells and occur at low frequencies in healthy individuals and at higher frequencies in patients with CML. The increased response in patients after SCT suggests a quantitative explanation for the greater effect of allogeneic SCT.
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PMID:Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation. 1507 Jul 13


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