Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the serum concentrations of tumor necrosis factor (TNF-alpha), interleukin 1-beta (IL-1-beta), p24 antigen, CD4+/CD8+ cells and immunoglobulins in 35 children at various stages of human immunodeficiency virus infection. Serum TNF-alpha concentrations were significantly higher in children with lymphocytic interstitial pneumonitis and in children with mildly symptomatic illness than in asymptomatic children or children with acquired immunodeficiency syndrome. In addition serum IL-1 concentrations were significantly higher in patients with lymphocytic interstitial pneumonitis than in asymptomatic, mildly symptomatic, or acquired immunodeficiency syndrome patients. Children with lymphocytic interstitial pneumonitis had the highest serum TNF-alpha and IL-1 concentrations. Among symptomatic children serum TNF-alpha concentrations correlated positively with those of IL-1, and both were inversely related to the amount of p24 antigen. TNF-alpha values in excess of 50 pg/ml were observed more frequently among patients with CD4+ cell count greater than 400/mm3 than in those with CD4+ cell count less than 400/mm3. We did not find any association between elevated TNF-alpha concentrations and cachexia, opportunistic infections or progressive encephalopathy.
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PMID:Serum tumor necrosis factor alpha, interleukin 1-beta, p24 antigen concentrations and CD4+ cells at various stages of human immunodeficiency virus 1 infection in children. 167 77

The blood coagulation and fibrinolysis of 33 patients with compensated liver cirrhosis and 31 patients with hepatocellular carcinoma were examined using several markers, namely thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), antithrombin-III (AT-III) and prothrombin time, and the relationship between these markers, endotoxemia, and TNF-alpha was examined. These patients had no complications due to hepatic failure, such as infections, encephalopathy, ascites, G-I bleeding and clinical DIC. PIC was not elevated, but TAT tended to be elevated in LC and significantly elevated in HCC. AT-III was decreased in LC and HCC, and the blood endotoxin was partly positive in LC and HCC, but was not correlated with AT-III or PT. The TAT level in the blood-endotoxin-positive patients measured by endospecy methods was higher than that in the negative patients, and was significantly correlated with the blood endotoxin level in the LC and HCC patients (r = 0.57, r = 0.88, p < 0.01). No relationship was observed between TNF-alpha and blood endotoxin. In conclusion, (1) blood coagulability was activated already in compensated LC and HCC, but was not connected with fibrinolysis, (2) the activation of coagulability was closely related with endotoxemia, and (3) TNF-alpha was not correlated with blood endotoxin or TAT.
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PMID:[Blood coagulation and fibrinolysis in relation to endotoxemia in liver cirrhosis and hepatocellular carcinoma]. 756 21

Microglial cell activation, myelin alteration, and abundant tumor necrosis factor (TNF)-alpha message have been observed in the brains of some human immunodeficiency virus type 1 (HIV-1)-infected and demented patients. We therefore used cultures of purified human microglia and oligodendrocytes derived from adult human brain to examine the role of TNF-alpha in HIV-1 encephalopathy. Human microglia synthesize TNF-alpha message and protein in vitro. When these cells were infected with HIV-1 JrFL and maintained in the presence of TNF-alpha antibodies, soluble TNF-alpha receptors, or the TNF-alpha inhibitor pentoxifylline, viral replication was delayed or strongly inhibited. Both human microglia and oligodendrocytes express the two TNF receptors, TNF-R1, which has been implicated in cytotoxicity, and TNF-R2. While TNF-alpha may enhance HIV-1 replication in an autocrine manner, it is not toxic for microglia. In contrast, recombinant human TNF-alpha causes oligodendrocyte death in a dose-dependent manner. In situ detection of DNA fragmentation in some cells indicated that oligodendrocyte death may occur by apoptosis. Addition of live microglia or medium conditioned by these cells also resulted in 30 to 40% oligodendrocyte death, which was largely prevented by TNF-alpha inhibitors. We propose that TNF-alpha plays a dual role in HIV-1 encephalopathy, enhancing viral replication by activated microglia and damaging oligodendrocytes. Thus, TNF-alpha inhibitors may alleviate some of the neurological manifestations of acquired immunodeficiency syndrome.
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PMID:In vitro evidence for a dual role of tumor necrosis factor-alpha in human immunodeficiency virus type 1 encephalopathy. 766 40

Human immunodeficiency virus infection leads to a deregulated production of a number of cytokines. Some of them (IL-1, IL-6, TNF-alpha, interferon-gamma) are produced in increased amounts in vivo, whereas the production of IL-2 is decreased. This latter abnormality plays a pivotal role in the establishment of the immunodeficiency. Some cytokines (IL-1, IL-6, TNF-alpha) stimulate the in vitro replication of HIV, whereas others (mainly the interferons) inhibit it. The effect of cytokines in vivo in the spreading of HIV remains, however, largely unknown. Cytokines may also be involved in the development of many clinical manifestations associated with HIV infection. IL-1, IL-6 and TNF-alpha may play a role in tissue damages associated with opportunistic infections, in HIV-related encephalopathy and in cachexia. Cytokines, mainly IL-6, IL-10 and IL-13, may stimulate the growth of malignant cells during Kaposi sarcoma or lymphomas. Better knowledge of the role of cytokines during HIV infection should allow new therapeutic approaches based on the use of either recombinant cytokines or specific antagonists, with the aim of limiting both HIV spreading and the clinical manifestations of this infection.
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PMID:Cytokines in HIV infection. 792 84

Recent studies in our laboratory and that of Dr. Howard Gendelman have revealed two important pathways for neuronal damage during HIV-1 encephalopathy in children. First, substantial numbers of astrocytes are actively or latently infected with HIV-1. Astrocyte infection may lead to neuronal dysfunction through loss of supporting growth factors, excitotoxicity due to dysregulation of neurotransmitter reuptake, and loosening of the blood-brain barrier permitting further seeding of HIV-1 in the CNS. Significantly, infection of astrocytes is marked by near-exclusive synthesis of early regulatory gene products of HIV-1, while structural proteins characteristic of productive infection are found in macrophages, microglia and multinucleated giant cells. We propose the term 'restricted' to denote the non-productive infection found in astrocytes. Second, HIV-1-infected macrophages initiate inflammatory processes which are amplified through cell-cell interactions with astrocytes. Macrophage-astrocyte interactions produce arachidonic metabolites and potentially neurotoxic cytokines (TNF-alpha and IL-1 beta), leading to astroglial activation and proliferation which then amplifies these cellular processes. These new findings suggest that two major pathways leading to neurotoxicity in pediatric AIDS encephalopathy are linked to HIV-1 infection through astrocyte-mediated processes, and help explain how small numbers of productivity infected cells indirectly cause widespread tissue pathology and elicit profound neurological impairment.
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PMID:HIV-1 infection of the developing nervous system: central role of astrocytes in pathogenesis. 806 56

Monocytes/macrophages play a critical role in the pathogenesis of HIV infection, both as targets for virus replication and as sources of production of multifunctional cytokines. Endothelins, peptides with potent vasoconstricting activities originally isolated from endothelial cells, are also produced and secreted by macrophages in a manner similar to that of other cytokines. In an attempt to explore the potential role of endothelins in HIV-infection, we investigated the effect of the HIV-1 envelope glycoprotein, glycoprotein 120, on monocytic endothelin-1 production. This glycoprotein has been identified as a potent stimulator of monokines such as TNF-alpha and IL-6, which have been implicated as potential mediators of HIV-encephalopathy. We found that glycoprotein 120, similar to LPS, stimulates the secretion of endothelin-1, as well as TNF-alpha, from macrophages in a concentration-dependent manner. Using reverse transcriptase polymerase chain reaction, we found that circulating monocytes in HIV-infected individuals show a distinct expression of the endothelin-1 gene that is not detectable in healthy controls, indicating chronic activation of this gene in HIV-infection. In addition, cerebral macrophages in patients with HIV-encephalopathy were strongly positive for endothelin. Thus, monocytic endothelins appear to be stimulated during HIV infection. Their potent vasoactive properties render them potential candidates for mediating alterations in the cerebral perfusion pattern associated with the AIDS dementia complex.
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PMID:Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. 848 49

Human immunodeficiency virus type I (HIV-1)-derived envelope glycoprotein 120 (gp120) is proposed to play an important role in HIV-1 neuropathology. Gp120 may act through mediators including proinflammatory cytokines. Here, we investigated the regulation of the IL-1beta system [IL-1beta, IL-1 receptor type I (IL-1RI), IL-1 receptor antagonist (IL-1Ra)], TNF-alpha and TGF-alpha mRNAs in the rat central nervous system (CNS) in response to the constant intracerebroventricular (ICV) microinfusion of HIV-1 gp120 for 72 h and 144 h. The results show that gp120: (1) increased IL-1beta and IL-1Ra mRNAs levels in the same samples from the cerebellum, hypothalamus and midbrain, with the largest increase in the hypothalamus; (2) induced profiles of IL-1beta mRNA and IL-1Ra mRNA that were highly intercorrelated; (3) increased the hypothalamic TNF-alpha mRNA levels; and (4) did not affect the IL-1RI mRNA and TGF-alpha mRNA levels in any brain region. A dysregulation in the IL-1beta/IL-1Ra CNS balance and a mutual induction and synergistic activity of IL-1beta and TNF-alpha could result in a deleterious amplification cycle of cellular activation and cytotoxicity with implications to HIV-1-associated encephalitis, encephalopathy, and neurological manifestations.
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PMID:HIV-1 envelope glycoprotein 120 regulates brain IL-1beta system and TNF-alpha mRNAs in vivo. 928 32

To examine the role of tumor necrosis factor (TNF)-alpha in the pathogenesis of degenerative disorders of the central nervous system (CNS), transgenic mice were developed in which expression of murine TNF-alpha was targeted to astrocytes using a glial fibrillary acidic protein (GFAP)-TNF-alpha fusion gene. In two independent GFAP-TNFalpha transgenic lines (termed GT-8 or GT-2) adult (>4 months of age) animals developed a progressive ataxia (GT-8) or total paralysis affecting the lower body (GT-2). Symptomatic mice had prominent meningoencephalitis (GT-8) or encephalomyelitis (GT-2) in which large numbers of B cells and CD4+ and CD8+ T cells accumulated at predominantly perivascular sites. The majority of these lymphocytes displayed a memory cell phenotype (CD44high, CD62Llow, CD25-) and expressed an early activation marker (CD69). Parenchymal lesions contained mostly CD45+ high, MHC class II+, and Mac-1+ cells of the macrophage microglial lineage with lower numbers of neutrophils and few CD4+ and CD8+ T cells. Cerebral expression of the cellular adhesion molecules ICAM-1, VCAM-1, and MAdCAM as well as a number of alpha- and beta-chemokines was induced or upregulated and preceded the development of inflammation, suggesting an important signaling role for these molecules in the CNS leukocyte migration. Degenerative changes in the CNS of the GFAP-TNFalpha mice paralleled the development of the inflammatory lesions and included primary and secondary demyelination and neurodegeneration. Disease exacerbation with more extensive inflammatory lesions that contained activated cells of the macrophage/microglial lineage occurred in GFAP-TNFalpha mice with severe combined immune deficiency. Thus, persistent astrocyte expression of murine TNF-alpha in the CNS induces a late-onset chronic inflammatory encephalopathy in which macrophage/microglial cells but not lymphocytes play a central role in mediating injury.
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PMID:Late-onset chronic inflammatory encephalopathy in immune-competent and severe combined immune-deficient (SCID) mice with astrocyte-targeted expression of tumor necrosis factor. 973 27

Human immunodeficiency virus type 1 (HIV-1) infection of astrocytes has been demonstrated in the brains of patients with AIDS dementia complex (ADC) and may play an important role in neuropathological pathways of HIV-related encephalopathy. SIVmac-infected monkeys develop an acquired immunodeficiency syndrome (AIDS) with CNS involvement which is quite similar to that seen in human AIDS. We investigated the in vitro infection of primary astrocytes derived from adult macaques with SIVmac251 or an isogenic virus that expresses a non-functional Nef protein (SIVmac251-DeltaNef). In both cases we observed that viral expression was mostly limited to early regulatory genes after a transient phase of late viral gene expression (i.e. env and gag), as reported for HIV-1-infected astrocytes in vivo. Late viral gene expression could be reactivated by TNF-alpha, GM-CSF and IFN-gamma treatment of SIVmac251-infected astrocytes but not by similarly treated SIVmac251-DeltaNef-infected cells. Our findings suggest that Nef is not involved in the restricted expression of SIV in astrocytes, but may be important for astrocytes to function as a viral reservoir in the CNS. In additional experiments, we demonstrated Rev and Nef expression in 17 of 27 primary astrocyte cultures derived from macaques infected by SIVmac251. Nef was located in the cytoplasm of astrocytes infected by SIVmac251 in vivo, but displayed perinuclear localisation after infection in vitro. Attempts to activate late viral gene expression by astrocytes infected in vivo using cytokines or by coculture with human cord blood mononuclear cells were unsuccessful.
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PMID:Simian immunodeficiency virus mac251 infection of astrocytes. 1087 8

Clinical studies of the preterm neonate and animal models of asphyxial brain injury both support a role for proinflammatory cytokines in central nervous system (CNS) injury. There are fewer studies of perinatal CNS injury in the full-term neonate. We have performed a prospective cohort study of full-term infants with perinatal asphyxia. Using archived neonatal blood samples, we have analyzed the serum levels of several proinflammatory cytokines. Preliminary results demonstrate an increase in IL-1, IL-6, and TNF-alpha in those children who are deceased at 1 year or who have a diagnosis of cerebral palsy versus those with normal neuromotor outcome. Further analysis will include correlations of cytokine levels with injury on MRI spectroscopy, with neonatal clinical markers of encephalopathy, and with later neurodevelopmental outcome.
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PMID:Human perinatal asphyxia: correlation of neonatal cytokines with MRI and outcome. 1159 23


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