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 cytokine tumor necrosis factor (TNF) was assayed in the sera (n = 31) and cerebrospinal fluid (n = 26) of children with acquired immunodeficiency syndrome, using a competitive radioimmunoassay. Elevated serum levels of TNF were found in 15 (79%) of 19 patients with progressive encephalopathy (PE), compared with 1 (8%) of 12 patients without neurologic involvement. There was a significant association of PE with elevated serum TNF levels. Conversely, of 16 patients with elevated serum TNF levels, 15 (94%) were found to have PE, and of 8 patients with serum TNF levels greater than 100 pg/ml, all 8 (100%) had PE. No association was found between cerebrospinal fluid levels of TNF and PE. Neither serum nor cerebrospinal fluid TNF levels correlated with the degree of cachexia. These data suggest that circulating TNF may be responsible for the myelin damage that occurs in human immunodeficiency virus type 1-associated PE.
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PMID:Elevated serum levels of tumor necrosis factor are associated with progressive encephalopathy in children with acquired immunodeficiency syndrome. 274 45

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 type 1 (HIV) infection of the central nervous system is characterized by neuronal loss in discrete areas of the central nervous system. We have previously demonstrated that HIV-infected monocytes in culture with astroglial cells produce high levels (> or = 200 pg/ml) of the cytokine tumor necrosis factor-alpha (TNF alpha). We now demonstrate that TNF alpha (> or = 200 pg/ml) is neurotoxic to cultured primary human fetal cortical neurons at both light and electron microscopic levels. Subtoxic doses of TNF alpha (50 pg/ml) are neurotoxic in combination with the glutamate (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) subtype receptor agonist AMPA (100 microM). The neurotoxic effects of TNF alpha (200 pg/ml) are blocked in part by the AMPA receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione (10 microM). This suggests that TNF alpha may exert neurotoxic effects on human neurons by indirect activation of AMPA receptors, which may be important in the pathogenesis and treatment of HIV-mediated encephalopathy.
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PMID:Neurotoxic effects of tumor necrosis factor alpha in primary human neuronal cultures are mediated by activation of the glutamate AMPA receptor subtype: implications for AIDS neuropathogenesis. 783 47

The cytokine release syndrome (CRS) accompanying OKT3 therapy is a major cause of posttransplant morbidity. The pathogenesis of this syndrome has been attributed to the synthesis of tumor necrosis factor, interleukin 2 (IL-2), interleukin 6 (IL-6), and gamma-interferon in response on T lymphocyte stimulation by OKT3. The hemorrheologic agent pentoxifylline (PTX) inhibits the synthesis of TNF alpha in vitro in response to a variety of stimuli, including OKT3. We performed a randomized, double-blinded trial of PTX during OKT3 induction in recipients of cadaveric renal allografts. Patients received either PTX 800 mg or placebo 2 hr before the initial dose of OKT3 and every 8 hr thereafter during the first 3 posttransplant days. Serum TNF alpha and IL-6 concentrations were measured pre-OKT3 and at 2 and 6 hr post-OKT3 on the first 3 posttransplant days. Despite the achievement of apparently adequate plasma levels of PTX and its active metabolites, no difference was observed in the incidence or severity of clinical manifestations of CRS. Serious manifestations of CRS--including acute pulmonary edema, encephalopathy, and aseptic meningitis--were not seen in either group. Serum TNF alpha and IL-6 concentrations were similar in PTX and control patients throughout the course of the study. Plasma levels of PTX and its active metabolites did not correlate with serum TNF alpha levels, serum IL-6 levels, or the incidence and severity of clinical manifestations of CRS.
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PMID:The effects of oral pentoxifylline on the cytokine release syndrome during inductive OKT3. 811 37

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are important cytokines in the development of brain inflammation during pathological process. During rabies virus infection, the level of these proinflammatory cytokines are enhanced in the brain. In the present study we determined the cellular localization of these two cytokines by immunocytochemistry in brains of rats infected with rabies virus, at different time-intervals of the disease (day 1, 3, 4, 5 and at final stage day 6 post-infection (p.i.)). Cellular identification of IL-1 beta (irIL-1 beta) and TNF alpha (irTNF alpha) immunopositive cells was studied using a polyclonal antibody against these cytokines and against glial fibrillary acidic protein (GFAP) to detect astrocytes and GSA-I-B4 isolectin to detect microglial cells and/or infiltrating macrophages. In brains of control and early infected rats, irIL-1 beta was only detected in fibers located in the hypothalamus, supraoptic and tractus optic nuclei and infundibular nucleus. From day 4 onwards until day 6 p.i., enhanced irIL-1 beta was found and identified either in activated ameboid and/or infiltrated macrophages (amygdala, thalamus, internal capsula, subtantia nigra, septal nuclei and around blood vessels), or in activated ramified cells (hypothalamus and periventricular nucleus, piriformis and cingulate cortex, hippocampus). IrTNF alpha was observed in the brains of rats at a final stage of disease (day 5 and 6 p.i.): in the hypothalamus, the amygdala, the internal capsula, the thalamus, the septal nuclei, the hippocampus, the habenular nuclei and around the blood vessels. Ir-TNF alpha was detected in round cells identified as ameboid microglia and/or infiltrated macrophages. A marked activation of microglial and astroglial cells was observed mainly in the hypothalamus, the thalamus and hippocampus and around the blood vessels, at day 4 p.i. and later, revealing a high central inflammatory reaction in brains of rabies virus infected rats. These results showed that IL-1 beta and TNF alpha are produced in the brain both by local microglial cells and infiltrating macrophages during rabies infection. Thus, these cytokines may play an important role in coordinating the dramatic inflammatory response associated with the rabies-encephalopathy as well as in the neural modification and alteration of brain functions.
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PMID:Induction of immunoreactive interleukin-1 beta and tumor necrosis factor-alpha in the brains of rabies virus infected rats. 878 59

A 28-year-old Japanese woman with Balo's concentric sclerosis developed a rapidly progressive form of encephalopathy. Magnetic resonance imaging (MRI) showed multiple concentric lesions in the central white matter and the cerebellum. The administration of corticosteroid regimen resulted in little benefit. Immunoadsorption plasmapheresis led to a remission within 1 month of onset. Serial MRI study was described here for the first time, which allowed us to observe the development of concentric structures. The observation indicated that, initially, a central core, a round demyelinated area, and surrounding edema appeared around a vessel. Subsequently, concentric demyelinated bands formed simultaneously, not centrifugally, with diminution of the edema. Analysis of cerebrospinal fluid showed elevated levels of interleukin-6 and tumor necrosis factor-alpha. The success of immunoadsorption plasmapheresis therapy in this patient suggests that both humoral demyelinating factors and cell-mediated immunity may be involved in the pathogenesis of this disorder.
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PMID:Serial magnetic resonance imaging (MRI) study of a patient with Balo's concentric sclerosis treated with immunoadsorption plasmapheresis. 906 20

Both in vitro and in vivo studies have implicated a role for tumor necrosis factor-alpha (TNF alpha) in various demyelinating diseases, including HIV-related encephalopathy. To investigate whether intravitreal TNF alpha can induce optic nerve axonal damage in a rabbit eye model, fifteen rabbit eyes were initially injected with TNF alpha (final concentrations: 2U, 20U, and 200U respectively) and studied at varying time intervals for up to 24 weeks post-injection, using light and electron microscopy. Control optic nerves (no injection or diluent injection only) had normal myelinated axons and glia; the myelinated regions, neural retina, retinal glia and vasculature of control retinas were normal. In TNF alpha-exposed optic nerves, intact, degenerating and demyelinated axons were interspersed. Astrogliosis was present, particularly from 8 weeks p.i. and was noted up to 24 weeks. Oligodendrocytes were not severely affected in TNF alpha-exposed optic nerves, and activated macrophages or microglia were not obvious. Axonal degeneration was visible among the more superficial myelinated fibers in TNF alpha-exposed retinas however the neural retina glia were unaffected. These observations suggest that the axonal degeneration induced in TNF alpha-exposed rabbit optic nerves over a 24 week period was most likely related to direct effects of TNF alpha on optic nerve axons, and not primarily due to anterograde degeneration from retinal lesions. In-so-far as neurological pathology in general, and optic nerve degeneration in particular, has been described in AIDS, and TNF alpha levels may be elevated in this disease, it is of great clinical significance that TNF alpha has the capacity to mediate neuronal or axonal injury. If so, strategies to block or inhibit TNF alpha can be pursued for treatment for the neurological symptoms of AIDS.
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PMID:Tumor necrosis factor-alpha (TNF-alpha)-induced optic neuropathy in rabbits. 916 75

A diffuse macular erythroderma and subsequent desquamation after 1 to 2 weeks are two of the five major diagnostic criteria of toxic shock syndrome (TSS). We present the case of a 15-month-old girl with TSS, but without erythroderma or desquamation. She was admitted with high fever, shock, and multiorgan involvement. Minimal or no cutaneous signs were present. Initially the diagnosis of the syndrome of hemorrhagic shock and encephalopathy was made. After 7 days, a TSS toxin 1-producing strain of Staphylococcus aureus was cultured from an inguinal lymph node, where inflammation had already been noticed on admission. Moreover, the girl had no antibodies against this toxin. The serum cytokine profile during the acute phase of her illness showed high levels of tumor necrosis factor-alpha, interleukin-6 and interferon-gamma, as is seen during activation of the immune system by TSS toxin 1. Other possible causes for the patient's illness were excluded. We conclude that the patient had TSS without rash. Without the evidence implicating a TSS toxin 1-producing strain of S. aureus as the cause of her disease, a diagnosis of syndrome of hemorrhagic shock and encephalopathy would have been made. It is possible that some cases of syndrome of hemorrhagic shock and encephalopathy represent a variant of TSS in small children.
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PMID:Toxic shock syndrome without rash in a young child: link with syndrome of hemorrhagic shock and encephalopathy? 967 39

The central nervous system (CNS) is often affected by HIV-1 infection. Over 40% of AIDS cases present with neurological symptoms and CNS lesion are detected by anatomical and pathological studies in 80 to 90% of AIDS cases. There may be infections and tumors secondary to the immunodeficiency and pathologies may occur directly due to the neurotropism of the virus. Neurological problems associated with HIV-infection include encephalopathies, myelopathies, neuropathies and myopathies. HIV-1-induced encephalopathy may develop at any stages of HIV-1 infection and affects all risk groups equally. Its frequency worldwide is between 4 and 65% among individuals seropositive for HIV-1. The frequencies reported differ between studies due to differences in sampling methods, geographical factors, diagnostic criteria and investigative methods used. The pathogenesis of HIV-1-associated encephalopathy is not understood, but there are several hypotheses. The involvement of HIV-1 infected macrophages and microglial cells has been demonstrated. Indirect mechanisms such as release of lymphokines (tumor necrosis factor-TNF alpha- and interleukin-1) and neurotoxicity of the HIV envelope protein, gp 120, have also been suggested. This disorder is known as HIV-1-associated cognitive and motor syndrome. It presents clinically as a form of sub-cortical dementia with cognitive problems, motor deficits and behavioral disorders depending on the type and stage of HIV infection. The diagnosis can only be made after all other infections and tumors common in HIV-1 patients have been ruled out by appropriate investigations such as cerebrospinal fluid analysis, cerebral scan and magnetic resonance imaging. Electrophysiological studies, such as evoked responses and electroencephalograms, are particularly useful in its diagnosis. Anatomical examination shows diffuse paleness of the white matter, multi-nucleated giant cells and microglial nodes. Neuropsychological studies could be of value in diagnosis and in assessing the response to anti-retroviral treatment. There is currently no specific therapy for HIV-1-associated cognitive and motor syndrome. The use of new nucleoside analogue drugs in combination with existing drugs may provide new approaches to managing these patients.
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PMID:[HIV-1 cognitive and motor syndrome]. 929 10


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