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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor is a cytokine that participates in the mediation of numerous diseases associated with inflammation, cachexia, shock, and tissue injury. Early studies of the biology of TNF delineated its hormonal actions as well as its systemic toxicity. More recent investigations have drawn attention to its paracrine actions that predominate when it is produced locally in the brain or vital organs. For instance, when compartmentalized production of TNF occurs in the central nervous system it directly mediates fever, anorexia, and altered whole-body metabolism. Since these changes are mediated within the neural network they occur independently of simultaneously sampled serum TNF levels. These paracrine actions of TNF have implications for diseases associated with production of TNF in tissues (e.g. HIV cerebritis, multiple sclerosis, cerebral malaria and cancer), because they may differ markedly from the hormone like-actions associated with systemic release. Since TNF may be beneficial in some diseases yet injurious in others, both the hormonal and paracrine actions must be precisely defined in order to formulate novel treatment strategies based on either enhancing its useful effects, or suppressing toxicity.
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PMID:Tumor necrosis factor in metabolism of disease: hormonal actions versus local tissue effects. 134 May 27

The authors report the results of a study realized at National Hospital of Niamey (Republic of Niger) from october 1981 to may 1986. Among 4820 patients living in Western Niger, 410 (8.5%) had neurological disorders. Out of 16 recognized syndromes 6 constitute 75.2%: comas, paraplegias, cranial nerves palsies, convulsions, hemiplegias and sciaticas. An etiological diagnosis is made in 269 patients. From 15 diseases 4 totalize 73.5%: there are medullar compressions, infections of the central nervous system (bacterial meningitis, cerebral malaria), cerebral vascular disturbances and metabolic encephalopathies. POTT's disease is the most common cause of medullar compression with paraplegia and arterial hypertension is a very important etiologic factor of cerebral vascular attack (42.2 and 44.4% respectively). Parkinsonian syndrome and multiple sclerosis seem rare. The diagnosis of cerebral tumor is very uncommon but this is in relation to the absence of autopsy and of recent investigation (scanner). No case of tuberculous meningitis is noted and this can't be explained by the authors in a major tuberculous endemic area.
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PMID:[Neurologic diseases in Niger]. 189 15

Cytokines are now recognized to play important roles in the physiology of the central nervous system (CNS) during health and disease. Tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of several human CNS disorders including multiple sclerosis, AIDS dementia, and cerebral malaria. We have generated transgenic mice that constitutively express a murine TNF-alpha transgene, under the control of its own promoter, specifically in their CNS and that spontaneously develop a chronic inflammatory demyelinating disease with 100% penetrance from around 3-8 weeks of age. High-level expression of the transgene was seen in neurons distributed throughout the brain. Disease is manifested by ataxia, seizures, and paresis and leads to early death. Histopathological analysis revealed infiltration of the meninges and CNS parenchyma by CD4+ and CD8+ T lymphocytes, widespread reactive astrocytosis and microgliosis, and focal demyelination. The direct action of TNF-alpha in the pathogenesis of this disease was confirmed by peripheral administration of a neutralizing anti-murine TNF-alpha antibody. This treatment completely prevented the development of neurological symptoms, T-cell infiltration into the CNS parenchyma, astrocytosis, and demyelination, and greatly reduced the severity of reactive microgliosis. These results demonstrate that overexpression of TNF-alpha in the CNS can cause abnormalities in nervous system structure and function. The disease induced in TNF-alpha transgenic mice shows clinical and histopathological features characteristic of inflammatory demyelinating CNS disorders in humans, and these mice represent a relevant in vivo model for their further study.
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PMID:Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha. 747 82

TNF, a potent immunoregulatory cytokine, is associated with inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and cerebral malaria when produced in excess. Antimalarial agents such as chloroquine and hydroxychloroquine have been used to treat some rheumatic diseases. Chloroquine was reported to inhibit production of TNF, although the underlying mechanism is poorly understood. In RAW 264.7 cells stimulated with LPS, addition of chloroquine at nontoxic concentrations did not inhibit induction of TNF mRNA and NF-kappaB activity. In the same cells, synthesis and steady state level of 26-kDa pro-TNF were also not significantly reduced by addition of chloroquine, while only small amount of 17-kDa mature TNF was detected in the medium. A pulse-chase experiment of pro-TNF produced in chloroquine-treated cells showed significant inhibition of processing of prohormone. Hydroxychloroquine showed similar inhibitory effect, whereas other lysosomal inhibitors such as ammonium chloride and methylamine had no effect on the production of TNF. Our results suggest that chloroquine inhibits production of TNF at the step of processing of membrane-bound pro-TNF to make soluble mature protein in a lysosome-independent manner.
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PMID:Chloroquine inhibits processing of tumor necrosis factor in lipopolysaccharide-stimulated RAW 264.7 macrophages. 914 7

This study was undertaken to attempt to identify correlations between microsporidial seroprevalence data in man, clinical diseases and groups of people at the risk of HIV/AIDS infection. Groups of patients were selected according to the predilection of members of the genus Encephalitozoon for nervous and kidney tissue. Female prostitutes and alcohol and intravenous drug abusers were selected as groups at risk of HIV/AIDS infections. A total of 401 samples of human sera were examined for the presence of antimicrosporidial IgG antibodies by ELISA test with a titre of 600 considered borderline positivity. The highest occurrence of antimicrosporidial antibodies was found in the groups of alcohol abusers (16% from 43 patients), intravenous drug abusers (11% from 9 patients) and prostitutes (10% from 80 women) for E. cuniculi antigen and in the groups of psychiatric patients (14% from 44 patients), malaria patients (11% from 38 patients) and alcohol abusers (7% from 43 patients) for E. hellem antigen. The occurrence of specific antibodies of the six examined diagnostic units (glomerulonephritis chronica, pyelonephritis chronica, schizophrenia, dementia, multiple sclerosis and cerebral stroke) was statistically significant only in patients with pyelonephritis chronica and dementia (p < 0.05). No cases of microsporidial infection were found among the female prostitutes by parasitological examination, although one case of giardiasis was identified. Sera of patients with high anti-E. cuniculi and anti-E. hellem antibodies (titres in ELISA of 600 and above) were confirmed by Western blot using E. cuniculi and E. hellem polypeptides, respectively. These results suggest that the examined patients could show residual antibodies from past or latent infections.
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PMID:The serological surveillance of several groups of patients using antigens of Encephalitozoon hellem and E. cuniculi antibodies to microsporidia in patients. 968 20

Tumor necrosis factor alpha (TNFalpha), an early cytokine produced by activated macrophages, plays an essential role in normal and pathological inflammatory reactions. The excessive production of TNFalpha is prevented by the so-called "macrophage-deactivating factors." This study examines the role of two structurally related neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating peptide (PACAP), as inhibitors of TNFalpha. Both VIP and PACAP inhibit TNFalpha production from lipopolysaccharide-stimulated RAW 246.7 cells in a dose- and time-dependent manner. Although the activated cells express mRNA for all three VIP/PACAP receptors, agonist and antagonist studies indicate that the major receptor involved is VIP1R. VIP/PACAP inhibit TNFalpha gene expression by affecting both NF-kB binding and the composition of the cAMP responsive element binding complex (CREB/c-Jun). Two transduction pathways, a cAMP-dependent and a cAMP-independent pathway, are involved in the inhibition of TNFalpha gene expression and appear to differentially regulate the transcriptional factors involved. Because TNFalpha plays a central role in various inflammatory diseases such as endotoxic shock, multiple sclerosis, cerebral malaria, and various autoimmune conditions, the down-regulatory effect of VIP/PACAP may have a significant therapeutic potential.
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PMID:Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit tumor necrosis factor alpha transcriptional activation by regulating nuclear factor-kB and cAMP response element-binding protein/c-Jun. 981 54

Adhesion molecules on the endothelial surface of the blood-brain barrier (BBB) play an important role in the pathogenesis of many encephalopathies, including multiple sclerosis (MS) and cerebral malaria (CM). The expression of four surface molecules of relevance to MS and CM on the immortalized human umbilical vein endothelial cell line, ECV304, was investigated using immunofluorescence flow cytometry. We found that ECV304 cells express intercellular adhesion molecule-1 (ICAM-1) and low levels of CD36, but not vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. This expression pattern was unaltered on ECV304 cells which were co-cultured with C6 glioma cells; conditions under which the endothelial cells display enhanced barrier formation. Tumour necrosis factor-alpha (TNF-alpha), which is elevated in MS and CM, decreased the integrity of the barrier in co-cultured endothelial cells and upregulated the expression of ICAM-1 nine-fold. The significance of elevated ICAM-1 expression in relation to the binding of parasitised erythrocytes at the BBB in CM is discussed.
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PMID:Upregulation of intercellular adhesion molecule-1 expression on human endothelial cells by tumour necrosis factor-alpha in an in vitro model of the blood-brain barrier. 1036 90

The heme oxygenase (HO) system was identified in the early 1970s as a distinct microsomal enzyme system that catalyzes formation of bile pigments (Maines and Kappas, 1974). Up to the early 1990s the system was considered only as a "molecular wrecking ball" (Lane, 1998) for degradation of the heme molecule and production of toxic waste products, CO and bile pigments. For those years, the HO system remained relatively unknown to the research community. In a rather short span of the past 10 years following the discovery of high levels of a second form of the enzyme, HO-2, in the brain, suggesting that "heme oxygenase in the brain has functions aside from heme degradation" (Sun et al., 1990); concomitant with finding that another toxic gas, NO, is a signal molecule for generation of cGMP (Ignarro et al., 1982), the system was propelled into main stream research. This propulsion was fueled by the realization of the multiple and diverse functions of heme degradation products. Heme oxygenase has now found relevance in all kinds of human pathophysiology ranging from stroke, cancer, multiple sclerosis, and malaria to transplantation and immune response. As it turns out, its potential benefits are mesmerizing investigators in diverse fields (Lane, 1998). The most recent findings with HO-2 being a hemoprotein and potentially an intracellular "sink" for NO (McCoubrey et al., 1997a; Ding et al., 1999), together with the discovery of the third form of the enzyme, HO-3 (McCoubrey et al., 1997b), are likely to insure the widespread interest in the enzyme system in the coming years. The present review is intended to highlight molecular properties of HO isozymes and their likely functions in the brain. Extended reviews of the system are found in Maines (1992, 1997).
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PMID:The heme oxygenase system and its functions in the brain. 1087 44

Association and linkage studies have established the importance of the major histocompatibility complex (MHC) in the susceptibility for multiple sclerosis (MS). We carried out a case-control study to investigate the ancestral haplotype A30B18DR3 and MS in the Nuoro population of Sardinia, which is isolated and genetically distinct from other populations in the Mediterranean basin and characterized by genetic homogeneity, high level of inbreeding, low migration, high prevalence of MS, high frequency of the relevant haplotype, and high past malaria prevalence. Cases and controls were serologically typed for the currently recognized HLA-A, B, and DR antigens. We used a log-linear approach to fit a wide class of models. We tested our hypothesis comparing different models via a likelihood ratio test. We overcame the complication due to unknown gametic phase using expectation-maximization (EM) algorithm as the estimation method. We estimated confidence intervals for odds ratio by using a profile likelihood approach. We found that: (1) the ancestral haplotype A30B18DR3 was associated to MS after allowing for a possible stratification in cases and controls; (2) DR3 allele was conditional independent on disease status, given A30B18 haplotype; (3) there was a tendency for ORs for the high-risk haplotypes to be higher in the high malaria strata; however, this indication did not achieve statistical significance (P = 0.11).
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PMID:Association between the ancestral haplotype HLA A30B18DR3 and multiple sclerosis in central Sardinia. 1118 Apr 52

Though many details are known about the epidemiology of multiple sclerosis (MS), its aetiology has remained an enigma. To find a solution to this problem, the concept of so called 'anophelism without malaria' was put on trial. 'Anophelism without malaria' is a basic assumption of the epidemiology of malaria. It means that there is no transmission of malaria in the temperate zone, although the insect vector (the different species of anopheles) can be found nearly everywhere. Starting with the results from blood tests of five patients suffering from MS which indicate an infection with plasmodia, the old hypothesis of the malarial aetiology of MS (Mannaberg 1899) is reappraised and compared with today's pathological findings. A comparison of the old map of malaria with the later distribution of MS in the USA has been made, supporting the assumption that an infection with plasmodia in early childhood prevents a later disease, while a silent infection at the time of adolescence or later is its cause.
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PMID:Is multiple sclerosis caused by a silent infection with malarial parasites? A historico-epidemiological approach: part I. 1151 18


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