Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the past several years immunologists have been fascinated by a series of experiments showing that transforming growth factor beta (TGF beta) suppresses T- and B-lymphocyte growth as well as IgM and IgG production by B cells. Moreover, while exerting chemotactic activity on monocytes and inducing expression of interleukin-1 and interleukin-6 by these cells, TGF beta interferes with bacterially induced tumor necrosis factor alpha production, oxygen radical formation and the adhesiveness of granulocytes to endothelial cells. These mechanisms may provide the basis for the effect of TGF beta to prevent the microvascular changes associated with brain edema formation in bacterial meningitis. Given the potential of lymphocytes as well as macrophages to produce TGF beta 1, this cytokine may exert negative feedback signals on the immune response, provided the cytokine is processed from its latent form to the bioactive homodimer. Potent effects of TGF beta have been observed in experimental animals including the inhibition of the generation of virus-specific cytotoxic T cells and antiviral antibodies as well as the diminution of cellular infiltrates with decreased major histocompatibility complex class-II expression and CD8+ T cells in the tissue of virally infected animals. TGF beta may also be of importance in tumor immunology. By the production of bioactive TGF beta as detected in glioblastoma and acute T-cell leukemia, tumor cells may induce an immunodeficiency state and escape immune surveillance. In inflammation, monitoring of TGF beta in the tissue will bring light on the immune regulation in acute and chronic inflammatory diseases.
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PMID:Modulation of the immune response by transforming growth factor beta. 148 57

We examined the mechanism of increase of manganese superoxide dismutase (Mn SOD) in the cerebrospinal fluid (CSF) in bacterial meningitis (BM). The elevated levels of Mn SOD in the CSF in BM, measured with an enzyme immunoassay method, were more prominent than those in aseptic meningitis (AM) and encephalitis (EN). In AM and EN Mn SOD levels well correlated with levels of neuron-specific enolase and S-100b protein, which are markers of damages to nervous tissues, but did not with any of them in BM. CSF concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) were higher in BM than in AM and EN. From the serial measurements in BM, the peak values of these cytokines chronologically preceded or corresponded to those of Mn SOD. Immunohistochemically, a large number of the glial cells were stained for Mn SOD in the cerebral cortex from a patient with BM. By contrast, in the normal cerebral cortex, the glial cells were negative for Mn SOD staining. These results suggest that the marked increase of Mn SOD in the CSF in BM may be related to the increase of such cytokines as TNF-alpha and IL-1 alpha and that these cytokines may play a role in the induction of Mn SOD in nervous tissues.
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PMID:Elevated cerebrospinal fluid levels of manganese superoxide dismutase in bacterial meningitis. 756 47

Recent studies using a rat model of pneumococcal meningitis have shown that nitric oxide synthase (NOS) inhibitors greatly attenuated microvascular changes and brain edema formation. The site of NO production during bacterial meningitis is unknown. In this study we tested whether primary astrocyte cultures from neonatal rat cortex can be induced to release NO upon stimulation with pneumococci. NO production was assessed by measuring nitrite in the cell culture supernatant using the Griess reaction. Stimulation with heat-killed unencapsulated pneumococci (HKP) increased nitrite concentrations in astrocyte culture supernatants in a dose-dependent fashion. Administration of N-nitro-L-arginine (L-NA), aminoguanidine, L-canavanine, cycloheximide, and dexamethasone prevented the increase in nitrite concentrations. Addition of L-arginine, but not of D-arginine, partially reversed the inhibitory effect of L-NA. Administration of SOD increased nitrite accumulation. Moreover, at 72 h after stimulation with heat-killed pneumococci (10(7) cfu/ml) astrocytes showed an inducible NOS-like immunoreactivity. Accumulation of nitrite was also observed when rat cerebellar neurons and microglia were stimulated with HKP, whereas there was only a slight increase of nitrite in media of rat C6 glioma cells, but no increase of nitrite when the human glioblastoma cell line LN-229 was stimulated with HKP. There was a stronger increase in nitrite levels when astrocytes from Lewis rats were used compared to that from Wistar rats. In conclusion, our study indicates that astrocytes, neurons and microglia are inducible for NO production upon stimulation with pneumococci.
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PMID:Production of nitrite by primary rat astrocytes in response to pneumococci. 764 48

We measured cerebrospinal fluid (CSF) levels of Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) using enzyme immunoassays in 196 neurological patients and 44 controls. The mean Cu/Zn SOD level was 55.8 +/- 27.6 (SD) ng/ml and the Mn SOD, 8.0 +/- 2.5 ng/ml in the controls. Cu/Zn SOD or Mn SOD levels showed neither age-nor sex-related differences in the controls. Both SODs were markedly elevated in cerebrovascular diseases, bacterial meningitis and encephalitis. Mn SOD alone was significantly elevated in neurodegenerative diseases. We compared SODs with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in cerebral infarction and bacterial meningitis. Both SODs were correlated with NSE and S-100b in patients with cerebral infarction, but not in those with bacterial meningitis. This means that elevations of SODs in CSF may not only be due to leakage from damaged nervous tissues, but also to the induction of SOD in lesions. We conclude that the mean SOD levels were elevated in various neurological diseases, and their varied magnitudes may be associated with the underlying diseases.
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PMID:Cerebrospinal fluid levels of superoxide dismutases in neurological diseases detected by sensitive enzyme immunoassays. 793 17

We measured cerebrospinal fluid (CSF) levels of manganese superoxide dismutase (Mn SOD) using an enzyme immunoassay method in 19 patients with bacterial meningitis (BM), 33 with aseptic meningitis (AM) and 13 with encephalitis (EN), and examined the significance of their elevations, especially in BM. 1) In BM, the Mn SOD levels were obviously high, ranging from 10.4 to 1179.2 ng/ml. The mean level of Mn SOD was 234.6 +/- 306.7 (SD) ng/ml and 18 patients showed abnormal levels of Mn SOD (more than 13.1 ng/ml). On the other hand, in the remaining 2 diseases, the elevation of SOD levels was not remarkable: the mean levels of Mn SOD in AM and EN were 20.6 +/- 11.6 ng/ml and 41.9 +/- 23.6 ng/ml, respectively. 2) In AM and EN, Mn SOD levels well correlated with NSE or S-100b levels which are the markers of nervous tissue damages. But there was no correlation between the Mn SOD levels in BM and these markers. 3) In BM, there was a positive relationship between Mn SOD and total protein levels, but the disease days showing peak levels were different between them. In addition, Mn SOD levels showed no correlation with cell counts in CSF. 4) In BM, CSF levels of TNF-alpha and IL-1 alpha were remarkably high, whereas in AM and EN, the increases of these cytokines were not marked. And these cytokines in BM showed the peak values in the disease day before or when Mn SOD reached the peak levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The significance of elevated Mn SOD level in cerebrospinal fluid of patients with bacterial meningitis--its relation to cytokine]. 802 25

To evaluate significance of superoxide dismutase in neurological diseases, we measured cerebrospinal fluid (CSF) levels of copper-zinc superoxide dismutase (Cu/Zn SOD) and manganese superoxide dismutase (Mn SOD) using enzyme immunoassay methods in 181 neurological patients and 43 controls. The mean level of Cu/Zn SOD in CSF of controls was 54.4 +/- 28.7 ng/ml, and that of Mn SOD 8.1 +/- 2.5 ng/ml, although other methods have reported that Mn SOD is undetectable in CSF. Cu/Zn SOD or Mn SOD showed no statistical difference in age or sex of the controls. The elevation of both SOD levels was marked in acute diseases such as cerebrovascular diseases (CVD), bacterial meningitis and encephalitis, but mild in aseptic meningitis. The elevation of Cu/Zn SOD level was more prominent than that of Mn SOD in CVD, whereas vice versa in bacterial meningitis and encephalitis. In neurodegenerative diseases and cervical spondylosis, only Mn SOD level was significantly elevated. To examine the source of CSF SOD, we compared it with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in cerebral infarction and bacterial meningitis. Both SOD levels were correlated with NSE and S-100b levels in patients with cerebral infarction, but in bacterial meningitis no significant relationship was found among SOD levels, NSE and S-100b levels. This means that elevations of SODs in CSF may be due to not only damage of the nervous tissues but also the other mechanisms, as induction of SOD in the lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Superoxide dismutase in cerebrospinal fluid in patients with neurological diseases]. 833 70

Neisseria meningitidis serogroup C is a major cause of bacterial meningitis and septicaemia. This human pathogen is protected by a capsule composed of alpha2,9-linked polysialic acid that represents an important virulence factor. In the majority of strains, the capsular polysaccharide is modified by O-acetylation at C-7 or C-8 of the sialic acid residues. The gene encoding the capsule modifying O-acetyltransferase is part of the capsule gene complex and shares no sequence similarities with other proteins. Here, we describe the purification and biochemical characterization of recombinant OatC. The enzyme was found as a homodimer, with the first 34 amino acids forming an efficient oligomerization domain that worked even in a different protein context. Using acetyl-CoA as donor substrate, OatC transferred acetyl groups exclusively onto polysialic acid joined by alpha2,9-linkages and did not act on free or CMP-activated sialic acid. Motif scanning revealed a nucleophile elbow motif (GXS286XGG), which is a hallmark of alpha/beta-hydrolase fold enzymes. In a comprehensive site-directed mutagenesis study, we identified a catalytic triad composed of Ser-286, Asp-376, and His-399. Consistent with a double-displacement mechanism common to alpha/beta-hydrolase fold enzymes, a covalent acetylenzyme intermediate was found. Together with secondary structure prediction highlighting an alpha/beta-hydrolase fold topology, our data provide strong evidence that OatC belongs to the alpha/beta-hydrolase fold family. This clearly distinguishes OatC from all other bacterial sialate O-acetyltransferases known so far because these are members of the hexapeptide repeat family, a class of acyltransferases that adopt a left-handed beta-helix fold and assemble into catalytic trimers.
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PMID:The polysialic acid-specific O-acetyltransferase OatC from Neisseria meningitidis serogroup C evolved apart from other bacterial sialate O-acetyltransferases. 1898 88