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)

The neurologic symptoms in human shigellosis have often been attributed to Shiga toxin, although its exact role has not been determined. By use of a [3H] thymidine-labeled HeLa cell assay, cytotoxic activity was demonstrated in stool but not cerebrospinal fluid or serum from five patients with shigellosis presenting with seizures or encephalopathy. Bacterial isolates produced 16.0-88.2 CD50 (50% cytotoxic dose) of cytotoxin/mg of protein. The toxin activity in stool and the cytotoxic activity of the isolates were not neutralized by antiserum to purified Shiga toxin. DNA hybridization studies showed that Shigella isolates from these patients lacked the structural genes for Shiga toxin. The cytotoxin produced was also distinct from Shiga-like toxins I and II. Sonicates of the Shigella strains injected intraperitoneally into mice caused lethargy and lethality. The toxin activity was heat-labile and sensitive to trypsin, indicating that its active component is protein. Ultrafiltration and gel filtration chromatography showed a molecular mass of 100-125 kDa. Thus Shiga toxin production is not essential for the development of neurologic manifestations of shigellosis; other toxic products may play a role.
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PMID:The association of Shiga toxin and other cytotoxins with the neurologic manifestations of shigellosis. 232 46

A 71-year-old woman presented with altered level of consciousness following episodes of diarrhea and abdominal pain. Shigella sonnei was later cultured from her stool. Although neurological complications, primarily seizures, have been reported sequelae in children afflicted shigellosis, there are only rare cases of encephalopathy in affected adults. A brief discussion of the neurological complications of Shigella infection and the yet undetermined role of Shiga toxin in producing neurotoxicity are presented.
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PMID:Shigella-induced encephalopathy in an adult. 892 41

We report 81 of 107 cases of hemolytic uremic syndrome (HUS), admitted between July 1994 and February 1996, following an outbreak of Shigella dysenteriae type 1 dysentery in Kwazulu/Natal. All patients, excluding 1, were black with a mean age of 38 months (range 1-121); 50 (61.7%) were males. The mean duration of dysentery was 11.3 days (range 1-41) and HUS 15 days (range 1-91). Most patients had acute oliguric renal failure (90.1%), 42 (51.6%) required peritoneal dialysis. Complications included encephalopathy 30 (37.0%), convulsions 12 (14.8%) and hemiplegia 2 (2.3%), gastrointestinal perforation 8 (9.9%), protein losing enteropathy 26 (32.1%), toxic megacolon 4 (4.9%), rectal prolapse 5 (6.2%), hepatitis 11 (13.6%), myocarditis 5 (6.2%), congestive cardiac failure 3 (3.7%), cardiomyopathy 3 (3.7%), infective endocarditis 1 (1.2%), septicemia 15 (18.5%), disseminated intravascular coagulation 17 (21%). Leukemoid reactions were found in 74 (91.3%) patients, hyponatremia in 56 (69.1%), and hypoalbuminemia in 67 (82.7%). Stool culture for Shigella dysenteriae type I was positive in only 7 (8.6%) patients; Shiga toxin assays were not performed. Outcome was as follows: recovery 32 (39.5%), impaired renal function 8 (9.9%), chronic renal failure 26 (32.1%), end-stage renal disease 1 (1.2%), and death 14 (17.3%) patients.
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PMID:Post-dysenteric hemolytic uremic syndrome in children during an epidemic of Shigella dysentery in Kwazulu/Natal. 932 80

The initial brain lesions in rabbits given intravenous Shiga toxin 2 (Stx2) were noted at 24 h in an area around the third ventricle (Fujii et al., Infect Immun 1996, 64: 5053-60). This result implied that Stx2 is present in the cerebrospinal fluid (CSF) despite the fact that the toxin was administered intravenously. We measured Stx2 activity in CSF by using a Vero cell cytotoxicity assay at various times after an intravenous injection of Stx2. Stx2 was detected from 2 h after the injection, and its concentration in CSF remained at a high level for a further 6 h. Fifty percent lethal doses (LD 50) of Stx2 were measured in rabbits after intravenous and intrathecal Stx2 injections; The LD 50 after an intrathecal injection of Stx2 was 0. 36 microg/kg, which was 9.2-fold lower than that of an intravenous injection of Stx2 (3.4 microg/kg). Magnetic resonance images obtained after an intrathecal Stx2 injection (5 microg/kg) were compared with those obtained after an intravenous Stx2 injection (5 microg/kg). At 48 h, the cerebellar lesions had spread from the area in contact with the CSF on a T2-weighted image, which suggests that the intrathecal Stx2 may invade the cerebellum directly. We then examined whether anti-Stx2 antiserum injected intrathecally protects rabbits against brain damage. Eighty percent of the rabbits infected with Stx2 at 5 microg/kg died within 8 days from brain damage. Rabbit anti-Stx2 sera (with titres of x16 and x64 by the Ouchterlony precipitation method) were administered into the CSF space through the cisterna magna. All the rabbits ( n=10) survived when they were given an intrathecal injection of rabbit anti-Stx2 antiserum 2 h before the intravenous injection of Stx2. Our results suggest that a leakage of Stx2 into the CSF from the choroid plexus causes brain damage, and that an intrathecal injection of anti-Stx2 antiserum could be a therapy for acute encephalopathy caused by Stx2-producing Escherichia coli.
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PMID:Neurotoxicity of intrathecal Shiga toxin 2 and protection by intrathecal injection of anti-Shiga toxin 2 antiserum in rabbits. 979 Aug 73

Two hundred and two cases of CP in Shiga Prefecture, born between April 1977 and March 1987, were classified at 6 years of age into 5 groups: 69 with spastic diplegia (34%), 62 with tetraplegia (31%), 33 with hemiplegia (16%), 23 with the dyskinetic type (11%) and 15 with the ataxic type (7%). The rate of preterm birth was 32%, being highest in the spastic diplegia group. The etiological and risk factors were analysed in these cases. In term infants with spastic diplegia, the presumptive causes were unknown in 55%, prenatal in 28%, and perinatal in only 17%. In preterm infants with spastic diplegia, periventricular leukomalacia was the most important. In term infants with tetraplegia, brain anomalies and hypoxic-ischemic encephalopathy were the two main causes. In preterm infants with tetraplegia, the presumptive causes were perinatal in 67%. In most of the patients with hemiplegia, there were unilateral lesions such as middle cerebral artery infarction and cerebral hemiatrophy. Most of the dyskinetic cases had perinatal causes such as bilirubin encephalopathy in 9 patients. In 40% of the ataxic cases, there were brain anomalies.
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PMID:[A clinical study of cerebral palsy in Shiga; 1977-1986--I. Etiological analysis of various types of cerebral palsy]. 1042 82

Antibiotic therapy for infection with Shiga-toxin-producing Escherichia coli O157:H7 is controversial because of the possibility of its inducing hemolytic uremic syndrome and acute encephalopathy. In a previous study, mice with protein-calorie malnutrition were found to be highly susceptible to this pathogen. The efficacy of oral antibiotic therapy in malnourished mice infected with O157 organisms was assessed. Mice fed a low-protein calorie diet were infected intragastrically with 2 x 10(6) colony-forming units of a Shiga-toxin-producing strain of Escherichia coli O157:H7. Infected mice were orally given a therapeutic dose of an antibiotic, including norfloxacin, fosfomycin, kanamycin, ampicillin, clarithromycin or trimethoprim-sulfamethoxazole for 3 days: mice on protocol A received the antibiotic on days 1-3, starting on the day after infection, and mice on protocol B received the antibiotic on days 3-5. The duration of fecal pathogen excretion was shorter and the toxin level in the stool and blood lower in the mice that received protocol A than in untreated mice; all of the mice treated on protocol A survived the lethal infection. All antibiotics except trimethoprim-sulfamethoxazole, administered on protocol B, exhibited the same effect as that exhibited by the respective antibiotic administered on protocol A. Only the mice treated with protocol B of trimethoprim-sulfamethoxazole had a higher toxin level in the blood than untreated controls, resulting in 95% mortality. These results suggest that the antibiotics used in this study, except for trimethoprim-sulfamethoxazole, could reduce the risk of hemolytic uremic syndrome and acute encephalopathy following Escherichia coli O157:H7 infection in humans, and that fosfomycin, in particular, may be relevant for testing in humans.
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PMID:Efficacy of antibiotic therapy for infection with Shiga-like toxin-producing Escherichia coli O157:H7 in mice with protein-calorie malnutrition. 1051 88

We report a 20-month-old girl with postdiarrheal (Shiga toxin) hemolytic uremic syndrome and severe encephalopathy. Magnetic resonance (MR) images were obtained in the acute phase of the disease and after 10 months. The first MR images showed widespread high signal intensity on T2-weighted and low signal intensity on T1-weighted images, in deep and subcortical white matter; the splenium of the corpus callosum was also involved, as well as cerebellar hemispheres. Neurological symptoms and signs gradually disappeared within 35 days. Follow-up MR imaging showed almost complete resolution of the previous findings, and the patient recovered without central nervous system impairment. The neurological lesions were probably due to hypoxia, although several other mechanisms could be involved, such as metabolic derangements and the action of Shiga toxin. In spite of the dramatic clinical manifestations, we observed a good outcome, indicating that patients with similar lesions do not necessarily have a poor prognosis.
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PMID:Central nervous system involvement in a child with hemolytic uremic syndrome. 1097 13

Convulsions and encephalopathy are common complications of Shiga toxin (Stx)-producing Shigella and enterohemorrhagic Escherichia coli infections. In previous studies, we demonstrated that Stx and lipopolysaccharide (LPS) act in concert to enhance mice sensitivity to pentylenetetrazole (PTZ)-induced seizures via mechanisms involving tumor necrosis factor alpha (TNFalpha), interleukinl beta and nitric oxide. To further elucidate the role of the host response in Shigella-related seizures, we studied the ability of Shigella dysenteriae and its products to modulate seizures in C3H/HeJ (lps(d/d)) and in C3H/HeN (lps(n/n) mice. Injection of S. dysenteriae 60R sonicate elevated plasma TNFalpha and enhanced the convulsive response to PTZ in both mouse strains. Induced TNFalpha levels were markedly lower in LPS-hyporesponsive C3H/HeJ mice than in LPS- responsive C3H/HeN mice: 7.4 ng/ml vs 44 ng/ml (induced by 4LD50). Accordingly, a higher dose of S. dysenteriae sonicate was needed to sensitize the C3H/HeJ mice to seizures. Stx or LPS alone did not enhance seizures in either strain. Stx together with LPS enhanced seizures in LPS-responsive mice, but not in LPS-hyporesponsive mice in which they induced only a minor elevation in TNFalpha levels (1.5 ng/ml). As compared to LPS-responsive mice, the LPS-hyporesponsive mice were less susceptible to the lethal effects of Shigella sonicate and were resistant to the lethal effect of purified Stx with LPS. These results demonstrate the crucial role of the host response with regard to the sensitivity to to LPS, and specifically TNFalpha production, in Shigella lethality and Shigella-related seizures.
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PMID:Enhancement of pentylenetetrazole-induced seizures by Shigella dysenteriae in LPS-resistant C3H/HeJ mice: role of the host response. 1200 30

Shiga toxins (Stxs) have been specifically implicated as a causal factor of hemolytic uremic syndrome and acute encephalopathy. The first step of Stx-induced brain damage is considered to injure endothelial cells cooperating with tumor necrosis factor-alpha (TNF-alpha). Gamma interferon (IFN-gamma) is one of the proinflammatory cytokines as well as TNF-alpha is critical in activation of endothelial cells. Therefore we focused on the possibility of IFN-gamma-mediated lethality of Stx1 or Stx2 in mice. All of mice died within 3-4 days after injection with 400 ng of Stx1 and 37.5% of mice, which had been injected with 133 ng, survived. In contrast, a lethal dose of Stx2 was 40 times lower than that of Stx1. When mice were given 400 ng of Stx1 or 10 ng of Stx2, IFN-gamma mRNA was detected in the spleens 24h after injection. Moreover, when mice were injected with 133 ng of Stx1 or 3.3 ng of Stx2, survival rates of IFN-gamma-deficient mice and TNF-alpha-deficient mice were significantly higher than that of wild-type mice. The present study using cytokine-gene knockout mice directly demonstrated that not only TNF-alpha but also IFN-gamma is involved in lethality of Stx1 and Stx2.
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PMID:Roles of gamma interferon and tumor necrosis factor-alpha in shiga toxin lethality. 1212 99

Shiga toxin 1 (Stx1) represents an AB5 toxin produced by enterohemorrhagic Escherichia coli, which cause gastrointestinal diseases in humans that are often followed by potentially fatal systemic complications, such as acute encephalopathy and hemolytic uremic syndrome. The expression of the preferential Stx1 receptor, Gb3Cer/CD77 (Gal alpha1-4Gal beta1-4Glc beta1-1Cer), is one of the primary determinants of susceptibility to tissue injury. Due to the clinical importance of this life-threatening toxin, a combined strategy of preparative high-performance thin-layer chromatography (HPTLC) overlay assay and mass spectrometry was developed for the detection and structural characterization of Stx1-binding glycosphingolipids (GSLs). A preparation of neutral GSLs from human erythrocytes, comprising 21.4% and 59.1% of the high- and low-affinity Stx1-binding ligands Gb3Cer/CD77 and Gb4Cer, respectively, was separated on silica gel precoated HPTLC plates and probed for the presence of Stx1 receptors. Stx1 positive on the one hand and anti-Gb3Cer/CD77 and anti-Gb4Cer antibody positive bands from parallel reference runs on the other hand were extracted with chloroform/methanol/water (30/60/8, v/v/v). These crude extracts were used without any further purification for a detailed structural analysis by nanoelectrospray ionization quadrupole time-of-flight mass spectrometry (nanoESI-QTOF-MS) in the negative ion mode. In all extracts investigated, neutral GSLs were detected as singly charged deprotonated molecular ions, [M-H]-, and neither buffer-derived salt adducts nor coextracted contaminants from the overlay assay procedure or the silica gel layer were observed. For the structural characterization of Stx1- and antibody-binding GSLs low-energy collision-induced dissociation (CID) was applied to high and low abundant receptor species of the crude extracts. All MS/MS spectra obtained contained full series of Y-type ions, B-type ions and additional ions generated by ring cleavages of the sugar moiety. Only analytical quantities in the microgram scale of a single GSL species within the complex GSL mixture were required for the structural MS characterization of Stx1 ligands as Gb3Cer/CD77 and Gb4Cer. This effective combined HPTLC/MS procedure offers a broad range of applications, not only for toxins of bacterial origin, but also for any GSL-binding agents such as plant-derived lectins or human proteins with yet unknown binding specificities.
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PMID:Application of combined high-performance thin-layer chromatography immunostaining and nanoelectrospray ionization quadrupole time-of-flight tandem mass spectrometry to the structural characterization of high- and low-affinity binding ligands of Shiga toxin 1. 1628 17


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