g(m1)-ganglioside and Diarrhea

The pathogenetic significance of toxin receptor interaction in disease is examplified by infectious diarrhoea. The world-wide problem of infectious diarrhoea is presented with regard to epidemiology, etiology, and pathophysiology. Enterotoxigenic diarrhoea is examined in the light of recent knowledge on toxin receptor interaction, which has greatly contributed to new vaccine as well as drug development in this disease condition.

Topics: Adenylyl Cyclases; Animals; Chlorpromazine; Cholera; Cholera Toxin; Cholera Vaccines; Combined Modality Therapy; Diarrhea; Enterotoxins; Enzyme Activation; Escherichia coli; Fluid Therapy; G(M1) Ganglioside; Guanylate Cyclase; Humans; Intestinal Mucosa; Intestinal Secretions; Rabbits; Receptors, Cell Surface; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Immunologic; Receptors, Peptide; Vibrio cholerae

Enteric infections cause more than a billion episodes of diarrhoeal disease in humans each year killing many millions of people, especially young children, in developing countries. Recent progress, reviewed in this article, has enabled that a specific pathogen now can be isolated in the majority of patients with acute diarrhoea, and has also elucidated fundamental pathogenic mechanisms and their pathophysiological effects for several of these agents. Based on this understanding it now seems possible to devise new techniques for the treatment and prevention of diarrhoeal disease to complement those based on fluid replacement therapy and sanitation; prospects for the development of new or improved vaccines, receptor-prophylactic binding agents, and antisecretory drugs are discussed.. Enteric infections cause more than 1 billion episodes of diarrheal disease in humans each year killing many millions of people, especially young children, in developing countries. Recent progress, reviewed here, has enabled that a specific pathogen can now be isolated in the majority of patients with acute diarrhea, and has also elucidated fundamental pathogenic mechanisms and their pathophysiological effects for several of these agents. Based on this understanding, it now seems possible to devise new techniques for the treatment and prevention of diarrheal disease to complement those based on fluid replacement therapy and sanitation. Prospects for the development of new or improved vaccines, receptor-prophylactic binding agents, and antisecretory drugs are discussed.

Topics: Antidiarrheals; Bacterial Vaccines; Calcium; Cholera; Cyclic AMP; Cyclic GMP; Diarrhea; Dysentery, Amebic; Escherichia coli Infections; G(M1) Ganglioside; Humans; Reoviridae Infections; Rotavirus; Viral Vaccines

Molecular modelling approach was used to investigate the intermolecular interactions of selected 20 polyphenolic compounds from three plants with CT using DOCK6. Based on intermolecular interactions, two phenolic acids, Ellagic acid (EA) and Chlorogenic acid (CHL); two flavonoids, Rutin (RTN) and Phloridzin (PHD) were selected along with their respective standards, Gallic acid (GA) and Quercetrin (QRTN). The stability of docked complexes was corroborated using molecular dynamics simulation. Furthermore, in vitro inhibitory activity of six compounds against CT was assessed using GM1 ELISA and cAMP assay. EA and CHL that showed prominent activity against CT in. The molecular modelling study revealed significant structural stability of the CT-EA, CT-CHL, and CT-PHD complexes compared to their respective controls. All the selected six compounds significantly reduced CT-induced cAMP levels, whereas EA, CHL, and PHD exhibited > 50% binding inhibition of CT to GM1. The EA and CHL that showed prominent neutralization activity against CT from

Topics: Animals; Cholera; Cholera Toxin; Diarrhea; G(M1) Ganglioside; Mice; Polyphenols; Pomegranate; Psidium

Approximately 15%-20% of patients with Guillain-Barré syndrome (GBS) are unable to walk independently at 6 months from the onset of neurological symptom. The modified Erasmus GBS outcome score (mEGOS) has been reported as a prognostic tool.Herein we investigated the association between a poor outcome, inability to walk independently at 6 months and presence of antiganglioside antibodies.. The clinical and serological data of 177 patients with GBS were retrospectively collected in Japan to assess the associations between a poor outcome and serum IgG antibodies against each ganglioside (GM1, GD1a, GalNAc-GD1a, GQ1b and GT1a). In addition, we investigated whether the combination of mEGOS and serum IgG antibodies against gangliosides is useful in predicting a poor outcome.. The patients with IgG anti-GD1a antibodies more frequently showed poor outcomes than those without these antibodies (9 (36%) of 25 vs 8 (6%) of 127 patients, p<0.001). Particularly, 80% showed a poor outcome when they had both serum IgG anti-GD1a antibody and a high mEGOS of ≥10 on day 7 of admission.. The combination of serum IgG anti-GD1a antibodies and a high mEGOS could help in making a more accurate prognosis of patients than mEGOS alone, especially for predicting poor outcomes.

Topics: Age Factors; Autoantibodies; Diarrhea; Electrodiagnosis; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Mobility Limitation; Prognosis; Respiration, Artificial; Retrospective Studies

Ginger is one of the most commonly used fresh herbs and spices. Enterotoxigenic Escherichia coli heat-labile enterotoxin (LT)-induced diarrhea is the leading cause of infant death in developing countries. In this study, we demonstrated that ginger significantly blocked the binding of LT to cell-surface receptor G M1, resulting in the inhibition of fluid accumulation in the closed ileal loops of mice. Biological-activity-guided searching for active components showed that zingerone (vanillylacetone) was the likely active constituent responsible for the antidiarrheal efficacy of ginger. Further analysis of chemically synthesized zingerone derivatives revealed that compound 31 (2-[(4-methoxybenzyl)oxy]benzoic acid) significantly suppressed LT-induced diarrhea in mice via an excellent surface complementarity with the B subunits of LT. In conclusion, our findings provide evidence that ginger and its derivatives may be effective herbal supplements for the clinical treatment of enterotoxigenic Escherichia coli diarrhea.

Topics: Animals; Bacterial Toxins; Diarrhea; Enterotoxins; Escherichia coli Proteins; Female; G(M1) Ganglioside; Guaiacol; Mice; Mice, Inbred BALB C; Phytotherapy; Plant Roots; Zingiber officinale

Guillain-Barré syndrome (GBS) is an acute, immune-mediated flaccid paralysis frequently associated with Campylobacter infection. Of two predominant GBS subtypes, a demyelinating subtype (acute inflammatory demyelinative polyneuropathy [AIDP]) predominates in the United States and Europe, and axonal subtype (acute motor axonal neuropathy [AMAN]) is the predominant form in China. Previous clinical studies suggested that AMAN also occurs in Mexican children. The purpose of this study was to describe the subtypes of GBS in children from Mexico City.. We prospectively studied 121 children admitted to two pediatric hospitals in Mexico City from 1996 to 2002. Clinical histories were obtained, electrophysiologic studies were performed to determine GBS subtype, and microbiologic studies were performed.. Of the 121 children, 46 had AMAN and 32 had AIDP. The male to female ratio was 1.3 for AMAN cases (mean age = 6.3) and 3.0 for AIDP cases (mean age = 7.0). There was a strong seasonal distribution of AMAN cases in July to September. Children with AMAN, but not AIDP, had worsening of illness during hospitalization as judged by peak severity scores. Vomiting was more likely in AIDP (28.1%) vs AMAN (6.5%) (p = 0.012) and diarrhea was more common in AMAN (32.6%) than AIDP (12.5%) (p = 0.06). IgG anti-GM1 antibody titers were higher in patients with AMAN vs AIDP (p = 0.067). Anti-GD1a antibodies were equally present in both groups. Anti GQ1b titers were higher in AMAN vs AIDP (p = 0.009). Campylobacter antibody responses were positive in 44.1% of patients with AMAN and 37.0% of patients with AIDP. Twenty patients (14 = AMAN, 6 = AIDP) had positive stool cultures for C jejuni. Two serotypes, HS:19 and HS:41, accounted for 6 of 10 Campylobacter isolates available for serotyping from these cases.. This study confirms that acute motor axonal neuropathy is an important Guillain-Barré syndrome subtype in Mexican children, is associated with diarrhea, and occurs seasonally.

Topics: Adolescent; Campylobacter Infections; Child; Child, Preschool; Diarrhea; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Infant; Male; Mexico; Motor Neurons; Seasons

Enterotoxigenic Escherichia coli (ETEC) is the most frequently isolated enteropathogen, accounting for approximately 210 million diarrhea episodes annually. ETEC-induced diarrhea is initiated by the binding of B subunit of heat-labile enterotoxin (LTB) to the ganglioside G(M1) on the surface of intestinal epithelial cell. Therefore, we evaluated the inhibitory effects of 297 Chinese medicinal herbs on the LTB and G(M1) interaction by G(M1)-enzyme-linked immunosorbent assay. Galla Chinensis extract (GCE) exhibited anti-LT-induced diarrheal effect in the patent mouse gut assay, with IC50 value of 4.7+/-1.3 mg/ml. GCE also inhibited the binding of LTB to G(M1), suggesting that GCE suppressed the LT-induced fluid accumulation by blocking the binding of LTB to G(M1). Furthermore, the ethyl acetate (EA) soluble fraction was the most active fraction of Galla Chinensis that inhibiting the binding of LTB to G(M1) with an IC50 value of 153.6+/-3.4 microg/ml. The major components of the EA fraction should be phenolic derivatives according to a thin-layer chromatography analysis. Gallic acid, the major component of EA fraction, blocked the binding of LTB to G(M1), resulting in the suppression of LT-induced diarrhea. In conclusion, these data suggested that Galla Chinensis and gallic acid might be potent drugs for the treatment of LT-induced diarrhea.

Topics: Animals; Antidiarrheals; Bacterial Toxins; Binding, Competitive; Diarrhea; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drugs, Chinese Herbal; Enterotoxins; Escherichia coli Proteins; Female; G(M1) Ganglioside; Gallic Acid; Mice; Mice, Inbred BALB C; Plant Tumors; Rhus

Anti-GM(1) antibodies of the immunoglobulin M (IgM) isotype are normal components of the antibody repertoire of adult human serum. Using a sensitive high-performance thin-layer chromatography (HPTLC) immunostaining assay, we found that these antibodies were absent in the umbilical vein and children <1 month of age but could be detected after 1 month of age. Although most of the children older than 6 months of age were positive, there were still a few negative children. The appearance of anti-GM(1) IgM antibodies showed a perfect concordance with two well-characterized antibacterial antibodies, anti-Forssman and anti-blood group A, which indicates a similar origin. We also studied IgM reactivity with lipopolysaccharides (LPSs) from gram-negative bacteria isolated from stool samples from healthy babies and from Escherichia coli HB101 in serum from individuals of different ages. We found a positive reaction with both LPSs in all the children more than 1 month of age analyzed, even in those that were negative for anti-GM(1) antibodies. Anti-GM(1) IgM antibodies were purified from adult serum by affinity chromatography and tested for the ability to bind LPSs from different bacteria. This highly specific preparation showed reactivity only with LPS from a strain of Campylobacter jejuni isolated from a patient with diarrhea. We conclude that normally occurring IgM antibodies are generated after birth, probably during the immune defense against specific bacterial strains.

Topics: Adult; Antibodies, Bacterial; Campylobacter Infections; Campylobacter jejuni; Diarrhea; Escherichia coli; G(M1) Ganglioside; Gram-Negative Bacteria; Humans; Immunoglobulin M; Infant; Infant, Newborn; Umbilical Veins

We have produced a functional heat labile enterotoxin (LT-) B subunit of Escherichia coli in maize. LT-B is a multimeric protein that presents an ideal model for an edible vaccine, displaying stability in the gut and inducing mucosal and systemic immune responses. Transgenic maize was engineered to synthesize the LT-B polypeptides, which assembled into oligomeric structures with affinity for G(M1) gangliosides. We orally immunized BALB/c mice by feeding transgenic maize meal expressing LT-B or non-transgenic maize meal spiked with bacterial LT-B. Both treatments stimulated elevated IgA and IgG antibodies against LT-B and the closely related cholera toxin B subunit (CT-B) in serum, and elevated IgA in fecal pellets. The transgenic maize induced a higher anti-LT-B and anti-CT-B mucosal and serum IgA response compared to the equivalent amount of bacterial LT-B spiked into maize. Following challenge by oral administration of the diarrhea inducing toxins LT and CT, transgenic maize-fed mice displayed reduced fluid accumulation in the gut compared to non-immunized mice. Moreover, the gut to carcass ratio of immunized mice was not significantly different from the PBS (non-toxin) challenged control group. We concluded that maize-synthesized LT-B had features of the native bacterial LT-B such as molecular weight, G(M1) binding ability, and induction of serum and mucosal immunity. We have demonstrated that maize, a major food and feed ingredient, can be efficiently transformed to produce, accumulate, and store a fully assembled and functional candidate vaccine antigen.

Topics: Administration, Oral; Animals; Bacterial Toxins; Blotting, Southern; Cholera Toxin; Diarrhea; Enterotoxins; Escherichia coli; Escherichia coli Proteins; Female; G(M1) Ganglioside; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin G; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Plants, Genetically Modified; Polymerase Chain Reaction; Vaccines, Edible; Water; Zea mays

To examine whether Guillain-Barré syndrome (GBS) can be classified in clinical and immunological subgroups based on the type of prior illness. Background - The existence of antecedent symptoms supports the diagnosis of GBS in patients who experience acute muscle weakness progression. However, little is known about additional meanings of determining antecedent symptoms.. Prospective investigation of prior infectious illness in GBS and related disorders (n=176).. The frequent antecedent symptoms in GBS and related disorders were fever (52%), cough (48%), sore throat (39%), nasal discharge (30%), and diarrhea (27%). Patients who had sore throats or coughs frequently had ophthalmoparesis (respectively P=0.0004, P=0.001) and IgG anti-GQ1b antibody (P=0.01, P=0.007). Fever was associated with bulbar palsy (P=0.047) and headache with facial palsy (P=0.04). Patients with diarrhea often had anti-ganglioside IgG (anti-GM1 [P=0.0006] and anti-GM1b [P=0.008]), IgM (anti-GM1 [P=0.03], anti-GM1b [P=0.02], and anti-GalNAc-GD1a [P=0.047]) antibodies and rarely showed ophthalmoparesis or bulbar palsy (respectively P=0.02, P=0.04). Diarrhea and abdominal pain were closely associated with Campylobacter jejuni serology (respectively P<0.0001, P=0.01), whereas other symptoms were not related to pathogens such as cytomegalovirus, Epstein-Barr virus, or Mycoplasma pneumoniae.. Our comprehensive study showed that GBS preceded by sore throat, cough, fever, headache, or diarrhea respectively forms clinical or serological subgroups, or both. This association is not necessarily dependent on infection by the known trigger pathogens.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cough; Diagnosis, Differential; Diarrhea; Female; Fever; G(M1) Ganglioside; Guillain-Barre Syndrome; Headache; Humans; Immunoglobulin G; Male; Middle Aged; Pharyngitis; Prognosis; Prospective Studies; Serologic Tests

To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillain-Barré syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 random enteritis-associated isolates of Campylobacter jejuni were analyzed. To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillan-Barre syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 enteritis-associated isolates, randomly collected in the United States, were analyzed using a cholera-toxin binding assay [corrected]. Overall, 26.2% of the isolates were positive for the GM1-like epitope. Of the 36 different O serotypes in the sample, 21 (58.3%) contained no strains positive for GM1, whereas in 6 serotypes (16.7%), >50% of isolates were positive for GM1. GBS-associated serotypes were more likely to contain strains positive for GM1 than were non-GBS-associated serotypes (37.8% vs. 15.1%, P=.0116). The results suggest that humans are frequently exposed to strains exhibiting GM1-like mimicry and, while certain serotypes may be more likely to possess GM1-like epitopes, the presence of GM1-like epitopes on Campylobacter strains does not itself trigger GBS.

Topics: Campylobacter Infections; Campylobacter jejuni; Cholera Toxin; Chromatography, Thin Layer; Diarrhea; Epitopes; G(M1) Ganglioside; Humans; Lipopolysaccharides; Molecular Mimicry; Polyradiculoneuropathy; Serotyping; United States

Transgenic potatoes were engineered to synthesize a cholera toxin B subunit (CTB) pentamer with affinity for GMI-ganglioside. Both serum and intestinal CTB-specific antibodies were induced in orally immunized mice. Mucosal antibody titers declined gradually after the last immunization but were restored following an oral booster of transgenic potato. The cytopathic effect of cholera holotoxin (CT) on Vero cells was neutralized by serum from mice immunized with transgenic potato tissues. Following intraileal injection with CT, the plant-immunized mice showed up to a 60% reduction in diarrheal fluid accumulation in the small intestine. Protection against CT was based on inhibition of enterotoxin binding to the cell-surface receptor GMI-ganglioside. These results demonstrate the ability of transgenic food plants to generate protective immunity in mice against a bacterial enterotoxin.

Topics: Animals; Antibodies; Chlorocebus aethiops; Cholera; Cholera Toxin; Diarrhea; Female; G(M1) Ganglioside; Immune Sera; Mice; Mice, Inbred Strains; Mucous Membrane; Plants, Genetically Modified; Solanum tuberosum; Vaccines; Vero Cells

IgA has an important role in the gastrointestinal immune system. We investigated IgA anti-GM1 antibodies in Guillain-Barré syndrome (GBS) subsequent to diarrhea. IgA anti-GM1 antibodies were detected more often in GBS patients with a history of antecedent diarrhea than in those without that. Between the GBS patients with a history of prior symptoms of upper respiratory tract infections and those without that, we found no difference of the frequency of increased IgA anti-GM1 antibody titers. Six GBS patients who had antecedent symptoms of upper respiratory tract infections had IgA anti-GM1 antibodies. However, 5 patients of them also had a history of antecedent diarrhea. Our findings show that IgA anti-GM1 antibodies are associated with GBS following diarrhea.

Topics: Autoantibodies; Diarrhea; G(M1) Ganglioside; Humans; Immunoglobulin A; Polyradiculoneuropathy; Retrospective Studies

A fusion protein, comprising the B subunit of the heat-labile enterotoxin and a portion of the precursor to the heat-stable enterotoxin of Escherichia coli, has been created by recombinant genetic techniques. It is exported successfully to the bacterial periplasm and assembles into pentamers which retain the ability to bind to GM1 ganglioside. Native toxin epitopes are displayed and the molecule can be easily purified from periplasmic extracts of cells expressing the gene fusion. Although the protein carries the natural sequence of the heat-stable enterotoxin, it is greatly attenuated in toxicity. Systemic immunization of mice or oral administration of the fusion elicits antibody responses against both classes of E. coli enterotoxin.

Topics: Administration, Oral; Amino Acid Sequence; Animals; Antibodies, Bacterial; Bacterial Toxins; Bacterial Vaccines; Base Sequence; Diarrhea; Enterotoxins; Escherichia coli Infections; Escherichia coli Proteins; Escherichia coli Vaccines; Female; G(M1) Ganglioside; Injections, Subcutaneous; Mice; Molecular Sequence Data; Protein Precursors; Recombinant Fusion Proteins; Vaccines, Synthetic

Campylobacter jejuni is one of the main etiologic agents of gastrointestinal illness in developing and developed areas throughout the world. Isolation of enterotoxin-producing C. jejuni has been associated with clinical symptoms of a watery-secretory type of diarrhea. Although physiological and immunological relatedness has been demonstrated between the C. jejuni enterotoxin (CJT), the Vibrio cholerae enterotoxin (CT), and the heat-labile cholera-like Escherichia coli enterotoxin (LT), nucleotide sequence similarity between C. jejuni DNA and either the toxA, toxB, eltA or eltB genes remained to be shown. We found that binding to ganglioside GM1 prevented recognition of CJT by monoclonal antibodies directed to either CT or LT. This indicates antigenic similarity between the three enterotoxins in the ganglioside GM1-binding site. Therefore we searched for corresponding similarities at the DNA level and found, by oligodeoxynucleotide hybridization, C. jejuni chromosomal nucleotide sequences similar to the coding region for a postulated ganglioside GM1-binding site on toxB and eltB.

Topics: Amino Acid Sequence; Antibodies, Monoclonal; Bacterial Toxins; Base Sequence; Campylobacter fetus; Child; Child, Preschool; Chromosomes, Bacterial; Diarrhea; DNA, Bacterial; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Escherichia coli Proteins; G(M1) Ganglioside; Humans; Molecular Sequence Data; Nucleic Acid Hybridization; Oligonucleotide Probes; Species Specificity; Vibrio cholerae

Enterotoxin production, a possible virulence factor, was determined in Campylobacter jejuni and Campylobacter coli by two different techniques, the CHO cell test and the GM1 enzyme-linked immunosorbent assay. The frequency of enterotoxigenic Campylobacter strains was 32% in strains from both humans with acute enteritis and healthy laying hens, as measured by the CHO cell test. The CHO cell test was significantly more sensitive than the GM1 enzyme-linked immunosorbent assay in the detection of enterotoxigenic strains. Enterotoxin production was compared with the presence of heat-stable and heat-labile antigens. There was no significant correlation between enterotoxin production and serogroups for C. jejuni or C. coli. The difference in enterotoxigenicity between C. jejuni (34.1%) and C. coli (21.9%) was not significant.

Topics: Acute Disease; Adolescent; Adult; Animals; Campylobacter; Campylobacter fetus; Campylobacter Infections; Carrier State; Cell Line; Chickens; Diarrhea; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Poultry Diseases; Serotyping; Virulence

Heat-labile enterotoxin producing strains of Escherichia coli were isolated from diarrheal faeces of humans and from the jejunum of pigs which had died of diarrhea. The heat-labile enterotoxin was assayed by three different enzyme-linked immunosorbent assays (ELISA). The first assay was based upon immunological cross-reactions between the heat-labile enterotoxins of E coli and Vibrio cholerae, the second on specific E coli heat-labile enterotoxin antibodies and the third on affinity of the toxin to the presumed cell membrane receptor, the ganglioside GM1. The heat-labile enterotoxins of human and porcine origin bound equally well to the same extent in the ELISA procedure, which utilized immunological cross-reactivity between the heat-labile enterotoxins of E coli and V cholerae. The reactivity, however, was quite different in the GM1-ELISA. The binding affinity was high between GM1 and enterotoxin produced by E coli strains of human origin, whereas the binding affinity was low for enterotoxin from porcine strains.

Topics: Animals; Antibodies, Bacterial; Binding, Competitive; Diarrhea; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Escherichia coli; G(M1) Ganglioside; Gangliosides; Humans; Swine

Topics: Charcoal; Cholera Toxin; Diarrhea; Female; G(M1) Ganglioside; Gangliosides; Humans; Intestinal Mucosa; Male