UMLS:C0009450 - FACTA Search

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Query: UMLS:C0009450 (infectious diseases)
83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute renal failure is one of the hallmarks of the hemolytic uremic syndrome (HUS). Infection with a verocytotoxin (VT)- or Shiga-like toxin (SLT)-producing Escherichia coli has been strongly implicated in the etiology of the epidemic form of HUS. The functional receptor for these closely related toxins appears to be a glycosphingolipid, globotriaosylceramide (Gb3). Endothelial damage in the glomeruli and arterioles of the kidney induced by VT is believed to play a crucial role in the pathogenesis of HUS. However, little information is available regarding the effects of VT on mesangial cells, which also play an important role in glomerular function. In this study, the effects of VT on human mesangial cells in vitro were investigated. Mesangial cells were enriched by collecting hillock-shaped outgrowths derived from adult human glomeruli and subsequently purified by elimination of contaminating epithelial cells by immunoseparation with ulex europaeus lectin-I (UEA-I)-coated dynabeads. The obtained and subcultured mesangial cell populations were >98% pure. Their mesangial nature was established by the presence of a-smooth muscle cell actin in highly confluent cultures and the absence of cytokeratin or platelet/endothelial cell adhesion molecule-1. Mesangial cells bound VT to bands of Gb3 and a closely related glycolipid, which is similar to a glycolipid involved in the VT-dependent cytokine production in monocytes. VT did not induce the release of cytokines or chemokines in mesangial cells. In VT-susceptible cells, binding of VT to Gb3 causes cell death by the inhibition of protein synthesis. Although protein synthesis was inhibited in mesangial cells, all cells remained viable, both under basal and tumor necrosis factor-alpha-stimulated conditions. However, the marked reduction in protein synthesis may impair a proper response of the cells in conditions of increased demand of newly synthesized proteins. Furthermore, VT markedly inhibited DNA synthesis and proliferation of mesangial cells. The inhibition of mitogenesis was also found with the B-subunit of VT-1 alone, albeit to a lesser extent, without a significant effect on protein synthesis. Because the inhibition of protein synthesis involves the A-subunit, this suggests that two distinct mechanisms contribute to the effects of VT on protein synthesis and mitogenesis. Intracellular routing of VT (A- and B-subunits) may vary between cell types and result in differential effects on human mesangial cells when compared with other cell types.
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PMID:Verocytotoxin inhibits mitogenesis and protein synthesis in purified human glomerular mesangial cells without affecting cell viability: evidence for two distinct mechanisms. 940 90

Low serum mannose-binding protein (MBP), a calcium-dependent serum lectin that acts as an opsonin to promote phagocytosis, has been characterized as the most common immune deficiency. It has been suggested that MBP acts as a binding protein for mycobacteria and other intracellular pathogens, enabling them to enter host macrophages. The present study investigated the association between variant MBP alleles and malaria, tuberculosis, and hepatitis B virus (HBV) in adults and children in The Gambia. Of the 2041 Gambians screened for MBP mutations, 944 (46%) were homozygous for the wild-type allele, 922 (45%) were carriers of a single variant allele, and 175 (8.6%) possessed 2 mutant alleles. Compared to healthy controls, neither homozygotes nor heterozygotes for MBP genotypes were at increased risk of severe malaria (n = 504), HBV carriage (n = 337), or tuberculosis (n = 397). Stratification of patients by ethnic group did not alter this lack of relationship. However, the most common mutation in Africans--the codon 57 variant allele--was weakly associated with resistance to tuberculosis in both cases and controls. Although MBP deficiency may predispose to recurrent infections, this study failed to provide evidence that such a deficiency is a major risk factor for infectious diseases.
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PMID:Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans. 951 8

The present article opens with a brief summary of the current knowledge of glycoproteins and their medical applications, as compared to the almost complete ignorance of these substances during the first half of the century. The author then relates how he became interested in carbohydrates in the 1950s, and subsequently in glycoproteins. He focuses on the identification of soybean agglutinin as the first known plant protein of this class, to which a widely occurring N-linked oligomannoside is attached, and continues with an account of his work on the coral tree lectin that contains plant-specific N-glycans. Moving at the same time deep into lectin research, he describes the discovery of the crucial role of bacterial surface lectins in the initiation of infectious diseases, thus providing the rationale for the current attempts to use carbohydrates for antiadhesion therapy of such diseases. The article ends with a survey of the author's contribution to spreading wide the knowledge of glycoproteins and of their great importance in biology and medicine.
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PMID:Glycoproteins now and then: a personal account. 978 Mar 49

Infection by human papillomavirus type 16 (HPV-16) has been linked to cervical cancer. The transcription of viral genes in HPV-16 is partially controlled by a number of cellular transcription factors. We have previously identified a novel cellular transcription factor, PEF-1, from its ability to interact with the long control region (LCR) of HPV-16. This factor has a molecular mass of about 110 kDa and binds to a GC-rich sequence in the section of the LCR responsible for cell type-specific transcription from viral DNA. The factor Sp1 has similar properties and also interacts with the HPV-16 LCR. We show that PEF-1 and Sp1 are distinct transcription factors: they recognize different DNA sequences, have different electrophoretic mobilities and different glycosylation patterns. Sp1 is O-glycosylated while PEF-1 appears to have a novel type of glycosylation, as shown by the interaction with pokeweed lectin and by the inhibition of this interaction by tunicamycin.
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PMID:PEF-1, an epithelial cell transcription factor which activates the long control region of human papillomavirus type 16, is glycosylated with N-acetylglucosamine. 982 Jan 51

Peanut (Arachis hypogaea) seed lectin, PNA is widely used to identify tumor specific antigen (T-antigen), Galbeta1-3GalNAc on the eukaryotic cell surface. The functional amino acid coding region of a cDNA clone, pBSH-PN was PCR amplified and cloned downstream of the polyhedrin promoter in the Autographa californica nucleopolyhedrovirus (AcNPV) based transfer vector pVL1393. Co-transfection of Spodoptera frugiperda cells (Sf9) with the transfer vector, pAcPNA and AcRP6 (a recombinant AcNPV having B-gal downstream of the polyhedrin promoter) DNAs produced a recombinant virus, AcPNA which expresses PNA. Infection of suspension culture of Sf9 cells with plaque purified AcPNA produced as much as 9.8 mg PNA per liter (2.0 x 10(6) cells/ml) of serum-free medium. Intracellularly expressed protein (re-PNA) was purified to apparent homogeneity by affinity chromatography using ECD-Sepharose. Polyclonal antibodies against natural PNA (n-PNA) cross-reacted with re-PNA. The subunit molecular weight (30 kDa), hemagglutination activity, and carbohydrate specificity of re-PNA were found to be identical to that of n-PNA, thus confirming the abundant production of a functionally active protein in the baculovirus expression system.
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PMID:Expression, purification and characterization of peanut (Arachis hypogaea) agglutinin (PNA) from baculovirus infected insect cells. 1051

Morphological characteristics and functions of hemocytes were used to compare the immunological effects of biological and chemical stress in the freshwater snail Lymnaea palustris. Animals were either infected by a trematode parasite (Metaleptocephalus sp.), or exposed to environmental contaminants, namely atrazine and hexachlorobenzene (HCB). Three populations of circulating hemocytes, morphologically and cytochemically distinct (round cells, hyalinocytes, granulocytes), were identified in both control and parasitized or pesticide-exposed snails. After 6 h of exposure, HCB and atrazine resulted in 8-fold increases in the mean total number of hemocytes, whereas only a 2.2-fold increase was observed 6 h after cercaria emission in parasitized snails. The impact of HCB was limited to the first 24 h of exposure, whereas long-lasting effects of atrazine were observed. Hyalinocytes and, to a lesser extent, round cells contributed most to the increases in hemocyte density in pesticide-exposed snails. Parasitism and atrazine treatment resulted in significant increases of lectin-stained hemocytes, whereas exposure to HCB did not affect the percentages of stained and unstained cells. Hemocyte phagocytic activity increased in HCB-exposed snails but with no concomitant change of the oxidative burst. Opposite results were obtained in atrazine-treated snail hemocytes, with unchanged phagocytosis and decreased phorbol 12-myristate 13-acetate-stimulated production of reactive oxygen intermediates. No increase in phagocytosis, or in the production of reactive oxygen intermediates, was observed in hemocytes from parasitized snails. Infection with the immunologically compatible trematode parasite Metaleptocephalus sp. and exposure to atrazine generated similar reactions from circulating hemocytes, whereas a different response pattern was observed in HCB-exposed snails.
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PMID:Effects of parasitism and pesticide exposure on characteristics and functions of hemocyte populations in the freshwater snail Lymnaea palustris (Gastropoda, Pulmonata). 1089 May 3

In the course of the past two decennia, a 3rd route of complement activation (next to the classical and the alternative routes) has been identified: the lectin route in which mannose-binding lectin (MBL) plays an essential role. MBL is produced in the liver. From the phylogenetic and functional points of view, complement activation via MBL falls in between the alternative and the classical routes and combines the advantages of the former (an early response, without the intervention of antibodies) with those of the latter (high specificity). The binding of MBL to the surface of a microorganism results in the activation of two serine proteases (MASP1 and MASP2) that are coupled to MBL. These enzymes can activate C4 and C2 so that, via the MBL route, the C3-convertase of the classical route (C4b2b) is produced long before there are any specific antibodies. The gene for MBL is located on the long arm of chromosome 10 and consists of a promoter gene and 4 exons coding for the protein. The prevalence of mutations in the MBL gene is about 10%, but in Africa South of the Sahara it is as high as 30%. MBL deficiency predisposes both children and adults to all sorts of infectious diseases, chronic diarrhoea, tonsillitis, otitis media, pneumonia, (meningococcal) meningitis, sepsis and osteomyelitis. Remarkably, MBL deficiency may actually be advantageous in some infections, because certain microorganisms use MBL or complement to invade the cell.
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PMID:[Immunology in the medical practice. XXVII. Mannose-binding lectin, an important link for nonspecific or hereditary immune reaction]. 1107 14

The majority of infectious diseases are initiated by adhesion of pathogenic organisms to the tissues of the host. In many cases, this adhesion is mediated by lectins present on the surface of the infectious organism that bind to complementary carbohydrates on the surface of the host tissues. Lectin-deficient mutants often lack ability to initiate infection. Soluble carbohydrates recognized by the bacterial lectins block the adhesion of the bacteria to animal cells in vitro. Moreover, they have also been shown to protect against experimental infection by lectin-carrying bacteria in different organs of mammals such as mice, rabbits, calves and monkeys. In a phase II clinical trial, a pentasaccharide shown to have anti-adhesive activity against Streptococcus pneumoniae and Hemophilus influenzae in vitro failed to protect young children from nasopharyngeal colonization with these organisms and from developing otitis media. This could be because insufficient drug was delivered via nasal spray, because bacteria express multiple specificities, the inhibition of which may require a cocktail of oligosaccharides, or because children have different carbohydrate receptors from those of adults. The results of a clinical trial in which N-acetylneuraminyl(alpha2-3)lactose was administered orally to Helicobacter pylori positive patients in an effort to reduce or eradicate bacterial colonization, are awaited with interest. Although the high cost of production of the required oligosaccharides is falling with the recent introduction of enzymatic methods of synthesis, new technologies, in particular the use of engineered bacteria, promise to lower it even further. Attachment of the oligosaccharides to soluble polymeric carriers will increase greatly their effectiveness as antiadhesion agents. There is no doubt that anti-adhesive oligosaccharides will in the near future join the arsenal of drugs for the therapy of bacterial diseases.
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PMID:Safe as mother's milk: carbohydrates as future anti-adhesion drugs for bacterial diseases. 1142 56

Infection of epithelial cells by some animal rotaviruses, but not human or most animal rotaviruses, requires the presence of N-acetylneuraminic (sialic) acid (SA) on the cell surface for efficient infectivity. To further understand how rotaviruses enter susceptible cells, six different polarized epithelial cell lines, grown on permeable filter membrane supports containing 0.4-microm pores, were infected apically or basolaterally with SA-independent or SA-dependent rotaviruses. SA-independent rotaviruses applied apically or basolaterally were capable of efficiently infecting both sides of the epithelium of all six polarized cell lines tested, while SA-dependent rotaviruses only infected efficiently through the apical surface of five of the polarized cell lines tested. Regardless of the route of virus entry, SA-dependent and SA-independent rotaviruses were released almost exclusively from the apical domain of the plasma membrane of polarized cells before monolayer disruption or cell lysis. The transepithelial electrical resistance (TER) of cells decreased at the same time, irrespective of whether infection with SA-independent rotaviruses occurred apically or basolaterally. The TER of cells infected apically with SA-dependent rotaviruses decreased earlier than that of cells infected basolaterally. Rotavirus infection decreased TER before the appearance of cytopathic effect and cell death and resulted in an increase in the paracellular permeability to [(3)H]inulin as a function of loss of TER. The presence of SA residues on either the apical or basolateral side was determined using a Texas Red-conjugated lectin, wheat germ agglutinin (WGA), which binds SA residues. WGA bound exclusively to SA residues on the apical surface of the cells, confirming the requirement for SA residues on the apical cell membrane for efficient infectivity of SA-dependent rotaviruses. These results indicate that the rotavirus SA-independent cellular receptor is present on both sides of the epithelium, but SA-dependent and SA-independent rotavirus strains infect polarized epithelial cells by different mechanisms, which may be relevant for pathogenesis and selection of vaccine strains. Finally, rotavirus-induced alterations of the epithelial barrier and paracellular permeability suggest that common mechanisms of pathogenesis may exist between viral and bacterial pathogens of the intestinal tract.
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PMID:Differential infection of polarized epithelial cell lines by sialic acid-dependent and sialic acid-independent rotavirus strains. 1168 65

The majority of infectious diseases are initiated by the adhesion of pathogenic organisms to the tissues of the host. In many cases this adhesion is mediated by lectins present on the surface of the infectious organism that bind to complementary carbohydrates on the surface of the host tissues. Soluble carbohydrates recognized by the bacterial lectins block the adhesion of the bacteria to animal cells in vitro. Moreover, such carbohydrates have been shown to protect against experimental infection by lectin-carrying bacteria of different mammals, such as mice, rabbits, calves, and monkeys. Agents other than carbohydrates also block adhesion, as demonstrated with cranberry juice as well as with low and high molecular weight preparations isolated from the juice. Both kinds of preparation inhibited the adhesion in vitro of Escherichia coli to different animal cells. In addition, the high molecular weight material acted similarly on the adhesion of Helicobacter pylori to human gasrointenstinal cells, and on the coaggregation of oral bacteria. Furthermore, in limited clinical studies regular drinking of cranberry juice had a significant preventive effect on bacteriuria, and the high molecular weight constituent of the juices was also effective in decreasing the salivary level of Streptococus mutans, the major cause of tooth decay. Because the inhibitors of adhesion examined are not bactericidal, the selection of resistant inhibitor strains is unlikely to occur. Together, these findings may lead to new therapeutic strategies that are in dire need because of the world-wide increase in antibiotic resistant bacteria.
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PMID:Fighting infectious diseases with inhibitors of microbial adhesion to host tissues. 1205 86

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