Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IgA nephropathy (IgAN) was first reported by Berger in 1968, and characterized by diffuse IgA deposition in the mesangium. Patients with IgAN have usually episodic macroscopic hematuria accompanied with pharyngitis, gastroenteritis, bronchitis, or sinusitis. These findings suggest that IgAN is an immune-complex disease resulting from a poorly controlled mucosal immune response to environmental antigens to which the patient was chronically exposed. We reported the glomerular deposition of the outer membrane of Haemophilus parainfluenzae (OMHP) antigens and the presence of IgA antibody against OMHP in the sera of patients with IgAN. These suggest that Haemophilus parainfluenzae plays a role in the aetiology of this disease. This study was conducted to determine whether OMHP antigens induced immunohistologically evident glomerular deposition of IgA and C3 in C3H/HeN mice. Female C3H/HeN mice (4 weeks old) received intraperitoneal injection (HP-IP group), and oral administration (HP-PO group) of OMHP antigens. The control group similarly received intraperitoneal injection of PBS, and oral intake of ordinary water. The mice were sacrificed at 10, 20, 30, 40, 50 weeks after the start of the experiment. The HP-IP group showed glomerular deposition of IgA, C3 and OMHP antigens, glomerular changes (Mesangial hypercellularity and increase in mesangial matrix) after 20 weeks. The HP-PO group showed only mild deposition of IgA, and mild increase in mesangial matrix. These results suggest that OMHP antigens play a role in the glomerular deposition of IgA and C3 in C3H/HeN mice. This is the first use of OMHP antigens to establish an active model of IgAN.
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PMID:[Haemophilus parainfluenzae and IgA nephropathy]. 1051 4

Historically, protection against virus infections has relied on the use of vaccines, but the induction of an immune response requires several days and in certain situations, like in newborn animals that may be infected at birth and die in a few days, there is not sufficient time to elicit a protective immune response. Immediate protection in new born could be provided either by vectors that express virus-interfering molecules in a tissue specific form, or by the production of animals expressing resistance to virus replication. The mucosal surface is the largest body surface susceptible to virus infection that can serve for virus entry. Then, it is of high interest to develop strategies to prevent infections of these areas. Virus growth can be interfered intracellularly, extracellularly or both. The antibodies neutralize virus intra- and extracellularly and their molecular biology is well known. In addition, antibodies efficiently neutralize viruses in the mucosal areas. The autonomy of antibody molecules in virus neutralization makes them functional in cells different from those that produce the antibodies and in the extracellular medium. These properties have identified antibodies as very useful molecules to be expressed by vectors or in transgenic animals to provide resistance to virus infection. A similar role could be played by antimicrobial peptides in the case of bacteria. Intracellular interference with virus growth (intracellular immunity) can be mediated by molecules of very different nature: (i) full length or single chain antibodies; (ii) mutant viral proteins that strongly interfere with the replication of the wild type virus (dominant-negative mutants); (iii) antisense RNA and ribozyme sequences; and (iv) the product of antiviral genes such as the Mx proteins. All these molecules inhibiting virus replication may be used to obtain transgenic animals with resistance to viral infection built in their genomes. We have developed two strategies to target into mucosal areas either antibodies to provide immediate protection, or antigens to elicit immune responses in the enteric or respiratory surfaces in order to prevent virus infection. One strategy is based on the development of expression vectors using coronavirus derived defective RNA minigenomes, and the other relies on the development of transgenic animals providing virus neutralizing antibodies in the milk during lactation. Two types of expression vectors are being engineered based on transmissible gastroenteritis coronavirus (TGEV) defective minigenomes. The first one is a helper virus dependent expression system and the second is based on self-replicating RNAs including the information required to encode the TGEV replicase. The minigenomes expressing the heterologous gene have been improved by using a two-step amplification system based on cytomegalovirus (CMV) and viral promoters. Expression levels around 5 micrograms per 10(6) cells were obtained. The engineered minigenomes will be useful to understand the mechanism of coronavirus replication and for the tissue specific expression of antigen, antibody or virus interfering molecules. To protect from viral infections of the enteric tract, transgenic animals secreting virus neutralizing recombinant antibodies in the milk during lactation have been developed. Neutralizing antibodies with isotypes IgG1 or IgA were produced in the milk with titers of 10(6) in RIA that reduced virus infectivity by one million-fold. The recombinant antibodies recognized a conserved epitope apparently essential for virus replication. Antibody expression levels were transgene transgene copy number independent and were related to the transgene integration site. This strategy may be of general use since it could be applied to protect newborn animals against infections of the enteric tract by viruses or bacteria for which a protective MAb has been identified. Alternatively, the same strategy could be used to target the expression of antibio
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PMID:Interference with virus and bacteria replication by the tissue specific expression of antibodies and interfering molecules. 1065 42

Recombinant live oral vaccines expressing pathogen-derived antigens offer a unique set of attractive properties. Among these are the simplicity of administration, the capacity to induce mucosal and systemic immunity, and the advantage of permitting genetic manipulation for optimal antigen presentation. In this study, the benefit of having a heterologous antigen expressed on the surface of a live vector rather than intracellularly was evaluated. Accordingly, the immune response of mice immunized with a Salmonella enterica serovar Typhimurium vaccine strain expressing the Escherichia coli 987P fimbrial antigen on its surface (Fas(+)) was compared with the expression in the periplasmic compartment (Fas(-)). Orally immunized BALB/c mice showed that 987P fimbriated Salmonella serovar Typhimurium CS3263 (aroA asd) with pCS151 (fas(+) asd(+)) elicited a significantly higher level of 987P-specific systemic immunoglobulin G (IgG) and mucosal IgA than serovar Typhimurium CS3263 with pCS152 (fasD mutant, asd(+)) expressing 987P periplasmic antigen. Further studies were aimed at determining whether the 987P fimbriae expressed by serovar Typhimurium chi4550 (cya crp asd) could be used as carriers of foreign epitopes. For this, the vaccine strain was genetically engineered to express chimeric fimbriae carrying the transmissible gastroenteritis virus (TGEV) C (379-388) and A (521-531) epitopes of the spike protein inserted into the 987P major fimbrial subunit FasA. BALB/c mice administered orally serovar Typhimurium chi4550 expressing the chimeric fimbriae from the tet promoter in pCS154 (fas(+) asd(+)) produced systemic antibodies against both fimbria and the TGEV C epitope but not against the TGEV A epitope. To improve the immunogenicity of the chimeric fimbriae, the in vivo inducible nirB promoter was inserted into pCS154, upstream of the fas genes, to create pCS155. In comparison with the previously used vaccine, BALB/c mice immunized orally with serovar Typhimurium chi4550/pCS155 demonstrated significantly higher levels of serum IgG and mucosal IgA against 987P fimbria. Moreover, mucosal IgA against the TGEV C epitope was only detected with serovar Typhimurium chi4550/pCS155. The induced antibodies also recognized the epitopes in the context of the full-length TGEV spike protein. Hence, immune responses to heterologous chimeric fimbriae on Salmonella vaccine vectors can be optimized by using promoters known to be activated in vivo.
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PMID:Mucosal and systemic immune responses to chimeric fimbriae expressed by Salmonella enterica serovar typhimurium vaccine strains. 1081 54

The immaturity of the infant's immune system and the rapid evolution of pathogens has created a demand for the mother to provide ready made specific defence factors to her offspring. This is achieved during the fetal period by transplacental transport of IgG antibodies, and after birth via IgA antibodies in the breast milk. The breast milk also contains a variety of nonspecific defence factors contributing to its antimicrobial effect. Breast feeding has been shown to decrease morbidity in gastroenteritis, septicemia, otitis media, urinary tract infection, encephalitis, pneumonia, and necrotizing enterocolitis. The antibody content in the mother's milk probably contributes not only to the immediate but also to the long term protection of the infant including both resistance to infection and development of immunological tolerance to harmless environmental antigens.
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PMID:Antibodies in milk. 1088 98

Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by viruses in genetically susceptible individuals. Rotavirus (RV), the most common cause of childhood gastroenteritis, contains peptide sequences highly similar to T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA-2), suggesting T-cells to RV could trigger islet autoimmunity by molecular mimicry. We therefore sought an association between RV infection and islet autoantibody markers in children at risk for diabetes who were followed from birth. There was a specific and highly significant association between RV seroconversion and increases in any of these antibodies: 86% of antibodies to IA-2, 62% to insulin, and 50% to GAD first appeared or increased with increases in RV IgG or IgA. RV infection may therefore trigger or exacerbate islet autoimmunity in genetically susceptible children.
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PMID:Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. 1092 32

Human breast milk contains an array of factors with anti-infectious potential, such as immunoglobulins (especially secretory IgA), oligosaccharides and glycoproteins with anti-adhesive capacity, and cytokines. Breast-feeding is associated with protection from the following infections or infection-related conditions: gastroenteritis, upper and lower respiratory tract infection, acute otitis media, urinary tract infection, neonatal septicaemia and necrotizing enterocolitis. Some of the protective effects may derive from an altered mucosal colonization pattern in the breast-fed infant. In other instances breast-fed infants develop less symptoms to the same microbe which causes disease in the bottle-fed infant. An example of an altered colonization pattern is that breast-fed infants have less P-fimbriated, but more type 1-fimbriated E. coli. This may protect against urinary tract infection in the breast-fed infant since P. fimbriae are the major virulence factor for urinary tract infection. An example of changed consequences of the same microbial colonization is that secretory IgA in the breast-milk protects very efficiently from translocation of intestinal bacteria across the gut mucosa by coating intestinal bacteria and blocking their interaction with the epithelium. This mechanism may protect the infant from septicaemia of gut origin and, possibly, necrotizing enterocolitis. Breast-milk is also highly anti-inflammatogenic and contains hormone like factors which counteract diarrhea. Thus, breast-fed infants may be colonized by recognized diarrheal pathogens and still remain healthy. Due to a less virulent intestinal microflora and decreased translocation breast-fed infants will obtain less stimuli for the gut immune system, resulting, in e.g., lower salivary IgA antibody titres.
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PMID:Breast feeding and the intestinal microflora of the infant--implications for protection against infectious diseases. 1106 62

Worldwide, it is estimated that rotaviruses cause more than 125 million diarrheal episodes and nearly 1 million deaths per year among infants and young children. In Brazil, these agents have been associated with 13%-40% of cases of acute diarrhea affecting pediatric in-patients and outpatients. Longitudinal community-based studies involving children followed from birth to the age of three years, yielded an average of 0.3 rotavirus-related episodes of diarrhea per child per year. While seasonality of rotavirus infections is not evident in the more northern tropical areas, a peak incidence during the driest months (May to September) has been noted in Brazil's central and southern states. All four epidemiologically important rotavirus serotypes have been identified in Brazil, with Gl and G2 accounting for about two-thirds of typed strains. The recent characterization of G- and P- genotypes has demonstrated that predominant strains are essentially the same as those most commonly identified worldwide: taken together, P[S]G1 and P[4]G2 rotaviruses account for over 50% of genotyped strains. In addition, the occurrence of unusual types, such as P[8]G5, and mixed infections, have been reported in about 10% and 20% of diarrheal cases, respectively. Outbreaks of rotavirus diarrhea have been reported in both urban and remote communities, G2 type being reported to cause severe gastroenteritis among adults and children. Among Indian populations the clinical attack rate has approached 90%. Rotavirus group C has been associated with outbreaks of diarrhea in day-care centers, yielding clinical attack rates of nearly 50%. Seroprevalence studies in several regions in Brazil indicate that at least 70% of children aged 4-5 years have antibodies to rotavirus. It has also been demonstrated in longitudinal studies that heterotypic immune response in a primary infection may be an intrinsic property of the rotavirus strain. A tetravalent rhesus-human reassortant rotavirus vaccine (4 x 10,000 pfu/dose) has been evaluated in northern Brazil with the following main results: a) the vaccine was safe with only low-grade fever on days 3-5 in 2%-3% of vaccinees after the first dose; b) an IgA antibody response occurred in 58% of vaccinees and 33% of placebo recipients; and c) the overall vaccine efficacy was 35% (p = 0.03) against any rotavirus diarrhea for the 2-year study period, but reached 57% (p = 0.008) during the first year of follow-up. In view of findings indicating strain diversity throughout Brazil, a country-wild surveillance system is urgently needed to monitor circulating rotavirus strains.
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PMID:Rotavirus Infection in Brazil: Epidemiology, Immunity, and Potential Vaccination. 1110 50

Five recombinant porcine adenoviruses of serotype 5 (PAdV-5) carrying the full-length or the 5' 2.2 kb half of the transmissible gastroenteritis virus (TGEV) spike (S) gene were generated by homologous recombination in E. coli strain BJ5183 cells and subsequent transfection of swine testicle cells. The foreign genes were inserted into the E3 region of PAdV-5. One recombinant virus had no deletion in the E3 region, whereas a 1.2 kb fragment was removed from the E3 region in the remainder of the recombinant viruses. One stable construct with a 4.4 kb insertion had a genome size of 109.6% of the wild-type genome, the largest reported for any recombinant adenovirus. Only those viruses that carried the S gene in the left to right orientation expressed the S gene. Three recombinant viruses were tested by oral immunization of pigs and both antibody response and virus shedding were monitored. None of the pigs showed clinical signs and the virus was recovered from rectal swabs until 6-7 days post-infection. Viruses expressing the S gene induced TGEV- and PAdV-5-specific virus-neutralizing antibodies. Moreover, TGEV-specific secretory IgA was detected in the small intestine and in the lungs of the immunized animals.
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PMID:Construction and characterization of recombinant porcine adenovirus serotype 5 expressing the transmissible gastroenteritis virus spike gene. 1112 71

Rotavirus (RV) is the main cause of severe gastroenteritis in young children; protection has been correlated with intestinal Ab responses. Using a mouse model of RV infection and beta(7)-deficient (beta(7)(-/-)) mice, which do not express alpha(4)beta(7) integrin, we demonstrated the importance of alpha(4)beta(7) integrin in B cell-mediated anti-RV immunity. beta(7)(-/-) mice acutely infected with murine RV resolved infection and developed normal serum IgG Abs but had diminished intestinal IgA responses. alpha(4)beta(7)(-/-) immune B cells did not resolve RV infection when adoptively transferred into RV-infected Rag-2-deficient mice. Fewer RV-specific B cells were found in the intestine of Rag-2-deficient mice transferred with beta(7)(-/-) B cells compared with wild type. The absence of alpha(4)beta(7) expression and/or a lower frequency of IgA-producing cells among transferred beta(7)(-/-) B cells could have accounted for the inability of these cells to resolve RV infection following passive transfer. To distinguish between these possibilities, we studied the importance of IgA production in RV infection using IgA-deficient (IgA(-/-)) mice. IgA(-/-) mice depleted of CD8(+) T cells were able to clear primary RV infection. Similarly, adoptive transfer of immune IgA(-/-) B cells into chronically infected Rag-2-deficient mice resolved RV infection. We further demonstrated in both wild-type and IgA(-/-) mice that, following oral RV infection, protective B cells reside in the alpha(4)beta(7)(high) population. Our findings suggest that alpha(4)beta(7) integrin expression is necessary for B cell-mediated immunity to RV independent of the presence of IgA.
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PMID:Protective intestinal anti-rotavirus B cell immunity is dependent on alpha 4 beta 7 integrin expression but does not require IgA antibody production. 1116 Feb 37

With an estimated 100 million victims, pandemically and epidemically occurring plague has been looked upon as a classical scourge of mankind during the last two millenia. Without treatment at least 50% of the affected individuals die from infection with Yersinia pestis, a bacterium belonging to the family of Enterobacteriaceae. The disease takes a fulminant course. After an incubation period of 2-6 days, bubonic plague primarily attacks one group of lymph nodes. The onset of pulmonic plague, transmitted by droplet infection, takes place within several hours and causes bronchopneumonia. Early recognition facilitates a promising antibiotic therapy with tetracycline, streptomycin or chloramphenicol. Human beings acquire the bacteria through bites of fleas from domestic rats in densely populated cities of countries with low hygienic standards, or sporadically in the open country from infected wild rodents. Laboratory procedure includes microscopy supplemented by immunofluorescence and cultivation of the bacterium from clinical material. Direct serology and PCR result in a fast detection of specific antigens or nucleotide sequences. Determination of serum antibodies is principally used for epidemiological investigation. Today, physicians in the civilized western world lack experience for the recognition of plague, and analytical techniques for diagnosis are only available in some specialized laboratories. Yersiniosis becomes primarily manifest as gastroenteritis caused by Yersinia enterocolitica or as pseudoappendicitis caused by Yersinia pseudotuberculosis and requires antibiotics only in severe septic cases. Different extraintestinal symptoms may be observed in dependence on the patient's HLA type and gender. The ubiquitous germ is mainly transmitted by the fecal-oral route via infected domestic or farm animals and contaminated food. The relevant virulence factors are encoded on a 70 kB plasmid common to all Yersinia species and strains that are human pathogens. The most important tools for laboratory diagnosis are culture from suitable body fluids and serological detection of specific antibodies. The infection rate among healthy individuals in Europe in terms of percentage of elevated IgA or IgG titers has been quoted to be 3-40% in different investigations but does not significantly correlate to direct bacteriological detection.
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PMID:Plague and other human infections caused by Yersinia species. 1159 7


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