Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rotaviruses are the commonest cause of diarrhea and are responsible for more than 25% of all deaths from diarrhea worldwide. Children become infected early in life and most infections in infants older than 3 months are symptomatic. These viruses account for 18 million cases of moderate or severe disease and 900,000 deaths each year. The incidence of rotaviral disease is similar in developed and developing countries but the number of deaths is higher in developing countries. Infections occur throughout the year in developing countries but are seasonal in developed countries, occurring mainly between October and March. The mean age at first infection is 6 to 9 months in developing countries and 9 to 15 months in developed countries. The greater severity of infections in developing countries is associated with malnutrition, lower hygiene standards and the lactose malabsorption and deficiencies of zinc and vitamin A that accompany diarrhea. Many mixed infections also increase the severity of the rotavirus infection. The clinical symptoms of the disease in hospitalized patients are diarrhea, vomiting and dehydration. There is more vomiting than with bacterial infections. The severity of the clinical symptoms depends on the virulence of different strains. The disease is more severe and persistent in patients with reduced immunity. Age also has an effect. All children may have rotavirus in their feces but the percentage of children developing diarrhea is highest at an age of 3 to 6 months and decreases steadily thereafter. Rotaviruses can survive in air and may remain on surfaces for several hours. They are thus often responsible for nosocomial infections. Rotavirus was first identified in cattle in 1969. The virulence of the strain and the age of the calf at infection are important in the pathogenesis of rotaviral infection in cattle. Replacement of villous enterocytes is slow in newborn calves. This means that newborn calves are susceptible to disease caused by strains that are only moderately virulent. They are, however, protected during the first days of life by antibodies transmitted via the colostrum. There is competition between the rate of replication of rotavirus and replacement of enterocytes in older animals so only more virulent strains cause diarrhea in six-week-old calves. Adult animals become resistant to disease, but not to infection. The rotavirus genome consists of 11 segments of double-stranded RNA. Genetic recombination between these segments occurs naturally and can be reproduced in vitro. Recombinants between human and bovine strains have been identified but the epidemiological importance of this is unknown. The genomic segments encode 6 structural proteins (VP) and 5 non-structural proteins (NSP). VP6, the major capsid antigen, present can be used to identify groups of rotaviruses. The presence of VP7 indicates that the virus belongs to the G (glycoprotein) group of serotypes. There are 14 G serotypes, 10 of which can infect humans. The four main G serotypes are G1 to G4, with G1 accounting for 60% of human serotypes. The presence of VP4 identifies the P (protease-sensitive) serotype. The serotypes have different geographic distributions with G1P8 responsible for more than 50% of epidemics worldwide. The WHO project for the control of rotaviral infections focuses on avoiding fecal contamination. This is achieved by ensuring high standards of food hygiene, sewage treatment and chlorinated running water and by introducing vaccination when vaccines become available. Recombinant animal (bovine or simian) and human rotaviruses are currently being tested in phase III studies. Attenuated live human viruses, including cold-adapted strains are being tested in phase I trials. The quadrivalent recombinant rhesuslhuman vaccine had only mild side-effects in children and was effective, giving 82-92% protection against severe diarrhea over two years and 50% protection on average. (ABSTRACT TRUNCATED)
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PMID:[Rotaviruses in human and veterinary medicine]. 929 11

The disease is characterised by cobalamin (Cbl) deficiency in children 0-5 years old, causing failure to thrive, infections, megaloblastic anaemia, neuropathy, and mild general malabsorption; slight proteinuria is common. Cbl injections produce remission, but Cbl malabsorption and proteinuria persist. About 250 cases have been reported. Dogs also have it. The heredity is autosomal and recessive. The physiological and pathological absorption mechanisms are described: Cbl liberated from food by digestion is first bound to haptocorrin, but in the intestine it is transferred to intrinsic factor. In the ileum the complex attaches to a receptor on the enterocytes; this requires neutral pH and Ca2+. The receptor is a membrane-bound glycoprotein consisting of multiple subunits. The receptor-ligand complex is endocytosed and degraded in lysosomes, and the vitamin is transferred to transcobalamin which carries it to tissues. The same receptor is strongly expressed in the kidneys, but urine also contains its activity which can be assayed for diagnosis. The basic lesion is an error in the ileal receptor. In the affected dogs the synthesised receptor is retained intracellularly. Urine and ileal biopsies from human cases contained little receptor but it had conserved affinity for the ligand. Recently examined Arab patients did not excrete reduced amounts of the receptor. Apparently, the disease has subsets, such as different structural errors in the receptor and possibly faulty transport inside the enterocyte. The cause of the proteinuria is unknown but kidney damage due to severe Cbl deficiency and an error in a multiligand renal receptor are among the possibilities.
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PMID:Selective cobalamin malabsorption and the cobalamin-intrinsic factor receptor. 958 52

Intestinal uptake of vitamin B12 (hereafter B12) is impaired in a significant proportion of the human population. This impairment is due to inherited or acquired defects in the expression or function of proteins involved in the binding of diet-derived B12 and its uptake into intestinal cells. Bovine milk is an abundant source of bioavailable B12 wherein it is complexed with transcobalamin. In humans, transcobalamin functions primarily as a circulatory protein, which binds B12 following its absorption and delivers it to peripheral tissues via its cognate receptor, CD320. In the current study, the transcobalamin-B12 complex was purified from cows' milk and its ability to stimulate uptake of B12 into cultured bovine, mouse and human cell lines was assessed. Bovine milk-derived transcobalamin-B12 complex was absorbed by all cell types tested, suggesting that the uptake mechanism is conserved across species. Furthermore, the complex stimulated the uptake of B12 via the apical surface of differentiated Caco-2 human intestinal epithelial cells. These findings suggest the presence of an alternative transcobalamin-mediated uptake pathway for B12 in the human intestine other than that mediated by the gastric glycoprotein, intrinsic factor. Our findings highlight the potential for transcobalamin-B12 complex derived from bovine milk to be used as a natural bioavailable alternative to orally administered free B12 to overcome B12 malabsorption.
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PMID:Transcobalamin derived from bovine milk stimulates apical uptake of vitamin B12 into human intestinal epithelial cells. 2491 91

Porcine epidemic diarrhea virus (PEDV), a coronavirus discovered more than 40 years ago, regained notoriety recently by its devastating outbreaks in East Asia and the Americas, causing substantial economic losses to the swine husbandry. The virus replicates extensively and almost exclusively in the epithelial cells of the small intestine resulting in villus atrophy, malabsorption and severe diarrhea. Cellular entry of this enveloped virus is mediated by the large spike (S) glycoprotein, trimers of which mediate virus attachment to the target cell and subsequent membrane fusion. The S protein has a multidomain architecture and has been reported to bind to carbohydrate (sialic acid) and proteinaceous (aminopeptidase N) cell surface molecules. PEDV propagation in vitro requires the presence of trypsin(-like) proteases in the culture medium, which capacitates the fusion function of the S protein. Here we review the current data on PEDV entry into its host cell, including therein our new observations regarding the functional role of the sialic acid binding activity of the S protein in virus infection. Moreover, we summarize the recent progress on the proteolytic activation of PEDV S proteins, and discuss factors that may determine tissue tropism of PEDV in vivo.
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PMID:Cellular entry of the porcine epidemic diarrhea virus. 2731 67


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