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)

A case of beta galactosidase deficiency is described in a 20-month-old boy. The child was hospitalized at 4 months of age for malabsorption syndrome. Biopsies of the small intestine and liver were performed and electron microscopy of the liver specimens strongly suggested a gangliosidosis. The cytoplasm of macrophages, Kupffer cells and hepatocytes contained membrane-bound lysosomes with a granular, fibrillar appearance and tubular structures interpreted as ganglioside deposits. Enzymatic deficiency was confirmed by biochemical investigation of leukocytes from both the patient and members of his immediate family. Although visceromegaly is typical of Landing disease, symptoms of malabsorption and hypertension have not been reported in its course.
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PMID:Landing disease, GM1 generalized gangliosidosis, and malabsorption syndrome. 250 73

Rotavirus and enterotoxigenic Escherichia coli (ETEC) are enteropathogens each capable of inducing diarrhoea in some animal species and man. Unstressed young animals develop an age-related resistance to infection with either rotavirus or ETEC which differs for each animal species. The effects of experimental infection of calves, lambs, foals and piglets with rotavirus and ETEC given either alone or in combination, have been examined. In general, dual infections tended to lengthen the period of age susceptibility and increase the severity of gastroenteritis, compared to infection with either agent alone. ETEC caused little or no pathological changes in the small intestine while rotavirus induced moderate inflammatory, morphological and physiological changes including reduced activity of membrane-bound digestive enzymes. In dual infections, mucosal lesions were more severe than those seen after rotavirus infection and ETEC proliferation in the lumen of the small intestine was greater than in animals infected with ETEC alone. Two distinct mechanisms of diarrhoea, presumably, were involved; net fluid hypersecretion into the lumen of the gut mediated by ETEC enterotoxin(s), and brush border maldigestion and malabsorption which was caused by rotavirus infection of the small intestine.
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PMID:The clinical manifestation and pathogenesis of enteritis associated with rotavirus and enterotoxigenic Escherichia coli infections in domestic animals. 636 57

Metallochemical and biochemical studies completed in the Department of Ophthalmology at the University of California, Irvine, offer a new perspective in understanding MS. Low plasma zinc levels were observed in MS patients, and this has been confirmed in laboratories elsewhere in the world. Generalized malabsorption could not be demonstrated in MS patients when using a double-blind, randomized study of 72-hours fecal fat. A double-blind, randomized zinc tolerance test confirmed the low plasma zinc levels in fasting MS patients, but once an oral zinc load had been given, the 7-hour post treatment levels were elevated to that of control patients. Intracellular erythrocyte zinc concentration was measured in controls and in MS patients. The controls had no change over 7 hours despite a large zinc load with consequent elevation in plasma levels. However, MS patients demonstrated a gradual elevation of intracellular zinc concentration over the 7-hour period, with P less than 0.01. Thus, the erythrocyte membranes of controls were able to maintain the zinc gradient between the extracellular and the intracellular compartments, while MS patients were not, suggesting a functional abnormality in plasma membranes outside of central nervous system. Erythrocyte membrane-bound CNP was observed to be abnormality low in MS patients when compared to controls. The study has been confirmed by a different laboratory using a different substrate on MS erythrocytes. The rationale for considering MS as a possible systemic disease is presented.
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PMID:[A hypothesis: multiple sclerosis a systemic disease]. 640 58

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

Cystic fibrosis (CF) is associated with deficiencies in certain essential fatty acids. These deficiencies have been studied in plasma, red blood cells, and mucus and were previously thought to be a result of malnutrition or malabsorption. More recent studies have indicated that these deficiencies are independent of nutritional status. However, these studies examined fatty acids in plasma but not in CF-regulated tissues. In the pancreas, lungs, and ileum of CF knock-out mice, membrane-bound arachidonic acid levels have been shown to be increased while docosahexaenoic acid levels are decreased. This lipid abnormality is reversed following oral administration of docosahexaenoic acid (DHA). In addition, DHA therapy reverses the increased neutrophil infiltration in the lungs of CF knock-out mice. Further studies are required to determine the mechanism by which CF gene mutations lead to this lipid abnormality.
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PMID:Fatty acids in cystic fibrosis. 1110 Sep 64

Some interesting advances in mechanisms and regulation of nutrient absorption were reported last year. Further evidence was obtained that the rate-limiting step in triacylglycerol absorption, especially with large doses of lipid, is transport of prechylomicrons from the endoplasmic reticulum to the Golgi apparatus. Targeted disruption of the adenosine triphosphate-binding cassette transporter in mice produced changes similar to human Tangier disease and suggested that this mouse may be a model for studying intestinal high-density lipoprotein assembly and secretion. A new mechanism for carbohydrate malabsorption was discovered: in sucrase-isomaltase deficiency, the enzyme fails to anchor in the brush border membrane and so is secreted into the lumen, where it is ineffective. Glycosylating insulin at B1 phenylalanine permitted it to bind to the brush border membrane and greatly enhanced its hypoglycemic activity when given orally. CaCo-2 cells and normal human enterocytes were shown to have two variants of the human sodium-dependent vitamin C transporter, hSVCT1; one is active and the other is an inactive splice variant. In rats, the divalent metal ion transporter, DMT1, appeared to be important for regulation of both absorption of iron and its movement into the liver.
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PMID:Nutrient absorption. 1122 65

Carbohydrates are hydrolyzed in the intestinal lumen by specific enzymes to monosaccharides before transport across the brush border membrane of epithelial cells into the cell interior. The enzymes implicated in the digestion of carbohydrates in the intestinal lumen are membrane-bound glycoproteins that are expressed at the apical domain of the enterocytes. Absent or reduced activity of one of these enzymes is the cause of disaccharide intolerance and malabsorption, the symptoms of which are abdominal pain, cramps or distention, flatulence, nausea and osmotic diarrhea. Lactose intolerance is the most common intestinal disorder that is associated with an absence or drastically reduced levels of an intestinal enzyme, in this case lactase-phlorizin hydrolase (LPH). The pattern of reduction of activity has been termed late onset of lactase deficiency or adult type hypolactasia. It was thought that the regulation of LPH was post-translational and was associated with altered structural features of the enzyme. Recent studies, however, suggest that the major mechanism of regulation of LPH is transcriptional. Other forms of lactose intolerance include the rare congenital lactase deficiency and secondary forms, such as those caused by mucosal injury, due to infectious gastroenteritis, celiac disease, parasitic infection, drug-induced enteritis and Crohn's disease. This review will shed light on important strucural and biosynthetic aspects of LPH, the role played by particular regions of the LPH protein in its transport, polarized sorting, and function, as well as on the gene expession and regulation of the activity of the enzyme.
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PMID:Molecular and cellular aspects and regulation of intestinal lactase-phlorizin hydrolase. 1133 11

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.
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PMID:Small bowel review: normal physiology part 1. 1176 47

Piecemeal degranulation is a unique pattern of cell secretion that consists of a slow release of granule contents from cytoplasmic secretory granules, which leaves empty chambers that do not fuse with each other or with the plasma membrane. To our knowledge, no cell types other than mast cells, basophils, and eosinophils have been reported in the literature to show morphological features of piecemeal degranulation. In the present study we provide evidence for ultrastructural morphologies characteristic of piecemeal degranulation in entero-endocrine cells of the human and murine gastrointestinal epithelia. Human biopsy samples were taken from the mucosa of the distal duodenum, proximal jejunum, and colon in 10 patients undergoing endoscopic examination for malabsorption, diarrhea, and/or abdominal pain. Murine gastrointestinal samples were obtained from 10 adult C57 mice. All specimens were prepared for transmission electron microscopy (TEM) according to standard protocols. Results showed that different types of gastrointestinal entero-endocrine cells, in both humans and mice, were recognizable with ultrastructural features diagnostic for piecemeal degranulation, including specific granule and cytoplasmic changes. In the granules, the content was found to be loosely packed or diminished. Notably, altered granules did not fuse with each other or with the plasma membrane, and were characteristically intermingled with normal, resting granules. At times, the release events transformed the granules into enlarged, empty containers. Numerous entero-endocrine cells presented a rich supply of membrane-bound vesicles (50-200 nm in diameter) that were free in the cytoplasm or attached to granules. This finding of piecemeal degranulation in gastrointestinal entero-endocrine cells suggests that such a secretory model might be a general degranulation pattern in cells involved in paracrine-endocrine secretion.
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PMID:Granule changes of human and murine endocrine cells in the gastrointestinal epithelia are characteristic of piecemeal degranulation. 1242 Feb 82

The 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase (C(27) 3beta-HSD) is a membrane-bound enzyme of the endoplasmic reticulum that catalyzes an early step in the synthesis of bile acids from cholesterol. Subjects with autosomal recessive mutations in the encoding gene, HSD3B7, on chromosome 16p11.2-12 fail to synthesize bile acids and develop a form of progressive liver disease characterized by cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract. The gene encoding the human C(27) 3beta-HSD enzyme was isolated previously, and a 2-bp deletion in exon 6 of HSD3B7 was identified in a well characterized subject with this disorder. Here, we report a molecular analysis of 15 additional patients from 13 kindreds with C(27) 3beta-HSD deficiency. Twelve different mutations were identified in the HSD3B7 gene on chromosome 16p11.2-12. Ten mutations were studied in detail and shown to cause complete loss of enzyme activity and, in two cases, alterations in the size or amount of the transcribed mRNA. Mutations were inherited in homozygous form in 13 subjects from 10 families and compound heterozygous form in four subjects from three families. We conclude that a diverse spectrum of mutations in the HSD3B7 gene underlies this rare form of neonatal cholestasis.
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PMID:Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease. 1267 81


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