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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intraluminal fate of orally administered radioactive vitamin B12 has been studied in control subjects with normal vitamin B12 absorption and those with vitamin B12 malabsorption due to tropical sprue. In control subjects 1 to 21% of the dose was bound to sedimentable material and 37 to 75% was bound to immunoreactive intrinsic factor. In subjects with vitamin B12 malabsorption due to tropical sprue, the results were identical with the control subjects. Bacteriological studies showed a statistically significant correlation between both the number of flora in the jejunum and the number of bacteroides in both the jejunum and ileum and vitamin B12 malabsorption. In patients with tropical sprue who have normal intrinsic factor secretion, the vitamin B12 absorptive defect is not due to binding of the vitamin to bacteria or to alteration to the intrinsic factor vitamin B12 complex in the intestinal lumen. The lesion appears to be one of the mucosal cell receptors or of the cells themselves, possibly caused by bacterial toxins.
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PMID:Vitamin B12 absorption--a study of intraluminal events in control subjects and patients with tropical sprue. 0 57

To determine the mechanism by which pancreatic extract (PE) corrects the malabsorption of vitamin B12 in chronic pancreatic insufficiency (CPI), the following hypotheses were investigated: Firstly, PE might stimulate the absorption of vitamin B12 by changing the intestinal pH, secondly PE might stimulate the intestinal uptake of unbound vitamin B12, thirdly PE might abolish the inhibitory effect of vitamin B12 binders on the intestinal uptake of vitamin B12 bound to intrinsic factor (IF). PE had no effect on the pH in the small intestine and did not stimulate the uptake of unbound 57CoB12 by perfused rat intestinal segments. Preincubation of 57CoB12-IF with a non-IF B12-binder from human saliva (R-binder) reduced the uptake of 57CoB12 from 18.5 pg per cm intestine +/- 3.4 S.E.M. to 7.8 +/- 1.6 (p less than 0.02). PE abolished this inhibitory effect (p less than 0.05). The results indicate that PE corrects the malabsorption of vitamin B12 in CPI by an effect on non-IF B12- binders.
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PMID:Pancreatic extract and the intestinal uptake of vitamin B12. III. Stimulatory effect in the presence of a non-intrinsic factor vitamin B12 binder. 1 12

Cobalamin (Cbl; vitamin B(12)) malabsorption in pancreatic insufficiency can be partially corrected by bicarbonate and completely corrected by pancreatic proteases but the mechanisms involved are unknown. Because saliva contains enough R-type Cbl-binding protein (R protein) to bind all of the dietary and biliary Cbl, it is possible that R protein acts as an inhibitor of Cbl absorption and that pancreatic proteases are required to alter R protein and prevent such inhibition. To test this hypothesis we studied the ability of R protein and intrinsic factor (IF) to compete for Cbl binding and ability of pancreatic proteases to alter this competition. Human salivary R protein bound Cbl with affinities that were 50- and 3-fold higher than those of human IF at pH 2 and 8, respectively. Cbl bound to IF was transferred to an equal amount of R protein with t((1/2))'s of 2 and 90 min at pH 2 and 8, respectively, and within several hours respective ratios of R protein-Cbl/IF-Cbl of 50 and 2 were observed. Cbl bound to R protein was not transferred to IF at either pH 2 or 8. Incubation of R protein with pancreatic proteases at pH 8 led to a 150-fold decrease in its affinity for Cbl. Incubation of R protein-Cbl with pancreatic proteases led to complete transfer of Cbl to IF within 10 min. Gel filtration studies with R protein-[(57)Co]Cbl and (125)I-R protein showed that pancreatic proteases partially degraded R protein. Pancreatic proteases differed in their ability to effect these changes with trypsin > chymotrypsin > elastase. Pancreatic proteases did not alter IF in any of the parameters mentioned above. Pepsin failed to alter either R protein or IF. THESE STUDIES SUGGEST THE FOLLOWING: (a) that Cbl is bound almost exclusively to R protein in the acid milieu of the stomach, rather than to IF as has been assumed previously; (b) that Cbl remains bound to R protein in the slightly alkaline environment of the intestine until pancreatic proteases partially degrade R protein and enable Cbl to become bound exclusively to IF; and (c) that the primary defect in Cbl absorption in pancreatic insufficiency is a lack of pancreatic proteases and a failure to alter R protein and effect the transfer of Cbl to IF. These studies also suggest that the partial correction of Cbl malabsorption observed with bicarbonate is due to neutralization of gastric HCl, since at slightly alkaline, pH IF can partially compete with R protein for the initial binding and retention of Cbl.
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PMID:Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency. 2 56

Pepsin had no effect on the vitamin B12 binder in human saliva (R-binder), while trypsin was found to reduce the apparent molecular weight of the R-binder and to release vitamin B12 from the R-B12complex of human saliva and human gastric juice (HGJ). Trypsin had no effect on the molecular weight and biological activity of intrinsic factor (IF) in HGJ, as demonstrated by gel filtration on Sephadex G-150 and the uptake of IF-B12 by guinea pig intestinal brush borders. An extract of purified guinea pig intestinal lysosomes was also without effect on the molecular weight and the biological activity of IF but was found to release vitamin B12 from the R-B12 complex. The results support the observation that the external pancreatic secretion corrects malabsorption of vitamin B12 by an effect on the non-IF protein in the intestinal juice. Moreover, the results indicate that lysosomal enzymes are not involved in the intestinal absorption of vitamin B12.
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PMID:The effect of proteolytic enzymes on the vitamin B12-binding proteins of human gastric juice and saliva. 12

In six patients with pernicious anemia, absorption of vitamin B12 bound to intrinsic factor was low as measured by the Schilling's test. Collection of urine was complete and the activity of intrinsic factor used was checked in other pernicious anemia patients. Nutritional deficiency, drug induced malabsorption, ileal or pancreatic diseases were excluded by clinical, radiological and biological investigations. This vitamin B12 malabsorption was selective and reversible within a few months after treatment with parenteral vitamin B12. Mechanisms of this ileal dysfunction are discussed.
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PMID:[Transient malabsorption of Vitamin B12 bound to intrinsic factor in pernicious anemia (author's transl)]. 12 17

A baby girl, born prematurely and with Down's syndrome, is hospitalized at the age of 51 days for a megaloblastic anemia. The anemia was caused by a selective malabsorption of vitamin B12 (Imerslund's syndrome), even in presence of intrinsic factor. The pathogenesis of different causes of vitamin B12 deficiency is discussed and the favourable development of this case after four years of treatment is shown.
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PMID:[Congenital malabsorption of vitamin B12 (Imerslund's syndrome) in a premature girl with Down's syndrome (author's transl)]. 15 16

The diagnostic interest of a search for anti-intrinsic factor antibodies is emphasized from the authors research on more than 200 patients or controls. Antibodies of type I, so-called blocking antibodies, were detected in 66% of cases where the diagnosis of pernicious anemia was made. Type II, so-called precipitating antibodies, were found in 47% of patients with antibodies of type I and only in the latter. Certain etiological factors, already noted in the world literature, were found, in particular the link with the female sex and with blood group A. The specificity of these antibodies is very great and false positives are exceptional. We did not find them in any of the 104 controls. They were observed, however, in 5 of the 56 patients where the diagnosis of pernicious anemia was not definite, but it is likely that, in these 5 cases, pernicious anemia existed with some other disease. Our study also showed the limits of other methods of investigation of this disease; hypovitaminimia B12 is often corrected by treatment without proper inductions and B12 malabsorption on the Schilling test may not be corrected by the addition of intrinsic factor.
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PMID:[Search for anti-intrinsic factor antibodies in the diagnosis of Biermer's anemia]. 16 41

A new rapid and accurate method for detecting vitamin B12-intrinsic factor (IF-B12) receptors was used to study the distribution of mucosal IF-B12 receptors in three human small intestines. IF-B12 receptors in human intestine are present in significant amounts in the entire distal three-fifths of intestine. Triokinase activity is absent in the distal two-fifths of intestine, and tryptophan oxygenase is present only in the distal one-sixth, or most terminal part of the ileum. These data suggest (1) biochemical functions in the ileum have different anatomical distributions, (2) IF-B12 receptors correspond most closely with the accepted anatomical definitions of the ileum, and (3) vitamin B12 malabsorption seen in resection or disease of terminal ileum may not be attributable solely to a deficiency of ileal receptors.
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PMID:Distribution of intrinsic factor-vitamin B12 receptors in human intestine. 19 33

Crude preparations of hog gastric intrinsic factor or their own previously collected gastric juices administered with labeled vitamin B12 did not enhance vitamin B12 absorption in patients with vitamin B12 malabsorption secondary to pancreatic insufficiency. However, when these sources of gastric intrinsic factor were incubated with three times crystallized preparations of insolubilized bovine trypsin or chymotrypsin, the proteolytic enzymes were removed by centrifugation, and the preparations of gastric intrinsic factor were readministered to these patients, the absorption of vitamin B12 was markedly enhanced. Studies of hog gastric intrinsic factor before and after exposure to proteolytic enzymes failed to show any difference on Sephadex chromatography or polyacrylamide gel electrophoresis or on its affinity for vitamin B12 or the ileal receptor in guinea pigs. These investigations demonstrate that: (1) gastric intrinsic factor as secreted by subjects with pancreatic insufficiency or obtained from hog pyloric mucosal extracts is ineffective in promoting vitamin B12 absorption in patients with pancreatic insufficiency, (2) incubation of crude preparations of gastric intrinsic factor with insolubilized pancreatic proteases modified these preparations of gastric intrinsic factor in an as yet undefined manner, allowing them to enhance vitamin B12 absorption, and (3) in vitro studies using gut sacs or brush border preparations do not reflect the abnormality in vitamin B12 absorption associated with pancreatic dysfunction.
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PMID:Evidence that pancreatic proteases enhance vitamin B12 absorption by acting on curde preparations of hog gastric intrinsic factor and human gastric juice. 31 82

Human bile incubated with vitamin B12 bound to intrinsic factor in human gastric juice will effectively dissociate this complex, and the vitamin will transfer to non-intrinsic factor unsaturated binding protein(s) contained in bile. Preincubation of the bile with pancreatic enzymes, particularly trypsin, and pepsin, decreases this effect of bile on the intrinsic factor--vitamin B12 complex by digesting the unsaturated binder(s) in the bile. These studies help explain why there is malabsorption of tracer amounts of vitamin B12 in some patients with pancreatic insufficiency, and why this abnormality is correctable by the administration of pancreatic extract.
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PMID:Dissociation of the intrinsic factor--vitamin B12 complex by bile: contributing factor to B12 malabsorption in pancreatic insufficiency. 38 77


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