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At least 667 records · Page 37Linked to original sources
PubMed1987

Immunohistochemical distribution of vitamin B12 R-binder in renal cell carcinoma.

Renal cell carcinomas and normal kidney tissues were examined for the expression of vitamin B12 R-binder by the indirect immunoperoxidase method. In normal kidney tissue, the presence of the vitamin B12 R-binder was shown to be confined to the straight portion (pars recta) of proximal tubules. Seven of the 38 cases of renal cell carcinoma (18%) expressed the vitamin B12 R-binder antigen. This provides a further evidence of the proximal tubular nature of renal cell carcinoma, and suggests that a small proportion of renal cell carcinomas originate from the straight portion of the renal proximal tubules.

Carcinoma, Renal Cell↗
PubMed1982

Influence of lithium and fluoride on degranulation from human neutrophils in vitro.

We have demonstrated that degranulation from normal human neutrophils in whole blood was stimulated by low concentrations of lithium salts and was produced by noncytolytic means. Significant amounts of beta-glucuronidase could be released from the primary granules, in addition to vitamin B12- binding protein from the secondary granules, by 10 mM lithium. Release was almost totally inhibited by 1 mM fluoride, under the same conditions. There was no release of lactate dehydrogenase and no loss of viability of cells incubated in either lithium or fluoride at the concentrations used. Lithium was also observed to have no effect on reactive oxygen production by phagocytic stimulation of isolated neutrophils. In addition, lithium and fluoride were shown to manipulate the intracellular levels of cAMP. The results demonstrated a direct effect of lithium on release of inflammatory mediators from neutrophils in vitro. The methods used also provide a simple and effective test to study an important function of neutrophil activity and can be used to evaluate degranulation in a number of clinical conditions.

Cyclic AMP↗
PubMed1984

Inhibition of human neutrophil secondary granule discharge by antiinflammatory agents.

Human neutrophil cobalamin binding protein (NCBP) is located exclusively in the neutrophil secondary granules. The soluble stimuli formlymethionyl-leucyl-phenylalanine and the low-molecular-weight complement fragment C5a both promote the dose-dependent release of NCBP from cytochalasin B-treated neutrophils in vitro. The extracellular discharge of NCBP induced by higher secretagogue is inhibited by prior exposure of neutrophils to the corticosteroids hydrocortisone and methylprednisolone and the nonsteroidal antiinflammatory agents indomethacin and ibuprofen. The four antiinflammatory agents function as competitive antagonists of neutrophil secondary granule discharge with a site of action at or near the cell surface. These findings support the hypothesis that antiinflammatory agents prevent neutrophil activation in vitro by inhibition of stimulus-receptor coupling. The significance of these observations with regard to the in vivo actions of these agents remains uncertain, however.

Anti-Inflammatory Agents↗
PubMed1994

In vitro studies of gastric juice in patients with food-cobalamin malabsorption.

Food-cobalamin absorption depends on the initial release of cobalamin from its binders in food. Therefore, the characterization of patients' gastric juices and their behavior in this process was undertaken. Pentagastrin-stimulated gastric juice specimens from three patients with severe food-cobalamin malabsorption, six patients with mild malabsorption, and five patients with normal absorption were tested for pH, pepsin, intrinsic factor content, and an in vitro method that quantitates transfer of cobalamin from egg yolk to gastric R binder. Transfer of cobalamin correlated best with in vivo egg yolk-cobalamin absorption test results in the 14 patients (r = 0.731, P < 0.005). Transfer also correlated inversely with gastric juice pH (r = -0.619, P < 0.02). Basal gastric juice specimens, with their higher pH, from the same subjects failed to promote cobalamin transfer until their pH was lowered to 1.0-1.3. Pepsin levels did not correlate with in vitro transfer or with absorption in vivo; nevertheless, raising the low pepsin concentration of one stimulated gastric juice improved transfer, while inhibiting pepsin activity with pepstatin A inhibited transfer. Mixing experiments with selected stimulated gastric juices demonstrated that poor in vitro transfer, which in a few cases seemed unrelated to pH or pepsin levels, was not due to any inhibitory activity of such gastric juices. These studies confirm that gastric acid and pepsin play a central role in releasing food-bound cobalamin and transferring it to R binder, but suggest that other, still unidentified gastric defects occasionally contribute to impaired transfer; the latter defects are not inhibitory in nature but seem to involve the absence of a permissive activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric Juice↗
PubMed1987

The absorption of free vitamin B12 and R protein-bound vitamin B12 in the diagnosis of pancreatic exocrine insufficiency in rats.

Vitamin B12 (B12) absorption was studied in rats following biliopancreatic duct ligation. The absorption of free B12, as well as of hog R protein-bound B12, was markedly impaired after both intragastric and intraduodenal administration in these rats. The intraduodenal administration of a mixture of pancreatic extract and sodium bicarbonate (NaHCO3) improved the absorption of both free and R protein-bound B12. However, pancreatic extract without NaHCO3 was ineffective in this respect. Intraduodenal administration of NaHCO3 without pancreatic extract worsened the R protein-bound B12 absorption. This finding would indicate that the degradation of R protein by proteolytic enzymes, in the intestine of rats with pancreatic juice exclusion, is inhibited by NaHCO3.

Animals↗
PubMed1985

Vitamin B12-binding proteins of the horseshoe crab Limulus polyphemus.

Vitamin B12-binding proteins were detected in the body fluids and/or tissues of horseshoe crabs (Limulus polyphemus), clams and sponges. Among the biological specimens tested the Limulus plasma was especially rich in free B12-binding proteins. Gel filtration experiments revealed that Limulus plasma contains two classes of B12-binding proteins. One class of proteins, molecular weight in excess of 100,000, bind B12 preferentially with affinity constant of 5 X 10(11)M-1. The second type of proteins, molecular weights around 50,000, bind B12 with specificity approaching that of mammalian intrinsic factors. The binding constant of these proteins for B12 is around 10(11)M-1.

Animals↗
PubMed1985

Properties of interleukin-1 as a complete secretagogue for human neutrophils.

Human monocyte-derived Interleukin-1 (IL-1) stimulated a concentration-dependent extracellular release of azurophil (myeloperoxidase) and specific (vitamin B12-binding protein) granule constituents from cytochalasin B-treated human neutrophils. The serine protease inhibitors, L-1-tosylamide-2-phenylethyl-chloromethyl ketone (TPCK) and N-alpha-p-tosyl-L-lysine-chloromethyl ketone (TPCK) as well as an inhibitor of thiol protease activity, p-hydroxymercuribenzoate (PHMB), suppressed granule enzyme release from neutrophils activated with IL-1. Cycloheximide, an inhibitor of protein synthesis, had no effect on IL-1-induced neutrophil degranulation. Neutrophils pretreated with IL-1 were rendered unresponsive to subsequent exposure to this stimulus. IL-1-elicited granule exocytosis appears to be stimulus specific in that N-formyl-methionyl-leucyl-phenylalanine (FMLP), 1-0-hexadecyl/octadecyl-2-0-acetyl-sn-glyceryl-3-phosphorycholine (AGEPC), and 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4) were capable of eliciting a secretory response from IL-1-pretreated cells.

Cycloheximide↗
PubMed1987

Human neutrophils contain subpopulations of specific granules exhibiting different sensitivities to changes in cytosolic free calcium.

We examined the role of mobilization of intracellular calcium in the ability of human neutrophils to discharge specific granule constituents upon stimulation with the synthetic chemotactic factor, N-formyl-met-leu-phe. Extracellular calcium was not required for optimal secretion of the specific granule markers lactoferrin and vitamin B12-binding protein. Depletion and chelation of intracellular calcium, as well as reconstitution experiments, however, revealed different calcium requirements for stimulated secretion of these markers. N-formyl-met-leu-phe-induced secretion of vitamin B12-binding protein required half-maximal change in intracellular calcium of greater than 20 nM, while lactoferrin requirements were approximately 140 nM. Thus, it appears that cytosolic free calcium modulates fusion of subpopulations of specific granules which with the neutrophil plasma membrane.

Benzofurans↗
PubMed1983

Sequestration of crystalline and endogenous cobalamin by R binders down to the distal ileum in exocrine pancreatic dysfunction.

It has been recently shown that crystalline cyanocobalamin in exocrine pancreatic insufficiency is sequestered by R binders down to the proximal jejunum, and that bile inhibits the binding of cobalamin to intrinsic factor. In freshly collected human bile, we have found a single type of apo R binder, with a relative molecular mass of 128 100, a molecular radius of 4.65 nm, and a mean isoelectric point of 3.72. Salivary and biliary holo R binders were incubated with normal human gastric juice and intestinal juice from healthy subjects and patients having exocrine pancreatic insufficiency. No degradation of these two holo R binders occurs with normal gastric juice and intestinal juice from patients after four hours incubation time at 37 degrees C, but a partial degradation of salivary holo R binders and a complete loss of biliary Cbl binding capacity were observed with normal intestinal juice in the same in vitro conditions. We have confirmed in vivo, using a triple-lumened tube, that a part of the salivary and biliary holo R binders remains undegraded down to the distal ileum in two patients with exocrine pancreatic insufficiency. These findings strongly suggest that the enterohepatic circulation of cobalamin is effective in healthy subjects, whereas it is partially interrupted in the patients. They provide a proof that a part of endogenous and crystalline exogenous cobalamin is sequestered to R binders down to the distal ileum, and confirm that the failure to degrade the digestive R binders is responsible for the malabsorption of crystalline cobalamin in exocrine pancreatic dysfunction.

Bile↗
PubMed1984

Cobalamin R binder as a possible model molecule for glycoprotein study in cystic fibrosis.

The isoprotein pattern of semi-purified R binder (an acidic glycoprotein which binds cobalamin) from saliva and sera of 8 cystic fibrosis patients was compared to that of R binder from samples of 5 healthy children. In cases of cystic fibrosis, the mean isoelectric point of salivary R binder was increased from 3.78 up to 4.34 and its microheterogeneity was reduced. These significant physicochemical modifications were not observed with R binder from cystic fibrosis sera and they did not correlate with the beta-galactosidase, alpha-mannosidase, alpha-L-fucosidase nor neuraminidase activity of saliva. We propose the R binder as a model molecule to study the glycoprotein metabolism in cystic fibrosis since it contains 30-40% carbohydrate, is easily complexed with cyano[57Co]cobalamin and is present in most tissues and fluids of the human organism.

Adolescent↗
PubMed1989

Immunohistochemical survey of cobalamin-binding proteins.

Dietary cobalamin is bound to intrinsic factor (IF) and nonintrinsic factor (R protein) in the gastrointestinal tract. Distribution of IF has previously been described only in the stomach (parietal, chief cells), duodenum (mucous cells), and pancreatic juice. Cells containing R protein have been reported to be more widespread, including mucin-secreting cells of the intestinal tract. To further clarify the cells producing these cobalamin binders in the various organs, we surveyed a number of tissues in four species, with monospecific antisera raised against rat IF and hog R protein, using indirect immunoperoxidase histochemistry. A positive staining pattern was confirmed after blocking with the appropriate protein purified to homogeneity. Strong IF staining was noted over chief cells in the rat stomach, with weaker but substantial staining in the parietal cells as well. Intrinsic factor was found only in parietal cells in all other species examined. R protein was found in parietal cells of all species tested, except in the hog, where mucous cells of the basal crypt stained. The area of the brush border and apical cytoplasm in small intestinal epithelial cells was also positive for both IF and R protein, probably reflecting uptake. Accessory digestive organs, such as salivary gland and pancreas were also positive for both IF and R protein in the secretory ducts. Accessory digestive organs contribute to the secretion of IF as well as R protein, but the physiologic importance of this IF secretion is not clear.

Animals↗