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Biomedical subjects

E Lebenthal

Publications and source records attributed to E Lebenthal.

At least 55 records · Page 3Linked to original sources
PubMed1991

Regulation of rat pancreatic nuclear triiodothyronine receptor by glucocorticoid.

The nuclear T3 receptors in rat pancreas exhibit a characteristic maturation pattern during development and are subjected to autologous regulation by thyroid hormones. To see if glucocorticoids also regulate T3 receptors in the pancreas, rats at various age groups were subjected to experimental conditions that altered their glucocorticoid status and the corresponding changes in nuclear T3 receptors, and exocrine enzymes in their pancreata were evaluated. Hydrocortisone administration to normal suckling and weaning rats did not change total T3 binding capacity or the dissociation constant as measured at 30 degrees C (Kd30). A significant increase in the degree of occupancy of the T3 receptor was found at 5-10 days after treatment with hydrocortisone (42.2 + 4.1% vs. 19.2 + 2.0%). T3 binding capacity and exocrine enzyme concentrations were significantly reduced in both adrenalectomized (Adx) pups and adults, indicating a continuous dependency on glucocorticoid from preweaning to adulthood. In adrenalectomized rat pups, either T4 or glucocorticoid replacement alone restored T3 binding capacity and exocrine enzyme concentrations. T4 and glucocorticoid were given together to Adx rats, the level of stimulation of both pancreatic T3 binding capacity and exocrine enzyme concentrations was found to be equal to the sum of the stimulation by each of these hormones when given alone. Furthermore, a good correlation was found between Bmax30 (Bmax measured at 30 degrees C, representing total sites) for T3 binding and exocrine enzyme activities in different groups following various experimental treatments. These findings provide further evidence that thyroxine can act directly on the rat pancreas presumably through the T3 receptor in regulating the postnatal development of the exocrine enzymes.

Adrenalectomy↗
PubMed1991

Reduced levels of galactose-terminated glycoproteins in rat serum during perinatal development.

Asialoglycoprotein receptor is an abundant protein localized in the sinusoidal domain of the hepatocyte plasma membrane. Its principle function is the clearance of serum glycoproteins which include several acute phase reactant proteins that have lost their terminal sialic acid residue. It has been reported that asialoglycoprotein receptor is nearly absent in mammalian fetal liver but rises to adult levels during the early postpartum period. The hypothesis to be tested was to determine whether defective glycoproteins, those lacking terminal sialic acid residues, are accumulated in fetal serum as a result of reduced receptor content. It was found that low levels of asialoglycoprotein receptor in 18-day-old fetal liver correlated to a threefold higher level of total asialoglycoproteins in fetal serum than adult serum as determined by a modified Western blot protocol employing radioiodinated ricinus communis agglutinin, a galactose-binding lectin. As hepatic asialoglycoprotein receptor accumulated at the time of birth, the elevated level of serum asialoglycoproteins decreased to adult values in an opposite manner. This study indicates that the hepatic asialoglycoprotein receptor plays an important role in reducing the amount of circulating defective glycoproteins at the time of birth.

Animals↗
PubMed1991

Human intestinal disaccharidase activities: correlations with age, biopsy technique, and degree of villus atrophy.

The relationship between intestinal morphology, disaccharidase activity, and disaccharide absorption is controversial. A retrospective study of 798 consecutive biopsies was performed to determine whether disaccharidase activities varied by subject age, biopsy technique, and degree of villus atrophy. Lactase activity was inversely correlated with age in the absence or presence of villus atrophy; sucrase, maltase, and palatinase activities did not correlate with age. Biopsies obtained by capsule or endoscopy had similar disaccharidase activities. In subjects 24 months of age or younger, the degree of mucosal injury was inversely correlated with lactase activity. In subjects older than 24 months, the degree of mucosal injury was inversely correlated with maltase and, to a lesser extent, lactase activities. The data suggest that disaccharidase activities in mucosal biopsies, whether obtained by endoscopy or capsule, are diminished in the presence of mucosal injury and correlate inversely with the degree of injury.

Adolescent↗
PubMed1990

The role of carbohydrate moieties of cholecystokinin receptors in cholecystokinin octapeptide binding: alteration of binding data by specific lectins.

Cholecystokinin (CCK) receptors on rat pancreatic acini have been demonstrated to be glycoproteins. In order to study whether their carbohydrate moieties play a role in ligand binding, membrane preparations (adjusted to 0.2 mg protein me) were incubated with 20 pM 125-I-CCK octapeptide (125I-CCK8) for 4 h at 30 degrees C in the presence of lectins with different sugar specificities. Concanavalin A, soy-bean agglutinin, and peanut agglutinin in concentrations up to 1 mM did not alter specific 125I-CCK8 binding. Ulex europeus lectin I showed a dose-dependent enhancement of CCK binding up to 150% of controls at a concentration of 1 mM. Wheat-germ agglutinin (WGA) was the only lectin found to have an inhibitory effect. Inhibition was dose-dependent, with maximal reduction attained at 42 nM, but CCK binding was only partially inhibited to 66.2 +/- 4.4%. Inhibition by WGA was prevented by the presence of N-acetyl-D-glucosamine or N,N',N"-triacetylchitotriose, sugars that are specific for WGA. The inhibitory effect of WGA was not due to an increase in non-specific binding, increased CCK degradation, or CCK binding to WGA. Binding data indicated that the presence of WGA resulted in a decrease in receptor affinity (Kd = 567 +/- 191 v. 299 +/- 50 pM). No significant change in the number of available binding sites was observed. This suggests that WGA is not binding to the active binding site. It is conceivable that binding of WGA to N-acetyl-D-glucosamine or its polymers can lead to a conformational change in the receptor protein, and that this carbohydrate moiety is essential for optimal receptor-ligand interaction.

Animals↗
PubMed1990

Modulation of extracellular matrix proteins in rat liver during development.

The expression and localization of extracellular matrix proteins in rat liver was investigated as a function of liver development. Levels of extracellular matrix proteins were measured by dot-blot or immunoblot protocols using monospecific antibodies prepared against collagen types I, III and IV; laminin; fibronectin; and fibronectin receptor. Proline and hydroxyproline levels from extracted liver collagen were quantitated by Pico Tag analysis. It was observed that the content of type IV collagen and fibronectin in the rat liver increased two to four times during the perinatal period. In contrast, levels of laminin and collagen types I and III decreased up to twofold in developing rat livers. The content of fibronectin receptor during ontogeny was decreased four times in an inverse relationship to fibronectin molecules. Fibronectin receptor and extracellular matrix proteins displayed no difference in apparent molecular weight as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots. Indirect immunofluorescence staining of frozen thin liver sections revealed that the pattern of localization of extracellular matrix proteins in the nonvascular regions of fetal liver was punctate rather than restricted to a specific region such as the perisinusoidal area of adult livers. Similarly, fibronectin receptor was also present, mainly in the sinusoidal area of adult livers, whereas fetal sections were diffusely stained. Our findings suggest that the differential modulation of extracellular matrix proteins and their localization in the developing rat livers undergo a dramatic alteration in the composition and structural organization of matrix material, which may act to modulate proliferation and to promote the differentiation of liver cells during development.

Animals↗
PubMed1990

Medium-chain acyl CoA dehydrogenase deficiency: electron microscopic differentiation from Reye syndrome.

Inborn errors involving the oxidative metabolism of fatty acids may present clinically with a Reye syndrome-like picture. This case report of a patient with medium-chain acyl CoA dehydrogenase (MCAD) deficiency illustrates that electron microscopy may help to differentiate this disorder from Reye syndrome even if a liver biopsy is performed in a patient who recovered from an acute metabolic decompensation. Together with this case, a review of the few reports in the literature of pathological findings in MCAD deficiency is given. Changes uncharacteristic for Reye syndrome are a large-droplet steatosis and the presence of distinctive mitochondrial abnormalities on electron microscopy. The detection of an electron dense mitochondrial matrix and a widened space of inner mitochondrial membranes rules out Reye syndrome and is suggestive of a disorder of mitochondrial fatty acid oxidation.

Acyl-CoA Dehydrogenase↗
PubMed1990

Hydrolysis and absorption of glucose polymers from rice compared with corn in chronic diarrhea of infancy.

Because rice remains the most available carbohydrate in developing countries, where chronic diarrhea is most prevalent, we compared the in vitro hydrolysis and clinical tolerance of rice glucose polymer with those of corn glucose polymer. Rice glucose polymer hydrolysis to D-glucose and short-chain polymers (polymers with two to four glucose units and those with five or more units) was similar to that for corn glucose polymers during incubation with saliva or duodenal aspirates. However, rice glucose polymers yielded more short-chain products than corn glucose polymers during incubation with pooled mucosal homogenates (p less than 0.01). In vivo tolerance testing of 16 infants with chronic diarrhea confirmed that rice glucose polymers were well tolerated and, compared with corn glucose polymers, achieved a higher maximal increase of serum glucose concentration (36.6 +/- 7.3 vs 27.6 +/- 10.3 mg/dl; p less than 0.02), a shorter time to peak serum glucose concentration (34.0 +/- 10.2 vs 52.5 +/- 25.7 minutes; p less than 0.02), and a greater area under the serum glucose response curve at 30 minutes (538 +/- 131 vs 1035 +/- 501 cm; p less than 0.02). We conclude that rice glucose polymers are rapidly hydrolyzed in vitro and in vivo and are more rapidly absorbed than are corn glucose polymers in children with chronic diarrhea.

Absorption↗
PubMed1990

The effect of protein-energy malnutrition and refeeding on the adherence of Salmonella typhimurium to small intestinal mucosa and isolated enterocytes in rats.

The adherence of fimbriated (Fim+) and nonfimbriated (Fim-) strains of Salmonella typhimurium to both isolated intestinal epithelial cells and intact intestinal mucosa of healthy and malnourished rats was investigated. Fim+ strains bound in significantly higher numbers than did Fim- strains to enterocytes isolated either from healthy or malnourished rats. Adherence to intact intestinal mucosa in situ was demonstrable with both Fim+ and Fim- bacteria, but Fim+ strains were preferred because they showed approximately twofold higher numbers of adhered bacteria compared to Fim- strains. Additionally, bacterial adherence to intact mucosa in situ was consistently higher in well-fed controls than in malnourished rats. Ultrastructural studies revealed marked cell destruction and lysis in malnourished rats, whereas no histological change was detected in the mucosa of control animals. These results suggest that malnutrition may lead to altered intestinal cell surfaces, thus increasing their susceptibility to infection through mechanisms that are different from adherence.

Animals↗
PubMed1990

Effect of vitamin A deficiency on the adherence of fimbriated and nonfimbriated Salmonella typhimurium to isolated small intestinal enterocytes.

In vitamin A-deficient children, increased rates of bacterial infections in the intestine have been observed. The adherence of bacteria is a prerequisite for invasion. Thus, the effect of vitamin A deficiency on the adherence of fimbriated and nonfimbriated Salmonella typhimurium to isolated small intestinal enterocytes was studied. Male weanling rats matched by weight were divided into three groups: one group was fed a vitamin A-free diet for 8-12 weeks; another was given the same diet supplemented with retinol acetate; a third group matched for age served as controls. The vitamin A-deficient group showed a significantly lower growth rate and lower serum retinol levels than either the retinol acetate-supplemented or control groups. In all the groups, S. typhimurium possessing mannose-sensitive fimbriae adhered to enterocytes in significantly larger numbers than the nonfimbriated strains. The number of fimbriated S. typhimurium bound to enterocytes from the proximal small intestine was significantly higher in the vitamin A-deficient rats than in the pair-fed vitamin A-supplemented group (19.3 +/- 14.9 versus 7.8 +/- 5.0; p less than 0.05) or the control group (19.3 +/- 14.9 versus 8.7 +/- 3.5, p = 0.01). The specific activities of the enterocytes lactase, sucrase, and maltase and the protein content in the vitamin A-deficient rats were similar to those in the controls. These results demonstrate that vitamin A deficiency in rats is associated with the increased ability of S. typhimurium to adhere to proximal small intestinal enterocytes. However, the possible changes in the membrane of the enterocyte do not include decreases in brush border disaccharidases or protein content.

Animals↗
PubMed1990

Effect of thyroxine on the maturation of cholecystokinin (CCK) receptors in pancreatic acini of neonatal rats.

Neonatal rat pancreata are not responsive to stimulation by cholecystokinin (CCK) and this has been shown to be due partly to low binding of CCK to pancreatic acinar cells of rats at this age. The effect of thyroxine on the maturation of CCK receptor binding and enzyme secretion is studied. One-day-old rat pups were injected daily with thyroxine (0.1 microgram/g of body weight) for 3 days and killed on day 5. Control littermates were injected with normal saline at the same volume and schedule as the thyroxine group. The pancreatic weight and amylase activity were significantly higher in pups from the thyroxine group. Amylase release after stimulation with various concentrations of CCK was also higher in the thyroxine group. The maximal binding to [125I]BH-CCK-8 was significantly higher in dispersed acini from the thyroxine group when compared to the control group (5.2 vs. 2.0%). Analysis of binding data showed that the higher binding was due to a higher maximal binding capacity in the thyroxine group (1.1 +/- 0.41 vs. 5.2 +/- 1.4 fmol/mg of protein). Thyroxine, therefore, induces a precocious maturation of the secretory function of the pancreatic acini, specifically by modulating the maximal binding capacity of the high-affinity binding sites.

Amylases↗
PubMed1990

Carnitine ester excretion in pediatric patients receiving parenteral nutrition.

Carnitine plasma concentrations and the excretion of carnitine and individual carnitine esters were determined in 25 children and adolescents with gastrointestinal diseases receiving carnitine-free parenteral nutrition for at least 1 mo using radiochemical and radioisotopic exchange HPLC methods. Children less than 12-y-old usually had carnitine plasma concentrations less than -2 SD from the normal mean for age, whereas patients greater than 12-y-old had carnitine plasma concentrations within the normal range. Age was the only variable to correlate significantly with plasma carnitine concentrations during parenteral nutrition. Free carnitine (FC) excretion was closely correlated with plasma FC concentrations and minimal at values less than 25 mumols/L. The excretion of FC and short-chain acylcarnitines was reduced by an order of magnitude in younger compared with older patients and controls, but the excretion of "other" acylcarnitines was less affected. Some of the latter were tentatively identified using gas-liquid chromatographic and mass spectroscopic techniques as unsaturated and/or branched medium-chain carnitine esters with a carbon chain of C8-C10. The results suggest that FC and short-chain acylcarnitine are conserved by the kidney in nutritional carnitine deficiency but that there may be an obligatory renal excretion of other carnitine esters that contributes to the development of hypocarnitinemia in the younger age group.

Absorption↗
PubMed1990

Role of rat intestinal glucoamylase in glucose polymer hydrolysis and absorption.

Rice starch is a main source of energy in many lesser developed countries. We studied different chain-lengths of rice glucose polymers (GP) to evaluate their possible use in feeding infants in developing countries. The initial GP of rice (G1 = 4.6, G2 = 4.5, G3 = 15.4, G4 = 7.3, G5 = 17.4, G6-G9 = 9.61 and greater than G9 = 31.3%) was analyzed by HPLC and then separated in a Bio-Gel P-2 column and compared to its short-chain GP of rice (G2 = 22.7, G3 = 28.2, G4 = 14.0, G5 = 16.6, G6 = 11.6, G7-G9 = 6.9%), long-chain GP of rice (greater than G9 = 100%), and D-glucose. Intraduodenal bolus infusion of 10% solution of short-chain rice GP when compared with long-chain rice GP, the initial rice GP, or D-glucose showed significantly higher values at peak absorption time (0 to 30 min) in the portal venous blood glucose response. The portal venous glycemic response of short-chain rice GP compared with D-glucose was as follows: 2.5 +/- 0.1 versus 2.0 +/- 0.2 cm2, area under the portal blood glucose curve at 0-30 min (p less than 0.01). Glucoamylase, the key enzyme for brush-border hydrolysis of short-chain GP, was assessed with a newly modified glucoamylase assay using GP G5-G8 as substrate. Our finding of faster glucose absorption with short-chain rice GP compared with isocaloric D-glucose might have important physiologic implications for carbohydrate absorption. The osmolality of short-chain rice GP is nearly one-fourth that of glucose. This might have important bearing in the design of infant feeding where increased caloric density with low osmolality is desirable.

Animals↗
PubMed1990

Thyroidal regulation of rat pancreatic nuclear triiodothyronine receptor during postnatal development.

We have shown previously that the rat pancreas contains nuclear T3 receptors which exhibit a characteristic maturation pattern during development. To investigate whether these receptors are subjected to autologous regulation by thyroid hormones, the effect of T4 on the binding capacity (Bmax), dissociation constant (Kd), and receptor occupancy were followed in intact rat pups at various ages. Hyperthyroidism (by daily injection of T4 0.1 micrograms/g body wt to intact pups starting 4 days before death at 5, 10, 15, and 20 days of age) increased while hypothyroidism (by propylthiouracil feeding) decreased the total T3 binding capacity during preweaning ages (mean maximal binding capacities as estimated by Scatchard analysis, at 30 C for 14-20 days old eu-, hyper-, and hypothyroid pups: 186, 229, and 129 fmol/mg non-histone protein (NHP). The thyroid conditions also affected the percentage of T3 receptor occupancy but not the affinity of binding (as measured by Kd). Concomitantly, these conditions also caused corresponding changes in pancreatic weights, DNA and protein contents, and the concentrations of amylase, trypsinogen, and lipase. The postnatal developmental retardation induced by 6-n-propyl-2-thiouracil treatment was reversed by T4 replacement. The results suggest that rat pancreatic T3 nuclear receptors during postnatal ages are modulated by T4, and such modulation apparently in turn affects the development of the exocrine enzymes.

Animals↗