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Biomedical subjects

E Lebenthal

Publications and source records attributed to E Lebenthal.

At least 19 recordsLinked to original sources

Chylous ascites: total parenteral nutrition as primary therapeutic modality.

A female infant with Down syndrome and congenital chylous ascites presented at birth with respiratory distress secondary to marked abdominal distension. Total parenteral nutrition (TPN) and paracentesis were the primary therapeutic modality. On hyperalimentation, however, ascites initially recurred, requiring additional paracenteses to improve respiratory distress. The chylous ascites, lymphopenia and hypoalbuminemia were relieved after 10 weeks of TPN administration. We recommend a long-term course (10 weeks) of TPN before an exploratory laparatomy and possible surgical intervention are considered.

Chylous Ascites

Transport of glucose polymer-derived glucose by rabbit jejunum.

Mechanisms for the assimilation of glucose polymers have been inferred from perfusion studies. To further define these mechanisms, the results of measurements of unidirectional glucose fluxes across short-circuited rabbit jejunal segments in vitro are reported. Glucose polymer-stimulated short-circuit current was similar to that of glucose [19 +/- 6.0 microA/cm2 (n = 7) and 26 +/- 5.7 microA/cm2 (n = 13), respectively] and was inhibited by both acarbose and phlorizin. Acarbose, an alpha-glucosidase inhibitor with no effects of glucose transport, was used to uncouple digestion from absorption. Mucosal-to-serosal flux of glucose polymer-derived glucose was lower than that of an equal weight/volume of glucose [124 +/- 62 nmol.h-1.cm-2 (n = 4) vs. 452 +/- 121 nmol.h-1.cm-2 (n = 6); P less than 0.05] and was inhibited by both phlorizin and acarbose. No glucose polymers were detected in the serosal bath solutions by thin-layer chromatography. It is concluded that glucose polymer-derived glucose is transported by a phlorizin-inhibitable process at a rate slower than that of free glucose, a finding that suggests that hydrolysis limits glucose polymer assimilation.

Analysis of Variance

Essential role for polyamine biosynthesis in thyroxine stimulated pancreatic development in neonatal rats.

Administration of thyroxine to rat pups leads to precocious development of the pancreas. The role of ornithine decarboxylase (ODC) and polyamines in thyroxine-induced pancreatic maturation was examined. Rat pups (aged 5 days) were given daily subcutaneous injection of thyroxine (0.1 micrograms/g body wt.) until the day before death. Serial ODC activities were measured in pancreatic homogenates after 1, 2, 3, 4, 5, 6, 7 and 10 days of thyroxine treatment. There was a biphasic induction of ODC activities by thyroxine: an early peak appeared on day 2 of treatment followed by a decrease on day 4; a second peak was evident on day 5 and then a decrease to control values by day 7. Significant increases in tissue concentrations of putrescine and spermidine were observed concomitant with two peaks of ODC activity. Pancreatic amylase concentration, DNA and protein also showed a significant increase after thyroxine treatment. Difluoromethyl ornithine (DFMO), a specific ODC inhibitor, given orally (8% in drinking water) to nursing dams at postnatal day 5 for 5 days caused an 83% inhibition of pancreatic ODC activity in thyroxine-treated pups when compared to thyroxine-treated pups not exposed to DFMO. Concomitantly, the thyroxine-induced increases in pancreatic weight, protein and amylase activity were suppressed. Our results suggest that increases in ODC activities and polyamine levels are critical intermediary steps in the precocious induction of pancreatic development by thyroxine.

Amylases

Gallstones in children. Characterization by age, etiology, and outcome.

Fifty children and adolescents were found to have gallstones at Children's Hospital of Buffalo (NY) during a period of 10 years. The mean (+/- SD) age was 12.2 +/- 6.2 years, with 21 boys and 29 girls. The majority of patients could be categorized into four groups: hemolytic disease (18 patients), parenteral nutrition (eight patients), adolescent pregnancy (seven patients), and idiopathic (10 patients), while seven patients had a variety of other etiologies. Right upper quadrant pain was the most common symptom (32 patients), followed by jaundice (15 patients), vomiting (13 patients), and nonspecific abdominal complaints (13 patients). Ten patients presented with jaundice and underlying hemolytic disease; seven patients were asymptomatic. Clinical presentation was found to vary with age and factors associated with the development of gallstones. Ultrasonography was the mode of diagnosis in 48 patients. Cholecystectomy was performed in 36 patients. In contrast to gallstones in adults, after exclusion of the patients with adolescent pregnancy, there was no female predominance. Pancreatitis was the most common complication, occurring in 8% of the patients; cholecystitis and cholangitis were absent.

Adolescent

Levels of Cu-Zn and Mn superoxide dismutases in rat liver during development.

Superoxide dismutase is the main scavenger of superoxide radicals in the mammalian body. The liver has high levels of two types of superoxide dismutase enzymes, cytosolic Cu-Zn and mitochondrial Mn enzymes. The aim of the present study was to investigate the content of two distinct superoxide dismutases in liver during the perinatal transition from a hypoxic to a hyperoxic environment. Both isozymes were purified to homogeneity and used as immunogens in rabbits. Antisera raised were found to recognize only polypeptides of molecular weight 16,900 or 23,400, which correspond to Cu-Zn and Mn superoxide dismutases, respectively. It was found that the level of Cu-Zn superoxide dismutase enzymatic activity and protein as assessed by immunoquantitation increased 10-fold during the postnatal period, reaching adult levels by 3 weeks. In contrast, the amount of Mn superoxide dismutase content increased only twofold to adult levels during the first week of life. Neither of the superoxide dismutases showed an alteration in specific activity or apparent molecular weight in rat livers during ontogeny. These results show that the levels of two intracellular superoxide dismutases are differentially elevated during the perinatal period. It is suggested that each dismutase plays a different physiological role for superoxide scavenging in liver as a function of the hypoxic/hyperoxic environment at birth.

Animals

Short-chain glucose polymer and anthracene-9-carboxylic acid inhibit water and electrolyte secretion induced by dibutyryl cyclic AMP in the small intestine.

Glucose-stimulated sodium absorption is the rationale for treatment with glucose-based oral rehydration solution in diarrhea. Concurrent treatment with pharmacological inhibitors, which specifically block chloride secretion, may be a useful adjunct to oral fluid therapy. To examine this hypothesis, the authors determined the intestinal water and ion transport rates in rat small intestine during the secretory phase induced by perfusion with N6-2'-0-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP), 1.0 mmol/L. A marker (polyethylene glycol 4000) dilution technique was used to evaluate the antisecretory effects of a defined short-chain glucose polymer, D-glucose, and a chloride channel blocker, anthracene-9-carboxylic acid (A-9-C). The results showed that dbcAMP induced small intestinal water and chloride ion secretion rapidly and reliably. The 2.5% concentration of rice short glucose polymer (G2, 22.7%; G3, 28.2%; G4, 14.0%; G5, 16.6%; G6, 11.6%; G7-9, 6.9%) is a better carbohydrate than the 2.5% concentration of D-glucose in reversing secretion of water, chloride, and sodium ions induced by dbcAMP. The combination of A-9-C and the glucose polymer can reverse dbcAMP-induced intestinal secretion and produces significantly (P less than 0.05) better antisecretory effect on water, sodium, and chloride ions than D-glucose with A-9-C.

Animals

Glucose polymers as an alternative to glucose in oral rehydration solutions.

Several issues involving glucose-based oral rehydration therapy may limit its acceptability and sustained use. Our studies suggest that defined short-chain glucose polymers (2 to 9 glucose units) are hydrolyzed and absorbed faster than isocaloric solutions of D-glucose in the small intestine of the rat. Glucose polymers, primarily from rice-based solutions, have been shown to be as effective as glucose-based solutions. They offer additional advantages in reducing the amount and duration of diarrhea with lesser volumes of solution, thereby reducing the costs of treatment. Rice-based solutions provide high caloric density and increase the absorption of sodium without an osmotic overload. The result is increased net absorption of glucose, sodium, and water. Glucose polymers from rice or other starches in oral rehydration solutions may be effective, inexpensive, easily used, and safe treatments for acute diarrhea.

Animals

A new direct pancreatic function test in pediatrics.

Traditional methods for collecting duodenal fluid are time consuming and technically difficult. A simple endoscopic method is proposed in this report as a means of collecting duodenal fluid to perform exocrine pancreatic function tests. Thirty-five patients between 24 and 36 months of age were studied for pancreatic exocrine function. Twenty-seven presented with chronic diarrhea and 8 with failure to thrive. In 20 patients (group 1), duodenal fluid was collected by means of a double-lumen tube and sequential administration of pancreozymin (PZN) and secretin (SEC). The rest (group 2) had duodenal aspiration from the level of the papilla of Vater through a fiberoptic endoscope following administration of SEC only. The procedure took approximately 3 h in group 1 and 45 min in group 2. Secretin administration produced comparable levels of enzymes in both groups. Pancreozymin produced the highest enzyme levels, but this was only significantly higher than SEC-induced levels in the case of lipase. Endoscopic collection of duodenal fluid following SEC administration is a safe, quick, and reliable method of collecting pancreatic secretion.

Child, Preschool

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

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

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

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

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

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