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E Seidman

Publications and source records attributed to E Seidman.

At least 19 recordsLinked to original sources

Modulation of apo A-IV transcript levels and synthesis by n-3, n-6, and n-9 fatty acids in CACO-2 cells.

It has been postulated that apolipoprotein (apo) A-IV plays various significant roles in lipid transport and lipoprotein metabolism. Although it is controlled by fat feeding, so far little else is known about its regulation by specific fatty acids. In this study, we focused on the modulation of apo A-IV mRNA levels, mass, and biogenesis by mono- and polyunsaturated fatty acids (FA) in the human intestinal Caco-2 cell line. In confluent cells incubated with 1 mM oleic (n-9), linoleic (n-6), alpha-linolenic (n-3), or docosahexaenoic (n-3) acids for a long-term period, both apo A-IV protein levels and de novo synthesis were increased. The induction resulted from the up-regulation of apo A-IV mRNA transcripts. In contrast, an inhibitory effect was evident with short-term incubation. FA chain length and degree of unsaturation had little effect altering apo A-IV transcript and biogenesis. These data offer evidence that isolated fatty acids regulate gene expression and the production of apo A-IV in the enterocyte.

Apolipoproteins A

The risk and protective functions of perceived family and peer microsystems among urban adolescents in poverty.

Utilized a pattern-based approach to discover the different constellations of perceived social transactions separately for family and peer systems and explored the risk and protective functions of these microsystem profiles for both depression and antisocial behavior among a sample of ethnically and racially diverse urban adolescents living in poverty. Measures of perceived social support, involvement and hassles with family and peers, as well as perceived social acceptance and peers' values were entered into two sets of iterative cluster analyses to identify distinct profiles of family and peer transactions. From each of the perceived family and peer transactional analyses, six replicated profiles emerged. Several of the profiles were consistent with expectations from prior literature such as Enmeshing families and Rejecting peer networks, while others were novel and intriguing such as Entangling peers. Family profiles were consistent in their risk and protective associations for both depression and antisocial behavior, while the peer profiles varied in their effects for each developmental outcome. For example, the Rejecting peer profile placed adolescents at increased risk for depression but protected them from antisocial behavior. Implications for future research and preventive intervention are discussed.

Adolescent

Accuracy of the [13C]-urea breath test in diagnosing Helicobacter pylori gastritis in pediatric patients.

BACKGROUND: The causal association between Helicobacter pylori (H. pylori) colonization of the gastric mucosa and gastritis is now well established. Histologic examination of endoscopic biopsy specimens has long been regarded as the gold standard for diagnosis. However, the changes can be focal in nature and presence of the organism may be missed in nonsampled areas. The urea breath test, which uses a stable isotope, offers distinct advantages, in that it is noninvasive and measures the activity of the micro-organism. It thus represents a potentially invaluable tool in the initial diagnosis of the infection and in verifying its eradication. METHODS: The study design was that of a prospective, blinded comparison of the [13C]-urea breath test with histologic assessment of antral biopsy specimens using the Warthin-Starry stain, to diagnose H. pylori infection in a group of 79 consecutive pediatric patients. RESULTS: Patients classified as negative by histology (n=67) had breath 13C enrichment of 0.97+/-0.07 delta per thousand (mean+/-SEM), with a range of -0.20 and 2.83 delta per thousand. In contrast, those with a positive histologic results (n=12) had an enrichment of 25.41+/-5.01 delta per thousand (range, 3.43-58.80; p < 0.001). At the chosen cutoff point of 3 delta per thousand, the sensitivity and specificity as well as the positive and negative predictive values of the breath test were uniformly 100%. CONCLUSION: The [13C]-urea breath test is a highly reliable, noninvasive method for the diagnosis of H. pylori gastritis in children and adolescents.

Adolescent

Bile duct cells: a novel in vitro model for the study of lipid metabolism and bile acid production.

Immortalized bile duct cells (BDC), derived from transgenic mice harboring the SV40 thermosensitive immortalizing mutant gene ts458, were utilized to investigate the role of the biliary epithelium in lipid and sterol metabolism. This cell model closely resembles the in vivo situation because it expresses the specific phenotypic marker cytokeratin 19 (CK-19), exhibits the formation of bile duct-like structures, and displays well-formed microvilli projected from the apical side to central lumen. The BDC were found to incorporate [14C]oleic acid (in nmol/mg protein) into triglycerides (121 +/- 6), phospholipids (PL; 59 +/- 3), and cholesteryl ester (16 +/- 1). The medium lipid content represented 5.90 +/- 0.16% (P < 0. 005) of the total intracellular production, indicating a limited lipid export capacity. Analysis of PL composition demonstrated the synthesis of all classes of polar lipids, with phosphatidylcholine and phosphatidylethanolamine accounting for 60 +/- 1 and 24 +/- 1%, respectively, of the total. Differences in PL distribution were apparent between cells and media. Substantial cholesterol synthesis was observed in BDC, as determined by the incorporation of [14C]acetate suggesting the presence of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. With the use of [14C]acetate and [14C]cholesterol as precursors, both tauro- and glycoconjugates of bile acids were synthesized, indicating the presence of cholesterol 7alpha- and 26R-hydroxylases, the key enzymes involved in bile acid formation. The transport of bile acids was not limited, as shown by their marked accumulation in the medium (>6-fold of cell content). HMG-CoA reductase (53.0 +/- 6.7), cholesterol 7alpha-hydroxylase (15. 5 +/- 0.5), and acyl-CoA:cholesterol acyltransferase (ACAT; 201.7 +/- 10.2) activities (in pmol. min-1. mg protein-1) were present in the microsomal fractions. Our data show that biliary epithelial cells actively synthesize lipids and may directly contribute bile acids to the biliary fluid in vivo. This BDC line thus represents an efficient experimental tool to evaluate biliary epithelium sterol metabolism and to study biliary physiology.

Acetates

Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder for which the gene (AIRE) has recently been identified on chromosome 21q22.3. We present the mutational analyses of a French-Canadian family with APECED, in which there are two affected siblings, as well as the response to cyclosporine A(CyA) therapy in the index patient, the eldest sibling. Haplotype analysis suggested compound heterozygozity at the AIRE locus. Direct sequencing of exon 8 revealed a previously described mutation, a 13-bp deletion (1085-1097) of maternal origin, found in the index patient, her affected sister, and her unaffected sister. A novel missense mutation characterized by a T-->G transversion at nucleotide position 398, resulting in a leu-->arg amino acid substitution (L93R), was found in exon 2. The mutation was present in the father, the brother, the index patient, and the affected sister. The presence of the mutation in the propositus was verified by cloning of PCR products from genomic DNA. The mutation destroys a PstI restriction enzyme site, as confirmed in the aforementioned patients. Screening of 50 French-Canadian controls with PstI digestion did not show destruction of the restriction-enzyme site. The index patient's phenotype was severe, manifested by classic features of the illness (adrenal insufficiency, hypoparathyroidism, candidiasis, and keratoconjunctivitis with alopecia universalis), as well as by severe exocrine pancreatic insufficiency, diabetes mellitus, hepatic inflammation, growth hormone (GH) deficiency due to lymphocytic hypophysitis, and primary ovarian failure. Oral CyA (5 mg/kg/day) was initiated at 13 yr of age. After 8 months of therapy, stimulated pancreatic lipase increased 24-fold with normalization of stool fat (from 31.5 g/day to 2.5 g/day, normal(N) < 5). There was complete resolution of her photophobia, and considerable hair regrowth was diffusely apparent. Minimal side effects were noted. Our experience supports the use of oral CyA for the treatment of severe APECED-associated exocrine pancreatic failure and keratoconjunctivitis.

Adolescent

Comparative analysis of serologic screening tests for the initial diagnosis of celiac disease.

OBJECTIVE: To prospectively evaluate and compare the sensitivity, specificity, and positive and negative predictive values of serum antigliadin (AGA) and antiendomysium antibodies (EMA) in predicting the initial diagnosis of celiac disease. DESIGN: Sera were tested prospectively for IgA and IgG AGA by enzymed-linked immunosorbent assay and IgA EMA by immunofluorescence techniques on monkey esophagus and human umbilical cord sections in 95 pediatric patients referred for duodenal biopsies. PATIENTS: Ninety-five pediatric patients were referred for duodenal biopsies, with a clinical suspicion of celiac disease; 24 of those patients had celiac disease by criteria of the European Society for Pediatric Gastroenterology and Nutrition. SETTING: A pediatric gastroenterology clinic of a tertiary care pediatric university hospital. RESULTS: EMA testing on human umbilical cords was the most specific but was also the least sensitive. All the patients with biopsy-proven celiac disease were identified by either one or both serologic tests (100% combined sensitivity). The combination of AGA and EMA on monkey esophagus resulted in a negative predictive value of 100% accuracy. CONCLUSIONS: A combination of AGA and EMA tests resulted in 100% sensitivity and 100% negative predictive value, useful in selecting patients for duodenal biopsy.

Adolescent

Structural and experiential neighborhood contexts, developmental stage, and antisocial behavior among urban adolescents in poverty.

This study explored the effects of structural and experiential neighborhood factors and developmental stage on antisocial behavior, among a sample of poor urban adolescents in New York City. Conceptually and empirically distinct profiles of neighborhood experience were derived from the data, based on measures of perceived neighborhood cohesion, poverty-related hassles, and involvement in neighborhood organizations and activities. Both the profiles of neighborhood experience and a measure of census-tract-level neighborhood hazard (poverty and violence) showed relationships to antisocial behavior. Contrary to expectation, higher levels of antisocial behavior were reported among adolescents residing in moderate-structural-risk neighborhoods than those in high-structural-risk neighborhoods. This effect held only for teens in middle (not early) adolescence and was stronger for teens perceiving their neighborhoods as hassling than for those who did not. Implications for future research and preventive intervention are discussed.

Adolescent

Inflammatory mediators in Escherichia coli O157:H7 hemorrhagic colitis and hemolytic-uremic syndrome.

BACKGROUND: Recent experimental data suggest that the inflammatory response of the host to verotoxin and/or lipopolysaccharides of Escherichia coli is involved in the pathophysiology of verotoxin-producing E. coli (VTEC) infections. METHODS: We measured the circulating concentrations of cytokines [TNF-alpha, interleukin (IL)-1-beta, IL-1 receptor antagonist (Ra), IL-6, IL-8, IL-10] and soluble leukocyte adhesion molecules (L-selectin, P-selectin, E-selectin, intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1) by sandwich enzyme-linked immunosorbent assay among (1) normal controls (n = 12), (2) disease controls with hemorrhagic colitis (HC) not associated with VTEC infections (n = 57), (3) patients with uncomplicated HC caused by E. coli O157:H7 (n = 30), and (4) children with hemolytic-uremic syndrome (HUS) (n = 28). Patients with HUS were matched with children who presented an uncomplicated HC caused by E. coli O157:H7 for the time interval elapsed between the onset of HC and that of blood sample collection. RESULTS: Concentrations of TNF-alpha and IL-1-beta were undetectable. Children with HUS were characterized by increased amounts of IL-6 and IL-8, lower values of soluble L-selectin as well as increased levels of IL-10 and IL-1Ra. The circulating concentrations of IL-1Ra were higher among children with O157:H7 HC who subsequently developed HUS. CONCLUSIONS: Increased pro- and antiinflammatory cytokine responses are produced by the host during the development of HUS among children with VTEC infections. Further studies are needed to determine their relative contribution to the pathophysiology of classic HUS.

Cell Adhesion Molecules

Acute intrahepatic portal vein thrombosis complicating cholangitis in biliary atresia.

UNLABELLED: A 2-year-old boy with Kasai portoenterostomy had systemic features suggestive of cholangitis and acute portal vein obstruction. The rapid rise in portal pressure caused a transient, severe decompensation of hepatic function. A superior mesenteric arterial angiogram confirmed the presence of diffuse intrahepatic portal vein thrombosis. CONCLUSION: This case provides clinical and radiological evidence supporting an association between ascending cholangitis and acute intrahepatic portal vein thrombosis.

Biliary Atresia

Lipid, apolipoprotein, and lipoprotein synthesis and secretion during cellular differentiation in Caco-2 cells.

Although Caco-2 cells are frequently employed for the study of enterocyte lipid metabolism, variable results have been reported regarding their ability to synthesize and secrete lipids and apolipoproteins. The major goal of this investigation is to examine the capacity of Caco-2 cells to elaborate and secrete lipids, lipoproteins, and apolipoproteins at different degrees of morphological and functional differentiation. Cells were cultured in medium with 5% fetal bovine serum (FBS), on permeable polycarbonate filters from 2 to 30 d in the presence of 14C-oleate or 35S-methionine. Cellular differentiation, as assessed by morphology (light and electron microscopy), transepithelial resistance, free fatty acid flux, and sucrase activity, progressed steadily up to 20 d of culture. Caco-2 cells esterified oleic acid mainly into phospholipids, triglycerides (TG), and smaller amounts of cholesterol esters. Lipid synthesis began as early as 2 d, and TG secretion was enhanced with increased duration of culture. However, very low efficiency of lipid export was observed at all levels of differentiation, reaching a maximum of only 6% of intracellular lipids. VLDL and LDL were the dominant lipoproteins secreted, with HDL comprising < 20% of the total. VLDL secretion increased, while LDL decreased, whereas the lipid composition of lipoproteins varied little with increasing duration of culture. Apoprotein B and A-I synthesis and secretion increased markedly from 11 to 20 d of culture. The ratio of apo B-100/B-48 decreased between 11 and 30 d, consistent with enhanced apo B editing of more mature enterocytes. Taken together, our data suggest that from 20 d of culture, Caco-2 cells are morphologically and functionally mature, capable of lipid esterification, and lipoprotein and apolipoprotein synthesis. However, despite their functional and morphological similarities to mature enterocytes, Caco-2 cells have a very limited lipid export capacity.

Apolipoproteins

Small bowel transplantation. A life-saving option for selected patients with intestinal failure.

Thirty-seven patients were listed for small bowel transplantation; 16 were transplanted and 15 died while waiting for a donor. Cyclosporine (N = 6) or tacrolimus (N = 10) were used for immune suppression. Graft rejection rates were lower in the combined liver/small bowel grafts than the isolated intestinal transplants (1/7 vs 5/7; P < 0.01) All of the cyclosporine group have died; the median survival was 25.7 months with two patients living more than five years. The tacrolimus group had fewer infections and a shorter hospital stay. All but two are alive with a median survival of 13 months. Seven of eight long-term survivors are off intravenous feedings. We conclude that small bowel transplantation is a life-saving option for patients with intestinal failure who cannot be maintained on total parenteral nutrition.

Adolescent

The impact of the transition to high school on the self-system and perceived social context of poor urban youth.

Examined the effects of the normative school transition to senior high school (n = 330) on the self-system and perceived school and peer social contexts of poor, black (n = 83), European American (n = 115), Latino (n = 105), and Asian American (n = 27) youth in the public school systems of three Eastern urban cities. The only negative effect of the school transition on the self-system was a decline in grade point average (GPA). Concurrently, the school transition was perceived to be associated with changes in the school and peer contexts. Across the transition, students reported increased disengagement from school (i.e., increased social support and extracurricular involvement) and increased engagement with peers (i.e., decreased daily hassles and increased involvement). These changes in the school and peer microsystems, like the changes in the self-system, were also common across race/ethnicity and gender. In addition, transition-associated school changes, and in particular changes in daily academic demands/hassles and involvement in school activities, were associated with changes in the academic dimensions of the self-system (i.e., academic efficacy expectations and GPA). Results and implications for preventive intervention are discussed within a developmental mismatch framework.

Achievement

Influence of loperamide on lactose handling and oral-caecal transit time.

BACKGROUND: The influence of pharmacologically prolonged oral caecal transit time on lactose handling is examined in the wake of finding improved lactose handling during naturally occurring prolonged oral-caecal transit time. METHODS: Sixteen normal male volunteers with lactose maldigestion were pretreated with 8 and 12 mg loperamide on different days and lactose handling was compared by measuring areas under the curve during lactose breath H2 testing (3 h). The oral-caecal transit time was similarly measured using lactulose and exhaled breath H2. Symptom scores were recorded and, in three subjects, blood sugar was simultaneously measured. RESULTS: The mean +/-S.E.M. baseline oral-caecal transit time was 56.9 +/- 5.9 min. Loperamide significantly prolonged oral-caecal transit time (90.3 +/- 11.1 and 82.1 +/- 13.9 min for 12 and 8 mg loperamide, respectively; P < 0.05). The lactose breath H2 area under the curve with 12 mg loperamide was significantly less than at baseline (7685 +/- 985.6 vs. 10243.1 +/- 1607, respectively; P < 0.05). Significantly fewer symptoms were recorded with both doses of loperamide during the 3 h test but with 12 mg loperamide only on follow-up. There was no significant rise in blood sugar at any time in the three subjects studied. CONCLUSIONS: Loperamide-induced graded prolongation of oral-caecal transit time is associated with significantly improved lactose handling as measured by a reduction of the area under the curve. Symptoms of lactose intolerance may also be improved with loperamide. Prolongation of oral-caecal transit time with loperamide may be useful as adjunctive or primary therapy of carbohydrate intolerance in patients with rapid transit.

Administration, Oral