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Biomedical subjects

E Seidman

Publications and source records attributed to E Seidman.

At least 55 records · Page 3Linked to original sources
PubMed1996

Leucocyte adhesion deficiency presenting as a chronic ileocolitis.

CD11/CD18 leucocyte glycoprotein deficiency is a rare, congenital adhesion molecule disorder which, in its severe form, is usually fatal. Leucocytes in affected subjects have abnormal migration and adherence, rendering patients susceptible to life threatening infections. The CD11/CD18 integrins, and other adhesion molecules, are considered essential to the normal inflammatory response. It has been postulated that adhesion molecules may be responsible for mediating in part, the inflammatory changes observed in inflammatory bowel diseases and related disorders. This report describes the first case of CD11/CD18 deficiency characterised by a chronic ileocolitis. Bone marrow transplantation completely resolved the gastrointestinal symptoms, supporting a role for neutrophil dysfunction in the pathogenesis of the gut lesions. This case suggests that specific blockade of CD11/CD18 integrins alone may not halt the chronic inflammatory response observed in immune mediated bowel disorders, and that abnormalities of leucocyte function must be included in the differential diagnosis of paediatric Crohn's disease.

Bone Marrow Transplantation↗
PubMed1996

Caco-2 cell disaccharidase activities are unaffected by gestational hormones.

We previously reported that lactose handling was significantly improved during late-phase pregnancy in women with a genetically determined adult-type hypolactasia. However, the adaptive mechanisms underlying the enhanced lactose digestion during pregnancy are not clear. Progesterone therapy has been associated in animals with increased intestinal lactase activity. To investigate the potential role of progesterone and estrogen as modulators of human lactase activity during pregnancy, we employed the human-derived intestinal epithelial Caco-2 cell line. Measurements of lactase and sucrase activities were performed in parallel with DNA content in progesterone- and estrogen-treated cells after 5, 10, and 30 days of confluency. Caco-2 monolayer DNA content was observed to increase with duration of culture to an equivalent extent in both hormone-treated and control cultures. Lactase and sucrase activities were similarly unaltered by incubation with either progesterone or estrogen, at any time point tested. These data demonstrate that gestational hormones do not influence intestinal cell number nor disaccharidase activity in Caco-2 cells, at the doses tested. Although these studies were carried out in a malignant cell line, our data suggest that the improved lactose handling observed during pregnancy is probably related to prolonged intestinal transit.

Caco-2 Cells↗
PubMed1996

Determinants of prolonged oral cecal transit time during late phase pregnancy.

We examined the course of delayed oral cecal transit time (OCTT) and the impact of different variables in late pregnancy. Thirty-three women in late trimester were evaluated and 29 were re-tested post partum. Results were compared with 17 controls. A breath hydrogen test was used to measure OCTT. The impact of 3 demographic and 5 biochemical parameters was evaluated. Oral cecal transit time (99.2 +/- 7.8 min) during pregnancy was significantly prolonged compared both with controls (63.5 +/- 8.7 min) (p = 0.0042) and post partum (68.5 +/- 6.4 min) (p < 0.002). However, 40% during pregnancy had a normal OCTT. Post partum, 8 (29.6%) continued to have delayed OCTT. Serum free T4 levels were significantly lower than in controls (p < 0.0001) and post partum (p < 0.001), but did not correlate with OCTT. Gravidity rank correlated with OCTT (p = 0.022). By multivariate analysis, only 17% of the observed variability during pregnancy could be explained by these parameters. In controls, a formula including progesterone and gastrin levels was significant in explaining 54.7% of variability. Application of both formulae to post-partum returnees overpredicted OCTT; however, the one from pregnancy was more accurate. We conclude that in pregnancy multiple factors account for delayed OCTT and these may be different from controls and post partum. Pregnancy may still influence OCTT post partum.

Adult↗
PubMed1996

Lactose handling by women with lactose malabsorption is improved during pregnancy.

OBJECTIVE: To evaluate lactose handling among women in late pregnancy and post partum to determine whether lactose handling is altered in pregnancy. DESIGN: Prospective study of lactose intolerance among pregnant women with and without lactose malabsorption. SETTING: Gastroenterology service of the Sir Mortimer B. Davis-Jewish General Hospital, Montreal. PATIENTS: Thirty-three pregnant women, of whom 18 had lactose malabsorption, 12 did not and 3 were excluded. OUTCOME MEASURES: Lactose breath hydrogen (BH2) concentration after ingestion of lactose or lactulose; comparison before and after delivery of area under the curve (AUC) for lactose, oral-cecal transit time (OCTT) for lactulose, lactose-BH2-derived transit time and estimated dietary lactose consumption. RESULTS: After weaning (at a median time of 9 months after delivery), 28 of the women returned for follow-up. Of the 12 who could absorb lactose before delivery, 4 could no longer absorb lactose. Of the other 16 women, lactose intolerance worsened in 12, remained the same in 2 and improved in 2. The AUC was greater (p < 0.005), the maximal BH2 concentration was higher (p = 0.004) and the number of women whose BH2 concentration peaked was fewer (p < 0.025) post partum than before delivery. The women's symptoms during and after lactose BH2 tests were also greater post partum. The OCTT (based on the lactulose BH2 test) was shorter post partum (p = 0.001). Transit time derived from lactose BH2 tests was also shorter, but not significantly so. The OCTT was not inversely correlated with the change in AUC before and after delivery, but the lactose-BH2-derived transit time was inversely correlated. Pregnant women consumed more lactose before delivery than afterward (p < 0.004). CONCLUSIONS: Women with lactose malabsorption handle lactose better than usual in late pregnancy. Slow intestinal transit and bacterial adaptation to increased lactose intake may be primarily responsible.

Breath Tests↗
PubMed1995

Hypertrophic cardiomyopathy associated with tacrolimus in paediatric transplant patients.

Reported side-effects of tacrolimus, a potent immunosuppressive agent, have not included cardiotoxicity. We describe 5 consecutive paediatric transplant recipients (3 small bowel with or without liver and 2 liver) who received tacrolimus. 2 developed congestive heart failure and hypertrophic obstructive cardiomyopathy which resolved after changing to cyclosporin. In the other 3 patients the cardiomyopathy regressed or improved with a lower dose of tacrolimus or after stopping the drug.

Blood Pressure↗
PubMed1995

Assessing the social networks of people with psychiatric disability from multiple perspectives.

The study uses a sample of 97 new members of a mutual-help organization for the seriously mentally ill and 97 of their significant others (61 family members and 36 friends) to examine 1) the degree to which respondents' perceptions of dyadic relationships can be corroborated by network members and 2) the relationship of congruence of perception between respondent-network member pairs, characteristics of respondents' social networks and self-reported symptoms and social adjustment. Results showed strong variability in the degree to which respondents' perceptions were corroborated by network members, with a higher degree of corroboration for factual information such as face-to-face contact than for global aspects of dyadic relationships. Congruence of perception between respondents and family was associated with respondents' feelings of satisfaction about the quality of network ties and better psychological and social functioning. In contrast, congruence of perception between respondents and friends was related to a sense of involvement from ones network, but unrelated to respondents' mental health. The advantages of multiple perspectives data in studying the social ties of people with psychiatric disability are discussed.

Adolescent↗
PubMed1995

Development and validation of adolescent-perceived microsystem scales: social support, daily hassles, and involvement.

Developed and validated instruments for urban and culturally diverse adolescents to assess their self-reported transactions with family, peer, school, and neighborhood microsystems for the constructs of social support, daily hassles, and involvement. The sample of 998 youth were from schools in three Eastern cities with high percentages of economically disadvantaged youth. Data were collected before and after the transition to junior high school or to senior high school. Blacks constituted 26%, whites 26%, and Latinos 37% of the sample. Factor analyses confirmed and enhanced the hypothesized four-factor microsystem factor structure for support, hassles, and involvement; internal consistency and stability coefficients were consistent with these structures. In general, the microsystem factors were common across gender, ethnicity, and age. However, when group differences did occur on these demographic variables, they tended to validate the salience of microsystem specificity. In contrast to the total scores, the microsystem-specific factors yielded more meaningful and differential information with regard to demographic differences and the mediating processes across a school transition.

Adolescent↗
PubMed1995

Caco-2 cells as a model for intestinal lipoprotein synthesis and secretion.

Caco-2 cells, an intestinal cell line derived from a human colorectal carcinoma that spontaneously differentiates under standard culture conditions, lends itself to the in vitro study of human gut in view of its efficient intestinal transport processes. Among its multiple biological functions are those related to the absorption, transport, and metabolism of lipids and lipoproteins. Despite their intestinal origin, confluent Caco-2 cell monolayers primarily express L-FABP for the uptake of apical dietary long chain fatty acids, incorporating them into triglycerides by the glycerol 3-phosphate pathway, and assembling very-low-density lipoprotein, high-density lipoprotein, and low-density lipoprotein. The monoacyl-glycerol pathway is inactive in Caco-2 cells. Furthermore, the secretion of newly synthesized triglyceride-rich lipoproteins is very restricted, despite abundant production of apolipoprotein (apo) B. The regulation of apoB synthesis and its mRNA editing at the enterocyte level has been intensively examined in Caco-2 cells. Luminal fatty acids, calcium ion, as well as vitamins and hormones are known to modulate the apoB-48/apoB-100 at the transcriptional and/or translational level. The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA: (cholesterol acyltransferase), the key enzymes governing intracellular cholesterol handling, have also been extensively examined in Caco-2 cells. In many respects this cell line provides an excellent in vitro model for the investigation of intestinal lipoprotein metabolism; however, their limited secretion capacity remains a potential drawback to comparisons with the in vivo physiological state.

Animals↗
PubMed1995

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells.

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

Apolipoproteins↗
PubMed1994

Lipid esterification and synthesis by the IEC-6 intestinal epithelial crypt cell line: effect of transforming growth factor beta.

The capacity of immature intestinal epithelial crypt cells to synthesize lipids and the factors that promote their differentiation remain largely unknown. We examined the profile of lipids synthesized by a normal rat intestinal epithelial crypt cell line (IEC-6) and determined the effects of transforming growth factor beta (TGF beta), a putative crypt cell differentiating factor, on their lipid handling. Incubation of IEC-6 cells with [14C]oleic acid (20 h) resulted in lipid esterification and synthesis, mainly as triglycerides (TGs, 57 +/- 0.6%) and phospholipids (PLs, 30 +/- 0.6%), with a PL/TG ratio of 0.53. When cells were pulsed (2.5 h) with [14C]oleic acid and then maintained 20 h in medium alone, a significant elevation of the PL/TG ratio (10.2 +/- 1.3, p < 0.01) was observed, primarily accounted for by a significant decrease of the TG fraction (p < 0.01). IEC-6 cells secreted only trace amounts of lipids under the latter experimental condition. Incubation with TGF beta (20 h) significantly inhibited IEC-6 cell proliferation but did not promote the expression of cell sucrase activity. TGF beta induced a significant increase in the cellular composition of PL (p < 0.05) and a decrease in the TG fraction (p < 0.02), after a 2.5-h pulse of [14C]oleic acid. Lipid production was unaffected by TGF beta during the 20-h incubation with [14C]oleic acid. Lipid secretion into the medium remained negligible in the presence of TGF beta, after 2.5 h of incubation with substrate as above. Our findings suggest that immature crypt IEC-6 cells are capable of lipid esterification and synthesis but secrete minute amounts of lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A conformational model for the human liver microsomal glucose-6-phosphatase system: evidence from rapid kinetics and defects in glycogen storage disease type 1.

Rapid kinetics of glucose-6-phosphate (G6P) uptake and hydrolysis as well as of orthophosphate uptake were investigated in microsomes prepared from normal and glycogen storage disease type 1a (GSD 1a) human livers using a fast sampling, rapid filtration apparatus and were compared to those of rat liver microsomes. As shown before with rat microsomes, the production of [U-14C]glucose from 0.2 mmol/L [U-14C]G6P by untreated normal human microsomes was characterized by a burst in activity during the first seconds of incubation, followed by a slower linear rate. The initial velocity of the burst was equal to the rate of glucose production in detergent-treated microsomes. In untreated and detergent-treated GSD 1a microsomes, no glucose-6-phosphatase activity was observed. When untreated normal human or rat microsomes were incubated in the presence of 0.2 mmol/L [U-14C]G6P, an accumulation of [U-14C]glucose was observed, whereas no radioactive compound (G6P and/or glucose) was taken up by GSD 1a microsomes. Orthophosphate uptake was, however, detectable in both GSD 1a and normal untreated vesicles. These results do not support a rate-limiting transport of G6P in untreated normal human microsomes and further show that in this case of GSD 1a, no distinct G6P transport activity is present.

Adolescent↗
PubMed1994

The impact of school transitions in early adolescence on the self-system and perceived social context of poor urban youth.

This study examined the effects of the normative school transition (n = 580) during early adolescence on the self-system and perceived school and peer social contexts of poor, black (n = 161), white (n = 146), and Latino (n = 273) youth in the public school systems of 3 eastern urban cities. The results revealed negative effects of the school transition on the affective and behavioral domains of the self-system. These declines in self-esteem, class preparation, and grade-point average (GPA) were common across race/ethnicity and gender. Concurrently, the school transition was perceived to be associated with changes in the school and peer contexts. Daily hassles with the school increased, while social support and extracurricular involvement decreased over the transition. Daily hassles with peers decreased, and peer values were perceived as more antisocial. These changes in the school and peer microsystems were also common across race/ethnicity and gender. In addition, transition-associated school and peer changes and, in particular, changes in daily hassles with the school were associated with changes in the academic dimensions of the self-system, that is, academic efficacy expectations, class preparation, and GPA. The results are discussed within a developmental mismatch framework.

Adolescent↗
PubMed1993

Cultural phenomena and the research enterprise: toward a culturally anchored methodology.

Highlights the points at which culture intersects major phases of the research enterprise--problem formulation, population definition, concept and measurement development, research design, methodology, and data analysis--and influences and constrains what researchers deem worthy of investigation and how they interpret what they observe. These ethnocentric biases inhibit the development of a knowledge base for understanding diverse cultural communities. At each step of the research process, the need to carefully examine and expose the underlying cultural assumptions and to generate and develop alternative choices is emphasized. Guidelines are provided to encourage researchers to be aware of and deliberately make choices toward the development of a culturally anchored methodology that balances the demands for rigor and sensitivity.

Culture↗
PubMed1993

Interleukin-2 activity of colonic lamina propria mononuclear cells in a rat model of experimental colitis.

BACKGROUND: Altered interleukin 2 (IL-2) production has been implicated in the pathogenesis of inflammatory bowel diseases. METHODS: The temporal relationship between IL-2, prostaglandin E2 (PGE2) production, and mucosal injury was evaluated by isolated colonic lamina propria mononuclear cells (LPMC), using the trinitrobenzene sulfonic acid model of rat colitis. RESULTS: Spontaneous LPMC IL-2 activity was significantly increased in chronic (5 weeks) but not acute (5 days) or resolved colitis groups. IL-2 activity after concanavalin A activation was highest in the groups with resolved and chronic colitis. PGE2 production was significantly increased in LPMC cultures in acute or chronic colitis as well as the ethanol control groups but not the resolved colitis group. The addition of indomethacin to LPMC cultures decreased PGE2 levels in all groups, whereas IL-2 activity increased only for the chronic and resolved colitis groups. No correlation was found between PGE2 and IL-2 production by LPMC. CONCLUSIONS: In this experimental model, LPMC IL-2 production varied according to the severity and duration of the inflammation. Increased PGE2 production does not appear to be responsible for the IL-2 alterations in colitis.

Acute Disease↗
PubMed1993

Beneficial effects of fish-oil supplements on lipids, lipoproteins, and lipoprotein lipase in patients with glycogen storage disease type I.

Glycogen storage disease type I (GSD-I) is frequently complicated by severe hyperlipoproteinemia and the increased potential risk of premature atherosclerosis. The effects of fish-oil supplementation [MaxEPA, 10 g.(1.73 m2)-1 for 3 mo] were investigated prospectively in seven hyperlipoproteinemic patients with GSD-I. Hypertriglyceridemia and hypercholesterolemia improved after 3 mo of fish-oil treatment, decreasing 49% (P < 0.005) and 23%, respectively. This was accompanied by a reduction in both low-density-lipoprotein (LDL) cholesterol (25%, P < 0.03) and apolipoprotein B (40%) and by increased high-density-lipoprotein increased (HDL) cholesterol (30%, P < 0.002) and apolipoprotein A-I (31%, P < 0.05). Low pretreatment ratios of HDL to total cholesterol and HDL to LDL, indicators of elevated atherosclerosis risk, increased significantly (P < 0.05). Plasma lipoprotein profile as well as lipoprotein composition [triglyceride (TG) enrichment and cholesteryl depletion] improved. Reduced TG concentrations were due to enhanced fat catabolism, as evidenced by the significantly increased hepatic and extrahepatic lipoprotein lipase activity (P < 0.05). Withdrawal of fish oil for 3 mo was associated with a return to pretreatment abnormalities in plasma lipids and lipoproteins. Fish-oil supplementation thus improves the hyperlipoproteinemia in GSD-I and may significantly reduce the risk of premature atherosclerotic cardiovascular disease.

Adolescent↗