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Biomedical subjects

E Granot

Publications and source records attributed to E Granot.

At least 37 records · Page 2Linked to original sources
PubMed2000

Time course of nitric oxide synthase generation after gluten exposure in the rectal mucosa of gluten-sensitive patients.

BACKGROUND: Nitric oxide is thought to play an important role in modulating chronic inflammatory responses as well as in immune-mediated inflammation. We reproduced a gluten-mediated mucosal response in the rectum of celiac and control subjects in order to determine the role of inducible and constitutive nitric oxide synthases in the pathogenesis of this process. MATERIAL: Nine patients with confirmed celiac disease and five healthy controls underwent a long-term rectal gluten challenge (48 h) after an enema of 6 g of crude gluten, and constitutive and inducible nitric oxide synthase activity were determined in rectal biopsies. The histological localization of inducible nitric oxide synthase was determined by immunohistochemistry. RESULTS: Activity of both isoforms of nitric oxide synthase in control subjects did not change significantly after gluten instillation. In celiac patients, constitutive nitric oxide synthase on rectal mucosa also showed no significant changes after challenge with gluten. Inducible nitric oxide synthase isoform exhibited a modest increase 4 h after gluten instillation in celiac patients (mean increase 35% compared with baseline levels) but, 8 h after challenge, generation of iNO synthase was significantly higher: 54% more than pre-challenge production (P < 0.05) and higher than control values (P < 0.05). Inducible nitric oxide synthase staining was mostly localized in mononuclear cells of the epithelium and the lamina propria. After gluten instillation, the enhanced staining was mainly localized in subepithelial areas of the lamina propria. CONCLUSION: Our data suggest a role for nitric oxide, generated by inducible nitric oxide synthase, in the process of rectal mucosa injury by local gluten instillation in sensitized patients. We could not, however, determine if the role of nitric oxide in the ensuing injury of this gluten-induced immune inflammation model is a protective one, or merely a by-product generated by the activation of the inflammatory cells.

Adult↗
PubMed2000

Th1/Th2 cytokines and ICAM-1 levels post-liver transplant do not predict early rejection.

Th1 derived cytokines IFN-gamma and IL-2, Th2 cytokine IL-4, and ICAM-1 have been implicated in liver allograft rejection. In order to determine whether monitoring of cytokine profiles during the first days post-liver transplant can predict early rejection we measured IFN-gg, IL-2, sIL-2 receptor, IL-4 and ICAM-1 in 22 patients, in plasma samples obtained within 4 h after liver perfusion (baseline) and between postoperative days (POD) 3-6. ICAM-1 and sIL-2R levels at POD 3-6 were significantly higher than at baseline but did not differ in presence or absence of rejection. Mean percentage increase of ICAM-1 levels was significantly lower in patients with Muromonab-C3 Orthoclone OKT3 (J.C. Health Care) (OKT3) whereas percentage increase of sIL-2R levels was higher in OKT3-treated patients. IFN-gamma levels at POD 3-6 increased from baseline while IL-4 levels were unchanged. Levels of IFN-gamma, IL-4 and their ratios did not correlate with rejection or immunosuppressive therapy. Thus, Th1/Th2 cytokine monitoring during the first week post-transplant does not predict early rejection and immunosuppressive therapy is the predominant factor affecting ICAM and sIL-2R levels after liver transplantation.

Female↗
PubMed2000

Breast-fed and formula-fed infants do not differ in immunocompetent cell cytokine production despite differences in cell membrane fatty acid composition.

BACKGROUND: Breast-fed and formula-fed infants differ in the amount and type of polyunsaturated fatty acids consumed. The fatty acid composition of cell membranes is related to dietary fatty acids and, in adults, changes in membrane fatty acid composition are accompanied by changes in monocyte cytokine production and hence a modification of the immunologic response. OBJECTIVE: Our objective was to determine whether production by immunocompetent cells of the proinflammatory cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) differs between breast-fed and formula-fed infants. DESIGN: Twenty-six healthy infants (13 breast-fed and 13 fed modified cow-milk formula) aged 2-4 mo were studied. The fatty acid composition of red blood cell (RBC) membrane phospholipids was measured by gas-liquid chromatography and IL-1 and TNF release were measured in whole blood culture in bacterial-endotoxin-stimulated and unstimulated cells. RESULTS: The infants' ages, weights, hemoglobin concentrations, and white blood cell counts did not differ significantly between groups. The percentage of n-3 fatty acids of total RBC phospholipid fatty acids was significantly higher in breast-fed than in formula-fed infants (6.31 +/- 2.5% compared with 2.98 +/- 0.97%); docosahexaenoic acid (22:6n-3) concentrations were also markedly higher in breast-fed infants (5.1 +/- 1.2% compared with 2.2 +/- 0.9%, P: < 0.001), but eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3) concentrations did not differ significantly between groups. The percentage of n-6 fatty acids was not significantly different between groups. The percentage of oleic acid (18:1) was higher in formula-fed than in breast-fed infants (16.2 +/- 0.7% compared with 20.6 +/- 1.1%; P: < 0.001). IL-1 and TNF release in whole blood culture did not differ significantly between groups. CONCLUSION: The release of proinflammatory cytokines by immunocompetent cells does not differ significantly in breast-fed and formula-fed infants despite differences in cell membrane fatty acid composition.

Breast Feeding↗
PubMed1999

Influence of external biliary drainage on cyclosporin A (Neoral) absorption in a pediatric liver transplant recipient.

We report on a patient who underwent a liver transplant 8 yr ago at the age of 2. The post-operative course and further follow-up were uneventful, maintaining immunosuppression with cyclosporin A (CsA) (Sandimmune) and prednisone; 1.5 yr ago, the patient was converted to Neoral. The mean +/- SD trough CsA level was 127 +/- 37.2 ng/mL, when the patient was maintained on a daily dose of 180 mg. Following an increase in gamma-GTP levels, a biliary-enteric anastomotic stricture was found. Dilatation was performed and a tube placed for external biliary drainage. Three days later the trough CsA level was at the limit of detection; consequently, the Neoral dose was increased to 480 mg/d. CsA concentration measured 5 days later reached 164 ng/mL. After restoring internal biliary drainage the dose was decreased to 180 mg/d and the CsA level was 142 ng/mL. Later on the CsA dose was further reduced to 160 mg/d (a third of the dose during external biliary drainage) and trough levels were maintained at 90-120 ng/mL. We suggest that CsA dose adjustment and continuous drug monitoring are necessary when bile flow is compromised, in order to prevent rejection of the transplanted liver.

Age Factors↗
PubMed1999

Lymphocyte subset profile of young healthy children residing in a rural area: possible role of recurrent gastrointestinal infections.

BACKGROUND: Lymphocyte subsets in healthy children are currently characterized by age-related standards. Because antigenic stimuli play a role in maturation of the immune system after birth, there is a question of whether cellular immune development differs in infants whose living conditions entail extensive antigenic exposure and infants growing up in a more protected environment. METHODS: Peripheral blood lymphocyte subsets were studied in two populations of children of similar age and nutritional status; children belonging to a rural population residing in proximity with farm animals and children from an economically privileged urban population. In each population, children studied included a group with an acute diarrheal episode and a healthy control group. RESULTS: Among rural population children, 65% had experienced at least one episode of gastroenteritis within the previous 3-month-period, compared with less than 10% of urban population children. In the rural population group 15% had experienced two or more episodes of gastroenteritis. The proportion of helper T cells was similar in rural population and urban population children. Among helper T cells, the proportion of CD29+ "memory" cells of the total CD4+ helper T cells was more than two times higher than those in rural population children. The proportion of CD8 cells was higher in rural population children than in urban population children, and the proportion of natural killer cells, CD56+ and CD57+, was two to three times higher in rural population children. Within each population, peripheral blood lymphocyte subsets did not differ between the healthy control group and those with acute diarrhea. CONCLUSIONS: In young children exposure to environmental pathogens and specifically to gastrointestinal antigenic stimuli is a major factor affecting development of the cellular immune response. Young children who have experienced enhanced infectious exposure have a peripheral blood lymphocyte profile similar to that of adults.

Acute Disease↗
PubMed1999

[EBV-related lymphoproliferative disorder after liver transplantation].

We describe a 4.5-year-old girl in whom post transplantation lymphoproliferative disorder was diagnosed 1 year after liver transplantation. She ran a complicated course with multiple organ involvement: respiratory failure which required mechanical ventilation, renal failure, bone marrow depression and severe protein-losing enteropathy.

Child, Preschool↗
PubMed1998

Lipoprotein changes in children after liver transplantation: mild hypertriglyceridemia and a decrease in HDL3/HDL2 ratio.

Hyperlipidemia is frequently observed in patients who undergo renal, cardiac, bone marrow, or liver transplantation, and its contribution to the long-term morbidity and survival of patients with organ transplants may be substantial. In the few studies that have focused on the pediatric age group, findings have been inconsistent. The lipoprotein profile of 10 children after liver transplantation was characterized and compared with those in normal population controls and 10 healthy siblings. Plasma triglyceride and cholesterol concentrations were determined, lipoprotein fractions (very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL], and high-density lipoproteins [HDL2 and HDL3]) were isolated, their chemical compositions were analyzed (protein, phospholipids, triglycerides, free cholesterol, and cholesteryl ester), and the percent relative weight composition of the particles was calculated. Plasma triglyceride and VLDL cholesterol levels were higher post-liver transplantation (P < .05): triglycerides (mean +/- SD), 115.1 +/- 58.7 mg% versus 76.6 +/- 20.9 mg% in siblings and 60.0 +/- 25.0 mg% in normal population controls; very-low-density lipoprotein cholesterol (VLDL-C), 23.0 +/- 11.7 mg% versus 15.3 +/- 4.7 mg% and 13.0 +/- 8.0 mg%, respectively. Plasma triglyceride levels did not correlate with the length of the period after liver transplantation. Levels of LDL-C and total HDL-C and the relative weight composition of VLDL, LDL, HDL2, and HDL3 particles did not differ between post-liver transplantation children and controls. Posttransplantation, levels of HDL3, the normally predominant HDL subfraction, were decreased relative to HDL2 levels (HDL3, 1.3; HDL2, 2.3). Because this observed relative increase in larger cholesteryl ester-rich HDL particles (HDL2) may result from inhibition of cholesteryl ester-triglyceride transfer processes, cholesteryl ester transfer protein activity was assayed. Cholesteryl ester transfer protein activity did not differ between patients and controls. Thus, the lipoprotein changes observed in children post-liver transplantation are mild hypertriglyceridemia and a significant increase in HDL2 relative to HDL3. Because HDL2 is regarded as protective against atherosclerosis, this may be of clinical relevance.

Child↗
PubMed1998

Immunologic response to infection with Giardia lamblia in children: effect of different clinical settings.

Infection with Giardia lamblia varies in both its severity and duration. A high incidence of giardiasis in immunoglobulin-deficient individuals suggests a role for the humoral immune response in resistance to Giardia infection. Levels of specific anti-Giardia antibodies were determined in three populations of children infected with the parasite: in children attending a day-care centre in which strict hygiene measures were practised and in whom all Giardia infections were asymptomatic; in a rural population residing under poor hygienic conditions in close proximity to farm animals in which children with Giardia-associated diarrhoeal episodes were studied; and in Bedouin infants followed from birth and in whom a previous study has shown that Giardia infection is almost universal by the age of 2 years. In day-care children, infection was accompanied by a significant increase in anti-Giardia IgM levels, compatible with an initial exposure to the parasite. In populations in which exposure to the parasite occurs at an early age and the prevalence of infestation is high, the pattern of specific antibodies to the parasite is rather uniform and cannot differentiate between current infection and previous exposure. Thus, other immune parameters such as salivary or urinary secretory IgA, which reflect the intestinal IgA response, should be studied in order to delineate further the humoral immune response to Giardia.

Animals↗
PubMed1998

Gastroesophageal reflux in infants with hydrocephalus before and after ventriculo-peritoneal shunt operation.

Gastroesophageal reflux (GER) is common in neurologically impaired children, especially those with central nervous system disorders. The cause of GER in these children has not yet been defined, but in animal studies, acute elevation of intracranial pressure (ICP) has been shown to result in a decrease in lower esophageal sphincter pressure. Ten infants with hydrocephalus underwent esophageal pH monitoring prior to and after a ventriculoperitoneal (V-P) shunt operation. A significant degree of reflux was present in 5 patients with hydrocephalus prior to shunt operation and reverted to normal in 2. In the other 3 infants, the degree of reflux decreased as evidenced by fewer abnormal parameters and lower scoring in each of the parameters measured. Our study supports the contention that increased ICP in infants is indeed associated with GER. As 4 of the 5 infants with significant reflux suffered from an Arnold-Chiari malformation, a causal relation between increased ICP due to defects involving the fourth ventricle floor and GER is suggested.

Acute Disease↗
PubMed1997

Crohn's disease in late adolescence: acute onset or long-standing disease?

We studied retrospectively a group of 53 patients with Crohn's disease, diagnosed between 18 and 21 years of age. They had all undergone a thorough medical evaluation at age 17 before military service. They thus served as a unique group in whom the natural course of the disease, duration of signs and symptoms before diagnosis, and delay in diagnosis could be assessed. Other than a more frequently elicited history of nonspecific mild recurrent abdominal pain in childhood in the patient group, medical history, physical growth, sexual development, and laboratory parameters of inflammation did not differ in the patient group and the healthy control group. Crohn's disease in this group of young adults is likely one of acute onset and did not begin as an exacerbation of a more subtle and prolonged process.

Acute Disease↗
PubMed1995

[Endoscopic retrograde cholangiopancreatography in diagnosis of biliary atresia].

The differential diagnosis between neonatal hepatitis and biliary atresia in the newborn is difficult and has therapeutic implications. Despite important advances in diagnostic tools, 10-20% of newborns with jaundice remain without definitive diagnosis. In recent years ERCP has played a decisive role in achieving definitive anatomic diagnosis, thus avoiding unnecessary exploratory laparotomy. We present our experience with ERCP using a pediatric duodenoscope in 18 newborns with inconclusive diagnoses of neonatal cholestasis.

Biliary Atresia↗
PubMed1995

Failure of exogenous apoprotein E-3 to enhance cholesterol egress from J-774 murine macrophages in culture.

HDL has been shown to enhance the removal of cholesterol from cultured fibroblasts, smooth muscle cells and macrophages, but fails to stimulate cholesterol removal from J-774 macrophages. Since J-774 macrophages do not synthesize or secrete apolipoprotein E, the effect of exogenous apolipoprotein E on HDL-mediated cellular cholesterol efflux was studied in this cell line. In cholesterol loaded J-774 macrophages total cellular cholesterol increased up to 6-7-fold, mainly cholesteryl esters. HDL3 removed up to 30% of total cellular cholesterol with a decrease in cholesteryl ester levels while free cholesterol levels remained unchanged. HDL3 was slightly superior to albumin in promoting cellular cholesterol removal. Exogenous apo E, over a wide range of apo E concentrations, did not enhance the ability of HDL3 to remove cellular cholesterol from cholesterol loaded J-774 cells. Exogenous apo E did not promote HDL-mediated cholesterol efflux from cells, thus suggesting a possible role for the intracellular route of newly synthesized apo E in these processes.

Albumins↗
PubMed1994

Effects of particle size on cell uptake of model triglyceride-rich particles with and without apoprotein E.

The effect of apoprotein E on cellular uptake of "VLDL-size" and "IDL-size" triacylglycerol-phospholipid emulsion particles was studied in J-774 macrophages and fibroblasts. In the absence of apoprotein E (apo E), uptake of the smaller IDL-size particles was up to 2-fold higher by mass and 100-fold higher as calculated by particle number. Apo E enhanced the uptake of both VLDL-size and IDL-size emulsion particles, but the effect was greater on the uptake of larger particles (4-5-fold) as compared to up to a 2-fold increase in the uptake of IDL-size particles. In fibroblasts, particle uptake was less than in macrophages (30-50%), but preferential uptake of smaller particles was similarly observed. Particle internalization was demonstrated by 125I-apo E degradation and resistance to particle release by heparin-suramin. In the absence of apo E, cholesteryl ester of emulsion particles (prepared with trace amounts of [3H]cholesteryl ester) was hydrolyzed to free cholesterol, proving internalization and intracellular metabolism. Double-label experiments using DiI-labeled emulsion particles, in the absence and presence of apo E, showed that emulsion particles are rapidly targeted to perinuclear lysosomes. Thus, at physiological concentrations of triglyceride-rich particles, non-receptor-mediated uptake is a mechanism for the uptake of VLDL-size and IDL-size particles into cells.

Apolipoproteins E↗