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Biomedical subjects

R Shamir

Publications and source records attributed to R Shamir.

At least 55 records · Page 3Linked to original sources
PubMed1999

Carboxyl ester lipase overexpression in rat hepatoma cells and CEL deficiency in mice have no impact on hepatic uptake or metabolism of chylomicron-retinyl ester.

To study the role of carboxyl ester lipase (CEL) in hepatic retinoid (vitamin A) metabolism, we investigated uptake and hydrolysis of chylomicron (CM)-retinyl esters (RE) by rat hepatoma (McArdle-RH7777) cells stably transfected with a rat CEL cDNA. We also studied tissue uptake of CM-RE in CEL-deficient mice generated by targeted disruption of the CEL gene. CEL-transfected cells secreted active enzyme into the medium. However, both control and CEL-transfected cells accumulated exogenously added CM-RE or CM remnant (CMR)-derived RE in equal amounts. Serum clearance of intravenously injected CM-RE and cholesteryl ester were not different between wild-type and CEL-deficient mice. Also, the uptake of the two compounds by the liver and other tissues did not differ. These data indicate that the lack of CEL expression does not affect the uptake of dietary CM-RE by the liver or other tissues. Moreover, the percentage of retinol formed in the liver after CM-RE uptake, the levels of retinol and retinol-binding protein in serum, and retinoid levels in various tissues did not differ, indicating that CEL deficiency does not affect hepatic retinoid metabolism and retinoid distribution throughout the body. Surprisingly, in both pancreas and liver of wild-type, heterozygous, and homozygous CEL-deficient mice, the levels of bile salt-dependent retinyl ester hydrolase (REH) activity were similar. This indicates that in the mouse pancreas and liver an REH enzyme activity, active in the presence of bile salt and distinct from CEL, is present, compatible with the results from our accompanying paper that the intestinal processing and absorption of RE were unimpaired in CEL-deficient mice.

Animals↗
PubMed1999

Parenteral selenium supplementation in extremely low birth weight infants: inadequate dosage but no correlation with hypothyroidism.

OBJECTIVE: Selenium is an essential trace element, known to be important in thyroid metabolism. We speculated that parenteral selenium supplementation is inadequate in preterm infants and may contribute to the development of hypothyroidism. STUDY DESIGN: Serum selenium and thyroid function were evaluated on day 10 of life in extremely low birth weight infants. Selenium intake provided by parenteral nutrition was prospectively evaluated. RESULTS: Selenium intake was close to the recommended 2 micrograms/kg per day. Serum selenium values were 0.54 +/- 0.13 microM (mean +/- SD, n = 29). Selenium serum levels were low in 26 of 29 infants. In infants with subnormal serum selenium levels, free T4 was transiently low in 10 of 26 infants but was normal in 16 of 26 infants. No significant correlation was found between serum selenium levels and hypothyroidism. CONCLUSION: Current selenium supplementation guidelines may be inadequate in extremely low birth weight infants. However, selenium deficiency does not seem to play a major role in neonatal hypothyroidism.

Birth Weight↗
PubMed1999

Construction of physical maps from oligonucleotide fingerprints data.

A new algorithm for the construction of physical maps from hybridization fingerprints of short oligonucleotide probes has been developed. Extensive simulations in high-noise scenarios show that the algorithm produces an essentially completely correct map in over 95% of trials. Tests for the influence of specific experimental parameters demonstrate that the algorithm is robust to both false positive and false negative experimental errors. The algorithm was also tested in simulations using real DNA sequences of C. elegans, E. coli, S. cerevisiae, and H. sapiens. To overcome the non-randomness of probe frequencies in these sequences, probes were preselected based on sequence statistics and a screening process of the hybridization data was developed. With these modifications, the algorithm produced very encouraging results.

Algorithms↗
PubMed1999

An algorithm combining discrete and continuous methods for optical mapping.

Optical mapping is a novel technique for generating the restriction map of a DNA molecule by observing many single, partially digested, copies of it, using fluorescence microscopy. The real-life problem is complicated by numerous factors: false positive and false negative cut observations, inaccurate location measurements, unknown orientations and faulty molecules. We present an algorithm for solving the real-life problem. The algorithm combines continuous optimization and combinatorial algorithms, applied to a non-uniform discretization of the data. We present encouraging results on real experimental data.

Algorithms↗
PubMed1998

QT interval in children and infants receiving cisapride.

OBJECTIVES: Life-threatening arrhythmias and prolonged QT interval have been reported in adults and children using cisapride, a medication structurally similar to procainamide. Premature infants have reduced activity of cytochrome p-450, the system responsible for metabolism of cisapride, which could lead to QT prolongation. Therefore, we prospectively studied premature infants and children receiving cisapride to analyze the effect of prolonged cisapride therapy on QT interval. DESIGN: Premature infants in a neonatal intensive care unit and children seen at a pediatric gastroenterology clinic in a tertiary care hospital had electrocardiography-analyzed and -corrected QT interval measured before cisapride (0.8/mg/kg per day) therapy, and again after 1 month of therapy. If baseline electrocardiography was not performed initially, it was obtained after cessation of therapy. RESULTS: A total of 30 children participated in the study. Mean corrected QT interval was similar at baseline and at 1 month after therapy. Significant QT prolongation was not found, and no adverse effects were recorded. CONCLUSIONS: Corrected QT interval during prolonged cisapride therapy at 0.8 mg/kg per day appears to be similar for premature infants and children. An inherent trend toward QT prolongation was not detected in either group. In the absence of other risk factors that alter cisapride metabolism or predispose to arrhythmia, cisapride may be safe for use in premature infants as well as in children. Additional studies are needed to confirm these data.

Arrhythmias, Cardiac↗
PubMed1998

Management of acute gastroenteritis in children in Israel.

OBJECTIVE: Diarrheal diseases are a major cause of morbidity and mortality worldwide. Guidelines about the use of oral rehydration solutions (ORS) and dietary management of acute gastroenteritis (GE) were recently revised and published by the American Academy of Pediatrics (AAP). Study aims were to examine Israeli pediatricians' knowledge and implementation of the revised AAP guidelines, the effect of medical school (Israeli versus foreign medical graduates) on the physicians' practice, and the effect of the type of practice (community vs hospital-based) on the management of gastroenteritis. METHODS: A multiple-choice, written questionnaire was distributed at two pediatrics annual meetings. RESULTS: A total of 87 pediatricians completed the questionnaire. They were aware of 73% of the current AAP guidelines and followed 60% of the guidelines. Most pediatricians (83%) use ORS for treatment of dehydration in GE, but 60% of pediatricians believe that full-strength feeds are inappropriate in the presence of GE, and 67% of them do not recommend full-strength formulas. In addition, 37% of the pediatricians stop feeding temporarily in the presence of GE, in contrast to the 1996 AAP guidelines. There were no differences in knowledge and management practices among pediatricians graduating in Israel, Europe, or the United States, and no differences between pediatricians working in an ambulatory setting or in a hospital. CONCLUSIONS: Pediatricians in Israel, regardless of country of origin, medical school, or place of practice, are aware of the correct use of ORS but do not follow nutritional practices recommended recently by the AAP. These findings suggest that steps for implementing the guidelines are needed in Israel and most probably worldwide.

Acute Disease↗
PubMed1998

Intravenous amino acids, cholestasis and kwashiorkor.

Kwashiorkor dermatosis has not been reported in children on parenteral nutrition (PN). We report a case of kwashiorkor developing in a partially PN dependent patient with cholestasis, when amino acids were removed from the PN solution in an effort to control the cholestasis. Although the kwashiorkor dermatosis improved within 24 hours after the addition of amino acids (1 g/kg) to the PN solution, the cholestasis worsened.

Amino Acids↗
PubMed1997

Pediatric cholesterol screening: missed opportunities.

The current recommendations for childhood cholesterol screening include screening children in whom 1) a parent/grandparent has premature heart or vascular disease or died suddenly; 2) a parent has an abnormal lipid profile; 3) the family history is unobtainable. Over a 3-year period, 256 children referred for hypercholesterolemia were evaluated for heritable hyperlipidemia. We reviewed their family histories and obtained lipoprotein profiles of all of their immediate family members. Of these families, 89 parents had unsuspected hypercholesterolemia of whom 38, whose average age was 36 years, died of a myocardial infarction. In addition, 83 children with no family history of premature coronary artery disease or hypercholesterolemia, were diagnosed with inherited hyperlipidemia (25 with hetrozygous familial hypercholesterolemia, and 58 with familial combined hyperlipidemia). Thus, many adults have no awareness of hyperlipidemia prior to a fatal heart attack, nor of their children as having hyperlipidemia, and a large percentage of children with inherited hyperlipidemia would not have been diagnosed if all of their immediate family members (parents and siblings) had not been screened for a complete lipid profile. These results suggest that in addition to screening, all family members of hypercholesterolemic children, pediatricians and family practitioners should urge parents who may be unaware of their cholesterol levels or have no knowledge of their family history to undergo cholesterol screening in order to comply with NCEP guidelines calling for serum cholesterol measurements in all adults above the age of twenty.

Adult↗
PubMed1996

Pancreatic carboxyl ester lipase: a circulating enzyme that modifies normal and oxidized lipoproteins in vitro.

Pancreatic carboxyl ester lipase (CEL) hydrolyzes cholesteryl esters (CE), triglycerides (TG), and lysophospholipids, with CE and TG hydrolysis stimulated by cholate. Originally thought to be confined to the gastrointestinal system, CEL has been reported in the plasma of humans and other mammals, implying its potential in vivo to modify lipids associated with LDL, HDL (CE, TG), and oxidized LDL (lysophosphatidylcholine, lysoPC). We measured the concentration of CEL in human plasma as 1.2+/-0.5 ng/ml (in the range reported for lipoprotein lipase). Human LDL and HDL3 reconstituted with radiolabeled lipids were incubated with purified porcine CEL without or with cholate (10 or 100 microM, concentrations achievable in systemic or portal plasma, respectively). Using a saturating concentration of lipoprotein-associated CE (4 microM), with increasing cholate concentration there was an increase in the hydrolysis of LDL- and HDL3-CE; at 100 microM cholate, the present hydrolysis per hour was 32+/-2 and 1.6+/-0.1, respectively, indicating that CEL interaction varied with lipoprotein class. HDL3-TG hydrolysis was also observed, but was only approximately 5-10% of that for HDL3-CE at either 10 or 100 microM cholate. Oxidized LDL (OxLDL) is enriched with lysoPC, a proatherogenic compound. After a 4-h incubation with CEL, the lysoPC content of OxLDL was depleted 57%. Colocalization of CEL in the vicinity of OxLDL formation was supported by demonstrating in human aortic homogenate a cholate-stimulated cholesteryl ester hydrolytic activity inhibited by anti-human CEL IgG. We conclude that CEL has the capability to modify normal human LDL and HDL composition and structure and to reduce the atherogenicity of OxLDL by decreasing its lysoPC content.

Animals↗
PubMed1996

The influence of age and relative weight on the presentation of familial combined hyperlipidemia in childhood.

BACKGROUND: Familial combined hyperlipidemia (FCHL) has been described as the leading cause of familial hyperlipidemia. FCHL is dominantly inherited, occurs in at least 1% of the population, and is responsible for about 10% of premature coronary artery disease (CAD). OBJECTIVE: Because FCHL in childhood is not well characterized, we evaluated the interrelationships among age, percentage of ideal body weight (%IBW) and plasma lipoprotein levels in FCHL children (age 2-18 years), exploring the possibility that obesity and age may influence the presentation of FCHL in childhood. METHODS: One hundred and eighty-nine children with FCHL were studied. Significant correlations within this group were further evaluated by examining a subset of 36 FCHL children, each of whom had an unaffected sibling who could serve as a control for comparison. RESULTS: When the full group was divided into those with TG levels > 90% and those with TG levels < 90%, the correlation with %IBW was stronger in the former (r = 0.45, P < 0.005) as compared with the latter (r = 0.25, P = 0.05). Within the subset of 36 FCHL children and their 36 unaffected siblings (controls), age and sex distributions were similar. Percentage IBW (mean +/- S.D.) (117.3 +/- 29.1 for FCHL and 111.2 +/- 19.4 for controls) was similar and in the overweight range. FCHL children had significantly higher levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B) and triglyceride (TG) levels compared with controls (P < 0.0005 for all comparisons). Of several significant correlations observed in the full group (n = 189), only the correlations of %IBW with plasma TG levels (r = 0.45, P = 0.006), and of age with plasma TG levels (r = 0.48, P = 0.003) persisted with a similar degree of magnitude in the subset of 36 FCHL children. No correlation was significant in the controls. By Fisher's Z-test, the correlation between %IBW and TG in the FCHL children was significantly different from controls. CONCLUSIONS: These results suggest that TG levels in FCHL children, but not in their unaffected siblings, and sensitive to the presence of obesity, implying an interaction between obesity and the underlying condition, in addition, the association between age and TG level in FCHL children suggests a gradual expression of the hyperlipidermia (i.e. TG) during childhood.

Adolescent↗
PubMed1995

Role of bile salt-dependent cholesteryl ester hydrolase in the uptake of micellar cholesterol by intestinal cells.

The bile salt-dependent cholesteryl ester hydrolase (CEH; EC 3.1.1.13) has been proposed to promote the intestinal absorption of both the free and esterified (FC, CE) forms of dietary cholesterol. For example, it was recently reported that in the human intestinal cell line CaCo2, addition of bovine CEH to the medium increased the uptake and intracellular esterification of micellar FC supplied at subphysiological concentrations [Lopez-Candales et al. (1993) Biochemistry 32, 12085-12089]. To test the ability of CEH to promote micellar cholesterol uptake in a CaCo2 system under more physiological conditions, an in vitro model was developed. Cells stably expressing rat CEH were created by DNA transfection (Tr cells), and the uptake of micellar FC and its intracellular esterification were measured using isotopic methods in Tr and control cells. Experimental parameters that were varied included micellar composition (monoolein or egg PC; FC, CE, or both), the final concentration of micellar cholesterol (1 nM to 50 microM), the origin of CEH (endogenously synthesized vs exogenously added), and the species source of enzyme (rat, pig, man). The uptake of cholesterol that was derived from micellar CE was significantly increased 5-10-fold (p < 0.001) in Tr vs control cells as a result of the hydrolysis of the CE by the CEH and subsequent uptake of the liberated free cholesterol. In contrast, the uptake of micellar FC was not increased by the presence of CEH, whether it was endogenous or exogenous. In addition, based on TLC analysis of extracted cellular lipids, there was no evidence that CEH promoted the esterification of the FC that was taken up.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1995

Increased turnover of intrahepatic bile ducts induced by bromobenzene.

Intrahepatic bile duct epithelium consists of two kinetic compartments: a progenitor (P) and a functional (Q) compartment. Hitherto bromobenzene was known to poison only hepatocytes in the third acinus zone. The present experiment aims to demonstrate that bromobenzene affects also bile duct turnover. Thirty male adult rats received one intraperitoneal injection of bromobenzene and were sacrificed in groups of five at the following times: 1, 2, 3, 4, 7, and 14 days. They received [3H]thymidine 1 hr before sacrificing. Autoradiography was done. Bile ducts were evaluated in all portal tracts of the section. The number of epithelial cells in each duct cross section was counted and defined as bile duct class, which is roughly proportional to bile duct size. In each cross section the number of labeled cells was counted. Initially the labeling index was 0.76 +/- 0.3%. By day 3, it reached a peak of 4.1 +/- 1.1%, and then declined to its initial level. Following bromobenzene poisoning, hepatocyte and bile duct epithelia turn over in the same fashion. In both, labeling index and progenitor compartment size initially rise and return by the end of the first week to their initial level. We propose that bile duct epithelia and hepatocytes originate in one determined uncommitted stem cell that resides in the Herring duct. Bromobenzene-induced necrosis triggers proliferation of progenitors in both cell lineages, as well as in the stem cell itself.

Animals↗
PubMed1995

Four strikes against physical mapping of DNA.

Physical mapping is a central problem in molecular biology and the human genome project. The problem is to reconstruct the relative position of fragments of DNA along the genome from information on their pairwise overlaps. We show that four simplified models of the problem lead to NP-complete decision problems: Colored unit interval graph completion, the maximum interval (or unit interval) subgraph, the pathwidth of a bipartite graph, and the k-consecutive ones problem for k > or = 2. These models have been chosen to reflect various features typical in biological data, including false-negative and positive errors, small width of the map, and chimericism.

Base Sequence↗