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At least 1,063 records · Page 59Linked to original sources
PubMed2006

Relative contribution of genetic and nongenetic modifiers to intestinal obstruction in cystic fibrosis.

BACKGROUND & AIMS: Neonatal intestinal obstruction (meconium ileus [MI]) occurs in 15% of patients with cystic fibrosis (CF). Our aim was to determine the relative contribution of genetic and nongenetic modifiers to the development of this major complication of CF. METHODS: A total of 65 monozygous twin pairs, 23 dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI status, significant covariates, and genome-wide linkage. RESULTS: Specific mutations in the CF transmembrane conductance regulator (CFTR), the gene responsible for CF, correlated with MI, indicating a role for CFTR genotype. Monozygous twins showed substantially greater concordance for MI than dizygous twins and siblings (P = 1 x 10(-5)), showing that modifier genes independent of CFTR contribute substantially to this trait. Regression analysis revealed that MI was correlated with distal intestinal obstruction syndrome (P = 8 x 10(-4)). Unlike MI, concordance analysis indicated that the risk for development of distal intestinal obstruction syndrome in CF patients is caused primarily by nongenetic factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0) for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide analyses. These analyses did not support the existence of a major modifier gene on chromosome 19 in a region previously linked to MI. CONCLUSIONS: The CFTR gene along with 2 or more modifier genes are the major determinants of intestinal obstruction in newborn CF patients, whereas intestinal obstruction in older CF patients is caused primarily by nongenetic factors.

Chromosomes, Human, Pair 11↗
PubMed2003

Modified syringe design prevents plunger-related contamination--results of contamination and flow-rate tests.

The usual mechanism for syringe contamination is spread of micro-organisms along the inside of the barrel. Two or more full strokes of the plunger will inevitably transport a contaminant from the inside wall into the sterile compartment. We modified syringes by replacing the plunger with a modified version that has an additional central O-ring seal. Conventional and modified syringes were tested for their susceptibility to contamination using standard microbiological and radioisotope methods, and the flow-rate stability of the modified syringe design was assessed in a model with commercially available infusion pumps. Although conventional syringes consistently became contaminated with the second full excursion of the plunger, no contamination was observed in modified syringes, even after 100 aspiration/injection cycles. With respect to flow-rate stability, the new syringe design complies with DIN (German Institute for Standardization) standards.

Cross Infection↗
PubMed2001

A biomechanical analysis of the modified Tsuge suture technique for repair of flexor tendon lacerations.

Thirty-six flexor tendons from fresh frozen cadavers were randomized to three types of repairs: a Kessler-Tajima, a 4-strand modified Tsuge, and a 6-strand modified Tsuge. All repairs were accompanied by a standard epitendinous suture. The repaired tendons were then tested to initial gap and ultimate failure in an Instron machine. The average forces to ultimate failure were 31.8 N (SD, 8.8), 48.4 N (SD, 10.7), and 64.2 N (SD, 11.0) respectively. The 6-strand modified Tsuge suture was significantly stronger than the other repairs and the 4-strand modified Tsuge was significantly stronger than the 2-strand Kessler-Tajima. The 6-strand and 4-strand modified Tsuge repairs appear strong enough to withstand the forces generated during early active range of motion flexor tendon rehabilitation protocols. Clinical trials are required to evaluate the usefulness of these repairs.

Biomechanical Phenomena↗
PubMed2001

Modified retrolabyrinthine approach with partial labyrinthectomy: anatomic study.

This study was undertaken to evaluate the feasability of the modified retrolabyrinthine approach (traditional retrolabyrinthine approach plus resection of the posterior semicircular canal) to expose the entire fundus of the internal auditory canal (IAC). This approach is advocated by its proponents to manage acoustic neuromas reaching the lateral IAC and with the preservation of hearing as the goal. Little anatomic data directly estimate the limitations of this exposure. Measurements were recorded from 25 cadaver temporal bones dissected with this modified approach. The distances were taken between the porus acousticus (inferior and superior portions), the dome of the jugular bulb, the midportion of the sigmoid sinus, and the fundus of the IAC (inferior and superior portions). All of the measurements were then compared with those of the translabyrithine approach. The current study shows that despite the sacrifice of the posterior semicircular canal, the superior lateral fundus cannot be completely visualized. There is a distance (on average 1.1 mm) that differentiates the superior area of the IAC accessible with translabyrithine and modified retrosigmoid techniques. This value is smaller than that observed in the classic retrosigmoid approach indicating that the modified technique affords a more adequate, even if not ideal, exposure to minimize the risk of recurrence. The modified retrolabyrinthine approach provided an optimal exposure of the inferior half of the IAC. A superior blind area, smaller than that of the traditional retrolabyrinthine technique, cannot be completely approached via this route. We believe that this approach can be considered as an alternative technique in selected cases especially for tumors involving the inferior vestibular nerve.

Colon, Sigmoid↗
PubMed2001

Comparison of reliability between the modified groin flap and the forearm flap in oral reconstruction.

OBJECTIVE: The groin flap has the advantage of minimum donor-site morbidity, while having the disadvantage of short vascular pedicle of small caliber. Modification of the groin flap has improved the former disadvantage, but the latter one remains. The purpose of this study was to compare the reliability of the modified groin flap with the forearm flap. STUDY DESIGN: Eleven modified groin flaps and 40 forearm flaps consecutively performed by a single surgeon in a hospital for patients with oral cancer were retrospectively reviewed. RESULTS: The rate of total flap loss in the modified groin flap group (8.3%) was higher than that in the forearm flap group (2.5%). The rates of partial flap loss in both flaps were similar to those of total flap loss. The failures of the modified groin flap and the forearm flap were due to arterial and venous complications, respectively. CONCLUSION: The modified groin flap appears to be a little less reliable than is forearm flap; nevertheless, it could be a good option for patients who desire less conspicuous postoperative scars.

Adult↗
PubMed2001

Effect of various surface protections on the margin microleakage of resin-modified glass ionomer cements.

STATEMENT OF PROBLEM: Because conventional glass ionomer cements are moisture sensitive, a surface coating is recommended during the initial setting stage. It is unknown whether resin-modified glass ionomer cements also need surface protection. PURPOSE: This study investigated the effect of various surface protections on microleakage with Class V resin-modified glass ionomer restorations. MATERIAL AND METHODS: Forty extracted molars with buccal and lingual Class V cavity preparations were restored with a resin-modified glass ionomer (Fuji II LC). The occlusal margin of each restoration was on enamel and the cervical margin on dentin. After immediate finishing and polishing, the teeth were divided into 4 groups according to the following surface protection treatments: group I, unprotected; group II, Fuji varnish; group III, resin adhesive; and group IV, acid etching and resin adhesive. After these procedures, all teeth were stored in isotonic saline for 24 hours, thermocycled 1500 times at 5 degrees C to 60 degrees C, and soaked in dye solution for 24 hours. The teeth then were longitudinally sectioned and observed under a stereomicroscope. The degree of dye penetration was recorded and analyzed with the Kruskal-Wallis and Mann-Whitney tests (P<.05) RESULTS: None of the 4 groups demonstrated complete margin sealing at either the occlusal or cervical margins. Groups II and III displayed the least microleakage at cervical margins; a significant difference existed between groups I and III (P=.034). Compared with the other 3 groups, group IV showed significantly greater microleakage at the cervical margins. CONCLUSION: Although resin-modified glass ionomers can be finished immediately, they remain moisture sensitive. Within the limitations of this study, the results suggest that resin adhesive should be used as a surface protection to reduce margin microleakage of resin-modified glass ionomer restorations.

Acid Etching, Dental↗
PubMed2005

Activated antigen-presenting cells select and present chemically modified peptides recognized by unique CD4 T cells.

CD4 T cells recognized posttranslationally modified peptides of the protein hen egg-white lysozyme (HEL), consisting of nitration of tyrosines and modifications of tryptophans in the T cell contact residues of the peptides. T cells were directed against modifications of a chemically dominant HEL peptide as well as a minor HEL peptide, bound to the class II histocompatibility molecule I-A(k). The modified peptides were generated in vivo after immunization with native HEL molecules or were generated ex vivo by peroxynitrite treatment of HEL. Moreover, antigen-presenting cells (APC), either macrophages or dendritic cells activated in culture or in vivo, generated the modified HEL epitopes that stimulated the T cells. In transgenic mice expressing HEL, the T cells to the modified epitopes escaped negative selection and were found, albeit fewer in number than in normal mice. Infection with Listeria monocytogenes of the transgenic HEL mice generated APC containing the modifications. T cells to modified epitopes induced by activation of APC may be a component of antimicrobial immunity and autoimmune reactions.

Animals↗
PubMed2006

Solution structure of Urm1 and its implications for the origin of protein modifiers.

Protein modifiers are involved in diverse biological processes and regulate the activity or function of target proteins by covalently conjugating to them. Although ubiquitin and a number of ubiquitin-like protein modifiers (Ubls) in eukaryotes have been identified, no protein modifier has been found in prokaryotes; thus, their evolutionary origin remains a puzzle. To infer the evolutionary relationships between the protein modifiers and sulfur carrier proteins, we solved the solution NMR structure of the Urm1 (ubiquitin-related modifier-1) protein from Saccharomyces cerevisiae. Both structural comparison and phylogenetic analysis of the ubiquitin superfamily, with emphasis on the Urm1 family, indicate that Urm1 is the unique "molecular fossil" that has the most conserved structural and sequence features of the common ancestor of the entire superfamily. The similarities of 3D structure and hydrophobic and electrostatic surface features between Urm1 and MoaD (molybdopterin synthase small subunit) suggest that they may interact with partners in a similar manner, and similarities between Urm1-Uba4 and MoaD-MoeB establish an evolutionary link between ATP-dependent protein conjugation in eukaryotes and ATP-dependent cofactor sulfuration.

Models, Molecular↗
PubMed1981

Phagocytosis of carbohydrate-modified phospholipid vesicles by macrophage.

Modification of the surface of distearoyl phosphatidylcholine vesicles with synthetic glycolipids dramatically affects the rate of uptake of these vesicles by mouse peritoneal macrophage. The high rate of uptake of 6-aminomannose-modified vesicles is effectively inhibited by cytochalasin B and chloroquine but not by colchicine, indicating that the mechanisms of vesicle uptake is phagocytosis. Other modified vesicles appear to have some effect on the rate of uptake of 6-aminomannose-modified vesicles suggesting that the various vesicle types compete for the same initial binding sites. Analysis of 6-aminomannose-modified vesicles by gamma-ray perturbed angular correlation spectroscopy shows that the rotational correlation time of the encapsulated 111In3+ does not change when the vesicles associate with macrophage. This result is consistent with transmission electron microscopy, which indicates that the aminomannose-modified vesicles remain intact after phagocytosis as aggregates of fused and intact vesicles surrounded by a single bilayer membrane structure.

Animals↗
PubMed1998

Consistent, persistent expression from modified retroviral vectors in murine hematopoietic stem cells.

Retroviral vectors based on the Moloney murine leukemia virus (MoMuLV) have shown inconsistent levels and duration of expression as well as a propensity for the acquisition of de novo methylation in vivo. MoMuLV-based vectors are known to contain sequences that are capable of suppressing or preventing expression from the long terminal repeat. Previously, we constructed a series of modified retroviral vectors and showed that they function significantly better than MoMuLV-based vectors in vitro. To test the efficacy of the modified vectors in hematopoietic stem cells in vivo, we examined gene expression and proviral methylation in differentiated hematopoietic colonies formed in the spleens of mice after serial transplantation with transduced bone marrow (2 degreesCFU-S). We found a significant increase in the frequency of expression with our modified vectors (>90% expression in vector DNA containing 2 degreesCFU-S) over the frequency observed with the standard MoMuLV-based vector (28% expression in vector containing 2 degreesCFU-S). Expression from the modified vectors was highly consistent, with expression in >50% of the vector-containing 2 degreesCFU-S from all 20 transplant recipients analyzed, whereas expression from the standard MoMuLV-based vector was inconsistent, with expression in 0-10% of the vector containing 2 degreesCFU-S from 8 recipients and expression in >50% of the vector-containing 2 degreesCFU-S from 4 other recipients. In addition, we established that the modified vectors had a lower level of DNA methylation than the control vector. These findings represent significant advances in the development and evaluation of effective retroviral vectors for application in vivo.

Animals↗
PubMed1997

Accumulation of pyrraline-modified albumin in phagocytes due to reduced degradation by lysosomal enzymes.

Previous studies suggested that the interaction between proteins modified by advanced glycation end products (AGEs) and cells, such as macrophages, may be involved in diabetic angiopathy. Pyrraline is one of the AGEs and known to be elevated in plasma of diabetic rats and humans, and is present in vascular lesions of diabetic and elderly subjects. We examined whether modification of albumin by pyrraline influences its degradation by macrophage-like cell line, P388D1 cells. Degradation of pyrraline-modified albumin by these cells was diminished, causing accumulation of the albumin in these cells. The susceptibility of pyrraline-modified albumin to lysosomal proteolytic enzymes was reduced by approximately 40% in vitro, while lysosomal activity in the cells per se was not affected. This phenomenon was also observed when human monocytes were used instead of P388D1 cells. Our results suggest that accumulation of pyrraline-modified albumin in P388D1 cells is due to the reduced susceptibility of the protein to lysosomal enzymatic degradation. Such alterations in the interaction between AGEs-modified protein and phagocytes may contribute to angiopathy in elderly subjects and patients with diabetes.

Albumins↗
PubMed1999

Reactive site-modified tissue inhibitor of metalloproteinases-2 inhibits the cell-mediated activation of progelatinase A.

Tissue inhibitor of metalloproteinases-2 (TIMP-2) is supposed to play a regulatory role in the cell-mediated activation of progelatinase A. To investigate the mechanism of the regulation, we prepared and characterized a chemically modified TIMP-2, and examined its effects on the activation of progelatinase A. We found that treatment of TIMP-2 with cyanate ion led to loss of inhibitory activity toward matrilysin or gelatinase A. Structural and functional analyses of the modified TIMP-2 showed that carbamylation of the alpha-amino group of the NH2-terminal Cys1 of TIMP-2 led to complete loss of the inhibitory activity. When the reactive-site modified TIMP-2 was added to culture medium of concanavalin A-stimulated HT1080 cells, the conversion of endogenous progelatinase A to the intermediate form was partially inhibited, whereas that of the intermediate form to the mature one was strongly inhibited. The reactive site-modified TIMP-2 also prevented an accumulation of active gelatinase A on the cell surface. We speculate that occupation of the hemopexin-like domain of gelatinase A by the reactive site-modified TIMP-2 makes it unable for gelatinase A to be retained on the cell surface, thus preventing the autocatalytic conversion of the intermediate form of gelatinase A to its mature form.

Amino Acid Sequence↗
PubMed1999

Generation of artificial proteoglycans containing glycosaminoglycan-modified CD44. Demonstration of the interaction between rantes and chondroitin sulfate.

All CD44 isoforms are modified with chondroitin sulfate (CS), while only those containing variably spliced exon V3 are modified with both CS and heparan sulfate (HS). The CS is added to a serine-glycine (SG) site in CD44 exon E5, while HS and CS are added to the SGSG site in exon V3. Site-directed mutagenesis and other molecular biology techniques were used to determine the minimal motifs responsible for the addition of CS and HS to CD44 (see accompanying paper (Greenfield, B., Wang, W.-C., Marquardt, H., Piepkorn, M., Wolff, E. A., Aruffo, A., and Bennett, K. L. (1999) J. Biol. Chem. 274, 2511-2517)). We have used this information to generate artificial proteoglycans containing the extracellular domain of the cell adhesion protein lymphocyte function-associated antigen-3 (LFA-3) (CD58) and CD44 motifs modified with CS or a combination of CS and HS. Analysis of the CD44-modified LFA-3 protein showed that it retains the ability to engage and trigger the function of its natural ligand CD2, resulting in T cell activation. In addition, the glycosaminoglycan-modified artificial proteoglycan is capable of binding the chemokine RANTES (regulated upon activation, normally T cell expressed and secreted) and delivering it to human T cells, resulting in enhanced T cell activation. These data demonstrate that artificial proteoglycans can be engineered with functional domains that have enhanced activity by codelivering glycosaminoglycan-binding molecules. The artificial proteoglycans were also used as a model system to explore the glycosaminoglycan binding properties of basic-fibroblast growth factor and the chemokine RANTES. While basic-fibroblast growth factor was shown to bind HS alone, this model revealed that RANTES binds not only HS, as has been demonstrated in the past, but also CS. Thus, artificial proteoglycans can be used for studying the glycosaminoglycan binding patterns of growth factors and chemokines and provide a means to manipulate the levels, types, and activity of glycosaminoglycan-binding proteins in vitro and in vivo.

Base Sequence↗
PubMed2000

p-hydroxyphenylacetaldehyde, an aldehyde generated by myeloperoxidase, modifies phospholipid amino groups of low density lipoprotein in human atherosclerotic intima.

Oxidation of low density lipoprotein (LDL) may be of critical importance in the pathogenesis of atherosclerosis. Recent studies suggest that oxidized phospholipids render LDL atherogenic. However, both the structures and the physiologically relevant pathways for the formation of modified phospholipids in oxidized LDL remain poorly understood. We previously showed that p-hydroxyphenylacetaldehyde (pHA) is the major product of L-tyrosine oxidation by the myeloperoxidase/hydrogen peroxide/chloride system of phagocytes. In the current studies, we demonstrate that this reactive aldehyde targets the aminophospholipids of LDL in vitro and in vivo. Activated human neutrophils generated pHA-ethanolamine, the reduced adduct of pHA with the amino group of phosphatidylethanolamine, on LDL phospholipids by a reaction that required myeloperoxidase, H(2)O(2), and L-tyrosine. The cellular system could be replaced by HOCl and L-tyrosine but not by a wide variety of other oxidation systems, indicating that pHA-ethanolamine is a specific marker for covalent modification of aminophospholipids by myeloperoxidase. To determine whether aldehydes modify aminophospholipids in vivo, we quantified levels of pHA-ethanolamine in acid hydrolysates of reduced lipid extracts through isotope dilution gas chromatography/mass spectrometry. Circulating LDL contained undetectable levels of pHA-modified phospholipid (<0.1 mmol/mol). In contrast, the concentration of pHA-ethanolamine in LDL isolated from human atherosclerotic lesions was strikingly elevated (4.5 mmol/mol). Collectively, these results demonstrate a novel, myeloperoxidase-based mechanism for modifying the amino group of LDL phospholipids. They also offer the first evidence that myeloperoxidase may damage LDL lipids in vivo, raising the possibility that aldehyde-modified aminophospholipids play a role in inflammation and vascular disease.

Acetaldehyde↗
PubMed2001

Second meal effect: modified sham feeding does not provoke the release of stored triacylglycerol from a previous high-fat meal.

The present study was carried out to determine whether cephalic stimulation, associated with eating a meal, was sufficient stimulus to provoke the release of stored triacylglycerol (TAG) from a previous high-fat meal. Ten subjects were studied on three separate occasions. Following a 12 h overnight fast, subjects were given a standard mixed test meal which contained 56 g fat. Blood samples were taken before the meal and for 5 h after the meal when the subjects were randomly allocated to receive either water (control) or were modified sham fed a low-fat (6 g fat) or moderate-fat (38 g fat) meal. Blood samples were collected for a further 3 h. Compared with the control, modified sham feeding a low- or moderate-fat meal did not provoke an early entry of TAG, analysed in either plasma or TAG-rich lipoprotein (TRL) fraction (density <1.006 kg/l). The TRL-retinyl ester data showed similar findings. A cephalic phase secretion of pancreatic polypeptide, without a significant increase in cholecystokinin levels, was observed on modified sham feeding. Although these data indicate that modified sham feeding was carried out successfully, analysis of the fat content of the expectorant showed that our subjects may have accidentally ingested a small amount of fat (0.7 g for the low-fat meal and 2.4 g for the moderate-fat meal). Nevertheless, an early TAG peak following modified sham feeding was not demonstrated in the present study, suggesting that significant ingestion of food, and not just oro-sensory stimulation, is necessary to provoke the release of any TAG stored from a previous meal.

Adult↗
PubMed1985

Temperature jump relaxation studies on the interactions between transfer RNAs with complementary anticodons. The effect of modified bases adjacent to the anticodon triplet.

We have used the temperature-jump relaxation technique to determine the kinetic and thermodynamic parameters for the association between the following tRNAs pairs having complementary anticodons: tRNA(Ser) with tRNA(Gly), tRNA(Cys) with tRNA(Ala) and tRNA(Trp) with tRNA(Pro). The anticodon sequence of E. coli tRNA(Ser), GGA, is complementary to the U*CC anticodon of E. coli tRNA(Gly(2] (where U* is a still unknown modified uridine base) and A37 is not modified in none of these two tRNAs. E. coli tRNA(Ala) has a VGC anticodon (V is 5-oxyacetic acid uridine) while tRNA(Cys) has the complementary GCA anticodon with a modified adenine on the 3' side, namely 2-methylthio N6-isopentenyl adenine (mS2i6A37) in E. Coli tRNA(Cys) and N6-isopentenyl adenine (i6A37) in yeast tRNA(Cys). The brewer yeast tRNA(Trp) (anticodon CmCA) differs from the wild type E. coli tRNA(Trp) (anticodon CCA) in several positions of the nucleotide sequence. Nevertheless, in the anticodon loop, only two interesting differences are present: A37 is not modified while C34 at the first anticodon position is modified into a ribose 2'-O methyl derivative (Cm). The corresponding complementary tRNA is E.coli tRNA(Pro) with the VGG anticodon. Our results indicate a dominant effect of the nature and sequence of the anticodon bases and their nearest neighbor in the anticodon loop (particularly at position 37 on the 3' side); no detectable influence of modifications in the other tRNA stems has been detected. We found a strong stabilizing effect of the methylthio group on i6A37 as compared to isopentenyl modification of the same residue. We have not been able so far to assess the effect of isopentenyl modification alone in comparison to unmodified A37. The results obtained with the complex yeast tRNA(Trp)-E.coli tRNA(Pro) also suggest that a modification of C34 to Cm34 does not significantly increase the stability of tRNA(Trp) association with its complementary anticodon in tRNA(Pro). The observations are discussed in the light of inter- and intra-strand stacking interactions among the anticodon triplets and with the purine base adjacent to them, and of possible biological implications.

Anticodon↗
PubMed2005

Nickel adsorption on the modified pine tree materials.

Removal of nickel ions from aqueous solutions containing 1-100 mg l(-1), using pine tree (Pinus nigra) materials modified with HCl, was investigated on a laboratory scale. For this purpose, two natural adsorbents such as the modified pine bark (MPB) and the modified pine cone (MPC) materials with HCl solution were studied. At first, the required concentration level of the HCl solution for the modification was observed, and then this was followed by the determinations of optimum levels of adsorbent amount, stirring rate, contact time and pH values. Various adsorption isotherms were also obtained by using different concentrations of the heavy metal cations tested in the experiment. As a result, the maximum removal efficiency levels obtained were as follows; 97% for the modified pine bark at pH 8 and 80% for the modified pine cone at pH 8.

Adsorption↗
PubMed1998

Increased metabolism of peroxynitrite-modified [125I] beta-VLDL by monocytes from hypercholesterolemic rabbits.

The metabolism (uptake and degradation) of peroxynitrite-modified beta-VLDL and native beta-VLDL labeled with [125I]iodine was studied in monocytes isolated from peripheral blood of hypercholesterolemic (HC) and normolipidemic rabbits (NC). The peroxynitrite-modified beta-VLDL uptake and degradation was up to 2-fold higher in monocytes from HC rabbits than monocytes from NC rabbits. In addition, monocytes from HC rabbits took up and degraded significantly more peroxynitrite-modified beta-VLDL than native beta-VLDL. In contrast, monocytes from NC rabbits took up both lipoproteins in a similar rate and degraded more native beta-VLDL than peroxynitrite-modified beta-VLDL. Our results suggest that hypercholesterolemia can affect monocyte metabolism enhancing foam cell formation by increasing the influx of peroxynitrite-modified beta-VLDL.

Animals↗