Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed2004

ProteoMod: A new tool to quantitate protein post-translational modifications.

Post-translational modifications (PTMs) are known to regulate biological processes by controlling protein function. The effect of a PTM on protein function depends critically on the position and the number of modifications. While there are convenient methods available to qualitatively examine modifications like phosphorylation, glycosylation, acetylation and methylation, methods available for their quantitative assessment are cumbersome. We have developed a new tool that allows quantitation of the number of phosphorylation events in proteins with ease. The "ProteoMod" tool depends on shifts in the isoelectric points of proteins upon post-translational change. The extent of shift exhibited upon phosphorylation is algorithmically converted into the number of phosphorylations conferred. The validity of ProteoMod was confirmed by examining proteins with previously known number of phosphorylations. The list of proteins examined included HSP27, HSP70 and tumor suppressor p53. The approach can also be applied to estimate modifications like acetylation, methylation and sialylation in proteins. We analyzed shifts in isoelectric points due to sialylation events in N-glycoproteins. Using influenza hemagglutinin we show that shifts in isoelectric points correlate with intracellular distribution of this model membrane protein. In addition to extending the application of two dimensional gel electrophoresis to quantitate modifications, our study also highlights its potential use in cell biology.

Algorithms↗
PubMed1994

Chemical modification of human UDP-glucuronosyltransferase UGT1*6 by diethyl pyrocarbonate: possible involvement of a histidine residue in the catalytic process.

Chemical modification with diethyl pyrocarbonate (DEPC) of the recombinant human liver UDP-glucuronosyltransferase UGT1*6 in enriched membrane fractions from a V79 cell line resulted in a rapid inactivation of the glucuronidation reaction, measured with 4-methyl-umbelliferone as aglycone substrate, with a second-order rate constant of 3110 M-1.min-1 at pH 6.0 and 25 degrees C. The enzymatic activity was restored by hydroxylamine. Chemical modification with 0.2 mM DEPC for 60 s decreased the apparent Vmax 2.4-fold without significantly affecting the apparent Km toward 4-methylumbelliferone and UDP-glucuronic acid. Similarly, the binding of the photoactivatable cosubstrate analog [beta-32P]5-azido-UDP-glucuronic acid to the active site was not affected by the chemical modification. The enzyme was protected against this inactivation by 4-methylumbelliferone, suggesting that the modified residue was located in or near the aglycone binding site. In contrast, the cosubstrate UDP-glucuronic acid potentiated the irreversible inhibition, indicating a conformational change in the protein upon binding. The pH-dependence of the inactivation was in agreement with the modification of an amino acid residue with a pKa of 6.1. On the other hand, analysis of the variation of Vmax and Vmax/Km values of the glucuronidation reaction as a function of the pH revealed the presence of two essential residues with a pKa within the range 5.7-6.0. The data of the chemical modification of the recombinant enzyme together with that of the pH dependence of the activity strongly suggest the involvement of a histidine residue, highly reactive toward DEPC, which could be the base catalyst of the glucuronidation reaction supported by human UGT1*6.

Affinity Labels↗
PubMed1995

Tyrosine modification by reactive nitrogen species: a closer look.

Peroxynitrite (ONOO-) is a powerful oxidant and cytotoxic species formed by the rapid reaction between nitrogen monoxide (nitric oxide, .NO) and superoxide (O2.-). At neutral pH ONOO- is partly protonated and this protonated form, peroxynitrous acid (ONOOH), decomposes rapidly to nitrate, forming (an) intermediate(s) with reactivity similar to .OH and .NO2. Peroxynitrite can hydroxylate and nitrate aromatic rings, and aromatic nitration of phenols such as tyrosine by ONOOH is proposed to proceed via a radical mechanism, with intermediate formation of .NO2. Modification of tyrosine by .NO2 also involves nitration via a radical mechanism. Aromatic nitration of phenols by ONOO- has been shown to be enhanced by superoxide dismutase or Fe(3+)-EDTA, which were proposed to catalyze heterolytic cleavage of ONOOH to form a nitrating species similar to the nitronium ion (NO2+). We investigated possible mechanisms of tyrosine modification by various reactive nitrogen species, including ONOO-, 3-morpholinosydnonimine (SIN-1), and .NO2. Reaction of tyrosine with ONOO- leads to formation of 3-nitrotyrosine and dityrosine, indicating intermediate formation of tyrosyl radicals. The pH dependence of formation of both 3-nitrotyrosine and dityrosine by ONOO- suggests that intermediate formation of ONOOH is required. Qualitatively similar results were obtained when ONOOH was generated continuously by H2O2 and NaNO2 at mildly acidic pH or with SIN-1, a compound which at neutral pH releases both .NO and O2.-, presumably producing ONOO-. However, relatively low yields of nitrotyrosine were obtained with SIN-1, possibly because of competing reactions of tyrosyl radicals with .NO or O2.-. Possible involvement of .NO2 in tyrosine modification by ONOO- was studied using hydroxyl radical scavengers, which can increase the radical yield during decomposition of ONOOH and thereby enhance generation of .NO2. Hydroxyl radical scavengers did not affect tyrosine modification by .NO2 directly and slightly inhibited tyrosine modification by authentic ONOO-. However, when ONOO- was produced at a slower rate, either by SIN-1 or by H2O2/NaNO2 at acidic pH, hydroxyl radical scavengers were found to significantly enhance tyrosine nitration. Our results suggest that ONOO- or ONOO(-)-generating systems induce nitration of tyrosine (or tyrosine residues in proteins) via intermediate formation of tyrosyl radicals and .NO2.

Free Radicals↗
PubMed1997

Cancer-preventive selenocompounds induce a specific redox modification of cysteine-rich regions in Ca(2+)-dependent isoenzymes of protein kinase C.

Since protein kinase C (PKC) serves as a receptor for phorbol ester type tumor promoters and oxidants and has unique redox-active cysteine-rich regions, we have determined whether various chemopreventive selenocompounds could affect this enzyme. At lower concentrations, selenite decreased the kinase activity (IC50 = 0.5 microM), while at higher concentrations it decreased phorbol ester binding. However, when the catalytic and regulatory domains of PKC were separated by proteolysis, the catalytic domain retained its sensitivity to selenite, while the regulatory domain lost its sensitivity. Cysteine residues were quantitated in PKC modified with selenite by using 5,5'-dithiobis(2-nitrobenzoic acid) and also by using 2-nitro-5-thiosulfobenzoic acid after sulfitolysis. At lower concentrations, selenite induced a modification of four cysteine residues resulting in the formation of two disulfides, while at higher concentrations it induced a modification of seven to eight cysteine residues resulting in the formation of three to four disulfides. Contrary to selenite, selenocystine and selenodiglutathione (GSSeSG) readily inactivated the kinase activity, but not the phorbol ester binding. These two agents induced a two-stage modification of PKC; a limited modification at low concentrations leads to a loss of affinity for ATP, while an excessive modification at high concentrations leads to a loss of Vmax. Selenocystine and GSSeSG were 100,000-fold more potent than GSSG in inactivating PKC. The isoenzymes alpha, beta, and gamma exhibited an identical susceptibility to these selenocompounds. These results suggested that the cysteine residues present within the catalytic domain of these isoenzymes, although apart in the sequence, may be clustered in the tertiary structure to react with selenite, as well as may be in close proximity to some of the cysteines in the regulatory domain. Selenite did not affect protein kinase A, whereas GSSeSG and selenocystine inactivated the catalytic subunit after dissociation from the regulatory subunit at concentrations 100- and 800-fold, respectively, higher than that required for PKC inactivation. All three selenocompounds did not affect the activities of phosphorylase kinase and protein phosphatase 2A. Taken together, these results suggest that the accessible redox-active cysteine residues present in the PKC catalytic domain can react with certain specificity with redox-active selenocompounds such as selenite, selenocystine, and GSSeSG relative to other protein kinases tested.

Animals↗
PubMed1996

Modifications of the water-insoluble human lens alpha-crystallins.

Since the water-insoluble crystallins of the lens may be the precursors of cataract, identifying the modifications that differentiate the water-insoluble from the water-soluble crystallins may provide the basis for understanding the chemistry leading to cataract. This investigation of the alpha-crystallins of the water-insoluble urea-soluble portion of 45-year-old normal clear lenses, isolated using gel filtration, ion exchange and reversed phase chromatography, has employed state-of-the-art mass spectrometric techniques to identify and locate the modifications of the water-insoluble alpha-crystallins. Modifications present in the isolated alpha-crystallins were identified by the molecular weights of the modified proteins, by the molecular weights of peptides produced by enzymatic digestion of the proteins, and by the fragmentation patterns produced by collisional activation of the peptides. Modifications that are either unique to the water-insoluble alpha-crystallins or are more prevalent in the water-soluble portion than in the water-soluble part include complete oxidation of the two Cys residues of alpha A-crystallin to form an intra-molecular disulfide bond, partial truncation at both the C-termini and N-termini of alpha A- and alpha B-crystallins, partial oxidation of Met residues to methionine sulfoxide, partial deamidation of several Asn and Gln residues, and evidence of peptide bond cleavage at some of the deamidated residues. Although many reactions have been proposed to contribute to the insolubility of crystallins, this compilation of in vivo post-translational modifications of water-insoluble alpha-crystallins delineates products that are actually present at levels of 5% or more. From these results, it is hypothesized that alpha-crystallin becomes water-insoluble following deamidation of various Asn and Gln residues which cause conformational changes leading to formation of an intra-molecular disulfide bond between the Cys residues of alpha A-crystallin.

Amino Acid Sequence↗
PubMed2001

Resistance of human betaB2-crystallin to in vivo modification.

Post-translational modifications and/or structural changes induced by modifications are likely causes of the decrease in crystallin solubility associated with aging and the development of cataract. Characterization of human lens crystallins by mass spectrometry has demonstrated that betaB2-crystallin undergoes less modification than any of the other crystallins. As the lens ages, betaB2-crystallin retains its hydrophilic N-terminus while the hydrophilic C-termini of alpha-crystallins and large portions of the N-termini of betaA3/A1 and betaB1 are truncated. The hydrophilic terminal regions of crystallins contribute to their solubility. Furthermore, deamidation and disulfide bond formation, other modifications that may affect solubility by altering conformation, are less extensive in betaB2 than in the other crystallins. This resistance to modification results in higher levels of betaB2 compared with the other crystallins in the water-soluble fraction of older lenses. The solubility of betaB2 and its propensity to form non-covalent associations with less soluble beta-crystallins may contribute to the solubility of the other beta-crystallins. A current hypothesis is that the chaperone-like properties of alpha-crystallins contribute to lens crystallin solubility, particularly in younger lenses. In older lenses, where most of the alpha-crystallins have become water-insoluble, betaB2-crystallins may play a dominant role in lens crystallin solubility.

Adolescent↗
PubMed1994

Analysis of action of wobble nucleoside modifications on codon-anticodon pairing within the ribosome.

Wobble rules for modified residues in the first anticodon position are derived. All known modifications are considered individually. Stereochemical analysis was made taking into account the interaction between the ribosomal A and P-site bound codon-anticodon duplexes. The wobble base-pair was considered as the right one if its formation did not lead to an uncompensated loss of hydrogen bonds or polar atom-ion bonds. From this requirement it follows that all modifications of U should restrict its translational specificity to purines (with the exception of xo5U, which should decode A, G and U). The restriction is carried out in a unified way: modifications inhibit the large propeller twist resulting from an increase of about 35 degrees in the torsion angle of the anticodon wobble base, interacting with the third codon base via a hydrogen-bonded water molecule. Such a twist is required to avoid a loss of the hydrogen bond of the bonded water molecule. The modifications in S2U, Se2U and Um should weaken their pairing with G, because they deform one of the two hydrogen bonds of the guanine NH2 group. G should be recognized by Se2U better than by S2U for the reason that the hydrogen bond Se...HN is weaker than the hydrogen bond S...HN. Among the modifications of C and G only that in k2C has a pronounced effect on wobble. The nucleoside k2C should pair only with A. The N-2 atom of k2C should be in the pyramidal state. The consequences following from the interduplex interaction are formulated. According to one of them, adenosine in the wobble position of the P-site tRNA should destabilize the A-site duplex. This can serve as an explanation for the fact that adenosine is very rarely observed in the anticodon wobble position.

Adenosine↗
PubMed1999

Reprogramming a somatic nucleus by trans-modification activity in germ cells.

The germ cell lineage is totipotent insofar as it provides a link between an individual and the subsequent generations. There is a series of characteristic genomic modifications in germ cells that distinguish this lineage from somatic cells. These modifications include extensive demethylation of the genome, erasure of allele-specific methylation of imprinted loci and re-activation of the silent X chromosome. To test if this is an active process capable of reprogramming a somatic nucleus, we prepared germ cell-somatic cell hybrids. A dominant trans modification activity was detected in germ cells that was capable of inducing similar modifications in the somatic nucleus. This experimental system can therefore be used to study how determined cell state can be reversed by specific genomic modifications.

Animals↗
PubMed1978

Effects of methylphenidate alone and in combination with behavior modification procedures on the behavior and academic performance of hyperactive children.

Twenty hyperactive 6- to 9-year-old children of normal intelligence were studied in a half-day laboratory classroom in a 2-week period baseline-treatment-reversal design for behavior modification. Under double-blind conditions half the children were placed on .3 mg/kg of Ritalin and half on placebo for the entire program. The classroom program consisted of a group period with immediate reinforcement possible, and an individual time period without immediate reinforcement possible. Behavior modification caused a significant decrease in nonattending, out-of-seat, inappropriate vocalizing and inappropriate peer interaction behavior in the group period. Fidgeting, a nontargeted behavior, was not significantly decreased during this period but did significantly decrease as a result of medication. No other drug effects occurred during this period. During the individual period, the results were essentially reversed. There were no significant behavior modification effects observed. Significant reductions resulted from medication in all behaviors except out-of-seat and fidgeting. Behavior modification alone significantly affected the two academic measures. No signigicant effects were seen on the Conners Abbreviated Teacher Rating Scale. No significant interactions were noted between medication and behavior modification.

Achievement↗
PubMed1990

Antigenic modification of polioviruses by host proteolytic enzymes.

Incubation of polioviruses with human intestinal fluid is known to result in molecular and antigenic modification of the virion surface. Studies with different inhibitors of serine proteases suggested that trypsin in the intestinal fluid is most likely responsible for the primary cleavage of VP 1. However, minor differences could be distinguished between the final cleavage products produced by purified trypsin and intestinal fluid, respectively. Other enzymes present in intestinal fluid may thus contribute to the modification of polioviruses in vivo. No evidence was obtained in favour of any biological significance of these further modifications. Another serine protease plasmin, which is generated in the body from its ubiquitous precursor plasminogen under various physiological and pathological conditions, was also shown to be able to cleave VP 1 of polioviruses and bring about the corresponding modification of antigenic site 1. This observation extends the potential pathogenetic consequences of the host enzyme-mediated proteolytic modification of polioviruses from intestinal mucosa to most other tissues.

Antigens, Viral↗
PubMed1994

The impact of patterns of nodal metastasis on modifications of neck dissection.

BACKGROUND: Radical neck dissection (RND) is standard treatment for cervical metastasis from head and neck cancer. Although effective, RND produces significant morbidity. In an effort to reduce this morbidity, modifications of RND have been developed. These modifications can be comprehensive yet spare some or all of the nonlymphatic structures removed in RND, or they can remove less than all the lymph node groups removed in RND and are termed selective neck dissections. We have reviewed the literature regarding the patterns of nodal metastasis from head and neck cancer to define the indications for these modifications of RND. METHODS: A review of the literature concerning patterns of nodal metastasis from head and neck cancer was performed. Using this information, recommendations on the use of modifications of neck dissection were formulated. RESULTS: In squamous cancers, with clinically negative neck supraomohyoid neck dissection is an adequate node sampling procedure for oral cavity and oropharyngeal lesions, and lateral (jugular) neck dissection for primary lesions of the hypopharynx, and larynx. In the clinically positive neck comprehensive neck dissection with preservation of the spinal accessory nerve is oncologically sound. CONCLUSIONS: Nodal metastasis of head and neck cancer occurs in predictable patterns. Based on these patterns of nodal metastasis, recommendations for the use of modifications of neck dissection are presented.

Head and Neck Neoplasms↗
PubMed1987

Membrane fatty acid modification in tumor cells: a potential therapeutic adjunct.

The fatty acid compositions of several tumors have been modified sufficiently to alter some of their properties and functions. These modifications were produced in culture by adding specific fatty acids to the growth medium or by feeding fat-supplemented diets to tumor-bearing mice. The phospholipid fatty acid composition of the plasma membrane was modified, but there were no changes in membrane phospholipid or cholesterol content or in phospholipid head group composition. Each of the most abundant membrane phosphoglyceride fractions exhibited some degree of fatty acid modification. Electron spin resonance measurements with nitroxystearate spin probes indicated that the fatty acid modifications were sufficient to alter the physical properties of the plasma membrane. The K'm for methotrexate uptake was reduced when the L1210 leukemia cells were enriched in linoleic acid. Even when the kinetics of uptake at 37 C were not altered, such as for melphalan and phenylalanine uptake, the temperature transition of transport was modified, indicating that these transport systems also are responsive to the membrane fatty acid modifications. Enrichment with highly polyunsaturated fatty acid did not affect either the growth rate or radiosensitivity of the L1210 leukemia. However, the sensitivity of the L1210 cells to the cytotoxic effects of Adriamycin and hyperthermia was increased. These findings suggest the possibility that fatty acid modification of tumors may be a useful adjunct to certain currently available therapeutic modalities.

Animals↗
PubMed1998

Effect of aluminum on iron-induced lipid peroxidation and protein oxidative modification of mouse brain homogenate.

In the present study the authors report on the enhancing effect of aluminum(III) (Al[III]) on iron(II)(Fe[II])-induced lipid peroxidation (LPO) of mice brain homogenate, which occurs in a concentration- and time-dependent manner. No evidence of LPO caused by Al alone was found. Both Al(III) and Fe(II) ions induced protein oxidative modifications in mice brain homogenate, in a time- and concentration-dependent manner. Aluminum enhances Fe(II)-induced protein oxidative modification at a concentration of 2:1 and 1:1 Al:Fe molar ratios. However, Al suppress Fe(II)-induced protein oxidative modification at a concentration of 0.5:1 Al:Fe molar ratio. Addition of ethylenediaminetetraacetic acid (EDTA) inhibits both LPO and protein oxidative modifications induced by Al(III) and Fe(II) ions. Addition of mannitol and of superoxide dismutase (SOD) did not show such effects. It is concluded that in mice brain homogenate, Al accelerates Fe(II)-induced LPO. Protein oxidative modifications caused by Fe(II) and/or Al ions are enhanced at high, but suppressed at low concentrations of Al ions. The latter observation suggests a possible biological role of Al as an antioxidant.

Aluminum↗
PubMed1996

Protein thiol modification and apoptotic cell death as cGMP-independent nitric oxide (NO) signaling pathways.

Nitric oxide signaling is achieved through both cGMP-dependent and cGMP-independent mechanisms. The latter are exemplified by protein thiol modification followed by subsequent NAD(+)-dependent automodification of the glycolytic enzyme GAPDH, or by mechanisms inducing accumulation of the tumor suppressor gene p53 and causing apoptotic cell death. Both cGMP-independent actions are initiated using NO-releasing compounds and an active LPS/cytokine-inducible NO synthase. NO-synthase inhibitors block the release of NO and hinder downstream signaling mechanisms; they are therefore valuable pharmacological tools linking a defined cellular response to various NO actions. Signal transducing mechanisms elicited by NO can be studied using GAPDH as a representative example of NO-induced protein modification and are grouped as follows: --S-Nitrosylation reactions initiated by NO+ --NAD(+)-dependent, post-translational covalent automodification of GAPDH --Oxidative modification (thiol oxidation) and inhibition of GAPDH by NO-related agents, probably ONOO- GAPDH and several other protein targets may serve as molecular sensors of elevated NO concentrations and may transmit this message through posttranslational modification and oxidation-induced conformational changes as cGMP-independent NO signaling pathways. Toxicity of NO seems to be linked to both apoptosis and necrosis, depending on the chemistry of NO it undergoes in a given biological milieu. Toxicity manifests as a relative excess of NOx, metal-NO interactions, and ONOO- formation in relation to cellular defense systems. Although accumulation of the tumor-suppressor gene product p53 in response to NO opens a regulatory mechanism known to be involved in apoptotic cell death, cGMP-independent signaling pathways remain to be elucidated. As NO-dependent modification of GAPDH would imply down-regulation of glycolysis and concomitant energy production followed by cell death, our data so far do not support this assumption. In recent years, NO has proved to be a beneficial messenger with a potentially toxic activity. It will be challenging to investigate NO biochemistry in closer detail and to elucidate how NO targets biological systems, especially in relation to its pathophysiological role.

Animals↗
PubMed1998

Functional modification of agonist-antagonist electromyographic activity for rapid movement inhibition.

Subjects made a fast elbow extension movement to designated target in response to a go signal. In 45% of trials a stop signal was presented after the go signal, to which subjects were asked to stop the movement as rapidly as possible. The interstimulus interval (ISI), or time interval between the go and stop signals, was randomly varied between 0 and 200 ms. Electromyographic (EMG) activity was recorded from biceps brachii and triceps brachii. Subjects could sometimes completely inhibit initiation of the movements when the ISI was 0 ms, but could rarely do so when the ISI exceeded 100 ms. For responses that were initiated but stopped on the way, the amplitude of the movement decreased linearly as the time interval (=modification time) from the stop signal to EMG onset increased. The peak velocity increased linearly as the movement amplitude increased. This tendency was similar to those previously reported in step-tracking movements with various amplitudes. In spite of the similarity in the kinematics of the movement, the EMG pattern was different from that of step-tracking movement. While the initial agonist burst (AG1) decreased linearly after the modification time exceeded 100 ms, the antagonist burst (ANT) increased compared with the go trial for the modification time from 0 to 200 ms and decreased after the modification time exceeded 300 ms. This change of activation is analogous to functional modification of middle-latency reflex EMG response to load, or cutaneous perturbation. In conclusion, it is suggested that adaptive mechanisms, which would functionally modify the reflex responses, are also continuously working during voluntary movements in response to sudden changes in environmental information.

Adaptation, Physiological↗
PubMed2005

Dynamics of learning-induced cellular modifications in the cortex.

This aim of this review is to describe the dynamics of learning-induced cellular modifications in the rat piriform (olfactory) cortex after olfactory discrimination learning and to describe their functional significance to long-term memory consolidation. The first change to occur is in the intrinsic properties of the neurons. One day after learning, pyramidal neurons show enhanced neuronal excitability. This enhancement results from reduction in calcium-dependent conductance that mediates the post burst after-hyperpolarization. Such enhanced excitability lasts for 3 days and is followed by a series of synaptic modifications. Several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons in the piriform cortex accompany olfactory learning. Enhanced synaptic release is indicated by reduced paired-pulse facilitation. Post-synaptic enhancement of synaptic transmission is indicated by reduced rise time of post-synaptic potentials and formation of new synaptic connections is indicated by increased spine density along dendrites of these neurons. Such modifications last for up to 5 days. Thus, olfactory discrimination rule learning is accompanied by a series of cellular modifications which occur and then disappear at different times. These modifications overlap partially, allowing the maintenance of the cortical system in a 'learning mode' in which memories for specific odors can be acquired rapidly and efficiently.

Animals↗
PubMed2000

A comparison of laparoscopic Nissen fundoplication and Rossetti's modification in 239 patients.

BACKGROUND: Laparoscopic Nissen fundoplication and the Rossetti modification represent two different surgical approaches to resolving gastroesophageal reflux disease (GERD). Concerns have arisen that the Rossetti modification results in increased postoperative dysphagia. In this study, we compared a group of patients who underwent a laparoscopic Nissen fundoplication with a group who had undergone the Rossetti modification to determine if there was a significant difference in postoperative dysphagia. Additionally, we wanted to confirm that the Nissen procedure performed laparoscopically could resolve GERD as successfully as the Rossetti modification, with no difference in operative complications. METHODS: We prospectively collected data on 101 patients who underwent laparoscopic Nissen fundoplication and compared outcomes with those of 138 patients who had undergone the laparoscopic Rossetti modification in a previous series. RESULTS: All patients experienced resolution of reflux symptoms. No statistically significant differences were found between the groups in terms of intraoperative or postoperative complications, conversions to open procedure, or length of hospitalization. Paradoxically, there was a significant difference in operating time between the Rossetti and the Nissen groups (70.6 min vs 45.6 min, p = 0.006). Postoperative dysphagia requiring dilation was significantly higher in the Rossetti group (21.7% vs 8.9%, p = 0.008). However, there was a significantly higher percentage of patients in the Rossetti group who had had esophagitis preoperatively (95.7% vs 86.1%, p = 0.009), although the proportion of patients having Barrett's esophagus was higher in the Nissen group (9.4% vs 24.8%, p = 0.001). CONCLUSIONS: Both approaches resolved reflux symptoms without significant differences in complications, conversions, or length of stay. Preoperative differences between groups, as well as the method of sequentially comparing the two different procedures, prevent us from attributing greater postoperative dysphagia in the Rossetti group solely to the choice of surgical approach. Prospective randomized studies are needed to control for variables, such as surgical team experience and patient differences.

Adolescent↗
PubMed2006

The moral difference between intragenic and transgenic modification of plants.

Public policy on the development and use of genetically modified organisms (GMOs) has mainly been concerned with defining proper strategies of risk management. However, surveys and focus group interviews show that although lay people are concerned with risks, they also emphasize that genetic modification is ethically questionable in itself. Many people feel that this technology "tampers with nature" in an unacceptable manner. This is often identified as an objection to the crossing of species borders in producing transgenic organisms. Most scientists reject these opinions as based on insufficient knowledge about biotechnology, the concept of species, and nature in general. Some recent projects of genetic modification aim to accommodate the above mentioned concerns by altering the expression of endogenous genes rather than introducing genes from other species. There can be good scientific reasons for this approach, in addition to strategic reasons related to greater public acceptability. But are there also moral reasons for choosing intragenic rather than transgenic modification? I suggest three interrelated moral reasons for giving priority to intragenic modification. First, we should respect the opinions of lay people even when their view is contrary to scientific consensus; they express an alternative world-view, not scientific ignorance. Second, staying within species borders by strengthening endogenous traits reduces the risks and scientific uncertainty. Third, we should show respect for nature as a complex system of laws and interconnections that we cannot fully control. The main moral reason for intragenic modification, in our view, is the need to respect the "otherness" of nature.

Community Participation↗