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PubMed1999

Physical polymer surface modification methods and applications in food packaging polymers.

Continued innovations in the polymer industry have made polymer surface modification methods a subject of intense research. The importance and necessity of surface modification of plastics are explained, and the advantages of physical surface treatments over the less-sophisticated chemical methods are outlined. Currently available physical surface modification methods for food packaging polymers are reviewed from the food packaging perspective. These physical surface modification methods include flame, corona discharge, UV, gamma-ray, electron beam, ion beam, plasma, and laser treatments. The principle of operation of each method is briefly described, and the advantages and disadvantages of each technique are cited. The extent to which each of these methods can produce the specific modifications desired is discussed. Furthermore, the effects of each treatment on barrier, mechanical, and adhesion properties of food packaging polymers are also examined. Finally, an overview of economic aspects of sophisticated surface modification techniques, including ion beam, plasma, and laser treatments, is presented.

Food Packaging↗
PubMed1998

SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex.

RanGAP1 is the GTPase-activating protein for Ran, a small ras-like GTPase involved in regulating nucleocytoplasmic transport. In vertebrates, RanGAP1 is present in two forms: one that is cytoplasmic, and another that is concentrated at the cytoplasmic fibers of nuclear pore complexes (NPCs). The NPC-associated form of RanGAP1 is covalently modified by the small ubiquitin-like protein, SUMO-1, and we have recently proposed that SUMO-1 modification functions to target RanGAP1 to the NPC. Here, we identify the domain of RanGAP1 that specifies SUMO-1 modification and demonstrate that mutations in this domain that inhibit modification also inhibit targeting to the NPC. Targeting of a heterologous protein to the NPC depended on determinants specifying SUMO-1 modification and also on additional determinants in the COOH-terminal domain of RanGAP1. SUMO-1 modification and these additional determinants were found to specify interaction between the COOH-terminal domain of RanGAP1 and a region of the nucleoporin, Nup358, between Ran-binding domains three and four. Together, these findings indicate that SUMO-1 modification targets RanGAP1 to the NPC by exposing, or creating, a Nup358 binding site in the COOH-terminal domain of RanGAP1. Surprisingly, the COOH-terminal domain of RanGAP1 was also found to harbor a nuclear localization signal. This nuclear localization signal, and the presence of nine leucine-rich nuclear export signal motifs, suggests that RanGAP1 may shuttle between the nucleus and the cytoplasm.

Amino Acid Sequence↗
PubMed2001

Internal modification of U2 small nuclear (sn)RNA occurs in nucleoli of Xenopus oocytes.

U2 small nuclear (sn)RNA contains a large number of posttranscriptionally modified nucleotides, including a 5' trimethylated guanosine cap, 13 pseudouridines, and 10 2'-O-methylated residues. Using Xenopus oocytes, we demonstrated previously that at least some of these modified nucleotides are essential for biogenesis of a functional snRNP. Here we address the subcellular site of U2 internal modification. Upon injection into the cytoplasm of oocytes, G-capped U2 that is transported to the nucleus becomes modified, whereas A-capped U2 that remains in the cytoplasm is not modified. Furthermore, by injecting U2 RNA into isolated nuclei or enucleated oocytes, we observe that U2 internal modifications occur exclusively in the nucleus. Analysis of the intranuclear localization of fluorescently labeled RNAs shows that injected wild-type U2 becomes localized to nucleoli and Cajal bodies. Both internal modification and nucleolar localization of U2 are dependent on the Sm binding site. An Sm-mutant U2 is targeted only to Cajal bodies. The Sm binding site can be replaced by a nucleolar localization signal derived from small nucleolar RNAs (the box C/D motif), resulting in rescue of internal modification as well as nucleolar localization. Analysis of additional chimeric U2 RNAs reveals a correlation between internal modification and nucleolar localization. Together, our results suggest that U2 internal modification occurs within the nucleolus.

Active Transport, Cell Nucleus↗
PubMed2000

Cysteine modification of a putative pore residue in ClC-0: implication for the pore stoichiometry of ClC chloride channels.

The ClC channel family consists of chloride channels important for various physiological functions. Two members in this family, ClC-0 and ClC-1, share approximately 50-60% amino acid identity and show similar gating behaviors. Although they both contain two subunits, the number of pores present in the homodimeric channel is controversial. The double-barrel model proposed for ClC-0 was recently challenged by a one-pore model partly based on experiments with ClC-1 exploiting cysteine mutagenesis followed by modification with methanethiosulfonate (MTS) reagents. To investigate the pore stoichiometry of ClC-0 more rigorously, we applied a similar strategy of MTS modification in an inactivation-suppressed mutant (C212S) of ClC-0. Mutation of lysine 165 to cysteine (K165C) rendered the channel nonfunctional, but modification of the introduced cysteine by 2-aminoethyl MTS (MTSEA) recovered functional channels with altered properties of gating-permeation coupling. The fast gate of the MTSEA-modified K165C homodimer responded to external Cl(-) less effectively, so the P(o)-V curve was shifted to a more depolarized potential by approximately 45 mV. The K165C-K165 heterodimer showed double-barrel-like channel activity after MTSEA modification, with the fast-gating behaviors mimicking a combination of those of the mutant and the wild-type pore, as expected for the two-pore model. Without MTSEA modification, the heterodimer showed only one pore, and was easier to inactivate than the two-pore channel. These results showed that K165 is important for both the fast and slow gating of ClC-0. Therefore, the effects of MTS reagents on channel gating need to be carefully considered when interpreting the apparent modification rate.

Animals↗
PubMed1991

BTX modification of Na channels in squid axons. I. State dependence of BTX action.

The state dependence of Na channel modification by batrachotoxin (BTX) was investigated in voltage-clamped and internally perfused squid giant axons before (control axons) and after the pharmacological removal of the fast inactivation by pronase, chloramine-T, or NBA (pretreated axons). In control axons, in the presence of 2-5 microM BTX, a repetitive depolarization to open the channels was required to achieve a complete BTX modification, characterized by the suppression of the fast inactivation and a simultaneous 50-mV shift of the activation voltage dependence in the hyperpolarizing direction, whereas a single long-lasting (10 min) depolarization to +50 mV could promote the modification of only a small fraction of the channels, the noninactivating ones. In pretreated axons, such a single sustained depolarization as well as the repetitive depolarization could induce a complete modification, as evidenced by a similar shift of the activation voltage dependence. Therefore, the fast inactivated channels were not modified by BTX. We compared the rate of BTX modification of the open and slow inactivated channels in control and pretreated axons using different protocols: (a) During a repetitive depolarization with either 4- or 100-ms conditioning pulses to +80 mV, all the channels were modified in the open state in control axons as well as in pretreated axons, with a similar time constant of approximately 1.2 s. (b) In pronase-treated axons, when all the channels were in the slow inactivated state before BTX application, BTX could modify all the channels, but at a very slow rate, with a time constant of approximately 9.5 min. We conclude that at the macroscopic level BTX modification can occur through two different pathways: (a) via the open state, and (b) via the slow inactivated state of the channels that lack the fast inactivation, spontaneously or pharmacologically, but at a rate approximately 500-fold slower than through the main open channel pathway.

Acetamides↗
PubMed2002

Quantification of oxidative/nitrosative modification of CYS(34) in human serum albumin using a fluorescence-based SDS-PAGE assay.

The SH group represented by cysteine in proteins is fundamental to the redox regulation of protein structure and function. Albumin is the most abundant serum protein whose redox modification modulates its physiologic function, as well as serves as a biomarker of oxidative stress. Measurement of selective Cys modification (S-oxidation/nitrosation, electrophilic substitution) on specific proteins, however, is problematic within complex biological mixtures such as plasma. We have utilized a maleimide fluorogenic SH reagent, ThioGlo-1, to develop a fluorescence-based quantitative assay of SH modification of human serum albumin (hSA) using SDS-PAGE. Fully reduced native albumin containing one free SH (Cys(34)) per molecule was utilized as a model protein to characterize the kinetics of ThioGlo-1 reaction using a solution-based spectrofluorometric assay. Optimum labeling of hSA Cys(34) was achieved within 10 min at 60 degrees C using a threefold molar excess of ThioGlo-1 relative to hSA and required SDS. Comparison of the solution spectrofluorometric assay to fluorescent image analysis of hSA bands localized by SDS-PAGE revealed that SH groups in hSA could be quantified after gel electrophoresis. The solution- and gel-based methods were in excellent concordance in their ability to quantify SH modification of hSA following exposure to phenoxyl radicals and nitric oxide. The application of ThioGlo-1 staining and SDS-PAGE quantified the degree of hSA modification in complex human plasma exposed to oxidative or nitrosative stress and revealed that hSA is more sensitive to S modification than other SH-containing plasma proteins.

Binding Sites↗
PubMed2005

Effect of amino acid residue and oligosaccharide chain chemical modifications on spectral and hemagglutinating activity of Millettia dielsiana Harms. ex Diels. lectin.

The effects of modifying the carbohydrate chain and amino acids on the conformation and activity of Millettia dielsiana Harms. ex Diels. lectin (MDL) were studied by hemagglutination, fluorescence and circular dichroism analysis. The modification of tryptophan residues led to a compete loss of hemagglutinating activity; however, the addition of mannose was able to prevent this loss of activity. The results indicate that two tryptophan residues are involved in the carbohydrate-binding site. Modifications of the carboxyl group residues produced an 80% loss of activity, but the presence of mannose protected against the modification. The results suggest that the carboxyl groups of aspartic and glutamic acids are involved in the carbohydrate-binding site of the lectin. However, oxidation of the carbohydrate chain and modification of the histidine and arginine residues did not affect the hemagglutinating activity of MDL. Fluorescence studies of MDL indicate that tryptophan residues are present in a relatively hydrophobic region, and the binding of mannose to MDL could quench tryptophan fluorescence without any change in lambda(max). The circular dichroism spectrum showed that all of these modifications affected the conformation of the MDL molecule to different extents, except the modification of arginine residues. Fluorescence quenching showed that acrylamide and iodoacetic acids are able to quench 77% and 98% of the fluorescence of tryptophan in MDL, respectively. However, KI produced a barely perceptible effect on the fluorescence of MDL, even when the concentration of I(-) was 0.15 M. This demonstrates that most of tryptophan residues are located in relatively hydrophobic or negatively charged areas near the surface of the MDL molecule.

Acrylamide↗
PubMed1994

Dose-responses in rat hepatic protein modification and expression following exposure to the rat hepatocarcinogen methapyrilene.

Dose-related effects of methapyrilene (MP) on protein modification and expression were examined using two-dimensional gel electrophoresis (2-D PAGE) coupled with computer analysis. Methapyrilene was administered ad libitum at doses of 0, 62.5, 125, 250 and 1000 p.p.m. to male F-344 rats for 12 weeks beginning at 8 weeks of age. Following treatment, livers were removed and frozen for 2-D PAGE analysis. Separation of hepatic proteins was conducted using ISO-DALT technology. Changes in abundance and modification of hepatic proteins were determined using the Kepler software package. Covalent modifications of three specific mitochondrial proteins were quantified using a charge modification index. Dose-response relationships were analyzed using Tukey's trend test. Results demonstrated that covalent modification of the three mitochondrial proteins was linearly related to dose and that a dose effect could be found at all dose levels in 2 out of 3 proteins. Two forms of change in protein expression were observed: (i) a dose-dependent change with effects at all doses and (ii) a change only at the toxic dose of 1000 p.p.m. MP. These results demonstrate a molecular effect of MP at doses that do not produce cellular responses including toxicity or increases in cell replication suggesting that these specific mitochondrial modifications are molecular dosimeters but are probably not direct factors and/or sufficient factors in carcinogenesis. This study also demonstrates the potential use of 2-D PAGE electrophoresis to delineate the effect of dose on expression of specific proteins.

Animals↗
PubMed2003

Modification of Sm small nuclear RNAs occurs in the nucleoplasmic Cajal body following import from the cytoplasm.

Biogenesis of functional spliceosomal small nuclear RNAs (snRNAs) includes the post-transcriptional covalent modification of numerous internal nucleotides. We have recently demonstrated that synthesis of 2'-O-methylated nucleotides and pseudouridines in the RNA polymerase II-synthesized Sm snRNAs is directed by sequence-specific guide RNAs. Here, we provide evidence supporting the notion that modification of Sm snRNAs occurs in nucleoplasmic Cajal bodies (CBs), where modification guide RNAs accumulate. We show that short fragments of Sm snRNAs are correctly and efficiently modified when targeted to CBs, but not when these same fragments are targeted to the nucleolus. We also demonstrate that internal modification of the U2 snRNA occurs exclusively after nuclear import of the newly assembled Sm snRNP from the cytoplasm. Finally, we show that p80 coilin, the CB marker protein, is not required for snRNA modification. In coilin knockout cells, Sm snRNAs and their modification guide RNAs colocalize in residual CBs, which do not stockpile fibrillarin and fail to recruit the U3 small nucleolar RNA.

Active Transport, Cell Nucleus↗
PubMed1993

O-linked fucose and other post-translational modifications unique to EGF modules.

Three types of unusual post-translational modification have been found within conserved amino acid sequences in epidermal growth factor homology regions (EGF modules) of some multidomain proteins. beta-Hydroxyaspartate and beta-hydroxyasparagine are found within -Cys-Xxx-Asp/Asn-Xxx-Xxx-Xxx-Xxx-Tyr/Phe-Xxx-Cys-Xxx-Cys- sequences. (Xyl alpha 1-->3)Xyl alpha 1-->3Glc beta 1-->O-Ser glycans at conserved sites within -Cys-Xxx-Ser-Xxx-Pro-Cys- sequences have been reported in several proteins. Fuc alpha 1-->O-Thr/Ser modifications have been found at conserved sites within -Cys-Xxx-Xxx-Gly-Gly-Thr/Ser-Cys- sequences. More recently, it has been discovered that the Ser residue corresponding to the potential O-fucosylation site in human factor IX carries the novel tetrasaccharide NeuAc alpha 2-->6Gal beta 1-->4GlcNAc beta 1-->3Fuc alpha 1-->O-Ser; this tetrasaccharide can be considered to be an extension of the Fuc alpha 1-->O moiety. The consensus sequences for these post-translational modifications are in close proximity to each other; e.g. human factor IX has all three unusual modifications within a 12 amino acid linear sequence. In proteins with multiple EGF modules, the O-glycosidic modifications have been found only within the N-terminal EGF module; beta-hydroxyaspartate/asparagine residues are not restricted in the same fashion. Little is known yet about the functions of, or possible relationships between, any of these modifications.

Amino Acid Sequence↗
PubMed1988

Modifications of guanine bases during oligonucleotide synthesis.

Guanine bases are sensitive to modification during automated DNA synthesis and processing reactions. Methods for the detection of two types of guanine modifications are described. The first method uses the higher reactivity of the modified G base to KMn04 oxidation than T bases, and thus allows detection by chemical DNA sequencing. The second method makes use of the Escherichia coli nucleotide excision repair enzyme UvrABC endonuclease which can detect "bulky" base modifications at each nucleotide in the synthetic DNA. Though the chemical structures of the two modifications are not known, they may be related. Both types of G modifications are often found in oligonucleotides synthesized by the methoxy-diisopropyl-phosphoramidite (MEDP) chemistry but non-detectable in the products of the beta-cyanoethyl-diisopropyl-phosphoramidite (CEDP) chemistry. The Rubin and Schmid pyrimidine-specific chemical DNA sequencing procedure (Rubin, C.M., and Schmid, C.W. (1980) Nucleic Acids Res. 8, 4613-4619) was found to be applicable to oligonucleotides synthesized by the CEDP chemistry, and to oligonucleotides synthesized by the MEDP chemistry if precautionary measures are taken to destroy the signals produced by the highly KMnO4 sensitive modified guanine bases. We also show how chemical DNA sequencing might be useful for diagnosing other chemical modifications in synthetic oligonucleotides.

Base Sequence↗
PubMed1990

Enzymatic recognition of DNA modifications induced by singlet oxygen and photosensitizers.

DNA modifications induced either by photosensitization (illumination in the presence of methylene blue) or by chemically generated singlet oxygen (thermal decomposition of an 1,4-etheno-2,3-benzodioxin) are recognized and incised by repair endonucleases present in crude bacterial cell extracts. Only a small fraction of the incised modifications are sites of base loss (AP-sites) sensitive to exonuclease III, endonuclease IV from E. coli or to the UV-endonuclease from M. luteus. Cell extracts from E. coli strains overproducing or defective in endonuclease III recognize the modifications induced by illumination in the presence of methylene blue just as well as do those from wild-type E. coli strains. This indicates that dihydropyrimidine derivatives, which are characteristic of hydroxyl radical-induced DNA modifications, are absent. In contrast, most of the modifications induced are not recognized by a cell extract from a fpg strain defective in formamidopyrimidine-DNA glycosylase FPG protein). Furthermore, incision by a cell extract from an E. coli strain overproducing FPG protein takes place at much lower protein concentration than with the wild-type strain. Experiments with purified FPG protein confirm that this enzyme is responsible for the recognition of singlet oxygen-induced DNA base modifications.

Coliphages↗
PubMed1996

Incidence of complete atrioventricular block following attempted radiofrequency catheter modification of the atrioventricular node in 880 patients. Results of the Multicenter European Radiofrequency Survey (MERFS) The Working Group on Arrhythmias of the European Society of Cardiology.

UNLABELLED: The Multicenter European Radiofrequency Survey (MERFS) retrospectively analysed the incidence of procedure-related complications in 4463 patients who had undergone radiofrequency catheter ablation in 69 European institutions between 1987 and 1992. Of these 4463 patients, 880 underwent modification of the atrioventricular node to cure atrioventricular nodal reentrant tachycardia. This report presents a detailed analysis of the incidence of complete atrioventricular block with respect to the target site and the number of patients reported per institution. The most common complication of modification of the atrioventricular node was the unintended induction of complete atrioventricular block (41 of 880 patients, 4.7%). In 684 of 880 patients (78%), detailed information about the approached target site for modification of the atrioventricular node was available. Complete atrioventricular block occurred significantly more often in patients who underwent ablation of the fast pathway (19/361, 5.3%) or in whom ablation of the slow and fast pathway was attempted after failure at the initial site (4/25, 16%) than in patients who underwent slow pathway ablation (6/298, 2.0%, P < 0.05). The overall incidence of complete atrioventricular block was significantly higher (6.3%) in centres with limited experience in radiofrequency modification of the atrioventricular node ( < or = 30 patients treated; group I: n = 526) compared to centres that had treated > 30 patients (group II: n = 354; 2.3%; P < 0.05). In addition, in those patients in whom the target site was available, the incidence of complete atrioventricular block after fast pathway ablation was significantly higher in group I (n = 168 patients) when compared to group II (n = 193 patients) (7.7% vs 3.1%, P < 0.05) and also tended to be higher after slow pathway ablation in group I (2.4% in group I vs 1.5% in group II; P = ns). CONCLUSIONS: In this analysis of collaborative data, radiofrequency catheter modification of the atrioventricular node carried a risk of approximately 5% of complete atrioventricular block. The incidence of complete atrioventricular block was significantly higher in patients who underwent fast pathway ablation or fast and slow pathway ablation after failure at the initial site compared with slow pathway ablation. In addition, the results indicate that there is a learning curve, regarding the incidence of complete atrioventricular block, which is a significant complication of the procedure, when modifying the atrioventricular node. Thus, caution is recommended when performing radiofrequency modification of the atrioventricular node using the so-called anterior approach to abolish fast pathway conduction, especially when the experience of the institution or investigator/s is limited.

Atrioventricular Node↗
PubMed1988

Chemical modification of tryptophanase by chloramine T: a possible involvement of the methionine residue in enzyme activity.

Tryptophanase purified from Escherichia coli B/1t7-A was irreversibly inactivated by chloramine T (sodium N-chloro-p-toluenesulfonamide). The mode of inactivation was rather complex and did not follow pseudo-first-order kinetics. The inactivation of the apoenzyme was much faster than that of the holoenzyme. The Km value for the synthetic substrate S-o-nitrophenyl-L-cysteine (SOPC) increased concomitantly with the modification. In contrast, the Km value for the coenzyme, pyridoxal 5'-phosphate (PLP), was not altered. L-Serine, another substrate, and L-alanine, a competitive inhibitor, protected the enzyme from inactivation. Determination of SH groups in the enzyme protein with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) showed that modification of two SH groups per enzyme subunit resulted in a complete inactivation. When the enzyme was subjected to chloramine T-modification following the SH group modification with DTNB, further inactivation was still observed, even after the addition of dithiothreitol. The SH-blocked enzyme preparation thus obtained, however, exhibited less pH dependency of inactivation by chloramine T than that of the native enzyme. The amino acid analysis of the chloramine T-modified enzyme showed that modification of four or five methionine residues among the 16 residues per subunit proceeded concomitantly with the complete inactivation. Modification of the enzyme with chloramine T quenched the absorption peak near 500 nm, characteristic of a quinoidal structure formed by labilization of the alpha-proton. These results suggest the possibility that chloramine T modifies not only the SH groups, but also methionine residues important for the catalytic activity of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1977

DTNB modification of SH groups of isocitrate dehydrogenase from Bacillus stearothermophilus purified by affinity chromatography.

A new method of affinity chromatography using blue dextran-Sepharose 4B resin was established to purify NADP+-dependent isocitrate dehydrogenase [EC 1.1.1.42] from Bacillus stearothermophilus in high yield. The purified preparation was found to be homogeneous on disc gel electrophoresis. The SH groups of the enzyme were modified with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) to determine the number of SH groups per molecule and their contribution to the enzyme activity. One SH group was titrated with DTNB per subunit (the native enzyme consisted of two subunits) and after complete denaturation with 4 M guanidine-HCl the number of titratable SH groups remained unchanged. ORD and CD measurements showed that the alpha-helical conformation of the polypeptide backbone was unaffected by DTNB modification, though the near ultraviolet CD spectrum was evidently altered. The fluorescence derived from tryptophanyl residue(s) was quenched by the modification to 30% of the native level, which may indicate the presence of SH in the vicinity of tryptophanyl residue(s). A remarkable decrease of the enzyme activity was detected upon modification with DTNB, but there was some discrepancy between the rate of inactivation and that of modification of SH groups. The presence of substrate and Mg2+ gave partial protection against modification of the SH groups by DTNB. Complete protection of the native enzyme activity against heating at 65 degrees was observed in the presence of substrate and Mg2+, but the thermostability of the enzyme was markedly reduced by modification of the SH groups.

Chromatography, Affinity↗
PubMed1979

Studies on regulatory functions of malic enzymes. IV. Effects of sulfhydryl group modification on the catalytic function of NAD-linked malic enzyme from Escherichia coli.

Reactions catalyzed by NAD-linked malic enzyme from Escherichia coli were investigated. In addition to L-malate oxidative decarboxylase activity (Activity 1) and oxaloacetate decarboxylase activity (Activity 2), the enzyme exhibited oxaloacetate reductase activity (Activity 3) and pyruvate reductase activity (Activity 4). Optimum pH's for Activities 3 and 4 were 4.0 and 5.0, and their specific activities were 1.7 and 0.07, respectively. Upon reaction with N-ethylmaleimide (NEM), Activity 1 decreased following pseudo-first order kinetics. Activity 2 decreased in parallel with Activity 1, while Activities 3 and 4 were about ten-fold enhanced by NEM modification. Modification of one or two sulfhydryl groups per enzyme subunit caused an alteration of the activities. Tartronate, a substrate analog, NAD+, and Mn2+ protected the enzyme against the modification. The Km values for the substrates and coenzymes were not significantly affected by NEM modification. Similarly, other sulfhydryl reagents such as p-hydroxymercuribenzoate (PMB), 5,5'-dithiobis(2-nitrobenzoate) (DTNB), and iodoacetate inhibited the decarboxylase activities and activated the reductase activities to various extents. Modification of the enzyme with PMB or DTNB was reversed by the addition of a sulfhydryl compound such as dithiothreitol or 2-mercaptoethanol. Based on the above results, the mechanism of the alteration of enzyme activities by sulfhydryl group modification is discussed.

Dithionitrobenzoic Acid↗
PubMed2006

Understanding estimation of time and age effect-modification of radiation-induced cancer risks among atomic-bomb survivors.

In radiation risk assessment based on follow-up data, estimation of the excess relative cancer rate involves evaluation of effect-modification by time-related factors such as age at exposure, time since exposure, and attained age. Because these variables are collinear, the regression coefficients purportedly measuring effect-modification of the radiation-related excess relative rate by time and age factors generally differ from the individual effects of these factors. For example, depending on whether it is an age-at-exposure/attained-age effect-modification model or an age-at-exposure/time-since-exposure model which is used, the regression coefficient for the effect of changes in age at exposure on the excess relative rate per Gray measures the combined effects of changes in both age at exposure and time since exposure, or of age at exposure and attained age, respectively, rather than the individual effect of changes in age at exposure, which is of interest for scientific purposes. Such insights should be integrated when reporting and interpreting estimates for time-related risk modification in cohort studies of radiation-exposed populations. Cancer incidence data for the Life Span Study of atomic-bomb survivors are used for illustration in parallel to theory. In summary, model coefficients for time-since-exposure, age-at-exposure, and attained-age effects on radiation-induced cancer risks among atomic-bomb survivors and in other cohort studies estimate combined effects (estimable combined effects are explicated). An appropriate unequivocal display of results for effect-modification is suggested. Goodness of fit appears unreliable for sorting out the most significant effect-modifiers. For example, a model including only one of the effect-modifiers may provide a fit similar to a model including the other two effect-modifiers, even when only the latter are actually related to effect-modification. Also, due to collinearity between these effect-modifier variables, all three models with two of the effect-modifiers necessarily show equivalent fits.

Age Factors↗
PubMed2007

Intraluminal pressure response in Baerveldt tube shunts: a comparison of modification techniques.

PURPOSE: To design an apparatus for in vitro quantification of effects of modifications to nonvalved tube shunts, and to compare the effects of these modifications done to prevent early postoperative hypotony. MATERIALS AND METHODS: A testing apparatus was designed and constructed to measure intraluminal pressure (ILP) during constant infusion of balanced salt solution at 2 microL/min through Baerveldt tube shunts mounted on cadaver eyes. Three different modifications were performed and 3 shunts were used for each modification. The modifications were partial tube occlusion with a 3-0 Supramid suture, tube perforation with a 27-gauge needle on an occluded tube, and a 1.2 mm longitudinal venting slit on an occluded tube. RESULTS: The final steady state ILP for the 3-0 Supramid partially occluded tube ranged between 1.6 and 2.8 mm Hg over 3 trials with an average final steady state ILP of 2.0 mm Hg. The 27-gauge needle perforation produced ILPs of 4.6 to 8.2 mm Hg over 3 trials with an average final steady state pressure of 5.9 mm Hg. The 1.2 mm longitudinal venting slit produced an ILP range of 12.6 to 17.3 mm Hg over 3 trials with an average final steady state ILP of 14.8 mm Hg. The differences in final steady state ILP between the 3 modification techniques were statistically significant (P=0.00036). CONCLUSIONS: The 3-0 Supramid occlusion and the 27-gauge perforation techniques produced hypotony, whereas the 1.2 mm longitudinal venting slit produced acceptable pressures in vitro.

Aqueous Humor↗