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Towards the human cancer epigenome: a first draft of histone modifications.

The disruption of genomic DNA methylation patterns was the first epigenetic abnormality to be described in human cancer. This imbalance involves the promoter CpG island hypermethylation of tumor-suppressor genes, causing transcriptional repression, and global genomic hypomethylation, leading to chromosomal instability and reactivation of endoparasitic sequences. The relationship between DNA methylation and histone modifications was initially described in the context of the inactivation of female X chromosomes and of the demonstration of strong interactions between the DNA methylation machinery and chromatin modifiers. The repression of tumor-suppressor genes by promoter hypermethylation was also found to be associated with a specific histone modification index. However, this jigsaw was missing a piece: a global view of how the histone modification landscape was distorted in cancer cells. We have recently discovered this piece of the puzzle, demonstrating that the association between DNA methylation and histone modification aberrations in cancer also occurs at the global level. In human and mouse tumors, histone H4 undergoes a loss of monoacetylated and trimethylated lysines 16 and 20, respectively. Most importantly, these alterations occur within the context of the repetitive DNA sequences that also become hypomethylated in transformed cells. The global alterations of histone acetylation status suggest novel pathways by which histone acetyltransferases (HATs), histone methyltransferases (HMTs), and histone deacetylases (HDACs) may play roles as tumor-suppressor genes or oncogenes. In this regard, we have shown how the generation of particular fusion proteins involving HATs in leukemias is associated with an erasure of the monoacetylated lysine 16-H4 marker, whilst the loss of trimethylation at lysine 20-H4 disrupts heterochromatic domains and may reduce the response to DNA damage of cancer cells.

Acetylation↗

Community participation in malaria surveillance and treatment. III. An evaluation of modifications in the Volunteer Collaborator Network of Guatemala.

In most rural areas of Latin America, malaria surveillance and treatment is carried out by a network of unpaid village malaria workers, known as Volunteer Collaborators, who are trained and supervised by the National Malaria Service. To identify ways in which the performance of these volunteer workers could be improved and to test changes that would make the Volunteer Collaborator Networks (VCNs) a more attractive model for community participation in malaria case detection and treatment in other regions, we tested a series of modifications in the VCN of Guatemala. These modifications included improved methods for selecting, supervising, and evaluating the volunteer workers and for collecting blood smears and reporting results, and the use of volunteer workers, known as Volunteer Medicators, who administered presumptive antimalarial therapy without taking a blood smear. A cost-effectiveness analysis of the modified VCN was also carried out. Two years after the modifications were introduced, Volunteer Collaborators identified nearly twice as high a percentage (33% versus 17%) of patients with suspected malaria in their villages. Delays in examining blood smears were reduced from 23 days to 11 days and delays from blood smear examination to curative treatment were reduced from 21 days to 7 days. The Volunteer Medicators identified and treated only a slightly higher percentage of patients than the Volunteer Collaborators (36% versus 33%). However, the cost of maintaining a network of Volunteer Medicators ($0.61 per patient treated) was much lower than the traditional VCN ($2.45) or the modified VCN ($1.85). Thus, with a few, simple and relatively inexpensive modifications, the efficiency and cost-effectiveness of Volunteer Collaborators can be markedly improved. Additionally, the VCN can be modified to make it a more suitable model for community-based malaria control and surveillance networks in other malarious areas of the world, which differ in terms of their level of endemicity, the goals of the malaria program, or the available health care infrastructure.

Community Health Workers↗

Efficacy of amitriptyline as a pharmacological adjunct to behavioral modification in the management of aggressive behaviors in dogs.

The efficacy of amitriptyline as a pharmacological adjunct to behavioral modification in the clinical management of aggressive behaviors in dogs was evaluated in two phases. Twelve dogs presenting for aggressive behaviors were treated sequentially with amitriptyline (2 mg/kg body weight, per os [PO] bid) and a placebo for 4 weeks in a prospective, randomized, double-blind, placebo-controlled trial. Standardized protocols for behavior modification were implemented throughout the trial. Owners maintained behavioral records and reported on the number of aggressive incidents as well as the dog's overall improvement at the end of each 4-week period. In the second phase, 27 cases of dogs presenting for aggressive behaviors and treated with amitriptyline were reviewed, and clients were contacted to record each dog's response to treatment. Reports were compared to those for dogs receiving behavior modification alone (i.e., placebo phase of prospective study). No significant difference was observed in the patients' responses to adjunctive amitriptyline versus behavior modification alone.

Aggression↗

Lifestyle modifications to prevent and control hypertension. 1. Methods and an overview of the Canadian recommendations. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada.

OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals on lifestyle changes to prevent and control hypertension in otherwise healthy adults (except pregnant women). OPTIONS: For people at risk for hypertension, there are a number of lifestyle options that may avert the condition--maintaining a healthy body weight, moderating consumption of alcohol, exercising, reducing sodium intake, altering intake of calcium, magnesium and potassium, and reducing stress. Following these options will maintain or reduce the risk of hypertension. For people who already have hypertension, the options for controlling the condition are lifestyle modification, antihypertensive medications or a combination of these options; with no treatment, these people remain at risk for the complications of hypertension. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period January 1996 to September 1996 for each of the interventions studied. Reference lists were scanned, experts were polled, and the personal files of the authors were used to identify other studies. All relevant articles were reviewed, classified according to study design and graded according to level of evidence. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: Lifestyle modification by means of weight loss (or maintenance of healthy body weight), regular exercise and low alcohol consumption will reduce the blood pressure of appropriately selected normotensive and hypertensive people. Sodium restriction and stress management will reduce the blood pressure of appropriately selected hypertensive patients. The side effects of these therapies are few, and the indirect benefits are well known. There are certainly costs associated with lifestyle modification, but they were not measured in the studies reviewed. Supplementing the diet with potassium, calcium and magnesium has not been associated with a clinically important reduction in blood pressure in people consuming a healthy diet. RECOMMENDATIONS: (1) It is recommended that health care professionals determine the body mass index (weight in kilograms/[height in metres]2) and alcohol consumption of all adult patients and assess sodium consumption and stress levels in all hypertensive patients. (2) To reduce blood pressure in the population at large, it is recommended that Canadians attain and maintain a healthy body mass index. For those who choose to drink alcohol intake should be limited to 2 or fewer standard drinks per day (maximum of 14/week for men and 9/week for women). Adults should exercise regularly. (3) To reduce blood pressure in hypertensive patients, individualized therapy is recommended. This therapy should emphasize weight loss for overweight patients, abstinence from or moderation in alcohol intake, regular exercise, restriction of sodium intake and, in appropriate circumstances, individualized cognitive behaviour modification to reduce the negative effects of stress. VALIDATION: The recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth international Conference on Preventive Cardiology. They are similar to those of the World Hypertension League and the Joint National committee, with the exception of the recommendations on stress management, which are based on new information. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at health Canada, and the Heart and Stroke Foundation of Canada.

Adult↗

[Interactions of derivatives of short oligonucleotides with nucleic acids. VII. Effect of conformation changes in the duplex structure on on the specificity and efficacy of modification of target DNA by alkylating oligonucleotide derivatives].

The modification of a target DNA by alkylating oligonucleotide derivatives possessing various capacities for complex formation was studied. The binding properties of oligonucleotides were changed either by increasing their length (tetra-, octa-, and dodecamers) or by introducing a point substitution and/or an N-(2-hydroxyethylphenazinium) residue. It was found that conformational changes occurring in the structure of the target.reagent complex upon elevating the reaction temperature affect the efficiency and site-specificity of the alkylation. In the case of complete saturation of the target with the reagent, an increase in the hybridization ability of the reagent reduced the efficiency of the target modification. It was found that the modification by the tetranucleotide reagent (in the presence of an effector adjacent to the 3' end) occurs exclusively at an intracomplex target base. In the case of the dodecamer, which forms a stable, highly cooperative complex with the target, several bases of the target undergo alkylation, and an increase in temperature changes the site-specificity of alkylation. In this process, the redistribution of the target modification sites toward stronger nucleophilic centers enhances alkylation at temperatures near the melting temperature of the target.dodecanucleotide complex despite a decrease in the extent of target association.

Alkylation↗

Modifications to standard guidelines and changes in blood pressure readings: use of an automatic blood pressure device.

The purpose of the study was to determine what effect modifications to American Heart Association (AHA) guidelines produce when taking blood pressures with an automatic device. Eight blood pressure measurements were taken at least 2 minutes apart; two with standard AHA guidelines and six with modifications. Findings of this study suggest that elevation of the arm can have a significant effect on both the systolic and diastolic blood pressure. Two modifications, talking and placing the arm beside the trunk, raised the diastolic pressure. However, some modifications did not have a statistically significant effect. Techniques used to take blood pressures with an automatic device can have a significant effect on the readings.

Adult↗

Technique of Hautmann ileal neobladder with chimney modification: interim results in 50 patients.

PURPOSE: We report our 4-year experience with the chimney modification of the Hautmann ileal neobladder. This modification involves use of an 8 to 12 cm. tubularized isoperistaltic ileal chimney for the ureterointestinal anastomosis. MATERIALS AND METHODS: Between April 1995 and March 1998, 50 men and women with invasive bladder cancer underwent radical cystectomy and creation of a Hautmann neobladder with chimney modification. Complications were assessed, divided as early and late, and subdivided as those related or unrelated to the neobladder. Continence was evaluated using a detailed patient questionnaire. RESULTS: There were no intraoperative deaths. Early complications in 11 of the 50 patients were neobladder related in 5 (10%) and unrelated to the neobladder in 6 (12%). The early reoperation rate was 6%. Late postoperative complications in 10 patients (20%) were neobladder related in 8 (16%) and unrelated to the neobladder in 2 (4%). After 1 year 93% and 86% of patients achieved good day and nighttime continence, respectively. In 2 patients (4%) clean intermittent catheterization is performed and 1 required placement of an artificial urinary sphincter. Ureterointestinal anastomotic strictures were detected in 6 of 100 ureteral units (6%), including 2 with failed initial endoscopic management. Open surgical revision of the ureterointestinal anastomotic site was easier due to the anterior position of the ureters, and identification and mobilization of the isoperistaltic limb. CONCLUSIONS: Our experience with the chimney modification of the Hautmann neobladder compares favorably to other forms of orthotopic urinary diversion in regard to ureteral stenosis, early and late postoperative complications, urinary continence and simplification of the ureterointestinal anastomosis.

Adult↗

Vitamin C protects against and reverses specific hypochlorous acid- and chloramine-dependent modifications of low-density lipoprotein.

Activated phagocytes produce the highly reactive oxidant hypochlorous acid (HOCl) via the myeloperoxidase-catalysed reaction of hydrogen peroxide with chloride ions. HOCl reacts readily with a number of susceptible targets on apolipoprotein B-100 of low-density lipoprotein (LDL), resulting in uncontrolled uptake of HOCl-modified LDL by macrophages. We have investigated the effects of vitamin C (ascorbate), an effective water-soluble antioxidant, on the HOCl- and chloramine-dependent modification of LDL. Co-incubation of vitamin C (25-200 microM) with LDL resulted in concentration-dependent protection against HOCl (25-200 microM)-mediated oxidation of tryptophan and lysine residues, formation of chloramines and increases in the relative electrophoretic mobility of LDL. Vitamin C also partially protected against oxidation of cysteine residues by HOCl, and fully protected against oxidation of these residues by the low-molecular-mass chloramines, N(alpha)-acetyl-lysine chloramine and taurine chloramine, and to a lesser extent monochloramine (each at 25-200 microM). Further, we found that HOCl (25-200 microM)-dependent formation of chloramines on apolipoprotein B-100 was fully reversed by 200 microM vitamin C; however, the loss of lysine residues and increase in relative electrophoretic mobility of LDL were only partially reversed, and the loss of tryptophan and cysteine residues was not reversed. Time-course experiments showed that the reversal by vitamin C of HOCl-dependent modifications became less efficient as the LDL was incubated for up to 4 h at 37 degrees C. These data show that vitamin C not only protects against, but also reverses, specific HOCl- and chloramine-dependent modifications of LDL. As HOCl-mediated LDL modifications have been strongly implicated in the pathogenesis of atherosclerosis, our data indicate that vitamin C could contribute to the anti-atherogenic defence against HOCl.

Ascorbic Acid↗

Modifications of alpha-tocopherol and fatty acid concentrations in blood and adipose tissue of obese patients during a weight loss programme.

BACKGROUND AND AIM: The aim of the study was to describe qualitative and/or quantitative modifications of lipoproteins, including their fatty acid composition, in obese patients during a hypocaloric diet, and determine whether the variations observed paralleled modifications of alpha-tocopherol concentration in adipose tissue and blood. METHODS AND RESULTS: 15 healthy, obese volunteers (5 males, 10 females; age: 32-69 yr; BMI: 28.4-60.5 kg/m2) were given a 3-week hypocaloric diet (3.9 MJ (941 kcal)). Adipose tissue and blood samples were taken at the beginning and at the end of this period. At baseline and after 3 weeks measurements were made for alpha-tocopherol and fatty acids in total serum, lipoproteins and adipose tissue; thiobarbituric acid-reactive substances (TBARS) in serum. A significant drop in cholesterol-rich particles (LDL and HDL) was observed, in parallel to a significant enrichment of n-6 polyunsaturated fatty acids (PUFA) at the expense of both saturated and monounsaturated fatty acids in serum. A drop in alpha-tocopherol concentration (expressed as mumol alpha-tocopherol/g lipid) in serum and lipoprotein fractions paralleled the decrease in cholesterol-rich lipoproteins. CONCLUSIONS: Our results suggest that a hypocaloric diet not only decreases cholesterol-rich particle levels in serum, but also leads to a significant modification of fatty acid composition which may reflect improvement of insulin sensitivity. We did not observe any modification in adipose tissue after diet with regard to both alpha-tocopherol and fatty acid concentrations. Despite a drop in alpha-tocopherol concentration and an increase in n-6 PUFA content in serum, we did not find any enhancement of serum lipid peroxidation level evaluated by the thiobarbituric acid-reactive substance (TBARS) assay. If we assume that dietary intakes of alpha-tocopherol were not modified during this diet, it can be supposed that adipose tissue released alpha-tocopherol without any specific regulation, in parallel to the release of fatty acids.

Adipose Tissue↗

[Oxidative modification of blood proteins in patients with psychiatric disorders (depression, depersonalization)].

We determined the oxidative modification of proteins (spontaneous and metal-catalysing oxidation, MKO) and the level of corticosteroids in patients with the depersonalization and depression. For detecting oxidative modification of plasma proteins we measured the concentration of protein carbonyl groups formed with 2,4dinitrophenylhydrazine 2,4dinitrophenylhydrazone derivatives; the formation of dityrosine by fluorescence method; protein aggregation and fragmentation. Polyacrylamide gel electrophoresis with sodium dodecyl sulfate (SDS)-PAGE in the presence beta-mercaptoethanol was used to determine the aggregation or fragmentation of proteins by oxygen radicals (OH). Acid-soluble peptides were analised as products of the fragmentation oxidative modification proteins. The level of the corticosteroids was determined using HPLS. The increase of the concentration of protein carbonyl groups in blood plasma of patients with mental disorders. In patients with depersonalization we determined the increase of the bityrosyl cross-link, and different degrees of fragmentation compared with depressive patients. The cortisol level was decreased and corticosterone was increased in the blood plasma of patients with depersonalization. In depressive patients the cortisol level was increased and corticosterone was decreased is discussed. We discussed the role oxidative modification proteins in the disturbance of the corticosteroid and opioid receptors functions in the patients with mental disorders.

Adult↗

[The aging lung: structural and functional modifications related to aging].

Ageing is accompanied by numerous structural and functionnel pulmonary modifications. Structural modifications concern the thoracic well- and the broncho-pulmonary system. Functionnel modifications are numerous and concern specially respiratory changes, pulmonary circulation, adaptation to exercise, biochemical system and pulmonary defences. The knowledge of these modification allows better care of the aged affected by respiratory diseases.

Age Factors↗

A modification to the Activated Sludge Model No. 2 based on the competition between phosphorus-accumulating organisms and glycogen-accumulating organisms.

A modification to the ASM2 is proposed which permits representation of the competition between phosphorus accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs) in a nutrient removal activated sludge system. Some important aspects, which are not considered in ASM2, are discussed. The proposed modification includes denitrification by PAOs, PAO glycogen storage capability and GAO metabolism model. It is shown that the proposed modification is capable of describing pilot plant data using a single set of stoichiometric and kinetic parameters over three different sludge ages (16, 14 and 12 days). The modified ASM2 may be applicable to a wide range of situations where PAOs and GAOs can compete. This modification may well provide a better understanding about GAO behaviour.

Aerobiosis↗

[Enhancement of antigen presenting function of dendritic cells by IL-2 gene modification and its mechanism].

OBJECTIVE: To investigate the effects of IL-2 gene modification enhancement of the antigen-presenting function of the mouse bone marrow derived dendritic cells and on the activation of CTL induced by MHC class I molecule restricted antigen peptides as well as the related immunological mechanisms. METHODS: DCs were prepared from mouse bone marrow and modified by recombinant IL-2 adenovirus (DC-IL-2). The IL-12 and IFN-gamma levels in culture supernatant of DC and CTL were examined by ELISA, the expression of costimulatory molecules and fluorescent intensity of endocytosis of OVA-FITC in DC by FACS, the capacity of presenting 3LL cell tumor antigen by (3)H-TdR incorporation method, the MHC class I-restricted tumor-antigen-peptide Mut1 of 3LL cells pulsed DC-IL-2 to induce CTL cytotoxicity by (51)Cr 4-hr releasing assay. RESULTS: After IL-2 gene modification, DC-IL-2 could produce high level of IL-12 [(78.4 +/- 6.6) pg.(1 x 10(6) cells)(-1).ml(-1)]. The expression of costimulatory molecules on DC-IL-2 was increased, the fluorescent intensity of DC captured OVA-FITC was enhanced, and the proliferation of allo-T cells from 3LL bearing mouse pulsed with Mut1 was also enhanced. Mut1 antigen peptide pulsed DC-IL-2 could induce more potent antigen-specific CTL cytotoxicity and excrete high concentration of IFN-gamma [(1 168 +/- 58.4) pg/ml] in vivo. CONCLUSION: IL-2 gene modification of DC can activate second signal for DC presenting antigen, and enhance the function for capturing and presenting tumor antigen. DC-IL-2 pulsed with MHC class I restricted tumor-antigen-peptide can induce specific anti-tumor immune response more effectively. Owing to IL-2 gene modification, the functions of IL-12 excretion and T cell activation of DC were promoted, so that the capacity of CTL excreting IFN-gamma was enhanced, which are relevant to the immune mechanism.

Adenoviridae↗

Oxidative Modification of Very Low Density Lipoprotein by Arterial Wall Cells.

Modification of VLDL by arterial wall cells was observed. After incubating VLDL (200 &mgr;g protein/ml) with bovine aortic endothelial cells (EC), rabbit aortic smooth muscle cells (SMC) or mouse peritoneal macrophages (Mpsi)for 24 hours, the TBARS in VLDL increased strikingly to 7.80+/-O.75, 1O.6+/-O.90 and 11.4+/-O.70 nmol/mg-protein respectively, much higher than those of their controls (5.1O+/-0.60, 7.20+/-0.89, 5.30+/-O.54 nmol/mg-protein). The cell-modified VLDL migrated faster than the controls on agarose electrophoregram and the SDS-PAGE of the apolipoproteins showed that apo B(100) of VLDL was degraded to fragments without distinct bands, while apo E was essentially kept intact. Phosphatidylcholine was hydrolyzed to lysophosphatidylcholine during the modification process. These changes were inhibited by BHT, indicating that the modification of VLDL was an oxidative process. The result suggests that since VLDL could be oxidatively modified by arterial wall cells including EC, SMC, Mpsi in vitro, suggesting the oxidative modification of VLDL may occur in vivo and play an important role in atherogenesis.

Journal Article↗

Inhibitors of post-translational modifications of G-proteins as probes to study the pancreatic beta cell function: potential therapeutic implications.

It is well established that glucose-induced insulin secretion involves generation of intracellular second messengers. Using specific inhibitors of guanosine triphosphate [GTP] biosynthesis [e.g., mycophenolic acid; MPA], we have identified a permissive role for GTP in glucose-stimulated insulin secretion. While the exact site of action for GTP within the islet beta cell remains to be identified and defined, recent evidence from several laboratories, including our own, indicate that it could involve activation of GTP-binding proteins [G-proteins]. These studies have identified both trimeric and monomeric forms of G-proteins within the pancreatic beta cell. Recent data also indicate that these G-proteins, specifically the monomeric G-proteins and the gamma subunits of trimeric G-proteins undergo a series of posttranslational modifications at their C-terminal cysteine. Such modifications include, isoprenylation, carboxyl methylation and palmitoylation. These modification steps appear to be essential for translocation of these proteins to the membrane sites for interaction with their respective effector proteins. This review primarily focuses on recent findings that clearly support the viewpoint that these posttranslational modification steps not only play obligatory roles in fuel-induced insulin secretion, but also in cytokine-mediated apoptotic demise of the beta cell. In this review, we also attempted to describe those findings involving the use of specific inhibitors for each of these pathways, and it is our hope that these aspects of beta cell metabolism and function generate interest in development of therapeutic intervention modalities to states of perturbed insulin release.

Apoptosis↗

Accidental germ-line modifications through somatic cell gene therapies: some ethical considerations.

Proposed somatic cell gene-therapies (especially those involving in utero therapies) may involve a small risk of germ-line modifications; this risk has engendered serious concern, and arguments have been made that such therapies ought not be pursued if such risks exists. We argue here that while pursuing deliberate germ-line modifications in humans would be inappropriate given the current state of the art, the risk of accidental germ-line modifications from most currently proposed in utero gene therapy is no different in kind or degree from other risks regularly taken in medical procedures. Given the possible benefits of such therapies, we argue that the risk of accidental germ-line modifications is well worth taking in these cases.

Genetic Engineering↗

The effect of histidine modification on the activity of myo-inositol monophosphatase from bovine brain.

The pH dependence of myo-inositol monophosphatase may indicate a role for histidine residues in the catalytic mechanism (Ganzhorn, A. J., and Chanal, M.-C. (1990) Biochemistry 29, 6065-6071). This possibility was investigated by chemical modification. At pH 6.0 and 25 degrees C, the enzyme was inactivated by diethylpyrocarbonate in a pseudo-first order reaction with a bimolecular rate constant of 0.37 M-1 s-1. Two histidines were modified rapidly with no effect on enzyme activity, while 3 residues were modified at a slower rate corresponding to the rate of inactivation. No noticeable changes in the secondary structure of the enzyme were observed by comparison of circular dichroic spectra before and after modification. Treatment of myo-inositol monophosphatase with diethylpyrocarbonate in the presence of inositol 1-phosphate, Mg2+, and Li+ protected 2 residues from modification and decreased the inactivation rate by about 5-fold. Spectrophotometric analysis, the restoration of enzyme activity by hydroxylamine, and the lack of any inhibitory effect with alkylating agents suggest that inactivation is due solely to modification of histidine. We conclude that a histidine residue is essential for activity and may act as a base catalyst during hydrolysis of the substrate.

Animals↗

[Preliminary study on conversion of RhD positive red blood cells to RhD negative by modification with methoxy polyethylene glycol].

Rh is a very important blood group like ABO blood system in transfusion medicine. It causes severe transfusion reaction and hemolytic disease of the newborn (HDN) if RhD blood group does not match between the donor and the recipient. The population of RhD negative is only about 0.2% - 0.5% in Chinese. Conversion of RhD positive RBCs to RhD negative is very important in clinical transfusion. This study was to try to modify RhD antigen located on the surface of A, B, O and AB red blood cells in order to convert RhD positive to RhD negative by the modification of four kinds of methoxypolyethylene glycol (mPEG) derivatives and to observe the effect of mPEG modification on cell morphology, structure and function. The result demonstrated that modification efficiency of mPEG-BTC (mPEG-benzotriazole carbonate) was better than other three kinds of mPEG derivatives. It could camouflage RhD antigen efficiently when the concentration reached to 1 mmol/L. The result also showed that there were no harmful effects of mPEG modification on cell morphology, osmotic fragility, hemolysis, AchE, cholesterol, ATP, 2,3-DPG and deformability. It is suggested that success in converting RhD positive RBCs to RhD negative was preliminarily achieved.

Erythrocytes↗