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Modified heparin inhibits P-selectin-mediated cell adhesion of human colon carcinoma cells to immobilized platelets under dynamic flow conditions.

Accumulating evidence indicates that the formation of tumor cell platelet emboli complexes in the blood stream is a very important step during metastases and that the anti-metastasis effects of heparin are partially due to a blockade of P-selectin on platelets. In this study, heparin and chemically modified heparins were tested as inhibitors of three human colon carcinoma cell lines (COLO320, LS174T, and CW-2) binding to P-selectin, adhering to CHO cells expressing a transfected human P-selectin cDNA, and adhering to surface-anchored platelets expressing P-selectin under static and flow conditions. The aim was to screen for heparin derivatives with high anti-adhesion activity but negligible anticoagulant activity. In this study, four modified heparins with high anti-adhesion activity were identified including RO-heparin, CR-heparin, 2/3ODS-heparin, and N/2/3DS-heparin. NMR analysis proved the reliability of structure of the four modified heparins. Our findings suggested that the 6-O-sulfate group of glucosamine units in heparin is critical for the inhibition of P-selectin-mediated tumor cell adhesion. Heparan sulfate-like proteoglycans on these tumor cell surfaces are implicated in adhesion of the tumor cells to P-selectin. Some chemically modified heparins with low anticoagulant activities, such as 2/3ODS-heparin, may have potential value as therapeutic agents that block P-selectin-mediated cell adhesion and prevent tumor metastasis.

Animals↗

Traditional v. modified dietary patterns and their influence on adolescents' nutritional profile.

Korea has experienced exceptionally rapid economic developments. Even though the country has managed to maintain aspects of its traditional diet, dietary habits are changing, especially among adolescents. This study was carried out to identify prevailing dietary patterns among Korean adolescents and to compare the nutrient intakes and dietary behaviours between the patterns. A 3 d diet record, collected from 671 Korean adolescents aged 12-14 years in Seoul, Korea, was assessed. By cluster analysis, subjects were classified into a modified (69.9 %) and a traditional (30.1 %) dietary pattern group. The modified group consumed more bread, noodles, cookies and pizza/hamburgers compared with the traditional group, which consumed mainly rice and kimchi (fermented cabbage). The modified group had significantly higher intakes of all nutrients. It had a higher total daily energy intake (7719 kJ), a higher daily energy intake from fat (29.8 %) and a higher cholesterol intake (326 mg/d), compared with the traditional group (6686 kJ, 24.8 % and 244 mg/d, respectively). The modified group was more likely to consume fast foods, fried foods and carbonated beverages even though they consumed more fresh fruits and milk, while the traditional group was more likely to have a rice-based diet and not to skip breakfast. These results suggest that monitoring dietary behaviours of adolescents, especially in a society experiencing a nutrition transition, is necessary in order to identify both negative and positive changes in respect of risk factors for nutrition-related chronic diseases as well as for undernutrition.

Adolescent↗

Reliability and validity of a modified gait scoring system and its use in assessing tibial dyschondroplasia in broilers.

1. The gait scoring system for broilers developed by Kestin et al. (Veterinary Record, 131: 190-194, 1992) has been widely used to evaluate leg problems. The many factors and measures associated with this scale have empirically established its external (biological) validity. However, published test-retest (within-observer) reliabilities are poor, and inter-observer reliabilities are unknown. We evaluated several modifications to this scale aimed at improving its objectivity and reliability. 2. Eighteen naïve observers scored a standardised video of birds exhibiting varying degrees of lameness, either using Kestin et al.'s system, or our modified system. 3. Test-retest reliability (0.906) for Kestin et al.'s system was higher than previously reported. Inter-rater reliability was also good (0.892). The modified system offered significantly better test-retest (0.948) and inter-rater reliabilities (0.943), without incurring costs in terms of time taken or difficulty of use. The systems were consistent, assigning individual birds the same score on average. 4. It is concluded that the modified system offers the advantages of reduced error within and between studies. 5. In a second experiment, we used our modified scoring system to examine the relationship between tibial dyschondroplasia (TD) and gait score in 267 selected broilers. 6. Neither the presence nor severity of TD affected gait score, suggesting that, at least in this strain of broilers, other leg problems like slipped tendons or torsional deformities had more influence on gait impairment than did TD.

Animals↗

Are modified procedures significantly better than conventional procedures in percutaneous transhepatic treatment for complicated right hepatolithiasis with intrahepatic biliary strictures?

BACKGROUND: Conventional percutaneous procedures for treating patients with recurrent hepatolithiasis associated with complicated intrahepatic biliary strictures require multiple dilation sessions before stone extraction. We modified the approach, reducing the number of dilation sessions required and using newer lithotripsy and irrigation methods. We suggest that the modified procedures are superior to conventional management and demonstrate their utility in clearing hepatolithiasis. METHODS: Percutaneous transhepatic stricture dilation and cholangioscopic lithotripsy were performed to treat patients with right recurrent hepatolithiasis with complicated intrahepatic biliary strictures. Conventional methods were used in 40 patients (Group A). Modified methods, including simplification of tract establishment and stricture dilation and electrohydraulic lithotripsy (EHL) were used in 60 patients (Group B). RESULTS: Group B patients had fewer complications (massive hemobilia: 0% versus 15%, P = 0.0032, cholangitis: 0% versus 17.5%, P=0.0012), tolerated the procedures better (intolerable pain: 0% versus 12.5%, P=0.0087), had a higher rate of success (residual stones: 3.3% versus 20%, P=0.0132; remaining asymptomatic and stone-free: 81% versus 50%, P = 0.0021), a shorter hospital stay (17.8 +/- 4.4 days versus 36.2 +/- 5.5 days, P < 0.001) and lower overall expense (USD 2689 versus USD 3848) than Group A patients. CONCLUSION: We believe that the modified methods are superior to conventional treatment in that they effectively decrease procedural complications and cost, and significantly improve treatment results.

Adult↗

Loupe-assisted modified one-layer vasovasostomy.

Several studies indicate that microsurgical modified one-layer vasovasostomy is comparable to the two-layer anastomosis with respect to patency and pregnancy rates. The objective of this study was to determine the feasibility and result of modified one-layer vasovasostomy under loupe magnification only. Thirty-two patients aged 28 to 64 years (mean 41.3 +/- 6 years) underwent vasovasostomy at CGMH from July 1997 to June 2002, with all operations being a modified on-layer anastomosis created with the aid of a 3 x loupe. The estimated duration of vasectomy ranged from 4 months to 27 years, with a mean of 9.2 +/- 4.8 years. Postoperative semen analysis and pregnancy were examined. Each patient was followed up at 1,4, and 12 weeks postoperatively. The total operation time ranged from 118 to 228 minutes (average 150 +/- 35 minutes). There was no operation-related complication such as hematoma or wound infection. The patency rate was 89% (25/28), and the pregnancy rate at 2 years or more of follow-up was 39% (11/28). The patency and pregnancy rates were similar to those obtained in most studies of microsurgical vasovasostomy. For uncomplicated vasectomy reversal, this simple loupe-assisted modified one-lyer vasovasostomy seems to provide an adequate anastomosis.

Adult↗

Comparison of standard eyelid margin closure using silk with a modified repair using 7/0 vicryl and a buried knot.

AIMS: To assess the efficacy and complications of eyelid margin closure with 7/0 Vicryl or Vicryl Rapide suture with a buried knot at the grey line and to compare this with standard closure using silk with an external knot. METHODS: Analysis of a prospective, non-comparative, interventional case series using 7/0 Vicryl or Vicryl Rapide with a buried grey-line knot (modified lid margin closure). Detailed assessment during the healing period was directed to (1) the lid margin profile, (2) the grey line suture and (3) the tissue reaction. Patients were seen for assessment within two days following surgery, at 14 days and at two months. A retrospective, comparative series of silk with an external knot (standard lid margin closure) and 7/0 Vicryl or Vicryl Rapide (modified lid margin closure) was also studied. An analysis was made of the hospital records of patients who had undergone direct lid margin closure with 7/0 Vicryl, Vicryl Rapide or silk. Short- and long-term complications were noted. RESULTS: The prospective series included 24 patients whose lid margin closure had been performed with the modified technique with 7/0 Vicryl or 7/0 Vicryl Rapide. All lids healed well and there was no difference between these two sutures. The retrospective series included 123 patients. Seventy-one patients had the modified technique using 7/0 Vicryl or Vicryl Rapide. Fifty-two patients had lid margin closure with the standard technique using 6/0 silk. All lids healed well. In summary, in both the prospective and retrospective groups, no significant complications were encountered and the healing was excellent. CONCLUSIONS: 7/0 Vicryl and Vicryl Rapide with a buried knot at the grey line allows excellent lid margin healing comparable with standard closure using silk. Vicryl sutures do not need to be removed.

Adult↗

Effects of modified-implement training on fast bowling in cricket.

The effects of training with overweight and underweight cricket balls on fast-bowling speed and accuracy were investigated in senior club cricket bowlers randomly assigned to either a traditional (n = 9) or modified-implement training (n = 7) group. Both groups performed bowling training three times a week for 10 weeks. The traditional training group bowled only regulation cricket balls (156 g), whereas the modified-implement training group bowled a combination of overweight (161-181 g), underweight (151-131 g) and regulation cricket balls. A radar gun measured the speed of 18 consecutive deliveries for each bowler before, during and after the training period. Video recordings of the deliveries were also analysed to determine bowling accuracy in terms of first-bounce distance from the stumps. Bowling speed, which was initially 108 +/- 5 km h(-1) (mean +/- standard deviation), increased in the modified-implement training group by 4.0 km x h(-1) and in the traditional training group by 1.3 km x h(-1) (difference, 2.7 km x h(-1); 90% confidence limits, 1.2 to 4.2 km x h(-1)). For a minimum worthwhile change of 5 km x h(-1), the chances that the true effect on bowling speed was practically beneficial/trivial/harmful were 1.0/99/< 0.1%. For bowling accuracy, the chances were 1/48/51%. This modified-implement training programme is not a useful training strategy for club cricketers.

Adult↗

Treatment for MICAs: design and implementation of the modified TC.

This article describes the main features of an innovative therapeutic community (TC) model adapted for use with mentally ill chemical abusers (MICAs). It describes the rationale for use of the modified TC with MICAs, the treatment structure and environment created, the essential components of the modified TC program, staffing, and the process and goals of client change. Details are given regarding issues and strategies for the implementation of the new program in terms of program planning, staff training, and system initiation. Evaluation data from the authors' research is summarized to support the adoption of the modified TC model. The article makes clear the feasibility of a modified TC model of established effectiveness with a MICA population. This model has now been successfully introduced into mental health, drug treatment, shelter, and correctional settings.

Aftercare↗

Minor-groove binding models for acetylaminofluorene modified DNA.

Minimized potential energy calculations have been employed to locate and evaluate energetically a number of different models for DNA modified at carbon-8 of guanine by acetylaminofluorene (AAF). Three different duplex nonamer sequences were investigated. In addition to syn guanine models which have some denaturation and a Z-DNA model, we have found two new types of structures in which guanine remains syn and the AAF is placed in the minor groove of a B-DNA helix. One type features Hoogsteen base pairing between the modified guanine and protonated cytosine, with a sharply bent helix. The other (here termed the "wedge" model because the aromatic amine is wedged into the minor groove) maintains a single hydrogen bond between O6 of the modified guanine and N3 of protonated cytosine, with much less deformation of the helix, and close Van der Waals contacts between the AAF and the walls of the minor groove. Both types of structures (as well as the related forms produced by deprotonation of cytosine) are energetically important in all three sequences examined. The wedge-type model, which is most favored except in alternating G-C sequences, has been previously observed in a combined NMR and computational characterization of an aminofluorene (AF) modified guanine opposite adenine in a DNA duplex undecamer (D. Norman, P. Abuaf, B.E. Hingerty, D. Live, D. Grunberger, S. Broyde and D.J. Patel, Biochemistry 28, 7462 (1989)).

2-Acetylaminofluorene↗

Molecular dynamics and free energy calculations of the B and Z forms of C8-arylguanine modified oligonucleotides.

Arylhydrazines found in the mushroom Agaricus bisporus have been shown to be carcinogenic. Upon metabolic activation, arylhydrazines are transformed into aryl radicals, forming 8-arylpurines, which may play a role in arylhydrazine carcinogenesis. These adducts are poorly read and inhibit chain extension but do alter the conformational preferences of oligonucleotides. We have shown that C8-phenylguanine modification of d(CGCGCG*CGCG) (G*= 8-phenylguanine) stabilizes it in the Z-DNA conformation (B/Z-DNA=1:1, 200 mM NaCl, pH 7.4). Here we have conducted molecular dynamics and free energy calculations to determine the sources(s) of these conformational affects and to predict the affect of the related C8-tolyl and C8-hydroxymethylphenyl guanine adducts on B/Z-DNA equilibrium. Force field parameters for the modified guanines were first developed using Guassian98 employing the B3LYP method and the standard 6-31G* basis set and fit to the Cornell 94 force field with RESP. Molecular dynamics simulations and free energy calculations, using the suite of programs contained in Amber 6 and 7 with the Cornell 94 force field, were used to determine the structural and thermodynamic properties of the DNA. The principal factors that drive conformation are stacking of the aryl group over the 5'-cytosine in the phenyl and tolyl modified oligonucleotides while hydrogen bonding opposes stacking in the hydroxymethylphenyl derivative. The phenyl and tolyl-modified DNA's favored the Z-DNA form as did the hydroxymethylphenyl derivative when hydrogen bonding was not present. The B-DNA conformation was preferred by the unmodified oligonucleotide and by the hydroxymethylphenyl-modified oligonucleotide when hydrogen bonding was considered. Z-DNA stability was not found to directly correlated with carcinogenicity and additional biological factors, such as recognition and repair, may also need to be considered in addition to Z-DNA formation.

DNA↗

Interactions of infectious symptoms and modifiable risk factors in sudden infant death syndrome. The Nordic Epidemiological SIDS study.

The aim of the study was to investigate the effect of infection on sudden infant death syndrome (SIDS) and to analyse whether modifiable risk factors of SIDS, prone sleeping, covered head and smoking act as effect modifiers. In a consecutive multicentre case-control study of SIDS in Denmark, Norway and Sweden, questionnaires on potential risk factors for SIDS were completed by parents of SIDS victims, and for at least two controls matched for gender, age and place of birth. All SIDS cases were verified by an autopsy. The study comprised 244 SIDS cases and 869 controls, analysed by conditional logistic regression. Significantly more cases than controls presenting symptoms of infectious diseases during the last week and/or last day were treated with antibiotics and had been seen by a physician. The finding is consistent with the hypothesis of an infectious mechanism in SIDS induced by local microorganism growth and toxin or cytokine production, and also adds further support to a possible association between infection and SIDS by loss of protective mechanisms, such as arousal. The risk of SIDS among infants with the combined presence of infectious symptoms and either of the other modifiable risk factors, prone sleeping, head covered or parental smoking, was far greater than the sum of each individual factor. These risk factors thus modify the dangerousness of infection in infancy.

Case-Control Studies↗

Differential effects of native and oxidatively modified low-density lipoproteins on platelet function.

Low-density lipoproteins (LDL) have been various reported to induce platelet aggregation independently and/or sensitise platelets to other agonists. In these earlier studies the extent of oxidation of LDL was not always reported or addressed. We have now investigated the effects of native, minimally modified and fully oxidised LDL (0-1g apolipoproteinB /l on platelet function using platelet aggregometry and fluorescence activated 100 flow cytometry. Native LDL did not activate isolated platelets but inhibited ADP- and thrombin-induced aggregation of isolated platelets by 51% in the presence or absence of added fibrinogen. Longer pre-incubations were required to produce a comparable inhibition by native LDL on platelets in plasma. Flow cytometric analysis showed that native LDL inhibited ADP-induced fibrinogen binding by up to 38%. In contrast, minimally modified LDL induced primary platelet aggregation and fibrinogen binding in the absence of other agonists, enhanced both submaximal (1 2 lmol/l) ADP-induced aggregation, fibrinogen binding and degranulation (CD63 and P-selectin expression). Fully oxidised LDL, however, inhibited ADP-induced platelet aggregation and fibrinogen binding. The effects of minimally modified LDL on platelet aggregation could be reproduced partially by adding 15-hydroperoxy-eicosatetraenoic acid to native LDL. These data indicate that the extent of oxidation of LDL is critical in determining their effects on platelet function. Native LDL did not activate platelets, whilst minimally modified LDL exerted a pro-aggregatory effect, possibly due to the presence of lipid hydroperoxides near to the concentration range found in pathological states.

Journal Article↗

Effect of hypochlorite (HOCl)-modified low density lipoproteins and high density lipoproteins on platelet function.

As hypochlorous acid (HOCl) might be a potential candidate for generation of modified (lipo)proteins in vivo , the present study was aimed at investigating the effects of HOCl-modified lipoproteins on platelet function in vitro. Lipoproteins modified with HOCl at concentrations that occur physiologically did not induce spontaneous platelet aggregation. However, low density lipoproteins (LDL; 100 to 500 microg protein/ml) increased platelet aggregation and fluorescence anisotropy in response to ADP (1 and 10 microM) and thrombin (0.1 and 0.5 U/ml) as well as malondialdehyde (MDA) formation as a function of increasing HOCl-concentrations (0.2 to 1.6 mM). HOCl-modified high density lipoprotein subfraction 3 (HDL3) had no effect on platelet function.

Journal Article↗

Removal of phosphorus from water using lignocellulosic material modified with iron species from acid mine drainage.

Lignocellulosic biosorbents, including juniper fiber, show promise as sorbents for removing pollutants from wastewater run-off because of their low cost. In this study, juniper fiber modified with iron species from acid mine drainage (AMD) was tested for its capacity to remove phosphorus from water compared to unmodified juniper fiber. In batch tests, the maximum adsorbate loading (Qmax) of phosphorus onto the modified adsorbent was 1.83 mg g(-1) at pH 4.0, obtained by fitting the isotherm results to the Langmuir isotherm model. This value is similar to the sorption capacity of other conventional adsorbents such as goethite, which implies that the modified lignocellulosic material would be effective as a sorbent for removing phosphorus from water. In the kinetic test, the pseudo-second order kinetic model fitted well the sorption of phosphorus onto the modified filter medium, showing the kinetic constant (k) of 8.09 x 10(-2) g(mg min)(-1) at initial phosphorus concentration of 10 mg l(-1).

Cellulose↗

Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity.

Burkitt and Burkitt-like lymphomas are rapidly growing tumors which require specialized therapy. Although intensive, multi-agent regimens have been effective in children, results are more variable in adults. Magrath et al. previously described a regimen that was highly effective in children and young adults. This phase II study of a modified Magrath regimen was designed to assess its efficacy in older adults and reduce treatment-related toxicity. Fourteen patients with Burkitt/Burkitt-like lymphoma and median age of 47 years were stratified into two categories: low-risk (normal LDH and a single focus of disease measuring less than 10 cm, 3 patients) and high risk (all other, 11 patients). Low-risk patients received three cycles of modified CODOX-M (cyclophosphamide, doxorubicin, adriamycin, vincristine with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate, regimen A). High-risk patients received four alternating cycles of regimens A and B (A-B-A-B). Regimen B consisted of ifosfamide, cytarabine, etoposide and intrathecal methotrexate (IVAC). The modified treatment regimen was associated with no grade 3/4 neuropathy and only one episode of grade 3/4 mucositis. All patients completed protocol therapy and there were no treatment-related deaths. Twelve patients (86%, 90% CI: 61 97%) achieved a complete response; 1 patient achieved a PR and 1 patient died of progressive disease. Nine patients (64%) are alive and disease free at a median follow-up of 29 months. This modified Magrath regimen is effective and well-tolerated in a representative group of older adult patients.

Adolescent↗

Removal of ammonia by biofilters: a study with flow-modified system and kinetics.

The characteristics of ammonia removal by two types of biofilter (a standard biofilter with vertical gas flow and a modified biofilter with horizontal gas flow) were investigated. A mixture of organic materials such as compost, bark, and peat was used as the biofilter media based on the small-scale column test for media selection. Complete removal capacity, defined as the maximum inlet load of ammonia that was completely removed, was obtained. The modified biofilter showed complete removal up to 1.0 g N/kg dry material/day. However, the removal capacity of the standard biofilter started to deviate from complete removal around 0.4 g N/kg dry material/day, indicating that the modified biofilter system has higher removal efficiency than the standard upflow one. In kinetic analysis of the biological removal of ammonia in each biofilter system, the maximum removal rate, Vm, was 0.93 g N/kg dry material/day and the saturation constant, Ks, was 32.55 ppm in the standard biofilter. On the other hand, the values of Vm and Ks were 1.66 g N/kg dry material/day and 74.25 ppm, respectively, in the modified biofilter system.

Air Movements↗

Sequential method of estimating the LD50 using a modified up-and-down rule.

In this paper, the original up-and-down method, modified up-and-down method, the Robbins-Monro method, and a fixed-sample Spearman-Kärber method are compared for the point estimator as well as the confidence interval of LD50. In particular, three different designs of the modified up-and-down approach based on the combination of experiments on one test space and reduced test space are investigated. The standard normal distribution and chi-square distribution are used as tolerance distributions. Simulation results indicate that the modified up-and-down method tends to be somewhat better than the original up-and-down method in terms of the mean squared error under normal tolerance distribution. In case of chi-square distribution, the modified method is shown to be substantially better when the test space is wide and the initial dose is further away from the LD50.

Lethal Dose 50↗

Modified poly(propylene imine) dendrimers as effective transfection agents for catalytic DNA enzymes (DNAzymes).

The major bottleneck in gene therapy remains the issue of delivery. In this work, various modified poly(propylene imine) (PPI) dendrimers are introduced as gene transfection agents. Commercially available PPI-dendrimers have been modified (i) at the exterior primary amines with acetyl groups or glycol gallate (PEG-like) groups, and (ii) at the interior tertiary amines with methyl iodide (MeI) or MeCl to produce multiple quaternized cationic sites in the core of the dendrimer. The prepared materials have been tested with respect to their binding capabilities to DNA, their toxicity in cell cultures, their in vitro transfection efficiency and their in vivo delivery possibilities. In all cases, a 33-mer oligonucleotide (DNAzyme) was used. Polyacrylamide gel electrophoresis (PAGE) studies have demonstrated strong but reversible binding, where the quarternized and higher generation dendrimer species have shown more potent binding. Typically, for the modified fourth PPI-dendrimers, binding is observed at a concentration of about 4 microM DNA and a dendrimer-DNA charge ratio of around 2:1-1:1. All the tested PPI-dendrimers display a low cellular toxicity, especially when higher serum contents are used in the culture medium. For example, most of the prepared fourth generation PPI-dendrimers are not or hardly toxic up to at least 20 microM in 20% serum. An in vitro characterization has revealed a high dendrimer-mediated intracellular uptake of the DNAzyme: all the tested fourth generation PPI-dendrimers display transfection efficiencies close to or exceeding 80%, even when the concentration of serum in the medium is increased from 10 to 40%. Finally, the potential of using modified PPI-dendrimers for in vivo gene therapy experiments is demonstrated. Injecting a G4-PEG(MeI)-ssDNA complex intravenously into Nude mice has resulted in a high nuclear uptake as confirmed by co-localization studies.

Animals↗