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S Lee

Publications and source records attributed to S Lee.

At least 37 records · Page 2Linked to original sources
PubMed2006

Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease.

INTRODUCTION: Interferon gamma is a potent proinflammatory cytokine implicated in the inflammation of Crohn's disease (CD). We evaluated the safety and efficacy of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe CD. METHODS: A total of 133 patients with Crohn's disease activity index (CDAI) scores between 250 and 450, inclusive, were randomised to receive placebo or fontolizumab 4 or 10 mg/kg. Forty two patients received one dose and 91 patients received two doses on days 0 and 28. Investigators and patients were unaware of assignment. Study end points were safety, clinical response (decrease in CDAI of 100 points or more), and remission (CDAI < or =150). RESULTS: There was no statistically significant difference in the primary end point of the study (clinical response) between the fontolizumab and placebo groups after a single dose at day 28. However, patients receiving two doses of fontolizumab demonstrated doubling in response rate at day 56 compared with placebo: 32% (9/28) versus 69% (22/32, p = 0.02) and 67% (21/31, p = 0.03) for the placebo, and 4 and 10 mg/kg fontolizumab groups, respectively. Stratification according to elevated baseline C reactive protein levels resulted in a decreased placebo response and pronounced differences in clinical benefit. Two grade 3 adverse events were reported and were considered to be related to CD. One death (during sleep) and one serious adverse event (an elective hospitalisation) occurred, both considered unrelated. CONCLUSION: Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.

Adult↗
PubMed2006

Differential display analysis of gene expression in two immunologically distinct strains of Eimeria maxima.

Gene expression during sporulation and sporozoite excystation of two strains of Eimeria maxima was analyzed using the mRNA differential display technique. The two strains, the Guelph strain (GS) and a single sporocyst-derived strain (M6) from Florida, have been shown to be immunologically distinct. We isolated and cloned a 453-bp complimentary DNA (cDNA) fragment (GS-453) found only in GS sporozoites. In GS, this mRNA begins to be expressed during the earliest stages of oocyst sporulation and is continuously expressed up to and including in the excysted sporozoite. In all Northern blots, digoxigenin (DIG)-labeled GS-453 probe recognized an mRNA of approximately 1.6 kb from GS but not from RNA of M6. Southern blots using various endonucleases and probed with DIG-labeled GS-453 demonstrated that the genomes of both strains contained sufficiently similar sequences to permit hybridization with the probe, but the pattern of hybridization differed between the two strains. Extensive searches of the GenBank, European Molecular Biology Laboratory, and various apicomplexan expressed sequence tag databases using the DNA or inferred amino acid sequences of GS-453 cDNA clone did not identify similarity to any existing sequences.

Animals↗
PubMed2006

Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells.

AIMS/HYPOTHESIS: We recently reported that expression of the gene encoding clusterin (Clu) is upregulated in the regenerating pancreas, particularly in tissues undergoing differentiation. This led us to propose that clusterin participates in the cytodifferentiation of pancreatic tissue, particularly the endocrine islet cells. The aim of this study was to investigate whether clusterin induces the differentiation of duct-lining cells into insulin-secreting cells. METHODS: We isolated ductal tissue from rat pancreas and cultured it to develop epithelial cell explants for transfection of the Clu cDNA as well as for treatment of clusterin protein. RESULTS: The number of newly differentiated insulin cells increased 6.9-fold upon Clu overexpression compared with controls. Ins1 mRNA and peptide levels were also increased. Furthermore, glucose-stimulated insulin secretion was observed in the differentiated insulin cells. These cells were immunoreactive for insulin and C-peptide, but negative for other islet hormones and for cytokeratin-20, which indicates a fully differentiated state. Insulin cell differentiation was also increased in a dose-dependent manner by treating duct cells in culture with clusterin, indicating a growth-factor-like action of clusterin in insulin cell differentiation. CONCLUSIONS/INTERPRETATION: These results suggest that clusterin can be considered as a potential morphogenic factor that promotes differentiation of pancreatic beta cells.

Animals↗
PubMed2006

Patterns of C-reactive protein release following allogeneic stem cell transplantation are correlated with leukemic relapse.

The C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes, and is a reliable marker of systemic inflammation, which is relevant to the release of the proinflammatory cytokines. The value of monitoring the CRP levels after stem cell transplantation (SCT) can identify patients at risk of treatment-related complications and mortality. Inflammatory cytokines facilitate donor T-cell activation via antigen presenting cells immediately after SCT. This study examined the relationship between the post-SCT CRP levels and a leukemic relapse. Fifty-four consecutively transplanted patients who relapsed after the allogeneic SCT were compared with nonrelapsing patients. The serum CRP levels were measured on day 0 and every 7 days thereafter until 4 weeks after the SCT. The mean CRP levels throughout the early post-SCT episode were significantly lower in the relapsing patients than in those who did not experience relapse (mean+/-s.e.: 26.8 +/- 6.3 vs 65.3 +/- 9.4 for first week, P = 0.001; 23.9 +/- 3.8 vs 44.6 +/- 6.6 for second week, P = 0.008). Univariate analysis showed that the CRP level on the first and second week, and graft-versus-host disease were significantly associated with a relapse. Multivariate analysis showed that the CRP level on the first week was the strongest independent variable predicting the risk of a relapse after SCT (P = 0.04). These results indicate that the serum CRP levels early after allogeneic SCT might display the graft-versus-leukemia (GvL) effect. CRP is a surrogate of the proinflammatory cytokine release that was not measured in this study. The GvL effect appears to be efficiently strengthened by the high CRP levels that may be reflecting T-cell activation.

Adolescent↗
PubMed2006

Retrocaval ureter.

Explore the source record for details and available documents.

Fluorodeoxyglucose F18↗
PubMed2006

[Comparative study of treatment of the dry eye syndrome due to disturbances of the tear film lipid layer with lipid-containing tear substitutes].

BACKGROUND: A deficiency in the tear film lipid layer is aetiological in about 80 % of the patients suffering from dry eye, which results in excessive evaporation (so-called hyperevaporative dry eye). The treatment with conventional artificial tears did not prove to be successful here. In this study the treatment with two tear substitutes containing lipids were set in contrast with each other. MATERIAL AND METHODS: The randomised, controlled, multicentre cross-over study included 74 patients suffering from dry eye caused by a deficiency of the tear film lipid layer, which were organised into two groups. Group A (n = 38) was treated for the first 6 weeks with a liposomal eye spray (Tears Again), while the patients of the group of B (n = 36) were treated with an eye gel containing triglycerides (Liposic) in the same period. After 6 weeks the crossover was performed. The patients were treated in the following 6 weeks with the product which was not used before. Control examinations by masked examiners took place at the beginning of the study as well as after 6 and 12 weeks, considering the following parameters: eyelid edge-parallel conjunctival folds (LIPCOF), BREAK UP time (BUT), Schimer-I test, measurement of the tear meniscus, investigation of the edges of eyelid and visual acuity. In addition. the subjective feelings of the patients were also determined by means of questionnaires. RESULTS: At the beginning of the study the two groups did not differ significantly with respect to the initial values. After the first treatment period the improvement of the examined parameters LIPCOF, BUT, Schirmer, visual acuity and inflammation of the lid margin in group A (eye spray) proved to be significantly superior in comparison to group B (eye gel). The results of the second treatment period after the crossover were similar and showed an analogous supremacy of the liposomal eye spray. The interviews with the patients revealed that the subjective evaluation concerning efficacy and compatibility of the eye spray turned out to be explicitly more favourable than that concerning the eye gel. 74.6 % of the patients favoured the application as an eye spray onto the closed eyelids over the eye gel into the conjunctival sac. 62.5 % of the patients rated the liposomal eye spray to be better all in all, 12.5 % rated that both preparations are equal and 25 % favoured the eye gel. CONCLUSIONS: The treatment with phospholipids liposomes shows statistically significant clinical advantages and proves to be favourably and explicitly superior compared to the conventional standard treatment all in all.

Adult↗
PubMed2006

Controlled delivery of a hydrophilic drug from a biodegradable microsphere system by supercritical anti-solvent precipitation technique.

The purpose of this study was to prepare microspheres loaded with hydrophilic drug, bupivacaine HCl using poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). Microspheres were prepared with varying the PLGA/PLLA ratio with two different levels of bupivacaine HCl (5 and 10%) using a supercritical anti-solvent (SAS) technique. Microspheres ranging from 4-10 microm in geometric mean diameter could be prepared, with high loading efficiency. Powder X-ray diffraction (PXRD) revealed that bupivacaine HCl retained its crystalline state within the polymer and was present as a dispersion within the polymer phase after SAS processing. The release of bupivacaine HCl from biodegradable polymer microspheres was rapid up to 4 h, thereafter bupivacaine HCl was continuously and slowly released for at least 7 days according to the PLGA/PLLA ratio and the molecular weight of PLLA.

Absorbable Implants↗
PubMed2006

Eugenol inhibits sodium currents in dental afferent neurons.

Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents (I(Na)) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and I(Na) in both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on I(Na), suggesting no involvement of TRPV1. Two types of I(Na), tetrodotoxin (TTX)-resistant and TTX-sensitive I(Na), were inhibited by eugenol. Our results demonstrated that eugenol inhibits I(Na) in a TRPV1-independent manner. We suggest that I(Na) inhibition by eugenol contributes to its analgesic effect.

Action Potentials↗
PubMed2006

Arthroplasty for advanced Kienböck's disease using a radial bone flap with a vascularised wrapping of pronator quadratus.

We have performed a form of lunate replacement arthroplasty, which included excision of the lunate and insertion of a vascularised radial bone flap wrapped in pronator quadratus, for stage IIIB or stage IV Kienböck's disease, in 41 patients who have been followed up for more than three years. All patients reported an improvement in their symptoms, and 20 of the 41 became free of pain after the operation. Extension and flexion of the wrist were increased by a mean of 9 degrees and 6 degrees , respectively (p < 0.05). The radioscaphoid angle and the carpal height ratio were not significantly changed and only minimal deterioration was observed due to degenerative change. The size, density or location of the inserted bone did not change with time. A vascularised radial bone flap wrapped in pronator quadratus can be a reliable treatment option for advanced Kienböck's disease, when the pedicled bone and muscle envelope acts as a stable spacer for the excised lunate.

Adult↗
PubMed2006

International standards for services activities relating to drinking water supply systems and wastewater systems: implications for developing countries.

In developing countries, the PPP (Public-Private-Partnerships) programs have been unsatisfied during the last decade. This study analyzed one of the main causes is low quality of the system. That is, no matter what supports developing countries may get through PPP, reforming water systems can be hardly successful without appropriate system quality. With this background, this study introduces service standards of ISO/TC 224 as an option to improve system quality of developing countries. To analyze its effects, system dynamic modeling was conducted. The results indicated that service standards, working with the PPP programs, can benefit all the stakeholders involved in the water systems in developing countries. Also this indicates further that this approach with service standards deserves more detailed study for improving the ailing water systems in developing countries.

Developing Countries↗
PubMed2006

Effects of flocculent aggregates on microfiltration with coagulation pretreatment of high turbidity waters.

Immersed membrane systems, and those with in-line coagulation, have been extensively applied in drinking water systems. Sedimentation is usually replaced by membrane processes in both systems. In these systems, voluminous flocculent aggregates formed during coagulation could be potential foulants. When raw waters with high turbidity are introduced, particle loadings to membrane due to coagulation pretreatment are enormous and thus could increase fouling. In general, during the rainy season, the turbidity of the Han River water, which supplies drinking water for the City of Seoul, Korea, is more than a hundred times higher than usual. Therefore, effects of floc on membrane fouling were investigated with highly turbid waters. Two turbidity concentrations, 40 and 200 NTU, were formulated by the addition of kaolin (used as a natural particle surrogate) to the Han River raw water. The results showed that the flux decline behaviours of the highly turbid waters were different from those of natural raw water. Coagulation pretreatment was very effective at reducing membrane fouling. Flocculent aggregates showed a negative effect on the flux decline but a positive effect on the membrane cleaning efficiency.

Filtration↗
PubMed2006

Study on performance of granular ANAMMOX process and characterization of the microbial community in sludge.

Anaerobic Ammonium Oxidation (ANAMMOX) is a novel biological nitrogen removal process, which is regarded as the most economical process at present. In this paper, two lab-scale UASB reactors, one of which was inoculated with the mixture of anaerobic sludge and aerobic sludge, the other with river sediments, were started up, using the inorganic synthetic water containing ammonium and nitrite as influent. After 421 days' and 356 days operation respectively, the ammonium removal efficiencies in two reactors reached 94% and 86% respectively, the total nitrogen volumetric loading rates were 2.5 and 1.6 kgN/m3 x d. ANAMMOX granules were obtained in both reactors; the color of most granules was brown, but some of them were red. Based on the observation and studies on the microstructure of the granules, three kinds of ANAMMOX granular sludge formation mechanisms were proposed: adhering biofilm and disintegrated granular core mechanism, adhering biofilm and inorganic core mechanism and the self-coherence mechanism. For phylogenetic characterization of anaerobic ammonium oxidizers, 16S rDNA approach was performed using Planctomycetales-specific PCR amplification. The dominant anammox bacteria occupied more than 90% of Planctomycetales-specific bacteria, and 27% of all bacteria in reactors. The dominant anammox bacteria distantly related to all currently reported candidate anammox genera. Functional gene of amoA was analyzed to investigate the 'aerobic' ammonium-oxidizing bacteria in beta-Proteobacteria. The 'aerobic' ammonium-oxidizing bacteria were more diverse than anammox bacteria, but most of them clustered in anoxic ammonium-oxidizing Nitrosomonas eutropha/europaea groups. The composition of 'aerobic' ammonium-oxidizing bacteria is only 2% of all of bacteria in reactors.

Ammonia↗
PubMed2006

The use of general anaesthesia for the extraction of children's teeth. Results from two UK dental hospitals.

AIM: To study the reasons forgiving children a general anaesthetic (GA) for the extraction of teeth, in two different paediatric dentistry centres and to compare them with draft guidelines disseminated for discussion by the British Society of Paediatric Dentistry (BSPD). METHODS: Data were collected on children who required GA extractions over a two month period (1st may to 30th June 2004) at the Paediatric Dental Units of Liverpool University Dental Hospital (LUDH) and the University Dental Hospital of Manchester (UDHM). The information collected included date of birth, gender, date of referral, date of assessment and date of GA. The reason for the GA was noted in terms of the proposed BSPD guidelines for short GA. RESULTS: A total of 264 and 268 children required extractions under GA at LUDH and UDHM respectively. At LUDH the main reason in 189 (72%) children was severe pulpitis requiring immediate relief of pain where a child does not have the intellectual maturity to cope with treatment under local analgesia (LA). This was followed by failed extractions under LA in 53 (20%) children. This reason is not listed under the proposed BSPD guidelines. At UDHM the main reason for GA in 114 (42%) children was symptomatic teeth causing pain in more than two quadrants (or in two quadrants necessitating the use of bilateral inferior dental blocks). CONCLUSIONS: There were differences in the clinical rationale for GA between children attending the two centres. Further information is needed to refine the proposed guidelines on the use of GA for dental extractions in paediatric dentistry. The guidelines need to be flexible and updated to reflect changes in practice and service provision.

Anesthesia, Dental↗
PubMed2005

APOE epsilon2/epsilon4 polymorphism and cerebral microbleeds on gradient-echo MRI.

The association of APOE genotypes with cerebral microbleeds (CMBs) was examined on the basis of the location of CMBs in 414 patients who were admitted primarily because of stroke. With respect to possession of the epsilon2 or epsilon4 allele, the adjusted odds ratio was 1.94 (1.05 to 3.58) for lobar CMBs but 1.21 (0.69 to 2.11) for nonlobar CMBs. This suggests that the pathogenesis of CMBs may differ depending on their location.

Age Factors↗
PubMed2005

JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila.

Although recent progresses have unveiled the diverse in vivo functions of LKB1, detailed molecular mechanisms governing these processes still remain enigmatic. Here, we showed that Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis, without affecting cell size and cell cycle progression. Through genetic screening for LKB1 modifiers, we discovered the JNK pathway as a novel component of LKB1 signaling; the JNK pathway was activated by LKB1 and mediated the LKB1-dependent apoptosis. Consistently, LKB1-null mutant was defective in embryonic apoptosis and displayed a drastic hyperplasia in the central nervous system; these phenotypes were fully rescued by ectopic JNK activation as well as wild-type LKB1 expression. Furthermore, inhibition of LKB1 resulted in epithelial morphogenesis failure, which was associated with a decrease in JNK activity. Collectively, our studies unprecedentedly elucidate JNK as the downstream mediator of the LKB1-dependent apoptosis, and provide a new paradigm for understanding the diverse LKB1 functions in vivo.

AMP-Activated Protein Kinase Kinases↗