bluuebunny/crossref_metadata_2025_split huggingface dataset:
Replication Termination inEscherichia coli: Structure and Antihelicase Activity of the Tus-TerComplex
Authors: Neylon Cameron , Kralicek Andrew V. , Hill Thomas M. , Dixon Nicholas E. 
Published: September 2005

SUMMARYThe arrest of DNA replication inEscherichia coliis triggered by the encounter of a replisome with a Tus protein-TerDNA complex. A replication fork can pass through a Tus-Tercomplex when traveling in one direction but not the other, and the chromosomalTersites are oriented so replication forks can enter, but not exit, the terminus region. The Tus-Tercomplex acts by blocking the action of the replicative DnaB helicase, but details of the mechanism are uncertain. One proposed mechanism involves a specific interaction between Tus-Terand the helicase that prevents further DNA unwinding, while another is that the Tus-Tercomplex itself is sufficient to block the helicase in a polar manner, without the need for specific protein-protein interactions. This review integrates three decades of experimental information on the action of the Tus-Tercomplex with information available from the Tus-TerAcrystal structure. We conclude that while it is possible to explain polar fork arrest by a mechanism involving only the Tus-Terinteraction, there are also strong indications of a role for specific Tus-DnaB interactions. The evidence suggests, therefore, that the termination system is more subtle and complex than may have been assumed. We describe some further experiments and insights that may assist in unraveling the details of this fascinating process.
Clinical Trial of Herbal Formula on Weight Loss in Obese Korean Children
Authors: Yoo Jung-Hee , Lee Eui-Ju , Kwak Chang-Kyu , Sohn Eun-Hae , Koh Byung-Hee , Song Il-Byung , Lee Kyung-Sub 
Published: September 2005

A traditional Korean herbal formula (KH), which is based on Taeumjowi-tang, is currently the most widely used herbal formula in Korea. In this study, KH was administered to obese children for 30 days, and was found to be clinically safe and effective. The subjects were children admitted to hospital to be treated for obesity with relative body weights (%RBW) of 20% or more. Originally, there were 31 subjects, but nine dropped out during the experiment. There were eight girls and 14 boys, whose average age was 11.00 ± 2.62 years, average weight was 53.37 ± 17.29 kg , and average period (30-day amount) of KH dosage was 51.18 ± 22.58 days.The short-term effects of KH on obese children were the reduction of their BMI from 24.34 ± 3.10 to 23.26 ± 3.00 kg/m2, of %RBW from 34.41 ± 10.90 to 25.94 ± 11.18% ( p < 0.01), of body fat mass from 17.99 ± 5.37 to 16.50 ± 4.82 kg , and of body fat from 34.16 ± 3.75 to 32.08 ± 3.15% ( p < 0.01). Concerning anthropometrical measurements, abdominal skin-fold decreased from 26.16 ± 9.08 to 22.90 ± 8.35 mm , as did subscapular skin-fold from 20.86 ± 5.20 to 18.46 ± 5.31 mm ( p < 0.01). In terms of serum lipid levels, which are indices of heart disease, their total cholesterol decreased from 195.38 ± 31.39 to 183.25 ± 33.27 mg/dl , the arteriosclerosis index from 4.100 ± 0.81 to 3.84 ± 0.64 mg/dl ( p < 0.05), and serum leptin level from 14.91 ± 6.59 to 12.24 ± 4.98 ng/ml ( p < 0.01). Concerning the safety of KH, there were no significant changes in the subjects' livers, hearts, or kidneys. Nor were there any short-term signs of clinically serious side effects or withdrawal symptoms observed. The short-term effects of KH on obese children are weight loss and a decrease in obesity.
Dimethylarginine Dimethylaminohydrolase Overexpression Suppresses Graft Coronary Artery Disease
Authors: Tanaka Masashi , Sydow Karsten , Gunawan Feny , Jacobi Johannes , Tsao Phil S. , Robbins Robert C. , Cooke John P. 
Published: September 2005

Background—Graft coronary artery disease (GCAD) is the leading cause of death after the first year of heart transplantation. The reduced bioavailability of endothelium-derived nitric oxide (NO) may play a role in endothelial vasodilator dysfunction and the structural changes that are characteristic of GCAD. A potential contributor to endothelial pathobiology is asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor. We hypothesized that lowering ADMA concentrations by dimethylarginine dimethylaminohydrolase (DDAH) overexpression in the recipient might suppress GCAD and long-term immune responses in murine cardiac allografts.Methods and Results—In one series, donor hearts of C-H-2bm12KhEg (H-2bm12) wild-type (WT) mice were heterotopically transplanted into C57BL/6 (H-2b) transgenic mice overexpressing human DDAH-I or WT littermates and procured after 4 hours of reperfusion (WT and DDAH-I recipients, n=6 each). In a second series, donor hearts were transplanted into DDAH-I–transgenic or WT mice and procured 30 days after transplantation (n=7 each). In DDAH-I recipients, plasma ADMA concentrations were lower, in association with reduced myocardial generation of superoxide anion (WT versus DDAH-I, 465.7±79.8 versus 173.4±32.3 μmol · L−1· mg−1· h−1;P=0.02), inflammatory cytokines, adhesion molecules, and chemokines. GCAD was markedly reduced in cardiac allografts of DDAH-I–transgenic recipients as assessed by luminal narrowing (WT versus DDAH, 79±2% versus 33±7%;P<0.01), intima-media ratio (WT versus DDAH, 1.1±0.1 versus 0.5±0.1;P<0.01), and the percentage of diseased vessels (WT versus DDAH, 100±0% versus 62±10%;P<0.01).Conclusions—Overexpression of DDAH-I attenuated oxidative stress, inflammatory cytokines, and GCAD in murine cardiac allografts. The effect of DDAH overexpression may be mediated by its reduction of plasma and tissue ADMA concentrations.
Targeting endoplasmic reticulum protein transport: a novel strategy to kill malignant B cells and overcome fludarabine resistance in CLL
Authors: Carew Jennifer S. , Nawrocki Steffan T. , Krupnik Yelena V. , Dunner Kenneth , McConkey David J. , Keating Michael J. , Huang Peng 
Published: September 2005

AbstractPrevious studies showed that chronic lymphocytic leukemia (CLL) cells exhibit certain mitochondrial abnormalities including mtDNA mutations, increased superoxide generation, and aberrant mitochondrial biogenesis, which are associated with impaired apoptosis and reduced sensitivity to fludarabine. Here we report that CLL cells and multiple myeloma cells are highly sensitive to brefeldin A, an inhibitor of endoplasmic reticulum (ER) to Golgi protein transport currently being developed as a novel anticancer agent in a prodrug formulation. Of importance, brefeldin A effectively induced apoptosis in fludarabine-refractory CLL cells. Disruption of protein trafficking by brefeldin A caused the sequestration of the prosurvival factors APRIL and VEGF in the ER, leading to abnormal ER swelling and a decrease in VEGF secretion. Such ER stress and blockage of secretory protein traffic eventually resulted in Golgi collapse, activation of caspases, and cell death. Notably, the cellular sensitivity to this compound appeared to be independent of p53 status. Taken together, these findings suggest that malignant B cells may be highly dependent on ER-Golgi protein transport and that targeting this process may be a promising therapeutic strategy for B-cell malignancies, especially for those that respond poorly to conventional treatments.
Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis
Authors: Fransson Mattias , Adner Mikael , Erjefält Jonas , Jansson Lennart , Uddman Rolf , Cardell Lars-Olaf 
Published: September 2005

Abstract

Background
Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has been shown in several studies, but their possible function as mediators in allergy and asthma remains to be established. The present study was designed to examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with intermittent allergic rhinitis, focusing on changes induced by exposure to pollen.

Methods
27 healthy controls and 42 patients with seasonal allergic rhinitis volunteered for the study. Nasal biopsies were obtained before and during pollen season as well as before and after allergen challenge. The seasonal material was used for mRNA quantification of Toll-like receptors 2, 3 and 4 with real-time polymerase chain reaction, whereas specimens achieved in conjunction with allergen challenge were used for immunohistochemical localization and quantification of corresponding proteins.

Results
mRNA and protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all specimens. An increase in protein expression for all three receptors could be seen following allergen challenge, whereas a significant increase of mRNA only could be obtained for Toll-like receptor 3 during pollen season.

Conclusion
The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation.
Rhinosinusitis derived Staphylococcal enterotoxin B possibly associates with pathogenesis of ulcerative colitis
Authors: Yang Ping-Chang , Liu Tao , Wang Bin-Quan , Zhang Tao-Yuan , An Zi-Yuan , Zheng Peng-Yuan , Tian Dao-Fa 
Published: September 2005

AbstractBackgroundDuring clinical practice, we noticed that some patients with both ulcerative colitis (UC) and chronic rhinosinusitis (CRS) showed amelioration of UC after treatment of CRS. This study was designed to identify a possible association between CRS and UC.MethodsThirty-two patients with both CRS and UC received treatment with functional endoscopic sinus surgery (FESS) for CRS. Clinical symptom scores for CRS and UC, as well as serum levels of anti-Staphylococcal enterotoxin B (SEB) were evaluated at week 0 and week 12. Sinus wash fluid SEB content was measured with enzyme-linked immunosorbent assay (ELISA). The surgically removed tissues were cultured to identify growth ofStaphylococcus. aureus(S. aureus). Immunohistochemistry was employed to identify anti-SEB positive cells in the colonic mucosa. Colonic biopsies were obtained and incubated with SEB. Mast cell activation in the colonic mucosa in response to incubation with SEB was observed with electron microscopy and immunoassay.ResultsThe clinical symptom scores of CRS and UC severe scores (UCSS) were significantly reduced in the UC-CRS patients after FESS. The number of culturedS. aureuscolonies from the surgically removed sinus mucosa significantly correlated with the decrease in UCSS. High levels of SEB were detected in the sinus wash fluids of the patients with UC-CRS. Histamine and tryptase release was significantly higher in the culture supernate in the patients with UC-CRS than the patients with UC-only and normal controls. Anti-SEB positive cells were located in the colonic mucosa.ConclusionThe pathogenesis of UC in some patients may be associated with their pre-existing CRS by a mechanism of swallowing sinusitis-derived SEB. We speculate that SEB initiates inappropriate immune reactions and inflammation in the colonic mucosa that further progresses to UC.
Persistence of Natural Killer (NK) cell lymphocytosis with hyposplenism without development of leukaemia
Authors: Khan Sujoy , Myers K 
Published: September 2005

Abstract
Background
Natural killer (NK) cell lymphocytosis usually has an indolent course and can progress into massive lymphocytosis with development of cytopenias and neoplastic diseases. NK-cells usually express one or more "NK-associated" antigens (CD16, CD56, CD57). Reactive expansions are seen in autoimmune diseases, viral infections, solid tumours and non-Hodgkin's lymphoma.

Case presentation
We report a lady with a benign clinical course over 10 years and persistent CD8+/CD3-/CD57+/CD16+ LGL proliferation with presence of Howell-Jolly bodies (functional hyposplenism), an association not previously described.

Conclusion
We discuss the possible causes of clonal expansion and conclude that this may be part of the spectrum of immune dysregulation associated with NK-cell lymphocytosis.
Classification of the extracellular fields produced by activated neural structures
Authors: Richerson Samantha , Ingram Mark , Perry Danielle , Stecker Mark M 
Published: September 2005

Abstract

Background
Classifying the types of extracellular potentials recorded when neural structures are activated is an important component in understanding nerve pathophysiology. Varying definitions and approaches to understanding the factors that influence the potentials recorded during neural activity have made this issue complex.

Methods
In this article, many of the factors which influence the distribution of electric potential produced by a traveling action potential are discussed from a theoretical standpoint with illustrative simulations.

Results
For an axon of arbitrary shape, it is shown that a quadrupolar potential is generated by action potentials traveling along a straight axon. However, a dipole moment is generated at any point where an axon bends or its diameter changes. Next, it is shown how asymmetric disturbances in the conductivity of the medium surrounding an axon produce dipolar potentials, even during propagation along a straight axon. Next, by studying the electric fields generated by a dipole source in an insulating cylinder, it is shown that in finite volume conductors, the extracellular potentials can be very different from those in infinite volume conductors. Finally, the effects of impulses propagating along axons with inhomogeneous cable properties are analyzed.

Conclusion
Because of the well-defined factors affecting extracellular potentials, the vague terms far-field and near-field potentials should be abandoned in favor of more accurate descriptions of the potentials.
Response shift masks the treatment impact on patient reported outcomes (PROs): the example of individual quality of life in edentulous patients
Authors: Ring Lena , Höfer Stefan , Heuston Frank , Harris David , O'Boyle Ciaran A 
Published: September 2005

Abstract

Background
Quality of life (QoL) is now established as an important outcome for evaluating the impact of disease, and for assessing the efficacy of treatments. However, individuals change with time and the basis on which they make a QoL judgement may also change, a phenomenon increasingly referred to as response shift. Here, the individual may change his or her internal standards, values, and/or conceptualization on the target construct as a result of external factors such as a treatment or a change in health status. This has important implications for assessing the effects of treatments as a change in QoL may reflect a response shift, a treatment effect, or a complex combination of both. In this study, we used an individualised quality of life (IQoL) measure, the SEIQoL, together with a then-test to determine whether response shift would influence the measurement of treatment efficacy in edentulous patients.

Methods
Data are reported here for the first phase of a randomised controlled clinical trial designed to assess the impact, on IQoL, of implant supported dentures compared with high quality conventional dentures. IQoL was measured using the SEIQoL-DW in 117 patients (mean age 64.8; 32% male) at baseline (T1) and 3 months (T2) after receiving high quality conventional dentures. The work was carried out in dental teaching hospitals in Dublin and Belfast.

Results
Unadjusted SEIQoL index scores revealed no significant impact of treatment at three months (baseline: 75.0; 3 months: 73.2, p = .33, n.s.). However, the then-test at 3 months revealed that patients retrospectively rated their baseline IQoL as significantly lower (P < .001) than they had rated it at the time (then-test baseline: 69.2). Comparison of the 3 month scores with this readjusted baseline indicated a significant treatment effect (then-test baseline: 69.2; 3 months: 73.2, p = 0.016). 81% of patients nominated at least one different IQoL domain at 3 months.

Conclusion
The positive impact of denture treatment for edentulous patients on IQoL was seen only when response shifts were taken into consideration. The nature of the response shifts was highly complex but the data indicated a degree of re-conceptualisation and reprioritisation. Assessment of the impact of treatments using patient-generated reports must take account of the adaptive nature of patients.
Boundary effects influence velocity of transverse propagation of simulated cardiac action potentials
Authors: Sperelakis Nicholas , Kalloor Bijoy , Ramasamy Lakshminarayanan 
Published: September 2005

Abstract

Background
We previously demonstrated that transverse propagation of excitation (cardiac action potentials simulated with PSpice) could occur in the absence of low-resistance connections (gap – junction channels) between parallel chains of myocardial cells. The transverse transmission of excitation between the chains was strongly dependent on the longitudinal resistance of the interstitial fluid space between the chains: the higher this resistance, the closer the packing of the parallel chains within the bundle. The earlier experiments were carried out with 2-dimensional sheets of cells: 2 × 3, 3 × 4, and 5 × 5 models (where the first number is the number of parallel chains and the second is the number of cells in each chain). The purpose of the present study was to enlarge the model size to 7 × 7, thus enabling the transverse velocities to be compared in models of different sizes (where all circuit parameters are identical in all models). This procedure should enable the significance of the role of edge (boundary) effects in transverse propagation to be determined.

Results
It was found that transverse velocity increased with increase in model size. This held true whether stimulation was applied to the entire first chain of cells or only to the first cell of the first chain. It also held true for retrograde propagation (stimulation of the last chain). The transverse resistance at the two ends of the bundle had almost no effect on transverse velocity until it was increased to very high values (e.g., 100 or 1,000 megohms).

Conclusion
Because the larger the model size, the smaller the relative edge area, we conclude that the edge effects slow the transverse velocity.
A comparative study of a theoretical neural net model with MEG data from epileptic patients and normal individuals
Authors: Kotini A , Anninos P , Anastasiadis AN , Tamiolakis D 
Published: September 2005

Abstract

Objective
The aim of this study was to compare a theoretical neural net model with MEG data from epileptic patients and normal individuals.

Methods
Our experimental study population included 10 epilepsy sufferers and 10 healthy subjects. The recordings were obtained with a one-channel biomagnetometer SQUID in a magnetically shielded room.

Results
Using the method of x2-fitting it was found that the MEG amplitudes in epileptic patients and normal subjects had Poisson and Gauss distributions respectively. The Poisson connectivity derived from the theoretical neural model represents the state of epilepsy, whereas the Gauss connectivity represents normal behavior. The MEG data obtained from epileptic areas had higher amplitudes than the MEG from normal regions and were comparable with the theoretical magnetic fields from Poisson and Gauss distributions. Furthermore, the magnetic field derived from the theoretical model had amplitudes in the same order as the recorded MEG from the 20 participants.

Conclusion
The approximation of the theoretical neural net model with real MEG data provides information about the structure of the brain function in epileptic and normal states encouraging further studies to be conducted.
Gene Expression Profile Predicts Patient Survival of Gastric Cancer After Surgical Resection
Authors: Chen Chiung-Nien , Lin Jen-Jen , Chen Jeremy J. W. , Lee Po-Huang , Yang Ching-Yao , Kuo Min-Liang , Chang King-Jen , Hsieh Fon-Jou 
Published: September 2005

Purpose This study was conducted to characterize gene expression profile of survival in patients with surgically curable gastric cancer by using an in-house membrane microarray and developing a survival prediction model. Materials and Methods Data of cDNA microarrays were obtained from 18 pairs of cancerous and noncancerous gastric tissues. Nine patients who survived > 30 months were identified as good survival, and the other nine, who survived < 12 months, were identified as poor survival. Supervised analysis was performed to identify a gene expression profile by good and poor survival. Semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the microarray data in 10 patients with sufficient RNA. Using these 10 patients and another 10 patients selected randomly from 40 newly enrolled patients as the training group, the RT-PCR status of the confirmed genes was used for predicting good versus poor survival. Finally, the prediction model was tested in the remaining 30 newly enrolled gastric cancer patients. Results A survival prediction model consisting of three genes (CD36, SLAM, PIM-1) was developed. This model could correctly predict poor or good survival in 23 (76.7%) of 30 newly enrolled patients, and yielded a specificity of 80% and a sensitivity of 73.3%. The survival rate of the patients predicted to have good survival was significantly higher than that of those predicted to have poor survival in the test group as a whole (N = 30; P = .00531) and in stage III patients (n = 16; P = .04467). Conclusion The semiquantitative RT-PCR gene expression profiling of three genes extracted from microarray study can accurately predict surgery-related outcome in gastric cancer patients.
Phase I Pharmacokinetic Study of S-1 Plus Cisplatin in Patients With Advanced Gastric Carcinoma
Authors: Ajani Jaffer A. , Faust Josephine , Ikeda Kazumasa , Yao James C. , Anbe Hiroshi , Carr Kelli L. , Houghton Michele , Urrea Peter 
Published: September 2005

Purpose The conversion rate of tegafur (a component of S-1) to fluorouracil (FU) differs in Asians and whites because of polymorphic differences in the CYP2A6 gene. S-1 with cisplatin is considered highly active in Japanese gastric cancer patients. Therefore, we initiated a phase I pharmacokinetic study of this combination in our gastric cancer patients. Patients and Methods Patients received cisplatin intravenously on day 1 and S-1 orally, twice daily, on days 1 to 21 every 28 days. At level 1, the S-1 dose was 25 mg/m2/dose (50 mg/m2/d), but it was increased by 5 mg/m2/dose for the next level. Cisplatin was administered at 75 mg/m2 (for levels 1 and 2) but was then reduced to 60 mg/m2 (level 1A). At every level, a cohort of three patients, which could be expanded to six patients, was studied. Maximum-tolerated dose (MTD) was determined based on the dose-limiting toxicity (DLT) in the first cycle. Patients with histologic proof of gastric adenocarcinoma and near-normal organ function were studied. Results Sixteen patients were enrolled. No DLTs occurred at level 1. However, DLTs occurred at levels 2 and 1A. The area under the curve for FU correlated significantly with DLT (P = .006) and grade 3 to 4 diarrhea (P = .004). Six partial responses were confirmed, including three at the MTD. Conclusion At the established MTD of S-1 plus cisplatin, the S-1 dose (50 mg/m2/d for 21 days) is lower in our study than in the Japanese study (80 mg/m2/d for 21 days). A multi-institutional phase II study of this active combination is currently accruing patients.