bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study
Authors: Clayton Richard H , Taggart Peter 
Published: September 2005

Abstract

Background
Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood.

Methods
We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution.

Results
Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms).

Conclusion
Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve.
5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia
Authors: Ayasolla Kamesh R , Giri Shailendra , Singh Avtar K , Singh Inderjit 
Published: September 2005

Abstract

Background
Alzheimer's disease (AD) pathology shows characteristic 'plaques' rich in amyloid beta (Aβ) peptide deposits. Inflammatory process-related proteins such as pro-inflammatory cytokines have been detected in AD brain suggesting that an inflammatory immune reaction also plays a role in the pathogenesis of AD. Glial cells in culture respond to LPS and Aβ stimuli by upregulating the expression of cytokines TNF-α, IL-1β, and IL-6, and also the expression of proinflammatory genes iNOS and COX-2. We have earlier reported that LPS/Aβ stimulation-induced ceramide and ROS generation leads to iNOS expression and nitric oxide production in glial cells. The present study was undertaken to investigate the neuroprotective function of AICAR (a potent activator of AMP-activated protein kinase) in blocking the pro-oxidant/proinflammatory responses induced in primary glial cultures treated with LPS and Aβ peptide.

Methods
To test the anti-inflammatory/anti-oxidant functions of AICAR, we tested its inhibitory potential in blocking the expression of pro-inflammatory cytokines and iNOS, expression of COX-2, generation of ROS, and associated signaling following treatment of glial cells with LPS and Aβ peptide. We also investigated the neuroprotective effects of AICAR against the effects of cytokines and inflammatory mediators (released by the glia), in blocking neurite outgrowth inhibition, and in nerve growth factor-(NGF) induced neurite extension by PC-12 cells.

Results
AICAR blocked LPS/Aβ-induced inflammatory processes by blocking the expression of proinflammatory cytokine, iNOS, COX-2 and MnSOD genes, and by inhibition of ROS generation and depletion of glutathione in astroglial cells. AICAR also inhibited down-stream signaling leading to the regulation of transcriptional factors such as NFκB and C/EBP which are critical for the expression of iNOS, COX-2, MnSOD and cytokines (TNF-α/IL-1β and IL-6). AICAR promoted NGF-induced neurite growth and reduced neurite outgrowth inhibition in PC-12 cells treated with astroglial conditioned medium.

Conclusion
The observed anti-inflammatory/anti-oxidant and neuroprotective functions of AICAR suggest it as a viable candidate for use in treatment of Alzheimer's disease.
Dietary protein intake and renal function
Authors: Martin William F , Armstrong Lawrence E , Rodriguez Nancy R 
Published: September 2005

AbstractRecent trends in weight loss diets have led to a substantial increase in protein intake by individuals. As a result, the safety of habitually consuming dietary protein in excess of recommended intakes has been questioned. In particular, there is concern that high protein intake may promote renal damage by chronically increasing glomerular pressure and hyperfiltration. There is, however, a serious question as to whether there is significant evidence to support this relationship in healthy individuals. In fact, some studies suggest that hyperfiltration, the purported mechanism for renal damage, is a normal adaptative mechanism that occurs in response to several physiological conditions. This paper reviews the available evidence that increased dietary protein intake is a health concern in terms of the potential to initiate or promote renal disease. While protein restriction may be appropriate for treatment of existing kidney disease, we find no significant evidence for a detrimental effect of high protein intakes on kidney function in healthy persons after centuries of a high protein Western diet.
Integration of the subarachnoid space and lymphatics: Is it time to embrace a new concept of cerebrospinal fluid absorption?
Authors: Koh Lena , Zakharov Andrei , Johnston Miles 
Published: September 2005

Abstract
In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinal fluid (CSF) absorption. The experimental data seems to warrant a re-examination of CSF dynamics and consideration of a new conceptual foundation on which to base our understanding of disorders of the CSF system. The objective of this paper is to review the key studies pertaining to the role of the lymphatic system in CSF absorption.
Induction of a B-cell-dependent chronic arthritis with glucose-6-phosphate isomerase
Authors: Bockermann Robert , Schubert David , Kamradt Thomas , Holmdahl Rikard 
Published: September 2005

AbstractAntibodies specific for glucose-6-phosphate isomerase (G6PI) from T-cell receptor transgenic K/BxN mice are known to induce arthritis in mice, and immunization of DBA/1 mice with G6PI led to acute arthritis without permanent deformation of their joints. Because rheumatoid arthritis is a chronic disease, we set out to identify the capacity of G6PI to induce chronic arthritis in mice. Immunization with recombinant human G6PI induced a chronically active arthritis in mice with a C3H genomic background, whereas the DBA/1 background allowed only acute arthritis and the C57BL/10 background permitted no or very mild arthritis. The disease was associated with the major histocompatibility region sharing an allelic association similar to that of collagen-induced arthritis (i.e. q > p > r). All strains developed a strong antibody response to G6PI that correlated only in the C3H.NB strain with arthritis severity. Similarly, a weak response to type II collagen in a few mice was observed, which was associated with arthritis in C3H.NB mice. Mice on the C3H background also developed ankylosing spondylitis in the vertebrae of the tail. Both C3H.Q and B10.Q mice deficient for B cells were resistant to arthritis. We conclude that G6PI has the ability to induce a chronic arthritis, which is MHC associated and B-cell dependent. Thus, there are striking similarities between this and the collagen-induced arthritis model.
Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells
Authors: Daniel Kenyon G , Chen Di , Orlu Shirley , Cui Qiuzhi Cindy , Miller Fred R , Dou Q Ping 
Published: September 2005

Abstract
Introduction
A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome inhibitors and apoptosis inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper chelator currently being tested in clinical trials, is used as a comparison.

Methods
Breast cell lines, normal, immortalized MCF-10A, premalignant MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ or PDTC with or without prior interaction with copper, followed by measurement of proteasome inhibition and cell death. Inhibition of the proteasome was determined by levels of the proteasomal chymotrypsin-like activity and ubiquitinated proteins in protein extracts of the treated cells. Apoptotic cell death was measured by morphological changes, Hoechst staining, and poly(ADP-ribose) polymerase cleavage.

Results
When in complex with copper, both CQ and PDTC, but not TM, can inhibit the proteasome chymotrypsin-like activity, block proliferation, and induce apoptotic cell death preferentially in breast cancer cells, less in premalignant breast cells, but are non-toxic to normal/non-transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM or copper alone had no effects on any of the cells. Breast premalignant or cancer cells that contain copper at concentrations similar to those found in patients, when treated with just CQ or PDTC alone, but not TM, undergo proteasome inhibition and apoptosis.

Conclusion
The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper.
Phase I Study of Gefitinib Plus Celecoxib in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Wirth Lori J. , Haddad Robert I. , Lindeman Neal I. , Zhao Xiaojun , Lee Jeffrey C. , Joshi Victoria A. , Norris Charles M. , Posner Marshall R. 
Published: September 2005

Purpose Effective and tolerable palliative treatments are needed for patients with incurable squamous cell carcinoma of the head and neck (SCCHN). Single-agent targeted therapies have limited activity in this setting. The feasibility of adding celecoxib to gefitinib for the treatment of incurable SCCHN is unknown. Patients and Methods Nineteen patients with unresectable recurrent locoregional and/or distant metastatic SCCHN with progressive disease after at least one prior chemotherapy or chemoradiotherapy regimen were enrolled onto this single-institution phase I study. Three dose levels were explored: (1) celecoxib 200 mg twice daily plus gefitinib 250 mg daily; (2) celecoxib 400 mg twice daily plus gefitinib 250 mg daily; and (3) celecoxib 400 mg twice daily plus gefitinib 500 mg daily. Results No dose-limiting toxicities were encountered at any dose level. The most common toxicities were acneiform rash, diarrhea, hand reaction, dyspepsia, and anemia. Four of 18 patients assessable for response (22%; 95% CI, 2% to 42%) achieved a confirmed partial response. Conclusion The combination of gefitinib 500 mg daily plus celecoxib 400 mg twice daily is well-tolerated. The encouraging responses seen in this early study suggest further evaluation of epidermal growth factor receptor and cyclooxygenase-2 inhibitors in SCCHN is warranted.
ABVD Versus Modified Stanford V Versus MOPPEBVCAD With Optional and Limited Radiotherapy in Intermediate- and Advanced-Stage Hodgkin's Lymphoma: Final Results of a Multicenter Randomized Trial by the Intergruppo Italiano Linfomi
Authors: Gobbi Paolo G. , Levis Alessandro , Chisesi Teodoro , Broglia Chiara , Vitolo Umberto , Stelitano Caterina , Pavone Vincenzo , Cavanna Luigi , Santini Gino , Merli Francesco , Liberati Marina , Baldini Luca , Deliliers Giorgio Lambertenghi , Angelucci Emanuele , Bordonaro Roberto , Federico Massimo 
Published: September 2005

Purpose In this multicenter, prospective, randomized clinical trial on advanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to ≤ two sites of either previous bulky or partially remitting disease (a modification of the original Stanford program). Patients and Methods Three hundred fifty-five patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and received six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n = 106); radiotherapy was administered to 76, 71, and 50 patients in these three arms, respectively. Results The complete response rates for ABVD, Stanford V, and MOPPEBVCAD were 89%, 76% and 94%, respectively; 5-year failure-free survival (FFS) and progression-free survival rates were 78%, 54%, 81% and 85%, 73%, and 94%, respectively (P < .01 for comparison of Stanford V with the other two regimens). Corresponding 5-year overall survival rates were 90%, 82%, and 89% for ABVD, Stanford V, and MOPPEBVCAD, respectively. Stanford V was more myelotoxic than ABVD but less myelotoxic than MOPPEBVCAD, which had larger reductions in the prescribed drug doses. Conclusion When associated with conditioned and limited (not adjuvant) radiotherapy, ABVD and MOPPEBVCAD were superior to Stanford V chemotherapy in terms of response rate and FFS and progression-free survival. Patients were irradiated less often after MOPPEBVCAD, but this regimen was more toxic. ABVD is still the best choice when it is combined with optional, limited irradiation.
Phase I and Pharmacokinetic Study of Aplidine, a New Marine Cyclodepsipeptide in Patients With Advanced Malignancies
Authors: Faivre Sandrine , Chièze Stéphanie , Delbaldo Catherine , Ady-vago Nora , Guzman Cecilia , Lopez-Lazaro Luis , Lozahic Stéphanie , Jimeno José , Pico Fernando , Armand Jean Pierre , Martin José Antonio Lopez , Raymond Eric 
Published: September 2005

Purpose To establish the safety, pharmacokinetic parameters, maximum-tolerated dose, and recommended dose of aplidine, a novel marine cyclodepsipeptide, in patients with advanced cancer. Patients and Methods Using a modified Fibonacci method, we performed a phase I and pharmacokinetic study of aplidine administered as a 24-hour intravenous infusion every 2 weeks. Results Sixty-seven patients received aplidine at a dose ranging from 0.2 to 8 mg/m2. Dose-limiting myotoxicity corresponding to grade 2 to 3 creatine phosphokinase elevation and grade 1 to 2 myalgia and muscle weakness occurred in two of six patients at 6 mg/m2. No cardiac toxicity was observed. Electron microscopy analysis showed the disappearance of thick filaments of myosin. Grade 3 muscle toxicity occurred in three of 14 patients at the recommended dose of 5 mg/m2 and seemed to be more readily reversible with oral carnitine (1 g/10 kg). Therefore, dose escalation was resumed using carnitine prophylactically, allowing an increase in the recommended dose to 7 mg/m2. Other toxicities were nausea and vomiting, diarrhea, asthenia, and transaminase elevation with mild hematologic toxicity. Aplidine displayed a long half-life (21 to 44 hours), low clearance (45 to 49 L/h), and a high volume of distribution (1,036 to 1,124 L) with high interpatient variability in plasma, whereas in whole blood, clearance ranged from 3.0 to 6.2 L/h. Minor responses and prolonged tumor stabilizations were observed in patients with medullary thyroid carcinoma. Conclusion Muscle toxicity was dose limiting in this study. Recommended doses of aplidine were 5 and 7 mg/m2 without and with carnitine, respectively. The role of carnitine will be further explored in phase II studies.
End-of-Life Care Preferences of Pediatric Patients With Cancer
Authors: Hinds Pamela S. , Drew Donna , Oakes Linda L. , Fouladi Maryam , Spunt Sheri L. , Church Christopher , Furman Wayne L. 
Published: September 2005

Purpose The viewpoint of the terminally ill child at the time of an end-of-life decision has not been formally investigated. We identified the preferences of children and adolescents with advanced cancer about their end-of-life care and the factors that influenced their decisions. Patients and Methods Pediatric patients 10 or more years of age were interviewed within 7 days of participating in one of the following three end-of-life decisions: enrollment onto a phase I trial (n = 7), adoption of a do not resuscitate order (n = 5), or initiation of terminal care (n = 8). The patient, a parent, and the primary pediatric oncologist were interviewed separately by using open-ended interview questions. Results Twenty patients, aged 10 to 20 years (mean, 17 years and 4 months), with a refractory solid tumor (n = 12), brain tumor (n = 4), or leukemia (n = 4) participated. Eighteen patients (90%) accurately recalled all of their treatment options and identified their own death as a consequence of their decision. The factors that were most frequently identified included the following: for patients, caring about others (n = 19 patients); for parents, the child's preferences (n = 18 parents); and for physicians, the patient's prognosis and comorbid conditions (n = 14 physicians). Conclusion These children and adolescents with advanced cancer realized that they were involved in an end-of-life decision, understood the consequences of their decision, and were capable of participating in a complex decision process involving risks to themselves and others. The decision factors most frequently reported by patients were relationship based; this finding is contrary to existing developmental theories.
A Cyclotron Maser Instability with Application to Space and Laboratory Plasmas
Authors: Cairns R A , Speirs D C , Ronald K , Vorgul I , Kellett B J , Phelps A D R , Bingham R 
Published: September 2005

When a beam of electrons moves into a converging magnetic field, the velocity distribution function takes on a horseshoe shape as a result of conservation of magnetic moment. A few years ago it was pointed out that such a distribution is unstable to a cyclotron maser type of instability and it was suggested that this instability might be the source of auroral kilometric radiation (Bingham, R. and Cairns, R. A., Phys. Plasmas 7, 3089 (2000).) and also of emission from certain types of star (Bingham, R., Cairns, R. A. and Kellett, B. J., Astron. Astrophys. 370, 1000 (2001).).
Here we present more recent work on this topic. Since the dispersion relation which describes the instability only depends on the factor by which the magnetic field increases and on ratios of the wave plasma and cyclotron frequencies, it is possible to scale the effect to laboratory dimensions. An experiment to do this is being carried out at the University of Strathclyde and is expected to be operational during the summer of 2004. The objective is to investigate whether this mechanism might produce a useful radiation source, as well as to give a laboratory simulation of auroral kilometric radiation. The design of this experiment and its current status are described.
On the theoretical side we discuss computer simulations showing the instability and its quasilinear saturation in the geometry of the experiment. We also describe a much more detailed theory of the linear instability than we have presented in previous work. Growth rates have been calculated in cylindrical geometry with various electron beam configurations and different cylindrical mode structures. These, and the simulations, support the conclusion of our earlier work that the instability has a high growth rate.
Ion Acoustic Shock Waves in a Dusty Plasma
Authors: Khan Manoranjan , Ghosh Samiran , Sarkar Susmita , Gupta M R 
Published: September 2005

A dispersive shock wave is generated in a plasma when wave breaking due to the nonlinearity is balanced by the combined action of dispersion and dissipation. In the absence of dissipation, the dispersive effect leads to the generation of solitons described by a KdV equation. On the other hand, when dissipation dominates, the shock front exhibits a monotonic transition of plasma density, while the shock transition is of oscillatory nature when the dissipation is weak. In a dusty plasma, when viscosity and Landau damping effects are not important, the nonadiabaticity of the dust charge variation provides shocks for which both monotonic and oscillatory structures are possible, and such shocks can be described by a K-dV Burger equation.
In this paper the evolution of the Dust Ion Acoustic (DIA) shock waves is discussed. In addition, analytical studies of the propagation of DIA waves governed by K-dV Burger equation are presented.
Radiation Effects on Electrical Conductivity of Proton Conducting Oxide Ceramics
Authors: B Tsuchiya  , A Moroño  , E R Hodgson  , T Shikama  
Published: September 2005

Radiation Induced Conductivity (RIC) of proton conducting oxide ceramics (SrCe0.95Yb0.05O3-δ) was studied using 1.8 MeV electrons at an ionization dose rate of 10 Gy/s. The observed RIC was enhanced by an increase of the base conductivity without radiation as the irradiation temperature was increased from 298 to 673 K, due to Radiation Induced Electrical Degradation (RIED). It was found that the degradation rate of the base conductivity was strongly dependent on irradiation temperature and fluence.
It was also found that the base conductivity at temperatures above about 433 K did not change due to electron irradiation at the total ionization dose of 2.85 MGy. The result indicates that the radiation effect by the electrons has no influence on protonic or ionic conduction.
PM10 and PM2.5 Mass Concentration Measurements in Belgrade Urban Area
Authors: M D Tasić  , S F Rajšić  , V T Novaković  , Z R Mijić  , M N Tomašević  
Published: September 2005

In order to assess the level of mass concentrations of ambient suspended particles PM10 and PM2.5, a pilot study was performed in the urban area of Belgrade, in winter and summer period from June 2002 to June 2003. The PM10 mass concentrations in Belgrade urban area were high (average value being 72 µg m-3) in comparison to other European cities and more than 68% of daily samples exceeded the limit value of 50 µg m-3. Average PM2.5 mass concentration was 61 µg m-3. Analysis of the PM10 mass concentrations indicated seasonal variation. Frequency distribution of PM10 and PM2.5 mass concentrations and wind speed was best represented by log-normal distribution. Physical and chemical characterization of suspended particulate matter was accomplished by electron microscopy methods.