bluuebunny/crossref_metadata_2025 huggingface dataset:
The synthesis rate of albumin decreases during laparoscopic surgery
Authors: Barle Hans , Hållström Lars , Essèn Pia , Thörne Anders , McNurlan Margaret A. , Garlick Peter J. , Wernerman Jan
Published: March 2004

In previous studies, a decline in total liver protein synthesis during elective laparoscopic surgery has been observed. However, when albumin synthesis was measured in parallel no apparent influence of the procedure was detected. The aim of the present study was to specifically investigate the effect of a laparoscopic procedure on albumin synthesis. Female (n = 9) patients scheduled for elective laparoscopic cholecystectomy as a consequence of cholecystolithiasis were investigated. The fractional synthesis rate (FSR) of albumin was investigated twice in each patient, before and during surgery (2–3 h apart), employing l‐[2H5]phenylalanine and gas chromatography mass spectrometry. The FSR of albumin decreased from 7·3 ± 1·2% per day before surgery to 6·2 ± 1·4% per day during the procedure (P<0·01), whereas the corresponding absolute synthesis rates of albumin decreased from 114 ± 24 to 86 ± 16 mg kg−1 day−1, respectively (P<0·001). In conclusion, the synthesis rate of albumin decreased during a laparoscopic surgery procedure. However, the characteristics for this decrease differ from those previously observed for total liver protein synthesis.
Blood flow and flow resistance in the vertebral arteries of patients with and without carotid atherosclerosis
Authors: Hallerstam Staffan , Rosfors Stefan
Published: March 2004

In the present prospective study colour duplex ultrasound was used to investigate the vertebral arteries in 117 patients referred for carotid duplex examination. The study aimed to identify flow abnormalities and factors influencing blood flow haemodynamics by calculating the resistance index (RI) in the vertebral and common carotid arteries. Vertebral artery RI was decreased in patients with severe carotid artery disease (≥80% stenosis or occlusion) caused mainly by an increased diastolic flow velocity. By contrast, patients without severe carotid artery disease showed an age‐related increase in vertebral artery RI. The RI in the common carotid artery was increased in patients with local atherosclerosis in the carotid bulb, and was increased with age. There was significantly better visualization of the right vertebral artery origin than of the left (75% versus 62%, P<0·05). Stenotic lesions were found in 15% of the carotid bifurcations and in 7% of the vertebral arteries. It is concluded that vertebral artery haemodynamics can be evaluated using colour duplex ultrasound; however, there are difficulties in visualizing the vertebral artery origin, especially on the left side. Even at advanced age, the vertebral arteries can reduce flow resistance to maintain cerebral blood flow in patients with occluded or severely stenosed carotid arteries. RI in vertebral arteries in patients without severe carotid occlusive disease, and in common carotid arteries, is mainly affected by local atherosclerosis and age, which increase the flow resistance.
Practical Evaluation of Methods for Detection and Specificity of Autoantibodies to Extractable Nuclear Antigens
Authors: Orton Susan M. , Peace-Brewer Amy , Schmitz John L. , Freeman Kristie , Miller William C. , Folds James D.
Published: March 2004

Detection and specificity of autoantibodies against extractable nuclear antigens (ENA) play a critical role in the diagnosis and management of autoimmune disease. Historically, the detection of these antibodies has employed double immunodiffusion (DID). Autoantibody specificity was correlated with diagnoses by this technique. Enzyme immunoassays have been developed by multiple manufacturers to detect and identify the specificity ENA autoantibodies. To address the relationship of ENA detection by DID and enzyme immunoassay, the performances of five immunoassays were compared. These included two DID and three enzyme-linked immunoassays (ELISA) (both screening and individual antigen profile kits). The sample set included 83 ENA-positive, antinuclear-antibody (ANA)-positive specimens, 77 ENA-negative, ANA-positive specimens, and 20 ENA- and ANA-negative specimens. Sensitivity and specificity were calculated by two methods: first, by using the in-house DID result as the reference standard, and second, by using latent class analysis, which evaluates each kit result independently. Overall, the results showed that the ELISA methods were more sensitive for detection of ENA autoantibodies than DID techniques, but presence and/or specific type of ENA autoantibody did not always correlate with the patient's clinical presentation. Regardless of the testing strategy an individual laboratory uses, clear communication with the clinical staff regarding the significance of a positive result is imperative. The laboratory and the clinician must both be aware of the sensitivity and specificity of each testing method in use in the clinical laboratory.
OUTPUT AND FIDELITY OF IMPERFECT TELEPORTATION
Authors: GU YONG-JIAN , YAO CHUN-MEI , ZHOU ZHENG-WEI , GUO GUANG-CAN
Published: March 2004

Noisy entangled resource and non-standard teleportation operations result in imperfect teleportation. In this paper, we derive an explicit expression for the output states of imperfect teleportation processes, thereby establishing a correspondence between teleportation and quantum channels. This result offers a different insight into teleportation. Also, it enables us to derive an expression for the fidelity of teleportation. Our results analytically reveal the dependence of the output states and the fidelity on the entangled resource and teleportation operations. The Nielsen–Caves teleportation formalism is used in the derivation.
MIXED ALKALI EFFECT IN BORATE GLASSES — EPR AND OPTICAL BAND GAP STUDIES IN xNa2O-(30-x)K2O-70 B2O3 GLASSES DOPED WITH Gd3+ IONS
Authors: SREEKANTH CHAKRADHAR R. P. , RAMESH K. P. , RAO J. L. , RAMAKRISHNA J.
Published: March 2004

Mixed alkali borate x Na 2 O -(30-x) K 2 O -70 B 2 O 3(5≤x≤25) glasses doped with 0.5 mol% of gadolinium ions have been investigated by using electron paramagnetic resonance (EPR) and optical absorption techniques, as a function of alkali content, to look for the "mixed alkali effect" on the spectral properties of the glasses. The EPR spectrum consists of three prominent features with effective g-values, g≈5.6, 2.8 and 2.0, and two weak features at g≈3.3 and 4.3. The three EPR signals at g≈2.0, g≈2.8 and g≈5.6 are attributed to Gd 3+ ions located at sites with weak, intermediate and strong cubic symmetry fields, respectively. In principle these sites may be of network forming and network modifying types. Ionic radius considerations suggest that gadolinium ions cannot substitute the much smaller boron ions and thus only the network modifier site is acceptable. The number of spins (N) participating in resonance and its paramagnetic susceptibility (χ) for g≈5.6 resonance line have been calculated. It is interesting to note that N and χ increase with x and reach a maximum around x=15 and thereafter decrease showing the mixed alkali effect in these glasses. From ultraviolet absorption edges, the optical band gap energies were evaluated. It is interesting to note that the optical band gap energies for these glasses decrease slightly with increasing x and reach a minimum around x=10, and thereafter increase showing the mixed alkali effect. Optical band gap energies (E opt ) obtained in the present work vary from 2.20–3.35 eV for both the direct and indirect transitions. The physical parameters of the glasses have been evaluated with respect to the composition.
BEYOND DENSITY FUNCTIONAL THEORY: THE DOMESTICATION OF NONLOCAL POTENTIALS
Authors: NESBET ROBERT K.
Published: March 2004

Due to efficient scaling with electron number N, density functional theory (DFT) is widely used for studies of large molecules and solids. Restriction of an exact mean-field theory to local potential functions has recently been questioned. This review summarizes motivation for extending current DFT to include nonlocal one-electron potentials, and proposes methodology for implementation of the theory. The theoretical model, orbital functional theory (OFT), is shown to be exact in principle for the general N-electron problem. In practice it must depend on a parametrized correlation energy functional. Functionals are proposed suitable for short-range Coulomb-cusp correlation and for long-range polarization response correlation. A linearized variational cellular method (LVCM) is proposed as a common formalism for molecules and solids. Implementation of nonlocal potentials is reduced to independent calculations for each inequivalent atomic cell.
PLASTIC INFRARED DETECTORS BASED ON POLY(3,4-ETHYLENEDIOXYTHIOPHENE):POLY(STYRENE SULFONIC ACID)
Authors: MESKERS STEFAN C. J. , VAN DUREN JEROEN K. J. , JANSSEN RENÉ A. J.
Published: March 2004

Illumination of films of the π-conjugated polymeric conductor poly(3,4-ethylene-dioxythiophene):poly(styrenesulfonate) with infrared radiation results in a transient enhancement of its electrical conductivity. This phenomenon can be employed to detect infrared light. Recent experimental evidence is reviewed indicating that the transient increment in the conductivity can be understood in terms of a local heating effect. Thermalization of the carriers, a process which can be studied by optical techniques, is found to proceed very rapidly.
A MODIFIED ONE-CENTER METHOD FOR MOLECULAR ELECTRONIC STRUCTURE CALCULATION: AN APPLICATION TO ${\rm H}^+_2$
Authors: SHI TING-YUN , ZHANG ZHAN-JUN , LI BAI-WEN
Published: March 2004

A modified one-center expansion method for calculating the electronic structures of the single-electron molecule is developed. Both the radial and the angular wave functions are expanded in terms of B-splines. Using the special properties of B-splines, we build the nuclear positions into the basis functions, which makes our method approximate well the cusps of the electronic wave functions and accordingly considerably improve the convergence of eigenenergies. As a test, the five lowest σ electronic states of the [Formula: see text] molecule are calculated at the equilibrium bond length (about 2 a.u.). The energies reach an accuracy of 10-5 a.u. and partly even of 10-6 a.u. In addition, the potential applications of the present method to the electron-capture processes in ion-atom collisions are discussed.
ENTROPY OF EQUILIBRIUM MEASURES OF CONTINUOUS PIECEWISE MONOTONIC MAPS
Authors: BUZZI JÉRÔME
Published: March 2004

Considering the thermodynamical formalism of dynamical systems, P. Walters showed that for β-transformations all Lipschitz weights define quasi-compact transfer operators and therefore unique equilibrium measures which additionally have positive entropy and good mixing properties. In this note we generalize this to continuous piecewise monotonic maps of the interval. The case of piecewise monotonic maps with discontinuities remains open.
SCALING LIMITS FOR BEAM WAVE PROPAGATION IN ATMOSPHERIC TURBULENCE
Authors: FANNJIANG ALBERT C. , SOLNA KNUT
Published: March 2004

We prove the convergence of the solutions of the parabolic wave equation to that of the Gaussian white-noise model widely used in the physical literature. The random medium is isotropic and is assumed to have integrable correlation coefficient in the propagation direction. We discuss the limits of vanishing inner scale and divergent outer scale of the turbulent medium.
THE CENTRAL LIMIT THEOREM FOR STATIONARY MARKOV CHAINS UNDER INVARIANT SPLITTINGS
Authors: GORDIN MIKHAIL , HOLZMANN HAJO
Published: March 2004

The central limit theorem (CLT) for stationary ergodic Markov chains is investigated. We give a short survey of related results on the CLT for general (not necessarily Harris recurrent) chains and formulate a new sufficient condition for its validity. Furthermore, Markov operators are considered which admit invariant orthogonal splittings of the space of square-integrable functions. We show how conditions for the CLT can be improved if this additional structure is taken into account. Finally we give examples of this situation, namely endomorphisms of compact Abelian groups and random walks on compact homogeneous spaces.
Properties of Mouse Cutaneous Rapidly Adapting Afferents: Relationship to Skin Viscoelasticity
Authors: Grigg P. , Robichaud D. R. , Del Prete Z.
Published: March 2004

When skin is stretched, stimuli experienced by a cutaneous mechanoreceptor neuron are transmitted to the nerve ending through the skin. In these experiments, we tested the hypothesis that the viscoelastic response of the skin influences the dynamic response of cutaneous rapidly adapting (RA) neurons. Cutaneous RA afferent neurons were recorded in 3 species of mice (Tsk, Pallid, and C57BL6) whose skin has different viscoelastic properties. Isolated samples of skin and nerve were stimulated mechanically with a dynamic stretch stimulus, which followed a pseudo Gaussian waveform with a bandwidth of 0–60 Hz. The mechanical response of the skin was measured as were responses of single RA cutaneous mechanoreceptor neurons. For each neuron, the strength of association between spike responses and the dynamic and static components of stimuli were determined with multiple logistic regression analysis. The viscoelastic material properties of each skin sample were determined indirectly, by creating a nonlinear (Wiener–Volterra) model of the stress–strain relationship, and using the model to predict the complex compliance (i.e., the viscoelastic material properties). The dynamic sensitivity of RA mechanoreceptor neurons in mouse hairy skin was weakly related to the viscoelastic properties of the skin. Loss modulus and phase angle were lower (indicating a decreased viscous component of response) in Tsk and Pallid than in C57BL6 mice. However, RA mechanoreceptor neurons in Tsk and Pallid skin did not differ from those in C57 skin with regard to their sensitivity to the rate of change of stress or to the rate of change of incremental strain energy. They did have a decreased sensitivity to the rate of change of tensile strain. Thus the skin samples with lower dynamic mechanical response contained neurons with a somewhat lower sensitivity to dynamic stimuli.
Foreign Intelligence and the Historiography of the Cold War
Authors: Garthoff Raymond L.
Published: March 2004

Foreign intelligence played a number of important roles in the Cold War, but this topic has not received the scholarly attention it deserves. This survey article provides a broad overview of some of the new literature and documentation pertaining to Cold War era intelligence, as well as the key dimensions of the topic. Despite the continued obstacles posed by secrecy and the mixed reliability of sources, the publication of numerous memoirs and the release of a huge volume of fresh archival material in the post— Cold War era have opened new opportunities to study the role of intelligence in Cold War history. Scholars should explore not only the “micro level” of the problem (the impact of intelligence on specific events) but also the “macro level,” looking at the many ways that the Cold War as a whole (its origins, its course, and its outcome) was influenced, perhaps even shaped, by the intelligence agencies of the United States, the Soviet Union, and other key countries. It is also crucial to examine the unintended consequences of intelligence activities. Some interesting examples of “blowback” (effects that boomerang against the country that initiated them) have recently come to light from intelligence operations that the United States undertook against the Soviet Union. Only by understanding the complex nature of the role of intelligence during the Cold War will we be able to come to grips with the historiographic challenge that the topic poses.
HOSTAGES DURING THE FIRST CENTURY OF THE CRUSADES
Authors: Kosto Adam
Published: March 2004

The use of hostages as a means of guarantee was most common in the medieval period in diplomatic and military encounters. The Crusades offer an excellent opportunity to study this institution in the context of intercultural relations and conflict. After briefly considering precedent traditions in Western Europe, Byzantium, and the Islamic world, this article examines the various specific functions hostages served: as guarantors of short-term agreements, such as those for safe passage or for the end of a siege, and of longer-term undertakings, such as treaties, alliances, and promises of ransom. The siege of Acre brings together many of these various functions in a single episode. The article closes by addressing two questions: the effectiveness of hostages as a means of surety; and the role of cultural difference in determining the outcome of hostage transactions and how they were viewed by contemporaries.
SUFISM'S ROLE IN AL-GHAZĀLĪ'S FIRST CRISIS OF KNOWLEDGE
Authors: Bargeron Carol
Published: March 2004

This paper reconstructs the chronology, content, and consequences of al-Ghazālī's first crisis of knowledge for his epistemological doctrine. In so doing, we explore his teaching on: 1) sense perceptions, 2) axiomatic cognitions, and 3) the knowledge-claims which are made on the basis of each source. We also explain why his skepticism emerged, what its exact dimensions were, how his skeptical interlude ended, and what the restoration of certitude about rational knowledge entailed for him in the approximate period between 461/1068-1069 and 488/1094-1095. In answering these questions, we emphasize and clarify the role that popular Sufism, especially in terms of its doctrine of esoteric knowledge or ma'rifa, played in the formation of al-Ghazālī's essential perspective on rational knowledge.
TRANSLATING SICILY
Authors: Mallette Karla
Published: March 2004

This article sketches a theoretical strategy for approaching the literary history of Norman Sicily (centuries XI-XII). Because of its linguistic complexity—during the Norman era, Sicilians wrote in Arabic, Greek, and Latin—literary historians have resisted treating Siculo-Norman literature as a literary-historical category. Rather, the literature has been divided into three discrete, linguistically defined traditions, understood as colonial extensions of mainland literary traditions. Using a reading of Sicilian coins with multilingual inscriptions in order to examine the parallel use of multiple languages in a single "text," this article argues for a reconsideration of Sicilian literature of the era, one that looks at multilingualism not as a challenge to literary coherence but as constitutive of a literary culture.
Sustainable Development Diplomacy in the Private Business Sector: An Integrative Perspective on Game Change Strategies at Multiple Levels
Authors: Usui Mikoto
Published: March 2004

This article attempts to offer an "integral" perspective for locating the business and industry sector in both political and socio-organizational realms and for capturing major game change strategies envisaged by this sector to contribute more or less actively to emerging sustainable development (SD) regimes. Corporate SD strategies are construed in terms of "three-level games": Level I - changing products through individual management systems; Level II - changing individual business environments; and Level III - changing the international institutional setting. This perspective will help address two overarching preoccupations: (1) how to free the business-society relationship from excess structural biases and reconstruct it through industry and other major social actors engaged in a joint process of "structuration" and (2) how to harness control over the local-global nexus or "vertical inter-linkages" in an operationally meaningful way that would help deepen and broaden existing major multilateral SD agreements.
Sequencing, Acoustic Separation, and 3-D Negotiation of Complex Barriers: Charlene Barshefsky and IP Rights in China
Authors: Sebenius James , Hulse Rebecca
Published: March 2004

Taking the perspective of the lead U.S. negotiator, Charlene Barshefsky, this article details and analyzes the negotiations that took place in the mid-1990s between the United States and the People's Republic of China over intellectual property rights (IPR). Employing a "negotiation analytic" methodology,Charlene Barshefsky's actions are interpreted to suggest a number of promising approaches to managing the daunting complexities of trade and other negotiations: recognizing the multiparty aspects of apparently bilateral dealings and capturing them in a "deal diagram;" carefully assessing "barriers" to agreement; sequencing to build a winning coalition and overcome potentially blocking ones; "acoustic separation" of issue-frames; and, most broadly, changing the game advantageously relative to a purely tactical orientation "at the table" through 3-D actions "away from the table."
Ending Ethnic War: The South Asian Experience
Authors: Sahadevan P.
Published: March 2004

Underscoring the linkage between war strategies and peace processes in seven ethnic wars in the South Asian region, this article examines the conditions under which two wars have ended in military victory, another two in negotiated settlement and the remaining three wars still continue. War strategies of the South Asian governments have effectively combined military tactics with a wide range of political measures to strengthen war processes that, in turn, determine the result of peace processes. This article finds that the pattern of ending a war or its effective prolongation is determined by the nature of power relations between the adversaries, which is factored into the level of mobilization of support in the society, structural cohesion of rebel groups, patterns of goal setting, and the nature of rebel leadership and its commitment to the declared goal.
Apoptosis Gene Network: Description in the GeneNet and TRRD Databases
Authors: STEPANENKO IRINA , KOLCHANOV NIKOLAY
Published: March 2004

Abstract: The large volume of experimental data on apoptosis requires computer processing to systematize and provide an integrated “description of operation” of the gene network that regulates apoptosis in various cell types under varying effects. The database GeneNet contains the description of the apoptosis gene network: (http://wwwmgs.bionet.nsc.ru/systems/mgl/genenet), and the Transcription Regulatory Regions Database (TRRD) contains experimental data on transcription regulation of various genes, including apoptosis genes: (http://wwwmgs.bionet.nsc.ru/mgs/gnw/trrd/).
Mitochondrial Apoptosis Induced by the HIV‐1 Envelope
Authors: CASTEDO MARIA , PERFETTINI JEAN‐LUC , ANDREAU KARINE , ROUMIER THOMAS , PIACENTINI MAURO , KROEMER GUIDO
Published: March 2004

Abstract: The envelope glycoprotein complex (Env), encoded by the human immunodeficiency virus (HIV‐1), kills uninfected cells expressing CD4 and/or the chemokine receptor CXCR4 or CCR5, via at least three independent mechanisms. First, the soluble Env product gp120 can induce the apoptotic cell death of lymphocytes, neurons, and myocardiocytes, via interaction with surface receptors. Second, Env present on the surface of HIV‐1 infected cells can transiently interact with cells expressing CD4 and CXCR4/CCR5, thereby provoking a hemifusion event that results in the death of the uninfected cell. Third, the interaction between Env on infected cells and its receptors on uninfected cells can result in syncytium formation. Such syncytia undergo apoptosis after a phase of latency. In several models of Env‐induced apoptosis, early signs of mitochondrial membrane permeabilization (MMP) become manifest. Such signs include a loss of the mitochondrial transmembrane potential and the release of cytochrome c and AIF. The mechanisms of Env‐triggered apoptotic MMP may involve an elevation of cytosolic Ca2+, reactive oxygen species and/or the transcriptional activation of p53, with the consequent expression of pro‐apoptotic proteins such as Bax, which permeabilizes mitochondrial membranes. The implications of these findings for the pathophysiology of HIV‐1 infection is discussed.
On the Role of Interferon Regulatory Factors in HIV‐1 Replication
Authors: MARSILI GIULIA , BORSETTI ALESSANDRA , SGARBANTI MARCO , REMOLI ANNA LISA , RIDOLFI BARBARA , STELLACCI EMILIA , ENSOLI BARBARA , BATTISTINI ANGELA
Published: March 2004

Abstract: Interferons (IFNs) are pleiotropic cytokines that possess several biological activities and play a central role in basic and applied research as mediators of antiviral and antigrowth responses, modulators of the immune system, and therapeutic agents against viral diseases and cancer. Interferon regulatory factors (IRFs) have been identified together with signal transducers and activators of transcription (STAT) from studies on the type I IFN as well as IFN‐stimulated (ISG) gene regulation and signaling. IRFs constitute a family of transcriptional activators and repressors implicated in multiple biological processes including regulation of immune responses and host defence, cytokine signaling, cell growth regulation, and hematopoietic development. All members share a well‐conserved DNA binding domain at the NH2‐terminal region that recognizes similar DNA sequences, termed IRF element (IRF‐E)/interferon‐stimulated response element (ISRE), present on the promoter of target genes. Recently, a sequence homologous to the ISRE has been identified downstream from the 5′ human immunodeficiency virus type 1 (HIV‐1) long terminal repeat (LTR). This sequence is a binding site for IRF‐1 and IRF‐2. Here we briefly summarize the role of IRFs in the regulation of HIV‐1 LTR transcriptional activity and virus replication. The overall effect of IRFs on HIV‐1 replication will also be discussed in the context of strategies carried out by the virus to counteract the IFN‐mediated host defences both in active replication and during the establishment of viral latency.
An Investigation of the MEK/ERK Inhibitor U0126 in Acute Myeloid Leukemia
Authors: KERR A H J. , JAMES J A. , SMITH M A. , WILLSON C , COURT E L. , SMITH J G.
Published: March 2004

Abstract: Blockade of mitogen‐activated protein kinase kinase (MEK1/2), part of the extracellular signal‐regulated kinase (ERK) or p44/42 mitogen‐activated protein kinase (MAPK) pathway, has been shown in some instances to cause apoptosis in leukemic blast cells. This investigation examined the effect of the potent MEK/ERK inhibitor U0126 on apoptosis in acute myeloblastic leukemia (AML) cell lines, and acute leukemic and non‐leukemic patient samples. The pro‐apoptotic effect of the inhibitor varied across the five cell lines tested (KG1a, HEL, TF‐1, MO7e, and THP‐1) from highly significant induction of apoptosis to no apparent response. The pro‐apoptotic effect of U0126 in the most sensitive cell line, KG1a, appeared to be related to its CD34 positivity. Three of five leukemic bone marrow samples showed considerable sensitivity to the inhibitor and a similar association with CD34 expression was evident. Interestingly, control marrow cells from six non‐leukemic patients did not show a significant effect when exposed to U0126. These results suggest that this agent may offer a potential alternative to standard chemotherapy with a particular role in the most primitive types of leukemia, these often being the most resistant to standard chemotherapy.
The Effect of p38 Mitogen‐Activated Protein Kinase on Mucin Gene Expression and Apoptosis in Helicobacter pylori‐Infected Gastric Epithelial Cells
Authors: KIM HYEYOUNG , SEO JI HYE , KIM KYUNG HWAN
Published: March 2004

Abstract: The loss of mucus coat continuity and apoptosis have been shown in Helicobacter pylori (H. pylori)‐infected gastric tissues. Blockade of p38 mitogen‐activated kinase (MAPK) produced reversal in the LPS‐induced reduction in mucin synthesis and apoptosis in gastric epithelial cells. This study investigates whether H. pylori induces apoptosis, alterations in mucin gene (MUC) expression, and p38 MAPK activation in human gastric epithelial AGS cells. After treatment of AGS cells with H. pylori at the ratio of 1:300, apoptosis was determined by DNA fragmentation and DNA laddering. MUC expression was assessed by RT‐PCR. p38 MAPK activation and mucin protein level, using anti‐mucin antibody for MUC5/6, were determined by Western blot analysis. As a result, H. pylori induced apoptosis and loss of mucin, which was supported by reduced mRNA expression of MUC5AC by H. pylori in AGS cells. MUC7/8 expression and p38 MAPK activation were induced in H. pylori‐infected AGS cells. In conclusion, H. pylori induces p38 MAPK activation, wh3.ich may be the underlying mechanism of alterations in MUC expression and apoptosis in gastric epithelial cells.
Inhibition of JNK by HGF/SF Prevents Apoptosis Induced by TNF‐α
Authors: REVENEAU SYLVIE , PAUMELLE RÉJANE , DEHEUNINCK JULIEN , LEROY CATHERINE , DE LAUNOIT YVAN , FAFEUR VÉRONIQUE
Published: March 2004

Abstract: We investigated whether repression of JNK by hepatocyte growth factor/scatter factor (HGF/SF) in MDCK epithelial cells is linked to its ability to protect cells from apoptosis. To this purpose, cells were treated by TNF‐α, a well‐known inducer of JNK and of cell death, and the effects of HGF/SF were investigated under these conditions. We identified repression of JNK as a signaling target of HGF/SF for protection against TNF‐α‐induced cell death. This effect of HGF/SF occurs via the activation of the PI3K and MEK1 pathways.
A Recombinant Fragment of Human Surfactant Protein D Reduces Alveolar Macrophage Apoptosis and Pro‐Inflammatory Cytokines in Mice Developing Pulmonary Emphysema
Authors: CLARK HOWARD , PALANIYAR NADES , HAWGOOD SAMUEL , REID KENNETH B M.
Published: March 2004

Abstract: Rapid removal of apoptotic cells is an important mechanism for immune homeostasis and the resolution of inflammation. Delayed clearance of apoptotic alveolar macrophages may cause activation of healthy bystander macrophages and contribute to high macrophage number and emphysema in surfactant protein D (SP‐D) knock‐out mice. Using flow cytometry and Annexin V and propidium iodide as markers for apoptosis and necrosis, respectively, SP‐D‐deficient mice were found to have a 5‐ to 10‐fold increase in the number of apoptotic and necrotic alveolar macrophages in the lungs. SP‐D‐deficient mice accumulate apoptotic macrophages in the lung, and this accumulation can be reduced by treatment with recombinant SP‐D (but not SP‐A). The recombinant SP‐D binds preferentially to apoptotic cells. The data are consistent with a specific role in vivo for SP‐D in promoting apoptotic cell clearance in the lungs to limit macrophage‐mediated inflammation and reveal a potential new mechanism for therapeutic targeting in the prevention of emphysema.
Bcl‐2 Prevents Loss of Cell Viability and Caspase Activation Induced by 3‐Nitropropionic Acid in GT1‐7 Cells
Authors: BRITO OLGA , ALMEIDA SANDRA , OLIVEIRA CATARINA R. , REGO A CRISTINA
Published: March 2004

Abstract: In this study, we analyzed the effect of Bcl‐2 overexpression, an important anti‐apoptotic protein, by using two hypothalamic cell lines, GT1‐7puro or GT1‐7bcl‐2. 3‐Nitropropionic acid (3‐NP) mediated a dose‐dependent decrease in cell viability in GT1‐7puro cells, as determined by following the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) reduction, which was significantly prevented in GT1‐7bcl‐2 cells. In addition, activation of caspases−2, −3, and −6 induced by 3‐NP was prevented by Bcl‐2 overexpression. The data suggest that irreversible inhibition of mitochondrial complex II induces apoptotic features of cell death in a process prevented by Bcl‐2.
Cisplatin‐Induced Apoptosis in HL‐60 Human Promyelocytic Leukemia Cells
Authors: FLOROS KOSTAS V. , THOMADAKI HELLINIDA , LALLAS GEORGE , KATSAROS NIKOS , TALIERI MAROULIO , SCORILAS ANDREAS
Published: March 2004

Abstract: The anti‐apoptotic molecule BCL2 delays cell‐cycle entry from quiescence. We have recently cloned a new member of the BCL2 family of apoptosis‐related genes, BCL2L12. In the present study, the expression of BCL2 and BCL2L12 genes during cisplatin‐induced apoptosis in HL‐60 leukemic cells was investigated. The kinetics of apoptosis induction and cell toxicity were evaluated by DNA laddering and the MTT method, respectively. BCL2 and BCL2L12 expression was analyzed by RT‐PCR using gene‐specific primers. The ratio of apoptotic cells increased with increasing concentrations of cisplatin and exposure time of cell culture to the drug. Gradual, time‐dependent downregulation of BCL2 gene was observed during cisplatin treatment. Up‐regulation of BCL2L12 was observed 3 h (no DNA fragmentation) and 6 h (initiation of the DNA fragmentation) after treatment with cisplatin, followed by a decrease of its expression after 12‐h continuous treatment with the drug. It is known that the main anti‐carcinogenic effect of cisplatin is due to the induction of cell apoptosis. Present results indicate that downregulation of the BCL2 and upregulation of the BCL2L12 gene may be the underlying mechanisms.
TNFα Potentiates 2‐Methoxyestradiol‐Induced Mitochondrial Death Pathway
Authors: DJAVAHERI‐MERGNY MOJGAN , WIETZERBIN JUANA , ROUILLARD DANY , BESANÇON FRANÇOISE
Published: March 2004

Abstract: Ewing sarcoma cells are resistant to TNFα‐induced cell death and this resistance results from the activation of the transcription factor NF‐κB. Here, we investigated whether NF‐κB activation interferes with 2‐Me‐induced cell death signaling in Ewing sarcoma cells and we examined the effect of treatment of these cells with 2‐Me either alone or in combination with TNFα. Our results show that TNFa cooperates with 2‐Me to induce apoptosis in Ewing tumor cells through mitochondrial cell death signaling. These results suggest that the use of TNFα in combination with 2‐Me may be beneficial for Ewing tumor treatment.
Orphan Nuclear Receptor Nur77 Translocates to Mitochondria in the Early Phase of Apoptosis Induced by Synthetic Chenodeoxycholic Acid Derivatives in Human Stomach Cancer Cell Line SNU‐1
Authors: JEONG JIN HEE , PARK JOO‐SUNG , MOON BONGKYUNG , KIM MIN CHAN , KIM JAE‐KON , LEE SUNGEUN , SUH HONGSUK , KIM NAM DEUK , KIM JONG‐MIN , PARK YOUNG CHUL , YOO YOUNG HYUN
Published: March 2004

Abstract: Apoptosis‐inducing activity of synthetic CDCA derivatives, HS‐1199 and HS‐1200, on gastric cancer cell line SNU‐1 cells was explored. CDCA derivatives demonstrated various apoptosis hallmarks, such as mitochondrial changes, activation of caspase, DNA fragmentation, and nuclear condensation. Importantly, the orphan receptor Nur77 (TR3) was shown to translocate from the nucleus to mitochondria at the early time points after CDCA derivatives treatment. These data support the theory that CDCA derivatives‐induced apoptosis of SNU‐1 gastric cancer cell lines is mediated by mitochondria and caspase, and, at least in part, by Nur77.
A Novel Antioxidant‐Inhibited Dexamethasone‐Mediated and Caspase‐3‐Independent Muscle Cell Death
Authors: ORZECHOWSKI ARKADIUSZ , JANK MICHAL , GAJKOWSKA BARBARA , SADKOWSKI TOMASZ , GODLEWSKIA MICHAL MAREK
Published: March 2004

Abstract: Dexamethasone (Dex)‐mediated cell death is associated with repression of survival factors (AP‐1, c‐myc, NF‐κB). Dex suppressed the activity of genes encoding antioxidant enzymes leading to impaired viability and apoptotic cell death. These findings suggest that reactive oxygen species inhibit protein synthesis and amplify m‐calpain‐dependent proteolysis. The events that led to death of L6 muscle cells were most likely triggered by Dex‐mediated repression of antioxidative defenses on the genomic level.
Caspase Inhibitors as a Supplement in Immune Activation Therapies to Achieve Eradication of HIV in Its Latent Reservoirs
Authors: SCHELLER CARSTEN , SOPPER SIEGHART , KOUTSILIERI ELENI , LUDWIG STEPHAN , TER MEULEN VOLKER , JASSOY CHRISTIAN
Published: March 2004

Abstract: Synthetic caspase inhibitors are known to block death receptor‐induced apoptosis. We have reported previously that in addition to apoptosis inhibition, caspase inhibitors induce a switch from proapoptotic to proinflammatory signaling in T cells. This switch sensitizes TNF‐R1 to trigger TNF‐α‐induced reactivation of HIV in latently infected T cells. Here we ponder the prospects of caspase inhibitors as a supplement in immune activation therapies (IAT) to achieve eradication of HIV from the latent virus reservoirs in HIV‐infected patients.
Apoptotic Cell Death of Cybrid Cells Bearing Leber's Hereditary Optic Neuropathy Mutations Is Caspase Independent
Authors: ZANNA CLAUDIA , GHELLI ANNA , PORCELLI ANNA MARIA , CARELLI VALERIO , MARTINUZZI ANDREA , RUGOLO MICHELA
Published: March 2004

Abstract: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by selective death of retinal ganglion cells. Three pathogenic mtDNA point mutations induce an impairment of oxidative phosphorylation. We have investigated whether the release of cytochrome c during incubation of LHON cybrids in galactose medium leads to activation of the executive caspase‐3 and to alteration of the energetic status of cells. From our research, it can be concluded that apoptotic cell death induced in LHON cybrid by galactose medium is caspase independent. It remains to be explained how the significant fragmentation of intranucleosomal DNA observed in LHON cybrids could also occur in the absence of caspase activation.
Involvement of the Change in Chromatin Structure in Thymocyte Apoptosis Induced by Phosphorylation of Histones
Authors: ENOMOTO RIYO , YOSHIDA YUKARI , KOMAI TOMOE , SUGAHARA CHIYOKO , YASUOKA YUKA , LEE EIBAI
Published: March 2004

Abstract: The inhibitors of protein phosphatase such as calyculin A and okadaic acid induced thymocyte apoptosis. DNA fragmentation was increased in the nuclei from thymocytes treated with calyculin A, which accelerated phosphorylation of histones. Judging from the circular dichroism analysis, the structure of soluble chromatin was changed by the treatment with calyculin A. These results suggest that the change in chromatin structure may be one of the molecular mechanisms of internucleosomal DNA fragmentation.
Convergence of the NF‐κB and Interferon Signaling Pathways in the Regulation of Antiviral Defense and Apoptosis
Authors: HISCOTT JOHN , GRANDVAUX NATHALIE , SHARMA SONIA , TENOEVER BENJAMIN R. , SERVANT MARC J. , LIN RONGTUAN
Published: March 2004

Abstract: The ubiquitously expressed interferon regulatory factor 3 (IRF‐3) is directly activated following virus infection and functions as a key activator of the immediate‐early Type 1 interferon (IFN) genes. Using DNA microarray analysis (8,556 genes) in Jurkat T cells inducibly expressing constitutively active IRF‐3, several target genes directly regulated by IRF‐3 were identified. Among the genes upregulated by IRF‐3 were transcripts for a subset of known IFN‐stimulated genes (ISGs), including ISG56, which functions as an inhibitor of translation initiation. Phosphorylation of C‐terminal Ser/Thr residues—‐382GGASSLENTVDLHISNSHPLSLTSDQY408—is required for IRF‐3 activation. Using C‐terminal point mutations and a novel phosphospecific antibody, Ser396 was characterized as the minimal phosphoacceptor site required in vivo for IRF‐3 activation following Sendai virus (SeV) infection, expression of viral nucleocapsid, or double‐stranded RNA (dsRNA) treatment. The identity of the virus‐activated kinase (VAK) activity that targets and activates IRF‐3 and IRF‐7 has remained a critical missing link in the understanding of interferon signaling. We report that the IKK‐related kinases—IKKε/TBK‐1—are components of VAK that mediate IRF‐3 and IRF‐7 phosphorylation and thus functionally link the NF‐κB and IRF pathways in the development of the antiviral response.
Translational Upregulation of the X‐Linked Inhibitor of Apoptosis
Authors: HOLCIK MARTIN
Published: March 2004

Abstract: The X‐linked inhibitor of apoptosis protein (XIAP) is the most potent and best studied intrinsic regulator of programmed cell death. The critical role XIAP plays in the control of apoptosis is also reflected in the complex ways the activity of XIAP is regulated. In addition to regulating the function of the protein, the synthesis of XIAP is also selectively regulated. XIAP is translated by a cap‐independent mechanism of translation initiation that is mediated by a unique internal ribosome entry site (IRES) sequence element located in its 5′ untranslated region. This allows XIAP mRNA to be actively translated during conditions of cellular stress when the majority of cellular protein synthesis is inhibited. The IRES regulation of XIAP translation points to an important mechanism in the control and regulation of apoptosis.
PLAG Proteins
Authors: DECLERCQ JEROEN , HENSEN KAREN , VAN DE VEN WIM J. , CHAVEZ MARCELA
Published: March 2004

Abstract: Pleomorphic adenoma gene 1 product (PLAG1) a transcription factor with zinc finger domains, is upregulated in several tumors, such as pleomorphic adenomas and lipoblastomas. PLAGL2 is a second member of the same subfamily of zinc finger proteins. Cells overexpressing either of these two genes display the typical markers of neoplastic transformation. We investigated whether PLAG1 and PLAGL2 could prevent cells from undergoing apoptosis, leading them to grow uncontrollably.
How the Nucleolar Sequestration of p53 Protein or Its Interplayers Contributes to Its (Re)‐Activation
Authors: WĘSIERSKA‐GĄDEK JÓZEFA , HORKYA MARCEL
Published: March 2004

Abstract: The tumor suppressor p53 is a short‐lived protein that under normal conditions is reduced to a barely detectable level. The stability of p53 protein is primarily regulated in normal non‐transformed cells by two interplayers: Mdm2 and p14ARF. Relocation of p53, Mdm2, and p14ARF to the nucleolus seems to regulate, at least partially, the steady‐state of p53. Moreover, there are alternative pathways of the regulation of p53 stability in unstressed cells. Jun‐N(amino)‐terminal kinase (JNK) and poly(ADP‐ribose) polymerase‐1 (PARP‐1) are involved in the regulation of the steady‐state of wild‐type (wt) p53 protein. However, in most human cervical carcinomas, which express the high‐risk human papilloma viruses (HPVs) E6 protein, a complete switch from Mdm2 to HPV E6‐mediated degradation of p53 occurs. Virally encoded E6 protein utilizes the cellular ubiquitin‐protein ligase termed E6‐associated protein (E6‐AP) to target p53 protein for proteolytic degradation. We recently addressed the question of whether p53 protein can be generally reactivated by chemotherapy in HeLa cells despite the E6 activity. We observed an increase of cellular p53 after cisplatin (CP) treatment. p53 protein accumulated preferentially in the nucleoli. We checked the cellular level of E6 during CP therapy. Six hours after application of CP the expression of E6 protein was markedly reduced. This coincided with the increase of cellular p53 level and preceded the nucleolar accumulation of p53 protein, thereby indicating that repression of virally coded E6 protein by CP contributes to the restoration of p53 expression.
MNNG Induces Dramatic DNA Damage and Non‐Apoptotic Changes in Cervical Carcinoma HeLa Cells
Authors: WĘSIERSKA‐GĄDEK JÓZEFA , GUEORGUIEVA MARIETA , WOJCIECHOWSKI JACEK
Published: March 2004

Abstract: It has been previously reported that a short treatment of human cervix carcinoma HeLa cells with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) induced apoptosis. We examined the action of MNNG on HeLa cells and compared it with that of cisplatin. MNNG damaged the integrity of the cell membrane and killed the cells within 3 hours. During this period no changes characteristic for apoptosis, such as cell shrinkage, condensation of nuclei, chromatin fragmentation or activation of caspases, could be detected. However, the exposure of HeLa cells to 50 μM MNNG for 1 h resulted in dramatic DNA damage. The MNNG‐induced disruption of cell membrane associated with cell death indicates that HeLa cells die by necrosis.
Oxalate Exposure Promotes Reinitiation of the DNA Synthesis and Apoptosis of HK‐2 Cells, a Line of Human Renal Epithelial Cells
Authors: KOUL SWEATY , FU SHERRY , KOUL HARI
Published: March 2004

Abstract: Oxalate, a metabolic end product, is a major constituent of kidney stones. Previously, we and others have demonstrated that oxalate is toxic to renal epithelial cells. In the present study, we characterized oxalate‐induced cell death in HK2 cells, a line of renal epithelial cells from the human kidney. For these studies, HK2 cells were exposed to oxalate for various time points. Cells were examined for nuclear morphology, DNA fragmentation, and expression of various apoptosis‐related proteins. Apoptotic mode of cell death was also confirmed by TUNEL assay. Results from these studies revealed that oxalate exposure resulted in time‐dependent increase in DNA fragmentation. Maximum DNA fragmentation was observed at 2–24 hours following oxalate exposure. Results from Western blot analysis demonstrated an increased expression of the FAS ligand. Taken together, these data reveal that oxalate‐associated nephrotoxicity results from oxalate‐induced apoptosis of renal epithelial cells.
1‐Trichloromethyl‐1,2,3,4‐tetrahydro‐β‐carboline (TaClo) Induces Apoptosis inHuman Neuroblastoma Cell Lines
Authors: AKUNDI RAVI SHANKAR , HÜLL MICHAEL , CLEMENT HANS WILLI , FIEBICH BERND L.
Published: March 2004

Abstract: The former popular hypnotic chloral hydrate has been known to spontaneously condense with tryptamine in the body to give rise to a highly unpolar 1‐trichloromethyl‐1,2,3,4‐tetrahydro‐β‐carboline (TaClo) derivative. Earlier studies have revealed the relative permeability of the molecule through the body, and its ability to induce Parkinson‐like symptoms in rats. In this study, we report that TaClo is a highly cytotoxic agent that leads to apoptosis in human neuroblastoma cells involving caspase‐3 activation.
Induction of Apoptosis by Erucylphospho‐N,N,N‐trimethylammonium Is Associated with Changes in Signal Molecule Expressionand Location
Authors: BERGER MARTIN R. , TSONEVA IANA , KONSTANTINOV SPIRO M. , EIBL HANSJÖRG
Published: March 2004

Abstract: At concentrations effecting apoptosis, the alkylphosphocholine ErPC3 induced increased expression of the Rb protein in breast cancer (MCF‐7) and leukemia (SKW‐3, AR‐230) cell lines as well as hypophosphorylation (K‐562, CMLT‐1, DOHH‐2) and fragmentation of Rb (BV‐173, SKW‐3) in leukemia cell lines. ErPC3 exerts at least part of its antineoplastic activity by apoptosis, and this chain of events comprises early changes in the lipid raft fraction of the cellular membrane as well as modulation of different signal molecules, such as Abl, Bcr‐Abl (fusion protein), and Rb.
Antiproliferative and Apoptosis‐Inducing Effects of Hemin in Hepatoma Cells
Authors: DIACONU CARMEN‐CRISTINA , SZATHMÁRI MARGIT , VENETIANER ANIKO
Published: March 2004

Abstract: Hemin is an extremely versatile molecule that may have cytotoxic or cytoprotective effects on certain cells. We investigated the effect of hemin on the growth of hepatoma cells, including the multidrug‐resistant ones. Searching for new tools that interfere with the growth of hepatomas is an important area of clinical research. Cell viability and proliferation of drug‐sensitive and multidrug‐resistant hepatoma cell lines was determined using the trypan‐blue exclusion test XTT/PMS and colony‐forming ability assays. Apoptosis was assessed by confocal microscopy and DNA ladder assay. Hemin inhibited the proliferation and induced apoptosis in both drug‐sensitive and multidrug‐resistant hepatoma cells overexpressing functional P‐glycoprotein. zVAD‐fmk inhibited the hemin‐induced decrease in cell viability, pointing to a role of caspases in hemin‐induced apoptosis. The antiproliferative and apoptosis‐inducing effects of hemin might be considered in the design of treatment for patients with hepatoma.
The Role of β‐Glucuronidase in Induction of Apoptosis by Genistein Combined Polysaccharide (GCP) in Xenogeneic Mice Bearing Human Mammary Cancer Cells
Authors: YUAN LAN , WAGATSUMA CHIHIRO , SUN BUXIANG , KIM JUNG‐HWAN , SURH YOUNG‐JOON
Published: March 2004

Abstract: In order to reveal the mechanisms underlying genistein combined polysaccharide (GCP) inhibition of tumor proliferation, we investigated the effects of GCP on the growth of human breast cancer cells transplanted to athymic nude mice. We further investigated the metabolism of genistein and its association with the β‐glucuronidase activity in tumor and normal tissues.