bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral-Based Myocardial Gene Therapy Approaches to Alter Cardiac Function
Authors: Williams Matthew L. , Koch Walter J.
Published: February 2004

▪ Abstract  In recent years there has been a rapid expansion in our understanding of the molecular biology that underpins human physiology. In the heart, elegant molecular pathways have been elucidated, and derangements in these pathways have been identified as factors in cardiac disease. However, as our understanding has grown, we have recognized that there exist only relatively crude tools to effect changes in molecular pathophysiology. The ultimate promise of gene therapy is to correct the molecular derangements that cause illness. To bring this promise to fruition in the clinical arena, many problems need to be solved, and chief among these remains reliable and robust delivery of genes to the target organ. To this end, viral vectors have been utilized with success more frequently than any other method of gene delivery. The use of these vectors in the heart has already offered promising novel benefit for human ischemic heart disease, and studies in animal models have given glimpses of hope that gene therapy may provide future therapeutic benefit in heart failure by improving cardiac function.
Molecular and Integrative Physiology of Intestinal Peptide Transport
Authors: Daniel Hannelore
Published: February 2004

▪ Abstract  Intestinal protein digestion generates a huge variety and quantity of short chain peptides that are absorbed into intestinal epithelial cells by the PEPT1 transporter in the apical membrane of enterocytes. PEPT1 operates as an electrogenic proton/peptide symporter with the ability to transport essentially every possible di- and tripeptide. Transport is enantio-selective and involves a variable proton-to-substrate stoichiometry for uptake of neutral and mono- or polyvalently charged peptides. Neither free amino acids nor peptides containing four or more amino acids are accepted as substrates. The structural similarity of a variety of drugs with the basic structure of di- or tripeptides explains the transport of aminocephalosporins and aminopenicillins, selected angiotensin-converting inhibitors, and amino acid–conjugated nucleoside-based antiviral agents by PEPT1. The high transport capacity of PEPT1 allows fast and efficient intestinal uptake of the drugs but also of amino acid nitrogen even in states of impaired mucosal functions. Transcriptional and post-transcriptional regulation of PEPT1 occurs in response to alterations in the nutritional status and in disease states, suggesting a prime role of this transporter in amino acid absorption.
Recent Advances in Carrier-Mediated Intestinal Absorption of Water-Soluble Vitamins
Authors: Said Hamid M.
Published: February 2004

▪ Abstract  Significant progress has been made in recent years toward understanding the mechanisms and regulation of intestinal absorption of water-soluble vitamins from the diet, especially those that are transported by a specialized carrier-mediated mechanism (i.e., ascorbic acid, biotin, folate, riboflavin, thiamin, and pyridoxine). The driving force involved in the uptake events and the molecular identity of the systems involved have been identified for a number of these vitamins. In addition, information about regulation of the uptake process of these micronutrients by intracellular and extracellular factors has been forthcoming. Furthermore, the 5′ regulatory region of the genes that encode a number of these transporters has been characterized, thus providing information about transcriptional regulation of the transport events. Also of interest is the identification of existence of carrier-mediated mechanisms in human colonocytes that are capable of absorbing some of the vitamins that are synthesized by normal microflora of the large intestine. Although the contribution of the latter source of vitamins toward overall host nutrition is not clear and requires further investigations, it is highly likely that it does contribute toward the cellular homeostasis of these vitamins in the localized colonocytes.
Bacteriorhodopsin
Authors: Lanyi Janos K.
Published: February 2004

▪ Abstract  Fourier transform infrared and Raman spectroscopy, solid-state NMR, and X-ray crystallography have contributed detailed information about the structural changes in the proton transport cycle of the light-driven pump, bacteriorhodopsin. The results over the past few years add up to a step-by-step description of the configurational changes of the photoisomerized retinal, how these changes result in internal proton transfers and the release of a proton to the extracellular surface and uptake on the other side, as well as the conservation and transformation of excess free energy during the cycle.
The Cytochrome bc1 Complex: Function in the Context of Structure
Authors: Crofts Antony R.
Published: February 2004

▪ Abstract  The bc 1 complexes are intrinsic membrane proteins that catalyze the oxidation of ubihydroquinone and the reduction of cytochrome c in mitochondrial respiratory chains and bacterial photosynthetic and respiratory chains. The bc 1 complex operates through a Q-cycle mechanism that couples electron transfer to generation of the proton gradient that drives ATP synthesis.

Genetic defects leading to mutations in proteins of the respiratory chain, including the subunits of the bc 1 complex, result in mitochondrial myopathies, many of which are a direct result of dysfunction at catalytic sites. Some myopathies, especially those in the cytochrome b subunit, exacerbate free-radical damage by enhancing superoxide production at the ubihydroquinone oxidation site. This bypass reaction appears to be an unavoidable feature of the reaction mechanism. Cellular aging is largely attributable to damage to DNA and proteins from the reactive oxygen species arising from superoxide and is a major contributing factor in many diseases of old age. An understanding of the mechanism of the bc 1 complex is therefore central to our understanding of the aging process. In addition, a wide range of inhibitors that mimic the quinone substrates are finding important applications in clinical therapy and agronomy. Recent structural studies have shown how many of these inhibitors bind, and have provided important clues to the mechanism of action and the basis of resistance through mutation.

This paper reviews recent advances in our understanding of the mechanism of the bc 1 complex and their relation to these physiologically important issues in the context of the structural information available.
Mechanism of Rectification in Inward-Rectifier K+ Channels
Authors: Lu Zhe
Published: February 2004

▪ Abstract  Inward rectifiers are a class of K+ channels that can conduct much larger inward currents at membrane voltages negative to the K+ equilibrium potential than outward currents at voltages positive to it, even when K+ concentrations on both sides of the membrane are made equal. This conduction property, called inward rectification, enables inward rectifiers to perform many important physiological tasks. Rectification is not an inherent property of the channel protein itself, but reflects strong voltage dependence of channel block by intracellular cations such as Mg2+ and polyamines. This voltage dependence results primarily from the movement of K+ ions across the transmembrane electric field along the pore, which is energetically coupled to the blocker binding and unbinding. This mutual displacement mechanism between several K+ ions and a blocker explains the signature feature of inward rectifier K+ channels, namely, that at a given concentration of intracellular K+, their macroscopic conductance depends on the difference between membrane voltage and the K+ equilibrium potential rather than on membrane voltage itself.
Estrogens in the Nervous System: Mechanisms and Nonreproductive Functions
Authors: Maggi Adriana , Ciana Paolo , Belcredito Silvia , Vegeto Elisabetta
Published: February 2004

▪ Abstract  The past decade has witnessed a growing interest in estrogens and their activity in the central nervous system, which was originally believed to be restricted to the control of reproduction. It is now well accepted that estrogens modulate the activity of all types of neural cells through a multiplicity of mechanisms. Estrogens, by binding to two cognate receptors ERα and ERβ, may interact with selected promoters to initiate the synthesis of target proteins. Alternatively, the hormone receptor complex may interfere with intracellular signaling at both cytoplasmic and nuclear levels. The generation of cellular and animal models, combined with clinical and epidemiological studies, has allowed us to appreciate the neurotrophic and neuroprotective effects of estrogens. These findings are of major interest because estradiol might become an important therapeutic agent to maintain neural functions during aging and in selected neural diseases.
The Role of Corepressors in Transcriptional Regulation by Nuclear Hormone Receptors
Authors: Privalsky Martin L.
Published: February 2004

▪ Abstract  Nuclear receptors (also known as nuclear hormone receptors) are hormone-regulated transcription factors that control many important physiological and developmental processes in animals and humans. Defects in receptor function result in disease. The diverse biological roles of these receptors reflect their surprisingly versatile transcriptional properties, with many receptors possessing the ability to both repress and activate target gene expression. These bipolar transcriptional properties are mediated through the interactions of the receptors with two distinct classes of auxiliary proteins: corepressors and coactivators. This review focuses on how corepressors work together with nuclear receptors to repress gene transcription in the normal organism and on the aberrations in this process that lead to neoplasia and endocrine disorders. The actions of coactivators and the contributions of the same corepressors to the functions of nonreceptor transcription factors are also touched on.
Some Early History of Membrane Molecular Biology
Authors: Singer S. Jonathan
Published: February 2004

▪ Abstract  This article is mostly about the beginnings of the molecular biology of membranes, covering the decade 1964–1974. It is difficult to read (or write) this article because of a sense of déja vu. Most of the material in it is considered commonplace today, having been established experimentally since then. But at the time this work was begun, practically nothing was known about the molecular structure and the mechanisms of the functions of membranes. This situation existed because no membrane proteins of the kind I called integral had as yet been isolated in a pure state, and therefore none had had their amino acid sequence determined. The first integral membrane protein to be so characterized was human erythrocyte glycophorin, in 1978. It was the use of the thermodynamic reasoning that had been developed for the study of water-soluble proteins, together with the information from several key experiments carried out in a number of laboratories during the early decade, that led us to the fluid mosaic model of membrane structure in 1972. Without direct evidence to confirm the model in 1971–1972, my colleagues and I nevertheless had the confidence in it to pursue some of the consequences of the model for a new understanding of many membrane functions, which I present here in some detail. Finally, I discuss two recent high-resolution X-ray crystallographic studies of integral proteins to ask how well the structural and functional proposals that we derived from the fluid mosaic model fit these remarkably detailed X-ray results.
Oral Rehydration Therapy: New Explanations for an Old Remedy
Authors: Rao Mrinalini C.
Published: February 2004

▪ Abstract  Diarrheal diseases are among the most devastating illnesses globally, but the introduction of oral rehydration therapy has reduced mortality due to diarrhea from >5 million children, under the age of 5, in 1978 to 1.3 million in 2002. Variations of this simple therapy of salts and sugars are prevalent in traditional remedies in cultures world-wide, but only in the past four decades have the scientific bases for these remedies begun to be elucidated. This review aims to provide a broad understanding of the cellular basis of oral rehydration therapy. The features integral to the success of oral rehydration therapy are active glucose transport in the small intestine, commensal bacteria, and short-chain fatty acid transport in the colon. The review examines these processes and their regulation and considers new approaches that might supplement oral rehydration therapy in controlling diarrheal diseases.
Metabolic Regulation of Potassium Channels
Authors: Tang Xiang Dong , Santarelli Lindsey Ciali , H. Heinemann Stefan , Hoshi Toshinori
Published: February 2004

▪ Abstract  Potassium (K+) channels exist in all three domains of organisms: eubacteria, archaebacteria, and eukaryotes. In higher animals, these membrane proteins participate in a multitude of critical physiological processes, including food and fluid intake, locomotion, stress response, and cognitive functions. Metabolic regulatory factors such as O2, CO2/pH, redox equivalents, glucose/ATP/ADP, hormones, eicosanoids, cell volume, and electrolytes regulate a diverse group of K+channels to maintain homeostasis.
Structure and Function of Glutamate Receptor Ion Channels
Authors: Mayer Mark L. , Armstrong Neali
Published: February 2004

▪ Abstract  A vast number of proteins are involved in synaptic function. Many have been cloned and their functional role defined with varying degrees of success, but their number and complexity currently defy any molecular understanding of the physiology of synapses. A beacon of success in this medieval era of synaptic biology is an emerging understanding of the mechanisms underlying the activity of the neurotransmitter receptors for glutamate. Largely as a result of structural studies performed in the past three years we now have a mechanistic explanation for the activation of channel gating by agonists and partial agonists; the process of desensitization, and its block by allosteric modulators, is also mostly explained; and the basis of receptor subtype selectivity is emerging with clarity as more and more structures are solved. In the space of months we have gone from cartoons of postulated mechanisms to hard fact. It is anticipated that this level of understanding will emerge for other synaptic proteins in the coming decade.
Control of the Size of the Human Muscle Mass
Authors: Rennie Michael J. , Wackerhage Henning , Spangenburg Espen E. , Booth Frank W.
Published: February 2004

▪ Abstract  This review is divided into two parts, the first dealing with the cell and molecular biology of muscle in terms of growth and wasting and the second being an account of current knowledge of physiological mechanisms involved in the alteration of size of the human muscle mass. Wherever possible, attempts have been made to interrelate the information in each part and to provide the most likely explanation for phenomena that are currently only partially understood. The review should be of interest to cell and molecular biologists who know little of human muscle physiology and to physicians, physiotherapists, and kinesiologists who may be familiar with the gross behavior of human muscle but wish to understand more about the underlying mechanisms of change.
Developmental Regulation of Lung Liquid Transport
Authors: Olver Richard E. , Walters Dafydd V. , M. Wilson Stuart
Published: February 2004

▪ Abstract  The developing distal lung epithelium displays an evolving liquid transport phenotype, reflecting a changing and dynamic balance between Cl−ion secretion and Na+ion absorption, which in turn reflects changing functional requirements. Thus in the fetus, Cl−-driven liquid secretion predominates throughout gestation and generates a distending pressure to stretch the lung and stimulate growth. Increasing Na+absorptive capacity develops toward term, anticipating the switch to an absorptive phenotype at birth and beyond. There is some empirical evidence of ligand-gated regulation of Cl−transport and of regulation via changes in the driving force for Cl−secretion. Epinephrine, O2, glucocorticoid, and thyroid hormones interact to stimulate Na+absorption by increasing Na+pump activity and apical Na+conductance (GNa+) to bring about the switch from net secretion to net absorption as lung liquid is cleared from the lung at birth. Postnatally, the lung lumen contains a small Cl−-based liquid secretion that generates a surface liquid layer, but the lung retains a large absorptive capacity to prevent alveolar flooding and clear edema fluid. This review explores the mechanisms underlying the functional development of the lung epithelium and draws upon evidence from classic integrative physiological studies combined with molecular physiology approaches.
Interpreting the BOLD Signal
Authors: Logothetis Nikos K. , Wandell Brian A.
Published: February 2004

▪ Abstract  The development of functional magnetic resonance imaging (fMRI) has brought together a broad community of scientists interested in measuring the neural basis of the human mind. Because fMRI signals are an indirect measure of neural activity, interpreting these signals to make deductions about the nervous system requires some understanding of the signaling mechanisms. We describe our current understanding of the causal relationships between neural activity and the blood-oxygen-level-dependent (BOLD) signal, and we review how these analyses have challenged some basic assumptions that have guided neuroscience. We conclude with a discussion of how to use the BOLD signal to make inferences about the neural signal.
Live Optical Imaging of Nervous System Development
Authors: Niell Cristopher M. , Smith Stephen J
Published: February 2004

▪ Abstract  Although development of the nervous system is inherently a process of dynamic change, until recently it has generally been investigated by inference from static images. However, advances in live optical imaging are now allowing direct observation of growth, synapse formation, and even incipient function in the developing nervous system, at length scales from molecules to cortical regions, and over timescales from milliseconds to months. In this review, we provide technical background and present examples of how these new methods, including confocal and two-photon microscopy, GFP-based markers, and functional indicators, are being applied to provide fresh insight into long-standing questions of neural development.
On a trivial zero problem
Authors: Zhang Shaowei
Published: February 2004

One trivial zero phenomenon for p‐adic analytic function is considered. We then prove that the first derivative of this function is essentially the Kummer class associated with p.
Dunkl wavelets and applications to inversion of the Dunkl intertwining operator and its dual
Authors: Jouini Abdellatif
Published: February 2004

We define and study Dunkl wavelets and the corresponding Dunkl
wavelets transforms, and we prove for these transforms Plancherel and reconstruction formulas. We give as application the inversion of the Dunkl intertwining operator and its dual.
Determinantal generating functions of colored spanning forests
Authors: Constantine Gregory M. , Buliga Marius G.
Published: February 2004

The color type of a spanning forest of a graph with colored edges
is defined and, subsequently, it is proved that the generating function of such spanning forests is obtained as the formal expansion of a certain determinant. An analogous determinantal expansion yields the generating function of all spanning forests
of a given color type that contain a specific subforest. Algorithms are described for obtaining a list of all colored spanning trees and spanning forests of any graph with colored edges based on symbolic calculation.
Meromorphic functions with positive coefficients
Authors: Darus Maslina
Published: February 2004

Let ∑∗(α, β, k) be a class of meromorphic functions f(z) with positive coefficients in D = {0 < |z| < 1}. The aim of the present note is to prove some properties for the class ∑∗(α, β, k).
Another extension of Orlicz‐Sobolev spaces to metric spaces
Authors: Aïssaoui Noureddine
Published: February 2004

We propose another extension of Orlicz‐Sobolev spaces to metric spaces based on the concepts of the Φ‐modulus and Φ‐capacity. The resulting space is a Banach space. The relationship between and (the first extension defined in Aïssaoui (2002)) is studied. We also explore and compare different definitions of capacities and give a criterion under which is strictly smaller than the Orlicz space LΦ.
Regularity of minimizers for nonconvex vectorial integrals withp‐q growth via relaxation methods
Authors: Benedetti Irene , Mascolo Elvira
Published: February 2004

Local Lipschitz continuity of local minimizers of vectorial integrals ∫Ω f(x, Du)dx is proved when f satisfies p‐q growth condition and ξ ↦ f(x, ξ) is not convex. The uniform convexity and the radial structure condition with respect to the last variable are assumed only at infinity. In the proof, we use semicontinuity and relaxation results for functionals with nonstandard growth.
Thrombin activatable fibrinolysis inhibitor (TAFI) and markers of endothelial cell injury in dialyzed patients with diabetic nephropathy
Authors: Małyszko Jacek , Hryszko Tomasz , Myśliwiec Michał , Małyszko Jolanta
Published: February 2004

Patients dialyzed due to diabetic nephropathy are at a higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Disturbances in hemostasis may play a role in the vascular complications of diabetes mellitus. It has been postulated that TAFI-thrombin activatable fibrinolysis inhibitor, which couples two opposite systems: coagulation and fibrinolysis, may be involved in the mechanism of vascular endothelial damage in diabetic patients. We assessed: TAFI and TAFIa, markers of ongoing coagulation: thrombin-antithrombin complexes, prothrombin fragments 1+2, a marker of ongoing fibrinolysis: plasmin-antiplasmin complexes in diabetic and non-diabetic patients on hemodialyses-HD, peritoneal dialysesCAPD, patietns with chronic renal failure with and without diabetic nephropathy on conservative treatment. Both groups of dialyzed diabetic patients have a higher concentration of markers of ongoing coagulation and TAFI activity when compared to dialyzed non-diabetic patients. Linear regression analysis showed that TAFI concentration was directly related to albumin in HD and CAPD patients without diabetic nephropathy, whereas TAFIa correlated with triglycerides, fibrinogen and leukocytes count in this group. When evaluated separately (HD, CAPD), significant correlations between TAFIa and triglycerides and fibrinogen were found only in diabetic CAPD patients. Multivariate analysis showed no correlation between TAFI and other parameters studied. In conclusion, elevated circulating TAFI and TAFIa might be a new link in the pathogenesis of impaired fibrinolysis in diabetic nephropathy, and thus atherosclerosis progression, particularly in CAPD patients. Hypercoagulable state observed in diabetic patients on conservative treatment and maintained on dialyses may contribute to the higher cardiovascular mortality in this population. In these patients there is also evidence of endothelial injury, and probably secondary activation of the coagulation cascade.
Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities
Authors: Huang Ping , Li Shan , Han Ming , Xiao Zhi , Yang Ren , Qiu Lu , Han Zhong
Published: February 2004

Treatment of severe arteriosclerosis obliterans of lower extremities (ASOLE) remains a clinical challenge. To develop a more effective approach, we evaluated the clinical efficacy of autologous transplantation of mobilized peripheral blood stem cells (PBSCs) in 5 patients with ASOLE. The patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 600 μg/day) for 5 consecutive days. On day 5, PBSCs were collected, sorted from blood circulation of patients, and then intramuscularly injected into their ischemic lower limbs. A significant improvement of clinical manifestations including severe pain, skin temperature and ulcer, was observed, without obvious adverse effect. The patient’s limb was successfully saved. Satisfactory remission was obtained 3 months after transplantation as shown by significant improvement in anklebrachial pressure index (ABI), blood flow in personal vascular laboratory (PVL), laser Doppler blood perfusion, and the angiographic scores. Our data suggest for the first time that autologous transplantation of mobilized PBSCs provides a practical, safe, and effective method of treatment for lower limb ischemia.
Expression of tissue factor pathway inhibitor-2 in murine and human liver regulation during inflammation
Authors: Hisaka Toru , Lardeux Bernard , Lamireau Thierry , Wüestefeld Torsten , Lalor Patricia , Neaud Véronique , Maurel Patrick , Desmoulière Alexis , Kisiel Walter , Trautwein Christian , Rosenbaum Jean
Published: February 2004

Tissue factor pathway inhibitor-2 (TFPI-2) is a recently described serine proteinase inhibitor. Human and murine TFPI-2 share about 50% homology. The aim of this study was to investigate the cellular localization of human and murine TFPI-2 in the liver and the regulation of their expression during acute inflammation. Northern blot, in situ hybridization and studies on isolated hepatocytes demonstrated a high-level expression of TFPI-2 in murine hepatocytes. On the other hand, very little TFPI-2 mRNA expression could be detected in human liver. Studies with isolated human liver cells suggested that TFPI-2 expression in human liver was mainly observed in liver sinusoidal endothelial cells rather than hepatocytes. Liver murine TFPI-2 expression was greatly increased after lipopolysaccharide administration with a delayed kinetics as compared to α1-acid glycoprotein, a classical acute-phase reactant. Accordingly, studies with isolated cells showed that the increase in TFPI-2 transcripts occurred in non-hepatocytic cells. Moreover, the LPS response was abolished in mice with a hepatocyte-specific KO for the gp130 receptor, thus indicating that a mediator from hepatocytes is involved in the up-regulation of TFPI-2 in non-parenchymal cells. In conclusion, murine TFPI-2 is highly expressed in hepatocytes in the normal murine liver and is upregulated in non-parenchymal cells in the context of inflammation. The large difference in the level of liver expression of human and murine TFPI-2 suggests that despite significant sequence similarities, these proteins presumably have different functions in the two species.
Platelet kinetics and scintigraphic imaging in thrombocytopenic malaria patients
Authors: Zedwitz-Liebenstein Konstantin , Eidherr Harald , Schuetz Matthias , Sauerman Robert , Dudczak Robert , Winkler Stefan , Pabinger Ingrid , Kletter Kurt , Karanikas Georgios
Published: February 2004

Thrombocytopenia is a common occurrence in acute malaria. It is attributed, among other factors, to excessive splenic platelet pooling and a shortened platelet lifespan. The aim of our study was to evaluate the platelet kinetics and sequestration site by isotopic studies in uncomplicated malaria-induced thrombocytopenia. Seven thrombocytopenic malaria patients (74,000±36,000 platelets/µl) were included in the study. Autologous 111In-labeled platelet scintigraphy was performed up to 96 hours (h) post injection (p.i.) to evaluate the platelet sequestration site. Late sequestration for the spleen (S) and the liver (L) was analyzed according to the following activity ratios: S (spleen count on the last day of the platelet lifespan / spleen count at 30 min) and L (liver count on the last day of the platelet lifespan / liver count at 30 min). Additionally, platelet survival studies were performed. A normal late sequestration (S: 0.95±0.06 and L: 1.04±0.08; normal values, S and L: 1 ± 0.2.) was observed in all of our patients. The platelet lifespan was reduced (1 to 4 days; normal range, 7-9 days), recovery was normal (mean, 63±6%; normal range, 55-75%), and the turnover rate was enhanced (mean, 95,000±80,000/µl/day; normal value, 35,000±4,500/µl/ day). According to the results of scintigraphy, the sequestration site by uncomplicated malaria-induced thrombocytopenia appears to be non-splenic and/or hepatic, yet diffuse.
Serum albumin predicts cardiac adverse events in patients with advanced atherosclerosis – interrelation with traditional cardiovascular risk factors
Authors: Exner Markus , Mlekusch Wolfgang , Amighi Jasmin , Sabeti Schila , Schlager Oliver , Wagner Oswald , Minar Erich , Schillinger Martin
Published: February 2004

Low serum albumin is a powerful predictor of cardiovascular adverse events in healthy subjects and patients with subclinical atherosclerosis. We investigated the association between serum albumin, traditional cardiovascular risk factors, markers of inflammation and cardiovascular outcome in 515 patients with advanced atherosclerosis and severe peripheral artery disease. Cardiovascular risk profile, serum albumin, serum amyloid A (SAA) and fibrinogen were obtained at baseline, and patients were followed for median 21 months (interquartile range 12 to 25) for the occurrence of major adverse cardiac events (MACE: myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, and death). We observed 135 MACE in 109 patients (21%). Cumulative event-free survival rates at 6, 12, and 24 months were 95%, 91%, and 80%, respectively. Low albumin predicted MACE independently of SAA and fibrinogen. Adjusted hazard ratios for the occurrence of MACE, any death, and the composite of death and MI according to increasing quartiles of albumin were 2.40, 1.14 and 1.09 (p<0.001), 2.94, 1.34 and 1.11 (p=0.003) and 3.63, 1.86 and 1.29 (p<0.001), respectively, as compared to the highest quartile. Considering albumin in conjunction with traditional cardiovascular risk factors (smoking, hyperlipidemia, hypertension and diabetes), we found that low albumin predicted MACE only in patients with a low risk profile (less than 3 risk factors) (p<0.001), whereas low albumin was not associated with MACE in patients with three or more risk factors (p=0.66). We conclude that low serum albumin is associated with cardiovascular outcome of patients with advanced atherosclerosis adding to the prognostic information of other inflammatory markers, and may be particularly useful for risk prediction in patients with few traditional risk factors.
Impaired brain angiogenesis and neuronal apoptosis induced by conditional homozygous inactivation of vascular endothelial growth factor
Authors: Raab Sabine , Beck Heike , Gaumann Andreas , Yüce Ali , Gerber Hans-Peter , Plate Karl , Hammes Hans-Peter , Ferrara Napoleone , Breier Georg
Published: February 2004

Vascular endothelial growth factor (VEGF) is essential for the differentiation of the primitive embryonic vascular system and has been implicated in the vascularization of organs. Recently, VEGF has also been proposed to play a role in neural development, neuroprotection, and adult neurogenesis. Here we have investigated the function of VEGF in the developing brain by cre-lox technology. We show that VEGF produced by the embryonic neuroectoderm is required for the vascularization and the development of the brain. Both the invasion and the directed growth of capillaries were severely impaired in the fore-, midand hindbrain of VEGFlox/lox/nestin-cre mouse embryos homozygous for a VEGF mutation in the neural tube. These observations demonstrate thatVEGF, via local secretion by neural progenitors, induces brain angiogenesis and guides the growth of capillaries toward the ventricular zone. VEGF deficiency led to developmental retardation and progressive destruction of neural tissue in all brain regions.The defect was most pronounced in telencephalic structures, such as the hippocampus, and caused microcephaly.Taken together, the findings establish the critical importance of neuroectoderm-derived VEGF in the morphogenesis of the brain. VEGF acts as a key regulator of brain angiogenesis and provides instructive cues for the correct spatial organization of the vasculature.
Age- and sex-specific incidence, risk, and latency period of a perioperative acute thromboembolism syndrome (PATS)
Authors: Takada Tomosue , Sato Shigehito , Kikura Mutsuhito
Published: February 2004

We investigated age- and sex-specific incidence, risk factors, and latency period of a perioperative acute thromboembolism syndrome (PATS) in a large cohort study. We prospectively analyzed data on 21903 consecutive surgery patients to determine the incidence of myocardial infarction, pulmonary embolism, deep venous thrombosis, stroke, and cardiovascular death within 30 postoperative days. Among 255 (1.2 percent) patients with thromboembolism, 105 (0.48 percent) suffered myocardial infarction (mean latency: 5 days), 30 (0.14 percent) suffered pulmonary embolism (6 days), 23 (0.11 percent) suffered deep venous thrombosis (10 days), 97 (0.44 percent) suffered stroke (11 days), and 13 (0.06 percent) died (12 days). The critical period was postoperative week 1 for myocardial infarction and pulmonary embolism, and postoperative week 1 and 2 for deep venous thrombosis, stroke, and death. Risk of all events increased with age (P<0.0001), particularly for over 70 years (odds ratio: 12.5; 95 percent confidence interval, 7.8 to 19.9). Males had an increased risk (P<0.0001) of myocardial infarction (odds ratio; 1.5; 95 percent confidence interval, 1.0 to 2.3). Females had an increased risk (P<0.0001) of pulmonary embolism (odds ratio: 2.7; 95 percent confidence interval, 1.3 to 5.9) and deep venous thrombosis (odds ratio: 9.8; 95 percent confidence interval, 3.3 to 29.3). Risk of thromboembolic event was higher (P<0.0001) in patients with a history of arterial thrombotic events or cancer. Trend analysis indicates that thromboembolic events will increase 3-fold over the next decade. Our findings enable identification of higher risk patients for prophylactic anti-thromboembolic treatment and awareness of the critical postoperative period.
Treatment with anticoagulants in cerebral events (TRACE)
Authors: Woessner Ralph , Grauer Markus , Bianchi Oliver , Mueller Martin , Moersdorf Stefan , Berlit Peter , Goertler Michael , Grotemeyer Karl-Heinz , Sliwka Ulrich , Stoll Martin , Treib Johannes
Published: February 2004

90 patients with acute stroke and a concomitant cardiac embolism source or a symptomatic high-grade stenosis of an extraor intracranial vessel received in a mulitcenter, randomized, controlled study either Enoxaparin 1 mg/kg BW s.c. b.i.d. or i.v. heparin aPTT-adjusted daily for 8 +/−2 days as secondary prophylaxis. There were no significant differences between the two groups regarding cerebral and systemic embolic events, bleeding complications, length of hospital stay, number of diagnostic and therapeutic measures and outcome after three months. This suggests that Enoxaparin, which is easier to administer and monitor, is a safe drug in patients with acute cerebral events.
The structural basis for the pathophysiological relevance of PAI-1 in cardiovascular diseases and the development of potential PAI-1 inhibitors
Authors: Gils Ann , Declerck Paul
Published: February 2004

Plasminogen activator inhibitor-1 (PAI-1) is an important component of the plasminogen/plasmin system as it is the main inhibitor of tissue-type and urokinase-type plasminogen activator. Consequently, PAI-1 plays an important role in cardiovascular diseases (mainly through inhibition of t-PA), and in cell migration and tumor development (mainly through inhibition of u-PA and interaction with vitronectin). As a member of the serpin superfamily, PAI-1 shares important structural properties with other serpins. However, PAI-1 also exhibits unique conformational and functional properties. The current review provides an overview of the knowledge on PAI-1 gathered since its discovery two decades ago. We discuss (a) its structural properties of the protein and their subsequent relation to functional activities, (b) its role in a wide variety of (patho) physiological processes and (c) a number of strategies to interfere with its functional properties eventually aiming at pharmacological modulation of this risk factor.
If Horses Had Hands …
Authors: Tyler Tom
Published: February 2004

This paper examines the contentious and confused notion of anthropomorphism. Beginning with an overview of the term's etymology and present use, it examines the arguments of those who believe it to be unscientific and demeaning, and those who believe it to be an inevitable and useful pragmatic strategy. The German philosopher Heidegger (1937/1984) raises the more serious objection, though, that as a concept anthropomorphism is not even meaningful. Supplementing his argument with examples drawn from evolutionary theory and elsewhere, the paper concludes that use of the term, anthropomorphism, commits one to an undesirable anthropocentrism, which shackles thought concerning the possible relationships between human and nonhuman animal beings.
Crossover Animal Fantasy Series: Crossing Cultural and Species as Well as Age Boundaries
Authors: Copeland Marion
Published: February 2004

Crossover fantasy series such as Harry Potter (Rowling, 1997, 1999, 2000, 2003), designed to appeal to readers of all ages, have received much popular and critical attention. Series like His Dark Materials (Pullman, 1995, 1997, 2000), more sophisticated and complex than Rowling's, have benefited from Harry Potter's press. In Rowling, nonhuman animals play roles but are not foregrounded. They are not central to action or theme or, in any sense, developed characters. Pullman's books foreground nonhumans and develop their characters. His three novels, however, belong to their human protagonists. In the worlds of true Crossover Animal Fantasy Series such as The Wolves of Time and The Duncton Trilogies (Horwood, 1997, 1989), the novels belong to their nonhuman protagonists. This review essay suggests how understanding the characteristics of Crossover Animal Fantasy Series enhances readers' imaginative grasp of the lives of other species. The best of these series cross cultural, species, and age boundaries, and are an unsung force in bringing about a paradigm shift that will affect our cultural perception of nonhumans.
The Impact of Household Slaves on the Jewish Family in Roman Palestine
Authors: Hezser Catherine
Published: February 2004

In late antiquity most of the slaves owned by Jewish slave owners in Roman Palestine seem to have been domestic slaves. These slaves formed an integral part of the Jewish household and played an important role within the family economy. In a number of respects the master-slave relationship resembled the wife-husband, child-father, and student-teacher relationships, and affectionate bonds between the slave and his master (or nursling) would have an impact on relationships between other members of the family. Master and slave were linked to each other through mutual ties of dependency which counteracted the basic powerlessness of slaves. On the other hand, slaves had to suffer sexual exploitation and were considered honorless. Rabbinic sources reveal both similarities and differences between Jewish and Graeco-Roman attitudes toward slaves. The Jewish view of the master-slave relationship also served as the basis for its metaphorical use.
The Dream of Alexander in Josephus ANT. 11.325-39
Authors: Kim Tae Hun
Published: February 2004

In dialogue with the remarkably insightful publication "Alexander the Great and Jaddua the High Priest According to Josephus" by Shaye J. D. Cohen (1982-83), this article argues that the story of Alexander-Jaddua meeting in Antiquities may be more persuasively explained as a propagandistic mixture of elements found in several types of ancient dream narratives rather than as a single type such as the soteriological epiphany as defined by Cohen. Cohen's classification relies heavily upon how Alexander's dream narrative functions in the larger context, but the theme and content of Alexander's dream narrative are in themselves not soteriological but a propagandistic divine legitimization of his conquest.
Die Drei Jüdischen Schulrichtungen Nach Josephus Und Hippolyt Von Rom: Zu den Paralleltexten Josephus, B.J. 2,119-166 und Hippolyt, Haer. IX 18,2-29,4
Authors: Bergmeier Roland
Published: February 2004

A solid literary analysis of all the ancient texts referring to the Essenes leads to the conclusion that common sources are needed to explain the similarities between the different accounts of the group. So the correspondences between Philo's accounts and those of Josephus are best explained by the thesis of a common Hellenistic Jewish source on the Essaeans. Further, we have to pay attention to the fact that the longest account of the Essenes is a composite text, partly referring to a three-school description, i.e. the Pharisees, the Sadducees, and the Essenes. Whenever Josephus speaks of the Essenes as determined in B.J. 2.119-161 he uses references to this text. Some scholars believe that this Josephan text and Hippolytus, Haer. 9.18-28, go back to a common source, too. But the validity of this thesis cannot be proved. First of all, these two texts must not be reduced to the description of the Essenes. All in all (B.J. 2.119-166; Haer. 9.18.2-29.4) they are three-school descriptions and this in the same manner and sequence, with the same lacks, and often by the same words. The correspondences between Philo's accounts and those of Josephus are no longer present in Hippolytus' version. The additional and unparalleled features in Hippolytus' text are no older core material that was lost in the Josephus version but contributions of the Church Father himself which bear all signs of his apologetic interests, his style and his theology. So Josephus, B.J. 2.119-166, was the very source of Hippolytus. Contra E. Puech, the sayings of the Church Father cannot give evidence of the eschatology of the Qumran community.
Gender and Divine Relativity in Philo of Alexandria
Authors: Conway Colleen
Published: February 2004

Philo's apparent divinization of Moses is considered vis-à-vis ancient conceptions of gender. Philo's Moses is a perfect illustration of the ideology of masculinity evident in a wide range of Greco-Roman literature. Moreover, with Philo's Moses, perfect masculinity is commensurate with divinity, but both remain relative to the "asexual masculinity" of God.
Effects of the components of positive airway pressure on work of breathing during bronchospasm
Authors: Miro Adelaida M , Pinsky Michael R , Rogers Paul L
Published: February 2004

Introduction

Partial assist ventilation reduces work of breathing in patients with bronchospasm; however, it is not clear which components of the ventilatory cycle contribute to this process. Theoretically, expiratory positive airway pressure (EPAP), by reducing expiratory breaking, may be as important as inspiratory positive airway pressure (IPAP) in reducing work of breathing during acute bronchospasm.

Method

We compared the effects of 10 cmH2O of IPAP, EPAP, and continuous positive airwaypressure (CPAP) on inspiratory work of breathing and end-expiratory lung volume (EELV) in a canine model of methacholine-induced bronchospasm.

Results

Methacholine infusion increased airway resistance and work of breathing. During bronchospasm IPAP and CPAP reduced work of breathing primarily through reductions in transdiaphragmatic pressure per tidal volume (from 69.4 ± 10.8 cmH2O/l to 45.6 ± 5.9 cmH2O/l and to 36.9 ± 4.6 cmH2O/l, respectively; P < 0.05) and in diaphragmatic pressure–time product (from 306 ± 31 to 268 ± 25 and to 224 ± 23, respectively; P < 0.05). Pleural pressure indices of work of breathing were not reduced by IPAP and CPAP. EPAP significantly increased all pleural and transdiaphragmatic work of breathing indices. CPAP and EPAP similarly increased EELV above control by 93 ± 16 ml and 69 ± 12 ml, respectively. The increase in EELV by IPAP of 48 ± 8 ml (P < 0.01) was significantly less than that by CPAP and EPAP.

Conclusion

The reduction in work of breathing during bronchospasm is primarily induced by the IPAP component, and that for the same reduction in work of breathing by CPAP, EELV increases more.
On: “The Equivalent Source Technique,” by C. N. G. Dampney (GEOPHYSICS, February 1969, p. 39–53)
Authors: Green Ronald
Published: February 2004

The usual situation that arises when a gravity survey is carried out is that the stations are located otherwise than on a regular grid, and, furthermore, the stations are at different heights. This areal spread and range of heights can be indicated by designating the gravity at the [Formula: see text] station as [Formula: see text] The above set of measurements constitutes the entire raw data from which all the elements of the interpretation must be derived. To be more specific, it is usual to present the gravity information in the form of a contoured Bouguer gravity map, which is equivalent to interpolating gravity waves on a regular grid on a horizontal plane. To obtain the data in such a regular form is the nub of the problem, because the continuous values of a contoured gravity map can be obtained by convolution of the regular values with a two-dimensional gate function II [Formula: see text] where a is the interpolated station spacing in the x direction, and b for the y direction, respectively.
A comparative study of figurative language in children with autistic spectrum disorders
Authors: MacKay Gilbert , Shaw Adrienne
Published: February 2004

Difficulties with figurative language have been highlighted by many researchers and people with autistic spectrum disorders (ASDs) as a core problem of the condition. However, few tests exist which describe and assess the responses of children with autism to figurative language. This paper reports a study which evaluated figurative language skills in able children with ASD. A group of children with ASD and a group of age-matched peers with no ASD were compared using a test of figurative language devised for the investigation. The test focused on understanding the meaning of an utterance and understanding the intentionality behind an utterance. Six categories of figurative language were examined. In all six, the controls with no ASD performed more successfully than the group with ASD, at statistically significant levels in most cases. The study also showed qualitative idiosyncrasies among those with ASD. The results are discussed in terms of their clinical and theoretical importance.
Occupational therapy for children with cerebral palsy: a systematic review
Authors: Steultjens Esther MJ , Dekker Joost , Bouter Lex M , van de Nes Jos CM , Lambregts Brigitte LM , van den Ende Cornelia HM
Published: February 2004

Objective: Occupational therapy (OT) for cerebral palsy focuses on the development of skills necessary for the performance of activities of daily living. The aim of this systematic review was to determine whether OT interventions improve outcome for children with cerebral palsy (CP).

Methods: An extensive search in MEDLINE, CINAHL, EMBASE, AMED and SCISEARCH was performed. Studies with controlled and uncontrolled designs were included. Six intervention categories were distinguished and individually analysed using a best-evidence synthesis. This synthesis is based on the type of design, the methodological quality, the type of outcome measures and the statistical significance of the findings.

Results: Seventeen studies were included in this review, seven of which were randomized controlled trials (RCTs). One RCT had a high methodological quality. The analyses resulted in insufficient evidence of the efficacy of occupational therapy in all intervention categories, due to the low methodological quality of studies presenting statistically nonsignificant results.

Conclusion: Despite the reasonable number of studies identified, the inconclusive findings regarding the efficacy of occupational therapy for children with cerebral palsy may be a reflection of the difficulties in efficacy research in OT for children with CP. Future research should critically reflect on methodological issues.