bluuebunny/crossref_metadata_2025 huggingface dataset:
Colonization processes on a central Alpine glacier foreland
Authors: Erschbamer Brigitta , Niederfriniger Schlag Ruth , Winkler Eckart
Published: May 2008

Questions:

What are the colonization trends in vegetated vs. bare‐ground plots over a 10‐year period in a central Alpine glacier foreland? What are the long‐term effects of artificial seed addition to these plots?

Location:

Glacier foreland of the Rotmoosferner in the Central Alps, Obergurgl, Tyrol, Austria, 2380 – 2400 m a.s.l.

Methods:

A total of 40 permanent plots were established on moraines ice‐free for 35 and 50 years on vegetated and bare‐ground areas. Half of them were treated with a seed mixture in 1996 and 1997. Number and cover of the species were recorded in 1996 and from 2002/2003 to 2006.

Results:

Species richness doubled in the control plots and tripled in seeded plots on the 35‐year‐ice‐free moraine. On the 50‐year‐ice‐free moraine the increase in species number was more modest. Significant site, seeding and time effects were found. Seed addition had no effects in the bare‐ground plots on the older moraine and low effects in those on the younger moraine. All plots showed significant changes in cover of single species. The pioneer species decreased significantly in both moraines, in the control as well as in the seeded plots. A disappearance during the next years is predicted.

Conclusions:

Colonization in bare‐ground plots is limited by a lack of safe sites, whereas vegetated plots facilitate recruitment and establishment. Colonization on the glacier foreland is also dispersal limited. Seed addition enhanced the presence of already established species, and late successional species were newly introduced.
Glycans: Array‐Based Techniques
Authors: Oyelaran Oyindasola , Manimala Joseph C. , Gildersleeve Jeffrey C.
Published: May 2008

Glycan arrays are powerful tools for high throughput analysis of carbohydrate–macromolecule interactions. A glycan array is composed of many different carbohydrate structures immobilized on a solid support in an orderly arrangement. This review describes the challenges and considerations in the development of a glycan array. Various array formats, immobilization techniques, and assay systems are discussed. In addition, several interesting applications of glycan array technology are described, such as assessing the specificities of carbohydrate‐binding lectins and antibodies, profiling antiglycan antibodies in serum as biomarkers of disease, and evaluating carbohydrate‐dependent cell binding.
Förster Resonance Energy Transfer (FRET) for Proteins
Authors: Chao Lambert K. , Clegg Robert M.
Published: May 2008

Förster Resonance Energy Transfer (FRET) is a spectroscopic technique applied throughout physics, chemistry, and biology to measure quantitatively the distance between selected locations on macromolecules and to determine the close association between interacting molecular components. Because FRET typically occurs over distances from 0.5 to 10 nm, it is especially useful for investigating many interesting biological molecular structures. It is also particularly valuable for following the dynamics and structural fluctuations of biological molecular systems. FRET can be applied in solution or under imaging conditions (such as in fluorescence microscopy, nanoscience, and even macroscopic imaging). In this article, we discuss the fundamentals of FRET. These principles apply to every FRET measurement. We present the basic rudiments and the relevant literature of FRET to provide the reader with the necessary background essential for understanding much of the past and modern literature. At the end of the article, we give a short discussion of several applications of FRET to proteins. The literature for FRET is vast, and many new applications are constantly being developed. We could not do justice to the many practitioners of FRET in such a short space, but armed with the background that is presented, we hope this basic information will help readers follow much of the literature and apply it in their own work.
Integrin Signaling
Authors: Wu Xiaoyang , Guan Jun‐Lin
Published: May 2008

Integrins are a large family of heterodimeric receptors that mediate the adhesive behavior of cells. Most integrins bind to extracellular matrix (ECM) molecules, and they transmit signals that are critical in growth, development, tissue homeostasis, and host defense. A central feature of these receptors is their ability to transduce bidirectional signals into and out of the cell. In this article, we will give an overview of our current understanding of the structure and cellular signaling functions of integrins.
Lipid Bilayers: Properties
Authors: Vaz Winchil L. C.
Published: May 2008

Lipid bilayers are the structural basis of biological membranes; they provide excellent structures for microencapsulation and are interesting objects of study as thermotropic and lyotropic smectic liquid crystals. This article introduces the fundamental principles that lead to the formation of lipid bilayers and briefly lists some amphiphiles that form lipid bilayers in biological systems. The temperature‐dependent phase behavior of bilayers formed from a single lipid species is discussed briefly followed by a discussion of bilayer dimensions and hydration. The article then introduces the reader to phase behavior of bilayers formed from mixtures of lipids and the consequences of phase coexistence for component compartmentalization and percolation in lipid bilayers. Special emphasis is placed on the phase behavior of bilayers that contain sterols. The article introduces the reader to some physical properties of lipid bilayers, which include the hydration force, elasto‐mechanical properties, and the resistance of bilayers to lateral stretching and/or compression and bending. Brief discussions of molecular dynamics in lipid bilayers fromtrans/gaucheisomerism and rotation of lipid chains in bilayers to rotational, wobbling, and translational diffusion of lipids in bilayers is followed by an introduction to the dynamics of insertion, desorption, and transverse translocation of lipids in bilayers. Lipid bilayers are then discussed in terms of their permeability to aqueous solutes and some models for bilayer permeation are mentioned briefly. Finally, the reader is introduced to the electrical properties of lipid bilayers with brief discussions of the dipolar potential, the surface electrostatic potential, and the transmembrane potential. The article ends with a brief discussion of lipid compositional asymmetry across the lipid bilayer in biological membranes and its possible causes. Key references are cited wherever relevant.
Metalloproteinases, Biophysics and Chemistry of
Authors: Solomon Ariel , Selzer Tzvia , E. Milla Marcos , Sagi Irit
Published: May 2008

Zinc‐dependent metalloproteases constitute a large family of enzymes, part of the proteinase superfamily. Fundamental to the structural integrity and catalytic activity of metalloproteases is the presence of both zinc and calcium ions in the structure of the protein. This article will focus on matrix metalloproteinases that are involved in extracellular matrix (ECM) catabolism and serve as important enzymes in many aspects of biology, ranging from cell proliferation, differentiation, and proliferation to cancer, tumor metastasis, inflammation, and other pathologic states. Despite their key role in many normal and pathologic processes, the molecular mechanisms by which zinc‐dependent proteases hydrolyze their physiologic substrates are only known partly. Recent theoretical analyses have suggested reaction models for which limited and controversial experimental evidence exists. Here we will discuss the importance of quantifying the biophysical properties and the structural dynamic behavior of these enzymes to reveal their underlying molecular mechanisms. Such molecular knowledge holds promise in providing the basis for the novel design of specific antagonists as drug candidates for these important enzymes. In addition, we will discuss the use of real‐time spectroscopic tools for studying the reactive metal sites in these enzymes.
PLP‐Dependent Enzymes, Chemistry of
Authors: Toney Michael D.
Published: May 2008

Pyridoxal phosphate‐dependent enzymes catalyze a wide variety of reaction types on amines and amino acids, generally by stabilizing carbanionic intermediates, which makes them very common in both primary and secondary metabolism. A fundamental mechanism by which reaction specificity is enforced is stereoelectronic effects; the bond to Cα that gets broken in the universal external aldimine intermediate is that which is aligned parallel to theporbitals of the conjugated, electron‐deficient π system. When a bond to Cα has been broken, enzymes must also carefully control the fate of the resulting carbanionic intermediate. Structurally, all known pyridoxal 5′‐phosphate (PLP)‐dependent enzymes are separated into five groups. The largest of these, Type 1, is the aminotransferase group, of which aspartate aminotransferase is the prototype. The prototypes for the other groups are as follows: Type 2, tryptophan synthetase; Type 3, alanine racemase; Type 4, D‐amino acid aminotransferase; and Type 5, glycogen phosphorylase.
Proteins: Chemistry and Chemical Reactivity
Authors: Tilley S. David , Joshi Neel S. , Francis Matthew B.
Published: May 2008

Protein bioconjugation is a critically important tool for the elucidation of enzyme mechanisms, the tracking of biomolecules in living systems, the improvement of pharmacokinetic properties, and the construction of new materials. All these applications rely on a continually expanding set of chemical reactions that can modify native protein functionality in aqueous solution under mild pH and temperature conditions. To survey these techniques, this article provides an introduction to the chemical reactivity of the amino acid side chains, with an emphasis on the selectivity that can be achieved using a particular reactive strategy. Site‐selective techniques that target the unique reactive properties of N‐terminal residues are also reviewed, as are native chemical ligation methods for the modification of the C‐terminus. Whenever possible, the mechanistic aspects of the reactions are discussed, as these considerations provide the foundation for future reaction development. The article concludes with a brief description of labeling reactions that selectively target unnatural functional groups in the presence of native protein functionality.
Receptor–Ligand Interactions in Biological Systems
Authors: Li Liwei , Meroueh Samy O.
Published: May 2008

Despite the significant research that has been invested in understanding molecular recognition in biological systems, accurate prediction of macroscopic properties based on microscopic interactions remains elusive, which makes it difficult to identify systematically tight binding inhibitors in computational drug design. In the past, most ligand design efforts have centered on descriptors derived mainly from structure, neglecting entropic effects that develop from receptor flexibility. The lack of explicit incorporation of receptor motion has meant that compensatory effects between enthalpy and entropy, which are essential for the accurate estimation of free energy, have also been neglected. In addition, cooperative effects, which develop from alteration in the motion of the receptor because of ligand binding, are not captured. These effects pose a challenge for the design of small molecules that allosterically modulate protein‐protein and protein‐small‐molecule interactions. Here, we describe macroscopic properties of receptor‐ligand interactions, which are followed by a discussion of how these properties are predicted with microscopic interactions. A discussion then ensues on some fundamental aspects of the molecular recognition process that have attracted renewed attention, such as conformational selection versus induced‐fit binding, entropy‐enthalpy compensation, and allostery.
RNA
Interference to Treat Human Diseases
Authors: Shan Ge , Jin Peng
Published: May 2008

Discovery of the RNA interference (RNAi) pathway has been revolutionary to biology and biologically based therapeutics. The messenger RNA (mRNA) targets once believed to be “undruggable” by conventional methods are now being enthusiastically pursued with RNAi‐based therapeutics. Fundamental research into the RNAi pathway and biotechnological research on the application of RNAi may one day make a new class of drugs a reality by targeting the mRNA of disease‐causing or disease‐promoting genes directly. The whole process begins with the design and validation of short‐interference RNA (siRNA) using bioinformatics and cell culture systems. siRNA that has high specificity and potency (knockdown efficiency) then could be applied to animal models of human diseases for more evaluation, with the ultimate hope of advancing to clinical trails. Numerous chemical modifications of siRNA are currently being investigated in an effort to enhance their stability, to extend their stay in the body, and, perhaps, to avoid immune stimulation. Different delivery methods are developed depending on the diseases, tissues, or organs being targeted. In short, this relatively new biotechnology is advancing quickly as we learn from its failures and successes. In the current article, we will explore the background and current state of research as well as discuss some hurdles and future directions in the application of RNAi to treat human diseases.
Solid‐Phase Synthesis of Biomolecules
Authors: Breinbauer Rolf
Published: May 2008

The synthesis of biopolymers, tool compounds, and molecular probes lies at the heart of any effort in chemical biology. Solution‐phase strategies are well established but usually require considerable efforts in time and labor during workup and purification steps. In contrast, solid‐phase synthesis, in which the substrate is covalently bound to an insoluble support, allows the simple removal of excess or consumed reagents by simple filtration. In the cases of oligonucleotides and peptides, the synthetic operations can be performed by robotic systems allowing the high‐throughput synthesis of these biopolymers at low cost within a short time. The solid‐phase synthesis of oligosaccharides and small‐molecule probes has made significant progress during the last several years.
Water, Properties of
Authors: Geiger Alfons , Paschek Dietmar
Published: May 2008

Water is well known for its unusual properties, which are the so‐called “anomalies” of the pure liquid, as well as for its special behavior as solvent, such as the hydrophobic hydration effects. During the past few years, a wealth of new insights into the origin of these features has been obtained by various experimental approaches and from computer simulation studies. In this review, we discuss points of special interest in the current water research. These points comprise the unusual properties of supercooled water, including the occurrence of liquid–liquid phase transitions, the related structural changes, and the onset of the unusual temperature dependence of the dynamics of the water molecules. The problem of the hydrogen‐bond network in the pure liquid, in aqueous mixtures and in solutions, can be approached by percolation theory. The properties of ionic and hydrophobic solvation are discussed in detail.
Catalytic Modes in Natural Ribozymes
Authors: Harris Michael E.
Published: May 2008

In nature, RNA transmits genetic information, and it catalyzes reactions that are universal in biology. The reactions of phosphorus and carbon esters that are catalyzed by natural ribozymes occur with specific geometries and are susceptible to both acid and base catalysis as well as catalysis that involves metal ions. High‐resolution structures of a few ribozymes implicate the involvement of individual nucleotides in performing these catalytic strategies. Detailed biochemical tests of the mechanisms of these ribozymes provide evidence for the involvement of nucleobase functional groups in acid/base catalysis, yet debate continues concerning their precise roles in proton transfer. Complementary structural and biochemical support has been gained for the involvement of specific RNA functional groups in positioning metal ions for catalysis. Still, only a few systems have been probed in sufficient depth to infer mechanistic detail and to achieve a complete chemical description of how ribozyme active sites enact specific catalytic strategies remains a key goal.
Base–Base Bifunctional Catalysis: A Practical Strategy for Asymmetric Michael Addition of Malonates to α,β‐Unsaturated Aldehydes
Authors: Wang Yongcan , Li Pengfei , Liang Xinmiao , Ye Jinxing
Published: May 2008

Lewis base–Brønsted base bifunctional catalysis is a novel and practical strategy for the asymmetric Michael addition. The addition of malonates to a series of α,β‐unsaturated aldehydes can take place under base–base bifunctional catalytic conditions using 0.5–5 mol% of (S)‐2‐[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as catalyst and 5–30 mol% of lithium 4‐fluorobenzoate as additive base with up to 99% ee.
Organocatalytic Enantioselective Hydrophosphonylation of Sulfonylimines having a Heteroarenesulfonyl Group as a Novel Stereocontroller
Authors: Nakamura Shuichi , Nakashima Hiroki , Yamamura Akiko , Shibata Norio , Toru Takeshi
Published: May 2008

Organocatalytic enantioselective hydrophosphonylation of imines having the a heteroarenesulfonyl group afforded the respective products with high enantioselectivity. Both enantiomers of α‐amino phosphonates were obtained by using different Cinchona alkaloids with up to 98% ee.
Fast and Scalable Route to Aryl Polyallyl Dendrons and Dendrimers
Authors: Nlate Sylvain , Plault Lauriane , Felpin François‐Xavier , Astruc Didier
Published: May 2008

In the quest for general and efficient synthetic procedures for dendrons and dendrimers, allylphenol, allylnaphthol and 6‐bromonaphthalene AB3 dendrons have been successfully prepared on a large‐scale by a rapid and clean route starting from commercially available esters and allyl bromide. In contrast to the known organoiron strategy, the above‐mentioned methodology enables the large‐scale synthesis of AB3 dendrons in only two days.
Total Synthesis of Marine Oxylipins Solandelactones A–H
Authors: Pietruszka Jörg , Rieche Anja C. M.
Published: May 2008

The Solandelactones A–H have been synthesized via a short convergent approach utilizing common building blocks. Based on the diastereoselectivity of the crucial final addition step and on the comparison of prominent NMR data, a structural revision was necessary.
Rapid quantitative assay of ADAMTS13 activity on an automated coagulation analyzer: Clinical applications and comparison with immunoblot method
Authors: Knovich Mary Ann , Lawson Heather L. , Burke Martha H. , McCoy Thomas P. , Owen John
Published: May 2008

Facile assays for ADAMTS13, the metalloprotease that is absent or impaired in thrombotic thrombocytopenic purpura, could allow for timely diagnosis and management of this potentially fatal hematologic disorder; unfortunately, available assays employ methodologies that restrict use to only a few reference laboratories, resulting in reporting delays. Measurement of ADAMTS13 on an automated analyzer could allow widespread accessibility by routine clinical laboratories. We adapted a previously published technique to demonstrate that ADAMTS13 activity could be measured on an Instrumentation Laboratory automated coagulation analyzer after plasma digestion of a commercial source of von Willebrand factor (VWF). Results were obtained using a commercially available immunoturbidimetric assay for residual VWF activity. Samples from 114 patients with suspected thrombotic microangiopathy were analyzed by both standard immunoblot and our new semiautomated method with excellent agreement, particularly at the clinically relevant low levels of ADAMTS13 activity. This new method is semiautomated and offers quantitative results within 2 hr; our modifications allow for widespread applicability on instrumentation already in use by routine clinical laboratories. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
The influence of infection early after allogeneic stem cell transplantation on the risk of leukemic relapse and graft‐versus‐host disease
Authors: Kim Sung‐Yong , Lee Dong‐Gun , Kim Myung‐Shin , Kim Hee‐Je , Lee Seok , Min Chang‐Ki
Published: May 2008

An infection after allogeneic stem cell transplantation (SCT) can affect the activity of immune cells and increase the level of proinflammatory cytokines. Further, a post‐SCT infection may influence the milieu of the graft‐versus‐leukemia (GVL) effect and graft‐versus‐host disease (GVHD). We performed a retrospective study of patients with acute leukemia who had undergone allogeneic SCT using the same preparative regimens and bone marrow as the stem cell source to determine if early post‐transplant infection was associated with the risk of leukemic relapse and GVHD. The analysis revealed that patients who had a febrile infection (FI) before post‐transplant day 21 (FI group) had a lower actuarial probability of leukemic relapse (P < 0.001) and a higher relapse‐free survival rate (P = 0.012) than those patients who did not have a FI before post‐transplant day 21 (non‐FI group). The experience of early post‐transplant FI (HR = 0.316; 95% CI = 0.174–0.575; P < 0.001), together with the presence of chronic GVHD and high risk cytogenetics, were independent predictive factors for post‐transplant leukemic relapse. The FI group had a trend towards a higher lymphocyte count on post‐transplant day 21 than the non‐FI group (P = 0.063), despite the delayed recovery of the platelet count and a trend towards delayed recovery of the neutrophil count. These findings suggest that a change in the immunologic network by infectious diseases in the early post‐transplant period favors the milieu of the GVL effect. The specific immunologic change during FI, which can potentiate the GVL effect, remains to be determined. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Liver Perfusion in Sepsis, Septic Shock, and Multiorgan Failure
Authors: Spapen Herbert
Published: May 2008

Sepsis causes significant alterations in the hepatic macro‐ and microcirculation. Diverging views exist on global hepatic blood flow during experimental sepsis because of the large variety in animal and sepsis models. Fluid‐resuscitated clinical sepsis is characterized by ongoing liver ischemia due to a defective oxygen extraction despite enhanced perfusion. The effects of vasoactive agents on the hepatosplanchnic circulation are variable, mostly anecdotal, and depend on baseline perfusion, time of drug administration, and use of concomitant medication. Microvascular blood flow disturbances are thought to play a pivotal role in the development of sepsis‐induced multiorgan failure. Redistribution of intrahepatic blood flow in concert with a complex interplay between sinusoidal endothelial cells, liver macrophages, and passing leukocytes lead to a decreased perfusion and blood flow velocity in the liver sinusoids. Activation and dysfunction of the endothelial cell barrier with subsequent invasion of neutrophils and formation of microthrombi further enhance liver tissue ischemia and damage. Substances that regulate (micro)vascular tone, such as nitric oxide, endothelin‐1, and carbon monoxide, are highly active during sepsis. Possible interactions between these mediators are not well understood, and their therapeutic manipulation produces equivocal or disappointing results. Whether and how standard resuscitation therapy influences the hepatic microvascular response to sepsis is unknown. Indirect evidence supports the concept that improving the microcirculation may prevent or ameliorate sepsis‐induced organ failure. Anat Rec, 291:714–720, 2008. © 2008 Wiley‐Liss, Inc.
Artificial Circulation of the Liver: Machine Perfusion as a Preservation Method in Liver Transplantation
Authors: Vekemans Katrien , Liu Qiang , Pirenne Jacques , Monbaliu Diethard
Published: May 2008

Due to the sharp increase in liver transplant candidates and the subsequent shortage of suitable donor livers, an extension of the current donor criteria is necessary. Simple cold storage, the current standard in organ preservation has proven to be insufficient to preserve extended criteria donor livers. Therefore a renewed interest grew toward alternative methods for liver preservation, such as hypothermic machine perfusion and normothermic machine perfusion. These “new” preservation methods were primarily assessed in rat models, and only a few clinically relevant large animal models have been described so far. This review will elaborate on these alternative preservation methods. Anat Rec, 291:735–740, 2008. © 2008 Wiley‐Liss, Inc.
The Hepatic Microvascular System in Health and Its Response to Toxicants
Authors: Mccuskey Robert S.
Published: May 2008

This review briefly summarizes what is known about the dynamic morphology of the hepatic microvascular system that includes all vessels in the liver with a diameter less than 300 μm and various morphological sites within these vessels that regulate the distribution of blood flow. The latter include the various segments of the afferent portal venules and hepatic arterioles, the sinusoids, and central and hepatic venules. Sinusoids are unique exchange vessels lined by fenestrated endothelial cells which have important endocytotic functions and phagocytic Kupffer cells which are important for host defense. These are encircled by extraluminal stellate cells that are specialized pericytes containing fat droplets that store vitamin A. The principle sites for regulating blood flow are in the sinusoidal network with stellate and endothelial cells playing a major role in regulating the diameters of sinusoids and the distribution of blood flow in individual sinusoids, lobules, or segments of lobules. The sinusoidal endothelial cells are a sensitive and early target for several toxicants. For example, as early as 30 minutes after the administration of acetaminophen, the endothelial cells become swollen and begin to lose the ability to endocytose ligands. Within 2 hr, gaps through the cytoplasm appear formed by the destruction and/or coalescence of fenestrae which permit red blood cells to penetrate into the space of Disse. Subsequently, the sinusoid may collapse or disintegrate reducing blood flow. Anat Rec, 291:661–671, 2008. © 2008 Wiley‐Liss, Inc.
Patent classifications as indicators of intellectual organization
Authors: Leydesdorff Loet
Published: May 2008

Using the 138,751 patents filed in 2006 under the Patent Cooperation Treaty, co‐classification analysis is pursued on the basis of three‐ and four‐digit codes in the International Patent Classification (IPC, 8th ed.). The co‐classifications among the patents enable us to analyze and visualize the relations among technologies at different levels of aggregation. The hypothesis that classifications might be considered as the organizers of patents into classes, and therefore that co‐classification patterns—more than co‐citation patterns—might be useful for mapping, is not corroborated. The classifications hang weakly together, even at the four‐digit level; at the country level, more specificity can be made visible. However, countries are not the appropriate units of analysis because patent portfolios are largely similar in many advanced countries in terms of the classes attributed. Instead of classes, one may wish to explore the mapping of title words as a better approach to visualize the intellectual organization of patents.
Synthesis and Characterization of Silica@Copper Core–Shell Nanoparticles: Application for Conjugate Addition Reactions
Authors: Sreedhar B. , Radhika P. , Neelima B. , Hebalkar Neha
Published: May 2008

Silica@copper (SiO2@Cu) core–shell nanoparticles were synthesized and well characterized by XRD, TEM, AFM, XPS, UV/Vis, TGA–MS, and ICP–AES techniques. The synthesized SiO2@Cu core–shell nanoparticles were employed as catalysts for the conjugate addition of amines to α,β‐unsaturated compounds in water to obtain β‐amino carbonyl compounds in excellent yields in shorter reaction times. Furthermore, the catalyst works well for hetero‐Michael addition reactions of heteroatom nucleophiles such as thiols to α,β‐unsaturated compounds. As the reaction is performed in water, it allows for easy recycling of the catalyst with consistent activity.
Mechanism of the Reaction of Radicals with Peroxides and Dimethyl Sulfoxide in Aqueous Solution
Authors: Herscu‐Kluska Ronit , Masarwa Alexandra , Saphier Magal , Cohen Haim , Meyerstein Dan
Published: May 2008

The reactions of methyl and methylperoxyl radicals derived from dimethyl sulfoxide (DMSO) with hydrogen peroxide, peroxymonocarbonate (HCO4−), and persulfate were studied. The major reaction observed for the hydroperoxides was the abstraction of the hydrogen atom by the radicals. The radicals interact with a lone pair of electrons on the peroxide to produce methanol and formaldehyde. Furthermore, the results indicate that in RO2H and RO2R′, electron‐withdrawing groups cause a considerable increase in the reactivity of the peroxides towards the radicals and not only towards nucleophiles. The HO2./O2.− and CO3.− radicals react with DMSO to produce methyl radicals. Thus, the formation of the .CH3 radicals in the presence of DMSO is not proof of the formation of the .OH radicals in the system. These reactions must be considered when radical processes, such as in biological and catalytic systems, are studied. Especially, the plausible role of HCO4− ions in biological systems as a source of oxidative stress cannot be overlooked.
Phase 2 trial of talactoferrin in previously treated patients with metastatic renal cell carcinoma
Authors: Jonasch Eric , Stadler Walter M. , Bukowski Ronald M. , Hayes Teresa G. , Varadhachary Atul , Malik Rajesh , Figlin Robert A. , Srinivas Sandy
Published: May 2008

BACKGROUND.

Talactoferrin (TLF), a recombinant form of human lactoferrin (hLF), is an immunomodulatory iron‐binding glycoprotein first identified in breast milk. Its immunomodulatory functions include activation of natural killer (NK) and lymphokine‐activated killer cells and enhancement of polymorphonuclear cells and macrophage cytotoxicity. Studies in animal models have shown promising anticancer activity, and clinical antitumor activity has been observed in nonsmall cell lung cancer and other tumor types. The purpose of the current study was to evaluate the activity and safety of TLF in patients with refractory metastatic renal cell carcinoma (RCC).

METHODS.

Forty‐four adult patients with progressive advanced or metastatic RCC who had failed prior systemic therapy received oral talactoferrin at a dose of 1.5 g twice daily on a 12‐week‐on 2‐week‐off schedule. Patients were evaluated for progression‐free survival at 14 weeks, overall response rate, and progression‐free and overall survival.

RESULTS.

TLF was well tolerated. No significant hematologic, hepatic, or renal toxicities were reported. The study met its predefined target with a 14‐week progression‐free survival rate of 59%. The response rate was 4.5%. The mMedian progression‐free survival was 6.4 months and the median overall survival was 21.1 months.

CONCLUSIONS.

TLF is a well‐tolerated new agent that has demonstrated preliminary signs of clinical activity. Given the lack of toxicity, the lack of rapid disease progression in this cohort, and the preclinical data on immune activation, a randomized study assessing its effects on disease progression in patients with metastatic RCC is rational. Cancer 2008. © 2008 American Cancer Society.
High prevalence of triple‐negative tumors in an urban cancer center
Authors: Lund Mary Jo B. , Butler Ebonee N. , Bumpers Harvey L. , Okoli Joel , Rizzo Monica , Hatchett Nadjo , Green Victoria L. , Brawley Otis W. , Oprea‐Ilies Gabriela M. , Gabram Sheryl G. A.
Published: May 2008

BACKGROUND.

A disparate proportion of breast cancer deaths occur among young women, those of African‐American (AA) ancestry, and particularly young AA women. Estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor‐2 (HER‐2) are key clinically informative biomarkers. The triple‐negative (ER‐/PR‐/HER‐2‐) tumor subgroup is intrinsically resistant to treatment and portends a poor prognosis. Age, race, and socioeconomic status have been associated with triple‐negative tumors (TNT). In the current study, the authors investigated breast cancer subgroups among patients in an urban cancer center serving a multiracial, low socioeconomic population.

METHODS.

This case series analyzed female invasive breast cancers diagnosed and/or treated between 2003 and 2004 in the AVON Comprehensive Breast Center at Grady Hospital in Atlanta, Georgia. Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, and augmented by the hospital registry and pathology reports. Statistical analyses utilized frequency distributions and logistic regression.

RESULTS.

Of 190 breast cancers; 167 (88%) were diagnosed among AA and 23 (12%) were diagnosed among non‐AA women. The median age at diagnosis in the 2 groups was 58 years and 57 years, respectively. TNT prevalence was found to differ by race (29.3% among AA women and 13.0% among non‐AA women; P = .010). Differences persisted after adjustment for age and stage (odds ratio [OR] of 3.1; 95%confidence interval [95% CI], 0.8–11.6). The majority of recurrences (40.0%) occurred among women with TNT, who were also most likely to experience a fatal event (OR of 3.7; 95%CI, 1.1–13.0).

CONCLUSIONS.

Despite a similarity in their age at diagnosis, AA women in our urban cancer center presented with a higher prevalence of TNT and TNT was found to predict the poorest outcomes. Institutional interactive breast conferences and intervention/navigation programs could help to dispel breast cancer disparities and improve outcomes. Cancer 2008. © 2008 American Cancer Society.
Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma
Authors: Navid Fariba , Willert Jennifer Reikes , McCarville M. Beth , Furman Wayne , Watkins Amy , Roberts William , Daw Najat C.
Published: May 2008

BACKGROUND.

The combination of gemcitabine and docetaxel has demonstrated promise in sarcomas diagnosed in adults. In the current study, the toxicity and efficacy of this combination were evaluated in pediatric sarcomas.

METHODS.

A retrospective case review of 22 patients with recurrent or refractory bone or soft‐tissue sarcomas who received gemcitabine (at a dose of 675 mg/m2 intravenously on Days 1 and 8) and docetaxel (at a dose of 75–100 mg/m2 intravenously on Day 8) was undertaken.

RESULTS.

The patients (ages 8–23 years) received a total of 109 courses of chemotherapy (median, 4 courses; range, 1–13 courses). Seventeen patients had osteosarcoma, 2 patients had Ewing sarcoma family of tumors (ESFT), 1 patient had a malignant fibrous histiocytoma (MFH), 1 patient had a chondrosarcoma, and 1 patient had an undifferentiated sarcoma. Of the 14 patients evaluable for response, the patient with an MFH achieved a complete response (CR), 3 patients with osteosarcoma achieved a partial response (PR), and 2 patients (1 with ESFT and 1 with osteosarcoma) had stable disease (SD). The overall objective response (CR + PR) rate was 29%. Median duration of response (CR + PR + SD) was 4.8 months (range, 1.6‐13 months). The toxicity was manageable and consisted primarily of thrombocytopenia and neutropenia.

CONCLUSIONS.

In the current study, gemcitabine in combination with docetaxel was found to be well tolerated and demonstrated antitumor activity in children and adolescents with recurrent or refractory osteosarcoma and MFH. Further evaluation of this drug combination is warranted in these patients. Cancer 2008. © 2008 American Cancer Society.
Beyond breaking bad news
Authors: Whitney Simon N. , McCullough Laurence B. , Frugé Ernest , McGuire Amy L. , Volk Robert J.
Published: May 2008

BACKGROUND.

Hope is important to patients, yet physicians are sometimes unsure how to promote hope in the face of life‐threatening illness.

ANALYSIS.

Hope in medicine is of two kinds: specific (hope for specific outcomes) and generalized (a nonspecific sense of hopefulness). At the time of diagnosis of a life‐ending condition, the specific goal of a long life is dashed, and there may be no medically plausible specific outcome that the patient feels is worth wishing for. Yet the physician may nonetheless maintain an open‐ended hopefulness that is compatible with the physician's obligation to be truthful; this hopefulness can help sustain patient and family through the turbulent period of adaptation to the unwelcome reality of major illness. As this adaptation evolves, the physician can help patients and families adapt to suffering and loss of control by selecting and achieving specific goals such as improvement of the patient's environment in hospital or hospice, pain control, and relief of sleeplessness. Thus hope for specific (but far more modest) future events can again become a positive part of the patient s emotional landscape. The authors do not propose that physicians remain upbeat no matter the circumstance, for they must respect the constraints of reality and the patients' mortality. However, physicians can provide both cognitive and affective support as patients learn how to adapt. Hope and hopefulness are both important in this process.

Hope is always important to patients. Physicians can and should promote hopefulness without endorsing unrealistic hope. Cancer 2008. © 2008 American Cancer Society.
Impact of computed tomography screening for lung cancer on participants in a randomized controlled trial (NELSON trial)
Authors: van den Bergh Karien A. M. , Essink‐Bot Marie‐Louise , Bunge Eveline M. , Scholten Ernst Th. , Prokop Mathias , van Iersel Carola A. , van Klaveren Rob J. , de Koning Harry J.
Published: May 2008

BACKGROUND.

Computed tomography (CT) screening is an important new tool for the early detection of lung cancer. In the current study, the authors assessed the discomfort associated with CT scanning and the subsequent wait for results and health‐related quality of life (HRQoL) over time.

METHODS.

A total of 351 participants in the Dutch‐Belgian randomized controlled trial for lung cancer screening in high‐risk subjects (the NELSON trial) who had an appointment for a baseline CT scan were asked to complete questionnaires regarding their experienced discomfort and HRQoL before, 1 day after, and approximately 6 months after the CT scan. HRQoL was measured as generic HRQoL (12‐item Short Form [SF‐12] and EuroQol questionnaire [EQ‐5D]), generic anxiety (State‐Trait Anxiety Inventory [STAI‐6]), and lung cancer‐specific distress (Impact of Event Scale [IES]). Approximately 76.9% of the participants completed all 3 questionnaires.

RESULTS.

Approximately 87% to 99% of participants reported experiencing no discomfort related to the CT scan. The median SF‐12, EQ‐5D, STAI‐6, and IES scores did not appear to change relevantly over time. Approximately 46.0% and 51.3%, respectively, of the participants reported discomfort in connection with having to wait for the results of the CT scan and dreading those results. These patients had relevantly higher STAI‐6 and IES scores (P < .01) (unfavorable) at all 3 assessments.

CONCLUSIONS.

The current evaluation of the potential adverse effects of CT screening for lung cancer on HRQoL demonstrated no negative effects. However, waiting for the CT scan results was reported to be discomforting by approximately half of the participants. Minimizing the waiting time for the test results is therefore recommended. Cancer 2008. © 2008 American Cancer Society.
High‐sensitive determination of human α‐thrombin by its 29‐mer aptamer in affinity probe capillary electrophoresis
Authors: Li Yilin , Guo Lei , Zhang Fucheng , Zhang Zhaoyang , Tang Jijun , Xie Jianwei
Published: May 2008

ACE technique provides an effective tool for the separation and identification of disease‐related biomarkers in clinical analysis. In recent years, a couple of synthetic DNA or RNA oligonucleotides, known as aptamers, rival the specificity and affinity for targets to antibodies and are employed as one kind of powerful affinity probe in ACE. In this work, based on high affinity between antithrombin aptamer and thrombin (their dissociation constant is 0.5 nM), a carboxyfluorescein‐labeled 29‐nucleotide (nt) aptamer (F29‐mer) was used and an aptamer‐based affinity probe CE (aptamer‐based APCE) method was successfully established for high‐sensitive detection and quantitative analysis of thrombin. Experimental conditions including incubation temperature and time, buffer composition, and concentration of cations were investigated and optimized. Under the optimized condition, the linear range was from 0 to 400 nM and the LOD was 2 nM (74 ng/mL, S/N = 3), i.e., 40 amol, both in running buffer and in 5% v/v human serum. This LOD is the lowest one than those achieved by the previous APCE methods but based on a 15‐mer aptamer. This approach offers a promising method for the rapid, selective, and sensitive detection of thrombin in practical utility. Further binding experiments using one carboxyfluorescein‐labeled aptamer and the other nonlabeled aptamer or vice versa were carried out to deduce the formation of ternary complex when these two aptamers coexisted in the free solution with thrombin.
Analysis of mouse brain microvascular endothelium using immuno‐laser capture microdissection coupled to a hybrid linear ion trap with Fourier transform‐mass spectrometry proteomics platform
Authors: Lu Qiaozhen , Murugesan Nivetha , Macdonald Jennifer A. , Wu Shiaw‐Lin , Pachter Joel S. , Hancock William S.
Published: May 2008

The purpose of this study was to identify the protein profile of the mouse brain microvascular endothelium in situ. This involved coupling of a double‐label, immuno‐laser capture microdissection (LCM) process with LTQ‐FT mass spectrometry to perform the in situ proteomic analysis. LCM was utilized to isolate cells from frozen mouse brain tissue sections. Following cell capture, samples were solubilized and proteins separated by gel electrophoresis in preparation for enzymatic digestion and LC‐MS analysis. Processed samples were subsequently analyzed using a linear IT coupled with a Fourier transform mass spectrometer (LTQ‐FT MS). Overall, in this study, 881 proteins were identified from a specific cell category using immuno‐guided LCM to probe these cell types along the entirety of the cerebral microvascular tree. The identification of sufficient numbers of proteins with high biological interest should allow us to study protein expression by specific cell types – as defined by certain cell markers – in complex tissues.
Screening for copy‐number alterations and loss of heterozygosity in chronic lymphocytic leukemia—A comparative study of four differently designed, high resolution microarray platforms
Authors: Gunnarsson Rebeqa , Staaf Johan , Jansson Mattias , Ottesen Anne Marie , Göransson Hanna , Liljedahl Ulrika , Ralfkiær Ulrik , Mansouri Mahmoud , Buhl Anne Mette , Smedby Karin Ekström , Hjalgrim Henrik , Syvänen Ann‐Christine , Borg Åke , Isaksson Anders , Jurlander Jesper , Juliusson Gunnar , Rosenquist Richard
Published: May 2008

Screening for gene copy‐number alterations (CNAs) has improved by applying genome‐wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high‐resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross‐platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2–3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy‐number variations. LOH analysis using dChip revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy‐number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform‐specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large‐scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested. © 2008 Wiley‐Liss, Inc.
Equality of what in health? Distinguishing between outcome egalitarianism and gain egalitarianism
Authors: Tsuchiya Aki , Dolan Paul
Published: May 2008

When deciding how to weigh benefits to different groups, standard economic models assume that people focus on the final distribution of utility, health or whatever. Thus, an egalitarian is assumed to be an egalitarian in the outcome space. But what about egalitarianism in the gains space, such that people focus instead on how equally benefits are distributed? This paper reports on a study in which members of the public were asked to rank a number of health programmes that differed in the distribution of benefits and final outcomes in ways that enabled us to distinguish between different types of egalitarianism. The results suggest that outcome egalitarianism dominates, particularly for differences in health by social class, but a sizeable minority of respondents appear to be gain egalitarians, especially when the health differences are by sex. These results have important implications for how we think about outcome‐based social welfare functions in economics. Copyright © 2008 John Wiley & Sons, Ltd.
Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen–positive chronic hepatitis B
Authors: Marcellin Patrick , Chang Ting-Tsung , Lim Seng G. Lee , Sievert William , Tong Myron , Arterburn Sarah , Borroto-Esoda Katyna , Frederick David , Rousseau Franck
Published: May 2008

Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log10 copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 × upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log10 copies/mL and −50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV.

Conclusion:

Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement. (Hepatology 2008;48:750–758.)