bluuebunny/crossref_metadata_2025 huggingface dataset:
Race, Ethnicity, and the Patient-Caregiver Relationship
Authors: Dedier Julien , Penson Richard , Williams Winfred , Lynch Thomas
Published: August 2004

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, gives support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.

Racial discrimination is a pervasive problem with multiple damaging effects. It is naïve to believe that medicine is somehow immune to race-based practices, but there is a growing literature detailing poorer disease-specific outcomes in minority populations for a range of illnesses. A recent study in the New England Journal of Medicine has implicated physician prejudice as a significant contributing factor. The March 1999 Schwartz Center Rounds sought to explore the influence of ethnic bias on the patient-provider interaction and the quality of health care delivery. Using a different format with a current affairs video clip and an interactive panel discussion, participants were encouraged to identify the often subconscious racial prejudices which may undermine their relationships with patients. Staff members were challenged to think creatively about how institutions and individuals might promote “cultural competence” and a more equitable health care environment.
Cancer Vaccines
Authors: Espinoza-Delgado Igor
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to: Explain the relationship between the tumor and host immune system.Recognize the mechanisms by which tumor cells escape the immune surveillance.Recognize the potential of vaccines in the treatment and prevention of cancer.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Although cancer immunotherapy was initiated by William Coley more than a century ago, the field of cancer vaccines is in an early stage of development. Only recently, major advances in cellular and molecular immunology have allowed a comprehensive understanding of the complex and high rate of interactions between the immune system and tumor cells. We have learned that these tumor–immune system interactions may result either in strong immune antitumor response or tolerance to tumor-associated antigens. This article will discuss the profound interest in cancer vaccines derived from their potential to induce antitumor responses in vivo. Substantial data from several preclinical models and early human clinical trials have confirmed the ability of cancer vaccines to induce immune responses that are tumor-specific and, in some cases, associated with clinical responses. One future challenge will be to determine how to appropriately stimulate the pathways leading to effective interaction among antigen-presenting cells, T lymphocytes, and tumor cells. It also is critical to develop monitoring strategies that may allow the identification of patients who may benefit from cancer vaccines.
The Status of Cancer Fatigue on the Island of Ireland: AIFC Professional and Interim Patient Surveys
Authors: Dillon Eileen , Kelly Joan
Published: August 2004

The objectives of the All Ireland Fatigue Surveys are: A) to learn more about the nature of cancer patients' fatigue; B) to explore the impact that fatigue has on the lives of these patients; C) to determine physicians' and nurses' perceptions of fatigue in patients; and D) to find the current level of management of cancer fatigue in Ireland. In two surveys, one involving 109 physicians and another involving 160 nurses, the vast majority of respondents reported that they believe nausea to be the side effect of most concern to their cancer patients. In contrast, 41% of 143 patient respondents to a third survey reported that fatigue was the side effect that had the greatest impact on them. Patients indicated that fatigue affected them physically, mentally, emotionally, and economically. Yet, approximately half the patients who reported their fatigue to their physician or nurse received no treatment to relieve their fatigue. The number one recommendation made to patients who did receive treatment to help reduce their fatigue was rest/relaxation, even though research suggests that exercise can be of greater benefit. Thus, it appears that cancer patients' fatigue has been largely under-recognized and poorly managed or ignored. With the formation of interdisciplinary groups of health care professionals focused solely on cancer fatigue, efforts are under way on the island of Ireland to address this too long misunderstood and neglected aspect of cancer patients' lives.
Cancer Fatigue: The Way Forward
Authors: Curt Gregory , Johnston Patrick G.
Published: August 2004

Research in cancer-related fatigue lags far behind research in cancer-related pain and is astonishingly underdeveloped given the magnitude of the problem among cancer patients. This was recently recognized at the State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue, held at the U.S. National Institutes of Health in July 2002. The results of patient surveys on fatigue being conducted in Ireland by the All Ireland Fatigue Coalition (AIFC) closely mirror results from similar surveys conducted in the U.S., in some regards, with 53% of patients experiencing significant fatigue at least daily, and 80% at least monthly on both sides of the Atlantic. In other respects, such as duration of bouts of fatigue, how much and with whom patients discuss their fatigue symptoms, and economic impacts of fatigue, there are significant differences between survey findings in the U.S. and in Ireland. But in both places, the condition is underreported and undertreated and takes an enormous toll. Work by the AIFC to document the problem in Ireland, expand public awareness, and conduct research on which to base guidelines for diagnosis and treatment is an excellent beginning to tackling this long understudied condition that afflicts the overwhelming majority of cancer patients.
Biotransformation Studies Using Rat Proximal Tubule Cells
Authors: Schaaf G. J. , Maas R. F. M. , Fink‐Gremmels J.
Published: August 2004

The proximal tubule is the main target for nephrotoxic substances due to its specific properties, including efficient drug transport and biotransformation potential. The availability of a pure population of proximal tubule cells (PT cells) as a model to study a range of biological, pharmacological, and toxicological parameters is, therefore, of great value. A two‐step PT cell–isolation procedure, based on density‐gradient centrifugation, is described; this procedure can easily be introduced into each laboratory setting. The procedure routinely yields a highly pure PT cell population, comprising 20–40 × 106 cells, which can be used for preparation of subcellular fractions or brought into primary culture.
Overview of Affinity Tags for Protein Purification
Authors: Kimple Michelle E. , Sondek John
Published: August 2004

Addition of an affinity tag is a useful method for differentiating recombinant proteins expressed in bacterial and eukaryotic expression systems from the background of total cellular proteins, and for detecting protein‐protein interactions. This overview describes the historical basis for the development of affinity tags, affinity tags that are commonly used today, how to choose an appropriate affinity tag for a particular purpose, and several recently developed affinity tag technologies that may prove useful in the near future.
Determination of Disulfide‐Bond Linkages in Proteins
Authors: Tang Hsin‐Yao , Speicher David W.
Published: August 2004

The formation of disulfide bonds in proteins is an important post‐translational modification that is critical for stabilizing the native structures of proteins. The disulfide linkages in a protein cannot be predicted from its amino acid sequence; therefore, determination of disulfide bond linkages in the protein will provide insights into its three‐dimensional structure and contribute to the understanding of its structural‐functional relationship. This unit details a series of protocols that have been applied successfully to locate disulfide bonds in proteins. The general strategy involves chemical or proteolytic cleavage of the protein followed by chromatographic separation of the resultant peptides. Disulfide‐containing peptides are identified by the alteration of mobility as a consequence of disulfide bond reduction, and are further characterized by mass spectrometry and/or N‐terminal sequencing. A partial reduction and alkylation strategy for mapping disulfide linkages in peptides with multiple disulfide bonds is also presented.
Protein Expression in the Drosophila Schneider 2 Cell System
Authors: Schetz John A. , Shankar Eswar P.N.
Published: August 2004

The Schneider‐2 (S2) Drosophila cell line is well suited for the stable overexpression of recombinant proteins using plasmid‐based protein expression vectors. Following drug selection, a polyclonal S2 cell line can be induced to express on the order of 2 to 100 pmol/mg membrane protein for G‐coupled protein receptors, 4000 to 100,000 sites/cell for other membrane receptors and 3 to 35 mg/liter for soluble and secreted proteins.
Cued and Contextual Fear Conditioning in Mice
Authors: Wehner Jeanne M. , Radcliffe Richard A.
Published: August 2004

Contextual and cued fear conditioning is a robust form of learning in which an association is made between stimuli and their aversive consequences. Fear conditioning has been used in laboratory rodents in part because it is a highly conserved form of behavior that is exhibited in both laboratory situations and in normal environments. Training requires only a single trial and this makes it adaptable to genetic, pharmacological, and biochemical studies. Clinically, it is has relevance to human behavior in that fear conditioning can be produced in humans, and damage to the amygdala prevents fear conditioning.
Handling and Restraint
Authors: Donovan John , Brown Patricia
Published: August 2004

For the safety of the handler and the animal, proper methods for handling and restraining laboratory animals should be followed. Improper handling can result in increased stress and injury to the animal. In addition, the handler risks injury from bite wounds or scratches inflicted when the animal becomes fearful or anxious. By using sure, direct movements with a determined attitude, the animal can be easily handled and restrained. Animals can be restrained either manually or in a plastic restrainer. The protocols in this unit describe handling and manual restraint of mice, rats, hamsters, and rabbits. Alternate protocols describe restraint using the plastic restrainer.
Animal Identification
Authors: Donovan John , Brown Patricia
Published: August 2004

Proper identification of animals is crucial in research, whether the animals are being used as experimental subjects, for breeding purposes, or as a source for tissues, cells, or fluids. This unit provides specific protocols for the ear punch (notch) and ear tag methods for mouse, rat and hamster; tattoos for mouse, rat and rabbit; and the correct use of a subcutaneous transponder system for all of the above species.
Two‐Dimensional Gel Electrophoresis
Authors: Adams Lonnie D. , Gallagher Sean R.
Published: August 2004

Two‐dimensional gel electrophoresis is the combination of two high‐resolution electrophoretic procedures (isoelectric focusing and SDS‐polyacrylamide gel electrophoresis) to provide much greater resolution than either procedure alone. In the first‐dimension gel, solubilized proteins are separated according to their isoelectric point (pI) by isoelectric focusing. This gel is then applied to the top of an SDS‐slab gel and electrophoresed. The proteins in the first‐dimension gel migrate into the second‐dimension gel where they are separated on the basis of their molecular weight. The basic protocols in this unit are based on the type of equipment originally described by O'Farrell in 1975. For very basic or very acidic proteins, two alternate protocols are provided. A third alternate protocol describes how two‐dimensional electrophoresis can be performed using a minigel system. Protein sample preparation is presented in the support protocol.
Detection of MAP Kinase Signaling
Authors: Rubinfeld Hadara , Seger Rony
Published: August 2004

Elucidation of intracellular signaling pathway is essential to understanding the regulatory mechanisms of cellular function. Mitogen‐activated protein kinase (MAPK) signaling cascades are a major pathway in intracellular signaling. The methods used to detect cascade activation involve measurements of protein kinase activities. This unit describes an assay for specific immunoprecipitation of a protein kinase and detection of phosphorylation of the appropriate substrate, an in‐gel kinase assay for kinases of unknown identity or for which there are no specific antibodies, and the JNK assay, which involves a broad‐based immunoaffinity purification followed by phosphorylation.
Competition‐Based Cellular Peptide Binding Assay for HLA Class I
Authors: Kessler Jan H. , Benckhuijsen Willemien E. , Mutis Tuna , Melief Cornelis J.M. , van der Burg Sjoerd H. , Drijfhout Jan W.
Published: August 2004

This unit describes a competition assay to determine binding of unlabeled test peptides to thirteen of the most prevalent HLA class I molecules. It uses cells expressing the HLA class I molecule of interest on their surface, fluorescently labeled reference peptides, and unlabeled test peptides. Cells of interest are stripped from their natural HLA‐bound peptides using acid treatment and subsequently incubated with a mixture of labeled reference peptide and titrating concentrations of test peptide. Subsequently, FACS analysis is performed to determine the amount of bound reference peptide, which is a measure of the ability of test peptide to compete for binding to HLA. The assay provides IC50 values for binding of test peptides to HLA molecules. It can be performed in a normally equipped cellular laboratory, requires no additional equipment besides a flow cytometer (FACS), and is relatively easy to perform. Assay‐specific parameters for several HLA alleles are provided.
Comparative Bioinformatics for Mouse and Human Genes: Getting Started
Authors: Mortlock Douglas P.
Published: August 2004

The primary goal of this unit is to describe methods for using online bioinformatic resources to identify data pertaining to specific mouse genes or genomic regions, from the perspective of a researcher who has identified a human gene(s) of interest and wishes to obtain some basic information about the orthologous murine gene‐such as the mouse genomic sequence containing the gene, cDNA sequence and exon/intron structure, and conserved noncoding regions that may indicate regulatory elements.

describes how to obtain mouse gene sequences via Ensembl. describes a sequence homology search for locating a mouse ortholog of a human gene using the UCSC genome browser. Basic Protocols 3 and 4 provide instructions for performing comparative analysis of large human and mouse genomics sequences, using the PipMaker (Schwartz et al., ) and VISTA (Mayor et al., ) online tools.
Principles and Applications of PRINS in Cytogenetics
Authors: Koch Jørn
Published: August 2004

A flexible, low‐cost alternative to FISH, primed in situ labeling (PRINS) has traditionally been used to detect tandemly repeated target sequences in chromosomes and nuclei. The technique is capable of discriminating among closely related DNA sequences in situ and has the advantage of using very small probes which easily penetrate to almost any target. This unit describes basic PRINS and the alternative version, dideoxy‐PRINS, which can increase the sensitivity of the reaction by an order of magnitude. New material on multicolor PRINS and quantitative PRINS has been added. Protocols for detection of single‐copy sequences and for application to the study of in‐vivo activity of DNA‐modifying enzymes are planned.
Estimation of Microbial Viability Using Flow Cytometry
Authors: Davey Hazel M. , Kell Douglas B. , Weichart Dieter H. , Kaprelyants Arseny S.
Published: August 2004

For microorganisms in particular, viability is a term that is difficult to define and a state consequently difficult to measure. The traditional (and gold‐standard) usage equates viability and culturability (i.e., the ability to multiply), but the process of determining culturability is often too slow. Flow cytometry provides the opportunity to make rapid and quantitative measurements of dye uptake in large numbers of cells, and we can therefore exploit the flow cytometric approach to evaluate so‐called viability stains and to develop protocols for more routine assessments of microbial viability. This unit is primarily commentary, but several basic protocols have been included to ensure that users have a firm basis for attempting these reasonably difficult assays on traditional flow cytometer instruments. What is clear is that each assay must be carefully validated with the particular microorganism of interest before being applied in any research, clinical, or service form.
Overview of Cytogenetic Chromosome Analysis
Authors: Bayani Jane , Squire Jeremy A.
Published: August 2004

This unit provides a brief overview of cytogenetic analysis of interphase ansd metaphase chromosomes. It includes a description of the methods provided in the units that follow.
Traditional Banding of Chromosomes for Cytogenetic Analysis
Authors: Bayani Jane , Squire Jeremy A.
Published: August 2004

Traditional banding of metaphase chromosomes allows identification of individual chromosomes and detection of gross chromosomal anomalies and abnormal chromosome structures. Giemsa (G) banding is the older and more familiar nonfluorescent technique that produces characteristic banding patterns. DAPI , a fluorescent DNA stain, produces banding patterns similar to those of G‐banding and is much simpler to perform.
Fluorescence In Situ Hybridization (FISH)
Authors: Bayani Jane , Squire Jeremy A.
Published: August 2004

Fluorescence in situ Hybridization (FISH) involves the preparation of two main components: the DNA probe and the target DNA to which the probe will be hybridized. The DNA probe typically comes from cloned sources such as plasmids, cosmids, PACs, YACs, or BACs; where the insert may contain a specific gene or originate from a specific chromosomal locus. Whole‐chromosome paints may also be used but are usually applicable to metaphase preparations. The purified DNA can then be labeled and detected indirectly using haptens, or labeled directly using fluorochrome or dye‐conjugated nucleotides. Labeling strategies are also variable, employing standard nick translation or PCR labeling methods. The target DNA can take the form of chromosomes spreads or interphase nuclei. The sources of interphase targets may come from cytogenetic preparations or from paraffin‐embedded tissues. Both the labeled DNA probe and DNA target are denatured to a single‐stranded state and permitted to hybridize to each other. Post‐hybridization washes and fluorescently‐labeled antibody incubations follow the 24‐hour hybridization, and the specimen is ready for visualization by fluorescent microscopy. Successful interpretation of FISH experiments is dependent on the quality of the starting materials, hybridization efficiencies, and stringency of post‐hybridization washes and antibody detections.
RNAi: Design and Analysis
Authors: Sachidanandam Ravi
Published: August 2004

RNAi is a novel genetic tool that is poised to revolutionize the study of genetics and gene networks. Use of this tool requires knowledge of the underlying mechanisms and application of this knowledge to the construction of a gene‐silencing library. This unit discusses approaches to rational design of this library and its use in experiments. It focuses on the design algorithms developed so far and briefly discuss several issues that could lead to improvements in the current design algorithms.
Ionische Flüssigkeiten für die Synthese funktioneller Nanopartikel und anderer anorganischer Nanostrukturen
Authors: Antonietti Markus , Kuang Daibin , Smarsly Bernd , Zhou Yong
Published: August 2004

Ionische Flüssigkeiten sind eine neue Klasse organischer Lösungsmittel mit hoher Polarität und einer vororganisierten Lösungsmittelstruktur. In diesen Flüssigkeiten können in Abwesenheit oder bei einem kontrollierten Anteil von Wasser sehr polare Reaktionen durchgeführt werden, die auf einfache Weise und bei moderaten Temperaturen zu kristallinen Nanopartikeln führen. Die ausgeprägte Organisation dieser Lösungsmittel kann für die Herstellung selbstanordnender, hoch organisierter Hybrid‐Nanostrukturen von bisher nicht bekannter Qualität genutzt werden. Das außergewöhnliche Potenzial ionischer Flüssigkeiten für die Materialsynthese soll in diesem Kurzaufsatz von einem physikalisch‐chemischen Standpunkt aus dargelegt werden.
Epoxy resin/polyurethane functionally graded material prepared by microwave irradiation
Authors: Liu X. Q. , Wang Y. S. , Zhu J. H.
Published: August 2004

The glass‐transition temperature (Tg) and modulus (E) of graded material in a plastic–elastomer system prepared with layer‐by‐layer casting in connection with microwave curing were studied. Epoxy (EP) resin and polyurethane (PU) were selected as the plastic and elastomer components, respectively. The structure of the functionally graded material (FGM) was such that EP (E = 3.2 GPa, and Tg = 162°C) and PU (E = 0.069 GPa and Tg = −54°C) were both surfaces, with a stepwise gradient in EP and PU content existing between the two over a thickness of 9 mm. Fourier transform infrared spectroscopy and scanning electron microscopy were used to investigate the PU content and the morphologies of the FGMs separately. Finite element analysis (FEA) was used to simulate the temperature and thermal stress distribution along the graded direction under a steady‐state, nonuniform temperature field. The results of FEA showed that the temperature and thermal stress distribution decreased along the graded direction. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 994–999, 2004
Engineering analysis of the reactive extrusion of ϵ‐caprolactone: The influence of processing on molecular degradation during reactive extrusion
Authors: Kim Byong Jun , White James L.
Published: August 2004

We have observed that earlier models of the reactive extrusion of ϵ‐caprolactone (CL), which do not include a consideration of mechanical degradation, significantly overpredict the molecular weights of the product. We have performed an engineering analysis of the increase in the molecular weight and the shear‐induced reduction of the molecular weight after the polymerization of CL during reactive extrusion. The variation of the molecular weight has been correlated to the polymerization rate and the mechanical power input into the poly(ϵ‐caprolactone) (PCL) melt. We first compute the increase in the molecular weight of PCL during reactive extrusion as a function of the mean residence time until the conversion is completed. Subsequently, we compute the shear‐induced reduction of the molecular weight after polymerization through the reactive extrusion of CL. The influence of the mechanical load on the PCL melt with increasing shear stress is important for predicting the molecular weight of the final product, particularly after polymerization. Our approach to the prediction of the reduction of the molecular weight is based on the correlation between the specific mechanical energy (i.e., the energy consumed per unit of mass of the material extruded) and the molecular weight. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1007–1017, 2004
Dyeing kinetics of methacrylic acid grafted polyester fabric with astrazonrot violet and rhodamine red basic dyes
Authors: El‐Gendy E. H.
Published: August 2004

The low‐temperature dyeing kinetics of radiation‐grafted poly(ethylene terephthalate) fabric were studied. The effects of the graft yield (GY), dye concentration, and dyeing temperature on the color difference (CD) of methacrylic acid grafted polyester fabric were studied for astrazonrot violet (AV) and rhodamine red (RR) basic dyes. CD increased sharply with an increase in GY and tended to level off at higher degrees of grafting. The best dyeing conditions were achieved for both dyes at pH 11.5. CD of the grafted fabric increased rapidly as the dyeing time increased; this was followed by a relatively slow dyeing rate within a few minutes, which depended on the concentration and temperature of the dye bath. The initial dyeing rates and rate constants for the AV dye were higher than those for the RR dye. The dyeing process followed 0.14‐order kinetics and was independent of the dyeing temperature or the type of dye. The dyeing rates and rate constants increased with an increase in the dyeing temperature. An Arrhenius‐type plot of the natural logarithm of the dyeing rate constant versus the inverse of the absolute temperature yielded apparent activation energies of 4.9 and 13.8 kJ/mol and pre‐exponential rate constants of 9.4 and 100.6 (CD/GY)s−1 for the AV and RR dyes, respectively. The mechanism of the dyeing process for the two dyes was diffusion‐controlled, and their dyeing rates depended on the type of basic dye. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1070–1076, 2004
Optimal therapeutic approaches to femoropopliteal artery intervention
Authors: Das Tony
Published: August 2004

Superficial femoral artery disease presents a complex challenge for therapy. The extent of vascular involvement may vary from focal disease with symptoms of intermittent claudication to long total occlusions manifest as critical limb ischemia. Optimal therapy requires understanding the available options including exercise programs, pharmacologic medical therapy, surgery and interventional endovascular therapy. Rapidly advancing endovascular technology for enabling safe intervention in complex, long occlusive segments of the superficial femoral artery continues to emerge. New devices like the SafeCross wire, Excimer laser, Silverhawk Atherectomy catheter, Cryoplasty catheter and new generations of bare metal and drug‐eluting nitinol stents are shifting the paradigm for therapy from surgical to more endovascular treatment even for the most complex disease presentation. Catheter Cardiovasc Interv 2004;63:21–30. © 2004 Wiley‐Liss, Inc.
Transcatheter closure of fistula between the right pulmonary artery and left atrium using the Amplatzer duct occluder
Authors: Francis Edwin , Sivakumar Kothandam , Kumar Raman Krishna
Published: August 2004

A congenital fistula between the right pulmonary artery and the left atrium is a rare condition that results in cyanosis. We report a successful catheter‐based closure of such a fistula in a 12‐year‐old using an Amplatzer duct occluder. The patient also had an atrial septal defect that was closed with an Amplatzer septal occluder. Catheter Cardiovasc Interv 2004;63:83–86. © 2004 Wiley‐Liss, Inc.
Wireless laser‐assisted angioplasty of the superficial femoral artery in patients with critical limb ischemia who have failed conventional percutaneous revascularization
Authors: Boccalandro Fernando , Muench Andreas , Sdringola Stefano , Rosales Oscar R.
Published: August 2004

Percutaneous revascularization has become an effective treatment for patients suffering from chronic critical limb ischemia (CLI) due to chronic atherosclerotic obstructions, including total occlusions. Unlike other vascular beds, total chronic occlusions of the femoropopliteal arteries are frequently found in patients with severe claudication or CLI. As a consequence, patients with long chronic total occlusions of the femoropopliteal arteries are generally not considered optimal candidates for percutaneous revascularization and are frequently referred for surgical revascularization. In the present study, we sought to evaluate the feasibility, safety, and outcome of a modified wireless laser ablation technique to recanalize total occlusions in patients with CLI who had failed conventional percutaneous techniques for limb salvage. Procedural success, complications, actuarial freedom of limb loss, and surgical revascularization were evaluated in 25 patients after a mean follow‐up of 13 ± 8 months. Procedural success was achieved in 21 patients (84%). Actuarial freedom from surgical revascularization or limb loss was 72%. There was one vascular perforation. No deaths or distal embolization occurred. Three patients (12%) required limb amputation during follow‐up, whereas four patients (16%) had surgical revascularization in the presence of feasible vascular targets. Limb salvage was achieved in 88% of patients when laser recanalization was combined with surgical revascularization. These results suggest that the use of laser ablation is safe and facilitates angioplasty and stenting in patients with CLI that failed conventional endovascular revascularization. This technique might prevent limb loss in patients with CLI due to femoropopliteal total occlusions, particularly in patients with unsuitable anatomy for surgical revascularization. Catheter Cardiovasc Interv 2004;63:7–12. © 2004 Wiley‐Liss, Inc.
Contribution of early lumen loss after balloon angioplasty for in‐stent restenosis to lumen loss at follow‐up
Authors: Fujii Kenichi , Masutani Motomaru , Kobayashi Yoshio , Tateishi Jun , Kawasaki Daizo , Ohyanagi Mitsumasa , Mintz Gary S. , Leon Martin B.
Published: August 2004

The treatment of in‐stent restenosis using balloon angioplasty alone often produces excellent early results, but is associated with high rate of recurrence. Previous studies have demonstrated significant tissue reintrusion shortly after the treatment of in‐stent restenosis with balloon angioplasty. The study was designed to elucidate the contribution of early lumen loss 6 hr after balloon angioplasty to lumen loss at follow‐up. We prospectively performed quantitative coronary angiography and intravascular ultrasound in 12 patients with in‐stent restenosis before intervention, after the final procedure, 6 hr later (5.6 ± 1.4 hr), and at follow‐up (7.7 ± 2.3 months). Compared with immediately after balloon angioplasty, by 6 hr postintervention, the minimum lumen diameter (MLD) and lumen cross‐sectional area had decreased significantly (2.48 ± 0.44 to 2.01 ± 0.57 mm, P = 0.01, and 7.0 ± 1.2 to 5.5 ± 1.4 mm2, P = 0.004, respectively). Furthermore, the MLD decreased further between 6 hr postintervention and long‐term follow‐up (2.01 ± 0.57 to 1.55 ± 0.64 mm; P = 0.001). Patients who showed recurrence of restenosis at follow‐up had greater early lumen loss than patients without recurrence of restenosis (0.71 ± 0.31 vs. 0.23 ± 0.13 mm; P = 0.006). Diffuse lesions had greater early lumen loss compared to focal lesions (0.75 ± 0.35 vs. 0.28 ± 0.13 mm; P = 0.008). Early lumen loss is common after the treatment of in‐stent restenosis by balloon angioplasty. Within the first 6 hr postintervention, 32% ± 29% of acute lumen gain is lost, and early lumen loss contributed to 42% ± 18% of total lumen loss at follow‐up. Catheter Cardiovasc Interv 2004;63:52–56. © 2004 Wiley‐Liss, Inc.
Balloon angioplasty plus cilostazol administration versus primary stenting of small coronary artery disease: Final results of COMPASS
Authors: Tsuchikane Etsuo , Takeda Yoshihiro , Nasu Kenya , Awata Nobuhisa , Kobayashi Tohru
Published: August 2004

Efficacy of primary stenting in small coronary artery disease is still controversial. Cilostazol has been reported to control restenosis after balloon angioplasty (BA). The aim was to compare primary stenting with BA plus cilostazol administration in small coronary artery disease. Of 106 lesions located in small coronary artery (reference < 3.0 mm), 50 lesions were randomly assigned to the stenting and 56 lesions to the BA‐cilostazol group. Multilink stent was implanted in the stenting group. In the BA‐cilostazol group, cilostazol (200 mg/day) without aspirin was administered for 6 months after BA. Ticlopidine was given for 1 month when bailout stent was implanted. Serial quantitative angiography was performed at the procedure and 6 months. The primary endpoint was 6‐month angiographic restenosis. Clinical event rates at 1 year were also assessed. Baseline characteristics were similar. All procedures were successful. Bailout stenting was performed in three lesions in the BA‐cilostazol group. No side effects of cilostazol were observed. Postprocedural lumen diameter was significantly larger (2.69 vs. 2.03 mm; P < 0.0001) in the stenting group. However, the follow‐up lumen diameter was not different (1.76 vs. 1.85 mm, stenting vs. BA‐cilostazol). Although the difference was not statistically significant, restenosis rate was lower in the BA‐cilostazol group (13.2% vs. 24.5%; P = 0.11). Subacute thrombosis occurred in one patient and target revascularization rate was higher in the stenting group (22.0% vs. 10.7%; P = 0.10). BA plus cilostazol administration seems to be a favorable strategy for small coronary artery disease. Catheter Cardiovasc Interv 2004;63:44–51. © 2004 Wiley‐Liss, Inc.
Percutaneous stent‐mounted valve for treatment of aortic or pulmonary valve disease
Authors: Webb John G. , Munt Bradley , Makkar Raj R. , Naqvi Tasneem Z. , Dang Ninh
Published: August 2004

The objective of this study was to develop a prosthetic cardiac valve designed for percutaneous transcatheter implantation. Percutaneous catheter‐based therapies play a limited role in the management of cardiac valve disease. Surgical implantation of prosthetic valves usually requires thoracotomy and cardiopulmonary bypass. The stent‐valve is constructed of a rolled sheet of heat‐treated nitinol. Although malleable when cooled, once released from a restraining sheath at body temperature the stent unrolls, becomes rigid, and assumes its predetermined cylindrical conformation. A ratcheting lock‐out mechanism prevents recoil and external protrusions facilitate anchoring. Valve leaflets are constructed of bovine pericardium. The feasibility of catheter implantation, prosthetic valve function, and survival were investigated in an animal model. In vitro and pulse duplicator testing documented valve durability. Endovascular delivery of the prototype stent‐valve to the aortic or pulmonary position was feasible. Accurate positioning was required to ensure exclusion of the native valve leaflets and, in the case of the aortic valve, to avoid compromise of the coronary ostia or mitral apparatus. Oversizing of the stent in relation to the valve annulus was desirable to facilitate anchoring and prevent paravalvular insufficiency. Stent‐valve implantation proved feasible and compatible with survival in an animal model. Transcatheter implantation of prosthetic valves is possible. Further evolution of this technology will involve lower‐profile devices with design features that facilitate vascular delivery, visualization, positioning, deployment, and valvular function. Catheter Cardiovasc Interv 2004;63:89–93. © 2004 Wiley‐Liss, Inc.
Stent implantation for coarctation of aorta caused by a Rashkind patent ductus arteriosus umbrella
Authors: Beck Avi , Birk Einat , Blieden Leonard C. , Bruckheimer Elchanan
Published: August 2004

This case demonstrates a novel use of stent implantation for relief of coarctation of the aorta caused by protrusion of a Rashkind patent ductus arteriosus umbrella. Follow‐up 3 years after stent implantation shows complete relief of obstruction. Catheter Cardiovasc Interv 2004;63:80–82. © 2004 Wiley‐Liss, Inc.
Fine Structures of Zeolite‐Linde‐L (LTL): Surface Structures, Growth Unit and Defects
Authors: Ohsuna Tetsu , Slater Ben , Gao Feifei , Yu Jihong , Sakamoto Yasahiro , Zhu Gaugshan , Terasaki Osamu , Vaughan David E. W. , Qiu Shilun , Catlow C. Richard A.
Published: August 2004

High‐resolution electron microscopy (HREM) has been used to image the surface structure of nano‐ and micrometer‐sized synthetic crystals of zeolite‐Linde‐L (LTL). Columnar holes and rotational, nano‐sized, wheel‐like defects were observed within the crystals, where the hole has a minimum size equal to that of the rotational defect. Predictions of surface structure from atomistic computer simulation concur with the observations from HREM and provide insight into the crystal growth mechanism of perfect and defective LTL. Analysis of the energetics of the formation of rotational defect structures reveals that the driving force for defect creation is thermodynamic and furthermore, the rotational defects could be created in high concentrations. Formation of a columnar hole is found to be slightly energetically unfavourable and therefore we speculate that the incidence of both rotational and nano‐sized vacancy defects is strongly dependent on kinetic factors and reaction conditions. The morphology of nano‐ and microcrystalline LTL is contradistinct and we use insights from simulation to propose an explanation of the disparity in crystal shape.
Participation of disabled children in individual decisions about their lives and in public decisions about service development
Authors: Cavet Judith , Sloper Patricia
Published: August 2004

A literature review was carried out to establish what evidence exists about disabled children's participation in decision‐making, both regarding their own lives and about the shape of service delivery. There is evidence that disabled children hold and can express views, given the right environment. However, participation of disabled children needs further development. Measures proposed include addressing organisational systems so that they promote participation, extending advocacy services, the adoption of inclusive approaches and staff training, plus education and information for disabled children and their parents. There remain significant gaps in the research evidence available.
Fathers matter: a research review
Authors: Featherstone Brid
Published: August 2004

This review outlines key areas of research in relation to the following: the nature of father involvement; factors influencing involvement; the influence of fathers on children; and social policy developments. It reviews the practice oriented research which has emerged in the UK as engaging fathers has become part of the agenda for many child welfare agencies. It highlights the gaps in research and policy developments in relation to statutory agencies such as social services.
Effective use of preparative chiral HPLC in a preclinical drug synthesis
Authors: Nelson Todd D. , Welch Christopher J. , Rosen Jonathan D. , Smitrovich Jacqueline H. , Huffman Mark A. , McNamara James M. , Mathre David J.
Published: August 2004

Access to a key 3‐aryl‐δ‐lactone intermediate in enantiopure form using preparative chiral chromatography allowed expedited preparation of an important drug discovery target. A preclinical drug discovery strategy that combines rapid route discovery with effective use of preparative chiral chromatography can result in significant savings of both time and labor. Chirality 16:609–613, 2004. © 2004 Wiley‐Liss, Inc.
First optically active selenurane oxide: Resolution of C2‐symmetric 3,3,3′,3′‐tetramethyl‐1,1′‐spirobi [3h,2,1]‐benzoxaselenole oxide
Authors: Drabowicz Józef , Luczak Jerzy , Mikolajczyk Marian , Yamamoto Yohsuke , Matsukawa Shiro , Akiba Kin‐Ya
Published: August 2004

The enantiomers of the first optically active selenurane oxide ever reported, C2‐symmetric 3,3,3′,3′‐tetramethyl‐1,1′‐spirobi[3h,2,1]‐benzoxaselenole oxide, were isolated via enantioselective liquid chromatography of the racemate or by spontaneous resolution that occurs during the slow evaporation of its acetonitrile solution or the slow crystallization from the same solvent. Chirality 16:598–601, 2004. © 2004 Wiley‐Liss, Inc.
Central nervous system metastases in patients with high‐risk breast carcinoma after multimodality treatment
Authors: Gonzalez‐Angulo Ana M. , Cristofanilli Massimo , Strom Eric A. , Buzdar Aman U. , Kau Shu‐Wan , Broglio Kristine R. , Smith Terry L. , Hortobagyi Gabriel N.
Published: August 2004

BACKGROUND

The current study was performed to determine the incidence of central nervous system (CNS) metastases and to examine associated disease characteristics in a group of patients with locally advanced breast carcinoma (LABC) or inflammatory breast carcinoma (IBC) treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX).

METHODS

Seven hundred sixty‐eight patients treated with multimodality therapy between 1982 and 2000 in any of 6 neoadjuvant trials were eligible for the current study. Five hundred ninety‐two patients (77%) had LABC, and 176 (23%) had IBC. CNS disease was defined as the presence of brain metastases or leptomeningeal disease. Time to detection of CNS disease and overall survival were estimated using the Kaplan–Meier product‐limit method, and differences were evaluated using log‐rank tests.

RESULTS

The median patient age was 48 years. Most tumors were classified as T4 lesions (58%) and exhibited lymph node involvement (78%). Fifty‐one percent of all tumors had positive hormone receptor status. At a median follow‐up duration of 9.5 years, 61 patients (8%) had developed CNS metastases, with the CNS representing the first site of recurrence for 38 of these 61 (63%). Characteristics associated with the development of CNS metastases over time included negative hormone receptor status (P = 0.03), Grade 3 disease (P = 0.01), and larger tumor size (P = 0.02). The median time to detection of CNS metastases was 2.3 years. Ten patients (16%) remained alive after treatment for CNS metastases. The median survival from the time of diagnosis of CNS metastases was 8 months.

CONCLUSIONS

CNS metastases from breast carcinoma were relatively uncommon and were strongly associated with more aggressive clinical presentation. Survival from the time of diagnosis of such metastases generally was short. Cancer 2004. © 2004 American Cancer Society.
Fluorescent CXCL12AF647 as a novel probe for nonradioactive CXCL12/CXCR4 cellular interaction studies
Authors: Hatse Sigrid , Princen Katrien , Liekens Sandra , Vermeire Kurt , De Clercq Erik , Schols Dominique
Published: August 2004

Background

Chemokines drive the migration of leukocytes via interaction with specific G protein–coupled 7‐transmembrane receptors. The chemokine ligand/receptor pair stromal cell–derived factor‐1 (SDF‐1, CXCL12)/CXCR4 is gaining increasing interest because of its involvement in the metastasis of several types of cancer and in certain inflammatory autoimmune disorders such as rheumatoid arthritis. In addition, CXCR4 serves as an important coreceptor for cellular entry of T‐tropic strains of human immunodeficiency virus (HIV). Therefore, potent and specific CXCR4 antagonists may have therapeutic potential as anti‐HIV, anti‐cancer, and anti‐inflammatory drugs.

Methods and Results

Chemokine receptor antagonists can be identified by their ability to inhibit ligand binding to the receptor protein. Until now, chemokine binding assays were mostly performed with radiolabeled chemokine ligands such as [125I]CXCL12. To overcome the practical problems associated with such radioactive chemokine binding assays, we have developed a flow cytometric technique using a new, commercially available Alexa Fluor 647 conjugate of CXCL12 (CXCL12AF647). Calcium flux, chemotaxis, and p44/42 mitogen‐activated protein kinase phosphorylation assays showed that the agonistic activity of the fluorescent CXCL12 was unchanged as compared with that of unlabeled CXCL12. Human T‐lymphoid (CXCR4+) SupT1 cells and CXCR4‐transfected, but not CCR5‐ or CXCR3‐transfected, human astroglioma U87.CD4 cells specifically bound CXCL12AF647 in a concentration‐dependent manner. Unlabeled CXCL12 and the well‐known CXCR4 inhibitors, AMD3100 and T22, blocked the binding of CXCL12AF647 to SupT1 cells with 50% inhibitory concentrations of 92, 13, and 8 ng/ml, respectively. We have also used this method to evaluate CXCL12 binding and CXCR4 expression level in different subsets of human peripheral blood mononuclear cells.

Conclusion

CXCL12AF647 is a valuable, more convenient alternative for [125I]CXCL12 in ligand/receptor interaction studies. © 2004 Wiley‐Liss, Inc.
Cholesterol sensitivity of detergent resistance: A rapid flow cytometric test for detecting constitutive or induced raft association of membrane proteins
Authors: Gombos Imre , Bacsó Zsolt , Detre Cynthia , Nagy Henrietta , Goda Katalin , Andrásfalvy Márton , Szabó Gábor , Matkó János
Published: August 2004

Background

Lipid rafts are cholesterol‐ and glycosphingolipid‐rich microdomains in the cellular plasma membranes that play critical roles in compartmentalization (concentration, coupling, and isolation) of receptors and signal molecules. Therefore, detecting constitutive or induced raft associations of such proteins is of central interest in cell biology. This has mostly been done with time‐ and cell‐consuming immunobiochemical techniques affected by several sources of artifacts. A flow cytometric analysis of immunocytochemical staining under differential circumstances of detergent treatment offers a new alternative to this method.

Methods

Membrane microdomains are resistant to nonionic detergents due to extensive, strong interactions between their molecular constituents. We used this feature to develop a rapid flow cytometric assay of differential detergent resistance based on immunocytochemical labeling of extracellular domain epitopes in membrane proteins. Data evaluation is based on comparative detection of their detergent solubility without and with cholesterol depletion of cell membranes, resolved by moderate concentrations of nonionic detergents.

Results

Nonionic detergents Triton X‐100 and Nonidet‐40 (0.05–0.1%) in cold or Brij‐98 (0.1–0.5%) at 37°C efficiently resolved detergent solubility or resistance of many lymphocyte cell surface proteins. Kinetic data revealed that a short (5–10 min) detergent treatment is sufficient for this assay. Comparison of detergent solubility in untreated and cholesterol‐depleted cells differentiated membrane proteins associated with or excluded from raft microdomains, respectively. Confocal microscopy showed that this mild detergent treatment leaves the cytoskeleton of the cells intact, with a detectable expression of raft marker detergent‐resistant proteins attached to it. An induced association with rafts of immunoglobulin E receptors upon antigen cross‐linking was also easily detectable in rat mast cells by this approach.

Conclusions

A protocol is proposed for a rapid (5–10 min) test of detergent resistance of membrane proteins in cells. The approach requires only a small amount of cells (104/sample) and offers a good resolution of detergent solubility or resistance of membrane proteins, also in terms of the underlying mechanisms, with an advantage of applicability for all conventional bench‐top flow cytometers. © 2004 Wiley‐Liss, Inc.