bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxaliplatin-induced hypersensitivity reaction displaying marked elevation of immunoglobulin E
Authors: Kitada Noriaki , Dan Toshiyuki , Takara Kohji , Tsuji Takashi , Yamasaki Hajime , Yokoyama Teruyoshi , Watari Masakatsu
Published: November 2007

A 74-year-old female has been diagnosed with stage IIIB rectal cancer in 2003. Following anterior resection, she received adjuvant chemotherapy with three different regimens. In August 2005, she was started on a modified FOLFOX6 regimen, and the sixth cycle of chemotherapy induced a severe hypersensitivity reaction (HSR). Immediate cessation of the infusion resulted in a disappearance of the allergic reaction 60 min later. Blood tests just after the reaction demonstrated a marked elevation of immunoglobulin E to 300 IU L-1 (normal range: <170 IU L-1). This change implies the involvement of a type I reaction in the HSR. In addition, a drug lymphocyte stimulating test against oxaliplatin and levofolinate calcium (an isomer of leucovorin calcium) gave values of 696% and 107 % respectively, as compared with control serum. This suggests that the patient had an adverse reaction not only of type I but partly of type IV allergic reaction also. Oxaliplatin appears to have caused a HSR in this Japanese patient, and thus pharmacists, physicians, and other medical staff must keep a careful watch of a patient's clinical condition during chemotherapy including oxaliplatin. J Oncol Pharm Practice (2007) 13: 233—235.
Overview of targeted therapies in Oncology
Authors: Kalyn Rhonda
Published: November 2007

Background: Recent scientific advances have provided a map of the human genome along with a better understanding of the processes that transform healthy cells into diseased cells. This has led to the emergence of a new class of drugs called targeted therapies.

Objective: To describe the classifications and basic pharmacology of targeted therapies.

Methods: A literature search was performed for peer reviewed journal articles using Medline (1996—2007), Embase (1996—2007) and Google. The search was performed using keywords such as angiogenesis inhibitors, cancer vaccines, gene therapy, monoclonal antibodies, small molecules, proteasome inhibitors, targeted therapy and tyrosine kinase inhibitors.

Conclusions: A review of the basic pharmacology is described in this article, including the following major categories of targeted therapies: • Small molecule drugs • Monoclonal antibodies • Apoptosis-inducing drugs • Angiogenesis Inhibitors • Cancer vaccines • Gene therapy J Oncol Pharm Practice (2007) 13: 199—205.
Therapeutic drug monitoring of cancer chemotherapy
Authors: Alnaim Lamya
Published: November 2007

Therapeutic drug monitoring is not routinely used for chemotherapy agents. There are Several reasons, but one major drawback is the lack of established therapeutic Concentration ranges. Combination chemotherapy makes the establishment of Therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as when that drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centers, and some of these protocols are now part of large multicentre trials. Nonetheless, TDM clearly has the potential to improve the clinical use of chemotherapy gents, most of which have very narrow therapeutic indices and highly variable pharmacokinetics. A substantial body of literature accumulating during the past 15 years demonstrates relationships between systemic exposure to various chemotherapy agents and their toxic or therapeutic effects. This article reviews TDM concepts in addition to tools based on pharmacokinetic modeling of chemotherapy agents. The administered dose of chemotherapy agents is sometimes adjusted individually using either a priori or a posteriori methods. These models can only be applied by using the same dose and schedule as the original study. Bayesian estimation offers more flexibility in blood sampling times and, owing to its precision and to the amount of information provided is the method of choice for ensuring that a given patient benefits from the desired systemic exposure. Moreover, the role and application of Pharmacogenetics as a tool for individualizing chemotherapy is discussed highlighting the agents and mechanisms that have been well studied and defined and their relevance to clinical practice. Finally, this paper address issues critical to the optimal use of TDM in a clinical setting, and the role of clinical pharmacist in this regard. In addition, it discusses future developments in this field that can contribute to improving cancer chemotherapy In terms of patient outcome and survival. J Oncol Pharm Practice (2007) 13: 207—221.
Influence of Dietary Sorghum (Sorghum vulgare) and Corn Supplemented with Methionine on Cut-Up Pieces Weights of Broiler Carcass and Quality Properties of Breast and Drumsticks Meat
Authors: Aksu M.İ. , İmik H. , Karaoğlu M.
Published: November 2007

This research was carried out to determine the effects of sorghum (BS = basal diets containing 30% sorghum), corn (BC = basal diets containing corn) and supplemental methionine (BSM = diet BS plus 0.69% methionine, BCM = diet BC plus 0.69% methionine) in broiler diets on the cold carcass weight and cut-up pieces weight of broilers and some chemical, physical and microbiological properties of breast and drumstick meats. A total 240 male (120) or female (120) broiler chicks (Ross-308) were allocated to four dietary treatments (BS, BSM, BC, and BCM groups) in a completely randomized experimental design. At the end of the trial all chicks were slaughtered, and then were stored at 3°C for 24 h. After standard dissection of carcasses, cut-up pieces are weighed. The breasts and drumstick muscles were analyzed for moisture, pH, ash, fat, thiobarbituric acid reactive substances (TBARS), color (L*, a*, and b*), total psychrotrophic, lactic acid, Micrococcus/Staphylococcus, S. aureus, and Enterobacteriaceae counts. Although cold carcass and cut-up pieces weights were positively affected from supplemental methionine containing corn diet. However, weight were not influenced by supplemental methionine in diet containing sorghum and the other groups. While the highest whole breast weight is determined from broilers fed with corn and 0.69% methionine (BCM), the highest drumstick weight was determined from broilers fed with only sorghum (BS). The weights of cold carcasses and cut-up pieces of male broilers were higher than that of female. Except for redness (a* value), other parameters are affected by treatments. The effects of type of meat (breast and drumstick meats) and gender were also variable. The moisture, pH, TBARS, fat, a*, Micrococcus/Staphylococcus and Enterobacteriaceae count were lower ( p<0.05) in breast fillets than drumstick muscles. The moisture, fat, L*, lactic acid bacteria, Micrococcus/Staphylococcus and S. aureus counts were lower ( p<0.05) in female broiler meats than male broiler meats.
Uptake Kinetics and Absorption of Calcium in Apple Matrices
Authors: Salvatori D.M. , González-Fesler M. , Weisstaub A. , Portela M.L. , Alzamora S.M.
Published: November 2007

The purpose of this paper was to study the kinetics of calcium uptake of blanched and not blanched apple tissue during impregnation treatments under vacuum or/and at atmospheric pressure. The relative absorption of calcium in rats, regarding calcium carbonate as reference substance, was also analyzed as a first approach. Apple impregnation is conducted (with and without previous blanching in saturated vapor) in isotonic glucose aqueous solutions containing calcium gluconate and lactate. A 50 mm Hg vacuum pressure is applied for a time t1 (0—180 min) or atmospheric pressure is used for a process time t2 (0—7.5 h). Calcium uptake by apple tissue is influenced by system pressure, blanching, and impregnation time, reaching 500—4600 μg Ca/g according to process variables. Preliminary data of true calcium absorption ranges between 74 and 86% regarding calcium carbonate.
Everywhere and nowhere
Authors: Brooker Will
Published: November 2007

This article discusses fan pilgrimage, using as a case study the city of Vancouver, Canada — a location that has been used as the basis for several cult television series. It draws on theories of urban geography, particularly of postmodern suburbia (Edward Relph, Jean Baudrillard, Umberto Eco, Fredric Jameson, Edward Soja) to argue that while Vancouver may be valued by film and television producers as a generic, anonymous, `flat' environment, to fan pilgrims who bring their own imaginary maps (based on the fictional geographies of Smallville, The X-Files and Battlestar Galactica ), the city is a rich intersection of possible worlds. The article uses science fiction and superhero metaphors of parallel universes and `infinite earths' to explore this fan experience, arguing finally that pilgrimage can be an act of creation, performance, disguise and carnival that symbolically transforms the location in question, temporarily inverting social structures and making the city into a liberating, playful space. •
Catching them at it
Authors: Iszatt-White Marian
Published: November 2007

Based on an ethnographic study within the road maintenance sector, this article explores the occurrence of rule violations in industrial settings subject to a high level of regulation, and is specifically concerned with operatives' risk perceptions in relation to health and safety rules and with management strategies for their successful mitigation. The study contrasts two different, but related, types of risk. First, it considers those aspects of health and safety where the limits of `best practice' working are insufficient to eliminate or control major sources of risk, and second, it looks at risks the known outcomes of which are underestimated as a result of being delayed or indeterminate. The article considers the sources of rule violation, such as operatives' sense of self-efficacy; the need for heedfulness as well as compliance; and the dangers of risk displacement and the creation of a `second-order' focus.
`Code talk' in soft work
Authors: Higgins Allen
Published: November 2007

The performance of writing software is an under-studied phenomenon in Information Systems (IS) studies. Key aspects of the process of software development — the practice of writing code, coding texts collectively, maintaining and extending source code — are too often glossed or treated unproblematically as technical `givens' rather than social accomplishments. Although ethnographic methods are now considered a valid mode of study in the software industry, there is a relative scarcity of ethnographic studies of the performance of programming itself. Utilizing data drawn from an ethnographic study of an Irish software development company, this article presents an intensive study of what I term `code talk', the verbal interactions which attend the performance of programming software. `Code talk' is then situated as a crucial element of a broader social understanding of collaborative knowledge work.
`You need tits to get on round here'
Authors: Fisher Ginny
Published: November 2007

Drawing upon five open-ended interviews with academic staff and two years of participant observation, this article presents an ethnographic study of gendered and sexualized work cultures in the Business School of a large British university I shall call Maxi which is struggling to find a place for itself in the new managerialist climate of early 21st-century British higher education. Despite significant increases in the number of female academics and academic managers, women in this organization are still subject to unfair and differential treatment, attitudes and expectations by (some) men. Women academic managers are still seen as `other' whilst men academics and managers represent the norm.
Room to View
Authors: Holloway Donell , Green Lelia
Published: November 2007

Although Australian media consumption follows general Western trends toward increasingly media rich households, there seems to be a distinctly regional response to how media technologies are incorporated into the Australian home. Although a majority of Australian families with children have a second (and many a third) television set, few choose to locate these technologies in children's bedrooms. Thus, Australia's high level of screen entertainment media is not associated with a high level of children's bedroom access, as would generally be expected. When family conflict does arise regarding television viewing, it is just as likely to be about “where to watch” as “what to watch.” Through the use of an audience ethnography approach, this article explores how Australian parents and their children make sense of their television viewing in the home environment, highlighting how new and multiple media technologies are integrated into the spatial geography of the antipodean family home.
Watching Television Without Pity
Authors: Andrejevic Mark
Published: November 2007

Increasingly, online fan sites are providing instant feedback to television writers and scriptwriters, who are starting to pay more attention to the chatter of “the boards.” At the same time, the boards have become a marketing strategy for TV shows that takes advantage of interactivity to create fan communities and build viewer loyalty. Drawing on a case study of the popular web site TelevisionWithoutPity.com, this article explores the way in which online viewer activity doubles as a form of value-enhancing labor for television producers in two ways: by allowing fans to take on part of the work of making a show interesting for themselves and by providing instant (if not necessarily statistically representative) feedback to producers. Based on interviews with producers and contributors to a bulletin board they frequent, the article explores both sides of interactivity: the promise of shared control and the ability to off-load some market research labor onto viewers.
Information-theory based surrogate marker evaluation from several randomized clinical trials with continuous true and binary surrogate endpoints
Authors: Pryseley Assam , Tilahun Abel , Alonso Ariel , Molenberghs Geert
Published: November 2007

Background Surrogate endpoints potentially reduce the duration and/or increase the amount of information available in a study, thereby diminishing patient burden and cost. They may also increase the effectiveness and reliability of research, through beneficial impact on noncompliance and missingness.

Purpose In this article, we review the meta-analytic approach of Buyse et al. (2000) and its extension to mixed continuous and binary endpoints by Molenberghs Geys, and Buyse (2001).

Methods An information-theoretic alternative, based on Alonso and Molenberghs (2007a) is proposed. The method is evaluated using simulations and application to data from an ophthalmologic trial, with lines of vision lost at 6 months as candidate surrogate endpoints for lines of vision lost at 12 months. The method is implemented as an R function.

Results The information-theoretic approach is based on solid theory, easy to apply, and enjoys elegant properties. While the information-theoretic approach appears to be somewhat biased downwards, this is due to fact that it operates at explicitly observed outcomes, without the need for unobserved, latent scales. This is a desirable property.

Limitations While easy-to-use and implement, the theoretical foundation of the information-theory approach is more mathematical. It produces some bias for small to moderate trial/center sizes, and hence is recommended primarily for sufficiently large trials.

Conclusions Since the meta-analytic framework can be computationally extremely expensive, the information-theoretic approach of Alonso and Molenberghs (2007a) is a viable alternative. For the ophthalmologic case study, the conclusion is that the lines of vision lost at sixth month do have some, but not overwhelming promise as a surrogate endpoint. Clinical Trials 2007; 4: 587—597. http://ctj.sagepub.com
The Veterans Affairs Low Vision Intervention Trial (LOVIT): Design and Methodology
Authors: Stelmack Joan A , Tang X. Charlene , Reda Domenic J. , Moran D'Anna , Rinne Stephen , Mancil Rickilyn M. , Cummings Roger , Mancil Gary , Stroupe Kevin , Ellis Nancy , Massof Robert W.
Published: November 2007

Background Visual impairment is a major public health problem. Vision rehabilitation programs have the potential to restore independence and improve quality of life for persons with permanent vision loss, and few have been evaluated in randomized controlled trials.

Purpose The Veterans Affairs (VA) Low Vision Intervention Trial is a multicenter randomized clinical trial to evaluate the effectiveness of a new outpatient low vision rehabilitation program.

Methods 126 patients with moderate and severe vision loss due to macular diseases are randomized to low vision treatment in an outpatient setting or a usual care control group at two VA facilities in Hines, Illinois, and Salisbury, North Carolina. The primary outcome is the change in visual reading ability from baseline to four months measured with the Veterans Affairs Low Vision Visual Functioning Questionnaire-48 (VA LV VFQ-48). Secondary outcomes compare the mean change in visual ability measured with the VA LV VFQ-48 (overall ability, mobility, visual information processing, visual motor skills) for the treatment and control groups. Costs and cost effectiveness of outpatient treatment are evaluated.

Results The low vision rehabilitation setting, use of a waiting list control group to address ethical issues, development of the treatment protocol, development of a vision function questionnaire for patients to self-report the difficulty they experience performing daily activities, and the use of Rasch analysis to develop and estimate this outcome measure are described.

Limitations If the new low vision rehabilitation program is proven effective, studies will be needed to determine which of the multiple aspects of the intervention are necessary and sufficient.

Conclusions The challenges of conducting clinical trials in a rehabilitation setting and use of a waiting list (deferred treatment) control group extend beyond LOVIT. The design and methods of LOVIT may be applicable to other trials of rehabilitation services and to outcomes for which reliable and valid measurement tools must be developed. Clinical Trials 2007; 4: 650—660. http://ctj.sagepub.com
Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy
Authors: Nefedova Yulia , Sullivan Daniel M. , Bolick Sophia C. , Dalton William S. , Gabrilovich Dmitry I.
Published: November 2007

Drug resistance remains a critical problem in the treatment of patients with multiple myeloma. Recent studies have de-termined that Notch signaling plays a major role in bone marrow (BM) stroma-mediated protection of myeloma cells from de novo drug-induced apoptosis. Here, we investigated whether pharmacologic inhibition of Notch signaling could affect the viability of myeloma cells and their sensitivity to chemotherapy. Treatment with a γ-secretase inhibitor (GSI) alone induced apoptosis of myeloma cells via specific inhibition of Notch signaling. At concentrations toxic for myeloma cell lines and primary myeloma cells, GSI did not affect normal BM or peripheral blood mononuclear cells. Treatment with GSI prevented BM stroma-mediated protection of myeloma cells from drug-induced apoptosis. The cytotoxic effect of GSI was mediated via Hes-1 and up-regulation of the proapoptotic protein Noxa. In vivo experiments using xenograft and SCID-hu models of multiple myeloma demonstrated substantial antitumor effect of GSI. In addition, GSI significantly improved the cytotoxicity of the chemotherapeutic drugs doxorubicin and melphalan. Thus, this study demonstrates that inhibition of Notch signaling prevents BM-mediated drug resistance and sensitizes myeloma cells to chemotherapy. This may represent a promising approach for therapeutic intervention in multiple myeloma.
In situ analysis of cross-hybridisation on microarrays and the inference of expression correlation
Authors: Casneuf Tineke , Van de Peer Yves , Huber Wolfgang
Published: November 2007

Background

Microarray co-expression signatures are an important tool for studying gene function and relations between genes. In addition to genuine biological co-expression, correlated signals can result from technical deficiencies like hybridization of reporters with off-target transcripts. An approach that is able to distinguish these factors permits the detection of more biologically relevant co-expression signatures.

Results

We demonstrate a positive relation between off-target reporter alignment strength and expression correlation in data from oligonucleotide genechips. Furthermore, we describe a method that allows the identification, from their expression data, of individual probe sets affected by off-target hybridization.

Conclusion

The effects of off-target hybridization on expression correlation coefficients can be substantial, and can be alleviated by more accurate mapping between microarray reporters and the target transcriptome. We recommend attention to the mapping for any microarray analysis of gene expression patterns.
Effect of spatial resolution on cluster detection: a simulation study
Authors: Ozonoff Al , Jeffery Caroline , Manjourides Justin , White Laura Forsberg , Pagano Marcello
Published: November 2007

Background

Aggregation of spatial data is intended to protect privacy, but some effects of aggregation on spatial methods have not yet been quantified.

Methods

We generated 3,000 spatial data sets and evaluated power of detection at 12 different levels of aggregation using the spatial scan statistic implemented in SaTScan v6.0.

Results

Power to detect clusters decreased from nearly 100% when using exact locations to roughly 40% at the coarsest level of spatial resolution.

Conclusion

Aggregation has the potential for obfuscation.
Localization of HIV-1 Vpr to the nuclear envelope: Impact on Vpr functions and virus replication in macrophages
Authors: Jacquot Guillaume , Le Rouzic Erwann , David Annie , Mazzolini Julie , Bouchet Jérôme , Bouaziz Serge , Niedergang Florence , Pancino Gianfranco , Benichou Serge
Published: November 2007

Background

HIV-1 Vpr is a dynamic protein that primarily localizes in the nucleus, but a significant fraction is concentrated at the nuclear envelope (NE), supporting an interaction between Vpr and components of the nuclear pore complex, including the nucleoporin hCG1. In the present study, we have explored the contribution of Vpr accumulation at the NE to the Vpr functions, including G2-arrest and pro-apoptotic activities, and virus replication in primary macrophages.

Results

In order to define the functional role of Vpr localization at the NE, we have characterized a set of single-point Vpr mutants, and selected two new mutants with substitutions within the first α-helix of the protein, Vpr-L23F and Vpr-K27M, that failed to associate with hCG1, but were still able to interact with other known relevant host partners of Vpr. In mammalian cells, these mutants failed to localize at the NE resulting in a diffuse nucleocytoplasmic distribution both in HeLa cells and in primary human monocyte-derived macrophages. Other mutants with substitutions in the first α-helix (Vpr-A30L and Vpr-F34I) were similarly distributed between the nucleus and cytoplasm, demonstrating that this helix contains the determinants required for localization of Vpr at the NE. All these mutations also impaired the Vpr-mediated G2-arrest of the cell cycle and the subsequent cell death induction, indicating a functional link between these activities and the Vpr accumulation at the NE. However, this localization is not sufficient, since mutations within the C-terminal basic region of Vpr (Vpr-R80A and Vpr-R90K), disrupted the G2-arrest and apoptotic activities without altering NE localization. Finally, the replication of the Vpr-L23F and Vpr-K27M hCG1-binding deficient mutant viruses was also affected in primary macrophages from some but not all donors.

Conclusion

These results indicate that the targeting of Vpr to the nuclear pore complex may constitute an early step toward Vpr-induced G2-arrest and subsequent apoptosis; they also suggest that Vpr targeting to the nuclear pore complex is not absolutely required, but can improve HIV-1 replication in macrophages.
Glucocorticoid Receptor Is Required for Skin Barrier Competence
Authors: Bayo Pilar , Sanchis Ana , Bravo Ana , Cascallana Jose Luis , Buder Katrin , Tuckermann Jan , Schütz Günther , Pérez Paloma
Published: November 2007

To investigate the contribution of the glucocorticoid receptor (GR) in skin development and the mechanisms underlying this function, we have analyzed two mouse models in which GR has been functionally inactivated: the knockout GR−/− mice and the dimerization mutant GRdim/dim that mediates defective DNA binding-dependent transcription. Because GR null mice die perinatally, we evaluated skin architecture of late embryos by histological, immunohistochemical, and electron microscopy studies. Loss of function of GR resulted in incomplete epidermal stratification with dramatically abnormal differentiation of GR−/−, but not GR+/− embryos, as demonstrated by the lack of loricrin, filaggrin, and involucrin markers. Skin sections of GR−/− embryos revealed edematous basal and lower spinous cells, and electron micrographs showed increased intercellular spaces between keratinocytes and reduced number of desmosomes. The absent terminal differentiation in GR−/− embryos correlated with an impaired activation of caspase-14, which is required for the processing of profilaggrin into filaggrin at late embryo stages. Accordingly, the skin barrier competence was severely compromised in GR−/− embryos. Cultured mouse primary keratinocytes from GR−/− mice formed colonies with cells of heterogeneous size and morphology that showed increased growth and apoptosis, indicating that GR regulates these processes in a cell-autonomous manner. The activity of ERK1/2 was constitutively augmented in GR−/− skin and mouse primary keratinocytes relative to wild type, which suggests that GR modulates skin homeostasis, at least partially, by antagonizing ERK function. Moreover, the epidermis of GR+/dim and GRdim/dim embryos appeared normal, thus suggesting that DNA-binding-independent actions of GR are sufficient to mediate epidermal and hair follicle development during embryogenesis.
Cyclooxygenase-2 Regulates Survival, Migration, and Invasion of Human Endometriotic Cells through Multiple Mechanisms
Authors: Banu S. K. , Lee J. , Speights V. O. , Starzinski-Powitz A. , Arosh J. A.
Published: November 2007

Endometriosis is a debilitating disease characterized by the presence of functional endometrial glandular epithelium and stroma outside the uterine cavity that affects up to 20% of women of child-bearing age. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the biosynthesis of prostaglandin E2 (PGE2), is highly expressed in endometriotic tissues and results in increased concentrations of peritoneal PGE2 in women. In this study, we determined the expression of COX-2 protein in ectopic and eutopic endometria in humans and the role of COX-2 in endometriotic cell survival, migration, and invasion in humans. Our results indicate that COX-2 protein is abundantly expressed in ectopic endometria compared with eutopic endometria. Comparatively, expression of COX-2 protein is higher in eutopic endometria from women with endometriosis compared with women without endometriosis. Inhibition of COX-2 decreases survival, migration, and invasion of endometriotic cells that are associated with decreased production of PGE2. Cell growth inhibitory effects of COX-2 inhibition/silencing are mediated through nuclear poly (ADP-ribose) polymerase-mediated apoptosis. Cell motility and invasion inhibitory effects of COX-2 inhibition/silencing are mediated through matrix metalloproteinase-2 and -9 activities. Interestingly, effects of COX-2 inhibition is more profound in endometriotic epithelial than in stromal cells. Furthermore, inhibition of COX-2 affects invasion rather than migration of endometriotic epithelial and stromal cells. It is the first evidence showing that inhibition of COX-2 decreases endometriotic epithelial and stromal cell survival, migration, and invasion in humans. Our results support the emerging concept that COX-2/PGE2 promotes the pathophysiology and pathogenesis of endometriosis in humans.
The Passivity of the Administration
Authors: Ringeling Arthur
Published: November 2007

The welfare state claims to provide for its inhabitants. Normally the duration of this provision is specified: from the cradle to the grave. This implies a specific role for the state, the role of distributor of public commodities and services. Among the possible ways of bringing about a distribution of commodities and services in a community, there are two extremes. The one extreme is distribution by way of the market mechanism. The other extreme is distribution by bureaucratic procedure. The development of the welfare state brought with it the transfer of the distribution of public goods from the market sector to the bureaucratic sector, as well as to various intermediate forms.

There are many methods conceivable, by which the government can distribute its commodities and services. It is possible to do it by means of a lottery, as is the case with the admittance to particular university courses in Holland. Another method, based on the adage ‘the early bird catches the worm’, is frequently applied in public transport and theatre performances. One may offer the provision to anyone who is at a particular place, as with traffic lights at a busy crossing.
Immunogold Electron Microscopic Demonstration of Distinct Submembranous Localization of the Activated γPKC Depending on the Stimulation
Authors: Oyasu Miho , Fujimiya Mineko , Kashiwagi Kaori , Ohmori Shiho , Imaeda Hirotsugu , Saito Naoaki
Published: November 2007

We examined the precise intracellular translocation of γ subtype of protein kinase C (γPKC) after various extracellular stimuli using confocal laser-scanning fluorescent microscopy (CLSM) and immunogold electron microscopy. By CLSM, treatment with 12- O-tetradecanoylphorbol-13-acetate (TPA) resulted in a slow and irreversible accumulation of green fluorescent protein (GFP)-tagged γPKC (γPKC–GFP) on the plasma membrane. In contrast, treatment with Ca2+ ionophore and activation of purinergic or NMDA receptors induced a rapid and transient membrane translocation of γPKC–GFP. Although each stimulus resulted in PKC localization at the plasma membrane, electron microscopy revealed that γPKC showed a subtle but significantly different localization depending on stimulation. Whereas TPA and UTP induced a sustained localization of γPKC–GFP on the plasma membrane, Ca2+ ionophore and NMDA rapidly translocated γPKC–GFP to the plasma membrane and then restricted γPKC–GFP in submembranous area (<500 nm from the plasma membrane). These results suggest that Ca2+ influx alone induced the association of γPKC with the plasma membrane for only a moment and then located this enzyme at a proper distance in a touch-and-go manner, whereas diacylglycerol or TPA tightly anchored this enzyme on the plasma membrane. The distinct subcellular targeting of γPKC in response to various stimuli suggests a novel mechanism for PKC activation.
Immunolocalization of a Novel Collectin CL-K1 in Murine Tissues
Authors: Motomura Wataru , Yoshizaki Takayuki , Ohtani Katsuki , Okumura Toshikatsu , Fukuda Mituko , Fukuzawa Jun , Mori Kenichiro , Jang Seong-Jae , Nomura Naoki , Yoshida Itsuro , Suzuki Yasuhiko , Kohgo Yutaka , Wakamiya Nobutaka
Published: November 2007

We have recently identified a novel collectin, CL-K1, that may play a role in innate immunity as a member of the collectin family. In this study using mice, we investigated the tissue distribution of CL-K1 for better understanding of its pathophysiological relevance. Real-time PCR analyses demonstrated that CL-K1 mRNA was expressed in all tissues tested. Immunohistochemical analyses demonstrated that CL-K1 was expressed in proximal tubules of kidney, in mucosa of the gastrointestinal tract, and in bronchial glands of bronchioles similar to the localization of SP-A and SP-D in these pulmonary structures. Immunohistochemistry also showed that CL-K1 was highly expressed in hepatocytes around the central veins in liver, which suggests that murine CL-K1 may be mainly produced in the liver and secreted into the blood stream as is human CL-K1. CL-K1 was especially detected in vascular smooth muscle in several types of tissues. In addition, it was also expressed in intestinal Paneth cells, in mesangial cells of kidney, in pancreatic islet D cells, and in neurons of the brain. It is of interest that this profile of CL-K1 expression is unique among the collectins. Together these histological findings may be useful for understanding the biological function of this novel collectin.
Daptomycin versus Vancomycin for Complicated Skin and Skin Structure Infections: Clinical and Economic Outcomes
Authors: Davis Susan L. , McKinnon Peggy S. , Hall Levi M. , Delgado George , Rose Warren , Wilson Robert F. , Rybak Michael J.
Published: November 2007

Study Objective. To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections.

Design. Prospective, open‐label study.

Setting. Level 1 trauma center in Detroit, Michigan.

Patients. Fifty‐three adult patients with complicated skin and skin structure infections at risk for methicillin‐resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin.

Intervention. Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5–20 μg/ml.

Measurements and Main Results. Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001).

Conclusions. Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost‐effective alternative to vancomycin for complicated skin and skin structure infections.
Overview of Parkinson's Disease
Authors: Lew Mark
Published: November 2007

This overview of Parkinson's disease is designed to serve as a background to the discussion elsewhere in this supplement on the pharmacotherapy used in its management. Parkinson's disease is a common progressive neurodegenerative condition associated with significant disability and negative impact on quality of life. Although the cause of Parkinson's disease is unknown, the pathologic manifestation involves the loss or dysfunction of dopaminergic neurons in the substantia nigra pars compacta. Characteristic clinical manifestations include difficulty with coordinated movement such as asymmetric resting tremor, rigidity, and bradykinesia. These symptoms and their response to levodopa constitute the basis for a clinical diagnosis of Parkinson's disease. Postural instability and gait abnormalities occur in more advanced disease. Although there is no cure for Parkinson's disease, a number of pharmacologic treatments are available for managing the motor and nonmotor symptoms. Research is under way to assess the disease‐modifying ability of both standard and newer treatments.
Pharmacotherapy for Parkinson's Disease
Authors: Chen Jack J. , Swope David M.
Published: November 2007

The available pharmacotherapies for Parkinson's disease address symptomatology because no agent has been demonstrated to provide definite neuroprotection against the disease. Choice of pharmacotherapy must include consideration of short‐term benefits as well as long‐term consequences. Patients with mild Parkinson's disease often function adequately without symptomatic treatment. However, recent data suggest that initiation of treatment with a well‐tolerated agent (e.g., the monoamine oxidase [MAO]‐B inhibitor rasagiline) in the absence of functional impairment is associated with improved long‐term outcomes. Consideration should also be given to many patient‐specific factors, including patient expectations, level of disability, employment status, functional as well as chronologic age, expected efficacy and tolerability of drugs, and response to previous Parkinson's disease therapies. Increasingly, initial monotherapy begins with a nondopaminergic agent or, if the patient is considered functionally young, a dopamine agonist. Since Parkinson's disease is a progressive disorder, adjustments to pharmacotherapy must be expected over time. When greater symptomatic relief is desired, or in the more frail elderly patient, levodopa therapy should be considered. If motor fluctuations develop, addition of a catechol‐O‐methyltransferase inhibitor or MAO‐B inhibitor should be considered. For management of levodopa‐induced dyskinesias, addition of amantadine is an option. Surgery may be considered when patients need additional symptomatic control or are experiencing severe motor complications despite pharmacologically optimized therapy.
Monoamine Oxidase‐B Inhibition in the Treatment of Parkinson's Disease
Authors: Fernandez Hubert H. , Chen Jack J.
Published: November 2007

Inhibitors of monoamine oxidase (MAO) with selectivity and specificity for MAO type B prolong the activity of both endogenously and exogenously derived dopamine, making them an option either as monotherapy in early Parkinson's disease or as adjunctive therapy in patients treated with levodopa who are experiencing motor complications. In addition to symptomatic benefits, experimental data suggest that MAO‐B inhibitors may be neuroprotective through MAO‐B inhibition and other mechanisms that have yet to be clearly defined. The two available MAO‐B inhibitors approved for use in the United States, rasagiline and selegiline, each provide symptomatic relief as monotherapy and as adjunctive therapy, and have shown potential disease‐modifying effects in experimental models and clinical studies. Selegiline in a conventional tablet formulation is less bioavailable than rasagiline, resulting in limited potency. It also has amphetamine metabolites that may produce adverse effects and interfere with any putative disease‐modifying effects. The oral disintegrating tablet formulation of selegiline allows pregastric absorption, minimizing first‐pass metabolism, thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites. Rasagiline, more potent than selegiline, exhibits disease‐modifying effects in experimental models and lacks amphetamine metabolites. Both the symptomatic and potential disease‐modifying effects of rasagiline are under investigation. A third agent with MAO‐B inhibition properties, safinamide, is in phase III development. Although not yet approved, safinamide may offer the added advantage of combined MAO‐B and dopamine reuptake inhibition.
Trans-border (east Serbia/west Bulgaria) correlation of the Jurassic sediments: Main Jurassic paleogeographic units
Authors: Tchoumatchenco Platon , Rabrenovic Dragoman , Radulovic Barbara , Radulovic Vladan
Published: November 2007

In the region across the Serbian/Bulgarian state border, there are individualized 5 Jurassic paleogeographic units (from West to East): (1) the Thracian Massif Unit without Jurassic sediments; (2) the Luznica-Koniavo Unit - partially with Liassic in Grsten facies and with deep water Middle Callovian-Kimmeridgian (p. p) sediments of the type "ammonitico rosso", and Upper Kimmeridgian-Tithonian siliciclastics flysch; (3) The Getic Unit subdivided into two subunits - the Western Getic Sub-Uni - without Lower Jurassic sediments and the Eastern Getic Sub-Unit with Lower Jurassic continental and marine sediments, which are followed in both sub-units by carbonate platform limestones (type Stramberk); (4) the Infra (Sub)-Getic Unit - with relatively deep water Liassic and Dogger sediments (the Dogger of type "black shales with Bossitra alpine") and Middle Callovian-Tithonian of type "ammonitico rosso"; (5) the Danubian Unit - with shallow water Liassic, Dogger and Malm (Miroc-Vrska Cuka Zone, deep water Dogger and Malm (Donjomilanovacko-Novokoritska Zone).
Spectroscopic study of barite from the Kremikovtsi Deposit (Bulgaria) with implication for its origin
Authors: Dimova Maya , Panczer Gerard , Gaft Michael
Published: November 2007

Different genetic types (endogene and supergene) of barite from the Kremikovtsi deposit (Bulgaria) were studied by Laser-induced time-resolved luminescence (LITRL), Infrared (IR) and Raman spectroscopy. The IR spectra of the endogene barites are quite similar to those reported in the literature and do not show appreciable differences among them. The IR spectra of the supergene barites are almost identical to those of the endogene ones in respect to the positions of the vibrational modes ?1, ?2 and ?4 of SO4 2 except for a shift of 3 cm-1 for the ? 3 band. They displayed a presence of additional bands, which are close to the ?3 and ?1 modes of CO3 2- in calcite. The Raman studies support the suggestion that the supergene barite contains traces of calcite. The modern LITRL technique allowed the detection of several luminescent centers in the endogene barite. Eu3+ luminescence was identified for the first time in barite. The different emission spectra at 266 and 532 nm excitations suggest there are at least 2 structural positions for Eu3+ in the barite crystal lattice. The luminescent spectra also revealed a rather unusual violet-blue Nd3+ emission, which usually occurs in the IR spectral range, as well as emissions of Ce3+, Eu2+, Tb3+, Ag+, Sn2+(?) and UO2 2+. The oxidation state of cations isomorphically present in the barite crystal lattice suggests the endogene barite in the Kremikovtsi deposit precipitated from reduced fluids supposedly subjected to cooling (conductive/convective) and oxidation (mixing with seawater).
Electrochemistry of vanadium(II) and the electrodeposition of aluminum-vanadium alloys in the aluminum chloride-1-ethyl-3-methylimidazolium chloride molten salt
Authors: Tsuda T. , Hussey C.L.
Published: November 2007

The electrochemical behavior of vanadium(II) was examined in the 66.7-33.3 mole percent aluminum chloride-1-ethyl-3-methylimidazolium chloride molten salt containing dissolved VCl2 at 353 K. Voltammetry experiments revealed that V(II) could be electrochemically oxidized to V(III) and V(IV). However at slow scan rates the V(II)/V(III) electrode reaction is complicated by the rapid precipitation of V(III) as VCl3. The reduction of V(II) occurs at potentials considerably negative of the Al(III)/Al electrode reaction, and Al-V alloys cannot be electrodeposited from this melt. However electrodeposition experiments conducted in VCl2-saturated melt containing the additive, 1-ethyl-3-methylimidazolium tetrafluoroborate, resulted in Al-V alloys. The vanadium content of these alloys increased with increasing cathodic current density or more negative applied potentials. X-ray analysis of Al-V alloys that were electrodeposited on a rotating copper wire substrate indicated that these alloys did not form or contain an intermetallic compound, but were non-equilibrium or metastable solid solutions. The chloride-pitting corrosion properties of these alloys were examined in aqueous NaCl by using potentiodynamic polarization techniques. Alloys containing ~10 a/o vanadium exhibited a pitting potential that was 0.3 V positive of that for pure aluminum.
Electrochemistry of silicon in chloro-fluoride and carbonate melts
Authors: Devyatkin S.V.
Published: November 2007

The electrochemical behavior of K2SiF6 in chloro-fluoride melts and that of SiO2 in carbonate melts has been studied. Silicon, titanium silicides, boron silicide and ternary compounds Ti-Si-B have been deposited from chloro-fluoride melts. Only SiC was deposited from carbonate-silica melts under carbon dioxide atmosphere (that is, excessive pressure of CO2).
Melting of andesite in a microwave oven
Authors: Znamenácková I. , Lovás M. , Hájek M. , Jakabský S.
Published: November 2007

The positive influence of the microwave radiation on the melting of rocks is described. Local melting-down of specimens and subsequent flowing-out of red-hot magmatic mass was observed when andesite samples from the location of Ruskov (Slovakia) were heated in a microwave own with an output of 900 W. After 30 min of microwave heating of an andesite specimen of defined dimensions, its complete melting was observed and the temperature measured reached the range of 1260-1280?C.
Microstructure and mechanical properties of CuNiMo austempered ductile iron
Authors: Eric Olivera , Jovanovic Marina , Sidjanin Leposava , Rajnovic Dragan
Published: November 2007

Microstructure and mechanical properties of Cu, Ni and Mo alloyed cast ductile iron have been investigated after austempering. Samples were austenitised at 860oC for 1h and then austempered at 320oC and 400oC in the interval from 0,5 to 5h. The X-ray diffraction technique and the light microscopy were utilized to investigate the bainitic transformation, while tensile and impact tests were performed for characterization of mechanical properties. By austempering at 320oC in the range between 2 and 5h, a microstructure typical for austempered ductile iron was produced, i.e. a mixture of free bainitic ferrite and highly carbon enriched retained austenite. The characteristic of the whole range of austempering at 400oC is the appearance of martensitic structure. The maximum impact energy (133 J) coincides with the maximum value of volume fraction of retained austenite that was obtained after 2,5h of austempering at 320oC. The appearance of martensite during austempering at 400oC is the main cause for much lower tensile properties than at 320oC.