bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the risk of pressure ulcer development: is it truly evidence based?
Authors: Sharp Catherine A , McLaws Mary‐Louise
Published: December 2006

The aim of the current method of screening patients is to identify risk factors that are considered to cause, or contribute to, pressure ulcer (PU) development. Yet screening has not resulted in a reduction in pressure ulcer development. The literature was reviewed to identify the level of evidence for the inclusion of risk factors in six published pressure ulcer risk‐screening tools. Evidence for each risk factor was ranked according to the National Health and Medical Research Council levels of evidence with a modification. Three of 19 risk factors (mobility, continence and nutrition) included in more than one screening tool have been tested for association with pressure ulcer development. While varying degrees of immobility and decreased serum albumin are reported to significantly increase the risk for PU development, the direction of the relationship, i.e. causal or resultant of PU, is not always clear. No publications reported a significant causal link between incontinence and PU development. Inclusion of risk factors for PU in screening tools must be evidence based. Until other risk factors have been tested for positive predictive value, the Ramstadius approach to screening is the only evidence‐based tool.
The potential of microscopic sterile sponge particles to induce foreign body reaction
Authors: Sari Alper , Basterzi Yavuz , Karabacak Tuba , Tasdelen Bahar , Demirkan Ferit
Published: December 2006

The sterile sponges may lose a significant amount of lint during their routine use in surgery, which is usually neglected. We designed an experimental model to evaluate the potential of sterile sponges to lose lint and to induce foreign body reaction in surgically created wounds. In 15 Wistar rats, separate subcutaneous pockets were created. Left‐sided pockets were temporarily packed with sterile sponges, while the right‐sided pockets remained empty. All the pockets were then irrigated with sterile saline. The presence of microscopic sponge particles was evaluated in the irrigation materials. After 4 weeks, the presence of inflammation and foreign body reaction were evaluated histologically. Microscopic sponge remnants were present in 14 of 15 samples collected from the left sides. The presence of foreign body giant cells with ingested sponge particles and formation of well‐defined foreign body granulomas were observed only in samples collected from the left sides. A statistically significant difference was observed between the two sides when the intensity of inflammation was graded (P= 0·012). Cotton sponges used in surgery are shown to have a potential of losing invisible microscopic particles that have a potential to induce foreign body reaction.
Silver dressings: their role in wound management
Authors: Leaper David J
Published: December 2006

Dressings have a part to play in the management of wounds; whether they are sutured or open, usually chronic wounds of many aetiologies which are healing by secondary intention. They traditionally provide a moist wound environment, but this property has been extended through simple to complex, active dressings which can handle excessive exudate, aid in debridement, and promote disorganised, stalled healing. The control of infection remains a major challenge. Inappropriate antibiotic use risks allergy, toxicity and most importantly resistance, which is much reduced by the use of topical antiseptics (such as povidone iodine and chlorhexidine). The definition of what is an antimicrobial and the recognition of infection has proven difficult. Although silver has been recognised for centuries to inhibit infection its use in wound care is relatively recent. Evidence of the efficacy of the growing number of silver dressings in clinical trials, judged by the criteria of the Cochrane Collaboration, is lacking, but there are good indications for the use of silver dressings, to remove or reduce an increasing bioburden in burns and open wounds healing by secondary intention, or to act as a barrier against cross contamination of resistant organisms such as MRSA. More laboratory, and clinical data in particular, are needed to prove the value of the many silver dressings which are now available. Some confusion persists over the measurement of toxicity and antibacterial activity but all dressings provide an antibacterial action, involving several methods of delivery. Nanocrystalline technology appears to give the highest, sustained release of silver to a wound without clear risk of toxicity.
Analysis of 3D rigid-body motion using photogrammetry: A simple model based on a mechanical analogy
Authors: Page A. , Candelas P. , Belmar F. , De Rosario H.
Published: December 2006

We present a technique based on 3D video photogrammetry for analyzing rigid body kinematics. The technique is based on a method for calculating the kinematic variables associated with rigid body motion. To illustrate the technique an analysis of the rolling motion of a truncated cone on a floor is performed. From the coordinates of a set of markers, kinematic parameters such as linear velocity, angular velocity, and the instantaneous axis of rotation can be measured. The complexity is appropriate for undergraduates using a mechanical analogy that relates linear and angular momentum to linear and angular velocities, respectively. The possibility of compounding simple rotational motions to achieve a more complex motion is also addressed.
Relativistic treatment of a spin-zero particle subject to a Kratzer-type potential
Authors: Berkdemir Cüneyt
Published: December 2006

The Kratzer potential is commonly used for obtaining bound state solutions and describing the vibrational motion of a single particle. The Klein-Gordon equation for Kratzer-type potentials is solved systematically by using the Nikiforov-Uvarov method. The exact bound state energy eigenvalues and the corresponding wave functions of the Klein-Gordon equation are obtained with equal scalar and vector potentials.
On the relation between angular momentum and angular velocity
Authors: Silva J. P. , Tavares J. M.
Published: December 2006

Students of mechanics usually have difficulties when they learn about the rotation of a rigid body. These difficulties are rooted in the relation between angular momentum and angular velocity, because these vectors are not parallel, and we need in general to utilize a rotating frame of reference or a time dependent inertia tensor. We discuss a series of problems that introduce both difficulties.
Modulation of Host Gene Expression by the K15 Protein of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Brinkmann Melanie M. , Pietrek Marcel , Dittrich-Breiholz Oliver , Kracht Michael , Schulz Thomas F.
Published: December 2006

Kaposi's sarcoma-associated herpesvirus (KSHV) contains several open reading frames (ORFs) encoding proteins capable of initiating signal transduction pathways. Among them is the K15 ORF, which consists of eight exons encoding a protein with 12 predicted transmembrane domains and a cytoplasmic C terminus. When transiently expressed, the 8-exon K15 transcript gives rise to a protein with an apparent molecular mass of 45 kDa. K15 interacts with cellular proteins, TRAF (tumor necrosis factor receptor-associated factor) and Src kinases, and activates AP-1, NF-κB, and the mitogen-activated protein kinases (MAPKs) c-jun-N-terminal kinase and extracellular signal-regulated kinase. This signaling activity of K15 is related to phosphorylation of Y481of the K15 SH2-B motif Y481EEV. In this study we demonstrate the expression of an endogenous 45-kDa K15 protein in KSHV BAC36-infected epithelial cells. This endogenous K15 protein shows the same intracellular localization as transiently expressed K15, and expression kinetic studies suggest it to be a lytic gene. We have further determined the downstream target genes of K15 signaling using DNA oligonucleotide microarrays. We demonstrate that K15 is capable of inducing expression of multiple cytokines and chemokines, including interleukin-8 (IL-8), IL-6, CCL20, CCL2, CXCL3, and IL-1α/β, as well as expression of Dscr1 and Cox-2. In epithelial cells, K15-induced upregulation of most genes was dependent on phosphorylation of Y481, whereas in endothelial cells mutation of Y481did not result in a complete loss of Dscr1 and Cox-2 expression and NFAT-activity. Our study establishes K15 as one of the KSHV lytic genes that are inducing expression of multiple cytokines, which have been shown to play an important role in KSHV-associated pathogenesis.
Inhibition of Alpha Interferon Signaling by Hepatitis B Virus
Authors: Christen Verena , Duong Francois , Bernsmeier Christine , Sun Dianxing , Nassal Michael , Heim Markus H.
Published: December 2006

Alpha interferon (IFN-α) and pegylated IFN-α (pegIFN-α) are used for the treatment of chronic hepatitis B (CHB). Unfortunately, only a minority of patients can be cured. The mechanisms responsible for hepatitis B virus (HBV) resistance to pegIFN-α treatment are not known. pegIFN-α is also used to treat patients with chronic hepatitis C (CHC). As with chronic hepatitis B, many patients with chronic hepatitis C cannot be cured. In CHC, IFN-α signaling has been found to be inhibited by an upregulation of protein phosphatase 2A (PP2A). PP2A inhibits protein arginine methyltransferase 1 (PRMT1), the enzyme that catalyzes the methylation of the important IFN-α signal transducer STAT1. Hypomethylated STAT1 is less active because it is bound by its inhibitor, PIAS1. In the present work, we investigated whether similar molecular mechanisms are also responsible for the IFN-α resistance found in many patients with chronic hepatitis B. We analyzed the expression of PP2A, the enzymatic activity of PRMT1 (methylation assays), the phosphorylation and methylation of STAT1, the association of STAT1 with PIAS1 (via coimmunoprecipitation assays), the binding of activated STAT1 to interferon-stimulated response elements (via electrophoretic mobility shift assays), and the induction of interferon target genes (via real-time RT-PCR) in human hepatoma cells expressing HBV proteins as well as in liver biopsies from patients with chronic hepatitis B and from controls. We found an increased expression of PP2A and an inhibition of IFN-α signaling in cells expressing HBV proteins and in liver biopsies of patients with CHB. The molecular mechanisms involved are similar to those found in chronic hepatitis C.
Pradimicin A, a Carbohydrate-Binding Nonpeptidic Lead Compound for Treatment of Infections with Viruses with Highly Glycosylated Envelopes, Such as Human Immunodeficiency Virus
Authors: Balzarini Jan , Van Laethem Kristel , Daelemans Dirk , Hatse Sigrid , Bugatti Antonella , Rusnati Marco , Igarashi Yasuhiro , Oki Toshikazu , Schols Dominique
Published: December 2006

Pradimicin A (PRM-A), an antifungal nonpeptidic benzonaphtacenequinone antibiotic, is a low-molecular-weight (molecular weight, 838) carbohydrate binding agent (CBA) endowed with a selective inhibitory activity against human immunodeficiency virus (HIV). It invariably inhibits representative virus strains of a variety of HIV-1 clades with X4 and R5 tropisms at nontoxic concentrations. Time-of-addition studies revealed that PRM-A acts as a true virus entry inhibitor. PRM-A specifically interacts with HIV-1 gp120 and efficiently prevents virus transmission in cocultures of HUT-78/HIV-1 and Sup T1 cells. Upon prolonged exposure of HIV-1-infected CEM cell cultures, PRM-A drug pressure selects for mutant HIV-1 strains containing N-glycosylation site deletions in gp120 but not gp41. A relatively long exposure time to PRM-A is required before drug-resistant virus strains emerge. PRM-A has a high genetic barrier, since more than five N-glycosylation site deletions in gp120 are required to afford moderate drug resistance. Such mutated virus strains keep full sensitivity to the other known clinically used anti-HIV drugs. PRM-A represents the first prototype compound of a nonpeptidic CBA lead and, together with peptide-based lectins, belongs to a conceptually novel type of potential therapeutics for which drug pressure results in the selection of glycan deletions in the HIV gp120 envelope.
Newcastle Disease Virus-Based Live Attenuated Vaccine Completely Protects Chickens and Mice from Lethal Challenge of Homologous and Heterologous H5N1 Avian Influenza Viruses
Authors: Ge Jinying , Deng Guohua , Wen Zhiyuan , Tian Guobing , Wang Yong , Shi Jianzhong , Wang Xijun , Li Yanbing , Hu Sen , Jiang Yongping , Yang Chinglai , Yu Kangzhen , Bu Zhigao , Chen Hualan
Published: December 2006

H5N1 highly pathogenic avian influenza virus (HPAIV) has continued to spread and poses a significant threat to both animal and human health. Current influenza vaccine strategies have limitations that prevent their effective use for widespread inoculation of animals in the field. Vaccine strains of Newcastle disease virus (NDV), however, have been used successfully to easily vaccinate large numbers of animals. In this study, we used reverse genetics to construct a NDV that expressed an H5 subtype avian influenza virus (AIV) hemagglutinin (HA). Both a wild-type and a mutated HA open reading frame (ORF) from the HPAIV wild bird isolate, A/Bar-headed goose/Qinghai/3/2005 (H5N1), were inserted into the intergenic region between the P and M genes of the LaSota NDV vaccine strain. The recombinant viruses stably expressing the wild-type and mutant HA genes were found to be innocuous after intracerebral inoculation of 1-day-old chickens. A single dose of the recombinant viruses in chickens induced both NDV- and AIV H5-specific antibodies and completely protected chickens from challenge with a lethal dose of both velogenic NDV and homologous and heterologous H5N1 HPAIV. In addition, BALB/c mice immunized with the recombinant NDV-based vaccine produced H5 AIV-specific antibodies and were completely protected from homologous and heterologous lethal virus challenge. Our results indicate that recombinant NDV is suitable as a bivalent live attenuated vaccine against both NDV and AIV infection in poultry. The recombinant NDV vaccine may also have potential use in high-risk human individuals to control the pandemic spread of lethal avian influenza.
Differential Induction of Type I Interferon Responses in Myeloid Dendritic Cells by Mosquito and Mammalian-Cell-Derived Alphaviruses
Authors: Shabman Reed S. , Morrison Thomas E. , Moore Christopher , White Laura , Suthar Mehul S. , Hueston Linda , Rulli Nestor , Lidbury Brett , Ting Jenny P.-Y. , Mahalingam Suresh , Heise Mark T.
Published: December 2006

Dendritic cells (DCs) are an important early target cell for many mosquito-borne viruses, and in many cases mosquito-cell-derived arboviruses more efficiently infect DCs than viruses derived from mammalian cells. However, whether mosquito-cell-derived viruses differ from mammalian-cell-derived viruses in their ability to induce antiviral responses in the infected dendritic cell has not been evaluated. In this report, alphaviruses, which are mosquito-borne viruses that cause diseases ranging from encephalitis to arthritis, were used to determine whether viruses grown in mosquito cells differed from mammalian-cell-derived viruses in their ability to induce type I interferon (IFN) responses in infected primary dendritic cells. Consistent with previous results, mosquito-cell-derived Ross River virus (mos-RRV) and Venezuelan equine encephalitis virus (mos-VEE) exhibited enhanced infection of primary myeloid dendritic cells (mDCs) compared to mammalian-cell-derived virus preparations. However, unlike the mammalian-cell-derived viruses, which induced high levels of type I IFN in the infected mDC cultures, mos-RRV and mos-VEE were poor IFN inducers. Furthermore, the poor IFN induction by mos-RRV contributed to the enhanced infection of mDCs by mos-RRV. These results suggest that the viruses initially delivered by the mosquito vector differ from those generated in subsequent rounds of replication in the host, not just with respect to their ability to infect dendritic cells but also in their ability to induce or inhibit antiviral type I IFN responses. This difference may have an important impact on the mosquito-borne virus's ability to successfully make the transition from the arthropod vector to the vertebrate host.
Cytomegalovirus InducesInterferon-Stimulated Gene Expression and Is Attenuated by Interferon in the DevelopingBrain
Authors: van den Pol Anthony N. , Robek Michael D. , Ghosh Prabhat K. , Ozduman Koray , Bandi Prasanthi , Whim Matthew D. , Wollmann Guido
Published: December 2006

Cytomegalovirus (CMV) is considered the most common infectious agent causing permanent neurological dysfunction in the developing brain. We have previously shown that CMV infects developing brain cells more easily than it infects mature brain cells and that this preference is independent of the host B- and T-cell responses. In the present study, we examined the innate antiviral defenses against mouse (m) and human (h) CMVs in developing and mature brain and brain cells. mCMV infection induced interferon (IFN)-stimulated gene expression by 10- to 100-fold in both glia- and neuron-enriched cultures. Treatment of primary brain cultures with IFN-α, -β, and -γ or a synthetic RNA, poly(I:C), reduced the number of mCMV-infected cells, both in older cells and in fresh cultures from embryonic mouse brains. When a viral dose that killed almost all unprotected cells was used, IFN-protected cells had a natural appearance, and when they were tested with whole-cell patch clamp recording, they appeared physiologically normal with typical resting membrane potentials and action potentials. mCMV infection increased expression of representative IFN-stimulated genes (IFIT3, OAS, LMP2, TGTP, and USP18) in both neonatal and adult brains to similarly large degrees. The robust upregulation of gene expression in the neonatal brain was associated with a much higher degree of viral replication at this stage of development. In contrast to the case for downstream gene induction, CMV upregulated IFN-α/β expression to a greater degree in the adult brain than in the neonatal brain. Similar to the case with cultured brain cells, IFN treatment of the developing brain in vivo depressed mCMV replication. In parallel work with cultured primary human brain cells, IFN and poly(I:C) treatment reduced hCMV infection and prevented virus-mediated cell death. These results suggest that coupling IFN administration with current treatments may reduce CMV infections in the developing brain.
Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques
Authors: De Rose Robert , Batten C. Jane , Smith Miranda Z. , Fernandez Caroline S. , Peut Viv , Thomson Scott , Ramshaw Ian A. , Coupar Barbara E. H. , Boyle David B. , Venturi Vanessa , Davenport Miles P. , Kent Stephen J.
Published: December 2006

Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HIV) strains. Heterologous B-subtype-based simian-human immunodeficiency virus (SHIV) DNA prime and poxvirus boost vaccine regimens can induce partial, T-cell-mediated, protective immunity in macaques. We analyzed a set of DNA, recombinant fowlpox viruses (FPV), and vaccinia viruses (VV) expressing subtype AE HIV type 1 (HIV-1) Tat, Rev, and Env proteins and SIV Gag/Pol in 30 pigtail macaques. SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic. The SHIV AE DNA prime, FPV boost regimens were significantly less immunogenic than comparable B-subtype SHIV vaccination. Peak viral load was modestly (0.4 log
10
copies/ml) lower among the AE subtype SHIV-immunized animals compared to controls following the virulent B subtype SHIV challenge. Protection from persistent high levels of viremia and CD4 T-cell depletion was less in AE subtype compared to B subtype SHIV-vaccinated macaques. Gag was highly immunodominant over the other AE subtype SHIV vaccine proteins after vaccination, and this immunodominance was exacerbated after challenge. Interestingly, the lower level of priming of immune responses did not blunt postchallenge Gag-specific recall responses, despite more modest protection. These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles.
Proliferative Capacity of Epitope-Specific CD8 T-Cell Responses Is Inversely Related to Viral Load in Chronic Human Immunodeficiency Virus Type 1 Infection
Authors: Day Cheryl L. , Kiepiela Photini , Leslie Alasdair J. , van der Stok Mary , Nair Kriebashne , Ismail Nasreen , Honeyborne Isobella , Crawford Hayley , Coovadia Hoosen M. , Goulder Philip J. R. , Walker Bruce D. , Klenerman Paul
Published: December 2006

The relationship between the function of human immunodeficiency virus (HIV)-specific CD8 T-cell responses and viral load has not been defined. In this study, we used a panel of major histocompatibility complex class I tetramers to examine responses to frequently targeted CD8 T-cell epitopes in a large cohort of antiretroviral-therapy-naïve HIV type 1 clade C virus-infected persons in KwaZulu Natal, South Africa. In terms of effector functions of proliferation, cytokine production, and degranulation, only proliferation showed a significant correlation with viral load. This robust inverse relationship provides an important functional correlate of viral control relevant to both vaccine design and evaluation.
Cytoplasmic Residues of Herpes Simplex Virus Glycoprotein gE Required for Secondary Envelopment and Binding of Tegument Proteins VP22 and UL11 to gE and gD
Authors: Farnsworth Aaron , Wisner Todd W. , Johnson David C.
Published: December 2006

The final assembly of herpes simplex virus (HSV) involves binding of tegument-coated capsids to viral glycoprotein-enriched regions of the
trans
-Golgi network (TGN) as enveloped virions bud into TGN membranes. We previously demonstrated that HSV glycoproteins gE/gI and gD, acting in a redundant fashion, are essential for this secondary envelopment. To define regions of the cytoplasmic (CT) domain of gE required for secondary envelopment, HSVs lacking gD and expressing truncated gE molecules were constructed. A central region (amino acids 470 to 495) of the gE CT domain was important for secondary envelopment, although more C-terminal residues also contributed. Tandem affinity purification (TAP) proteins including fragments of the gE CT domain were used to identify tegument proteins VP22 and UL11 as binding partners, and gE CT residues 470 to 495 were important in this binding. VP22 and UL11 were precipitated from HSV-infected cells in conjunction with full-length gE and gE molecules with more-C-terminal residues of the CT domain. gD also bound VP22 and UL11. Expression of VP22 and gD or gE/gI in cells by use of adenovirus (Ad) vectors provided evidence that other viral proteins were not necessary for tegument/glycoprotein interactions. Substantial quantities of VP22 and UL11 bound nonspecifically onto or were precipitated with gE and gD molecules lacking all CT sequences, something that is very unlikely in vivo. VP16 was precipitated equally whether gE/gI or gD was present in extracts or not. These observations illustrated important properties of tegument proteins. VP22, UL11, and VP16 are highly prone to binding nonspecifically to other proteins, and this did not represent insolubility during our assays. Rather, it likely reflects an inherent “stickiness” related to the formation of tegument. Nevertheless, assays involving TAP proteins and viral proteins expressed by HSV and Ad vectors supported the conclusion that VP22 and UL11 interact specifically with the CT domains of gD and gE.
Binding of oxovanadium ions to the major and minor grooves of DNA duplex: stability and structural models
Authors: Ahmed Ouameur A. , Arakawa H. , Tajmir-Riahi H.A.
Published: December 2006

Vanadate induces DNA strand breaks in cultured human fibroblasts at doses that are relative to the occupational exposure. Oxovanadium compounds also exert preventive effects against chemical carcinogenesis in animals and form complexes with DNA in vivo. This study was designed to examine the interaction of calf-thymus DNA with VO2+and VO3¯ions in aqueous solution at physiological pH, with a constant DNA concentration of 12.5 mmol/L and vanadium–DNA (phosphate) molar ratios (r) of 1:160 to 1:2. Capillary electrophoresis and Fourier transform infrared difference spectroscopy were used to determine the cation binding site, the binding constant, the helix stability, and DNA conformation in the oxovanadium–DNA complexes. Structural analysis showed that VO2+binds DNA through guanine and adenine N-7 atoms and the backbone PO2group with apparent binding constants of KG= 8.8 × 105(mol/L)–1and KA= 3.4 × 105(mol/L)–1. The VO3¯shows weaker binding through thymine, adenine, and guanine bases, with K = 1.9 × 104(mol/L)–1and no interaction with the backbone phosphate group. A partial B-to-A DNA transition occurred upon VO–DNA complexation, while DNA remains in the B-family structure in the VO3¯complexes.
BOUNDED SIZE DICTIONARY COMPRESSION: RELAXING THE LRU DELETION HEURISTIC
Authors: DE AGOSTINO SERGIO
Published: December 2006

The unbounded version of the Lempel-Ziv dynamic dictionary compression method is P-complete. Therefore, it is unlikely to implement it with sublinear work space unless a deletion heuristic is applied to bound the dictionary. The well-known LRU (least recently used) strategy provides the best compression performance among the existent deletion heuristics. We show experimental results on the compression effectiveness of a relaxed version (RLRUp) of the LRU heuristic. RLRUp partitions the dictionary in p equivalence classes, so that all the elements in each class are considered to have the same "age" for the LRU strategy. Such heuristic turns out to be as good as LRU when p is greater or equal to 2 (RLRU2). RLRU2 is slightly easier to implement than LRU in addition to be more space efficient.
Biology and Evolution of Adelgidae
Authors: Havill Nathan P. , Foottit Robert G.
Published: December 2006

The Adelgidae form a small clade of insects within the Aphidoidea (Hemiptera) that includes some of the most destructive introduced pest species threatening North American forest ecosystems. Despite their importance, little is known about their evolutionary history and their taxonomy remains unresolved. Adelgids are cyclically parthenogenetic and exhibit multigeneration complex life cycles. They can be holocyclic, with a sexual generation and host alternation, or anholocyclic, entirely asexual and without host alternation. We discuss adelgid behavior and ecology, emphasizing plant-insect interactions, and we explore ways that the biogeographic history of their host plants may have affected adelgid phylogeny and evolution of adelgid life cycles. Finally, we highlight several areas in which additional research into speciation, population genetics, multitrophic interactions, and life-history evolution would improve our understanding of adelgid biology and evolution.
Dissociation between adipose tissue fluxes and lipogenic gene expression inob/obmice
Authors: Turner S. M. , Roy S. , Sul H. S. , Neese R. A. , Murphy E. J. , Samandi W. , Roohk D. J. , Hellerstein M. K.
Published: December 2006

Recent evidence has been presented that expression of lipogenic genes is downregulated in adipose tissue of ob/ob mice as well as in human obesity, suggesting a functionally lipoatrophic state. Using2H2O labeling, we measured three adipose tissue biosynthetic processes concurrently: triglyceride (TG) synthesis, palmitate de novo lipogenesis (DNL), and cell proliferation (adipogenesis). To determine the effect of the ob/ob mutation (leptin deficiency) on these parameters, adipose dynamics were compared in ob/ob, leptin-treated ob/ob, food-restricted ob/ob, and lean control mice. Adipose tissue fluxes for TG synthesis, de novo lipogenesis (DNL), and adipogenesis were dramatically increased in ob/ob mice compared with lean controls. Low-dose leptin treatment (2 μg/day) via miniosmotic pump suppressed all fluxes to control levels or below. Food restriction in ob/ob mice only modestly reduced DNL, with no change in TG synthesis or adipogenesis. Measurement of mRNA levels in age-matched ob/ob mice showed generally normal expression levels for most of the selected lipid anabolic genes, and leptin treatment had, with few exceptions, only modest effects on their expression. We conclude that leptin deficiency per se results in marked elevations in flux through diverse lipid anabolic pathways in adipose tissue (DNL, TG synthesis, and cell proliferation), independent of food intake, but that gene expression fails to reflect these changes in flux.
P1 and Traveling Alpha Waves: Evidence for Evoked Oscillations
Authors: Klimesch Wolfgang , Hanslmayr Simon , Sauseng Paul , Gruber Walter R. , Doppelmayr Michael
Published: December 2006

The hypothesis is tested whether the P1 of the event-related potential (ERP) component behaves like an evoked, traveling alpha wave. This hypothesis is based on different kinds of evidence showing, e.g., that—after undergoing phase reorganization—frequencies in the broad alpha range become synchronized (aligned) in absolute phase and contribute significantly to the generation of the P1. We investigated data from a Stroop task in which subjects had to respond only to the color and ignore the meaning of the presented words. Analyzing topographical phase relationships expressed in terms of traveling speed (with respect to Pz as trailing site) revealed that a systematic posterior to anterior traveling pattern appeared only in the broad time window of the P1-N1 complex and in the extended alpha frequency range. The obtained findings are consistent with the oscillatory ERP model and suggest that the P1 component may be considered a manifestation of an evoked, traveling alpha wave. We assume that the P1 reflects a top-down process in a sense that traveling alpha waves control or “gate” the direction of information processing in the brain.
The Association of Physical Activity with Lung Cancer Incidence in a Cohort of Older Women: The Iowa Women's Health Study
Authors: Sinner Penny , Folsom Aaron R. , Harnack Lisa , Eberly Lynn E. , Schmitz Kathryn H.
Published: December 2006

Background: We examined the potential association between physical activity and lung cancer in women.

Methods: In 1986, 36,929 women from Iowa, who were free of prior cancer, completed a questionnaire regarding physical activity, smoking, body mass index, and other life-style factors. Women were followed through 2002 for cancer incidence.

Results: After adjusting for potential confounders, women with high physical activity levels were less likely [hazard ratio, 0.77; 95% confidence intervals (CI), 0.64-0.94] to develop lung cancer than women with low activity levels. This hazard ratio was 0.72 (95% CI, 0.55-0.94) in current smokers and 0.63 (95% CI, 0.43-0.92) in former smokers, but was not significant in never smokers.

Conclusion: These results suggest that physical activity might reduce the risk of lung cancer in women who are current or former smokers. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2359–64)
The Effect of Modifiable Risk Factors on Pancreatic Cancer Mortality in Populations of the Asia-Pacific Region
Authors: Ansary-Moghaddam Alireza , Huxley Rachel , Barzi Federica , Lawes Carlene , Ohkubo Takayoshi , Fang Xianghua , Jee Sun Ha , Woodward Mark ,   Asia Pacific Cohort Studies Collaboration
Published: December 2006

Background: Pancreatic cancer accounts for about 220,000 deaths each year. Known risk factors are smoking and type 2 diabetes. It remains to be seen whether these risk factors are equally important in Asia and whether other modifiable risk factors have important associations with pancreatic cancer.

Methods: An individual participant data analysis of 30 cohort studies was carried out, involving 420,310 Asian participants (33% female) and 99,333 from Australia/New Zealand (45% female). Cox proportional hazard models, stratified by study and sex and adjusted for age, were used to quantify risk factors for death from pancreatic cancer.

Results: During 3,558,733 person-years of follow-up, there were 324 deaths from pancreatic cancer (54% Asia and 33% female). Mortality rates (per 100,000 person-years) from pancreatic cancer were 10 for men and 8 for women. The following are age-adjusted hazard ratios (95% confidence interval) for death from pancreatic cancer: for current smoking, 1.61 (1.12-2.32); for diabetes, 1.76 (1.15-2.69); for a 2-cm increase in waist circumference, 1.08 (1.02-1.14). All three relationships remained significant (P < 0.05) after adjustment for other risk factors. There was no evidence of heterogeneity in the strength of these associations between either cohorts from Asia and Australia/New Zealand or between the sexes. In men, the combination of cigarette smoking and diabetes more than doubled the likelihood of pancreatic cancer (2.47; 95% confidence interval, 1.17-5.21) in both regions.

Conclusions: Smoking, obesity, and diabetes are important and are potentially modifiable risk factors for pancreatic cancer in populations of the Asia-Pacific region. Activities to prevent them can be expected to lead to a major reduction in the number of deaths from this cancer, particularly in Asia with its enormous population. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2435–40)
XRCC1, XRCC3, and XPD Polymorphisms as Modifiers of the Effect of Smoking and Alcohol on Colorectal Adenoma Risk
Authors: Stern Mariana C. , Siegmund Kimberly D. , Conti David V. , Corral Román , Haile Robert W.
Published: December 2006

Using a sigmoidoscopy-based case-control study (753 cases, 799 controls) in Los Angeles County, we investigated the potential modifier role in the effect of alcohol and smoking of single-nucleotide polymorphisms (SNP) in three DNA repair genes, XRCC1 (Arg194Trp and Arg399Gln), XRCC3 (Thr241Met), and XPD (Lys751Gln). We have previously reported an inverse association between the XRCC1 codon 399 SNP and adenoma risk among these subjects. We now report that subjects with the XPD Gln/Gln genotype were inversely associated with adenoma risk [odds ratio (OR), 0.7; 95% confidence interval (95% CI), 0.5-1.0] when compared with subjects with the Lys/Lys and Lys/Gln genotypes combined. This association differed between different ethnic groups (gene × race heterogeneity likelihood ratio test, P = 0.009), with a stronger inverse association among Latinos (OR, 0.1; 95% CI, 0.01-0.5) than among non-Latinos (OR, 0.9; 95% CI, 0.-1.3). We found no evidence of an XRCC3 × smoking or alcohol interaction or an XRCC1 × alcohol interaction. Instead, our data supported an XRCC1 × smoking interaction (P = 0.048). Whereas XPD did not modify the effect of smoking, our data suggested an XPD × alcohol interaction. Analyses ignoring XPD showed no association between alcohol intake and adenoma prevalence; however, among carriers of the codon 751 Gln/Gln genotype, we found a significant positive association (OR, 2.5; 95% CI, 1.2-5.2 for ever drinkers; test of interaction P = 0.04). Our data suggest that the effects of smoking and alcohol may vary depending on the genetic background of proteins that participate in the base excision repair and nucleotide excision repair pathways. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2384–90)
Host Immune Status and Incidence of Hepatocellular Carcinoma among Subjects Infected with Hepatitis C Virus: A Nested Case-Control Study in Japan
Authors: Suruki Robert Y. , Mueller Nancy , Hayashi Katsuhiro , Harn Donald , DeGruttola Victor , Raker Christina A. , Tsubouchi Hirohito , Stuver Sherri O.
Published: December 2006

A nested case-control study was conducted to examine the association between host immune status, as characterized by serum immune marker levels, and the development of hepatocellular carcinoma (HCC) up to 8 years later in persons with chronic hepatitis C virus (HCV) infection. Cases (n = 39) and matched controls (n = 117) were selected from participants of the Town C HCV Study in Japan between 1996 and 2004 and matched on age at first available sample (±1 year), gender, and length of follow-up. Separate analyses were done for each of three serum immune markers: soluble tumor necrosis factor-receptor II (sTNF-R2) and soluble intercellular adhesion molecule-1 (sICAM-1), as indicators of type 1, cell-mediated immune response, and soluble CD30 (sCD30), as an indicator of type 2, humoral immune response. The median concentrations of sTNF-R2, sICAM-1, and sCD30 among controls were 3,170 pg/mL, 305 ng/mL, and 3.0 units/mL, respectively, and were higher among cases (3,870 pg/mL, 372 ng/mL, and 3.3 units/mL, respectively). The risk of developing HCC among subjects with immune marker concentrations above the median levels of the controls was >2-fold greater than among subjects with lower concentrations for all three markers [sTNF-R2: odds ratio (OR), 6.9; 95% confidence interval (95% CI), 2.4-20.5; sICAM-1: OR, 2.0; 95% CI, 0.9-4.1; and sCD30: OR, 2.1; 95% CI, 1.0-4.7]. Simultaneous adjustment for all three markers revealed only sTNF-R2 to be associated with HCC risk (OR, 6.4; 95% CI, 2.0-20.6). Adjustment for alcohol consumption and HCV serotype did not materially alter these associations. Results from this prospective, community-based study suggest that a dysregulation in both type 1–related and type 2–related host immunity contributes to the development of HCV-associated HCC. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2521–5)
Birthweight and Body Size throughout Life in Relation to Sex Hormones and Prolactin Concentrations in Premenopausal Women
Authors: Tworoger Shelley S. , Eliassen A. Heather , Missmer Stacey A. , Baer Heather , Rich-Edwards Janet , Michels Karin B. , Barbieri Robert L. , Dowsett Mitch , Hankinson Susan E.
Published: December 2006

The association of birthweight and body size throughout life with premenopausal breast cancer risk may be due, in part, to relationships with sex hormones. Therefore, we assessed whether birthweight, body shape at ages 5 and 10, body mass index (BMI) at age 18 and adulthood, adult waist circumference and waist-to-hip ratio (WHR), and attained height were associated with the plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone–binding globulin (SHBG) in 592 premenopausal women, ages 33 to 52 years old, from the Nurses' Health Study II. About 85% of women provided blood samples during follicular and luteal menstrual phases; other women had a single untimed sample. We observed few associations between sex hormone levels and birthweight or body shape in childhood. However, adult BMI was inversely associated with SHBG (P trend < 0.001) and positively associated with free testosterone (P trend < 0.001) concentrations. Adult BMI was not associated with follicular or luteal free estradiol levels (P trend ≥ 0.15) because it was inversely associated with total estradiol levels (P trend < 0.001 for follicular and luteal estradiol levels). Testosterone, androstenedione, and progesterone were inversely associated with BMI. Comparing women with a BMI of ≥30 versus <20 kg/m2, levels were higher by 53% for free testosterone and lower by 51% for SHBG, 39% for follicular estradiol, 20% for luteal estradiol, 14% for androstenedione, 13% for testosterone, and 20% for progesterone. We observed no clear associations between BMI at age 18, waist circumference, WHR, or height, and sex hormone concentrations. Our results suggest that effects on premenopausal sex hormone levels may be one mechanism through which adult adiposity, but not birthweight or childhood body size, affects premenopausal breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2494–501)
Oxidative Modification of Proteins: Age-Related Changes
Authors: Chakravarti Bulbul , Chakravarti Deb N.
Published: December 2006

Aging is a complex biological phenomenon which involves progressive loss of different physiological functions of various tissues of living organisms. It is the inevitable fate of life and is a major risk factor for death and different pathological disorders. Based on a wide variety of studies performed in humans as well as in various animal models and microbial systems, reactive oxygen species (ROS) are believed to play a key role in the aging process. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since, in general, proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms, this review will focus on the age-related oxidative modifications of proteins as well as on mechanism for removal or repair of the oxidized proteins. The topics covered include protein oxidation as a marker of oxidative stress, experimental evidence indicating the role of ROS in protein oxidation, protein carbonyl content, enzymatic degradation of oxidized proteins, and effects of caloric restriction on protein oxidation in the context of aging. Finally, we will discuss different strategies which have been or can be undertaken to slow down the oxidative damage of proteins and the aging process.
Effect of Antiestrogens on EGF-Mediated Movement of Human Breast Cancer Cells
Authors: Tong Gina M. , Rajah Talitha T. , Zang Xiao-Ping , Bahr Steven J. , Pento J. Thomas
Published: December 2006

In a previous study we compared the influence of several growth factors on breast cancer cells in culture and observed that epidermal growth factor (EGF) enhanced the invasiveness of estrogen receptor-positive breast cancer cells. The objective of the present study was to determine the influence of three unique antiestrogens on EGF-mediated movement of human breast cancer cells. The rate of movement of MCF-7 breast cancer cells was measured using time-lapse videomicroscopy (TLVM). The MCF-7 cells were pretreated with antiestrogen (either tamoxifen, ICI-182-780 (ICI) or 1,1-dichloro-cis-2,3-diarylcyclopropane (AII)) at 10–6 mol/l for 4 days, and then treated with EGF (10–10 mol/l) immediately prior to TLVM. EGF enhanced the motility of the MCF-7 cells at 30–90 min post-administration. However, EGF-mediated motility of the MCF-7 cells was inhibited by antiestrogen pretreatment, with TAM and ICI producing complete inhibition of EGF-induced motility. In conclusion, this study demonstrates that EGF enhances the rate of movement of MCF-7 breast cancer cells and that antiestrogen pretreatment inhibits EGF-mediated motility.
Hypofractionated Stereotactic Radiotherapy Using Intensity-Modulated Radiotherapy in Patients with One or Two Brain Metastases
Authors: Narayana Ashwatha , Chang Jenghwa , Yenice Kamil , Chan Kelvin , Lymberis Stella , Brennan Cameron , Gutin Philip H.
Published: December 2006

Purpose: A small fraction of patients with 1–2 brain metastases will not be suitable candidates to either surgical resection or stereotactic radiosurgery (SRS) due to either their location or their size. The objective of this study was to determine the local control, survival, patterns of relapse and the incidence of brain injury following a course of hypofractionated stereotactic radiotherapy while avoiding upfront whole brain radiation therapy (WBRT) in this subgroup of patients. Methods: A Gill-Thomas removable head frame system was used for immobilization. Brain LAB software with dynamic multileaf collimator hardware was used to design and deliver an intensity-modulated radiation therapy treatment plan. A dose of 600 cGy was prescribed to the 100% isodose line that would encompass the lesion with a 3-mm margin. A total dose of 3,000 cGy was delivered in 5 fractions using 2 fractions per week. The patients were followed with neurological examination and serial MRI images done every 3 months following the procedure. Results: Twenty patients have been treated using this fractionation schedule since April 2004. The 1-year local control at the site of original disease is 70%. The complete response, partial response and stable disease at the last follow-up were 15, 30 and 45%, respectively. Two patients had local recurrence at the site of original disease, while 5 had evidence of leptomeningeal disease. Two additional patients developed new brain metastases, resulting in a 1-year brain relapse-free survival of 36% following this approach. The median overall survival was 8.5 months. Three patients (15%) developed steroid dependency lasting 3 months or longer following the procedure. Four patients (20%) needed WBRT as salvage following this approach. Conclusions: The preliminary results of hypofractionated SRS are comparable to both surgery and SRS data for solitary brain metastases in terms of local control and overall survival with acceptable morbidity in this cohort of unfavorable patients.
Maintenance or Consolidation Therapy in Advanced Ovarian Cancer
Authors: Pectasides D. , Pectasides E.
Published: December 2006

Most patients with advanced epithelial ovarian cancer (EOC) achieve a clinical complete response (CR) or have no clinical evidence of disease after aggressive cytoreductive surgery and 6 cycles of platinum-/taxane-based chemotherapy. From the reported randomized trials using different durations or different cycles of chemotherapy, none of these showed improvement in survival beyond 6 cycles. Data from the literature do not support a relationship between the number of cycles and response or between the cumulative dose and response. In addition, no benefit in survival was detected with high-dose and intensity chemotherapy administered for a short time compared with standard-dose chemotherapy given for a longer time. However, statistically significant differences in progression-free survival were found in patients who achieved a clinically defined CR to a platinum (CDDP)-/paclitaxel-based chemotherapy and who continued single-agent paclitaxel for an extended time period. Notably, this randomized trial most likely did not offer any survival advantage, as it was closed prematurely by the Data Safety Monitoring Committee in accordance with the guidelines planned for interim analysis of primary end-points.
PET Scans for Decision-Making in Metastatic Renal Cell Carcinoma: A Single-Institution Evaluation
Authors: Dilhuydy M.S. , Durieux A. , Pariente A. , de Clermont H. , Pasticier G. , Monteil J. , Ravaud A.
Published: December 2006

Objective: Therapeutic decision-making in metastatic renal cell carcinoma (MRCC) is based on conventional radiological evaluation. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans may modify this strategy. Methods: Patients with MRCC for whom a therapeutic decision had been made underwent an FDG-PET scan in order to complete the standard radiological evaluation. Results: Twenty-four patients and 26 FDG-PET scans were eligible. In 18 patients, metastatic disease was evaluable on the computed tomography (CT) scan; the FDG-PET scan was positive in 16 patients and negative in 10. In 2 patients, the FDG-PET scan was positive while they were considered disease free on radiological evaluation. In 5 patients (20.8%), the previous therapeutic decision was changed. Thirteen patients had a pathological evaluation for 19 sites. One patient out of 13 had a false-positive FDG-PET scan, while 4 sites out of 6 were false-negative. The sensitivity was 75% (95% CI: 47.6–92.7) and the predictive positive value was 92.3% (95% CI: 64–99.8). With a median follow-up of 24 months, 3 patients developed new metastatic sites. Conclusion: Our data suggest that, when positive, an FDG-PET scan may modify the decision made; when negative, it should not modify decision-making especially for surgery, owing to its sensitivity.