bluuebunny/crossref_metadata_2025 huggingface dataset:
ERV3 and Related Sequences in Humans: Structure and RNA Expression
Authors: Andersson Ann-Catrin , Yun Zhihong , Sperber Göran O. , Larsson Erik , Blomberg Jonas
Published: July 2005

The ERV3 locus at chromosome 7q11 is a much studied human endogenous retroviral (HERV) sequence, owing to an
env
open reading frame (ORF) and placental RNA and protein expression. An analysis of the human genome demonstrated that ERV3 is one of a group of 41 highly related elements (ERV3-like HERVs) which use proline, isoleucine, or arginine tRNA in their primer binding sites. In addition to elements closely related to ERV3, the group included the previously known retinoic acid-inducible element, RRHERVI, also referred to as HERV15, but was separate from the related HERV-E elements. The ERV3-like elements are defective. The only element with an ORF among
gag
,
pro
,
pol
, and
env
genes was the
env
ORF of the original ERV3 locus. A search in dbEST revealed ERV3 RNA expression in placenta, skin, carcinoid tumor, and adrenal glands. Expression was also studied with newly developed real-time quantitative PCRs (QPCR) of ERV3 and HERV-E(4-1)
env
sequences. Results from a novel histone 3.3 RNA QPCR result served as the expression control. QPCR results for ERV3 were compatible with previously published results, with a stronger expression in adrenal gland and placenta than in 15 other human tissues. The expression of the envelope (
env
) of ERV3 at chromosome 7q11 was also studied by using stringent in situ hybridization. Expression was found in corpus luteum, testis, adrenal gland, Hassal's bodies in thymus, brown fat, pituitary gland, and epithelium of the lung. We conclude that ERV3
env
is most strongly expressed in adrenal and sebaceous glands as well as in placenta.
Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Mediate Inhibition of Stat2 Expression and Alpha/Beta Interferon Responsiveness
Authors: Lo Mindy S. , Brazas Robert M. , Holtzman Michael J.
Published: July 2005

Respiratory syncytial virus (RSV) subverts the antiviral interferon (IFN) response, but the mechanism for this evasion was unclear. Here we show that RSV preferentially inhibits IFN-α/β signaling by expression of viral NS1 and NS2. Thus, RSV infection or expression of recombinant NS1 and NS2 in epithelial host cells causes a marked decrease in Stat2 levels and the consequent downstream IFN-α/β response. Similarly, NS1/NS2-deficient RSV no longer decreases Stat2 levels or IFN responsiveness. RSV infection decreased human but not mouse Stat2 levels, so this mechanism of IFN antagonism may contribute to viral host range, as well as immune subversion.
Comparison of the Genetic Recombination Rates of Human Immunodeficiency Virus Type 1 in Macrophages and T Cells
Authors: Chen Jianbo , Rhodes Terence D. , Hu Wei-Shau
Published: July 2005

Human immunodeficiency virus type 1 (HIV-1) exhibits a high level of genetic variation generated by frequent mutation and genetic recombination during reverse transcription. We have measured HIV-1 recombination rates in T cells in one round of virus replication. It was recently proposed that HIV-1 recombines far more frequently in macrophages than in T cells. In an attempt to delineate the mechanisms that elevate recombination, we measured HIV-1 recombination rates in macrophages at three different marker distances. Surprisingly, the recombination rates were comparable in macrophages and in T cells. In addition, we observed similar recombination rates in two monocytic cell lines regardless of the differentiation status. These results indicate that HIV-1 undergoes similar numbers of recombination events when infecting macrophages and T cells.
Herpes Simplex Virus Type 1 Single-Strand DNA Binding Protein ICP8 Enhances the Nuclease Activity of the UL12 Alkaline Nuclease by Increasing Its Processivity
Authors: Reuven Nina Bacher , Weller Sandra K.
Published: July 2005

UL12 is a 5′- to 3′-exonuclease encoded by herpes simplex virus type 1 (HSV-1) which degrades single- and double-stranded DNA. UL12 and the single-strand DNA binding protein ICP8 mediate a strand exchange reaction. We found that ICP8 inhibited UL12 digestion of single-stranded DNA but stimulated digestion of double-stranded DNA threefold. The stimulatory effect of ICP8 was independent of a strand exchange reaction; furthermore, the effect was specific to ICP8, as it could not be reproduced by
Escherichia coli
single-stranded DNA binding protein. The effect of ICP8 on the rate of UL12 double-stranded DNA digestion is attributable to an increase in processivity in the presence of ICP8.
Making regulations and drawing up legislation in Islamic countries under conditions of uncertainty, with special reference to embryonic stem cell research
Authors: Aksoy S
Published: July 2005

Stem cell research is a newly emerging technology that promises a wide variety of benefits for humanity. It has, however, also caused much ethical, legal, and theological debate. While some forms of its application were prohibited in the beginning, they have now started to be used in many countries. This fact obliges us to discuss the regulation of stem cell research at national and international level. It is obvious that in order to make regulations and to draw up legislation at national or international levels it helps to know the perspectives of different cultures and faith traditions. In this article the issue is explored from an Islamic perspective. Firstly, some basic information is given about Islam to explain how laws are drawn up and regulations made in this tradition. Secondly, the principles on which the laws and regulations are based are applied to stem cell research, and finally the permitted and prohibited methods of stem cell research are described. The discussions throughout the paper demonstrate that while some ethicists argue that stem cell research is unethical in the Islamic tradition, tradition permits it as long as such research is aimed at improving human health.
The physician charter on medical professionalism: a Jewish ethical perspective
Authors: Jotkowitz A B , Glick S
Published: July 2005

The physician charter on medical professionalism creates standards of ethical behaviour for physicians and has been endorsed by professional organisations worldwide. It is based on the cardinal principles of the primacy of patient welfare, patient autonomy, and social welfare. There has been little discussion in the bioethics community of the doctrine of the charter and none from a Jewish ethical perspective. In this essay the authors discuss the obligations of the charter from a Jewish ethical viewpoint and call on other cultures to develop their own unique perspectives on this important document.
Informed consent, participation in, and withdrawal from a population based cohort study involving genetic analysis
Authors: Matsui K , Kita Y , Ueshima H
Published: July 2005

Objective:Population based cohort studies involving genetic research have been initiated in several countries. However, research published to date provides little information on the willingness of the general population to participate in such studies. Furthermore, there is a need to discover the optimal methods for acquiring fully informed consent from the general population. We therefore examined the results of a population based genetic cohort study to identify the factors affecting the participation rate by members of the general public and also specifically to examine the impact of different consent procedures on the rate of participation by prospective candidates and their subsequent withdrawal rate from the study.

Design:Descriptive analyses.

Setting and participants:The study evaluated two non-genetic subcohorts comprising 3166 people attending for a health checkup during 2002, and two genetic subcohorts comprising 2195 people who underwent a checkup during 2003.

Main outcome measurements:Analysis endpoints were differences in participation rates between the non-genetic and genetic subcohorts, differences between providing non-extensive and extensive preliminary information, and changes in participation status between baseline and at 6 months.

Results:Participation rates in the genetic subcohorts were 4·7–9·3% lower than those in the non-genetic subcohorts. The odds ratios (OR) of participation in genetic research were between 0·60 and 0·77, and the OR for withdrawal from the research was over 7·70; providing preliminary extensive information about genetic research reduced the withdrawal risks (OR 0·15 for all dependent variables) but worsened participation rates (OR 0·63–0·74).

Conclusions:The general population responded sceptically towards genetic research. It is crucial that genetic researchers utilise an informative and educational consent process worthy of public trust.
SCCI-HYBRID METHODS FOR 2D CURVE TRACING
Authors: RATSCHEK HELMUT , ROKNE JON
Published: July 2005

A hybrid method for plotting 2-dimensional curves, defined implicitly by equations of the form f(x,y) = 0 is presented. The method is extremely robust and reliable and consists of Space Covering techniques, Continuation principles and Interval analysis (i.e. SCCI). The space covering, based on iterated subdivision, guarantees that no curve branches or isolated curve parts or even points are lost (which can happen if grid methods are used). The continuation method is initiated in a subarea as soon as it is proven that the subarea contains only one smooth curve. Such a subarea does not need to be subdivided further so that the computation is accelerated as far as possible with respect to the subdivision process. The novelty of the SCCI-hybrid method is the intense use of the implicit function theorem for controlling the steps of the method. Although the implicit function theorem has a rather local nature, it is empowered with global properties by evaluating it in an interval environment. This means that the theorem can provide global information about the curve in a subarea such as existence, non-existence, uniqueness of the curve or even the presence of singular points. The information gained allows the above-mentioned control of the subarea and the decision of its further processing, i.e. deleting it, subdividing it, switching to the continuation method or preparing the plotting of the curve in this subarea. The curves can be processed mathematically in such a manner, that the derivation of the plotted curve from the exact curve is as small as desired (modulo the screen resolution).
LOCALLY ADAPTIVE CHROMATIC RESTORATION OF DIGITALLY ACQUIRED PAINTINGS
Authors: DRAGO FRÉDÉRIC , CHIBA NORISHIGE
Published: July 2005

This article presents a semi-automatic procedure to restore the visual appearance of aged paintings converted to a digital form. The innovative implementation of an image-processing algorithm based on the Retinex theory of human vision alleviates layers of yellowed varnish and dust, restores chromatic balance and contrast, and recovers some of the original painted details. This virtual cleaning of artwork is totally non-intrusive and can be applied automatically to color images of paintings or ancient illustrations. Cleaned virtual reproductions help art historians and restorers in their research and classification work, and also show the artwork in good condition to a wide audience while avoiding an always costly and dangerous manual restoration.
SEMI-CLASSICAL PROPAGATION AND SPECTRAL ANALYSIS IN THE H- ION INTERACTING WITH A METALLIC SURFACE
Authors: ZULUAGA JOHN JAIRO , MAHECHA JORGE , CHULKOV EUGENE
Published: July 2005

A semi-classical propagator method combined with harmonic inversion of short time signals is used to find the resonant states of an electron interacting with a hydrogen atom near a metallic surface. The atom-electron interaction corresponds to one electron in the presence of a neutral compact core, which can be described by a simple local potential proposed by Cohen. On the other hand, the electron-surface interaction is described by a model proposed by Jennings, the so-called Jelly Model, or by a more realistic local potential that takes into account the shell structure of the metal. A semi-classical propagator approach, proposed by Herman and Kluk, is used to calculate an approximation to the autocorrelation function A(t) = <ψt|ψ0> entirely in terms of classical trajectories. A filter-diagonalization method for harmonic inversion of the complex time signal A(t) is applied to extract the resonances. We verified that the spectral analysis of the signal obtained by semi-classical methods gives satisfactory numerical results for the position and width of the lowest lying resonances.
ADDITIVITY SCHEMES IN CONFORMATIONAL ANALYSIS: CONCEPT AND DEMONSTRATION
Authors: WU ZHENGYU , GLASER RAINER
Published: July 2005

Additivity schemes are of fundamental importance in molecular modeling. It is the goal of an additivity scheme to predict the value of parameter for a complex system based on the knowledge of the respective parameters for prototypical systems. The commonly employed method is based on the identification of energy factors, the quantification of these energy factors, and the evaluation of trial functions that depend on these factors. We describe a non-iterative method to derive energy factor expressions. While energy factors occur in the derivation of the energy factor expressions, the values of the energy factors are not determined and they are expressed instead as series of the known parameters of the minimal set of prototypes. The non-iterative energy factor analysis is illustrated by application to conformational preference energies for a series of spiro(THF)cyclohexanes for which the results of a traditional analysis are available. We demonstrate that the contributions to the conformational preference energy are additive, clarify the precise meaning of the terms "gauche interaction" and "1,3-interaction", and state a more general hypothesis that provides opportunities for testing by future experimental and computational studies.
MOLECULAR DYNAMICS SIMULATIONS OF DNA DIMERS BASED ON REPLICA-EXCHANGE UMBRELLA SAMPLING II: FREE ENERGY ANALYSIS
Authors: MURATA KATSUMI , SUGITA YUJI , OKAMOTO YUKO
Published: July 2005

The free energy change of the stacking process of DNA dimers has been investigated by potential of mean force (PMF) calculations. Two reaction coordinates were considered. One is the distance R between the glycosidic nitrogen atoms of the bases. The other is the pseudo dihedral angle X (N–Cl′–Cl′–N) . All 16 possible DNA dimers composed of the adenine, cytosine, guanine, or thymine bases in 5′ and 3′ positions were considered. From the free energy profiles, we observed good stacking for all DNA dimers and sequence-dependent stacking stability. This sequence dependence of the stacking free energy is in good agreement with the experimental results. We also observed that the PMF is the lowest at R = 4.0~4.4 Å and X = 20~40° for all the DNA dimers except for the dGpdA dimer. These values are close to those of the canonical B-DNA (4.4 Å and 29°).
MOLECULAR DYNAMICS SIMULATIONS OF DNA DIMERS BASED ON REPLICA-EXCHANGE UMBRELLA SAMPLING I: TEST OF SAMPLING EFFICIENCY
Authors: MURATA KATSUMI , SUGITA YUJI , OKAMOTO YUKO
Published: July 2005

In order to elucidate the stacking-unstacking process of DNA dimers, we have performed molecular dynamics simulations based on replica-exchange umbrella sampling (REUS), which is one of powerful conformational sampling techniques. We studied four DNA dimers composed of the adenine and thymine bases in both the 5′ and the 3′ positions (dApdA, dApdT, dTpdA, and dTpdT). We examined the time series of the distance between the glycosidic nitrogen atoms, root-mean-square deviations from A-DNA and B-DNA, various backbone and glycosidic torsion angles, and the pseudorotation phase angles as functions of the simulation time step. All these time series imply that the present simulation has indeed sampled a very wide conformational space. The results for the backbone and glycosidic torsion angles and pseudorotation phase angles imply that B-DNA structures are the dominant motif of the stacked dimers, while a small population of A-DNA also exists in the stacked states.
VOICE, CONTROL, AND BELONGING: The Double-Edged Sword of Procedural Fairness
Authors: MacCoun Robert J.
Published: July 2005

▪ Abstract  The procedural justice literature has grown enormously since the early work of Thibaut and Walker in the 1970s. Since then, the finding that citizens care enormously about the process by which outcomes are reached—even unfavorable outcomes—has been replicated a wide range of methodologies (including panel surveys, psychometric work, and experimentation), cultures (throughout North America, Europe, and Asia), and settings (including tort litigation, policing, taxpayer compliance, support for public policies, and organizational citizenship). We have learned a great deal about the antecedents and consequences of these judgments. In particular, the work of Tom Tyler and Allan Lind and their colleagues suggests that people care about voice, dignity, and respect for relational and symbolic reasons rather than (or in addition to) instrumental reasons. This finding has benevolent implications for governance and social cooperation, but also some troubling implications, leaving people susceptible to manipulation and exploitation.
Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats
Authors: Schwetz Ines , McRoberts James A. , Coutinho Santosh V. , Bradesi Sylvie , Gale Greg , Fanselow Michael , Million Mulugeta , Ohning Gordon , Taché Yvette , Plotsky Paul M. , Mayer Emeran A.
Published: July 2005

In rodents, maternal pup interactions play an important role in programming the stress responsiveness of the adult organism. The aims of this study were 1) to determine the effect of different neonatal rearing conditions on acute and delayed stress-induced visceral sensitivity as well as on other measures of stress sensitivity of the adult animal; and 2) to determine the role of corticotropin-releasing factor receptor (CRF-R) subtype 1 (CRF1R) in mediating visceral hypersensitivity. Three groups of male Long-Evans rat pups were used: separation from their dam for 180 min daily from postnatal days 2–14 (MS180), daily separation (handling) for 15 min (H), or no handling. The visceromotor responses (VMR) to colorectal distension, stress-induced colonic motility, and anxiety-like behavior were assessed in the adult rats. The VMR was assessed at baseline, immediately after a 1-h water avoidance (WA) stress, and 24 h poststress. Astressin B, a nonselective CRF-R antagonist, or CP-154,526, a selective CRF1R antagonist, was administered before the stressor and/or before the 24-h measurement. MS rats developed acute and delayed stress-induced visceral hyperalgesia. In contrast, H rats showed hypoalgesia immediately after WA and no change in VMR on day 2. MS rats with visceral hyperalgesia also exhibited enhanced stress-induced colonic motility and increased anxiety-like behavior. In MS rats, both CRF-R antagonists abolished acute and delayed increases in VMR. Rearing conditions have a significant effect on adult stress responsiveness including immediate and delayed visceral pain responses to an acute stressor. Both acute and delayed stress-induced visceral hypersensitivity in MS rats are mediated by the CRF/CRF1R system.
Influence of Cheyne-Stokes respiration on ventricular response to atrial fibrillation in heart failure
Authors: Leung Richard S. T. , Bowman Michael E. , Diep Tung M. , Lorenzi-Filho Geraldo , Floras John S. , Bradley T. Douglas
Published: July 2005

In subjects with sinus rhythm, respiration has a profound effect on heart rate variability (HRV) at high frequencies (HF). Because this HF respiratory arrhythmia is lost in atrial fibrillation (AF), it has been assumed that respiration does not influence the ventricular response. However, previous investigations have not considered the possibility that respiration might influence HRV at lower frequencies. We hypothesized that Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) would entrain HRV at very low frequency (VLF) in AF by modulating atrioventricular (AV) nodal refractory period and concealed conduction. Power spectral analysis of R-wave-to-R-wave (R-R) intervals and respiration during sleep were performed in 13 subjects with AF and CSR-CSA. As anticipated, no modulation of HRV was detected at HF during regular breathing. In contrast, VLF HRV was entrained by CSR-CSA [coherence between respiration and HRV of 0.69 (SD 0.22) at VLF during CSR-CSA vs. 0.20 (SD 0.19) at HF during regular breathing, P < 0.001]. Comparison of R-R intervals during CSR-CSA demonstrated a shorter AV node refractory period during hyperpnea than apnea [minimum R-R of 684 (SD 126) vs. 735 ms (SD 147), P < 0.001] and a lesser degree of concealed conduction [scatter of 178 (SD 56) vs. 246 ms (SD 72), P = 0.001]. We conclude that CSR-CSA entrains the ventricular response to AF, even in the absence of HF respiratory arrhythmia, by inducing rhythmic oscillations in AV node refractoriness and the degree of concealed conduction that may be a function of autonomic modulation of the AV node.
Effects of eccentric exercise on microcirculation and microvascular oxygen pressures in rat spinotrapezius muscle
Authors: Kano Yutaka , Padilla Danielle J. , Behnke Brad J. , Hageman K. Sue , Musch Timothy I. , Poole David C.
Published: July 2005

A single bout of eccentric exercise results in muscle damage, but it is not known whether this is correlated with microcirculatory dysfunction. We tested the following hypotheses in the spinotrapezius muscle of rats either 1 (DH-1; n = 6) or 3 (DH-3; n = 6) days after a downhill run to exhaustion (90–120 min; −14° grade): 1) in resting muscle, capillary hemodynamics would be impaired, and 2) at the onset of subsequent acute concentric contractions, the decrease of microvascular O2 pressure (P mvo2), which reflects the dynamic balance between O2 delivery and O2 utilization, would be accelerated compared with control (Con, n = 6) rats. In contrast to Con muscles, intravital microscopy observations revealed the presence of sarcomere disruptions in DH-1 and DH-3 and increased capillary diameter in DH-3 (Con: 5.2 ± 0.1; DH-1: 5.1 ± 0.1; DH-3: 5.6 ± 0.1 μm; both P < 0.05 vs. DH-3). At rest, there was a significant reduction in the percentage of capillaries that sustained continuous red blood cell (RBC) flux in both DH running groups (Con: 90.0 ± 2.1; DH-1: 66.4 ± 5.2; DH-3: 72.9 ± 4.1%, both P < 0.05 vs. Con). Capillary tube hematocrit was elevated in DH-1 but reduced in DH-3 (Con: 22 ± 2; DH-1: 28 ± 1; DH-3: 16 ± 1%; all P < 0.05). Although capillary RBC flux did not differ between groups ( P > 0.05), RBC velocity was lower in DH-1 compared with Con (Con: 324 ± 43; DH-1: 212 ± 30; DH-3: 266 ± 45 μm/s; P < 0.05 DH-1 vs. Con). Baseline P mvO2 before contractions was not different between groups ( P > 0.05), but the time constant of the exponential fall to contracting P mvO2 values was accelerated in the DH running groups (Con: 14.7 ± 1.4; DH-1: 8.9 ± 1.4; DH-3: 8.7 ± 1.4 s, both P < 0.05 vs. Con). These findings are consistent with the presence of substantial microvascular dysfunction after downhill eccentric running, which slows the exercise hyperemic response at the onset of contractions and reduces the P mvO2 available to drive blood-muscle O2 delivery.
Effects of inactivity on fiber size and myonuclear number in rat soleus muscle
Authors: Zhong Hui , Roy Roland R. , Siengthai Boonclaire , Edgerton V. Reggie
Published: July 2005

The effects of short-term (4 days) and long-term (60 days) neuromuscular inactivity on myonuclear number, size, and myosin heavy chain (MHC) composition of isolated rat soleus fibers were determined using confocal microscopy and gel electrophoresis. Inactivity was produced via spinal cord isolation (SI), i.e., complete spinal cord transections at a midthoracic and a high sacral level and bilateral deafferentation between the transection sites. Compared with control, there was an increase in the percentage of fibers containing the faster MHC isoforms after 60, but not 4, days of SI. The mean sizes of type I and type I+IIa fibers were 41 and 27% and 66 and 56% smaller after 4 and 60 days of SI, respectively. Thus atrophy occurred earlier than the shift in myosin heavy chain (MHC) profile. The number of myonuclei was ∼30% higher in type I than type I+IIa fibers in control soleus, but after 60 days of SI these values were similar. The number of myonuclei per millimeter in type I fibers was significantly lower than control after 60 days of SI, whereas there was no change in type I+IIa fibers. Thus myonuclei were eliminated from fibers containing only type I MHC. Because the magnitude of the loss of myonuclei was less than the level of atrophy, the myonuclear domains of both type I and type I+IIa fibers were significantly lower than control. Thus chronic (60 days) inactivity results in smaller, faster fibers that contain a higher than normal amount of DNA per unit of cytoplasm. The absence of activation of muscle fibers that are normally the most active (pure type I fibers) resulted in most, but not all, fibers expressing some fast MHC isoforms. The results also indicate that a loss of myonuclei is not a prerequisite for sustained muscle fiber atrophy.
Stimulatory effect of CO2 on vagal bronchopulmonary C-fiber afferents during airway inflammation
Authors: Lin Ruei-Lung , Gu Qihai , Lin You-Shuei , Lee Lu-Yuan
Published: July 2005

This study investigated 1) whether pulmonary C fibers are activated by a transient increase in the CO2 concentration of alveolar gas; and 2) if the CO2 sensitivity of these afferents is altered during airway inflammation. Single-unit pulmonary C-fiber activity was recorded in anesthetized, open-chest rats. Transient alveolar hypercapnia (HPC) was induced by administering a CO2-enriched gas mixture (25–30% CO2, 21% O2, balance N2) for five to eight breaths, which increased alveolar CO2 concentration progressively to near or above 13% for 3–5 s and lowered the arterial pH transiently to 7.10 ± 0.05. Our results showed the following. 1) HPC evoked only a mild stimulation in a small fraction (4/47) of pulmonary C fibers, and there was no significant change in fiber activity (change in fiber activity = 0.22 ± 0.16 imp/s; P > 0.1, n = 47). 2) In sharp contrast, after airway exposure to poly-l-lysine, a cationic protein known to induce mucosal injury, the same challenge of transient HPC activated 87.5% of the pulmonary C fibers tested and evoked a distinct stimulatory effect on these afferents (change in fiber activity = 6.59 ± 1.78 imp/s; P < 0. 01, n = 8). 3) Similar potentiation of the C-fiber response to HPC was also observed after acute exposure to ozone ( n = 6) and during a constant infusion of inflammatory mediators such as adenosine ( n = 15) or prostaglandin E2 ( n = 12). 4) The enhanced C-fiber sensitivity to CO2 after poly-l-lysine was completely abrogated by infusion of NaHCO3 (1.82 mmol·kg−1·min−1) that prevented the reduction in pH during HPC ( n = 6). In conclusion, only a small percentage (<10%) of the bronchopulmonary C fibers exhibit CO2 sensitivity under control conditions, but alveolar HPC exerts a consistent and pronounced stimulatory effect on the C-fiber endings during airway inflammation. This effect of CO2 is probably mediated through the action of hydrogen ions.
Interferon Treatment for Hypereosinophilic Syndromes and Systemic Mastocytosis
Authors: Butterfield J.H.
Published: July 2005

Hypereosinophilic syndromes (HES) and systemic mastocytosis (SMCD) are heterogeneous disorders with clinical symptoms from local and remote effects of excessive proliferation of eosinophils and mast cells, respec tively. Interferon α (IFN-α), alone or in combination with other medications, can be a useful, and at times life-saving, treatment for patients with HES. Receptors for IFN-α are present on eosinophils, and clinical benefits are due to its effect on eosinophil proliferation, migration, activation, and survival. These effects are likely mediated through multiple pathways including, but not limited to, inhibition of eosinophil colony-forming cells, upregulation of IFN-γ synthesis, and inhibition of production of eosinophil-active cytokines by T cells, mast cells, and mononuclear cells. IFN-α has been life-saving for patients with intractable HES that were resistant to prednisone, hydroxyurea, and other agents. Resistance to the eosinopenic effect of IFN-α does not develop and the dose of IFN-α necessary to maintain control of eosinophilia often decreases with time. The combination of IFN-α and hydroxyurea is very useful and allows dosage reduction of IFN-α and better control of hypereosinophilia than with either agent alone. The efficacy of IFN-α for treatment of SMCD has been more difficult to establish, with both favorable and unfavorable results reported. The disparate results may have resulted from the small number of patients with SMCD treated with IFN-α, the use of various criteria for a ‘successful’ treatment outcome, short duration of treatment and follow-up, and the use of modest dosages. In reported series, side effects from IFN-α have frequently been dose-limiting. IFN-α improves many of the clinical symptoms of SMCD including dermatological, hematological, gastrointestinal, and systemic symptoms associated with histamine release. IFN-α has a beneficial effect on skeletal symptoms because of its ability to increase bone density and reduce painful episodes from vertebral fractures. No consistent improvement in bone marrow infiltration by mast cells has been demonstrated except in a recent study employing high dosages of IFN-α. A beneficial effect from the combination of IFN-α and prednisone has been reported for several patients, suggesting that combined use of these two medications may provide synergism in treatment outcomes.
Modern Diagnosis and Treatment of Primary Eosinophilia
Authors: Tefferi A.
Published: July 2005

The recent discovery of an eosinophilia-specific, imatinib-sensitive, karyotypically occult but fluorescence in situ hybridization-apparent molecular lesion in a subset of patients with blood eosinophilia has transformed the diagnostic as well as treatment approach to eosinophilic disorders. Primary (i.e. nonreactive) eosinophilia is considered either ‘clonal’ or ‘idiopathic’ based on the presence or absence, respectively, of either a molecular or bone marrow histological evidence for a myeloid neoplasm. Clonal eosinophilia might accompany a spectrum of clinicopathological entities, the minority of whom are molecularly characterized; Fip1-like-1-platelet-derived growth factor receptor α (FIP1L1-PDGFRA+) systemic mastocytosis, platelet-derived growth factor receptor β (PDGFRB)-rearranged atypical myeloproliferative disorder, chronic myeloid leukemia, and the 8p11 syndrome that is associated with fibroblast growth factor receptor 1 (FGFR1) rearrangement. Hypereosinophilic syndrome (HES) is a subcategory of idiopathic eosinophilia and is characterized by an absolute eosinophil count of ≧1.5 × 109/l for at least 6 months as well as eosinophil-mediated tissue damage. At present, a working diagnosis of primary eosinophilia mandates a bone marrow examination, karyotype analysis, and additional molecular studies in order to provide the patient with accurate prognostic information as well as select appropriate therapy. For example, the presence of either PDGFRA or PDGFRB mutations warrants the use of imatinib in clonal eosinophilia. In HES, prednisone, hydroxyurea, and interferon-α constitute first-line therapy, whereas imatinib, cladribine, and monoclonal antibodies to either interleukin-5 (mepolizumab) or CD52 (alemtuzumab) are considered investigational. Allogeneic transplantation offers a viable treatment option for drug-refractory cases.
Traumatic Vertebral Artery Dissection in a Child with Brachial Plexus Injury
Authors: Park Seong-Hyun , Sung Joo-Kyung , Hwang Sung-Kyoo
Published: July 2005

Traumatic vertebral artery dissection is an unusual event in children, but early recognition and treatment are important to prevent neurological deficits. The authors present a case of a 4-year-old boy with a traumatic extracranial vertebral artery dissection, who suffers from left arm monoplegia due to brachial plexus injury.
Bifrontal Decompressive Craniotomy in a 6-Month-Old Infant with Posttraumatic Refractory Intracranial Hypertension
Authors: El-Watidy Sherif
Published: July 2005

Objective: To document the outcome of bifrontal decompressive craniotomy (BDC) in an infant who developed refractory intracranial hypertension (IH) and massive brain infarction following severe head injury. Clinical Presentation: A 6-month-old girl sustained a severe closed head injury in a car accident. Her Glasgow coma score dropped from 10 to 6/15 within 6 h after admission, and her pupils became dilated and fixed. CT brain scans showed severe brain swelling and extensive infarction in both cerebral hemispheres with no grey-white mater differentiation. She developed a state of refractory IH despite maximal medical treatment. Intervention: She hadBDC and duraplasty carried out 8 h after admission. She made a quick recovery to Glasgow outcome score 3, and her total hospital stay was 10 weeks. Conclusion: BDC can be a life-saving procedure for infants with refractory IH and massive brain infarction.
Promoter Polymorphisms of the Interferon-α Receptor Gene and Development of Interferon-Induced Depressive Symptoms in Patients with Chronic Hepatitis C: Preliminary Findings
Authors: Yoshida Keizo , Alagbe Oyetunde , Wang Xiaohong , Woolwine Bobbi , Thornbury Marie , Raison Charles L. , Miller Andrew H.
Published: July 2005

Background: Interferon (IFN)-α treatment frequently induces depression, which can impair quality of life and reduce treatment adherence. Defining relevant risk factors for IFN-α-induced depression is essential for designing preventative treatment strategies. Objective: The purpose of the present study was to determine whether promoter polymorphisms of –408C/T, –3C/T and GT repeat dinucleotide microsatellite in the IFN-α/β receptor 1 (IFNAR1) gene are associated with the development of IFN-induced depression. Method: Fifty patients with chronic hepatitis C were treated with pegylated IFN α-2b plus a standard or weight-based dose of ribavirin. Severity of depression was assessed using the Zung Self-Rating Depression Scale (SDS) at baseline and at 4, 8, 12 and 24 weeks of treatment. Result: The baseline to maximum difference in the SDS index score of neurovegetative/somatic symptoms was higher in patients with the 5/14 genotype of the GT repeat dinucleotide microsatellite polymorphism than in those patients with other genotypes (p = 0.0084). Conclusion: This preliminary result suggests that the promoter GT repeat dinucleotide microsatellite polymorphism of the IFNAR1 gene may represent a risk factor for the development of depressive symptoms during IFN-α therapy for hepatitis C and other conditions.
Alpha-Helical CRH Exerts CRH Agonistic Effects on Sleep-Endocrine Activity in Humans
Authors: Held Katja , Antonijevic Irina , Murck Harald , Künzel Heike , Steiger Axel
Published: July 2005

CRH is known to enhance wakefulness and to reduce SWS. In addition, some but not all, studies suggest that CRH promotes REM sleep. Alpha-helical CRH exerts CRH-antagonistic effects in various studies. We studied its effect on sleep EEG and nocturnal secretion of ACTH, cortisol, GH (n = 7) in young normal male subjects. After administering the substance cortisol and ACTH levels were enhanced during the total night compared to placebo. We found an increase of the time spent awake for the first half. ACTH (2nd half of the night) and cortisol (total night and 1st half of the night) increased. The results of the present study correspond to a mixture of agonistic and antagonistic effects of alpha-helical CRH.
Influence of Age, Gender, Health Status, and Depression on Quantitative EEG
Authors: Morgan Melinda L. , Witte Elise A. , Cook Ian A. , Leuchter Andrew F. , Abrams Michelle , Siegman Barbara
Published: July 2005

Quantitative electroencephalography (QEEG) has shown increasing utility in assessing brain function in clinical research studies of depression. QEEG findings may be influenced by a variety of factors other than the presence of depression, including age, gender, depression severity, and physical health status. Many of these factors have not been systematically evaluated. We therefore examined QEEG measures in 104 subjects with depression and normal controls to determine the influence of these factors. We examined QEEG power as well as cordance, a QEEG measure that has a stronger association with cerebral perfusion than conventional QEEG measures. Prefrontal cordance in the theta band has been associated with the pathophysiology of depression and response to treatment. We found that prefrontal cordance and relative power in the theta band were unaffected by age, gender, severity of depression, and health status, while prefrontal absolute power was higher in women than men. All of these measures were different from global measures of absolute and relative power, which were influenced by age, gender, and health status. These findings suggest that prefrontal cordance in depressed patients is not significantly affected by factors of age, gender, severity of depression, or physical illness. Global measures of power, and to a lesser extent prefrontal absolute power, must be interpreted with regard to confounding factors of age, gender, physical illness, and severity of depression.
Role of Extracellular Superoxide Dismutase in Patients under Maintenance Hemodialysis
Authors: Nakamura Masaaki , Ando Yukio , Sasada Keiko , Haraoka Katsuki , Ueda Mitsuharu , Okabe Hiroaki , Motomiya Yoshihiro
Published: July 2005

Background: It has been well documented that free radical injury is involved in the progression of chronic renal failure. Extracellular superoxide dismutase (EC-SOD), localized on the endothelial cell surface, plays an important role in reducing oxidative stress especially in the vessels by binding to the endothelial cell surface via the heparin-binding domain. Although EC-SOD Arg213Gly, which cannot bind on endothelial cells, has been considered a polymorphism, the effect of EC-SOD on hemodialysis patients has not been well examined. Methods: In 178 hemodialysis patients, the following examinations were performed. EC-SOD Arg213Gly was examined by polymerase chain reaction (PCR)-induced mutation restriction analysis (PCR-IMRA). As indexes of atherosclerosis, the annual progression in intima-media thickness (ΔIMT), plaque score, pulse wave velocity (PWV) and plasma-oxidized low-density lipoprotein (OxLDL) values were examined. Results: PCR-IMRA revealed that 20 of 178 patients possessed the mutation (11.2%), and the incidence was about twice as high as that in a previously reported Japanese population. Although there were no statistical differences in plaque score and PWV with and without EC-SOD Arg213Gly, ΔIMT and plasma OxLDL values in patients with EC-SOD Arg213Gly were significantly higher than those in patients without the mutation. Conclusion: EC-SOD Arg213Gly is an accelerating factor for the progression of renal failure and atherosclerosis.
Stimulation of the Posterior Hypothalamus for Medically Intractable Impulsive and Violent Behavior
Authors: Franzini Angelo , Marras Carlo , Ferroli Paolo , Bugiani Orso , Broggi Giovanni
Published: July 2005

Objective: To describe the therapeutic effect of deep brain stimulation for the treatment of patients with below-average IQs who are affected by aggressive and disruptive behavior and who are resistant to any drug and/or conservative treatment (including occupational therapy). Patients and Methods: Two consecutive patients suffering from mental retardation with aggressive and disruptive behavior and resistant to any pharmacological treatment underwent deep brain stimulation electrode placement in the posteromedial hypothalamus for continuous chronic high-frequency stimulation (HFS). The stereotactic coordinates of the target were chosen according to the study by Sano et al., which involved hypothalamic stereotactic lesions. Results: HFS of the posteromedial hypothalamus demonstrated consistent improvement of disruptive behavior in both patients at the follow-up evaluation 1 year later. Conclusions: HFS of the posteromedial hypothalamus showed similar results to those obtained by Sano et al. in the 1960s with radiofrequency lesions of the same target volume. The reversibility of neurostimulation allows HFS to control disruptive behavior when conservative treatments are ineffective, and drug therapy is uneventful or causes severe side effects. In conclusion, this neuromodulation procedure improved the quality of life and the range of social relationships for both of the treated patients.
Amyotrophic Lateral Sclerosis Mortality in the United States, 1979–2001
Authors: Sejvar James J. , Holman Robert C. , Bresee Joseph S. , Kochanek Kenneth D. , Schonberger Lawrence B.
Published: July 2005

The etiology of nonfamilial amyotrophic lateral sclerosis (ALS) remains unknown. Earlier studies have suggested an increase in the incidence of ALS over time. We performed a retrospective analysis of ALS-associated death rates and trends in the United States for 1979–2001 using death records from the national multiple cause-of-death database. The US average annual age-adjusted ALS death rate was 1.84 per 100,000 persons for 1979 through 1998. Most deaths were among adults ≧65 years of age and the median age at death was 67 years. A small overall increase in the death rate was observed primarily between 1979 and 1983, with a subsequent plateau. This slight change in the overall rate reflected apparent increases in the rates among those persons ≧65 years of age, particularly women, and persons in the 20- to 49-year-old age group. The ALS-associated death rate appeared to differ by geographic area, with a higher occurrence among most northern states. Our findings suggest that the epidemiology of ALS-associated deaths in the United States demonstrated small increases in the overall age-adjusted death rate and in the death rates among elderly women and adults 20–49 years of age. Subpopulations at higher risk for ALS were males, whites, persons ≧65 years of age, and residents of northern states. This study provides information for further studies to examine the epidemiology and risk factors associated with ALS.
Mortality in Dementia
Authors: Guehne Uta , Riedel-Heller Steffi , Angermeyer Matthias C.
Published: July 2005

The objective of this work is to provide a review of the mortality risk in dementia and potential influencing factors. In order to do so, studies on mortality in dementia based on population-based samples of the last 15 years published in PubMed, Web of Science and PSYNDEXplus were considered. Without exception, all types of dementia are associated with a considerably increased mortality risk. Moreover, the risk of death rises with advancing severity of the disorder. Often, a more favorable course of the disease can be found in Alzheimer’s disease. Further questions, such as the influence of age and sex, cannot be answered conclusively. Very little information can be found on aspects concerning comorbidity, APOE polymorphism or depressive symptomatology.
Common Visions: In fluences of the Nisga'a Final Agreement on Lheidli T'enneh Negotiations in the BC Treaty Process
Authors: Krehbiel Richard
Published: July 2005

Rati fication of the Nisga'a Final Agreement has had an inevitable effect on the conduct of negotiations for First Nations in the British Columbia treaty process. These effects include a general sense of encouragement set against British Columbia's historical denial of First Nation interests, direct support of negotiations, litigation and coping with special interest group resistance to aboriginal progress. This article examines these in fluences in the context of negotiations being conducted by the Lheidli T'enneh First Nation in the Northern interior of British Columbia.
Our Treaty, Our Inherent Right to Self-Government: An Overview of the Nisga'a Final Agreement
Authors: Allen Edward
Published: July 2005

This article provides an overview of the Nisga'a Final Agreement (the Treaty), the first comprehensive claims agreement to include recognition of the inherent right of self-government and constitutional protection of this right. This right is of long history to the Nisga'a people (as evidenced by a brief review of the 1913 Petition), to the Nisga'a Final Agreement, and, ultimately, to our defence of the Treaty against the legal challenge to the self-government provisions by Gordon Campbell (then leader of the opposition in the British Columbia legislature, now Premier of BC). It is this consistent thread in respect of the importance of self-government which has defined the Nisga'a approach to treaty making with the federal and provincial governments. Moreover, the Treaty also represents a unique example of legal pluralism whereby a distinct system of law making and governance successfully and peacefully operates within and in accordance with the constitutional framework of the Canadian State.
Networked Acoustic Modems for Real-Time Data Telemetry from Distributed Subsurface Instruments in the Coastal Ocean: Application to Array of Bottom-Mounted ADCPs
Authors: Codiga Daniel L. , Rice Joseph A. , Baxley Paul A. , Hebert David
Published: July 2005

Through the winter and spring of 2002, networked acoustic modems demonstrated real-time wireless data telemetry from an array of bottom-mounted acoustic Doppler current profilers (ADCPs) on the inner continental shelf 20–60 m deep off of Montauk Point, New York. To achieve typical temporal and spatial sampling needs for data assimilative numerical modeling, the array spanned 10 km × 10 km and transmitted data each ∼2 h. Network nodes included five sensors, each an ADCP with acoustic modem housed in a trawl-resistant bottom frame; five repeaters that are individual acoustic modems on near-bottom taut-wire moorings; and two gateways, each a buoy with a subsurface acoustic modem and topside cellular modem allowing for two-way communication with the shore. Deliveries from an ADCP adjacent to the gateway buoy were more than 97% successful through both winter and spring. Deliveries from ADCPs 5 km from the gateway averaged 25% (86%) reliability in winter (spring). Winter performance degrades because of upward-refracting sound speed profiles that limit direct acoustic paths, and strong winds that disrupt sea surface reflectivity and increase ambient noise. Reliability improved up to 36% due to the receive-all gateway mode, and more than doubled for certain node pairs due to a handshake protocol incorporating an automatic repeat request. Shore-based network control demonstrated adaptive sampling by changing ADCP vertical and temporal resolution, and network data path rerouting in response to unplanned events, such as trawling impacts. Networked acoustic modems are well suited for coastal ocean-observing systems, particularly at sites such as this where seafloor cables and surface buoys are vulnerable to fishing and shipping activities.
The romance of human resource management and business performance, and the case for big science
Authors: Wall Toby D. , Wood Stephen J.
Published: July 2005

It is often assumed that research over the last decade has established an effect of human resource management (HRM) practices on organizational performance. Our critical assessment of existing studies finds that, although collectively they have opened up a promising line of inquiry, their methodological limitations make such a conclusion premature. We argue that future progress depends on using stronger research methods and design that, in turn, will require large-scale long-term research at a level of magnitude that probably can only be achieved through partnerships between research, practitioner and government communities. We conclude that progress so far justifies investment in such big science.