bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine D2Receptor-Activated Ca2+Signaling Modulates Voltage-Sensitive Sodium Currents in Rat Nucleus Accumbens Neurons
Authors: Hu Xiu-Ti , Dong Yan , Zhang Xu-Feng , White Francis J.
Published: February 2005

Receptor-mediated dopamine (DA) modulation of neuronal excitability in the nucleus accumbens (NAc) has been shown to be critically involved in drug addiction and a variety of brain diseases. However, the mechanisms underlying the physiological or pathological molecular process of DA modulation remain largely elusive. Here, we demonstrate that stimulation of DA D2class receptors (D2R) enhanced voltage-sensitive sodium currents (VSSCs, INa) in freshly dissociated NAc neurons via suppressing tonic activity of the cyclic AMP/PKA cascade and facilitating intracellular Ca2+signaling. D2R-mediated INaenhancement depended on activation of Gi/oproteins and was mimicked by direct inhibition of PKA. Furthermore, increasing free [Ca2+]inby activating inositol 1,4,5-triphosphate receptors (IP3Rs), blocking Ca2+reuptake, or adding buffered Ca2+, all enhanced INa. Under these circumstances, D2R-mediated INaenhancement was occluded. In contrast, D2R-mediated INaenhancement was blocked by inhibition of IP3Rs, chelation of free Ca2+, or inhibition of Ca2+/calmodulin-activated calcineurin (CaN), but not by inhibition of phospholipase C (PLC). Although stimulation of muscarinic cholinergic receptors (mAChRs) also increased INa, this action was blocked by PLC inhibitors. Our findings indicate that D2Rs mediate an enhancement of VSSCs in NAc neurons, in which cytosolic free Ca2+plays a crucial role. Our results also suggest that D2R-mediated reduction in tonic PKA activity may increase free [Ca2+]in, primarily via disinhibition of IP3Rs. IP3R activation then facilitates Ca2+signaling and subsequently enhances VSSCs via decreasing PKA-induced phosphorylation and increasing CaN-induced dephosphorylation of Na+channels. This study provides insight into the complex and dynamic role of D2Rs in the NAc.
North Atlantic Winter SLP Anomalies Based on the Autumn ENSO State
Authors: Pozo-Vázquez D. , Gámiz-Fortis S. R. , Tovar-Pescador J. , Esteban-Parra M. J. , Castro-DÍez Y.
Published: February 2005

The winter sea level pressure (SLP) anomalies in the Northern Hemisphere have been analyzed over the period 1873–2000 based on the ENSO state during the previous autumn. First, a set of extreme cold and warm ENSO events and periods that may be regarded as normal is selected using the SST data of the Niño-3 region. This selection is carried out for autumn and with the constraint that the ENSO event is well developed. For the winters following these selected autumn events, composites of Northern Hemisphere SLP anomalies have been obtained and compared to each other. A study of the consistency among events of the relationship between ENSO and SLP anomalies was also carried out. Results show the preference for a positive NAO-like SLP anomaly pattern in the North Atlantic region during the winters following autumns of strong cold ENSO events and, thus, suggest the existence of a potential source of predictability for the North Atlantic climate. An additional analysis of the winter North Atlantic Oscillation (NAO) index confirms this finding. The possible physical basis of this source of predictability for the North Atlantic climate is discussed.
Importance of the Salinity Barrier Layer for the Buildup of El Niño
Authors: Maes Christophe , Picaut Joël , Belamari Sophie
Published: February 2005

Several studies using sea level observations and coupled models have shown that heat buildup in the western equatorial Pacific is a necessary condition for a major El Niño to develop. However, none of these studies has considered the potential influence of the vertical salinity stratification on the heat buildup and thus on El Niño. In the warm pool, this stratification results in the presence of a barrier layer that controls the base of the ocean mixed layer. Analyses of in situ and TOPEX/Poseidon data, associated with indirect estimates of the vertical salinity stratification, reveal the concomitant presence of heat buildup and a significant barrier layer in the western equatorial Pacific. This relationship occurs during periods of about one year prior to the mature phase of El Niño events over the period 1993–2002. Analyses from a coupled ocean–atmosphere general circulation model suggest that this relationship is statistically robust. The ability of the coupled model to reproduce a realistic El Niño together with heat buildup, westerly wind bursts, and a salinity barrier layer suggests further investigations of the nature of this relationship. In order to remove the barrier layer, modifications to the vertical ocean mixing scheme are applied in the equatorial warm pool and during the 1-yr period of the heat buildup. At the bottom of the ocean mixed layer, the heat buildup is locally attenuated, as expected from switching on the entrainment cooling. At the surface, the coupled response over the warm pool increases the fetch of westerly winds and favors the displacement of the atmospheric deep convection toward the central equatorial Pacific. These westerly winds generate a series of downwelling equatorial Kelvin waves whose associated eastward currents drain the heat buildup toward the eastern Pacific Ocean. The overall reduction of the heat buildup before the onset of El Niño results in the failure of El Niño. These coupled model analyses confirm that the buildup is a necessary condition for El Niño development and show that the barrier layer in the western equatorial Pacific is important for maintaining the heat buildup.
The Semidirect Aerosol Effect: Comparison of a Single-Column Model with Large Eddy Simulation for Marine Stratocumulus
Authors: Johnson B. T.
Published: February 2005

Large eddy simulations (LES) show that the presence of black carbon aerosols in marine boundary layers leads to a marked reduction of stratocumulus liquid water path (LWP) by heating the cloud layer and suppressing convection in the boundary layer. The reduction of LWP leads to a positive radiative forcing known as the semidirect effect. In this study LES results are compared with results from the National Center for Atmospheric Research (NCAR) Single-Column Community Climate Model (SCCM). The SCCM represents clouds and boundary layer processes through simple parameterization schemes that are typical of general circulation models (GCMs) used for climate experiments. In a case study in which black carbon aerosols were introduced in a stratocumulus-capped boundary layer the SCCM gave a semidirect aerosol radiative forcing that was a factor of 5 smaller than the value obtained from the LES. The cloud response to absorbing aerosols was underestimated because of the way that cloud cover and cloud radiative properties were parameterized in the SCCM. Furthermore, the SCCM gave a poor representation of processes, such as entrainment and boundary layer decoupling, that are crucial to determining stratocumulus LWP. This study shows that GCMs may not include all the physical processes necessary to adequately capture the semidirect aerosol effect. Previous GCM estimates of the semidirect effect that have incorporated simple cloud parameterizations should, therefore, be treated with some caution.
The Variability of Seasonality
Authors: Pezzulli S. , Stephenson D. B. , Hannachi A.
Published: February 2005

Seasons are the complex nonlinear response of the physical climate system to regular annual solar forcing. There is no a priori reason why they should remain fixed/invariant from year to year, as is often assumed in climate studies when extracting the seasonal component. The widely used econometric variant of Census Method II Seasonal Adjustment Program (X-11), which allows for year-to-year variations in seasonal shape, is shown here to have some advantages for diagnosing climate variability. The X-11 procedure is applied to the monthly mean Niño-3.4 sea surface temperature (SST) index and global gridded NCEP–NCAR reanalyses of 2-m surface air temperature. The resulting seasonal component shows statistically significant interannual variations over many parts of the globe. By taking these variations in seasonality into account, it is shown that one can define less ambiguous ENSO indices. Furthermore, using the X-11 seasonal adjustment approach, it is shown that the three cold ENSO episodes after 1998 are due to an increase in amplitude of seasonality rather than being three distinct La Niña events. Globally, variations in the seasonal component represent a substantial fraction of the year-to-year variability in monthly mean temperatures. In addition, strong teleconnections can be discerned between the magnitude of seasonal variations across the globe. It might be possible to exploit such relationships to improve the skill of seasonal climate forecasts.
Spatial and Temporal Variability of Canadian Seasonal Streamflows
Authors: Coulibaly Paulin , Burn Donald H.
Published: February 2005

Wavelet and cross-wavelet analysis are used to identify and describe spatial and temporal variability in Canadian seasonal streamflows, and to gain insights into the dynamical relationship between the seasonal streamflows and the dominant modes of climate variability in the Northern Hemisphere. Results from applying continuous wavelet transform to mean seasonal streamflows from 79 rivers selected from the Canadian Reference Hydrometric Basin Network (RHBN) reveal striking climate-related features before and after the 1950s. The span of available observations, 1911–99, allows for depicting variance and covariance for periods up to 12 yr. Scale-averaged wavelet power spectra are used to simultaneously assess the temporal and spatial variability in each set of 79 seasonal streamflow time series. The most striking feature, in the 2–3-yr period and in the 3–6-yr period—the 6–12-yr period is dominated by white noise and is not considered further—is a net distinction between the timing and intensity of the temporal variability in autumn, winter, and spring–summer streamflows. It is found that the autumn season exhibits the most intense activity (or variance) in both the 2–3- and the 3–6-yr periods. The spring–summer season corresponds to the least intense activity for the 2–3-yr period, but it exhibits more activity than winter for the 3–6-yr period.

Cross-wavelet analysis is provided between the seasonal streamflows and three selected climatic indices: the Pacific–North America (PNA), the North Atlantic Oscillation (NAO), and the sea surface temperature series over the Niño-3 region (ENSO3). The wavelet cross-spectra reveal strong climate–streamflow activity (or covariance) in the 2–6-yr period starting after 1950 whatever the climatic index and the season. Prior to 1950, local and weaker 2–6-yr activity is revealed in central and western Canada essentially in winter and autumn, but overall a non-significant streamflow–climate relationship is observed prior to 1950. Correlation analysis in the 2–6-yr band between the seasonal streamflow and the selected climatic indices revealed strong positive correlations with the ENSO in the spring–summer and winter seasons for the post-1950 period for both eastern and western Canada. A similar correlation pattern is revealed in the west with the NAO, while in the east moderate negative NAO correlations are observed only in the autumn season prior to 1950. After 1950 strong NAO correlations emerge for all the seasons. The cross-wavelet spectra and the correlation analysis in the 2–6-yr band suggest the presence of a change point around 1950 in the east and west seasonal streamflows.
Gridded Area-Averaged Daily Precipitation via Conditional Interpolation
Authors: Hewitson B. C. , Crane R. G.
Published: February 2005

A growing need for gridded observational datasets of area-average values to support research, specifically in relation to climate models, raises questions about the adequacy of traditional interpolation techniques. Conventional interpolation techniques (particularly for precipitation) suffer from not recognizing the changing spatial representivity of stations as a function of the driving synoptic state, nor the bounded nature of the precipitation field—that the precipitation field is spatially discontinuous. Further, many interpolation techniques explicitly estimate new point location values, and do not directly address the need arising from climate modeling for area-average values.

A new procedure, termed conditional interpolation, is presented to estimate daily gridded area-average precipitation from station observations. The approach explicitly recognizes that the point observations represent a mixture of synoptic forcing shared in common with surrounding stations, and a response that is unique to the station. Consequently the spatial representivity of a station is conditional on the synoptic forcing and is a function of the radial direction from the station. The conditional interpolation accommodates this in a two-stage process through conditioning the interpolation parameters as a function of the synoptic state. First, the spatial pattern of wet/dry conditions is estimated, following which the magnitude of the precipitation is derived for those locations determined as “wet.” In a test based on a high-resolution dataset for South Africa the conditional interpolation is very effective in defining the spatial extent of the precipitation field. It then derives gridded values that are representative of the area average. In comparison, both these characteristics appear to be significantly overestimated by one of the commonly used interpolation schemes (Cressman interpolation). Overall the interpolation conditioned by the synoptic state appears to better estimate realistic gridded area-average values.
Comparison of TRMM Precipitation Retrievals with Rain Gauge Data from Ocean Buoys
Authors: Bowman Kenneth P.
Published: February 2005

Four years of precipitation retrievals from the Tropical Rainfall Measuring Mission (TRMM) satellite are compared with data from 25 surface rain gauges on the National Oceanic and Atmospheric Administration/Pacific Marine Environment Laboratory (NOAA/PMEL) Tropical Atmosphere–Ocean Array/Triangle Trans-Ocean Buoy Network TAO/TRITON buoy array in the tropical Pacific. The buoy gauges have a significant advantage over island-based gauges for this purpose because they represent open-ocean conditions and are not affected by island orography or surface heating. Because precipitation is correlated with itself in both space and time, comparisons between the two data sources can be improved by properly averaging in space and/or time. When comparing gauges with individual satellite overpasses, the optimal averaging time for the gauge (centered on the satellite overpass time) depends on the area over which the satellite data are averaged. For 1° × 1° areas there is a broad maximum in the correlation for gauge-averaging periods of ∼2 to 10 h. Maximum correlations r are in the range 0.6 to 0.7. For larger satellite averaging areas, correlations with the gauges are smaller (because a single gauge becomes less representative of the precipitation in the box) and the optimum gauge-averaging time is longer. For individual satellite overpasses averaged over a 1° × 1° box, the relative rms difference with respect to a rain gauge centered in the box is ∼200% to 300%. For 32-day time means over 1° × 1° boxes, the relative rms difference between the satellite data and a gauge is in the range of 40% to 70%. The bias between the gauges and the satellite retrievals is estimated by correlating the long-term time-mean precipitation estimates across the set of gauges. The TRMM Microwave Imager (TMI) gives an r2 of 0.97 and a slope of 0.970, indicating very little bias with respect to the gauges. For the Precipitation Radar (PR) the comparable numbers are 0.92 and 0.699. The results of this study are consistent with the sampling error estimates from the statistical model of Bell and Kundu.
Criminalizing Attractions: Perceptions of Stalking and the Stalker
Authors: Kinkade Patrick , Burns Ronald , Fuentes Angel Ilarraza
Published: February 2005

In the late 1980s and early 1990s, the conceptualization of the predatory stalker came to the forefront of the criminal concerns imagined by the American public. With this growing public concern and the associated media coverage, legislation designed to enhance punishments against those who might stalk became a political asset and a significant plank for reelection campaigns. Adequate definition for the phenomena, however, has yet to be established, and idiosyncratic application of the law at the policing level remains a problem. This study works toward providing a better definition of the problem from the public’s perspective. Variables significant to the definition of the problem were identified and used in survey work to assess their importance in the individual’s interpretation of the stalking label. Several of these variables are significantly tied to the individual’s willingness to ascribe a stalking label to a given behavioral transaction.
An Examination of Police Officers’ Insights Into Problem Identification and Problem Solving
Authors: Bichler Gisela , Gaines Larry
Published: February 2005

Problem solving begins with problem identification. Conventional knowledge suggests that because patrol officers work specific geographical areas (beats) on a fairly constant basis, they come to see where the problems exist; thus, police experience alone can be relied on to identify crime problems. However, few have examined whether officers are effective in identifying problems in their areas. This research examined the consistency of officer problem identification across focus groups for an entire police department in terms of the kinds of problems identified, the location of problems, and the suggested responses. Although there was little consistency across focus groups, officers were able to identify specific sites or properties thought to generate high levels of disorder-related calls. Solutions to crime problems tended to involve increased police presence for complex problems affecting areas and crime prevention for specific sites facing single-crime problems.
The Perennial Pentecost
Authors: Forrester Duncan B.
Published: February 2005

Traditional barriers of purity and pollution have been an issue which has faced most churches from the beginning, and still persists. Acts 2 deals with the overcoming of cultural and linguistic barriers among Jews. Mission involves constant confrontation with the issue. Its resolution is vital if the Church is indeed to be the Church, inclusive and open.
Shattered Glass, Movies, and the Free Press Myth
Authors: Ehrlich Matthew C.
Published: February 2005

Myth is central to a critical understanding of journalism, communication, and culture. This article uses the 2003 movie Shattered Glass as a case study of the free press myth in action: the popular belief that a privately owned, market-driven press is necessary for the functioning of American democracy and the survival of a free people. The movie, which has been called the most significant about journalism since All the President’s Men, tells of how reporter Stephen Glass fictionalized stories for The New Republic magazine before he was found out and fired in 1998. Contrary to the fears of some journalists that writer-director Billy Ray’s film would encourage public skepticism toward the press, Shattered Glass actually does what films about journalism more often do: It underscores the press’s centrality in American life, in particular the notion that self-regulation of the press works.
Constructing a Transnational, Multilocal Sense of Belonging: An Analysis of Ming Pao (West Canadian Edition)
Authors: Cheng Hau Ling
Published: February 2005

Globalization has challenged the traditional conceptualization of the sense of belonging between people and places. This article takes up social theorist Ulrich Beck’s notion of place polygamy as a theoretical departure to understand immigrants and their sense of belonging to multiple places. The author analyzes Ming Pao (West Canadian Edition) , a Cantonese newspaper in Vancouver, Canada, to argue that the immigrant press is constructing two locals, one place oriented and one people oriented, on a daily basis. The notions of multiple homelands and multiple attachments provide a new perspective to study how the community can be imaged and narrated across national borders. It also challenges traditional immigrant scholarship that treats the home country and the host society as an either-or dichotomy for winning immigrants’ affection and loyalty.
Valuing the Priceless: Christian Convictions in Public Debate as a Critical Resource and as ‘Delaying Veto’ (J. Habermas)
Authors: Junker-Kenny Maureen
Published: February 2005

In three respects, ethics can be marked by the category of the ‘priceless’. Its key reference point, ‘human dignity’, was described by Kant as the exact opposite to what can be priced in equivalents. As an enterprise, ethics is ‘priceless’ as a commitment of the human spirit which goes beyond and against the attitude of success calculation. Yet, an understanding of ethics as unconditional recognition and the anticipatory, asymmetric, innovative praxis (Helmut Peukert) that expresses it have a cost. Where does the motivation to forego, for example, ethically problematic therapies, originate? How can respect for what is priceless be sustained in the face of the relentless spread of market categories diagnosed, among others, by Jürgen Habermas and Paul Ricoeur, against which religions may raise a delaying veto? Only a Christology that can adequately conceptualise the experience of the graciousness and superabundance of God’s gift is able to support the increasingly counter-cultural conviction of something beyond our disposition.
Healthcare Resource Allocation and the ‘Recovery of Virtue’
Authors: Messer Neil
Published: February 2005

This paper maps the different levels of the problem of healthcare resource allocation — micro, macro and international — with reference to three cases. It is argued that two standard approaches to the issue of distributive justice in healthcare, the QALY (quality-adjusted life year) approach and the social-contract approach developed by Norman Daniels, are fundamentally unsatisfactory for reasons identified by Alasdair MacIntyre. Although the virtue theory articulated by MacIntyre and others has been influential in many areas of healthcare ethics, there seems to have been relatively little discussion of the difference it might make to the problems of resource allocation. The potential of such an approach is explored in the later sections of the paper. Two apparently promising ways of bringing virtue ethics to bear on resource allocation are examined and found wanting to greater or lesser extents. Firstly, Beauchamp and Childress’s account of the virtues as a supplement to their ‘Four Principles’ is found to have little or no substantive contribution to make to this issue. Secondly, the ‘liberal communitarian’ system of resource allocation proposed by Ezekiel Emanuel, while a considerable improvement on the account of Beauchamp and Childress, remains problematic in some respects. An alternative Christian account is developed by identifying significant influences that might shape the ‘political prudence’ which would enable Christian communities to form sound judgments about distributive justice in healthcare. The paper concludes with some remarks about the relationship between this tradition-constituted account and the wider public sphere of policy-making and practice.
Azithromycin in bronchiolitis obliterans complicating bone marrow transplantation: a preliminary study
Authors: Khalid M. , Al Saghir A. , Saleemi S. , Al Dammas S. , Zeitouni M. , Al Mobeireek A. , Chaudhry N. , Sahovic E.
Published: February 2005

Bronchiolitis obliterans (BO) is a serious noninfectious pulmonary complication following allogeneic bone marrow transplantation (BMT). Azithromycin, a macrolide antibiotic, may have a beneficial effect in BO through its anti-inflammatory effect. The aim of the current study was to investigate the potential effect of azithromycin on pulmonary function tests (PFTs) in BO complicating BMT.

PFTs of 153 post-BMT patients were followed; eight patients out of 153 (12%) developed obstructive airway disease on their PFTs, along with characteristic findings of BO on high-resolution computed tomography of the chest. These patients were given azithromycin 500 mgq.d.for 3 days, followed by 250 mg three times a week for 12 weeks.

Clinically significant improvements were achieved both in forced vital capacity, where the mean (95% confidence interval) increase reported was 410 mL (0.16–0.65), which was an average improvement of 21.57%, and in the forced expiratory volume in one second, where the mean increase noticed was 280 mL (0.10–0.44), which was an average improvement of 20.58%.

In conclusion, the potential role of azithromycin in the treatment of bronchiolitis obliterans is intriguing and it warrants further testing.
Determinants of airway responsiveness to histamine in children
Authors: Turner S. W. , Palmer L. J. , Rye P. J. , Gibson N. A. , Young S. , Goldblatt J. , Landau L. I. , Le Souëf P. N.
Published: February 2005

Increased airway responsiveness (AR) is associated with asthma, but not all individuals with increased AR have asthma. The aim of this study was to identify factors, other than physician-diagnosed asthma (PDA), which are associated with increased AR.

In a longitudinal study, data were collected on atopy and lower respiratory tract illness (LRTI) in infancy, and AR (expressed as dose–response slope (DRS)), atopy, tobacco-smoke exposure and PDA in childhood.

At age 6 yrs, DRS was assessed in 102 children, of whom 22 (22%) had PDA; the corresponding figures at 11 yrs of age were 176 and 29 (15%). At age 6 yrs, DRS was significantly associated with PDA, current atopy and parental smoking (n = 83). At age 11 yrs, DRS was significantly associated with PDA, current atopy and LRTI in the first six months (n = 75). There was a significant positive interaction between atopy at age 12 months and PDA age 11 yrs.

In conclusion, these data suggest that factors other than asthma or atopy may determine the level of airway responsiveness in children. In children with asthma, airway responsiveness may be influenced by the early onset of atopy. The current findings may explain the inconsistent relationship between airway responsiveness and asthma.
All-cause mortality in males with sleep apnoea syndrome: declining mortality rates with age
Authors: Lavie P. , Lavie L. , Herer P.
Published: February 2005

The objective of this study was to assess whether an increasing severity of sleep apnoea is associated with increased all-cause mortality hazards and to assess whether the syndrome is associated with excess mortality, in comparison with the general population.

Participants included 14,589 adult males, aged 20–93 yrs, referred to the sleep clinics with suspected sleep apnoea or diagnosed with sleep apnoea.

Altogether, 372 deaths were recorded after a median follow-up of 4.6 yrs. The crude all-cause mortality rate was 5.55/1,000 patient yrs, increasing with apnoea severity. Cox proportional analysis revealed that both respiratory disturbance index (RDI) and body mass index significantly influenced all-cause mortality hazard but there was no interaction between them. Males with respiratory disturbance index >30 had a significantly higher mortality hazard rate than the reference group of males with RDI ≤10. Comparing mortality rates of males with moderate/severe sleep apnoea to the general population revealed that only males aged <50 yrs showed an excess mortality rate.

The hazard of mortality in sleep apnoea increases with apnoea severity as indexed by respiratory disturbance index. Moderate and severe levels of sleep apnoea are moderately associated with an increased risk of all-cause mortality, in comparison with the general population, particularly in males aged <50 yrs. The lack of information about possible confounders and treatment effects should be taken into consideration in the interpretation of these results.
Skeletal muscle microbiopsy: a validation study of a minimally invasive technique
Authors: Hayot M. , Michaud A. , Koechlin C. , Caron M-A. , LeBlanc P. , Préfaut C. , Maltais F.
Published: February 2005

The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease (COPD) is of growing interest, but often requires biopsies, usually with the Bergström technique. The current study was designed to test the validity of a minimally invasive technique: the microbiopsy.

In 17 patients with COPD and four normal subjects, two specimens of the vastus lateralis were taken percutaneously under local anaesthesia, one with a 16-gauge needle (microbiopsy) and the other with the Bergström needle. The enzymatic activity of citrate synthase (CS) and phosphofructokinase (PFK), and the myosin heavy chain (MyoHC) composition were measured for both techniques.

The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy. The microbiopsy sample weight reached 55±17 mg. The two techniques showed excellent agreement for CS activity and MyoHC composition. The PFK activity did not differ statistically between the techniques, but the agreement was moderate. The agreement between both biopsy techniques was stable over time. The median (range) fibre number within the microbiopsy specimens was 144 (38–286).

In conclusion, the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects, compared with the Bergström technique.
Blunted γδ T-lymphocyte response in chronic obstructive pulmonary disease
Authors: Pons J. , Sauleda J. , Ferrer J. M. , Barceló B. , Fuster A. , Regueiro V. , Julià M. R. , Agustí A. G. N.
Published: February 2005

Chronic obstructive pulmonary disease (COPD) is characterised by an excessive inflammatory response to inhaled particles, mostly tobacco smoking. Although inflammation is present in all smokers, only a percentage of them develop COPD. T-lymphocytes are important effector and regulatory cells that participate actively in the inflammatory response of COPD. They comprise the T-cell receptor (TCR)-αβ (CD4+ and CD8+) and TCR-γδ T-lymphocytes. The latter represent a small percentage of the total T-cell population, but play a key role in tissue repair and mucosal homeostasis.

To investigate TCR-αβ (CD4+ and CD8+) and TCR-γδ T-lymphocytes in COPD, the present authors determined, by flow cytometry, the distribution of both subpopulations in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from patients with COPD, smokers with normal lung function and never-smokers.

The present study found that: 1) the distribution of CD4+ and CD8+ lymphocytes in blood and BAL was similar in all three groups; 2) compared with nonsmokers, γδ T-lymphocytes were significantly increased in smokers with preserved lung function; and 3) this response was blunted in patients with COPD.

These results highlight a novel, potentially relevant, pathogenic mechanism in chronic obstructive pulmonary disease.
Cyclophosphamide and low-dose prednisolone in idiopathic pulmonary fibrosis and fibrosing nonspecific interstitial pneumonia
Authors: Kondoh Y. , Taniguchi H. , Yokoi T. , Nishiyama O. , Ohishi T. , Kato T. , Suzuki K. , Suzuki R.
Published: February 2005

The present study compared the efficacy of cyclophosphamide combined with low-dose prednisolone in the treatment of idiopathic pulmonary fibrosis (IPF) with efficacy in idiopathic fibrosing nonspecific interstitial pneumonia fibrosing (NSIP).

A total of 27 patients with IPF and 12 patients with fibrosing NSIP were included in this study. All patients had undergone surgical lung biopsy. The diagnoses were made based on clinical, radiological and pathological findings. All patients were treated with intermittent pulse therapy with methylprednisolone for 4 weeks, followed by cyclophosphamide with low-dose prednisolone.

According to pulmonary function tests, four of 27 patients with IPF had improved, 22 remained unchanged, and one had worsened at the completion of pulse therapy. After 1 yr of combination therapy, four of 27 patients had improved, 14 remained unchanged, and nine had worsened. After pulse therapy, four of 12 patients with fibrosing NSIP had improved, and eight remained unchanged. After 1 yr of combination therapy, eight of 12 patients had improved, four remained unchanged, and none had worsened. Median survival of IPF patients was 4.1 yrs, which is significantly worse than that of fibrosing NSIP patients.

In conclusion, patients with fibrosing nonspecific interstitial pneumonia had a more favourable response to combination therapy and a better survival than those with idiopathic pulmonary fibrosis.
Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation
Authors: Hodge S. , Hodge G. , Holmes M. , Reynolds P. N.
Published: February 2005

There is heterogeneity in the propensity of smokers to develop chronic obstructive pulmonary disease (COPD), and improved treatment strategies are hindered by limited understanding of COPD pathogenesis, especially as distinct from the effects of smokingper se. Although apoptosis is essential for tissue homeostasis, increased apoptosis may cause tissue damage and inflammation.

This study addressed whether airway T-lymphocytes and airway epithelial cells (AEC) show an increased likelihood of undergoing apoptosis in COPD and if this was related to smoking.

Apoptosis (7-amino-actinomycin D, Annexin, single-stranded DNA and caspase), Bcl-2, Bax and p53 were assessed in cells obtained from bronchial bushing and bronchoalveolar lavage from ex- and continuing smokers with COPD, and nonsmoking controls, using flow cytometry.

A mean 87% increase in apoptosis of AEC and a 103% increase in T-lymphocyte apoptosis were found in COPD. There were no significant differences in apoptosis of AEC between current and ex-smokers with COPD.

Apoptosis may contribute to chronic obstructive pulmonary disease pathogenesis, and continued excess apoptosis after smoking cessation may offer a new target for therapeutic interventions. Whether the persistence of increased apoptosis after smoking cessation results from changes in the pulmonary milleau after years of noxious insult, or whether some individuals have a natural predisposition toward increased apoptosis and possible development of chronic obstructive pulmonary disease remains to be determined.
Bosentan therapy for portopulmonary hypertension
Authors: Hoeper M. M. , Halank M. , Marx C. , Hoeffken G. , Seyfarth H. J. , Schauer J. , Niedermeyer J. , Winkler J.
Published: February 2005

The dual endothelin receptor antagonist bosentan has been approved in several countries for pulmonary arterial hypertension, and patients with portopulmonary hypertension (PPHTN) have not specifically been excluded. However, no data have been published on the efficacy and safety of bosentan in this patient population. Here, the first clinical experiences with bosentan in patients with Child A cirrhosis and severe PPHTN are reported.

In total, 11 consecutive patients with cirrhosis and severe PPHTN in New York Heart Association Functional Classes III and IV were treated for >1 yr with bosentan.

After 1 yr of treatment with bosentan, all patients showed improved symptoms and exercise capacity. The 6-min walking distance increased from 310±102 m at baseline to 388±81 m at 1 yr. Cardiopulmonary exercise testing disclosed a significant increase in peak oxygen uptake, from 12.6±3.5 to 16.6±2.8 mL·min−1·kg−1. Pulmonary vascular resistance fell from 944±519 to 635±321 dynes·s·L−1. The medication was well tolerated by all patients, and there was no evidence of drug-related liver injury.

In conclusion, bosentan proved to be efficacious and safe in a small number of patients with portopulmonary hypertension.
The accuracy of EUS-FNA in assessing mediastinal lymphadenopathy and staging patients with NSCLC
Authors: Caddy G. , Conron M. , Wright G. , Desmond P. , Hart D. , Chen R. Y.
Published: February 2005

Optimal management of nonsmall cell lung cancer (NSCLC) depends on tissue diagnosis and accurate staging. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is minimally invasive and provides cytological confirmation of malignant mediastinal disease. The aim was to assess the accuracy of EUS-FNA in cases of enlarged mediastinal lymphadenopathy (LN) of unknown aetiology and in the staging of NSCLC.

A total of 52 consecutive patients with stage I–IIIb NSCLC or enlarged mediastinal LN of unknown aetiology underwent EUS-FNA. Negative results were confirmed with a surgical procedure: mediastinoscopy, video-assisted thoracic surgery (VATS) or lobectomy with systematic mediastinal lymph node dissection.

In total, 34 patients had EUS-FNA performed for diagnosis, whilst the remaining 18 had EUS-FNA for staging. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (95% confidence interval) were 93% (77–99), 100% (78–100), 100% (87–100), 88% (63–99) and 95% (84–99), respectively. When EUS-FNA was used in patients with NSCLC, the sensitivity, specificity, PPV, NPV and accuracy were 92% (73–99), 100% (69–100), 100% (85–100), 83% (51–98) and 94% (80–99), respectively. For mediastinal LN of unknown aetiology, no malignant disease was missed.

Endoscopic ultrasound-guided fine-needle aspiration is an accurate tool for assessing mediastinal lymph node involvement in nonsmall cell lung cancer and in the diagnosis of unexplained mediastinal lymphadenopathy. Endoscopic ultrasound-guided fine-needle aspiration is a minimally invasive procedure that can be used as an adjunct or alternative to mediastinoscopy.
N-terminal-pro-brain natriuretic peptide as a haemodynamic marker in idiopathic pulmonary arterial hypertension
Authors: Souza R. , Bogossian H. B. , Humbert M. , Jardim C. , Rabelo R. , Amato M. B. P. , Carvalho C. R. R.
Published: February 2005

Patients with idiopathic pulmonary arterial hypertension usually undergo acute vasodilator tests with nitric oxide (NO) for haemodynamic evaluation and therapeutical planning. The aim of this study was to evaluate the link between the variation of N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and haemodynamic parameters during the acute vasodilator test.

A total of 22 idiopathic pulmonary arterial hypertension patients who underwent acute vasodilator tests were studied. Blood samples were collected at baseline and after 30 and 60 min of NO inhalation. NT-pro-BNP levels were measured in each sample.

A receiver-operating characteristic curve was used to evaluate the capability of the NT-pro-BNP level variation during NO inhalation in recognising nonresponders. To distinguish responders from nonresponders, the increase of the NT-pro-BNP (0% as cut-off value) determined a 50% specificity and 100% sensitivity (positive predictive value of 38% and a negative predictive value of 100%).

These results suggest that N-terminal-pro-brain natriuretic peptide was able to distinguish nonresponder patients with the acute vasodilator test. N-terminal-pro-brain natriuretic peptide may be an interesting additional biological tool in the evaluation of idiopathic pulmonary arterial hypertension patients.
Prone position reduces lung stress and strain in severe acute respiratory distress syndrome
Authors: Mentzelopoulos S. D. , Roussos C. , Zakynthinos S. G.
Published: February 2005

The present authors hypothesised that in severe acute respiratory distress syndrome (ARDS), pronation may reduce ventilator-induced overall stress (i.e.transpulmonary pressure (PL)) and strain of lung parenchyma (i.e.tidal volume (VT)/end-expiratory lung volume (EELV) ratio), which constitute major ventilator-induced lung injury determinants. The authors sought to determine whether potential pronation benefits are maintained in post-prone semirecumbent (SRPP) posture under pressure-volume curve-dependent optimisation of positive end-expiratory pressure (PEEP).

A total of 10 anesthetised/paralysed, mechanically ventilated (VT = 9.0±0.9 mL·kg−1predicted body weight; flow = 0.91±0.04 L·s−1; PEEP = 9.4±1.3 cmH2O) patients with early/severe ARDS were studied in pre-prone semirecumbent (SRBAS), prone, and SRPPpositions. Partitioned respiratory mechanics were determined during iso-flow (0.91 L·s−1) experiments (VTvaried within 0.2–1.0 L), along with haemodynamics, gas exchange, and EELV.

Compared with SRBAS, pronation/SRPPresulted in reduced peak/plateauPLatVTs≥0.6 L; static lung elastance and additional lung resistance decreased and chest wall elastance (in prone position) increased; EELV increased (23–33%);VT/EELV decreased (27–33%); arterial oxygen tension/inspiratory oxygen fraction and arterial carbon dioxide tension improved (21–43/10–14%, respectively), and shunt fraction/physiological dead space decreased (21–50/20–47%, respectively).

In early/severe acute respiratory distress syndrome, pronation under positive end-expiratory pressure optimisation may reduce ventilator-induced lung injury risk. Pronation benefits may be maintained in post-prone semirecumbent position.
Histone acetylation and deacetylation: importance in inflammatory lung diseases
Authors: Barnes P. J. , Adcock I. M. , Ito K.
Published: February 2005

Inflammatory lung diseases are characterised by increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-κB. Gene expression is regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein, with intrinsic histone acetyltransferase (HAT) activity.

Conversely, gene repression is mediatedviahistone deacetylases (HDACs) and other corepressors. In asthma, there is an increase in HAT activity and some reduction in HDAC activity, which is restored by corticosteroid therapy. Corticosteroids switch off inflammatory genes in asthma through the inhibition of HAT activity and by the recruitment of HDAC2 to the activated inflammatory gene complex. In chronic obstructive pulmonary disease, there is a reduction in HDAC2 activity and expression, which may account for the amplified inflammation and resistance to the actions of corticosteroids. The reduction in HDAC2 may be secondary to oxidative and nitrative stress as a result of cigarette smoking and severe inflammation, and may also occur in severe asthma, smoking asthmatic patients and cystic fibrosis.

Similar mechanisms may also account for the steroid resistance seen with latent adenovirus infections. The reduction in histone deacetylase activity can be restored by theophylline, which may be able to reverse steroid resistance in chronic obstructive pulmonary disease and other inflammatory diseases.
Evolution of previous sarcoidosis under type 1 interferons given for severe associated disease: Table. 1—
Authors: Charlier C. , Nunes H. , Trinchet J-C. , Roullet E. , Mouthon L. , Beaugrand M. , Valeyre D.
Published: February 2005

Sarcoidosis is a granulomatous disorder with a well-known T helper (Th) type 1 cell commitment and a key pathogenic role of interferon (IFN)-γ. However, little is known about the influence of type 1 IFNs, such as IFN-α and IFN-β, on the course of previous sarcoidosis.

The aim of this study was to determine whether type 1 IFNs can safely be used in patients with sarcoidosis for severe associated disease.

The present study examined a series of four patients with sarcoidosis, treated by IFN-α or IFN-β for viral hepatitis (three cases) or multiple sclerosis (one case).

IFN was initiated soon after apparent recovery (three cases) or during a worsening phase of sarcoidosis (one case). Hydroxychloroquine was added in the case with active disease. Patients received interferon for 6–24 months and had close monitoring during and after IFN therapy. Interestingly, no recurrence or exacerbation of sarcoidosis had occurred at 4 yrs of follow up. Two patients were cured from viral hepatitis, whilst treatment for another failed. No neurological progression was observed in the remaining patient.

This series suggests that, despite the T helper type 1 phenotype of sarcoid granulomatous reaction, type 1 interferons do not exacerbate sarcoidosis in remission and this makes their use possible if indicated. However, their effect in persistent forms of the disease needs further evaluation.
An experimental study of the time-domain electromagnetic response of a buried conductive plate
Authors: Everett Mark E. , Benavides Alfonso , Pierce Carl J.
Published: February 2005

It is important to understand the effects of a buried metal object on electromagnetic data, whether the object is a source of cultural noise or a target of interest. The time-domain electromagnetic response of a buried metal plate exhibits several remarkable properties. An experimental study has been undertaken to confirm these properties. The spatial response of a shallow-buried plate is temporally self-similar and exhibits a late-time dipolelike response. Clutter-generated noise can be significant if the plate is poorly coupled to the primary transmitter flux. A vertical plate exhibits a transition from a horizontal to a vertical mode of eddy current induction.
A fundamental limitation for the reconstruction of impedance profiles from seismic data
Authors: Delprat-Jannaud Florence , Lailly Patrick
Published: February 2005

Waveform inversion aims at a quantitative estimation of the subsurface model. Such a quantitative estimation is a nonlinear problem: the relation between elastic parameters and waveform data is basically nonlinear. Perturbations in the velocity give rise to severe nonlinear perturbations in the wavefield. Other severe nonlinear effects appear when the impedance profile is very irregular (i.e., rapidly oscillating). In this paper, we avoid these drastic nonlinear effects by assuming the velocity distribution is known, and we restrict our analysis to the reconstruction of “regular” impedance profiles. Even in this simple framework, deviations between a linear and a nonlinear model are cumulative as time increases, and the deviations cannot be neglected for propagation times of the order of standard seismic recordings. A nonlinear approach appears to be essential for quantitative imaging of deep targets. However a nonlinear approach requires the wavelet to be known with an accuracy that cannot be reached today. Our sensitivity analysis shows that the wavelet/model ambiguity is much more severe than the one met in linear inversion. As a consequence of the error accumulation inherent in a nonlinear wave propagation model, a small disturbance in the wavelet leads to a strong disturbance in the deep parts of the solution model. In this context, the classical approach for estimating the wavelet by minimizing the energy of the primary reflection waveform is not likely to provide the required accuracy except for very special cases. Accurate wavelet measurements thus appear to be a major challenge for a sound reconstruction of impedance profiles.