bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of YggX Results in Chronic Oxidative Stress and Uncovers Subtle Defects in Fe-S Cluster Metabolism in
Salmonella enterica
Authors: Skovran Elizabeth , Lauhon C. T. , Downs D. M.
Published: October 2004

As components involved in Fe-S cluster metabolism are described, the challenge becomes defining the integrated process that occurs in vivo based on the individual functions characterized in vitro. Strains lacking
yggX
have been used here to mimic chronic oxidative stress and uncover subtle defects in Fe-S cluster metabolism. We describe the in vivo similarities and differences between
isc
mutants, which have a known function in cluster assembly, and mutants disrupted in four additional loci,
gshA, apbC, apbE
, and
rseC
. The latter mutants share similarities with
isc
mutants: (i) a sensitivity to oxidative stress, (ii) a thiamine auxotrophy in the absence of the YggX protein, and (iii) decreased activities of Fe-S proteins, including aconitase, succinate dehydrogenase, and MiaB. However, they differ from
isc
mutants by displaying a phenotypic dependence on metals and a distinct defect in the SoxRS response to superoxides. Results presented herein support the proposed role of YggX in iron trafficking and protection against oxidative stress, describe additional phenotypes of
isc
mutants, and suggest a working model in which the ApbC, ApbE, and RseC proteins and glutathione participate in Fe-S cluster repair.
Purification and Characterization of the Repressor of the Shiga Toxin-Encoding Bacteriophage 933W: DNA Binding, Gene Regulation, and Autocleavage
Authors: Koudelka Astrid P. , Hufnagel Lisa A. , Koudelka Gerald B.
Published: October 2004

The genes encoding Shiga toxin (stx), the major virulence factor of Shiga toxin-encoding
Escherichia coli
(STEC) strains, are carried on lambdoid prophages resident in all known STEC strains. The
stx
genes are expressed only during lytic growth of these temperate bacteriophages. We cloned the gene encoding the repressor of the Shiga toxin-encoding bacteriophage 933W and examined the DNA binding and transcriptional regulatory activities of the overexpressed, purified protein. Typical of nearly all lambdoid phage repressors, 933W repressor binds to three sites in 933W right operator (O
R
). Also typical, when bound at O
R
, 933W repressor functions as an activator at the P
RM
promoter and a repressor at the P
R
promoter. In contrast to other lambdoid bacteriophages, 933W left operator (O
L
) contains only two repressor binding sites, but the O
L
-bound repressor still efficiently represses P
L
transcription. Lambdoid prophage induction requires inactivation of the repressor's DNA binding activity. In all phages examined thus far, this inactivation requires a RecA-stimulated repressor autoproteolysis event, with cleavage occurring precisely in an Ala-Gly dipeptide sequence that is found within a “linker ” region that joins the two domains of these proteins. However, 933W repressor protein contains neither an Ala-Gly nor an alternative Cys-Gly dipeptide cleavage site anywhere in its linker sequence. We show here that the autocleavage occurs at a Leu-Gly dipeptide. Thus, the specificity of the repressor autocleavage site is more variable than thought previously.
8-Oxo-7,8-Dihydroguanine Is Removed by a Nucleotide Excision Repair-Like Mechanism in
Porphyromonas gingivalis
W83
Authors: Johnson N. A. , McKenzie R. , McLean L. , Sowers L. C. , Fletcher H. M.
Published: October 2004

A consequence of oxidative stress is DNA damage. The survival of
Porphyromonas gingivalis
in the inflammatory microenvironment of the periodontal pocket requires an ability to overcome oxidative stress caused by reactive oxygen species (ROS). 8-Oxo-7,8-dihydroguanine (8-oxoG) is typical of oxidative damage induced by ROS. There is no information on the presence of 8-oxoG in
P. gingivalis
under oxidative stress conditions or on a putative mechanism for its repair. High-pressure liquid chromatography with electrochemical detection analysis of chromosomal DNA revealed higher levels of 8-oxoG in
P. gingivalis
FLL92, a nonpigmented isogenic mutant, than in the wild-type strain. 8-OxoG repair activity was also increased in cell extracts from
P. gingivalis
FLL92 compared to those from the parent strain. Enzymatic removal of 8-oxoG was catalyzed by a nucleotide excision repair (NER)-like mechanism rather than the base excision repair (BER) observed in
Escherichia coli
. In addition, in comparison with other anaerobic periodontal pathogens, the removal of 8-oxoG was unique to
P. gingivalis
. Taken together, the increased 8-oxoG levels in
P. gingivalis
FLL92 could further support a role for the hemin layer as a unique mechanism in oxidative stress resistance in this organism. In addition, this is the first observation of an NER-like mechanism as the major mechanism for removal of 8-oxoG in
P. gingivalis
.
Transcription of the Rod-Shaped Viruses SIRV1 and SIRV2 of the Hyperthermophilic ArchaeonSulfolobus
Authors: Kessler Alexandra , Brinkman Arie B. , van der Oost John , Prangishvili David
Published: October 2004

The double-stranded DNA genomes of the crenarchaeal rudiviruses SIRV1 (32 kb) and SIRV2 (35 kb) were previously sequenced. Here we present results of the analysis of gene expression of these viruses at different time points after infection of the host cell,Sulfolobus islandicus, and of the mapping of transcriptional start sites. Transcription of both genomes starts simultaneously at multiple sites spread over the total length of the genome and from both strands. The earliest time point when viral transcripts could be detected in cells was 30 min after infection. At this time point all the viral genes, except one, were transcribed. Many genes were clustered and appeared to be transcribed as polycistronic messengers. Although the coat protein-encoding gene was initially also transcribed as a polycistronic messenger, an abundant monocistronic transcript of this gene was detected 2 to 3 h after infection, just before assembly of viral particles. The expression of a single gene, adjacent to the coat protein gene, was upregulated at the late phase of infection, suggesting that it might be involved in specific processing and activation of the coat protein messenger. Start sites of 13 transcripts from the SIRV1 genome have been mapped by primer extension, and promoter sequences have been identified. Similar to host promoters, these viral promoters all contain potential binding sites for the archaeal transcription factors TATA binding protein and transcription factor B. In addition, most of them contain a virus-specific consensus element, suggesting the involvement of alternative transcription factors.
Identification and Functional Verification of Archaeal-Type Phosphoenolpyruvate Carboxylase, a Missing Link in Archaeal Central Carbohydrate Metabolism
Authors: Ettema Thijs J. G. , Makarova Kira S. , Jellema Gera L. , Gierman Hinco J. , Koonin Eugene V. , Huynen Martijn A. , de Vos Willem M. , van der Oost John
Published: October 2004

Despite the fact that phosphoenolpyruvate carboxylase (PEPC) activity has been measured and in some cases even purified from some
Archaea
, the gene responsible for this activity has not been elucidated. Using sensitive sequence comparison methods, we detected a highly conserved, uncharacterized archaeal gene family that is distantly related to the catalytic core of the canonical PEPC. To verify the predicted function of this archaeal gene family, we cloned a representative from the hyperthermophilic acidophile
Sulfolobus solfataricus
and functionally produced the corresponding enzyme as a fusion with the
Escherichia coli
maltose-binding protein. The purified fusion protein indeed displayed highly thermostable PEPC activity. The structural and biochemical properties of the characterized archaeal-type PEPC (atPEPC) from
S. solfataricus
are in good agreement with previously reported biochemical analyses of other archaeal PEPC enzymes. The newly identified atPEPC, with its distinct properties, constitutes yet another example of the versatility of the enzymes of the central carbon metabolic pathways in the archaeal domain.
Single-Molecule Approach to Bacterial Genomic Comparisons via Optical Mapping
Authors: Zhou Shiguo , Kile Andrew , Bechner Michael , Place Michael , Kvikstad Erika , Deng Wen , Wei Jun , Severin Jessica , Runnheim Rodney , Churas Christopher , Forrest Daniel , Dimalanta Eileen T. , Lamers Casey , Burland Valerie , Blattner Frederick R. , Schwartz David C.
Published: October 2004

Modern comparative genomics has been established, in part, by the sequencing and annotation of a broad range of microbial species. To gain further insights, new sequencing efforts are now dealing with the variety of strains or isolates that gives a species definition and range; however, this number vastly outstrips our ability to sequence them. Given the availability of a large number of microbial species, new whole genome approaches must be developed to fully leverage this information at the level of strain diversity that maximize discovery. Here, we describe how optical mapping, a single-molecule system, was used to identify and annotate chromosomal alterations between bacterial strains represented by several species. Since whole-genome optical maps are ordered restriction maps, sequenced strains ofShigella flexneriserotype 2a (2457T and 301),Yersinia pestis(CO 92 and KIM), andEscherichia coliwere aligned as maps to identify regions of homology and to further characterize them as possible insertions, deletions, inversions, or translocations. Importantly, an unsequencedShigella flexneristrain (serotype Y strain AMC[328Y]) was optically mapped and aligned with two sequenced ones to reveal one novel locus implicated in serotype conversion and several other loci containing insertion sequence elements or phage-related gene insertions. Our results suggest that genomic rearrangements and chromosomal breakpoints are readily identified and annotated against a prototypic sequenced strain by using the tools of optical mapping.
Functional Characterization of a Catabolic Plasmid from Polychlorinated- Biphenyl-Degrading
Rhodococcus
sp. Strain RHA1
Authors: Warren René , Hsiao William W. L. , Kudo Hisashi , Myhre Matt , Dosanjh Manisha , Petrescu Anca , Kobayashi Hiroyuki , Shimizu Satoru , Miyauchi Keisuke , Masai Eiji , Yang George , Stott Jeff M. , Schein Jacquie E. , Shin Heesun , Khattra Jaswinder , Smailus Duane , Butterfield Yaron S. , Siddiqui Asim , Holt Robert , Marra Marco A. , Jones Steven J. M. , Mohn William W. , Brinkman Fiona S. L. , Fukuda Masao , Davies Julian , Eltis Lindsay D.
Published: October 2004

Rhodococcus
sp. strain RHA1, a potent polychlorinated-biphenyl (PCB)-degrading strain, contains three linear plasmids ranging in size from 330 to 1,100 kb. As part of a genome sequencing project, we report here the complete sequence and characterization of the smallest and least-well-characterized of the RHA1 plasmids, pRHL3. The plasmid is an actinomycete invertron, containing large terminal inverted repeats with a tightly associated protein and a predicted open reading frame (ORF) that is similar to that of a mycobacterial
rep
gene. The pRHL3 plasmid has 300 putative genes, almost 21% of which are predicted to have a catabolic function. Most of these are organized into three clusters. One of the catabolic clusters was predicted to include limonene degradation genes. Consistent with this prediction, RHA1 grew on limonene, carveol, or carvone as the sole carbon source. The plasmid carries three cytochrome P450-encoding (CYP) genes, a finding consistent with the high number of CYP genes found in other actinomycetes. Two of the CYP genes appear to belong to novel families; the third belongs to CYP family 116 but appears to belong to a novel class based on the predicted domain structure of its reductase. Analyses indicate that pRHL3 also contains four putative “genomic islands” (likely to have been acquired by horizontal transfer), insertion sequence elements, 19 transposase genes, and a duplication that spans two ORFs. One of the genomic islands appears to encode resistance to heavy metals. The plasmid does not appear to contain any housekeeping genes. However, each of the three catabolic clusters contains related genes that appear to be involved in glucose metabolism.
Cuprous Oxidase Activity of CueO from
Escherichia coli
Authors: Singh Satish K. , Grass Gregor , Rensing Christopher , Montfort William R.
Published: October 2004

We have found CueO from
Escherichia coli
to have a robust cuprous oxidase activity, severalfold higher than any homologue. These data suggest that a functional role for CueO in protecting against copper toxicity in vivo includes the removal of Cu(I).
Determinants of coronary blood flow in humans: quantification by intracoronary Doppler and ultrasound
Authors: Wieneke Heinrich , von Birgelen Clemens , Haude Michael , Eggebrecht Holger , Möhlenkamp Stefan , Schmermund Axel , Böse Dirk , Altmann Christoph , Bartel Thomas , Erbel Raimund
Published: October 2004

The direct determinants of coronary flow are lumen area and blood flow velocity; however, the precise mechanisms that control these factors are not fully understood. The aim of the present study was to assess by which mechanisms lumen area and coronary flow velocity interact with hemodynamic and morphometric factors, thereby influencing coronary flow. Intracoronary Doppler and ultrasound measurements were performed in 28 patients without coronary lumen irregularities. Flow velocity and lumen cross-sectional area were measured in the proximal segments of all three coronary arteries. Global lumen cross-sectional area and global flow were obtained by adding up the values of all three coronary arteries. Left ventricular mass was assessed by echocardiography. Stress-mass-heart rate and pressure-rate products reflecting myocardial oxygen demand were calculated. Global coronary flow increased during adenosine-induced hyperemia from 197 ± 72 to 637 ± 204 ml/min ( P < 0.001). Global coronary flow closely correlated with the stress-mass-heart rate product ( r = 0.62; P < 0.001). Looking at the two constituents of flow separately, global coronary cross-sectional area was closely related to left ventricular muscle mass ( r = 0.61; P < 0.001), whereas mean coronary flow velocity at rest showed a strong linear relation with the pressure-rate product ( r = 0.64; P < 0.001). There was no interaction between cross-sectional area and blood flow velocity in any of the coronary vessels. Coronary lumen size and flow velocity, the two determinants of coronary flow, are principally determined by different physiological factors. Long-term flow adaptation is achieved by an increase in coronary lumen size, whereas short-term myocardial oxygen requirements are met by changes in resting flow velocity.
Experimental muscle pain reduces initial motor unit discharge rates during sustained submaximal contractions
Authors: Farina Dario , Arendt-Nielsen Lars , Graven-Nielsen Thomas
Published: October 2004

The aim of this human study was to investigate the effect of experimentally induced muscle pain on the modifications of motor unit discharge rate during sustained, constant-force contractions. Intramuscular and multichannel surface electromyographic (EMG) signals were collected from the right and left tibialis anterior muscle of 11 volunteers. The subjects performed two 4-min-long isometric contractions at 25% of the maximal dorsiflexion torque, separated by a 20-min rest. Before the beginning of the second contraction, hypertonic (painful; right leg) or isotonic (nonpainful; left leg) saline was injected into the tibialis anterior. Pain intensity scores did not change significantly in the first 150 s of the painful contraction. Exerted torque and its coefficient of variation were the same for the painful and nonpainful contractions. Motor unit discharge rate was higher in the beginning of the nonpainful contraction than the painful contraction on the right side [means ± SE, 11.3 ± 0.2 vs. 10.6 ± 0.2 pulses/s (pps); P < 0.01] whereas it was the same for the two contractions on the left side (11.6 ± 0.2 vs. 11.5 ± 0.2 pps). The decrease in discharge rate in 4 min was smaller for the painful (0.4 ± 0.1 pps) than for the control contractions (1.3 ± 0.1 pps). Initial value and decrease in motor unit conduction velocity were not different in the four contractions (right leg, 4.0 ± 0.1 m/s with decrease of 0.6 ± 0.1 m/s in 4 min; left leg, 4.1 ± 0.1 m/s with 0.7 ± 0.1 m/s decrease). In conclusion, stimulation of nociceptive afferents by injection of hypertonic saline did not alter motor unit conduction velocity but reduced the initial motor unit discharge rates and the difference between initial and final discharge rates during sustained contraction.
On dependent elements in rings
Authors: Vukman Joso , Kosi-Ulbl Irena
Published: October 2004

Let R be an associative ring. An element a ∈ R is said to be dependent on a mapping F : R → R in case F(x)a = ax holds for all x ∈ R. In this paper, elements dependent on certain mappings on prime and semiprime rings are investigated. We prove, for example, that in case we have a semiprime ring R, there are no nonzero elements which are dependent on the mapping α + β, where α and β are automorphisms of R.
Positively expansive homeomorphisms of compact spaces
Authors: Richeson David , Wiseman Jim
Published: October 2004

We give a new and elementary proof showing that a homeomorphism f : X → X of a compact metric space is positively expansive if and only if X is finite.
Differential resolvents of minimal order and weight
Authors: Nahay John Michael
Published: October 2004

We will determine the number of powers of α that appear with nonzero coefficient in an α‐power linear differential resolvent of smallest possible order of a univariate polynomial P(t) whose coefficients lie in an ordinary differential field and whose distinct roots are differentially independent over constants. We will then give an upper bound on the weight of an α‐resolvent of smallest possible weight. We will then compute the indicial equation, apparent singularities, and Wronskian of the Cockle α‐resolvent of a trinomial and finish with a related determinantal formula.
A commutativity‐or‐finiteness condition for rings
Authors: Klein Abraham A. , Bell Howard E.
Published: October 2004

We show that a ring with only finitely many noncentral subrings must be either commutative or finite.
An iteration for finding a common random fixed point
Authors: Choudhury Binayak S.
Published: October 2004

We define a random iteration scheme and consider its convergence
to a common random fixed point of two random operators defined
on a convex subset of a separable Hilbert space. We also consider
the case when the subset is further compact.
Assessment of18F-fluorodeoxyglucose dual-head gamma camera in asbestos lung diseases
Authors: Melloni B. , Monteil J. , Vincent F. , Bertin F. , Gaillard S. , Ducloux T. , Verbeke S. , Maubon A. , Vandroux J-C. , Bonnaud F.
Published: October 2004

The purpose of this study was to evaluate the performance of18F-fluorodeoxyglucose (18FDG) imagingviacoincidence detection emission tomography (CDET) in identifying malignant lesions in subjects exposed to asbestos.

A total of 30 patients exposed to asbestos underwent18FDG-CDET between January 2000 and June 2003. A CDET scan of the thorax and abdomen was performed 60 min after injection of18FDG in fasting patients, and results were obtained in slices in three axes. The CDET results were compared to those from computed tomography (CT), and pleural or surgical biopsy in patients with positive18FDG-CDET results.

All primary malignant mesotheliomas accumulated18FDG (n=6), and, in two patients, CDET findings were superior to those of CT, allowing early detection. In two cases, lung carcinomas with malignant pleural effusion were also detected. There were five false positive CDET results: three unilateral pleural thickening, one rounded atelectasis, and one benign lung nodule. All patients with pleural plaques showed no significant18FDG uptake. Malignant diseases were detected by18FDG-CDET imaging with a sensitivity of 89% and specificity of 71%.

Coincidence detection emission tomography can identify malignant mesothelioma in selected subjects exposed to asbestos. Coincidence detection emission tomography appears to be a useful noninvasive method for the follow-up of subjects with exposure risk of asbestosis.
Oesophageal pH monitoring is of limited value in the diagnosis of “reflux-cough”
Authors: Patterson R.N. , Johnston B.T. , MacMahon J. , Heaney L.G. , McGarvey L.P.A.
Published: October 2004

Reflux-cough is a diagnosis based on demonstrating both gastro-oesophageal reflux and a positive response to anti-reflux therapy. The authors sought to determine early and long-term response to therapy in patients with a “positive” 24 h oesophageal pH study, and identify any features which might predict response.

Patients with chronic cough were recruited from July 1998 to July 2002. Those with a positive pH study were given dietary advice and an 8-week trial of omeprazole (20 mgb.i.d.). Response was judged after 8 weeks (clinical follow-up), and at long-term follow-up (telephone questionnaire).

A total of 146 patients underwent pH monitoring with 82 (56.2%) “positive” studies. Follow-up data was available in 60 patients, with 49 receiving anti-reflux therapy, of which 20 (40.8%) reported a positive treatment response. At long-term follow-up (median 30 months), there was a significantly lower response (14 out of 49, 28.5%), with no significant difference in either acid exposure times (distal/proximal) or symptom correlation between responders and nonresponders at early or long-term follow-up.

In conclusion, despite “positive” pH studies, over half of the patients (55.1%) failed torespond to therapy. No features on pH monitoring accurately predicted response. Short-term response did not predict long-term response. The precise role for pH monitoring in the assessment of chronic cough remains to be defined.
Morning levels of fibrinogen in children with sleep-disordered breathing
Authors: Kaditis A.G. , Alexopoulos E.I. , Kalampouka E. , Kostadima E. , Angelopoulos N. , Germenis A. , Zintzaras E. , Gourgoulianis K.
Published: October 2004

Elevated fibrinogen level is a predictor of cardiovascular disease in adults, and it is associated with sleep-disordered breathing. Levels of fibrinogen in adults are affected by other co-existing cardiovascular risk factors, which are not usually present in children.

To investigate the association between fibrinogen and sleep-disordered breathing, a case-control study was carried out in children with and without habitual snoring. All snoring children underwent polysomnography.

Morning fibrinogen values in 30 children with snoring and an apnoea-hypopnoea index (AHI) ≥5 episodes·h−1(median (interquartile range) 318 mg·dL−1(290–374)) were similar to values in 61 children with snoring and an AHI <5 episodes·h−1(307 (269–346)). Both groups had higher fibrinogen values than those in 23 controls without snoring (271 mg·dL−1(244–294)). There was no correlation between fibrinogen values and AHI, respiratory movement/arousal index or haemoglobin desaturation index.

In conclusion, fibrinogen values are higher in children with snoring than in controls, but there is no association between these values and polysomnography indices.
Prevalence and rate of diagnosis of allergic rhinitis in Europe
Authors: Bauchau V. , Durham S.R.
Published: October 2004

To measure the prevalence of allergic rhinitis among European adults and the proportion of undiagnosed subjects, a two-step, cross-sectional, population-based survey in Belgium, France, Germany, Italy, Spain, and the UK was undertaken.

Step one of the study involved screening for allergic rhinitis by telephone interview, based on history of symptoms and/or self-awareness of the condition. Step two undertook confirmation of allergic rhinitis in a subset of the subjects screened positive; this was performed by a clinical diagnosis conducted in three to five clinical centres per country, including specific immunoglobulin E tests and a disease-specific questionnaire.

A total of 9,646 telephone interviews were conducted between February and April 2001. Self-awareness of allergic rhinitis was reported by 19% of the subjects. Physician-based diagnosis of allergic rhinitis was reported by 13% of the subjects. In step two, 725 clinical assessments were conducted between May and August 2001. A total of 411 of patients, who underwent step two, had investigator-confirmed allergic rhinitis. Among patients with investigator-confirmed allergic rhinitis, 45% had not reported a previous diagnosis by a physician. Prevalence of subjects with clinically confirmable allergic rhinitis estimated by combining step one and step two data ranged from 17% in Italy to 29% in Belgium with an overall value of 23%.

This large-scale study confirms that allergic rhinitis has a high prevalence in western Europe and is frequently undiagnosed.
No serological evidence ofRickettsia helveticainfection in Scandinavian sarcoidosis patients: Table 1—
Authors: Planck A. , Eklund A. , Grunewald J. , Vene S.
Published: October 2004

Many agents have been suggested to elicit sarcoidosis, and, recently, an association was presented between this disease and the bacteriumRickettsia helvetica.

The aim of this study was to investigate if serological support for such an association could be detected.

Sera from 20 well-characterised sarcoidosis patients were investigated for anti-rickettsial immunoglobulin G antibodies with a micro-immunofluorescence technique.R. helvetica,R. conoriiandR. typhiserved as antigens.

In conclusion, none of the investigated sera displayed detectable titres of anti-rickettsial immunoglobulin G antibodies. Thus, the current study does not support an association between rickettsia and sarcoidosis.
Magnetic stimulation for the measurement of respiratory and skeletal muscle function
Authors: Man W.D-C. , Moxham J. , Polkey M.I.
Published: October 2004

Respiratory and skeletal muscle function is of interest in many areas of pulmonary and critical care medicine. The capacity of the respiratory muscle pump to respond to the load imposed by disease is the basis of an understanding of ventilatory failure. Over the last four decades, considerable progress has been made in quantifying the capacity of the respiratory muscles, in terms of strength, endurance and fatigue. With the development of magnetic stimulation, it has recently become possible to nonvolitionally assess the respiratory muscles in a clinically acceptable way. This is of particular interest in the investigation of patients receiving critical care, those with neuromuscular disease, and in children where volitional efforts are either not possible or likely to be sub-maximal. Furthermore, the adaptation of these techniques to quantify the strength of peripheral muscles, such as the quadriceps, has allowed the effects of muscle training or rehabilitation, uninfluenced by learning effect, to be assessed. This article focuses on the physiological basis of magnetic nerve stimulation, and reviews how the technique has been applied to measure muscle strength and fatigue, with particular emphasis upon the diaphragm. The translation of magnetic stimulation into a clinical tool is described, and how it may be of diagnostic, prognostic and therapeutic value in several areas of pulmonary medicine. In particular, the use of magnetic stimulation in neuromuscular disease, the intensive care setting, chronic obstructive pulmonary disease and paediatrics will be discussed.
Asthma and cigarette smoking
Authors: Thomson N.C. , Chaudhuri R. , Livingston E.
Published: October 2004

In most developed countries ∼25% of adults with asthma are current cigarette smokers. Asthma and active cigarette smoking interact to cause more severe symptoms, accelerated decline in lung function, and impaired short-term therapeutic response to corticosteroids.

Cigarette smoking may modify inflammation that is associated with asthma, although there is limited published data on airway pathology in smokers with asthma. To date, the evidence points towards a combination of both heightened and suppressed inflammatory responses in smokers compared with nonsmokers with asthma.

The mechanisms of corticosteroid resistance in asthmatic smokers are unexplained, but could be as a result of alterations in airway inflammatory cell phenotypes (e.g.increased neutrophils or reduced eosinophils), changes in the glucocorticoid receptor-α to -β ratio (e.g.overexpression of glucocorticoid receptor β), and increased activation of pro-inflammatory transcription factors (e.g.nuclear factor-κB) or reduced histone deacetylase activity.

In conclusion, every effort should be made to encourage asthmatics who smoke to stop, although the effects of smoking cessation upon reversing the adverse effects of tobacco smoke on asthma control, therapeutic response to corticosteroids and airway pathology have yet to be fully elucidated. Alternative or additional therapies to inhaled corticosteroids are needed for asthmatic patients who are unable to quit smoking.
Impaired pulmonary status in cystic fibrosis adults with two mutatedMBL-2alleles
Authors: Davies J.C. , Turner M.W. , Klein N. ,   and the London MBL CF Study Group The London MBL CF Study Group: C. Booth, M. Johnson, N. Shen, K. Fidler, S. Sharma, J. Burgess, A. Bush, D.M. Geddes, E.W.F.W. Alton.
Published: October 2004

Mannose-binding lectin has recently been identified as a modifier of severity in cystic fibrosis, although studies have produced differing results and the mechanism of action remains unclear.

The current authors have studied large cohorts of adults (n=298) and children (n=260) to explore this apparent relationship further.

Adults with two structural mutations, but not heterozygotes, had significantly reduced lung function and oxygen saturations, more frequent hospital admissions and raised systemic inflammatory markers. This was not related to increased rates of infection withPseudomonas aeruginosa, and there was no increased susceptibility toBurkholderia cepacia. None of these findings was mirrored in the paediatric cohort.

In conclusion, severe mannose-binding lectin deficiency appears to be detrimental to cystic fibrosis adults, although heterozygotes are not affected. It is suggested that this is not related to impaired complement-mediated bacterial killing, and a link with the host inflammatory response is hypothesised. If mannose-binding lectin replacement is developed as a new approach to treatment for this disease, the present study would suggest that the small group of severely deficient patients with two structural mutations may be the group to benefit.
Effect ofin uterogrowth retardation on lung function at follow-up of prematurely born infants: Table 1—
Authors: Greenough A. , Yuksel B. , Cheeseman P.
Published: October 2004

The aim of the study was to determine if prematurely born children who had suffered intra-uterine growth retardation (IUGR) had more severe lung function abnormalities than those born an appropriate weight for gestational age (AGA).

Analysis of the lung function results of 119 infants (median (range) gestational age of 30 (23–35) weeks) was undertaken. In total, 31 of the infants had suffered IUGR and were born small for gestational age (SGA). Functional residual capacity and airways resistance (Raw) were measured at a median post-natal age of 10 (6–24) months. Specific airway conductance (sGaw) was calculated from thoracic gas volume andRaw.

The SGA children were born at a greater gestational age and had a lower body weight at testing than the AGA children.Rawand sGawdiffered between the SGA and AGA children. Regression analysis demonstrated that lung volumes were significantly related to body weight at testing,Rawwas related to IUGR, maternal smoking and bronchopulmonary dysplasia, and sGawto maternal smoking.

In conclusion, these results suggest that prematurely born infants who have suffered intra-uterine growth retardation may be at increased risk of impaired lung function at follow-up.
Paediatric lung transplantation
Authors: Mallory G.B. , Spray T.L.
Published: October 2004

Since 1990, lung transplantation has been performed in infants, children and adolescents in small numbers, and the numbers, in comparison with adult transplants, remain small today. The indications for lung transplantation are similar in childhood when compared with adults, but the disease entities are distinct.

In children, severe pulmonary vascular disease is most commonly associated with developmental abnormalities or congenital heart disease, as opposed to idiopathic pulmonary hypertension. Cystic fibrosis is the dominant indication for lung transplantation in older childhood and adolescence.

The operative approach to lung transplantation in early life differs from that in adults, in that cardiopulmonary bypass is more likely to be utilised and bilateral lung transplantation is strongly preferred to single lung transplantation. Living donor lung transplantation is proportionately more common in children and adolescents than in adults. Post-transplant complications related to viral infection and post-transplant lymphoproliferative disease are more common and more likely to be severe and life-threatening. Bronchiolitis obliterans is the most important complication after paediatric lung transplantation and limits both the quality of life and duration of survival, as in adults.
Medical thoracoscopy: hormone receptor content in pleural metastases due to breast cancer
Authors: Schwarz C. , Lübbert H. , Rahn W. , Schönfeld N. , Serke M. , Loddenkemper R.
Published: October 2004

Pleural metastases are common in the course of breast cancer, but, to date, the role of oestrogen receptor (OR) and progesterone receptor (PgR) content in metastatic tissue has been poorly evaluated.

A series of 50 consecutive patients with a history of breast cancer (median age 64 yrs, range 40–86 yrs), which presented with pleural effusion and therefore underwent medical thoracoscopy, was analysed. Metastatic pleural involvement was histologically confirmed in all patients. The hormone receptor status of the pleural metastases was investigated using the immunohistochemical method in 49 and the biochemical method in 31 cases. The immunohistochemical test was performed using monoclonal antibodies. Biochemical analysis was performed on specimens quick-frozen in liquid nitrogen. OR and PgR were measured with the dextran-coated charcoal assay and Scatchard analysis.

Immunohistochemical analysis yielded 29 OR-positive and 25 PgR-positive cases and biochemical analysis yielded 16 OR-positive and four PgR-positive cases, sometimes discrepant to hormone status of the primary breast cancer. Using a semiquantitative immunoreactive score, there was a significant association between receptor positivity and survival, but only for PgR positivity.

Immunohistochemical and biochemical detection of hormone receptors (oestrogen and progesterone) in pleural metastases of breast cancer is feasible based on medical thoracoscopy as the method of choice, by which sufficient specimens may be obtained. The receptor status may enable a decision on antihormonal treatment. Whether a positive receptor status in pleural metastatic tissue is associated with a better prognosis remains to be confirmed.
Azithromycin for cystic fibrosis
Authors: Southern K.W. , Barker P.M.
Published: October 2004

During what is a relatively barren time for new therapies for cystic fibrosis (CF), azithromycin has received a lot of attention as a potential treatment for CF lung disease. Laboratory studies suggest that azithromycin may have indirect actions, including anti-inflammatory, in addition to the standard antibacterial properties. The unique pharmacokinetics of azithromycin sets it aside from other macrolide antibiotics, but may result in increased resistance patterns.

Three well-designed randomised controlled trials have demonstrated a small but significant improvement in respiratory function (forced expiratory volume in one second) with azithromycin compared with placebo. These trial results are confirmed by a recent meta-analysis. Mild adverse events (wheeze, diarrhoea and nausea) were significantly increased in one trial. There is no clear consensus regarding the correct dose and length of treatment with azithromycin.

The present review discusses the role of azithromycin in the management of cystic fibrosis and the need for close monitoring of patients started on this drug. In addition, clinics should liaise closely with their microbiology departments and monitor resistance patterns.
Body mass index and asthma incidence among USA adults
Authors: Ford E.S. , Mannino D.M. , Redd S.C. , Mokdad A.H. , Mott J.A.
Published: October 2004

The aim of this study was to examine the association between body mass index (BMI) and asthma incidence.

Data from the baseline examination conducted during 1971–1975, and the first follow-up conducted during 1982–1984, of the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (a cohort study) was used. Asthma was self-reported or reported by proxies. BMI was calculated from measured height and weight obtained during the baseline examination.

Among 9,456 participants aged 25–74 yrs who were free of asthma at baseline, 317 participants reported a diagnosis of asthma during the follow-up interview. Compared with participants with a BMI of 18.5–<25.0 kg·m−2, the odds ratio (OR) for those with a BMI of ≥35 kg·m−2was 1.87 (95% confidence interval (CI) 1.12–3.13). ORs were similar for males and females. However, only 125 of the 298 participants who recalled a date of onset reported a diagnosis that occurred after their baseline examination. Among this group of participants, BMI was not significantly associated with asthma incidence (OR 1.52, 95% CI 0.62–3.77).

In conclusion, although obese people reported more “incident” asthma during follow-up, it remains unclear whether this represents reactivation of previously diagnosed asthma or the onset of new cases, and whether these new cases actually represent true asthma or respiratory symptoms misdiagnosed as asthma.
Smoking and asthma in adults
Authors: Piipari R. , Jaakkola J.J.K. , Jaakkola N. , Jaakkola M.S.
Published: October 2004

Studies on the effect of smoking on adulthood asthma have provided contradictory results. The current authors conducted a population-based incident case-control study to assess the effects of current and past smoking on the development of asthma in adults.

During a 2.5 yr study period, all new asthma cases clinically diagnosed (n=521) and randomly selected controls (n=932) from a geographically defined district in southern Finland were recruited.

The risk of developing asthma was significantly higher among current smokers with an adjusted odds ratio (OR) of 1.33 (95% confidence interval 1.00–1.77) and among ex-smokers with an adjusted OR 1.49 (1.12–1.97) compared with never-smokers. Among current smokers, the risk increased up to 14 cigarettes·day−1, and a similar trend was observed in relation to cumulative smoking.

In conclusion, the current results support the hypothesis that smoking causes asthma in adulthood.
Severe community-acquired pneumonia: assessment of microbial aetiology as mortality factor
Authors: Paganin F. , Lilienthal F. , Bourdin A. , Lugagne N. , Tixier F. , Génin R. , Yvin J-L.
Published: October 2004

Community-acquired pneumonia (CAP) remains a major cause of mortality. The aetiology of CAP has rarely been identified as a mortality risk factor. A prospective study was conducted to assess the prognostic factors of CAP patients admitted to the intensive care unit (Centre Hospitalier Departmental Félix Guyon, St Denis de la Réunion, France), with a special emphasis on microbial aetiology.

All variables assessing severity were collected, with a special emphasis on microbial investigations. Among 112 immunocompetent patients (mean±sdage 54.7±15.1 yrs), 84% were male. Severity of CAP was demonstrated by mortality rate (43%), shock (48%), simplified acute physiology score (SAPS; 46.4±21.6) and mechanical ventilation support (82%). Mean risk factor score was 2.2±1.2. Microbiological identification was obtained in 78.6% of cases, with positive blood culture in 33%. Most frequently, microbial agents wereStreptococcus pneumoniaeandKlebsiella pneumoniae(42% and 22%, respectively).

The univariate analysis recorded the usual mortality variables: age, alcohol consumption, SAPS, shock, mechanical ventilation, positive end expiratory pressure level, positive blood culture, multilobar infiltrates on chest radiograph, neutropenia, and acidosis, and foundK. pneumoniae(versusS. pneumoniae, and all CAP) as a mortality factor. The multivariate analysis demonstrated that septic shock (relative risk (RR) 141),K. pneumoniaeCAP (RR 27), SAPS (RR 10.7) and positive blood culture (RR 2.7) were independent factors related to death.

In conclusion, the present study found that the microbial aetiology,Klebsiella pneumoniae, was an independent risk factor for mortality in severe community-acquired pneumonia.
Manganese superoxide dismutase is increased in the airways of smokers' lungs
Authors: Harju T. , Kaarteenaho-Wiik R. , Sirviö R. , Pääkkö P. , Crapo J.D. , Oury T.D. , Soini Y. , Kinnula V.L.
Published: October 2004

Oxidant stress is a key mechanism for smoking-induced chronic obstructive pulmonary disease (COPD). Smoking has been shown to upregulate several antioxidant enzymes, with potential effects on the prevention of the disease and/or its progression. Superoxide dismutases (SOD)s are the only enzymes capable of consuming superoxide radicals. The purpose of the present study was to investigate SODs in the lungs of nonsmokers, smokers and COPD patients.

Manganese superoxide dismutase (MnSOD), copper zinc SOD (CuZnSOD), and extracellular SOD (ECSOD), were investigated by immunohistochemistry in the airways of 13 nonsmokers, 20 smokers and 22 COPD patients with mild-to-moderate disease. Lung tissue homogenates of three nonsmokers and four smokers were used for Western blot and enzyme activity analysis.

The expression of MnSOD was higher in the central bronchial epithelium of smokers with COPD and in the alveolar epithelium of smokers without or with COPD than innonsmokers. Lung MnSOD immunoreactivity, evaluated by Western blotting and specific activity, were 33% and 51% higher, respectively, in smokers than in nonsmokers. No major changes could be observed in lung CuZnSOD or ECSOD immunoreactivities.

Manganese superoxide dismutase is elevated in the alveolar epithelium of cigarette smokers, probably due to the increased oxidant burden in smokers' lungs.
Eosinophil degranulation status in allergic rhinitis: observations before and during seasonal allergen exposure
Authors: Ahlstrom-Emanuelsson C.A. , Greiff L. , Andersson M. , Persson C.G.A. , Erjefält J.S.
Published: October 2004

Despite the fact that extensive degranulation is a likely prerequisite for a pathogenic role of eosinophils, little is known about the degranulation status of these cells in eosinophilic conditions. The present study of the ultrastructure of tissue eosinophils explores eosinophil degranulation in allergic rhinitis before and during seasonal allergen exposure.

A total of 23 patients scored symptomsq.d., prior to and during the pollen season. The numbers of mucosal eosinophils and their degranulation status were determined in nasal biopsies. Furthermore, nasal lavage fluid levels of eosinophil cationic protein (ECP) and α2-macroglobulin were assessed as indices of eosinophil activity and plasma exudation, respectively.

Seasonal allergen exposure was associated with increased nasal symptoms, increased lavage fluid levels of ECP and α2-macroglobulin, and increased numbers of tissue eosinophils. In the tissue, transmission electron microscopy revealed a moderate piecemeal degranulation already prior to the season (mean±sd37±2.7% altered granules). Seasonal allergen exposure increased this degranulation (87±1.8%), and produced local areas with extensive deposition of granule proteins. The degree of eosinophil degranulation correlated with levels of ECP in lavage fluids obtained at histamine challenge.

In conclusion, this study demonstrated that the nasal mucosa in allergic rhinitis features moderately degranulated eosinophils already at nonsymptomatic baseline conditions. In association with the development of symptomatic seasonal allergic rhinitis, the tissue deposition of eosinophil granule proteins is dramatically elevated through increased eosinophil numbers, together with markedly augmented degranulation of individual cells.
Enhanced PMN response in chronic bronchitis and community-acquired pneumonia
Authors: Strassburg A. , Droemann D. , van Zandbergen G. , Kothe H. , Dalhoff K.
Published: October 2004

Chronic bronchitis is a frequent underlying disease in community-acquired pneumonia (CAP). It is unclear to what extent an impaired or exaggerated innate immune response contributes to disease manifestations and severity.

To assess the role of neutrophil activation and recruitment during acute pneumonic episodes, peripheral polymorphonulcear neutrophil (PMN) activation, chemotactic activity, interleukin-8 (CXCL-8) and CXCL-8 receptor (CXCR) expression and apoptosis rate were evaluated in CAP patients with and without chronic bronchitis. In addition, the expression of CXCRs and CXCL-8 was assessed on pulmonary neutrophils in chronic bronchitis patients to compare the activation of the chemokine system in different compartments. CAP severity was assessed by the simplified acute physiology score II and the prognosis of disease was assessed by the pneumonia severity index (PSI).

An increased chemotactic activity of PMN from chronic bronchitis patients with CAP was found, which was not related to the expression of CXCRs. In addition, a decreased apoptosis rate of PMN was observed. Chemotactic activity was related to the PSI. Comparison of peripheral and pulmonary PMN revealed enhanced CXCL-8 levels and a decreased CXCR expression in the lung.

In conclusion, neutrophil function in patients with chronic bronchitis and community-acquired pneumonia is characterised by an increased chemotactic activity combined with a decreased apoptosis rate. The downregulation of interleukin-8 receptors in the pulmonary compartment deserves further investigation.
Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection
Authors: Choi G. , Schultz M.J. , van Till J.W.O. , Bresser P. , van der Zee J.S. , Boermeester M.A. , Levi M. , van der Poll T.
Published: October 2004

Severe infection is associated with profound alterations in the systemic haemostatic balance, with activation of coagulation and suppressed fibrinolysis. Within the alveolar compartment, similar disturbances have been described during pulmonary inflammation. The current authors investigated whether local haemostasis was influenced during ventilator-associated pneumonia (VAP).

In five patients with unilateral VAP, bronchoalveolar lavage fluid (BALF) was obtained from both the infected site (as identified on chest radiograph) and the contralateral noninfected lung (with no clinical or radiographic abnormalities). Markers for coagulation and fibrinolysis were compared between infected and noninfected lungs. A total of 10 healthy volunteers and 10 mechanically ventilated patients without pneumonia served as controls.

Strong activation of coagulation (high levels of thrombin-antithrombin complexes, soluble tissue factor and factor VIIa) was detected in BALF from infected lungs, compared with that from noninfected lungs and controls. Furthermore, in infected lungs, fibrinolysis was depressed, with high levels of plasminogen activator inhibitor type 1.

In conclusion, ventilator-associated pneumonia is characterised by a hypercoagulant state at the site of infection.