bluuebunny/crossref_metadata_2025 huggingface dataset:
Photic Zone Euxinia During the Permian-Triassic Superanoxic Event
Authors: Grice Kliti , Cao Changqun , Love Gordon D. , Böttcher Michael E. , Twitchett Richard J. , Grosjean Emmanuelle , Summons Roger E. , Turgeon Steven C. , Dunning William , Jin Yugan
Published: January 2005

Carbon and sulfur isotopic data, together with biomarker and iron speciation analyses of the Hovea-3 core that was drilled in the Perth Basin, Western Australia, indicate that euxinic conditions prevailed in the paleowater column during the Permian-Triassic superanoxic event. Biomarkers diagnostic for anoxygenic photosynthesis by Chlorobiaceae are particularly abundant at the boundary and into the Early Triassic. Similar conditions prevailed in the contemporaneous seas off South China. Our evidence for widespread photiczone euxinic conditions suggests that sulfide toxicity was a driver of the extinction and a factor in the protracted recovery.
Antibody-Mediated Protection againstCryptococcus neoformansPulmonary Infection Is Dependent on B Cells
Authors: Rivera Johanna , Zaragoza Oscar , Casadevall Arturo
Published: January 2005

The pathogenesis of pulmonaryCryptococcus neoformansinfection and the efficacy of passive immunoglobulin G1 (IgG1) administration were investigated in B-cell-deficient and C57BL/6J mice. C57BL/6J mice lived longer than B-cell-deficient mice after both intratracheal and intravenous infections. Administration of IgG1 prior to infection prolonged the survival of C57BL/6J mice but had no effect on the survival or numbers of CFU in the lungs of B-cell-deficient mice.C. neoformansinfection in B-cell-deficient mice resulted in significantly higher levels of gamma interferon (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) than in C57BL/6J mice. IgG1 administration reduced IFN-γ and MCP-1 levels in C57BL/6J mice but not in B-cell-deficient mice. In addition, compared to its effect in C57BL/6J mice,C. neoformansinfection in FcRγIII-deficient, athymic, and SCID mice significantly increased IFN-γ and MCP-1 levels. IgG1 administration was associated with reduced IFN-γ levels in C57BL/6J mice but not in FcRγIII-deficient, athymic, and SCID mice. These observations suggest that IgG1-mediated protection in this system is a consequence of alterations in the inflammatory response that translate into less damage to the host without directly reducing the fungal burden. For hosts with impaired immunities, the ineffectiveness of passive antibody (Ab) may reflect an inability to down-regulate inflammation and avoid self-damage. The results indicate an important role for B cells in host defense againstC. neoformansinfection and demonstrate a surprising dependence of Ab-mediated protection on B cells in this system.
Peroxisome Proliferator-Activated Receptor γ and Retinoid X Receptor Agonists Have Minimal Effects on the Interaction of Endothelial Cells withPlasmodium falciparum-Infected Erythrocytes
Authors: Serghides Lena , Kain Kevin C.
Published: January 2005

Peroxisome proliferator-activated receptor γ-retinoid X receptor (PPARγ-RXR) agonists had minimal effects on the surface levels of CD36, intercellular cell adhesion molecule-1, or platelet-endothelial cell adhesion molecule-1 and had no effect on the cytoadherence of infected erythrocytes to either human umbilical vein endothelial cells or human microvascular endothelial cells or on malaria-induced interleukin-6 secretion from these cells. PPARγ-RXR agonists do not significantly modify malaria-infected erythrocyte-endothelial cell interactions in vitro.
Age-Dependent Changes in Susceptibility of Suckling Mice to Individual Strains of
Helicobacter pylori
Authors: Suto Hiroyuki , Zhang Maojun , Berg Douglas E.
Published: January 2005

To model establishment of
Helicobacter pylori
infection in infants, suckling mice were inoculated with mixtures of strains that preferentially colonize different gastric regions and coexist in vivo. Characterization of
H. pylori
recovered 2 weeks later showed that susceptibility begins earlier for some strains than for others and that the onset of susceptibility varies among mouse lines.
Lactobacillus johnsoniiLa1 AntagonizesGiardia intestinalisIn Vivo
Authors: Humen Martín A. , De Antoni Graciela L. , Benyacoub Jalil , Costas María E. , Cardozo Marta I. , Kozubsky Leonora , Saudan Kim-Yen , Boenzli-Bruand Angele , Blum Stephanie , Schiffrin Eduardo J. , Pérez Pablo F.
Published: January 2005

This study describes the in vivo activity ofLactobacillus johnsoniiLa1 (NCC533) inGiardia intestinalis-infected gerbils (Meriones unguiculatus). Daily administration of lactobacilli in the drinking water from 7 days before inoculation withGiardiatrophozoites efficiently preventedG. intestinalisstrain WB clone C6 from infecting gerbils. More specifically, shedding of fecalGiardiaantigens (GSA65 protein) was diminished in the La1-treated group, and resolution of infection was observed by 21 days postinoculation. Histology and analysis of enzymatic markers of microvillus membrane integrity revealed that probiotic administration also protected against parasite-induced mucosal damage. In addition, a cellular response toGiardiaantigens was stimulated in spleen cells from La1-treated gerbils. Results show for the first time the antigiardial effect of probiotic lactobacilli in vivo and provide further insight into the antagonistic properties of lactic acid bacteria against protozoa involved in intestinal infections.
EspJ Is a Prophage-Carried Type III Effector Protein of Attaching and Effacing Pathogens That Modulates Infection Dynamics
Authors: Dahan Sivan , Wiles Siouxsie , La Ragione Roberto M. , Best Angus , Woodward Martin J. , Stevens Mark P. , Shaw Robert K. , Chong Yuwen , Knutton Stuart , Phillips Alan , Frankel Gad
Published: January 2005

Enterohemorrhagic
Escherichia coli
, enteropathogenic
E. coli
, and
Citrobacter rodentium
are highly adapted enteropathogens that successfully colonize their host's gastrointestinal tract via the formation of attaching and effacing (A/E) lesions. These pathogens utilize a type III secretion system (TTSS) apparatus, encoded by the locus of enterocyte effacement, to translocate bacterial effector proteins into epithelial cells. Here, we report the identification of EspJ (
E. coli
-secreted protein J), a translocated TTSS effector that is carried on the 5′ end of the cryptic prophage CP-933U. Infection of epithelial cells in culture revealed that EspJ is not required for A/E lesion activity in vivo and ex vivo. However, in vivo studies performed with mice demonstrated that EspJ possesses properties that influence the dynamics of clearance of the pathogen from the host's intestinal tract, suggesting a role in host survival and pathogen transmission.
Identification of an Iron-Regulated Hemin-Binding Outer Membrane Protein, HupO, in
Vibrio fluvialis
: Effects on Hemolytic Activity and the Oxidative Stress Response
Authors: Ahn Sun-Hee , Han Jeong-Hyun , Lee Jong-Hee , Park Kee-Jai , Kong In-Soo
Published: January 2005

In pathogenic bacteria, iron acquisition is important for colonization and proliferation in the host under iron-limited conditions. The ability of
Vibrio
spp. to acquire iron is often critical to their virulence, causing gastroenteritis or excessive watery diarrhea in humans. In the study described here, we cloned the 2,100-bp heme utilization protein gene
hupO
in
Vibrio fluvialis
. HupO had high homology to iron-regulated outer membrane receptor proteins in
Vibrio
sp. and contained motifs that are common to bacterial heme receptors, including a consensus TonB box, a FRAP domain, and an NPNL domain. To characterize the hemin-binding activity of HupO, we purified the recombinant HupO protein (rHupO) from
Escherichia coli
by using an overexpression system. HupO was found to bind to hemin but not to hemoglobin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting demonstrated that the 77-kDa outer membrane protein HupO of
V. fluvialis
was induced under iron-restricted conditions. We constructed a
hupO
mutant, HP1, to investigate the biochemical function of HupO in
V. fluvialis
. The hemolytic activity of HP1 was reduced compared to that of wild-type cells and, when exposed to hydrogen peroxide, significantly lower numbers of HP1 survived than was the case in the wild type. These results suggest that HupO is associated with virulence expression in
V. fluvialis
through stimulation of hemolysin production and resistance to oxidative stress. In experimentally infected mice, the 50% lethal dose value of the wild-type was lower than that of the mutant, HP1.
Monoacyl Lipoteichoic Acid from Pneumococci Stimulates Human Cells but Not Mouse Cells
Authors: Kim Je Hak , Seo Hoseong , Han Seung Hyun , Lin Jisheng , Park Moon-Kook , Sorensen Uffe B. S. , Nahm Moon H.
Published: January 2005

We have developed a method for obtaining pneumococcal lipoteichoic acid (LTA) with none, one, or two acyl chains. Anion-exchange chromatography at pH 9.5 yields pneumococcal LTA (labeled LTA-9.5) that has a mass spectrum identical to that of pre-ion-exchange LTA and loses 500 mass units after deacylation by alkali hydrolysis. Anion exchange at pH 10.5 produces LTA (labeled LTA-10.5) with mass peaks that are 264 mass units lower than those of pre-ion-exchange LTA, and deacylation of LTA-10.5 by alkali hydrolysis reduces the mass by only 239 mass units. This result indicates that LTA-10.5 has lost one of the two acyl chains, whereas LTA-9.5 has both acyl chains. When the biological properties of LTA-9.5 and LTA-10.5 are examined with mouse cells, only LTA-9.5 (and not LTA-10.5) is able to stimulate mouse cells to produce tumor necrosis factor alpha, interleukin-1β, and nitric oxide. In contrast, both LTA-9.5 and LTA-10.5 can stimulate human cells. LTA became inactive when both acyl chains were removed. Thus, acyl chains are critical for LTA function, and small variations in acyl chains can alter biological properties of LTA.
Staphylococcus aureus
Virulence Factors Identified by Using a High-Throughput
Caenorhabditis elegans-
Killing Model
Authors: Begun Jakob , Sifri Costi D. , Goldman Samuel , Calderwood Stephen B. , Ausubel Frederick M.
Published: January 2005

Staphylococcus aureus
is an important human pathogen that is also able to kill the model nematode
Caenorhabditis elegans
. We constructed a 2,950-member Tn
917
transposon insertion library in
S. aureus
strain NCTC 8325. Twenty-one of these insertions exhibited attenuated
C. elegans
killing, and of these, 12 contained insertions in different genes or chromosomal locations. Ten of these 12 insertions showed attenuated killing phenotypes when transduced into two different
S. aureus
strains, and 5 of the 10 mutants correspond to genes that have not been previously identified in signature-tagged mutagenesis studies. These latter five mutants were tested in a murine renal abscess model, and one mutant harboring an insertion in
nagD
exhibited attenuated virulence. Interestingly, Tn
917
was shown to have a very strong bias for insertions near the terminus of DNA replication.
Meningococcal Transferrin-Binding Proteins A and B Show Cooperation in Their Binding Kinetics for Human Transferrin
Authors: Stokes Russell H. , Oakhill Jonathan S. , Joannou Christopher L. , Gorringe Andrew R. , Evans Robert W.
Published: January 2005

Neisseria meningitidis
, a causative agent of bacterial meningitis and septicemia, obtains transferrin-bound iron by expressing two outer membrane-located transferrin-binding proteins, TbpA and TbpB. A novel system was developed to investigate the interaction between Tbps and human transferrin. Copurified TbpA-TbpB, recombined TbpA-TbpB, and individual TbpA and TbpB were reconstituted into liposomes and fused onto an HPA chip (BIAcore). All preparations formed stable monolayers, which, with the exception of TbpB, could be regenerated by removing bound transferrin. The ligand binding properties of these monolayers were characterized with surface plasmon resonance and shown to be specific for human transferrin. Kinetic data for diferric human transferrin binding showed that recombined TbpA-TbpB had

K
a

and

K
d

values similar to those of copurified TbpA-TbpB. Individual TbpA and TbpB also displayed

K
a

values similar to those of copurified TbpA-TbpB, but their

K
d

values were one order of magnitude higher. Chemical cross-linking studies revealed that TbpA and TbpB, in the absence of human transferrin, formed large complexes with TbpA as the predominant species. Upon human transferrin binding, a complex was formed with a molecular mass corresponding to that of a TbpB-human transferrin heterodimer as well as a higher-molecular-mass complex of this heterodimer cross-linked to TbpA. This indicates that TbpA and TbpB form a functional meningococcal receptor complex in which there is cooperativity in the human transferrin binding kinetics. However, iron loss from the diferric human transferrin-TbpA-TbpB complex was not greater than that from human transferrin alone, suggesting that additional meningococcal transport components are involved in the process of iron removal.
Protective Levels of Polysaccharide-Specific Maternal Antibodies May Enhance the Immune Response Elicited by Pneumococcal Conjugates in Neonatal and Infant Mice
Authors: Richter Margret Y. , Jakobsen Havard , Haeuw Jean-François , Power Ultan F. , Jonsdottir Ingileif
Published: January 2005

Maternal antibodies (MatAbs) may protect the offspring against infections but may also interfere with their immune responses to vaccination. We have previously shown that maternal immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus protein (Pnc-TT) protected the offspring against infections caused by three important pediatric serotypes. To study the influence of MatAb on the immune response to Pnc-TT early in life, adult female mice were immunized twice with Pnc-TT of serotype 1 (Pnc1-TT), and their offspring received Pnc1-TT subcutaneously three times at 3-week intervals starting at 1 week (neonatal) or 3 weeks (infant) of age. High levels of PPS-1-specific MatAb (>3 log) in offspring of Pnc1-TT-immunized dams completely inhibited their anti-PPS-1 response elicited by Pnc1-TT. In contrast, low or moderate (∼1 to 2 log) levels of MatAb did not interfere with and even enhanced the immune response of the offspring, and a booster response to a second Pnc1-TT dose was observed. Carrier-specific MatAbs had little effect on the response of offspring to the conjugate. All Pnc1-TT-immunized offspring were protected against pneumococcal bacteremia and had reduced lung infection. These results demonstrate that in the presence of MatAb, Pnc1-TT may elicit a protective PPS-1-specific antibody response and prime for PPS-1-specific memory in young offspring. Importantly, low or moderate levels of PPS-1-specific MatAb not only provided protection against pneumococcal infections but also enhanced the immune response elicited by Pnc1-TT in neonatal and infant mice. This murine model will be used to develop novel strategies combining maternal and neonatal immunization to protect against infections caused by encapsulated bacteria in early life.
Second-Generation Recombination-Based In Vivo Expression Technology for Large-Scale Screening for
Vibrio cholerae
Genes Induced during Infection of the Mouse Small Intestine
Authors: Osorio C. G. , Crawford J. A. , Michalski J. , Martinez-Wilson H. , Kaper J. B. , Camilli A.
Published: January 2005

We have constructed an improved recombination-based in vivo expression technology (RIVET) and used it as a screening method to identify
Vibrio cholerae
genes that are transcriptionally induced during infection of infant mice. The improvements include the introduction of modified substrate cassettes for resolvase that can be positively and negatively selected for, allowing selection of resolved strains from intestinal homogenates, and three different
tnpR
alleles that cover a range of translation initiation efficiencies, allowing identification of infection-induced genes that have low-to-moderate basal levels of transcription during growth in vitro. A transcriptional fusion library of 8,734 isolates of a
V. cholerae
El Tor strain that remain unresolved when the vibrios are grown in vitro was passed through infant mice, and 40 infection-induced genes were identified. Nine of these genes were inactivated by in-frame deletions, and their roles in growth in vitro and fitness during infection were measured by competition assays. Four mutant strains were attenuated >10-fold in vivo compared with the parental strain, demonstrating that infection-induced genes are enriched in genes essential for virulence.
Role of σ
B
in the Expression of
Staphylococcus aureus
Cell Wall Adhesins ClfA and FnbA and Contribution to Infectivity in a Rat Model of Experimental Endocarditis
Authors: Entenza Jose-Manuel , Moreillon Philippe , Senn Maria Magdalena , Kormanec Jan , Dunman Paul M. , Berger-Bächi Brigitte , Projan Steven , Bischoff Markus
Published: January 2005

Isogenic
Staphylococcus aureus
strains with different capacities to produce σ
B
activity were analyzed for their ability to attach to fibrinogen- or fibronectin-coated surfaces or platelet-fibrin clots and to cause endocarditis in rats. In comparison to the σ
B
-deficient strain, BB255, which harbors an
rsbU
mutation, both
rsbU
-complemented and σ
B
-overproducing derivatives exhibited at least five times greater attachment to fibrinogen- and fibronectin-coated surfaces and showed increased adherence to platelet-fibrin clots. No differences in adherence were seen between BB255 and a Δ
rsbUVWsigB
isogen. Northern blotting analyses revealed that transcription of
clfA
, encoding fibrinogen-binding protein clumping factor A, and
fnbA
, encoding fibronectin-binding protein A, were positively influenced by σ
B
. σ
B
overproduction resulted in a statistically significant increase in positive spleen cultures and enhanced bacterial densities in both the aortic vegetations and spleens at 16 h postinoculation. In contrast, at 72 h postinoculation, tissues infected with the σ
B
overproducer had lower bacterial densities than did those infected with BB255. These results suggest that although σ
B
appears to increase the adhesion of
S. aureus
to various host cell-matrix proteins in vitro, it has limited effect on pathogenesis in the rat endocarditis model. σ
B
appears to have a transient enhancing effect on bacterial density in the early stages of infection that is lost during progression.
Vaccination with Recombinant N-Terminal Domain of Als1p Improves Survival during Murine Disseminated Candidiasis by Enhancing Cell-Mediated, Not Humoral, Immunity
Authors: Ibrahim Ashraf S. , Spellberg Brad J. , Avenissian Valentina , Fu Yue , Filler Scott G. , Edwards John E.
Published: January 2005

Candidaspp. are opportunistic fungal pathogens that are among the most common causes of nosocomial bloodstream infections. The mortality attributable to disseminated candidiasis is 40 to 50% despite antifungal therapy. Clearly, new strategies are needed to prevent this life-threatening infection. Because risk factors for disseminated candidiasis are well defined and frequently of limited duration, vaccination is an appealing prophylactic strategy. We have identified a cell surface protein, Als1p, that mediates adherence ofCandida albicansto a variety of human substrates and plastic. Here we report that immunizing BALB/c mice with the recombinant N-terminal domain of Als1p (rAls1p-N) improved survival during a subsequent challenge with a lethal inoculum ofC. albicans. The protective 20-μg dose of rAls1p-N significantly increasedCandidastimulation of Th1 splenocytes and increased in vivo delayed-type hypersensitivity. In contrast, antibody titers did not correlate with protection. Finally, the vaccine was not protective in T-cell-deficient mice but was protective in B-cell-deficient mice. These data indicate that the mechanism of action of the rAls1p-N vaccine is stimulation of cell-mediated, rather than humoral, immunity againstC. albicans. The majority of efforts to date have focused on the development of passive immunization strategies to prevent or treat disseminated candidiasis. In contrast, our results provide proof of principle for vaccination with an adhesin ofC. albicansand emphasize the potential for cell-mediated immune modulation as a prophylactic or therapeutic strategy against disseminated candidiasis.
Long-Range Polar Effect on the C-ON Bond Homolysis in (tert-Butyl[1-(diethylphosphonyl)-2,2-dimethylpropyl]aminoxyl) SG1-Based Alkoxyamines
Authors: Bertin Denis , Gigmes Didier , Marque Sylvain R. A. , Milardo Stephan , Peri Jérôme , Tordo Paul
Published: January 2005

Alkoxyamines and persistent nitroxyl radicals are important regulators of nitroxide-mediated radical polymerization. Because the polymerization times decrease with the increasing rate constant of the homolysis of the C-ON bond between the polymer chain and the nitroxyl moiety, the factors influencing the cleavage rate constant are of considerable interest. Because alkyl acrylate monomers are among the most used in polymerization, we present the measures of the rate constants (kd) of the C-ON bond cleavage for new SG1 based alkoxyamine models containingpara-substituted aromatic acrylates (4-XC6H4OC(O)C(Me)H-SG1). It appears that the values ofkdincrease with the electron-withdrawing properties of thepara-substituent groups (4-X) of the ester SG1-based alkoxyamines.
Cost effectiveness of adding magnetic resonance imaging to the usual management of suspected scaphoid fractures
Authors: Brooks S , Cicuttini F M , Lim S , Taylor D , Stuckey S L , Wluka A E
Published: January 2005

Objective:To determine the cost effectiveness of a magnetic resonance imaging scan (MRI) within 5 days of injury compared with the usual management of occult scaphoid fracture.

Methods:All patients with suspected scaphoid fractures in five hospitals were invited to participate in a randomised controlled trial of usual treatment with or without an MRI scan. Healthcare costs were compared, and a cost effectiveness analysis of the use of MRI in this scenario was performed.

Results:Twenty eight of the 37 patients identified were randomised: 17 in the control group, 11 in the MRI group. The groups were similar at baseline and follow up in terms of number of scaphoid fractures, other injuries, pain, and function. Of the patients without fracture, the MRI group had significantly fewer days immobilised: a median of 3.0 (interquartile range 3.0–3.0)v10.0 (7–12) in the control group (p  =  0.006). The MRI group used fewer healthcare units (median 3.0, interquartile range 2.0–4.25) than the control group (5.0, 3.0–6.5) (p  =  0.03 for the difference). However, the median cost of health care in the MRI group ($594.35 AUD, $551.35–667.23) was slightly higher than in the control group ($428.15, $124.40–702.65) (p  =  0.19 for the difference). The mean incremental cost effectiveness ratio derived from this simulation was that MRI costs $44.37 per day saved from unnecessary immobilisation (95% confidence interval $4.29 to $101.02). An illustrative willingness to pay was calculated using a combination of the trials measure of the subjects’ individual productivity losses and the average daily earnings.

Conclusions:Use of MRI in the management of occult scaphoid fracture reduces the number of days of unnecessary immobilisation and use of healthcare units. Healthcare costs increased non-significantly in relation to the use of MRI in this setting. However, when productivity losses are considered, MRI may be considered cost effective, depending on the individual case.
Effect of dry needling of gluteal muscles on straight leg raise: a randomised, placebo controlled, double blind trial
Authors: Huguenin L , Brukner P D , McCrory P , Smith P , Wajswelner H , Bennell K
Published: January 2005

Objectives:To use a randomised, double blind, placebo controlled trial to establish the effect on straight leg raise, hip internal rotation, and muscle pain of dry needling treatment to the gluteal muscles in athletes with posterior thigh pain referred from gluteal trigger points.

Methods:A randomised, double blind, placebo controlled trial of 59 male runners was performed during the 2002 Australian Rules football season. Subjects were thoroughly screened and had magnetic resonance imaging of their hamstring muscles to exclude local pathology. The inclusion criterion was reproduction of recognisable posterior thigh pain with the application of digital pressure to the gluteal trigger points. Subjects randomly received either therapeutic or placebo needle treatment on one occasion at their gluteal trigger points. Range of motion and visual analogue scale data were collected immediately before, immediately after, 24 hours after, and 72 hours after the intervention. Range of motion was measured with passive straight leg raise and hip internal rotation. Visual analogue scales were completed for hamstring and gluteal pain and tightness at rest and during a running task.

Results:Magnetic resonance imaging scans revealed normal hamstring musculature in most subjects. Straight leg raise and hip internal rotation remained unchanged in both groups at all times. Visual analogue scale assessment of hamstring pain and tightness and gluteal tightness after running showed improvements immediately after the intervention in both groups (p  =  0.001), which were maintained at 24 and 72 hours. The magnitude of this improvement was the same for therapeutic and placebo interventions. Resting muscle pain and tightness were unaffected.

Conclusions:Neither dry needling nor placebo needling of the gluteal muscles resulted in any change in straight leg raise or hip internal rotation. Both interventions resulted in subjective improvement in activity related muscle pain and tightness. Despite being commonly used clinical tests in this situation, straight leg raise and hip internal rotation are not likely to help the therapist assess response to treatment. Patient reports of response to such treatment are better indicators of its success. The mechanisms by which these responses occur and the reasons for the success of the placebo needling treatment are areas for further investigation.
Effects of training period on haemorheological variables in regularly trained footballers
Authors: Karakoc Y , Duzova H , Polat A , Emre M H , Arabaci I
Published: January 2005

Objective:To investigate the effects of one football training period on haemorheological variables in regularly trained footballers.

Method:Ten subjects were randomly selected from the reserve team of a football club in the Turkish Premier League. During the last week of the football season, one day before a standard training session and two days after the previous league match, venous blood samples were taken (pre-exercise). After 90 minutes of standard training, further blood samples were taken (post-exercise). Blood lactate, blood viscosity, plasma fibrinogen, blood clotting time, acid-base variables, and plasma Na+, K+, and Ca2+were determined.

Results:Haemoglobin, packed cell volume, and mean corpuscular volume were all significantly decreased, whereas white blood cells and platelets were both increased after training. Blood viscosity decreased but the reduction was not significant. Blood lactate, plasma glucose, and Na+content were significantly increased, but standard bicarbonate, actual bicarbonate, and Ca2+were significantly decreased. Blood clotting time had shortened significantly after training. Blood viscosity was inversely correlated with plasma glucose concentration (r =  −0.48 and p  =  0.032).

Conclusions:The results show that blood viscosity tends to decrease as the result of this type of training. This is due to a reduction in packed cell volume and mean corpuscular volume. The increased blood lactate does not have an adverse effect on the blood viscosity of these subjects because protective mechanisms develop with regular training throughout the season.
Do non-steroidal anti-inflammatory drugs adversely affect stress fracture healing? A short review
Authors: Wheeler P , Batt M E
Published: January 2005

A literature search was performed to determine whether non-steroidal anti-inflammatory drugs (NSAIDs) adversely affect the healing of stress fractures. Evidence exists from laboratory studies and animal subjects that NSAIDs can affect fracture healing. This link has not been proved or disproved in human subjects, particularly for stress fractures. In view of the high usage of NSAIDs in treating musculoskeletal disorders, research is required to investigate whether the healing of stress fractures is affected by these drugs.
Quadrilateral space syndrome: a case study and review of the literature: Table 1
Authors: Hoskins W T , Pollard H P , McDonald A J
Published: January 2005

Quadrilateral space syndrome is an uncommon injury. The true prevalence is unknown because of a lack of literature and possible misdiagnosis. Prevalence may increase as knowledge of the syndrome increases. The case is presented of a recreational triathlete who had a spontaneous onset of quadrilateral space syndrome. The diagnosis was made by physical examination and confirmed with magnetic resonance imaging. A conservative, yet aggressive rehabilitation programme resulted in functional improvement within six weeks. Results have been maintained for eight weeks.
Gender differences in the association of age with physical workload and functioning
Authors: Aittomäki A , Lahelma E , Roos E , Leino-Arjas P , Martikainen P
Published: January 2005

Aims:To test whether (1) physically demanding work is less frequent for older than younger employees, and whether (2) the association of physically demanding work with decline of physical functioning is stronger for older employees than their younger counterparts. The gender differences in these associations were examined.

Methods:Subjects of the study were 40–60 year old employees of the City of Helsinki. Data (n = 5802) were collected with mail questionnaires in 2000 and 2001. Functioning was measured with the Role Limitations due to Physical Health Problems scale of the SF36 health questionnaire. Logistic regression models were used to analyse the data.

Results:There was a linear trend of less physically demanding work in older than in younger age groups. This trend was more marked for men than women. Age and physically demanding work were associated with poor functioning. In women the association of physically demanding work with poor functioning tended to be stronger for older than for younger age groups, while the opposite was observed in men.

Conclusions:Results suggest that physically demanding work causes more ailments in women of high age than men. It is possible that less men than women are still employed in physically demanding occupations at high age, even though direct evidence of exit from physically demanding work cannot be obtained from cross-sectional data. In these data the physically demanding occupations for men and women were largely different. High physical workload among women working in social and health care is likely to contribute to the gender differences.
Mortality of workers at a nickel carbonyl refinery, 1958–2000
Authors: Sorahan T , Williams S P
Published: January 2005

Background:Excess risks of respiratory cancer have been shown in some groups of nickel exposed workers. It is clear, however, that not all forms of nickel exposure are implicated in these excess risks.

Aim:To determine whether occupational exposures received in a modern nickel carbonyl refinery lead to increased risks of cancer, in particular nasal cancer and lung cancer.

Methods:The mortality experienced by a cohort of 812 workers employed at a nickel refinery was investigated. Study subjects were all male workforce employees first employed in the period 1953–92 who had at least five years’ employment with the company. Observed numbers of cause specific deaths were compared with expectations based on national mortality rates; SMRs were also calculated by period from commencing employment, year of commencing employment, and type of work.

Results:Overall, standardised mortality ratios (SMRs) were close to 100 for all causes (Obs 191, SMR 96, 95% CI 83 to 111), all neoplasms (Obs 63, SMR 104, 95% CI 80 to 133), non-malignant diseases of the respiratory system (Obs 18, SMR 97, 95% CI 57 to 153), and diseases of the circulatory system (Obs 85, SMR 94, 95% CI 75 to 116). There were no significantly increased SMRs for any site of cancer. There was a non-significant excess for lung cancer (Obs 28, Exp 20.17, SMR 139, 95% CI 92 to 201), and in subgroup analyses a significantly increased SMR of 231 (Obs 9) was found for those 142 workers with at least five years’ employment in the feed handling and nickel extraction departments. In the total cohort there was a single death from nasal cancer (Exp 0.10).

Conclusions:The non-significant excess of lung cancer deaths may well be a chance finding, but in light of previous studies some role for nickel exposures cannot be excluded.
Patient satisfaction with occupational health physicians, development of a questionnaire
Authors: Verbeek J H , de Boer A G , van der Weide W E , Piirainen H , Anema J R , van Amstel R J , Hartog F
Published: January 2005

Aims:To develop a questionnaire that measures specific aspects of patient satisfaction with occupational health physicians.

Methods:General patient satisfaction questionnaires, a literature survey, and interviews with patients were used. An initial questionnaire was distributed among sick listed patients (n = 432) of occupational physicians (n = 90) from different occupational health services. To reduce items and to develop scales exploratory factor analysis and reliability analysis was used. A linear regression model was used to predict satisfaction ratings from the scales of the questionnaire.

Results:Questions about independence of the occupational physician were difficult to ask unambiguously. The factor analysis revealed five relevant factors which were named “being taken seriously as a patient”, “attitude towards occupational health services”, “trust and confidentiality”, “expectations”, and “comfort and access”. All scales could be reduced to a maximum of five items without reducing the scale reliability too much. In the regression analysis, 71% of the variance of satisfaction ratings was explained by the first four scales and most by the first scale. “Comfort and access” did not contribute significantly to the model.

Conclusions:A short questionnaire was developed to measure different aspects of patient satisfaction specific for occupational health. Whether the questionnaire can effectively lead to quality improvement in occupational health services should be investigated.
Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone
Authors: Iwasaki Tomoyuki , Mukasa Koji , Yoneda Masato , Ito Satoshi , Yamada Yoshihiko , Mori Yasumichi , Fujisawa Nobutaka , Fujisawa Toshio , Wada Koichiro , Sekihara Hisahiko , Nakajima Atsushi
Published: January 2005

Dehydroepiandrosterone (DHEA) is a type of adrenal steroid. The concentrations of DHEA and its sulfate (DHEA-S) in serum reach a peak between the ages of 25 and 30 yr and thereafter decline steadily. It was reported that DHEA-S concentration in humans is inversely related to death from cardiovascular diseases. In this study, we examined the effects of DHEA on regulation of collagen mRNA and collagen synthesis in cultured cardiac fibroblasts. Treatment with DHEA (10−6 M) resulted in a significant decrease in procollagen type I mRNA expression compared with controls. This was accompanied by a significant decrease in procollagen type I protein accumulation in the medium and also a significant decrease in procollagen type I protein synthesis in the cellular matrix. Furthermore, to confirm in vitro results, we administered DHEA to Sprague-Dawley rats, which were treated with angiotensin II for 8 wk to induce cardiac damage. Procollagen type I mRNA expression was significantly decreased and cardiac fibrosis significantly inhibited in DHEA-treated rat hearts without lowering the systolic blood pressure. These results strongly indicate that DHEA can directly attenuate collagen type I synthesis at the transcriptional level in vivo and in vitro in cardiac fibroblasts.
H2O2: a mediator of esophagitis-induced damage to calcium-release mechanisms in cat lower esophageal sphincter
Authors: Cao Weibiao , Harnett Karen M. , Cheng Ling , Kirber Michael T. , Behar Jose , Biancani Piero
Published: January 2005

We previously reported that induction of acute experimental esophagitis by repeated perfusion of HCl may affect release of intracellular Ca2+stores. We therefore measured cytosolic Ca2+in response to a maximally effective dose of ACh in fura 2-AM-loaded lower esophageal sphincter (LES) circular muscle cells and examined the contribution of H2O2to the reduction in Ca2+signal. In normal cells, the ACh-induced Ca2+increase was the same in normal-Ca2+and Ca2+-free medium and was abolished by the phosphatidylinositol 4,5-bisphosphate-specific phospholipase C inhibitor U-73122, confirming that the initial ACh-induced contraction depends on Ca2+release from intracellular stores through production of inositol trisphosphate. In LES cells, the ACh-induced Ca2+increase in normal-Ca2+medium was significantly lower in esophagitis than in normal cells and was further reduced (∼70%) when the cells were incubated in Ca2+-free medium. This reduction was partially reversed by the H2O2scavenger catalase. H2O2measurements in LES circular muscle showed significantly higher levels in esophagitis than in normal cells. When normal LES cells were incubated with H2O2, the ACh-induced Ca2+increase was significantly reduced in normal-Ca2+and Ca2+-free medium and was similar to that observed in animals with esophagitis. The initial ACh-induced contraction was also reduced in normal cells incubated with H2O2. H2O2, when applied to cells at sufficiently high concentration, produced a visible and prolonged Ca2+signal in normal cells. H2O2-induced cell contraction was also sensitive to depletion of stores by thapsigargin (TG); conversely, H2O2reduced TG-induced contraction, suggesting that TG and H2O2may operate through similar mechanisms. Ca2+-ATPase activity measurement indicates that H2O2and TG reduced Ca2+-ATPase activity, confirming similarity of mechanism of action. We conclude that H2O2may be at least partly responsible for impairment of Ca2+release in acute experimental esophagitis by inhibiting Ca2+uptake and refilling Ca2+stores.
Glucocorticoids increase osmotic water permeability (Pf) of neonatal rabbit renal brush border membrane vesicles
Authors: Mulder Jaap , Chakravarty Sumana , Haddad Maha N. , Baum Michel , Quigley Raymond
Published: January 2005

During postnatal maturation, there is an increase in renal brush border membrane vesicle (BBMV) osmotic water permeability and a parallel increase in aquaporin-1 (AQP1) protein abundance. The mechanisms responsible for these changes remain unknown. Because serum glucocorticoid levels rise postnatally and have previously been linked to other maturational changes in renal function, we examined the effects of glucocorticoids on osmotic (Pf) and diffusional (PDW) water permeability and AQP1 protein abundance of renal BBMV. Neonatal rabbits were treated with dexamethasone (10 μg/100 g) for three days and compared with control neonates and adults. Pfand PDWwere measured at 20°C with a stopped-flow apparatus using light-scattering and aminonaphthalene trisulfonic acid (ANTS) fluorescence, respectively. Pfwas significantly higher in BBMV from dexamethasone-treated neonates compared with vehicle-treated neonates, but remained lower than in BBMV from adults ( P < 0.05). PDWin dexamethasone and vehicle-treated neonatal BBMV was lower than in adult BBMV. Pf/PDWratio increased from neonate (5.1 ± 0.3) to dexamethasone (7.0 ± 0.1) and adult BBMV (6.3 ± 0.1). AQP1 expression was increased by dexamethasone treatment to adult levels. Membrane fluidity, which is inversely related to generalized polarization (GP) of steady-state laurdan fluorescence, was significantly higher in neonatal BBMV than both dexamethasone and adult BBMV (GP: neonate 0.285 ± 0.002, dexamethasone treatment 0.302 ± 0.006, and adult 0.300 ± 0.005; P < 0.05). These combined results show that dexamethasone-treatment during days 4–7 of life increases BBMV water permeability despite a decrease in membrane fluidity. This occurs by increasing channel-mediated water transport, as reflected in an increase in AQP1 protein abundance and a higher Pf/PDWratio. This mimics the maturational changes and suggests a physiological role for glucocorticoids in maturation of proximal tubule water transport.
Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP
Authors: Wlodek Mary E. , Westcott Kerryn T. , O’Dowd Rachael , Serruto Anne , Wassef Lesley , Moritz Karen M. , Moseley Jane M.
Published: January 2005

During pregnancy, parathyroid hormone-related protein (PTHrP) is one of many growth factors that play important roles to promote fetal growth and development, including stimulation of placental calcium transport. Angiotensin II, acting through the AT1areceptor, is also known to promote placental growth. We examined the effects of bilateral uterine artery and vein ligation (restriction), which mimics placental insufficiency in humans, on growth, intrauterine PTHrP, placental AT1a, and pup calcium. Growth restriction was surgically induced on day 18 of pregnancy in Wistar-Kyoto female rats by uterine vessel ligation. Uteroplacental insufficiency reduced fetal body weight by 15% and litter size ( P < 0.001) compared with the control rats with no effect on placental weight or amniotic fluid volume. Uteroplacental insufficiency reduced placental PTHrP content by 46%, with increases in PTHrP (by 2.6-fold), parathyroid hormone (PTH)/PTHrP receptor (by 11.6-fold), and AT1a(by 1.7-fold) relative mRNA in placenta following restriction compared with results in control ( P < 0.05). There were no alterations in uterine PTHrP and PTH/PTHrP receptor mRNA expression. Maternal and fetal plasma PTHrP and calcium concentrations were unchanged. Although fetal total body calcium was not altered, placental restriction altered perinatal calcium homeostasis, as evidenced by lower pup total body calcium after birth ( P < 0.05). The increased uterine and amniotic fluid PTHrP ( P < 0.05) may be an attempt to compensate for the induced impaired placental function. The present study demonstrates that uteroplacental insufficiency alters intrauterine PTHrP, placental AT1aexpression, and perinatal calcium in association with a reduction in fetal growth. Uteroplacental insufficiency may provide an important model for exploring the early origins of adult diseases.
PKC-α-mediated remodeling of the actin cytoskeleton is involved in constitutive albumin uptake by proximal tubule cells
Authors: Hryciw Deanne H. , Pollock Carol A. , Poronnik Philip
Published: January 2005

One key role of the renal proximal tubule is the reabsorption of proteins from the glomerular filtrate by constitutive receptor-mediated endocytosis. In the opossum kidney (OK) renal proximal tubule cell line, inhibition of protein kinase C (PKC) reduces albumin uptake, although the isoforms involved and mechanisms by which this occurs have not been identified. We used pharmacological and molecular approaches to investigate the role of PKC-α in albumin endocytosis. We found that albumin uptake in OK cells was inhibited by the pan-PKC blocker bisindolylmaleimide-1 and the isoform-specific PKC blockers Gö-6976 and 2′,3,3′,4,4′-hexahydroxy-1,1′-biphenyl-6,6′-dimethanol dimethyl ether, indicating a role for PKC-α. Overexpression of a kinase deficient PKC-α(K368R) but not wild-type PKC-α significantly reduced albumin endocytosis. Western blot analysis of fractionated cells showed an increased association of PKC-α-green fluorescent protein with the membrane fraction within 10–20 min of exposure to albumin. We used phalloidin to demonstrate that albumin induces the formation of clusters of actin at the apical surface of OK cells and that these clusters correspond to the location of albumin uptake. These clusters were not present in cells grown in the absence of albumin. In cells treated either with PKC inhibitors or overexpressing kinase-deficient PKC-α(K368R) this actin cluster formation was significantly reduced. This study identifies a role for PKC-α in constitutive albumin uptake in OK cells by mediating assembly of actin microfilaments at the apical membrane.
Influence of phosphatidylglycerol on the uptake of liposomes by alveolar cells and on lung function
Authors: Poelma D. L. H. , Lachmann B. , Haitsma J. J. , Zimmermann L. J. , van Iwaarden J. F.
Published: January 2005

The effect of phosphatidylglycerol on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages as well as the effect on endogenous surfactant function was studied in vivo. Healthy ventilated rats were intratracheally instilled with fluorescent labeled liposomes with different concentrations of phosphatidylglycerol. Lung function was determined by monitoring arterial oxygenation and, at the end of the experiment, by recording static pressure-volume curves. In addition, alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that, in the presence of cofactors (Ca2+, Mg2+), phosphatidylglycerol stimulates the uptake by alveolar macrophages but hardly affects the uptake by alveolar type II cells. High concentrations of phosphatidylglycerol reduce the number of alveolar macrophages in the alveolar space and deteriorate lung function. On the other hand, the presence of cofactors protects the lung against the negative effects of phosphatidylglycerol on endogenous surfactant and alveolar macrophages. This study indicates that the phosphatidylglycerol concentration may play a fundamental role in the surfactant function and metabolism depending on the presence of so-called cofactors like calcium and magnesium; further study is needed to clarify the mechanisms involved.
Selective Blockade of the Intermediate-Conductance Ca
2+
-Activated K
+
Channel Suppresses Proliferation of Microvascular and Macrovascular Endothelial Cells and Angiogenesis In Vivo
Authors: Grgic Ivica , Eichler Ines , Heinau Philipp , Si Han , Brakemeier Susanne , Hoyer Joachim , Köhler Ralf
Published: January 2005

Objective—

Ca
2+
-activated K
+
(K
Ca
) channels have been proposed to promote mitogenesis in several cell types. Here, we tested whether the intermediate-conductance K
Ca
channel (IKCa1) and the large-conductance K
Ca
channel (BK
Ca
) contribute to endothelial cell (EC) proliferation and angiogenesis.

Material and Results—

Function and expression of IKCa1 and BK
Ca
/
Slo
were investigated by patch-clamp analysis and real-time RT-PCR in human umbilical vein ECs (HUVECs) and in dermal human microvascular ECs 1 (HMEC-1). HMEC-1 expressed IKCa1 and BK
Ca
/
Slo
, whereas HUVECs expressed IKCa1. A 48-hour exposure to basic fibroblast growth factor (bFGF) augmented IKCa1 current amplitudes and induced a 3-fold increase in IKCa1 mRNA expression in HUVECs and HMEC-1. Vascular endothelial growth factor (VEGF) was also effective in upregulating IKCa1. BK
Ca
/
Slo
expression and current amplitudes in HMEC-1 were not altered by bFGF. bFGF- and VEGF-induced EC proliferation was suppressed by charybdotoxin, clotrimazole, or the selective IKCa1 blocker 1-[(2-chlorophenyl)diphenylmethyl]-1
H
-pyrazole (TRAM-34), whereas inhibition of BK
Ca
/
Slo
by iberiotoxin was ineffective. In the Matrigel plug assay in mice, administration of TRAM-34 for 2 weeks significantly suppressed angiogenesis by ≈85%.

Conclusions—

bFGF and VEGF upregulate expression of IKCa1 in human ECs. This upregulation of IKCa1 seems to be required for mitogen-induced EC proliferation and angiogenesis in vivo. Selective IKCa1 blocker might be of therapeutic value to prevent tumor angiogenesis.