bluuebunny/crossref_metadata_2025_split huggingface dataset:
A double‐blind, placebo‐controlled investigation of the residual psychomotor and cognitive effects of zolpidem‐MR in healthy elderly volunteers
Authors: Hindmarch Ian , Legangneux Eric , Stanley Neil , Emegbo Steve , Dawson Jean 
Published: July 2006

AimTo assess residual psychomotor and cognitive effects of a modified‐release formulation of zolpidem (zolpidem‐MR), developed to provide sustained hypnotic efficacy during the whole night, compared with placebo and flurazepam.MethodsTwenty‐four healthy elderly volunteers received four study treatments (zolpidem‐MR 6.25 mg and 12.5 mg, placebo and flurazepam 30 mg) using a randomized, cross‐over, double‐blind design. Residual psychomotor and cognitive effects were assessed with a psychometric test battery. Quality of sleep and residual effects were evaluated subjectively with the Leeds Sleep Evaluation Questionnaire.ResultsPsychometric performance was significantly impaired with flurazepam but not with zolpidem‐MR at either dose. Ease of falling asleep and sleep quality were significantly improved with both doses of zolpidem‐MR and with flurazepam. Neither active drug modified perception of well‐being on awakening.ConclusionIn elderly subjects, zolpidem‐MR showed no residual functional impairment in psychometric or cognitive tests sensitive to flurazepam,
Evidence for extrathymic T cell maturation after thymectomy in infancy
Authors: Torfadottir H , Freysdottir J , Skaftadottir I , Haraldsson A , Sigfusson G , Ogmundsdottir H M 
Published: July 2006

Summary
Our previous study showed that children who had been partially or completely thymectomized during heart surgery as infants had lower proportions and numbers of total lymphocytes and reduced proportions of T cells (CD3+), helper T cells (CD4+) and naive T cells (CD3+ CD4+ CD45RA+), but normal proportion of cytotoxic T cells (CD8+). In this study T lymphocytes from a selected group of eight of these children and age- and gender-matched controls were characterized further using flow cytometry to determine phenotypes of T cells and T cell subsets related to T cell regulation and phenotypes suggestive of extrathymic maturation. Immune function was assessed by measuring autoantibodies and antibodies against vaccines. The study group had significantly lower numbers of all the main subsets of T lymphocytes and the composition was different. Thus, the proportions of lymphocytes with the following phenotypes: CD3+, CD2+, CD7+, CD4+, CD62L+, CD4+ CD62L+ and CD4+ CD69– were significantly reduced in the study group compared with the control group, but significantly higher proportions were seen of lymphocytes expressing CD8α+ CD8β– and TCRγδ+ CD8α+ CD8β–. The absolute number and proportion of CD4+ CD25+ cells were reduced but the proportions of the subgroup of naive regulatory T cells (CD4+ CD25+ CD62L+) and non-activated regulatory T cells (CD4+ CD25+ CD69–) were not reduced in the thymectomized children. We conclude that the phenotypic characteristics of T lymphocytes of children who have lost their thymus in infancy are indicative of extrathymic maturation. T regulatory cells appear to be less affected than other subsets by the general reduction in T cell numbers.
The emergence of Beijing family genotypes ofMycobacterium tuberculosisand low-level protection by bacille Calmette–Guérin (BCG) vaccines: is there a link?
Authors: Abebe F , Bjune G 
Published: July 2006

SummaryThe world is confronted with major tuberculosis (TB) outbreaks at a time when the protection of bacillus Calmette–Guérin (BCG) vaccine has become inconsistent and controversial. Major TB outbreaks are caused by a group of genetically similar strains of Mycobacterium tuberculosis (Mtb) strains, including the Beijing family genotypes. The Beijing family genotypes exhibit important pathogenic features such high virulence, multi-drug resistance and exogenous reinfection. These family strains have developed mechanisms that modulate/suppress immune responses by the host, such as inhibition of apoptosis of infected macrophages, diminished production of interleukin (IL)-2, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and elevated levels of IL-10 and IL-18. They demonstrate distinct expression of proteins, such as several species of α-crystallin (a known Mtb virulence factor), but decreased expression of some antigens such as heat shock protein of 65 kDa, phosphate transport subunit S and a 47-kDa protein. In addition, the Beijing family strains specifically produce a highly bioactive lipid (a polyketide synthase)-derived phenolic glycolipid. This altered expression of proteins/glycolipids may be important factors underlying the success of the Beijing family strains. The Beijing family strains are speculated to have originated from South-east Asia, where BCG vaccination has been used for more than 60 years. The hypothesis that mass BCG vaccination may have been a selective factor that favoured genotypic and phenotypic characteristic acquired by the Beijing family strains is discussed.
Effect of kidney transplantation on bone
Authors: Kodras K. , Haas M. 
Published: July 2006

AbstractA broad range of different factors aggravates renal osteodystrophy, which is present in virtually all patients with chronic kidney disease and after successful kidney transplantation. Altered hormonal status, including sex hormones and parathyroid hormone (PTH), a deficit of 1,25(OH)2 vitamin D3(calcitriol), immunosuppressive therapy and post‐operative immobilization contribute to a progressive loss of bone density and structure. The decrease of bone mass is particularly prominent during the first 6 months after kidney transplantation and is associated with an increased number of fractures, both compared with the normal population as well as with dialysis patients. At particular risk are patients with a history of diabetes, long duration of haemodialysis and post‐menopausal women.To prevent post‐transplant bone loss prescription of steroids should be minimized and withdrawn as early as possible. Additional intake of α‐calcidol [25(OH) vitamin D3] or calcitriol, despite normal serum levels, reduces persistent hyperparathyroidism after kidney transplantation, improves intestinal calcium absorption and activates osteoblasts. Inhibition of osteoclasts by biphosphonate therapy seems to effectively reverse bone loss during the early and late course of kidney transplantation. However, as the majority of transplant recipients have a low‐turnover bone disease, inhibition of osteoclasts, through which bone turnover is impaired, might further reduce osteoblast activity and promote osteoid synthesis.Most investigations were small‐scale studies with 10–100 participants and a follow up of only 12 months. This makes conclusions on the effect of any intervention on the fracture rate impossible. Larger, randomized multicentre studies investigating bone‐sparing therapy on hard end points are therefore advocated.
Function and effect of bone morphogenetic protein‐7 in kidney bone and the bone‐vascular links in chronic kidney disease
Authors: Mathew S. , Davies M. , Lund R. , Saab G. , Hruska K. A. 
Published: July 2006

AbstractIn two independent and separate studies, we have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreased the serum phosphate. In the first study, the serum Ca PO4, parathyroid hormone (PTH), and calcitriol were maintained normal after renal ablation in mice, and even mild renal injury equivalent to stage 3 CKD decreased bone formation rates. More recently, these observations were rediscovered in low‐density lipoprotein receptor null (LDLR‐/–) mice fed high‐fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia and insulin resistance). We demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial calcification. We have also shown that VC is made worse by CKD and ameliorated by bone morphogenetic protein‐7 (BMP‐7). The finding that high‐fat fed LDLR‐/– animals with CKD had hyperphosphatemia which was prevented in BMP‐7‐treated animals lead us to examine the skeletons of these mice. It was found that significant reductions in bone formation rates were associated with high‐fat feeding, and superimposing CKD resulted in the adynamic bone disorder (ABD), while VC was made worse. The effect of CKD to decrease skeletal anabolism (decreased bone formation rates and reduced number of bone modelling units) occurred despite secondary hyperparathyroidism. The BMP‐7 treatment corrected the ABD and hyperphosphatemia, owing to BMP‐7‐driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action.Thus, in the metabolic syndrome with CKD, a reduction in bone forming potential of osteogenic cells leads to the ABD producing hyperphosphatemia and VC, processes ameliorated by BMP‐7, in part through increased bone formation and skeletal deposition of phosphate and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury affecting the skeleton before demonstrable hyperphosphatemia and that they are preventable and treatable. Therefore, early intervention in the skeletal disorder associated with CKD is warranted and may affect mortality of the disease.
Vascular calcification and renal osteodystrophy relationship in chronic kidney disease
Authors: Moe S. M. 
Published: July 2006

AbstractCardiovascular disease and stroke account for 60–70% of all deaths in patients with end‐stage renal disease (ESRD), at a risk that is 10–20‐fold the age‐ and sex‐matched general population. There is also increased coronary artery calcification and increased cardiovascular mortality in chronic kidney disease (CKD) and dialysis patients compared with the general population. Bone is similarly abnormal in CKD. There is an increased incidence of low bone mass and fractures in dialysis patients compared with the general population. Furthermore, a hip fracture in a dialysis patient is associated with a doubling of the mortality observed in nondialysis patients with a hip fracture. These two problems may be linked, as cross‐sectional studies have demonstrated an inverse relationship between osteoporosis and coronary artery calcification in the general population and in ESRD patients. In vitro and ex vivo, there is clear evidence that vascular calcification is an active cell‐mediated process, made worse by disorders of mineral metabolism. Many factors known to be associated with cardiovascular disease in CKD patients can directly increase calcification in vitro. In addition, in CKD, there are many mechanisms by which bone may adversely affect vascular calcification including disorders of bone remodelling, altered secretion of parathyroid hormone (PTH), hyperphosphatemia, hypercalcaemia, use of calcium based binders, and excessive vitamin D therapy. The coexistence of vascular risk factors and abnormal bone represent a double threat to the well being of patients with CKD.
In situ growth stimulation of a temperate zone liana (Hedera helix) in elevated CO2
Authors: ZOTZ G. , CUENI N. , KÖRNER C. 
Published: July 2006

Summary

Lianas, which arguably benefit more than other growth forms from elevated CO2, have been associated with increasing turn‐over rates in tropical forests as observed in recent decades. Although rarely as prominent outside the tropics, an increase in abundance of climbing plants is likely to affect forest dynamics in the temperate zone as well. Hedera helix is the most abundant climber in western Europe and previous work in controlled conditions suggested CO2 effects similar to those observed in tropical lianas.
Here we present an in situ test of the hypothesis that this abundant climber will benefit from increasing CO2 concentrations primarily under light limitation in the forest understorey, but much less in the forest canopy. To this end, we studied growth responses to elevated CO2 for an entire growing season at the Swiss Canopy Crane site on the forest floor and 20–25 m above the ground in the forest canopy.
The relative stimulation of length and biomass increment of shoots by elevated CO2 (about 600 µl l−1) was indeed very pronounced in deep shade (c. +60%), about twice as much as in the subcanopy (c. +30%). Given the rapid depletion of non‐structural carbohydrate (NSC) pools at canopy closure in spring, carbon limitation under current ambient CO2 concentrations must be substantial in the understorey. In contrast to the understorey, where CO2 enrichment had no effect on NSC pools, there was a sharp increase in NSC concentration in subcanopy leaves exposed to elevated CO2.
We conclude that rising CO2 concentrations will allow Hedera to explore light‐limited understorey microhabitats more vigorously, which should increase the likelihood of reaching the forest canopy. There, however, Hedera benefits less from elevated CO2. Our results add one more explanation to Hedera's current success in European forests.
Immune challenge reduces reproductive output and growth in a lizard
Authors: ULLER T. , ISAKSSON C. , OLSSON M. 
Published: July 2006

SummaryA fundamental assumption in evolutionary immunology is that the immune system is costly to develop, maintain or activate.Two plausible costs of activation of the immune system are decreased resources for growth and reproductive investment. However, few studies have estimated direct effects of an immune challenge, in particular in ectotherm vertebrates. We studied the consequences of an immune challenge in reproductive female dragons,Ctenophorus fordi, and in their offspring by exposing lizards to bacterial lipopolysaccharides (LPS).The immune challenge led to decreased reproductive investment in terms of egg mass, but with no effect on probability of future reproduction.Maternal immune challenge did not influence the response of their offspring to the same challenge. However, juveniles that were induced to mount an immune response had a higher thermal preference and showed reduced growth, but the magnitude of the growth effect was dependent on the date of oviposition, indicating maternal effects on offspring immunity.Our results suggest that costs of immune activation may be important in shaping growth and reproductive strategies in ectotherms.
Presence of shelter reduces maintenance metabolism of juvenile salmon
Authors: MILLIDINE K. J. , ARMSTRONG J. D. , METCALFE N. B. 
Published: July 2006

SummaryShelter is of major importance to many animals in providing protection against both the physical environment and potential predators.We hypothesized that animals without shelter suffer metabolic costs associated with a need for increased vigilance and preparedness to escape attacks from predators or competitors. This possibility was tested by comparing the standard metabolic rates of inactive postdigestive juvenile Atlantic salmon,Salmo salar, held either with or without a shelter, which took the form of a semicircular ledge under which the fish could fit comfortably.The ledges were semitransparent (so did not substantially reduce light levels) and provided no protection against the minimal water velocities in the testing arena. Nonetheless, absence of ledge shelter resulted in a 30% higher rate of oxygen consumption.Fish without a ledge shelter typically positioned themselves against vertical walls of the observation arena, which presumably afforded the best available sheltering option, and adopted a significantly darker coloration (indicative of greater stress) than those under ledges. Fish with ledges rested outside and adjacent to rather than beneath the shelter. Therefore, it seems that awareness that a shelter is readily available, rather than the act of sheltering, results in reduced metabolism.We conclude that the presence of appropriate shelter not only reduces the risk of predation but also provides a metabolic benefit to fish that is likely to have implications for growth performance and activity budgets. Standard metabolic rate can be a function of habitat structure.
Effect of immune serum and role of individual Fcγ receptors on the intracellular distribution and survival of Salmonella enterica serovar Typhimurium in murine macrophages
Authors: Uppington Hazel , Menager Nathalie , Boross Peter , Wood James , Sheppard Mark , Verbeek Sjef , Mastroeni Pietro 
Published: July 2006

SummaryImmune serum has a protective role against Salmonella infections in mice, domestic animals and humans. In this study, the effect of antibody on the interaction between murine macrophages and S. enterica serovar Typhimurium was examined. Detailed analysis at the single‐cell level demonstrated that opsonization of the bacteria with immune serum enhanced bacterial uptake and altered bacterial distribution within individual phagocytic cells. Using gene‐targeted mice deficient in individual Fc gamma receptors it was shown that immune serum enhanced bacterial internalization by macrophages via the high‐affinity immunoglobulin G (IgG) receptor, Fc gamma receptor I. Exposure of murine macrophages to S. enterica serovar Typhimurium opsonized with immune serum resulted in increased production of superoxide, leading to enhanced antibacterial functions of the infected cells. However, opsonization of bacteria with immune serum did not increase either nitric oxide production in response to S. enterica serovar Typhimurium or fusion of phagosomes with lysosomes.
Altered localization of CXCL13 expressing cells in mice deficient in Pactolus following an inflammatory stimulus
Authors: Hojgaard Andrias , Close Rebecca , Dunn Dianne M. , Weiss Robert B. , Weis Janis J. , Weis John H. 
Published: July 2006

SummaryThe mouse Pactolus gene is an evolutionary paralogue to the CD18/β2 integrin subunit and is preferentially expressed by neutrophils. When first identified, it was assumed Pactolus would function as an adhesion receptor similar to other β integrin subunits. The analysis of mice genetically deficient in Pactolus, however, did not define any lesion in neutrophil migration, adhesion or phagocytosis. Therefore a wider analysis of the Pactolus deficiency was initiated using transcriptional profiling during an inflammatory insult. This screen identified a single transcript, CXCL13, that was elevated in cells from a peritoneal lavage of the wild type animal compared to the Pactolus‐deficient animal. Our analyses confirmed resident macrophages as being responsible for the chemokine using intracellular CXCL13 staining and additional cell markers to phenotypically characterize such cells. The resident CXCL13‐expressing cells (which do not express Pactolus) are functionally distinct from the macrophages recruited into the peritoneal cavity following the inflammatory stimulation since the recruited macrophages do not express detectable levels of the chemokine. The numbers and expression patterns of these resident CXCL13‐expressing cells do not vary in naïve animals of wild type or Pactolus‐deficient origin. Additionally, Pactolus‐deficient neutrophils do not preferentially kill (compared to wild type) CXC13‐expressing macrophages. These data suggest that during an inflammatory response, Pactolus may help retain CXCL13‐expressing cells within the peritoneal environment.
Increased expression of ribosome recycling factor is responsible for the enhanced protein synthesis during the late growth phase in an antibiotic‐overproducing Streptomyces coelicolor ribosomal rpsL mutant
Authors: Hosaka Takeshi , Xu Jun , Ochi Kozo 
Published: July 2006

SummaryK88E mutation within rpsL, which encodes the S12 ribosomal protein, enhanced the protein synthetic activity of Streptomyces coelicolor during the late growth phase, resulting in overproduction of the deep blue‐pigmented polyketide antibiotic actinorhodin. In vitro cross‐mixing experiments using the ribosomal and S‐150 fractions derived from wild‐type and K88E mutant strains suggested that one or more translation factors are enriched in the mutant's S‐150 fraction, while Western analysis using antibodies against various translation factors revealed ribosome recycling factor (RRF) to be one of the enriched mediators. RRF purified from overexpressing cells stimulated mRNA‐directed green fluorescent protein (GFP) synthesis in an in vitro protein synthesis system. GFP synthesis rates were complemented by RRF addition into wild‐type cell's S‐150 fraction, eliminating the difference between wild‐type and mutant S‐150 fractions. The frr gene encoding RRF was found to be transcribed from two distinct start points (frrp1 and frrp2), and increased expression from frrp1 could account for the elevated level of RRF in the K88E mutant during the late growth phase. Moreover, introduction of a plasmid harbouring a high copy number of frr gene into wild‐type S. coelicolor induced remarkable overproduction of antibiotic, demonstrating that the increased levels of RRF caused by the K88E mutation is responsible for an aberrant stationary‐phase event: overproduction of antibiotic.
The nitrosative stress response of Staphylococcus aureus is required for resistance to innate immunity
Authors: Richardson Anthony R. , Dunman Paul M. , Fang Ferric C. 
Published: July 2006

Summary Staphylococcus aureus is a highly virulent human pathogen with an extensive array of strategies to subvert the innate immune response. An important aspect of innate immunity is the production of the nitrogen monoxide radical (Nitric Oxide, NO·). Here we describe an adaptive response to nitrosative stress that allows S. aureus to replicate at high concentrations of NO·. Microarray analysis revealed 84 staphylococcal genes with significantly altered expression following NO· exposure. Of these, 30 are involved with iron‐homeostasis, potentially under the control of the Fur regulator. Another seven induced genes are involved in hypoxic/fermentative metabolism, including the flavohaemoprotein, Hmp. The SrrAB two‐component system has been shown to regulate the expression of many of the NO·‐induced metabolic genes. Indeed, inactivation of hmp, srrAB and fur resulted in heightened NO· sensitivity. Hmp was responsible for c. 90% of measurable staphylococcal NO· consumption and therefore critical for efficient NO· detoxification. While SrrAB was required for maximal hmp expression, srrAB mutants still exhibited significant NO· scavenging and NO·‐dependent induction of hmp. Yet S. aureus lacking SrrAB were more sensitive to nitrosative stress than hmp mutants, indicating that the contribution of SrrAB to NO· resistance extends beyond the regulation of hmp expression. Both Hmp and SrrAB were required for full virulence in a murine sepsis model, however, only the attenuation of the hmp mutant was restored by the abrogation of host NO· production. Thus, the S. aureus Hmp protein has evolved to serve as an iNOS‐dependent virulence determinant.