bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of endothelial function by pulse contour analysis: a protocol for drug administration and timing of pulse contour assessment
Authors: Gordon Sarah E. , Cartwright Neil , Griffiths Mark J. D. 
Published: June 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Pulse contour analysis is a relatively new technique used for non‐invasive assessment of endothelial function.• Endothelial dysfunction is a component of a number of common conditions including hypertension, diabetes mellitus and a variety of inflammatory conditions.• A standardized method for assessing endothelial function using pulse contour analysis is required to allow comparison between studies. WHAT THIS STUDY ADDS • This study recommends the optimal dose of vasoactive agents and timing of measurements for the assessment of endothelial function using pulse contour analysis.AIMSPulse contour analysis (PCA) obtained by finger photoplethysmography produces a digital volume pulse (DVP) including an inflection point in its down‐slope. The reflection index (RI: ratio of the inflection point height over the maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose and time interval for assessing endothelial function using PCA in healthy volunteers and patients with severe coronary artery disease.METHODSTime and dose to RI response relationships were constructed in 16 volunteers and nine patients to inhaled salbutamol (100–400 µg) or sublingual nitroglycerin (NTG; 25–400 µg).RESULTSFor the volunteers, the time to maximum RI response to inhaled salbutamol and sublingual NTG was 10.73 ± 0.41 and 3.66 ± 0.21 min, respectively. A plateau in the RI response to salbutamol occurred between 5 and 15 min after inhalation and results were averaged over this period. A dose‐dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05 and P < 0.001 by repeated‐measures anova, respectively) in healthy volunteers. By contrast, in patients with severe coronary artery disease inhaled salbutamol (100–400 µg) did not cause a significant change in RI.CONCLUSIONSIn healthy volunteers the RI response to inhaled salbutamol (100–200 µg) averaged over 5–15 min after administration may be used to investigate endothelial function by PCA. The response to sublingual NTG (50 µg) should be determined at 4 min. This technique may not be suitable for the assessment of endothelial function in subjects with extensive coronary artery disease owing to the small responses observed and potential confounding effect of vasoactive medication.
Short term effects of spironolactone on blood lipid profile: a 3‐month study on a cohort of young women with hirsutism
Authors: Nakhjavani Manouchehr , Hamidi Sepehr , Esteghamati Alireza , Abbasi Mehrshad , Nosratian‐Jahromi Simindokht , Pasalar Parvin 
Published: June 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Spironolactone is known to have antiandrogenic features and agonist activity at progesterone receptors, which are responsible for several of its hormonal side‐effects.• The potential unfavourable influences of this medication on serum lipoproteins have long been a concern but literature lacks sufficient data on this issue. WHAT THIS STUDY ADDS • Spironolactone can adversely affect serum lipids by decreasing high‐density lipoprotein and increasing low‐density lipoprotein in women treated for hirsutism on a short‐term basis.AIMSTo investigate the effects of spironolactone on serum lipids in women with hirsutism over a 3‐month period.METHODSIn a prospective setting, 27 hirsute women (20 with polycystic ovary syndrome and seven with idiopathic hirsutism) with a mean age of 23.0 ± 5.1 years were studied at baseline and 3 months after receiving a daily dose of 100 mg of spironolactone. Patients did not receive any other medications and did not go through a specific diet during the study. Lipid profile, fasting blood glucose, testosterone, dehydroepiandrosterone sulphate (DHEAS) and prolactin (PRL) were measured at baseline and 3 months after therapy.RESULTSMean body mass index of patients was 26.1 ± 5.1 kg m−2 before treatment and 25.9 ± 5.7 kg m−2 after treatment (NS). The therapy was associated with a significant decline of mean high‐density lipoprotein (HDL), 39.5 mg dl−1[95% confidence interval (CI) 35.6, 43.4]vs. 32.2 mg dl−1 (95% CI 29.2, 35.2), and a significant increase in mean low‐density lipoprotein (LDL), 133.1 mg dl−1 (95% CI 120.2, 146) vs. 150.8 mg dl−1 (95% CI 139.1, 162.5), and cholesterol/HDL ratio, 5 (95% CI 4.4, 5.6) vs. 6.4 (95% CI 5.7, 7.1) (P < 0.05). No significant change was noted in total cholesterol, triglyceride or fasting blood glucose levels. Serum values of testosterone, DHEAS and PRL decreased significantly after 3 months of therapy (P < 0.05).CONCLUSIONSSpironolactone might have adverse effects on serum lipoprotein levels by increasing LDL and decreasing HDL over a short course of treatment. While treating hirsutism with spironolactone, special care should be given to women with metabolic disorders such as dyslipidaemia.
Calcitonin and carcinoembryonic antigen doubling times as prognostic factors in medullary thyroid carcinoma: a structured meta‐analysis
Authors: Meijer Johannes A. A. , Le Cessie Saskia , Van Den Hout Wilbert B. , Kievit Job , Schoones Johannes W. , Romijn Johannes A. , Smit Johannes W. A. 
Published: June 2009

SummaryContext  In the management of patients with medullary thyroid carcinoma (MTC), calcitonin doubling time (dt) has gained interest as an independent predictor of recurrence and survival.Objective  To perform a structured meta‐analysis of the diagnostic value of calcitonin dt, carcinoembryonic antigen (CEA) dt and the combination and to define dt strata with the highest predictive power.Design  The study was a meta‐analysis using individual data.Methods  Ten studies containing data on the post‐operative kinetics of tumour marker(s) and (recurrence free) survival were included.Results  Calcitonin‐ and CEA‐dt are significant indicators for survival (hazard ratios (HR) 21·52 respectively infinite for dt 0–1 year compared to dt >1 year) and recurrence (HR 5·33 respectively 6·80 for dt 0–1 year compared to dt >1 year). The highest predictive power was found for the dt classification 0–1 year vs. >1 year. CEA dt has a higher predictive value than calcitonin dt in the subgroup of patients for which both parameters were available.Conclusion  The dts of both calcitonin and CEA are strong prognostic indicators for MTC recurrence and death. CEA dt has a higher predictive value than calcitonin dt and therefore measuring both tumour markers is essential for proper risk stratification.
Despite their apparent integration, spur length but not perianth size affects reproductive success in the moth‐pollinated orchidPlatanthera bifolia
Authors: Boberg Elin , Ågren Jon 
Published: June 2009

Summary1. The evolution of many floral traits is thought to have been shaped by pollinator‐mediated selection for increased attractiveness or an improved mechanical fit of flowers to pollinators. Yet, few studies have examined experimentally the independent and interactive effects of different aspects of flower morphology on plant reproductive success.2. In the orchidPlatanthera bifolia,perianth size and spur length are positively correlated within and among populations. To test the hypothesis that pollination success and seed output increases with increasing perianth size and spur length, we manipulated the two traits in a factorial design in a long‐spurred population ofP. bifoliapollinated by long‐tongued hawkmoths. Additionally, to determine whether differences in selfing rate can explain variation in fruit set and fruit size, we performed controlled self‐ and cross‐pollination.3. Plants with long spurs had more flowers pollinated, more pollen removed and produced more and larger fruits compared to plants with short spurs. In contrast, perianth size did not affect the pollination success or fruit production ofP. bifolia.4. Fruit production and fruit size did not differ among flowers pollinated with self‐ and cross pollen, respectively. This indicates that reduced pollen deposition rather than pollinator‐mediated self‐pollination caused the reduction in fruit set and fruit volume observed after shortening of the spur.5. The results demonstrate that spur length, but not perianth size, is critical for reproductive success inP. bifolia, and suggest that among‐population differentiation in perianth size may reflect a correlated response to selection on spur length. The results are consistent with the hypothesis that visual display is less important than other cues for the reproductive success ofP. bifolia, and underscore the necessity to experimentally examine the functional significance of putatively adaptive traits.
Ecological and physiological determinants of dive duration in the freshwater crocodile
Authors: Campbell Hamish A. , Sullivan Scott , Read Mark A. , Gordos Mathew A. , Franklin Craig E. 
Published: June 2009

Summary 1.
Body mass is a key determinant of diving performance in endotherms. In air‐breathing ectotherms however, this paradigm occurs with considerably less force. Here, through remote recordings of dive behaviour over a wide size range (5–42 kg body mass, n = 17) of freshwater crocodiles (Crocodylus johnstoni), we demonstrate why body mass is such a poor determinant of dive duration for ectothermic divers. 2.
Crocodiles were released into the wild with a time‐depth‐recorder attached to their dorsal scutes, and a movement activated radio‐tag attached to their tail. Over 15 days, 652·6 ± 58·4 (mean ± SE, n = 17) dives were recorded, with all individuals exhibiting two specific dive‐types. These were, a resting‐dive (62·7 ± 5·4% of total dive no.), where no activity occurred during the dive, and an active‐dive (37·1 ± 6·3% of total no.) associated with swimming. 3.
The durations of resting‐dives (∼12 min) were similar for all crocodiles. Smaller crocodiles (6·3 ± 0·7 kg, mean ± SE, n = 9) exhibited a significant correlation between dive duration and post‐dive surface‐interval, whilst larger crocodiles (17·9 ± 3·75 kg, mean ± SE, n = 8) did not. This demonstrated that aerobic dive duration was mass‐specific during resting‐dives, but other mass specific factors, presumably ecological, determined dive duration. 4.  The durations of active‐dives were never >1 min, showed no relationship with body mass and no correlation with the post‐dive‐surface interval. In crocodiles, aerobic metabolic scope is independent of body mass but anaerobic capacity is mass dependent, suggesting that active‐dive duration was determined by sustained activity and dives were terminated before anaerobic metabolism became significant. 5.  All individuals showed similar diel phase shifts in dive duration, type and depth, illustrating the overwhelming influence of the external environment on dive behaviour. Dive durations which resulted in significant anaerobic debt occurred rarely, but were undertaken in response to a potential threat. 6.
Body mass was a poor predictor of diving in C. johnstoni because the external environmental and ecological factors exerted a greater influence on dive duration than oxygen reserves.
The return of the vole cycle in southern Finland refutes the generality of the loss of cycles through ‘climatic forcing’
Authors: BROMMER JON E. , PIETIÄINEN HANNU , AHOLA KARI , KARELL PATRIK , KARSTINEN TEUVO , KOLUNEN HEIKKI 
Published: June 2009

AbstractMultiannual cycles in the abundance of voles and other animals have been collapsing in the last decades. It has been proposed that this phenomenon is ‘climatically forced’ by milder winters. We here consider the dynamics of bank and field voles during more than two decades in two localities (170 km apart) in southern Finland. Using wavelet analysis, we show that a clear 3‐year cycle disappeared in the mid 1990s. However, the vole cycle returned in both localities after about 5 years despite winters becoming increasingly milder. In both localities, vole cycles were mainly determined by bank voles after the period of noncyclic dynamics, whereas field voles were dominant before this irregularity. Wavelet coherency analysis shows that spatial synchrony temporarily broke down during the period of noncyclic dynamics, but was fully restored afterwards. The return of the cycle despite ongoing rapid climate change argues against ‘climatic forcing’ as a general explanation for loss of cycles. Rather, the population‐dynamical consequences of climate change may be dependent on the local species composition and mechanism of delayed density dependence.
Soil organic carbon stocks in Laos: spatial variations and controlling factors
Authors: CHAPLOT VINCENT , BOUAHOM BOUNTHONG , VALENTIN CHRISTIAN 
Published: June 2009

AbstractSurface soils, which contain the largest pool of terrestrial organic carbon (C), may be able to sequester atmospheric C and thus mitigate climate change. However, this remains controversial, largely due to insufficient data and knowledge gaps in respect of organic C contents and stocks in soils and the main factors of their control. Up to now and despite numerous evaluations of soil organic carbon (SOC) stocks worldwide, the sloping lands of southeast Asia, one of the most biogeochemically active regions of the world, remain uninvestigated. Our main objective was to quantify SOC stocks and to evaluate the impact of various environmental factors. We, therefore, selected Laos with 230 566 km2of mostly forested steep slopes, and where cultivation is still mainly traditional, i.e. a system of shifting cultivation without fertilization or mechanical tillage. Analytical data from 3471 soil profiles demonstrated that the top 1 m of soil depth holds an estimated 4.64 billion tons of SOC, 65% of which is in the first 0.3 m. SOC stocks to 0.3 m exhibit a high coefficient of variation (CV=62%) with values from 1.8 to 771 Mg C ha−1and a mean at 129 Mg C ha−1. Furthermore, these stocks are significantly (atP<0.05 level) affected by land use as shown by principal components analysis andt‐tests with the largest amount being found under forest, less under shifting cultivation and the smallest under continuous cultivation. Moreover, SOC stocks correlated regionally to total annual rainfalls and latitude, and locally at the hill‐slope level to the distance to the stream network and the slope angle. It is hypothesized that this correlation is through actions on mineral weathering, soil clay content, soil fertility and SOC redistributions in landscapes. These relationships between SOC stocks and environmental factors may be of further use in (1) predicting the impact of global changes on future SOC stocks; and (2) identifying optimal strategies for land use planning so as to minimize soil C emissions to the atmosphere while maximizing carbon sequestration in soils.
Immunological aspects and therapeutic significance of an autoantibody against histone H1 in a rat model of concanavalin A‐induced hepatitis
Authors: Nakano Toshiaki , Goto Shigeru , Lai Chia‐Yun , Hsu Li‐Wen , Takaoka Yuki , Kawamoto Seiji , Chiang Kuei‐Chen , Shimada Yayoi , Ohmori Naoya , Goto Takeshi , Sato Shuji , Ono Kazuhisa , Cheng Yu‐Fan , Chen Chao‐Long 
Published: June 2009

SummaryWe previously demonstrated the immunosuppressive activity of anti‐histone H1 autoantibody induced in experimental and clinical liver allograft tolerance. This study aimed to explore the immunological aspects of anti‐histone H1 autoantibody in liver injury induced by concanavalin A (Con A). To establish a Con A‐hepatitis model, 20 mg/kg Con A was intravenously injected into rats, after which liver function and histopathological analyses were performed. In this model, anti‐histone H1 autoantibody was transiently induced in the sera during the natural recovery stage, 3–7 days after Con A injection. To evaluate the therapeutic significance of anti‐histone H1 autoantibody, a polyclonal antibody against histone H1 was intraperitoneally injected immediately after Con A injection. We found that injection of anti‐histone H1 antibody could reduce Con A‐induced liver damage. Further mechanical analyses revealed that anti‐histone H1 antibody altered the intracellular activation of mitogen‐activated protein kinase, nuclear factor‐κB and calcineurin via T‐cell receptor signalling, suggesting that anti‐histone H1 antibody may protect the liver from Con A‐induced injury by inhibiting activation of effector T cells. These findings suggest that anti‐histone H1 autoantibody may be a natural immune regulatory factor that protects inflamed livers suffering from autoimmune hepatitis and may lead to T‐cell unresponsiveness through the selective regulation of mitogen‐activated protein kinase/nuclear factor‐κB and calcineurin signalling.
Cooperative action of CD8 T lymphocytes and natural killer cells controls tumour growth under conditions of restricted T‐cell receptor diversity
Authors: Shanker Anil , Buferne Michel , Schmitt‐Verhulst Anne‐Marie 
Published: June 2009

SummaryIn mice expressing a transgenic T‐cell receptor (TCR; TCRP1A) of DBA/2 origin with reactivity towards a cancer‐germline antigen P1A, the number of TCRP1A CD8+ T cells in lymphoid organs is lower in DBA/2 than in B10.D2 or B10.D2(× DBA/2)F1 mice. This reduction results from haemopoietic cell autonomous differences in the differentiation of the major histocompatibility complex class I‐restricted TCRP1A thymocytes controlled by DBA/2 versus B10.D2‐encoded genes. We report here that the lower number of TCRP1A CD8+ T cells in DBA/2 mice correlated with their poor resistance to P1A‐expressing mastocytoma solid tumours. Functional potency of CD8+ cytolytic T lymphocytes (CTL) from the above strains was not compromised, but their number after expansion appeared to be influenced by their genetic background. Intriguingly, non‐transgenic DBA/2 mice resisted P1A+ tumours more efficiently despite poor representation of P1A‐specific CTL. This was partly the result of their more heterogeneous TCR repertoire, including reactivity to non‐P1A tumour antigens because mice that had rejected a P1A+ tumour became resistant to a P1A− variant of the tumour. Such ‘cross‐resistance’ did not develop in the TCRP1A transgenic mice. Nonetheless, reconstitution of RAGº/º mice with TCRP1A CD8+ T cells, with or without CD4+ T cells, or exclusive representation of TCRP1A CD8+ T cells in RAGº/º TCRP1A transgenic mice efficiently resisted the growth of P1A‐expressing tumours. Natural killer cells present at a higher number in RAGº/º mice also contributed to tumour resistance, in part through an NKG2D‐dependent mechanism. Hence, in the absence of a polyclonal T‐cell repertoire, precursor frequencies of natural killer cells and tumour‐specific CTL affect tumour resistance.
Tumor necrosis factor‐α augments lipopolysaccharide‐induced suppressor of cytokine signalling 3 (SOCS‐3) protein expression by preventing the degradation
Authors: Dagvadorj Jargalsaikhan , Naiki Yoshikazu , Tumurkhuu Gantsetseg , Shadat Mohammod Noman Abu , Iftakhar‐E‐Khuda Imtiaz , Komatsu Takayuki , Koide Naoki , Yoshida Tomoaki , Yokochi Takashi 
Published: June 2009

SummaryThe regulatory role of tumour necrosis factor‐α (TNF‐α) on the expression of suppressor of cytokine signalling 3 (SOCS‐3) in response to lipopolysaccharide (LPS) was examined using peritoneal macrophages from TNF‐α‐deficient mice. The LPS‐induced SOCS‐3 expression was markedly augmented in macrophages from wild‐type mice whereas such augmentation was not seen in the cells from TNF‐α‐deficient mice. However, there was no significant difference in the level of SOCS‐3 messenger RNA expression between macrophages from wild‐type mice and those from TNF‐α‐deficient mice. The addition of exogenous TNF‐α augmented the LPS‐induced SOCS‐3 expression in macrophages from TNF‐α‐deficient mice. The pulse chase analysis suggested augmented degradation of LPS‐induced SOCS‐3 protein in macrophages from TNF‐α‐deficient mice. Moreover, MG 132, a 26S proteasome inhibitor, sustained the LPS‐induced SOCS‐3 expression in those cells. The tyrosine phosphorylation of SOCS‐3 was definitely induced in LPS‐stimulated macrophages from TNF‐α‐deficient mice but not wild‐type mice. A tyrosine phosphatase inhibitor enhanced the tyrosine phosphorylation of SOCS‐3 in wild‐type mice and accelerated the degradation. Therefore, it was suggested that TNF‐α prevented the degradation of SOCS‐3 protein via inhibition of the tyrosine phosphorylation in LPS‐stimulated macrophages.
Dissecting the essentiality of the bifunctional trypanothione synthetase‐amidase in Trypanosoma brucei using chemical and genetic methods
Authors: Wyllie Susan , Oza Sandra L. , Patterson Stephen , Spinks Daniel , Thompson Stephen , Fairlamb Alan H. 
Published: June 2009

SummaryThe bifunctional trypanothione synthetase‐amidase (TRYS) comprises two structurally distinct catalytic domains for synthesis and hydrolysis of trypanothione (N1,N8‐bis(glutathionyl)spermidine). This unique dithiol plays a pivotal role in thiol‐redox homeostasis and in defence against chemical and oxidative stress in trypanosomatids. A tetracycline‐dependent conditional double knockout of TRYS (cDKO) was generated in bloodstream Trypanosoma brucei. Culture of cDKO parasites without tetracycline induction resulted in loss of trypanothione and accumulation of glutathione, followed by growth inhibition and cell lysis after 6 days. In the absence of inducer, cDKO cells were unable to infect mice, confirming that this enzyme is essential for virulence in vivo as well as in vitro. To establish whether both enzymatic functions were essential, an amidase‐dead mutant cDKO line was generated. In the presence of inducer, this line showed decreased growth in vitro and decreased virulence in vivo, indicating that the amidase function is not absolutely required for viability. The druggability of TRYS was assessed using a potent small molecule inhibitor developed in our laboratory. Growth inhibition correlated in rank order cDKO, single KO, wild‐type and overexpressing lines and produced the predicted biochemical phenotype. The synthetase function of TRYS is thus unequivocally validated as a drug target by both chemical and genetic methods.
Viral vectors in malaria vaccine development
Authors: LIMBACH K. J. , RICHIE T. L. 
Published: June 2009

SummaryTraditional vaccine technologies have resulted in an impressive array of efficacious vaccines against a variety of infectious agents. However, several potentially deadly pathogens, including retroviruses and parasites, have proven less amenable to the application of traditional vaccine platforms, indicating the need for new approaches. Viral vectors represent an attractive way to deliver and present vaccine antigens that may offer advantages over traditional platforms. Due to their ability to induce strong cell‐mediated immunity (CMI) in addition to antibodies, viral vectors may be suitable for infectious agents, such as malaria parasites, where potent CMI is required for protection. Poxvirus‐vectored malaria vaccines have been the most extensively studied in the clinic, achieving significant reductions in liver‐stage parasite burden. More recently, adenovirus‐vectored malaria vaccines have entered clinical testing. The most promising approach – heterologous prime‐boost regimens, in which different viral vectors are sequentially paired with each other or with DNA or recombinant protein vaccines – is now being explored, and could provide high‐grade protection, if findings in animal models are translatable to humans. Significant barriers remain, however, such as pre‐existing immunity to the vector particle and an unexplained safety signal observed in one trial suggesting an increased risk of HIV acquisition in volunteers with pre‐existing immunity to the vector.