bluuebunny/crossref_metadata_2025 huggingface dataset:
Single step modified ink staining for Tzanck test: Quick detection of herpetic giant cells in Tzanck smear
Authors: MIZUTANI Hitoshi , AKEDA Tomoko , YAMANAKA Kei‐ichi , ISODA Kenichi , GABAZZA Esteban C.
Published: September 2011

Tzanck test has been recently re‐evaluated as a method for the diagnosis of herpes virus infection. Giemsa staining for the Tzanck test is time‐consuming and laborious. There is a need to develop simple and quick staining methods for bedside diagnosis of this disease. We report a single step and quick method for staining herpes giant cells in Tzanck smears using routinely available inks and physiological saline. A keratinocyte cell line (HaCaT) was cultured on a slide glass and stained with various commercially available blue, blue–black and black inks serially diluted with physiological saline. Clinical smear samples from herpes lesions were also stained with these solutions without specific pretreatment. The nuclei of HaCaT were clearly stained showing high contrast with the cytoplasm using 5% Parker–Quink blue–black ink saline solution. Concentration of ink solution higher or lower than 5% resulted in less contrast. Blue or black inks or other manufacturers’ inks can also be used, but staining of the cultured keratinocytes was less clear. Smear of clinical samples from herpes lesions were also stained with 5% ink solution. The nuclei of the multinucleated giant cells were clearly stained, and the sample could be immediately used for microscopic examination. One step staining of Tzanck smear using this diluted ink solution is an inexpensive and a convenient bedside diagnostic tool for the dermatologist.
Profile of vitiligo patients attending a training and research hospital in Central Anatolia: A retrospective study
Authors: GÖNÜL Müzeyyen , ÇAKMAK Seray K. , OĞUZ Deniz , GÜL Ülker , KILIÇ Selim
Published: September 2011

Clinical characteristics of vitiligo had been reported in different countries previously. This is the second report from Turkey and it is from a different region of Turkey, middle Anatolia, and a more detailed study. The age and sex of patients, onset age, duration, areas of involvement, course, clinical types and severity of the disease, family history of vitiligo, associated disorders, the values of vitamin B12, folic acid, ferritin, iron and hemoglobin, antithyroglobulin and antithyroid peroxidase antibodies and positivity of viral markers were obtained from the records of the patients retrospectively. The study involved 93 vitiligo patients with a mean age of 37.4 ± 17.05 years. The median age of onset disease was 33 years and onset age of disease was significantly lower in women. Of the patients, 24.8% had family history. The most frequent form of vitiligo was vitiligo vulgaris. Facial involvement was the most common localization. Trunk involvement was significantly higher in women but anogenital involvement was significantly higher in men. Of the patients, 40.3% had another autoimmune disease, 19.7% of the patients had low ferritin levels, 12% had low iron levels, 9.9% had anemia, 4.9% had low vitamin B12 levels, 3.8% had low folic acid levels and 4.3% had positivity of viral markers. The age of onset and the incidence of family history were higher and sites of involvement according to sex were different from the published work. The knowledge of clinical characteristics, course and associated conditions of vitiligo may improve the approach of dermatologists to vitiligo patients.
New strain typing method with Sporothrix schenckii using mitochondrial DNA and polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) technique
Authors: KAWASAKI Masako , ANZAWA Kazushi , MOCHIZUKI Takashi , ISHIZAKI Hiroshi
Published: September 2011

The complete sequences of mitochondrial DNA (mtDNA) from two strains of different genotypes, American Type Culture Collection 10268 of mtDNA type 1 and KMU2025 of mtDNA type 4, were determined. These are circular molecules, 27 125 and 26 095 bp in length, respectively. The greatest difference between the two strains was found in the region encompassed by atp9 and cox2 genes, which was amplified with polymerase chain reaction (PCR) and used for preliminary restriction fragment length polymorphism (RFLP) analysis. Eight isolates of five mtDNA types were used and RFLP patterns obtained with the restriction enzyme AseI showed that this method seems to have greater discrimination power than the other PCR–RFLP typing method using internal transcribed spacer regions of nuclear DNA.
Transcriptome analysis of muscle in horses suffering from recurrent exertional rhabdomyolysis revealed energetic pathway alterations and disruption in the cytosolic calcium regulation
Authors: Barrey E. , Jayr L. , Mucher E. , Gospodnetic S. , Joly F. , Benech P. , Alibert O. , Gidrol X. , Mata X. , Vaiman A. , Guérin G.
Published: September 2011

Recurrent exertional rhabdomyolysis (RER) is frequently observed in race horses like trotters. Some predisposing genetic factors have been described in epidemiological studies. However, the exact aetiology is still unknown. A calcium homeostasis disruption was suspected in previous experimental studies, and we suggested that a transcriptome analysis of RER muscles would be a possible way to investigate the pathway disorder. The purpose of this study was to compare the gene expression profile of RER vs. control muscles in the French Trotter to determine any metabolic or structural disruption. Total RNA was extracted from the gluteal medius and longissimus lumborum muscles after biopsies in 15 French Trotter horses, including 10 controls and 5 RER horses affected by ‘tying‐up’ with high plasmatic muscular enzyme activities. Gene expression analysis was performed on the muscle biopsies using a 25K oligonucleotide microarray, which consisted of 24 009 mouse and 384 horse probes. Transcriptome analysis revealed 191 genes significantly modulated in RER vs. control muscles (P < 0.05). Many genes involved in fatty acid oxidation (CD36/FAT,SLC25A17), the Krebs cycle (SLC25A11,SLC25A12,MDH2) and the mitochondrial respiratory chain were severely down‐regulated (tRNA,MT‐ND5, MT‐ND6, MT‐COX1). According to the down‐regulation ofRYR1,SLC8A1andUCP2and up‐regulation ofAPPandHSPA5, the muscle fibre calcium homeostasis seemed to be greatly affected by an increased cytosolic calcium and a depletion of the sarcoplasmic reticulum calcium. Gene expression analysis suggested an alteration of ATP synthesis, with severe mitochondrial dysfunction that could explain the disruption of cytosolic calcium homeostasis and inhibition of muscular relaxation.
Carbamazepine differentially affects the pharmacokinetics of fexofenadine enantiomers
Authors: Akamine Yumiko , Miura Masatomo , Yasui‐Furukori Norio , Kojima Midori , Uno Tsukasa
Published: September 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• We have shown that P‐glycoprotein (P‐gp) inhibitors such as itraconazole and verapamil significantly increase the plasma concentrations of fexofenadine enantiomers, and their effects are greater for (S)‐fexofenadine compared with the (R)‐enantiomer. These mechanisms are likely to be due to inhibition of intestinal P‐gp because the t1/2 and CLR were constant during the study, and suggest that intestinal P‐gp plays an important role in the pharmacokinetics of fexofenadine enantiomers. To date, there is no information whether the P‐gp inducer carbamazepine affects the pharmacokinetics of either fexofenadine enantiomer.

WHAT THIS STUDY ADDS

• This study indicates that the stereoselectivity of fexofenadine pharmacokinetics may be influenced by carbamazepine primarily due to the induction of intestinal P‐gp, and this effect may be greater for (S)‐fexofenadine compared with (R)‐fexofenadine. However, since the inductive effect of carbamazepine did not eliminate the difference between the pharmacokinetics of the fexofenadine enantiomers, it is likely that other transporters, including OATP2B1 and MRP2, also contribute to the stereoselective pharmacokinetics of fexofenadine.

AIM This aim of this study was to characterize the impact of the P‐glycoprotein (P‐gp) inducer, carbamazepine, on fexofenadine enantiomer pharmacokinetics.

METHODS Twelve healthy volunteers initially received a 60 mg dose of fexofenadine alone. Subsequently, a 100 mg dose of carbamazepine was administered three times daily (300 mg day−1), and on day 7, fexofenadine was co‐administered.

RESULTS Carbamazepine significantly decreased the area under the plasma concentration–time curve and the amount excreted into the urine of (S)‐ and (R)‐fexofenadine. The P‐gp inducer showed a greater effect on the pharmacokinetic parameters of (S)‐fexofenadine.

CONCLUSION This study indicates that carbamazepine may alter the pharmacokinetics of fexofenadine enantiomers.
African ancestry, early life exposures, and respiratory morbidity in early childhood
Authors: Kumar R. , Tsai H.‐J. , Hong X. , Gignoux C. , Pearson C. , Ortiz K. , Fu M. , Pongracic J. A. , Burchard E. G. , Bauchner H. , Wang X.
Published: September 2011

Background

Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors.

Objective

To evaluate the associations of genetic ancestry and self‐identified race with early childhood recurrent wheezing, accounting for socio‐economic status (SES) and early life exposures.

Methods

We studied 1034 children in an urban, multi‐racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self‐identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio‐economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles.

Results

Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02–1.31) was significantly associated with recurrent wheezing. By self‐reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19–1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14–1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05–1.34) and European ancestry (OR: 0.84, 95% CI: 0.74–0.94) retained a significant association with recurrent wheezing, as compared with self‐identified race (ORwhites: 0.31, 95% CI: 0.09–1.14; ORhispanic: 0.47, 95% CI: 0.20–1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing.

Conclusions and Clinical Relevance

In contrast to self‐identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and early life risk factors associated with childhood recurrent wheezing.
Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia–reperfusion injury in a rat syngenic kidney transplantation model
Authors: Cicora F , Roberti J , Vasquez D , Guerrieri D , Lausada N , Cicora P , Palti G , Chuluyan E , Gonzalez P , Stringa P , Raimondi C
Published: September 2011

Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia–reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty-four hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.
Atrial fibrillation and hyperthyroidism: relation between transoesophageal markers of a thrombogenic milieu and clinical risk factors for thromboembolism
Authors: de Souza Marcus Vinicius Leitão , Duarte Martha Maria Turano , Coeli Claudia Medina , Vaisman Mario
Published: September 2011

Hyperthyroidism is a questionable risk factor for thromboembolism among patients with atrial fibrillation.

Objective  To correlate clinical risk factors for thromboembolism from a group of patients with atrial fibrillation related to hyperthyroidism with transoesophageal echocardiography (TOE) markers of a thrombogenic milieu.

Design  Clinical risk factors for thromboembolism, thyroid hormonal status, time since diagnosis of hyperthyroidism and TOE markers of a thrombogenic milieu were assessed in consecutive patients with atrial fibrillation related to hyperthyroidism. The following TOE parameters were assessed to define the presence of thrombogenic milieu: dense spontaneous echo contrast, thrombi or left atrial appendage blood flow velocities <0·20 m/s. Clinical risk factors for thromboembolism were based on CHADS2 (Cardiac failure, Hypertension, Age, Diabetes and Stroke) classification.

Patients  This study included 31 consecutive patients aged between 18 and 65 years with atrial fibrillation related to hyperthyroidism scheduled for TOE.

Results  Thrombogenic milieu was present in 14 of 31 (45·2%) patients. The thyroid status could not predict the presence of a thrombogenic milieu. Despite low CHADS2 score of 0/1, 6 of 13 (46·1%) patients had a thrombogenic milieu, whereas 10 of 18 (55·6%) patients with score ≥2 had none. The probability of having a thrombogenic milieu did not correlate with the number of clinical risk factors.

Conclusion  Among patients younger than 65 years of age with atrial fibrillation related to hyperthyroidism, there is no association between clinical risk factors with TOE markers of a thrombogenic milieu. TOE adds useful information that may affect antithrombotic therapy guided by clinical risk classification.
Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre‐eclampsia
Authors: Miehle Konstanze , Stepan Holger , Fasshauer Mathias
Published: September 2011

Proteins secreted from adipocytes – so‐called adipokines – influence metabolic and vascular function. Recent data suggest that various adipokines are dysregulated in gestational diabetes mellitus (GDM) and pre‐eclampsia (PE) and might be of pathophysiological and prognostic significance in these complications of pregnancy. This review gives an overview on the regulation and pathophysiology of leptin and adiponectin in GDM and PE. Furthermore, data on novel adipokines including resistin, visfatin, retinol‐binding protein 4 and vaspin are summarized.
Altered intestinal tight junctions’ expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability
Authors: Assimakopoulos Stelios F. , Tsamandas Athanassios C. , Tsiaoussis Georgios I. , Karatza Elli , Triantos Christos , Vagianos Constantine E. , Spiliopoulou Iris , Kaltezioti Valeria , Charonis Aristidis , Nikolopoulou Vassiliki N. , Scopa Chrisoula D. , Thomopoulos Konstantinos C.
Published: September 2011

Eur J Clin Invest 2012; 42 (4): 439–446

Background  Increased intestinal permeability in cirrhosis exerts a pivotal role in the pathogenesis of spontaneous bacterial peritonitis and other complications of cirrhosis through promotion of systemic endotoxemia. This study was designed to investigate whether the expression of tight junction (TJ) proteins, which regulate gut paracellular permeability, is altered in the intestinal mucosa of patients with liver cirrhosis and study its potential association with the stage of liver disease and the development of systemic endotoxemia.

Design  Twenty‐four patients with cirrhosis at a decompensated (n = 12, group A) or compensated condition (n = 12, group B) and 12 healthy controls (group C) were subjected to duodenal biopsy. The expression of the TJ proteins occludin and claudin‐1 in the intestinal epithelium was evaluated by immunohistochemistry. Plasma endotoxin concentrations were also determined.

Results  Patients with cirrhosis presented significantly higher serum endotoxin concentrations as compared to healthy controls (P < 0·001), whilst endotoxemia was higher in decompensated disease (P < 0·05 vs. compensated cirrhosis). Patients with decompensated and compensated cirrhosis presented significantly reduced expression of occludin and claudin‐1 as compared to controls (P < 0·01, respectively). These alterations were significantly more pronounced in decompensated patients as compared to compensated (P < 0·05). Regarding occludin, in patients with cirrhosis, a specific pattern of expression in the intestinal epithelium was observed, with a gradually increasing loss of expression from crypt to tip of the villi. Occludin and claudin‐1 expression were inversely correlated with Child–Pugh score (P < 0·001), the grade of oesophageal varices (P < 0·01) and endotoxin concentrations (P < 0·001).

Conclusions  This study demonstrates for the first time that human liver cirrhosis induces significant alterations in enterocytes’ TJs. These changes might represent an important cellular mechanism for intestinal barrier dysfunction and hyperpermeability in patients with liver cirrhosis.
Comparison of pseudo‐random binary sequence and square‐wave transient controlled‐source electromagnetic data over the Peon gas discovery, Norway
Authors: Ziolkowski Anton , Wright David , Mattsson Johan
Published: September 2011

We discuss the problem of source control in controlled‐source electromagnetic (CSEM) surveying and compare and contrast equal energy transient square‐wave and transient pseudo‐random binary sequence source signatures for the same towed‐streamer electromagnetic survey line over the Peon gasfield in the Norwegian sector of the North Sea. The received response of the transient square‐wave data was 11 dB greater than that of the pseudo‐random binary sequence data, due to diffusive attenuation of higher frequencies present in the more broadband pseudo‐random binary sequence signature. Deconvolution of the pseudo‐random binary sequence data recovers the total impulse response function, increases the signal‐to‐noise ratio by 32.6 dB and separates most of the air wave from the earth impulse response by the causality principle. The recovered impulse responses have more detailed information in the frequency domain than the transient square‐wave data. The pseudo‐random binary sequence data were acquired with a 10 Hz source bit rate but contain no information about the Peon gasfield at frequencies above 2 Hz. The bit rate could have been reduced to 4 Hz, increasing the signal energy below 2 Hz by 150% and thus, potentially, increasing the signal‐to‐noise ratio by a further 4 dB.

Because the total earth impulse response can be recovered from the broad‐bandwidth pseudo‐random binary sequence data, further time‐domain processing may be applied, including correlated noise removal, which can increase the signal‐to‐noise ratio by as much as 20 dB, and air wave removal using the causality principle. The information in the arrival time of the peak of the earth response provides the potential for traveltime to resistivity mapping to provide a starting model for inversion.
Increased nitrate availability in the soil of a mixed mature temperate forest subjected to elevated CO2 concentration (canopy FACE)
Authors: Schleppi Patrick , Bucher‐Wallin Inga , Hagedorn Frank , Körner Christian
Published: September 2011

In a mature temperate forest in Hofstetten, Switzerland, deciduous tree canopies were subjected to a free‐air CO2 enrichment (FACE) for a period of 8 years. The effect of this treatment on the availability of nitrogen (N) in the soil was assessed along three transects across the experimental area, one under Fagus sylvatica, one under Quercus robur and Q. petraea and one under Carpinus betulus. Nitrate, ammonium and dissolved organic N (DON) were analysed in soil solution obtained with suction cups. Nitrate and ammonium were also captured in buried ion‐exchange resin bags. These parameters were related to the local intensity of the FACE treatment as measured from the 13C depletion of dissolved inorganic carbon in the soil solution. Over the 8 years of experiment, the CO2 enrichment reduced DON concentrations, did not affect ammonium, but induced higher nitrate concentrations, both in soil solution and resin bags. In the nitrate captured in the resin bags, the natural abundance of the isotope 15N increased strongly. This indicates that the CO2 enrichment accelerated net nitrification, probably as an effect of the higher soil moisture resulting from the reduced transpiration of the CO2‐enriched trees. It is also possible that N mineralization was enhanced by root exudates (priming effect) or that the uptake of inorganic N by these trees decreased slightly as the result of a reduced N demand for fine‐root growth. In this mature deciduous forest, we did not observe any progressive N limitation due to elevated atmospheric CO2 concentrations; on the contrary, we observed an enhanced N availability over the 8 years of our measurements. This may, together with the global warming projected, exacerbate problems related to N saturation and nitrate leaching, although it is uncertain how long the observed trends will last in the future.
Radiocarbon bomb spike reveals biological effects of Antarctic climate change
Authors: Clarke Laurence J. , Robinson Sharon A. , Hua Quan , Ayre David J. , Fink David
Published: September 2011

The Antarctic has experienced major changes in temperature, wind speed and stratospheric ozone levels during the last 50 years. However, until recently continental Antarctica appeared to be little impacted by climate warming, thus biological changes were predicted to be relatively slow. Detecting the biological effects of Antarctic climate change has been hindered by the paucity of long‐term data sets, particularly for organisms that have been exposed to these changes throughout their lives. We show that radiocarbon signals are preserved along shoots of the dominant Antarctic moss flora and use these to determine accurate growth rates over a period of several decades, allowing us to explore the influence of environmental variables on growth and providing a dramatic demonstration of the effects of climate change. We have generated detailed 50‐year growth records for Ceratodon purpureus and three other Antarctic moss species using the 1960s radiocarbon bomb spike. Our growth rate and stable carbon isotope (δ13C) data show that C. purpureus’ growth rates are correlated with key climatic variables, and furthermore that the observed effects of climate variation on growth are mediated through changes in water availability. Our results indicate the timing and balance between warming, high‐wind speeds and elevated UV fluxes may determine the fate of these mosses and the associated communities that form oases of Antarctic biodiversity.
Climate change and spotted owls: potentially contrasting responses in the Southwestern United States
Authors: Peery Marcus Zachariah , Gutiérrez Ralph J. , Kirby Rebecca , LeDee Olivia E. , LaHaye William
Published: September 2011

Developing strategies that reduce the impacts of climate change on biodiversity will require projections of the future status of species under alternative climate change scenarios. Demographic models based on empirical data that link temporal variation in climate with vital rates can improve the accuracy of such predictions and help guide conservation efforts. Here, we characterized how population dynamics and extinction risk might be affected by climate change for three spotted owl (Strix occidentalis) populations in the Southwestern United States over the next century. Specifically, we used stochastic, stage‐based matrix models parameterized with vital rates linked to annual variation in temperature and precipitation to project owl populations forward in time under three IPCC emissions scenarios relative to contemporary climate. Owl populations in Arizona and New Mexico were predicted to decline rapidly over the next century and had a much greater probability of extinction under all three emissions scenarios than under current climate conditions. In contrast, owl population dynamics in Southern California were relatively insensitive to predicted changes in climate, and extinction risk was low for this population under all scenarios. The difference in predicted climate change impacts between these areas was due to negative associations between warm, dry conditions and owl vital rates in Arizona and New Mexico, whereas cold, wet springs reduced reproduction in Southern California. Predicted changes in population growth rates were mediated more by weather‐induced changes in fecundity than survival, and were generally more sensitive to increases in temperature than declines in precipitation. Our results indicate that spotted owls in arid environments may be highly vulnerable to climate change, even in core parts of the owl's range. More broadly, contrasting responses to climate change among populations highlight the need to tailor conservation strategies regionally, and modeling efforts such as ours can help prioritize the allocation of resources in this regard.
Toll‐like receptor‐mediated inhibition of Gas6 and ProS expression facilitates inflammatory cytokine production in mouse macrophages
Authors: Deng Tingting , Zhang Yue , Chen Qiaoyuan , Yan Keqin , Han Daishu
Published: September 2011

Activation of Toll‐like receptors (TLRs) triggers rapid inflammatory cytokine production in various cell types. The exogenous product of growth‐arrest‐specific gene 6 (Gas6) and Protein S (ProS) inhibit the TLR‐triggered inflammatory responses through the activation of Tyro3, Axl and Mer (TAM) receptors. However, regulation of the Gas6/ProS‐TAM system remains largely unknown. In the current study, mouse macrophages are shown to constitutively express Gas6 and ProS, which synergistically suppress the basal and TLR‐triggered production of inflammatory cytokines, including those of tumour necrosis factor‐α, interleukin‐6 and interleukin‐1β, by the macrophages in an autocrine manner. Notably, TLR signalling markedly decreases Gas6 and ProS expression in macrophages through the activation of the nuclear factor‐κB. Further, the down‐regulation of Gas6 and ProS by TLR signalling facilitates the TLR‐mediated inflammatory cytokine production in mouse macrophages. These results describe a self‐regulatory mechanism of TLR signalling through the suppression of Gas6 and ProS expression.
Effect of oestradiol and pathogen‐associated molecular patterns on class II‐mediated antigen presentation and immunomodulatory molecule expression in the mouse female reproductive tract
Authors: Ochiel Daniel O. , Rossoll Richard M. , Schaefer Todd M. , Wira Charles R.
Published: September 2011

Cells of the female reproductive tract (FRT) can present antigen to naive and memory T cells. However, the effects of oestrogen, known to modulate immune responses, on antigen presentation in the FRT remain undefined. In the present study, DO11.10 T‐cell antigen receptor transgenic mice specific for the class II MHC‐restricted ovalbumin (OVA) 323–339 peptide were used to study the effects of oestradiol and pathogen‐associated molecular patterns on antigen presentation in the FRT. We report here that oestradiol inhibited antigen presentation of OVA by uterine epithelial cells, uterine stromal cells and vaginal cells to OVA‐specific memory T cells. When ovariectomized animals were treated with oestradiol for 1 or 3 days, antigen presentation was decreased by 20–80%. In contrast, incubation with PAMP increased antigen presentation by epithelial cells (Pam3Cys), stromal cells (peptidoglycan, Pam3Cys) and vaginal cells (Pam3Cys). In contrast, CpG inhibited both stromal and vaginal cell antigen presentation. Analysis of mRNA expression by reverse transcription PCR indicated that oestradiol inhibited CD40, CD80 and class II in the uterus and CD40, CD86 and class II in the vagina. Expression in isolated uterine and vaginal cells paralleled that seen in whole tissues. In contrast, oestradiol increased polymeric immunoglobulin receptor mRNA expression in the uterus and decreased it in the vagina. These results indicate that antigen‐presenting cells in the uterus and vagina are responsive to oestradiol, which inhibits antigen presentation and co‐stimulatory molecule expression. Further, these findings suggest that antigen‐presenting cells in the uterus and vagina respond to selected Toll‐like receptor agonists with altered antigen presentation.
Interleukin‐32 enhances cytotoxic effect of natural killer cells to cancer cells via activation of death receptor 3
Authors: Park Mi H. , Song Min J. , Cho Min‐Chul , Moon Dong C. , Yoon Do Y. , Han Sang B. , Hong Jin T.
Published: September 2011

Studies have demonstrated that the anti‐tumour effect of natural killer (NK) cells is successful for patients with several cancers. Although interleukin‐32 (IL‐32) is endogenously expressed in NK cells, cytolytic function of NK cells against cancer cells has not been fully demonstrated. In the present study, we found that the growth of cancer cells was suppressed when colon cancer cells or prostate cancer cells were co‐cultured with NK‐92 cells, an NK cell line. We also found that the expression of tumour necrosis factor receptor 2 and death receptor 3 (DR3) was increased in PC3 cells, and the expression of FAS and DR3 was increased in SW620 cells by co‐culture with NK‐92 cells. However, cancer cell growth inhibition and IL‐32 expression were abolished when cancer cells were co‐cultured with NK cells transfected with small interfering (si) RNA of IL‐32. DR3 expression was also diminished by co‐culture with IL‐32‐specific siRNA‐transfected NK‐92 cells. Expression of APO3L, a ligand of DR3, was elevated in NK cells that were co‐cultured with cancer cells. It was also found that expression of apoptosis‐related proteins such as cleaved caspase‐3 and bax was increased in cancer cells co‐cultured with NK‐92 cells, but their expression was abolished by co‐culture with IL‐32 siRNA‐transfected NK‐92 cells. Moreover, knockdown of DR3 in co‐culture of NK‐92 cells with cancer cells by siRNA or antibodies of DR3 and APO3L reversed the growth inhibitory effect of NK‐92 cells. In conclusion, our study showed that IL‐32 enhanced the cytotoxic effect of NK‐92 cells on the cancer cells through activation of DR3 and caspase‐3.
Male accessory gland infection frequency in infertile patients with chronic microbial prostatitis and irritable bowel syndrome
Authors: Vicari E. , Calogero A. E. , Condorelli R. A. , Vicari L. O. , La Vignera S.
Published: September 2011

Recently, we reported an increased prevalence of chronic bacterial prostatitis (CBP) in patients with prostatitis syndromes (PS) and irritable bowel syndrome (IBS) compared with patients with PS alone. The aim of this study was to evaluate the frequency of male accessory gland infections (MAGI) in patients with CBP plus IBS and to compare the sperm parameters of patients with or without MAGI. Fifty consecutive patients with the following criteria were enrolled: (i) infertility; (ii) diagnosis of CBP; and (iii) diagnosis of IBS according to the Rome III criteria. The following two aged‐matched control groups were also studied: infertile patients with CBP alone (n = 56) and fertile men (n = 30) who fathered a child within the previous 3 months. Patients and controls underwent to an accurate anamnesis, administration of the NIH‐Chronic Prostatitis Symptom Index (NIH‐CPSI) and the Rome III questionnaires for prostatitis and IBS, respectively, physical examination, and semen analysis. A significantly higher frequency of MAGI was found in patients with CBP plus IBS (82.0%) compared with the patients with CBP alone (53.6%) or the fertile men (0%). The presence of MAGI in the patients with CBP plus IBS was associated with a significantly lower sperm concentration, total number, and forward motility, and with a higher seminal leucocyte concentration compared with the patients with CBP alone and MAGI. Sperm normal morphology was similar in the groups of patients. All sperm parameters did not differ significantly in both the groups of patients without MAGI. The patients with CBP plus IBS had a significantly higher frequency of MAGI compared with the patients with CBP alone. This was associated with worse sperm parameters and, hence, poorer reproductive prognosis. We suggest to search for the presence of IBS in the patients with PS and in particular when CBP and/or worse sperm parameters are present.
Ubiquitin‐activating enzyme (UBA1) is required for sperm capacitation, acrosomal exocytosis and sperm–egg coat penetration during porcine fertilization
Authors: Yi Y.‐J. , Zimmerman S. W. , Manandhar G. , Odhiambo J. F. , Kennedy C. , Jonáková V. , Maňásková‐Postlerová P. , Sutovsky M. , Park C.‐S. , Sutovsky P.
Published: September 2011

Protein ubiquitination is a stable, covalent post‐translational modification that alters protein activity and/or targets proteins for proteolysis by the 26S proteasome. The E1‐type ubiquitin‐activating enzyme (UBA1) is responsible for ubiquitin activation, the initial step of ubiquitin–protein ligation. Proteasomal proteolysis of ubiquitinated spermatozoa and oocyte proteins occurs during mammalian fertilization, particularly at the site of sperm acrosome contact with oocyte zona pellucida. However, it is not clear whether the substrates are solely proteins ubiquitinated during gametogenesis or if de novo ubiquitination also occurs during fertilization supported by ubiquitin‐activating and ‐conjugating enzymes present in the sperm acrosome. Along this line of inquiry, UBA1 was detected in boar sperm‐acrosomal extracts by Western blotting (WB). Immunofluorescence revealed accumulation of UBA1 in the nuclei of spermatogonia, spermatocytes and spermatids, and in the acrosomal caps of round and elongating spermatids. Thiol ester assays utilizing biotinylated ubiquitin and isolated sperm acrosomes confirmed the enzymatic activity of the resident UBA1. A specific UBA1 inhibitor, PYR‐41, altered the remodelling of the outer acrosomal membrane (OAM) during sperm capacitation, monitored using flow cytometry of fluorescein isothiocyanate‐conjugated peanut agglutinin (FITC‐PNA). Although viable and motile, the spermatozoa capacitated in the presence of PYR‐41, showed significantly reduced fertilization rates during in vitro fertilization (IVF; p < 0.05). Similarly, the fertilization rate was lowered by the addition of PYR‐41 directly into fertilization medium during IVF. In WB, high Mr bands, suggestive of protein ubiquitination, were detected in non‐capacitated spermatozoa by antibodies against ubiquitin; WB with anti‐phosphotyrosine antibodies and antibodies against acrosomal proteins SPINK2 (acrosin inhibitor) and AQN1 (spermadhesin) revealed that the capacitation‐induced modification of those proteins was altered by PYR‐41. In summary, it appears that de novo protein ubiquitination involving UBA1 contributes to sperm capacitation and acrosomal function during fertilization.
Evaluation of the impact of nurse consultant roles in the United Kingdom: a mixed method systematic literature review
Authors: Kennedy Fiona , McDonnell Ann , Gerrish Kate , Howarth Amanda , Pollard Carol , Redman Judith
Published: September 2011

kennedy f., mcdonnell a., gerrish k., howarth a., pollard c. & redman j. (2011) Evaluation of the impact of nurse consultant roles in the United Kingdom: a mixed method systematic literature review. Journal of Advanced Nursing 68(4), 721–742.

Aim.  This paper reports a mixed methods systematic review examining the impact of nurse consultant roles in adult healthcare settings, with a view to identifying indicators for demonstrating their impact on patient and professional outcomes.

Background.  Nurse consultants were introduced in England in 2000 with the intention to achieve better outcomes for patients by improving quality and services. Previous studies have investigated the impact of nurse consultants, but attempts to amalgamate this evidence have been methodologically limited. Since these reviews were published, the importance of demonstrating the contribution of nurse consultants has prompted new research. A robust review of the evidence is now required.

Data sources.  A broad search strategy was adapted for eight databases. Grey literature was sought from various sources.

Review methods.  Quantitative and qualitative studies were included. Study quality was assessed using appropriate instruments. Cross‐study synthesis combined the quantitative and qualitative findings in relation to the dimensions of impact identified. Measures of impact were mapped against a framework for assessing clinical and professional outcomes.

Results.  Thirty‐six studies were included. The findings suggest a largely positive influence of nurse consultants on a range of clinical and professional outcomes, which map onto the proposed framework of impact. However, there was very little robust evidence and the methodological quality of studies was often weak.

Conclusion.  Further robust research is required to explore nurse consultants’ impact on patient and professional outcomes. The proposed framework for assessing impact could be used to guide future research and assist nurse consultants assess their impact.
Territory quality determines social group composition in Ethiopian wolves Canis simensis
Authors: Tallents Lucy A. , Randall Deborah A. , Williams Stuart D. , Macdonald David W.
Published: September 2011

1. We contrast the value of four different models to predict variation in territory size as follows: resource density (the ideal free distribution), population density, group size and intruder pressure (relative resource‐holding potential). In the framework of the resource dispersion hypothesis, we test the effect of resource abundance and spatial variation in resource distribution on the age/sex composition of social groups.

2. We explore these drivers of territory size and group size/composition in Ethiopian wolves Canis simensis in the Bale Mountains, Ethiopia, using fine‐scale distribution maps of their major prey species based on satellite‐derived vegetation maps.

3. The number of adult males is correlated with territory size, while prey density, wolf population density and intruder pressure are not associated with territory size. On average, each additional adult male increases territory size by 1·18 km2.

4. Prey abundance increases with territory size (average biomass accumulation of 6·5 kg km−2), and larger territories provide greater per capita access to prime foraging habitat and prey.

5. The age/sex composition of wolf packs is more closely related to territory quality than territory size. Subordinate adult females are more likely to be present in territories with greater proportions of prime giant molerat Tachyoryctes macrocephalus habitat (i.e. >80% of Web Valley territories and >20% in Sanetti/Morebawa), and more yearlings (aged 12–23 months) occur in territories with greater overall prey biomass.

6. Wolf packs with restricted access to good foraging habitat tend to defend more exclusive territories, having a lower degree of overlap with neighbouring packs.

7. The greater per capita access to prey in large groups suggests a strong evolutionary advantage of collaborative territorial defence in this species, although the relative costs of territorial expansion vs. exclusion depend upon the spatial distribution of resources. We propose a model whereby territory size is determined by the number of adult males, with the presence of subordinate females and yearlings dependent on the quality of habitat, and the abundance and distribution of prey, incorporated within territory boundaries.
Marine megaherbivore grazing may increase seagrass tolerance to high nutrient loads
Authors: Christianen Marjolijn J. A. , Govers Laura L. , Bouma Tjeerd J. , Kiswara Wawan , Roelofs Jan G.M. , Lamers Leon P. M. , van Katwijk Marieke M.
Published: September 2011

1. Populations of marine megaherbivores including green turtle (Chelonia mydas) have declined dramatically at a global scale as a result of overharvesting and habitat loss. This decline can be expected to also affect the tolerance of seagrass systems to coastal eutrophication. Until now, however, simultaneous effects of top–down control by megaherbivore grazing and bottom–up control by nutrient input have not been tested experimentally.

2. We therefore investigated the interacting effects of nutrient (N and P) addition and mimicked green turtle grazing on seagrass and epiphyte productivity, seagrass biomass and nutrient contents in exclosures at a pristine seagrass site in the Indo‐Pacific region (Kalimantan, Indonesia).

3. Grazing almost doubled leaf biomass production rates, while nutrient addition (N+P, slow‐release granules) did not have an effect on these rates. Rhizome biomass was, however, strongly reduced by nutrient addition. In contrast to phosphorus, tissue nitrogen contents increased after nutrient addition, showing that nitrogen was not limiting primary productivity. Epiphyte growth was, however, strongly correlated with high water column P concentrations, indicating an indirect negative effect of eutrophication when turtle grazing would be absent. We calculated that green turtle leaf grazing leads to substantial exports of N and P, at rates of at least 8% of the standing stock per day equalling the daily seagrass production, up to 13 (N) and 1.4 (P) mg m−2 day−1.

4. Synthesis. By combining our quantified effects with literature data, we propose a conceptual model of seagrass functioning under megaherbivore leaf grazing and eutrophication. In tropical seagrass systems with high green turtle grazing pressure, grazing alleviates the negative effects of eutrophication by the stimulation of seagrass production and concomitant nutrient uptake, the increased export of nutrients and the indirect prevention of low below‐ground biomass. Similar to the role of terrestrial megaherbivores, these strong top–down controls show the pivotal role of green turtles in current coastal systems, which is lacking in systems where their numbers have greatly declined. These marine megaherbivores do not only drive structure and functioning of their foraging grounds but also increase the tolerance of seagrass ecosystems to eutrophication.
Receptor subtype‐dependent galanin actions on gamma‐aminobutyric acidergic neurotransmission and ethanol responses in the central amygdala
Authors: Bajo Michal , Madamba Samuel G. , Lu Xiaoying , Sharkey Lisa M. , Bartfai Tamas , Siggins George Robert
Published: September 2011

The neuropeptide galanin and its three receptor subtypes (GalR1‐3) are expressed in the central amygdala (CeA), a brain region involved in stress‐ and anxiety‐related behaviors, as well as alcohol dependence. Galanin also has been suggested to play a role in alcohol intake and alcohol dependence. We examined the effects of galanin in CeA slices from wild‐type and knockout (KO) mice deficient of GalR2 and both GalR1 and GalR2 receptors. Galanin had dual effects on gamma‐aminobutyric acid (GABA)‐ergic transmission, decreasing the amplitudes of pharmacologically isolated GABAergic inhibitory postsynaptic potentials (IPSPs) in over half of CeA neurons but augmenting IPSPs in the others. The increase in IPSP size was absent after superfusion of the GalR3 antagonist SNAP 37889, whereas the IPSP depression was absent in CeA neurons of GalR1 × GalR2 double KO and GalR2 KO mice. Paired‐pulse facilitation studies showed weak or infrequent effects of galanin on GABA release. Thus, galanin may act postsynaptically through GalR3 to augment GABAergic transmission in some CeA neurons, whereas GalR2 receptors likely are involved in the depression of IPSPs. Co‐superfusion of ethanol, which augments IPSPs presynaptically, together with galanin caused summated effects of ethanol and galanin in those CeA neurons showing galanin‐augmented IPSPs, suggesting the two agents act via different mechanisms in this population. However, in neurons showing IPSP‐diminishing galanin effects, galanin blunted the ethanol effects, suggesting a preemptive effect of galanin. These findings may increase understanding of the complex cellular mechanisms that underlie the anxiety‐related behavioral effects of galanin and ethanol in CeA.
EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference
Authors: Schram M. E. , Spuls Ph. I. , Leeflang M. M. G. , Lindeboom R. , Bos J. D. , Schmitt J.
Published: September 2011

To cite this article: Schram ME, Spuls PI, Leeflang MMG, Lindeboom R, Bos JD, Schmitt J. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy 2012; 67: 99–106.

Background:  Demonstration of adequate reliability and validity is sufficient for concluding that an instrument is applicable for descriptive and predictive purposes, but before we can confidently use an outcome measure in clinical trials, the responsiveness (synonymous with sensitivity to change) and minimal clinically important difference (MCID) should be known. With this study, we aimed to assess responsiveness and MCID of four outcome measures used in atopic eczema: the Severity Scoring of Atopic Dermatitis (SCORAD), the objective SCORAD, Eczema Area and Severity Index (EASI), and the Patient‐Oriented Eczema Measure (POEM).

Methods:  Data of three randomized controlled trials were used. To demonstrate responsiveness, we plotted receiver operating characteristic (ROC) curves. MCID was estimated using mean change scores of patients that showed a relevant improvement. Bland and Altman methods were used to quantify the limits of agreement.

Results:  Area under the ROC curve for the SCORAD was 0.70 [95% confidence interval (CI): 0.61–0.78], for the objective SCORAD, 0.73 (95% CI: 0.70–0.77), for the EASI, 0.67 (95% CI: 0.60–0.76), and for the POEM, 0.67 (95% CI: 0.59–0.75). Scores above 0.70 represent a fair responsiveness. The MCID was 8.7 points for the SCORAD, 8.2 for the objective SCORAD, 6.6 for the EASI, and 3.4 for the POEM.

Conclusion:  The objective SCORAD and SCORAD showed a fair responsiveness. The MCIDs are an important prerequisite for the interpretation of published eczema trials and for the planning/sample size estimation of future trials.