bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shiga toxin 1 and ricin A chain bind to human polymorphonuclear leucocytes through a common receptor
Authors: Arfilli Valentina , Carnicelli Domenica , Rocchi Laura , Ricci Francesca , Pagliaro Pasqualepaolo , Tazzari Pier Luigi , Brigotti Maurizio 
Published: September 2010

The main cause of acute renal failure in children is HUS (haemolytic uraemic syndrome), a consequence of intestinal infections with Escherichia coli strains producing Stx (Shiga toxins). Stx released in the gut by the non-invasive bacteria reach the bloodstream and are targeted to cerebral and renal endothelium triggering HUS. PMN (polymorphonuclear leucocytes) seem to be involved in Stx delivery through an unidentified membrane receptor (Kd=10−8 M; 2×105 binding sites) which does not allow internalization. Some experts in the field have defined the Stx–PMN interaction as non-specific and of little biological significance. In the present study, we show that the A chain of ricin, the well-known plant RIP (ribosome-inactivating protein), interacts with PMN (Kd=10−9 M; 2×105 binding sites) competing for the same receptor that recognizes Stx, whereas diphtheria toxin and several agonists of TLRs (Toll-like receptors) or the mannose receptor were ineffective. No toxic effects of ricin A chain on PMN were observed, as assessed by measuring protein synthesis and the rate of spontaneous apoptosis of leucocytes. Moreover, two single-chain RIPs (gelonin and saporin S6) had the same competing effect. Thus RIPs and Stx1 share structural similarities, the same enzymatic activity and a common receptor on PMN. These observations reveal that the Stx–PMN interaction is specific, confirming that PMN recognize molecular patterns common to different foreign molecules.
In vitroexposure of human fibroblasts to local anaesthetics impairs cell growth
Authors: Fedder C , Beck-Schimmer B , Aguirre J , Hasler M , Roth-Z'graggen B , Urner M , Kalberer S , Schlicker A , Votta-Velis G , Bonvini J M , Graetz K , Borgeat A 
Published: September 2010

SummaryLidocaine, bupivacaine or ropivacaine are used routinely to manage perioperative pain. Sparse data exist evaluating the effects of local anaesthetics (LA) on fibroblasts, which are involved actively in wound healing. Therefore, we investigated the effects of the three LA to assess the survival, viability and proliferation rate of fibroblasts. Human fibroblasts were exposed to 0·3 mg/ml and 0·6 mg/ml of each LA for 2 days, followed by incubation with normal medium for another 1, 4 or 7 days (group 1). Alternatively, cells were incubated permanently with LA for 3, 6 or 9 days (group 2). Live cell count was assessed using trypan blue staining. Viability was measured by the tetrazolium bromide assay. Proliferation tests were performed with the help of the colorimetric bromodeoxyuridine assay. Production of reactive oxygen species (ROS) was determined, measuring the oxidation of non-fluorescent-2,7′-dichlorofluorescin. Treatment of cells with the three LA showed a concentration-dependent decrease of live cells, mitochondrial activity and proliferation rate. Group arrangement played a significant role for cell count and proliferation, while exposure time influenced viability. Among the analysed LA, bupivacaine showed the most severe cytotoxic effects. Increased production of ROS correlated with decreased viability of fibroblasts in lidocaine- and bupivacaine-exposed cells, but not upon stimulation with ropivacaine. This study shows a concentration-dependent cytotoxic effect of lidocaine, bupivacaine and ropivacaine on fibroblasts in vitro, with more pronounced effects after continuous incubation. A possible mechanism of cell impairment could be triggered by production of ROS upon stimulation with lidocaine and bupivacaine.
Historical dynamics of a native cerambycid,Enaphalodes rufulus, in relation to climate in the Ozark and Ouachita Mountains of Arkansas
Authors: HAAVIK LAUREL J. , STEPHEN FREDERICK M. 
Published: September 2010

1. Tree‐ring techniques were used to date larval gallery scars of a native wood borer,Enaphalodes rufulus(Haldeman), in hostQuercus rubraL. from eight sites within the Ozark and Ouachita National Forests of Arkansas.2. Borer densities were quantified throughout the past century as indicated by scars within host tree boles and per capita rate of increase was calculated from one generation to the next. Both of these variables were extrapolated to the regional level.3. Scar data from 78Q. rubrarevealed that at the regional level borer population growth increased from 1976 to 2000, or 11 generations prior to a recent outbreak. Duration and intensity of eruptive behaviour were variable geographically.4. Sites with higher outbreak densities also sustained incipient (i.e. growing) populations for a longer time period than sites with lower outbreak densities, which indicates that a greater potential for exponential increase existed at these sites because more borers were present when conditions became favourable for an outbreak.5. An index of summer soil moisture availability explained almost half of the variation inE. rufuluspopulation growth, which suggests that drought may have been an important causal factor in the recent outbreak.
Management of menorrhagia in women with inherited bleeding disorders: general principles and use of desmopressin
Authors: RODEGHIERO F. 
Published: September 2010

Summary.  The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by inherited bleeding disorders. Whereas irregular, premenarchal or postmenopausal uterine bleeding is unusual in inherited or acquired heamorrhagic disorders, severe acute bleeding and menorrhagia at menarche and chronic menorrhagia during the entire reproductive life are common manifestations. Prevalence and morbidity of menorrhagia in inherited bleeding disorders have been poorly investigated. It can be estimated that 40% to 60% of currently menstruating women with type 1 or 2 and more than 60% of women with type 3 VWD complain of menorrhagia with a significant impact on their quality of life. Menorrhagia may be particularly distressing in adolescents because of their delicate emotional equilibrium. Similar epidermiology has been described in other inherited disorders like factor XI deficiency, platelet functional defects and in carriers of haemophilia A and B. Women presenting with ‘‘isolated’’ menorrhagia, that is without significant additional bleeding symptoms, a situation reported by up to 15% of healthy women, do not demand investigation to exclude an occult bleeding disorder.A multidisciplinary approach is required for diagnosis and treatment. Gynaecological supervision is always required to exclude organic causes unmasked by the bleeding disorder. Treatment options are similar to those for menorrhagia in general with the addition of desmopressin and replacement therapy and the exclusion of non‐steroidal anti‐inflammatory drugs. The therapeutic plan should take into consideration the patient's preferences, age and severity of bleeding. Iron supplementation is of paramount importance. Remedies used in clinical practice for menorrhagia in general (tranexamic acid, combined oral contraceptives [COC], levonorgestrel intrauterine system [LNG‐IUS]) are first tried. In case of failure or contraIindication (COC and LNG‐IUS are best avoided in adolescents), before considering surgical options, treatment with desmopressin becomes the preferred choice in patients known to be responsive. The availability of desmopressin preparations for self‐administration makes home treatment feasible in well selected cases. The treatment is efficacious and safe provided that patients are instructed to self‐administer the agent only during the first two or three more heavy days of menstrual period, for a maximum of three to four doses and no more than two consecutive administrations at a 12‐h interval.
Beitrag zur Erweiterung experimenteller Untersuchungs‐methoden beim Schwein
Authors: Hill H. , Prinz W. , Cloos E. 
Published: September 2010

ZusammenfassungEs werden neuere eigene Methoden zur Gewinnung von Harn, peripherem und Pfortaderblut sowie von Darminhalt zur Prüfung von Fragen der Verdauung, der Resorption und des Stoffwechsels beim Schwein beschrieben.SummaryContribution to perfecting experimental methods in the pigOriginal methods are described and illustrated for collecting urine, peripheral and portal blood, and intestinal contents for a study of digestion, absorption and metabolism in the pig.RésuméContribution au perfectionnement des méthodes expérimentales d'examen chez le porcLes auteurs décrivent des méthodes personnelles nouvelles permettant de recueillir l'urine, le sang de la veine porte périphérique ainsi que le contenu intestinal pour étudier certains problèmes de la disgestion, de la résorption et du métabolisme chez le porc.ResumenContribución al estudio de la técnica de análisis clínico experimental en el cerdoSe describen nuevas técnicas originales para la obtención de orina, sangre periférica de la vena porta, así como de contenido intestinal para estudiar problemas digestivos, de la reabsorción y del metabolismo del cerdo.
Zur Anatomie der Lunge des Sumpfbibers (Myocastor s. Myopotamus coypus)
Authors: Koch Tankred 
Published: September 2010

ZusammenfassungNach der Beschreibung der Pleurahöhlen, der Trachea und des Bronchalbaums, der Lungenlappung und der Topographie des Mediastinum werden die für den Sumpfbiber charakteristischen Merkmale besonders zusammengefaßt. Diese sind: Weit kranial verschobene Lage des Herzens und Aortenbogens, hingegen verhältnismäßig starke Kaudalverlagerung der Bifurkation und damit der gesamten Lunge, starke Zwerchfellwölbung und tiefer, aber schimaler Sinus phrenicocostalis. Daraus ergibt sich, daß die gegenseitige Beeinflussung des Kreislauf‐ und Respirationssystems bei diesem Tier auf ein Minimum herabgesetzt ist, was offenbar mit dem ethologisch bedingten Tauchien in funktionellem Zusammenhang stent.SummaryThe anatomy of the lung of the beaver (Myocastor s. Myopotamus coypus)After describing the pleural cavities, trachea and bronchial tree, lung lobes, and the topography of the mediastinum, the author deals with the features which are characteristic of this species. These are: the extremely cranial situation of the heart and aortic arch, whereas the bifurcation of the bronchi and the lungs occupy a markedly caudal situation; the marked convexity of the diaphragm and a deep but narrow phrenicocostal sinus. These features indicate that the reciprocal effects of the circulatory and respiratory systems are reduced to a minimum, a fact which seems to be related functionally to the animal's diving habits.RésuméL'anatomie du poumon chez le myocastorAprès avoir décrit les cavités pleurales, la trachée, les ramifications des branches, les lobes pulmonaires et la topographie du médiastin, l'auteur résume spécialement les particularités observées chez le castor. Ce sont: la position très craniale du coeur et de l'aorte, tandis que la bifurcation des branches, et par suite tout le poumon, se trouvent ainsi déplacés caudalement; une forte convexité du diaphragme et un sinus phrenicocostalis profond mais étroit. Il en résulte que les systèmes circulatoires et respiratoires ont chez cet animal une influence réciproque réduite au minimum, ce qui est semble‐t‐il en rapport fonctionnel avec les plongeons fréquents déterminés par des facteurs éthologiques.ResumenSobre la anatomía del pulmón del miopótamoTras la descripción de las cavidades pleurales, de la tráquea y del árbol bronquial, de la lobulación pulmonar y de la topografía del mediastino, se resumen las características especiales para el miopótamo. Estas son: situación del corazón y del cayado de la aorta muy desplazada en sentido craneal, en cambio se registra un desplazamiento caudal relativamente considerable de la bifurcación y con ello de todo el pulmón; fuerte bóveda diafragmática y seno costofrénico profundo, aunque estrecho. De aquí resulta que la mutua influencia de los sistemas circulatorio y respiratorio en este animal está reducida a un mínimo, lo que evidentemente está en relación funcional con la inmersión etológicamente condicionada.
Development and validation of a photonumeric grading scale for assessing lip volume and thickness
Authors: Rossi AB , Nkengne A , Stamatas G , Bertin C 
Published: September 2010

AbstractBackground  Currently, there is the need of a validated grading scale for assessing lip volume/thickness.Objective  The aim of this study was to assist clinicians in managing individuals seeking lip rejuvenation and to provide an objective method for evaluating the efficacy and longevity of such treatments.Methods  Using accepted criteria for the development of dermatological grading scales, we have developed and validated a photographic grading scale for assessing lip volume and thickness based on digital parallel‐polarized light imaging.Results  The photographic grading scale was shown to be a valid and reliable instrument for assessing lip volume and thickness, with good inter‐ and intra‐grader consistency. The validity of the scale was demonstrated by its correlation with clinical evaluation and 3‐dimensional measurements.Conclusions  This validated lip‐volume/thickness grading scale should prove helpful in clinical trial settings to standardize clinical evaluations and to quantify results and measure the longevity of dermal fillers and other procedures for lip rejuvenation.
Tubulin-Targeting Chemotherapy Impairs Androgen Receptor Activity in Prostate Cancer
Authors: Zhu Meng-Lei , Horbinski Craig M. , Garzotto Mark , Qian David Z. , Beer Tomasz M. , Kyprianou Natasha 
Published: September 2010

Abstract
Recent insights into the regulation of the androgen receptor (AR) activity led to novel therapeutic targeting of AR function in prostate cancer patients. Docetaxel is an approved chemotherapy for treatment of castration-resistant prostate cancer; however, the mechanism underlying the action of this tubulin-targeting drug is not fully understood. This study investigates the contribution of microtubules and the cytoskeleton to androgen-mediated signaling and the consequences of their inhibition on AR activity in human prostate cancer. Tissue microarrays from docetaxel-treated and untreated prostate cancer patients were comparatively analyzed for prostate-specific antigen (PSA) and AR immunoreactivity. The AR transcriptional activity was determined in prostate cancer cells in vitro, based on PSA mRNA expression and the androgen response element reporter activity. The interaction of AR with tubulin was examined by immunoprecipitation and immunofluorescence. Treatment of prostate cancer patients with docetaxel led to a significant translocation of AR. In untreated specimens, 50% prostate tumor cells exhibited nuclear accumulation of AR, compared with docetaxel-treated tumors that had significantly depleted nuclear AR (38%), paralleled by an increase in cytosolic AR. AR nuclear localization correlated with PSA expression. In vitro, exposure of prostate cancer cells to paclitaxel (1 μmol/L) or nocodazole (5 μg/mL) inhibited androgen-dependent AR nuclear translocation by targeting AR association with tubulin. Introduction of a truncated AR indicated the requirement of the NH2-terminal domain for AR-tubulin interaction. Our findings show that in addition to blocking cell division, docetaxel impairs AR signaling, evidence that enables new insights into the therapeutic efficacy of microtubule-targeting drugs in prostate cancer. Cancer Res; 70(20); 7992–8002. ©2010 AACR.
A Novel, Selective, and Efficacious Nanomolar Pyridopyrazinone Inhibitor of V600EBRAF
Authors: Whittaker Steven , Ménard Delphine , Kirk Ruth , Ogilvie Lesley , Hedley Douglas , Zambon Alfonso , Lopes Filipa , Preece Natasha , Manne Helen , Rana Sareena , Lambros Maryou , Reis-Filho Jorge S. , Marais Richard , Springer Caroline J. 
Published: September 2010

Abstract
Oncogenic BRAF is a critical driver of proliferation and survival and is thus a validated therapeutic target in cancer. We have developed a potent inhibitor, termed 1t (CCT239065), of the mutant protein kinase, V600EBRAF. 1t inhibits signaling downstream of V600EBRAF in cancer cells, blocking DNA synthesis, and inhibiting proliferation. Importantly, we show that 1t is considerably more selective for mutated BRAF cancer cell lines compared with wild-type BRAF lines. The inhibitor is well tolerated in mice and exhibits excellent oral bioavailability (F = 71%). Suppression of V600EBRAF-mediated signaling in human tumor xenografts was observed following oral administration of a single dose of 1t. As expected, the growth rate in vivo of a wild-type BRAF human tumor xenograft model is unaffected by inhibitor 1t. In contrast, 1t elicits significant therapeutic responses in mutant BRAF–driven human melanoma xenografts. Cancer Res; 70(20); 8036–44. ©2010 AACR.
CRLF2 and JAK2 in B-Progenitor Acute Lymphoblastic Leukemia: A Novel Association in Oncogenesis
Authors: Roll J. Devon , Reuther Gary W. 
Published: September 2010

AbstractExpression of cytokine receptor-like factor 2 (CRLF2) has recently been shown to be upregulated as well as mutated in populations of B-progenitor acute lymphoblastic leukemia (B-ALL), including Down syndrome (DS-ALL) patients, lacking recurring chromosomal translocations. Increased CRLF2 expression associates with JAK2 mutation, a combination that transforms hematopoietic cells, suggesting that mutant JAK2 and CRLF2 may cooperate to contribute to B-ALL formation. Importantly, elevated CRLF2 expression correlates with poor outcome in high-risk B-ALL patients. Therefore, CRLF2 may provide a new prognostic marker for high-risk B-ALL, and inhibition of CRLF2/JAK2 signaling may represent a therapeutic approach for this population of ALL patients. Cancer Res; 70(19); 7347–52. ©2010 AACR.
Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-Defined Morbidity and Mortality Associated With Pediatric Ventricular Assist Device Support at a Single US Center
Authors: Stein Mary Lynette , Robbins Robert , Sabati Arash Alen , Reinhartz Olaf , Chin Clifford , Liu Esther , Bernstein Daniel , Roth Stephen , Wright Gail , Reitz Bruce , Rosenthal David 
Published: September 2010

Background—
The use of ventricular assist devices (VADs) to bridge pediatric patients to heart transplantation has increased dramatically over the last 15 years. In this report, we present the largest US single-center report of pediatric VAD use to date. We present detailed descriptions of morbidity and mortality associated with VAD support, using standard Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria for pediatrics to facilitate the comparison of these results to other studies.

Methods and Results—
We retrospectively identified 25 patients younger than 18 years with 27 episodes of mechanical circulatory support using VADs as bridge to heart transplantation from January 1998 to December 2007. Survival to transplant for the entire cohort was 74%. The most common major morbidities, as defined by INTERMACS criteria for a pediatric population, were respiratory failure, major localized infections, major bleeding events, hepatic dysfunction, and right heart failure. Major neurological events occurred in 48% of the study population. The median time to the first occurrence of an adverse event was less than 14 days for respiratory failure, right heart failure, major localized infection, and major bleeding. Patients who died before transplantation had significantly more adverse events per day of support than did those who were successfully transplanted. Episodes of major bleeding, tamponade, acute renal failure, respiratory failure, and right heart failure were all associated with increased risk of mortality.

Conclusions—
INTERMACS criteria can be successfully used to analyze pediatric VAD outcomes. These data serve as a baseline for future studies of VAD support in children and indicate good survival rates but considerable morbidity.
The Effect of Dietary Patterns on Estimated Coronary Heart Disease Risk
Authors: Chen Steven T. , Maruthur Nisa M. , Appel Lawrence J. 
Published: September 2010

Background—
The Dietary Approaches to Stop Hypertension (DASH) diet is recommended in the 2005 US Dietary Guidelines. To understand the potential benefits of DASH on coronary heart disease (CHD), we applied the Framingham risk equations to calculate 10-year risk of developing CHD using data from the DASH trial.

Methods and Results—

In the DASH trial, 459 individuals with prehypertension or stage-1 hypertension not taking antihypertensive medication were randomly assigned to 1 of 3 diets: control, fruits and vegetables (F/V), or DASH (rich in fruits, vegetables, low-fat dairy, and reduced in fats and cholesterol). Weight was held constant. Estimated 10-year CHD risk was the primary outcome of this secondary analysis. Among 436 participants with complete data, mean (SD) age was 44.7 (10.7) years, 51% were male, and 60% were African-American. Median 10-year CHD risk was 0.98% at baseline and decreased in all groups. Compared with control, the relative risk ratio comparing 8-week with baseline 10-year CHD risk was 0.93 (95% confidence interval, 0.85 to 1.02;
P
=0.12) for F/V and 0.82 (95% confidence interval, 0.75 to 0.90;
P
<0.001) for DASH. Comparing DASH with F/V, the relative risk ratio was 0.89 (95% confidence interval, 0.81 to 0.97;
P
=0.012). With the exception of an interaction between dietary pattern and race suggesting a greater risk reduction in blacks than whites (
P
for interaction=0.038), results were similar across subgroups.

Conclusions—
Compared with control and F/V, the DASH diet reduced estimated 10-year CHD risk by 18% and 11%, respectively. In addition to reducing blood pressure, the DASH diet should substantially reduce the risk of CHD.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00000544.
Evaluation of the consequences associated with diffuse vascular disease history in patients diagnosed with peripheral arterial disease: estimates from Saskatchewan health data
Authors: Migliaccio-Walle Kristen , Stokes Michael , Proskorovsky Irina , Popovici-Toma Dan , El-Hadi Wissam 
Published: September 2010

Abstract

Background
Peripheral arterial disease (PAD) is caused by narrowing of the arteries in the lower extremities. Limited data exist concerning the impact of diffuse vascular disease (DVD) on prognosis and costs. Thus, the objective of this study is to estimate the impact of DVD on morbidity, mortality and costs.

Methods
PAD was identified between 1985 and 1995 and classified by extent of DVD at diagnosis: none (PAD only, reference group), prior myocardial infarction (MI), prior stroke, prior MI and stroke (MI + stroke), prior transient ischemic attack (TIA). Deaths and hospitalizations were identified through December 2000. Hospitalization costs were estimated from the Ontario Case Cost Project, reported in 2002 $CAD. Proportional hazards analyses measured the impact of vascular involvement on mortality while controlling for risk factors (e.g., age, cardiovascular history).

Results
Overall, 16,439 patients with PAD were included; 14.8% had a prior MI, 10.2% a prior stroke, 2.6% prior MI + stroke, 6.4% prior TIA, two-thirds had PAD only. Median survival was shorter for patients with prior MI (9.3 yrs), TIA (6.3), stroke (4.7), and MI+stroke (4.1) versus the reference group (9.9, p < 0.05, all comparisons). Analyses revealed that the death risk was 60% higher in patients with prior stroke and 84% higher for MI + stroke. Atherothrombotic and bleeding event-related costs were $712, $337, $268, and $170 higher per patient/year of follow-up in patients with a history of MI+stroke, MI, stroke, and TIA, respectively.

Conclusion
Patients diagnosed with PAD with DVD have higher risk of poor outcomes and increased costs.